Sepsis

• Sepsis is a heterogeneous syndrome characterized by widespread

inflammation and potential organ harm initiated by a microorganism.
• As sepsis severity increases, a multifactorial series of events lead to
impairments in oxygen delivery, secondary to macro- and
microvascular malperfusion, as well as direct cellular damage
secondary to inflammation multisystem organ failure occurs, and
mortality is high.
• The varying clinical presentation,
• The incidence is increasing and is multifactorial in origin; a key
component of this increase relates to an aging patient population
Definitions
• Sepsis syndromes are a continuum, with specific definitions
regularly updated to include children
• In general, sepsis is defined as suspected or confirmed infection
with evidence of systemic inflammation (demonstrated either
through evidence of the systemic immune response syndrome or
laboratory abnormalities),
• severe sepsis is generally defined as sepsis plus evidence of new
organ dysfunction thought to be secondary to tissue hypoperfusion.
• Septic shock exists when cardiovascular failure occurs, evidenced as
persistent hypotension or need for vasopressors despite adequate
fluid resuscitation; this latter category has a particularly poor
prognosis.
SIRS Prognosis
• The systemic inflammatory response syndrome response is not a diagnosis or a good
indicator of outcome; it is a crude means of stratification of patients with systemic
inflammation.
• Serum lactate across a wide spectrum provides excellent prognostic data in those with
sepsis, but is not a singular test to diagnose or exclude sepsis.
• Lactate has traditionally been attributed to anaerobic metabolism secondary to tissue
hypoperfusion; it also accumulates from changes in aerobic metabolism that occur in
response to widespread inflammation.
• Patients with sepsis who do not clear lactate (adequate is at least a 10% drop with therapy
over the first few hours) have a higher mortality rate than patients who do clear the lactate
• The major limitation is that lactate is nonspecific and can be elevated in a number of
conditions, and it must be used together with clinical judgment.
Clinical Features
• Given that systemic inflammation produces physiologic changes, vital sign abnormalities—
notably fever, hypotension, and/or tachycardia— are a hint to sepsis
• Although traditionally sepsis is categorized as an example of distributive shock (peripheral
vasodilation evidenced by warm extremities with a compensatory increased cardiac output),
this presentation does not accurately describe all patients with sepsis.
• ED patients with sepsis are often volume depleted from decreased intake and increased fluid
losses (from emesis, diarrhea, or insensible losses associated with fever and tachypnea).
• Intravascular volume depletion directly affects preload, cardiac output, and ultimately
peripheral perfusion.
• Further complicating matters is septic cardiomyopathy, a reversible process characterized by
impaired systolic function and diastolic relaxation
• Finally, the combination of intravascular volume depletion and septic cardiomyopathy may
manifest as “cold shock,” impaired peripheral perfusion and cool extremities.
Pulmonary injury
• Widespread inflammation secondary to sepsis commonly affects pulmonary function even in the
absence of pneumonia.
• Acute lung injury is common and may result in acute respiratory distress syndrome, which is
characterized by new lung edema from increased alveolar and capillary permeability.
• Classification of acute respiratory distress syndrome is based primarily on the degree of hypoxemia.
• The three mutually exclusive categories are
• within 1mild (PaO2 divided by fraction of inspired oxygen [FIO2] of 200 to 300),
• moderate (PaO2/FIO2 of 100 to 200),
• severe (PaO2/ FIO2 <100)
• Clinically, severe refractory hypoxemia, noncompliant lungs noted on mechanical ventilation, and a
chest radiograph showing bilateral pulmonary alveolar infiltrates suggest the diagnosis.
• Mortality increases from 27% to 45% with increasing severity of acute respiratory distress
syndrome.
Renal injury
• The kidney is another common sepsis target; acute kidney injury can
present with azotemia, oliguria, or anuria.
• Factors increasing acute kidney injury risk include pre-existing kidney
dysfunction or vasculopathy, depth and duration of hypotension,
dehydration, and use of nephrotoxic substances (e.g., aminoglycoside
antibiotics, nonionic intravenous contrast).
• Renal ischemic injury from hypoperfusion is a major factor in the
pathogenesis of acute kidney injury in sepsis
Hepatic injury
• The most frequent hepatic abnormality is cholestatic jaundice, although it
occurs infrequently.
• Increased concentrations of transaminase, alkaline phosphatase (one to
three times the normal level), and bilirubin (usually not >10 milligrams/dL)
may be observedless common unless septic shock is present; if seen,
consider a biliary source of infection.
• Smaller elevations in liver function tests can result from intermittent or
prolonged macro- or microvascular hypoperfusion and ischemia or can be
secondary to direct endotoxin, cytokines, or immune complex damage.
• Red blood cell hemolysis from microvascular coagulation can also rarely
cause jaundice.
GI changes
• The most common GI manifestation of sepsis is ileus, which may
persist for days after shock resolves.
• Major blood loss secondary to upper GI bleeding is rare in septic
patients.
• Minor GI blood loss within 24 hours of developing severe sepsis can
result from painless erosions in the mucosal layer of the stomach or
duodenum.
Hematologic changes
• Multiple abnormalities are possible in the hematologic system in the
setting of sepsis, including neutropenia or neutrophilia,
thrombocytopenia, or disseminated intravascular coagulation.
Neutrophilic leukocytosis with a “left shift” results from
demargination and release of newer granulocytes from the marrow
storage pools. However, the presence of excessive bands (the
immature neutrophil) is neither sensitive nor specific for infection.
• Neutropenia occurs rarely and is associated with an increase in
mortality; it results from increased peripheral use of neutrophils,
damage to neutrophils by bacterial by-products, or depression of
marrow granulocyte production by inflammatory mediators.
Functional neutropenia also creates a relative immunosuppression,
Metabolic changes
• Sepsis induces multiple metabolic changes. Abnormalities in lactate metabolism due
to tissue hypoperfusion with resultant anaerobic metabolism as well as increased
aerobic production of lactate have been discussed previously (see “Systemic
Inflammatory Response Syndrome Prognosis”). Hyperglycemia is seen even in
patients without a history of diabetes; in this latter group, it is associated with a
worse prognosis, in contrast to less impact of glucose elevations in those with known
diabetes.34 Hypoglycemia with glucose levels as low as 10 to 20 milligrams/dL is
reported but uncommon, and may result due to depletion of hepatic glycogen and
inhibition of gluconeogenesis and/or adrenal insufficiency. Adrenal insufficiency can
occur,35 caused by hypoperfusion of the adrenal glands, adrenal or pituitary
hemorrhage, cytokine dysfunction of the adrenals, drug-induced hypermetabolism,
inhibition of steroidogenesis by chemotherapeutics (e.g., ketoconazole), and
desensitization of glucocorticoid responsiveness at the cellular level.
Skin
• There are five potential cutaneous manifestations of sepsis:
• direct bacterial involvement of the skin and underlying soft tissues (cellulitis,
erysipelas, and fasciitis);
• lesions from hematogenous seeding of the skin or the underlying tissue (petechiae,
pustules, cellulitis, ecthyma gangrenosum);
• lesions from hypotension and/or disseminated intravascular coagulation
(acrocyanosis and necrosis of peripheral tissues);
• lesions from intravascular infections (microemboli and/or immune complex
vasculitis); and
• lesions caused by toxins (toxic shock syndrome).
• Look for any necrotizing or surgical source of sepsis, and recall that the toxic
shock syndromes present in an overlapping fashion
Diagnosis
• In the ED, sepsis is a clinical diagnosis predicated on suspicion or confirmation of infection,
systemic inflammation, and evidence of new organ dysfunction and/or tissue hypoperfusion.
• Septic shock is present or likely in any individual with the preceding signs (Table 151-1) and a
systolic blood pressure of <90 mmHg (or 2 standard deviations below normal for age in
children) after an initial fluid bolus (often cited as 20 to 30 mL/kg crystalloid, generally 1,5 to 3L
in adults), or who displays evidence of inadequate organ perfusion
• The differential diagnosis of severe sepsis and septic shock includes other causes of shock. This
includes cardiogenic, hypovolemic, anaphylactic, neurogenic, or obstructive shock (pulmonary
embolism, cardiac tamponade), or endocrine disorders (adrenal insufficiency, thyroid storm)
that mimic sepsis.
• Children may not have hypotension until very late in the course of the disease process due to
an ability to upregulate their heart rate as a compensatory response to tissue hypoperfusion
considering compensated shock and occult sepsis in infected children who do not appear well,
even with normotension
• Once sepsis is diagnosed, seek the source, but do not withhold interventions such as resuscitative measures and
antimicrobials.
• The most frequent causative organisms are Streptococcus pneumoniae, S. aureus, gram-negative bacilli, and
Legionella pneumophila.
• A chest radiograph may identify air space changes and pneumonia, although radiograph findings can lag behind
the clinical presentation (see also chapter 65, “Pneumonia and Pulmonary Infiltrates”).
• Acute pyelonephritis, typically due to gram-negative enteric bacteria or enterococci, is another frequent cause
of severe sepsis.
• Other abdominal triggers include cholecystitis and cholangitis, each rare but particularly devastating sources of
septic shock, and both require immediate surgical assessment. If there is abdominal tenderness or peritonitis,
the possibilities include perforated viscous, appendicitis, diffuse colitis, or intra-abdominal abscesses.
• Acute pancreatitis can result in a presentation identical to that of septic shock due to widespread inflammation.
• If peritonitis or organ ischemia/necrosis exists, early surgical consultation is needed.
• In women of childbearing age, septic abortion and postpartum endometritis or myometritis are unusual
etiologies of septic shock.
• The most common skin and soft tissue infection triggering a sepsis syndrome is cellulitis due to S. aureus or
Streptococcus pyogenes.
• Soft tissue infections caused by gram-negative organisms are indistinguishable from those caused by
staphylococci or streptococci.
• Shock associated with a generalized erythematous macular rash may be a toxic shock syndrome. Necrotizing
soft tissue infections are usually seen in immunocompromised patients, diabetic patients, or patients with a
history of poor vascular circulation
• Pay close attention to skin and soft tissue infections, particularly in elderly or obtunded patients.
• Individuals without an obvious source of septic shock may have a primary bacteremia or endocarditis. The
most prevalent causes of primary bacteremia in outpatients are S. aureus, S. pneumoniae, and Neisseria
meningitidis.
• Pseudomonas aeruginosa and other gram-negative bacteria are occasional causes of bacteremia and
endocarditis in injection drug users.
• Secondary bacteremia from indwelling medical devices, including intraperitoneal or intravascular dialysis
catheters, chemotherapy ports, peripherally inserted central catheters, ventriculoperitoneal shunts, and
pacemaker/defibrillators, is possible
Laboratory Testing and Imanging
• Common tests include a CBC with platelet count; serum electrolytes (including calcium and
glucose); renal function panel (BUN and creatinine levels); lactic acid level; liver function panel
(bilirubin, alkaline phosphate, and aspartate and alanine aminotransferase levels); and urinalysis.
• An arterial blood gas
• prothrombin time, activated partial thromboplastin time, fibrinogen, and d-dimer.
• chest radiograph.
• Abdominal plain radiographs or CT
• Soft tissue CT scans
• Perform head CT and lumbar puncture
• MRI is
• In adults with sepsis, obtain at least two separate sets of specimens for blood culture from
different venipuncture sites when possible.
• Order Gram staining and culture of secretions
• Other tests of interest in the assessment of sepsis include C-reactive protein and procalcitonin,
both of which reflect systemic inflammation
Treatment
• The cornerstones of the initial treatment and stabilization of severe sepsis are early
recognition, early reversal of hemodynamic compromise, and early infection control.
• Base the resuscitation on administering fluids, frequently assessing response, and adding
adjunct therapies including vasopressors based on the conditions
• The goals of resuscitation are to improve preload, tissue perfusion, and oxygen delivery.
• There is no “set amount of fluid,” although most patients will require a total (bolus plus
infusion) of 2 to 5 L of crystalloid in the first 6 hours to achieve optimal outcomes.
Similarly, do not delay vasopressors when blood pressure does not respond to volume or
if volume overload seems likely. Administer appropriate antibiotics, and remove any nidus
of infection. Each of these interventions will be discussed in detail below. Once the
patient is stabilized, other interventions such as appropriate management of oxygenation
and ventilation, fever control to reduce metabolic demand, and control of hyperglycemia
may be needed to improve patient outcomes.