Septic Shock Differential Diagnoses

  • Author: Michael R Pinsky, MD, CM, FCCP, FCCM; Chief Editor: Michael R Pinsky, MD, CM, FCCP, FCCM   more...
 
Updated: Oct 25, 2011
 
 

Diagnostic Considerations

A continuum of severity exists from sepsis to septic shock and multiple organ dysfunction syndrome (MODS). The clinical spectrum usually begins with infection that potentially leads to sepsis and organ dysfunction. In one study, 2527 patients were evaluated, 26% developed sepsis, 18% developed severe sepsis, and 4% developed septic shock. The incidence of positive results on blood culture was 17% in patients with sepsis and 69% in patients with septic shock.

Recognition of septic shock requires features of systemic inflammatory response syndrome (SIRS)—such as mental changes; hyperventilation; distributive hemodynamics; hyperthermia or hypothermia; reduced, elevated, or left shift of white blood cells (WBCs)—in addition to a potential source of infection.

Any patient presenting with shock must have an early working diagnosis, an approach to urgent resuscitation, and then confirmation of the working diagnosis. The following points should be considered for early diagnosis of sepsis:

  • Patients with sepsis may present in a myriad of ways, and high clinical suspicion is necessary to identify subtle presentations.
  • Septic patients should be screened for evidence of tissue hypo-perfusion.
  • Cool or clammy skin, mottling, and elevated shock index (heart rate/systolic blood pressure > 0.9) may be signs of tissue hypoperfusion.
  • A lactic acid level higher than 4 mmol/dL has been used as an entry criterion for early goal-directed therapy (EGDT; see Treatment and Management) and an indicator of severe tissue hypoperfusion.

A septic patient admitted to the intensive care unit (ICU) should be monitored carefully to prevent and treat the infectious complications, which may perpetuate SIRS or trigger relapse of sepsis after the initial improvement. Such complications include sinusitis, urinary tract infection, intravascular catheter–related infections, acalculous cholecystis, and translocation of bacteria or endotoxin from the gut lumen. As several of these ailments fail to manifest clinically, a high index of suspicion is crucial for early diagnosis and treatment.

Differential Diagnoses

Proceed to Workup
 
 
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

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

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.
Acute respiratory distress syndrome (ARDS) in a patient who developed septic shock secondary to toxic shock syndrome.
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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.
An 8-year-old boy developed septic shock secondary to Blastomycosis pneumonia. Fungal infections are a rare cause of septic shock.
A 28-year-old woman who is a previous intravenous drug user (HIV-negative status) developed septic shock secondary to bilateral pneumococcal pneumonia.
Table 1. Mediators of Sepsis
TypeMediatorActivity
Cellular mediatorsLipopolysaccharideActivation of macrophages, neutrophils, platelets, and endothelium releases various cytokines and other mediators
Lipoteichoic acid
Peptidoglycan
Superantigens
Endotoxin
Humoral mediatorsCytokinesPotent proinflammatory effect



Neutrophil chemotactic factor



Acts as pyrogen, stimulates B and T lymphocyte proliferation, inhibits cytokine production, induces immunosuppression



Activation and degranulation of neutrophils



Cytotoxic, augments vascular permeability, contributes to shock



Involved in hemodynamic alterations of septic shock



Promote neutrophil and macrophage, platelet activation and chemotaxis, other proinflammatory effects



Enhance vascular permeability and contributes to lung injury



Enhance neutrophil-endothelial cell interaction, regulate leukocyte migration and adhesion, and play a role in pathogenesis of sepsis



TNF-alpha and IL-1β



IL-8



IL-6



IL-10



MIF



G-CSF



Complement
Nitric oxide
Lipid mediators



Phospholipase A2



PAF



Eicosanoids



Arachidonic acid metabolites
Adhesion molecules



Selectins



Leukocyte integrins



G-CSF = Granulocyte colony-stimulating factor; IL = interleukin; MIF = macrophage inhibitory factor; PAF = platelet-activating factor; TNF = tumor necrosis factor.
Table 2. Criteria for Organ Dysfunction
Organ System Mild Criteria Severe Criteria
PulmonaryHypoxia/hypercarbia requiring assisted ventilation for 3-5 dARDS 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 dStress ulceration with need for transfusion, acalculous cholecystitis
HematologicaPTT >125% of reference range, platelets < 50-80,000DIC
CardiovascularDecreased ejection fraction with persistent capillary leakHyperdynamic state not responsive to pressors
CNSConfusionComa
Peripheral nervous systemMild sensory neuropathyCombined 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.
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