Septic Shock Workup

Updated: Jan 11, 2019
  • Author: Andre Kalil, MD, MPH; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM  more...
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Approach Considerations

Early recognition and management are key in patients with severe sepsis or septic shock. Cardiac monitoring, noninvasive blood pressure monitoring, and pulse oximetry are indicated in patients with septic shock. These measures are necessary because these patients often require admission to an intensive care unit (ICU) for invasive monitoring and support. Once patients are stabilized, clinicians can determine their approach to the diagnostic workup.

Investigative studies include laboratory tests, imaging modalities, and possibly lumbar puncture/spinal fluid testing to detect a clinically suspected focal infection, the presence of a clinically occult focal infection, and complications of sepsis and septic shock.


Initial Laboratory Studies

Complete blood cell count with differential

The white blood cell (WBC) count and the WBC differential can be somewhat helpful in predicting bacterial infection, though an elevated WBC count is not specific to infection. In the setting of fever without localizing signs of infection, a WBC count higher than 15,000/µL or a neutrophil band count higher than 1500/µL has about a 50% correlation with bacterial infection. WBC counts higher than 50,000/µL or lower than 300/µL are associated with significantly decreased survival rates.

Hemoglobin concentration dictates oxygen-carrying capacity in blood, which is crucial in shock to maintain adequate tissue perfusion. Although there is no specific hematocrit or hemoglobin target, keeping the hemoglobin concentration above 7 g/dL is usually practiced, and studies comparing this versus 9 g/dL have shown no increased survival benefit from either arm.

Platelets, as acute-phase reactants, usually increase at the onset of any serious stress and are typically elevated in the setting of inflammation. However, the platelet count will fall with persistent sepsis, and disseminated intravascular coagulation (DIC) may develop.

Coagulation studies

Coagulation status should be assessed by measuring the prothrombin time (PT) and the activated partial thromboplastin time (aPTT). Patients with clinical evidence of a coagulopathy require additional tests to detect the presence of DIC. The PT and the aPTT are elevated in DIC, fibrinogen levels are decreased, and fibrin split products are increased.

Blood chemistries

At regular intervals, metabolic assessment should be carried out by measuring serum levels of electrolytes, including magnesium, calcium, phosphate, and glucose. Sodium and chloride levels are abnormal in severe dehydration. Decreased bicarbonate can point to acute acidosis—however, sodium bicarbonate therapy is not recommended to improve hemodynamics or replace vasopressor requirements in patients with metabolic acidemia from hypoperfusion whose pH level is 7.15 or greater. [11, 60]

Glucose control is important in the management of sepsis: Hyperglycemia is associated with higher mortality.

Serum lactate is perhaps the best serum marker for tissue perfusion, in that it is elevated under conditions of anaerobic metabolism, which occurs when tissue oxygen demand exceeds supply. This can result from decreased arterial oxygen content (hypoxemia), decreased perfusion pressure (hypotension), maldistribution of flow, and decreased diffusion of oxygen across capillary membranes to target tissues, as well as decreased oxygen utilization on a cellular level.

There is also evidence that lactate can be elevated in sepsis in the absence of tissue hypoxia, as a consequence of mitochondrial dysfunction and downregulation of pyruvate dehydrogenase, which is the first step in oxidative phosphorylation. [61]

Lactate levels higher than 2.5 mmol/L are associated with an increase in mortality. The higher the serum lactate, the worse the degree of shock and the higher the mortality. Lactate levels higher than 4 mmol/L in patients with suspected infection have been shown to yield a 5-fold increase in the risk of death and are associated with a mortality approaching 30%. [62] It has been hypothesized that lactate clearance is a measure of tissue reperfusion and an indication of adequate therapy. [63, 64]

Renal and hepatic function should be assessed with the following chemistry studies:

  • Serum creatinine level

  • Blood urea nitrogen (BUN) level

  • Bilirubin level

  • Alkaline phosphatase (ALP) level

  • Alanine aminotransferase (ALT) level

  • Aspartate aminotransferase (AST) level

  • Albumin level

Liver function tests (LFTs) and levels of bilirubin, ALP, and lipase are important in evaluating multiorgan dysfunction or a potential causative source (eg, biliary disease, pancreatitis, or hepatitis). Increased BUN and creatinine levels can point to severe dehydration or renal failure.

In severely ill patients suspected of having adrenal insufficiency, a delta cortisol level below 9 µg/dL (after administration of 250 µg of cosyntropin) or a random total cortisol level below 10 µg/dL is diagnostic. [65] It should be kept in mind that the adrenocorticotropic hormone (ACTH) stimulation test is not recommended for identifying the subset of patients with septic shock or acute respiratory distress syndrome (ARDS) who should receive corticosteroid therapy. [65]

The American College of Critical Care Medicine (ACCCM) does not recommend the routine use of free cortisol measurements in critically ill patients. [65] There are no clear parameters for the normal range of free cortisol in such patients, and the free cortisol assay is not widely available, despite its advantages over the total serum cortisol assay. [65]


Microbiology Studies

Blood cultures

Blood cultures should be obtained in patients with suspected sepsis (or blood infection) to facilitate isolation of a specific organism and tailoring of antibiotic therapy. These cultures are the primary means of diagnosing intravascular infections (eg, endocarditis) and infections of indwelling intravascular devices. Individuals at high risk for endocarditis are intravenous (IV) drug abusers and patients with prosthetic heart valves.

Patients at risk for bacteremia include adults who are febrile with an elevated WBC or neutrophil band count, elderly patients who are febrile, and neutropenic patients who are febrile. These populations have a 20-30% incidence of bacteremia. The incidence of bacteremia increases to at least 50% in patients with sepsis and evidence of end-organ dysfunction.

The Surviving Sepsis Campaign recommends obtaining at least 2 blood cultures before antibiotics are administered, with 1 percutaneously drawn and the other(s) obtained through each vascular access (unless the device was inserted < 48 hours beforehand). [11, 60] Again, however, it must be remembered that blood cultures are positive in fewer than 50% of cases of sepsis. [3, 4, 5]

To optimize recovery of aerobic bacteria from patients with suspected intra-abdominal infection, 1-10 mL of fluid can be directly inoculated into an aerobic blood culture; an additional 0.5 mL of fluid should be sent for Gram staining and, if indicated, fungal cultures. [2] For anaerobic bacteria, 1-10 mL of fluid can also be directly inoculated into an anaerobic blood culture bottle.

Susceptibility testing for organisms that have a high risk for resistance (eg, Pseudomonas, Proteus, Acinetobacter, Staphylococcus aureus, and predominant [moderate to heavy growth] Enterobacteriaceae) should be performed. [2] Unfortunately, in patients with community-acquired intra-abdominal infection, blood cultures are not of much clinical utility; Gram staining of the infected material also is not generally useful in such cases.

Urinalysis and urine culture

Urinalysis and urine culture are indicated for every patient who is in a septic state. Urinary tract infection (UTI) is a common source for sepsis, especially in elderly individuals. Adults who are febrile without localizing symptoms or signs have a 10-15% incidence of occult UTI. Obtaining a culture is important for isolating a specified organism and tailoring antibiotic therapy.

Gram stain and culture of secretions and tissue

The Gram stain is the only immediately available test that can document the presence of bacterial infection and guide the choice of initial antibiotic therapy. Secretions or tissue for Gram stain and culture from the sites of potential infection (eg, cerebrospinal fluid [CSF], wounds, respiratory secretions, or other body fluids) may be are obtained as they are identified, preferably before administering antibiotic therapy. [11, 60]

At least 1 mL of fluid or tissue is needed for cultures. [2] For aerobic or anaerobic cultures, 0.5 mL of fluid or 0.5 g of tissue should be transported to the laboratory in the appropriate aerobic or anaerobic transport medium. [2]

If pneumonia is suspected, a sputum specimen should be obtained for Gram stain and culture, provided that the patient has a productive cough and that a good-quality specimen can be obtained. [66] Any abscess should be drained promptly and purulent material sent to the microbiology laboratory for analysis. If meningitis is suspected, a CSF specimen should be obtained.

Routine culture and susceptibility studies should be obtained in the following cases [2] :

  • Perforated appendicitis and other community-acquired intra-abdominal infections in which there is significant resistance of a common community isolate to an antimicrobial regimen in widespread use locally

  • Higher-risk patients who have a greater risk of harboring resistant pathogens, such as those with previous antibiotic exposure

Although Gram staining may be helpful for identifying healthcare-related infections (eg, presence of yeast), it has not proved to be of clinical value in community-acquired intra-abdominal infections. [2] Anaerobic cultures are not necessary for community-acquired intra-abdominal infections if empiric antimicrobial therapy against common anaerobic pathogens is administered.


Plain Radiography


Because most patients who present with sepsis have pneumonia, and because the clinical examination is unreliable for the detection of pneumonia (especially in elderly patients), a chest radiograph is warranted. Chest radiography detects infiltrates in about 5% of febrile adults without localizing signs of infection; accordingly, it should be routine in adults who are febrile without localizing symptoms or signs and in patients who are febrile with neutropenia and without pulmonary symptoms.

Chest radiography is useful in detecting radiographic evidence of ARDS (see the images below), which carries a high mortality. The discovery of such evidence on a chest radiograph should prompt consideration of early intubation and mechanical ventilation, even if the patient has not yet shown signs of overt respiratory distress.

Acute respiratory distress syndrome (ARDS) in a pa Acute respiratory distress syndrome (ARDS) in a patient who developed septic shock secondary to toxic shock syndrome.
Bilateral airspace disease and acute respiratory f Bilateral airspace disease and acute respiratory failure in a patient with gram-negative septic shock. The source of the sepsis was urosepsis.
A 45-year-old woman was admitted to the intensive A 45-year-old woman was admitted to the intensive care unit with septic shock secondary to spontaneous biliary peritonitis. She subsequently developed acute respiratory distress syndrome (ARDS) and multiorgan failure.

In early ARDS, the chest radiograph may appear normal. The typical findings of noncardiogenic pulmonary edema are bilateral hazy, symmetric homogeneous opacities, which may demonstrate air bronchograms. The margins of pulmonary vessels become indistinct and obscured with disease progression.

The usual findings of metastatic pulmonary edema, such as Kerley A or B lines, are not usually observed; a perihilar distribution of opacities is also absent. Furthermore, other findings of cardiogenic pulmonary edema, such as cardiomegaly, vascular redistribution, and pleural effusions, are absent as well.

With disease progression, the ground-glass opacities change into heterogeneous linear or reticular infiltrates. Days to weeks later, either persistent chronic fibrosis may develop or the chest radiograph appearance becomes more normal. Periodic chest radiographs during the management of ARDS are particularly important for diagnosing barotrauma, confirming adequate positioning of an endotracheal tube or intravascular catheters, and detecting nosocomial pneumonia.


Supine and upright or lateral decubitus abdominal radiographs should be obtained; these may be useful when an intra-abdominal source of sepsis is suspected. Abdominal plain films should be obtained if clinical evidence of bowel obstruction or perforation exists. However, if obvious signs of diffuse peritonitis are present and immediate surgical intervention is planned, further diagnostic imaging is not required. [2]

In adult patients with suspected intra-abdominal infection who are not undergoing immediate laparotomy, computed tomography (CT) of the abdomen is preferable to abdominal radiography. [2]


Plain radiographs of the extremities may be helpful when deep soft-tissue infection is suspected. These films can show evidence of soft-tissue gas formation; however, it is important to emphasize that necrotizing fasciitis is a clinical diagnosis (signaled, for example, by extreme pain, crepitus, bullae, hemorrhage, and foul-smelling exudates).

If clinical suspicion of necrotizing fasciitis is high, a surgical consultation should be obtained immediately, and the patient should be taken promptly to the operating room for intervention, often without the need for any imaging. CT and magnetic resonance imaging (MRI) cannot be relied on to make this diagnosis.

Plain radiographs can also show evidence of osteomyelitis. However, MRI is much more sensitive for making this diagnosis.



Abdominal ultrasonography is indicated when patients have evidence of acute cholecystitis or ascending cholangitis exists [2] (eg, right upper quadrant abdominal tenderness, fever, vomiting, elevated LFT results, elevated bilirubin level, or elevated alkaline phosphatase level). Surgery or endoscopic retrograde cholangiopancreatography (ERCP) may be urgently necessary in the setting of sepsis with acute cholecystitis or ascending cholangitis.

Echocardiography has a number of uses in assessing patients with septic shock and may be considered. [67] This imaging modality can provide a comprehensive cardiac evaluation in patients with hemodynamic instability and can be helpful for guiding fluid therapy and monitoring treatment effects. Other conditions that can be assessed include sepsis-induced myocardial dysfunction, right heart failure, dynamic left ventricular obstruction, and tamponade. [67]


CT and MRI

CT is the imaging modality of choice for excluding an intra-abdominal abscess or a retroperitoneal source of infection. Obesity or the presence of excessive intestinal gas markedly interferes with abdominal imaging by ultrasonography; therefore, CT is preferred in this setting.

Obtain an abdominal CT scan if the patient has abdominal or flank tenderness in the setting of sepsis. Certain abdominal processes (eg, diverticular abscess, ischemic bowel, appendicitis, perinephric abscess) may necessitate urgent operative intervention.

When clinical evidence of a deep soft tissue infection exists, such as crepitus, bullae, hemorrhage, or foul-smelling exudate, obtain a plain radiograph. The presence of soft-tissue gas often dictates surgical exploration.

Although either CT or MRI may reveal evidence of subcutaneous and deep-tissue inflammation, neither modality is sensitive or specific in the setting of necrotizing deep-tissue infection, and neither should be relied upon to make this diagnosis. MRI is much more sensitive for osteomyelitis than plain radiography is.

If there is evidence of increased intracranial pressure (eg, papilledema) or focal mass lesions (focal defects, preceding sinusitis or otitis, or recent intracranial surgery), antibiotic therapy should be initiated, and a head CT scan should be obtained. Antibiotics will not begin to affect CSF cultures for at least several hours; therefore, proper antibiotic administration should not be delayed by the procedure if there is a high suspicion for meningitis.

If bacterial meningitis is strongly suspected, a lumbar puncture should be performed promptly, without any delay to obtain a CT scan.


Lumbar Puncture

A lumbar puncture (spinal fluid test) is indicated when there is clinical evidence or suspicion of meningitis or encephalitis. If the opening pressure is elevated, only as much CSF as is needed for culture should be obtained. Broad-spectrum antibiotics to cover meningitis should be administered before the start of the procedure. In patients with an acute fulminant presentation, rapid onset of septic shock, and severely impaired mental status, this procedure is used to rule out bacterial meningitis.