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Distributive Shock

  • Author: Klaus-Dieter Lessnau, MD, FCCP; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM  more...
Updated: Oct 08, 2015


Distributive shock results from excessive vasodilation and the impaired distribution of blood flow. Septic shock is the most common form of distributive shock and is characterized by considerable mortality (treated, around 30%; untreated, probably >80%). In the United States, this is the leading cause of noncardiac death in intensive care units (ICUs). (See Pathophysiology, Etiology, Epidemiology, and Prognosis.)

Other causes of distributive shock include systemic inflammatory response syndrome (SIRS) due to noninfectious inflammatory conditions such as burns and pancreatitis; toxic shock syndrome (TSS); anaphylaxis; reactions to drugs or toxins, including insect bites, transfusion reaction, and heavy metal poisoning; addisonian crisis; hepatic insufficiency; and neurogenic shock due to brain or spinal cord injury. (See Pathophysiology and Etiology.)

Types of shock

Shock is a clinical syndrome characterized by inadequate tissue perfusion that results in end-organ dysfunction. It can be divided into the following 4 categories:

  • Distributive shock (vasodilation), which is a hyperdynamic process
  • Cardiogenic shock (pump failure)
  • Hypovolemic shock (intravascular volume loss)
  • Obstructive shock (physical obstruction of blood circulation and inadequate blood oxygenation)

Systemic inflammatory response syndrome

The American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) Consensus Conference Committee defined SIRS as the presence of at least 2 of the following 4 criteria (see Presentation)[1] :

  • Core temperature of higher than 38°C (100.0°F) or lower than 36°C (96.8°F)
  • Heart rate of more than 90 beats per minute
  • Respiratory rate of more than 20 breaths per minute or arterial carbon dioxide tension (PaCO 2) less than 32mm Hg
  • White blood cell (WBC) count of more than 12,000/µL, less than 4,000/µL, or more than 10% immature (band) forms

The clinical suspicion of systemic inflammatory response syndrome by an experienced clinician is of utmost importance.

Patient education

For patient education information, see Shock and Cardiopulmonary Resuscitation (CPR).



In distributive shock, the inadequate tissue perfusion is caused by loss of the normal responses of vascular smooth muscle to vasoconstrictive agents coupled with a direct vasodilating effect. The net result in a fluid-resuscitated patient is a hyperdynamic, hypotensive state associated with increased mixed venous O2 saturation; however, evidence of tissue ischemia as manifest by an increased serum lactate, presumably due to intraorgan functional shunts.

Early septic shock (warm or hyperdynamic) causes reduced diastolic blood pressure; widened pulse pressure; flushed, warm extremities; and brisk capillary refill from peripheral vasodilation, with a compensatory increase in cardiac output. In late septic shock (cold or hypodynamic), myocardial contractility combines with peripheral vascular paralysis to induce a pressure-dependent reduction in organ perfusion. The result is hypoperfusion of critical organs such as the heart, brain, and liver.

The hemodynamic derangements observed in septic shock and SIRS are due to a complicated cascade of inflammatory mediators. Inflammatory mediators are released in response to any of a number of factors, such as infection, inflammation, or tissue injury. For example, bacterial products such as endotoxin activate the host inflammatory response, leading to increased pro-inflammatory cytokines (eg, tumor necrosis factor (TNF), interleukin (IL) –1, and IL-6. Toll-like receptors are thought to play a critical role in responding to pathogens as well as in the excessive inflammatory response that characterizes distributive shock; these receptors are considered possible drug targets.

Cytokines and phospholipid-derived mediators act synergistically to produce the complex alterations in vasculature (eg, increased microvascular permeability, impaired microvascular response to endogenous vasoconstrictors such as norepinephrine) and myocardial function (direct inhibition of myocyte function), which leads to maldistribution of blood flow and hypoxia. Hypoxia also induces the upregulation of enzymes that create nitric oxide, a potent vasodilator, thereby further exacerbating hypoperfusion.

The coagulation cascade is also affected in septic shock. Activated monocytes and endothelial cells are sources of tissue factors that activate the coagulation cascade; cytokines, such as IL-6, also play a role. The coagulation response is broadly disrupted, including impairment of antithrombin and fibrinolysis. Thrombin generated as part of the inflammatory response can trigger disseminated intravascular coagulation (DIC). DIC is found in 25-50% of patients with sepsis and is a significant risk factor for mortality.[2, 3]

During distributive shock, patients are at risk for diverse organ system dysfunction that may progress to multiple organ failure (MOF). Mortality from severe sepsis increases markedly with the duration of sepsis and the number of organs failing.

In distributive shock due to anaphylaxis, decreased SVR is due primarily to massive histamine release from mast cells after activation by antigen-bound immunoglobulin E (IgE), as well as increased synthesis and release of prostaglandins.

Neurogenic shock is due to loss of sympathetic vascular tone from severe injury to the nervous system.



The most common etiology of distributive shock is sepsis. Other causes include the following:

  • SIRS due to noninfectious conditions such as pancreatitis, burns, or trauma
  • TSS
  • Anaphylaxis
  • Adrenal insufficiency
  • Reactions to drugs or toxins
  • Heavy metal poisoning
  • Hepatic insufficiency
  • Neurogenic shock

All of these conditions share the common characteristic of hypotension due to decreased SVR and low effective circulating plasma volume.

Septic shock

The most common sites of infection, in decreasing order of frequency, include the chest, abdomen, and genitourinary tract.

Septic shock is commonly caused by bacteria, although viruses, fungi, and parasites are also implicated. Gram-positive bacteria are being isolated more, with their numbers almost similar to those of gram-negative bacteria, which in the past were considered to be the predominant organisms. Multidrug-resistant organisms are increasingly common.[4]

Systemic inflammatory response syndrome

Causes of SIRS include the following:

  • Infection
  • Burns
  • Surgery
  • Trauma
  • Pancreatitis
  • Fulminant hepatic failure

Toxic shock syndrome

TSS can result from infection with Streptococcus pyogenes (group A Streptococcus) or Staphylococcus aureus.

Adrenal insufficiency

Adrenal insufficiency can result from the following:

  • Destruction of adrenal glands due to autoimmune disease, infection (tuberculosis, fungal infection, acquired immunodeficiency syndrome [AIDS]), hemorrhage, cancer, or surgical removal
  • Suppression of hypothalamic-pituitary-adrenal axis by exogenous steroid, usually with doses at 20 mg daily or higher
  • Hypopituitarism
  • Metabolic failure in hormone production due to congenital conditions or drug-induced inhibition of synthetic enzymes (eg, metyrapone, ketoconazole)


Anaphylaxis can develop as a result of the following:

  • Drugs such as penicillins and cephalosporins
  • Heterologous proteins such as Hymenoptera venom, foods, pollen, and blood serum products


Occurrence in the United States

Sepsis develops in more than 750,000 patients per year in the United States. Angus and colleagues estimated that, by 2010, 1 million people per year would be diagnosed with sepsis.[5] From 1979-2000, the incidence of sepsis increased by 9% per year.

International occurrence

Sepsis is a common cause of death throughout the world and kills approximately 1,400 people worldwide every day.[6, 7]

Age-related demographics

Increased age correlates with increased risk of death from sepsis.



The mortality rate after development of septic shock is 20-80%.[8] Data suggest that mortality due to septic shock has decreased slightly because of new therapeutic interventions.[9] Early recognition and appropriate therapy are central to maximizing good outcomes. Identifying patients with septic shock in the emergency department, as opposed to identifying them outside of it, results in significantly improved mortality. In one study, the mortality rate for emergency department-identified patients was 27.7%, compared with 41.1% for patients identified outside of the emergency department.[10]

Higher mortality rates have also been associated with the following:

  • Advanced age
  • The finding of positive blood cultures
  • Infection with antibiotic-resistant organisms such as Pseudomonas aeruginosa
  • Elevated serum lactate levels
  • Impaired immune function
  • Alcohol use
  • Poor functional status prior to the onset of sepsis.

Mortality rates associated with other forms of distributive shock are not well documented.


Duration of delirium is an independent predictor of long-term cognitive impairment. At 3-month and 12-month follow-up, as many as 79% and 71% of patients have cognitive impairment. About one third remain severely impaired.[11, 12, 13]

Contributor Information and Disclosures

Klaus-Dieter Lessnau, MD, FCCP Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Nothing to disclose.


Ruben Peralta, MD, FACS Professor of Surgery, Anesthesia and Emergency Medicine, Senior Medical Advisor, Board of Directors, Program Chief of Trauma, Emergency and Critical Care, Consulting Staff, Professor Juan Bosch Trauma Hospital, Dominican Republic

Ruben Peralta, MD, FACS is a member of the following medical societies: American Association of Blood Banks, American College of Surgeons, American Medical Association, Association for Academic Surgery, Massachusetts Medical Society, Society of Critical Care Medicine, Society of Laparoendoscopic Surgeons, Eastern Association for the Surgery of Trauma, American College of Healthcare Executives

Disclosure: Nothing to disclose.

Chief Editor

Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease, Clinical and Translational Science and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine

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

Disclosure: Received income in an amount equal to or greater than $250 from: Masimo<br/>Received honoraria from LiDCO Ltd for consulting; Received intellectual property rights from iNTELOMED for board membership; Received honoraria from Edwards Lifesciences for consulting; Received honoraria from Masimo, Inc for board membership.

Additional Contributors

Lalit K Kanaparthi, MD Attending Physician, North Florida Lung Associates

Lalit K Kanaparthi, MD is a member of the following medical societies: American College of Chest Physicians, American Medical Association, American Thoracic Society

Disclosure: Nothing to disclose.


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.

Sarah C Langenfeld, MD Assistant Professor, Department of Psychiatry, University of Massachusetts Medical School; Attending Psychiatrist, Community HealthLink

Sarah Langenfeld, MD is a member of the following medical societies: American Medical Association, American Psychiatric Association, and Massachusetts Medical Society

Disclosure: Nothing to disclose.

Scott P Neeley, MD Medical Director, Intensive Care Unit, St Alexius Medical Center

Scott P Neeley, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physician Executives, American College of Physicians, American Thoracic Society, Phi Beta Kappa, and Sigma Xi

Disclosure: Nothing to disclose.

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: 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

  1. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr. 31(4):1250-6. [Medline].

  2. Vervloet MG, Thijs LG, Hack CE. Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock. Semin Thromb Hemost. 1998. 24(1):33-44. [Medline].

  3. Levi M. Pathogenesis and treatment of disseminated intravascular coagulation in the septic patient. J Crit Care. 2001 Dec. 16(4):167-77. [Medline].

  4. Friedman, Gilberto MD; Silva, Eliezer MD; Vincent, Jean-Louis MD, PhD, FCCM. Has the mortality of septic shock changed with time?. Critical Care Medicine. December 1998. 26(12):2078-2086. [Full Text].

  5. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001 Jul. 29(7):1303-10. [Medline].

  6. Rubulotta FM, Ramsay G, Parker MM, Dellinger RP, Levy MM, Poeze M. An international survey: Public awareness and perception of sepsis. Crit Care Med. 2009 Jan. 37(1):167-70. [Medline].

  7. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992 Jun. 101(6):1644-55. [Medline].

  8. Parrillo JE. Pathogenetic mechanisms of septic shock. N Engl J Med. 1993 May 20. 328(20):1471-7. [Medline].

  9. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001 Mar 8. 344(10):699-709. [Medline].

  10. Bastani A, Galens S, Rocchini A, Walch R, Shaqiri B, Palomba K, et al. ED identification of patients with severe sepsis/septic shock decreases mortality in a community hospital. Am J Emerg Med. 2011 Dec 26. [Medline].

  11. Girard TD, Jackson JC, Pandharipande PP, et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med. 2010 Jul. 38(7):1513-20. [Medline].

  12. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14. 291(14):1753-62. [Medline].

  13. Desai SV, Law TJ, Needham DM. Long-term complications of critical care. Crit Care Med. 2011 Feb. 39(2):371-9. [Medline].

  14. Marik PE, Kiminyo K, Zaloga GP. Adrenal insufficiency in critically ill patients with human immunodeficiency virus. Crit Care Med. 2002 Jun. 30(6):1267-73. [Medline].

  15. Sandham JD, Hull RD, Brant RF, et al. A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. N Engl J Med. 2003 Jan 2. 348(1):5-14. [Medline].

  16. Shah MR, Hasselblad V, Stevenson LW, Binanay C, O'Connor CM, Sopko G. Impact of the pulmonary artery catheter in critically ill patients: meta-analysis of randomized clinical trials. JAMA. 2005 Oct 5. 294(13):1664-70. [Medline].

  17. Ince C. The microcirculation is the motor of sepsis. Crit Care. 2005. 9 Suppl 4:S13-9.

  18. Elbers PW, Ince C. Mechanisms of critical illness--classifying microcirculatory flow abnormalities in distributive shock. Crit Care. 2006. 10(4):221. [Medline]. [Full Text].

  19. Micek ST, Roubinian N, Heuring T, et al. Before-after study of a standardized hospital order set for the management of septic shock. Crit Care Med. 2006 Nov. 34(11):2707-13. [Medline].

  20. Nguyen HB, Corbett SW, Steele R, et al. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med. 2007 Apr. 35(4):1105-12. [Medline].

  21. Sebat F, Johnson D, Musthafa AA, et al. A multidisciplinary community hospital program for early and rapid resuscitation of shock in nontrauma patients. Chest. 2005 May. 127(5):1729-43. [Medline].

  22. Trzeciak S, Dellinger RP, Abate NL, et al. Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department. Chest. 2006 Feb. 129(2):225-32. [Medline].

  23. Lagu T, Rothberg MB, Nathanson BH, Pekow PS, Steingrub JS, Lindenauer PK. Variation in the care of septic shock: The impact of patient and hospital characteristics. J Crit Care. 2012 Jan 31. [Medline].

  24. Zambon M, Ceola M, Almeida-de-Castro R, Gullo A, Vincent JL. Implementation of the Surviving Sepsis Campaign guidelines for severe sepsis and septic shock: we could go faster. J Crit Care. 2008 Dec. 23(4):455-60. [Medline].

  25. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun. 34(6):1589-96. [Medline].

  26. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8. 345(19):1368-77. [Medline].

  27. Jones AE, Focht A, Horton JM, Kline JA. Prospective external validation of the clinical effectiveness of an emergency department-based early goal-directed therapy protocol for severe sepsis and septic shock. Chest. 2007 Aug. 132(2):425-32. [Medline].

  28. Kortgen A, Niederprum P, Bauer M. Implementation of an evidence-based "standard operating procedure" and outcome in septic shock. Crit Care Med. 2006 Apr. 34(4):943-9. [Medline].

  29. McIntyre LA, Fergusson D, Cook DJ, et al. Resuscitating patients with early severe sepsis: a Canadian multicentre observational study. Can J Anaesth. 2007 Oct. 54(10):790-8. [Medline].

  30. McIntyre LA, Hebert PC, Fergusson D, Cook DJ, Aziz A. A survey of Canadian intensivists' resuscitation practices in early septic shock. Crit Care. 2007. 11(4):R74. [Medline].

  31. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med. 2008 Jan. 34(1):17-60. [Medline].

  32. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008 Jan. 36(1):296-327. [Medline].

  33. Gunn SR, Fink MP, Wallace B. Equipment review: the success of early goal-directed therapy for septic shock prompts evaluation of current approaches for monitoring the adequacy of resuscitation. Crit Care. 2005 Aug. 9(4):349-59. [Medline].

  34. ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014 Oct 16. 371 (16):1496-506. [Medline].

  35. ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1. 370 (18):1683-93. [Medline].

  36. Pearse RM, Harrison DA, MacDonald N, Gillies MA, Blunt M, Ackland G, et al. Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review. JAMA. 2014 Jun 4. 311 (21):2181-90. [Medline].

  37. Dubois MJ, Orellana-Jimenez C, Melot C, et al. Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled, pilot study. Crit Care Med. 2006 Oct. 34(10):2536-40. [Medline].

  38. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004 May 27. 350(22):2247-56. [Medline].

  39. Finfer S, Bellomo R, McEvoy S, Lo SK, Myburgh J, Neal B, et al. Effect of baseline serum albumin concentration on outcome of resuscitation with albumin or saline in patients in intensive care units: analysis of data from the saline versus albumin fluid evaluation (SAFE) study. BMJ. 2006 Nov 18. 333(7577):1044. [Medline].

  40. Finfer S, Myburgh J, Bellomo R. Albumin supplementation and organ function. Crit Care Med. 2007 Mar. 35(3):987-8. [Medline].

  41. Myburgh J, Cooper DJ, Finfer S, et al. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med. 2007 Aug 30. 357(9):874-84. [Medline].

  42. Cavallaro F, Sandroni C, Marano C, La Torre G, Mannocci A, De Waure C, et al. Diagnostic accuracy of passive leg raising for prediction of fluid responsiveness in adults: systematic review and meta-analysis of clinical studies. Intensive Care Med. 2010 Sep. 36(9):1475-83. [Medline].

  43. Hassan M, Pham TN, Cuschieri J, Warner KJ, Nester T, Maier RV, et al. The association between the transfusion of older blood and outcomes after trauma. Shock. 2011 Jan. 35(1):3-8. [Medline].

  44. Zander R, Boldt J, Engelmann L, Mertzlufft F, Sirtl C, Stuttmann R. [The design of the VISEP trial. Critical appraisal]. Anaesthesist. 2007 Jan. 56(1):71-7. [Medline].

  45. Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008 Jan 10. 358(2):125-39. [Medline].

  46. Holmes CL, Patel BM, Russell JA, Walley KR. Physiology of vasopressin relevant to management of septic shock. Chest. 2001 Sep. 120(3):989-1002. [Medline].

  47. Landry DW, Oliver JA. Vasopressin and relativity: on the matter of deficiency and sensitivity. Crit Care Med. 2006 Apr. 34(4):1275-7. [Medline].

  48. Lauzier F, Levy B, Lamarre P, Lesur O. Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized clinical trial. Intensive Care Med. 2006 Nov. 32(11):1782-9. [Medline].

  49. Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008 Feb 28. 358(9):877-87. [Medline].

  50. Serpa Neto A, Nassar Junior AP, Cardoso SO, Manettta JA, Pereira VG, Esposito DC, et al. Vasopressin and terlipressin in adult vasodilatory shock: a systematic review and meta-analysis of nine randomized controlled trials. Crit Care. 2012 Aug 14. 16(4):R154. [Medline].

  51. Holmes CL. Vasoactive drugs in the intensive care unit. Curr Opin Crit Care. 2005 Oct. 11(5):413-7. [Medline].

  52. Kinasewitz GT, Zein JG, Lee GL, et al. Prognostic value of a simple evolving disseminated intravascular coagulation score in patients with severe sepsis. Crit Care Med. 2005 Oct. 33(10):2214-21.

  53. Zeerleder S, Hack CE, Wuillemin WA. Disseminated intravascular coagulation in sepsis. Chest. 2005 Oct. 128(4):2864-75. [Medline].

  54. Hoffmann JN, Vollmar B, Laschke MW, et al. Microcirculatory alterations in ischemia-reperfusion injury and sepsis: effects of activated protein C and thrombin inhibition. Crit Care. 2005. 9 Suppl 4:S33-7.

  55. Mackenzie AF. Activated protein C: do more survive?. Intensive Care Med. 2005 Dec. 31(12):1624-6.

  56. O'Brien LA, Gupta A, Grinnell BW. Activated protein C and sepsis. Front Biosci. 2006. 11:676-98. [Medline].

  57. Parrillo JE. Severe sepsis and therapy with activated protein C. N Engl J Med. 2005 Sep 29. 353(13):1398-400. [Medline].

  58. Wiedermann CJ, Kaneider NC. A meta-analysis of controlled trials of recombinant human activated protein C therapy in patients with sepsis. BMC Emerg Med. 2005 Oct 14. 5:7. [Medline].

  59. Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y. Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. BMJ. 2004 Aug 28. 329(7464):480. [Medline]. [Full Text].

  60. Raurich JM, Llompart-Pou JA, Ibanez J, et al. Low-dose steroid therapy does not affect hemodynamic response in septic shock patients. J Crit Care. 2007 Dec. 22(4):324-9. [Medline].

  61. Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008 Jan 10. 358(2):111-24. [Medline].

  62. Bruno JJ, Dee BM, Anderegg BA, Hernandez M, Pravinkumar SE. US practitioner opinions and prescribing practices regarding corticosteroid therapy for severe sepsis and septic shock. J Crit Care. 2012 Feb 14. [Medline].

  63. Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21. 288(7):862-71. [Medline].

  64. Kinasewitz GT, Privalle CT, Imm A, et al. Multicenter, randomized, placebo-controlled study of the nitric oxide scavenger pyridoxalated hemoglobin polyoxyethylene in distributive shock. Crit Care Med. 2008 Jul. 36(7):1999-2007. [Medline].

  65. Jimenez MF, Marshall JC. Source control in the management of sepsis. Intensive Care Med. 2001. 27 Suppl 1:S49-62. [Medline].

  66. Vincent JL, Ince C, Bakker J. Clinical review: Circulatory shock--an update: a tribute to Professor Max Harry Weil. Crit Care. 2012 Nov 20. 16 (6):239. [Medline].

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 was a previous intravenous drug user (human immunodeficiency virus [HIV] status: negative) developed septic shock secondary to bilateral pneumococcal pneumonia.
Microcirculatory abnormalities in distributive shock. Each image represents a venule (large, curved tube) and 2 capillaries (smaller tubes) and demonstrates the 2 main capillary flow patterns found in each class of microcirculatory abnormality, as they occur in distributive shock. This classification system was introduced by Elbers and Ince. Elbers P, Ince C. Bench-to-bedside review: mechanisms of critical illness—classifying microcirculatory flow abnormalities in distributive shock. Crit Care. July 19 2006;10(4):221.
Table 1. Pulmonary Artery Catheter Findings in Common Shock States
Diagnosis Pulmonary Capillary Wedge Pressure Cardiac Output
Cardiogenic shock* Increased Decreased
Extracardiac obstructive shock

1. Pericardial tamponade†

2. Pulmonary embolism


Normal or decreased



Hypovolemic shock Decreased Decreased
Distributive shock

1. Septic shock

2. Anaphylactic shock

Normal or decreased

Normal or decreased

Increased or normal

Increased or normal

*In cardiogenic shock due to a mechanical defect, such as mitral regurgitation, forward cardiac output is reduced, although the measured cardiac output may be unreliable. Large V waves are commonly observed in the pulmonary capillary wedge tracing in mitral regurgitation.

†The hallmark finding is equalization of right atrial mean, right ventricular end-diastolic, pulmonary artery (PA) end-diastolic, and pulmonary capillary wedge pressures.

Table 2. Vasoactive Drugs in Sepsis and the Usual Hemodynamic Responses
Drug Dose Principal Mechanism Cardiac Output Blood Pressure SVR
Inotropic agents
Dobutamine 2-20 mcg/kg/min Beta 1 ++ + +

(low dose)

5-10 mcg/kg/min Beta 1, dopamine ++ + +
Epinephrine (low dose) 0.06-0.20 mcg/kg/min Beta 1, beta 2 >alpha ++ + +
Inotropic agents and vasoconstrictors
Dopamine (high dose) >10 mcg/kg/min Alpha, beta 1, dopamine ++ ++ +

(high dose)

0.21-0.42 mcg/kg/min Alpha >beta 1, beta 2 ++ ++ +
Norepinephrine 0.02-0.25 mcg/kg/min Alpha >beta 1, beta 2 + ++ ++
Phenylephrine 0.2-2.5 mcg/kg/min Alpha + ++ ++
Vasopressin 0.10-0.40 U/min V1 receptor + + ++

(very low dose)

1-4 mcg/kg/min Dopamine +/- +/- -
Milrinone 0.4-0.6 mcg/kg/min after loading dose; 50 mcg/kg bolus over 5 min Phosphodiesterase inhibitor + +/- -
Alpha and beta refer to agonist activity at these adrenergic receptor sites.

Beta 1-adrenergic effects are inotropic and increase contractility.

Beta 2-adrenergic effects are chronotropic.[51]

Table 3. Empiric Antimicrobial Therapy in Septic Shock Based on Suspected Site of Infection
Suspected Source Recommended Antibiotic Therapy Alternative Therapy
No source evident in a healthy host Third-generation cephalosporin, eg, ceftriaxone 2 g IV q12h, ceftizoxime, ceftazidime Nafcillin and aminoglycoside, imipenem, piperacillin/tazobactam
No source evident in an immunocompromised host Ceftazidime 2 g IV q8h plus aminoglycoside Imipenem or piperacillin/tazobactam plus aminoglycoside
No source evident in a user of intravenous drugs Nafcillin 2 g IV q4h plus aminoglycoside Vancomycin plus aminoglycoside, ceftazidime, imipenem, or piperacillin/tazobactam
Bacterial pneumonia, community acquired Ceftriaxone 2 g IV q12-24 h plus macrolide Levofloxacin 750mg IV q24h, cotrimoxazole or imipenem plus macrolide
Bacterial pneumonia, hospital acquired Piperacillin/tazobactam 4.5 g IV q6h plus aminoglycoside, plus levofloxacin 750 mg IV q24h Imipenem plus aminoglycoside, plus macrolide
Urinary tract infection Ampicillin 2 g IV q4h plus aminoglycoside Fluoroquinolone or third-generation cephalosporin plus aminoglycoside
Mixed aerobic and anaerobic abdominal sepsis, aspiration pneumonia, pelvic infection, and necrotizing cellulitis Third-generation cephalosporin or ampicillin 2 g IV q4h plus aminoglycoside plus clindamycin 600 mg IV q8h or metronidazole 500 mg IV q6h Fluoroquinolone plus clindamycin, imipenem, piperacillin/tazobactam
Meningitis Ceftriaxone 2 g IV q12h plus vancomycin Meropenem plus vancomycin, chloramphenicol plus cotrimoxazole plus vancomycin
Cellulitis/erysipelas Nafcillin 2 g IV q4h Cefazolin, vancomycin, clindamycin
Toxic shock syndrome (TSS) or streptococcal necrotizing fasciitis Clindamycin 600 mg IV q8h Cephalosporin, vancomycin, nafcillin
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