Sepsis in adults - Symptoms, Causes, Images, and Treatment Options

Diseases

Highlights & Basics

Key Highlights

Sepsis can progress rapidly to multiorgan failure and shock, and is often fatal. Survival is dependent on a high index of suspicion of sepsis, early recognition, and timely intervention.
Findings are generally nonspecific and secondary to primary infection. They include malaise, leukocytosis, tachypnea, tachycardia, and altered mental status.
Patients with evidence of sepsis, including signs of organ dysfunction, require immediate hospital assessment.
Empiric broad-spectrum antibiotic therapy (based on the most probable pathogens and site of infection) should be administered as soon as possible, and preferably within the first hour if the patient is progressing to shock.
Blood cultures, as well as cultures of all potentially infected body fluids, should be obtained as indicated by symptoms and the risk profile of the patient, ideally before the initiation of antimicrobial treatment.

Severe purpura fulminans, most commonly associated with pneumococcal septicemia

From the collection of Ron Daniels, MB, ChB, FRCA; used with permission

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Definition

Epidemiology

Etiology

Pathophysiology

Images

National Early Warning Score 2 (NEWS2) is an early warning score produced by the Royal College of Physicians in the UK. It is based on the evaluation of six individual parameters, which are assigned a score of between 0 and 3: respiratory rate, oxygen saturations, temperature, blood pressure, heart rate, and level of consciousness. There are different scales for oxygen saturation levels based on a patient's physiologic target (with scale 2 being used for patients at risk of hypercapnic respiratory failure). The score is then aggregated to give a final total score; the higher the score, the higher the risk of clinical deterioration
Sequential (or Sepsis-related) Organ Failure Assessment (SOFA) criteria
Severe purpura fulminans, most commonly associated with pneumococcal septicemia
Capillary refill time. Top image: normal skin tone; middle image: pressure applied for 5 seconds; bottom image: time to hyperemia measured
BMJ Rapid Recommendations: intravenous corticosteroids plus usual care versus usual care only

Citations

Key Articles

Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10.[Abstract][Full Text]
National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication].[Full Text]
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 Nov 1;49(11):e1063-143.[Abstract][Full Text]

Other Online Resources

BMJ Rapid Recommendations: corticosteroid therapy for sepsis - a clinical practice guideline
MAGICapp: recommendations, evidence summaries and consultation decision aids

Referenced Articles

1. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10.[Abstract][Full Text]
2. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6.[Abstract]
3. 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. [Abstract][Full Text]
4. Castle SC, Norman DC, Yeh M, et al. Fever response in elderly nursing home residents: are the older truly colder? J Am Geriatr Soc. 1991 Sep;39(9):853-7.[Abstract]
5. National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication].[Full Text]
6. Singer M, Inada-Kim M, Shankar-Hari M. Sepsis hysteria: excess hype and unrealistic expectations. Lancet. 2019 Oct 26;394(10208):1513-4.[Abstract]
7. 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 Jan 18;395(10219):200-11.[Abstract][Full Text]
8. World Health Organization. Global report on the epidemiology and burden of sepsis. Sep 2020 [internet publication]. [Full Text]
9. Buchman TG, Simpson SQ, Sciarretta KL, et al. Sepsis among Medicare beneficiaries: 1. The burdens of sepsis, 2012-2018. Crit Care Med. 2020 Mar;48(3):276-88.[Abstract][Full Text]
10. Rhee C, Jones TM, Hamad Y, et al. Prevalence, underlying causes, and preventability of sepsis-associated mortality in US acute care hospitals. JAMA Netw Open. 2019 Feb 1;2(2):e187571.[Abstract][Full Text]
11. Martin GS, Mannino DM, Eaton S, et al. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003 Apr 17;348(16):1546-54.[Abstract][Full Text]
12. Angus DC, Wax RS. Epidemiology of sepsis: an update. Crit Care Med. 2001 Jul;29(suppl 7):S109-16.[Abstract]
13. Karlsson S, Varpula M, Ruokonen E. Incidence, treatment, and outcome of severe sepsis in ICU-treated adults in Finland: the Finnsepsis Study. Intensive Care Med. 2007 Mar;33(3):435-43.[Abstract]
14. Blanco J, Muriel-Bombin A, Sagredo V, et al. Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study. Crit Care. 2008;12(6):R158. [Abstract][Full Text]
15. Laupland KB, Gregson DB, Zygun DA, et al. Severe bloodstream infections: a population-based assessment. Crit Care Med. 2004 Apr;32(4):992-7.[Abstract]
16. Martin GS, Mannino DM, Moss M. The effect of age on the development and outcome of adult sepsis. Crit Care Med. 2006 Jan;34(1):15-21.[Abstract]
17. Annane D, Aegerter P, Jars-Guincestre MC, et al. Current epidemiology of septic shock: the CUB-Réa Network. Am J Respir Crit Care Med. 2003 Jul 15;168(2):165-72.[Abstract][Full Text]
18. Pronovost P, Needham D, Berenholtz S, et al. An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med. 2006 Dec 28;355(26):2725-32.[Abstract][Full Text]
19. Arduino MJ, Tokars JI. Why is an infection control program needed in the hemodialysis setting? Nephrol News Issues. 2005 Jun;19(7):44;46-9.[Abstract]
20. Berenholtz SM, Milanovich S, Faircloth A, et al. Improving care for the ventilated patient. Jt Comm J Qual Saf. 2004 Apr;30(4):195-204.[Abstract]
21. World Health Organization. WHO guidelines on hand hygiene in health care. Jan 2009 [internet publication].[Full Text]
22. Llop J, Badia MB, Comas D, et al. Colonization and bacteremia risk factors in parenteral nutrition catheterization. Clin Nutr. 2001 Dec;20(6):527-34.[Abstract]
23. Danai PA, Sinha S, Moss M, et al. Seasonal variation in the epidemiology of sepsis. Crit Care Med. 2007 Feb;35(2):410-5.[Abstract]
24. Raymond NJ, Blackmore TK, Humble MW, et al. Bloodstream infections in a secondary and tertiary care hospital setting. Intern Med J. 2006 Dec;36(12):765-72.[Abstract]
25. Gea-Banacloche JC, Opal SM, Jorgensen J, et al. Sepsis associated with immunosuppressive medications: an evidence based review. Crit Care Med. 2004 Nov;32(suppl 11):S578-90.[Abstract]
26. Cohen J, Brun-Buisson C, Torres A, et al. Diagnosis of infection in sepsis: an evidenced based review. Crit Care Med. 2004 Nov;32(11 Suppl):S466-94.[Abstract]
27. National Confidential Enquiry into Patient Outcome and Death. Just say sepsis! A review of the process of care received by patients with sepsis. Nov 2015 [internet publication].[Full Text]
28. Pfaller MA, Messer SA, Hollis RJ, et al. Variation in susceptibility of bloodstream isolates of Candida glabrata to fluconazole according to patient age and geographic location in the United States in 2001 to 2007. J Clin Microbiol. 2009 Oct;47(10):3185-90. [Abstract][Full Text]
29. Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006 Feb;34(2):344-53.[Abstract]
30. Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med. 2010 Feb;38(2):367-74.[Abstract]
31. Vincent JL, Rello J, Marshall J, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009 Dec 2;302(21):2323-9.[Abstract][Full Text]
32. Gauer RL. Early recognition and management of sepsis in adults: the first six hours. Am Fam Physician. 2013 Jul 1;88(1):44-53.[Abstract][Full Text]
33. Russell JA. Management of sepsis. N Engl J Med. 2006 Oct 19;355(16):1699-713.[Abstract]
34. Shapiro NI, Wolfe RE, Moore RB, et al. Mortality in Emergency Department Sepsis (MEDS) score: a prospectively derived and validated clinical prediction rule. Crit Care Med. 2003 Mar;31(3):670-5.[Abstract]
35. Danai PA, Moss M, Mannino DM, et al. The epidemiology of sepsis in patients with malignancy. Chest. 2006 Jun;129(6):1432-40.[Abstract]
36. Page DB, Donnelly JP, Wang HE. Community-, healthcare-, and hospital-acquired severe sepsis hospitalizations in the University HealthSystem Consortium. Crit Care Med. 2015 Sep;43(9):1945-51.[Abstract][Full Text]
37. Goldman DA, Huskins WC. Control of nosocomial antimicrobial-resistant bacteria: a strategic priority for hospitals worldwide. Clin Infect Dis. 1997 Jan;24(suppl 1):S139-45.[Abstract]
38. Pitout JD, Laupland KB. Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis. 2008 Mar;8(3):159-66.[Abstract]
39. Centers for Disease Control and Prevention. Pregnancy mortality surveillance system. Mar 2023 [internet publication].[Full Text]
40. Acosta CD, Knight M, Lee HC, et al. The continuum of maternal sepsis severity: incidence and risk factors in a population-based cohort study. PLoS One. 2013;8(7):e67175.[Abstract][Full Text]
41. Plante LA, Pacheco LD, et al; Society for Maternal-Fetal Medicine (SMFM). SMFM Consult Series #47: sepsis during pregnancy and the puerperium. Am J Obstet Gynecol. 2019 Apr;220(4):B2-10.[Abstract][Full Text]
42. Vincent JL, Bihari DJ, Suter PM, et al. The prevalence of nosocomial infection in intensive care units in Europe: results of the European Prevalence of Infection in Intensive Care (EPIC) Study. JAMA. 1995 Aug 23-30;274(8):639-44.[Abstract]
43. Solomkin JS, Mazuski J. Intra-abdominal sepsis: newer interventional and antimicrobial therapies. Infect Dis Clin North Am. 2009 Sep;23(3):593-608.[Abstract]
44. Montravers P, Dupont H, Gauzit R, et al. Candida as a risk factor for mortality in peritonitis. Crit Care Med. 2006 Mar;34(3):646-52.[Abstract]
45. Donelli G. Vascular catheter-related infection and sepsis. Surg Infect (Larchmt). 2006;7(suppl 2):S25-7.[Abstract]
46. Wenzel RP. Treating sepsis. N Engl J Med. 2002 Sep 26;347(13):966-7.[Abstract]
47. Tsujimoto H, Ono S, Efron PA, et al. Role of Toll-like receptors in the development of sepsis. Shock. 2008 Mar;29(3):315-21. [Abstract]
48. Hopkins P, Cohen J. Toll-like receptors: the key to the stable door? Crit Care. 2002 Apr;6(2):99-101.[Abstract][Full Text]
49. Kumpf O, Giamarellos-Bourboulis EJ, Koch A, et al. Influence of genetic variations in TLR4 and TIRAP/Mal on the course of sepsis and pneumonia and cytokine release: an observational study in three cohorts. Crit Care. 2010;14(3):R103.[Abstract][Full Text]
50. Daniels R, Nutbeam T (eds). The ABC of sepsis. Chichester, West Sussex: Wiley-Blackwell; 2010.
51. Hauser B, Bracht H, Matejovic M, et al. Nitric oxide synthase inhibition in sepsis? Lessons learned from large-animal studies. Anesth Analg. 2005 Aug;101(2):488-98.[Abstract]
52. Remick DG. Pathophysiology of sepsis. Am J Pathol. 2007 May;170(5):1435-44.[Abstract][Full Text]
53. Faust SN, Heyderman RS, Levin M. Coagulation in severe sepsis: a central role for thrombomodulin and active protein C. Crit Care Med. 2001 Jul;29(suppl 7):S62-7;discussion S67-8.[Abstract]
54. Fourrier F, Chopin C, Goudemand J, et al. Septic shock, multiple organ failure, and disseminated intravascular coagulation: compared patterns of antithrombin III, protein C, and protein S deficiencies. Chest. 1992 Mar;101(3):816-23.[Abstract]
55. Ince C. The microcirculation is the motor of sepsis. Crit Care. 2005;9(suppl 4):S13-9.[Abstract][Full Text]
56. Balk RA. Severe sepsis and septic shock. Definitions, epidemiology, and clinical manifestations. Crit Care Clin. 2000 Apr;16(2):179-92.[Abstract]
57. Abraham E, Singer M. Mechanisms of sepsis-induced organ dysfunction. Crit Care Med. 2007 Oct;35(10):2408-16.[Abstract]
58. Waljee AK, Rogers MA, Lin P, et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ. 2017 Apr 12;357:j1415.[Abstract][Full Text]
59. Vogel TR, Dombrovskiy VY, Carson JL, et al. Postoperative sepsis in the United States. Ann Surg. 2010 Dec;252(6):1065-71.[Abstract][Full Text]
60. 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.[Abstract][Full Text]
61. Gao F, Melody T, Daniels R, et al. The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study. Crit Care. 2005;9(6):R764-70.[Abstract][Full Text]
62. Jones AE, Focht A, Horton JM, et al. 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.[Abstract][Full Text]
63. Puskarich MA, Marchick MR, Kline JA, et al. One year mortality of patients treated with an emergency department based early goal directed therapy protocol for severe sepsis and septic shock: a before and after study. Crit Care. 2009;13(5):R167.[Abstract][Full Text]
64. Daniels R, Nutbeam I, McNamara G, et al. The sepsis six and the severe sepsis resuscitation bundle: a prospective observational cohort study. Emerg Med J. 2011 Jun;28(6):507-12.[Abstract]
65. Yealy DM, Mohr NM, Shapiro NI, et al. Early care of adults with suspected sepsis in the emergency department and out-of-hospital environment: a consensus-based task force Report. Ann Emerg Med. 2021 Jul;78(1):1-19.[Abstract][Full Text]
66. Sundén-Cullberg J, Rylance R, Svefors J, et al. Fever in the emergency department predicts survival of patients with severe sepsis and septic shock admitted to the ICU. Crit Care Med. 2017 Apr;45(4):591-9.[Abstract]
67. Esper AM, Moss M, Lewis CA, et al. The role of infection and comorbidity: factors that influence disparities in sepsis. Crit Care Med. 2006 Oct;34(10):2576-82.[Abstract][Full Text]
68. 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 Nov 1;49(11):e1063-143.[Abstract][Full Text]
69. Churpek MM, Snyder A, Han X, et al. Quick Sepsis-related Organ Failure Assessment, Systemic Inflammatory Response Syndrome, and Early Warning Scores for detecting clinical deterioration in infected patients outside the intensive care unit. Am J Respir Crit Care Med. 2017 Apr 1;195(7):906-11.[Abstract][Full Text]
70. Fernando SM, Tran A, Taljaard M, et al. Prognostic accuracy of the Quick Sequential Organ Failure Assessment for mortality in patients with suspected infection: a systematic review and meta-analysis. Ann Intern Med. 2018 Feb 20;168(4):266-75.[Abstract]
71. Smith GB, Prytherch DR, Meredith P, et al. The ability of the National Early Warning Score (NEWS) to discriminate patients at risk of early cardiac arrest, unanticipated intensive care unit admission, and death. Resuscitation. 2013 Apr;84(4):465-70.[Abstract]
72. Goulden R, Hoyle MC, Monis J, et al. qSOFA, SIRS and NEWS for predicting inhospital mortality and ICU admission in emergency admissions treated as sepsis. Emerg Med J. 2018 Jun;35(6):345-9.[Abstract][Full Text]
73. Keep JW, Messmer AS, Sladden R, et al. National early warning score at emergency department triage may allow earlier identification of patients with severe sepsis and septic shock: a retrospective observational study. Emerg Med J. 2016 Jan;33(1):37-41.[Abstract]
74. Corfield AR, Lees F, Zealley I, et al; Scottish Trauma Audit Group Sepsis Steering Group. Utility of a single early warning score in patients with sepsis in the emergency department. Emerg Med J. 2014 Jun;31(6):482-7.[Abstract]
75. Royal College of Physicians. National Early Warning Score (NEWS) 2. Dec 2017 [internet publication].[Full Text]
76. NHS England. Sepsis guidance implementation advice for adults. Sep 2017 [internet publication].[Full Text]
77. Academy of Medical Royal Colleges. Statement on the initial antimicrobial treatment of sepsis. Oct 2022 [internet publication].[Full Text]
78. American College of Emergency Physicians (ACEP) Expert Panel on Sepsis. DART: an evidence-driven tool to guide the early recognition and treatment of sepsis and septic shock. 2016 [internet publication].[Full Text]
79. American College of Chest Physicians/Society of Critical Care Medicine. Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992 Jun;20(6):864-74.[Abstract]
80. O'Grady NP, Alexander E, Alhazzani W, et al. Society of Critical Care Medicine and the Infectious Diseases Society of America guidelines for evaluating new fever in adult patients in the ICU. Crit Care Med. 2023 Nov 1;51(11):1570-86.[Abstract][Full Text]
81. Weinstein MP, Reller RB, Murphy JR, et al. The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and epidemiologic observations. Rev Infect Dis. 1983 Jan-Feb;5(1):35-53.[Abstract]
82. Diament D, Salomão R, Rigatto O, et al. Guidelines for the treatment of severe sepsis and septic shock: management of the infectious agent - diagnosis. Rev Bras Ter Intensiva. 2011 Jun;23(2):134-44.[Abstract][Full Text]
83. Jimenez MF, Marshall JC. Source control in the management of sepsis. Intensive Care Med. 2001;27(suppl 1):S49-62.[Abstract]
84. Trzeciak S, Chansky ME, Dellinger PR, et al. Operationalizing the use of serum lactate measurement for identifying high risk of death in a clinical practice algorithm for suspected severe sepsis. Acad Emerg Med. 2006;13:150-1.
85. Schuetz P, Birkhahn R, Sherwin R, et al. Serial procalcitonin predicts mortality in severe sepsis patients: results from the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study. Crit Care Med. 2017 May;45(5):781-9.[Abstract][Full Text]
86. Kip MM, Kusters R, Ijzerman MJ, et al. A PCT algorithm for discontinuation of antibiotic therapy is a cost-effective way to reduce antibiotic exposure in adult intensive care patients with sepsis. J Med Econ. 2015;18(11):944-53.[Abstract]
87. American Society for Clinical Pathology. Thirty five things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2021 [internet publication].[Full Text]
88. Expert Panels on Thoracic, Gastrointestinal, and Urological Imaging, Brixey AG, Fung A, et al. ACR appropriateness criteria® sepsis. J Am Coll Radiol. 2024 Jun;21(6s):S292-309.[Abstract][Full Text]
89. Merx MW, Weber C. Sepsis and the heart. Circulation. 2007 Aug 14;116(7):793-802.[Abstract][Full Text]
90. Nguyen HB, Rivers EP, Knoblich BP, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004 Aug;32(8):1637-42.[Abstract]
91. Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010 Feb 24;303(8):739-46.[Abstract][Full Text]
92. Billeter A, Turina M, Seifert B, et al. Early serum procalcitonin, interleukin-6, and 24-hour lactate clearance: useful indicators of septic infections in severely traumatized patients. World J Surg. 2009 Mar;33(3):558-66.[Abstract]
93. Schuetz P, Wirz Y, Sager R, et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis. 2018 Jan;18(1):95-107.[Abstract][Full Text]
94. Shehabi Y, Sterba M, Garrett PM, et al. Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis: a randomized controlled trial. Am J Respir Crit Care Med. 2014 Nov 15;190(10):1102-10.[Abstract][Full Text]
95. Andriolo BN, Andriolo RB, Salomão R, et al. Effectiveness and safety of procalcitonin evaluation for reducing mortality in adults with sepsis, severe sepsis or septic shock. Cochrane Database Syst Rev. 2017 Jan 18;(1):CD010959.[Abstract][Full Text]
96. Lam SW, Bauer SR, Fowler R, et al. Systematic review and meta-analysis of procalcitonin-guidance versus usual care for antimicrobial management in critically ill patients: focus on subgroups based on antibiotic initiation, cessation, or mixed strategies. Crit Care Med. 2018 May;46(5):684-90.[Abstract]
97. Phua J, Koay ES, Lee KH. Lactate, procalcitonin, and amino-terminal pro-B-type natriuretic peptide versus cytokine measurements and clinical severity scores for prognostication in septic shock. Shock. 2008 Mar;29(3):328-33.[Abstract]
98. Rady MY, Smithline HA, Blake H, et al. Comparison of the shock index and conventional vital signs to identify acute, critical illness in the emergency department. Ann Emerg Med. 1994 Oct;24(4):685-90.[Abstract]
99. Napoli AM, Machan JT, Corl K, et al. The use of impedance cardiography in predicting mortality in emergency department patients with severe sepsis and septic shock. Acad Emerg Med. 2010 Apr;17(4):452-5.[Abstract][Full Text]
100. Havaldar AA. Evaluation of sepsis induced cardiac dysfunction as a predictor of mortality. Cardiovasc Ultrasound. 2018 Nov 30;16(1):31.[Abstract][Full Text]
101. Lavi R, Yarnitsky D, Rowe JM, et al. Standard vs atraumatic Whitacre needle for diagnostic lumbar puncture: a randomized trial. Neurology. 2006 Oct 24;67(8):1492-4.[Abstract]
102. Arendt K, Demaerschalk BM, Wingerchuk DM, et al. Atraumatic lumbar puncture needles: after all these years, are we still missing the point? Neurologist. 2009 Jan;15(1):17-20.[Abstract]
103. Nath S, Koziarz A, Badhiwala JH, et al. Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis. Lancet. 2018 Mar 24;391(10126):1197-204.[Abstract]
104. Rochwerg B, Almenawer SA, Siemieniuk RAC, et al. Atraumatic (pencil-point) versus conventional needles for lumbar puncture: a clinical practice guideline. BMJ. 2018 May 22;361:k1920.[Abstract][Full Text]
105. Ahmed SV, Jayawarna C, Jude E. Post lumbar puncture headache: diagnosis and management. Postgrad Med J. 2006 Nov;82(973):713-6.[Abstract][Full Text]
106. Arevalo-Rodriguez I, Ciapponi A, Roqué i Figuls M, et al. Posture and fluids for preventing post-dural puncture headache. Cochrane Database Syst Rev. 2016 Mar 7;(3):CD009199.[Abstract][Full Text]
107. Simundic AM, Bölenius K, Cadamuro J, et al. Joint EFLM-COLABIOCLI recommendation for venous blood sampling. Clin Chem Lab Med. 2018;56(12):2015-38.[Abstract]
108. US Food and Drug Administration. FDA allows marketing of test to identify organisms that cause bloodstream infections and provide antibiotic sensitivity results. Feb 2017 [internet publication].[Full Text]
109. Pancholi P, Carroll KC, Buchan BW, et al. Multicenter evaluation of the Accelerate PhenoTest BC kit for rapid identification and phenotypic antimicrobial susceptibility testing using morphokinetic cellular analysis. J Clin Microbiol. 2018 Apr;56(4):e01329-17.[Abstract][Full Text]
110. Blauwkamp TA, Thair S, Rosen MJ, et al. Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease. Nat Microbiol. 2019 Apr;4(4):663-74.[Abstract]
111. Freire AX, Bridges L, Umpierrez GE, et al. Admission hyperglycemia and other risk factors as predictors of hospital mortality in a medical ICU population. Chest. 2005 Nov;128(5):3109-16.[Abstract]
112. Howell G, Tisherman SA. Management of sepsis. Surg Clin North Am. 2006 Dec;86(6):1523-39.[Abstract]
113. Simon HB. Hyperthermia. N Engl J Med. 1993 Aug 12;329(7):483-7.[Abstract]
114. Brandom BW. Genetics of malignant hyperthermia. Anesthesiol Clin North America. 2005 Dec;23(4):615-9;viii.[Abstract]
115. Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a severity of disease classification system. Crit Care Med. 1985 Oct;13(10):818-29.[Abstract]
116. Knaus WA, Wagner DP, Draper EA, et al. The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults. Chest. 1991 Dec;100(6):1619-36.[Abstract]
117. Rivers EP, Nguyen, HB, Amponsah D. Sepsis: a landscape from the emergency department to the intensive care unit. Crit Care Med. 2003 Mar;31(3):968-9.[Abstract]
118. Macdonald SP, Arendts G, Fatovich DM, et al. Comparison of PIRO, SOFA, and MEDS scores for predicting mortality in emergency department patients with severe sepsis and septic shock. Acad Emerg Med. 2014 Nov;21(11):1257-63.[Abstract][Full Text]
119. Albright CM, Ali TN, Lopes V, et al. The sepsis in obstetrics score: a model to identify risk of morbidity from sepsis in pregnancy. Am J Obstet Gynecol. 2014 Jul;211(1):39;e1-8.[Abstract]
120. Vasquez DN, Das Neves AV, Vidal L, et al. Characteristics, outcomes, and predictability of critically ill obstetric patients: a multicenter prospective cohort study. Crit Care Med. 2015 Sep;43(9):1887-97.[Abstract]
121. Warhurst G, Dunn G, Chadwick P, et al. Clinical diagnostic accuracy of rapid detection of healthcare-associated bloodstream infection in critical care using multi-pathogen real-time polymerase chain reaction (RT-PCR) technology. Health Technol Assess. 2015 May;19(35):1-142.[Abstract][Full Text]
122. Levy MM, Rhodes A, Phillips GS, et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Intensive Care Med. 2014 Nov;40(11):1623-33.[Abstract][Full Text]
123. Seymour CW, Gesten F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017 Jun 8;376(23):2235-44.[Abstract][Full Text]
124. Kahn JM, Davis BS, Yabes JG, et al. Association between state-mandated protocolized sepsis care and in-hospital mortality among adults with sepsis. JAMA. 2019 Jul 16;322(3):240-50.[Abstract][Full Text]
125. Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign bundle: 2018 update. Intensive Care Med. 2018 Jun;44(6):925-8.[Abstract][Full Text]
126. Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018 Apr 28;391(10131):1693-705.[Abstract]
127. Kumar A, Ellis P, Arabi Y, et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009 Nov;136(5):1237-48.[Abstract]
128. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension prior to initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun;34(6):1589-96.[Abstract]
129. Kalil AC, Johnson DW, Lisco SJ, et al. Early goal-directed therapy for sepsis: a novel solution for discordant survival outcomes in clinical trials. Crit Care Med. 2017 Apr;45(4):607-14.[Abstract]
130. Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010 Apr;38(4):1045-53. [Abstract]
131. Johnston AN, Park J, Doi SA, et al. Effect of immediate administration of antibiotics in patients with sepsis in tertiary care: a systematic review and meta-analysis. Clin Ther. 2017 Jan;39(1):190-202;e6.[Abstract]
132. National Institute for Health Research. NIHR Alert: giving immediate antibiotics reduces deaths from sepsis. Apr 2017 [internet publication].[Full Text]
133. 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 Oct;53(4):588-95.[Abstract]
134. Baghdadi JD, Brook RH, Uslan DZ, et al. Association of a care bundle for early sepsis management with mortality among patients with hospital-onset or community-onset sepsis. JAMA Intern Med. 2020 May 1;180(5):707-16.[Abstract]
135. Bisarya R, Song X, Salle J, et al. Antibiotic timing and progression to septic shock among patients in the ED with suspected infection. Chest. 2022 Jan;161(1):112-20.[Abstract]
136. Bassetti M, Rello J, Blasi F, et al. Systematic review of the impact of appropriate versus inappropriate initial antibiotic therapy on outcomes of patients with severe bacterial infections. Int J Antimicrob Agents. 2020 Dec;56(6):106184.[Abstract]
137. Vardakas KZ, Voulgaris GL, Maliaros A, et al. Prolonged versus short-term intravenous infusion of antipseudomonal beta-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials. Lancet Infect Dis. 2018 Jan;18(1):108-20.[Abstract]
138. Angus DC, Linde-Zwirble WT, Lidicker J, et al. 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.[Abstract]
139. Paul M, Dickstein Y, Raz-Pasteur A. Antibiotic de-escalation for bloodstream infections and pneumonia: systematic review and meta-analysis. Clin Microbiol Infect. 2016 Dec;22(12):960-7.[Abstract]
140. European Medicines Agency. Quinolone- and fluoroquinolone-containing medicinal products. Nov 2018 [internet publication].[Full Text]
141. US Food and Drug Administration. FDA drug safety communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects. Jul 2016 [internet publication].[Full Text]
142. US Food and Drug Administration. FDA drug safety communication. FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients. Dec 2018 [internet publication].[Full Text]
143. US Food and Drug Administration. FDA drug safety communication. FDA reinforces safety information about serious low blood sugar levels and mental health side effects with fluoroquinolone antibiotics; requires label changes. Jul 2018 [internet publication].[Full Text]
144. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.[Abstract][Full Text]
145. Sartelli M, Coccolini F, Kluger Y, et al. WSES/GAIS/SIS-E/WSIS/AAST global clinical pathways for patients with intra-abdominal infections. World J Emerg Surg. 2021 Sep 25;16(1):49.[Abstract][Full Text]
146. Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Feb 15;62(4):e1-50.[Abstract][Full Text]
147. Brouwer MC, McIntyre P, Prasad K, et al. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2015 Sep 12;(9):CD004405.[Abstract][Full Text]
148. Choi PTL, Yip G, Quinonez LG, et al. Crystalloids vs. colloids in fluid resuscitation: a systematic review. Crit Care Med. 1999 Jan;27(1):200-10.[Abstract]
149. Finfer S, Bellomo R, Boyce N, et al; the SAFE Study Investigators. 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.[Abstract][Full Text]
150. Lewis SR, Pritchard MW, Evans DJ, et al. Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database Syst Rev. 2018 Aug 3;(8):CD000567.[Abstract][Full Text]
151. Roberts I, Blackhall K, Alderson P, et al. Human albumin solution for resuscitation and volume expansion in critically ill patients. Cochrane Database Syst Rev. 2011 Nov 9;(11):CD001208.[Abstract][Full Text]
152. Rochwerg B, Alhazzani W, Sindi A, et al. Fluid resuscitation in sepsis: a systematic review and network meta-analysis. Ann Intern Med. 2014 Sep 2;161(5):347-55.[Abstract]
153. Patel A, Laffan MA, Waheed U, et al. Randomised trials of human albumin for adults with sepsis: systematic review and meta-analysis with trial sequential analysis of all-cause mortality. BMJ. 2014 Jul 22;349:g4561. [Erratum in: BMJ. 2014;349:g4850.][Abstract][Full Text]
154. 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 Feb;39(2):386-91.[Abstract]
155. Zou Y, Ma K, Xiong JB, et al. Comparison of the effects of albumin and crystalloid on mortality among patients with septic shock: systematic review with meta-analysis and trial sequential analysis. Sao Paulo Med J. 2018 Sep-Oct;136(5):421-32.[Abstract][Full Text]
156. Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018 Mar 1;378(9):829-39.[Abstract]
157. Food and Drug Administration. Labeling changes on mortality, kidney injury, and excess bleeding with hydroxyethyl starch products. Jul 2021 [internet publication].[Full Text]
158. Zarychanski R, Abou-Setta AM, Turgeon AF, et al. Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis. JAMA. 2013 Feb 20;309(7):678-88. [Abstract][Full Text]
159. European Medicines Agency. PRAC recommends suspending hydroxyethyl-starch solutions for infusion from the market. Feb 2022 [internet publication].[Full Text]
160. 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 Oct 9;371(15):1381-91.[Abstract][Full Text]
161. Hollenberg SM, Ahrens TS, Annane D, et al. Practice parameters for hemodynamic support of sepsis in adult patients; 2004 update. Crit Care Med. 2004 Sep;32(9):1928-48.[Abstract]
162. 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 Jan 10;358(2):125-39.[Abstract][Full Text]
163. Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA. 2008 Aug 27;300(8):933-44.[Abstract][Full Text]
164. Finfer S, Chittock DR, Yu-Shuo Su S, et al; NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009 Mar 26;360(13):1283-97.[Abstract][Full Text]
165. American Diabetes Association Professional Practice Committee. 16. diabetes care in the hospital: standards of care in diabetes-2024. Diabetes Care. 2024 Jan 1;47(suppl 1):S295-306.[Abstract][Full Text]
166. Avni T, Lador A, Lev S, et al. Vasopressors for the treatment of septic shock: systematic review and meta-analysis. PLoS One. 2015 Aug 3;10(8):e0129305.[Abstract][Full Text]
167. Møller MH, Claudius C, Junttila E, et al. Scandinavian SSAI clinical practice guideline on choice of first-line vasopressor for patients with acute circulatory failure. Acta Anaesthesiol Scand. 2016 Nov;60(10):1347-66.[Abstract][Full Text]
168. Rivers PE, McIntyre L, Morro DC, et al. Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity. CMAJ. 2005 Oct 25;173(9):1054-65.[Abstract][Full Text]
169. Annane D, Pastores SM, Rochwerg B, et al. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Crit Care Med. 2017 Dec;45(12):2078-88.[Abstract]
170. Annane D, Bellissant E, Bollaert PE, et al. Corticosteroids for treating sepsis in children and adults. Cochrane Database Syst Rev. 2019 Dec 6;(12):CD002243.[Abstract][Full Text]
171. Kalil AC, Sun J. Low-dose steroids for septic shock and severe sepsis: the use of Bayesian statistics to resolve clinical trial controversies. Intensive Care Med. 2011 Mar;37(3):420-9.[Abstract]
172. Rygård SL, Butler E, Granholm A, et al. Low-dose corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis. Intensive Care Med. 2018 Jul;44(7):1003-16.[Abstract]
173. Lamontagne F, Rochwerg B, Lytvyn L, et al. Corticosteroid therapy for sepsis: a clinical practice guideline. BMJ. 2018 Aug 10;362:k3284.[Abstract][Full Text]
174. Rochwerg B, Oczkowski SJ, Siemieniuk RAC, et al. Corticosteroids in sepsis: an updated systematic review and meta-analysis. Crit Care Med. 2018 Sep;46(9):1411-20.[Abstract]
175. Climo MW, Yokoe DS, Warren DK, et al. Effect of daily chlorhexidine bathing on hospital-acquired infection. N Engl J Med. 2013 Feb 7;368(6):533-42.[Abstract][Full Text]
176. Szakmany T, Hauser B, Radermacher P. N-acetylcysteine for sepsis and systemic inflammatory response in adults. Cochrane Database Syst Rev. 2012 Sep 12;(9):CD006616.[Abstract][Full Text]
177. Trzeciak S, Dellinger RP. Other supportive therapies in sepsis: an evidence-based review. Crit Care Med. 2004 Nov;32(suppl 11):S571-7.[Abstract]
178. Nguyen HB, Rivers EP, Abrahamian FM, et al; Emergency Department Sepsis Education Program and Strategies to Improve Survival (ED-SEPSIS) Working Group. Severe sepsis and septic shock: review of the literature and emergency department management guidelines. Ann Emerg Med. 2006 Jul;48(1):28-54.[Abstract]
179. Wang Y, Ye Z, Ge L, et al. Efficacy and safety of gastrointestinal bleeding prophylaxis in critically ill patients: systematic review and network meta-analysis. BMJ. 2020 Jan 6;368:l6744.[Abstract][Full Text]
180. Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med. 1999 Feb 11;340(6):409-17.[Abstract][Full Text]
181. Brower RG, Matthay MA, Morris A, et al; Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8.[Abstract][Full Text]
182. Soar J, Böttiger BW, Carli P, et al. European Resuscitation Council guidelines 2021: adult advanced life support. Resuscitation. 2021 Apr;161:115-51.[Abstract][Full Text]
183. Colquhoun MC, Handley AJ, Evans TR. ABC of resuscitation. 5th ed. London: BMJ Publishing Group; 2004.
184. Chrimes N, Higgs A, Hagberg CA, et al. Preventing unrecognised oesophageal intubation: a consensus guideline from the Project for Universal Management of Airways and international airway societies. Anaesthesia. 2022 Dec;77(12):1395-415. [Abstract][Full Text]
185. Kusminsky RE. Complications of central venous catheterization. J Am Coll Surg. 2007 Apr;204(4):681-96.[Abstract]
186. McGee DC, Gould MK. Preventing complications of central venous catheterization. N Engl J Med. 2003 Mar 20;348(12):1123-33.[Abstract][Full Text]
187. Smith RN, Nolan JP. Central venous catheters. BMJ. 2013 Nov 11;347:f6570.[Abstract][Full Text]
188. Reich DL. Monitoring in anesthesia and perioperative care. Cambridge: Cambridge University Press; 2011.
189. Abbott Northwestern Hospital Internal Medicine Residency. Internal jugular central venous line. 2022 [internet publication].[Full Text]
190. Bishop L, Dougherty L, Bodenham A, et al. Guidelines on the insertion and management of central venous access devices in adults. Int J Lab Hematol. 2007 Aug;29(4):261-78.[Abstract]
191. Practice guidelines for central venous access 2020: an updated report by the American Society of Anesthesiologists Task Force on Central Venous Access. Anesthesiology. 2020 Jan;132(1):8-43.[Abstract][Full Text]
192. Fletcher SJ, Bodenham AR. Safe placement of central venous catheters: where should the tip of the catheter lie? Br J Anaesth. 2000 Aug;85(2):188-91.[Abstract]
193. Gibson F, Bodenham A. Misplaced central venous catheters: applied anatomy and practical management. Br J Anaesth. 2013 Mar;110(3):333-46.[Abstract][Full Text]
194. Schuster M, Nave H, Piepenbrock S, et al. The carina as a landmark in central venous catheter placement. Br J Anaesth. 2000 Aug;85(2):192-4.[Abstract]
195. Webster J, Osborne S, Rickard CM, et al. Clinically-indicated replacement versus routine replacement of peripheral venous catheters. Cochrane Database Syst Rev. 2019 Jan 23;(1):CD007798.[Abstract][Full Text]
196. Royal College of Nursing. Catheter care: RCN guidance for health care professionals. Jul 2021 [internet publication].[Full Text]
197. Royal College of Nursing. Catheter care: guidance for health care professionals. Jul 2021 [internet publication].[Full Text]
198. Cherpanath TG, Hirsch A, Geerts BF, et al. Predicting fluid responsiveness by passive leg raising: a systematic review and meta-analysis of 23 clinical trials. Crit Care Med. 2016 May;44(5):981-91.[Abstract]
199. Khanna A, English SW, Wang XS, et al; ATHOS-3 Investigators. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017 Aug 3;377(5):419-30.[Abstract][Full Text]
200. Zhanel GG, Lawrence CK, Adam H, et al. Imipenem-relebactam and meropenem-vaborbactam: two novel carbapenem-beta-lactamase inhibitor combinations. Drugs. 2018 Jan;78(1):65-98. [Erratum in: Drugs. 2018 May;78(7):787.][Abstract]
201. Sands KE, Bates DW, Lanken PN, et al. Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA. 1997 Jul 16;278(3):234-40.[Abstract]
202. Zeni F, Freeman B, Natanson C. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med. 1997 Jul;25(7):1095-100.[Abstract]
203. Shankar-Hari M, Harrison DA, Ferrando-Vivas P, et al. Risk factors at index hospitalization associated with longer-term mortality in adult sepsis survivors. JAMA Netw Open. 2019 May 3;2(5):e194900.[Abstract][Full Text]
204. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50.[Abstract]
205. Hadjihambi A, Arias N, Sheikh M, et al. Hepatic encephalopathy: a critical current review. Hepatol Int. 2018 Feb;12(suppl 1):135-47.[Abstract][Full Text]
206. American Association for the Study of Liver Diseases; European Association for the Study of the Liver. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014 Sep;61(3):642-59.[Abstract][Full Text]
207. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1334-49.[Abstract]
208. Wheeler AP, Bernard GR. Treating patients with severe sepsis. N Engl J Med. 1999 Jan 21;340(3):207-14.[Abstract]
209. Messmore HL Jr, Wehrmacher WH. Disseminated intravascular coagulation: a primer for primary care physicians. Postgrad Med. 2002;111(3).
210. Hermans G, De Jonghe B, Bruyninckx F, et al. Clinical review: critical illness polyneuropathy and myopathy. Crit Care. 2008;12(6):238.[Abstract][Full Text]
211. Bolton CF. Neuromuscular complications of sepsis. Intensive Care Med. 1993;19(suppl 2):S58-63.[Abstract]
212. Perl TM, Dvorak L, Hwang T, et al. Long term survival and function after suspected gram negative sepsis. JAMA. 1995 Jul 26;274(4):338-45.[Abstract]
213. Quartin AA, Shein M, Kett DH, et al. Magnitude and duration of the effect of sepsis on survival. Department of Veterans Affairs, Systemic Sepsis Co-operative Studies Group. JAMA. 1997 Apr 2;277(13):1058-63.[Abstract]
214. Chemtob RA, Eskesen TG, Moeller-Soerensen H, et al. Systematic review of the association of venous oxygenation and outcome in adult hospitalized patients. Acta Anaesthesiol Scand. 2016 Nov;60(10):1367-78.[Abstract]