Sections

Distributive Shock

DDx

Diagnostic Considerations

Conditions to consider in the differential diagnosis of distributive shock include the following:

Anaphylaxis
Burns
Carbon monoxide poisoning
Drug reaction
Heavy metal poisoning
Insect bite
Major surgery
Neurogenic shock
Thyrotoxicosis
Toxic shock syndrome (TSS)
Cyanide toxicity
Thrombotic thrombocytopenic purpura (TTP)

Differential Diagnoses

Workup

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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].
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Ince C. The microcirculation is the motor of sepsis. Crit Care. 2005. 9 Suppl 4:S13-9.
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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].
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].
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].
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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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
Finfer S, Myburgh J, Bellomo R. Albumin supplementation and organ function. Crit Care Med. 2007 Mar. 35(3):987-8. [Medline].
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].
[Guideline] Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar. 43 (3):304-377. [Medline].
Feissel M, Michard F, Faller JP, Teboul JL. The respiratory variation in inferior vena cava diameter as a guide to fluid therapy. Intensive Care Med. 2004 Sep. 30 (9):1834-7. [Medline].
Barbier C, Loubières Y, Schmit C, Hayon J, Ricôme JL, Jardin F, et al. Respiratory changes in inferior vena cava diameter are helpful in predicting fluid responsiveness in ventilated septic patients. Intensive Care Med. 2004 Sep. 30 (9):1740-6. [Medline].
Lichtenstein D. Fluid administration limited by lung sonography: the place of lung ultrasound in assessment of acute circulatory failure (the FALLS-protocol). Expert Rev Respir Med. 2012 Apr. 6 (2):155-62. [Medline].
Lichtenstein DA, Mezière GA, Lagoueyte JF, Biderman P, Goldstein I, Gepner A. A-lines and B-lines: lung ultrasound as a bedside tool for predicting pulmonary artery occlusion pressure in the critically ill. Chest. 2009 Oct. 136 (4):1014-1020. [Medline].
Volpicelli G, Skurzak S, Boero E, Carpinteri G, Tengattini M, Stefanone V, et al. Lung ultrasound predicts well extravascular lung water but is of limited usefulness in the prediction of wedge pressure. Anesthesiology. 2014 Aug. 121 (2):320-7. [Medline].
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].
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].
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].
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].
Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, et al. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Aug 3. 377 (5):419-430. [Medline].
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].
Landry DW, Oliver JA. Vasopressin and relativity: on the matter of deficiency and sensitivity. Crit Care Med. 2006 Apr. 34(4):1275-7. [Medline].
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].
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].
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].
Holmes CL. Vasoactive drugs in the intensive care unit. Curr Opin Crit Care. 2005 Oct. 11(5):413-7. [Medline].
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.
Zeerleder S, Hack CE, Wuillemin WA. Disseminated intravascular coagulation in sepsis. Chest. 2005 Oct. 128(4):2864-75. [Medline].
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.
Mackenzie AF. Activated protein C: do more survive?. Intensive Care Med. 2005 Dec. 31(12):1624-6.
O'Brien LA, Gupta A, Grinnell BW. Activated protein C and sepsis. Front Biosci. 2006. 11:676-98. [Medline].
Parrillo JE. Severe sepsis and therapy with activated protein C. N Engl J Med. 2005 Sep 29. 353(13):1398-400. [Medline].
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].
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].
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].
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].
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].
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].
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].
Jimenez MF, Marshall JC. Source control in the management of sepsis. Intensive Care Med. 2001. 27 Suppl 1:S49-62. [Medline].

Media Gallery

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.
Ultrasound clip demonstrating a collapsing inferior vena cava (IVC) on inspiration. A change in IVC diameter with respiration of at least 12-18% has been associated with fluid responsiveness (defined as an increase in cardiac output of >15% after a fluid bolus).
Lung ultrasound image over one lung zone showing the A-line pattern. This represents normal aeration and absence of pulmonary edema. A patient who demonstrates this pattern in conjunction with an inferior vena cava diameter that shows respirophasic variation of at least 12-18% will likely be fluid responsive.

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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	Increased Normal or decreased	Decreased 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	++	+	+
Dopamine (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	++	++	+
Epinephrine (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	+	++	++
Vasoconstrictors
Synthetic human angiotensin II	20 ng/kg/min; up to 80 ng/kg/min during first 3 h of therapy Maintenance: 1.25-40 ng/kg/min	Renin-angiotensin-aldosterone system (RAAS)	+/-	++	+/-
Phenylephrine	0.2-2.5 mcg/kg/min	Alpha	+	++	++
Vasopressin	0.10-0.40 U/min	V1 receptor	+	+	++
Vasodilators
Dopamine (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.^[58]

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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Author

Klaus-Dieter Lessnau, MD, FCCP Former 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.

Coauthor(s)

Kevin Gerard G Lazo, DO Attending Hospitalist, Division of Hospital Medicine, Department of Medicine, Northwell Health; Assistant Professor of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell

Kevin Gerard G Lazo, DO is a member of the following medical societies: American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Oki Ishikawa, MD Chief Resident Physician, Department of Internal Medicine, Lenox Hill Hospital, Northwell Health

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.

Chuan Jiang, MD Physician, Lenox Hill Hospital, Northwell Health

Chuan Jiang, MD is a member of the following medical societies: American College of Physicians, Society of Hospital Medicine

Disclosure: Nothing to disclose.

Chief Editor

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

Disclosure: Received income in an amount equal to or greater than $250 from: Baxter Medical, Exostat, LiDCO<br/>Received honoraria from LiDCO Ltd for consulting; Received intellectual property rights from iNTELOMED.

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.

Acknowledgements

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

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