var title_f6_18_6432="CNS lymphoma flow study";

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" &copy;2013 UpToDate",
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" Flow cytometry of cerebrospinal fluid demonstrates lymphoma",
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" </div>",
" <div class=\"lgnd\">",
" This flow cytometry study of a sample of lymphocytes obtained from the
cerebrospinal fluid of a patient with suspected lymphoma shows a population of B-
lymphocytes (green color, asterisk) which stains positive for kappa light chains (Y
axis) and positive for CD19 expression (x axis). This same CD19 positive cell
population stained negative for lambda light chain expression (not shown here),
identifying this as a monoclonal population of lymphocytes, and suggesting that
these cells represent involvement of the neuraxis with lymphoma.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_18_6432=[""].join("\n");
var outline_f6_18_6432=null;
var title_f6_18_6433="Palpation of palmar fascia";
var content_f6_18_6433=[" <div id=\"graphicsToolbar\">",
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" &reg;",
"}",
" </div>",
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" <a href=\"?imageKey=RHEUM
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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=RHEUM
%2F69444&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: 470px\">",
" <div class=\"ttl\">",
" Palpation of the palmar fascia for nodularity",
" </div>",
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p8BUHaOlFFaxSejMpux//Z);\">",
" </div>",
" <div class=\"lgnd\">",
" The hand is placed in the palm up position. Each of the four digits are
passively stretched in extension, noting any differences in flexibility and tendon
scarring between the fingers. Next, the tendons are palpated for thickening or
nodularity along their course through the palm.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Bruce C Anderson, MD.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_18_6433=[""].join("\n");
var outline_f6_18_6433=null;
var title_f6_18_6434="Patient information: Hypoparathyroidism (The Basics)";
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" <p class=\"headingAnchor\" id=\"H9646588\">",
" <span class=\"h1\">",
" What is hypoparathyroidism?",
" </span>",
" &nbsp;&mdash;&nbsp;Hypoparathyroidism is a rare condition of the parathyroid
glands in your neck (",
" <a class=\"graphic graphic_figure graphicRef66834 \" href=\"UTD.htm?
14/43/15024\">",
" figure 1",
" </a>",
" ). These glands make a hormone that helps control the amount of calcium in
the blood. The hormone is called &ldquo;parathyroid hormone,&rdquo; or
&ldquo;PTH.&rdquo;",
" </p>",
" <p>",
" You get hypoparathyroidism when you have too little PTH in your body. This
causes the levels of calcium in your blood to get too low.",
" </p>",
" <p>",
" Neck surgery on the thyroid or parathyroid glands or major surgery for head
and neck cancer is the most common cause of hypoparathyroidism. After this surgery,
some people have hypoparathyroidism that lasts only a short time. Other people have
hypoparathyroidism for the rest of their lives, but this is less common. Other
conditions can also cause hypoparathyroidism. &nbsp;",
" </p>",
" <p class=\"headingAnchor\" id=\"H9646603\">",
" <span class=\"h1\">",
" What are the symptoms of hypoparathyroidism?",
" </span>",
" &nbsp;&mdash;&nbsp;The symptoms are different depending on the cause of
hypoparathyroidism.",
" </p>",
" <p>",
" People who develop hypoparathyroidism after neck surgery can have the
following symptoms:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Tingling in the hands or feet, or around the mouth",
" </li>",
" <li>",
" Unusual muscle movements, such as jerking, twitching, or spasms",
" </li>",
" <li>",
" Muscle cramps",
" </li>",
" <li>",
" Feeling tired, irritable, anxious, or depressed",
" </li>",
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" <p>",
" People with long-lasting hypoparathyroidism caused by other medical
conditions can have:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Eye problems, especially cataracts",
" </li>",
" <li>",
" Dry, thick skin",
" </li>",
" <li>",
" Coarse hair that breaks easily and can fall out, causing bald spots
&nbsp;",
" </li>",
" <li>",
" Fingernails that break easily, with ridges that go from left to right",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H9646618\">",
" <span class=\"h1\">",
" Is there a test for hypoparathyroidism?",
" </span>",
" &nbsp;&mdash;&nbsp;Yes. A doctor or nurse should be able to tell if you have
hypoparathyroidism by doing blood tests to measure your calcium and PTH levels. He
or she might also test the levels of other minerals and vitamin D in your blood.
You might have tests to measure calcium and magnesium levels in your urine.
&nbsp;",
" </p>",
" <p>",
" Long-lasting hypoparathyroidism that is not treated can cause calcium to
build up in the brain. Your doctor might order an X-ray of your head to look for
calcium buildups. If the X-ray does not show anything, but your doctor still thinks
you might have hypoparathyroidism, he or she might order an imaging test called a
&ldquo;CT scan.&rdquo; This test creates a better image of your brain than an X-ray
does. &nbsp;",
" </p>",
" <p class=\"headingAnchor\" id=\"H9646632\">",
" <span class=\"h1\">",
" How is hypoparathyroidism treated?",
" </span>",
" &nbsp;&mdash;&nbsp;Taking calcium and vitamin D supplements is the main
treatment for hypoparathyroidism. Your doctor might also give you medicines, such
as diuretics (water pills) to prevent too much calcium from leaving your body in
your urine.",
" </p>",
" <p>",
" When you start taking supplements, your doctor or nurse will test your blood
and urine every week. The tests will show if your calcium level is coming back to
normal. Your doctor or nurse can also check that the supplements are not causing
other health problems. When your calcium level is normal again, you only need blood
and urine tests every 3 to 6 months. &nbsp;",
" </p>",
" <p>",
" If you have permanent hypoparathyroidism, you will need to take supplements
for life. If your parathyroid glands stop working for a short time, such as after
surgery, you might only need treatment until the glands start working again.",
" </p>",
" <p class=\"headingAnchor\" id=\"H9646647\">",
" <span class=\"h1\">",
" What if I want to get pregnant?",
" </span>",
" &nbsp;&mdash;&nbsp;If you want to get pregnant, talk to your doctor, nurse,
or midwife about your hypoparathyroidism. He or she will measure your levels of
calcium, PTH, and vitamin D while you are pregnant and after you give birth.
Testing is especially important in the later months of pregnancy and while you are
nursing your baby. Your doctor, nurse, or midwife can help you get the right
supplements and any medicines you need to have a healthy baby.",
" </p>",
" <p class=\"headingAnchor\" id=\"H9646662\">",
" <span class=\"h1\">",
" What will my life be like?",
" </span>",
" &nbsp;&mdash;&nbsp;Most people with hypoparathyroidism are able to live
normal lives. If your doctor or nurse gives you supplements or medicines, take them
the way he or she tells you to. Make sure you get any tests you need on time. If
you have questions, ask your doctor or nurse. He or she will watch for problems and
treat them if they happen.",
" </p>",
" <p class=\"headingAnchor\" id=\"H9646677\">",
" <span class=\"h1\">",
" More on this topic",
" </span>",
" </p>",
" <p>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?3/54/3938?
source=see_link\">",
" Patient information: Hypothyroidism (underactive thyroid) (The Basics)",
" </a>",
" </p>",
" <p>",
" <a class=\"medical medical_patient\" href=\"UTD.htm?14/54/15203?
source=see_link\">",
" Patient information: Hypothyroidism (underactive thyroid) (Beyond the
Basics)",
" </a>",
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" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Ken Hatch, MD.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_18_6435=[""].join("\n");
var outline_f6_18_6435=null;
var title_f6_18_6436="Erythema migrans - early disseminated Lyme";
var content_f6_18_6436=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=DERM
%2F64784&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
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" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=DERM
%2F64784&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: 470px\">",
" <div class=\"ttl\">",
" Early disseminated Lyme disease",
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" <div class=\"lgnd\">",
" Multiple lesions of erythema migrans are present.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
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var title_f6_18_6437="Liver biopsy in a child with indeterminate acute liver
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KACiiigAooooAKKKKAP/9k=);\">",
" </div>",
" <div class=\"lgnd\">",
" Example of a liver biopsy in a child with acute liver failure of indeterminate
etiology, with falling ALT (1250 IU/L to 275 IU/L), rising total bilirubin (12.5
mg/dL to 25 mg/dL) and rising prothrombin time (rising from 20 to 26 seconds).
Histology reveals a dense infiltrate dominated by lymphocytes, but with scattered
neutrophils and eosinophils, and with hepatic necrosis and biliary damage.",
" <br/>",
" (A) Low power view.",
" <br/>",
" (B) High power view.",
" <div class=\"footnotes\">",
" ALT: alanine aminotransferase; IU: international unit.",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: Squires RH, Alonso EM. Acute liver failure
in children. In: Liver Disease in Children, 4th ed, Suchy FJ, Sokol RJ, Balistreri
WF (Eds), Cambridge University Press, New York 2012. Copyright &copy; 2012
Cambridge University Press.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_18_6437=[""].join("\n");
var outline_f6_18_6437=null;
var title_f6_18_6438="Echocardiographic evaluation of prosthetic heart valves";
var content_f6_18_6438=[" <noscript>",
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" <div id=\"topicContent\">",
" <div id=\"topicTitle\">",
" Echocardiographic evaluation of prosthetic heart valves",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/18/6438/contributors\">",
" Author",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/18/6438/contributors\">",
" Elyse Foster, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/18/6438/contributors\">",
" Section Editors",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/18/6438/contributors\">",
" Warren J Manning, MD",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/18/6438/contributors\">",
" William H Gaasch, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/18/6438/contributors\">",
" Deputy Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/18/6438/contributors\">",
" Susan B Yeon, MD, JD, FACC",
" </a>",
" <br/>",
" </div>",
" </div>",
" <div id=\"disclosures\">",
" <a href=\"UTD.htm?6/18/6438/contributor-disclosure\" target=\"_blank\">",
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" <div id=\"literatureReviewDate\">",
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" Literature review current through:",
" </span>",
" Oct 2013.",
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" This topic last updated:",
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" Oct 20, 2011.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;Delineation of normal prosthetic valve function is often
possible with transthoracic echocardiography. Despite the prominent acoustic
shadowing that accompanies mechanical prostheses, a Doppler signal that
demonstrates normal transprosthetic flow velocity and flow duration is usually
sufficient to exclude a stenotic valve. Exclusion of valvular regurgitation is
often more difficult, especially for mechanical prostheses in the mitral position.
As an example, one study of 170 patients who underwent surgery for valve
dysfunction found that diagnostic errors, ie, findings on the echocardiogram that
were not confirmed at surgery, occurred in 12 percent, and were primarily related
to paravalvular regurgitation [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/1\">",
" 1",
" </a>",
" ].",
" </p>",
" <p>",
" Transthoracic Doppler echocardiography provides important hemodynamic
information with regard to prosthetic valve pressure gradients and is extremely
useful in long-term follow-up. The \"normal gradient\" across a prosthetic valve
depends upon the type, size, and position of the prosthesis as well as the cardiac
output;",
" <a class=\"external\"
href=\"file://www.asecho.org/files/public/PVText.pdf\">",
" guidelines",
" </a>",
" are available for the acceptable range of Doppler gradients encountered in
properly functioning valves (",
" <a class=\"graphic graphic_table graphicRef67758 \" href=\"UTD.htm?
33/35/34355\">",
" table 1",
" </a>",
" )[",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/2,3\">",
" 2,3",
" </a>",
" ].",
" </p>",
" <p>",
" Acoustic shadowing caused by the prosthetic material may limit transthoracic
visualization of prosthetic leaflets, vegetations, abscesses, and thrombi. In
addition, while prosthetic aortic valve regurgitation is usually well visualized on
surface color Doppler imaging, prosthetic mitral regurgitation is frequently
undetectable [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/4\">",
" 4",
" </a>",
" ]. As a result, transesophageal echocardiography (TEE) is the imaging method
of choice when the transthoracic echocardiogram is technically inadequate or when
there are borderline findings on the transthoracic echocardiogram in a patient in
whom there is a strong clinical suspicion of malfunction [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/3\">",
" 3",
" </a>",
" ].",
" </p>",
" <p>",
" Transthoracic echocardiography images anteriorly, and thus is usually
sufficient for evaluation of aortic prostheses. However, since the atria are
situated in the far field where resolution is low, they are shadowed by a
mechanical mitral prosthesis. Since TEE images are taken from a position posterior
to the heart, the atrial side of the mitral and tricuspid valves can be seen. On
the other hand, transthoracic echocardiography demonstrates the ventricular side of
the valve that lies in its near field, whereas TEE does not. Both methods may have
difficulty with the evaluation of aortic prostheses, and the presence of mitral and
aortic devices in the same patient may make the task of the echocardiographer more
difficult. In most cases, however, both echocardiographic methods are
complementary.",
" </p>",
" <p>",
" The physician evaluating a prosthetic device with TEE should be aware of the
range of abnormalities that are possible in these devices and should match those
possibilities to the patient's presentation. Complications of prosthetic valves
detected by TEE include:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Paravalvular leak",
" </li>",
" <li>",
" Endocarditis (",
" <a class=\"graphic graphic_movie graphicRef58762 \" href=\"UTD.htm?
40/16/41230\">",
" movie 1",
" </a>",
" and",
" <a class=\"graphic graphic_movie graphicRef74517 \" href=\"UTD.htm?
25/30/26082\">",
" movie 2",
" </a>",
" )",
" </li>",
" <li>",
" Extrinsic interference of function (pannus, thrombus, vegetation) resulting
in obstruction or regurgitation (",
" <a class=\"graphic graphic_movie graphicRef64234 \" href=\"UTD.htm?
30/38/31343\">",
" movie 3",
" </a>",
" )",
" </li>",
" <li>",
" Ball variance",
" </li>",
" <li>",
" Strut fracture and component escape",
" </li>",
" <li>",
" Leaflet tears of bioprosthesis",
" </li>",
" <li>",
" Leaflet",
" <span class=\"nowrap\">",
" calcification/stenosis",
" </span>",
" of bioprosthesis",
" </li>",
" </ul>",
" </p>",
" <p>",
" The role of the TEE for evaluating the abnormalities associated with
prosthetic valves will be reviewed here. The major complications encountered with
these valves and the role of echocardiography in the evaluation of infective
endocarditis are discussed fully elsewhere. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/57/25497?
source=see_link\">",
" \"Complications of prosthetic heart valves\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/8/20617?
source=see_link\">",
" \"Role of echocardiography in infective endocarditis\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" PARAVALVULAR REGURGITATION",
" </span>",
" &nbsp;&mdash;&nbsp;Paravalvular regurgitation can arise from broken or
dehisced sutures, from a poorly seated ring, or from endocarditis (dehiscence).
Hemolysis is a common, but generally underappreciated, complication of these leaks,
especially when they occur with a mitral valve prosthesis [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/5,6\">",
" 5,6",
" </a>",
" ]. A TEE is required to detect paravalvular leakage and should routinely be
performed when a patient with a prosthetic valve presents with severe anemia.
Severe hemolysis can also occur after mitral valve repair, when regurgitation
develops around the annuloplasty ring. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?8/62/9194?
source=see_link&amp;anchor=H13#H13\">",
" \"Extrinsic nonimmune hemolytic anemia due to mechanical damage:
Fragmentation hemolysis and hypersplenism\", section on 'Malfunctioning cardiac
valves'",
" </a>",
" .)",
" </p>",
" <p>",
" To recognize a paravalvular leak, multiplane TEE must be performed with a high
color frame rate and middle range Nyquist limits (35 to 50",
" <span class=\"nowrap\">",
" cm/sec)",
" </span>",
" in several views from several angles outside the sewing ring [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/7\">",
" 7",
" </a>",
" ]. There should be a careful search for periprosthetic leaks around as much of
the valve circumference as possible and an attempt made to define the extent of the
regurgitation once it is identified. The origin of a periprosthetic leak may appear
deceivingly narrow when it is related to disruption of a limited number of sutures.
In some cases, these jets are seen inadvertently when one examines other
structures, such as the interatrial septum.",
" </p>",
" <p>",
" The most severe form of paravalvular regurgitation is seen when there is
dehiscence of a substantial portion of the sewing ring [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/8\">",
" 8",
" </a>",
" ]. In this setting, there may be such severe regurgitation that the
regurgitant flow is almost laminar. As in angiography, the sewing ring on
echocardiography is seen to rock with each cardiac cycle; mobile echo densities
representing the liberated suture material often can be visualized. Both the
laminar flow and the rocking motion of the ring may elude the inexperienced
echocardiographer, delaying recognition of this life threatening condition.",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h1\">",
" PROSTHETIC VALVE OBSTRUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;When, in a newly symptomatic patient, there is an
unexpected rise in transprosthetic gradient from a baseline determination or from
established normal values for valves of that type and size, the possibility of
progressive obstruction should be considered.",
" <a class=\"external\"
href=\"file://www.asecho.org/files/public/PVText.pdf\">",
" Guidelines",
" </a>",
" are available that contain the acceptable range of Doppler gradients
encountered in properly functioning valves (",
" <a class=\"graphic graphic_table graphicRef67758 \" href=\"UTD.htm?
33/35/34355\">",
" table 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/2,3\">",
" 2,3",
" </a>",
" ]. Causes of obstruction include pannus ingrowth, thrombus, and vegetation.
Clinical clues to this possibility include the age of the valve and the adequacy of
anticoagulation. In a bioprosthesis or heterograft, the leaflets themselves may
become calcified and immobile.",
" </p>",
" <p>",
" Once there is a high suspicion of obstruction, TEE should be strongly
considered for etiologic definition with both mechanical and bioprosthetic valves.
Doppler TEE is the primary means to diagnose prosthetic aortic valve obstruction;
hemodynamic cardiac catheterization is not routinely needed [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/9\">",
" 9",
" </a>",
" ].",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" In the case of suspected aortic pannus, the distal end of the left
ventricular outflow tract should be examined both with imaging and with color flow.
Pannus tends to lie close to the valve ring and can be easily overlooked. There can
be a prevalve jet that suggests pannus, which, on further searching with a variety
of frequencies, angles, and gain settings, will be detected.",
" </li>",
" <li>",
" In the mitral position, the same procedure should be followed. Finding a
high grade of spontaneous contrast in the left atrium, with or without thrombi, or
finding thrombus around the sewing ring in the setting of adequate anticoagulation
should heighten suspicion of pannus formation. Thin fibrillar strands are also
encountered on the mitral annulus and the left ventricular outflow tract. These
structures are brightly reflective and highly mobile and may or may not be
associated with a pathologic process.",
" </li>",
" </ul>",
" </p>",
" <p>",
" When a thrombus is present in the vicinity of the sewing ring and when
obstruction is clinically plausible and suggested by Doppler imaging, consideration
should be given to the use of thrombolysis or surgery (",
" <a class=\"graphic graphic_movie graphicRef58762 \" href=\"UTD.htm?
40/16/41230\">",
" movie 1",
" </a>",
" and",
" <a class=\"graphic graphic_movie graphicRef74517 \" href=\"UTD.htm?
25/30/26082\">",
" movie 2",
" </a>",
" and",
" <a class=\"graphic graphic_movie graphicRef64234 \" href=\"UTD.htm?
30/38/31343\">",
" movie 3",
" </a>",
" )&nbsp;[",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/10\">",
" 10",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/57/25497?
source=see_link\">",
" \"Complications of prosthetic heart valves\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h2\">",
" Distinction between thrombus and pannus",
" </span>",
" &nbsp;&mdash;&nbsp;The most common etiology for prosthetic valve obstruction
is thrombus formation; pannus formation due to fibrous tissue ingrowth is far less
common. In one surgical study of 112 obstructed mechanical valves, pannus formation
was the underlying cause in 11 percent of valves, pannus formation in combination
with thrombus was present in 12 percent, while thrombus alone was the etiology in
the remaining cases [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/11\">",
" 11",
" </a>",
" ]. Though associated with modest morbidity and mortality, thrombolytic therapy
is often an effective alternative to surgery for hemodynamic treatment of thrombus.
Therefore, it is important to distinguish between these two causes. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/57/25497?
source=see_link&amp;anchor=H13#H13\">",
" \"Complications of prosthetic heart valves\", section on 'Pannus formation'",
" </a>",
" .)",
" </p>",
" <p>",
" Echocardiographic differentiation of pannus and thrombus may be difficult. In
general:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Thrombus tends to be mobile, somewhat less echo-dense, and associated with
spontaneous contrast",
" </li>",
" <li>",
" Pannus is highly echogenic, consistent with its fibrous composition, and is
usually firmly fixed (minimal mobility) to the valve apparatus",
" </li>",
" </ul>",
" </p>",
" <p>",
" In order to establish factors associated with the presence of thrombus, one
study evaluated the findings on a preoperative TEE in 53 patients with an
intraoperative diagnosis of pannus or thrombus [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/12\">",
" 12",
" </a>",
" ]. Predictors of thrombus or a mixed presentation (pannus and thrombus)
included:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Mobile mass",
" </li>",
" <li>",
" Attachment of mass to valve occluder",
" </li>",
" <li>",
" Elevated gradients",
" </li>",
" <li>",
" An international normalized ratio (INR) &le;2.5",
" </li>",
" </ul>",
" </p>",
" <p>",
" All patients with thrombus or a mixed presentation had one or more of these
features. The prevalence of thrombus with &le;1, 2, and &ge;3 features was 14, 69,
and 91 percent, respectively.",
" </p>",
" <p>",
" Color flow aliasing with proximal acceleration of the flow jet in the vicinity
of the mass may aid in the identification of pannus. In one study of 23 patients
who presented with 24 obstructed valves, clinical, transthoracic, and TEE data were
compared to pathology at surgery in order to determine the clinical and
echocardiographic characteristics that differentiate thrombus from pannus formation
[",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/13\">",
" 13",
" </a>",
" ]. Thrombus was established in 14 valves and pannus in 10. Pannus formation
was more common in the aortic position. From the standpoint of echocardiography,
thrombus was more likely to be associated with soft ultrasound density (92 versus
29 percent).",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h1\">",
" PROSTHETIC VALVE REGURGITATION",
" </span>",
" &nbsp;&mdash;&nbsp;Physiologic regurgitation, the so-called seating puff of
angiography, is universally encountered and dependent in degree on the type of
prosthesis used. However, severe regurgitation may result from bioprosthetic valve
degeneration, mechanical valve pannus, thrombus, or vegetation.",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h2\">",
" Physiologic regurgitation",
" </span>",
" &nbsp;&mdash;&nbsp;All mechanical valves exhibit some degree of obligatory
regurgitation of up to 15 mL of blood [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/14\">",
" 14",
" </a>",
" ]. Seating regurgitation or \"closure backflow\" appears only briefly and is
due to retrograde volume displacement as the valve leaflets close. This type of
regurgitation is detected by highly sensitive color flow Doppler imaging on TEE. In
addition, a certain amount of more prolonged \"leakage backflow\" regurgitation
occurs after the valve closes [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/15\">",
" 15",
" </a>",
" ].",
" </p>",
" <p>",
" In an evaluation of 136 mechanical prosthetic valves, TEE color Doppler
imaging revealed regurgitant jets in 95 percent of the mitral prostheses and 44
percent of the aortic prostheses [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/16\">",
" 16",
" </a>",
" ]. In contrast transthoracic echocardiography documented regurgitant jets in
only 28 and 29 percent, respectively. The lower incidence of detected regurgitation
in the aortic position may be explained by the shadowing of the left ventricular
outflow tract in TEE imaging [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/17\">",
" 17",
" </a>",
" ].",
" </p>",
" <p>",
" Normally functioning mechanical valves, such as the bileaflet St. Jude,
usually have two to four centrally directed regurgitant jets. Features associated
with these jets include a low intensity and only minimal penetration into the
atrium, generally less than 3 cm [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/15,18,19\">",
" 15,18,19",
" </a>",
" ]. The monodisc Medtronic-Hall valve has two jets, one of which is prominent
and longer [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/19,20\">",
" 19,20",
" </a>",
" ]. Normally functioning bioprosthetic and heterografts are less likely to have
these small regurgitant signals; when mild regurgitation is present, there is
usually one central jet [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/16,21\">",
" 16,21",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h2\">",
" Pathologic regurgitation",
" </span>",
" &nbsp;&mdash;&nbsp;Pathologic jets tend to be high velocity, central, intense,
broad, and highly aliased; they tend to be eccentric, hugging the wall of the
atrium (Coanda effect), penetrating to its roof, continuing around its perimeter
and terminating where they began. The offending mass or tissue can usually be seen,
but the actual locus of obstruction causing the regurgitation may not be visible.",
" </p>",
" <p>",
" In contrast to mechanical valves, bioprostheses with leaflet degeneration may
exhibit central pathologic regurgitation that is broad-based when severe. The
bioprosthetic leaflets can usually be seen and are often thickened and calcified
with possible perforation or disruption leading to a flail leaflet. Forward flow
velocities measured by spectral Doppler may be increased due to the larger flow
volume associated with regurgitation as well as concurrent obstruction.",
" </p>",
" <p>",
" A review of 134 patients with a prosthetic valve attempted to derive
echocardiographic indices of valvular dysfunction [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/22\">",
" 22",
" </a>",
" ]. The results suggested that a peak transmitral flow velocity exceeding 1.9",
" <span class=\"nowrap\">",
" m/sec",
" </span>",
" or a ratio of peak diastolic transmitral flow to left ventricular outflow
tract velocity greater than 2.2 identifies prosthetic valve regurgitation
(sensitivity 92 percent, specificity 78 percent) provided that the valve is not
stenotic (pressure half-time less than 130 msec) [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/22\">",
" 22",
" </a>",
" ]. On the other hand, a prosthetic valve with a peak inflow Doppler velocity
of less than 1.9",
" <span class=\"nowrap\">",
" m/sec,",
" </span>",
" a ratio of peak diastolic transmitral flow velocity to left ventricular
outflow velocity of less than 2.2, and a pressure half-time of less than 130 msec
has a 98 percent chance of being normal (neither stenotic nor regurgitant).",
" </p>",
" <p class=\"headingAnchor\" id=\"H8\">",
" <span class=\"h1\">",
" REGURGITATION DUE TO STRUT FRACTURE",
" </span>",
" &nbsp;&mdash;&nbsp;There had been considerable concern about Bjork-Shiley
convexoconcave valves because of their low, but significant, incidence of strut
fracture, leading to migration of the disk and rapid hemodynamic compromise.
Fortunately, this uncommon occurrence has vanished due to the retirement of this
valve. When it did occur, clinical deterioration was so rapid that diagnostic TEE
could not be performed and survivors were taken directly to surgery based on
clinical suspicion alone. The current generation of prosthetic valves over the past
decade has been free of disk dislodgement.",
" </p>",
" <p class=\"headingAnchor\" id=\"H9\">",
" <span class=\"h1\">",
" SYSTEMIC EMBOLI",
" </span>",
" &nbsp;&mdash;&nbsp;In patients with a suspected cardiac cause for embolism,
the source may be a thrombus from a nonobstructed prosthetic heart valve; TEE is
helpful for establishing this diagnosis. In a series of 52 patients with a
prosthetic heart valve who underwent TEE after a suspected systemic embolic event,
12 percent had a definitive prosthetic valve thrombus and 10 percent had fibrous
strands on the valve, which were suggestive of thrombus [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6438/abstract/23\">",
" 23",
" </a>",
" ].",
" </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>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/1\">",
" Faletra F, Constantin C, De Chiara F, et al. Incorrect echocardiographic
diagnosis in patients with mechanical prosthetic valve dysfunction: correlation
with surgical findings. Am J Med 2000; 108:531.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/2\">",
" Reisner SA, Meltzer RS. Normal values of prosthetic valve Doppler
echocardiographic parameters: a review. J Am Soc Echocardiogr 1988; 1:201.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/3\">",
" Khandheria BK. Transesophageal echocardiography in the evaluation of
prosthetic valves. Cardiol Clin 1993; 11:427.",
" </a>",
" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/4\">",
" Cohen GI, Davison MB, Klein AL, et al. A comparison of flow convergence with
other transthoracic echocardiographic indexes of prosthetic mitral regurgitation. J
Am Soc Echocardiogr 1992; 5:620.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/5\">",
" Dilip KA, Vachaspathy P, Clarke B, et al. Haemolysis following mitral valve
repair. J Cardiovasc Surg (Torino) 1992; 33:568.",
" </a>",
" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/6\">",
" Smith RE, Berg D. Occult paravalvular leak in a clinically normal St. Jude's
mitral valve presenting with life-threatening microangiopathic hemolytic anemia. J
Cardiovasc Surg (Torino) 1991; 32:56.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/7\">",
" Groundstroem K, Rittoo D, Hoffman P, et al. Additional value of biplane
transoesophageal imaging in assessment of mitral valve prostheses. Br Heart J 1993;
70:259.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/8\">",
" Akamatsu S, Ueda N, Terazawa E, et al. Mitral prosthetic dehiscence with
laminar regurgitant flow signals assessed by transesophageal echocardiography.
Chest 1993; 104:1911.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/9\">",
" Girard SE, Miller FA Jr, Orszulak TA, et al. Reoperation for prosthetic
aortic valve obstruction in the era of echocardiography: trends in diagnostic
testing and comparison with surgical findings. J Am Coll Cardiol 2001; 37:579.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/10\">",
" Lengyel M, Fuster V, Keltai M, et al. Guidelines for management of left-
sided prosthetic valve thrombosis: a role for thrombolytic therapy. Consensus
Conference on Prosthetic Valve Thrombosis. J Am Coll Cardiol 1997; 30:1521.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/11\">",
" Deviri E, Sareli P, Wisenbaugh T, Cronje SL. Obstruction of mechanical heart
valve prostheses: clinical aspects and surgical management. J Am Coll Cardiol 1991;
17:646.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/12\">",
" Lin SS, Tiong IY, Asher CR, et al. Prediction of thrombus-related mechanical
prosthetic valve dysfunction using transesophageal echocardiography. Am J Cardiol
2000; 86:1097.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/13\">",
" Barbetseas J, Nagueh SF, Pitsavos C, et al. Differentiating thrombus from
pannus formation in obstructed mechanical prosthetic valves: an evaluation of
clinical, transthoracic and transesophageal echocardiographic parameters. J Am Coll
Cardiol 1998; 32:1410.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/14\">",
" Baumgartner, H, Czer, L, DeRobertis, M, et al. Normal regurgitation in
mechanical valve prostheses: Impact on Doppler Studies. American College of
Cardiology Learning Center Highlights 1992; 8:1.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/15\">",
" Baumgartner H, Khan S, DeRobertis M, et al. Color Doppler regurgitant
characteristics of normal mechanical mitral valve prostheses in vitro. Circulation
1992; 85:323.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/16\">",
" Mohr-Kahaly S, Kupferwasser I, Erbel R, et al. Regurgitant flow in
apparently normal valve prostheses: improved detection and semiquantitative
analysis by transesophageal two-dimensional color-coded Doppler echocardiography. J
Am Soc Echocardiogr 1990; 3:187.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/17\">",
" Karalis DG, Chandrasekaran K, Ross JJ Jr, et al. Single-plane
transesophageal echocardiography for assessing function of mechanical or
bioprosthetic valves in the aortic valve position. Am J Cardiol 1992; 69:1310.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/18\">",
" Lange HW, Olson JD, Pedersen WR, et al. Transesophageal color Doppler
echocardiography of the normal St. Jude Medical mitral valve prosthesis. Am Heart J
1991; 122:489.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/19\">",
" Flachskampf FA, O'Shea JP, Griffin BP, et al. Patterns of normal
transvalvular regurgitation in mechanical valve prostheses. J Am Coll Cardiol 1991;
18:1493.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/20\">",
" Hixson CS, Smith MD, Mattson MD, et al. Comparison of transesophageal color
flow Doppler imaging of normal mitral regurgitant jets in St. Jude Medical and
Medtronic Hall cardiac prostheses. J Am Soc Echocardiogr 1992; 5:57.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/21\">",
" Chen YT, Kan MN, Chen JS, et al. Detection of prosthetic mitral valve leak:
a comparative study using transesophageal echocardiography, transthoracic
echocardiography, and auscultation. J Clin Ultrasound 1990; 18:557.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/22\">",
" Fernandes V, Olmos L, Nagueh SF, et al. Peak early diastolic velocity rather
than pressure half-time is the best index of mechanical prosthetic mitral valve
function. Am J Cardiol 2002; 89:704.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6438/abstract/23\">",
" Shiran A, Weissman NJ, Merdler A, et al. Transesophageal echocardiographic
findings in patients with nonobstructed prosthetic valves and suspected cardiac
source of embolism. Am J Cardiol 2001; 88:1441.",
" </a>",
" </li>",
" </ol>",
" </div>",
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" Topic 5333 Version 3.0",
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" </div>",
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var script_f6_18_6438=[""].join("\n");
var outline_f6_18_6438=[" <div id=\"toggleOutline\">",
" <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 class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H1\">",
" INTRODUCTION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H2\">",
" PARAVALVULAR REGURGITATION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H3\">",
" PROSTHETIC VALVE OBSTRUCTION",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H4\">",
" Distinction between thrombus and pannus",
" </a>",
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" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H5\">",
" PROSTHETIC VALVE REGURGITATION",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H6\">",
" Physiologic regurgitation",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H7\">",
" Pathologic regurgitation",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H8\">",
" REGURGITATION DUE TO STRUT FRACTURE",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H9\">",
" SYSTEMIC EMBOLI",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"CARD/5333\" rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
" </div>",
" </h1>",
" <div id=\"relatedGraphics\">",
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" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_movie\" href=\"UTD.htm?40/16/41230\" title=\"movie
1\">",
" TEE prosthetic mitral valve vegetation",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_movie\" href=\"UTD.htm?25/30/26082\" title=\"movie
2\">",
" TEE mechanical mitral valve vegetations",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_movie\" href=\"UTD.htm?30/38/31343\" title=\"movie
3\">",
" TEE LA and prosthetic MV thrombus",
" </a>",
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" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?33/35/34355\" title=\"table
1\">",
" Normal echocardiography values for prosthetic mitral valves",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/57/25497?
source=related_link\">",
" Complications of prosthetic heart valves",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?8/62/9194?
source=related_link\">",
" Extrinsic nonimmune hemolytic anemia due to mechanical damage: Fragmentation
hemolysis and hypersplenism",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/8/20617?
source=related_link\">",
" Role of echocardiography in infective endocarditis",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f6_18_6439="Mycology, pathogenesis, and epidemiology of Fusarium
infection";
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" <div id=\"topicTitle\">",
" Mycology, pathogenesis, and epidemiology of Fusarium infection",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/18/6439/contributors\">",
" Authors",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/18/6439/contributors\">",
" Marcio Nucci, MD",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/18/6439/contributors\">",
" Elias Anaissie, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/18/6439/contributors\">",
" Section Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/18/6439/contributors\">",
" Carol A Kauffman, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/18/6439/contributors\">",
" Deputy Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/18/6439/contributors\">",
" Anna R Thorner, MD",
" </a>",
" <br/>",
" </div>",
" </div>",
" <div id=\"disclosures\">",
" <a href=\"UTD.htm?6/18/6439/contributor-disclosure\" target=\"_blank\">",
" Disclosures",
" </a>",
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" <span>",
" All topics are updated as new evidence becomes available and our",
" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
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" </a>",
" <span>",
" is complete.",
" </span>",
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" <span class=\"emphasis\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
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" This topic last updated:",
" </span>",
" Jul 20, 2012.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;Fusarium species cause a broad spectrum of infections in
humans including superficial infections, such as keratitis and onychomycosis, as
well as locally invasive and disseminated infections; invasive and disseminated
infections occur almost exclusively in severely immunocompromised patients [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/1\">",
" 1",
" </a>",
" ]. Fusarium species may also cause allergic diseases such as sinusitis in
immunocompetent individuals [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/2\">",
" 2",
" </a>",
" ], and mycotoxicosis following ingestion of food contaminated by toxin-
producing Fusarium species [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/3\">",
" 3",
" </a>",
" ]. Fusarium species are also important plant pathogens that cause various
diseases on cereal grains [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/3\">",
" 3",
" </a>",
" ], and occasionally cause infection in animals [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/4\">",
" 4",
" </a>",
" ].",
" </p>",
" <p>",
" The mycology, pathogenesis, and epidemiology of fusariosis will be reviewed
here. The clinical manifestations, diagnosis, treatment, and prevention of
fusariosis are discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?10/29/10712?
source=see_link\">",
" \"Clinical manifestations and diagnosis of Fusarium infection\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?3/42/3753?
source=see_link\">",
" \"Treatment and prevention of Fusarium infection\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" MYCOLOGY",
" </span>",
" &nbsp;&mdash;&nbsp;Fusarium species are widely distributed in soil,
subterranean and aerial plant parts, plant debris, and other organic matter [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/3\">",
" 3",
" </a>",
" ]. They are also present in water worldwide [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/5\">",
" 5",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H516901989\">",
" <span class=\"h2\">",
" Growth in vitro",
" </span>",
" &nbsp;&mdash;&nbsp;Fusarium species grow rapidly on many media that do not
contain cycloheximide, which inhibits its growth. On potato dextrose agar, Fusarium
species produce white-, lavender-, pink-, salmon-, or gray-colored colonies with
velvety or cottony surfaces [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/6\">",
" 6",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H516902309\">",
" <span class=\"h2\">",
" Microscopic appearance",
" </span>",
" &nbsp;&mdash;&nbsp;Microscopically, the hyphae of Fusarium in tissue resemble
those of Aspergillus species, with septate hyaline hyphae 3 to 8 microns in
diameter that typically branch at acute angles (",
" <a class=\"graphic graphic_picture graphicRef69801 \" href=\"UTD.htm?
20/16/20738\">",
" picture 1",
" </a>",
" and",
" <a class=\"graphic graphic_picture graphicRef74308 \" href=\"UTD.htm?
23/33/24080\">",
" picture 2",
" </a>",
" ). Adventitious sporulation, which is the ability to sporulate in tissue and
blood, may be present [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/7\">",
" 7",
" </a>",
" ]; the identification of hyphal and yeast-like structures in the same specimen
is highly suggestive of fusariosis in high-risk patients.",
" </p>",
" <p>",
" In cultures, the production of both fusoid macroconidia (hyaline,
multicellular, banana-like clusters with foot cells at the base) (",
" <a class=\"graphic graphic_picture graphicRef72385 \" href=\"UTD.htm?
25/6/25701\">",
" picture 3",
" </a>",
" and",
" <a class=\"graphic graphic_picture graphicRef61073 \" href=\"UTD.htm?
7/27/7602\">",
" picture 4",
" </a>",
" ), and microconidia (hyaline, unicellular, ovoid to cylindrical) are
characteristic of the genus Fusarium.",
" </p>",
" <p class=\"headingAnchor\" id=\"H516901982\">",
" <span class=\"h2\">",
" Species identification",
" </span>",
" &nbsp;&mdash;&nbsp;The characteristic appearance of Fusarium macroconidia can
be used for identification (",
" <a class=\"graphic graphic_picture graphicRef72385 \" href=\"UTD.htm?
25/6/25701\">",
" picture 3",
" </a>",
" and",
" <a class=\"graphic graphic_picture graphicRef61073 \" href=\"UTD.htm?
7/27/7602\">",
" picture 4",
" </a>",
" ), but species identification is difficult and often requires molecular
methods [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/8,9\">",
" 8,9",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H19276811\">",
" <span class=\"h2\">",
" Species prevalence",
" </span>",
" &nbsp;&mdash;&nbsp;More than 100 species of Fusarium have been identified, but
only a few cause infections in humans [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/10\">",
" 10",
" </a>",
" ]. Fusarium solani is the most frequent cause of invasive disease (in
approximately half of all cases), followed by F. oxysporum, F. moniliforme
(previously F. verticillioides), and F. proliferatum [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/11\">",
" 11",
" </a>",
" ]. Other species that rarely cause infections in humans include F. dimerum, F.
chlamydosporum, F. sacchari, F. antophilum, and others. Fusarial keratitis is most
commonly caused by F. solani [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/12\">",
" 12",
" </a>",
" ], whereas fusarial onychomycosis is most commonly caused by F. oxysporum [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/13-15\">",
" 13-15",
" </a>",
" ].",
" </p>",
" <p>",
" Molecular phylogenetic studies have revealed that these pathogens comprise
species complexes (eg, Fusarium solani",
" <em>",
" </em>",
" complex, Fusarium oxysporum",
" <em>",
" </em>",
" complex), which include at least 70 species [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/16,17\">",
" 16,17",
" </a>",
" ]. The clinical relevance of these species complexes remains to be
determined.",
" </p>",
" <p class=\"headingAnchor\" id=\"H524569980\">",
" <span class=\"h1\">",
" PATHOGENESIS",
" </span>",
" &nbsp;&mdash;&nbsp;Fusarium spp cause invasive disease by angioinvasion and
direct tissue destruction [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/3,11\">",
" 3,11",
" </a>",
" ]. Fusarium species possess several virulence factors including mycotoxins,
which suppress humoral and cellular immunity and can also cause allergic reactions
[",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/3\">",
" 3",
" </a>",
" ]. Fusarium spp also have the ability to adhere to prosthetic material [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/3\">",
" 3",
" </a>",
" ], and to produce proteases and collagenases [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/18\">",
" 18",
" </a>",
" ]. Fusarium solani is thought to be the most virulent Fusarium species [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/19\">",
" 19",
" </a>",
" ]. Some Fusarium species produce mycotoxins that are destructive to crops and
can cause human disease when ingested with heavily contaminated grains [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/14\">",
" 14",
" </a>",
" ]. &nbsp;",
" </p>",
" <p class=\"headingAnchor\" id=\"H524570005\">",
" <span class=\"h2\">",
" Immune response",
" </span>",
" &nbsp;&mdash;&nbsp;Innate immunity plays a major role in the defense against
Fusarium species [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/20\">",
" 20",
" </a>",
" ]. Macrophages and neutrophils damage fusarial hyphae, and their effect is
primed by interferon-gamma,",
" <a class=\"drug drug_general\" href=\"UTD.htm?23/13/23767?source=see_link\">",
" granulocyte colony-stimulating factor",
" </a>",
" , granulocyte-macrophage colony-stimulating factor [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/21\">",
" 21",
" </a>",
" ], and interleukin (IL)-15 [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/22\">",
" 22",
" </a>",
" ]. The effect of IL-15 is mediated by the release of IL-8 and by direct
stimulation of hyphal damage. The role of toll-like receptors in the innate immune
recognition of fungi is increasingly being recognized [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/23\">",
" 23",
" </a>",
" ], and although little is known about fusariosis and toll-like receptors, this
system is likely to be important in invasive fusariosis.",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h1\">",
" EPIDEMIOLOGY",
" </span>",
" &nbsp;&mdash;&nbsp;Fusarium species cause a broad spectrum of infections in
humans, including superficial, locally invasive, and disseminated infections. The
clinical form of infection depends upon the immune status of the host and the
portal of entry of the pathogen [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/1\">",
" 1",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H473991960\">",
" <span class=\"h2\">",
" Immunocompetent hosts",
" </span>",
" &nbsp;&mdash;&nbsp;Keratitis and onychomycosis are the most common infections
in immunocompetent patients. Other sites of infection have also been reported (",
" <a class=\"graphic graphic_table graphicRef64555 \" href=\"UTD.htm?
8/5/8285\">",
" table 1",
" </a>",
" )",
" <strong>",
" </strong>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/24-36\">",
" 24-36",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H420413563\">",
" <span class=\"h3\">",
" Keratitis",
" </span>",
" &nbsp;&mdash;&nbsp;Fusarium spp are a common cause of fungal keratitis, which
may develop following the traumatic introduction of Fusarium-contaminated soil or
plant material or due to poor hygiene practices of soft contact lens wearers,
particularly in patients using glucocorticoid eye drops. A large international
outbreak of fusarial keratitis between 2004 and 2006 was linked to use of a
specific contact lens solution (ReNu with MoistureLoc) [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/37-41\">",
" 37-41",
" </a>",
" ]. The solution was not intrinsically contaminated. The fungicidal action of
the solution was diminished, allowing Fusarium that had been introduced by the
wearer while caring for his or her lenses to grow and contaminate the contact lens
and the lens case. The solution was recalled in the United States in 2006, and
rates of contact lens-associated Fusarium keratitis have declined since then [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/42\">",
" 42",
" </a>",
" ].",
" </p>",
" <p>",
" The incidence of fungal keratitis caused by Fusarium species is highly
variable and depends largely upon the geographic location. For example, the
incidence ranges from 8 percent in India to 25 percent in Pennsylvania, 63 percent
in Florida, and 75 percent in Tanzania [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/12,43,44\">",
" 12,43,44",
" </a>",
" ]. These variable rates are probably related to climate characteristics, with
tropical and subtropical areas exhibiting the highest rates [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/12\">",
" 12",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H420413570\">",
" <span class=\"h3\">",
" Onychomycosis",
" </span>",
" &nbsp;&mdash;&nbsp;Fusarium species have been reported as agents of
onychomycosis with increasing frequency among immunocompetent individuals [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/45,46\">",
" 45,46",
" </a>",
" ] with variable rates reported from different regions. As an example, in a
study from central Italy, fewer than 2 percent of cases of onychomycosis were
caused by Fusarium spp [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/47\">",
" 47",
" </a>",
" ], compared with more than 8 percent in a study of onychomycosis cases from
the Northeast region of Brazil [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/13\">",
" 13",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H473991967\">",
" <span class=\"h2\">",
" Immunocompromised patients",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H524570268\">",
" <span class=\"h3\">",
" Portals of entry",
" </span>",
" &nbsp;&mdash;&nbsp;Invasive fusariosis has been reported worldwide and may be
acquired both in the community and in the hospital setting. The principal modes of
infection are airborne or via direct inoculation at various sites (skin and others)
of Fusarium-contaminated material, including water (",
" <a class=\"graphic graphic_table graphicRef57202 \" href=\"UTD.htm?
1/40/1676\">",
" table 2",
" </a>",
" ). Preexisting skin breakdown or onychomycosis may facilitate direct
introduction of Fusarium spp. Airborne infection results from the inhalation of
fusarial conidia that in some circumstances can be associated with aerosolization
of conidia from a water source [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/48\">",
" 48",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H524570275\">",
" <span class=\"h3\">",
" Risk factors",
" </span>",
" &nbsp;&mdash;&nbsp;Patients with compromised immune function are at high risk
for invasive fusariosis, particularly in the setting of prolonged and profound
neutropenia",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" severe T cell immunodeficiency [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/49\">",
" 49",
" </a>",
" ]. Unlike infection in normal hosts, fusariosis in the immunocompromised
population is typically invasive and disseminated [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/24\">",
" 24",
" </a>",
" ]. Among patients with hematologic malignancy, the infection predominates
during periods of neutropenia, typically among patients with leukemia receiving
induction chemotherapy [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/50\">",
" 50",
" </a>",
" ].",
" </p>",
" <p>",
" Invasive fusariosis also occurs with an increased frequency among
hematopoietic cell transplant recipients. A trimodal distribution of infection has
been identified among allogeneic hematopoietic cell transplant (HCT) recipients [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/51\">",
" 51",
" </a>",
" ]. The first peak occurs during the first 30 days following transplantation
and is associated with neutropenia. Severe T cell immunodeficiency (but not
neutropenia) is the major risk factor for fusariosis that develops after
engraftment and which occurs at a median of 70 days after HCT, commonly in the
setting of acute graft-versus-host disease (GVHD) and therapy with glucocorticoids.
The third peak is observed &gt;1 year after HCT during treatment for extensive
chronic GVHD. The overall incidence of fusariosis among HCT recipients is
approximately 6 cases per 1000 patients and is lowest after autologous HCT
(approximately 1.5 to 2 per 1000 patients). Following allogeneic HCT, the risk is
lower in matched-related and matched-unrelated HCTs (approximately 2.5 to 5 per
1000 patients) compared with mismatched-related HCTs (20 per 1000 patients) [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/51\">",
" 51",
" </a>",
" ].",
" </p>",
" <p>",
" The prognosis of fusariosis is directly related to the patient&rsquo;s immune
status, with high death rates in patients with persistent immunodeficiencies. In a
series of 84 patients with fusariosis and an underlying hematologic malignancy,
persistent neutropenia and recent glucocorticoid therapy were the only independent
factors associated with poor outcome [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/50\">",
" 50",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?3/42/3753?
source=see_link&amp;anchor=H5519506#H5519506\">",
" \"Treatment and prevention of Fusarium infection\", section on 'Prognosis'",
" </a>",
" .)",
" </p>",
" <p>",
" Locally invasive Fusarium infections occur occasionally among solid organ
transplant recipients, typically during the late post-transplant period;
disseminated infections have been reported rarely in such patients [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6439/abstract/52\">",
" 52",
" </a>",
" ].",
" </p>",
" <p>",
" The clinical manifestations of fusariosis are discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?10/29/10712?
source=see_link\">",
" \"Clinical manifestations and diagnosis of Fusarium infection\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H22\">",
" <span class=\"h1\">",
" SUMMARY",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Fusarium species are important plant pathogens that cause various diseases
on cereal grains, and occasionally cause infection in animals. In humans, Fusarium
species cause a broad spectrum of infections including superficial infections such
as keratitis and onychomycosis, as well as locally invasive and disseminated
infections; invasive and disseminated infections occur almost exclusively in
severely immunocompromised patients. (See",
" <a class=\"local\" href=\"#H1\">",
" 'Introduction'",
" </a>",
" above.)",
" </li>",
" <li>",
" Fusarium species are widely distributed in soil, subterranean and aerial
plant parts, plant debris and other organic matter. They are also present in water.
(See",
" <a class=\"local\" href=\"#H2\">",
" 'Mycology'",
" </a>",
" above.)",
" </li>",
" <li>",
" Microscopically, the hyphae of Fusarium in tissue resemble those of
Aspergillus species, with septate hyaline hyphae 3 to 8 microns in diameter that
typically branch at acute angles (",
" <a class=\"graphic graphic_picture graphicRef69801 \" href=\"UTD.htm?
20/16/20738\">",
" picture 1",
" </a>",
" ). The production of both fusoid macroconidia (hyaline, multicellular,
banana-like clusters with foot cells at the base) (",
" <a class=\"graphic graphic_picture graphicRef72385 \" href=\"UTD.htm?
25/6/25701\">",
" picture 3",
" </a>",
" and",
" <a class=\"graphic graphic_picture graphicRef61073 \" href=\"UTD.htm?
7/27/7602\">",
" picture 4",
" </a>",
" ),",
" <strong>",
" </strong>",
" and microconidia (hyaline, unicellular, ovoid to cylindrical) are
characteristic of the genus Fusarium. (See",
" <a class=\"local\" href=\"#H516902309\">",
" 'Microscopic appearance'",
" </a>",
" above.)",
" </li>",
" <li>",
" The characteristic appearance of Fusarium macroconidia is used for
identification (",
" <a class=\"graphic graphic_picture graphicRef72385 \" href=\"UTD.htm?
25/6/25701\">",
" picture 3",
" </a>",
" and",
" <a class=\"graphic graphic_picture graphicRef61073 \" href=\"UTD.htm?
7/27/7602\">",
" picture 4",
" </a>",
" ), but species identification is difficult and often requires molecular
methods. (See",
" <a class=\"local\" href=\"#H516901982\">",
" 'Species identification'",
" </a>",
" above.)",
" </li>",
" <li>",
" More than 100 species of Fusarium have been identified, but only a few cause
infections in humans. Fusarium solani is the most frequent cause of invasive
disease (in approximately half of all cases), followed by F. oxysporum, F.
moniliforme (previously F. verticillioides), and F. proliferatum. (See",
" <a class=\"local\" href=\"#H19276811\">",
" 'Species prevalence'",
" </a>",
" above.)",
" </li>",
" <li>",
" Fusarium species cause invasive disease by angioinvasion and direct tissue
destruction. Innate immunity plays a major role in the defense against various
molds, including Fusarium species. Macrophages and neutrophils damage fusarial
hyphae, and their effect is primed by interferon-gamma,",
" <a class=\"drug drug_general\" href=\"UTD.htm?23/13/23767?
source=see_link\">",
" granulocyte colony-stimulating factor",
" </a>",
" , granulocyte-macrophage colony-stimulating factor, and interleukin-15.
(See",
" <a class=\"local\" href=\"#H524569980\">",
" 'Pathogenesis'",
" </a>",
" above.)",
" </li>",
" <li>",
" Fusarium species cause a broad spectrum of infections in humans, including
superficial, locally invasive, and disseminated infections. The clinical form of
infection depends upon the immune status of the host and the portal of entry of the
pathogen (",
" <a class=\"graphic graphic_table graphicRef64555 \" href=\"UTD.htm?
8/5/8285\">",
" table 1",
" </a>",
" ). (See",
" <a class=\"local\" href=\"#H4\">",
" 'Epidemiology'",
" </a>",
" above.)",
" </li>",
" <li>",
" Patients with compromised immune function are at high risk for invasive
fusariosis, particularly in the setting of prolonged and profound neutropenia",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" severe T cell immunodeficiency, such as in patients with hematologic
malignancies receiving induction chemotherapy or hematopoietic cell
transplantation. (See",
" <a class=\"local\" href=\"#H524570275\">",
" 'Risk factors'",
" </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>",
" REFERENCES",
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" Shoham S, Levitz SM. The immune response to fungal infections. Br J Haematol
2005; 129:569.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/21\">",
" Gaviria JM, van Burik JA, Dale DC, et al. Comparison of interferon-gamma,
granulocyte colony-stimulating factor, and granulocyte-macrophage colony-
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fungal pathogens. J Infect Dis 1999; 179:1038.",
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" Romani L. Immunity to fungal infections. Nat Rev Immunol 2004; 4:1.",
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" Nucci M, Anaissie E. Cutaneous infection by Fusarium species in healthy and
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" Kerr CM, Perfect JR, Craven PC, et al. Fungal peritonitis in patients on
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" Flynn JT, Meislich D, Kaiser BA, et al. Fusarium peritonitis in a child on
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16:52.",
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" Kurien M, Anandi V, Raman R, Brahmadathan KN. Maxillary sinus fusariosis in
immunocompetent hosts. J Laryngol Otol 1992; 106:733.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/29\">",
" Madhavan M, Ratnakar C, Veliath AJ, et al. Primary disseminated fusarial
infection. Postgrad Med J 1992; 68:143.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/30\">",
" Sander A, Beyer U, Amberg R. Systemic Fusarium oxysporum infection in an
immunocompetent patient with an adult respiratory distress syndrome (ARDS) and
extracorporal membrane oxygenation (ECMO). Mycoses 1998; 41:109.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/31\">",
" Murray CK, Beckius ML, McAllister K. Fusarium proliferatum superficial
suppurative thrombophlebitis. Mil Med 2003; 168:426.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/32\">",
" Sturm AW, Grave W, Kwee WS. Disseminated Fusarium oxysporum infection in
patient with heatstroke. Lancet 1989; 1:968.",
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" Pflugfelder SC, Flynn HW, Jr., et al. fungal endophthalmitis. Ophthlamology
1988; 95:19.",
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" Gabriele P, Hutchins RK. Fusarium endophthalmitis in an intravenous drug
abuser. Am J Ophthalmol 1996; 122:119.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/35\">",
" Jakle C, Leek JC, Olson DA, Robbins DL. Septic arthritis due to Fusarium
solani. J Rheumatol 1983; 10:151.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/36\">",
" Bourguignon RL, Walsh AF, Flynn JC, et al. Fusarium species osteomyelitis.
Case report. J Bone Joint Surg Am 1976; 58:722.",
" </a>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/37\">",
" Chang DC, Grant GB, O'Donnell K, et al. Multistate outbreak of Fusarium
keratitis associated with use of a contact lens solution. JAMA 2006; 296:953.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/38\">",
" Khor WB, Aung T, Saw SM, et al. An outbreak of Fusarium keratitis associated
with contact lens wear in Singapore. JAMA 2006; 295:2867.",
" </a>",
" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/39\">",
" Patel A, Hammersmith K. Contact lens-related microbial keratitis: recent
outbreaks. Curr Opin Ophthalmol 2008; 19:302.",
" </a>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/40\">",
" Saw SM, Ooi PL, Tan DT, et al. Risk factors for contact lens-related
fusarium keratitis: a case-control study in Singapore. Arch Ophthalmol 2007;
125:611.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/41\">",
" Bullock JD, Elder BL, Khamis HJ, Warwar RE. Effects of time, temperature,
and storage container on the growth of Fusarium species: implications for the
worldwide Fusarium keratitis epidemic of 2004-2006. Arch Ophthalmol 2011;
129:133.",
" </a>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/42\">",
" Yildiz EH, Abdalla YF, Elsahn AF, et al. Update on fungal keratitis from
1999 to 2008. Cornea 2010; 29:1406.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/43\">",
" Tanure MA, Cohen EJ, Sudesh S, et al. Spectrum of fungal keratitis at Wills
Eye Hospital, Philadelphia, Pennsylvania. Cornea 2000; 19:307.",
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" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/44\">",
" Rosa RH Jr, Miller D, Alfonso EC. The changing spectrum of fungal keratitis
in south Florida. Ophthalmology 1994; 101:1005.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/45\">",
" Guilhermetti E, Takahachi G, Shinobu CS, Svidzinski TI. Fusarium spp. as
agents of onychomycosis in immunocompetent hosts. Int J Dermatol 2007; 46:822.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/46\">",
" Hilmio��lu-Polat S, Metin DY, Inci R, et al. Non-dermatophytic molds as
agents of onychomycosis in Izmir, Turkey - a prospective study. Mycopathologia
2005; 160:125.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/47\">",
" Romano C, Papini M, Ghilardi A, Gianni C. Onychomycosis in children: a
survey of 46 cases. Mycoses 2005; 48:430.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/48\">",
" Anaissie EJ, Kuchar RT, Rex JH, et al. Fusariosis associated with pathogenic
fusarium species colonization of a hospital water system: a new paradigm for the
epidemiology of opportunistic mold infections. Clin Infect Dis 2001; 33:1871.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/49\">",
" Boutati EI, Anaissie EJ. Fusarium, a significant emerging pathogen in
patients with hematologic malignancy: ten years' experience at a cancer center and
implications for management. Blood 1997; 90:999.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/50\">",
" Nucci M, Anaissie EJ, Queiroz-Telles F, et al. Outcome predictors of 84
patients with hematologic malignancies and Fusarium infection. Cancer 2003;
98:315.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/51\">",
" Nucci M, Marr KA, Queiroz-Telles F, et al. Fusarium infection in
hematopoietic stem cell transplant recipients. Clin Infect Dis 2004; 38:1237.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6439/abstract/52\">",
" Sampathkumar P, Paya CV. Fusarium infection after solid-organ
transplantation. Clin Infect Dis 2001; 32:1237.",
" </a>",
" </li>",
" </ol>",
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" <ul>",
" <li>",
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" <span>",
" SUMMARY",
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" INTRODUCTION",
" </a>",
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" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H2\">",
" MYCOLOGY",
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" Growth in vitro",
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" Microscopic appearance",
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" Species prevalence",
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" PATHOGENESIS",
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" Immune response",
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" EPIDEMIOLOGY",
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" Immunocompetent hosts",
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" </li>",
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" <a class=\"outlineLink\" href=\"#H420413563\">",
" - Keratitis",
" </a>",
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" - Onychomycosis",
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" Immunocompromised patients",
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" </li>",
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" <a class=\"outlineLink\" href=\"#H524570268\">",
" - Portals of entry",
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" - Risk factors",
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" SUMMARY",
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" REFERENCES",
" </a>",
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" <h1>",
" <div class=\"openRelatedGraphics\" id=\"ID/2426\" rel=\"outline_link\">",
" GRAPHICS",
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" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?20/16/20738\"
title=\"picture 1\">",
" Fusarium hyphae",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?23/33/24080\"
title=\"picture 2\">",
" Fusarium hematoxylin and eosin stain",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?25/6/25701\"
title=\"picture 3\">",
" Fusarium macroconidia",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?7/27/7602\"
title=\"picture 4\">",
" F solani microscopy",
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" <div class=\"openRelatedGraphics\" id=\"ID/2426|TAB\">",
" <a href=\"#\" title=\"TABLES\">",
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" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?8/5/8285\" title=\"table
1\">",
" Clinical spectrum of fusariosis",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?1/40/1676\" title=\"table
2\">",
" Portals of entry for fusariosis",
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" RELATED TOPICS",
" </h1>",
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" <ul>",
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" <a class=\"medical medical_review\" href=\"UTD.htm?10/29/10712?
source=related_link\">",
" Clinical manifestations and diagnosis of Fusarium infection",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?3/42/3753?
source=related_link\">",
" Treatment and prevention of Fusarium infection",
" </a>",
" </li>",
" </ul>",
" </div>",
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var title_f6_18_6440="Common bile duct exploration";
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" Common bile duct exploration",
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" Authors",
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6/18/6440/contributors\">",
" W Scott Melvin, MD",
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" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/18/6440/contributors\">",
" Peter Muscarella, MD",
" </a>",
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" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/18/6440/contributors\">",
" Section Editor",
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6/18/6440/contributors\">",
" Stanley W Ashley, MD",
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href=\"UTD.htm?6/18/6440/contributors\">",
" Deputy Editor",
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6/18/6440/contributors\">",
" Kathryn A Collins, MD, PhD, FACS",
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" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H25286312\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;Common bile duct (CBD) stones are identified in 10 to 15
percent of patients undergoing surgery for symptomatic cholelithiasis [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/1\">",
" 1",
" </a>",
" ]. CBD stones require extraction to avoid complications, such as acute
suppurative cholangitis, obstructive jaundice, hepatic abscess, and acute
pancreatitis.",
" </p>",
" <p>",
" Traditionally, CBD stones were diagnosed with intraoperative cholangiography
and treated with open CBD exploration. Advances in preoperative imaging technology
such as magnetic resonance cholangiopancreatography (MRCP) (",
" <a class=\"graphic graphic_diagnosticimage graphicRef70104 \" href=\"UTD.htm?
33/40/34447\">",
" image 1",
" </a>",
" and",
" <a class=\"graphic graphic_diagnosticimage graphicRef68630 \" href=\"UTD.htm?
43/14/44256\">",
" image 2",
" </a>",
" ) and endoscopic ultrasound (",
" <a class=\"graphic graphic_diagnosticimage graphicRef78437 \" href=\"UTD.htm?
18/33/18963\">",
" image 3",
" </a>",
" ), as well as the development of endoscopic retrograde
cholangiopancreatography (ERCP), and minimally invasive surgical techniques have
allowed for less invasive and more accurate methods of identifying and treating CBD
stones.",
" </p>",
" <p>",
" This topic will review laparoscopic and open CBD exploration. The diagnosis
and the endoscopic treatment of choledocholithiasis are discussed elsewhere. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?39/62/40936?
source=see_link\">",
" \"Approach to the patient with suspected choledocholithiasis\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?22/23/22905?
source=see_link\">",
" \"Endoscopic management of bile duct stones: Standard techniques and
mechanical lithotripsy\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H25286320\">",
" <span class=\"h1\">",
" IDENTIFICATION OF CBD STONES",
" </span>",
" &nbsp;&mdash;&nbsp;All patients with symptomatic cholelithiasis must be
evaluated to avoid the complications of retained stones. Clinical findings
suggestive of CBD stones include right upper quadrant pain with radiation to the
back, jaundice, cholangitis, and pancreatitis.",
" </p>",
" <p>",
" Transabdominal right upper quadrant ultrasonography and liver function tests
are the initial studies of choice for patients with cholelithiasis. Elevated liver
function tests, age &gt;55 years, and CBD dilation are all predictive of CBD stones
and mandate further evaluation [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/2\">",
" 2",
" </a>",
" ]. These results along with the clinical presentation can be used to stratify
the risk of CBD stones prior to performing cholecystectomy. The probability of
having CBD stones can then be used to plan appropriate intervention (",
" <a class=\"graphic graphic_algorithm graphicRef66945 \" href=\"UTD.htm?
26/3/26686\">",
" algorithm 1",
" </a>",
" ). The preoperative evaluation of suspected choledocholithiasis is discussed
in detail elsewhere. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?39/62/40936?
source=see_link\">",
" \"Approach to the patient with suspected choledocholithiasis\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H11839322\">",
" <span class=\"h1\">",
" INDICATIONS FOR CBD EXPLORATION",
" </span>",
" &nbsp;&mdash;&nbsp;Exploration of the CBD should be performed in all patients
in whom CBD stones have been identified and who are surgical candidates and have
failed, or are not candidates for, endoscopic therapy. Percutaneous transhepatic
cholangiography, electrohydraulic lithotripsy, and laser lithotripsy may be useful
in a small number of selected patients who are not candidates for surgery or
endoscopic therapy. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/39/37491?
source=see_link\">",
" \"Percutaneous transhepatic cholangiography\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?12/35/12854?
source=see_link\">",
" \"Electrohydraulic lithotripsy in the treatment of bile and pancreatic duct
stones\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/29/16856?
source=see_link\">",
" \"Laser lithotripsy for the treatment of gallstones\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H11839696\">",
" <span class=\"h1\">",
" PREOPERATIVE PREPARATION",
" </span>",
" &nbsp;&mdash;&nbsp;Informed consent should include a discussion of the risks,
benefits, and alternatives of CBD exploration. The patient should be counseled
regarding the possibility of bile duct leak, abscess, and retained stones.",
" </p>",
" <p class=\"headingAnchor\" id=\"H1382386448\">",
" <span class=\"h2\">",
" Prophylactic antibiotics",
" </span>",
" &nbsp;&mdash;&nbsp;Patients with suspected and confirmed CBD stones should be
given perioperative antibiotics. A first- or second-generation cephalosporin is
recommended within one hour of the incision (",
" <a class=\"graphic graphic_table graphicRef65369 \" href=\"UTD.htm?
23/52/24397\">",
" table 1",
" </a>",
" ). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/35/31290?
source=see_link&amp;anchor=H7#H7\">",
" \"Overview of control measures to prevent surgical site infection\", section
on 'Antimicrobial prophylaxis'",
" </a>",
" .)",
" </p>",
" <p>",
" <strong>",
" Equipment",
" </strong>",
" ��� Appropriate equipment should be readily available including 3 to 5 French
(F) biliary Fogarty catheters, wire baskets, 0.0035 inch guidewire, balloon (8 mm
outer diameter)",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" mechanical (7 to 12 F) dilators, 3 to 5 mm choledochoscope with 1.1 mm or
larger working channel, loop ligatures, and T-tubes. Additional choledochoscopic
equipment includes a separate light source, an adaptor to allow simultaneous
irrigation via biopsy channel, second camera, second monitor, or picture-in-picture
display with video switcher.",
" </p>",
" <p>",
" <strong>",
" Fluoroscopy &minus;",
" </strong>",
" Fluoroscopy support should be available for all patients undergoing
cholecystectomy, and radiology should be contacted for a C-arm fluoroscope and
appropriate support personnel as soon as the necessity for intraoperative
cholangiography is identified.",
" </p>",
" <p>",
" <strong>",
" Deep venous thrombosis prophylaxis &mdash;",
" </strong>",
" For patients undergoing general anesthesia, primary prophylaxis for prevention
of deep venous thrombosis, such as sequential compression devices, should be
employed (",
" <a class=\"graphic graphic_table graphicRef50947 \" href=\"UTD.htm?
34/54/35693\">",
" table 2",
" </a>",
" ). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/52/41802?
source=see_link\">",
" \"Prevention of venous thromboembolic disease in surgical patients\"",
" </a>",
" .)",
" </p>",
" <p>",
" A surgical timeout should be performed with the entire operating room team
(anesthesiologist, surgeon, nurse, scrub technician) to assure correct patient
identity, intended operation, and the informed consent (",
" <a class=\"graphic graphic_table graphicRef59666 \" href=\"UTD.htm?
39/28/40395\">",
" table 3",
" </a>",
" ). A preoperative checklist is a good way to assure that all safety issues
have been addressed.",
" </p>",
" <p class=\"headingAnchor\" id=\"H813094\">",
" <span class=\"h1\">",
" INTRAOPERATIVE CHOLANGIOGRAPHY",
" </span>",
" &nbsp;&mdash;&nbsp;When a decision has been made to perform CBD exploration,
intraoperative cholangiography may be performed to confirm the diagnosis and
outline the biliary anatomy before the CBD exploration is undertaken. Although some
surgeons perform routine intraoperative cholangiography before CBD exploration, we
selectively perform intraoperative cholangiography based upon findings of elevated
liver function tests, a dilated common bile duct (&gt;6 mm), or a history of
pancreatitis. Patients who present with jaundice may be best evaluated
preoperatively using ERCP [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/3\">",
" 3",
" </a>",
" ].",
" </p>",
" <p>",
" The catheter for intraoperative cholangiography is placed after careful
dissection achieves the critical view of safety (",
" <a class=\"graphic graphic_figure graphicRef66207 \" href=\"UTD.htm?
25/3/25649\">",
" figure 1",
" </a>",
" ). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/4/11338?
source=see_link&amp;anchor=H20#H20\">",
" \"Laparoscopic cholecystectomy: Techniques\", section on 'Critical view of
safety'",
" </a>",
" .)",
" </p>",
" <p>",
" For laparoscopic intraoperative cholangiography, a clip is applied proximally
across the cystic duct once it is well seen. Stay sutures may be placed on either
side of the planned bile duct incision. An incomplete vertical ductotomy is
created, taking care not to injure the posterior wall of the duct, and the contents
of the duct are milked toward the ductotomy. A cholangiogram catheter (4 to 5 F)
with a metal reinforced tip is inserted through a transabdominal 14-gauge
angiocatheter that has been placed in the right upper quadrant and into the
abdomen.",
" </p>",
" <p>",
" The catheter is manipulated into the cystic duct with laparoscopic
instruments. There are cholangiogram catheters available on the market that secure
the catheter and occlude the duct after placement either via grasping jaws or an
inflatable balloon. Alternatively, a clip or a cholangiogram clamp can be loosely
applied around the duct with the catheter. Placement of a hydrophilic guidewire
through the cholangiogram catheter facilitates placement of instruments for CBD
stone extraction and dilatation of the cystic duct with balloon catheters or
mechanical dilators if necessary [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/4\">",
" 4",
" </a>",
" ].",
" </p>",
" <p>",
" The position and seal of the catheter should be first tested with injection of
saline. The saline and water-soluble contrast fluid and tubing must be free of
bubbles before performing the cholangiogram, since bubbles can create filling
defects which can be confused for stones.",
" </p>",
" <p>",
" Contrast is then injected under continuous fluoroscopic visualization with a
1:1 dilution of water-soluble contrast and water. The images should be evaluated
for the length of the cystic duct and the junction with the CBD, the size of the
CBD, free flow of contrast into the duodenum, the intra and extrahepatic biliary
anatomy, and the presence of filling defects. If the contrast does not flow freely
into the duodenum, administration of sublingual",
" <a class=\"drug drug_general\" href=\"UTD.htm?11/24/11656?source=see_link\">",
" nitroglycerin",
" </a>",
" or IV",
" <a class=\"drug drug_general\" href=\"UTD.htm?24/32/25093?source=see_link\">",
" glucagon",
" </a>",
" is sometimes helpful in relaxing the sphincter of Oddi.",
" </p>",
" <p>",
" Proximal visualization of the bile ducts must also be confirmed, and
techniques to facilitate this include administration of intravenous",
" <a class=\"drug drug_general\" href=\"UTD.htm?19/31/19962?source=see_link\">",
" morphine",
" </a>",
" (to contract the sphincter of Oddi), positioning the patient in steep
Trendelenburg, and application of pressure to the distal bile duct with a
laparoscopic instrument. Misplacement of the catheter in the CBD should be
considered when the proximal biliary tree cannot be visualized. Findings on
cholangiography that are suggestive of CBD stones include dilated bile ducts,
filling defects, or failure of contrast flow into the duodenum (",
" <a class=\"graphic graphic_diagnosticimage graphicRef81939 \" href=\"UTD.htm?
10/29/10707\">",
" image 4",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/5\">",
" 5",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H25286327\">",
" <span class=\"h1\">",
" SURGICAL APPROACHES FOR CBD EXPLORATION",
" </span>",
" &nbsp;&mdash;&nbsp;Laparoscopic CBD exploration, open CBD exploration, and
postoperative ERCP with stone removal are all options for the treatment of CBD
stones identified by intraoperative cholangiography. In experienced hands,
laparoscopic CBD exploration has a success rate of over 90 percent [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/6\">",
" 6",
" </a>",
" ]. The choice of procedure should be guided by patient-specific
considerations, training and experience of the surgeon, and available endoscopic
expertise.",
" </p>",
" <p class=\"headingAnchor\" id=\"H25286334\">",
" <span class=\"h2\">",
" Laparoscopic transcystic exploration",
" </span>",
" &nbsp;&mdash;&nbsp;Laparoscopic transcystic exploration of the CBD is the
preferred initial technique for most patients requiring CBD exploration [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/7-10\">",
" 7-10",
" </a>",
" ].",
" </p>",
" <p>",
" For patients with stones smaller than 10 mm and a small bile duct,
laparoscopic transcystic exploration of the CBD is the fastest, safest, and least
invasive initial approach to CBD exploration compared with laparoscopic
choledochotomy. Morbidity is equivalent to that of a standard laparoscopic
cholecystectomy alone [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/8,9\">",
" 8,9",
" </a>",
" ]. As an example, in an observational series of 113 patients undergoing CBD
exploration, operative time (97 versus 75 minutes), and length of hospital stay (6
versus 2 days) were significantly longer for choledochotomy than for transcystic
exploration, although stone clearance and morbidity were similar [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/10\">",
" 10",
" </a>",
" ].",
" </p>",
" <p>",
" Choledochotomy should be reserved for patients with large occluding stones or
those in whom the duct cannot be cleared using a transcystic approach. (See",
" <a class=\"local\" href=\"#H25286341\">",
" 'Laparoscopic choledochotomy'",
" </a>",
" below.) &nbsp;",
" </p>",
" <p>",
" Conditions for successful and safe transcystic laparoscopic CBD exploration
include [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/11\">",
" 11",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" CBD diameter &lt;6 mm",
" </li>",
" <li>",
" Stone location distal to the cystic",
" <span class=\"nowrap\">",
" duct/CBD",
" </span>",
" junction",
" </li>",
" <li>",
" Cystic duct diameter &gt;4 mm",
" </li>",
" <li>",
" Fewer than 6 to 8 stones within the CBD",
" </li>",
" <li>",
" Stones smaller than 10 mm",
" </li>",
" </ul>",
" </p>",
" <p>",
" For laparoscopic transcystic exploration, the gallbladder is left in situ and
the dome of the gallbladder is grasped and retracted cephalad to facilitate
visualization and manipulation (",
" <a class=\"graphic graphic_figure graphicRef54280 \" href=\"UTD.htm?
13/62/14304\">",
" figure 2",
" </a>",
" ). After intraoperative cholangiography is performed, potential maneuvers and
the general sequence that they should be attempted include [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/12\">",
" 12",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" <strong>",
" Flushing of the CBD",
" </strong>",
" ��� Flushing of the distal CBD with warm saline should be the initial
maneuver performed for clearance of CBD stones and can be facilitated by
intravenous administration of",
" <a class=\"drug drug_general\" href=\"UTD.htm?24/32/25093?
source=see_link\">",
" glucagon",
" </a>",
" or dilatation of the cystic duct with a 4 to 6 mm balloon. A laparoscopic
grasper can be left secured to the dome of the gallbladder in order to facilitate
retraction and visualization throughout the procedure. Flushing of the proximal
duct is avoided because small stones could be pushed into hepatic ducts, and may
not be retrievable.",
" </li>",
" <li>",
" <strong>",
" Biliary balloon catheter extraction",
" </strong>",
" ��� Biliary balloon catheter extraction is useful for cases with a dilated
cystic duct [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/13\">",
" 13",
" </a>",
" ]. A 3- to 5-F biliary Fogarty catheter is advanced transcystically under
fluoroscopic control distally into the duodenum. Duodenal placement can be
confirmed by fluoroscopy or by resistance upon withdrawal of the catheter,
indicating that the balloon is adjacent to the ampulla of Vater. The balloon should
be deflated and withdrawn slightly. The balloon can then be gently inflated and
withdrawn carefully until stones and debris exit from the cystic ductotomy for
retrieval with forceps. There is a risk of stone displacement into the common
hepatic duct with this procedure since the stones are not grasped directly.",
" </li>",
" </ul>",
" </p>",
" <p>",
" Once the duct has been cleared with flushing and balloon catheters, either
transcystic choledochoscopy or fluoroscopically-guided wire basket retrieval can be
employed to retrieve any remaining stones. The choice between approaches depends on
available expertise and equipment as both have been used successfully.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" <strong>",
" Transcystic choledochoscopy",
" </strong>",
" &minus; Transcystic choledochoscopy may require dilatation of the cystic
duct to accommodate the scope, although the cystic duct is usually enlarged due to
the passage of stones. The choledochoscope is placed through a 5 mm port and
manipulated into the cystic duct with atraumatic instruments. The choledochoscope
can then be advanced through the CBD and into the duodenum. The choledochoscope
should be connected to high-pressure saline for irrigation of the duct and to
improve visualization. Adaptors for insertion of wire retrieval baskets are
necessary. Additional video monitors, or screen-in-screen technology, are utilized
for monitoring.",
" <br/>",
" <br/>",
" If a stone is seen through the choledochoscope, wire basket retrieval can be
performed through the working channel of the scope and offers the advantage of
direct visualization of stone capture and withdrawal as compared with
fluoroscopically-guided wire basket retrieval. Distal CBD stones can be pushed into
the duodenum with the choledochoscope. Proximal stones may require treatment with
other techniques since choledochoscopic visualization of the proximal biliary tree
is technically challenging.",
" <br/>",
" <br/>",
" In an observational series of 113 patients undergoing CBD exploration,
operative time (107 versus 75 minutes) was significantly longer for
fluoroscopically guided stone retrieval than with choledochoscopy, although stone
clearance and morbidity were similar [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/10\">",
" 10",
" </a>",
" ].",
" </li>",
" <li>",
" <strong>",
" Fluoroscopically-guided wire basket retrieval",
" </strong>",
" ��� Fluoroscopically-guided wire basket retrieval of stones can be performed
if fluoroscopy and specialized equipment are available [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/13\">",
" 13",
" </a>",
" ]. The use of spiral wire baskets with flexible leaders will help avoid CBD
injury. The basket is placed through the wire for guidance and advanced under
fluoroscopic guidance into the lower common duct or duodenum, then opened and
pulled back until the stone is captured. Rates of successful stone retrieval with
this technique are reported as 95 percent in several case series [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/14,15\">",
" 14,15",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" <p>",
" Following laparoscopic transcystic exploration, cholangiographic confirmation
of duct clearance should be performed with intraoperative cholangiography (",
" <a class=\"graphic graphic_diagnosticimage graphicRef59179 \" href=\"UTD.htm?
27/63/28657\">",
" image 5",
" </a>",
" ). The cholecystectomy is completed and the cystic duct stump is secured with
a clip or a loop ligature. Loop ligatures minimize the possibility of postoperative
bile leak for patients with cystic duct dilation, trauma, or inflammation.
Placement of a closed suction drain in the hepatic fossa may be considered to
identify and control any bile leakage. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/4/11338?
source=see_link&amp;anchor=H12#H12\">",
" \"Laparoscopic cholecystectomy: Techniques\", section on 'Procedure'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H25286341\">",
" <span class=\"h2\">",
" Laparoscopic choledochotomy",
" </span>",
" &nbsp;&mdash;&nbsp;Laparoscopic choledochotomy (LCD) is more technically
challenging than laparoscopic transcystic exploration. LCD may be attempted
following failed laparoscopic transcystic exploration or for patients who are not
candidates for the transcystic approach. Laparoscopic CBD exploration is preferable
to postoperative ERCP for stone removal [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/6,16-19\">",
" 6,16-19",
" </a>",
" ]. A metaanalysis of surgical versus endoscopic treatment of CBD stones
including 1351 patients in 13 randomized trials showed that laparoscopic CBD stone
clearance was more successful as well as more efficient than pre- and postoperative
ERCP with no significant difference in morbidity and mortality [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/6\">",
" 6",
" </a>",
" ].",
" </p>",
" <p>",
" LCD is indicated for patients with [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/12\">",
" 12",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Failed laparoscopic transcystic exploration or preoperative endoscopic stone
extraction",
" </li>",
" <li>",
" <span class=\"nowrap\">",
" Narrow/tortuous",
" </span>",
" cystic duct",
" </li>",
" <li>",
" Dilated CBD (6 to 10 mm)",
" </li>",
" <li>",
" Large stones (&gt;10 mm)",
" </li>",
" <li>",
" Multiple stones",
" </li>",
" <li>",
" Stone location proximal to the cystic",
" <span class=\"nowrap\">",
" duct/CBD",
" </span>",
" junction",
" </li>",
" </ul>",
" </p>",
" <p>",
" As is the case for laparoscopic transcystic exploration, the gallbladder is
left in situ and the dome of the gallbladder can be grasped and retracted cephalad
to facilitate visualization and manipulation. A 30 degree laparoscope should be
used to assist with visualization of the supraduodenal CBD.",
" </p>",
" <p>",
" The cystic duct should be dissected down to the level of the CBD and the
tissue overlying the anterior CBD should be cleared. Care should be taken to avoid
excessive dissection because this may endanger the blood supply to the duct and
thus impair healing. An approximately 1 cm longitudinal ductotomy is created with
laparoscopic scissors; stay sutures will help to facilitate manipulation and
maintain a seal when saline infusion is used for choledochoscopy. Various
techniques such as saline infusion, fluoroscopically-guided balloon or wire basket
retrieval, and choledochoscopy should be utilized for extraction of CBD stones and
to ensure that the CBD is no longer obstructed, as described above. (See",
" <a class=\"local\" href=\"#H25286334\">",
" 'Laparoscopic transcystic exploration'",
" </a>",
" above.)",
" </p>",
" <p>",
" Primary closure of the choledochotomy with interrupted fine monofilament
absorbable suture is safer than closure around a T-tube and results in decreased
operating time, decreased postoperative and biliary complications, shorter time
until return to work, and decreased hospital costs [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/20-23\">",
" 20-23",
" </a>",
" ]. Absorbable sutures should be used in the bile duct since permanent suture
is lithogenic [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/1\">",
" 1",
" </a>",
" ]. Residual stones may be extracted with the use of ERCP.",
" </p>",
" <p>",
" In cases where there is concern that additional manipulation may be necessary
and ERCP expertise is not available, a T-tube (12- to 16-F) can be placed through
the ductotomy and secured in place using fine monofilament absorbable sutures. T-
tube drainage has traditionally provided a method for post-operative biliary
decompression and postoperative access to the bile duct for cholangiography and
possible stone extraction. However, T-tubes can be complicated by bile leak,
infection, tube dislodgement, or bile duct obstruction [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/7\">",
" 7",
" </a>",
" ]. In addition, the T-tube can act as a foreign body around which bile
pigments and bile salts may precipitate, potentially leading to stone recurrence.
If a T-tube is placed, cholangiography should always be performed prior to closure
in order to confirm duct clearance and to rule out bile leaks.",
" </p>",
" <p>",
" Some surgeons place transcystic biliary drainage catheters as an alternative
to T-tubes [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/24\">",
" 24",
" </a>",
" ]. These catheters are easier to place than T-tubes and allow for biliary
access in the case of retained stones. However, in a study of 63 patients,
transcystic biliary drainage catheters resulted in a significantly higher rate of
bile leakage as compared to T-tubes (14 versus 3.5 percent respectively).",
" </p>",
" <p class=\"headingAnchor\" id=\"H25286348\">",
" <span class=\"h2\">",
" Open CBD exploration",
" </span>",
" &nbsp;&mdash;&nbsp;Open CBD exploration remains an important technique and
should be part of every gastrointestinal surgeon's armamentarium for treating
hepatobiliary diseases. Surgeons performing laparoscopic cholecystectomy should be
prepared to convert to open CBD exploration if necessary.",
" </p>",
" <p>",
" Open CBD exploration should be performed in the following situations:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Patients with CBD stones who are undergoing open cholecystectomy",
" </li>",
" <li>",
" Patients who have failed or suffered complications from laparoscopic CBD
exploration",
" </li>",
" <li>",
" Patients with severe inflammation in the triangle of Calot",
" </li>",
" <li>",
" When laparoscopic equipment, experience,",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" resources are limited",
" </li>",
" </ul>",
" </p>",
" <p>",
" The abdomen is most commonly opened through a right upper quadrant subcostal
incision; although a midline approach is acceptable as well. The liver should be
retracted superiorly, the duodenum retracted inferiorly, and the stomach retracted
to the left. A generous Kocher maneuver should be performed, which will allow for
manual palpation and manipulation of the distal common bile duct.",
" </p>",
" <p>",
" The proximal cystic duct should be ligated to prevent gallstones from
migrating from the gallbladder into the cystic duct and CBD. Dissection is carried
out on the anterolateral CBD, stay sutures (fine monofilament, absorbable suture)
are placed just above the level of the duodenum and the duct is opened
longitudinally. The choledochotomy can then be extended with Potts scissors to a
length of approximately 1.5 cm.",
" </p>",
" <p>",
" Stones can initially be extracted using manual manipulation of the CBD. If
this is not possible, balloon extraction can be performed with biliary Fogarty
catheters, clearing the proximal duct before the distal duct. These catheters are
preferred because they are less traumatic than metal forceps [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/25\">",
" 25",
" </a>",
" ]. Saline irrigation can facilitate the removal of fragmented debris by
flushing. Choledochoscopy with wire basket retrieval can be employed in the
unlikely event that balloon extraction is unsuccessful.",
" </p>",
" <p>",
" As is the case for LCD exploration, primary closure of the choledochotomy is a
safe alternative to T-tube placement in patients undergoing open CBD exploration
[",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/20,22,26,27\">",
" 20,22,26,27",
" </a>",
" ]. &nbsp;",
" </p>",
" <p class=\"headingAnchor\" id=\"H813533\">",
" <span class=\"h1\">",
" PERSISTENT STONES",
" </span>",
" &nbsp;&mdash;&nbsp;Laparoscopic CBD exploration results in stone clearance in
over 90 percent of patients [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/5,28,29\">",
" 5,28,29",
" </a>",
" ]. Options for management of persistent CBD stones after laparoscopic
transcystic exploration include conversion to laparoscopic or open choledochotomy
and CBD exploration, postoperative ERCP and stone extraction, percutaneous stone
removal, or observation (in the case of stones &lt;2 mm) (",
" <a class=\"graphic graphic_diagnosticimage graphicRef60642 \" href=\"UTD.htm?
8/60/9153\">",
" image 6",
" </a>",
" and",
" <a class=\"graphic graphic_diagnosticimage graphicRef81598 \" href=\"UTD.htm?
32/58/33696\">",
" image 7",
" </a>",
" ). The choice of procedure should be guided by patient-specific considerations
(discussed above), training and experience of the surgeon, and available endoscopic
expertise.",
" </p>",
" <p>",
" Rarely, severely impacted stones are encountered (",
" <a class=\"graphic graphic_diagnosticimage graphicRef60965 \" href=\"UTD.htm?
7/48/7936\">",
" image 8",
" </a>",
" ). Impacted stones are difficult to remove with laparoscopic techniques and
remain one of the indications for open CBD exploration. Surgeons who have
experience with lithotripsy or duodenotomy with sphincterotomy may be able to
complete stone extraction with one of these techniques [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/30\">",
" 30",
" </a>",
" ]. However, if experience in sphincterotomy or lithotripsy is not available,
the surgeon should place a T-tube and terminate the procedure [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/31\">",
" 31",
" </a>",
" ]. The patient should be referred postoperatively to a specialized center
where endoscopic or percutaneous removal is usually successful with the use of
electrohydraulic or laser lithotripsy in conjunction with sphincterotomy. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/29/16856?
source=see_link\">",
" \"Laser lithotripsy for the treatment of gallstones\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?22/23/22905?
source=see_link\">",
" \"Endoscopic management of bile duct stones: Standard techniques and
mechanical lithotripsy\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?12/35/12854?
source=see_link\">",
" \"Electrohydraulic lithotripsy in the treatment of bile and pancreatic duct
stones\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H25286355\">",
" <span class=\"h1\">",
" POSTOPERATIVE MANAGEMENT",
" </span>",
" &nbsp;&mdash;&nbsp;Postoperative care is routine. If closed suction drains
were placed at the time of surgery, they are removed within 24 to 48 hours as long
as the output is not bilious. Liver function tests (LFTs) should be measured if
patients develop complications or if there is a concern for retained stones, but
LFTs may take over a week to normalize after surgery [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/32\">",
" 32",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/57/19353?
source=see_link\">",
" \"Enzymatic measures of cholestasis (eg, alkaline phosphatase, 5&rsquo;-
nucleotidase, gamma-glutamyl transpeptidase)\"",
" </a>",
" .)",
" </p>",
" <p>",
" If a T-tube has been placed, it is clamped when the patient is discharged and
flushed with 10 mL of sterile normal saline one to two times a day. A T-tube
cholangiogram and measurement of LFTs should be performed prior to T-tube removal
in order to confirm duct clearance and integrity. The T-tube may be safely removed
in the office setting after a tract has had time to develop; this generally
requires four weeks.",
" </p>",
" <p class=\"headingAnchor\" id=\"H813477\">",
" <span class=\"h1\">",
" COMPLICATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;Complications of open and laparoscopic CBD exploration
include bile duct leak (2 to 6 percent), subhepatic abscess (0.7 percent) and
retained stones (3 to 6 percent) [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/29,33,34\">",
" 29,33,34",
" </a>",
" ]. Compared with patients who had open surgery, patients who had laparoscopic
CBD exploration had significantly lower mortality (0.25 versus 5.5 percent),
surgical site infection (1.2 versus 10 percent) and overall morbidity (3.7 versus
22 percent) in the American College of Surgeons National Surgical Quality
Improvement Program (ACS NSQIP) database [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/35\">",
" 35",
" </a>",
" ]. The increased morbidity and mortality in patients who underwent open
surgery is likely a reflection of underlying comorbidities or more complicated
disease requiring an open approach [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6440/abstract/36\">",
" 36",
" </a>",
" ].",
" </p>",
" <p>",
" Patients who present with persistent fever and leukocytosis, persistent pain,
bile leakage around the T-tube or drain, jaundice or rigors after CBD exploration
should be evaluated for fluid collections or CBD blockage with ultrasound and a
computed tomography (CT) scan. The clinical and radiologic evaluation of a bile
leak or obstruction is discussed in detail elsewhere. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/22/18792?
source=see_link&amp;anchor=H14#H14\">",
" \"Complications of laparoscopic cholecystectomy\", section on 'Radiologic
workup'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H465889\">",
" <span class=\"h1\">",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Common bile duct (CBD) stones are identified in 10 to 15 percent of patients
undergoing surgery for symptomatic cholelithiasis. Complications of CBD stones
include acute suppurative cholangitis, obstructive jaundice, hepatic abscess, and
acute pancreatitis. (See",
" <a class=\"local\" href=\"#H25286312\">",
" 'Introduction'",
" </a>",
" above.)",
" </li>",
" <li>",
" Patients with symptomatic cholelithiasis should be evaluated for possible
CBD stones. Clinical findings suggestive of CBD stones include right upper quadrant
pain with radiation to the back, jaundice, cholangitis, and pancreatitis. The
preoperative evaluation includes liver function tests and imaging (typically
ultrasonography). Although some surgeons perform routine intraoperative
cholangiography prior to CBD exploration, we selectively perform intraoperative
cholangiography based upon findings of elevated liver function tests, a dilated
common bile duct (&gt;6 mm), or a history of pancreatitis. Patients who present
with jaundice may be best evaluated preoperatively using ERCP. (See",
" <a class=\"local\" href=\"#H813094\">",
" 'Intraoperative cholangiography'",
" </a>",
" above.)",
" </li>",
" <li>",
" Exploration of the CBD should be performed in all patients with CBD stones
who have either failed, or are not candidates for, endoscopic therapy and who do
not have medical conditions that prohibit surgical intervention. (See",
" <a class=\"local\" href=\"#H11839322\">",
" 'Indications for CBD exploration'",
" </a>",
" above.)",
" </li>",
" <li>",
" Laparoscopic CBD exploration, open CBD exploration, and postoperative ERCP
with stone removal are all options for the treatment of CBD stones identified by
intraoperative cholangiography. Laparoscopic CBD exploration may be performed by a
transcystic approach or by choledochotomy. The choice of procedure should be guided
by patient-specific considerations, training and experience of the surgeon, and
available endoscopic expertise. (See",
" <a class=\"local\" href=\"#H25286327\">",
" 'Surgical approaches for CBD exploration'",
" </a>",
" above.)",
" </li>",
" <li>",
" For patients undergoing laparoscopic surgery, we recommend laparoscopic
transcystic exploration of the CBD as the initial surgical approach for patients
with stones smaller than 10 mm and a small bile duct (",
" <a class=\"grade\" href=\"._grade_3?title=Grade 1C\">",
" Grade 1C",
" </a>",
" ) . Choledochotomy should be reserved for patients in whom the duct cannot
be cleared using a transcystic approach. (See",
" <a class=\"local\" href=\"#H25286334\">",
" 'Laparoscopic transcystic exploration'",
" </a>",
" above.)",
" </li>",
" <li>",
" Surgeons performing laparoscopic cholecystectomy should be prepared to
convert to open CBD exploration if necessary. (See",
" <a class=\"local\" href=\"#H25286348\">",
" 'Open CBD exploration'",
" </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>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/2\">",
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" Rojas-Ortega S, Arizpe-Bravo D, Mar&iacute;n L&oacute;pez ER, et al.
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choledocholithiasis. J Gastrointest Surg 2003; 7:492.",
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" Matthews, BD, Strasberg, SM. Management of common duct stones. In: Current
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" Memon MA, Hassaballa H, Memon MI. Laparoscopic common bile duct exploration:
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82:666.",
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laparoscopic transcystic common bile duct exploration for stones. Effectiveness and
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/16\">",
" Nathanson LK, O'Rourke NA, Martin IJ, et al. Postoperative ERCP versus
laparoscopic choledochotomy for clearance of selected bile duct calculi: a
randomized trial. Ann Surg 2005; 242:188.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/17\">",
" Rhodes M, Sussman L, Cohen L, Lewis MP. Randomised trial of laparoscopic
exploration of common bile duct versus postoperative endoscopic retrograde
cholangiography for common bile duct stones. Lancet 1998; 351:159.",
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randomized trial comparing two-stage vs single-stage management of patients with
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" Williams EJ, Green J, Beckingham I, et al. Guidelines on the management of
common bile duct stones (CBDS). Gut 2008; 57:1004.",
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" Gurusamy KS, Samraj K. Primary closure versus T-tube drainage after
laparoscopic common bile duct stone exploration. Cochrane Database Syst Rev
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/21\">",
" Jameel M, Darmas B, Baker AL. Trend towards primary closure following
laparoscopic exploration of the common bile duct. Ann R Coll Surg Engl 2008;
90:29.",
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" Zhu QD, Tao CL, Zhou MT, et al. Primary closure versus T-tube drainage after
common bile duct exploration for choledocholithiasis. Langenbecks Arch Surg 2011;
396:53.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/23\">",
" Leida Z, Ping B, Shuguang W, Yu H. A randomized comparison of primary
closure and T-tube drainage of the common bile duct after laparoscopic
choledochotomy. Surg Endosc 2008; 22:1595.",
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" Tang CN, Tai CK, Ha JP, et al. Antegrade biliary stenting versus T-tube
drainage after laparoscopic choledochotomy--a comparative cohort study.
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" Cushieri, A. Common bile duct exploration. In: Maingot's abdominal
operations, Zinner, MJ, Schwartz, SI, Ellis, H (Eds), Appleton and Lange, Stamford
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/26\">",
" Ahmed I, Pradhan C, Beckingham IJ, et al. Is a T-tube necessary after common
bile duct exploration? World J Surg 2008; 32:1485.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/27\">",
" Yamazaki M, Yasuda H, Tsukamoto S, et al. Primary closure of the common bile
duct in open laparotomy for common bile duct stones. J Hepatobiliary Pancreat Surg
2006; 13:398.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/28\">",
" Tinoco R, Tinoco A, El-Kadre L, et al. Laparoscopic common bile duct
exploration. Ann Surg 2008; 247:674.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/29\">",
" Petelin JB. Laparoscopic common bile duct exploration. Surg Endosc 2003;
17:1705.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/30\">",
" Lo Menzo E, Schnall R, Von Rueden D. Lithotripsy in the laparoscopic era.
JSLS 2005; 9:358.",
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Current Surgical Therapy, Ninth Edition, Cameron, JL (Eds), Mosby Elsevier, 2008.
p.412.",
" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/32\">",
" Saber AA, Laraja RD, Nalbandian HI, et al. Changes in liver function tests
after laparoscopic cholecystectomy: not so rare, not always ominous. Am Surg 2000;
66:699.",
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" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/33\">",
" Paganini AM, Feliciotti F, Guerrieri M, et al. Laparoscopic common bile duct
exploration. J Laparoendosc Adv Surg Tech A 2001; 11:391.",
" </a>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/34\">",
" Horwood J, Akbar F, Davis K, Morgan R. Prospective evaluation of a selective
approach to cholangiography for suspected common bile duct stones. Ann R Coll Surg
Engl 2010; 92:206.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/35\">",
" Ingraham AM, Cohen ME, Ko CY, Hall BL. A current profile and assessment of
north american cholecystectomy: results from the american college of surgeons
national surgical quality improvement program. J Am Coll Surg 2010; 211:176.",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6440/abstract/36\">",
" Wolf AS, Nijsse BA, Sokal SM, et al. Surgical outcomes of open
cholecystectomy in the laparoscopic era. Am J Surg 2009; 197:781.",
" </a>",
" </li>",
" </ol>",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 15093 Version 6.0",
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" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li>",
" <a class=\"sr_button\" href=\"#H465889\" id=\"summRecButton\">",
" <span>",
" SUMMARY &amp; RECOMMENDATIONS",
" </span>",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H25286312\">",
" INTRODUCTION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H25286320\">",
" IDENTIFICATION OF CBD STONES",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H11839322\">",
" INDICATIONS FOR CBD EXPLORATION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H11839696\">",
" PREOPERATIVE PREPARATION",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H1382386448\">",
" Prophylactic antibiotics",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H813094\">",
" INTRAOPERATIVE CHOLANGIOGRAPHY",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H25286327\">",
" SURGICAL APPROACHES FOR CBD EXPLORATION",
" </a>",
" </li>",
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" <a class=\"outlineLink\" href=\"#H25286334\">",
" Laparoscopic transcystic exploration",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
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" Laparoscopic choledochotomy",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H25286348\">",
" Open CBD exploration",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H813533\">",
" PERSISTENT STONES",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H25286355\">",
" POSTOPERATIVE MANAGEMENT",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H813477\">",
" COMPLICATIONS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H465889\">",
" SUMMARY AND RECOMMENDATIONS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"SURG/15093\" rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
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" </h1>",
" <div id=\"relatedGraphics\">",
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" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"SURG/15093|ALG\">",
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" ALGORITHMS",
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" </div>",
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" <a href=\"#\" title=\"DIAGNOSTIC IMAGES\">",
" DIAGNOSTIC IMAGES",
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" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?33/40/34447\"
title=\"diagnostic image 1\">",
" Common bile duct stone on MRCP",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?43/14/44256\"
title=\"diagnostic image 2\">",
" MR cholangiogram showing common bile duct stones",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?18/33/18963\"
title=\"diagnostic image 3\">",
" Endoscopic ultrasound image of a gallstone in the gallbladder",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?10/29/10707\"
title=\"diagnostic image 4\">",
" Common bile duct stone on cholangiography",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?27/63/28657\"
title=\"diagnostic image 5\">",
" Normal intraoperative cholangiogram after cholecystectomy",
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" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?8/60/9153\"
title=\"diagnostic image 6\">",
" Balloon extraction of common bile duct stones",
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" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?32/58/33696\"
title=\"diagnostic image 7\">",
" ERCP showing common bile duct stones",
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" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?7/48/7936\"
title=\"diagnostic image 8\">",
" Impacted common bile duct stone",
" </a>",
" </li>",
" <li class=\"plainItem\">",
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var title_f6_18_6441="Perimesencephalic nonaneurysmal subarachnoid hemorrhage";
var content_f6_18_6441=[" <noscript>",
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" Perimesencephalic nonaneurysmal subarachnoid hemorrhage",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/18/6441/contributors\">",
" Authors",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/18/6441/contributors\">",
" Farhan Siddiq, MD",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/18/6441/contributors\">",
" Amir S Khan, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/18/6441/contributors\">",
" Section Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/18/6441/contributors\">",
" Jose Biller, MD, FACP, FAAN, FAHA",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/18/6441/contributors\">",
" Deputy Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/18/6441/contributors\">",
" Janet L Wilterdink, MD",
" </a>",
" <br/>",
" </div>",
" </div>",
" <div id=\"disclosures\">",
" <a href=\"UTD.htm?6/18/6441/contributor-disclosure\" target=\"_blank\">",
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" <span>",
" All topics are updated as new evidence becomes available and our",
" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
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" </a>",
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" is complete.",
" </span>",
" </div>",
" <div id=\"literatureReviewDate\">",
" <span class=\"emphasis\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <span class=\"emphasis\">",
" This topic last updated:",
" </span>",
" Jun 8, 2011.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION AND DEFINITION",
" </span>",
" &nbsp;&mdash;&nbsp;Subarachnoid hemorrhage (SAH) refers to bleeding within the
subarachnoid space, which lies between the arachnoid and pia mater and is normally
filled with cerebrospinal fluid. Most cases of subarachnoid hemorrhage are caused
by rupture of an intracranial aneurysm, but approximately 15 to 20 percent of
patients do not have an established vascular lesion on initial four-vessel cerebral
angiography [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1,2\">",
" 1,2",
" </a>",
" ]. The causes of nonaneurysmal SAH (NASAH) are potentially diverse, and often
the mechanism of bleeding in these cases is not identified.",
" </p>",
" <p>",
" In 1985, a subtype of NASAH, so-called perimesencephalic nonaneurysmal SAH was
identified in a case series of 13 patients who had a characteristic pattern of
localized blood on computed tomography (CT), normal cerebral angiography, and a
benign course that distinguished these patients from both aneurysmal SAH and other
patients with nonaneurysmal SAH [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/3\">",
" 3",
" </a>",
" ]. This observation has subsequently been confirmed by other reports [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/2,4-7\">",
" 2,4-7",
" </a>",
" ].",
" </p>",
" <p>",
" The CT finding that defines perimesencephalic NASAH (PM-NASAH) is blood
isolated to the perimesencephalic cisterns anterior to the brainstem; there may
also be extension into the ambient cisterns or basal parts of the sylvian fissures,
but not into the lateral sylvian fissure, anterior interhemispheric fissure, or
lateral ventricles (",
" <a class=\"graphic graphic_diagnosticimage graphicRef76973 \" href=\"UTD.htm?
40/12/41158\">",
" image 1",
" </a>",
" and",
" <a class=\"graphic graphic_figure graphicRef74410 \" href=\"UTD.htm?
38/9/39063\">",
" figure 1",
" </a>",
" ). This CT pattern of hemorrhage is not specific to PM-NASAH; a subset of
cases of perimesencephalic SAH are caused by aneurysm rupture. It is important,
however, to recognize this pattern of bleeding because invasive diagnostic testing
can be limited in these patients and morbidity thereby reduced.",
" </p>",
" <p>",
" This topic reviews perimesencephalic SAH. Aneurysmal SAH and other causes of
NASAH are discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?37/39/38522?
source=see_link\">",
" \"Etiology, clinical manifestations, and diagnosis of aneurysmal subarachnoid
hemorrhage\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/54/37738?
source=see_link\">",
" \"Treatment of aneurysmal subarachnoid hemorrhage\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?37/50/38696?
source=see_link\">",
" \"Nonaneurysmal subarachnoid hemorrhage\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" EPIDEMIOLOGY",
" </span>",
" &nbsp;&mdash;&nbsp;The reported proportion of cases of NASAH that are PM-NASAH
varies between 21 to 68 percent [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1,2,6,8-11\">",
" 1,2,6,8-11",
" </a>",
" ]. In a biracial, population-based, epidemiologic study, the annual rate of
PM-NASAH was estimated to be 0.5 per 100,000 persons over 18 years of age [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/8\">",
" 8",
" </a>",
" ].",
" </p>",
" <p>",
" The mean age of occurrence of PM-NASAH in several series was between 50 and 55
years [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/8,12,13\">",
" 8,12,13",
" </a>",
" ]. However, the age in reported cases ranges from 3 to 72 years old [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1,7,14-16\">",
" 1,7,14-16",
" </a>",
" ]. In contrast to aneurysmal SAH, there is no clear female predisposition for
PM-NASAH [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/8,12,13\">",
" 8,12,13",
" </a>",
" ].",
" </p>",
" <p>",
" Case-control studies suggest that hypertension and cigarette smoking are risk
factors for PM-NASAH, but these appear to be somewhat less prevalent among patients
with PM-NASAH compared with patients with aneurysmal SAH [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/8,17,18\">",
" 8,17,18",
" </a>",
" ]. PM-NASAH is not known to have a familial predisposition; however two cases
in first-degree relatives have been described [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/19\">",
" 19",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h1\">",
" ETIOLOGY AND PATHOGENESIS",
" </span>",
" &nbsp;&mdash;&nbsp;A ruptured saccular aneurysm is the cause of
perimesencephalic SAH in 2 to 9 percent of patients [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1,3,5,20-23\">",
" 1,3,5,20-23",
" </a>",
" ]. The aneurysm in these cases arises from the posterior circulation: the
basilar tip, vertebrobasilar junction, or the posterior inferior cerebellar,
superior cerebellar, posterior cerebral artery [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/5,15,24,25\">",
" 5,15,24,25",
" </a>",
" ]. Posterior circulation aneurysms are less common than those arising from the
anterior circulation. When posterior circulation aneurysms rupture, this pattern of
SAH results less than 17 percent of the time [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/22-24\">",
" 22-24",
" </a>",
" ].",
" </p>",
" <p>",
" In the majority of cases of PM-NASAH, the etiology is not defined, even after
extensive evaluation. Theories regarding its origin in some or all cases include
[",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/26\">",
" 26",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" <strong>",
" Rupture of a perforating artery",
" </strong>",
" &mdash; The perimesencephalic location of the blood clots is consistent with
bleeding from a perforating artery arising from the posterior circulation [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/27\">",
" 27",
" </a>",
" ]. In one case, this pathogenesis has been substantiated pathologically [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/28\">",
" 28",
" </a>",
" ]. In addition, hypertension, a known risk factor for perforating artery
disease, is also a risk factor for PM-NASAH (see",
" <a class=\"local\" href=\"#H2\">",
" 'Epidemiology'",
" </a>",
" above).",
" <br/>",
" <br/>",
" In one case series of 25 patients with PM-NASAH, an acute lacunar infarction
(usually attributed to occlusive disease of the perforating arteries) was found in
four patients [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/29\">",
" 29",
" </a>",
" ]. However, the acute lacunar infarctions in this and other reports have
been in the distribution of the anterior circulation, and their relationship to the
PM-NASAH is not clear [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1,30\">",
" 1,30",
" </a>",
" ].",
" </li>",
" <li>",
" <strong>",
" Venous origin",
" </strong>",
" &mdash; A venous source for PM-NASAH is suggested by the limited extension
of blood and low rate of subsequent rebleeding, both suggesting a low pressure
bleeding source. PM-NASAH often occurs in the setting of physical exertion, which
in this paradigm sequentially produces increased intrathoracic pressure, impaired
internal jugular venous return, elevated intracranial venous pressure, and leakage
of venous blood from susceptible blood vessels [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/31\">",
" 31",
" </a>",
" ]. Physical exertion is also believed to increase rupture from arterial
pathology, including saccular aneurysms.",
" <br/>",
" <br/>",
" In two case series, a higher incidence of primitive venous drainage on
conventional or computed tomography (CT) venography was found in patients with PM-
NASAH when compared with aneurysmal SAH [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/32,33\">",
" 32,33",
" </a>",
" ]. In these patients, the basal vein of Rosenthal",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" the perimesencephalic veins drain directly into the dural sinuses rather
than the vein of Galen, potentially making them more susceptible to venous
congestion. Two additional reported cases of PM-NASAH have documented a vein of
Galen stenosis on conventional and CT venography respectively, providing evidence
of a venous origin of bleeding in these cases [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/34\">",
" 34",
" </a>",
" ]. Another case report documented PM-NASAH along with venous infarction and
cerebral venous thrombosis [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/35\">",
" 35",
" </a>",
" ].",
" </li>",
" <li>",
" <strong>",
" Basilar artery wall hematoma",
" </strong>",
" &mdash; In some cases of PM-NASAH, an abnormal contour of the basilar artery
has been observed, either a small bulge or luminal narrowing [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/26,36\">",
" 26,36",
" </a>",
" ]. This was interpreted as possible vasospasm in some reports, but others
have speculated that an intramural hematoma could account for the abnormal blood
vessel appearance and also be the source of bleeding. It is postulated that rupture
of the vasa vasorum is the source of the relatively limited bleeding that occurs in
PM-NASAH. This is in contrast to an arterial dissection that results from an
intimal tear and produces massive SAH. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?37/50/38696?
source=see_link&amp;anchor=H8#H8\">",
" \"Nonaneurysmal subarachnoid hemorrhage\", section on 'Intracranial
arterial dissection'",
" </a>",
" .)",
" <br/>",
" <br/>",
" The role of a putative basilar artery wall hematoma in PM-NASAH remains
unproven. In one case series, systematic examination of basilar artery contours in
27 patients with PM-NASAH found no variations that suggested this origin of
bleeding [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/9\">",
" 9",
" </a>",
" ]. This hypothesis awaits further study with high-resolution neuroimaging
studies.",
" </li>",
" </ul>",
" </p>",
" <p>",
" Other potential causes of PM-NASAH include rupture of a cryptic vascular
malformation, high cervical spinal dural arteriovenous fistula, cavernous angioma,
or capillary telangiectasia [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/37-39\">",
" 37-39",
" </a>",
" ]. Some patients with PM-NASAH may have an occult aneurysm; however, the low
incidence of rebleeding in these patients suggests that this is rare. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?37/50/38696?
source=see_link\">",
" \"Nonaneurysmal subarachnoid hemorrhage\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h1\">",
" CLINICAL PRESENTATION",
" </span>",
" &nbsp;&mdash;&nbsp;The clinical manifestations of PM-NASAH are generally less
severe than those of aneurysmal SAH, but the presentation is otherwise similar,
with sudden onset of headache, meningismus, photophobia, and nausea being the most
common symptoms [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1,7\">",
" 1,7",
" </a>",
" ]. Individual patients with PM-NASAH and other forms of SAH cannot be
distinguished based upon their clinical symptoms [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/23\">",
" 23",
" </a>",
" ].",
" </p>",
" <p>",
" Group comparisons of patients with PM-NASAH and aneurysmal SAH find
differences in the prevalence of certain clinical features and measures of disease
severity. Some examples of these differences, as well as similarities, are:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" On initial evaluation in the hospital, over 90 percent of patients with PM-
NASAH are categorized in lower Hunt and Hess grades, a measure of the clinical
severity of the SAH (",
" <a class=\"graphic graphic_table graphicRef69179 \" href=\"UTD.htm?
8/57/9115\">",
" table 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1,6,7,13,14,40\">",
" 1,6,7,13,14,40",
" </a>",
" ]. In contrast, less than 50 percent of patients with aneurysmal SAH present
with these relatively benign clinical features [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/6,14\">",
" 6,14",
" </a>",
" ].",
" </li>",
" <li>",
" Frank loss of consciousness at the onset of SAH is reported to be less
common in patients with PM-NASAH than in patients with aneurysmal rupture. However,
this clinical feature is variably reported, and in one series, occurred in one-
third of patients with PM-NASAH [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/41\">",
" 41",
" </a>",
" ]. Another case series reported that one-third of patients with PM-NASAH
suffered an episode of amnesia at the ictus [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/42\">",
" 42",
" </a>",
" ]. The speculative cause was transient hydrocephalus, with enlarged temporal
horns causing temporary hypoperfusion of the hippocampus.",
" </li>",
" <li>",
" The onset of headache in PM-NASAH appeared to be somewhat less abrupt (a few
minutes rather than a few seconds) than in patients with aneurysmal SAH in one case
series [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/3\">",
" 3",
" </a>",
" ]. However, the relatively small differences in the time course were not
statistically significant.",
" </li>",
" <li>",
" Sentinel headache, a prodromal feature of up to 40 percent of patients with
aneurysmal SAH, is not reported in PM-NASAH [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1\">",
" 1",
" </a>",
" ].",
" </li>",
" <li>",
" The clinical setting of physical exertion appears to be as common in PM-
NASAH as in aneurysmal SAH [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/3,7,26,31\">",
" 3,7,26,31",
" </a>",
" ]. The onset of both PM-NASAH and aneurysmal SAH are more common during
daytime and evening hours compared with nighttime [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/43\">",
" 43",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h1\">",
" DIAGNOSTIC EVALUATION",
" </span>",
" &nbsp;&mdash;&nbsp;Subarachnoid hemorrhage (SAH) should be considered in any
patient complaining of severe headache of sudden onset. Emergent computed
tomography (CT) of the head should immediately follow consideration of the
diagnosis. If the suspicion is high and the CT scan fails to show blood in
subarachnoid space, a lumbar puncture must be obtained. CT scan can detect SAH, but
cerebral angiography is required to exclude aneurysmal bleeding. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?37/39/38522?
source=see_link&amp;anchor=H26#H26\">",
" \"Etiology, clinical manifestations, and diagnosis of aneurysmal subarachnoid
hemorrhage\", section on 'Diagnosis'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h2\">",
" Computed tomography",
" </span>",
" &nbsp;&mdash;&nbsp;The pattern of blood on CT scan identifies a patient with
perimesencephalic SAH. Blood is isolated to the perimesencephalic cisterns anterior
to the brainstem; there may be extension into the ambient cisterns or basal parts
of the sylvian fissures, but not into the lateral sylvian fissure, anterior
interhemispheric fissure, chiasmatic cistern, or lateral ventricles (",
" <a class=\"graphic graphic_diagnosticimage graphicRef76973 \" href=\"UTD.htm?
40/12/41158\">",
" image 1",
" </a>",
" and",
" <a class=\"graphic graphic_figure graphicRef74410 \" href=\"UTD.htm?
38/9/39063\">",
" figure 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1,5,44,45\">",
" 1,5,44,45",
" </a>",
" ]. In some patients, the visualized blood is limited to the quadrigeminal or
pretruncal cisterns [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/44-46\">",
" 44-46",
" </a>",
" ]. There is high inter-observer agreement among radiologists in the
identification of perimesencephalic SAH (kappa 0.87) [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/5\">",
" 5",
" </a>",
" ].",
" </p>",
" <p>",
" The timing of the CT scan is critical. A diagnosis of perimesencephalic SAH
should not be considered reliable on a CT performed more than 48 to 72 hours after
the clinical ictus, as washout and resorption of blood may have taken place and
obscured the initial extent of hemorrhage [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1,7,47\">",
" 1,7,47",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h2\">",
" Cerebral angiography",
" </span>",
" &nbsp;&mdash;&nbsp;The likelihood of finding an aneurysm on angiogram in a
patient with a perimesencephalic SAH has varied from 2 to 9 percent in different
reports. (See",
" <a class=\"local\" href=\"#H3\">",
" 'Etiology and pathogenesis'",
" </a>",
" above.) Because of the very high and immediate morbidity and mortality
associated with aneurysmal bleeding, every patient with perimesencephalic SAH must
undergo angiographic evaluation. The commonly used angiographic techniques include
CT angiography (CTA), magnetic resonance angiography (MRA), and conventional
digital subtraction angiography (DSA). The best modality for evaluation of cerebral
vasculature in perimesencephalic SAH is controversial.",
" </p>",
" <p class=\"headingAnchor\" id=\"H8\">",
" <span class=\"h3\">",
" Choice of first test",
" </span>",
" &nbsp;&mdash;&nbsp;Of the available tests, DSA is believed to have the highest
resolution for the detection of intracranial aneurysms and remains the gold
standard test. While invasive with an associated risk of serious complications, DSA
has a relatively low morbidity in this setting. In one meta-analysis, the combined
risk of permanent and transient neurologic complications following DSA was
significantly lower in patients with SAH compared with those with a TIA or stroke
(1.8 versus 3.7 percent) [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/48\">",
" 48",
" </a>",
" ].",
" </p>",
" <p>",
" Of the two noninvasive angiographic techniques, CTA and MRA, CTA has been best
studied in the setting of acute SAH. A 2003 meta-analysis of 21 studies involving
1251 patients estimated the overall sensitivity and specificity of CTA for aneurysm
detection to be 93 and 88 percent, respectively [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/49\">",
" 49",
" </a>",
" ]. However, there is likely to be appreciable inter-institutional variability.
A subsequently reported series of 336 patients found a lower per-aneurysm
sensitivity and specificity of 83 and 93 percent [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/50\">",
" 50",
" </a>",
" ]. Aneurysms smaller than 3 mm were particularly likely to be missed by CTA.
As technology improves, the sensitivity and specificity of noninvasive imaging is
also likely to improve. [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/51\">",
" 51",
" </a>",
" ]. A 2011 meta-analysis of CTA diagnosis of intracranial aneurysms found that,
compared with single-detector CTA, use of multidetector CTA was associated with an
overall improved sensitivity and specificity for aneurysm detection (both &gt;97
percent) as well as improved detection of smaller aneurysms &le;4 mm in diameter
[",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/52\">",
" 52",
" </a>",
" ]. Another systematic review and meta-analysis restricted to patients with SAH
had similar findings [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/53\">",
" 53",
" </a>",
" ].",
" </p>",
" <p>",
" Specific information regarding the performance of CTA for posterior
circulation aneurysms and perimesencephalic SAH is more limited. In one study of 40
patients with SAH localized to the posterior fossa, CTA detected aneurysms in 16
patients. In all 40 patients, the presence and absence of aneurysm as determined by
CTA was confirmed by DSA or autopsy [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/21\">",
" 21",
" </a>",
" ]. However, none of the 15 patients with PM-SAH in this series was found to
have an intracranial aneurysm. Similarly, DSA confirmed the negative findings on
CTA in another case series of 30 patients with PM-SAH [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/54\">",
" 54",
" </a>",
" ].",
" </p>",
" <p>",
" A decision analysis reported that CTA alone had higher utilities in the
setting of perimesencephalic SAH compared with other diagnostic strategies
including no investigation, DSA alone, and CTA plus DSA [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/20\">",
" 20",
" </a>",
" ]. However, certain assumptions in the analysis, including a low prevalence of
aneurysm (4 percent), a high complication rate of angiography (2.7 morbidity and
mortality), and a 97 percent sensitivity and specificity of CTA, favored this
outcome and can be disputed.",
" </p>",
" <p>",
" CTA technology is continuously evolving and varies, along with expertise of
interpretation, at different institutions. As a result, we recommend DSA over CTA
as a first test for most patients with PM-SAH. Centers with a high volume of cases
of SAH and demonstrated, documented experience with CTA for this purpose may choose
CTA over DSA.",
" </p>",
" <p class=\"headingAnchor\" id=\"H9\">",
" <span class=\"h3\">",
" Repeated testing",
" </span>",
" &nbsp;&mdash;&nbsp;When DSA is repeated after an initial first study in
patients with SAH, an aneurysm may be revealed in 2 to 24 percent of patients [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1,6,10,55\">",
" 1,6,10,55",
" </a>",
" ]. Reasons for an initial false negative angiogram include technical or
reading errors, small aneurysm size, and obscuration of the aneurysm because of
vasospasm, hematoma, or thrombosis within the aneurysm [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/6,25\">",
" 6,25",
" </a>",
" ].",
" </p>",
" <p>",
" A false negative angiogram in the setting of perimesencephalic SAH is a rare
but reported event [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/6,10,13,25,55-57\">",
" 6,10,13,25,55-57",
" </a>",
" ]. Many clinicians feel that repeat angiography is not necessary for patients
with perimesencephalic SAH unless the initial angiogram is felt to be technically
compromised because of vasospasm or other factors [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1-4,58\">",
" 1-4,58",
" </a>",
" ]. Others disagree and advocate repeating DSA in all patients [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/47\">",
" 47",
" </a>",
" ]. A conservative, middle-road approach advocates follow-up imaging with
noninvasive CTA [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/6,57\">",
" 6,57",
" </a>",
" ]. It is our practice to repeat CTA seven days after the onset of PM-SAH.
Rebleeding suggests the presence of an occult aneurysm and is an indication for
repeat DSA.",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h2\">",
" Magnetic resonance imaging",
" </span>",
" &nbsp;&mdash;&nbsp;Magnetic resonance imaging (MRI) may demonstrate
angiographically occult vascular lesions that can cause SAH. Such lesions include
vascular malformations in the brain or spinal cord, tumors, including pituitary
adenoma, and arterial wall hematoma suggesting arterial dissection. These rarely,
if ever, underlie PM-NASAH. In one series of 18 patients with PM-NASAH, MRI
revealed a potential causative vascular lesion, a pontine capillary telangiectasia,
in just one patient [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/38,59\">",
" 38,59",
" </a>",
" ]. In another series of 25 patients with PM-SAH, MRI demonstrated acute
lacunar-type infarctions in four individuals [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/29\">",
" 29",
" </a>",
" ]. Arguably, these findings did not contribute to the care of the patient.
Many clinicians feel that MRI is not cost effective in the evaluation of patients
with PM-SAH [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/4,7,55\">",
" 4,7,55",
" </a>",
" ]. However, we recommend MRI and MRA in all patients with PM-NASAH; it is
noninvasive and safe and may rarely reveal an occult aneurysm as well as other less
common causes of PM-NASAH.",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h2\">",
" Other testing",
" </span>",
" &nbsp;&mdash;&nbsp;Patients with SAH should undergo basic laboratory testing
including complete blood count, serum chemistries, and coagulation studies. A
baseline electrocardiogram should also be obtained.",
" </p>",
" <p class=\"headingAnchor\" id=\"H12\">",
" <span class=\"h1\">",
" COMPLICATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;Most clinical case series report that patients with
nonaneurysmal PM-SAH have a lower incidence and severity of complications compared
with patients with aneurysmal SAH and patients with nonaneurysmal,
nonperimesencephalic SAH [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/2,11,14,60,61\">",
" 2,11,14,60,61",
" </a>",
" ].",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Rebleeding is rare among patients with PM-SAH after an initial negative
angiography [",
" <a class=\"abstract\" href=\"UTD.htm?
6/18/6441/abstract/2,4,6,7,14,60,62\">",
" 2,4,6,7,14,60,62",
" </a>",
" ]. In those patients in whom rebleeding occurs, an occult cerebral aneurysm
seems likely because the pattern of recurrent hemorrhage is often not
perimesencephalic [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/6,41\">",
" 6,41",
" </a>",
" ]. Rebleeding represents an indication for repeat DSA.",
" </li>",
" <li>",
" Vasospasm with cerebral ischemia is the leading cause of death and
disability after aneurysm rupture, occurring in 20 to 30 percent of patients with
aneurysmal SAH [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/63\">",
" 63",
" </a>",
" ]. In PM-NASAH, vasospasm appears to be somewhat less common and to be
associated with somewhat milder clinical symptoms [",
" <a class=\"abstract\" href=\"UTD.htm?
6/18/6441/abstract/4,6,7,14,41,47,60\">",
" 4,6,7,14,41,47,60",
" </a>",
" ]. However, there are reported cases of symptomatic, diffuse, and severe
vasospasm affecting the anterior and posterior circulations in patients with PM-
NASAH [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/2,64-66\">",
" 2,64-66",
" </a>",
" ]. Symptomatic vasospasm has been precipitated by DSA in some cases [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1,7,60\">",
" 1,7,60",
" </a>",
" ]. The lower incidence of vasospasm in PM-NASAH may be due to the lower
volume or concentration of blood in these patients, although this specific
association has not been demonstrated.",
" <br/>",
" <br/>",
" Transcranial Doppler (TCD) sonography is useful for detecting and monitoring
vasospasm in spontaneous SAH [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/67,68\">",
" 67,68",
" </a>",
" ]. The pathogenesis of vasospasm in SAH is discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?37/39/38522?
source=see_link&amp;anchor=H15#H15\">",
" \"Etiology, clinical manifestations, and diagnosis of aneurysmal
subarachnoid hemorrhage\", section on 'Vasospasm'",
" </a>",
" .)",
" </li>",
" <li>",
" Hydrocephalus can be an early or delayed complication of SAH. In PM-NASAH,
acute hydrocephalus occurs in 3 to 27 percent [",
" <a class=\"abstract\" href=\"UTD.htm?
6/18/6441/abstract/2,4,6,7,13,14,41,60,69\">",
" 2,4,6,7,13,14,41,60,69",
" </a>",
" ], a rate similar to aneurysmal SAH. One case series found that among their
patients with PM-NASAH, filling of all perimesencephalic cisterns was a
prerequisite for developing hydrocephalus [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/69\">",
" 69",
" </a>",
" ]. In more than half of the cases, hydrocephalus resolved spontaneously
without intervention (ventriculostomy",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" shunting), perhaps because of rapid washout of blood limited to the
cisterns.",
" </li>",
" <li>",
" Acute seizures have been described in PM-NASAH, but this is uncommon [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/41\">",
" 41",
" </a>",
" ]. PM-NASAH does not appear to be associated with the later development of
epilepsy.",
" </li>",
" <li>",
" Hyponatremia following SAH is due to increased secretion of antidiuretic
hormone. In one series, 10 of 35 patients with PM-NASAH developed hyponatremia,
only five of whom had sodium levels less than 130",
" <span class=\"nowrap\">",
" mmol/liter",
" </span>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/60\">",
" 60",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?8/23/8567?
source=see_link\">",
" \"Cerebral salt-wasting\"",
" </a>",
" .)",
" </li>",
" <li>",
" Cardiac abnormalities and electrocardiographic (ECG) changes are commonly
seen after SAH, ranging in severity from transient ST segment depression to life-
threatening cardiac arrhythmias. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?37/39/38522?
source=see_link&amp;anchor=H24#H24\">",
" \"Etiology, clinical manifestations, and diagnosis of aneurysmal
subarachnoid hemorrhage\", section on 'Cardiac abnormalities'",
" </a>",
" .) In one case series of PM-NASAH, baseline ECG changes were found in 22
percent on admission and transient ECG changes occurred in most [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1,60\">",
" 1,60",
" </a>",
" ]. No clinically significant cardiac complications have been reported in the
setting of PM-NASAH.",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H13\">",
" <span class=\"h1\">",
" TREATMENT",
" </span>",
" &nbsp;&mdash;&nbsp;Patients with PM-SAH should be treated as though there is
an underlying aneurysm until this has been satisfactorily excluded. Patients are
admitted to an intensive care setting for constant hemodynamic and cardiac
monitoring, given stool softeners, kept at bedrest, and given analgesia to diminish
hemodynamic fluctuations and lower the risk of rebleeding. Pneumatic compression
stockings to limit risk of deep vein thrombosis should be utilized while patients
are immobile. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/54/37738?
source=see_link\">",
" \"Treatment of aneurysmal subarachnoid hemorrhage\"",
" </a>",
" .)",
" </p>",
" <p>",
" After exclusion of cerebral aneurysm, patients with PM-NASAH should continue
to receive symptomatic care with analgesics as needed, cardiac monitoring, serum
chemistry monitoring, and monitoring of neurologic status [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/1\">",
" 1",
" </a>",
" ]. Blood pressure should be monitored and controlled, but strict bed rest is
not required. The risk of epileptic seizures is low and prophylactic antiepileptic
drugs are not recommended [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/7\">",
" 7",
" </a>",
" ].",
" </p>",
" <p>",
" The calcium channel blocker",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/20/16710?source=see_link\">",
" nimodipine",
" </a>",
" has been shown to improve outcomes in patients with aneurysmal SAH [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/70\">",
" 70",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/54/37738?
source=see_link&amp;anchor=H7#H7\">",
" \"Treatment of aneurysmal subarachnoid hemorrhage\", section on
'Nimodipine'",
" </a>",
" .) The mechanism of its action is uncertain, but may involve some type of
neuroprotection against vasospasm-induced cerebral ischemia. It is less certain
that patients with other mechanisms of SAH also benefit from nimodipine; meta-
analyses of trial results in traumatic SAH, for example, have provided conflicting
results [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/71,72\">",
" 71,72",
" </a>",
" ].",
" </p>",
" <p>",
" There is no data as to whether",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/20/16710?source=see_link\">",
" nimodipine",
" </a>",
" provides any benefit for patients with PM-NASAH, who as a group incur little
if any serious neurologic mortality and morbidity. At the same time, nimodipine is
unlikely to be associated with significant adverse effects in this group. We
suggest that patients with PM-SAH be treated and monitored as if there is a
cerebral aneurysm with nimodipine and transcranial Doppler monitoring until follow-
up imaging has excluded an aneurysm. (See",
" <a class=\"local\" href=\"#H9\">",
" 'Repeated testing'",
" </a>",
" above.)",
" </p>",
" <p>",
" While complications following PM-NASAH, are less likely than after aneurysmal
SAH, they should be managed similarly. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/54/37738?
source=see_link&amp;anchor=H24#H24\">",
" \"Treatment of aneurysmal subarachnoid hemorrhage\", section on 'Management
of complications'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H14\">",
" <span class=\"h1\">",
" LONG-TERM PROGNOSIS",
" </span>",
" &nbsp;&mdash;&nbsp;Compared with aneurysmal SAH, patients with PM-NASAH have a
good outcome [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/2,6,60\">",
" 2,6,60",
" </a>",
" ]. Long-term follow-up studies reveal that rebleeding is exceptional and life
expectancy is not altered [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/12,14,62,73\">",
" 12,14,62,73",
" </a>",
" ]. With rare exception, patients do not have significant neurologic deficits
after PM-NASAH. Some uncontrolled studies suggest that many patients report
residual headaches, depression, minor cognitive deficits, and fatigue several years
after the PM-NASAH, in some cases affecting employment status [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/4,12,73,74\">",
" 4,12,73,74",
" </a>",
" ]. Persistent anosmia is an infrequent (5 percent) complication of PM-NASAH
[",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/75\">",
" 75",
" </a>",
" ]. However, one study found that quality of life after PM-NASAH two years
after hemorrhage was not significantly different from controls [",
" <a class=\"abstract\" href=\"UTD.htm?6/18/6441/abstract/76\">",
" 76",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H15\">",
" <span class=\"h1\">",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;Perimesencephalic nonaneurysmal subarachnoid hemorrhage
(PM-NASAH) refers to a subset of SAH patients with characteristic pattern of
localized blood on computed tomography (CT), normal cerebral angiography, and a
benign course.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Between 4 and 9 percent of perimesencephalic SAH are caused by rupture of an
aneurysm arising from the posterior circulation. Most of the remainder of PM-NASAH
do not have an identified etiology. (See",
" <a class=\"local\" href=\"#H3\">",
" 'Etiology and pathogenesis'",
" </a>",
" above.)",
" </li>",
" <li>",
" The clinical presentation of PM-NASAH overlaps with aneurysmal SAH with
abrupt onset of headache, meningismus, photophobia, and nausea. As a group,
patients with PM-NASAH have milder clinical features than those with aneurysmal
SAH. (See",
" <a class=\"local\" href=\"#H4\">",
" 'Clinical presentation'",
" </a>",
" above.)",
" </li>",
" <li>",
" The diagnosis of perimesencephalic SAH is made by CT of the brain, which
should always be performed emergently in a patient with an abrupt onset of
headache. The CT findings that define perimesencephalic SAH include blood isolated
to the perimesencephalic cisterns anterior to the brainstem; there may be extension
into the ambient cisterns or basal parts of the sylvian fissures, but not into the
lateral sylvian fissure, anterior interhemispheric fissure, or lateral ventricles.
(See",
" <a class=\"local\" href=\"#H6\">",
" 'Computed tomography'",
" </a>",
" above.)",
" </li>",
" <li>",
" An intracranial aneurysm should be excluded in all patients with
perimesencephalic SAH. We suggest using digital subtraction cerebral angiography
(DSA). In centers that have a large experience with reliable CT angiography (CTA),
this may replace DSA. Repeat angiography should be done in patients in whom
concerns for underlying aneurysm remain because of underlying vasospasm or the
technical quality of the initial study. Patients who have recurrent bleeding should
also have a repeat study. We also recommend a follow-up CTA in all patients one
week after the onset of PM-SAH. (See",
" <a class=\"local\" href=\"#H7\">",
" 'Cerebral angiography'",
" </a>",
" above.)",
" </li>",
" <li>",
" Patients with perimesencephalic SAH who are found to have a cerebral
aneurysm should be managed as are other patients with aneurysmal SAH. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/54/37738?
source=see_link\">",
" \"Treatment of aneurysmal subarachnoid hemorrhage\"",
" </a>",
" .)",
" </li>",
" <li>",
" Patients with perimesencephalic nonaneurysmal SAH (PM-NASAH) have a lower
incidence of complications than patients with aneurysmal SAH. Patients should be
clinically monitored for the development of clinical vasospasm, hydrocephalus,
hyponatremia, and cardiac complications. (See",
" <a class=\"local\" href=\"#H12\">",
" 'Complications'",
" </a>",
" above.)",
" </li>",
" <li>",
" Aside from monitoring, specific treatments are not required for patients
with PM-NASAH. However, until a cerebral aneurysm has been excluded on follow-up
imaging, we suggest using prophylactic",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/20/16710?
source=see_link\">",
" nimodipine",
" </a>",
" to ameliorate complications of potential vasospasm (",
" <a class=\"grade\" href=\"._grade_5?title=Grade 2B\">",
" Grade 2B",
" </a>",
" ). (See",
" <a class=\"local\" href=\"#H13\">",
" 'Treatment'",
" </a>",
" above.)",
" </li>",
" <li>",
" The long-term prognosis for patients with PM-NASAH is in general excellent.
(See",
" <a class=\"local\" href=\"#H14\">",
" 'Long-term prognosis'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H31890620\">",
" <span class=\"h1\">",
" ACKNOWLEDGMENT",
" </span>",
" &nbsp;&mdash;&nbsp;The editorial staff at UpToDate, Inc. would like to
acknowledge Dr. David Brock, who contributed to an earlier version of this topic
review.",
" </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>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6441/abstract/1\">",
" Schwartz TH, Solomon RA. Perimesencephalic nonaneurysmal subarachnoid
hemorrhage: review of the literature. Neurosurgery 1996; 39:433.",
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" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/18/6441/abstract/2\">",
" Rinkel GJ, Wijdicks EF, Hasan D, et al. Outcome in patients with
subarachnoid haemorrhage and negative angiography according to pattern of
haemorrhage on computed tomography. Lancet 1991; 338:964.",
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" SUMMARY &amp; RECOMMENDATIONS",
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" INTRODUCTION AND DEFINITION",
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" EPIDEMIOLOGY",
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" CLINICAL PRESENTATION",
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" <a class=\"outlineLink\" href=\"#H6\">",
" Computed tomography",
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" Cerebral angiography",
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" - Choice of first test",
" </a>",
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" - Repeated testing",
" </a>",
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" Magnetic resonance imaging",
" </a>",
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" Other testing",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H12\">",
" COMPLICATIONS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H13\">",
" TREATMENT",
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" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H14\">",
" LONG-TERM PROGNOSIS",
" </a>",
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" <a class=\"outlineLink\" href=\"#H15\">",
" SUMMARY AND RECOMMENDATIONS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H31890620\">",
" ACKNOWLEDGMENT",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
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" <div class=\"openRelatedGraphics\" id=\"NEURO/1114\" rel=\"outline_link\">",
" GRAPHICS",
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" <a class=\"graphic graphic_diagnosticimage\" href=\"UTD.htm?40/12/41158\"
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" CT perimesencephalic nonaneursymal SAH",
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" <a class=\"graphic graphic_figure\" href=\"UTD.htm?38/9/39063\"
title=\"figure 1\">",
" Subarachnoid spaces and cisterns",
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" <a class=\"graphic graphic_table\" href=\"UTD.htm?8/57/9115\" title=\"table
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" Hunt and Hess grading system",
" </a>",
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" RELATED TOPICS",
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" <ul>",
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" <a class=\"medical medical_review\" href=\"UTD.htm?8/23/8567?
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" </a>",
" </li>",
" <li class=\"plainItem\">",
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source=related_link\">",
" Etiology, clinical manifestations, and diagnosis of aneurysmal subarachnoid
hemorrhage",
" </a>",
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" <a class=\"medical medical_review\" href=\"UTD.htm?37/50/38696?
source=related_link\">",
" Nonaneurysmal subarachnoid hemorrhage",
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source=related_link\">",
" Treatment of aneurysmal subarachnoid hemorrhage",
" </a>",
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var title_f6_18_6442="Dexamethasone (systemic): Pediatric drug information";
var content_f6_18_6442=[" <noscript>",
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" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"drugTitle\">",
" Dexamethasone (systemic): Pediatric drug information",
" </div>",
" <div id=\"lexiTitleImg\">",
" <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
width=\"71\"/>",
" </div>",
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" </div>",
" <div id=\"drugCopy\">",
" Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
" </div>",
" <div id=\"topicText\">",
" (For additional information",
" <a class=\"drug drug_general\" href=\"UTD.htm?13/45/14042?source=see_link\">",
" see \"Dexamethasone (systemic): Drug information\"",
" </a>",
" and",
" <a class=\"drug drug_patient\" href=\"UTD.htm?40/45/41686?source=see_link\">",
" see \"Dexamethasone (systemic): Patient drug information\"",
" </a>",
" )",
" <br/>",
" For abbreviations and symbols that may be used in Lexicomp (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
" show table",
" </a>",
" )",
" <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F8015648\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: U.S.",
" </span>",
" <ul>",
" <li>",
" Baycadron&trade;;",
" </li>",
" <li>",
" Dexamethasone Intensol&trade;;",
" </li>",
" <li>",
" DexPak&reg; 10 Day TaperPak&reg;;",
" </li>",
" <li>",
" DexPak&reg; 13 Day TaperPak&reg;;",
" </li>",
" <li>",
" DexPak&reg; 6 Day TaperPak&reg;",
" </li>",
" </ul>",
" </div>",
" <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F8015649\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: Canada",
" </span>",
" <ul>",
" <li>",
" Apo-Dexamethasone&reg;;",
" </li>",
" <li>",
" Dexasone&reg;;",
" </li>",
" <li>",
" Dom-Dexamethasone;",
" </li>",
" <li>",
" PHL-Dexamethasone;",
" </li>",
" <li>",
" PMS-Dexamethasone;",
" </li>",
" <li>",
" PRO-Dexamethasone;",
" </li>",
" <li>",
" ratio-Dexamethasone",
" </li>",
" </ul>",
" </div>",
" <div class=\"list_set htclist drugH1Div drugBrandNames\" id=\"F10473457\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Therapeutic Category",
" </span>",
" <ul>",
" <li>",
" <span class=\"list-set-name\">",
" Adrenal Corticosteroid",
" </span>",
" </li>",
" <li>",
" <span class=\"list-set-name\">",
" Anti-inflammatory Agent",
" </span>",
" </li>",
" <li>",
" <span class=\"list-set-name\">",
" Antiemetic",
" </span>",
" </li>",
" <li>",
" <span class=\"list-set-name\">",
" Corticosteroid, Systemic",
" </span>",
" </li>",
" <li>",
" <span class=\"list-set-name\">",
" Glucocorticoid",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"block don drugH1Div\" id=\"F11442279\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Neonatal",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Airway edema or extubation:",
" </b>",
" I.V.: 0.25 mg/kg/dose given ~4 hours prior to scheduled extubation then every
8 hours for a total of 3 doses (Couser, 1992); others have used 0.5 mg/kg/dose
every 8 hours for 3 doses with last dose administered 1 hour prior to scheduled
extubation (Davis, 2001); range: 0.25-0.5 mg/kg/dose for 1-3 doses; maximum dose:
1.5 mg/kg/day; limited data available, reported dosing regimens variable.",
" <b>",
" Note:",
" </b>",
" A longer duration of therapy may be needed with more severe cases. A recent
meta-analysis concluded that future neonatal clinical trials should study a
multiple dose strategy with initiation of dexamethasone at least 12 hours before
extubation (Khemani, 2009).",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Bronchopulmonary dysplasia, facilitation of ventilator wean:",
" </b>",
" PNA &ge;7 days: Oral, I.V.: Initial: 0.15 mg/kg/day given in divided doses
every 12 hours for 3 days, then tapered every 3 days over 7 days; total
dexamethasone dose: 0.89 mg/kg given over 10 days (Doyle, 2006); others have used
0.2 mg/kg/day given once daily and tapered every 3 days over 7 days (total
dexamethasone dose: 1 mg/kg) (Durand, 2002) or tapered over 14 days (total
dexamethasone dose: 1.9 mg/kg) (Whalther, 2003).",
" <b>",
" Note:",
" </b>",
" High doses (~0.5 mg/kg/day) do not confer additional benefit over lower
doses, are associated with higher incidence of adverse effects (including adverse
neurodevelopmental outcomes), and are not recommended for use (Watterberg, 2010).
However, a meta-analysis reported total cumulative doses &gt;4 mg/kg reduced the
relative risk for the combined outcome, mortality, or bronchopulmonary dysplasia;
further studies are needed (Onland, 2009).",
" </p>",
" </div>",
" <div class=\"block dos drugH1Div\" id=\"F10473887\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Usual",
" </span>",
" <p>",
" (For additional information",
" <a class=\"drug drug_general\" href=\"UTD.htm?13/45/14042?
source=see_link\">",
" see \"Dexamethasone (systemic): Drug information\"",
" </a>",
" )",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Infants and Children:",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Acute mountain sickness (AMS) (moderate)/high altitude cerebral edema
(HACE); treatment:",
" </b>",
" Oral, I.M., I.V.: 0.15 mg/kg/dose every 6 hours; consider using for high
altitude pulmonary edema because of associated HACE with this condition (Luks,
2010; Pollard, 2001)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Airway edema or extubation:",
" </b>",
" Oral, I.M., I.V.: 0.5 mg/kg/dose given at 6-12 hours prior to extubation then
every 6 hours for 6 doses (total dexamethasone dose: 3 mg/kg); maximum dose: 10 mg
(Anene, 1996; Khemani, 2009; Tellez, 1991)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Antiemetic (chemotherapy-induced)",
" </b>",
" : Refer to individual protocols and emetogenic potential: I.V.: Severely
emetogenic chemotherapy: Usual: 10 mg/m",
" ^{",
" 2",
"}",
" /dose once daily on days of chemotherapy; some patients may require every 12
hour dosing; usual range: 8-14 mg/m",
" ^{",
" 2",
"}",
" /dose (Holdsworth, 2006; Jordan, 2010; Phillips, 2010); others have used:
Initial: 10 mg/m",
" ^{",
" 2",
"}",
" /dose (maximum dose: 20 mg) then 5 mg/m",
" ^{",
" 2",
"}",
" /dose every 6 hours",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Anti-inflammatory:",
" </b>",
" Oral, I.M., I.V.: 0.08-0.3 mg/kg/day or 2.5-10 mg/m",
" ^{",
" 2",
"}",
" /day in divided doses every 6-12 hours",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Asthma exacerbation:",
" </b>",
" Oral, I.M., I.V.: 0.6 mg/kg once (maximum dose: 16 mg) (Hegenbarth, 2008 )",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Bacterial meningitis (",
" <i>",
" H. influenzae",
" </i>",
" type b):",
" </b>",
" Infants and Children &gt;6 weeks: I.V.: 0.15 mg/kg/dose every 6 hours for the
first 2-4 days of antibiotic treatment; start dexamethasone 10-20 minutes before or
with the first dose of antibiotic; if antibiotics have already been administered,
dexamethasone use has not been shown to improve patient outcome and is not
recommended (Tunkel, 2004).",
" <b>",
" Note:",
" </b>",
" For pneumococcal meningitis, data has not shown clear benefit from
dexamethasone administration; risk and benefits should be considered prior to use
(",
" <i>",
" Red Book",
" </i>",
" , 2009).",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Cerebral edema:",
" </b>",
" Oral, I.M., I.V.: Loading dose: 1-2 mg/kg/dose as a single dose; maintenance:
1-1.5 mg/kg/day (maximum dose: 16 mg/day) in divided doses every 4-6 hours",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Croup (laryngotracheobronchitis):",
" </b>",
" Oral, I.M., I.V.: 0.6 mg/kg once; usual maximum dose: 16 mg (doses as high as
20 mg have been used) (Bjornson, 2004; Hegenbarth, 2008; Rittichier, 2000);",
" <b>",
" Note:",
" </b>",
" A single oral dose of 0.15 mg/kg has been shown effective in children with
mild to moderate croup (Russell, 2004; Sparrow, 2006)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Physiologic replacement:",
" </b>",
" Oral, I.M., I.V.: 0.03-0.15 mg/kg/day or 0.6-0.75 mg/m",
" ^{",
" 2",
"}",
" /day in divided doses every 6-12 hours",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Adults:",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Acute mountain sickness (AMS)/high altitude cerebral edema (HACE):",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
" Prevention: Oral: 2 mg every 6 hours or 4 mg every 12 hours starting on the
day of ascent; may be discontinued after staying at the same elevation for 2-3 days
or if descent is initiated; do not exceed a 10-day duration (Luks, 2010).",
" <b>",
" Note:",
" </b>",
" In situations of rapid ascent to altitudes &gt;3500 meters (such as rescue or
military operations), 4 mg every 6 hours may be considered (Luks, 2010).",
" </p>",
" <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
" Treatment: Oral, I.M., I.V.:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
" AMS: 4 mg every 6 hours (Luks, 2010)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
" HACE: Initial: 8 mg as a single dose; Maintenance: 4 mg every 6 hours until
symptoms resolve (Luks, 2010)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Anti-inflammatory:",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
" Oral, I.M., I.V.: 0.75-9 mg/day in divided doses every 6-12 hours",
" </p>",
" <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
" Intra-articular, intralesional, or soft tissue: 0.4-6 mg/day",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Extubation or airway edema:",
" </b>",
" Oral, I.M., I.V.: 0.5-2 mg/kg/day in divided doses every 6 hours beginning 24
hours prior to extubation and continuing for 4-6 doses afterwards",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Antiemetic:",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
" Prophylaxis: Oral, I.V.: 10-20 mg 15-30 minutes before treatment on each
treatment day; continuous infusion regimen: Oral or I.V.: 10 mg every 12 hours on
each treatment day",
" </p>",
" <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
" Mildly emetogenic therapy: Oral, I.M., I.V.: 4 mg every 4-6 hours",
" </p>",
" <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
" Delayed nausea/vomiting: Oral: 4-10 mg 1-2 times/day for 2-4 days",
" <b>",
" or",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
" 8 mg every 12 hours for 2 days; then",
" </p>",
" <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
" 4 mg every 12 hours for 2 days",
" <b>",
" or",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
" 20 mg 1 hour before chemotherapy; then",
" </p>",
" <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
" 10 mg 12 hours after chemotherapy; then",
" </p>",
" <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
" 8 mg every 12 hours for 4 doses; then",
" </p>",
" <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
" 4 mg every 12 hours for 4 doses",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Multiple myeloma:",
" </b>",
" Oral, I.V.: 40 mg/day, days 1-4, 9-12, and 17-20, repeated every 4 weeks
(alone or as part of a regimen)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Cerebral edema:",
" </b>",
" I.V.: 10 mg stat, then 4 mg I.M./I.V. (should be given as sodium phosphate)
every 6 hours until response is maximized, then switch to oral regimen, then taper
off if appropriate; dosage may be reduced after 2-4 days and gradually discontinued
over 5-7 days",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Cushing's syndrome, diagnostic:",
" </b>",
" Oral: 1 mg at 11 PM, draw blood at 8 AM; greater accuracy for Cushing's
syndrome may be achieved by the following:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
" Dexamethasone: 0.5 mg by mouth every 6 hours for 48 hours (with 24-hour urine
collection for 17-hydroxycorticosteroid excretion)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
" Differentiation of Cushing's syndrome due to ACTH excess from Cushing's due
to other causes: Oral: Dexamethasone 2 mg every 6 hours for 48 hours (with 24-hour
urine collection for 17-hydroxycorticosteroid excretion)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Multiple sclerosis (acute exacerbation):",
" </b>",
" Oral: 30 mg/day for 1 week, followed by 4-12 mg/day for 1 month",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Shock, treatment:",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
" Addisonian crisis/shock (eg, adrenal insufficiency/responsive to steroid
therapy): I.V.: 4-10 mg as a single dose, which may be repeated if necessary",
" </p>",
" <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
" Unresponsive shock (eg, unresponsive to steroid therapy): I.V.: 1-6 mg/kg as
a single I.V. dose or up to 40 mg initially followed by repeat doses every 2-6
hours while shock persists",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" <b>",
" Physiological replacement:",
" </b>",
" Oral, I.M., I.V. (should be given as sodium phosphate): 0.03-0.15 mg/kg/day",
" <b>",
" or",
" </b>",
" 0.6-0.75 mg/m",
" ^{",
" 2",
"}",
" /day in divided doses every 6-12 hours",
" </p>",
" </div>",
" <div class=\"block foc drugH1Div\" id=\"F8016329\"
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;\">",
" Elixir, oral: 0.5 mg/5 mL (237 mL)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Baycadron&trade;: 0.5 mg/5 mL (237 mL) [contains benzoic acid, ethanol 5.1%,
propylene glycol; raspberry flavor]",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Injection, solution, as sodium phosphate: 4 mg/mL (1 mL, 5 mL, 30 mL); 10
mg/mL (1 mL, 10 mL)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Injection, solution, as sodium phosphate [preservative free]: 10 mg/mL (1
mL)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Solution, oral: 0.5 mg/5 mL (240 mL, 500 mL)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Solution, oral [concentrate]:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Dexamethasone Intensol&trade;: 1 mg/mL (30 mL) [dye free, sugar free;
contains benzoic acid, ethanol 30%, propylene glycol]",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Tablet, oral: 0.5 mg, 0.75 mg, 1 mg, 1.5 mg, 2 mg, 4 mg, 6 mg",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" DexPak&reg; 6 Day TaperPak&reg;: 1.5 mg [scored; 21 tablets on taper dose
card]",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" DexPak&reg; 10 Day TaperPak&reg;: 1.5 mg [scored; 35 tablets on taper dose
card]",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" DexPak&reg; 13 Day TaperPak&reg;: 1.5 mg [scored; 51 tablets on taper dose
card]",
" </p>",
" </div>",
" <div class=\"block geq drugH1Div\" id=\"F8015651\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Generic Equivalent Available: U.S.",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Yes: Excludes concentrated oral solution",
" </p>",
" </div>",
" <div class=\"block adm drugH1Div\" id=\"F10476979\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Administration",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Oral: May administer with food or milk to decrease GI adverse effects; in
some pediatric croup trials, dose was prepared using a parenteral dexamethasone
formulation and mixing it with an oral flavored syrup (Bjornson, 2004)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Parenteral: I.V.: For doses &lt;10 mg, administer undiluted solution (4
mg/mL) I.V. push over 1-4 minutes; high-dose therapy must be diluted in D",
" _{",
" 5",
"}",
" W or NS and administered by I.V. intermittent infusion over 15-30 minutes;
pH: 7.0-8.5",
" </p>",
" </div>",
" <div class=\"block scp drugH1Div\" id=\"F8015720\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Compatibility",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Stable in D",
" _{",
" 5",
"}",
" W, NS.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Y-site administration: Compatible:",
" </b>",
" Acetaminophen, acyclovir, allopurinol, amifostine, amikacin, amphotericin B
cholesteryl sulfate complex, amsacrine, anidulafungin, aztreonam, bivalirudin,
caffeine citrate, cefepime, cisatracurium, cisplatin, cladribine, cyclophosphamide,
cytarabine, dexmedetomidine, docetaxel, doripenem, doxorubicin, doxorubicin
liposome, etoposide phosphate, famotidine, fentanyl, filgrastim, fluconazole,
fludarabine, foscarnet, gallium nitrate, gemcitabine, granisetron, heparin, heparin
with hydrocortisone sodium succinate, hetastarch in lactate electrolyte injection
(Hextend&reg;), levofloxacin, linezolid, lorazepam, melphalan, meperidine,
meropenem, methadone, milrinone, ondansetron, oxaliplatin, paclitaxel, pemetrexed,
piperacillin/tazobactam, potassium chloride, propofol, remifentanil, sargramostim,
sodium bicarbonate, sufentanil, tacrolimus, telavancin, teniposide, theophylline,
thiotepa, vinorelbine, vitamin B complex with C, zidovudine.",
" <b>",
" Incompatible:",
" </b>",
" Ciprofloxacin, diphenhydramine, fenoldopam, fosaprepitant, haloperidol,
idarubicin, midazolam, pantoprazole, topotecan.",
" <b>",
" Variable (consult detailed reference):",
" </b>",
" Hydromorphone, methotrexate, metoclopramide, morphine.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Compatibility in syringe: Compatible:",
" </b>",
" Caffeine citrate, dimenhydrinate, droperidol, furosemide, granisetron,
ketamine, ketorolac, metoclopramide, palonosetron, ranitidine, sufentanil.",
" <b>",
" Incompatible:",
" </b>",
" Doxapram, famotidine, glycopyrrolate, pantoprazole, promethazine.",
" <b>",
" Variable (consult detailed reference):",
" </b>",
" Diphenhydramine, hydromorphone, midazolam, ondansetron.",
" </p>",
" </div>",
" <div class=\"block sta drugH1Div\" id=\"F10473765\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Stability",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Elixir: Store at 15&deg;C to 30&deg;C (59&deg;F to 86&deg;F); avoid freezing;
dispense in tightly closed container",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Injection: Store at 20&deg;C to 25&deg;C (68&deg;F to 77&deg;F), excursions
permitted to 15&deg;C to 30&deg;C (59&deg;F to 86&deg;F); protect from light and
freezing; dilution with D",
" _{",
" 5",
"}",
" W or NS is stable for at least 24 hours at room temperature or 2 days under
refrigeration temperature (4&deg;C).",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Oral concentrated solution (Intensol&trade;): Store at 20&deg;C to 25&deg;C
(68&deg;F to 77&deg;F); do not freeze; do not use if precipitate is present;
dispense only in original bottle and only with manufacturer-supplied calibrated
dropper; discard open bottle after 90 days.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Oral solution: Store at 20&deg;C to 25&deg;C (68&deg;F to 77&deg;F); dispense
in tightly closed, light-resistant container.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Tablets: Store at 20&deg;C to 25&deg;C (68&deg;F to 77&deg;F); protect from
moisture; dispense in tightly closed, light-resistant container.",
" </p>",
" </div>",
" <div class=\"block use drugH1Div\" id=\"F10473616\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Use",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Oral, parenteral: Primarily as an anti-inflammatory or immunosuppressant
agent in the treatment of a variety of diseases, including those of allergic,
hematologic, dermatologic, neoplastic, rheumatic, autoimmune, nervous system,
renal, and respiratory origin [FDA approved in pediatric patients (age not
specified) and adults]; primary or secondary adrenocorticoid deficiency (not first
line) [FDA approved in pediatric patients (age not specified) and adults];
management of cerebral edema, shock, and as a diagnostic agent [FDA approved in
pediatric patients (age not specified) and adults]. Has also been used as
adjunctive antiemetic agent in the treatment of chemotherapy-induced emesis,
treatment of croup (laryngotracheobronchitis), treatment of airway edema prior to
extubation, treatment of acute mountain sickness (AMS) and high altitude cerebral
edema (HACE), and in neonates with bronchopulmonary dysplasia to facilitate
ventilator weaning",
" </p>",
" </div>",
" <div class=\"block mst drugH1Div\" id=\"F8015647\"
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;\">",
" Dexamethasone may be confused with desoximetasone, dextroamphetamine",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Decadron&reg; may be confused with Percodan&reg;",
" </p>",
" </div>",
" </div>",
" </div>",
" <div class=\"block arm drugH1Div\" id=\"F8015708\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Adverse Reactions",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Cardiovascular: Arrhythmia, bradycardia, cardiac arrest, cardiomyopathy, CHF,
circulatory collapse, edema, hypertension, myocardial rupture (post-MI), syncope,
thromboembolism, vasculitis",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Central nervous system: Depression, emotional instability, euphoria,
headache, intracranial pressure increased, insomnia, malaise, mood swings,
neuritis, personality changes, pseudotumor cerebri (usually following
discontinuation), psychic disorders, seizure, vertigo",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Dermatologic: Acne, allergic dermatitis, alopecia, angioedema, bruising, dry
skin, erythema, fragile skin, hirsutism, hyper-/hypopigmentation, hypertrichosis,
perianal pruritus (following I.V. injection), petechiae, rash, skin atrophy, skin
test reaction impaired, striae, urticaria, wound healing impaired",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Endocrine &amp; metabolic: Adrenal suppression, carbohydrate tolerance
decreased, Cushing's syndrome, diabetes mellitus, glucose intolerance decreased,
growth suppression (children), hyperglycemia, hypokalemic alkalosis, menstrual
irregularities, negative nitrogen balance, pituitary-adrenal axis suppression,
protein catabolism, sodium retention",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Gastrointestinal: Abdominal distention, appetite increased, gastrointestinal
hemorrhage, gastrointestinal perforation, nausea, pancreatitis, peptic ulcer,
ulcerative esophagitis, weight gain",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Genitourinary: Altered (increased or decreased) spermatogenesis",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Hepatic: Hepatomegaly, transaminases increased",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Local: Postinjection flare (intra-articular use), thrombophlebitis",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Neuromuscular &amp; skeletal: Arthropathy, aseptic necrosis (femoral and
humoral heads), fractures, muscle mass loss, myopathy (particularly in conjunction
with neuromuscular disease or neuromuscular-blocking agents), neuropathy,
osteoporosis, parasthesia, tendon rupture, vertebral compression fractures,
weakness",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Ocular: Cataracts, exophthalmos, glaucoma, intraocular pressure increased",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Renal: Glucosuria",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Respiratory: Pulmonary edema",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Miscellaneous: Abnormal fat deposition, anaphylactoid reaction, anaphylaxis,
avascular necrosis, diaphoresis, hiccups, hypersensitivity, impaired wound healing,
infections, Kaposi's sarcoma, moon face, secondary malignancy",
" </p>",
" </div>",
" <div class=\"block coi drugH1Div\" id=\"F10473617\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Contraindications",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Hypersensitivity to dexamethasone or any component, active untreated
infections, systemic fungal infections, cerebral malaria",
" </p>",
" </div>",
" <div class=\"block pre drugH1Div\" id=\"F10473619\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Precautions",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Avoid using higher than recommended doses; suppression of HPA function,
suppression of linear growth (ie, reduction of growth velocity), reduced bone
mineral density, hypercorticism (Cushing's syndrome), hyperglycemia, or glucosuria
may occur; titrate to lowest effective dose. Reduction in growth velocity may occur
when corticosteroids are administered to pediatric patients by any route (monitor
growth). Use with extreme caution in patients with respiratory tuberculosis or
untreated systemic infections. Use with caution in patients with hypertension,
heart failure, or renal impairment; long-term use has been associated with fluid
retention and hypertension. Use with caution in patients with GI diseases
(diverticulitis, peptic ulcer, ulcerative colitis) due to risk of GI bleeding and
perforation. High-dose corticosteroids should not be used for management of head
injury; increased mortality was observed in patients receiving high-dose I.V.
methylprednisolone. Use with caution in patients with myasthenia gravis;
exacerbation of symptoms has occurred especially during initial treatment with
corticosteroids. Use with caution in patients with hepatic impairment, including
cirrhosis; enhanced pharmacologic effect due to decreased metabolism and long-term
use has been associated with fluid retention. Use with caution following acute MI;
corticosteroids have been associated with myocardial rupture; hypertrophic
cardiomyopathy has been reported in premature neonates.",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;\">",
" Use with caution in patients with diabetes; corticosteroids may alter glucose
regulation leading to hyperglycemia. Use with caution in patients with cataracts
and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts
have occurred with prolonged use, consider routine eye exams in chronic users. Use
with caution in patients with a history of seizure disorder; seizures have been
reported with adrenal crisis. Use with caution in patients with thyroid
dysfunction; changes in thyroid status may necessitate dosage adjustments;
metabolic clearance of corticosteroids increases in hyperthyroid patients and
decreases in hypothyroid ones. Dexamethasone does not provide adequate
mineralocorticoid activity in adrenal insufficiency (may be employed as a single
dose while cortisol assays are performed). Prolonged treatment with corticosteroids
has been associated with the development of Kaposi's sarcoma (case reports); if
noted, discontinuation of therapy should be considered. Use with caution in
patients with thromboembolic tendencies or thrombophlebitis.",
" </p>",
" </div>",
" <div class=\"block war drugH1Div\" id=\"F10473618\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Warnings",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Hypothalamic-pituitary-adrenal (HPA) suppression may occur, particularly in
younger children or in patients receiving high doses for prolonged periods; acute
adrenal insufficiency (adrenal crisis) may occur with abrupt withdrawal after long-
term therapy or with stress; withdrawal and discontinuation of corticosteroids
should be tapered slowly and carefully; patients with HPA axis suppression may
require doses of systemic glucocorticosteroids prior to, during, and after unusual
stress (eg, surgery).",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;text-align:justify;\">",
" Immunosuppression may occur; patients may be more susceptible to infections;
prolonged use of corticosteroids may also increase the incidence of secondary
infection, mask acute infection (including fungal infections), prolong or
exacerbate viral or fungal infections, activate latent opportunistic infections, or
limit response to vaccines. Exposure to chickenpox should be avoided;
corticosteroids should not be used to treat ocular herpes simplex; use caution in
patients with a history of ocular herpes simplex. Corticosteroids should not be
used for cerebral malaria or viral hepatitis. Close observation is required in
patients with latent tuberculosis and/or TB reactivity; restrict use in active TB
(only in conjunction with antituberculosis treatment).",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;text-align:justify;\">",
" May cause osteoporosis (at any age) or inhibition of bone growth in pediatric
patients. Use with caution in patients with osteoporosis. In a population-based
study of children, risk of fracture was shown to be increased with &gt;4 courses of
corticosteroids; underlying clinical condition may also impact bone health and
osteoporotic effect of corticosteroids (Leonard, 2006).",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;text-align:justify;\">",
" Corticosteroid use may cause psychiatric disturbances, including depression,
euphoria, insomnia, mood swings, and personality changes. Pre-existing psychiatric
conditions may be exacerbated by corticosteroid use. In premature neonates, the
use of high-dose dexamethasone (approximately &gt;0.5 mg/kg/day) for the prevention
or treatment of BPD has been associated with adverse neurodevelopmental outcomes,
including higher rates of cerebral palsy without additional clinical benefit over
lower doses; current data does not support use of high doses, further studies are
needed (Watterberg, 2010).",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;text-align:justify;\">",
" Acute myopathy may occur with high doses, usually in patients with
neuromuscular transmission disorders; myopathy may involve ocular and/or
respiratory muscles; monitor creatine kinase; recovery may be delayed. Increased
IOP may occur especially with prolonged use; in children, increased IOP has been
shown to be dose-dependent and produce a greater IOP in children &lt;6 years than
older children (Lam, 2005).",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;text-align:justify;\">",
" Rare cases of anaphylactoid reactions have been reported with
corticosteroids.",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;text-align:justify;\">",
" Injection may contain sulfites and 0.5 mg tablet may contain tartrazine,
either may cause allergic reactions in susceptible individuals. Concentrated oral
solution (Intensol&trade;) and elixir may contain ethanol (30% and 5.1%,
respectively). Concentrated oral solution (Intensol&trade;) and elixir contain
propylene glycol; in neonates large amounts of propylene glycol delivered orally,
intravenously (eg, &gt;3000 mg/day), or topically have been associated with
potentially fatal toxicities which can include metabolic acidosis, seizures, renal
failure, and CNS depression; use dosage forms containing propylene glycol with
caution in neonates. Elixir may contain benzoic acid; benzoic acid (benzoate) is a
metabolite of benzyl alcohol; large amounts of benzyl alcohol (&ge;99 mg/kg/day)
have been associated with a potentially fatal toxicity (&ldquo;gasping
syndrome&rdquo;) in neonates; the &ldquo;gasping syndrome&rdquo; consists of
metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction
(including convulsions, intracranial hemorrhage), hypotension and cardiovascular
collapse; use dexamethasone products containing benzoic acid with caution in
neonates;",
" <i>",
" in vitro",
" </i>",
" and animal studies have shown that benzoate displaces bilirubin from protein
binding sites.",
" </p>",
" </div>",
" <div class=\"block cyt drugH1Div\" id=\"F8015710\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Metabolism/Transport Effects",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" <b>",
" Substrate",
" </b>",
" of CYP3A4 (major), P-glycoprotein;",
" <b>",
" Note:",
" </b>",
" Assignment of Major/Minor substrate status based on clinically relevant drug
interaction potential;",
" <b>",
" Inhibits",
" </b>",
" P-glycoprotein;",
" <b>",
" Induces",
" </b>",
" CYP2A6 (weak/moderate), CYP2B6 (weak/moderate), CYP2C9 (weak/moderate),
CYP3A4 (strong), P-glycoprotein",
" </p>",
" </div>",
" <div class=\"block dri drugH1Div\" id=\"F8015711\"
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;\">",
" Acetylcholinesterase Inhibitors: Corticosteroids (Systemic) may enhance the
adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular
weakness may occur.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Aldesleukin: Corticosteroids may diminish the antineoplastic effect of
Aldesleukin.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Aminoglutethimide: May increase the metabolism of Corticosteroids
(Systemic).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Amphotericin B: Corticosteroids (Systemic) may enhance the hypokalemic effect
of Amphotericin B.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Antacids: May decrease the bioavailability of Corticosteroids (Oral).
Management: Consider separating doses by 2 or more hours. Budesonide enteric coated
tablets could dissolve prematurely if given with drugs that lower gastric acid,
with unknown impact on budesonide therapeutic effects.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Antidiabetic Agents: Corticosteroids (Systemic) may diminish the hypoglycemic
effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis
suppression has led to episodes of acute adrenal crisis, which may manifest as
enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic
agent use.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism
of Corticosteroids (Systemic).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Apixaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Apixaban.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Aprepitant: May increase the serum concentration of Corticosteroids
(Systemic).",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" ARIPiprazole: CYP3A4 Inducers may decrease the serum concentration of
ARIPiprazole. Management: Double the oral aripiprazole dose and closely monitor
clinical response. Reduce the oral aripiprazole dose to 10-15 mg/day if the
inducer is discontinued. Avoid use of CYP3A4 inducers for more than 14 days with
extended-release injectable aripiprazole.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Asparaginase (E. coli): May increase the serum concentration of Dexamethasone
(Systemic). This is thought to be due to an asparaginase-related decrease in
hepatic proteins responsible for dexamethasone metabolism.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Asparaginase (Erwinia): May increase the serum concentration of Dexamethasone
(Systemic). This is thought to be due to an asparaginase-related decrease in
hepatic proteins responsible for dexamethasone metabolism.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Axitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Axitinib.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Barbiturates: May decrease the serum concentration of Corticosteroids
(Systemic).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" BCG: Immunosuppressants may diminish the therapeutic effect of BCG.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Bedaquiline: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Bedaquiline.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Bile Acid Sequestrants: May decrease the absorption of Corticosteroids
(Oral).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Boceprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Boceprevir. Management: Avoid strong CYP3A4 inducers with boceprevir when
possible, and closely monitor response to boceprevir if such a combination cannot
be avoided. Carbamazepine, phenytoin, phenobarbital, rifampin, and St. John's wort
are considered contraindicated.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Bosutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Bosutinib.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum
concentration of Brentuximab Vedotin. Specifically, concentrations of the active
monomethyl auristatin E (MMAE) component may be decreased.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Cabozantinib: CYP3A4 Inducers (Strong) may decrease the serum concentration
of Cabozantinib.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Calcitriol: Corticosteroids (Systemic) may diminish the therapeutic effect of
Calcitriol.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Calcium Channel Blockers (Nondihydropyridine): May decrease the metabolism of
Corticosteroids (Systemic).",
" <b>",
" Exceptions:",
" </b>",
" Bepridil [Off Market].",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Caspofungin: Inducers of Drug Clearance may decrease the serum concentration
of Caspofungin. Management: Consider using an increased caspofungin dose of 70 mg
daily in adults (or 70 mg/m",
" ^{",
" 2",
"}",
" , up to a maximum of 70 mg, daily in pediatric patients) when coadministered
with known inducers of drug clearance.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Cobicistat: Dexamethasone (Systemic) may decrease the serum concentration of
Cobicistat.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect
of Coccidioidin Skin Test.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Conivaptan: May increase the serum concentration of CYP3A4 Substrates.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Corticorelin: Corticosteroids may diminish the therapeutic effect of
Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted
by recent or current corticosteroid therapy.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Crizotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Crizotinib.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" CycloSPORINE (Systemic): May increase the serum concentration of
Dexamethasone (Systemic). Dexamethasone (Systemic) may decrease the serum
concentration of CycloSPORINE (Systemic). Dexamethasone (Systemic) may increase the
serum concentration of CycloSPORINE (Systemic).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates.
Management: Consider an alternative for one of the interacting drugs. Some
combinations may be specifically contraindicated. Consult appropriate manufacturer
labeling.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4
Substrates.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4
Substrates.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" CYP3A4 Substrates: CYP3A4 Inducers (Strong) may increase the metabolism of
CYP3A4 Substrates. Management: Consider an alternative for one of the interacting
drugs. Some combinations may be specifically contraindicated. Consult appropriate
manufacturer labeling.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Dabigatran Etexilate: P-glycoprotein/ABCB1 Inducers may decrease the serum
concentration of Dabigatran Etexilate. Management: Avoid concurrent use of
dabigatran with p-glycoprotein inducers when possible. Closely monitor for
decreased levels/effects of dabigatran if concomitantly administering p-
glycoprotein inducers, particularly strong inducers.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Dasatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Dasatinib. Management: Avoid when possible. If such a combination cannot be
avoided, consider increasing dasatinib dose and monitor clinical response and
toxicity closely.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Dasatinib: May increase the serum concentration of CYP3A4 Substrates.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Deferasirox: Corticosteroids (Systemic) may enhance the adverse/toxic effect
of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding
may be increased.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Deferasirox: Corticosteroids may enhance the adverse/toxic effect of
Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may
be increased.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Denosumab: May enhance the adverse/toxic effect of Immunosuppressants.
Specifically, the risk for serious infections may be increased.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Dronedarone: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Dronedarone.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Echinacea: May diminish the therapeutic effect of Immunosuppressants.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Elvitegravir: Dexamethasone (Systemic) may decrease the serum concentration
of Elvitegravir.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Enzalutamide: CYP3A4 Inducers (Strong) may decrease the serum concentration
of Enzalutamide.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Estrogen Derivatives: May increase the serum concentration of Corticosteroids
(Systemic).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Everolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Everolimus. Management: Avoid concurrent use of strong CYP3A4 inducers, but if
strong CYP3A4 inducers cannot be avoided, consider gradually (in 5 mg increments)
increasing the everolimus dose from 10 mg/day to 20 mg/day (adult doses).",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Exemestane: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Exemestane. Management: Exemestane U.S. product labeling recommends using an
increased dose (50 mg/day) in patients receiving concurrent strong CYP3A4 inducers.
The Canadian product labeling does not recommend a dose adjustment with concurrent
use of strong CYP3A4 inducers.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Fluconazole: May decrease the metabolism of Corticosteroids (Systemic).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Fosaprepitant: May increase the serum concentration of Corticosteroids
(Systemic). The active metabolite aprepitant is likely responsible for this
effect.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Gefitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Gefitinib. Management: In the absence of severe adverse drug reactions, consider
increasing gefitinib dose to 500 mg daily in patients receiving strong CYP3A4
inducers. Carefully monitor clinical response and development of adverse
reactions.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" GuanFACINE: CYP3A4 Inducers (Strong) may decrease the serum concentration of
GuanFACINE. Management: Consider increasing the guanfacine dose by 2-fold when
adding a strong CYP3A4 inducer. Titrate the guanfacine dose up to a max of 8
mg/day when starting guanfacine in a patient who is taking a strong CYP3A4
inhibitor.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates.
Management: Consider avoiding CYP3A4 inducing herbs in order to avoid therapeutic
failure of the substrate. Some combinations may be specifically contraindicated.
Consult appropriate manufacturer labeling.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Hyaluronidase: Corticosteroids may diminish the therapeutic effect of
Hyaluronidase. Management: Patients receiving corticosteroids (particularly at
larger doses) may not experience the desired clinical response to standard doses of
hyaluronidase. Larger doses of hyaluronidase may be required.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Ifosfamide: CYP3A4 Inducers (Strong) may increase serum concentrations of the
active metabolite(s) of Ifosfamide.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Imatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Imatinib. Management: Avoid concurrent use of imatinib with strong CYP3A4 inducers
when possible. If such a combination must be used, increase imatinib dose by at
least 50% and monitor the patient's clinical response closely.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Indacaterol: May enhance the hypokalemic effect of Corticosteroids
(Systemic).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Isoniazid: Corticosteroids (Systemic) may decrease the serum concentration of
Isoniazid.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Ivacaftor.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Ivacaftor: May increase the serum concentration of CYP3A4 Substrates.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Ixabepilone: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Ixabepilone. Management: Avoid this combination whenever possible. If this
combination must be used, a gradual increase in ixabepilone dose from 40 mg/m",
" ^{",
" 2",
"}",
" to 60 mg/m",
" ^{",
" 2",
"}",
" (given as a 4-hour infusion), as tolerated, should be considered.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Lapatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Lapatinib. Management: If therapy overlap cannot be avoided, consider titrating
lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic
breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive
breast cancer) as tolerated.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of
Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider
not using a leflunomide loading dose in patients receiving other
immunosuppressants. Patients receiving both leflunomide and another
immunosuppressant should be monitored for bone marrow suppression at least
monthly.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Lenalidomide: Dexamethasone (Systemic) may enhance the thrombogenic effect of
Lenalidomide.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Loop Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect
of Loop Diuretics.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Lurasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Lurasidone.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Macrolide Antibiotics: May decrease the metabolism of Corticosteroids
(Systemic).",
" <b>",
" Exceptions:",
" </b>",
" Azithromycin (Systemic); Fidaxomicin; Spiramycin.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Maraviroc: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice daily when
used with strong CYP3A4 inducers. This does not apply to patients also receiving
strong CYP3A4 inhibitors. Do not use maraviroc with strong CYP3A4 inducers in
patients with Clcr less than 30 mL/min.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Mifepristone: May diminish the therapeutic effect of Corticosteroids
(Systemic). Mifepristone may increase the serum concentration of Corticosteroids
(Systemic). Management: Avoid mifepristone in patients who require long-term
corticosteroid treatment of serious illnesses or conditions (e.g., for
immunosuppression following transplantation). Corticosteroid effects may be reduced
by mifepristone treatment.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Mitotane: May decrease the serum concentration of Corticosteroids
(Systemic).",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of
Natalizumab. Specifically, the risk of concurrent infection may be increased.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Neuromuscular-Blocking Agents (Nondepolarizing): May enhance the adverse
neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness,
possibly progressing to polyneuropathies and myopathies, may occur.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" NIFEdipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of
NIFEdipine. Management: Consider alternatives to nifedipine for patients who are
using strong CYP3A4 inducers. At least one specific brand of nifedipine (Adalat
CC) lists this combination as contraindicated.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Nilotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Nilotinib.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Nisoldipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Nisoldipine.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" NSAID (COX-2 Inhibitor): Corticosteroids (Systemic) may enhance the
adverse/toxic effect of NSAID (COX-2 Inhibitor).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" NSAID (Nonselective): Corticosteroids (Systemic) may enhance the
adverse/toxic effect of NSAID (Nonselective).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Pazopanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Pazopanib.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Perampanel: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Perampanel. Management: Avoid use of perampanel with strong CYP3A inducers other
than enzyme-inducing antiepileptic drugs (EIAEDs). Increase perampanel starting
dose to 4 mg/day when used with EIAEDs such as phenytoin, carbamazepine, or
oxcarbazepine.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-
glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the
distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-
glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes,
etc.).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-
glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the
distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-
glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes,
etc.).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inducers may decrease
the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers
may also further limit the distribution of p-glycoprotein substrates to specific
cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain,
T-lymphocytes, testes, etc.).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Pomalidomide: P-glycoprotein/ABCB1 Inducers may decrease the serum
concentration of Pomalidomide.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Ponatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Ponatinib.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Praziquantel: CYP3A4 Inducers (Strong) may decrease the serum concentration
of Praziquantel. Management: Avoid concomitant use of praziquantel with strong
CYP3A4 inducers. Discontinue rifampin 4 weeks prior to initiation of praziquantel
therapy. Rifampin may be resumed the day following praziquantel completion.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Primidone: May decrease the serum concentration of Corticosteroids
(Systemic).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Quinolone Antibiotics: May enhance the adverse/toxic effect of
Corticosteroids (Systemic). Risk of tendon-related side effects, including
tendonitis and rupture, may be enhanced.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Ranolazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Ranolazine.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Regorafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Regorafenib.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Rifamycin Derivatives: May increase the metabolism of Corticosteroids
(Systemic).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Rilpivirine: Dexamethasone (Systemic) may decrease the serum concentration of
Rilpivirine.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Rivaroxaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Rivaroxaban.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Roflumilast: May enhance the immunosuppressive effect of
Immunosuppressants.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" RomiDEPsin: CYP3A4 Inducers (Strong) may decrease the serum concentration of
RomiDEPsin.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Salicylates: May enhance the adverse/toxic effect of Corticosteroids
(Systemic). These specifically include gastrointestinal ulceration and bleeding.
Corticosteroids (Systemic) may decrease the serum concentration of Salicylates.
Withdrawal of corticosteroids may result in salicylate toxicity.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of
Sipuleucel-T.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" SORAfenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
SORAfenib.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" SUNItinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
SUNItinib. Management: Avoid when possible. If such a combination cannot be
avoided, consider increasing sunitinib dose and monitor clinical response and
toxicity closely.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Tacrolimus (Topical): May enhance the adverse/toxic effect of
Immunosuppressants.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Tadalafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Tadalafil. Management: Erectile dysfunction: monitor for decreased effectiveness -
no standard dose adjustments recommended. Avoid use of tadalafil for pulmonary
arterial hypertension in patients receiving a strong CYP3A4 inducer.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Telaprevir: May increase the serum concentration of Corticosteroids
(Systemic). Corticosteroids (Systemic) may decrease the serum concentration of
Telaprevir. Management: Concurrent use of telaprevir and systemic corticosteroids
is not recommended. When possible, consider alternatives. If used together,
employ extra caution and monitor closely for excessive corticosteroid effects and
diminished telaprevir effects.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Telaprevir: Corticosteroids may decrease the serum concentration of
Telaprevir. Telaprevir may increase the serum concentration of Corticosteroids.
Management: Concurrent use of telaprevir and systemic corticosteroids is not
recommended. When possible, consider alternatives. If used together, employ extra
caution and monitor closely for excessive corticosteroid effects and diminished
telaprevir effects.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Thalidomide: Dexamethasone (Systemic) may enhance the dermatologic adverse
effect of Thalidomide. Dexamethasone (Systemic) may enhance the thrombogenic effect
of Thalidomide.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Thiazide Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic
effect of Thiazide Diuretics.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Ticagrelor: CYP3A4 Inducers (Strong) may decrease serum concentrations of the
active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Strong) may decrease the serum
concentration of Ticagrelor.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of
Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate
or other non-disease modifying antirheumatic drugs (non-DMARDs) is permitted, and
this warning seems to particularly focused on more potent immunosuppressants.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Tolvaptan: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Tolvaptan. Management: If concurrent use is necessary, increased doses of
tolvaptan (with close monitoring for toxicity and clinical response) may be
needed.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Toremifene: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Toremifene.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Trastuzumab: May enhance the neutropenic effect of Immunosuppressants.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Ulipristal: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Ulipristal.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic
effect of Vaccines (Inactivated).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Vaccines (Live): Corticosteroids (Systemic) may enhance the adverse/toxic
effect of Vaccines (Live).",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Vandetanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Vandetanib.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Vemurafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of
Vemurafenib.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" VinCRIStine (Liposomal): CYP3A4 Inducers (Strong) may decrease the serum
concentration of VinCRIStine (Liposomal).",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inducers may decrease the serum
concentration of VinCRIStine (Liposomal).",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Warfarin: Corticosteroids (Systemic) may enhance the anticoagulant effect of
Warfarin.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease the serum concentration
of Zuclopenthixol.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" </div>",
" <div class=\"block foi drugH1Div\" id=\"F10473764\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Food Interactions",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Systemic use of corticosteroids may require a diet with increased potassium,
vitamins A, B",
" _{",
" 6",
"}",
" , C, D, folate, calcium, zinc, and phosphorus and decreased sodium",
" </p>",
" </div>",
" <div class=\"block prf drugH1Div\" id=\"F8015698\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pregnancy Risk Factor",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" C (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
" show table",
" </a>",
" )",
" </p>",
" </div>",
" <div class=\"block pri drugH1Div\" id=\"F8015699\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pregnancy Implications",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Adverse events have been observed with corticosteroids in animal reproduction
studies. Dexamethasone crosses the placenta; and is partially metabolized to an
inactive metabolite by placental enzymes. Due to its positive effect on stimulating
fetal lung maturation, the injection is often used in patients with premature labor
(24-34 weeks gestation). Some studies have shown an association between first
trimester systemic corticosteroid use and oral clefts; adverse events in the
fetus/neonate have been noted in case reports following large doses of systemic
corticosteroids during pregnancy. Women exposed to dexamethasone during pregnancy
for the treatment of an autoimmune disease may contact the OTIS Autoimmune Diseases
Study at 877-311-8972.",
" </p>",
" </div>",
" <div class=\"block mop drugH1Div\" id=\"F10477064\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Monitoring Parameters",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Hemoglobin, occult blood loss, blood pressure, serum potassium and glucose;
IOP with systemic use &gt;6 weeks; weight and height in children",
" </p>",
" </div>",
" <div class=\"block rer drugH1Div\" id=\"F10477065\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Reference Range",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Dexamethasone suppression test: 8 AM cortisol &lt;6 mcg/100 mL in adults
given dexamethasone 1 mg at 11 PM the previous night",
" </p>",
" </div>",
" <div class=\"block pha drugH1Div\" id=\"F10473766\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Mechanism of Action",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Decreases inflammation by suppression of migration of polymorphonuclear
leukocytes and reversal of increased capillary permeability; suppresses normal
immune response",
" </p>",
" </div>",
" <div class=\"block phd drugH1Div\" id=\"F10473767\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pharmacodynamics",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Duration: Metabolic effects can last for 72 hours",
" </p>",
" </div>",
" <div class=\"block phk drugH1Div\" id=\"F10473768\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pharmacokinetics (Adult data unless noted)",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Metabolism: In the liver",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Half-life: Terminal:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" Extremely low birth-weight infants with BPD: 9.3 hours",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" Children 3 months to 16 years: 4.3 hours",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" Healthy adults: 3 hours",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Time to peak serum concentration:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" Oral: Within 1-2 hours",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" I.M.: Within 8 hours",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Elimination: In urine and bile",
" </p>",
" </div>",
" <div class=\"block pai drugH1Div\" id=\"F10477067\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Patient Information",
" </span>",
" <p>",
" (For additional information",
" <a class=\"drug drug_patient\" href=\"UTD.htm?40/45/41686?
source=see_link\">",
" see \"Dexamethasone (systemic): Patient drug information\"",
" </a>",
" )",
" </p>",
" <p style=\"text-indent:0em;display:inline\">",
" Do not take any new medication during therapy unless approved by prescriber.
Take exactly as directed, do not increase dose or discontinue abruptly without
consulting prescriber.",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;\">",
" Oral: Take with or after meals. Avoid alcohol and limit intake of caffeine or
stimulants. Prescriber may recommend increased dietary vitamins, minerals, or iron.
If you have diabetes, monitor glucose levels closely (antidiabetic medication may
need to be adjusted). Inform prescriber if you are experiencing greater-than-normal
levels of stress (medication may need adjustment). You may be more susceptible to
infection (avoid crowds and persons with contagious or infective conditions and do
not have any vaccinations unless approved by prescriber). Avoid exposure to measles
or chicken pox; advise physician immediately if exposed; notify physician if acute
illness including fever or other signs of infection occurs. Some forms of this
medication may cause GI upset (small frequent meals and frequent mouth care may
help). Report promptly excessive nervousness or sleep disturbances; signs of
infection (eg, sore throat, unhealed injuries); excessive growth of body hair or
loss of skin color; vision changes; weight gain; swelling of face or extremities;
respiratory difficulty; muscle weakness; tarry stool, persistent abdominal pain;
worsening of condition or failure to improve. Inform physician you are taking
corticosteroid prior to any surgery or with any injury.",
" </p>",
" </div>",
" <div class=\"block adi drugH1Div\" id=\"F10477068\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Additional Information",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Systemic: Due to the long duration of effect (36-54 hours), alternate day
dosing does not allow time for adrenal recovery between doses.",
" </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\">",
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target=\"_blank\">",
" 17332238",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Luks AM, McIntosh SE, Grissom CK, et al, \"Wilderness Medical Society
Consensus Guidelines for the Prevention and Treatment of Acute Altitude
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" Wilderness Environ Med",
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" , 2010, 21(2):146-55.",
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" 20591379",
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" <li>",
" <div class=\"reference\">",
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" JAMA",
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" , 2008, 299(17):2048-55.",
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" Onland W, Offringa M, De Jaegere AP, et al, \"Finding the Optimal Postnatal
Dexamethasone Regimen for Preterm Infants at Risk of Bronchopulmonary Dysplasia: A
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" ]",
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" Phillips RS, Gopaul S, Gibson F, et al, \"Antiemetic Medication for
Prevention and Treatment of Chemotherapy Induced Nausea and Vomiting in
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" Cochrane Database Syst Rev",
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" , 2010, (9):CD007786.",
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" <div class=\"reference\">",
" Pollard AJ, Niermeyer S, Barry P, et al, \"Children at High Altitude: An
International Consensus Statement by an Ad Hoc Committee of the International
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" <i>",
" High Alt Med Biol",
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" , 2001, 2(3):389-403.",
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" <i>",
" Red Book: 2009 Report of the Committee on Infectious Diseases",
" </i>",
" , 28th ed, Pickering LK, ed, Elk Grove Village, IL: American Academy of
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" Rittichier KK and Ledwith CA, \"Outpatient Treatment of Moderate Croup With
Dexamethasone: Intramuscular Versus Oral Dosing,\"",
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" , 2000, 106(6):1344-8.",
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" Russell K, Wiebe N, Saenz A, et al, \"Glucocorticoids for Croup,\"",
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" Cochrane Database Syst Rev",
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" , 2004, (1):CD001955.",
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" </span>",
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" </li>",
" <li>",
" <div class=\"reference\">",
" Sparrow A and Geelhoed G, \"Prednisolone Versus Dexamethasone in Croup: A
Randomised Equivalence Trial,\"",
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" Arch Dis Child",
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" , 2006, 91(7):580-3.",
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" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Tellez DW, Galvis AG, Storgion SA, et al, \"Dexamethasone in the Prevention
of Postextubation Stridor in Children,\"",
" <i>",
" J Pediatr",
" </i>",
" , 1991, 118(2):289-94.",
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" <a href=\"UTD.htm?6/18/6442/abstract-text/1993963/pubmed\" id=\"1993963\"
target=\"_blank\">",
" 1993963",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Tunkel AR, Hartman BJ, Kaplan SL, et al, \"Practice Guidelines for the
Management of Bacterial Meningitis,\"",
" <i>",
" Clin Infect Dis",
" </i>",
" , 2004, 39(9):1267-84.",
" <span class=\"pubmed-id\">",
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" <a href=\"UTD.htm?6/18/6442/abstract-text/15494903/pubmed\" id=\"15494903\"
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" 15494903",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" van de Beek D, Farrar JJ, de Gans J, et al, \"Adjunctive Dexamethasone in
Bacterial Meningitis: A Meta-analysis of Individual Patient Data,\"",
" <i>",
" Lancet Neurol",
" </i>",
" , 2010, 9(3):254-63.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/18/6442/abstract-text/20138011/pubmed\" id=\"20138011\"
target=\"_blank\">",
" 20138011",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Walther FJ, Findlay RD, and Durand M, \"Adrenal Suppression and Extubation
Rate After Moderately Early Low-Dose Dexamethasone Therapy in Very Preterm
Infants,\"",
" <i>",
" Early Hum Dev",
" </i>",
" , 2003, 74(1):37-45.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/18/6442/abstract-text/14512180/pubmed\" id=\"14512180\"
target=\"_blank\">",
" 14512180",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Watterberg KL and American Academy of Pediatrics. Committee on Fetus and
Newborn, \"Policy Statement--Postnatal Corticosteroids to Prevent or Treat
Bronchopulmonary Dysplasia,\"",
" <i>",
" Pediatrics",
" </i>",
" , 2010, 126(4):800-8.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/18/6442/abstract-text/20819899/pubmed\" id=\"20819899\"
target=\"_blank\">",
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" Brand Names: U.S.",
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" Pharmacodynamics",
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" Patient Information",
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source=related_link\">",
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source=related_link\">",
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" Adapted from: Moore, EE, Cogbill, TH, Jurkovich, GJ, et al. Organ injury
scaling: spleen and liver (1994 revision). J Trauma 1995; 38:323.",
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" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=ID
%2F71663&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=ID
%2F71663&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\">",
" <div class=\"ttl\">",
" Differential diagnosis of fever and rash based upon appearance of the rash",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <colgroup span=\"4\" width=\"25%\">",
" </colgroup>",
" <tbody>",
" <tr>",
" <td class=\"subtitle1\">",
" Macules, papules, nodules, or plaques",
" </td>",
" <td class=\"subtitle1\">",
" Vesicles, bullae, or pustules",
" </td>",
" <td class=\"subtitle1\">",
" Purpuric macules, purpuric papules, or purpuric vesicles",
" </td>",
" <td class=\"subtitle1\">",
" Widespread erythema with or without edema followed by desquamation",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle2_left\" colspan=\"4\">",
" Protozoal/parasitic",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" <p>",
" Leishmania braziliensis",
" </p>",
" <p>",
" Leishmania mexicana",
" </p>",
" <p>",
" Leishmania tropica",
" </p>",
" <p>",
" Necator americanus",
" </p>",
" <p>",
" Onchocerca volvulus",
" </p>",
" <p>",
" Schistosoma",
" </p>",
" <p>",
" Strongyloides stercoralis",
" </p>",
" <p>",
" Toxoplasma gondii (toxoplasmosis)",
" </p>",
" <p>",
" Trichinella spiralis (trichinosis)",
" </p>",
" <p>",
" Trypanosoma sp.",
" </p>",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td>",
" <p>",
" Plasmodium falciparum (blackwater fever)*",
" </p>",
" <p>",
" Trichinella spiralis (trichinosis)",
" </p>",
" <p>",
" Toxoplasma gondii",
" </p>",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle2_left\" colspan=\"4\">",
" Noninfectious",
" </td>",
" </tr>",
" <tr>",
" <td class=\"indent1\">",
" <p>",
" Erythema multiforme",
" </p>",
" <p>",
" Systemic lupus erythematosus",
" </p>",
" <p>",
" Dermatomyositis",
" </p>",
" <p>",
" Drug hypersensitivities",
" </p>",
" <p>",
" Gianotti-Crosti syndrome",
" </p>",
" <p>",
" Inflammatory bowel disease",
" </p>",
" <p>",
" Pityriasis rosea (fever rare)",
" </p>",
" <p>",
" Sarcoidosis",
" </p>",
" <p>",
" \"Serum sickness\"",
" ^{",
" &bull;",
"}",
" </p>",
" <p>",
" Sweet's syndrome (acute febrile neutrophilic dermatosis)",
" </p>",
" <p>",
" Still's disease (juvenile idiopathic arthritis)",
" </p>",
" </td>",
" <td>",
" <p>",
" Erythema multiforme bullosum",
" </p>",
" <p>",
" Toxic epidermal necrolysis",
" </p>",
" <p>",
" Dermatitis from plants",
" </p>",
" <p>",
" Drug hypersensitivities",
" </p>",
" </td>",
" <td>",
" <p>",
" \"Allergic\" vasculitis",
" ^{",
" &bull;",
"}",
" </p>",
" <p>",
" Erythroderma",
" </p>",
" <p>",
" Cholesterol embolization",
" </p>",
" <p>",
" Disseminated intravascular coagulation (purpura fulminans)",
" ^{",
" &Delta;",
"}",
" </p>",
" <p>",
" Drug hypersensitivities",
" </p>",
" <p>",
" Fat embolism",
" </p>",
" <p>",
" Henoch-Sch&ouml;nlein purpura",
" </p>",
" <p>",
" Immune thrombocytopenic purpura",
" </p>",
" <p>",
" Granulomatosis with polyangiitis (Wegener's)",
" </p>",
" </td>",
" <td>",
" <p>",
" Erythroderma",
" </p>",
" <p>",
" Drug hypersensitivities",
" </p>",
" <p>",
" Graft-versus-host reaction",
" </p>",
" <p>",
" Stevens-Johnson syndrome",
" </p>",
" <p>",
" Toxic epidermal necrolysis",
" </p>",
" <p>",
" von Zumbusch pustular psoriasis",
" </p>",
" </td>",
" </tr>",
" </tbody>",
" </table>",
" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" * Reportable disease.",
" <br/>",
" <span class=\"bullet\">",
" &bull;",
" </span>",
" May have arthralgia or musculoskeletal pain.",
" <br/>",
" &Delta; Often present as infarcts.",
" </div>",
" <div class=\"reference\">",
" Adapted with permission from: Sanders CV. Diagnosis of the patient with fever
and rash. In: The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt
LT (Eds), Williams &amp; Wilkins, Baltimore, 1995. Originally modified with
permission from: Fitzpatrick TB, et al: Color Atlas &amp; Synopsis of Clinical
Dermatology - Common and Serious Diseases. Fitzgerald TB, et al (Eds), McGraw-Hill,
New York, 1992.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_18_6445=[""].join("\n");
var outline_f6_18_6445=null;
var title_f6_18_6446="Drug effect on AV node";
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" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
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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=CARD
%2F51932&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
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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\" style=\"width: 481px\">",
" <div class=\"ttl\">",
" Effect of drugs on AV function in AF",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" Various drugs can slow conduction through the atrioventricular node in atrial
fibrillation by altering its physiology. The calcium (Ca++) channel blockers,
primarily diltiazem and verapamil, block the influx of calcium and therefore slow
conduction by reducing the upstroke of the action potential; digoxin, carotid
massage, Valsalva maneuver, and edrophonium are vagotonic and slow conduction by
increasing parasympathetic effects on the node; beta blockers slow conduction by
offsetting sympathetic inputs; and adenosine slows conduction only transiently by
increasing potassium conduction and decreasing calcium influx.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
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var outline_f6_18_6446=null;
var title_f6_18_6447="Popliteal aneurysm on CT angiography";
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" &copy;2013 UpToDate",
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" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
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" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Popliteal aneurysm on CT angiography",
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" </div>",
" <div class=\"lgnd\">",
" The CT angiogram demonstrates a large right popliteal artery aneurysm and
tortuous distal superficial femoral artery. The true diameter of the aneurysm must
be measured from cross-sectional two-dimensional images; this three-dimensional CT
reconstruction shows only regions where intravenous contrast is present.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Amy B Reed, MD.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
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