Sepsis: Diagnosis and Management


Am Fam Physician. 2020 Apr 1;101(7):409-418.

Author disclosure: No relevant financial affiliations.

Guidelines published in 2016 provide a revised definition of sepsis: life-threatening organ dysfunction caused by a dysregulated host response to infection. The guidelines define septic shock as sepsis with circulatory, cellular, and metabolic dysfunction that is associated with a higher risk of mortality. The measurement of serum lactate has been incorporated into the latest septic shock definition. The guidelines recommend the Sequential Organ Failure Assessment (original and quick versions) as an important tool for early diagnosis. Respiratory, gastrointestinal, genitourinary, and skin and soft tissue infections are the most common sources of sepsis. Pneumonia is the most common cause of sepsis. Although many patients with sepsis have fever, the clinical manifestation can be subtle, particularly in older patients and those who are immunocompromised. Initial evaluation of patients with suspected sepsis includes basic laboratory tests, cultures, imaging studies as indicated, and sepsis biomarkers such as procalcitonin and lactate levels. Fluid resuscitation is the priority in early management, including administering an intravenous crystalloid at 30 mL per kg within the first three hours. Antimicrobial therapy should also be initiated early. Most research indicates that antimicrobial therapy should be started within three hours of presentation. The latest guidelines recommend starting antimicrobials within one hour, but this is controversial. Vasopressor therapy is indicated if hypotension persists despite fluid administration. Future trials of sepsis management are focusing on improving long-term rates of readmission and death, physical disability, cognitive impairment, and quality of life.

Sepsis is a substantial global health burden and is the leading cause of death among adults in intensive care units (ICUs).1 It affects more than 900,000 people annually in the United States, with an incidence of 535 cases per 100,000 person-years.2 Medical advances over the past decade, standardized protocols, and physician awareness have significantly improved survival, but mortality rates remain between 20% and 36%, with approximately 270,000 deaths annually in the United States.35



2016 guidelines provide a new definition for sepsis: a life-threatening organ dysfunction caused by a dysregulated host response to infection. The guidelines define septic shock as sepsis with circulatory, cellular, and metabolic dysfunction that is associated with a higher risk of mortality; the presence of hypotension is no longer required.*

Medical advances over the past decade, standardized protocols, and physician awareness have significantly improved survival in patients with sepsis, but mortality rates remain between 20% and 36%, with approximately 270,000 deaths annually in the United States.

Lactate-guided resuscitation (i.e., measuring lactate every four to six hours until levels have normalized) reduces overall mortality compared with no lactate monitoring.

SIRS = systemic inflammatory response syndrome; SOFA = Sequential Organ Failure Assessment.

*—The 2016 guidelines include the SOFA and quick SOFA to aid in diagnosis. Online calculators are available at and Although the SIRS criteria ( are no longer endorsed in the guidelines, they still have a role in the identification of acute infection.

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Clinical recommendationEvidence ratingComments

In settings other than the intensive care unit, the quick Sequential Organ Failure Assessment ( can help clinicians recognize possible sepsis early in the evaluation.9,1214


Validation studies and retrospective analysis of observational studies

Sepsis care protocols decrease sepsis-related mortality and should be implemented in all medical facilities.2124


Multiple prospective cohort trials

Patients with sepsis should complete the sepsis bundle (fluid resuscitation, antibiotics, lactate measurement, and cultures) within three hours of presentation.2427


Systematic reviews and retrospective trials

As part of fluid resuscitation, patients with sepsis should receive an intravenous crystalloid at 30 mL per kg.21


Expert consensus guideline

Norepinephrine is the first-line vasopressor agent for patients with septic shock if initial fluid resuscitation fails to restore mean arterial pressure to 65 mm Hg or greater.21,28,29


Multiple studies with head-to-head comparisons of norepinephrine and other vasopressors and a meta-analysis showing that norepinephrine reduces sepsis-related mortality

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented

The Authors

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ROBERT GAUER, MD, is a hospitalist in the Department of Internal Medicine at Womack Army Medical Center, Fort Bragg, N.C....

DAMON FORBES, MD, is medical director of critical care service in the Department of Medicine and associate program director for critical care, hospitalist fellowship, in the Department of Family Medicine at Womack Army Medical Center. He is also a pulmonary/critical care staff physician at Womack Army Medical Center.

NATHAN BOYER, MD, is chief of pulmonary medicine in the Department of Internal Medicine at Landstuhl Regional Medical Center, Germany. At the time this article was written, he was chief of pulmonary medicine in the Department of Internal Medicine at Womack Army Medical Center.

Address correspondence to Robert Gauer, MD, Womack Army Medical Center, Family Medicine Residency Clinic, Bldg. 4-2817, Riley Rd., Fort Bragg, NC 28310 (email: Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


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1. Keeley A, Hine P, Nsutebu E. The recognition and management of sepsis and septic shock: a guide for non-intensivists. Postgrad Med J. 2017;93(1104):626–634....

2. Fleischmann C, Scherag A, Adhikari NK, et al.; International Forum of Acute Care Trialists. Assessment of global incidence and mortality of hospital-treated sepsis. Am J Respir Crit Care Med. 2016;193(3):259–272.

3. Minasyan H. Sepsis and septic shock: pathogenesis and treatment perspectives. J Crit Care. 2017;40:229–242.

4. Sherwin R, Winters ME, Vilke GM, et al. Does early and appropriate antibiotic administration improve mortality in emergency department patients with severe sepsis or septic shock? J Emerg Med. 2017;53(4):588–595.

5. Rhee C, Dantes R, Epstein L, et al.; CDC Prevention Epicenter Program. Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009–2014. JAMA. 2017;318(13):1241–1249.

6. Armstrong BA, Betzold RD, May AK. Sepsis and septic shock strategies. Surg Clin North Am. 2017;97(6):1339–1379.

7. Yende S, Austin S, Rhodes A, et al. Long-term quality of life among survivors of severe sepsis: analyses of two international trials. Crit Care Med. 2016;44(8):1461–1467.

8. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–810.

9. Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of Clinical Criteria for Sepsis: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) [published correction appears in JAMA. 2016;315(20):2237]. JAMA. 2016;315(8):762–774.

10. Tusgul S, Carron PN, Yersin B, et al. Low sensitivity of qSOFA, SIRS criteria and sepsis definition to identify infected patients at risk of complication in the prehospital setting and at the emergency department triage. Scand J Trauma Resusc Emerg Med. 2017;25(1):108.

11. Kaukonen KM, Bailey M, Pilcher D, et al. Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med. 2015;372(17):1629–1638.

12. Marik PE, Taeb AM. SIRS, qSOFA and new sepsis definition. J Thorac Dis. 2017;9(4):943–945.

13. Raith EP, Udy AA, Bailey M, et al. Prognostic accuracy of the SOFA score, SIRS criteria, and qSOFA score for in-hospital mortality among adults with suspected infection admitted to the intensive care unit. JAMA. 2017;317(3):290–300.

14. Maitra S, Som A, Bhattacharjee S. Accuracy of quick Sequential Organ Failure Assessment (qSOFA) score and systemic inflammatory response syndrome (SIRS) criteria for predicting mortality in hospitalized patients with suspected infection: a meta-analysis of observational studies. Clin Microbiol Infect. 2018;24(11):1123–1129.

15. Berg D, Gerlach H. Recent advances in understanding and managing sepsis. F1000Res. 2018;7. Accessed January 4, 2018.

16. Esme M, Topeli A, Yavuz BB, et al. Infections in the elderly critically-ill patients. Front Med (Lausanne). 2019;6:118.

17. Gupta S, Sakhuja A, Kumar G, et al. Culture-negative severe sepsis: nationwide trends and outcomes. Chest. 2016;150(6):1251–1259.

18. Mayr FB, Yende S, Angus DC. Epidemiology of severe sepsis. Virulence. 2014;5(1):4–11.

19. Angus DC, van der Poll T. Severe sepsis and septic shock [published correction appears in N Engl J Med. 2013;369(21):2069]. N Engl J Med. 2013;369(9):840–851.

20. Nannan Panday RS, Lammers EMJ, Alam N, et al. An overview of positive cultures and clinical outcomes in septic patients. Crit Care. 2019;23(1):182.

21. 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;45(3):486–552.

22. Rhodes A, Phillips G, Beale R, et al. The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study). Intensive Care Med. 2015;41(9):1620–1628.

23. Westphal GA, Koenig Á, Caldeira Filho M, et al. Reduced mortality after the implementation of a protocol for the early detection of severe sepsis. J Crit Care. 2011;26(1):76–81.

24. Seymour CW, Gesten F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376(23):2235–2244.

25. Levy MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update. Intensive Care Med. 2018;44(6):925–928.

26. Bansal M, Farrugia A, Balboni S, et al. Relative survival benefit and morbidity with fluids in severe sepsis. Curr Drug Saf. 2013;8(4):236–245.

27. Sterling SA, Miller WR, Pryor J, et al. The impact of timing of antibiotics on outcomes in severe sepsis and septic shock: a systematic review and meta-analysis. Crit Care Med. 2015;43(9):1907–1915.

28. Dellinger RP, Schorr CA, Levy MM. A users' guide to the 2016 surviving sepsis guidelines. Crit Care Med. 2017;45(3):381–385.

29. Avni T, Lador A, Lev S, et al. Vasopressors for the treatment of septic shock. PLoS One. 2015;10(8):e0129305. Accessed October 2, 2019.

30. Cunha BA. Sepsis and septic shock: selection of empiric antimicrobial therapy. Crit Care Clin. 2008;24(2):313–334, ix.

31. Harris RL, Musher DM, Bloom K, et al. Manifestations of sepsis. Arch Intern Med. 1987;147(11):1895–1906.

32. Rumbus Z, Matics R, Hegyi P, et al. Fever is associated with reduced, hypothermia with increased mortality in septic patients: a meta-analysis of clinical trials. PLoS One. 2017;12(1):e0170152.

33. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;348(2):138–150.

34. Balk RA. Severe sepsis and septic shock. Definitions, epidemiology, and clinical manifestations. Crit Care Clin. 2000;16(2):179–192.

35. White HD, Vazquez-Sandoval A, Quiroga PF, et al. Utility of venous blood gases in severe sepsis and septic shock. Proc (Bayl Univ Med Cent). 2018;31(3):269–275.

36. Rello J, Valenzuela-Sánchez F, Ruiz-Rodriguez M, et al. Sepsis: a review of advances in management. Adv Ther. 2017;34(11):2393–2411.

37. Vijayan AL, Vanimaya, Ravindran S, et al. Procalcitonin: a promising diagnostic marker for sepsis and antibiotic therapy. J Intensive Care. 2017;5:51.

38. Jacobs L, Wong HR. Emerging infection and sepsis biomarkers. Expert Rev Anti Infect Ther. 2016;14(10):929–941.

39. Yunus I, Fasih A, Wang Y. The use of procalcitonin in the determination of severity of sepsis, patient outcomes and infection characteristics. PLoS One. 2018;13(11):e0206527.

40. Schuetz P, Chiappa V, Briel M, et al. Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Intern Med. 2011;171(15):1322–1331.

41. Gu WJ, Zhang Z, Bakker J. Early lactate clearance-guided therapy in patients with sepsis: a meta-analysis with trial sequential analysis of randomized controlled trials. Intensive Care Med. 2015;41(10):1862–1863.

42. Ryoo SM, Lee J, Lee YS, et al. Lactate level versus lactate clearance for predicting mortality in patients with septic shock defined by Sepsis-3. Crit Care Med. 2018;46(6):e489–e495.

43. McIntyre L, Rowe BH, Walsh TS, et al.; Canadian Critical Care Trials Group. Multicountry survey of emergency and critical care medicine physicians' fluid resuscitation practices for adult patients with early septic shock. BMJ Open. 2016;6(7):e010041.

44. Glassford NJ, Eastwood GM, Bellomo R. Physiological changes after fluid bolus therapy in sepsis: a systematic review of contemporary data. Crit Care. 2014;18(6):696.

45. Caironi P, Tognoni G, Masson S, et al. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370(15):1412–1421.

46. Delaney AP, Dan A, McCaffrey J, et al. The role of albumin as a resuscitation fluid for patients with sepsis: a systematic review and meta-analysis. Crit Care Med. 2011;39(2):386–391.

47. Lewis SR, Pritchard MW, Evans DJ, et al. Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database Syst Rev. 2018;(8):CD000567.

48. Semler MW, Self WH, Wanderer JP, et al.; SMART Investigators and the Pragmatic Critical Care Research Group. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018;378(9):829–839.

49. Long B, Koyfman A, Modisett KL, et al. Practical considerations in sepsis resuscitation. J Emerg Med. 2017;52(4):472–483.

50. Sakr Y, Rubatto Birri PN, Kotfis K, et al.; Intensive Care Over Nations Investigators. Higher fluid balance increases the risk of death from sepsis: results from a large international audit. Crit Care Med. 2017;45(3):386–394.

51. Boyd JH, Forbes J, Nakada TA, et al. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med. 2011;39(2):259–265.

52. Brown RM, Semler MW. Fluid management in sepsis. J Intensive Care Med. 2019;34(5):364–373.

53. Ferrer R, Martin-Loeches I, Phillips G, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014;42(8):1749–1755.

54. Whiles BB, Deis AS, Simpson SQ. Increased time to initial antimicrobial administration is associated with progression to septic shock in severe sepsis patients. Crit Care Med. 2017;45(4):623–629.

55. 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;34(6):1589–1596.

56. Seymour CW, Kahn JM, Martin-Gill C, et al. Delays from first medical contact to antibiotic administration for sepsis. Crit Care Med. 2017;45(5):759–765.

57. Levy MM, Rhodes A, Evans LE; Steering and Executive Committee of the Surviving Sepsis Campaign. Counterpoint: should the surviving sepsis campaign guidelines be retired? No. Chest. 2019;155(1):14–17.

58. Peltan ID, Brown SM, Bledsoe JR, et al. ED door-to-antibiotic time and long-term mortality in sepsis. Chest. 2019;155(5):938–946.

59. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society [published corrections appear in Clin Infect Dis. 2017;64(9):1298, Clin Infect Dis. 2017;65(8):1435, and Clin Infect Dis. 2017;65(12):2161]. Clin Infect Dis. 2016;63(5):e61–e111.

60. Allison MG, Heil EL, Hayes BD. Appropriate antibiotic therapy. Emerg Med Clin North Am. 2017;35(1):25–42.

61. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52(4):e56–e93.

62. Stanford Antimicrobial Safety and Sustainability Program. Severe sepsis and septic shock antibiotic guide. May 2017. Accessed July 13, 2019.

63. Paul M, Shani V, Muchtar E, et al. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Anti-microb Agents Chemother. 2010;54(11):4851–4863.

64. Kumar A, Ellis P, Arabi Y, et al.; Cooperative Antimicrobial Therapy of Septic Shock Database Research Group. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009;136(5):1237–1248.

65. Bai X, Yu W, Ji W, et al. Early versus delayed administration of norepinephrine in patients with septic shock. Crit Care. 2014;18(5):532.

66. Polito A, Parisini E, Ricci Z, et al. Vasopressin for treatment of vasodilatory shock: an ESICM systematic review and meta-analysis. Intensive Care Med. 2012;38(1):9–19.

67. Permpikul C, Tongyoo S, Viarasilpa T, et al. Early use of norepinephrine in septic shock resuscitation (CENSER): a randomized trial. Am J Respir Crit Care Med. 2019;199(9):1097–1105.

68. Lewis T, Merchan C, Altshuler D, et al. Safety of the peripheral administration of vasopressor agents. J Intensive Care Med. 2019;34(1):26–33.

69. Holst LB, Haase N, Wetterslev J, et al.; TRISS Trial Group; Scandinavian Critical Care Trials Group. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371(15):1381–1391.

70. Annane D, Bellissant E, Bollaert PE, et al. Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review. JAMA. 2009;301(22):2362–2375.

71. Finfer S, Chittock DR, Su SY, et al.; NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360(13):1283–1297.

72. Zhang Z, Xu X. Lactate clearance is a useful biomarker for the prediction of all-cause mortality in critically ill patients: a systematic review and meta-analysis. Crit Care Med. 2014;42(9):2118–2125.

73. Asfar P, Meziani F, Hamel JF, et al.; SEPSISPAM Investigators. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370(17):1583–1593.

74. Marik PE, Khangoora V, Rivera R, et al. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. Chest. 2017;151(6):1229–1238.

75. Moskowitz A, Andersen LW, Huang DT, et al. Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation. Crit Care. 2018;22(1):283.

76. Rubin R. Wide interest in a vitamin C drug cocktail for sepsis despite lagging evidence. JAMA. 2019;322(4):291–293.

77. U.S. National Library of Medicine. Vitamin C, thiamine, and steroids in sepsis (VICTAS). Accessed July 13, 2019.

78. Seymour CW, Kennedy JN, Wang S, et al. Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis. JAMA. 2019;321(20):2003–2017.

79. Gauer RL. Early recognition and management of sepsis in adults: the first six hours. Am Fam Physician. 2013;88(1):44–53. Accessed November 11, 2019.



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