Septic Shock Workup

Author: Michael R Pinsky, MD, CM, FCCP, FCCM; Chief Editor: Michael R Pinsky, MD, CM, FCCP, FCCM more...

Updated: Oct 25, 2011

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Approach Considerations
Complete Blood Count With Differential
Blood Chemistry
Coagulation Studies
Blood Culture
Urinalysis and Urine Culture
Gram Stain and Culture of Secretions and Tissue
Radiography
Ultrasonography
Computed Tomography
Lumbar Puncture
Other Evaluations
Staging
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Approach Considerations

Several imaging modalities are used to detect a clinically suspected focal infection, the presence of a clinically occult focal infection, and a complication of sepsis and septic shock.

Complete Blood Count With Differential

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

Hemoglobin concentration dictates oxygen-carrying capacity in blood, which is crucial in shock to maintain adequate tissue perfusion. The goal is to maintain a hematocrit of greater than 30% and a hemoglobin concentration higher than 10 g/dL.

Platelets, an acute-phase reactant, 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.

Blood Chemistry

At regular intervals, obtain metabolic assessment with serum electrolytes, including magnesium, calcium, phosphate, and glucose. Sodium and chloride levels are abnormal in severe dehydration. Decreased bicarbonate can point to acute acidosis. Glucose control is important in the management of sepsis, with hyperglycemia associated with higher mortality.

Serum lactate is perhaps the best serum marker for tissue perfusion given that it is elevated in 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, and 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.^[32]

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 rate. levels higher than 4 mmol/L in patients with suspected infection have been shown to increase mortality odds 5-fold and are associated with a mortality rate approaching 30%.^[33]It has been hypothesized that lactate clearance is a measure of tissue reperfusion and an indication of adequate therapy.^{[34, 35]}

Assess renal and hepatic function with the following:

Serum creatinine
Blood urea nitrogen (BUN)
Bilirubin
Alkaline phosphatase
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Albumin

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

Coagulation Studies

Assess the coagulation status with 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 increased in the setting of DIC.

Blood Culture

Blood cultures should be obtained in patients who have suspected sepsis in order to isolate a specific organism and tailor antibiotic therapy. Note, however, that blood cultures are positive in fewer than 50% of cases of sepsis.

The blood culture is the primary means for the diagnosis for intravascular infections (eg, endocarditis) and infections of indwelling intravascular devices. The individuals at high risk for endocarditis are intravenous (IV) drug abusers and patients with prosthetic heart valves.

The patients at risk for bacteremia include adults who are febrile with an elevated WBC count or neutrophil band count, elderly patients who are febrile, and patients who are febrile with neutropenia. 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.

Urinalysis and Urine Culture

Perform a urinalysis and urine culture for every patient who is septic. 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 urinary tract infection. Again, obtaining a culture is important in order to isolate a specified organism and to tailor antibiotic therapy.

Gram Stain and Culture of Secretions and Tissue

Obtain secretions or tissue for Gram stain and culture from the sites of potential infection. 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.

If pneumonia is suspected, a sputum specimen should be obtained. Any abscess should be drained promptly, and purulent material sent to the microbiology laboratory for analysis. If meningitis is suspected, a cerebrospinal fluid (CSF) specimen should be obtained.

Chest

Since most patients that present with sepsis have pneumonia, one should obtain a chest radiograph because the clinical examination is unreliable for the detection of pneumonia, especially in elderly patients. Infiltrates are detected with a chest radiograph in about 5% of febrile adults without localizing signs of infection; therefore, chest radiography 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 acute respiratory distress syndrome (ARDS), which carries a high mortality rate (see the images below). Evidence of ARDS on a chest radiograph should prompt consideration for 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 patient who developed septic shock secondary to toxic shock syndrome.

Bilateral airspace disease and acute respiratory failure in a patient with gram-negative septic shock The source of sepsis was urosepsis.

A 45-year-old woman is 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 results may be normal. The typical findings of noncardiogenic pulmonary edema are bilateral, hazy, symmetric homogenous 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, also are not present.

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 to diagnose barotrauma, adequate positioning of an endotracheal tube and intravascular catheters, and occurrence of nosocomial pneumonia.

A scheme to grade the severity of lung injury, the lung injury score, has been proposed. The lung injury score is calculated after evaluating the severity of 4 components—the chest roentgenogram score, hypoxemia score, the positive end-expiratory pressure (PEEP) score, and the respiratory system compliance score. A lung injury score of greater than 2.5 is associated with severe lung injury or ARDS.

Abdomen

Acquire supine and upright or lateral decubitus abdominal films because they 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.

Extremities

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 (eg, extreme pain, crepitus, bullae, hemorrhage, foul-smelling exudates).

If clinical suspicion of necrotizing fasciitis is high, a surgical consultation should be obtained immediately; such a patient should be taken promptly to the operating room (OR) for intervention, often without the need for any imaging. Computed tomography (CT) or magnetic resonance imaging (MRI) can show evidence of subcutaneous and deep tissue inflammation; however, neither modality is sensitive or specific in the setting of necrotizing deep tissue infection, and neither should be relied upon to make this diagnosis.

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

Ultrasonography

Abdominal ultrasonography is indicated when evidence of acute cholecystitis or ascending cholangitis exists (eg, right upper quadrant abdominal tenderness, fever, vomiting, elevated LFTs, bilirubin, and alkaline phosphatase levels). Surgery or endoscopic retrograde cholangiopancreatography (ERCP) may be urgently necessary in the setting of sepsis with acute cholecystitis or ascending cholangitis.

Computed Tomography

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

An abdominal CT scan should be obtained 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 require urgent operative intervention.

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

If evidence of increased intracranial pressure (ICP) (eg, papilledema) or focal mass lesions (focal defects, preceding sinusitis or otitis, recent intracranial surgery) exists, antibiotics should be started and a head CT scan should be obtained. CSF cultures will not be affected by the administration of antibiotics 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, then a lumbar puncture (LP) should be performed without the delay of obtaining a CT scan. If the opening pressure is elevated, then only as much CSF as is needed for culture should be obtained.

Lumbar Puncture

A lumbar puncture should be performed if clinical evidence or suspicion for meningitis or encephalitis exists. Broad-spectrum antibiotics to cover meningitis should be administered before starting the procedure. In patients with an acute fulminant presentation, a rapid onset of septic shock, and a severe impairment of mental status, use this procedure to rule out bacterial meningitis.

Other Evaluations

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.

Echocardiography is another modality that may be considered. It has a number of uses in assessing patients with septic shock.^[36]

Staging

Two well-defined forms of MODS of sepsis exist. In either, the development of acute lung injury (ALI) or ARDS is of key importance to the natural history, although ARDS is the earliest manifestation in all cases.

In the more common form of MODS, the lungs are the predominant, and often the only, organ system affected until very late in the disease. These patients most often present with primary pulmonary disorder (eg, pneumonia, aspiration, lung contusion, near drowning, chronic obstructive pulmonary disease [COPD] exacerbation, hemorrhage, pulmonary embolism).

Progression of lung disease occurs to meet the ARDS criteria. Pulmonary dysfunction may be accompanied by encephalopathy or mild coagulopathy and persists for 2-3 weeks. At this time, the patient either begins to recover or progresses to develop fulminant dysfunction in other organ systems. Once another major organ dysfunction occurs, these patients often do not survive.

In the second, less common, form of MODS, the presentation is quite different. These patients often have an inciting source of sepsis in organs other than the lung (the common source being intra-abdominal sepsis), extensive blood loss, pancreatitis, and vascular catastrophes.

ALI or ARDS develops early, but dysfunction in other organ systems also develops much sooner. The organ systems affected are hepatic, hematologic, cardiovascular, central nervous system (CNS), and renal. Patients remain in a pattern of compensated dysfunction for several weeks and then either recover or deteriorate further and die.

Criteria for mild and severe organ dysfunction have been established (see the table below).

Table 2. Criteria for Organ Dysfunction (Open Table in a new window)

Organ System	Mild Criteria	Severe Criteria
Pulmonary	Hypoxia/hypercarbia requiring assisted ventilation for 3-5 d	ARDS requiring PEEP >10 cm H₂ O and FiO₂ < 0.5
Hepatic	Bilirubin 2-3 mg/dL or other liver function tests more than twice normal, PT elevated to twice normal	Jaundice with bilirubin 8-10 mg/dL
Renal	Oliguria ( < 500 mL/d or increasing creatinine) 2-3 mg/dL	Dialysis
Gastrointestinal	Intolerance of gastric feeding for more than 5 d	Stress ulceration with need for transfusion, acalculous cholecystitis
Hematologic	aPTT >125% of reference range, platelets < 50-80,000	DIC
Cardiovascular	Decreased ejection fraction with persistent capillary leak	Hyperdynamic state not responsive to pressors
CNS	Confusion	Coma
Peripheral nervous system	Mild sensory neuropathy	Combined motor and sensory deficit
aPTT = Activated partial thromboplastin time; ARDS = acute respiratory distress syndrome; CNS = central nervous system; DIC = disseminated intravascular coagulation; FiO₂ = fraction of inspired oxygen; PEEP = positive end-expiratory pressure; PT = prothrombin time.

Proceed to Treatment & Management

Contributor Information and Disclosures

Author

Michael R Pinsky, MD, CM, FCCP, FCCM Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center

Michael R Pinsky, MD, CM, FCCP, FCCM is a member of the following medical societies: American College of Chest Physicians, American College of Critical Care Medicine, American Heart Association, American Thoracic Society, Association of University Anesthetists, European Society of Intensive Care Medicine, Shock Society, and Society of Critical Care Medicine

Disclosure: LiDCO Ltd Honoraria Consulting; iNTELOMED Intellectual property rights Board membership; Edwards Lifesciences Honoraria Consulting; Applied Physiology, Ltd Honoraria Consulting; Cheetah Medical Consulting fee Consulting

Coauthor(s)

Fatima Al Faresi, MD Dermatologist, Tawam Hospital, Al Ain, UAE

Disclosure: Nothing to disclose.

Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Daniel J Dire, MD, FACEP, FAAP, FAAEM Clinical Professor, Department of Emergency Medicine, University of Texas Medical School at Houston; Clinical Professor, Department of Pediatrics, University of Texas Health Sciences Center San Antonio

Daniel J Dire, MD, FACEP, FAAP, FAAEM is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American Academy of Pediatrics, American College of Emergency Physicians, and Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

Michael R Filbin, MD Clinical Instructor, Department of Emergency Medicine, Massachusetts General Hospital

Michael R Filbin, MD is a member of the following medical societies: American College of Emergency Physicians, Massachusetts Medical Society, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Franklin Flowers, MD Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, Affiliate Associate Professor of Pediatrics and Pathology, University of Florida College of Medicine

Franklin Flowers, MD, is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology

Disclosure: Nothing to disclose.

Theodore J Gaeta, DO, MPH, FACEP Clinical Associate Professor, Department of Emergency Medicine, Weill Cornell Medical College; Vice Chairman and Program Director of Emergency Medicine Residency Program, Department of Emergency Medicine, New York Methodist Hospital; Academic Chair, Adjunct Professor, Department of Emergency Medicine, St George's University School of Medicine

Theodore J Gaeta, DO, MPH, FACEP is a member of the following medical societies: Alliance for Clinical Education, American College of Emergency Physicians, Clerkship Directors in Emergency Medicine, Council of Emergency Medicine Residency Directors, New York Academy of Medicine, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Hassan I Galadari, MD Assistant Professor of Dermatology, Faculty of Medicine and Health Sciences, United Arab Emirates University

Hassan I Galadari, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Medical Student Association/Foundation, and American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Paul Krusinski, MD Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine

Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Steven Mink, MD Head, Section of Pulmonary Medicine, Department of Internal Medicine, St Boniface Hospital; Professor of Medicine, University of Manitoba, Canada

Steven Mink, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Mark L Plaster, MD, JD Executive Editor, Emergency Physicians Monthly

Mark L Plaster, MD, JD is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians

Disclosure: M L Plaster Publishing Co LLC Ownership interest Management position

Sat Sharma, MD, FRCPC Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital

Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association

Disclosure: Nothing to disclose.

Vicken Y Totten, MD, MS, FACEP, FAAFP Assistant Professor, Case Western Reserve University School of Medicine; Director of Research, Department of Emergency Medicine, University Hospitals, Case Medical Center

Vicken Y Totten, MD, MS, FACEP, FAAFP is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

Eric L Weiss, MD, DTM&H Medical Director, Office of Service Continuity and Disaster Planning, Fellowship Director, Stanford University Medical Center Disaster Medicine Fellowship, Chairman, SUMC and LPCH Bioterrorism and Emergency Preparedness Task Force, Clinical Associate Progressor, Department of Surgery (Emergency Medicine), Stanford University Medical Center

Eric L Weiss, MD, DTM&H is a member of the following medical societies: American College of Emergency Physicians, American College of Occupational and Environmental Medicine, American Medical Association, American Society of Tropical Medicine and Hygiene, Physicians for Social Responsibility, Southeastern Surgical Congress, Southern Association for Oncology, Southern Clinical Neurological Society, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Cory Franklin, MD Professor, Department of Medicine, Rosalind Franklin University of Medicine and Science; Director, Division of Critical Care Medicine, Cook County Hospital

Cory Franklin, MD is a member of the following medical societies: New York Academy of Sciences and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

John L Brusch, MD, FACP Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance

John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors R Phillip Dellinger, MD, Ismail Cinel, MD, PhD,Steven Manders, MD, Clara-Dina Cokonis, MD, and Dane Salandy, MD†,to the development and writing of the source articles.

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Venn diagram showing overlap of infection, bacteremia, sepsis, systemic inflammatory response syndrome (SIRS), and multiorgan dysfunction.

A 26-year-old woman developed rapidly progressive shock associated with purpura and signs of meningitis. The blood culture confirmed Neisseria meningitidis. The skin manifestation is characteristic of severe meningococcal infection and is called purpura fulminans.

Gram stain of blood showing presence of Neisseria meningitidis.

Acute respiratory distress syndrome (ARDS), commonly observed in septic shock as a part of multiorgan failure syndrome, is pathologically diffuse alveolar damage (DAD). This photomicrograph shows an early stage (exudative stage) of DAD.

Acute respiratory distress syndrome (ARDS), commonly observed in septic shock as a part of multiorgan failure syndrome, is pathologically diffuse alveolar damage (DAD). This is a high-powered photomicrograph of an early stage (exudative stage) of DAD.

This photomicrograph shows a delayed stage (proliferative or organizing stage) of diffuse alveolar damage (DAD). Proliferation of type II pneumocytes has occurred, hyaline membranes are present, and collagen and fibroblasts are present.

This photomicrograph shows a delayed stage (proliferative or organizing stage) of diffuse alveolar damage (DAD). This is fibrin stain showing collagenous tissue, which may develop into the fibrotic stage of DAD.