Sepsis and Septic Shock: Evolving Evidence, Evolving Paradigms

Abstract

Sepsis and septic shock represent important infection-related medical emergencies that result in significant morbidity and mortality. The prevalence and microbiology of these processes are evolving. Nonetheless, timely and appropriate antibiotic therapy continues to represent the most important determinant of survival. Recent trials have clarified that crystalloids are preferred for initial resuscitation, and balanced crystalloids appear superior to 0.9% saline. Controversy remains regarding not only the rate and rapidity of fluid resuscitation but also about the timing and use of vasopressors to maintain blood pressure. While some newer alternative vasopressors may have a role in sepsis, more evidence supporting their use is required. Conflicting data exist regarding the impact of corticosteroids on mortality in septic shock. However, these reports indicate that adjunctive hydrocortisone can lead to more rapid shock reversal.

Keywords

antibiotics - corticosteroids - fluids - sepsis - resuscitation - vasopressors

Publication History

Article published online:
16 February 2022

• References

• 1 Rhee C, Klompas M. Sepsis trends: increasing incidence and decreasing mortality, or changing denominator?. J Thorac Dis 2020; 12 (Suppl. 01) S89-S100
• 2 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 (03) 486-552
• 3 Paoli CJ, Reynolds MA, Sinha M, Gitlin M, Crouser E. Epidemiology and costs of sepsis in the United States - an analysis based on timing of diagnosis and severity level. Crit Care Med 2018; 46 (12) 1889-1897
• 4 Buchman TG, Simpson SQ, Sciarretta KL. et al. Sepsis among Medicare beneficiaries: 1. The burdens of sepsis, 2012-2018. Crit Care Med 2020; 48 (03) 276-288
• 5 Rhee C, Jones TM, Hamad Y. et al; Centers for Disease Control and Prevention (CDC) Prevention Epicenters Program. Prevalence, underlying causes, and preventability of sepsis-associated mortality in US acute care hospitals. JAMA Netw Open 2019; 2 (02) e187571
• 6 Rudd KE, Johnson SC, Agesa KM. et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet 2020; 395 (10219): 200-211
• 7 Bone RC. Toward an epidemiology and natural history of SIRS (systemic inflammatory response syndrome). JAMA 1992; 268 (24) 3452-3455
• 8 Levy MM, Fink MP, Marshall JC. et al; International Sepsis Definitions Conference. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 2003; 29 (04) 530-538
• 9 Singer M, Deutschman CS, Seymour CW. et al. The Third International Consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016; 315 (08) 801-810
• 10 Vincent JL, Sakr Y, Singer M. et al; EPIC III Investigators. Prevalence and outcomes of infection among patients in intensive care units in 2017. JAMA 2020; 323 (15) 1478-1487
• 11 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 (06) 1589-1596
• 12 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
• 13 Zilberberg MD, Shorr AF, Micek ST, Vazquez-Guillamet C, Kollef MH. Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study. Crit Care 2014; 18 (06) 596
• 14 Vazquez-Guillamet C, Scolari M, Zilberberg MD, Shorr AF, Micek ST, Kollef M. Using the number needed to treat to assess appropriate antimicrobial therapy as a determinant of outcome in severe sepsis and septic shock. Crit Care Med 2014; 42 (11) 2342-2349
• 15 Kaufman D, Haas CE, Edinger R, Hollick G. Antibiotic susceptibility in the surgical intensive care unit compared with the hospital-wide antibiogram. Arch Surg 1998; 133 (10) 1041-1045
• 16 Brunkhorst FM, Engel C, Bloos F. et al; German Competence Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008; 358 (02) 125-139
• 17 Perner A, Haase N, Wetterslev J. et al; Scandinavian Critical Care Trials Group. Comparing the effect of hydroxyethyl starch 130/0.4 with balanced crystalloid solution on mortality and kidney failure in patients with severe sepsis (6S–Scandinavian Starch for Severe Sepsis/Septic Shock trial): study protocol, design and rationale for a double-blinded, randomised clinical trial. Trials 2011; 12: 24
• 18 Myburgh J, Cooper DJ, Finfer S. et al; SAFE Study Investigators, Australian and New Zealand Intensive Care Society Clinical Trials Group, Australian Red Cross Blood Service, George Institute for International Health. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med 2007; 357 (09) 874-884
• 19 Caironi P, Tognoni G, Masson S. et al; ALBIOS Study Investigators. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med 2014; 370 (15) 1412-1421
• 20 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 (09) 829-839
• 21 Marik PE, Linde-Zwirble WT, Bittner EA, Sahatjian J, Hansell D. Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database. Intensive Care Med 2017; 43 (05) 625-632
• 22 Maitland K, Kiguli S, Opoka RO. et al; FEAST Trial Group. Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011; 364 (26) 2483-2495
• 23 Rivers E, Nguyen B, Havstad S. et al; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345 (19) 1368-1377
• 24 Yealy DM, Kellum JA, Huang DT. et al; ProCESS Investigators. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014; 370 (18) 1683-1693
• 25 Mouncey PR, Osborn TM, Power GS. et al; ProMISe Trial Investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015; 372 (14) 1301-1311
• 26 Peake SL, Delaney A, Bellomo R. ARISE Investigators. Goal-directed resuscitation in septic shock. N Engl J Med 2015; 372 (02) 190-191
• 27 Marik PE, Byrne L, van Haren F. Fluid resuscitation in sepsis: the great 30 mL per kg hoax. J Thorac Dis 2020; 12 (Suppl. 01) S37-S47
• 28 De Backer D, Biston P, Devriendt J. et al; SOAP II Investigators. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010; 362 (09) 779-789
• 29 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; 319 (18) 1889-1900
• 30 Annane D, Vignon P, Renault A. et al; CATS Study Group. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet 2007; 370 (9588): 676-684
• 31 Belletti A, Nagy A, Sartorelli M. et al. Effect of continuous epinephrine infusion on survival in critically ill patients: a meta-analysis of randomized trials. Crit Care Med 2020; 48 (03) 398-405
• 32 Russell JA, Walley KR, Singer J. et al; VASST Investigators. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008; 358 (09) 877-887
• 33 Nagendran M, Russell JA, Walley KR. et al. Vasopressin in septic shock: an individual patient data meta-analysis of randomised controlled trials. Intensive Care Med 2019; 45 (06) 844-855
• 34 Liu ZM, Chen J, Kou Q. et al; Study Group of investigators. Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial. Intensive Care Med 2018; 44 (11) 1816-1825
• 35 Angus DC, Laterre PF, Lewis RJ. SEPSIS-ACT Investigators. Selepressin for patients with septic shock-reply. JAMA 2020; 323 (07) 667-668
• 36 Khanna A, English SW, Wang XS. et al; ATHOS-3 Investigators. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med 2017; 377 (05) 419-430
• 37 Bellomo R, Forni LG, Busse LW. et al. Renin and survival in patients given angiotensin II for catecholamine-resistant vasodilatory shock. A clinical trial. Am J Respir Crit Care Med 2020; 202 (09) 1253-1261
• 38 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
• 39 Permpikul C, Tongyoo S, Viarasilpa T, Trainarongsakul T, Chakorn T, Udompanturak S. Early use of norepinephrine in septic shock resuscitation (CENSER). A randomized trial. Am J Respir Crit Care Med 2019; 199 (09) 1097-1105
• 40 Douglas IS, Alapat PM, Corl KA. et al. Fluid response evaluation in sepsis hypotension and shock: a randomized clinical trial. Chest 2020; 158 (04) 1431-1445
• 41 Annane D, Sébille V, Charpentier C. et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288 (07) 862-871
• 42 Sprung CL, Annane D, Keh D. et al; CORTICUS Study Group. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008; 358 (02) 111-124
• 43 Annane D, Cariou A, Maxime V. et al; COIITSS Study Investigators. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA 2010; 303 (04) 341-348
• 44 Annane D, Renault A, Brun-Buisson C. et al; CRICS-TRIGGERSEP Network. Hydrocortisone plus fludrocortisone for adults with septic shock. N Engl J Med 2018; 378 (09) 809-818
• 45 Venkatesh B, Finfer S, Cohen J. et al; ADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med 2018; 378 (09) 797-808
• 46 Cohen J, Bellomo R, Billot L. et al. Plasma cortisol, aldosterone, and ascorbic acid concentrations in patients with septic shock do not predict treatment effect of hydrocortisone on mortality. A nested cohort study. Am J Respir Crit Care Med 2020; 202 (05) 700-707
• 47 Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. Chest 2017; 151 (06) 1229-1238
• 48 Damiani E, Donati A, Serafini G. et al. Effect of performance improvement programs on compliance with sepsis bundles and mortality: a systematic review and meta-analysis of observational studies. PLoS One 2015; 10 (05) e0125827