Mediastinitis

Background
Mediastinitis is an infection involving the mediastinum. It is a surgical emergency with a high
mortality rate. Mediastinitis may begin primarily from structures in the mediastinum, or it may be
the result of an infection extending downward from the oropharynx, in which case it is called
descending necrotizing mediastinitis.

Pathophysiology
Infection of the mediastinum is typically polymicrobial in nature resulting from a disruption of
normal mucosal and tissue barriers. Infection may result from a rupture of the esophagus or
trachea or from surgical intervention. When infection extends from the head and neck downward
into the mediastinum, the condition is described as descending necrotizing mediastinitis
because the infection uses the fascial planes in the neck to gain access to the mediastinum.
The spread downward is facilitated by gravity, breathing and negative intrathoracic pressure. It is
necrotizing, as the infection is often polymicrobial in etiology with gas-producing organisms. This
is the most lethal form of mediastinitis, partly due to delayed diagnosis and treatment.
Odontogenic infection is the most common cause.The potential spaces that can allow infections
from the head or neck to enter the mediastinum include the following:
Carotid space
The carotid sheath is a thick, matted, fibrous investment over the main longitudinal vessels of
the neck. Lymph nodes are contained within the sheath, and infection in these nodes potentially
could spread downward into the mediastinum. The carotid sheath extends from the arch of the
aorta to the base of the skull.
Prevertebral space
This space is bounded anteriorly by the prevertebral fascia, which overlies the prevertebral
muscles in the neck. The prevertebral fascia extends from the base of the skull to the lower limit
of the longus colli muscle, which is approximately at the level of T3 vertebra.
Danger space
This potential space lies between the alar and prevertebral fasciae. It is patent from the skull
base to the diaphragm. Its upper part is the retropharyngeal space, which lies between the
prevertebral fascia and the buccopharyngeal fascia on the outer surface of the pharynx. Lymph
nodes are present in this space. Seventy percent of cases of descending necrotizing
mediastinitis occur in this space.
Pathological walling-off of infection usually occurs in the retropharyngeal space, but no
anatomical barrier exists to the spread of infection downward into the mediastinum. The lower
part of this potential space extends behind the esophagus, through the superior mediastinum,
and into the posterior mediastinum. Because cervico-mediastinal spaces contain loose areolar
tissue with poor vascularization and few defensive mechanisms, pathogens may easily spread
across fascial planes. For this reason, any cervical infection may involve the entire
mediastinum.

More than 90% of cases of acute mediastinitis are caused by esophageal rupture. This may be
due to trauma (eg, MVA, chicken bone), neoplasm, surgery, or endoscopy.
Comorbid conditions (eg, diabetes) may make certain patients highly susceptible to spreading
cellulitis. Mediastinitis may also result from direct extension from an adjacent source of infection
including osteomyelitis of the sternoclavicular junction. Pulmonary infections may also extend
into the mediastinal space. Mediastinitis may also result from extension of granulomatous
disease from mediastinal lymph nodes.
Pathogens
This is often a mixed infection, with facultative and strict aerobes acting together. Obligate
anaerobes usually outnumber facultative organisms by 10:1. Streptococcus species are the
most common facultative organisms, while Bacteroides species are the most common strict
aerobes. Other organisms implicated includeStaphylococcus, Escherichia coli,
Peptostreptococcus, Fusobacterium, Haemophilus influenzae, Enterobacter cloacae,
Histoplasmosis, Tuberculosis and Pseudomonas aeruginosa.

Frequency
United States
Esophageal rupture is the most common cause of mediastinitis currently. Descending
necrotizing infection is relatively rare in the era of antibiotic use.
International
In developing countries, mediastinitis still is a common devastating potential complication of
head and neck infections.
Mortality/Morbidity

Morbidity is significant for a mean hospital length of stay greater than 1 month, as well
as a long period of outpatient recovery.
Data suggest an overall lifetime mortality rate of 19-47%; however, a review by Ridder et
al suggests an improved mortality of 11.1%.

Studies of descending necrotizing mediastinitis in the last decade indicate mortality rates
ranging between 11.1-34.9%.

Mortality likely has improved secondary to the widespread use of antibiotics and
improved oral hygiene.

In the presence of comorbid conditions, the mortality rate for patients presenting with
established infections may be as high as 67%.

Race
Age and risk factors are better predictors for the development of descending necrotizing
mediastinitis than race.
Sex
Prevalence is higher among males than females, with a male-to-female ratio of 6:1.

Age

Mediastinitis appears to be a disease of young men with a mean age in the mid fourth
decade of life.
Most persons with mediastinitis are in their third to fifth decades of life; however, case
reports have documented mediastinitis in patients as young as 2 months and as old as
the eighth decade.

Clinical
History
Patients usually have experienced symptoms for a few days before presentation to the ED.
Occasionally, patients present with a fulminant course and symptoms that have lasted only a
few hours.

Common symptoms and signs of patients with mediastinitis include the following:
o History of an upper respiratory tract infection or a recent dental infection
(common), or thoracic surgery/instrumentation
o

Fever, chills

Pleuritic, retrosternal chest pain radiating to the neck or interscapular pain

Shortness of breath

Confusion

Sore throat

Swelling in the neck

Odynophagia

History may be significant for recent endoscopy, bronchoscopy, intubation, or surgery.

Some patients are at an increased risk for mediastinitis. Obtaining the patient's medical
history, which should include explicit questions about diabetes, possible
immunocompromise (eg, malignancy/chemotherapy, HIV, autoimmune disease), and
drug abuse, is very important.

Physical
A complete examination of the head and neck, including the oral cavity, is essential. Such an
examination may yield findings such as the following:

Ill appearance
Fever

Edema of the neck and face

Crepitus of chest or neck

Hamman sign (crunching sound upon auscultation of the heart)

Stridor

Trismus

Cranial nerve deficits

Laboratory Studies

The diagnosis of mediastinitis is often a clinical one. No single laboratory investigation

can confirm the diagnosis; however, studies that may help in the diagnosis of
mediastinitis include the following:
o WBC count may be significantly elevated.
o

Electrolytes and glucose measurements may reveal anion gap or indication of

underlying diabetes.

Blood cultures

Swab from any site of infection

It is important to notify the laboratory of the possible presence of anaerobic organisms

and the strong possibility of mixed growth.
o

Many laboratories routinely report only a single predominant organism.

Close coordination with the laboratory is vital to optimize the antibiotic regimen.

Imaging Studies

Plain-film radiography
o Soft tissue radiography of the neck may show widening of the precervical and
retropharyngeal soft tissues.
o

Any patient who presents with gas in the soft tissues of the neck and concern for
possible mediastinitis probably should undergo further investigation (ie, CT, MRI)
to determine if mediastinal spread of the infection has occurred.

Plain-film chest radiographs may show widening of the paratracheal soft tissues.

The lateral chest radiograph may show an anterior bulge on the posterior wall of
the trachea.

Pleural effusions and lower lobe consolidation are not unusual findings.

Prehospital Care
Mediastinitis may result in airway compromise. Protection of the airway is vital. Since patients
may present in septic shock, adequate volume resuscitation is essential.
Emergency Department Care

Ensure an adequate airway.

o Do not allow a patient who is potentially unstable to be placed into the CT
scanner without ensuring that the airway is adequately protected.

Intubation may be difficult because of soft tissue swelling. Fiberoptic assistance

may be required and the patient may need an emergent cricothyrotomy or
tracheostomy.

In addition to the usual complications of intubation, it may be further complicated

by trauma to the retropharyngeal wall, laryngospasm, or aspiration of purulent
material.

Antibiotic therapy should be initiated without delay.

Fluid resuscitation and management of sepsis are essential.

Consultations

Immediately make arrangements for surgical consultation.

o Extensive and aggressive debridement of necrotic tissues with exploration of all
mediastinal fascial spaces may be required.
o

Controversy exists about whether the cervical approach or the transthoracic

approach is best. Some physicians support a combination of the two approaches.
In some case series, the combination approach has been associated with a lower
mortality rate.

Depending upon the resources available, consultations may include

otorhinolaryngology, cardiothoracic surgery, and general surgery.

The necessity for extensive drainage may mandate the transfer of some patients to a
tertiary referral center.

Medication
Because mediastinitis usually is a mixed growth infection, wide antimicrobial coverage is
required. The cause of infection should be determined. Extension of a Staphylococcus
aureus osteomyelitis should be managed differently from an esophageal rupture; however, in
the absence of a source and definitive microbiological data, broad-spectrum therapy is
indicated. Combinations such as piperacillin-tazobactam with vancomycin or ceftazidime with
vancomycin or vancomycin with a fluoroquinolone and clindamycin should be used. An
aminoglycoside may be added to broaden gram-negative coverage.
Antibiotics
Therapy must cover all likely pathogens in the context of the clinical setting.

Further Inpatient Care

As for any abscess, the essential management of this condition involves extensive
surgical debridement.
The use of hyperbaric oxygen for this condition is controversial.
Recent studies have looked at the use of intravenous immunoglobulins for mediastinitis,
particularly when the condition arises as a complication of cardiothoracic surgery.

Broad-spectrum antibiotics are necessary. Antibiotics should be capable of treating

aerobes, anaerobes, and gram-positive and gram-negative infection.

Complications
Complications of mediastinitis may include the following:

Death
Pericarditis

Sepsis

Multiorgan system failure

Adult respiratory distress syndrome

Cardiac tamponade

Empyema

Vascular thrombosis

Arterial hemorrhage via erosion of infection

Prognosis

Early diagnosis and aggressive therapy seem to provide the best chance for recovery.
Despite vast improvements in IV antibiotics, critical care medicine and CT imaging in the
last 30 years, the frequency of deaths from descending necrotizing mediastinitis remains
high.

Brain abscess
Brain abscess (or cerebral abscess) is an abscess caused by inflammation and collection of
infected material, coming from local (ear infection, dental abscess, infection of paranasal
sinuses, infection of the mastoid air cells of the temporal bone, epidural abscess) or remote
(lung, heart, kidney etc.) infectious sources, within the brain tissue. The infection may also be
introduced through a skull fracture following a head trauma or surgical procedures. It may occur
at any age but is most frequent in the third decade of life.
Features
The symptoms of brain abscess are caused by a combination of increased intracranial
pressure due to a space-occupying lesion (headache, vomiting, confusion, coma), infection
(fever, fatigue etc.) and focal neurologic brain tissue damage (hemiparesis, aphasia etc.). The
most frequent presenting symptoms are headache,
drowsiness, confusion, seizures, hemiparesis or speech difficulties together with fever with a

rapidly progressive course. The symptoms and findings depend largely on the specific location
of the abscess in the brain. An abscess in the cerebellum, for instance, may cause additional
complaints as a result of brain stem compression and hydrocephalus. Neurological
examination may reveal a stiff neck in occasional cases (erroneously suggesting meningitis).
The famous triad of fever, headache and focal neurologic findings are highly suggestive of brain
abscess.
Bacterial
Anaerobic and microaerophilic cocci and gram-negative and gram-positive anaerobic bacilli are
the predominate bacterial isolates. Many brain abscesses are polymicrobical. The predominant
organisms include: Staphylococcus aureus, aerobic and anaerobic streptococci
(especially Streptococcus intermedius), Bacteroides, Prevotella, and Fusobacterium species,
Enterobacteriaceae, Pseudomonas species, and other anaerobes. Less common organisma
include: Haemophillus influenzae, Streptococcus pneumoniae and Neisseria meningitides.
These organisms are associated with certain predisposing conditions: Sinus and dental
infections - Aerobic and anaerobic streptococci, anaerobic gram-negative bacilli (eg, Prevotella,
Porphyromonas, Bacteroides), Fusobacterium, S aureus, and Enterobacteriaceae;

Diagnosis
The diagnosis is established by a computed tomography (CT) (with contrast) examination. At
the initial phase of the inflammation (which is referred to as cerebritis), the immature lesion does
not have a capsule and it may be difficult to distinguish it from other space-occupying lesions or
infarcts of the brain. Within 45 days the inflammation and the concomitant dead brain tissue
are surrounded with a capsule, which gives the lesion the famous ring-enhancing
lesion appearance on CT examination with contrast (since intravenously applied contrast
material can not pass through the capsule, it is collected around the lesion and looks as a ring
surrounding the relatively dark lesion). Ring enhancement may also be observed in cerebral
hemorrhages (bleeding) and some brain tumors. However, in the presence of the rapidly
progressive course with fever, focal neurologic findings (hemiparesis, aphasia etc) and signs of
increased intracranial pressure, the most likely diagnosis should be the brain abscess.

Treatment
The treatment includes lowering the increased intracranial pressure and starting
intravenous antibiotics (and meanwhile identifying the causative organism mainly by blood
culture studies).
Surgical drainage of the abscess remains part of the standard management of bacterial brain
abscesses. The location and treatment of the primary lesion also crucial, as is the removal of
any foreign material (bone, dirt, bullets, and so forth).
Prognosis
it was once fatal before the CT era, now, if the abscess is treated before the person goes into a
coma, then the death rate has been estimated from 5% to 20% although it is greater in cases of
multiple abscesses, when raised intracranial pressure is observed and depending on the level of
neurological dysfunction on presentation. Early treatment and the patients overall health has an
effect on prognosis. Other factors include: antibiotic resistance or the abscess location. An
abscess deep within the brain is more difficult to treat than others.

Cavernous sinus thrombosis

Cavernous sinus thrombosis (CST) is the formation of a blood clot within the cavernous
sinus, a cavity at the base of the brain which drains deoxygenated blood from the brain back to
the heart. The cause is usually from a spreading infection in the nose, sinuses, ears, or
teeth. Staphylococcus aureus and Streptococcus are often the associated bacteria. Cavernous
sinus thrombosis symptoms include; decrease or loss of
vision, chemosis, exophthalmos (bulging eyes), headaches, and paralysis of the cranial
nerves which course through the cavernous sinus. This infection is life-threatening and requires
immediate treatment, which usually includes antibiotics and sometimes surgical drainage.
Classic presentations are abrupt onset of unilateral periorbital edema, headache, photophobia,
and bulging of the eye (proptosis).
Other common signs and symptoms include:
Ptosis, chemosis, cranial nerve palsies (III, IV, V, VI). Sixth nerve palsy is the most common.
Sensory deficits of the ophthalmic and maxillary branch of the fifth nerve are common.
Periorbital sensory loss and impaired corneal reflex may be noted. Papilledema, retinal
hemorrhages, and decreased visual acuity and blindness may occur from venous congestion
within the retina. Fever, tachycardia and sepsis may be present. Headache with nuchal

rigidity may occur. Pupil may be dilated and sluggishly reactive. Infection can spread to
contralateral cavernous sinus within 2448 hours of initial presentation.
Etiology
CST most commonly results from contiguous spread of infection from the nasal furuncle (50%),
sphenoidal or ethmoidal sinuses (30%) and dental infections (10%). Less common primary sites
of infection include tonsils, soft palate, middle ear, or orbit (orbital cellulitis). The highly
anastomotic and valveless venous system of the paranasal sinuses allows retrograde spread of
infection to the cavernous sinus via the superior and inferior ophthalmic veins.
Staphylococcus aureus is the most common infectious microbe, found in 70% of the
cases. Streptococcus is the second leading cause. Gram-negative rods and anaerobes may
also lead to cavernous sinus thrombosis.
Diagnosis
The diagnosis of cavernous sinus thrombosis is made clinically, with imaging studies to confirm
the clinical impression. Proptosis, ptosis, chemosis, and cranial nerve palsy beginning in one
eye and progressing to the other eye establish the diagnosis.
Treatment
According to the ICD-9M code, cavernous sinus thrombosis has a mortality rate of less than
20% in areas with access to antibiotics. Before antibiotics were available, the mortality was 80100%. Morbidity rates also dropped from 70% to 22% due to earlier diagnosis and treatment.
Non-pharmacologic therapy
Recognizing the primary source of infection (i.e., facial cellulitis, middle ear, and sinus
infections) and treating the primary source expeditiously is the best way to prevent cavernous
sinus thrombosis.
Acute general treatment
Broad-spectrum intravenous antibiotics are used until a definite pathogen is found.
1. Nafcillin 1.5 g IV q4h
2. Cefotaxime 1.5 to 2 g IV q4h
3. Metronidazole 15 mg/kg load followed by 7.5 mg/kg IV q6h
Long-term treatment
Surgical drainage with sphenoidotomy is indicated if the primary site of infection is thought to be
the sphenoidal sinuses.

All patients with CST are usually treated with prolonged courses (34 weeks) of IV antibiotics. If
there is evidence of complications such as intracranial suppuration, 68 weeks of total therapy
may be warranted.
All patients should be monitored for signs of complicated infection, continued sepsis, or septic
emboli while antibiotic therapy is being administered.

Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord,
known collectively as the meninges. The inflammation may be caused by infection
with viruses, bacteria, or other microorganisms, and less commonly by certain drugs. Meningitis
can be life-threatening because of the inflammation's proximity to the brain and spinal cord;
therefore the condition is classified as a medical emergency.
The most common symptoms of meningitis are headache and neck stiffness associated
with fever, confusion or altered consciousness, vomiting, and an inability to tolerate light
(photophobia) or loud noises (phonophobia). Sometimes, especially in small children, only
nonspecific symptoms may be present, such as irritability and drowsiness. If a rash is present, it
may indicate a particular cause of meningitis; for instance, meningitis caused by meningococcal
bacteria may be accompanied by a characteristic rash.
A lumbar puncture may be used to diagnose or exclude meningitis. This involves inserting a
needle into the spinal canal to extract a sample of cerebrospinal fluid (CSF), the fluid that
envelops the brain and spinal cord. The CSF is then examined in a medical laboratory. The
usual treatment for meningitis is the prompt application of antibiotics and sometimes antiviral
drugs. In some situations, corticosteroid drugs can also be used to prevent complications from
overactive inflammation. Meningitis can lead to serious long-term consequences such as
deafness, epilepsy, hydrocephalus and cognitive deficits, especially if not treated quickly. Some
forms of meningitis (such as those associated with meningococci, Haemophilus influenzae type
B, pneumococci or mumps virus infections) may be prevented by immunization.
Clinical features
In adults, a severe headache is the most common symptom of meningitis occurring in almost
90% of cases of bacterial meningitis, followed by nuchal rigidity (inability to flex the neck forward
passively due to increased neck muscle tone and stiffness). The classic triad of diagnostic signs
consists of nuchal rigidity, sudden high fever, and altered mental status; however, all three
features are present in only 4446% of all cases of bacterial meningitis. If none of the three

signs is present, meningitis is extremely unlikely. Other signs commonly associated with
meningitis include photophobia (intolerance to bright light) and phonophobia (intolerance to loud
noises). Small children often do not exhibit the aforementioned symptoms, and may only
be irritable and looking unwell. In infants up to 6 months of age, bulging of the fontanelle (the
soft spot on top of a baby's head) may be present. Other features that might distinguish
meningitis from less severe illnesses in young children are leg pain, cold extremities, and an
abnormal skin color.
Nuchal rigidity occurs in 70% of adult cases of bacterial meningitis. Other signs
of meningism include the presence of positive Kernig's sign or Brudzinski's sign. Kernig's sign is
assessed with the patient lying supine, with the hip and knee flexed to 90 degrees. In a patient
with a positive Kernig's sign, pain limits passive extension of the knee. A positive Brudzinski's
sign occurs when flexion of the neck causes involuntary flexion of the knee and hip. Although
Kernig's and Brudzinski's signs are both commonly used to screen for meningitis,
the sensitivity of these tests is limited. They do, however, have very good specificity for
meningitis: the signs rarely occur in other diseases. Another test, known as the "jolt
accentuation maneuver" helps determine whether meningitis is present in patients reporting
fever and headache. The patient is told to rapidly rotate his or her head horizontally; if this does
not make the headache worse, meningitis is unlikely.
Meningitis caused by the bacterium Neisseria meningitidis (known as "meningococcal
meningitis") can be differentiated from meningitis with other causes by a rapidly spreading
petechial rash which may precede other symptoms. The rash consists of numerous small,
irregular purple or red spots ("petechiae") on the trunk, lower extremities, mucous membranes,
conjuctiva, and (occasionally) the palms of the hands or soles of the feet. The rash is typically
non-blanching: the redness does not disappear when pressed with a finger or a glass tumbler.
Although this rash is not necessarily present in meningococcal meningitis, it is relatively specific
for the disease; it does, however, occasionally occur in meningitis due to other bacteria. Other
clues as to the nature of the cause of meningitis may be the skin signs of hand, foot and mouth
disease and genital herpes, both of which are associated with various forms of viral meningitis
Causes
Meningitis is usually caused by infection from viruses or micro-organisms. Most cases are due
to infection with viruses, with bacteria, fungi, and parasites being the next most common
causes. It may also result from various non-infectious causes.

Treatment
Initial treatment
Meningitis is potentially life-threatening and has a high mortality rate if untreated; delay in
treatment has been associated with a poorer outcome. Thus treatment with wide-spectrum
antibiotics should not be delayed while confirmatory tests are being conducted. If
meningococcal disease is suspected in primary care, guidelines recommend
that benzylpenicillin be administered before transfer to hospital. Intravenous fluids should be
administered if hypotension (low blood pressure) or shock are present. Given that meningitis
can cause a number of early severe complications, regular medical review is recommended to
identify these complications early, as well as admission to an intensive care unit if deemed
necessary.
Mechanical ventilation may be needed if the level of consciousness is very low, or if there is
evidence of respiratory failure. If there are signs of raised intracranial pressure, measures to
monitor the pressure may be taken; this would allow the optimization of the cerebral perfusion
pressure and various treatments to decrease the intracranial pressure with medication
(e.g.mannitol). Seizures are treated with anticonvulsants. Hydrocephalus (obstructed flow of
CSF) may require insertion of a temporary or long-term drainage device, such as a cerebral
shunt.
Antibiotics
Structural formula of ceftriaxone, one of the third-generation cefalosporin antibiotics
recommended for the initial treatment of bacterial meningitis.
Empiric antibiotics (treatment without exact diagnosis) must be started immediately, even before
the results of the lumbar puncture and CSF analysis are known. The choice of initial treatment
depends largely on the kind of bacteria that cause meningitis in a particular place. For instance,
in the United Kingdom empirical treatment consists of a third-generation cefalosporin such
as cefotaxime or ceftriaxone. In the USA, where resistance to cefalosporins is increasingly
found in streptococci, addition of vancomycin to the initial treatment is recommended. For
instance, in young children and those over 50 years of age, as well as those who are
immunocompromised, addition of ampicillin is recommended to cover Listeria
monocytogenes. Once the Gram stain results become available, and the broad type of bacterial
cause is known, it may be possible to change the antibiotics to those likely to deal with the
presumed group of pathogens.
The results of the CSF culture generally take longer to become available (2448 hours). Once
they do, empiric therapy may be switched to specific antibiotic therapy targeted to the specific

causative organism and its sensitivities to antibiotics. For an antibiotic to be effective in

meningitis, it must not only be active against the pathogenic bacterium, but also reach the
meninges in adequate quantities; some antibiotics have inadequate penetrance and therefore
have little use in meningitis. Most of the antibiotics used in meningitis have not been tested
directly on meningitis patients in clinical trials. Rather, the relevant knowledge has mostly
derived from laboratory studies in rabbits.
Steroids
Adjuvant treatment with corticosteroids (usually dexamethasone) has been shown in some
studies to reduce rates of mortality, severe hearing loss and neurological damage in
adolescents and adults from high income countries which have low rates of HIV. The likely
mechanism is suppression of overactive inflammation. Professional guidelines therefore
recommend the commencement of dexamethasone or a similar corticosteroid just before the
first dose of antibiotics is given, and continued for four days. Given that most of the benefit of
the treatment is confined to those with pneumococcal meningitis, some guidelines suggest that
dexamethasone be discontinued if another cause for meningitis is identified.

Meningoencephalitis
Meningoencephalitis (pronounced /mn.nsflats/,
from Greek: meninges- membranes; enkephalos brain; and -itis inflammation) is a medical
condition that simultaneously resembles both meningitis, which is an infection or inflammation of
the meninges, andencephalitis, which is an infection or inflammation of the brain.
Causes
Causative organisms include protozoans, viral and bacterial pathogens.
Specific types include:
Bacterial

Listeria monocytogenes

Neisseria meningitidis

Rickettsia prowazekii

Septic shock

Septic shock is a medical emergency caused by decreased tissue perfusion and oxygen
delivery as a result of severe infection and sepsis, though the microbe may be systemic or
localized to a particular site. It can cause multiple organ dysfunction syndrome (formerly known
as multiple organ failure) and death. Its most common victims are
children, immunocompromised individuals, and the elderly, as their immune systems cannot
deal with the infection as effectively as those of healthy adults. Frequently, patients suffering
from septic shock are cared for in intensive care units. The mortality rate from septic shock is
approximately 25%-50%
Causes
When bacteria or viruses get into the blood stream, it produces a condition known
as bacteremia or viremia. If the organisms are particularly virulent, or the host is
immunocompromised, then the host organism may develop a condition known as systemic
inflammatory response syndrome (or SIRS). Sepsis is by definition bacteremia, combined with
SIRS. If sepsis worsens to the point of end-organ dysfunction (renal failure, liver dysfunction,
altered mental status, or heart damage), then the condition is called severe sepsis. Once severe
sepsis worsens to the point where blood pressure can no longer be maintained with intravenous
fluids alone, then the criteria have been met for septic shock. The precipitating infections which
may lead to septic shock if severe enough
include pneumonia, bacteremia, diverticulitis, pyelonephritis, meningitis, pancreatitis,
and necrotizing fasciitis.
Treatment
Treatment primarily consists of the following. The mnemonic OVERS may be helpful.
1. Oxygen administration and airway support.
2. Volume resuscitation.
3. Early antibiotic administration.
4. Rapid source identification and control.
5. Support of major organ dysfunction.
Antimediator agents may be of some limited use in severe clinical situations:

Low dose steroids (hydrocortisone) for 5 7 days led to improved outcomes.

Recombinant activated protein C (drotrecogin alpha) has been shown in large

randomized clinical trials to be associated with reduced mortality (Number needed to

treat (NNT) of 16) in patients with multi-organ failure. If this is given, heparin should probably
be discontinued.

Cardiogenic shock

Cardiogenic shock is based upon an inadequate circulation of blood due to primary

failure of the ventricles of the heart to function effectively.

Since this is a type of shock there is insufficient perfusion of tissue (i.e. the heart) to
meet the required demands for oxygen and nutrients. This leads to cell death
from oxygen starvation (hypoxia) and nutrient starvation (e.g. hypoglycemia). Because of
this it may lead tocardiac arrest (or circulatory arrest) which is an acute cessation of
cardiac pump function.

Cardiogenic shock is defined by sustained hypotension with tissue hypoperfusion

despite adequate left ventricular filling pressure. Signs of tissue hypoperfusion
include oliguria (<30 mL/h), cool extremities, and altered level of consciousness.

Signs and symptoms

Anxiety, restlessness, altered mental state due to decreased cerebral perfusion and
subsequent hypoxia.

Hypotension due to decrease in cardiac output.

A rapid, weak, thready pulse due to decreased circulation combined with tachycardia.

Cool, clammy, and mottled skin (cutis marmorata), due to vasoconstriction and
subsequent hypoperfusion of the skin.

Distended jugular veins due to increased jugular venous pressure.

Oliguria (low urine output) due to insufficient renal perfusion if condition persists.

Rapid and deep respirations (hyperventilation) due to sympathetic nervous system

stimulation and acidosis.

Fatigue due to hyperventilation and hypoxia.

Absent pulse in tachyarrhythmia.

Pulmonary edema, involving fluid back-up in the lungs due to insufficient pumping of the
heart..

Treatment
In cardiogenic shock: depending on the type of myocardal infarction one can infuse fluids or in
shock refractory to infusing fluids inotropica. In case of cardiac arrhythmia several antiarrhythmic agents may be administered, i.e. adenosine, verapamil, amiodarone, blocker or glucagon. Positive inotropic agents, which enhance the heart's pumping capabilities,
are used to improve the contractility and correct the hypotension. Should that not suffice
an intra-aortic balloon pump (which reduces workload for the heart, and improves perfusion of
the coronary arteries) can be considered or a left ventricular assist device (which augments the
pump-function of the heart).
Cardiogenic shock may be treated with intravenous dobutamine, which acts on 1 receptors of
the heart leading to increased contractility and heart rate.

Bacteremia
Bacteremia (also Bacteraemia or Bactermia) is the presence of bacteria in the blood. The
blood is normally a sterile environment, so the detection of bacteria in the blood (most
commonly with blood cultures) is always abnormal.
Bacteria can enter the bloodstream as a severe complication
of infections (like pneumonia or meningitis), during surgery (especially when involving mucous
membranes such as the gastrointestinal tract), or due to catheters and other foreign
bodies entering the arteries or veins(including intravenous drug abuse).
Bacteremia can have several consequences. The immune response to the bacteria can
cause sepsis and septic shock, which has a relatively high mortality rate. Bacteria can also use
the blood to spread to other parts of the body (which is called hematogenous spread), causing
infections away from the original site of infection. Examples
include endocarditis or osteomyelitis. Treatment is with antibiotics, and prevention with antibiotic
prophylaxis can be given in situations where problems are to be expected.
Definition
Bacteremia is the presence of viable bacteria in the blood stream.
Bacteremia is different from sepsis (so-called blood poisoning or toxemia), which is a condition
where bacteremia is associated with an inflammatory response from the body (causing systemic
inflammatory response syndrome, characterised by rapid breathing, low blood pressure, fever,
etc.). Common dental procedures, such as brushing teeth, are the most common cause of

bacteremia, introducing a detectable amount of bacteria into the bloodstream, even if these
rarely cause any clinical condition. Some patients with prosthetic heart valves however
need antibiotic prophylaxis for dental surgery because bacteremia might lead
to endocarditis (infection of the interior lining of the heart).

Septicemia
Septicemia is an ill-defined non-scientific term introducing more confusion between sepsis and
bacteremia: it suggests there is something in the bloodstream causing sepsis.
Causes
In the hospital, indwelling catheters are a frequent cause of bacteremia and
subsequent nosocomial infections, because they provide a means by which bacteria normally
found on the skin can enter the bloodstream. Other causes of bacteremia include dental
procedures (occasionally including simple tooth brushing), herpes (including herpetic
whitlow), urinary tract infections, peritonitis, Clostridium difficile colitis, intravenous drug use,
and colorectal cancer. Bacteremia may also be seen
in oropharyngeal, gastrointestinal or genitourinary surgery or exploration.
Consequences
Bacteremia, as noted above, frequently elicits a vigorous immune system response. The
constellation of findings related to this response (such as fever, chills, or hypotension) is
referred to as sepsis. In the setting of more severe disturbances of temperature, respiration,
heart rate or white blood cell count, the response is characterized as septic shock, and may
result in multiple organ dysfunction syndrome.
Bacteremia is the principal means by which local infections are spread to distant organs
(referred to as hematogenous spread). Bacteremia is typically transient rather than continuous,
due to a vigorous immune system response when bacteria are detected in the blood.
Hematogenous dissemination of bacteria is part of the pathophysiology of meningitis and
endocarditis, and of Pott's disease and many other forms of osteomyelitis.
Diagnosis
Bacteremia is most commonly diagnosed by blood culture, in which a sample of blood is
allowed to incubate with a medium that promotes bacterial growth. Since blood is normally
sterile, this process does not normally lead to the isolation of bacteria. If, however, bacteria are
present in the bloodstream at the time the sample is obtained, the bacteria will multiply and can

thereby be detected. Any bacteria that incidentally find their way to the culture medium will also
multiply. For this reason, blood cultures must be drawn with great attention to sterile process.
Occasionally, blood cultures will reveal the presence of bacteria that represent contamination
from the skin through which the culture was obtained. Blood cultures must be repeated at
intervals to determine if persistent rather than transient bacteremia is present.

Sepsis
Sepsis (from Gr. : the state of putrefaction or decay) is a potentially
serious medical condition that is characterized by a whole-body inflammatory state (called
a systemic inflammatory response syndrome or SIRS) and the presence of a known or
suspected infection. The body may develop this inflammatory response by the immune
system to microbes in the blood, urine, lungs, skin, or other tissues. A lay term for sepsis
is blood poisoning, more aptly applied to septicemia, below. Severe sepsis is the systemic
inflammatory response, plus infection, plus the presence of organ dysfunction.
Septicemia (also septicaemia or septicmia [septicmia],) is a related medical term
referring to the presence of pathogenic organisms in the bloodstream, leading to sepsis. The
term has not been sharply defined. It has been inconsistently used in the past by medical
professionals, for example as a synonym of bacteremia, causing some confusion. International
medical consensus, since 1992, is that the term "septicemia" is problematic and should be
avoided.
Severe sepsis is usually treated in the intensive care unit with intravenous fluids and antibiotics.
If fluid replacement is insufficient to maintain blood pressure, specific vasopressor medications
can be used. Mechanical ventilation and dialysis may be needed to support the function of the
lungs and kidneys, respectively. To guide therapy, a central venous catheter and an arterial
catheter may be placed; measurement of other hemodynamic variables (such as cardiac output,
or mixed venous oxygen saturation) may also be used. Sepsis patients require preventive
measures for deep vein thrombosis, stress ulcers and pressure ulcers, unless other conditions
prevent this. Some patients might benefit from tight control of blood sugar
levels with insulin (targeting stress hyperglycemia), low-dose corticosteroids or activated
drotrecogin alfa (recombinant protein C).
Signs and symptoms
In addition to symptoms related to the provoking infection, sepsis is characterized by presence
of acute inflammation present throughout the entire body, and is, therefore, frequently

associated with fever and elevated white blood cell count (leukocytosis) or low white blood cell
count and lower-than-average temperature, and vommiting. The modern concept of sepsis is
that the host's immune response to the infection causes most of the symptoms of sepsis,
resulting in hemodynamic consequences and damage to organs. This host response has been
termed systemic inflammatory response syndrome (SIRS) and is characterized by an elevated
heart rate (above 90 beats per minute), high respiratory rate (above 20 breaths per minute or a
partial pressure of carbon dioxide in the blood of less than 32), abnormal white blood cell count
(above 12,000, lower than 4,000, or greater than 10% band forms) and elevated or lowered
body temperature, i.e. under 36 C (97 F) or over 38 C (100 F). Sepsis is differentiated from
SIRS by the presence of a known or suspected pathogen. For example SIRS and a positive
blood culture for a pathogen indicates the presence of sepsis. However, in many cases of
sepsis no specific pathogen is identified.
This immunological response causes widespread activation of acute-phase proteins, affecting
the complement system and the coagulation pathways, which then cause damage to the
vasculature as well as to the organs. Various neuroendocrine counter-regulatory systems are
then activated as well, often compounding the problem. Even with immediate and aggressive
treatment, this may progress to multiple organ dysfunction syndrome and eventually death.
Diagnosis
According to the American College of Chest Physicians and the Society of Critical Care
Medicine\\ there are different levels of sepsis:
Systemic inflammatory response syndrome (SIRS). Defined by the presence of two

or more of the following findings:

Body temperature < 36 C (97 F) or > 38 C (100 F) (hypothermia or fever).

Heart rate > 90 beats per minute.

Respiratory rate > 20 breaths per minute or, on blood gas, a PaCO2 less than
32 mm Hg (4.3 kPa) (tachypnea or hypocapnia due to hyperventilation).

White blood cell count < 4,000 cells/mm3 or > 12,000 cells/mm3 (< 4 109 or >
12 109 cells/L), or greater than 10% band forms (immature white blood cells).
(leukopenia,leukocytosis, or bandemia).

Sepsis. Defined as SIRS in response to a confirmed infectious process. Infection can be

suspected or proven (by culture, stain, or polymerase chain reaction (PCR)), or a clinical
syndrome pathognomonic for infection. Specific evidence for infection includes WBCs in

normally sterile fluid (such as urine or cerebrospinal fluid (CSF)); evidence of a perforated
viscus (free air on abdominal x-ray or CT scan; signs of acute peritonitis); abnormal chest xray (CXR) consistent with pneumonia (with focal opacification); or petechiae, purpura,
orpurpura fulminans.

Severe sepsis. Defined as sepsis with organ dysfunction, hypoperfusion, or

hypotension.

Septic shock. Defined as sepsis with refractory arterial hypotension or hypoperfusion

abnormalities in spite of adequate fluid resuscitation. Signs of systemic hypoperfusion may
be either end-organ dysfunction or serum lactate greater than 4 mmol/dL. Other signs
include oliguria and altered mental status. Patients are defined as having septic shock if
they have sepsis plus hypotension after aggressive fluid resuscitation (typically upwards of 6
liters or 40 ml/kg of crystalloid).

Treatment
Adults and children
The therapy of sepsis rests on antibiotics, surgical drainage of infected fluid collections, fluid
replacement and appropriate support for organ dysfunction. This may include hemodialysis
in kidney failure, mechanical ventilation in pulmonary dysfunction, transfusion of blood products,
and drug and fluid therapy for circulatory failure. Ensuring adequate nutritionpreferably by
enteral feeding, but if necessary by parenteral nutritionis important during prolonged illness.
A problem in the adequate management of septic patients has been the delay in administering
therapy after sepsis has been recognized. Published studies have demonstrated that for every
hour delay in the administration of appropriate antibiotic therapy there is an associated 7% rise
in mortality. Early Goal Directed Therapy (EGDT), developed at Henry Ford
Hospital by Emaneul Rivers, MD, is a systematic approach to resuscitation that has been
validated in the treatment of severe sepsis and septic shock. It is meant to be started in the
Emergency Department. The theory is that one should use a step-wise approach, having the
patient meet physiologic goals, to optimize cardiac preload, afterload, and contractility, thus
optimizing oxygen delivery to the tissues. A recent meta-analysis showed that EGDT provides a
benefit on mortality in patients with sepsis. As of December 2008 some controversy around its
uses remains and a number of trials are ongoing in an attempt to resolve this.
In EGDT, fluids are administered until the central venous pressure (CVP), as measured by
a central venous catheter, reaches 812 cm of water (or 1015 cm of water in mechanically
ventilated patients). Rapid administration of several liters of isotonic crystalloid solution is

usually required to achieve this. If the mean arterial pressure is less than 65 mmHg or greater
than 90 mmHg, vasopressors or vasodilators are given as needed to reach the goal. Once
these goals are met, the mixed venous oxygen saturation (SvO2), i.e., the oxygen saturation of
venous blood as it returns to the heart as measured at the vena cava, is optimized. If the SvO2
is less than 70%, blood is given to reach a hemoglobin of 10 g/dl and then inotropes are added
until the SvO2 is optimized. Elective intubation may be performed to reduce oxygen demand if
the SvO2 remains low despite optimization of hemodynamics. Urine output is also monitored,
with a minimum goal of 0.5 ml/kg/h. In the original trial, mortality was cut from 46.5% in the
control group to 30.5% in the intervention group. The Surviving Sepsis Campaign guidelines
recommend EGDT for the initial resuscitation of the septic patient with a level B strength of
evidence (single randomized control trial).
Most therapies aimed at the inflammation process itself have failed to improve outcome,
however drotrecogin alfa (activated protein C, one of the coagulation factors) has been shown
to decrease mortality from about 31% to about 25% in severe sepsis. To qualify for drotrecogin
alfa, a patient must have severe sepsis or septic shock with an APACHE II score of 25 or
greater and a low risk of bleeding.[14] However, since further trials have failed to replicate this
result, the use of activated protein C is controversial and is currently the subject of a large trial
that was demanded by the European Medicines Regulator.[15]
During critical illness, a state of adrenal insufficiency and tissue resistance (the word 'relative'
resistance should be avoided[16]) to corticosteroids may occur. This has been termedcritical
illnessrelated corticosteroid insufficiency.[16] Treatment with corticosteroids might be most
beneficial in those with septic shock and early severe acute respiratory distress
syndrome (ARDS), whereas its role in other patients such as those with pancreatitis or
severe pneumonia is unclear.[16] These recommendations stem from studies showing benefits
from low dose hydrocortisone treatment for septic shock patients and methylprednisolone in
ARDS patients.[17][18][19][20][21][22] However, the exact way of determining corticosteroid insufficiency
remains problematic. It should be suspected in those poorly responding to resuscitation with
fluids and vasopressors. ACTH stimulation testing is not recommended to confirm the diagnosis.
[16]

The method of cessation of glucocorticoid drugs is variable, and it is unclear whether they

should be weaned or simply stopped abruptly.

In some cases, sepsis may lead to inadequate tissue perfusion and necrosis. As this may affect
the extremities, amputation may become necessary.
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually
involves the heart valves (native or prosthetic valves). Other structures which may be involved

include the interventricular septum, the chordae tendineae, the mural endocardium, or even on
intracardiac devices. Endocarditis is characterized by a prototypic lesion, the vegetation, which
is a mass of platelets, fibrin, microcolonies of microorganisms, and scant inammatory cells.[1] In
the subacute form of infective endocarditis, the vegetation may also include a center
of granulomatous tissue, which may fibrose or calcify.[2]
There are multiple ways to classify endocarditis. The simplest classification is based on etiology:
either infective or non-infective, depending on whether a microorganism is the source of the
inflammation. Regardless, diagnosis of endocarditis is based on the clinical features,
investigations such as echocardiogram, as well as any blood cultures demonstrating the
presence of endocarditis-causing microorganisms.
Infective endocarditis
Main article: Infective endocarditis
Since the valves of the heart do not receive any dedicated blood supply, defensive immune
mechanisms (such as white blood cells) cannot directly reach the valves via the bloodstream. If
an organism (such as bacteria) attaches to a valve surface and forms a vegetation, the host
immune response is blunted. The lack of blood supply to the valves also has implications on
treatment, since drugs also have difficulty reaching the infected valve.
Normally, blood flows smoothly through these valves. If they have been damaged
(from rheumatic fever, for example) the risk of bacteria attachment is increased.[2]