Management of Sepsis in Older Patients in the Emergency Department

  • Abdelouahab BellouEmail author
  • Hubert Blain
  • Vishal Sehgal


Sepsis is a serious problem among the older population as its incidence and mortality rates dramatically increase with advanced age. Although sepsis is a serious life-threatening disease, there is an under recognition as compared to other age-related diseases.

Older patients with severe comorbidities or with age greater than 80 years are often excluded in clinical research on sepsis. However, this population is frequently managed in the emergency department (ED), and their management is a daily challenge for emergency physicians and geriatricians. The diagnosis is often difficult because of atypical clinical presentation, which might delay the administration of appropriate treatment. To date, the management of sepsis and septic shock in older patients followed the most updated international guidelines from the Surviving Sepsis Campaign. The strategy of early identification and institution of appropriate management was proven to improve the outcomes in patients with sepsis including older patients, but stronger evidences are still needed in this specific population. Time is critical, and the treatment must be started as soon as a diagnosis of infection and sepsis is suspected.

Besides numerous prognostic scores that measure the risk of death in critically ill patients, frailty should be assessed with frailty score adapted to critically ill older sepsis patients (e.g., Clinical Frailty Score).


Older patients Sepsis Septic shock Emergency medicine department Surviving Sepsis Campaign guidelines 


  1. 1.
    Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310CrossRefGoogle Scholar
  2. 2.
    Umberger R, Callen B, Brown ML (2015) Severe sepsis in older adults. Crit Care Nurs Q 38(3):259–270CrossRefGoogle Scholar
  3. 3.
    Quenot JP, Binquet C, Kara F, Martinet O, Ganster F, Navellou JC, Castelain V, Barraud D, Cousson J, Louis G, Perez P, Kuteifan K, Noirot A, Badie J, Mezher C, Lessire H, Pavon A (2013) The epidemiology of septic shock in French intensive care units: the prospective multicenter cohort EPISS study. Crit Care 17(2):R65. doi:10.1186/cc12598 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Wang HE, Shapiro NI, Angus DC, Yealy DM (2007) National estimates of severe sepsis in United States emergency departments. Crit Care Med 35(8):1928–1936CrossRefGoogle Scholar
  5. 5.
    Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med 31:1250–1256CrossRefGoogle Scholar
  6. 6.
    Singer M, Deutschman CS, Seymour CW et al (2016) JAMA 315(8):801–810. doi:10.1001/jama.2016.0287 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the European society of intensive care medicine. Intensive Care Med 22(7):707–710CrossRefGoogle Scholar
  8. 8.
    Seymour CW, Liu VX VX, Iwashyna TJ et al (2016) Assessment of clinical criteria for sepsis for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315(8):762–774. doi:10.1001/jama.2016.0288 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Chen YX, Li CS (2014) Arterial lactate improves the prognostic performance of severity score systems in septic patients in the ED. Am J Emerg Med 32(9):982–986. doi:10.1016/j.ajem.2014.05.025. Epub 2014 May 24CrossRefPubMedGoogle Scholar
  10. 10.
    April MD, Aguirre J, Tannenbaum LI, Moore T, Pingree A, Thaxton RE, Sessions DJ, Md, Lantry JH (2016) Sepsis clinical criteria in emergency department patients admitted to an intensive care unit: an external validation study of quick sequential organ failure assessment. J Emerg Med. pii: S0736-4679(16)30887-3. doi:10.1016/j.jemermed.2016.10.012CrossRefGoogle Scholar
  11. 11.
    Giamarellos-Bourboulis EJ, Tsaganos T, Tsangaris I, et al, Hellenic Sepsis Study Group (2016) Validation of the new Sepsis-3 definitions: proposal for improvement in early risk identification. Clin Microbiol Infect. pii: S1198-743X(16)30558-4. [Epub ahead of print]. doi:10.1016/j.cmi.2016.11.003CrossRefGoogle Scholar
  12. 12.
    Freund Y, Lemachatti N, Krastinova E, Van Laer M, Claessens YE, Avondo A, Occelli C, Feral-Pierssens AL, Truchot J, Ortega M, Carneiro B, Pernet J, Claret PG, Dami F, Bloom B, Riou B, Beaune S, French Society of Emergency Medicine Collaborators Group (2017) Prognostic accuracy of sepsis-3 criteria for in-hospital mortality among patients with suspected infection presenting to the emergency department. JAMA 317(3):301–308. doi:10.1001/jama.2016.20329 CrossRefPubMedGoogle Scholar
  13. 13.
    Valencia AM, Vallejo CE, Alvarez AL, Jaimes FA (2016) Attenuation of the physiological response to infection on adults over 65 years old admitted to the emergency room (ER). Aging Clin Exp Res. doi:10.1007/s40520-016-0679-2 CrossRefGoogle Scholar
  14. 14.
    Valencia AM, Vallejo CE, Alvarez AL, Jaimes FA (2016) Attenuation of the physiological response to infection on adults over 65 years old admitted to the emergency room (ER). Aging Clin Exp Res Nov 16Google Scholar
  15. 15.
    Adhikari NK, Fowler RA, Bhagwanjee S, Rubenfeld GD (2010) Critical care and the global burden of critical illness in adults. Lancet 376:1339–1346CrossRefPubMedCentralGoogle Scholar
  16. 16.
    Linde-Zwirble WT, Angus DC (2004) Severe sepsis epidemiology: sampling, selection, and society. Crit Care 8:222–226CrossRefPubMedCentralGoogle Scholar
  17. 17.
    Brun-Buisson C, Meshaka P, Pinton P et al (2004) EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Med 30:580–588CrossRefGoogle Scholar
  18. 18.
    Dombrovskiy VY, Martin AA, Sunderram J, Paz HL (2007) Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med 35:1244–1250CrossRefGoogle Scholar
  19. 19.
    Nasa P, Juneja D, Singh O, Dang R, Arora V (2011) Severe sepsis and its impact on outcome in elderly and very elderly patients admitted in intensive care unit. J Intensive Care Med 27(3):179–183. Epub ahead of printCrossRefGoogle Scholar
  20. 20.
    Padkin A, Goldfrad C, Brady AR et al (2003) Epidemiology of severe sepsis occurring in the first 24 hrs in intensive care units in England, Wales, and Northern Ireland. Crit Care Med 31:2332–2338CrossRefGoogle Scholar
  21. 21.
    Yang Y, Yang KS, Hsann YM, Lim V, Ong BC (2010) The effect of comorbidity and age on hospital mortality and length of stay in patients with sepsis. J Crit Care 25:398–405CrossRefGoogle Scholar
  22. 22.
    Strehlow MC, Emond SD, Shapiro NI, Pelletier AJ, Camargo CA Jr (2006) National study of emergency department visits for sepsis, 1992 to 2001. Ann Emerg Med 48:326–331CrossRefGoogle Scholar
  23. 23.
    Lagu T, Rothberg MB, Shieh MS, Pekow PS, Steingrub JS, Lindenauer PK (2012) Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med 40:754–756. [Erratum, Crit Care Med 2012;40:2932]CrossRefGoogle Scholar
  24. 24.
    Ranieri VM, Thompson BT, Barie PS et al (2012) Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 366:2055–2064CrossRefGoogle Scholar
  25. 25.
    Vincent JL, Rello J, Marshall J et al (2009) International study of the prevalence and outcomes of infection in intensive care units. JAMA 302:2323–2329CrossRefGoogle Scholar
  26. 26.
    Dieckema DJ, Pfaller MA, Jones RN (2002) Age-related trends in pathogen frequency and antimicrobial susceptibility of bloodstream isolates in North America: SENTRY antimicrobial surveillance program, 1997–2000. Int J Antimicrobial Agents 20:412–418CrossRefGoogle Scholar
  27. 27.
    Rowe T, Araujo KLB, Van Ness PH, Pisani MA, Juthani-Mehta M (2016) Outcomes of older adults with sepsis at admission to an intensive care unit. Open Forum Infectious Diseases 1–6Google Scholar
  28. 28.
    Abraham E, Reinhart K, Opal S et al (2003) Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 290:238–247CrossRefGoogle Scholar
  29. 29.
    Opal SM, Garber GE, LaRosa SP et al (2003) Systemic host responses in severe sepsis analyzed by causative microorganism and treatment effects of drotrecogin alfa (activated). Clin Infect Dis 37:50–58CrossRefGoogle Scholar
  30. 30.
    Martin GS, Mannino DM, Eaton S, Moss M (2003a) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348:1546–1554CrossRefGoogle Scholar
  31. 31.
    Martin GS, Mannino DM, Moss M (2003b) Effect of age on the development and outcome with sepsis. Am J Respir Crit Care Med 167:A837Google Scholar
  32. 32.
    Girard TD, Opal SM, Ely EW (2005) Insights into severe sepsis in older patients: from epidemiology to evidence-based management. Clin Infect Dis 40:719–727CrossRefGoogle Scholar
  33. 33.
    Kirby JT, Fritsche TR, Jones RN (2006) Influence of patient age on the frequency of occurrence and antimicrobial resistance patterns of isolates from hematology/oncology patients: report from the chemotherapy alliance for neutropenics and the control of emerging resistance program (north America). Diagn Microbiol Infect Dis 56:75–82CrossRefGoogle Scholar
  34. 34.
    Weksler ME (2000) Changes in the B-cell repertoire with age. Vaccine 18:1624–1628CrossRefGoogle Scholar
  35. 35.
    Opal SM, Girard TD, Ely EW (2005) The immunopathogenesis of sepsis in elderly patients. Clin Infect Dis 41(Suppl 7):S504–S512CrossRefGoogle Scholar
  36. 36.
    Dewan SK1, Zheng SB, Xia SJ, Bill K (2012) Senescent remodeling of the immune system and its contribution to the predisposition of the elderly to infections. Chin Med J (Engl) 125(18):3325–3331Google Scholar
  37. 37.
    Suzuki K, Inoue S, Kametani Y, Komori Y, Chiba S, Sato T, Inokuchi S, Ogura S (2016) Reduced immunocompetent B cells and increased secondary infection in elderly patients with severe sepsis. Shock 46(3):270–278. doi:10.1097/SHK.0000000000000619 CrossRefPubMedGoogle Scholar
  38. 38.
    Inoue S, Suzuki K, Komori Y, Morishita Y, Suzuki-Utsunomiya K, Hozumi K, Inokuchi S, Takehito ST (2014) Persistent inflammation and T cell exhaustion in severe sepsis in the elderly. Crit Care 18:R130CrossRefPubMedCentralGoogle Scholar
  39. 39.
    Sánchez M, Lindroth K, Sverremark E, González Fernández A, Fernández C (2001) The response in old mice: positive and negative immune memory after priming in early age. Int Immunol 13:1213–1221CrossRefGoogle Scholar
  40. 40.
    Sandmand M, Bruunsgaard H, Kemp K, Andersen-Ranberg K, Pedersen AN, Skinhøj P, Pedersen BK (2002) Is ageing associated with a shift in the balance between Type 1 and Type 2 cytokines in humans? Clin Exp Immunol 127:107–114CrossRefPubMedCentralGoogle Scholar
  41. 41.
    De Gaudio AR, Rinaldi S, Chelazzi C, Borracci T (2009) Pathophysiology of sepsis in the elderly: clinical impact and therapeutic considerations. Curr Drug Targets 10:60–70CrossRefGoogle Scholar
  42. 42.
    Haynes L, Eaton SM, Swain SL (2002) Effect of age on naive CD4 responses: impact on effector generation and memory development. Springer Semin Immunopathol 24:53–60CrossRefGoogle Scholar
  43. 43.
    Renshaw M, Rockwell J, Engleman C, Gewirtz A, Katz J, Sambhara S (2002) Cutting edge: impaired toll-like receptor expression and function in aging. J Immunol 169:4697–4701CrossRefGoogle Scholar
  44. 44.
    Walter LC, Brand RJ, Counsell SR, Palmer RM, Landefeld CS, Fortinsky RH, Covinsky KE (2001) Development and validation of a prognostic index for 1-year mortality in older adults after hospitalization. JAMA 285(285):2987–2994CrossRefGoogle Scholar
  45. 45.
    Kale S, Yende S, Kong L, Perkins A, Kellum JA, Newman AB, Vallejo AN, Angus DC, GenIMS Investigators (2010) The effects of age on inflammatory and coagulation-fibrinolysis response in patients hospitalized for pneumonia. PLoS One 5(11):e13852. doi:10.1371/journal.pone.0013852 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Vieira da Silva Pellegrina D, Severino P, Vieira Barbeiro H, Maziero Andreghetto F, Tadeu Velasco I, Possolo de Souza H, Machado MC, Reis EM, Pinheiro da Silva F (2015) Septic shock in advanced age: transcriptome analysis reveals altered molecular signatures in neutrophil granulocytes. PLoS One 10(6):e0128341. doi:10.1371/journal.pone.0128341. eCollection 2015CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Angus DC, van der Poll T (2013) Severe sepsis and septic shock. N Engl J Med 369:840–851. doi:10.1056/NEJMra1208623 CrossRefPubMedGoogle Scholar
  48. 48.
    Bernard GR, Vincent JL, Laterre PF, SP LR, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709CrossRefGoogle Scholar
  49. 49.
    Kumar A, Thota V, Dee L, Olson J, Uretz E, Parrillo JE (1996) Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by human septic shock serum. J Exp Med 183:949–958CrossRefGoogle Scholar
  50. 50.
    Rozenberg S, Besse S, Brisson H, Jozefowicz E, Kandoussi A, Mebazaa A, Riou B, Vallet B, Tavernier B (2006) Endotoxin-induced myocardial dysfunction in senescent rats. Crit Care 10:R124CrossRefPubMedCentralGoogle Scholar
  51. 51.
    Saito H, Papaconstantinou J (2001) Age-associated differences in cardiovascular inflammatory gene induction during endotoxic stress. J Biol Chem 276:29307–29312CrossRefGoogle Scholar
  52. 52.
    Nasa P et al (2012) Severe sepsis and septic shock in the elderly: an overview. World J Crit Care Med 1(1):23–30CrossRefPubMedCentralGoogle Scholar
  53. 53.
    Ruiz M, Bottle A, Long S, Aylin P (2015) Multi-morbidity in hospitalised older patients: who are the complex elderly? PLoS One 10(12):e0145372. doi:10.1371/journal.pone.0145372 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Englert NC, Ross C (2015) The older adult experiencing sepsis. Crit Care Nurs Q 38(2):175–181CrossRefGoogle Scholar
  55. 55.
    Rudman D, Hontanosas A, Cohen Z, Mattson DE (1988) Clinical correlates of bacteremia in a veterans administration extended care facility. J Am Geriatr Soc 36:726–732CrossRefGoogle Scholar
  56. 56.
    Vardi M, Ghanem-Zoubi NO, Bitterman H, Abo-helo N, Yurin V, Weber G, Laor A (2013) Sepsis in nonagenarians admitted to internal medicine departments: a comparative study of outcomes. Q J Med 106:261–266CrossRefGoogle Scholar
  57. 57.
    Marwick C, Santiago VH, McCowan C, Broomhall J, Davey P (2013) Community acquired infections in older patients admitted to hospital from care homes versus the community: cohort study of microbiology and outcomes. BMC Geriatr 13:12. doi:10.1186/1471-2318-13-12 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Jensen GL, McGee M, Binkley J (2001) Nutrition in the elderly. Gastroenterol Clin N Am 30:313–334CrossRefGoogle Scholar
  59. 59.
    Carpenter CR, Shelton E, Fowler S, Suffoletto B, Platts-Mills TF, Rothman RE, Hogan TM (2015) Risk factors and screening instruments to predict adverse outcomes for undifferentiated older emergency department patients: a systematic review and meta-analysis. Acad Emerg Med 22:1–21CrossRefGoogle Scholar
  60. 60.
    Brummel NE, Bell SP, Girard TD, Pandharipande PP, Jackson JC, Morandi A, Thompson JL, Chandrasekhar R, Bernard GR, Dittus RS, Gill TM, Ely EW (2016) Frailty and subsequent disability and mortality among patients with critical illness. Am J Respir Crit Care Med. Published on 06-December-2016 as 10.1164/rccm.201605-0939OCGoogle Scholar
  61. 61.
    Chaudry H et al (2013) Role of cytokines as a double-edged sword in sepsis. In Vivo 27:669–684Google Scholar
  62. 62.
    Rockwood K, Mitnitski A (2011) Frailty defined by deficit accumulation and geriatric medicine defined by frailty. Clin Geriatr Med 27:17–26CrossRefGoogle Scholar
  63. 63.
    Lee WJ et al (2016) Are prognostic scores and biomarkers such a procalcitonin the appropriate prognostic precursors for elderly patients with sepsis in the emergency department? 2015. Aging Clin Exp Res 28(5):917–924CrossRefGoogle Scholar
  64. 64.
    González Del Castillo J, Escobar-Curbelo L, Martínez-Ortíz de Zárate M, Llopis-Roca F, García-Lamberechts J, Moreno-Cuervo Á, Fernández C, Martín-Sánchez FJ (2015) Representing the infectious disease group of spanish emergency medicine society. GYM score: 30-day mortality predictive model in elderly patients attended in the emergency department with infection. Eur J Emerg MedGoogle Scholar
  65. 65.
    Rajagopalan S, Yoshikawa TT (2001) Antimicrobial therapy in the elderly. Med Clin North Am 85:133–147CrossRefGoogle Scholar
  66. 66.
    Wester AL, Dunlop O, Melby KK, Dahle UR, Wyller TB (2013) Age-related differences in symptoms, diagnosis and prognosis of bacteremia. BMC Infect Dis 13:346. doi: 10.1186/1471-2334-13-346Google Scholar
  67. 67.
    Gavazzi G, Krause KH (2002) Ageing and infection. Lancet Infect Dis 2:659–666CrossRefGoogle Scholar
  68. 68.
    Norman DC (2009) Factors predisposing to infection. In: Yoshikawa T, Norman DC (eds) Infectious disease in the aging – a clinical handbook, 2nd edn. Humana Press, New York, pp 11–18CrossRefGoogle Scholar
  69. 69.
    Gauer RL (2013) Early recognition and management of sepsis in adults: the first six hours. Am Fam Physician 88(1):44–53PubMedGoogle Scholar
  70. 70.
    Iberti TJ, Bone RC, Balk R, Fein A, Perl TM, Wenzel RP (1993) Are the criteria used to determine sepsis applicable for patients 75 years of age? Crit Care Med 21:S130CrossRefGoogle Scholar
  71. 71.
    Gleckman R, Hibert D (1982) Afebrile bacteremia: a phenomenon in geriatric patients. JAMA 248:1478–1481CrossRefGoogle Scholar
  72. 72.
    Hernandez C, Feher C, Soriano A, Marco F, Almela M, Cobos-Trigueros N, De La Calle C, Morata L, Mensa J, Martinez JA (2015) Clinical characteristics and outcome of elderly patients with community-onset bacteremia. J Infect 70(2):135–143. doi:10.1016/j.jinf.2014.09.002. PMID:25224642CrossRefPubMedGoogle Scholar
  73. 73.
    Yahav D, Schlesinger A, Daitch V, Akayzen Y, Farbman L, Abu-Ghanem Y, Paul M, Leibovici L (2015) Presentation of infection in older patients–a prospective study. Ann Med 47(4):354–358. doi:10.3109/07853890.2015.1019915 CrossRefPubMedGoogle Scholar
  74. 74.
    Niven DJ, Gaudet JE, Laupland KB, Mrklas KJ, Roberts DJ, Stelfox HT (2015) Accuracy of peripheral thermometers for estimating temperature. A systematic review and meta-analysis. Ann Intern Med 163:768–777. doi:10.7326/M15-1150 CrossRefPubMedGoogle Scholar
  75. 75.
    Lu SH, Leasure AR, Dai YT (2010) A systematic review of body temperature variations in older people. J Clin Nurs 1(2):4–16CrossRefGoogle Scholar
  76. 76.
    Tiruvoipati R, Ong K, Gangopadhyay H et al (2010) Hypothermia predicts mortality in critically ill elderly patients with sepsis. BCM Geriat 10:70CrossRefGoogle Scholar
  77. 77.
    Mouton CP, Pierce B, Espino DV (2001) Common infections in older adults. Am Fam Physician 63(2):257–269PubMedGoogle Scholar
  78. 78.
    Su CP, Chen TH, Chen SY et al (2011) Predictive model for bacteremia in adult patients with blood cultures performed at the emergency department: a preliminary report. J Microbiol Immunol Infect 44:449–455CrossRefGoogle Scholar
  79. 79.
    Dellinger RP, Levy MM, Rodhes A et al (2012) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 39(2):165–228. doi:10.1007/s00134-012-2769-8 CrossRefGoogle Scholar
  80. 80.
    Rhodes A, Evans LE, Alhazzani W et al (2017) Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med 43(3):304–377. doi:10.1097/CCM.0000000000002255. [Epub ahead of print]CrossRefGoogle Scholar
  81. 81.
    Sehgal V, Bajwa SJ, Consalvo JA, Bajaj A (2015) Clinical conundrums in management of sepsis in the elderly. J Transl Int Med 3(3):106–112. Epub 2015 Sep 30CrossRefPubMedCentralGoogle Scholar
  82. 82.
    Heppner HJ, Singler K, Kwetkat A, Popp S, Esslinger AS, Bahrmann P, Kaiser M, Bertsch T, Sieber CC, Christ M (2012) Do clinical guidelines improve management of sepsis in critically ill elderly patients? A before-and-after study of the implementation of a sepsis protocol. Wien Klin Wochenschr 124(8):692–698. doi:10.1007/s00508-012-0229-7. Epub 2012 Sep 5CrossRefPubMedGoogle Scholar
  83. 83.
    Rhodes A, Phillips G, Beale R et al (2015) The surviving sepsis campaign bundles and outcome: results from the international multicentre prevalence study on sepsis (the IMPreSS study). Intensive Care Med 41(9):1620–1628CrossRefGoogle Scholar
  84. 84.
    Palomba H, Corrêa TD, Silva E, Pardini A, Assuncao MS (2015) Comparative analysis of survival between elderly and non-elderly severe sepsis and septic shock resuscitated patients. Einstein (Sao Paulo) 13(3):357–363. doi:10.1590/S1679-45082015AO3313. Epub 2015 Aug 21CrossRefGoogle Scholar
  85. 85.
    Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M (2001) Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345(19):1368–77CrossRefGoogle Scholar
  86. 86.
    El Solh AA, Akinnusi ME, Alsawalha LN, Pineda LA (2008) Outcome of septic shock in older adults after implementation of the sepsis “bundle”. J Am Geriatr Soc 56:272–278CrossRefGoogle Scholar
  87. 87.
    Mouncey PR, Osborn TM, Power GS et al (2015) Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 372:1301–1311. doi:10.1056/NEJMoa1500896 CrossRefPubMedGoogle Scholar
  88. 88.
    The ARISE Investigators and the ANZICS Clinical Trials Group (2014) Goal-directed resuscitation for patients with early septic shock. N Engl J Med 371:1496–1506. doi:10.1056/NEJMoa1404380 CrossRefGoogle Scholar
  89. 89.
    The ProCESS Investigators (2014) A randomized trial of protocol-based care for early septic shock. N Engl J Med 370:1683–1693. doi:10.1056/NEJMoa1401602 CrossRefPubMedCentralGoogle Scholar
  90. 90.
    Jones AE (2013) Lactate clearance for assessing response to resuscitation in severe sepsis. Acad Emerg Med 20:844–847CrossRefPubMedCentralGoogle Scholar
  91. 91.
    Jones AE, Shapiro NI, Trzeciak S et al (2010) Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 303:739–746CrossRefPubMedCentralGoogle Scholar
  92. 92.
    Jones AE (2011) Point: should lactate clearance be substituted for central venous oxygen saturation as goals of early severe sepsis and septic shock therapy? Yes. Chest 140:1406–1408CrossRefPubMedCentralGoogle Scholar
  93. 93.
    Dugas AF, Mackenhauer J, Salciccioli JD, Cocchi MN, Gautam S, Donnino MW (2012) Prevalence and characteristics of nonlactate and lactate expressors in septic shock. J Crit Care 27(4):344–350CrossRefPubMedCentralGoogle Scholar
  94. 94.
    Jansen TC, van Bommel J, Schoonderbeek FJ et al (2010) Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med 182(6):752–761CrossRefGoogle Scholar
  95. 95.
    Lyu X, Xu Q, Cai G, Yan J, Yan M (2015) Efficacies of fluid resuscitation as guided by lactate clearance rate and central venous oxygen saturation in patients with septic shock. Zhonghua Yi Xue Za Zhi 95(7):496–500PubMedGoogle Scholar
  96. 96.
    Yu B, Tian HY, Hu ZJ et al (2013) Comparison of the effect of fluid resuscitation as guided either by lactate clearance rate or by central venous oxygen saturation in patients with sepsis. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 25(10):578–583PubMedGoogle Scholar
  97. 97.
    Tian HH, Han SS, Lv CJ et al (2012) The effect of early goal lactate clearance rate on the outcome of septic shock patients with severe pneumonia. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 24(1):42–45PubMedGoogle Scholar
  98. 98.
    Zhang L, Zhu G, Han L, Fu P (2015) Early goal-directed therapy in the management of severe sepsis or septic shock in adults: a meta-analysis of randomized controlled trials. BMC Med 13:71. doi:10.1186/s12916-015-0312-9 CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Dettmer M, Holthaus CV, Fuller BM (2015) The impact of serial lactate monitoring on emergency department resuscitation interventions and clinical outcomes in severe sepsis and septic shock: an observational cohort study. Shock 43(1):55–61. doi:10.1097/SHK.0000000000000260 CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Gu WJ, Zhang Z, Bakker J (2015) Early lactate clearance-guided therapy in patients with sepsis: a meta-analysis with trial sequential analysis of randomized controlled trials. Intensive Care Med 41(10):1862–1863CrossRefGoogle Scholar
  101. 101.
    Simpson SQ, Gaines M, Hussein Y, Badgett RG (2016) Early goal-directed therapy for severe sepsis and septic shock: a living systematic review. J Crit Care 36:43–48CrossRefGoogle Scholar
  102. 102.
    Chen YX, Li CS (2015) Lactate on emergency department arrival as a predictor of mortality and site-of-care in pneumonia patients: a cohort study. Thorax 70:404–410. doi:10.1136/thoraxjnl-2014-20646 CrossRefPubMedGoogle Scholar
  103. 103.
    del Portal DA, Shofer F, Mikkelsen ME, Dorsey PJ Jr, Gaieski DF, Goyal M, Synnestvedt M, Weiner MG, Pines JM (2010) Emergency department lactate is associated with mortality in older adults admitted with and without infections. Acad Emerg Med 17(3):260–268. doi:10.1111/j.1553-2712.2010.00681.x CrossRefPubMedGoogle Scholar
  104. 104.
    Stalam M, Kaye D (2004) Antibiotic agents in the elderly. Infect Dis Clin N Am 18:533–549CrossRefGoogle Scholar
  105. 105.
    Wu WC, Rathore SS, Wang Y, Radford MJ, Krumholz HM (2001) Blood transfusion in elderly patients with acute myocardial infarction. N Engl J Med 345:1230–1236CrossRefGoogle Scholar
  106. 106.
    Herring AR, Williamson JC (2007) Principles of antimicrobial use in older adults. Clin Geriatr Med 23:481–497CrossRefGoogle Scholar
  107. 107.
    Garnacho-Montero J, Garcia-Garmendia JL, Barrero-Almodovar A, Jimenez-Jimenez FJ, Perez-Paredes C, Ortiz-Leyba C (2003) Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis. Crit Care Med 31:2742–2751CrossRefGoogle Scholar
  108. 108.
    Gaieski DF, Mikkelsen ME, Band RA, Pines JM, Massone R, Furia FF et al (2010) 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 38:1045–1053CrossRefGoogle Scholar
  109. 109.
    Harbarth S, Garbino J, Pugin J, Romand JA, Lew D, Pittet D (2003) Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis. Am J Med 115:529–535CrossRefGoogle Scholar
  110. 110.
    Houck PM, Bratzler DW, Nsa W, Ma A, Bartlett JG (2004) Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia. Arch Intern Med 164:637–644CrossRefGoogle Scholar
  111. 111.
    Iregui M, Ward S, Sherman G, Fraser VJ, Kollef MH (2002) Clinical importance of delays in the initiation of appropriate anti-biotic treatment for ventilator-associated pneumonia. Chest 122:262–268CrossRefGoogle Scholar
  112. 112.
    Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S et al (2006) Duration of hypotension prior to initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 34:1589–1596CrossRefGoogle Scholar
  113. 113.
    Martin GS, Mannino DM, Moss M (2006) The effect of age on the development and outcome of adult sepsis. Crit Care Med 34(1):15–21CrossRefGoogle Scholar
  114. 114.
    Luna CM, Aruj P, Niederman MS, Garzón J, Violi D, Prignoni A, Ríos F, Baquero S, Gando S (2006) Appropriateness and delay to initiate therapy in ventilator-associated pneumonia. Eur Respir J 27:158–164CrossRefGoogle Scholar
  115. 115.
    Curns AT, Holman RC, Sejvar JJ, Owings MF, Schonberger LB (2005) Infectious disease hospitalizations among older adults in the United States from 1990 through 2002. Arch Intern Med 165:2514–2520CrossRefGoogle Scholar
  116. 116.
    Ely EW, Angus DC, Williams MD, Bates B, Qualy R, Bernard GR (2003) Drotrecogin alfa (activated) treatment of older patients with severe sepsis. Clin Infect Dis 37:187–195CrossRefGoogle Scholar
  117. 117.
    Vosylius S, Sipylaite J, Ivaskevicius J (2005) Determinants of outcome in elderly patients admitted to the intensive care unit. Age Ageing 34:157–162CrossRefGoogle Scholar
  118. 118.
    Starr ME, Saito H (2014) Sepsis in old age: review in human and animal studies. Aging Dis 5(2):126–136PubMedPubMedCentralGoogle Scholar
  119. 119.
    Iwashyna TJ, Ely EW, Smith DM, Langa KM (2010) Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 304:1787–1794CrossRefPubMedCentralGoogle Scholar
  120. 120.
    Meurer WJ, Losman ED, Smith BL, Malani PN, Younger JG (2011) Short-term functional decline of older adults admitted for suspected sepsis. Am J Emerg Med 29(8):936–942. doi:10.1016/j.ajem.2010.04.003. Epub 2010 Jul 13CrossRefPubMedGoogle Scholar
  121. 121.
    Nguyen HB, Corbett SW, Steele R et al (2007) Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med 35:1105–1112CrossRefGoogle Scholar
  122. 122.
    Goodwin N, Sonola L, Thiel V, Kodner DL (2013) Co-ordinated care for people with complex chronic conditions. Key lessons and markers for success. Available at: Accessed 24 June 2015Google Scholar
  123. 123.
    Kuan WS, Ibrahim I, Leong BSH, Jain S, Lu Q, Cheung YB, Mahadevan M (2016) Emergency department management of sepsis patients: a randomized, goal-oriented, noninvasive sepsis trial. Ann Emerg Med 67:367–378CrossRefGoogle Scholar
  124. 124.
    Churpek MM, Edelson DP (2016) Moving beyond single-parameter early warning scores for rapid response system activation. Crit Care Med 44(12):2283–2285CrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2018

Authors and Affiliations

  • Abdelouahab Bellou
    • 1
    Email author
  • Hubert Blain
    • 2
  • Vishal Sehgal
    • 3
  1. 1.Department of Emergency MedicineBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA
  2. 2.Department of GeriatricsUniversity Hospital of Montpellier, University of MontpellierMontpellierFrance
  3. 3.Department of EndocrinologyIndiana University, St. Vincent HospitalCarmelUSA

Personalised recommendations