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    Hochgeladen von

    Carlos Hernández
    846 Ansichten205 Seiten
    The document contains the text and formatting for an algorithm treatment graphic for HBV in children. It includes copyright information and options to print or email the graphic. The main content is an image of an algorithm flowchart outlining the selection process for antiviral treatment of HBV in children.

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    61.txt

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    The document contains the text and formatting for an algorithm treatment graphic for HBV in children. It includes copyright information and options to print or email the graphic. The main content is an image of an algorithm flowchart outlining the selection process for antiviral treatment of HBV in children.

    Copyright:

    © All Rights Reserved
    Als TXT, PDF, TXT herunterladen oder online auf Scribd lesen
    Markieren Sie unangemessene Inhalte
    846 Ansichten205 Seiten

    61

    Hochgeladen von

    Carlos Hernández
    The document contains the text and formatting for an algorithm treatment graphic for HBV in children. It includes copyright information and options to print or email the graphic. The main content is an image of an algorithm flowchart outlining the selection process for antiviral treatment of HBV in children.

    Copyright:

    © All Rights Reserved
    Als TXT, PDF, TXT herunterladen oder online auf Scribd lesen
    Markieren Sie unangemessene Inhalte
    von 205

    var title_f0_61_976="Algorithm treatment HBV children";

    var content_f0_61_976=[" <div id=\"graphicsToolbar\">",


    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
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    " &reg;",
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    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
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    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=PEDS
    %2F78464&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\"
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    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
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    " <div class=\"graphic\">",
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    " Algorithm for selection of children for HBV antiviral treatment",
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    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " HBV: hepatitis B virus; HBsAg: hepatitis B s antigen; ALT: alanine
    aminotransferase; HBeAg: hepatitis B e antigen; HCC: hepatocellular carcinoma; IU:
    international unit.",
    " <br>",
    " * The upper limit of normal (ULN) for ALT in children is not well
    established; it varies with the testing laboratory and the age of the child. For
    the purposes of HBV monitoring, we suggest that a child's ALT be considered
    elevated if it is greater than the ULN established by the testing laboratory, or
    &gt;40 IU/L, whichever is lower. For older adolescents, we suggest using 30 IU/L
    for males and 19 IU/L for females (the same ULN used for adults).",
    " <br>",
    " <font class=\"bullet\">",
    " &bull;",
    " </font>",
    " Because of limited options with current drugs, it may be appropriate to
    treat older adolescents with immune active HBV with one of these newer agents using
    adult protocols, or to enroll children in clinical trials of newer agents, or even
    withhold treatment until the patient is old enough to be treated as adults (if
    liver fibrosis is only mild).",
    " </br>",
    " </br>",
    " </div>",
    " <div class=\"reference\">",
    " Jonas MM, Block JM, Haber BA, et al. Treatment of children with chronic
    hepatitis B virus infection in the United States: Patient selection and therapeutic
    options. Hepatology 2010. Copyright &copy; 2010 American Association for the Study
    of Liver Diseases. Reproduced with permission from John Wiley &amp; Sons.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_61_976=[""].join("\n");
    var outline_f0_61_976=null;
    var title_f0_61_977="Crowing rooster maneuver";
    var content_f0_61_977=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=RHEUM
    %2F80833&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=RHEUM
    %2F80833&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
    title=\"Print this page\">",
    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 470px\">",
    " <div class=\"ttl\">",
    " Crowing rooster maneuver",
    " </div>",
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    " </div>",
    " <div class=\"lgnd\">",
    " The crowing rooster maneuver is performed with the physician standing behind
    the patient, and exerting traction on the upper arms by pulling them backward and
    slightly superiorly. Both of these maneuvers may be done at the same time as neck
    extension or rotation.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_61_977=[""].join("\n");
    var outline_f0_61_977=null;
    var title_f0_61_978="Volar displaced fx";
    var content_f0_61_978=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=EM
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    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=EM
    %2F69020&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
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    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 474px\">",
    " <div class=\"ttl\">",
    " Displaced volar fracture",
    " </div>",
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    " </div>",
    " <div class=\"lgnd\">",
    " Reverse bayonet. Panel A) Typical volar bayonet fracture. Often the distal end
    of the proximal fragment is buttonholed through the extensor tendons (arrows).
    (Copyright &copy; 1994 American Academy of Orthopaedic Surgeons. Reprinted from
    Operative Management of Upper Extremity Fractures in Children p.27 with
    permission.) Panel B) Intact volar periosteum and disrupted dorsal periosteum
    (arrows). The extensor tendons are displaced to either side of the proximal
    fragment.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Reproduced with permission from: Waters PM, Mih AD. Fractures of the distal
    radius and ulna. In: Rockwood and Wilkins' Fractures in Children, 6th ed, Beaty JH,
    Kasser JR (Eds), Lippincott Williams &amp; Wilkins, Philadelphia 2006. Copyright
    &copy; 2006 Lippincott Williams &amp; Wilkins.",
    " </div>",
    " <div class=\"contractual\">",
    " <br/>",
    " <a href=\"file://www.lww.com\">",
    " file://www.lww.com",
    " </a>",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
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    " <a class=\"etacLink\" href=\"#\">",
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    " Email",
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    " <div class=\"graphic\">",
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    " <div class=\"ttl\">",
    " Clonorchiasis adult",
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    ">",
    " </div>",
    " <div class=\"lgnd\">",
    " (A) Adult of",
    " <em>",
    " C. sinensis",
    " </em>",
    " .",
    " <br>",
    " (B) Adult of",
    " <em>",
    " C. sinensis",
    " </em>",
    " stained with carmine. Clearly visible in this image are the oral sucker (OS),
    pharynx (PH), ceca (CE), acetabulum, or ventral sucker (AC), uterus (UT),
    vitellaria (VT), and testes (TE).",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Reproduced from: Centers for Disease Control and Prevention. Parasites and
    Health: Clonorchiasis. Available at:",
    " <a href=\"file://dpd.cdc.gov/dpdx/html/Clonorchiasis.htm\"
    target=\"_blank\">",
    " file://dpd.cdc.gov/dpdx/html/Clonorchiasis.htm",
    " </a>",
    " .",
    " </div>",
    " </br>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_61_979=[""].join("\n");
    var outline_f0_61_979=null;
    var title_f0_61_980="Transient dilation pharm stress";
    var content_f0_61_980=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=CARD
    %2F80109&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=CARD
    %2F80109&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\"
    title=\"Print this page\">",
    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 470px\">",
    " <div class=\"ttl\">",
    " Transient ischemic LV dilatation during pharmacologic stress",
    " </div>",
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    " </div>",
    " <div class=\"lgnd\">",
    " Stress images demonstrate reversible anterior and inferior perfusion
    abnormalities (red arrow). The short axis images demonstrate transient ischemic
    left ventricular (LV) dilatation, which is associated with higher cardiac events.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Courtesy of Muthu Velusamy, MD.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
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    >",
    " </div>",
    " <div class=\"lgnd\">",
    " Spirometry is a breathing test that measures how well the lungs are working.
    It involves breathing in as deeply as you can, and then breathing out fast and hard
    into a mouthpiece. The mouthpiece is attached to a machine called
    a \"spirometer\".",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Reproduced from: National Heart Lung and Blood Institute. Types of Lung
    Function Tests: Spirometry.",
    " <a href=\"file://www.nhlbi.nih.gov/health/health-
    topics/topics/lft/types.html\" style=\"FONT-STYLE: italic\" target=\"_blank\">",
    " file://www.nhlbi.nih.gov/health/health-topics/topics/lft/types.html",
    " </a>",
    " (Accessed June 19, 2012).",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_61_981=[""].join("\n");
    var outline_f0_61_981=null;
    var title_f0_61_982="Saphenous vein cutdown dissection and cannulation";
    var content_f0_61_982=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
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    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
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    " <a class=\"icontxt textLink\" href=\"?imageKey=EM
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    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
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    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 560px\">",
    " <div class=\"ttl\">",
    " Saphenous vein cutdown: dissection and cannulation",
    " </div>",
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    " </div>",
    " <div class=\"lgnd\">",
    " A) Isolate the saphenous vein by blunt dissection using a curved hemostat
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    the long axis of the vein to produce a flap halfway through the vein. C) Hold the
    vein flap open with a curved hook. Insert a beveled catheter into the vein opening.
    D) Advance the catheter into the vein. The catheter may be easier to advance when
    fluid is running through it.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
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    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
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    var title_f0_61_983="Cardiac resynchronization therapy in atrial fibrillation";
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    " <div id=\"topicContent\">",
    " <div id=\"topicTitle\">",
    " Cardiac resynchronization therapy in atrial fibrillation",
    " </div>",
    " <div id=\"topicContributors\">",
    " <div>",
    " <a id=\"authors\">",
    " </a>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/61/983/contributors\">",
    " Authors",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/61/983/contributors\">",
    " Leslie A Saxon, MD",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/61/983/contributors\">",
    " Michael Cao, MD",
    " </a>",
    " <br/>",
    " </div>",
    " <div>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/61/983/contributors\">",
    " Section Editors",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/61/983/contributors\">",
    " Wilson S Colucci, MD",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/61/983/contributors\">",
    " Bradley P Knight, MD, FACC",
    " </a>",
    " <br/>",
    " </div>",
    " <div>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/61/983/contributors\">",
    " Deputy Editor",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/61/983/contributors\">",
    " Susan B Yeon, MD, JD, FACC",
    " </a>",
    " <br/>",
    " </div>",
    " </div>",
    " <div id=\"disclosures\">",
    " <a href=\"UTD.htm?0/61/983/contributor-disclosure\" target=\"_blank\">",
    " Disclosures",
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    " is complete.",
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    " <div id=\"literatureReviewDate\">",
    " <span class=\"emphasis\">",
    " Literature review current through:",
    " </span>",
    " Oct 2013.",
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    " |",
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    " <span class=\"emphasis\">",
    " This topic last updated:",
    " </span>",
    " Mar 13, 2013.",
    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;In patients with significant dyssynchrony due to intrinsic
    conduction disease, cardiac resynchronization therapy (CRT) with biventricular
    (BiV) pacing can improve ventricular synchrony. This is accomplished with an
    additional pacemaker lead implanted on the lateral left ventricle via a coronary
    vein. Among selected patients with HF who are in sinus rhythm, CRT improves cardiac
    performance, symptoms, and overall survival. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?17/56/18314?
    source=see_link\">",
    " \"Cardiac resynchronization therapy in heart failure: Indications\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The prevalence of atrial fibrillation (AF) in patients with heart failure
    varies with severity, ranging from 5 percent in patients with NYHA functional class
    I HF to 40 percent in patients with NYHA class IV HF (",
    " <a class=\"graphic graphic_table graphicRef52683 \" href=\"UTD.htm?
    3/2/3117\">",
    " table 1",
    " </a>",
    " )&nbsp;[",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/1\">",
    " 1",
    " </a>",
    " ]",
    " </p>",
    " <p>",
    " The use of CRT in patients with AF will be reviewed here. The general use of
    CRT in patients in sinus rhythm and the rationale for and mechanisms of benefit of
    CRT are discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?17/56/18314?
    source=see_link\">",
    " \"Cardiac resynchronization therapy in heart failure: Indications\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?10/36/10823?
    source=see_link\">",
    " \"Rationale for and mechanisms of benefit of cardiac resynchronization
    therapy\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " USE OF CRT IN AF",
    " </span>",
    " &nbsp;&mdash;&nbsp;Among patients with chronic AF, CRT may be considered in
    two settings:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Patients with AF who have an indication for atrioventricular (AV) node
    ablation for the purpose of definitive rate control may, via CRT, avoid the
    negative effects of dyssynchrony that can be induced by right ventricular pacing.",
    " </li>",
    " <li>",
    " Patients with AF who have HF may benefit from CRT. In this setting, AV node
    ablation appears to promote the efficacy of CRT by eliminating native AV
    conduction, thereby ensuring almost 100 percent biventricular pacing.",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h2\">",
    " Patients with an indication for AV node ablation",
    " </span>",
    " &nbsp;&mdash;&nbsp;The most common nonpharmacologic method of ventricular rate
    control in AF is catheter-based radiofrequency ablation (RFA) of the AV node",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " the His bundle. Because of the invasive nature of the procedure and the
    associated requirement for permanent pacemaker implantation, this treatment is
    generally reserved for patients in whom pharmacologic rate control therapy is
    either unsuccessful or not tolerated. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/53/24408?
    source=see_link\">",
    " \"Control of ventricular rate in atrial fibrillation: Nonpharmacologic
    therapy\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The majority of well-selected patients improve hemodynamically following AV
    junction ablation and standard right ventricular (RV) pacing. However, RV pacing
    causes the RV to contract before the LV (interventricular dyssynchrony), causing
    the septum to contract before the lateral wall (intraventricular dyssynchrony).
    Thus, ventricular pacing can induce ventricular dyssynchrony [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/2,3\">",
    " 2,3",
    " </a>",
    " ], which may impair LV systolic function, reduce functional status, and
    increase mortality. Patients with moderate or severe mitral regurgitation",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " LV dysfunction appear to be at the highest risk of clinical deterioration with
    RV pacing. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?30/49/31510?
    source=see_link\">",
    " \"Overview of cardiac pacing in heart failure\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " These observations provide the rationale for prophylactic CRT in patients with
    AF who are undergoing AV node ablation. Observational studies and small randomized
    trials support the value of CRT in this setting, particularly for patients with
    reduced LV systolic function or heart failure (HF) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/4,5\">",
    " 4,5",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " In the randomized PAVE trial, 184 patients with chronic AF (83 percent with
    NYHA class II or III HF) underwent AV node ablation to treat medically refractory
    rapid ventricular rates and were randomly assigned to standard RV pacing or CRT [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/6\">",
    " 6",
    " </a>",
    " ]. At six month follow-up, the following results were noted:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " CRT resulted in significantly greater post-ablation increases in six-minute
    walking distance, peak oxygen consumption with exercise, and exercise duration
    compared to standard RV pacing (31 versus 24 percent improvement, respectively).",
    " </li>",
    " <li>",
    " CRT resulted in preservation of the left ventricular ejection fraction
    (LVEF) which was significantly greater than in patients treated with RV pacing.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " The benefits of CRT were more prominent in patients with an LVEF &le;45
    percent or with NYHA class II or III HF, compared to patients with less severe
    disease as manifested by a higher LVEF or NYHA class I HF.",
    " </p>",
    " <p>",
    " Based upon these observations, a CRT system was approved by the United States
    Food and Drug Administration in patients who have undergone AV node ablation and
    have NYHA class II or III HF [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/7\">",
    " 7",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h2\">",
    " Patients with heart failure",
    " </span>",
    " &nbsp;&mdash;&nbsp;Data on CRT in patients with AF and heart failure (HF) are
    limited and have not proven the efficacy of CRT in this setting. Patients with
    atrial arrhythmias were excluded from the major CRT trials, such as CARE-HF and
    COMPANION [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/8\">",
    " 8",
    " </a>",
    " ]. However, observational studies and a small randomized crossover trial
    suggest a benefit from CRT in AF patients [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/9-13\">",
    " 9-13",
    " </a>",
    " ]. In addition, in the CARE-HF trial, while mortality was higher for patients
    who developed AF, these patients still benefitted from CRT for all major study end
    points [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/14\">",
    " 14",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " A meta-analysis of observational data from five studies (four prospective
    cohort studies and the MUSTIC randomized trial [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/11\">",
    " 11",
    " </a>",
    " ]) compared responses to CRT in 797 patients in sinus rhythm and 367 patients
    in AF [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/9\">",
    " 9",
    " </a>",
    " ]. The overall use of AV node ablation was 56 percent. The NYHA functional
    class improved similarly for both groups although relative improvements in the 6
    minute walk test and Minnesota score were greater in sinus rhythm patients than AF
    patients.",
    " </p>",
    " <p>",
    " In 2011, a meta-analysis of 23 studies reported that patients with atrial
    fibrillation had higher rates of clinical non-response to CRT (34.5 versus 26.7
    percent) and higher mortality rates after CRT placement than patients with sinus
    rhythm. This meta-analysis was based on observations in a total of 7495 CRT
    recipients, 25.5 percent of whom had atrial fibrillation, and who were followed for
    a mean of 33 months. The presence of atrial fibrillation was associated with less
    improvement in quality of life, six-minute hall walk distance, and LV end-systolic
    volume but not LV ejection fraction [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/15\">",
    " 15",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The MUSTIC AF trial was not included in the meta-analysis since it did not
    include patients in sinus rhythm. This study included 59 patients with HF and
    chronic AF with wide QRS complex who required a permanent pacemaker because of a
    slow ventricular rate; the patients were randomly assigned to either single site
    right ventricular (RV) pacing or biventricular (BiV) pacing in a crossover fashion
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/10,11\">",
    " 10,11",
    " </a>",
    " ]. Sixty-three percent of AF patients had undergone AV node ablation.",
    " </p>",
    " <p>",
    " Only 39 patients completed the six month crossover trial, which limits any
    conclusions that can be drawn [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/10\">",
    " 10",
    " </a>",
    " ]. Using an intention-to-treat analysis, there were no significant differences
    in exercise tolerance or peak oxygen consumption. In contrast, when data from the
    37 patients who received effective therapy (97 to 100 percent paced cycles) were
    evaluated, BiV pacing was associated with a significant increase in six minute walk
    distance and peak oxygen consumption.",
    " </p>",
    " <p>",
    " In the RAFT trial, patients with permanent AF were randomly assigned to
    receive either an implantable cardioverter defibrillator (ICD, n = 115) or cardiac
    resynchronization combined with an implantable cardioverter defibrillator (CRT-D, n
    = 114) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/16\">",
    " 16",
    " </a>",
    " ]. The ICD and CRT-D groups were comparable in age (mean 70 and 72 years),
    LVEF (mean 22.3 and 22.9), and QRS duration (153.4&plusmn;24.7 ms and
    151.0&plusmn;23.6). There was no difference in the primary outcome of death or HF
    hospitalization, but there was a nearly significant trend for fewer HF
    hospitalizations with CRT-D (HR = 0.58, p = 0.052). The change in six-minute walk
    duration between baseline and 12 months was similar in the two groups, but the CRT-
    D group showed a nearly significant trend for greater improvement in Minnesota
    Living with Heart Failure Score between baseline and six months (p = 0.057). Of
    note, CRT was suboptimally delivered with only",
    " <span class=\"nowrap\">",
    " 1/3",
    " </span>",
    " of patients receiving &gt;95 percent ventricular pacing and only one patient
    underwent AV node ablation.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h3\">",
    " Role of AV node ablation",
    " </span>",
    " &nbsp;&mdash;&nbsp;For patients with LV dyssynchrony, benefit from CRT
    requires BiV pacing to occur most of the time (ie, intrinsic dyssynchronous
    conduction should be rare). This can be difficult to accomplish in patients with AF
    if conduction through the AV node is rapid. However, AV node ablation eliminates
    intrinsic conduction, resulting in ventricular pacing 100 percent of the time.",
    " </p>",
    " <p>",
    " The role of AV node ablation in combination with CRT was evaluated in a series
    of 673 patients receiving a CRT device for conventional indications (LVEF &le;35
    percent, NYHA class &ge;II, and a QRS duration &gt;120 msec) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/17\">",
    " 17",
    " </a>",
    " ]. Among the 162 patients in this cohort with chronic AF, 48 were given
    medical therapy for rate control and 114 underwent AV node ablation. In contrast to
    the above described studies in which AV node ablation was necessary for rate
    control, AV node ablation in this study was performed to ensure frequent BiV pacing
    (&gt;85 percent of the time).",
    " </p>",
    " <p>",
    " At four-year follow up, the following findings were noted:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Patients with AF and sinus rhythm had similar improvements in LVEF, reverse
    remodeling, and exercise tolerance.",
    " </li>",
    " <li>",
    " Among patients with AF, the benefits of CRT were only seen in those patients
    who had undergone AV node ablation. Despite BiV pacing more than 85 percent of the
    time, patients being treated with medications for rate control showed no
    improvement in LV function or functional capacity.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Another observational study suggested that AV node ablation plus CRT may
    significantly improve survival compared to CRT alone [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/18\">",
    " 18",
    " </a>",
    " ]. Among 1285 patients treated with CRT, 243 were in AF. Rate control was
    achieved by AV node ablation in 188 patients and medical therapy in 55; all
    patients had at least 85 percent BiV pacing. During 34 months median follow-up,
    mortality was significantly lower in patients treated with AV node ablation (4.3
    versus 15.2 percent in patients treated with drugs for rate control, adjusted
    hazard ratio 0.26 for all cause mortality and 0.15 for HF mortality).",
    " </p>",
    " <p>",
    " These results suggest that clinicians following CRT recipients should target
    complete (100 percent) BiV pacing for CRT to achieve maximum benefit. A study
    reporting on 36,935 patients whose CRT devices were followed in a remote monitoring
    network found that increased percentages of biventricular pacing were associated
    with significant mortality reduction. The optimal cut-point was 98.4 percent and
    patients with a biventricular pacing percentage above 99.6 percent experienced up
    to a 24 percent reduction in mortality risk compared to patients with lesser
    percentages of CRT [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/19\">",
    " 19",
    " </a>",
    " ]. This observation has not been confirmed by randomized trials. Until such
    data are available, the indications for BiV pacing in combination with AV junction
    ablation are uncertain. This modality may be considered particularly in patients
    with significant left ventricular dysfunction at baseline and those who deteriorate
    with RV pacing [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/4,20\">",
    " 4,20",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h3\">",
    " Comparison with pulmonary vein isolation",
    " </span>",
    " &nbsp;&mdash;&nbsp;Limited data are available comparing CRT with or without AV
    node ablation to other therapies for AF in patients with HF. A small randomized
    trial suggested that, in appropriately selected patients with AF and HF, pulmonary
    vein isolation may produce a greater increase in LVEF and greater improvements in
    six-minute walk distance and quality of life than CRT with AV node ablation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/21\">",
    " 21",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/30/24042?
    source=see_link\">",
    " \"Atrial fibrillation in patients with heart failure\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h1\">",
    " EFFECT OF CRT ON AF",
    " </span>",
    " &nbsp;&mdash;&nbsp;Cardiac resynchronization therapy has a favorable impact on
    potential risk factors for AF such as neurohormonal activation, left ventricular
    systolic dysfunction, atrial size and degree of mitral regurgitation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/10,22-24\">",
    " 10,22-24",
    " </a>",
    " ]. However, it is not clear if CRT reduces the incidence of AF. A small
    observational study found a reduced incidence of AF in CRT-treated patients
    compared with matched controls [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/25\">",
    " 25",
    " </a>",
    " ]. However, CRT did not decrease the incidence of AF in large randomized
    trials, although AF was not a prespecified end point [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/14,26\">",
    " 14,26",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H15416960\">",
    " <span class=\"h1\">",
    " OUR APPROACH",
    " </span>",
    " &nbsp;&mdash;&nbsp;Our recommendations for CRT in patients with AF are
    generally in agreement with the 2012",
    " <span class=\"nowrap\">",
    " ACC/AHA/HRS",
    " </span>",
    " guidelines [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/27\">",
    " 27",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " In patients with AF and a left ventricular ejection fraction (LVEF) &le;35
    percent who require ventricular pacing or otherwise meet CRT criteria",
    " <strong>",
    " and",
    " </strong>",
    " in whom AV nodal ablation or pharmacologic rate control will allow near 100
    percent ventricular pacing with CRT, we suggest CRT.",
    " </li>",
    " <li>",
    " In the above statement, &ldquo;otherwise meet CRT criteria&rdquo; means LBBB
    with QRS &ge;120 ms and NYHA class II, III, or ambulatory IV symptoms on optimal
    medical therapy.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " In patients with AF, CRT can be achieved with a VVIR or a DDDR pacing
    modality, depending upon whether or not the patient has chronic or paroxysmal AF.",
    " </p>",
    " <p>",
    " Most patients who satisfy either of the above criteria are also candidates for
    an ICD and should receive a combined device (CRT-D). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?18/55/19322?
    source=see_link&amp;anchor=H14#H14\">",
    " \"Secondary and primary prevention of sudden cardiac death in heart failure
    and cardiomyopathy\", section on 'Role of an ICD'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h1\">",
    " MAJOR SOCIETY GUIDELINES",
    " </span>",
    " &nbsp;&mdash;&nbsp;Major society guidelines have noted that the strength of
    evidence supporting CRT use in patients in sinus rhythm is greater than that
    supporting use in patients in atrial fibrillation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/28-30\">",
    " 28-30",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The 2012 focused update to the 2008 American College of",
    " <span class=\"nowrap\">",
    " Cardiology/American",
    " </span>",
    " Heart",
    " <span class=\"nowrap\">",
    " Association/Heart",
    " </span>",
    " Rhythm Society",
    " <span class=\"nowrap\">",
    " (ACC/AHA/HRS)",
    " </span>",
    " guidelines for device-based therapy include the following recommendations that
    apply to certain patients with AF [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/30\">",
    " 30",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " CRT can be useful in patients with AF who have a left ventricular ejection
    fraction (LVEF) &le;35 percent on guideline-directed medical therapy if a) the
    patient requires ventricular pacing or otherwise meets CRT criteria and b) AV nodal
    ablation or pharmacologic rate control will allow near 100 percent ventricular
    pacing with CRT.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &ldquo;Otherwise meets CRT criteria&rdquo; in this context means a QRS
    duration &ge;0.12 seconds and NYHA functional class III or ambulatory class IV HF
    symptoms on optimal recommended medical therapy.",
    " <br/>",
    " <br/>",
    " A similar recommendation was included in the 2010 European Society of
    Cardiology device therapy guidelines [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/31\">",
    " 31",
    " </a>",
    " ]. A similar recommendation limited to NYHA class III patients was included in
    the 2010 Heart Failure Society of America guidelines [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/983/abstract/32\">",
    " 32",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " CRT can be useful for patients on guideline-directed medical therapy who
    have an LVEF&le;35 percent and who are undergoing new or replacement implantation
    of a permanent pacemaker with anticipated requirement for significant (&gt;40
    percent) ventricular pacing.",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
    " <span class=\"h1\">",
    " INFORMATION FOR PATIENTS",
    " </span>",
    " &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education materials,
    &ldquo;The Basics&rdquo; and &ldquo;Beyond the Basics.&rdquo; The Basics patient
    education pieces are written in plain language, at the 5",
    " <sup>",
    " th",
    " </sup>",
    " to 6",
    " <sup>",
    " th",
    " </sup>",
    " grade reading level, and they answer the four or five key questions a patient
    might have about a given condition. These articles are best for patients who want a
    general overview and who prefer short, easy-to-read materials. Beyond the Basics
    patient education pieces are longer, more sophisticated, and more detailed. These
    articles are written at the 10",
    " <sup>",
    " th",
    " </sup>",
    " to 12",
    " <sup>",
    " th",
    " </sup>",
    " grade reading level and are best for patients who want in-depth information
    and are comfortable with some medical jargon.",
    " </p>",
    " <p>",
    " Here are the patient education articles that are relevant to this topic. We
    encourage you to print or e-mail these topics to your patients. (You can also
    locate patient education articles on a variety of subjects by searching on
    &ldquo;patient info&rdquo; and the keyword(s) of interest.)",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Basics topic (see",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?36/34/37410?
    source=see_link\">",
    " \"Patient information: Cardiac resynchronization therapy (The Basics)\"",
    " </a>",
    " )",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Although cardiac resynchronization therapy improves some potential risk
    factors for AF such as atrial size and left ventricular systolic function, CRT has
    NOT been shown to decrease the incidence of new AF.",
    " </li>",
    " <li>",
    " In patients with AF and a left ventricular ejection fraction (LVEF) &le;35
    percent who require ventricular pacing or otherwise meet CRT criteria",
    " <strong>",
    " and",
    " </strong>",
    " in whom AV nodal ablation or pharmacologic rate control will allow near 100
    percent ventricular pacing with CRT, we suggest CRT (",
    " <a class=\"grade\" href=\"._grade_5?title=Grade 2B\">",
    " Grade 2B",
    " </a>",
    " ). (See",
    " <a class=\"local\" href=\"#H15416960\">",
    " 'Our approach'",
    " </a>",
    " above.)",
    " <br/>",
    " <br/>",
    " In the above statement, &ldquo;otherwise meet CRT criteria&rdquo; means LBBB
    with QRS &ge;120 ms and NYHA class II, III, or ambulatory IV symptoms on optimal
    medical therapy.",
    " </li>",
    " <li>",
    " Most patients who satisfy either of the above criteria are also candidates
    for an ICD and should receive a combined device. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?18/55/19322?
    source=see_link&amp;anchor=H14#H14\">",
    " \"Secondary and primary prevention of sudden cardiac death in heart failure
    and cardiomyopathy\", section on 'Role of an ICD'",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " Pulmonary vein isolation is another potential treatment option in patients
    with AF and HF. (See",
    " <a class=\"local\" href=\"#H6\">",
    " 'Comparison with pulmonary vein isolation'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H954285\">",
    " <span class=\"h1\">",
    " ACKNOWLEDGMENT",
    " </span>",
    " &nbsp;&mdash;&nbsp;The UpToDate editorial staff would&nbsp;like to thank Dr.
    Leonard I. Ganz for his contributions as an author to previous versions of this
    topic review.",
    " </p>",
    " </div>",
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    " Use of UpToDate is subject to the",
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    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
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    " Gasparini M, Auricchio A, Regoli F, et al. Four-year efficacy of cardiac
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    " Gasparini M, Auricchio A, Metra M, et al. Long-term survival in patients
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    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/983/abstract/19\">",
    " Hayes DL, Boehmer JP, Day JD, et al. Cardiac resynchronization therapy and
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    " Wilkoff BL, Cook JR, Epstein AE, et al. Dual-chamber pacing or ventricular
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    " Khan MN, Ja&iuml;s P, Cummings J, et al. Pulmonary-vein isolation for atrial
    fibrillation in patients with heart failure. N Engl J Med 2008; 359:1778.",
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    " Saxon LA, De Marco T, Schafer J, et al. Effects of long-term biventricular
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    " St John Sutton MG, Plappert T, Abraham WT, et al. Effect of cardiac
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    " Higgins SL, Hummel JD, Niazi IK, et al. Cardiac resynchronization therapy
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/983/abstract/25\">",
    " Fung JW, Yu CM, Chan JY, et al. Effects of cardiac resynchronization therapy
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    " Saxon LA. Does cardiac resynchronization therapy reduce the incidence of
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    " Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines
    for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American
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    (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for
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    Thoracic Surgeons. Circulation 2008; 117:e350.",
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    " Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incorporated into
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    " . Electrophysiologic testing and the use of devices in heart failure. J Card
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    " Tracy CM, Epstein AE, Darbar D, et al. 2012 ACCF/AHA/HRS focused update of
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    Circulation 2012; 126:1784.",
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    " Dickstein K, Vardas PE, Auricchio A, et al. 2010 focused update of ESC
    Guidelines on device therapy in heart failure: an update of the 2008 ESC Guidelines
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    Association. Eur J Heart Fail 2010; 12:1143.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/983/abstract/32\">",
    " . HFSA 2006 Comprehensive Heart Failure Practice Guideline. J Card Fail
    2006; 12:e1.",
    " </a>",
    " </li>",
    " </ol>",
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    " Topic 3515 Version 4.0",
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    " <a href=\"#\" title=\"Collapse Topic Outline\">",
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    " <h1>",
    " TOPIC OUTLINE",
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    " <div id=\"outline\">",
    " <ul>",
    " <li>",
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    " <span>",
    " SUMMARY &amp; RECOMMENDATIONS",
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    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H1\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H2\">",
    " USE OF CRT IN AF",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H3\">",
    " Patients with an indication for AV node ablation",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H4\">",
    " Patients with heart failure",
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    " - Role of AV node ablation",
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    " <a class=\"outlineLink\" href=\"#H6\">",
    " - Comparison with pulmonary vein isolation",
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    " <a class=\"outlineLink\" href=\"#H7\">",
    " EFFECT OF CRT ON AF",
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    " <a class=\"outlineLink\" href=\"#H15416960\">",
    " OUR APPROACH",
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    " MAJOR SOCIETY GUIDELINES",
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    " INFORMATION FOR PATIENTS",
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    " SUMMARY AND RECOMMENDATIONS",
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    " ACKNOWLEDGMENT",
    " </a>",
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    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
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    " Methods to assess cardiovascular disability",
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    " RELATED TOPICS",
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    " <a class=\"medical medical_basics\" href=\"UTD.htm?36/34/37410?
    source=related_link\">",
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    source=related_link\">",
    " Rationale for and mechanisms of benefit of cardiac resynchronization
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    " Secondary and primary prevention of sudden cardiac death in heart failure
    and cardiomyopathy",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_61_984="Liquid ventilation";
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    " <div id=\"topicContent\">",
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    " Liquid ventilation",
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    " <div id=\"topicContributors\">",
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    " <a class=\"contributor contributor_credentials contributorType\"
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    " Authors",
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    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/61/984/contributors\">",
    " Karen J Tietze, PharmD",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/61/984/contributors\">",
    " Scott Manaker, MD, PhD",
    " </a>",
    " <br/>",
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    href=\"UTD.htm?0/61/984/contributors\">",
    " Section Editor",
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    0/61/984/contributors\">",
    " Polly E Parsons, MD",
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    href=\"UTD.htm?0/61/984/contributors\">",
    " Deputy Editor",
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    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;Liquid ventilation (LV) is a technique of mechanical
    ventilation in which the lungs are insufflated with an oxygenated perfluorochemical
    liquid rather than an oxygen-containing gas mixture. The use of perfluorochemicals,
    rather than nitrogen, as the inert carrier of oxygen and carbon dioxide offers a
    number of theoretical advantages for the treatment of acute lung injury,
    including:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Reducing surface tension by maintaining a fluid interface with alveoli",
    " </li>",
    " <li>",
    " Opening of collapsed alveoli by hydraulic pressure with a lower risk of
    barotrauma",
    " </li>",
    " <li>",
    " Providing a reservoir in which oxygen and carbon dioxide can be exchanged
    with pulmonary capillary blood",
    " </li>",
    " <li>",
    " Functioning as a high efficiency heat exchanger",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Despite its theoretical advantages, efficacy studies have been disappointing
    and the optimal clinical use of LV has yet to be defined [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/1\">",
    " 1",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The technique and potential applications of LV will be reviewed here.
    Conventional and alternative modes of gas-phase mechanical ventilation are
    discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?13/1/13336?
    source=see_link\">",
    " \"Overview of mechanical ventilation\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?42/48/43784?
    source=see_link\">",
    " \"Modes of mechanical ventilation\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " PROPERTIES",
    " </span>",
    " &nbsp;&mdash;&nbsp;The ideal fluid for liquid ventilation is nontoxic, has a
    low surface tension, is capable of dissolving large amounts of oxygen and carbon
    dioxide, has minimal systemic absorption, and is chemically stable [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/2\">",
    " 2",
    " </a>",
    " ]. Following work with hyperbaric saline ventilation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/3\">",
    " 3",
    " </a>",
    " ], researchers demonstrated that perfluorochemicals (PFCs) had many of these
    properties and could be used as a medium for liquid breathing in rodents [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/4\">",
    " 4",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h2\">",
    " Physical properties",
    " </span>",
    " &nbsp;&mdash;&nbsp;PFCs are organic compounds in which some carbon-bound
    hydrogen atoms have been replaced with fluorine atoms [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/5\">",
    " 5",
    " </a>",
    " ]. Perflubron (LiquiVent",
    " <sup>",
    " &reg;",
    " </sup>",
    " ), the only medical grade PFC available for use in human LV trials, consists
    of a long, linear-fluorinated hydrocarbon chain. Perflubron contains one bromide
    atom, making it radiopaque [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/5\">",
    " 5",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Hundreds of different PFC fluids with unique biomedical properties exist. The
    structure of several examples of these compounds is shown in the figure (",
    " <a class=\"graphic graphic_figure graphicRef80558 \" href=\"UTD.htm?
    6/20/6477\">",
    " figure 1",
    " </a>",
    " ). The table compares the physical properties of air, water, and saline with
    three PFCs that have been studied for liquid ventilation (",
    " <a class=\"graphic graphic_table graphicRef52864 \" href=\"UTD.htm?
    15/1/15388\">",
    " table 1",
    " </a>",
    " )&nbsp;[",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/6,7\">",
    " 6,7",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " PFC fluids are clear, colorless, odorless, and inert. Oxygen, carbon dioxide,
    and other gases are highly soluble in these fluids; they can dissolve over 15 times
    the amount of oxygen per given volume as plasma [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/8\">",
    " 8",
    " </a>",
    " ]. PFCs are poor solvents for most other biological compounds.",
    " </p>",
    " <p>",
    " PFCs are stable, insoluble in water, can be stored indefinitely at room
    temperature, and can be autoclaved [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/8,9\">",
    " 8,9",
    " </a>",
    " ]. In contrast to saline, PFCs do not wash out surfactant [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/1\">",
    " 1",
    " </a>",
    " ]. Almost all PFC fluids have low surface tension and are nonbiotransformable.
    However, PFCs have a high viscosity, which makes their flow characteristics
    problematic under certain circumstances.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h2\">",
    " Pharmacokinetics",
    " </span>",
    " &nbsp;&mdash;&nbsp;Very small amounts of PFCs diffuse into the pulmonary
    capillary blood and dissolve in blood lipids [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/10\">",
    " 10",
    " </a>",
    " ]. The rate of uptake in the blood depends upon the PFC vapor pressure,
    permeability coefficients of the blood vessels, solubility of the particular PFC
    used, and the degree of",
    " <span class=\"nowrap\">",
    " ventilation/perfusion",
    " </span>",
    " matching.",
    " </p>",
    " <p>",
    " Absorbed PFCs are scavenged by macrophages. The main route of PFC elimination
    is through the lungs via volatilization [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/11,12\">",
    " 11,12",
    " </a>",
    " ]. To a smaller degree, the chemicals are eliminated through the skin by
    transpiration. Perflubron blood concentrations are low but measurable, and persist
    for at least eight days following administration of the last dose of perflubron [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/13\">",
    " 13",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Perflubron may persist in extrapulmonary tissues for years following LV. Two
    case reports note the continued presence of perflubron in the mediastinum, the
    retroperitoneum, and the pleural space for nine and twelve years, respectively [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/14,15\">",
    " 14,15",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h1\">",
    " TECHNIQUES",
    " </span>",
    " &nbsp;&mdash;&nbsp;Two methods of PFC-based liquid ventilation have been used:
    total (tidal) liquid ventilation and partial liquid ventilation.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h2\">",
    " Total liquid ventilation",
    " </span>",
    " &nbsp;&mdash;&nbsp;In total liquid ventilation (TLV), the entire lung is
    filled with an oxygenated PFC liquid, and a liquid tidal volume of PFC is actively
    pumped into and out of the lungs. A specialized apparatus is required to deliver
    and remove the relatively dense, viscous PFC tidal volumes, and to extracorporeally
    oxygenate and remove carbon dioxide from the liquid [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/2,9,16\">",
    " 2,9,16",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " TLV is initiated by insufflating the desired volume of pre-oxygenated PFC
    liquid (functional residual capacity plus tidal volume) into the lungs using a
    gravity-assisted device or more specialized equipment [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/6,9\">",
    " 6,9",
    " </a>",
    " ]. Optimum ventilation and oxygenation depend upon adequate minute ventilation
    coupled with sufficient time for diffusion of respiratory gases to and from the PFC
    liquid [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/6,9\">",
    " 6,9",
    " </a>",
    " ]. During the maintenance phase of TLV, a low respiratory rate (eg, 4 to 6
    breaths per minute) is set with an inspiratory-to-expiratory (I:E) ratio of 1:2 to
    1:3 [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/17\">",
    " 17",
    " </a>",
    " ]. At these respiratory rates and timing ratios, PFC fluid dwells in the lung
    long enough for diffusion of respiratory gases to occur, thus effecting pulmonary
    gas exchange. Tidal volumes and peak inspiratory and positive end expiratory
    pressures (PEEP) are adjusted based upon pulmonary mechanics and blood gases in the
    same manner as when gas ventilation is employed. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?2/42/2730?
    source=see_link\">",
    " \"Mechanical ventilation in acute respiratory distress syndrome\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?29/60/30663?
    source=see_link\">",
    " \"Positive end-expiratory pressure (PEEP)\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " TLV is weaned when sufficient clinical improvement has occurred such that gas
    ventilation will be adequate to support the patient; specific weaning parameters
    and techniques have not been fully evaluated. The return to gas ventilation is
    accomplished by a transition through a period of partial liquid ventilation (see",
    " <a class=\"local\" href=\"#H7\">",
    " 'Partial liquid ventilation'",
    " </a>",
    " below). PFC liquid is removed at the end of the expiratory phase, leaving a
    volume of PFC fluid equivalent to the functional residual capacity of the lung. Gas
    ventilation is begun, and the PFC fluid is not replaced or augmented as it is
    evaporated; elimination from the lung by evaporation generally requires one to
    seven days [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/6,18\">",
    " 6,18",
    " </a>",
    " ]. In some cases, small amounts of PFC are radiographically apparent in the
    lungs for several weeks or longer without apparent ill effects [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/18\">",
    " 18",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h2\">",
    " Partial liquid ventilation",
    " </span>",
    " &nbsp;&mdash;&nbsp;In partial liquid ventilation (PLV), the lungs are slowly
    filled with a volume of PFC equivalent or close to the FRC during gas ventilation.
    The PFC within the lungs is oxygenated and carbon dioxide is removed by means of
    gas breaths cycling in the lungs by a conventional gas ventilator [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/6\">",
    " 6",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " PLV is initiated by insufflating PFC liquid (approximately 20 to 30",
    " <span class=\"nowrap\">",
    " mL/kg)",
    " </span>",
    " into the lungs using an intravenous syringe pump or by slowly pushing the
    fluid in over a 15-minute to one-hour period. The functional residual capacity is
    reached when a meniscus of PFC is present within the endotracheal tube at end-
    expiration [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/19\">",
    " 19",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " As the fluid evaporates out of the lungs, it is intermittently and gradually
    replaced with additional PFC at approximately 2 to 8",
    " <span class=\"nowrap\">",
    " mL/kg/hr",
    " </span>",
    " to maintain a total liquid volume of functional residual capacity [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/6,9\">",
    " 6,9",
    " </a>",
    " ]. Typically, but not exclusively, pressure-controlled ventilation with the
    addition of PEEP is used to deliver gas ventilation, and FIO",
    " <sub>",
    " 2",
    " </sub>",
    " and PEEP are adjusted based upon pulmonary mechanics and blood gases [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/20\">",
    " 20",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Airway suctioning is still required with PLV [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/1\">",
    " 1",
    " </a>",
    " ]. PLV is discontinued by ceasing to replace the PFC that is lost through
    evaporation. Most of the intrapulmonary PFC evaporates in the next one to seven
    days, allowing a transition to gas ventilation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/18\">",
    " 18",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h2\">",
    " Comparison",
    " </span>",
    " &nbsp;&mdash;&nbsp;TLV allows the lavage and removal of lung secretions,
    meconium, or alveolar edema from the lower airways to a greater extent than PLV. In
    addition, the distribution of PFC within the lungs may be more uniform during TLV
    than PLV. However, TLV requires a specialized delivery apparatus, and increased
    airway resistance can make the tidal delivery of viscous PFCs difficult.",
    " </p>",
    " <p>",
    " PLV provides some of the same benefits as TLV by maintaining a liquid
    interface in the alveoli, but does not require specialized equipment. The technique
    may also be possible in some patients in whom elevated airway resistance precludes
    the use of TLV. Periodic repositioning of the patient is required with both modes
    to ensure optimal distribution of PFC fluid within the lungs, but is more important
    in PLV to maintain a liquid interface in as many alveoli as possible.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9\">",
    " <span class=\"h1\">",
    " PHYSIOLOGIC OUTCOMES",
    " </span>",
    " &nbsp;&mdash;&nbsp;LV offers a number of theoretical advantages over
    conventional gas ventilation, including better gas exchange and functional lung
    recovery by any of several mechanisms:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Alveolar recruitment &ndash; Filling of alveoli with liquid rather than gas
    eliminates air-liquid interfaces and greatly reduces surface tension forces.
    Collapsed alveoli may also be recruited and stabilized by the hydraulic forces
    provided during LV. Alveolar expansion and stability is thus facilitated at much
    lower airway pressures, reducing the risk of barotrauma [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/16,21\">",
    " 16,21",
    " </a>",
    " ]. As more alveoli are filled with oxygen-rich PFC, the effective diffusing
    surface of the lung increases and is reflected by improvement in arterial
    oxygenation and compliance [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/22,23\">",
    " 22,23",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Better",
    " <span class=\"nowrap\">",
    " V/Q",
    " </span>",
    " matching &ndash; PFC fluids are denser than water and therefore deposit in
    dependent regions of the lungs. They improve",
    " <span class=\"nowrap\">",
    " ventilation/perfusion",
    " </span>",
    " matching by facilitating gas exchange in lung units that were previously
    perfused but unventilated. The weight of PFCs within dependent lung zones also may
    redistribute pulmonary blood flow to nondependent zones that were previously
    ventilated but unperfused [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/24\">",
    " 24",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Lavage &ndash; LV facilitates the removal of exudative material from the
    lung but does not interfere substantially with the production or function of
    surfactant [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/1,25\">",
    " 1,25",
    " </a>",
    " ]. During TLV, the cyclical removal and replacement of PFC liquid may
    cleanse the lungs while maintaining gas exchange [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/26\">",
    " 26",
    " </a>",
    " ]. During PLV, exudative material in the peripheral airways and alveoli is
    lavaged to the central airways for removal via suctioning [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/19\">",
    " 19",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Antiinflammatory effects &ndash; Some studies suggest reduced neutrophil and
    alveolar macrophage responses exist in the presence of PFCs, including attenuation
    of neutrophil adhesion, activation, and migration [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/27-33\">",
    " 27-33",
    " </a>",
    " ]. The removal of inflammatory cells and their mediators from the alveolar
    spaces may also provide benefit [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/28,34\">",
    " 28,34",
    " </a>",
    " ]. Finally, filling of the alveolus with PFCs may provide a mechanical
    barrier to intraalveolar exudation and leukocyte",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " red blood cell translocation, with potential beneficial effects in reducing
    the intensity of inflammation and secondary lung injury.",
    " </li>",
    " <li>",
    " Temperature regulation &ndash; PFC liquids have a higher heat capacity than
    conventional gas mixtures. This allows the lung and pulmonary circulation to act as
    an internal heat exchanger [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/35\">",
    " 35",
    " </a>",
    " ]. PFC liquids can be used to warm the lungs and increase core body
    temperature or cool the lungs and decrease core body temperature, as required by
    clinical circumstances [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/6,36\">",
    " 6,36",
    " </a>",
    " ].",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10\">",
    " <span class=\"h1\">",
    " POTENTIAL INDICATIONS",
    " </span>",
    " &nbsp;&mdash;&nbsp;The unique properties of PFC-based LV make the technique
    potentially useful in a variety of situations.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H11\">",
    " <span class=\"h2\">",
    " Neonatal applications",
    " </span>",
    " &nbsp;&mdash;&nbsp;Newborns can suffer from a variety of lung diseases that
    may respond favorably to LV.",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Respiratory distress syndrome &ndash; Exogenous surfactant therapy in
    infants with neonatal respiratory distress syndrome (hyaline membrane disease) is
    limited by unequal delivery and distribution within the injured or premature lung
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/37\">",
    " 37",
    " </a>",
    " ]. LV may facilitate more uniform endogenous surfactant distribution, and
    may be of use in surfactant-unresponsive cases. In either event, LV can reduce
    surface tension, thereby reducing inflation pressure and barotrauma, and may
    stimulate surfactant synthesis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/25,38\">",
    " 25,38",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Meconium aspiration &ndash; Lavage associated with TLV and PLV may remove
    meconium from the airways more effectively than conventional measures [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/39-41\">",
    " 39-41",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Persistent pulmonary hypertension of the newborn &ndash; LV provides uniform
    delivery of oxygen to the distal regions of the lungs, potentially improving",
    " <span class=\"nowrap\">",
    " ventilation/perfusion",
    " </span>",
    " matching and facilitating pulmonary vasodilation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/6\">",
    " 6",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Congenital diaphragmatic hernia &ndash; PLV may improve gas exchange more
    effectively than conventional gas ventilation in newborns with severe congenital
    diaphragmatic hernia and may provide mechanical stimuli that favor neonatal lung
    growth [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/42-45\">",
    " 42-45",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Temperature control &ndash; The heat exchange characteristic of PFCs may
    help maintain normothermia in premature infants with less reliance upon radiant
    warmers, which increase insensible water loss [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/6\">",
    " 6",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Lung protection during cardiopulmonary bypass &ndash; Full, functional
    residual capacity dosing prior to bypass may reduce cardiopulmonary bypass-
    associated lung injury [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/46\">",
    " 46",
    " </a>",
    " ]. Anti-inflammatory effects, alveolar distention, oxygen-carrying capacity,
    and surfactant-like properties may protect the lung before and during
    cardiopulmonary bypass.",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H12\">",
    " <span class=\"h2\">",
    " Adult applications",
    " </span>",
    " &nbsp;&mdash;&nbsp;LV appears most suited for use in adults with the acute
    respiratory distress syndrome (ARDS), and may also be useful in several other
    circumstances:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Acute respiratory distress syndrome &ndash; LV potentially can improve gas
    exchange in the acute respiratory distress syndrome (ARDS) by virtue of recruiting
    the atelectatic, consolidated, dependent regions of the lungs that contribute to
    the physiologic shunt observed during gas ventilation. Pulmonary blood flow is also
    redistributed to less severely injured",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " atelectatic regions of the lungs, thus improving",
    " <span class=\"nowrap\">",
    " ventilation/perfusion",
    " </span>",
    " matching [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/16,23,24,47\">",
    " 16,23,24,47",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Pneumonia &ndash; Lavage associated with TLV and PLV removes infectious and
    inflammatory debris from the airways [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/40,41\">",
    " 40,41",
    " </a>",
    " ]. Antibiotics such as",
    " <a class=\"drug drug_general\" href=\"UTD.htm?35/10/36000?
    source=see_link\">",
    " gentamicin",
    " </a>",
    " can be suspended within the PFC vehicle to potentially facilitate treatment
    or prevention of pneumonia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/48\">",
    " 48",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Cancer therapy &ndash; LV may augment the antineoplastic effects of
    radiotherapy and chemotherapy in the lung by inducing localized hyperthermia or
    hyperoxia of the lung surface. Concentrated, topical chemotherapeutic agents can
    also be delivered [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/5,8,49\">",
    " 5,8,49",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Drug delivery &ndash; Mechanical abnormalities of the lung, intrapulmonary
    shunting,",
    " <span class=\"nowrap\">",
    " ventilation/perfusion",
    " </span>",
    " mismatching, and elevated surface tension impede effective delivery of
    systemic and intratracheal drugs to the lungs during conventional gas ventilation
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/50\">",
    " 50",
    " </a>",
    " ]. Data from preliminary animal studies suggest that pulmonary uptake of
    antibiotics and the efficacy of vasoactive drugs are better following intratracheal
    administration during LV than when administered intravenously [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/50-52\">",
    " 50-52",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Donor lung preservation &ndash; Because perfluorochemicals have both direct
    antiinflammatory and alveolar stabilizing effects, these agents have been proposed
    as potential useful tools for organ preservation prior to lung transplantation.
    Preliminary investigations have suggested that LV results in decreased alveolar
    destruction when compared to standard (gas) ventilation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/53,54\">",
    " 53,54",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?5/32/5640?
    source=see_link\">",
    " \"Lung transplantation: Donor lung preservation\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?18/8/18566?
    source=see_link\">",
    " \"Management of the potential deceased donor\"",
    " </a>",
    " .)",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H13\">",
    " <span class=\"h1\">",
    " CLINICAL OUTCOME",
    " </span>",
    " &nbsp;&mdash;&nbsp;Most studies over the last three decades have evaluated the
    ability of liquid ventilation to improve gas exchange and pulmonary function in
    animal models. Far fewer investigations have been performed in humans [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/18,39,40,42,55-63\">",
    " 18,39,40,42,55-63",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Two trials have compared partial liquid ventilation (PLV) versus conventional
    mechanical ventilation (CMV) in adults with acute respiratory distress syndrome
    (ARDS):",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " In the larger trial, 311 patients were randomly assigned to receive CMV, low
    dose PLV (lungs filled to the carina in the supine position), or high dose PLV
    (lungs filled to 5 cm caudal to the incisors in the supine position) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/63\">",
    " 63",
    " </a>",
    " ]. There was no difference in mortality among the groups; however, patients
    who received PLV had fewer ventilator-free days and more adverse events including
    pneumothoraces, hypoxic episodes, and hypotensive episodes.",
    " </li>",
    " <li>",
    " In a trial of 90 patients, those who received PLV were less likely to have
    progressive deterioration of gas exchange; however, there was no difference in the
    number of ventilator-free days, the incidence of mortality, or any respiratory
    parameter [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/61\">",
    " 61",
    " </a>",
    " ].",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " In a small trial that included 13 neonates with congenital diaphragmatic
    hernias on extracorporeal life support (ECLS), patients who received PLV had a
    nonstatistically significant improvement in survival and time on ECLS compared to
    patients who received CMV [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/62\">",
    " 62",
    " </a>",
    " ]. However, ventilator-free days were greater in the CMV group.",
    " </p>",
    " <p>",
    " Based on these studies, routine use of PLV cannot be recommended.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H14\">",
    " <span class=\"h1\">",
    " ADVERSE EFFECTS",
    " </span>",
    " &nbsp;&mdash;&nbsp;The complete range of toxicity due to PFCs is not known.
    Early studies using TLV reported an increase in pulmonary vascular resistance with
    a decrease in cardiac index of approximately 40 percent, which resulted in lactic
    acidosis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/1\">",
    " 1",
    " </a>",
    " ]. This probably was a consequence of lung overexpansion, which may decrease
    cardiac output and arterial blood pressure. In contrast, adverse direct hemodynamic
    effects appear uncommon during PLV.",
    " </p>",
    " <p>",
    " Other adverse effects observed during PFC LV include mucous plug formation,
    pneumothoraces, and bleeding complications, but it is unclear to what degree these
    relate to LV rather than the underlying disease [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/39,40\">",
    " 39,40",
    " </a>",
    " ]. Morphologic, biochemical, and pathologic examination of numerous mature and
    immature species has revealed no adverse effects of PFCs [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/8\">",
    " 8",
    " </a>",
    " ]. The long-term adverse effects of breathing PFCs appear to be negligible but
    remain under investigation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/9\">",
    " 9",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " LV potentially can complicate some of the supportive and general care that
    ventilated patients receive in the intensive care unit:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " PFC fluid is almost twice as dense as saline, and patient weights should not
    be followed as the sole index of fluid balance when LV is used [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/6,7\">",
    " 6,7",
    " </a>",
    " ]. A dry weight should be obtained before the start of LV, and patients
    should be weighed again immediately after the lungs are filled with PFC fluid.",
    " </li>",
    " <li>",
    " PFCs are radiopaque and will eliminate much of the diagnostic utility of
    chest radiography. All lung tissue will appear opacified during TLV; during PLV, an
    anterior-posterior supine film may appear uniformly radiopaque, but a lateral view
    of the chest will reveal the distribution of PFC primarily within the dependent
    portions of the lung. A chest radiograph should be obtained prior to and within an
    hour of filling the lung with PFC fluid.",
    " </li>",
    " <li>",
    " Heart sounds are more distinct during TLV than PLV. Breath sounds during PLV
    are notable for the presence of fine rales and coarse rhonchi. No audible breath
    sounds are present during TLV.",
    " </li>",
    " <li>",
    " The impact of LV upon the development of nosocomial pneumonia is uncertain.
    Lavaging the lung of infectious exudate during LV may be beneficial, but this may
    be offset by the loss of diagnostic information usually provided by chest
    radiography [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/6,26,39\">",
    " 6,26,39",
    " </a>",
    " ]. PFCs are thought to be inert.",
    " </li>",
    " <li>",
    " Use of liquid ventilation is unpleasant for the patient, and therefore deep
    sedation and paralysis are necessary [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/6,16\">",
    " 6,16",
    " </a>",
    " ]. The principles of using sedative and paralytic agents are similar to
    those applied when conventional gas ventilation is employed. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/29/15833?
    source=see_link\">",
    " \"Sedative-analgesic medications in critically ill patients: Selection,
    initiation, maintenance, and withdrawal\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?42/44/43720?
    source=see_link\">",
    " \"Use of neuromuscular blocking medications in critically ill patients\"",
    " </a>",
    " .)",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H15\">",
    " <span class=\"h1\">",
    " FUTURE",
    " </span>",
    " &nbsp;&mdash;&nbsp;Excessive doses of perflubron may explain the negative
    results of early human trials [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/64\">",
    " 64",
    " </a>",
    " ]. This is supported by an animal study, in which rats given a low dose (7",
    " <span class=\"nowrap\">",
    " mL/kg)",
    " </span>",
    " of perflubron had less microvascular lung injury than rats given a near
    functional residual capacity dose (20",
    " <span class=\"nowrap\">",
    " mL/kg)",
    " </span>",
    " of perflubron [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/984/abstract/65\">",
    " 65",
    " </a>",
    " ]. Future efforts may involve studying the effects of various doses of
    perflubron.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H16\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Liquid ventilation (LV) is a technique of mechanical ventilation in which
    the lungs are insufflated with oxygenated perfluorochemical (PFC) liquid rather
    than gas. (See",
    " <a class=\"local\" href=\"#H1\">",
    " 'Introduction'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " PFC liquids are stable and nontoxic, with minimal systemic absorption. They
    dissolve large amounts of oxygen and carbon dioxide; thus, they are ideal for gas
    exchange. (See",
    " <a class=\"local\" href=\"#H2\">",
    " 'Properties'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Two techniques of PFC-based liquid ventilation have been used, total (tidal)
    liquid ventilation and partial liquid ventilation. (See",
    " <a class=\"local\" href=\"#H5\">",
    " 'Techniques'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Theoretical advantages of LV over conventional gas ventilation include
    recruitment and stabilization of alveoli, improvement in",
    " <span class=\"nowrap\">",
    " V/Q",
    " </span>",
    " matching, removal of exudative material from the lung, direct anti-
    inflammatory effects, and temperature regulation. (See",
    " <a class=\"local\" href=\"#H9\">",
    " 'Physiologic outcomes'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " In theory, LV may be of benefit for numerous neonatal and adult diseases.
    Clinical trials, however, have shown little improvement in important clinical
    outcomes. As a result, LV cannot be recommended in routine clinical care. (See",
    " <a class=\"local\" href=\"#H10\">",
    " 'Potential indications'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H13\">",
    " 'Clinical Outcome'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Adverse effects observed during LV include mucous plug formation,
    pneumothoraces, and bleeding complications, although it is unclear whether these
    were due to LV or the underlying disease. LV can complicate the supportive and
    general care of patients. For example, patient weight cannot be followed as an
    index of fluid balance and deep sedation and paralysis is required. (See",
    " <a class=\"local\" href=\"#H14\">",
    " 'Adverse Effects'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
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    " </h1>",
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    " Angelova M, Nakazawa K, Yokoyama K, Makita K. Effects of partial liquid
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    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/28\">",
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    the in vitro production of reactive oxygen species by alveolar macrophages. Crit
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    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/29\">",
    " Virmani R, Fink LM, Gunter K, English D. Effect of perfluorochemical blood
    substitutes on human neutrophil function. Transfusion 1984; 24:343.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/30\">",
    " Varani J, Hirschl RB, Dame M, Johnson K. Perfluorocarbon protects lung
    epithelial cells from neutrophil-mediated injury in an in vitro model of liquid
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    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/31\">",
    " Koch T, Ragaller M, Haufe D, et al. Perfluorohexane attenuates
    proinflammatory and procoagulatory response of activated monocytes and alveolar
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    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/32\">",
    " Nakstad B, Wolfson MR, Shaffer TH, et al. Perfluorochemical liquids modulate
    cell-mediated inflammatory responses. Crit Care Med 2001; 29:1731.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/33\">",
    " Woods CM, Neslund G, Kornbrust E, Flaim SF. Perflubron attenuates neutrophil
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    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/34\">",
    " Kelly KP. Partial liquid ventilation--turning back a PAGE on evolution. Br J
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    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/35\">",
    " Shaffer TH, Forman DL, Wolfson MR. Physiological effects of ventilation with
    liquid fluorocarbon at controlled temperatures. Undersea Biomed Res 1984; 11:287.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/36\">",
    " Forman DL, Bhutani VK, Tran N, Shaffer TH. A new approach to induced
    hypothermia. J Surg Res 1986; 40:36.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/37\">",
    " Antunes MJ, Greenspan JS, Zukowsky K. Advanced ventilation in the neonate.
    Nurs Clin North Am 1996; 31:405.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/38\">",
    " Leach, CL, Holm, BA, Morin, FC, et al. Partial liquid ventilation with
    LiquiVent' increases endogenous surfactant production in premature lambs with
    respiratory distress syndrome (RDS). Pediatr Res 1994; 35:220A.",
    " </a>",
    " </li>",
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    " Hirschl RB, Pranikoff T, Wise C, et al. Initial experience with partial
    liquid ventilation in adult patients with the acute respiratory distress syndrome.
    JAMA 1996; 275:383.",
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    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/40\">",
    " Hirschl RB, Pranikoff T, Gauger P, et al. Liquid ventilation in adults,
    children, and full-term neonates. Lancet 1995; 346:1201.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/41\">",
    " Shaffer TH, Lowe CA, Bhutani VK, Douglas PR. Liquid ventilation: effects on
    pulmonary function in distressed meconium-stained lambs. Pediatr Res 1984; 18:47.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/42\">",
    " Pranikoff T, Gauger PG, Hirschl RB. Partial liquid ventilation in newborn
    patients with congenital diaphragmatic hernia. J Pediatr Surg 1996; 31:613.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/43\">",
    " Wilcox DT, Glick PL, Karamanoukian HL, et al. Partial liquid ventilation and
    nitric oxide in congenital diaphragmatic hernia. J Pediatr Surg 1997; 32:1211.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/44\">",
    " Major D, Cadenas M, Cloutier R, et al. Combined gas ventilation and
    perfluorochemical tracheal instillation as an alternative treatment for lethal
    congenital diaphragmatic hernia in lambs. J Pediatr Surg 1995; 30:1178.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/45\">",
    " Wilcox DT, Glick PL, Karamanoukian HL, et al. Perfluorocarbon-associated gas
    exchange improves pulmonary mechanics, oxygenation, ventilation, and allows nitric
    oxide delivery in the hypoplastic lung congenital diaphragmatic hernia lamb model.
    Crit Care Med 1995; 23:1858.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/46\">",
    " Cannon ML, Cheifetz IM, Craig DM, et al. Optimizing liquid ventilation as a
    lung protection strategy for neonatal cardiopulmonary bypass: full functional
    residual capacity dosing is more effective than half functional residual capacity
    dosing. Crit Care Med 1999; 27:1140.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/47\">",
    " Hirschl RB, Parent A, Tooley R, et al. Liquid ventilation improves pulmonary
    function, gas exchange, and lung injury in a model of respiratory failure. Ann Surg
    1995; 221:79.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/48\">",
    " Cullen AB, Cox CA, Hipp SJ, et al. Intra-tracheal delivery strategy of
    gentamicin with partial liquid ventilation. Respir Med 1999; 93:770.",
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    " Sekins KM, Deilman GW, Shaffer TH, et al. Acoustic and physical properties of
    PFC liquids pertinent to ultrasound lung hyperthermia. 10th Annual North American
    Hyperthermia Group. Radiation Res Soc. April, 1990.",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/50\">",
    " Wolfson MR, Greenspan JS, Shaffer TH. Pulmonary administration of vasoactive
    substances by perfluorochemical ventilation. Pediatrics 1996; 97:449.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/51\">",
    " Dickson, EW, Heard, SO, Otto, S, et al. Efficacy of a novel perfluorocarbon-
    based intrapulmonary drug delivery system. Crit Care Med 1998; 26:143A.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/52\">",
    " Franz AR, R&ouml;hlke W, Franke RP, et al. Pulmonary administration of
    perfluorodecaline- gentamicin and perfluorodecaline- vancomycin emulsions. Am J
    Respir Crit Care Med 2001; 164:1595.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/53\">",
    " Yoshida S, Sekine Y, Shinozuka N, et al. The efficacy of partial liquid
    ventilation in lung protection during hypotension and cardiac arrest: preliminary
    study of lung transplantation using non-heart-beating donors. J Heart Lung
    Transplant 2005; 24:723.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/54\">",
    " Loehe F, Mueller C, Bittmann I, et al. Influence of long-term preservation
    with endobronchially administered perfluorodecalin on pulmonary graft function.
    Transplantation 2000; 70:1417.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/55\">",
    " Greenspan JS, Wolfson MR, Rubenstein SD, Shaffer TH. Liquid ventilation of
    human preterm neonates. J Pediatr 1990; 117:106.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/56\">",
    " Hirschl RB, Conrad S, Kaiser R, et al. Partial liquid ventilation in adult
    patients with ARDS: a multicenter phase I-II trial. Adult PLV Study Group. Ann Surg
    1998; 228:692.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/57\">",
    " Gauger PG, Pranikoff T, Schreiner RJ, et al. Initial experience with partial
    liquid ventilation in pediatric patients with the acute respiratory distress
    syndrome. Crit Care Med 1996; 24:16.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/58\">",
    " Greenspan JS, Fox WW, Rubenstein SD, et al. Partial liquid ventilation in
    critically ill infants receiving extracorporeal life support. Philadelphia Liquid
    Ventilation Consortium. Pediatrics 1997; 99:E2.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/59\">",
    " Croce MA, Fabian TC, Patton JH Jr, et al. Partial liquid ventilation
    decreases the inflammatory response in the alveolar environment of trauma patients.
    J Trauma 1998; 45:273.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/60\">",
    " Davies MW, Sargent PH. Partial liquid ventilation for the prevention of
    mortality and morbidity in paediatric acute lung injury and acute respiratory
    distress syndrome. Cochrane Database Syst Rev 2004; :CD003845.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/61\">",
    " Hirschl RB, Croce M, Gore D, et al. Prospective, randomized, controlled
    pilot study of partial liquid ventilation in adult acute respiratory distress
    syndrome. Am J Respir Crit Care Med 2002; 165:781.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/62\">",
    " Hirschl RB, Philip WF, Glick L, et al. A prospective, randomized pilot trial
    of perfluorocarbon-induced lung growth in newborns with congenital diaphragmatic
    hernia. J Pediatr Surg 2003; 38:283.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/63\">",
    " Kacmarek RM, Wiedemann HP, Lavin PT, et al. Partial liquid ventilation in
    adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med
    2006; 173:882.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/64\">",
    " Lemaire F. Low-dose perfluorocarbon: a revival for partial liquid
    ventilation? Crit Care Med 2007; 35:662.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/984/abstract/65\">",
    " Ricard JD, Iserin F, Dreyfuss D, Saumon G. Perflubron dosing affects
    ventilator-induced lung injury in rats with previous lung injury. Crit Care Med
    2007; 35:561.",
    " </a>",
    " </li>",
    " </ol>",
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    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li>",
    " <a class=\"sr_button\" href=\"#H16\" id=\"summRecButton\">",
    " <span>",
    " SUMMARY &amp; RECOMMENDATIONS",
    " </span>",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H1\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H2\">",
    " PROPERTIES",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
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    " Physical properties",
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    " Pharmacokinetics",
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    " TECHNIQUES",
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    " Total liquid ventilation",
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    " Partial liquid ventilation",
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    " Comparison",
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    " PHYSIOLOGIC OUTCOMES",
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    " POTENTIAL INDICATIONS",
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    " Neonatal applications",
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    " Adult applications",
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    " CLINICAL OUTCOME",
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    " <a class=\"outlineLink\" href=\"#H14\">",
    " ADVERSE EFFECTS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H15\">",
    " FUTURE",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H16\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"PULM/1608\" rel=\"outline_link\">",
    " GRAPHICS",
    " <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
    " View All",
    " </a>",
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    " </h1>",
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    " <div class=\"openRelatedGraphics\" id=\"PULM/1608|FIG\">",
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    " FIGURES",
    " </a>",
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    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?6/20/6477\" title=\"figure
    1\">",
    " Perfluorochemical structures",
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    " <div class=\"openRelatedGraphics\" id=\"PULM/1608|TAB\">",
    " <a href=\"#\" title=\"TABLES\">",
    " TABLES",
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    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?15/1/15388\" title=\"table
    1\">",
    " Comparison of PFC properties",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?5/32/5640?
    source=related_link\">",
    " Lung transplantation: Donor lung preservation",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?18/8/18566?
    source=related_link\">",
    " Management of the potential deceased donor",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?2/42/2730?
    source=related_link\">",
    " Mechanical ventilation in acute respiratory distress syndrome",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?42/48/43784?
    source=related_link\">",
    " Modes of mechanical ventilation",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?13/1/13336?
    source=related_link\">",
    " Overview of mechanical ventilation",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?29/60/30663?
    source=related_link\">",
    " Positive end-expiratory pressure (PEEP)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/29/15833?
    source=related_link\">",
    " Sedative-analgesic medications in critically ill patients: Selection,
    initiation, maintenance, and withdrawal",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?42/44/43720?
    source=related_link\">",
    " Use of neuromuscular blocking medications in critically ill patients",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_61_985="Influenza virus vaccine (inactivated): Drug information";
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    " Influenza virus vaccine (inactivated): Drug information",
    " </div>",
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    " Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
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    " <div id=\"topicText\">",
    " (For additional information",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?15/53/16209?source=see_link\">",
    " see \"Influenza virus vaccine (inactivated): Patient drug information\"",
    " </a>",
    " and",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?20/21/20824?
    source=see_link\">",
    " see \"Influenza virus vaccine (inactivated): Pediatric drug information\"",
    " </a>",
    " )",
    " <br/>",
    " For abbreviations and symbols that may be used in Lexicomp (",
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    " )",
    " <div class=\"block spa drugH1Div\" id=\"F14959458\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Special Alerts",
    " </span>",
    " <div class=\"collapsible\">",
    " <span class=\"collapsible-title\">",
    " Cell Culture-Derived Seasonal Influenza Vaccine (Flucelvax&reg;)",
    " </span>",
    " <span class=\"collapsible-date\">",
    " December 2012",
    " </span>",
    " <div class=\"collapsible-wrap\">",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " Flucelvax&reg; (trivalent influenza virus vaccine) has been approved by the
    Food and Drug Administration (FDA) to provide active immunity to influenza virus.
    Flucelvax&reg; is the only inactivated influenza vaccine manufactured using cell
    culture technology and provides an alternative to influenza vaccines cultured with
    chicken egg protein. Availability is currently limited, but full distribution is
    expected during the 2012-2013 influenza season.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " For additional information, refer to",
    " <a
    href=\"file://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm328982.htm\"
    target=\"_blank\">",
    " file://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm328982.htm",
    " </a>",
    " .",
    " </p>",
    " </div>",
    " </div>",
    " <div class=\"collapsible\">",
    " <span class=\"collapsible-title\">",
    " Distribution of Agriflu&trade; and Fluad&trade; in Canada: Update",
    " </span>",
    " <span class=\"collapsible-date\">",
    " October 2012",
    " </span>",
    " <div class=\"collapsible-wrap\">",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " After completing its safety information review, Health Canada has announced
    it is releasing two seasonal flu vaccines (Agriflu&trade; and Fluad&trade;) for
    immediate use in Canada. Recently, Health Canada announced that Novartis Canada had
    agreed to voluntarily suspend distribution of two seasonal flu vaccines
    (Agriflu&trade; and Fluad&trade;) in Canada. Several European countries recently
    suspended use of the vaccines pending examination of white floating material found
    clumping in the vaccines. This type of clumping has been noted previously in
    vaccines and has not resulted in decreased safety or effectiveness; Canadian
    healthcare professionals possessing the vaccines may start using them now. No
    reports of serious or unexpected adverse events related to the vaccines have been
    reported in Canada.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " For further information, refer to the following website: file://www.hc-
    sc.gc.ca/ahc-asc/media/advisories-avis/_2012/2012_164-eng.php",
    " </p>",
    " </div>",
    " </div>",
    " <div class=\"collapsible\">",
    " <span class=\"collapsible-title\">",
    " Influenza Virus Vaccine",
    " </span>",
    " <span class=\"collapsible-date\">",
    " 2012-2013",
    " </span>",
    " <div class=\"collapsible-wrap\">",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " The 2012-2013 influenza virus vaccine contains the same H1N1 virus as in
    the 2011-2012 vaccine, but different H3N2 and B viruses. The vaccine strains
    approved for this season in the United States are as follows: A/California/7/2009
    (H1N1)-like virus, A/Victoria/361/2011 (H3N2)-like virus, and B/Wisconsin/1/2010-
    like virus. Because immunity to influenza virus declines over time, and because two
    of the three strains of the virus are different this year than last, persons should
    be vaccinated every year even if vaccinated during the previous season.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " In addition, a variant influenza A virus (H3N2v) is currently circulating
    in pigs and infecting humans. Immunization with the 2012-2013 seasonal influenza
    vaccine is not expected to provide protection against this virus. Symptoms of
    H3N2v are generally similar to those of seasonal influenza infections.
    Unfortunately, standard tests used to detect influenza virus cannot differentiate
    between H3N2v virus from seasonal influenza A (H3N2) virus and there is a potential
    for false negatives with antigen detection tests. Clinicians who suspect probable
    H3N2v virus should contact their local or state health department for additional
    testing for H3N2v at a state public health laboratory. A link to recent swine
    exposure (within 1 week) of symptom onset should be considered a probable H3N2v
    case. Antiviral treatment of H3N2v influenza is the same as seasonal influenza.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " For additional information refer to the following websites:",
    " </p>",
    " <p style=\"text-indent:0em;margin-left:2em;margin-top:0em;\">",
    " FDA approves vaccines for the 2012-2013 influenza season:",
    " <a
    href=\"file://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm315365.htm\"
    target=\"_blank\">",
    " file://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm315365.htm",
    " </a>",
    " </p>",
    " <p style=\"text-indent:0em;margin-left:2em;margin-top:0em;\">",
    " CDC, Interim Information about Human Infections with H3N2v Virus:",
    " <a href=\"file://www.cdc.gov/flu/swineflu/h3n2v-clinician.htm\"
    target=\"_blank\">",
    " file://www.cdc.gov/flu/swineflu/h3n2v-clinician.htm",
    " </a>",
    " </p>",
    " </div>",
    " </div>",
    " </div>",
    " <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F9560252\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: U.S.",
    " </span>",
    " <ul>",
    " <li>",
    " Afluria&reg;;",
    " </li>",
    " <li>",
    " Fluarix&reg;;",
    " </li>",
    " <li>",
    " Flucelvax&reg;;",
    " </li>",
    " <li>",
    " FluLaval&reg;;",
    " </li>",
    " <li>",
    " Fluvirin&reg;;",
    " </li>",
    " <li>",
    " Fluzone&reg;;",
    " </li>",
    " <li>",
    " Fluzone&reg; High-Dose;",
    " </li>",
    " <li>",
    " Fluzone&reg; Intradermal",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F9560327\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: Canada",
    " </span>",
    " <ul>",
    " <li>",
    " Agriflu&trade;;",
    " </li>",
    " <li>",
    " Fluad&trade;;",
    " </li>",
    " <li>",
    " Fluviral&reg;;",
    " </li>",
    " <li>",
    " Influvac&reg;;",
    " </li>",
    " <li>",
    " Intanza&reg;;",
    " </li>",
    " <li>",
    " Vaxigrip&reg;",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ex_sect_xr thclist drugH1Div drugBrandNames\" id=\"F9560255\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacologic Category",
    " </span>",
    " <ul>",
    " <li>",
    " Vaccine, Inactivated (Viral)",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block doa drugH1Div\" id=\"F9600936\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Adult",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " It is important to note that influenza seasons vary in their timing and
    duration from year to year. In general, vaccination should begin soon after the
    vaccine becomes available and prior to onset of influenza activity in the
    community. However, vaccination should continue throughout the influenza season as
    long as vaccine is available. Unless noted, the ACIP does not have a preference for
    any given IIV formulation when used within their specified age indications.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:2em;text-
    align:justify;\">",
    " <b>",
    " Immunization:",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;margin-top:0em;text-
    align:justify;\">",
    " I.M.:",
    " <i>",
    " Afluria&reg;, Fluarix&reg;, Flucelvax&reg;, FluLaval&reg;, Fluvirin&reg;,
    Fluzone&reg;:",
    " </i>",
    " 0.5 mL/dose (1 dose per season)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;margin-top:0em;text-
    align:justify;\">",
    " Intradermal: Adults 18-64 years:",
    " <i>",
    " Fluzone&reg; Intradermal:",
    " </i>",
    " 0.1 mL/dose (1 dose per season)",
    " </p>",
    " <p style=\"text-indent:0em;margin-left:2em;margin-top:2em;\">",
    " Canadian labeling (products not available in U.S.):",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " I.M.:",
    " <i>",
    " Agriflu&trade;, Fluviral&reg;, Vaxigrip&reg;:",
    " </i>",
    " 0.5 mL/dose (1 dose per season)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " I.M., SubQ:",
    " <i>",
    " Influvac&reg;:",
    " </i>",
    " 0.5 mL/dose (1 per season)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Intradermal:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
    " Intanza&reg; 9 mcg/strain: Adults 18-59 years: 0.1 mL/dose (1 dose per
    season)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
    " Intanza&reg; 15 mcg/strain: Adults &ge;60 years: 0.1 mL/dose (1 dose per
    season)",
    " </p>",
    " </div>",
    " <div class=\"block dop drugH1Div\" id=\"F9560266\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Pediatric",
    " </span>",
    " <p>",
    " (For additional information",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?20/21/20824?
    source=see_link\">",
    " see \"Influenza virus vaccine (inactivated): Pediatric drug information\"",
    " </a>",
    " )",
    " </p>",
    " <p style=\"text-indent:0em;display:inline\">",
    " It is important to note that influenza seasons vary in their timing and
    duration from year to year. In general, vaccination should begin soon after the
    vaccine becomes available and prior to onset of influenza activity in the
    community. However, vaccination should continue throughout the influenza season as
    long as vaccine is available. Unless noted, the ACIP does not have a preference for
    any given IIV formulation when used within their specified age indications.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:2em;text-
    align:justify;\">",
    " <b>",
    " Immunization:",
    " </b>",
    " I.M.:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Afluria&reg;:",
    " </i>",
    " Although FDA-approved for use in children &ge;5 years of age, the ACIP does
    not recommend use of Afluria&reg; in children &lt;9 years due to an increased
    incidence of fever and febrile seizures noted during the 2010-2011 influenza
    season. However, if other age-appropriate vaccines are not available, children 5-8
    years of age who are also considered at risk for influenza complications may be
    given Afluria&reg;. The benefits and risks of this vaccine should be discussed with
    parents or caregivers prior to administration.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children 5-8 years: 0.5 mL/dose (1 or 2 doses per season; see",
    " <b>",
    " \"Note\"",
    " </b>",
    " )",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children &ge;9 years: Refer to adult dosing.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Fluarix&reg;:",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children 3-8 years: 0.5 mL/dose (1 or 2 doses per season; see",
    " <b>",
    " \"Note\"",
    " </b>",
    " )",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children &ge;9 years: Refer to adult dosing.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Fluzone&reg;:",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children 6-35 months: 0.25 mL/dose (1 or 2 doses per season; see",
    " <b>",
    " \"Note\"",
    " </b>",
    " )",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children 3-8 years: 0.5 mL/dose (1 or 2 doses per season; see",
    " <b>",
    " \"Note\"",
    " </b>",
    " )",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children &ge;9 years: Refer to adult dosing.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Fluvirin&reg;:",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children 4-8 years: 0.5 mL/dose (1 or 2 doses per season; see",
    " <b>",
    " \"Note\"",
    " </b>",
    " )",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children &ge;9 years: Refer to adult dosing.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;margin-top:2em;\">",
    " Canadian labeling (products not available in U.S.):",
    " <i>",
    " Agriflu&trade;, Fluviral&reg;, Vaxigrip&reg;:",
    " </i>",
    " I.M.:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children 6-35 months: Manufacturer labeling: 0.25 mL/dose; NACI
    recommendation: 0.5 mL/dose (NACI, 2011) (1 or 2 doses per season; see",
    " <b>",
    " Note",
    " </b>",
    " )",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children 3-8 years: 0.5 mL/dose (1 or 2 doses per season; see",
    " <b>",
    " \"Note\"",
    " </b>",
    " )",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children &ge;9 years: Refer to adult dosing.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " <b>",
    " Note:",
    " </b>",
    " Children 6 months to &lt;9 years who received a total of &ge;2 doses of
    seasonal influenza vaccine since July 1, 2010, need only 1 dose of the 2012-2013
    seasonal influenza vaccine. If a child did not receive a total of &ge;2 doses of
    seasonal vaccine since July 1, 2010, if they have never received seasonal influenza
    vaccine (ie, this is their first season of vaccination), or if their vaccination
    status cannot be determined, they should receive 2 doses separated by &ge;4 weeks,
    in order to achieve satisfactory antibody response. Additional dosing
    considerations are provided when vaccination history is available prior to the
    2010-2011 season; see current guidelines for additional information (CDC, 2012).",
    " </p>",
    " </div>",
    " <div class=\"block doe drugH1Div\" id=\"F9600937\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Geriatric",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " It is important to note that influenza seasons vary in their timing and
    duration from year to year. In general, vaccination should begin soon after the
    vaccine becomes available and prior to onset of influenza activity in the
    community. However, vaccination should continue throughout the influenza season as
    long as vaccine is available.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:2em;\">",
    " <b>",
    " Immunization:",
    " </b>",
    " Adults &ge;65 years:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;margin-top:0em;\">",
    " <i>",
    " Afluria&reg;, Fluarix&reg;, Flucelvax&reg;, FluLaval&reg;, Fluvirin&reg;,
    Fluzone&reg;, Fluzone&reg; High-Dose:",
    " </i>",
    " I.M.: 0.5 mL/dose (1 dose per season). The ACIP does not have a preference
    for any given IIV formulation when used within their specified age indications.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;margin-top:0em;\">",
    " Canadian labeling (product not available in U.S.):",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;margin-top:0em;\">",
    " <i>",
    " Fluad&trade;:",
    " </i>",
    " I.M.: 0.5 mL/dose (1 dose per season)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;margin-top:0em;\">",
    " <i>",
    " Intanza&reg; 15 mcg/strain:",
    " </i>",
    " Intradermal: Refer to adult dosing",
    " </p>",
    " </div>",
    " <div class=\"block dor drugH1Div\" id=\"F15897886\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Renal Impairment",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " No dosage adjustment provided in manufacturer&rsquo;s labeling.",
    " </p>",
    " </div>",
    " <div class=\"block doh drugH1Div\" id=\"F15897887\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Hepatic Impairment",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " No dosage adjustment provided in manufacturer&rsquo;s labeling.",
    " </p>",
    " </div>",
    " <div class=\"block foc drugH1Div\" id=\"F9600938\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosage Forms: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " Excipient information presented when available (limited, particularly for
    generics); consult specific product labeling.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Injection, suspension:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Afluria&reg;: Hemagglutinin 45 mcg/0.5 mL (5 mL) [contains chicken egg
    protein, neomycin (may have trace amounts), polymyxin B (may have trace amounts),
    thimerosal]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " FluLaval&reg;: Hemagglutinin 45 mcg/0.5 mL (5 mL) [contains chicken egg
    protein, thimerosal]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Fluvirin&reg;: Hemagglutinin 45 mcg/0.5 mL (5 mL) [contains chicken egg
    protein, neomycin (may have trace amounts), polymyxin B (may have trace amounts),
    thimerosal]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Fluzone&reg;: Hemagglutinin 45 mcg/0.5 mL (5 mL) [contains chicken egg
    protein, thimerosal]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Injection, suspension [preservative free]:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Afluria&reg;: Hemagglutinin 45 mcg/0.5 mL (0.5 mL) [contains chicken egg
    protein, neomycin (may have trace amounts), polymyxin B (may have trace amounts)]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Fluarix&reg;: Hemagglutinin 45 mcg/0.5 mL (0.5 mL) [contains chicken egg
    protein, gentamicin (may have trace amounts), hydrocortisone (may have trace
    amounts), may contain natural rubber/natural latex in prefilled syringe,
    polysorbate 80]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Flucelvax&reg;: Hemagglutinin 45 mcg/0.5 mL (0.5 mL) [contains polysorbate
    80, may contain natural rubber/natural latex in prefilled syringe]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Fluvirin&reg;: Hemagglutinin 45 mcg/0.5 mL (0.5 mL) [contains chicken egg
    protein, may contain natural rubber/natural latex in prefilled syringe, neomycin
    (may have trace amounts), polymyxin B (may have trace amounts)]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Fluzone&reg;: Hemagglutinin 22.5 mcg/0.25 mL (0.25 mL); Hemagglutinin 45
    mcg/0.5 mL (0.5 mL) [contains chicken egg protein]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Fluzone&reg; High-Dose: Hemagglutinin 180 mcg/0.5 mL (0.5 mL) [contains
    chicken egg protein]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Fluzone&reg; Intradermal: Hemagglutinin 27 mcg/0.1 mL (0.1 mL) [contains
    chicken egg protein]",
    " </p>",
    " </div>",
    " <div class=\"block foccan drugH1Div\" id=\"F13703758\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosage Forms: Canada",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " Excipient information presented when available (limited, particularly for
    generics); consult specific product labeling.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Injection, suspension:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Fluviral&reg;: Hemagglutinin 45 mcg/0.5 mL (5 mL) [contains chicken egg
    protein, thimerosal]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Vaxigrip&reg;: Hemagglutinin 45 mcg/0.5 mL (5 mL) [contains chicken egg
    protein, neomycin (may have trace amounts), thimerosal]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Injection, suspension [preservative free]:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Agriflu&trade;: Hemagglutinin 45 mcg/0.5 mL (0.5 mL) [contains chicken egg
    protein, neomycin (may have trace amounts), kanamycin (may have trace amounts),
    polysorbate 80]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Fluad&trade;: Hemagglutinin 45 mcg/0.5 mL (0.5 mL) [contains chicken egg
    protein, neomycin (may have trace amounts), kanamycin (may have trace amounts),
    polysorbate 80]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Influvac&reg;: Hemagglutinin 45 mcg/0.5 mL (0.5 mL) [contains chicken egg
    protein, gentamicin (may have trace amounts), polysorbate 80]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Intanza&reg;: Hemagglutinin 27 mcg/0.1 mL (0.1 mL) [contains chicken egg
    protein, neomycin (may have trace amounts)]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Intanza&reg;: Hemagglutinin 45 mcg/0.1 mL (0.1 mL) [contains chicken egg
    protein, neomycin (may have trace amounts)]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Vaxigrip&reg;: Hemagglutinin 45 mcg/0.5 mL (0.25 mL, 0.5 mL) [contains
    chicken egg protein, neomycin (may have trace amounts)]",
    " </p>",
    " </div>",
    " <div class=\"block geq drugH1Div\" id=\"F9560328\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Generic Equivalent Available: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " No",
    " </p>",
    " </div>",
    " <div class=\"block prod-avail drugH1Div\" id=\"F15840740\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Product Availability",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " <b>",
    " Fluarix&reg; Quadrivalent:",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " Fluarix&reg; Quadrivalent: FDA approved December 2012; availability expected
    during the 2013-2014 influenza season.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " Fluarix&reg; Quadrivalent is an inactivated influenza virus vaccine approved
    for patients &ge;3 years of age. Seasonal quadrivalent influenza vaccines contain
    two subtype A strains and two subtype B strains; trivalent influenza vaccines
    contain two subtype A strains and one subtype B strain.",
    " </p>",
    " </div>",
    " <div class=\"block adm drugH1Div\" id=\"F9560343\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Administration",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <i>",
    " Fluzone&reg; Intradermal, Intanza&reg; (Canadian availability):",
    " </i>",
    " For intradermal administration over the deltoid muscle only. Fluzone&reg;
    Intradermal should be shaken gently prior to use. Intanza&reg; should not be shaken
    prior to use. Hold system using the thumb and middle finger (do not place fingers
    on windows). Insert needle perpendicular to the skin; inject using index finger to
    push on plunger. Do not aspirate.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <i>",
    " Afluria&reg;, Fluarix&reg;, Flucelvax&reg;, FluLaval&reg;, Fluvirin&reg;,
    Fluzone&reg;, Fluzone&reg; High-Dose, Agriflu&trade; (Canadian availability),
    Fluad&trade; (Canadian availability), Fluviral&reg; (Canadian availability),
    Vaxigrip&reg; (Canadian availability):",
    " </i>",
    " For I.M. administration only. Inspect for particulate matter and
    discoloration prior to administration. Adults and older children should be
    vaccinated in the deltoid muscle using a &ge;1 inch needle length. Infants and
    young children &lt;12 months of age should be vaccinated in the anterolateral
    aspect of the thigh using a",
    " <sup>",
    " 7",
    " </sup>",
    " /",
    " <sub>",
    " 8",
    " </sub>",
    " inch to 1 inch needle length. Young children with adequate deltoid muscle
    mass should be vaccinated using a",
    " <sup>",
    " 7",
    " </sup>",
    " /",
    " <sub>",
    " 8",
    " </sub>",
    " inch to 1.25 inch needle. Do not inject into the gluteal region or areas
    where there may be a major nerve trunk. Suspensions should be shaken well prior to
    use. Some manufacturers recommend avoiding use if visible particles are present in
    the suspension after shaking. See manufacturer labeling for specific
    recommendations.",
    " </p>",
    " <p style=\"text-indent:0em;margin-left:0em;margin-top:2em;text-
    align:justify;\">",
    " <i>",
    " Influvac&reg; (Canadian availability):",
    " </i>",
    " May be administered by I.M. or deep subcutaneous injection. Shake well prior
    to use.",
    " </p>",
    " <p style=\"text-indent:0em;margin-left:0em;margin-top:2em;text-
    align:justify;\">",
    " Unless otherwise indicated in product labeling, jet injectors should",
    " <b>",
    " not",
    " </b>",
    " be used to administer inactivated influenza vaccines.",
    " </p>",
    " <p style=\"text-indent:0em;margin-left:0em;margin-top:2em;text-
    align:justify;\">",
    " If a pediatric vaccine (0.25 mL) is inadvertently administered to an adult,
    an additional 0.25 mL should be administered to provide the full adult dose (0.5
    mL). If the error is discovered after the patient has left, an adult dose should be
    given as soon as the patient can return. If an adult vaccine (0.5 mL) is
    inadvertently given to a child, no action needs to be taken.",
    " <i>",
    " Agriflu&trade; (Canadian availability):",
    " </i>",
    " If 0.25 mL dose is to be given, discard half the contained syringe volume
    prior to administration.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;text-align:justify;\">",
    " <b>",
    " Note:",
    " </b>",
    " For patients at risk of hemorrhage following intramuscular injection, the
    ACIP recommends &ldquo;it should be administered intramuscularly if, in the opinion
    of the physician familiar with the patient's bleeding risk, the vaccine can be
    administered by this route with reasonable safety. If the patient receives
    antihemophilia or other similar therapy, intramuscular vaccination can be scheduled
    shortly after such therapy is administered. A fine needle (23 gauge or smaller) can
    be used for the vaccination and firm pressure applied to the site (without rubbing)
    for at least 2 minutes. The patient should be instructed concerning the risk of
    hematoma from the injection.&rdquo; Patients on anticoagulant therapy should be
    considered to have the same bleeding risks and treated as those with clotting
    factor disorders (CDC, 2011).",
    " </p>",
    " <p style=\"text-indent:0em;margin-left:0em;margin-top:2em;text-
    align:justify;\">",
    " Simultaneous administration of vaccines helps ensure the patients will be
    fully vaccinated by the appropriate age. Simultaneous administration of vaccines is
    defined as administering &gt;1 vaccine on the same day at different anatomic sites.
    Separate vaccines should not be combined in the same syringe unless indicated by
    product specific labeling. Separate needles and syringes should be used for each
    injection. However, in general, vaccination should not be deferred if the brand
    name or route of the previous dose is not available or not known (CDC, 2011).
    Adolescents and adults should be vaccinated while seated or lying down. In general,
    preterm infants should be vaccinated at the same chronological age as full-term
    infants (CDC, 2011).",
    " </p>",
    " <p style=\"text-indent:0em;margin-left:0em;margin-top:2em;text-
    align:justify;\">",
    " Antipyretics have not been shown to prevent febrile seizures. Antipyretics
    may be used to treat fever or discomfort following vaccination (CDC, 2011). One
    study reported that routine prophylactic administration of acetaminophen to prevent
    fever prior to vaccination decreased the immune response of some vaccines; the
    clinical significance of this reduction in immune response has not been established
    (Prymula, 2009).",
    " </p>",
    " </div>",
    " <div class=\"block use drugH1Div\" id=\"F9560341\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Use",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Provide active immunity to influenza virus strains contained in the vaccine",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:2em;text-
    align:justify;\">",
    " The Advisory Committee on Immunization Practices (ACIP) recommends annual
    vaccination with the seasonal inactivated influenza vaccine (IIV) (injection) for
    all persons &ge;6 months of age.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:0em;text-
    align:justify;\">",
    " When vaccine supply is limited, target groups for vaccination (those at
    higher risk of complications from influenza infection and their close contacts)
    include the following:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Persons &ge;50 years of age",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Residents of nursing homes and other chronic-care facilities that
    house persons of any age with chronic medical conditions",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Adults and children with chronic disorders of the pulmonary or
    cardiovascular systems (except hypertension), including asthma",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Adults and children who have chronic metabolic diseases (including
    diabetes mellitus), hepatic disease, renal dysfunction, hematologic disorders, or
    immunosuppression (including immunosuppression caused by medications or HIV)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Adults and children with cognitive or neurologic/neuromuscular
    conditions (including conditions such as spinal cord injuries or seizure disorders)
    which may compromise respiratory function, the handling of respiratory secretions,
    or that can increase the risk of aspiration",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Children and adolescents (6 months to 18 years of age) who are
    receiving long-term aspirin therapy, and therefore, may be at risk for developing
    Reye's syndrome after influenza",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Women who are or will be pregnant during the influenza season",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Children 6-59 months of age",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Healthcare personnel",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Household contacts and caregivers of children &lt;5 years
    (particularly children &lt;6 months) and adults &ge;50 years",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Household contacts and caregivers of persons with medical conditions
    which put them at high risk of complications from influenza infection",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; American Indians/Alaska Natives",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Morbidly obese (BMI &ge;40)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:2em;text-
    align:justify;\">",
    " The Advisory Committee on Immunization Practices (ACIP) states that healthy,
    nonpregnant persons aged 2-49 years may receive vaccination with either the
    seasonal live, attenuated influenza vaccine (LAIV) (nasal spray) or the seasonal
    trivalent inactivated influenza vaccine (IIV) (injection).",
    " </p>",
    " </div>",
    " <div class=\"block mst drugH1Div\" id=\"F9560326\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Medication Safety Issues",
    " </span>",
    " <div class=\"collapsible\">",
    " <span class=\"collapsible-title\">",
    " Sound-alike/look-alike issues:",
    " </span>",
    " <div class=\"collapsible-wrap\">",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Fluarix&reg; may be confused with Flarex&reg;",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Influenza virus vaccine may be confused with flumazenil",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Influenza virus vaccine may be confused with tetanus toxoid and tuberculin
    products. Medication errors have occurred when tuberculin skin tests (PPD) have
    been inadvertently administered instead of tetanus toxoid products and influenza
    virus vaccine. These products are refrigerated and often stored in close proximity
    to each other.",
    " </p>",
    " </div>",
    " </div>",
    " <div class=\"collapsible\">",
    " <span class=\"collapsible-title\">",
    " International issues:",
    " </span>",
    " <div class=\"collapsible-wrap\">",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " Fluarix [U.S., Canada, and multiple international markets] may be confused
    with Flarex brand name for fluorometholone [U.S. and multiple international
    markets] and Fluorex brand name for fluoride [France]",
    " </p>",
    " </div>",
    " </div>",
    " </div>",
    " <div class=\"block ars drugH1Div\" id=\"F9560259\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Adverse Reactions Significant",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " <b>",
    " All serious adverse reactions must be reported to the U.S. Department of
    Health and Human Services (DHHS) Vaccine Adverse Event Reporting System (VAERS) 1-
    800-822-7967 or online at",
    " <a href=\"https://vaers.hhs.gov/esub/index\" target=\"_blank\">",
    " https://vaers.hhs.gov/esub/index",
    " </a>",
    " .",
    " </b>",
    " In Canada, adverse reactions may be reported to local provincial/territorial
    health agencies or to the Vaccine Safety Section at Public Health Agency of Canada
    (1-866-844-0018).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:2em;text-
    align:justify;\">",
    " Frequency not defined. Adverse reactions in adults &ge;65 years of age may be
    greater using the high-dose vaccine, but are typically mild and transient.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cardiovascular: Chest tightness, facial edema",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Central nervous system: Chills, drowsiness, fatigue, fever, headache,
    irritability, malaise, migraine, shivering",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Endocrine &amp; metabolic: Dysmenorrhea",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Gastrointestinal: Appetite decreased, diarrhea, nausea, sore throat, upper
    abdominal pain, vomiting",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Local: Injection site reactions (including bruising, erythema, induration,
    inflammation, pain, soreness [&le;64%; may last up to 2 days], pruritus, swelling,
    tenderness)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Neuromuscular &amp; skeletal: Arthralgia, back pain, myalgia (may start
    within 6-12 hours and last 1-2 days; incidence generally equal to placebo in
    adults; occurs more frequently than placebo in children)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Ocular: Red eyes",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Otic: Earache",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Respiratory: Cough, nasal congestion, nasopharyngitis, pharyngolaryngeal
    pain, rhinitis, upper respiratory tract infection, wheezing",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Miscellaneous: Diaphoresis",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Postmarketing and/or case reports (limited to important or life-threatening):
    Allergic reactions, anaphylaxis, angioedema, convulsions, erythema multiforme,
    facial palsy (Bell&rsquo;s palsy), Guillain-Barr&eacute; syndrome (GBS), Henoch-
    Sch&ouml;nlein purpura, hypersensitivity reaction, limb paralysis, lymphadenopathy,
    myelitis (including encephalomyelitis and transverse myelitis), neuralgia,
    oculorespiratory syndrome (ORS; acute, self-limited reaction with ocular and
    respiratory symptoms), optic neuritis/neuropathy, paralysis, photophobia, serum
    sickness, Stevens-Johnson syndrome, syncope, tachycardia, thrombocytopenia,
    urticaria, vasculitis, vertigo",
    " </p>",
    " </div>",
    " <div class=\"block coi drugH1Div\" id=\"F9560342\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Contraindications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Prior life-threatening reaction to previous influenza vaccination;
    hypersensitivity to any component of the formulation",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " Fluviral&reg; (not available in U.S.): Canadian labeling: Additional
    contraindications: Presence of acute respiratory infection, other active
    infections, or serious febrile illness",
    " </p>",
    " </div>",
    " <div class=\"block war drugH1Div\" id=\"F9600929\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Warnings/Precautions",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Concerns related to adverse effects:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Anaphylactoid/hypersensitivity reactions: Immediate treatment
    (including epinephrine 1:1000) for anaphylactoid and/or hypersensitivity reactions
    should be available during vaccine use.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Syncope: Syncope has been reported with use of injectable vaccines and
    may be accompanied by transient visual disturbances, weakness, or tonic-clonic
    movements. Procedures should be in place to avoid injuries from falling and to
    restore cerebral perfusion if syncope occurs (CDC, 2011).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Disease-related concerns:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Acute illness: May consider deferring administration in patients with
    moderate or severe acute illness (with or without fever); may administer to
    patients with mild acute illness (with or without fever) (CDC, 2011).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Bleeding disorders: Use with caution in patients with a history of
    bleeding disorders (including thrombocytopenia) and/or patients on anticoagulant
    therapy; bleeding/hematoma may occur from I.M. administration (CDC, 2011).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Febrile seizures: Postmarketing reports of increased incidence of
    fever and febrile seizures in children &lt;5 years of age has been observed with
    the use of the 2010 Southern Hemisphere formulation of the Afluria&reg; vaccine.
    Febrile events have also been reported in children 5 to &lt;9 years of age. Based
    on information from the CDC, an increased rate of febrile seizures has been
    reported in young children (&lt;5 years), especially among children 12 through 23
    months of age, who received vaccination with inactivated influenza vaccine (IIV)
    and the 13-valent pneumococcal conjugate vaccine (PCV13) simultaneously. However,
    due to the risks associated with delaying either vaccine, administering them at
    separate visits or deviating from the recommended vaccine schedule is not currently
    recommended.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Guillain-Barr&eacute; syndrome: Use with caution in patients with
    history of Guillain-Barr&eacute; syndrome (GBS); patients with history of GBS have
    a greater likelihood of developing GBS than those without. As a precaution, the
    ACIP recommends that patients with a history of GBS and who are at low risk for
    severe influenza complications, and patients known to have experienced GBS within 6
    weeks following previous vaccination should generally not be vaccinated (consider
    influenza antiviral chemoprophylaxis in these patients). The benefits of
    vaccination may outweigh the potential risks in persons with a history of GBS who
    are also at high risk for complications of influenza (CDC, 2011).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; HIV: Antigenic response may not be as great as expected in HIV-
    infected persons with CD4 cells &lt;100/mm",
    " <sup>",
    " 3",
    " </sup>",
    " and viral copies of HIV type 1 &gt;30,000/mL (CDC, 2010).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Neurologic disorders: Some Canadian product labeling recommends
    delaying therapy in patients with active neurologic disorders.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Concurrent drug therapy issues:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Vaccines: In order to maximize vaccination rates, the ACIP, as well as
    the Canadian National Advisory Committee on Immunization (NACI), recommends
    simultaneous administration of all age-appropriate vaccines (live or inactivated)
    for which a person is eligible at a single clinic visit, unless contraindications
    exist (CDC, 2011).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Special populations:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Altered immunocompetence: Use with caution in severely-
    immunocompromised patients (eg, patients receiving chemo/radiation therapy or other
    immunosuppressive therapy [including high-dose corticosteroid]); may have a reduced
    response to vaccination. Inactivated vaccine is preferred over live virus vaccine
    for household members, healthcare workers and others coming in close contact with
    severely-immunosuppressed persons requiring care in a protected environment (CDC,
    2011).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Elderly: Antibody responses may be lower in older adults &ge;65 years
    compared to younger adults.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Dosage form specific issues:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Chicken egg protein: Most products are manufactured with chicken egg
    protein (expressed as ovalbumin content). The ovalbumin content may vary from
    season to season and lot to lot of vaccine. Allergy to eggs must be distinguished
    from allergy to the vaccine. Recommendations are available from the CDC and NACI
    regarding influenza vaccination to persons who report egg allergies; however, a
    prior severe allergic reaction to influenza vaccine, regardless of the component
    suspected, is a contraindication to vaccination (CDC, 2012). NACI no longer
    considers an egg allergy as a contraindication to vaccination (NACI, 2011).
    Flucelvax&reg; is an inactivated influenza vaccine manufactured using cell culture
    technology and provides an alternative to vaccines cultured with chicken egg
    protein.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Gentamicin: Some products are manufactured with gentamicin.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Kanamycin: Some products are manufactured with kanamycin.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Latex: Packaging may contain natural latex rubber.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Neomycin: Some products are manufactured with neomycin.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Polymyxin: Some products are manufactured with polymyxin.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Thimerosal: Some products contain thimerosal; hypersensitivity
    reactions may occur.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Other warnings/precautions:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " &bull; Effective immunity: Vaccination may not result in effective immunity
    in all patients. Response depends upon multiple factors (eg, type of vaccine, age
    of patient) and may be improved by administering the vaccine at the recommended
    dose, route, and interval. Vaccines may not be effective if administered during
    periods of altered immune competence (CDC, 2011).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Previous season vaccines: Influenza vaccines from previous seasons
    must not be used.",
    " </p>",
    " </div>",
    " <div class=\"block cyt drugH1Div\" id=\"F13299519\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Metabolism/Transport Effects",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " None known.",
    " </p>",
    " </div>",
    " <div class=\"block dri drugH1Div\" id=\"F6221011\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Drug Interactions",
    " </span>",
    " <br/>",
    " <br/>",
    " <div class=\"lexi\" id=\"lexiInteractAddInfo\">",
    " (For additional information:",
    " <a class=\"dip\" href=\"./drug-interaction\" target=\"_blank\">",
    " Launch Lexi-Interact&trade; Drug Interactions Program",
    " </a>",
    " )",
    " </div>",
    " <div class=\"lexi\" id=\"lexiInteractImgB\">",
    " <img border=\"0\" height=\"17\"
    src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\" width=\"71\"/>",
    " </div>",
    " <div class=\"clear\">",
    " </div>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Belimumab: May diminish the therapeutic effect of Vaccines (Inactivated).",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Fingolimod: May diminish the therapeutic effect of Vaccines (Inactivated).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Immunosuppressants: May diminish the therapeutic effect of Vaccines
    (Inactivated).",
    " <b>",
    " Exceptions:",
    " </b>",
    " Cytarabine (Liposomal).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Pneumococcal Conjugate Vaccine (13-Valent): May diminish the therapeutic
    effect of Influenza Virus Vaccine (Inactivated). Influenza Virus Vaccine
    (Inactivated) may diminish the therapeutic effect of Pneumococcal Conjugate Vaccine
    (13-Valent). Management: Immune response to these vaccines may be diminished when
    given concomitantly to patients 65 years old or older. When practical, consider
    separating doses of these vaccines by 1 month or more for these patients.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " </div>",
    " <div class=\"block prf drugH1Div\" id=\"F9600925\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Risk Factor",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " B/C (manufacturer specific) (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
    " show table",
    " </a>",
    " )",
    " </p>",
    " </div>",
    " <div class=\"block pri drugH1Div\" id=\"F9600926\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Implications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Reproduction studies have not been conducted with all products. When
    conducted, adverse events were not observed in animal studies. Inactivated
    influenza vaccine has not been shown to cause fetal harm and has been shown to be
    safe and effective when given to pregnant women. Following maternal immunization
    with the influenza virus vaccine, vaccine specific antibodies are observed in the
    newborn.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " Pregnant women are at an increased risk of complications from influenza
    infection (Rasmussen, 2008). Influenza vaccination with the inactivated influenza
    vaccine (IIV) is recommended for all women who are or will become pregnant during
    the influenza season and who do not otherwise have contraindications to the
    vaccine. Pregnant women should observe the same precautions as nonpregnant women to
    reduce the risk of exposure to influenza and other respiratory infections. When
    vaccine supply is limited, focus on delivering the vaccine should be given to women
    who are pregnant or will be pregnant during the flu season, as well as mothers of
    newborns and contacts or caregivers of children &lt;5 years of age (CDC, 2010).
    Most available studies show a decrease in influenza-related illnesses in pregnant
    women as well as children &lt;6 months of age following maternal vaccination during
    pregnancy, thereby supporting current recommendations that all pregnant women
    should be vaccinated (Zaman, 2008).",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " Healthcare providers are encouraged to refer women exposed to the influenza
    vaccine during pregnancy to the",
    " <i>",
    " Vaccines and Medications in Pregnancy Surveillance System",
    " </i>",
    " (VAMPSS) by contacting The Organization of Teratology Information Specialists
    (OTIS) at (877) 311-8972. Women exposed to Flulaval&reg; or Fluarix&reg; during
    pregnancy may also contact the GlaxoSmithKline registry at 888-452-9622. Healthcare
    providers may enroll women exposed to Fluzone&reg; Intradermal during pregnancy in
    the Sanofi Pasteur vaccination registry at 800-822-2463.",
    " </p>",
    " </div>",
    " <div class=\"block lac drugH1Div\" id=\"F9600927\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Lactation",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Excretion in breast milk unknown/use caution",
    " </p>",
    " </div>",
    " <div class=\"block brc drugH1Div\" id=\"F9600928\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Breast-Feeding Considerations",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " It is not known if inactivated influenza vaccine is excreted into breast
    milk; however, breast-feeding is not a contraindication to vaccination. Postpartum
    women may be vaccinated with either IIV or LAIV. When vaccine supply is limited,
    focus on delivering the vaccine should be given to women who are pregnant or will
    be pregnant during the flu season, as well as mothers of newborns and contacts or
    caregivers of children &lt;5 years of age (CDC, 2010). Breast-feeding infants
    should be vaccinated according to the recommended schedules (CDC, 2011).",
    " </p>",
    " </div>",
    " <div class=\"block fee drugH1Div\" id=\"F16570492\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pricing: U.S. (Medi-Span&reg;)",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Device",
    " </b>",
    " (Fluzone Intradermal)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 9 mcg/strain (0.1 mL): $19.91",
    " </p>",
    " </div>",
    " <div class=\"block mop drugH1Div\" id=\"F13315042\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Monitoring Parameters",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Monitor for syncope for 15 minutes following administration. If seizure-like
    activity associated with syncope occurs, maintain patient in supine or
    Trendelenburg position to reestablish adequate cerebral perfusion. For those
    individuals who report a history of egg allergy but it is determined that the
    inactivated vaccine can be used, observe vaccine recipient for at least 30 minutes
    after receipt of vaccine.",
    " </p>",
    " </div>",
    " <div class=\"block pha drugH1Div\" id=\"F9600931\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Mechanism of Action",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Promotes immunity to seasonal influenza virus by inducing specific antibody
    production. Each year the formulation is standardized according to the U.S. Public
    Health Service. Preparations from previous seasons must not be used.",
    " </p>",
    " </div>",
    " <div class=\"block phk drugH1Div\" id=\"F9600933\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacodynamics/Kinetics",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Onset of action: Protective antibody titers achieved ~3 weeks after
    vaccination",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Duration: Protective antibody titers persist approximately &ge;6 months.
    Elderly: Protective antibody titers may fall &le;4 months after vaccination.",
    " </p>",
    " </div>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
    " <li>",
    " <div class=\"reference\">",
    " Ashkenazi S, Vertruyen A, Arisegui J, et al, &ldquo;Superior Relative
    Efficacy of Live Attenuated Influenza Vaccine Compared With Inactivated Influenza
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    " Pediatr Infect Dis J",
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    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Bentley DW, &ldquo;Vaccinations,&rdquo;",
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    " 1423132",
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    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Centers for Disease Control and Prevention (CDC), &ldquo;Prevention and
    Control of Influenza With Vaccines: Recommendations of the Advisory Committee on
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    " <i>",
    " MMWR Recomm Rep",
    " </i>",
    " , 2010, 59(RR-8):1-62. Available at:",
    " <a href=\"file://www.cdc.gov/mmwr/PDF/rr/rr5908.pdf\" target=\"_blank\">",
    " file://www.cdc.gov/mmwr/PDF/rr/rr5908.pdf",
    " </a>",
    " <span class=\"pubmed-id\">",
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    " 20689501",
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    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Centers for Disease Control and Prevention (CDC), &ldquo;Prevention and
    Control of Influenza With Vaccines: Recommendations of the Advisory Committee on
    Immunization Practices (ACIP), United States, 2012-13 Influenza Season,&rdquo;",
    " <i>",
    " MMWR Morb Mortal Wkly Rep",
    " </i>",
    " , 2012, 61(32):613-7. Available at",
    " <a href=\"file://www.cdc.gov/mmwr/preview/mmwrhtml/mm6132a3.htm?
    s_cid=mm6132a3_w\" target=\"_blank\">",
    " file://www.cdc.gov/mmwr/preview/mmwrhtml/mm6132a3.htm?s_cid=mm6132a3_w",
    " </a>",
    " <span class=\"pubmed-id\">",
    " [PubMed",
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    " 21866086",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Centers for Disease Control and Prevention (CDC), &ldquo;Recommendations of
    the Advisory Committee on Immunization Practices (ACIP): General Recommendations on
    Immunization,&rdquo;",
    " <i>",
    " MMWR Recomm Rep",
    " </i>",
    " , 2011, 60(2):1-64.",
    " <span class=\"pubmed-id\">",
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    " <a href=\"UTD.htm?0/61/985/abstract-text/21293327/pubmed\" id=\"21293327\"
    target=\"_blank\">",
    " 21293327",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Centers for Disease Control and Prevention (CDC), \"Tiered Use of
    Inactivated Influenza Vaccine in the Event of a Vaccine Shortage,\"",
    " <i>",
    " MMWR Morb Mortal Wkly Rep",
    " </i>",
    " , 2005, 54(30):749-50.",
    " <span class=\"pubmed-id\">",
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    " <a href=\"UTD.htm?0/61/985/abstract-text/16079741/pubmed\" id=\"16079741\"
    target=\"_blank\">",
    " 16079741",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Centers for Disease Control and Prevention (CDC), &ldquo;Update on Febrile
    Seizures in Children Following Vaccination With Influenza Vaccines and Pneumococcal
    Vaccines&rdquo;, updated October 2011. Available at",
    " <a href=\"file://www.cdc.gov/vaccinesafety/Concerns/FebrileSeizures.html\"
    target=\"_blank\">",
    " file://www.cdc.gov/vaccinesafety/Concerns/FebrileSeizures.html",
    " </a>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Gardner P and Schaffner W, &ldquo;Immunization of Adults,&rdquo;",
    " <i>",
    " N Engl J Med",
    " </i>",
    " , 1993, 328(17):1252-8.",
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    " <a href=\"UTD.htm?0/61/985/abstract-text/8464436/pubmed\" id=\"8464436\"
    target=\"_blank\">",
    " 8464436",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " National Advisory Committee on Immunization (NACI), &ldquo;Statement on
    Seasonal Influenza Vaccine for 2011-2012,&rdquo;",
    " <i>",
    " Can Commun Dis Rep",
    " </i>",
    " , 2011, 37(ACS-5):1-55. Available at file://www.phac-
    aspc.gc.ca/publicat/ccdr-rmtc/11vol37/acs-dcc-5/index-eng.php",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Prymula R, Siegrist CA, Chlibek R, et al, &ldquo;Effect of Prophylactic
    Paracetamol Administration at Time of Vaccination on Febrile Reactions and Antibody
    Responses in Children: Two Open-Label, Randomised Controlled Trials,&rdquo;",
    " <i>",
    " Lancet",
    " </i>",
    " , 2009, 374(9698):1339-50.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/61/985/abstract-text/19837254/pubmed\" id=\"19837254\"
    target=\"_blank\">",
    " 19837254",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Rasmussen SA, Jamieson DJ, and Bresee JS, \"Pandemic Influenza and Pregnant
    Women,\"",
    " <i>",
    " Emerg Infect Dis",
    " </i>",
    " , 2008, 14(1):95-100.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/61/985/abstract-text/18258087/pubmed\" id=\"18258087\"
    target=\"_blank\">",
    " 18258087",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Smith SC Jr, Benjamin EJ, Bonow RO, et al, &ldquo;AHA/ACCF Secondary
    Prevention and Risk Reduction Therapy for Patients With Coronary and Other
    Atherosclerotic Vascular Disease: 2011 Update: A Guideline From the American Heart
    Association and American College of Cardiology Foundation,&rdquo;",
    " <i>",
    " Circulation",
    " </i>",
    " , 2011, 124(22):2458-73.",
    " <span class=\"pubmed-id\">",
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    " <a href=\"UTD.htm?0/61/985/abstract-text/22052934/pubmed\" id=\"22052934\"
    target=\"_blank\">",
    " 22052934",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Steering Committee on Quality Improvement and Management, Subcommittee on
    Febrile Seizures American Academy of Pediatrics, &ldquo;Febrile seizures: Clinical
    Practice Guideline for the Long-Term Management of the Child With Simple Febrile
    Seizures,&rdquo;",
    " <i>",
    " Pediatrics",
    " </i>",
    " , 2008, 121(6):1281-6.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/61/985/abstract-text/18519501/pubmed\" id=\"18519501\"
    target=\"_blank\">",
    " 18519501",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " U.S. Food and Drug Administration, &ldquo;FDA Updated Communication on Use
    of Jet Injectors With Inactivated Influenza Vaccines&rdquo;, October 26, 2011.
    Available at",
    " <a
    href=\"file://www.fda.gov/BiologicsBloodVaccines/Vaccines/QuestionsaboutVaccines/uc
    m276773.htm\" target=\"_blank\">",
    "
    file://www.fda.gov/BiologicsBloodVaccines/Vaccines/QuestionsaboutVaccines/ucm276773
    .htm",
    " </a>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Zaman K, Roy E, Arifeen SE, et al, &ldquo;Effectiveness of Maternal
    Influenza Immunization in Mothers and Infants,&rdquo;",
    " <i>",
    " N Engl J Med",
    " </i>",
    " , 2008, 9(15):1555-64.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/61/985/abstract-text/18799552/pubmed\" id=\"18799552\"
    target=\"_blank\">",
    " 18799552",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " </ol>",
    " </div>",
    " <div id=\"topicVersionRevision\">",
    " Topic 9055 Version 41.0",
    " </div>",
    " </div>",
    " <div id=\"footer\">",
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    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F14959458\">",
    " Special Alerts",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9560252\">",
    " Brand Names: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9560327\">",
    " Brand Names: Canada",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9560255\">",
    " Pharmacologic Category",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9600936\">",
    " Dosing: Adult",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9560266\">",
    " Dosing: Pediatric",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9600937\">",
    " Dosing: Geriatric",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F15897886\">",
    " Dosing: Renal Impairment",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F15897887\">",
    " Dosing: Hepatic Impairment",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9600938\">",
    " Dosage Forms: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F13703758\">",
    " Dosage Forms: Canada",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9560328\">",
    " Generic Equivalent Available: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F15840740\">",
    " Product Availability",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9560343\">",
    " Administration",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9560341\">",
    " Use",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9560326\">",
    " Medication Safety Issues",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9560259\">",
    " Adverse Reactions Significant",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9560342\">",
    " Contraindications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9600929\">",
    " Warnings/Precautions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F13299519\">",
    " Metabolism/Transport Effects",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F6221011\">",
    " Drug Interactions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9600925\">",
    " Pregnancy Risk Factor",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9600926\">",
    " Pregnancy Implications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9600927\">",
    " Lactation",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9600928\">",
    " Breast-Feeding Considerations",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F16570492\">",
    " Pricing: U.S. (Medi-Span&reg;)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F13315042\">",
    " Monitoring Parameters",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9600931\">",
    " Mechanism of Action",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F9600933\">",
    " Pharmacodynamics/Kinetics",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/9055\" rel=\"outline_link\">",
    " GRAPHICS",
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    " </div>",
    " </div>"].join("\n");
    var title_f0_61_986="Counseling HIV-infected patients regarding potential side
    effects of antiretroviral therapy";
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    " <div id=\"topicContent\">",
    " <div id=\"topicTitle\">",
    " Counseling HIV-infected patients regarding potential side effects of
    antiretroviral therapy",
    " </div>",
    " <div id=\"topicContributors\">",
    " <div>",
    " <a id=\"authors\">",
    " </a>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/61/986/contributors\">",
    " Author",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/61/986/contributors\">",
    " John G Bartlett, MD",
    " </a>",
    " <br/>",
    " </div>",
    " <div>",
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    href=\"UTD.htm?0/61/986/contributors\">",
    " Section Editor",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/61/986/contributors\">",
    " Martin S Hirsch, MD",
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    " <br/>",
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    href=\"UTD.htm?0/61/986/contributors\">",
    " Deputy Editor",
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    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/61/986/contributors\">",
    " Allyson Bloom, MD",
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    " All topics are updated as new evidence becomes available and our",
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    " peer review process",
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    " Literature review current through:",
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    " Oct 2013.",
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    " This topic last updated:",
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    " Feb 7, 2013.",
    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;When an HIV-infected patient is prescribed antiretroviral
    therapy, it is important to review potential side effects of these medications.
    Patients need to understand what symptoms to anticipate and when they should seek
    help for adverse events, which can sometimes be associated with significant
    morbidity. It is important for clinicians to be responsive to the concerns of the
    patient, since side effects can lead to decreased adherence and drug resistance.",
    " </p>",
    " <p>",
    " This topic will highlight the major adverse events associated with use of
    specific medications; however, it is not intended to be a comprehensive review of
    all potential adverse events. Clinicians are advised to consult the drug
    information topics within UpToDate for individual drugs and other information
    resources, such as package inserts.",
    " </p>",
    " <p>",
    " Efficacy of various antiretroviral therapy regimens, patient evaluation,
    counseling regarding side effects, and laboratory monitoring are discussed
    elsewhere. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?9/35/9786?
    source=see_link\">",
    " \"When to initiate antiretroviral therapy in HIV-infected patients\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/17/38167?
    source=see_link\">",
    " \"Patient monitoring during HIV antiretroviral therapy\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?35/24/36234?
    source=see_link\">",
    " \"Selecting antiretroviral regimens for the treatment naive HIV-infected
    patient\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/18/3370?
    source=see_link\">",
    " \"Considerations prior to initiating antiretroviral therapy\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " GENERAL PRINCIPLES",
    " </span>",
    " &nbsp;&mdash;&nbsp;Side effects with ART are common; however, many side
    effects improve over time with continued administration. It is critically important
    for the clinician to differentiate between mild versus potentially serious adverse
    events when making decisions about continuing therapy.",
    " </p>",
    " <p>",
    " Some drug reactions are progressive with continued exposure and can be
    potentially life threatening. The patient must be counseled regarding these
    potentially serious adverse events and be told to stop therapy until the provider
    can evaluate them. However, drug cessation is advised with some trepidation since
    repeated stops with prolonged \"unstructured treatment interruptions\" promote
    resistance. Serious reactions are rare and are included in black box warnings from
    the Federal Drug Administration (FDA). Major serious or life-threatening reactions
    include:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/63/31734?
    source=see_link\">",
    " Abacavir",
    " </a>",
    " hypersensitivity reaction. (See",
    " <a class=\"local\" href=\"#H7\">",
    " 'Abacavir hypersensitivity reaction'",
    " </a>",
    " below.)",
    " </li>",
    " <li>",
    " Stevens-Johnson syndrome (SJS) or toxic epidermal necrosis (TEN), which is
    most commonly associated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/12/18633?
    source=see_link\">",
    " nevirapine",
    " </a>",
    " , but also reported with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?28/42/29353?
    source=see_link\">",
    " efavirenz",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?13/0/13320?
    source=see_link\">",
    " etravirine",
    " </a>",
    " , all PIs (except",
    " <a class=\"drug drug_general\" href=\"UTD.htm?3/25/3482?source=see_link\">",
    " saquinavir",
    " </a>",
    " ) and many NRTIs (eg,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?23/28/24008?
    source=see_link\">",
    " zidovudine",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?14/38/14952?
    source=see_link\">",
    " didanosine",
    " </a>",
    " , and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/63/31734?
    source=see_link\">",
    " abacavir",
    " </a>",
    " ). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?17/29/17882?
    source=see_link\">",
    " \"Stevens-Johnson syndrome and toxic epidermal necrolysis: Clinical
    manifestations; pathogenesis; and diagnosis\"",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " Hepatic necrosis due to",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/12/18633?
    source=see_link\">",
    " nevirapine",
    " </a>",
    " . (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/63/29690?
    source=see_link\">",
    " \"Drugs and the liver: Patterns of drug-induced liver injury\"",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " Hepatitis B flares due to discontinuation of agents active against both HIV
    and HBV (eg,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/47/19191?
    source=see_link\">",
    " tenofovir",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?37/7/38007?
    source=see_link\">",
    " lamivudine",
    " </a>",
    " , and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?5/15/5366?source=see_link\">",
    " emtricitabine",
    " </a>",
    " ) due to immune reconstitution inflammatory syndrome or due to HBV
    resistance to the NRTI. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/51/16185?
    source=see_link\">",
    " \"Treatment of hepatitis B in the HIV-infected patient\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?22/35/23098?
    source=see_link\">",
    " \"Immune reconstitution inflammatory syndrome\"",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " Progressive ascending neuromuscular weakness (similar to Guillain
    Barr&eacute; syndrome) usually due to",
    " <a class=\"drug drug_general\" href=\"UTD.htm?42/45/43734?
    source=see_link\">",
    " stavudine",
    " </a>",
    " . (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?35/1/35864?
    source=see_link\">",
    " \"Epidemiology, pathogenesis and clinical features of HIV-associated
    neuropathies\"",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " Lactic acidosis with weight loss, fatigue, and gastrointestinal symptoms,
    which is associated with mitochondrial toxicity secondary to certain nucleoside
    analogs. (See",
    " <a class=\"local\" href=\"#H5\">",
    " 'Nucleoside analogs'",
    " </a>",
    " below.)",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Even mild to moderate symptoms can also effect a patient's quality of life [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/1\">",
    " 1",
    " </a>",
    " ]. Patients need to be reassured that the provider will address symptoms as
    they arise and that many side effects can be easily addressed (eg, Imodium for
    diarrhea).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h1\">",
    " ADHERENCE",
    " </span>",
    " &nbsp;&mdash;&nbsp;Patients who are started on ART need to be counseled about
    the importance of adherence prior to initiation of medications [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/2,3\">",
    " 2,3",
    " </a>",
    " ]. Patients need to understand that lack of adherence may lead to drug
    resistance. Several factors can lead to poor adherence, including drug toxicity,
    complexity of the regimen, and other factors, such as substance abuse or mental
    illness.",
    " </p>",
    " <p>",
    " Adherence and risk of drug resistance is complicated due to variations in drug
    pharmacology, genetic barriers, and drug potency. The commonly quoted adage is the
    need to take 95 percent of prescribed doses [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/4\">",
    " 4",
    " </a>",
    " ]. However, this observation was shown with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/62/19433?source=see_link\">",
    " nelfinavir",
    " </a>",
    " -based ART, which is no longer used. The half-lives of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/12/18633?source=see_link\">",
    " nevirapine",
    " </a>",
    " and the preferred non-nucleoside reverse transcriptase inhibitor (NNRTI),",
    " <a class=\"drug drug_general\" href=\"UTD.htm?28/42/29353?source=see_link\">",
    " efavirenz",
    " </a>",
    " , are long (several days or weeks); therefore, 70 percent adherence with one
    to two days \"off\" does not result in failure to suppress viremia. However, NVP
    and EFV have low barriers to resistance so longer interruptions are likely to
    eliminate the future value of both drugs [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/5\">",
    " 5",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Generally speaking,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?11/58/12202?source=see_link\">",
    " ritonavir",
    " </a>",
    " -boosted protease inhibitors have improved pharmacokinetics allowing once
    daily dosing. Protease inhibitors are also associated with less overall drug
    resistance than the other five classes of antiretroviral medications. Thus, poor
    adherence with a protease inhibitor-containing regimen may lead to virologic
    failure, but not necessarily drug resistance due to the requisite for multiple
    mutations before drug potency is affected. Despite these observations, all patients
    should be encouraged to adhere to their regimen as much as possible.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h1\">",
    " CLASS SPECIFIC SIDE EFFECTS",
    " </span>",
    " &nbsp;&mdash;&nbsp;Drug intolerance was the leading reason for changing ART in
    a study of more than 1800 treatment-naive patients from the Swiss HIV Cohort Study
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/6\">",
    " 6",
    " </a>",
    " ]. Adverse reactions can sometimes apply to all or nearly all members of a
    drug class. Examples include mitochondrial toxicity and hyperlipidemia (",
    " <a class=\"graphic graphic_table graphicRef66245 graphicRef77005 \"
    href=\"UTD.htm?6/33/6686\">",
    " table 1A-B",
    " </a>",
    " ) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/7\">",
    " 7",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h1\">",
    " NUCLEOSIDE ANALOGS",
    " </span>",
    " &nbsp;&mdash;&nbsp;As noted above, the nucleoside analog class is associated
    with mitochondrial toxicity, which can manifest as lactic acidosis or symptomatic
    hyperlactatemia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/8,9\">",
    " 8,9",
    " </a>",
    " ]. Side effects can include weight loss, nausea, vomiting, right upper
    quadrant pain, abdominal bloating, myalgias, and fatigue. However, the drugs within
    this class vary in their propensity to lead to mitochondrial toxicity. The drugs of
    greatest concern include the thymidine analogues (",
    " <a class=\"drug drug_general\" href=\"UTD.htm?23/28/24008?source=see_link\">",
    " zidovudine",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?14/38/14952?source=see_link\">",
    " didanosine",
    " </a>",
    " and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?42/45/43734?source=see_link\">",
    " stavudine",
    " </a>",
    " ); this is one of the major reasons that these drugs are infrequently used for
    initial therapy. This topic is discussed in detail elsewhere. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?29/40/30345?
    source=see_link\">",
    " \"Mitochondrial toxicity of HIV nucleoside reverse transcriptase
    inhibitors\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Common side effects related to specific nucleoside analogs are discussed
    below.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h2\">",
    " Abacavir",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/63/31734?source=see_link\">",
    " Abacavir",
    " </a>",
    " (Ziagen; ABC) is generally well tolerated. However, abacavir can be associated
    with a drug hypersensitivity reaction that is seen in 3 to 5 percent of patients
    within the first six weeks of drug exposure.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h3\">",
    " Abacavir hypersensitivity reaction",
    " </span>",
    " &nbsp;&mdash;&nbsp;Symptoms and signs of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/63/31734?source=see_link\">",
    " abacavir",
    " </a>",
    " hypersensitivity reaction (AHR) may include fever, rash, and gastrointestinal
    and respiratory complaints [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/10\">",
    " 10",
    " </a>",
    " ]. The severity often increases with subsequent doses. Immediate
    discontinuation of abacavir is needed if the hypersensitivity reaction is
    suspected; rechallenge can be life-threatening and is contraindicated [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/11,12\">",
    " 11,12",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?20/35/21049?
    source=see_link\">",
    " \"Abacavir hypersensitivity reaction\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " However, the symptoms and signs of AHR can be difficult to distinguish from
    those of concomitant infection or reaction to other drugs. As a result,
    overdiagnosis of AHR has led to an inaccurate estimation of true prevalence.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h3\">",
    " Screening for AHR",
    " </span>",
    " &nbsp;&mdash;&nbsp;Several advances have improved the ability to predict and
    accurately diagnose",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/63/31734?source=see_link\">",
    " abacavir",
    " </a>",
    " hypersensitivity reaction (AHR). In 2002, an association between AHR and a
    specific HLA background was described in two separate studies [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/13,14\">",
    " 13,14",
    " </a>",
    " ]. In addition, abacavir patch testing was designed to identify patients who
    had an immunologically mediated hypersensitivity reaction, without the risks of
    systemic rechallenge. Patch testing, however, cannot be used to screen for AHR in a
    patient who has not been exposed to the drug.",
    " </p>",
    " <p>",
    " The benefits of prospective screening with HLA-B*5701 testing has been
    demonstrated in two studies [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/10,15\">",
    " 10,15",
    " </a>",
    " ]. In a large double-blind, prospective, randomized study (PREDICT-1), 1956
    patients were randomly assigned to undergo prospective HLA-B*5701 screening or no
    screening prior to initiating",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/63/31734?source=see_link\">",
    " abacavir",
    " </a>",
    " -containing ART [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/10\">",
    " 10",
    " </a>",
    " ]. Those patients in the screening arm who had a positive screening test were
    excluded from taking abacavir. All study participants were followed prospectively
    for six weeks for evidence of AHR. Abacavir patch testing was also performed on
    patients with a clinical suspicion of abacavir hypersensitivity to confirm the
    diagnosis. The following results were observed:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The prevalence of HLA-B*5701 was 5.6 percent.",
    " </li>",
    " <li>",
    " Screening eliminated immunologically confirmed AHR in the prospective
    screening group. Thus, the negative predictive value was 100 percent.",
    " </li>",
    " <li>",
    " Clinically diagnosed AHR occurred in 7.8 percent of the control group; 2.7
    percent of these reactions were confirmed by patch testing.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " These data demonstrate that HLA-B*5701 testing can be used to prevent AHR. All
    major guidelines from the US, Europe and Australia recommend screening prior to",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/63/31734?source=see_link\">",
    " abacavir",
    " </a>",
    " initiation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/16\">",
    " 16",
    " </a>",
    " ], and this is now routinely done in all clinics. Abacavir should not be
    initiated in a patient with a positive screening test; an abacavir allergy should
    be recorded in the medical record for anyone with a positive genetic test result
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/15-17\">",
    " 15-17",
    " </a>",
    " ]. Although abacavir hypersensitivity is less common in African-Americans,
    this genetic marker appears to have excellent performance characteristics in this
    patient population as well [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/18\">",
    " 18",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " A negative screening test virtually eliminates the risk of AHR. Nevertheless,
    it is appropriate to warn the patient of this risk even with a negative screening
    test [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/19\">",
    " 19",
    " </a>",
    " ].If HLA-B*5701 testing is not available, then it is reasonable to initiate",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/63/31734?source=see_link\">",
    " abacavir",
    " </a>",
    " with patient counseling regarding potential signs of AHR, including fever,
    malaise, rash, and flu-like symptoms [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/16\">",
    " 16",
    " </a>",
    " ]. Patients should be advised to contact their provider as soon as possible if
    they develop typical symptoms, since it is important to clarify if the patient has
    an intercurrent illness or possible drug hypersensitivity.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9\">",
    " <span class=\"h2\">",
    " Emtricitabine",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?5/15/5366?source=see_link\">",
    " Emtricitabine",
    " </a>",
    " (Emtriva; FTC) is extremely well-tolerated. This drug is also active against
    HBV infection so drug discontinuation can cause a flare of hepatitis that can be
    fatal. This drug also has a black-box warning for lactic acidosis, but reported
    cases are very rare. (See",
    " <a class=\"drug drug_general\" href=\"UTD.htm?5/15/5366?source=see_link\">",
    " \"Emtricitabine: Drug information\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/51/16185?
    source=see_link\">",
    " \"Treatment of hepatitis B in the HIV-infected patient\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10\">",
    " <span class=\"h2\">",
    " Lamivudine",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?37/7/38007?source=see_link\">",
    " Lamivudine",
    " </a>",
    " (Epivir; 3TC) is extremely well tolerated. This drug is active versus HBV so
    drug discontinuation or the development of HBV drug resistance can cause a flare of
    HBV hepatitis. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/51/16185?
    source=see_link\">",
    " \"Treatment of hepatitis B in the HIV-infected patient\"",
    " </a>",
    " and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?37/7/38007?source=see_link\">",
    " \"Lamivudine: Drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H11\">",
    " <span class=\"h2\">",
    " Didanosine",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?14/38/14952?source=see_link\">",
    " Didanosine",
    " </a>",
    " (Videx; ddI) can cause pancreatitis; the risk of this adverse event appears to
    be dose-related and was more common in earlier years when dosing exceeded that used
    today (eg, &gt;400 mg daily).",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " An analysis of 17 ACTG studies yielded a relatively low overall rate of 0.61
    per 100 person years for clinical pancreatitis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/20\">",
    " 20",
    " </a>",
    " ]. Of the various combinations of dual NRTIs studied,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?14/38/14952?
    source=see_link\">",
    " didanosine",
    " </a>",
    " and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?42/45/43734?
    source=see_link\">",
    " stavudine",
    " </a>",
    " were associated with the highest rates of pancreatitis.",
    " </li>",
    " <li>",
    " In the EuroSIDA database, there were 43 pancreatic events in 9678
    individuals for an incidence of",
    " <span class=\"nowrap\">",
    " 1.27/1000",
    " </span>",
    " person-years of follow-up [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/21\">",
    " 21",
    " </a>",
    " ]. In this large database, collected since 2001, there was no evidence of an
    association of pancreatitis with cumulative exposure to",
    " <a class=\"drug drug_general\" href=\"UTD.htm?14/38/14952?
    source=see_link\">",
    " didanosine",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?42/45/43734?
    source=see_link\">",
    " stavudine",
    " </a>",
    " , or the combination of both drugs.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Based on these data, the risk of pancreatitis appears low to negligible;
    however, patients should be advised to contact their provider if they develop
    abdominal pain. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?0/3/63?source=see_link\">",
    " \"Evaluation of abdominal pain in the HIV-infected patient\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The incidence of drug-related neuropathy correlates directly with the degree
    of mitochondrial toxicity of particular NRTIs; as noted above, dideoxynucleoside
    agents carry the greatest degree of concern. Combination therapy with both",
    " <a class=\"drug drug_general\" href=\"UTD.htm?14/38/14952?source=see_link\">",
    " didanosine",
    " </a>",
    " and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?42/45/43734?source=see_link\">",
    " stavudine",
    " </a>",
    " are associated with the highest risk of peripheral neuropathy and are no
    longer recommended as components of first-line therapy for",
    " <span class=\"nowrap\">",
    " HIV/AIDS.",
    " </span>",
    " Ongoing drug exposure can lead to severe disabling symptoms. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/56/29577?
    source=see_link&amp;anchor=H6#H6\">",
    " \"Epidemiology, clinical manifestations, diagnosis, and treatment of HIV-
    associated peripheral neuropathy\", section on 'Role of drugs'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The cumulative use of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?14/38/14952?source=see_link\">",
    " didanosine",
    " </a>",
    " is also associated with non-cirrhotic portal hypertension, which can lead to
    variceal bleeding and death [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/22,23\">",
    " 22,23",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?14/38/14952?source=see_link\">",
    " Didanosine",
    " </a>",
    " is no longer considered a first line nucleoside analog agent. If prescribed,
    patients should take ddI (400",
    " <span class=\"nowrap\">",
    " mg/day)",
    " </span>",
    " on an empty stomach. Those who weigh less than 60 kg should receive a lower
    dose of 250",
    " <span class=\"nowrap\">",
    " mg/day.",
    " </span>",
    " They should not take ddI with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?42/45/43734?source=see_link\">",
    " stavudine",
    " </a>",
    " or with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/47/19191?source=see_link\">",
    " tenofovir",
    " </a>",
    " . (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?35/24/36234?
    source=see_link\">",
    " \"Selecting antiretroviral regimens for the treatment naive HIV-infected
    patient\"",
    " </a>",
    " and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?14/38/14952?source=see_link\">",
    " \"Didanosine: Drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H12\">",
    " <span class=\"h2\">",
    " Stavudine",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?42/45/43734?source=see_link\">",
    " Stavudine",
    " </a>",
    " (Zerit; d4T) is associated with lactic acidosis, lipoatrophy, pancreatitis and
    peripheral neuropathy, particularly when used in combination with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?14/38/14952?source=see_link\">",
    " didanosine",
    " </a>",
    " . (See",
    " <a class=\"local\" href=\"#H11\">",
    " 'Didanosine'",
    " </a>",
    " above and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?0/3/63?source=see_link\">",
    " \"Evaluation of abdominal pain in the HIV-infected patient\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/56/29577?
    source=see_link&amp;anchor=H6#H6\">",
    " \"Epidemiology, clinical manifestations, diagnosis, and treatment of HIV-
    associated peripheral neuropathy\", section on 'Role of drugs'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Exposure to certain NRTIs is a major risk factor associated with lipoatrophy,
    possibly due to NRTI-induced inhibition of mitochondrial DNA polymerase gamma. In
    vitro and in vivo studies suggest that thymidine analogues, and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?42/45/43734?source=see_link\">",
    " stavudine",
    " </a>",
    " in particular, play an important role in pathogenesis of lipoatrophy. Clinical
    manifestations can include loss of buccal fat and thinning of the extremities.
    Stavudine also causes hypertriglyceridemia. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?25/43/26298?
    source=see_link&amp;anchor=H8#H8\">",
    " \"Epidemiology, clinical manifestations, and diagnosis of HIV-associated
    lipodystrophy\", section on 'Antiretroviral therapy'",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?26/1/26650?
    source=see_link\">",
    " \"Epidemiology of cardiovascular disease and risk factors in HIV-infected
    patients\"",
    " </a>",
    " and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?42/45/43734?source=see_link\">",
    " \"Stavudine: Drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?42/45/43734?source=see_link\">",
    " Stavudine",
    " </a>",
    " is no longer considered a first line nucleoside analog agent. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?35/24/36234?
    source=see_link\">",
    " \"Selecting antiretroviral regimens for the treatment naive HIV-infected
    patient\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H13\">",
    " <span class=\"h2\">",
    " Tenofovir",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/47/19191?source=see_link\">",
    " Tenofovir",
    " </a>",
    " (Viread; TDF) is very well tolerated with minimal nephrotoxicity reported in
    early trials. Postmarketing surveillance covering more than 455,392 person-years of
    tenofovir exposure showed a serious renal event in less than 0.5 percent of
    patients and elevations of creatinine in 2.2 percent [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/24\">",
    " 24",
    " </a>",
    " ]. Although uncommon, Fanconi syndrome and acute kidney injury have been
    reported; in one case series of 13 patients, histologic findings on biopsy
    demonstrated changes consistent with acute tubular necrosis with evidence of
    mitochondrial injury [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/24\">",
    " 24",
    " </a>",
    " ]. Patients on tenofovir should be counseled regarding the need for regular
    monitoring of renal function and urinalysis.",
    " </p>",
    " <p>",
    " TDF is active versus hepatitis B virus and advocated in combination with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?5/15/5366?source=see_link\">",
    " emtricitabine",
    " </a>",
    " (or with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?37/7/38007?source=see_link\">",
    " lamivudine",
    " </a>",
    " ) for patients who have HBV coinfection [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/25\">",
    " 25",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/51/16185?
    source=see_link\">",
    " \"Treatment of hepatitis B in the HIV-infected patient\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " There is some evidence that TDF treatment alters bone metabolism predisposing
    to osteoporosis with long-term use [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/26\">",
    " 26",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/18/3370?
    source=see_link\">",
    " \"Considerations prior to initiating antiretroviral therapy\"",
    " </a>",
    " and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/47/19191?source=see_link\">",
    " \"Tenofovir: Drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H14\">",
    " <span class=\"h2\">",
    " Zidovudine",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?23/28/24008?source=see_link\">",
    " Zidovudine",
    " </a>",
    " (Retrovir; AZT) can lead to gastrointestinal intolerance, headaches, and
    asthenia. Some of these adverse events, particularly headache, may improve with
    ongoing administration.",
    " </p>",
    " <p>",
    " Since",
    " <a class=\"drug drug_general\" href=\"UTD.htm?23/28/24008?source=see_link\">",
    " zidovudine",
    " </a>",
    " can also lead to anemia, patients should be counseled to contact their
    provider if they should develop dyspnea on exertion or shortness of breath. A
    complete blood count should be monitored since zidovudine can also cause
    neutropenia. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/18/3370?
    source=see_link\">",
    " \"Considerations prior to initiating antiretroviral therapy\"",
    " </a>",
    " and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?23/28/24008?source=see_link\">",
    " \"Zidovudine: Drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H15\">",
    " <span class=\"h1\">",
    " NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS",
    " </span>",
    " &nbsp;&mdash;&nbsp;Although all three agents (",
    " <a class=\"drug drug_general\" href=\"UTD.htm?28/42/29353?source=see_link\">",
    " efavirenz",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/12/18633?source=see_link\">",
    " nevirapine",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?27/10/27816?source=see_link\">",
    " delavirdine",
    " </a>",
    " ) of this class have the potential to cause rash and hepatotoxicity, most of
    the data concern nevirapine.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H16\">",
    " <span class=\"h2\">",
    " Efavirenz",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?28/42/29353?source=see_link\">",
    " Efavirenz",
    " </a>",
    " (Sustiva; EFV) can commonly lead to central nervous system toxicity, such as
    headaches, nightmares, and a feeling of being \"hung over\" or
    &ldquo;disassociated.&rdquo; Patients should be advised to avoid driving or
    operating heavy machinery if they have onset of this latter symptom, which usually
    resolves within one to three weeks of dosing. In one study of the neurologic
    symptoms associated with efavirenz use, 12 of 303 patients (6 percent) discontinued
    the drug due to central nervous system (CNS) toxicity [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/27\">",
    " 27",
    " </a>",
    " ]. Another study evaluated treatment changes related to toxicity in 508
    patients who had achieved viral suppression [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/28\">",
    " 28",
    " </a>",
    " ]. The most frequently reported adverse events involved the CNS (23 percent)
    and were only seen in patients taking efavirenz-based ART. This side effect is
    noted in about half of patients, the change is noted on the day treatment is
    started and it usually resolves over a period of two to three weeks. Patients
    should also be counseled that efavirenz can lead to mood changes, feelings of
    depression and nightmares. Some authorities consider major depression or suicide
    ideation to be contraindications to efavirenz use.",
    " </p>",
    " <p>",
    " Skin rash is another relatively common side effect (15 to 27 percent), but
    most patients can be &ldquo;treated through.&rdquo; Patients need to understand
    that they should contact their provider if a rash appears so the clinician can
    further evaluate whether the rash is severe enough to warrant discontinuation.",
    " </p>",
    " <p>",
    " Other side effects include hyperlipidemia and hepatotoxicity with increased
    transaminase levels. Patients should be counseled regarding the signs and symptoms
    of hepatotoxicity.",
    " </p>",
    " <p>",
    " Female patients must be advised to avoid pregnancy while taking",
    " <a class=\"drug drug_general\" href=\"UTD.htm?28/42/29353?source=see_link\">",
    " efavirenz",
    " </a>",
    " , since its use is associated with teratogenicity resulting in neural tube
    disorders when taken in the first trimester. (See",
    " <a class=\"drug drug_general\" href=\"UTD.htm?28/42/29353?source=see_link\">",
    " \"Efavirenz: Drug information\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/4/15433?
    source=see_link\">",
    " \"Prenatal evaluation and intrapartum management of the HIV-infected patient
    in resource-rich settings\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?24/44/25290?
    source=see_link\">",
    " \"Use of antiretroviral medications in pregnant HIV-infected patients and
    their infants in resource-rich settings\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Clinicians can also advise symptomatic patients to take",
    " <a class=\"drug drug_general\" href=\"UTD.htm?28/42/29353?source=see_link\">",
    " efavirenz",
    " </a>",
    " on an empty stomach since food improves absorption.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H17\">",
    " <span class=\"h2\">",
    " Nevirapine",
    " </span>",
    " &nbsp;&mdash;&nbsp;The side effects of greatest concern with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/12/18633?source=see_link\">",
    " nevirapine",
    " </a>",
    " (Viramune) use are rash",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " hepatotoxicity. About 15 percent develop a rash although this is only severe
    enough in one percent of all patients to require discontinuation. Patients should
    be counseled to contact a medical provider immediately if a diffuse rash should
    occur. Associated signs that may suggest nevirapine hypersensitivity syndrome
    include oral blistering and fever. Certain genetic factors, such as HLA type, may
    affect the risk of nevirapine hypersensitivity [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/29\">",
    " 29",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Development of a simple rash secondary to",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/12/18633?source=see_link\">",
    " nevirapine",
    " </a>",
    " does not preclude a trial of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?28/42/29353?source=see_link\">",
    " efavirenz",
    " </a>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/30\">",
    " 30",
    " </a>",
    " ]. Development of Stevens-Johnson syndrome should result in avoidance of the
    class as a whole [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/31\">",
    " 31",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Patients should also be instructed regarding symptoms of hepatotoxicity,
    including any of the following: right upper quadrant pain, nausea, vomiting,
    fatigue, weight loss, and jaundice.",
    " </p>",
    " <p>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/12/18633?source=see_link\">",
    " Nevirapine",
    " </a>",
    " should NOT be initiated in men with a baseline CD4 count &gt;400",
    " <span class=\"nowrap\">",
    " cells/microL",
    " </span>",
    " or women with a CD4 count &gt;250",
    " <span class=\"nowrap\">",
    " cells/microL",
    " </span>",
    " since these represent major risk factors for hepatic necrosis. However, two
    studies in treatment-experienced patients have demonstrated that switching to
    nevirapine from another regimen appears safe, even after immune reconstitution [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/32,33\">",
    " 32,33",
    " </a>",
    " ]. (See",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/12/18633?source=see_link\">",
    " \"Nevirapine: Drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4007170\">",
    " <span class=\"h2\">",
    " Rilpivirine",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?15/27/15798?source=see_link\">",
    " Rilpivirine",
    " </a>",
    " is generally well tolerated; the most common adverse drug reactions to
    rilpivirine in the phase 3 clinical trials were depression, insomnia, headache and
    rash. However, rash led to drug discontinuation in less than 1 percent of study
    participants [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/34\">",
    " 34",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18\">",
    " <span class=\"h2\">",
    " Delavirdine",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?27/10/27816?source=see_link\">",
    " Delavirdine",
    " </a>",
    " (Rescriptor; DLV) is associated with headache, fever, and nausea; rash is seen
    in a significant minority of patients. This drug is uncommonly prescribed due to
    the need for three times daily dosing. (See",
    " <a class=\"drug drug_general\" href=\"UTD.htm?27/10/27816?source=see_link\">",
    " \"Delavirdine: Drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H19\">",
    " <span class=\"h2\">",
    " Etravirine",
    " </span>",
    " &nbsp;&mdash;&nbsp;The most common adverse events that occurred during initial
    clinical trials with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?13/0/13320?source=see_link\">",
    " etravirine",
    " </a>",
    " included rash (9 percent) (including rare patients with Stevens-Johnson
    Syndrome or erythema multiforme) and nausea. Rash occurred primarily in the second
    week of therapy and was infrequent after week four. Rash generally resolved within
    one to two weeks of continued dosing. Other relatively uncommon side effects
    include hepatoxicity, and hyperlipidemia. CNS toxicity is significantly less common
    than with EFV.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H20\">",
    " <span class=\"h1\">",
    " PROTEASE INHIBITORS",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H21\">",
    " <span class=\"h2\">",
    " Atazanavir",
    " </span>",
    " &nbsp;&mdash;&nbsp;Side effects associated with use of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?0/31/506?source=see_link\">",
    " atazanavir",
    " </a>",
    " (Reyataz; ATV) include rash and nausea.",
    " </p>",
    " <p>",
    " Patients need to be advised that",
    " <a class=\"drug drug_general\" href=\"UTD.htm?0/31/506?source=see_link\">",
    " atazanavir",
    " </a>",
    " use may also lead to medically inconsequential jaundice that will easily
    resolve with drug discontinuation. However, patients need to be informed that they
    should contact their provider should this occur so the diagnosis can be confirmed.
    An elevated indirect bilirubin confirms the diagnosis of hyperbilirubinemia that is
    medically inconsequential; an elevated direct bilirubin would infer an alternate
    diagnosis and the possibility of liver injury. Patients at high risk for
    cardiovascular disease should be counseled regarding the favorable lipid profile of
    ATV and should be encouraged to follow a nutritious diet and to exercise. Note
    that",
    " <a class=\"drug drug_general\" href=\"UTD.htm?11/58/12202?source=see_link\">",
    " ritonavir",
    " </a>",
    " -boosted atazanavir is preferred for overall greater treatment efficacy
    although ritonavir leads to a modest increase in serum lipids. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/32/40458?
    source=see_link\">",
    " \"HIV protease inhibitors\"",
    " </a>",
    " and",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?8/51/9013?source=see_link\">",
    " \"Atazanavir: Patient drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H22\">",
    " <span class=\"h2\">",
    " Darunavir",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?35/39/36473?source=see_link\">",
    " Darunavir",
    " </a>",
    " (Prezista; DRV) is associated with gastrointestinal symptoms (nausea,
    vomiting, diarrhea) and rash. Darunavir contains a sulfonamide moiety and should be
    used with caution in patients with a known sulfonamide allergy. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/32/40458?
    source=see_link\">",
    " \"HIV protease inhibitors\"",
    " </a>",
    " and",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?32/26/33189?source=see_link\">",
    " \"Darunavir: Patient drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H23\">",
    " <span class=\"h2\">",
    " Fosamprenavir",
    " </span>",
    " &nbsp;&mdash;&nbsp;The most common adverse events associated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?43/11/44217?source=see_link\">",
    " fosamprenavir",
    " </a>",
    " (Lexiva; FPV) include gastrointestinal symptoms (nausea, vomiting and
    diarrhea) and rash, which is usually mild [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/35\">",
    " 35",
    " </a>",
    " ]. (See",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?32/5/32853?source=see_link\">",
    " \"Fosamprenavir: Patient drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H24\">",
    " <span class=\"h2\">",
    " Indinavir",
    " </span>",
    " &nbsp;&mdash;&nbsp;The most common side effects associated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?24/36/25161?source=see_link\">",
    " indinavir",
    " </a>",
    " (Crixivan; IDV) include gastrointestinal symptoms, dry eyes and mouth, and
    nephrolithiasis. Patients must be advised regarding potential symptoms of renal
    colic; ingestion of more than 48 oz of fluid daily decreases the risk of this
    adverse outcome.",
    " </p>",
    " <p>",
    " Indirect hyperbilirubinemia is also commonly seen on laboratory monitoring,
    but clinical jaundice is uncommon. Patients can take",
    " <a class=\"drug drug_general\" href=\"UTD.htm?24/36/25161?source=see_link\">",
    " indinavir",
    " </a>",
    " without regard to meals if pharmacokinetic boosting of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?11/58/12202?source=see_link\">",
    " ritonavir",
    " </a>",
    " is employed. This drug is rarely used and is not recommended by the 2009 DHHS
    Guidelines or the 2010 IAS-USA Guidelines. (See",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?3/28/3525?source=see_link\">",
    " \"Indinavir: Patient drug information\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/32/40458?
    source=see_link\">",
    " \"HIV protease inhibitors\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H25\">",
    " <span class=\"h2\">",
    " Lopinavir",
    " </span>",
    " &nbsp;&mdash;&nbsp;Lopinavir (Kaletra; LPV) is associated with nausea,
    headache, and diarrhea. This agent is the PI that is most clearly associated with
    hyperlipidemia and risk of cardiovascular disease. It also has relatively poor
    gastrointestinal tolerance compared with alternative PIs such as",
    " <span class=\"nowrap\">",
    " DRV/r",
    " </span>",
    " and",
    " <span class=\"nowrap\">",
    " ATV/r.",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H26\">",
    " <span class=\"h2\">",
    " Nelfinavir",
    " </span>",
    " &nbsp;&mdash;&nbsp;The",
    " most common side effect with use of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/62/19433?source=see_link\">",
    " nelfinavir",
    " </a>",
    " (Viracept; NFV) is diarrhea. Patients should take nelfinavir with meals. This
    PI is antiquated due to reduced potency and should not be used in contemporary
    practice except in unusual circumstances. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/32/40458?
    source=see_link\">",
    " \"HIV protease inhibitors\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H27\">",
    " <span class=\"h2\">",
    " Ritonavir",
    " </span>",
    " &nbsp;&mdash;&nbsp;When",
    " <a class=\"drug drug_general\" href=\"UTD.htm?11/58/12202?source=see_link\">",
    " ritonavir",
    " </a>",
    " (Norvir; RTV) was first introduced, it was dosed at 600 mg twice daily as a
    full independent component of ART. However, it became quickly evident that
    ritonavir was associated with significant side effects, including nausea, diarrhea,
    altered taste, circumoral paresthesia, and peripheral paresthesia.",
    " </p>",
    " <p>",
    " Subsequently the main role of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?11/58/12202?source=see_link\">",
    " ritonavir",
    " </a>",
    " switched to a \"pharmacologic enhancer\" by inhibiting the cytochrome p450 3A4
    isoenzymes and thereby increasing serum levels of other protease inhibitors. Use of
    ritonavir at a low dose for pharmacokinetic boosting is much better tolerated.
    (See",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?5/35/5686?source=see_link\">",
    " \"Ritonavir: Patient drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H28\">",
    " <span class=\"h2\">",
    " Saquinavir",
    " </span>",
    " &nbsp;&mdash;&nbsp;The most common side effects associated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?3/25/3482?source=see_link\">",
    " saquinavir",
    " </a>",
    " (Invirase; SQV) are gastrointestinal in nature (nausea, vomiting and
    diarrhea). (See",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?20/34/21029?source=see_link\">",
    " \"Saquinavir: Patient drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H29\">",
    " <span class=\"h2\">",
    " Tipranavir",
    " </span>",
    " &nbsp;&mdash;&nbsp;The principle adverse effects of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?19/33/19992?source=see_link\">",
    " tipranavir",
    " </a>",
    " (Aptivus; TPV) include nausea, diarrhea, hepatotoxicity, and rash. Tipranavir
    should be used with caution in patients with a known sulfonamide allergy since
    tipranavir contains a sulfonamide component. Hepatotoxicity is more frequent and
    severe than with other PIs and hepatic insufficiency is a contraindication.
    Patients should also be instructed regarding symptoms of hepatotoxicity, including
    any of the following symptoms: right upper quadrant pain, nausea, vomiting,
    fatigue, and jaundice.",
    " </p>",
    " <p>",
    " Intracranial hemorrhage has also been reported among patients taking",
    " <a class=\"drug drug_general\" href=\"UTD.htm?19/33/19992?source=see_link\">",
    " tipranavir",
    " </a>",
    " , although the relationship of this adverse event to tipranavir is unclear.
    (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/32/40458?
    source=see_link\">",
    " \"HIV protease inhibitors\"",
    " </a>",
    " and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?19/33/19992?source=see_link\">",
    " \"Tipranavir: Drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H30\">",
    " <span class=\"h1\">",
    " FUSION INHIBITORS",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H31\">",
    " <span class=\"h2\">",
    " Enfuvirtide",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?7/2/7205?source=see_link\">",
    " Enfuvirtide",
    " </a>",
    " (Fuzeon; T-20) is associated with mild to moderate hypersensitivity reactions
    at the injection site, including erythema, induration, nodules and cysts. Biopsies
    of these injection sites have demonstrated inflammatory infiltrates surrounding
    deposits of drug [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/36\">",
    " 36",
    " </a>",
    " ]. Patients should be instructed to rotate injection sites. Topical steroid
    creams can also be considered for local site reactions. Many patients simply cannot
    tolerate these injections. (See",
    " <a class=\"drug drug_general\" href=\"UTD.htm?7/2/7205?source=see_link\">",
    " \"Enfuvirtide: Drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H32\">",
    " <span class=\"h1\">",
    " CCR5 INHIBITORS",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H33\">",
    " <span class=\"h2\">",
    " Maraviroc",
    " </span>",
    " &nbsp;&mdash;&nbsp;In clinical trials of highly treatment-experienced patients
    with advanced AIDS, the most common adverse reactions associated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?19/45/20182?source=see_link\">",
    " maraviroc",
    " </a>",
    " (Selzentry; MVC) included cough, pyrexia, upper respiratory infections, rash,
    musculoskeletal symptoms, lightheadedness and abdominal pain. Failure to make dose
    adjustments with concurrent use of a CYP3A4 inhibitor and use of maraviroc in renal
    failure was associated with increased side effects. Better understanding of the
    side effects associated with maraviroc will come with the post-marketing
    experience.",
    " </p>",
    " <p>",
    " The US Federal Drug Administration is requiring long-term follow-up studies to
    examine",
    " <a class=\"drug drug_general\" href=\"UTD.htm?19/45/20182?source=see_link\">",
    " maraviroc",
    " </a>",
    " 's side effect profile more closely in terms of cardiovascular effects and
    liver toxicity. Patients should be instructed to contact their provider if they
    have any onset of cardiac symptoms, such as chest pain. Patients should also be
    educated on the symptoms of hepatotoxicity (eg, right upper quadrant pain, nausea,
    vomiting, jaundice, and fatigue) and instructed to contact their provider as soon
    as possible should symptoms consistent with hepatotoxicity ensue. This issue is
    discussed in detail elsewhere. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?32/9/32918?
    source=see_link\">",
    " \"Clinical trials of HIV antiretroviral therapy: CCR5 antagonists\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H34\">",
    " <span class=\"h1\">",
    " INTEGRASE INHIBITORS",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H35\">",
    " <span class=\"h2\">",
    " Raltegravir",
    " </span>",
    " &nbsp;&mdash;&nbsp;In general,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?10/27/10678?source=see_link\">",
    " raltegravir",
    " </a>",
    " (Isentress; RGV) is very well tolerated. Side effects have included nausea,
    headache, and diarrhea. There are rare cases of myositis but cause and effect is
    not clearly established. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/34/7720?
    source=see_link\">",
    " \"Clinical trials of HIV antiretroviral therapy: Integrase inhibitors\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H36\">",
    " <span class=\"h1\">",
    " PHARMACOGENOMICS",
    " </span>",
    " &nbsp;&mdash;&nbsp;Pharmacogenomics is a promising field that examines the
    influence of genetic variation on drug response in patients. Preliminary data
    suggest that the use of pharmacogenomics may help to avert adverse drug-related
    events [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/37\">",
    " 37",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " For example,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?28/42/29353?source=see_link\">",
    " efavirenz",
    " </a>",
    " is primarily metabolized by cytochrome P450 2B6 (CYP2B6). High plasma
    concentrations are associated with a G to T polymorphism at position 516 (516G to
    T) of CYP2B6 [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/38,39\">",
    " 38,39",
    " </a>",
    " ]. One study assessed CYP2B6 genotypes in 456 HIV-infected patients who were
    receiving or about to receive efavirenz treatment [",
    " <a class=\"abstract\" href=\"UTD.htm?0/61/986/abstract/40\">",
    " 40",
    " </a>",
    " ]. Patients with the 516G to T polymorphism were given a dose as low as 200",
    " <span class=\"nowrap\">",
    " mg/day",
    " </span>",
    " of efavirenz. Central nervous system-related side effects of efavirenz
    improved with dose reduction in 10 of 14 patients. However, this strategy is
    considered experimental and the test noted is not generally available.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
    " <span class=\"h1\">",
    " INFORMATION FOR PATIENTS",
    " </span>",
    " &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education materials,
    &ldquo;The Basics&rdquo; and &ldquo;Beyond the Basics.&rdquo; The Basics patient
    education pieces are written in plain language, at the 5",
    " <sup>",
    " th",
    " </sup>",
    " to 6",
    " <sup>",
    " th",
    " </sup>",
    " grade reading level, and they answer the four or five key questions a patient
    might have about a given condition. These articles are best for patients who want a
    general overview and who prefer short, easy-to-read materials. Beyond the Basics
    patient education pieces are longer, more sophisticated, and more detailed. These
    articles are written at the 10",
    " <sup>",
    " th",
    " </sup>",
    " to 12",
    " <sup>",
    " th",
    " </sup>",
    " grade reading level and are best for patients who want in-depth information
    and are comfortable with some medical jargon.",
    " </p>",
    " <p>",
    " Here are the patient education articles that are relevant to this topic. We
    encourage you to print or e-mail these topics to your patients. (You can also
    locate patient education articles on a variety of subjects by searching on
    &ldquo;patient info&rdquo; and the keyword(s) of interest.)",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Basics topics (see",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?21/44/22210?
    source=see_link\">",
    " \"Patient information: Starting treatment for HIV (The Basics)\"",
    " </a>",
    " and",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?21/25/21907?
    source=see_link\">",
    " \"Patient information: HIV/AIDS (The Basics)\"",
    " </a>",
    " )",
    " </li>",
    " <li>",
    " Beyond the Basics topics (see",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?15/31/15861?
    source=see_link\">",
    " \"Patient information: Initial treatment of HIV (Beyond the Basics)\"",
    " </a>",
    " and",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?2/56/2946?
    source=see_link\">",
    " \"Patient information: Tips for taking HIV medications (Beyond the
    Basics)\"",
    " </a>",
    " )",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H38\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " When an HIV-infected patient is initiated on antiretroviral therapy, it is
    important to review potential side effects of these medications. Patients need to
    understand what symptoms to anticipate and when they should seek help for adverse
    events, which can be associated with significant morbidity. (See",
    " <a class=\"local\" href=\"#H1\">",
    " 'Introduction'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Patients should be interviewed regarding their level of adherence at every
    clinic visit in a non-judgmental manner. The link between poor adherence and drug
    resistance should be clearly communicated. (See",
    " <a class=\"local\" href=\"#H3\">",
    " 'Adherence'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Patients should be instructed to contact their provider about any troubling
    side effects, but should not stop the regimen until speaking with the provider.
    Potential exceptions may include onset of serious rash or symptoms of
    hepatotoxicity. (See",
    " <a class=\"local\" href=\"#H2\">",
    " 'General principles'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Patients should be educated about side effects that can infer onset of
    mitochondrial toxicity, such as weight loss, nausea, vomiting, right upper quadrant
    pain, or abdominal bloating. This is particularly important for patients who are
    taking nucleoside analogs such as",
    " <a class=\"drug drug_general\" href=\"UTD.htm?23/28/24008?
    source=see_link\">",
    " zidovudine",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?42/45/43734?
    source=see_link\">",
    " stavudine",
    " </a>",
    " or",
    " <a class=\"drug drug_general\" href=\"UTD.htm?14/38/14952?
    source=see_link\">",
    " didanosine",
    " </a>",
    " , all drugs that are now rarely used. Peripheral neuropathy can also be seen
    with stavudine or didanosine; ongoing drug administration can lead to disabling
    symptoms. (See",
    " <a class=\"local\" href=\"#H5\">",
    " 'Nucleoside analogs'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/63/31734?
    source=see_link\">",
    " Abacavir",
    " </a>",
    " can be associated with a drug hypersensitivity reaction that is seen in 3 to
    5 percent of patients within the first six weeks of drug exposure. Prominent
    symptoms include fever, rash, and myalgias. However, genetic screening for HLA-
    B*5701 allows determination of those at risk for this adverse event. Abacavir
    should not be initiated in a patient with a positive screening test. Although a
    negative screening test virtually eliminates the risk of drug hypersensitivity, it
    is appropriate to warn the patient of the symptoms of hypersensitivity. (See",
    " <a class=\"local\" href=\"#H7\">",
    " 'Abacavir hypersensitivity reaction'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Agents within the non-nucleoside reverse transcriptase inhibitor class can
    be associated with rash and hepatotoxicity, although most data highlight the role
    of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/12/18633?
    source=see_link\">",
    " nevirapine",
    " </a>",
    " . Patients need to be educated about the symptoms of hepatotoxicity and
    hypersensitivity syndromes and be encouraged to see medical evaluation promptly.
    Patients taking",
    " <a class=\"drug drug_general\" href=\"UTD.htm?28/42/29353?
    source=see_link\">",
    " efavirenz",
    " </a>",
    " must be counseled regarding symptoms of dizziness with initiation of this
    agent; nightmares and depressive symptoms may develop after chronic use. (See",
    " <a class=\"local\" href=\"#H15\">",
    " 'Non-nucleoside reverse transcriptase inhibitors'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Common side effects of the protease inhibitor class include gastrointestinal
    symptoms, such as nausea, vomiting and diarrhea. All protease inhibitors except ATV
    are associated with hyperlipidemia. (See",
    " <a class=\"local\" href=\"#H20\">",
    " 'Protease inhibitors'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Systemic side effects are uncommon with the use of fusion inhibitors,
    although injection site reactions can be particularly troubling. Rotation of
    injection sites can be modestly helpful. (See",
    " <a class=\"local\" href=\"#H30\">",
    " 'Fusion inhibitors'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " The side effects associated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?19/45/20182?
    source=see_link\">",
    " maraviroc",
    " </a>",
    " are not yet clear. In clinical trials in patients with advanced AIDS,
    symptoms included cough, pyrexia, upper respiratory infections, rash,
    musculoskeletal symptoms, lightheadedness and abdominal pain. (See",
    " <a class=\"local\" href=\"#H32\">",
    " 'CCR5 inhibitors'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " The integrase inhibitor",
    " <a class=\"drug drug_general\" href=\"UTD.htm?10/27/10678?
    source=see_link\">",
    " raltegravir",
    " </a>",
    " is very well-tolerated. Side effects have included nausea, headache, and
    diarrhea. (See",
    " <a class=\"local\" href=\"#H34\">",
    " 'Integrase inhibitors'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
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    target=\"_blank\">",
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    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
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    " Chui CK, Brumme ZL, Brumme CJ, et al. A simple screening approach to reduce
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    " Saag M, Balu R, Phillips E, et al. High sensitivity of human leukocyte
    antigen-b*5701 as a marker for immunologically confirmed abacavir hypersensitivity
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    " Waters LJ, Mandalia S, Gazzard B, Nelson M. Prospective HLA-B*5701 screening
    and abacavir hypersensitivity: a single centre experience. AIDS 2007; 21:2533.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/20\">",
    " Reisler RB, Murphy RL, Redfield RR, Parker RA. Incidence of pancreatitis in
    HIV-1-infected individuals enrolled in 20 adult AIDS clinical trials group studies:
    lessons learned. J Acquir Immune Defic Syndr 2005; 39:159.",
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    " Smith CJ, Olsen CH, Mocroft A, et al. The role of antiretroviral therapy in
    the incidence of pancreatitis in HIV-positive individuals in the EuroSIDA study.
    AIDS 2008; 22:47.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/22\">",
    " Maida I, Garcia-Gasco P, Sotgiu G, et al. Antiretroviral-associated portal
    hypertension: a new clinical condition? Prevalence, predictors and outcome. Antivir
    Ther 2008; 13:103.",
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    ducts/ucm199343.htm (Accessed on October 14, 2011).",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/24\">",
    " Herlitz LC, Mohan S, Stokes MB, et al. Tenofovir nephrotoxicity: acute
    tubular necrosis with distinctive clinical, pathological, and mitochondrial
    abnormalities. Kidney Int 2010; 78:1171.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/25\">",
    " Martin-Carbonero L, Soriano V. New paradigms for treating hepatitis B in
    HIV/hepatitis B virus co-infected patients. J Antimicrob Chemother 2010; 65:379.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/26\">",
    " Mueller NJ, Fux CA, Ledergerber B, et al. High prevalence of severe vitamin
    D deficiency in combined antiretroviral therapy-naive and successfully treated
    Swiss HIV patients. AIDS 2010; 24:1127.",
    " </a>",
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    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/27\">",
    " Clifford DB, Evans S, Yang Y, et al. Impact of efavirenz on
    neuropsychological performance and symptoms in HIV-infected individuals. Ann Intern
    Med 2005; 143:714.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/28\">",
    " Lodwick RK, Smith CJ, Youle M, et al. Stability of antiretroviral regimens
    in patients with viral suppression. AIDS 2008; 22:1039.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/29\">",
    " Carr DF, Chaponda M, Jorgensen AL, et al. Association of Human Leukocyte
    Antigen Alleles and Nevirapine Hypersensitivity in a Malawian HIV-Infected
    Population. Clin Infect Dis 2013.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/30\">",
    " Mehta U, Maartens G. Is it safe to switch between efavirenz and nevirapine
    in the event of toxicity? Lancet Infect Dis 2007; 7:733.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/31\">",
    " Dodi F, Alessandrini A, Camera M, et al. Stevens-Johnson syndrome in HIV
    patients treated with nevirapine: two case reports. AIDS 2002; 16:1197.",
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    " </li>",
    " <li>",
    " Mocroft A, Lacombe K, Rockstroh J, et al. Risk of discontinuation of
    nevirapine due to toxicity in antiretroviral naive and experienced patients with
    high and low CD4 counts. IAS Toronto 2006 Abstract #THAB0104.",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/33\">",
    " Kumarasamy N, Venkatesh KK, Devaleenal B, et al. Safety of switching to
    nevirapine-based highly active antiretroviral therapy at elevated CD4 cell counts
    in a resource-constrained setting. J Acquir Immune Defic Syndr 2007; 45:598.",
    " </a>",
    " </li>",
    " <li>",
    " Cohen C, et al. XVIIIth International AIDS Conference, Vienna, Austria, 18-23
    July 2010. Abstract THLBB206 (Accessed on June 10, 2011).",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/35\">",
    " Chapman TM, Plosker GL, Perry CM. Fosamprenavir: a review of its use in the
    management of antiretroviral therapy-naive patients with HIV infection. Drugs 2004;
    64:2101.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/36\">",
    " Introcaso CE, Hines JM, Kovarik CL. Cutaneous toxicities of antiretroviral
    therapy for HIV: part II. Nonnucleoside reverse transcriptase inhibitors, entry and
    fusion inhibitors, integrase inhibitors, and immune reconstitution syndrome. J Am
    Acad Dermatol 2010; 63:563.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/37\">",
    " Lowenhaupt EA, Matson K, Qureishi B, et al. Psychosis in a 12-year-old HIV-
    positive girl with an increased serum concentration of efavirenz. Clin Infect Dis
    2007; 45:e128.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/38\">",
    " Haas DW, Ribaudo HJ, Kim RB, et al. Pharmacogenetics of efavirenz and
    central nervous system side effects: an Adult AIDS Clinical Trials Group study.
    AIDS 2004; 18:2391.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/39\">",
    " Gandhi M, Greenblatt RM, Bacchetti P, et al. A single-nucleotide
    polymorphism in CYP2B6 leads to &gt;3-fold increases in efavirenz concentrations in
    plasma and hair among HIV-infected women. J Infect Dis 2012; 206:1453.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/61/986/abstract/40\">",
    " Gatanaga H, Hayashida T, Tsuchiya K, et al. Successful efavirenz dose
    reduction in HIV type 1-infected individuals with cytochrome P450 2B6 *6 and *26.
    Clin Infect Dis 2007; 45:1230.",
    " </a>",
    " </li>",
    " </ol>",
    " </div>",
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    " Topic 3797 Version 11.0",
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    " <a href=\"#\" title=\"Collapse Topic Outline\">",
    " <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
    " </a>",
    " </div>",
    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li>",
    " <a class=\"sr_button\" href=\"#H38\" id=\"summRecButton\">",
    " <span>",
    " SUMMARY &amp; RECOMMENDATIONS",
    " </span>",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H1\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H2\">",
    " GENERAL PRINCIPLES",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H3\">",
    " ADHERENCE",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H4\">",
    " CLASS SPECIFIC SIDE EFFECTS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H5\">",
    " NUCLEOSIDE ANALOGS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H6\">",
    " Abacavir",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H7\">",
    " - Abacavir hypersensitivity reaction",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H8\">",
    " - Screening for AHR",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H9\">",
    " Emtricitabine",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H10\">",
    " Lamivudine",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H11\">",
    " Didanosine",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H12\">",
    " Stavudine",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H13\">",
    " Tenofovir",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H14\">",
    " Zidovudine",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H15\">",
    " NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H16\">",
    " Efavirenz",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H17\">",
    " Nevirapine",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H4007170\">",
    " Rilpivirine",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H18\">",
    " Delavirdine",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H19\">",
    " Etravirine",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H20\">",
    " PROTEASE INHIBITORS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H21\">",
    " Atazanavir",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H22\">",
    " Darunavir",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H23\">",
    " Fosamprenavir",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H24\">",
    " Indinavir",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H25\">",
    " Lopinavir",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H26\">",
    " Nelfinavir",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H27\">",
    " Ritonavir",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H28\">",
    " Saquinavir",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H29\">",
    " Tipranavir",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H30\">",
    " FUSION INHIBITORS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H31\">",
    " Enfuvirtide",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H32\">",
    " CCR5 INHIBITORS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H33\">",
    " Maraviroc",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H34\">",
    " INTEGRASE INHIBITORS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H35\">",
    " Raltegravir",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H36\">",
    " PHARMACOGENOMICS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
    " INFORMATION FOR PATIENTS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H38\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"ID/3797\" rel=\"outline_link\">",
    " GRAPHICS",
    " <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
    " View All",
    " </a>",
    " </div>",
    " </h1>",
    " <div id=\"relatedGraphics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"ID/3797|TAB\">",
    " <a href=\"#\" title=\"TABLES\">",
    " TABLES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?0/4/70\" title=\"table
    1A\">",
    " ARV class adverse reactions I",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?41/30/42476\" title=\"table
    1B\">",
    " ARV class adverse reactions II",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?20/35/21049?
    source=related_link\">",
    " Abacavir hypersensitivity reaction",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?8/51/9013?
    source=related_link\">",
    " Atazanavir: Patient drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?32/9/32918?
    source=related_link\">",
    " Clinical trials of HIV antiretroviral therapy: CCR5 antagonists",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/34/7720?
    source=related_link\">",
    " Clinical trials of HIV antiretroviral therapy: Integrase inhibitors",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/18/3370?
    source=related_link\">",
    " Considerations prior to initiating antiretroviral therapy",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?32/26/33189?
    source=related_link\">",
    " Darunavir: Patient drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?27/10/27816?
    source=related_link\">",
    " Delavirdine: Drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?14/38/14952?
    source=related_link\">",
    " Didanosine: Drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/63/29690?
    source=related_link\">",
    " Drugs and the liver: Patterns of drug-induced liver injury",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?28/42/29353?
    source=related_link\">",
    " Efavirenz: Drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?5/15/5366?
    source=related_link\">",
    " Emtricitabine: Drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?7/2/7205?
    source=related_link\">",
    " Enfuvirtide: Drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?26/1/26650?
    source=related_link\">",
    " Epidemiology of cardiovascular disease and risk factors in HIV-infected
    patients",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?25/43/26298?
    source=related_link\">",
    " Epidemiology, clinical manifestations, and diagnosis of HIV-associated
    lipodystrophy",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/56/29577?
    source=related_link\">",
    " Epidemiology, clinical manifestations, diagnosis, and treatment of HIV-
    associated peripheral neuropathy",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?35/1/35864?
    source=related_link\">",
    " Epidemiology, pathogenesis and clinical features of HIV-associated
    neuropathies",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?0/3/63?
    source=related_link\">",
    " Evaluation of abdominal pain in the HIV-infected patient",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?32/5/32853?
    source=related_link\">",
    " Fosamprenavir: Patient drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/32/40458?
    source=related_link\">",
    " HIV protease inhibitors",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?22/35/23098?
    source=related_link\">",
    " Immune reconstitution inflammatory syndrome",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?3/28/3525?
    source=related_link\">",
    " Indinavir: Patient drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?37/7/38007?
    source=related_link\">",
    " Lamivudine: Drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?29/40/30345?
    source=related_link\">",
    " Mitochondrial toxicity of HIV nucleoside reverse transcriptase inhibitors",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/12/18633?
    source=related_link\">",
    " Nevirapine: Drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?21/25/21907?
    source=related_link\">",
    " Patient information: HIV/AIDS (The Basics)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?15/31/15861?
    source=related_link\">",
    " Patient information: Initial treatment of HIV (Beyond the Basics)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?21/44/22210?
    source=related_link\">",
    " Patient information: Starting treatment for HIV (The Basics)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?2/56/2946?
    source=related_link\">",
    " Patient information: Tips for taking HIV medications (Beyond the Basics)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/17/38167?
    source=related_link\">",
    " Patient monitoring during HIV antiretroviral therapy",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/4/15433?
    source=related_link\">",
    " Prenatal evaluation and intrapartum management of the HIV-infected patient
    in resource-rich settings",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?5/35/5686?
    source=related_link\">",
    " Ritonavir: Patient drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?20/34/21029?
    source=related_link\">",
    " Saquinavir: Patient drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?35/24/36234?
    source=related_link\">",
    " Selecting antiretroviral regimens for the treatment naive HIV-infected
    patient",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?42/45/43734?
    source=related_link\">",
    " Stavudine: Drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?17/29/17882?
    source=related_link\">",
    " Stevens-Johnson syndrome and toxic epidermal necrolysis: Clinical
    manifestations; pathogenesis; and diagnosis",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?18/47/19191?
    source=related_link\">",
    " Tenofovir: Drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?19/33/19992?
    source=related_link\">",
    " Tipranavir: Drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?15/51/16185?
    source=related_link\">",
    " Treatment of hepatitis B in the HIV-infected patient",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?24/44/25290?
    source=related_link\">",
    " Use of antiretroviral medications in pregnant HIV-infected patients and
    their infants in resource-rich settings",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?9/35/9786?
    source=related_link\">",
    " When to initiate antiretroviral therapy in HIV-infected patients",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?23/28/24008?
    source=related_link\">",
    " Zidovudine: Drug information",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_61_987="Clinician factors difficult patients";
    var content_f0_61_987=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=PC
    %2F67125&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=PC
    %2F67125&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
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    " Email",
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    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Clinician factors associated with experiencing more patients as difficult",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td>",
    " Little psychosocial training",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Biomedical, rather than biopsychosocial, orientation",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Lack of personal awareness",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Fewer years out of training",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Female gender",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Higher perceived workload",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Lower job satisfaction",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Lack of communication skills training",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_61_987=[""].join("\n");
    var outline_f0_61_987=null;
    var title_f0_61_988="JSGE criteria for EMR";
    var content_f0_61_988=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=GAST
    %2F61975&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=6\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=GAST
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    " Print",
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    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Japanese Society for Gastroenterological Endoscopy criteria for endoscopic
    mucosal resection (EMR) of early endoluminal cancers",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td class=\"subtitle1\">",
    " Cancer",
    " </td>",
    " <td class=\"subtitle1\">",
    " JSGE type",
    " </td>",
    " <td class=\"subtitle1\">",
    " Criteria for EMR",
    " </td>",
    " </tr>",
    " <tr>",
    " <td rowspan=\"3\">",
    " Early gastric cancer",
    " </td>",
    " <td>",
    " I",
    " </td>",
    " <td>",
    " Less than or equal to 2 cm",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " IIb and IIc",
    " </td>",
    " <td>",
    " Less than or equal to 1 cm",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Intestinal type adenocarcinoma",
    " </td>",
    " <td>",
    " Limited to the mucosa",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"3\">",
    " Esophageal cancer",
    " </td>",
    " <td rowspan=\"3\">",
    " I, IIa, IIb, IIc",
    " </td>",
    " <td>",
    " Diameter of less than or equal to 2 cm",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Involvement of less than one-third of the circumference of the esophageal
    wall",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Limitation to the mucosa of the esophagus",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td rowspan=\"6\">",
    " Colon cancer",
    " </td>",
    " <td>",
    " I",
    " </td>",
    " <td>",
    " Less than 3 cm",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " IIa",
    " </td>",
    " <td>",
    " Less than 3 cm",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " IIb",
    " </td>",
    " <td>",
    " Less than 5 mm",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " IIc + IIa",
    " </td>",
    " <td>",
    " Less than 1 cm",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " IIa + IIc",
    " </td>",
    " <td>",
    " Less than 1 cm",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " IV",
    " </td>",
    " <td>",
    " Less than 3 cm",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Raju GS, Waxman I. High-frequency US probe sonography-assisted endoscopic
    mucosal resection. Gastrointest Endosc 2000; 52:S39.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
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    var outline_f0_61_988=null;
    var title_f0_61_989="Management of pediatric lead poisoning";
    var content_f0_61_989=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=PEDS
    %2F74425&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=5\" onclick=\"\">",
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    title=\"Print this page\"/>",
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    %2F74425&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=5\" onclick=\"\"
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    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Guidance for treatment actions for pediatric lead poisoning according to blood
    lead level (BLL)",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td class=\"subtitle1\">",
    " Blood lead level (microg/dL)*",
    " </td>",
    " <td class=\"subtitle1\">",
    " Treatment actions",
    " </td>",
    " </tr>",
    " <tr>",
    " <td rowspan=\"2\">",
    " &lt;10",
    " </td>",
    " <td>",
    " Provide lead education and regular developmental/behavioral surveillance",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Reassess or rescreen in&nbsp;one year, or sooner if the child is younger
    than two years, was tested at the onset of warm weather, is at high risk for lead
    exposure, or the exposure sources have changed",
    " </td>",
    " </tr>",
    " <tr>",
    " <td rowspan=\"2\">",
    " 10 - 14",
    " </td>",
    " <td>",
    " Provide lead education and regular developmental/behavioral surveillance",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Provide follow-up testing within one month, then every&nbsp;three
    to&nbsp;four months",
    " </td>",
    " </tr>",
    " <tr>",
    " <td rowspan=\"5\">",
    " 15 - 19",
    " </td>",
    " <td>",
    " Provide lead education and regular developmental/behavioral surveillance",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Provide follow-up testing within one month, then every&nbsp;three to four
    months",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Refer to social services",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Initiate professional environmental cleanup",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Follow guidelines for 20 - 44 g/dL if BLL remains &ge;15 microg/dL (on two
    samples obtained at least three months apart)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td rowspan=\"6\">",
    " 20 - 44",
    " </td>",
    " <td>",
    " Provide lead education and regular developmental/behavioral surveillance",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Refer to clinical center specializing in lead poisoning",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Provide case management",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Provide both clinical and environmental management",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Ensure lead hazard control",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Consider treating with DMSA",
    " </td>",
    " </tr>",
    " <tr>",
    " <td rowspan=\"8\">",
    " 45 - 69",
    " </td>",
    " <td>",
    " Provide lead education",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Refer to clinical center specializing in lead poisoning",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Provide coordination of care",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Provide diagnostic testing within 24 to 48 hours",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Perform clinical evaluation and management within 48 hours",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Provide appropriate chelation therapy",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Perform aggressive environmental intervention",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Provide follow-up testing at least once per month (in accordance with
    chelation therapy) and regular developmental/behavioral surveillance",
    " </td>",
    " </tr>",
    " <tr>",
    " <td rowspan=\"4\">",
    " &ge;70",
    " </td>",
    " <td>",
    " This is a medical emergency",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Perform diagnostic testing immediately (samples shouldbe processed
    emergently)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Hospitalize immediately and begin chelation therapy",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Begin other activities as above",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " * Based upon confirmatory venousblood lead level.",
    " </div>",
    " <div class=\"reference\">",
    " Adapted from Roberts JR, Reigart JR. Medical assessment and interventions.
    In: Managing Elevated Blood Lead Levels Among Young children:Recommendations from
    the Advisory Committee on Childhood Lead PoisoningPrevention. Centers for Disease
    Control and Prevention, Atlanta, GA, 2002.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
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    " </div>",
    " <div class=\"lgnd\">",
    " Pelagia noctiluca specimen.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Reproduced with permission from Junghanss, T, Bodio, M. Medically important
    venomous animals: Biology, prevention, first aid, and clinical management. CID
    2006; 32:1309. Copyright &copy; 2006 University of Chicago Press.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_61_991=[""].join("\n");
    var outline_f0_61_991=null;

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