Contents

Search

septic shock

Sepsis leading to hypotension & impaired organ perfusion, unresponsive to fluid therapy [3]. A subset of sepsis in which underlying circulatory & cellular/ metabolic abnormalities are profound enough to substantially increase mortality. [13] Etiology: 1) gram positive bacteria - peptidoglycan/teichoic acid complex 2) gram negative bacteria - endotoxins 3) fungi - polysaccharide substances in yeast walls 4) Rickettsia 5) toxins - toxic shock syndrome Epidemiology: - in New Zealand & Australia death from septic shock in 2012 18%, down from 35% in 2000 [7] Pathology: 1) hypoxemia 2) activation of complement, coagulation, cytokine & arachidonate cascade 3) vasodilation, capillary leak 4) disseminated intravascular coagulation (DIC) 5) myocardial depression 6) acute renal failure 7) acute liver failure Clinical manifestations: - hypotension requiring vasopressor for maintain mean arterial pressure > 65 mm Hg [3] Laboratory: - blood cultures - complete blood count (CBC) - serum lactate [18] within 1 hour [22] - remeasure with 2-4 hours if > 2 mmol/L - > 2 mmol/L despite adequate fluid resuscitation - normal serum lactate is one endpoint of resuscitation [22] - complete metabolic panel [18] a) electrolytes b) serum glucose c) renal function tests d) liver function tests - do not perform dexamethasone suppression test Differential diagnosis: 1) cardiogenic shock 2) hypovolemic shock 3) adrenal crisis 4) obstructive shock Complications: - adrenocortical insufficiency [33] Management: - see distributive shock & sepsis - support organ perfusion: maintain mean arterial pressure > 65 mm Hg - control infection - early intervention is more likely to make a difference than invasive monitoring [7] - one hour sepsis bundle - initial bolus of IV crystalloid 30 mL/kg [3,15] - no benefit to fluid restriction in patients with septic shock [32] - assessment of volume responsiveness after initial fluid bolus before initiating vasopressors [34] - intravenous empiric antimicrobial therapy within 1 hour [15] - combination of 2 antibiotics of different class directed at most likely organism(s) [3] - generally single active antibiotic agent [19] - neutropenic patients & those with P. aeruginosa may have improved outcomes with double-active antibiotic therapy [19] - no mortality benefit to antibiotics within 1 hour vs 1-3 hours after emergency department arrival in patients with sepsis or septic shock [31] - norepinephrine 1st choice as vasopressor for septic shock requiring vasopressors despite fluid resuscitation [4,5,15] - superior to dopamine, fewer deaths, arrhythmias [5] - patients with septic shock more likely to die during a norepinephrine shortage [16] - no differences between vasopressin & norepinephrine in preserving renal function [14] - norepinephrine + vasopressin associated with less atrial fibrillation but not lower mortality [23] - synthetic angiotensin II may have mortality benefit [17] - maintain mean arterial pressure >= 65 mm Hg [15] who have failed to respond to an initial fluid challenge [3,4] - higher mean arterial pressure target increases risk of atrial fibrillation [7] - no mortality benefit in maintaining mean arterial pressure >= 80 mm Hg [3] - central venous pressure monitoring & targeting do not improve outcomes [30] - consider drotrecogin alpha a) septic shock requiring vasopressors despite fluid resuscitation b) sepsis-induced ARDS requiring mechanical ventilation with at least two dysfunctional organs [3] - glucocorticoids - low certainty evidence [26] - high risk patients may benefit [26] - patients with adrenocortical insufficiency [33] - no benefit to added vitamin C & thiamine [29] - of no benefit [12] - not associated with reduced mortality in patients with septic shock who undergo mechanical ventilation [20] - low-dose glucocorticoid (hydrocortisone 200 mg QD) not recommended unless systolic blood pressure < 90 mm Hg despite fluids & vasopressors [3] - maximum 400 mg hydrocortisone QD [3] - 30-day mortality diminished with low-dose glucocorticoids in patients with highest APACHE II scores (51% vs 56%), but may be increased in those with lower scores [10] - hydrocortisone + fludrocortisone - no benefit for ventilator-free days - lower all-cause 90 day mortality (RR=0.88) [21] - blood transfusion (packed RBC) - use standard thresholds (see blood transfusion) - transfusion thresholds of 7 g/dL & 9 g/dL result in similar outcomes [9] - albumin of no survival benefit [7] - early albumin may increase need for renal replacement therapy & in-hospital mortality among hospitalized patients with septic shock & chronic renal failure [37] - esmolol infusion to maintain heart rate between 80-94/min - improved survival 51% vs 19% at 28 days - did not result in lower blood pressures - reduced the need for norepinephrine [6] - thiamine 500 mg every 8 hours for 72 hours may facilitate plasma lactate clearance & reduce mortality (RR=0.67) [25] - no mortality benefit to early renal replacement therapy [27] - strategy targeting normalization of capillary refill time vs strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality [28] - early enteral nutrition if possible [3] - glycemic control: insulin to maintain plasma glucose 140-180 mg/dL [3] - mechanical ventilation: - tidal volume 6 mg/kg ideal body weight [3] - do not use non-invasive ventilation [3] Prognosis: 1) 40-75% mortality 2) poor prognosis associated with: a) advanced age b) infection with antimicrobial-resistant organism(s) c) impaired immunity d) poor patient functional status 3) presention with vague symptoms not specific to infection may result in delayed antibiotic administration & higher risk of mortality [24] 4) prevention of septic shock is most important factor in reducing mortality Notes: - early goal-directed therapy (6 hour resuscitation protocol) of no benefit [8,11] - Severe Sepsis/Septic Shock Early Management Bundle (SEP-1)

Related

Severe Sepsis/Septic Shock Early Management Bundle (SEP-1)

General

distributive shock; vasodilatory shock (multiple organ dysfunction syndrome) sepsis

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 136
  2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 853-55
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2018, 2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Dellinger RP 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 PMID: 18158437 (corresponding NGC updated July 2013) - Dellinger RP et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock, 2012. Crit Care Med 2013 Feb; 41:580. PMID: 23353941 (corresponding NGC guideline withdrawn May 2017) - Annane D et al Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review. JAMA. 2009 Jun 10;301(22):2362-75. PMID: 19509383 - Jaeschke R, Angus DC. Living with uncertainty in the intensive care unit: should patients with sepsis be treated with steroids? JAMA. 2009 Jun 10;301(22):2388-90. PMID: 19509389 - Rhodes A, Evans LE, Alhazzani W et al Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med. 2017 Mar;45(3):486-552. PMID: 28098591
  5. Vasu TS et al. Norepinephrine or dopamine for septic shock: A systematic review of randomized clinical trials. J Intensive Care Med 2011 Mar 24 PMID: 21436167 http://jic.sagepub.com/content/early/2011/02/23/0885066610396312 - De Backer D et al. Dopamine versus norepinephrine in the treatment of septic shock: A meta-analysis. Crit Care Med 2012 Mar; 40:725. PMID: 22036860 - Annane D. Physicians no longer should consider dopamine for septic shock! Crit Care Med 2012 Mar; 40:981. PMID: 22343841
  6. Morelli A et al Effect of Heart Rate Control With Esmolol on Hemodynamic and Clinical Outcomes in Patients With Septic Shock. A Randomized Clinical Trial. JAMA. Published online October 09, 2013 PMID: 24108526 http://jama.jamanetwork.com/article.aspx?articleid=1752246 - Pinsky MR et al Is There a Role for beta-Blockade in Septic Shock? JAMA. Published online October 09, 2013 PMID: 24108438 http://jama.jamanetwork.com/article.aspx?articleid=1752240
  7. Physician's First Watch, March 18, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Asfar P et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med 2014 Mar 18 PMID: 24635770 http://www.nejm.org/doi/full/10.1056/NEJMoa1312173 - Caironi P et al. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med 2014 Mar 18 PMID: 24635772 http://www.nejm.org/doi/full/10.1056/NEJMoa1305727 - The ProCESS Investigators. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014 Mar 18 PMID: 24635773 http://www.nejm.org/doi/full/10.1056/NEJMoa1401602 - Kaukonen KM et al Mortality Related to Severe Sepsis and Septic Shock Among Critically Ill Patients in Australia and New Zealand, 2000-2012. JAMA. Published online March 18, 2014 PMID: 24638143 http://jama.jamanetwork.com/article.aspx?articleid=1850096
  8. Raja AS ARISE Confirms ProCESS: Usual Care Is as Effective as EGDT in Septic Shock NEJM Journal Watch. Oct 1, 2014 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - ARISE Investigators and the ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014 Oct 1 PMID: 25272316 http://www.nejm.org/doi/full/10.1056/NEJMoa1404380
  9. Holst LB et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 2014 Oct 9; 371:1381 PMID: 25270275
  10. Funk D et al. Low-dose corticosteroid treatment in septic shock: A propensity- matching study. Crit Care Med 2014 Nov; 42:2333 PMID: 25072758
  11. Mouncey PR et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015 Apr 2; 372:130 PMID: 25776532 http://www.nejm.org/doi/full/10.1056/NEJMoa1500896
  12. The NNT: Systemic Steroids for Sepsis Syndromes http://www.thennt.com/nnt/steroids-for-sepsis/ - Sprung CL et al, Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008, 358:111 PMID: 18184957 - Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y Corticosteroids for treating severe sepsis and septic shock. Cochrane Database Syst Rev. 2004;(1):CD002243. PMID: 14973984
  13. Singer M et al. The Third International Consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016 Feb 23; 315:801 PMID: 26903338 - Shankar-Hari M, Phillips GS, Levy ML et al Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):775-787. PMID: 26903336 - Abraham E. New definitions for sepsis and septic shock: Continuing evolution but with much still to be done. JAMA 2016 Feb 23; 315:757 PMID: 26903333
  14. Gordon AC et al. Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: The VANISH Randomized Clinical Trial. JAMA 2016 Aug 2; 316:509. PMID: 27483065
  15. Howell MD, Davis AM Management of Sepsis and Septic Shock. JAMA. 2017 Jan 19 PMID: 28114603 http://jamanetwork.com/journals/jama/fullarticle/2598892 - De Backer D, Dorman T Surviving Sepsis Guidelines. A Continuous Move Toward Better Care of Patients With Sepsis. JAMA. 2017 Jan 19 PMID: 28114630 http://jamanetwork.com/journals/jama/fullarticle/2598893 - 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 Jan 18 PMID: 28101605
  16. Vail E, Gershengorn HB, Hua M, Walkey AJ, Rubenfeld G, Wunsch H. Association between US norepinephrine shortage and mortality among patients with septic shock. JAMA 2017 Apr 11; 317:1433. PMID: 28322415 http://jamanetwork.com/journals/jama/article-abstract/2612912 - Donohue JM, Angus DC. National shortages of generic sterile injectable drugs: Norepinephrine as a case study of potential harm. JAMA 2017 Apr 11; 317:1415 PMID: 28322412 http://jamanetwork.com/journals/jama/article-abstract/2612910
  17. Khanna A, English SW, Wang XS et al. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med 2017 Aug 3; 377:419. PMID: 28528561
  18. Venkatesh AK et al. Preliminary performance on the new CMS sepsis-1 national quality measure: Early insights from the Emergency Quality Network (E-QUAL). Ann Emerg Med. 2017 Aug 5. pii: S0196-0644(17)30872-7 PMID: 28789803 http://www.annemergmed.com/article/S0196-0644(17)30872-7/fulltext
  19. Ripa M et al. Influence of empirical double-active combination antimicrobial therapy compared with active monotherapy on mortality in patients with septic shock: A propensity score-adjusted and matched analysis. J Antimicrob Chemother 2017 Aug 31 PMID: 28961801
  20. Venkatesh B, Finfer S, Cohen J et al Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med 2018; 378:797-808. Online Jan 19, 2018 PMID: 29347874 Free Article http://www.nejm.org/doi/full/10.1056/NEJMoa1705835
  21. Annane D, Renault A, Brun-Buisson C et al Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med 2018; 378:809-818. March 1, 2018 http://www.nejm.org/doi/full/10.1056/NEJMoa1705716
  22. Levy MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update. Intensive Care Med 2018 Apr 19 PMID: 29675566 https://link.springer.com/article/10.1007%2Fs00134-018-5085-0
  23. McIntyre WF, Um KJ, Alhazzani W et al Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock: A Systematic Review and Meta-analysis. JAMA. 2018 May 8;319(18):1889-1900. Review. PMID: 29801010
  24. Filbin MR, Lynch J, Gillingham TD et al. Presenting symptoms independently predict mortality in septic shock: Importance of a previously unmeasured confounder. Crit Care Med 2018 Jun 29; PMID: 29965833
  25. Woolum JA, Abner EL, Kelly A et al. Effect of thiamine administration on lactate clearance and mortality in patients with septic shock. Crit Care Med 2018 Jul 18; PMID: 30028362 https://insights.ovid.com/crossref?an=00003246-900000000-96192
  26. Rochwerg B, Oczkowski SJ, Siemieniuk RAC et al. Corticosteroids in sepsis: An updated systematic review and meta-analysis. Crit Care Med 2018 Sep; 46:1411. PMID: 29979221 - Lamontagne F, Rochwerg B, Lytvyn L et al. Corticosteroid therapy for sepsis: A clinical practice guideline. BMJ 2018 Aug 10; 362:k3284 PMID: 30097460 Free PMC Article
  27. Barbar SD et al. Timing of renal-replacement therapy in patients with acute kidney injury and sepsis. N Engl J Med 2018 Oct 11; 379:1431 PMID: 30304656 https://www.nejm.org/doi/10.1056/NEJMoa1803213
  28. Hernandez G, Ospina-Tascon GA, Damiani LP et al Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock. The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA. Published online February 17, 2019 PMID: 30772908 https://jamanetwork.com/journals/jama/fullarticle/2724361 - Angus DC. How Best to Resuscitate Patients With Septic Shock? JAMA. Published online February 17, 2019 PMID: 30772916 https://jamanetwork.com/journals/jama/fullarticle/2724360
  29. Fujii T, Luethi N, Young PJ et al Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial. JAMA. 2020 Jan 17. PMID: 31950979
  30. NEJM Knowledge+ Question of the Week. June 9, 2020 https://knowledgeplus.nejm.org/question-of-week/1781/
  31. Rothrock SG et al. Outcome of immediate versus early antibiotics in severe sepsis and septic shock: A systematic review and meta-analysis. Ann Emerg Med 2020 Jun 24; [e-pub]. (Review) PMID: 32593430 https://www.annemergmed.com/article/S0196-0644(20)30337-1/pdf
  32. The National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network. Early restrictive or liberal fluid management for sepsis-induced hypotension. N Engl J Med 2023 Feb 9; 388:499-510. PMID: 36688507 https://www.nejm.org/doi/10.1056/NEJMoa2212663
  33. NEJM Knowledge+ Endocrinology
  34. NEJM Knowledge+ Complex Medical Care
  35. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med. 2021;49:e1063-e1143. PMID: 34605781
  36. Nasa P, Juneja D, Singh O. Severe sepsis and septic shock in the elderly: An overview. World J Crit Care Med. 2012 Feb 4;1(1):23-30. PMID: 24701398 PMCID: PMC3956061 Free PMC article. Review.
  37. Patanwala AE, Flannery AH, Mehta HB et al Comparative effectiveness of albumin versus no albumin on renal replacement therapy and mortality in patients with septic shock and renal impairment. Chest. 2024 Oct 17:S0012-3692(24)05315-7. PMID: 39426720 https://journal.chestnet.org/article/S0012-3692(24)05315-7/abstract