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Multisystem Organ Failure of Sepsis: Differential Diagnoses & Workup

Coauthor(s): 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; Gregg Eschun, MD, Assistant Professor, Department of Internal Medicine, Sections of Respirology and Critical Care, St Boniface Hospital, University of Manitoba, Canada
Contributor Information and Disclosures

Updated: Apr 28, 2009

Differential Diagnoses

Acute Renal Failure
Shock, Distributive
Acute Respiratory Distress Syndrome
Shock, Hemorrhagic
Cardiogenic Shock
Streptococcus Group A Infections
Infective Endocarditis
Systemic Inflammatory Response Syndrome
Pneumococcal Infections
Toxic Shock Syndrome
Pneumonia, Bacterial
Urinary Tract Infection, Females
Sepsis, Bacterial
Urinary Tract Infection, Males
Septic Shock
Ventilation, Mechanical

Workup

Laboratory Studies

  • Laboratory tests are useful in suspected sepsis or septic shock to assess the general hematologic and metabolic condition of the patient. The microbiologic studies provide results, which may indicate occult bacterial infection or bacteremia, and indicate the specific microbial etiology.
  • CBC count with differential: An adequate hemoglobin concentration is necessary to ensure oxygen delivery in shock. Maintain the hemoglobin at a level of 8 g/dL.
  • Platelets: Acute phase reactants, platelets usually increase at the onset of any serious stress. The platelet count will fall with persistent sepsis, and DIC may develop.
  • WBC count: The white cell differential and the WBC count may predict the existence of a bacterial infection. In adults who are febrile, a WBC count greater than 15,000 cells/µL or a neutrophil band count greater than 1500 cells/µL is associated with a high likelihood of bacterial infection.5
  • Metabolic assessment: Perform metabolic assessment with serum electrolytes, including magnesium, calcium, phosphate, and glucose, at regular intervals.
  • Renal and hepatic function: Assess renal and hepatic function with serum creatinine, BUN, bilirubin, alkaline phosphate, and alanine aminotransferase (ALT).
  • ABG
    • Measurement of serum lactate provides an assessment of tissue hypoperfusion.
    • Elevated serum lactate indicates that significant tissue hypoperfusion exists with the shift from aerobic to anaerobic metabolism.
  • Serum lactate: Higher serum lactate indicates a worse degree of shock and a higher mortality.
  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT): Assess coagulation status with prothrombin time (PT) and activated partial thromboplastin time (aPTT). Patients with clinical evidence of coagulopathy require additional tests to detect the presence of DIC.
  • Blood cultures: Indiscriminate use of blood cultures has low utility.
    • Blood culture is the primary modality for aiding in the diagnosis for intravascular infections (eg, endocarditis) and infections of indwelling intravascular devices.
    • Two populations, people who abuse IV drugs and patients with prosthetic heart valves, are at high risk for endocarditis.
    • Patients at risk for bacteremia include adults who are febrile with an elevated WBC or neutrophil band counts, elderly patients who are febrile, and patients who are febrile and neutropenic. These populations have a 20-30% incidence of bacteremia.
    • The incidence of bacteremia is at least 50% in patients with sepsis and evidence of end-organ dysfunction.
  • Urinalysis and urine culture: Order a urinalysis and urine culture for every patient who is septic. Urinary infection 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 (UTI).
  • Tissue staining and culture: Obtain secretions or tissue for Gram stain and culture from sites of potential infection. Generally, the Gram stain is the only available test to immediately document the presence of bacterial infection and guide the choice of initial antibiotic therapy.

Imaging Studies

  • A variety of imaging modalities are employed to diagnose clinically suspected focal infection, detect the presence of a clinically occult focal infection, and detect complications of sepsis and septic shock.
    • Obtain a chest radiograph in patients with severe sepsis because the clinical examination is unreliable for pneumonia. Clinically occult infiltrates have been detected by routine use of chest radiography in adults who are febrile without localizing symptoms or signs and in patients who are febrile and neutropenic without pulmonary symptoms.
    • Supine and upright or lateral decubitus abdominal films may be useful when an intraabdominal source is suspected.
    • Ultrasound is the imaging modality of choice when a biliary tract source is suspected to be the source of sepsis.
    • CT scan is the imaging modality of choice for excluding intraabdominal abscess or a retroperitoneal source of infection.
    • Obtain a CT scan of the head in patients with evidence of increased intracranial pressure (papilledema) or suggestion of focal mass lesions (eg, focal defects, previous sinusitis or otitis, recent intracranial surgery) or prior to lumbar puncture (LP) when meningitis is suspected.
    • When there is clinical evidence 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 and the spread of infection beyond clinically detectable disease may require surgical exploration.

Procedures

  • The LP needs to be performed urgently when meningitis or encephalitis is suspected. In patients with an acute fulminant presentation, rapid onset of septic shock, and severe impairment of mental status, rule out bacterial meningitis by LP.
    • Procedures, such as cardiac monitoring, noninvasive BP monitoring, and pulse oximetry, are necessary because patients often require ICU admission for invasive monitoring and support.
    • Supplemental oxygen is provided during initial stabilization and resuscitation.
  • All patients in septic shock should have adequate venous access for volume resuscitation. A central venous line also can be used to monitor central venous pressure to assess intravascular volume status.
  • An indwelling urinary catheter used to monitor urinary output is used as a marker for adequate renal perfusion and cardiac output.
  • Patients who have developed septic shock require right heart catheterization with a pulmonary artery (Swan-Ganz) catheter. This catheter provides an accurate assessment of the volume status of a patient who is septic. The cardiac output measurement can be obtained. Furthermore, determination of mixed venous oxygenation is helpful in determining the status of tissue oxygenation.
  • Most patients who are septic develop respiratory distress secondary to severe sepsis or as a manifestation of septic shock. Pulmonary dysfunction of sepsis (ARDS) also may occur. These patients need intubation and mechanical ventilation for optimum respiratory support.

Staging

Two well-defined forms of multiorgan dysfunction syndrome exist. In both, the development of acute lung injury or ARDS is of key importance to the natural history. ARDS is the earliest manifestation in all cases.

  • In the more common form of multiorgan dysfunction syndrome, 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, such as pneumonia, aspiration, contusion, near drowning, exacerbation of chronic obstructive pulmonary disease (COPD), hemorrhage, or pulmonary embolism. Lung disease progresses to meet ARDS criteria. Encephalopathy or mild coagulopathy may accompany pulmonary dysfunction, which persists for 2-3 weeks. At this time, the patient either begins to recover or progresses to develop fulminant dysfunction in another organ system. Once another major organ dysfunction occurs, these patients frequently do not survive.
  • The second form of multiorgan dysfunction syndrome presents quite differently. These patients often have an inciting source of sepsis in organs other than the lungs, the most common being intraabdominal sepsis, extensive blood loss, pancreatitis, or vascular catastrophes. Acute lung injury or ARDS develops early, and dysfunction in other organ systems also develops much sooner than in the more common form of multiorgan dysfunction syndrome. The organ systems affected are hepatic, hematological, cardiovascular, and renal. Patients remain in a pattern of compensated dysfunction for several weeks, at which time they either recover or deteriorate further and die. Criteria for Organ Dysfunction

    Open table in new window

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    Table
    Organ SystemMild CriteriaSevere Criteria
    PulmonaryHypoxia/hypercarbia requiring assisted ventilation for 3-5 daysARDS requiring PEEP* >10 cm H2 O and FiO2 † <0.5
    HepaticBilirubin 2-3 mg/dL or other liver function tests more than twice normal, PT elevated to twice normalJaundice with bilirubin 8-10 mg/dL
    RenalOliguria ( <500 mL/d or increasing creatinine) 2-3 mg/dLDialysis
    GastrointestinalIntolerance of gastric feeding for more than 5 daysStress ulceration with need for transfusion, acalculous cholecystitis
    HematologicaPTT >125% of normal, platelets <50-80,000Disseminated intravascular coagulation
    CardiovascularDecreased ejection fraction with persistent capillary leakHyperdynamic state not responsive to pressors
    CNSConfusionComa
    Peripheral nervous systemMild sensory neuropathyCombined motor and sensory deficit
    Organ SystemMild CriteriaSevere Criteria
    PulmonaryHypoxia/hypercarbia requiring assisted ventilation for 3-5 daysARDS requiring PEEP* >10 cm H2 O and FiO2 † <0.5
    HepaticBilirubin 2-3 mg/dL or other liver function tests more than twice normal, PT elevated to twice normalJaundice with bilirubin 8-10 mg/dL
    RenalOliguria ( <500 mL/d or increasing creatinine) 2-3 mg/dLDialysis
    GastrointestinalIntolerance of gastric feeding for more than 5 daysStress ulceration with need for transfusion, acalculous cholecystitis
    HematologicaPTT >125% of normal, platelets <50-80,000Disseminated intravascular coagulation
    CardiovascularDecreased ejection fraction with persistent capillary leakHyperdynamic state not responsive to pressors
    CNSConfusionComa
    Peripheral nervous systemMild sensory neuropathyCombined motor and sensory deficit
    *Positive end-expiratory pressure
    †Fraction of inspired oxygen

More on Multisystem Organ Failure of Sepsis

Overview: Multisystem Organ Failure of Sepsis
Differential Diagnoses & Workup: Multisystem Organ Failure of Sepsis
Treatment & Medication: Multisystem Organ Failure of Sepsis
Follow-up: Multisystem Organ Failure of Sepsis
Multimedia: Multisystem Organ Failure of Sepsis
References
Further Reading
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References

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Further Reading

Clinical guidelines
Drotrecogin alfa (activated) for severe sepsis.
National Institute for Health and Clinical Excellence (NICE) - National Government Agency [Non-U.S.].  2004 Sep.  31 pages.  NGC:004523

Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update.
Society of Critical Care Medicine - Professional Association.  2004 Sep.  21 pages.  NGC:004181

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008.
Society of Critical Care Medicine - Professional Association.  2004 (revised 2008 Jan).  44 pages.  NGC:006316

Clinical trials
Regulation of Endocrine, Metabolic, Immune and Bioenergetic Responses in Sepsis

Uremic Toxins in the Intensive Care Unit (ICU): Patients With Sepsis

Effects of Voluven on Hemodynamics and Tolerability of Enteral Nutrition in Patients With Severe Sepsis


Related eMedicine topics

Acute Renal Failure

Acute Respiratory Distress Syndrome

Cardiogenic Shock

Sepsis, Bacterial

Septic Shock






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Keywords

multisystem organ failure of sepsis, sepsis, organ failure, multiple organ failure, organ failures, multiple system organ failure, multiple organ system failure, multiple organ dysfunction syndrome, MODS

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Contributor Information and Disclosures

Coauthor(s)

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.

Gregg Eschun, MD, Assistant Professor, Department of Internal Medicine, Sections of Respirology and Critical Care, St Boniface Hospital, University of Manitoba, Canada
Gregg Eschun, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, Canadian Medical Association, and College of Physicians and Surgeons of Manitoba
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Daniel R Ouellette, MD, FCCP, Associate Professor of Medicine, Wayne State University School of Medicine; Consulting Staff, Pulmonary Disease and Critical Care Medicine Service, Henry Ford Health System
Daniel R Ouellette, MD, FCCP is a member of the following medical societies: American College of Chest Physicians and American Thoracic Society
Disclosure: Boehringer Ingleheim Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Michael R Pinsky, MD, CM, FCCP, FCCM, Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease and Anesthesiology, Vice-Chair, Academic Affairs, 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, 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

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