Management of severe sepsis: Advances, challenges, and current status

Drug Design, Development and Therapy

Volumn 9, Issue , 2015, Pages 2079-2088

  Martin Loeches, Ignacio ^a   Levy, Mitchell M ^b   Artigas, Antonio ^c  

^a ST JAMES S HOSPITAL   (Ireland)

^b BROWN UNIVERSITY   (United States)

^c UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

Author keywords

Biomarkers; Critical care; Guidelines; Sepsis; Septic shock; Surviving sepsis campaign

Indexed keywords

ANTIBIOTIC AGENT; ANTIOXIDANT; BIOLOGICAL MARKER; CORTICOSTEROID; IMMUNOGLOBULIN; ANTIINFECTIVE AGENT;

DETOXIFICATION; DIAGNOSTIC PROCEDURE; DISEASE SEVERITY; DISEASE SURVEILLANCE; DRUG SUBSTITUTION; DRUG WITHDRAWAL; FLUID RESUSCITATION; GLYCEMIC CONTROL; HEALTH CARE PLANNING; HEMODYNAMIC MONITORING; HEMOPERFUSION; HUMAN; IMMUNE RESPONSE; IMMUNOMODULATION; INTENSIVE CARE; MEAN ARTERIAL PRESSURE; MESENCHYMAL STEM CELL TRANSPLANTATION; META ANALYSIS (TOPIC); PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SEPTIC SHOCK; SURVIVAL RATE; TREATMENT INDICATION; PRACTICE GUIDELINE; SEPSIS; SHOCK, SEPTIC;

ANTI-BACTERIAL AGENTS; BIOMARKERS; GUIDELINES AS TOPIC; HUMANS; SEPSIS; SHOCK, SEPTIC;

EID: 84929206816     PISSN: None     EISSN: 11778881     Source Type: Journal    
DOI: 10.2147/DDDT.S78757     Document Type: Review

References (64)

1. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303–1310.
2. Kaukonen K-M, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA. 2014;311(13):1308–1316. doi:10.1001/jama.2014.2637.
3. Levy MM, Rhodes A, Phillips GS, et al. Surviving sepsis campaign: association between performance metrics and outcomes in a 7.5-year study. Crit Care Med. 2015;43(1):3–12. doi:10.1097/CCM.0000000000000723.
4. Martin-Loeches I, de Haro C, Dellinger RP, et al. Effectiveness of an inspiratory pressure-limited approach to mechanical ventilation in septic patients. Eur Respir J. 2013;41(1):157–164. doi:10.1183/09031936.00221611.
5. Lyle NH, Pena OM, Boyd JH, Hancock REW. Barriers to the effective treatment of sepsis: antimicrobial agents, sepsis definitions, and host-directed therapies. Ann N Y Acad Sci. 2014;1323:101–114. doi:10.1111/nyas.12444.
6. Schorr CA, Zanotti S, Dellinger RP. Severe sepsis and septic shock: management and performance improvement. Virulence. 2014;5(1):190–199. doi:10.4161/viru.27409.
7. Vincent J-L, Marshall JC, Namendys-Silva SA, et al. Assessment of the worldwide burden of critical illness: the Intensive Care Over Nations (ICON) audit. Lancet Respir Med. 2014;2(5):380–386. doi:10.1016/S2213-2600(14)70061-X.
8. Rhee C, Gohil S, Klompas M. Regulatory mandates for sepsis care–reasons for caution. N Engl J Med. 2014;370(18):1673–1676. doi:10.1056/NEJMp1400276.
9. Surviving Sepsis Campaign Guidelines 2004.
10. Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 2010;36(2):222–231. doi:10.1007/s00134-009-1738-3.
11. Ferrer R, Artigas A, Levy MM, et al. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA. 2008;299(19):2294–2303. doi:10.1001/jama.299.19.2294.
12. Suarez D, Ferrer R, Artigas A, et al. Cost-effectiveness of the Surviving Sepsis Campaign protocol for severe sepsis: a prospective nation-wide study in Spain. Intensive Care Med. 2011;37(3):444–452. doi:10.1007/s00134-010-2102-3.
13. Castellanos-Ortega A, Suberviola B, García-Astudillo LA, et al. Impact of the Surviving Sepsis Campaign protocols on hospital length of stay and mortality in septic shock patients: results of a three-year follow-up quasi-experimental study. Crit Care Med. 2010;38(4):1036–1043. doi:10.1097/CCM.0b013e3181d455b6.
14. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228. doi:10.1007/s00134-012-2769-8.
15. Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32(3):858–873. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15090974. Accessed October 10, 2014.
16. Yealy DM, Kellum JA, Huang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683–1693. doi:10.1056/NEJMoa1401602.
17. ARISE Investigators; ANZICS Clinical Trials Group; Peake SL, Delaney A, Bailey M, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371(16):1496–1506. doi:10.1056/NEJMoa1404380.
18. Power GS, Harrison DA, Mouncey PR, Osborn TM, Harvey SE, Rowan KM. The Protocolised Management in Sepsis (ProMISe) trial statistical analysis plan. Crit Care Resusc. 2013;15(4):311–317. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24289513. Accessed October 9, 2014.
19. 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. doi:10.1097/01.CCM.0000217961.75225.E9.
20. 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. doi:10.1097/CCM.0000000000000330.
21. Díaz-Martín A, Martínez-González ML, Ferrer R, et al. Edusepsis Study Group. Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality. Crit Care. 2012;16(6).
22. Brunkhorst FM, Oppert M, Marx G, et al. Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial. JAMA. 2012;307(22):2390–2399. doi:10.1001/jama.2012.5833.
23. Garnacho-Montero J, Gutiérrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32–40. doi:10.1007/s00134-013-3077-7.
24. Leone M, Bechis C, Baumstarck K, et al. De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial. Intensive Care Med. 2014;40(10):1399–1408. Available from: http://icmjournal.esicm.org/journal/134/0/10/3411/0/.
25. Estrada CA, Murugan R. Hydroxyethyl starch in severe sepsis: end of starch era? Crit Care. 2013;17(2):310. doi:10.1186/cc12531.
26. Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis. N Engl J Med. 2012;367(2): 124–134. doi:10.1056/NEJMoa1204242.
27. Myburgh JA, Finfer S, Bellomo R, et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med. 2012;367(20): 1901–1911. doi:10.1056/NEJMoa1209759.
28. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.
29. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350(22):2247–2256. doi:10.1056/NEJMoa040232.
30. Annane D, Siami S, Jaber S, et al. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA. 2013;310(17):1809–1817. doi:10.1001/jama.2013.280502.
31. 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. doi:10.1056/NEJMoa1305727.
32. Asfar P, Meziani F, Hamel J-F, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370(17):1583–1593. doi:10.1056/NEJMoa1312173.
33. Mei SH, Haitsma JJ, Dos Santos CC, et al. Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis. Am J Respir Crit Care Med. 2010;182(8):1047–1057. doi:10.1164/rccm.201001-0010OC.
34. Weil BR, Markel TA, Herrmann JL, Abarbanell AM, Kelly ML, Meldrum DR. Stem cells in sepsis. Ann Surg. 2009;250(1):19–27. doi:10.1097/SLA.0b013e3181a77b9c.
35. Krasnodembskaya A, Samarani G, Song Y, et al. Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes. Am J Physiol Lung Cell Mol Physiol. 2012;302(10):L1003–L1013. doi:10.1152/ajplung.00180.2011.
36. Zhou F, Peng Z, Murugan R, Kellum JA. Blood purification and mortality in sepsis: a meta-analysis of randomized trials. Crit Care Med. 2013;41(9):2209–2220. doi:10.1097/CCM.0b013e31828cf412.
37. Marshall JC, Foster D, Vincent J-L, et al. Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study. J Infect Dis. 2004;190(3):527–534. doi:10.1086/422254.
38. Cruz DN, Antonelli M, Fumagalli R, et al. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA. 2009;301(23):2445–2452. doi:10.1001/jama.2009.856.
39. Norrby-Teglund A, Haque KN, Hammarstrom L. Intravenous polyclonal IgM-enriched immunoglobulin therapy in sepsis: a review of clinical efficacy in relation to microbiological aetiology and severity of sepsis. J Intern Med. 2006;260(6):509–516. doi:10.1111/j.1365-2796.2006.01726.x.
40. Tamayo E, Fernández A, Almansa R, et al. Beneficial role of endogenous immunoglobulin subclasses and isotypes in septic shock. J Crit Care. 2012;27(6):616–22.
41. Trefler S, Rodríguez A, Martín-Loeches I, et al. Oxidative stress in immunocompetent patients with severe community-acquired pneumonia. A pilot study. Med Intensiva. 2014;38(2):73–82.
42. Fink T, Glas M, Wolf A, et al. Melatonin receptors mediate improvements of survival in a model of polymicrobial sepsis. Crit Care Med. 2014;42(1):e22–e31. doi:10.1097/CCM.0b013e3182a63e2b.
43. Dungan KM, Braithwaite SS, Preiser J-C. Stress hyperglycaemia. Lancet. 2009;373(9677):1798–1807. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0140673609605535.
44. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354(5):449–461. doi:10.1056/NEJMoa052521.
45. Ellger B, Westphal M, Stubbe HD, Van den Heuvel I, Van Aken H, Van den Berghe G. Blutzuckerkontrolle bei Patienten mit Sepsis und septischem Schock [Glycemic control in sepsis and septic shock: friend or foe?]. Anaesthesist. 2008;57(1):43–48. doi:10.1007/s00101-007-1285-7.
46. Song F, Zhong L-J, Han L, et al. Intensive insulin therapy for septic patients: a meta-analysis of randomized controlled trials. Biomed Res Int. 2014;2014:698265. doi:10.1155/2014/698265.
47. Leelarathna L, English SW, Thabit H, et al. Feasibility of fully automated closed-loop glucose control using continuous subcutaneous glucose measurements in critical illness: a randomized controlled trial. Crit Care. 2013;17(4):R159. doi:10.1186/cc12838.
48. Goldstein IM, Roos D, Weissmann G, Kaplan HB. Influence of corticosteroids on human polymorphonuclear leukocyte function in vitro: reduction of lysosomal enzyme release and superoxide production. Inflammation. 1976;1(3):305–315. doi:10.1007/BF00917870.
49. Schumer W. Steroids in the treatment of clinical septic shock. Ann Surg. 1976;184(3):333–341. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1344393&tool=pmcentrez&rendertype=abstract. Accessed October 10, 2014.
50. Sprung CL, Caralis PV, Marcial EH, et al. The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study. N Engl J Med. 1984;311(18):1137–1143. doi:10.1056/NEJM198411013111801.
51. The Veterans Administration Systemic Sepsis Cooperative Study Group. Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N Engl J Med. 1987;317(11):659–665. doi:10.1056/NEJM198709103171102.
52. Cronin L, Cook DJ, Carlet J, et al. Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med. 1995;23(8):1430–1439. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7634816. Accessed October 10, 2014.
53. Bollaert PE, Charpentier C, Levy B, Debouverie M, Audibert G, Larcan A. Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med. 1998;26(4):645–650. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9559600. Accessed October 10, 2014.
54. Briegel J, Forst H, Haller M, et al. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med. 1999;27(4):723–732. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10321661. Accessed October 10, 2014.
55. 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(7):862–871. Available from:http://www.ncbi.nlm.nih.gov/pubmed/12186604. Accessed October 10, 2014.
56. Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008;358(2):111–124. doi:10.1056/NEJMoa071366.
57. Marik PE, Pastores SM, Annane D, et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med. 2008;36(6):1937–1949. doi:10.1097/CCM.0b013e31817603ba.
58. Lévy Y, Sereti I, Tambussi G, et al. Effects of recombinant human interleukin 7 on T-cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: results of a phase I/IIa randomized, placebo-controlled, multicenter study. Clin Infect Dis. 2012;55(2):291–300. doi:10.1093/cid/cis383.
59. Póvoa P, Salluh JI. Biomarker-guided antibiotic therapy in adult critically ill patients: a critical review. Ann Intensive Care. 2012;2(1):32. doi:10.1186/2110-5820-2-32.
60. Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13(12):862–874. doi:10.1038/nri3552.
61. Gaieski DF, Mikkelsen ME, Band RA. 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;38:1045–1053.
62. Daniels R, Nutbeam T, McNamara G, Galvin C. The sepsis six and the severe sepsis resuscitation bundle: a prospective observational cohort study. Emerg Med J. 2011;28(6):507–12.
63. Appelboam R, Tilley R, Blackburn J. Time to antibiotics in sepsis. Crit Care. 2010;14(Suppl 1):50.
64. 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; 38:1–8.