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Open Access 01-03-2018 | Systematic Review

Unexplained mortality differences between septic shock trials: a systematic analysis of population characteristics and control-group mortality rates

Authors: Harm-Jan de Grooth, Jonne Postema, Stephan A. Loer, Jean-Jacques Parienti, Heleen M. Oudemans-van Straaten, Armand R. Girbes

Published in: Intensive Care Medicine | Issue 3/2018

Abstract

Purpose

Although the definition of septic shock has been standardized, some variation in mortality rates among clinical trials is expected. Insights into the sources of heterogeneity may influence the design and interpretation of septic shock studies. We set out to identify inclusion criteria and baseline characteristics associated with between-trial differences in control group mortality rates.

Methods

We conducted a systematic review of RCTs published between 2006 and 2018 that included patients with septic shock. The percentage of variance in control-group mortality attributable to study heterogeneity rather than chance was measured by I². The association between control-group mortality and population characteristics was estimated using linear mixed models and a recursive partitioning algorithm.

Results

Sixty-five septic shock RCTs were included. Overall control-group mortality was 38.6%, with significant heterogeneity (I² = 93%, P < 0.0001) and a 95% prediction interval of 13.5–71.7%. The mean mortality rate did not differ between trials with different definitions of hypotension, infection or vasopressor or mechanical ventilation inclusion criteria. Population characteristics univariately associated with mortality rates were mean Sequential Organ Failure Assessment score (standardized regression coefficient (β) = 0.57, P = 0.007), mean serum creatinine (β = 0.48, P = 0.007), the proportion of patients on mechanical ventilation (β = 0.61, P < 0.001), and the proportion with vasopressors (β = 0.57, P = 0.002). Combinations of population characteristics selected with a linear model and recursive partitioning explained 41 and 42%, respectively, of the heterogeneity in mortality rates.

Conclusions

Among 65 septic shock trials, there was a clinically relevant amount of heterogeneity in control group mortality rates which was explained only partly by differences in inclusion criteria and reported baseline characteristics.

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Bone RC, Balk RA, Cerra FB et al (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–1655CrossRefPubMed

Levy MM, Fink MP, Marshall JC et al (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Intensive Care Med 29:530–538. https://doi.org/10.1007/s00134-003-1662-x CrossRefPubMed

Singer M, Deutschman CS, Seymour CW et al (2016) The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 315:801–810. https://doi.org/10.1001/jama.2016.0287 CrossRefPubMedPubMedCentral

Dellinger RP, Carlet JM, Masur H et al (2004) Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med 30:536–555. https://doi.org/10.1007/s00134-004-2210-z CrossRefPubMed

Shankar-Hari M, Phillips GS, Levy ML et al (2016) Developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 315:775–787. https://doi.org/10.1001/jama.2016.0289 CrossRefPubMedPubMedCentral

ARISE Investigators, ANZICS Clinical Trials Group, Peake SL et al (2014) Goal-directed resuscitation for patients with early septic shock. N Engl J Med 371:1496–1506. https://doi.org/10.1056/nejmoa1404380 CrossRef

Morelli A, Ertmer C, Westphal M et al (2013) Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA 310:1683–1691. https://doi.org/10.1001/jama.2013.278477 CrossRefPubMed

Vincent J-L, Hall JB, Slutsky AS (2015) Ten big mistakes in intensive care medicine. Intensive Care Med 41:505–507. https://doi.org/10.1007/s00134-014-3570-7 CrossRefPubMed

Marshall JC (2014) Why have clinical trials in sepsis failed? Trends Mol Med 20:195–203. https://doi.org/10.1016/j.molmed.2014.01.007 CrossRefPubMed

10.

Opal SM, Dellinger RP, Vincent J-L et al (2014) The next generation of sepsis clinical trial designs: what is next after the demise of recombinant human activated protein C? Crit Care Med 42:1714–1721. https://doi.org/10.1097/CCM.0000000000000325 CrossRefPubMedPubMedCentral

11.

Harhay MO, Wagner J, Ratcliffe SJ et al (2014) Outcomes and statistical power in adult critical care randomized trials. Am J Respir Crit Care Med 189:1469–1478. https://doi.org/10.1164/rccm.201401-0056CP CrossRefPubMedPubMedCentral

12.

de Grooth HJ, Oudemans-van Straaten HM, Girbes AR (2016) Heterogeneity in a decade of septic shock RCTs: a systematic analysis of mortality outcomes. PROSPERO 2016 CRD42016049330. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=49330. Accessed 3 Nov 2016

13.

Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535CrossRefPubMedPubMedCentral

14.

Jadad AR, Moore RA, Carroll D et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12. https://doi.org/10.1016/0197-2456(95)00134-4 CrossRefPubMed

15.

Deeks JJ, Higgins JPT, Altman DG (2011) Section 9.5: heterogeneity. Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated March 2011)

16.

IntHout J, Ioannidis JPA, Rovers MM, Goeman JJ (2016) Plea for routinely presenting prediction intervals in meta-analysis. BMJ Open 6:e010247. https://doi.org/10.1136/bmjopen-2015-010247 CrossRefPubMedPubMedCentral

17.

Breiman L, Friedman J, Olshen R, Stone C (1984) Classification and regression trees. CRC Press, Boca Raton, Florida, USA

18.

Atkinson EJ, Therneau TM (2017) An introduction to recursive partitioning using the RPART routines. Mayo Found, Rochester, Minnesota, USA

19.

Viechtbauer W (2010) Conducting meta-analyses in R with the metafor package. J Stat Softw. https://doi.org/10.18637/jss.v036.i03

20.

Van Buuren S, Groothuis-Oudshoorn K (2011) mice: Multivariate imputation by chained equations in R. J Stat Softw 45:1–67. https://doi.org/10.18637/jss.v045.i03 CrossRef

21.

Therneau T, Atkinson B, Ripley B (2017) rpart: recursive partitioning and regression trees. R Packag. version 4.1-11

22.

Annane D, Vignon P, Renault A et al (2007) Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet (London, England) 370:676–684. https://doi.org/10.1016/s0140-6736(07)61344-0 CrossRef

23.

Annane D, Timsit J-F, Megarbane B et al (2013) Recombinant human activated protein C for adults with septic shock: a randomized controlled trial. Am J Respir Crit Care Med 187:1091–1097. https://doi.org/10.1164/rccm.201211-2020OC CrossRefPubMed

24.

Asfar P, Meziani F, Hamel J-F et al (2014) High versus low blood-pressure target in patients with septic shock. N Engl J Med 370:1583–1593. https://doi.org/10.1056/NEJMoa1312173 CrossRefPubMed

25.

Bahloul M, Chaari A, Ben Mbarek MN et al (2012) Use of heptaminol hydrochloride for catecholamine weaning in septic shock. Am J Ther 19:e8–e17. https://doi.org/10.1097/MJT.0b013e3181e9b630 CrossRefPubMed

26.

Chakraborty A, Mathur S, Dhunna R (2007) Comparison of norepinephrine and dopamine in the management of septic shock using impedance cardiography. Indian J Crit Care Med 11:186. https://doi.org/10.4103/0972-5229.37713 CrossRef

27.

Chen C, Kollef MH (2015) Targeted fluid minimization following initial resuscitation in septic shock: a pilot study. Chest 148:1462–1469. https://doi.org/10.1378/chest.15-1525 CrossRefPubMed

28.

Cicarelli DD, Vieira JE, Benseñor FEM (2007) Early dexamethasone treatment for septic shock patients: a prospective randomized clinical trial. São Paulo Med J (Rev Paul Med) 125:237–241CrossRef

29.

COIITSS Study Investigators, Annane D, Cariou A et al (2010) Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA 303:341–348. https://doi.org/10.1001/jama.2010.2 CrossRef

30.

Dong W, Zhang G, Qu F (2015) Effects of Ringer’s sodium pyruvate solution on serum tumor necrosis factor-α and interleukin-6 upon septic shock. Pak J Med Sci 31:672–677. https://doi.org/10.12669/pjms.313.7170 PubMedPubMedCentral

31.

Donnino MW, Andersen LW, Chase M et al (2016) Randomized, double-blind, placebo-controlled trial of thiamine as a metabolic resuscitator in septic shock: a pilot study. Crit Care Med 44:360–367. https://doi.org/10.1097/CCM.0000000000001572 CrossRefPubMedPubMedCentral

32.

Dubin A, Pozo MO, Casabella CA et al (2010) Comparison of 6% hydroxyethyl starch 130/0.4 and saline solution for resuscitation of the microcirculation during the early goal-directed therapy of septic patients. J Crit Care 25:659.e1–659.e8. https://doi.org/10.1016/j.jcrc.2010.04.007 CrossRef

33.

Forceville X, Laviolle B, Annane D et al (2007) Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study. Crit Care 11:R73. https://doi.org/10.1186/cc5960 CrossRefPubMedPubMedCentral

34.

Garg M, Sen J, Goyal S, Chaudhry D (2016) Comparative evaluation of central venous pressure and sonographic inferior vena cava variability in assessing fluid responsiveness in septic shock. Indian J Crit Care Med 20:708–713. https://doi.org/10.4103/0972-5229.195706 CrossRefPubMedPubMedCentral

35.

Gordon AC, Mason AJ, Perkins GD et al (2014) The interaction of vasopressin and corticosteroids in septic shock: a pilot randomized controlled trial. Crit Care Med 42:1325–1333. https://doi.org/10.1097/CCM.0000000000000212 CrossRefPubMed

36.

Gordon AC, Mason AJ, Thirunavukkarasu N et al (2016) Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial. JAMA 316:509–518. https://doi.org/10.1001/jama.2016.10485 CrossRefPubMed

37.

Hajjej Z, Meddeb B, Sellami W et al (2017) Effects of levosimendan on cellular metabolic alterations in patients with septic shock: a randomized controlled pilot study. Shock 48:307–312. https://doi.org/10.1097/SHK.0000000000000851 CrossRefPubMedPubMedCentral

38.

Hjortrup PB, Haase N, Bundgaard H et al (2016) Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial. Intensive Care Med 42:1695–1705. https://doi.org/10.1007/s00134-016-4500-7 CrossRefPubMed

39.

Huh JW, Choi H-S, Lim C-M et al (2011) Low-dose hydrocortisone treatment for patients with septic shock: a pilot study comparing 3 days with 7days. Respirology 16:1088–1095. https://doi.org/10.1111/j.1440-1843.2011.02018.x CrossRefPubMed

40.

Hyvernat H, Barel R, Gentilhomme A et al (2016) Effects of increasing hydrocortisone to 300 mg per day in the treatment of septic shock: a pilot study. Shock 46:498–505. https://doi.org/10.1097/SHK.0000000000000665 CrossRefPubMed

41.

Juffermans NP, Vervloet MG, Daemen-Gubbels CRG et al (2010) A dose-finding study of methylene blue to inhibit nitric oxide actions in the hemodynamics of human septic shock. Nitric Oxide 22:275–280. https://doi.org/10.1016/j.niox.2010.01.006 CrossRefPubMed

42.

Li M-Q, Pan C-G, Wang X-M et al (2015) Effect of the shenfu injection combined with early goal-directed therapy on organ functions and outcomes of septic shock patients. Cell Biochem Biophys 72:807–812. https://doi.org/10.1007/s12013-015-0537-4 CrossRefPubMed

43.

Li Y, Zhang X, Lin P et al (2016) Effects of shenfu injection in the treatment of septic shock patients: a multicenter, controlled, randomized, open-label trial. Evid Based Complement Alternat Med 2016:2565169. https://doi.org/10.1155/2016/2565169 PubMedPubMedCentral

44.

Lin S-M, Huang C-D, Lin H-C et al (2006) A modified goal-directed protocol improves clinical outcomes in intensive care unit patients with septic shock: a randomized controlled trial. Shock 26:551–557. https://doi.org/10.1097/01.shk.0000232271.09440.8f CrossRefPubMed

45.

Livigni S, Bertolini G, Rossi C et al (2014) Efficacy of coupled plasma filtration adsorption (CPFA) in patients with septic shock: a multicenter randomised controlled clinical trial. BMJ Open 4:e003536. https://doi.org/10.1136/bmjopen-2013-003536 CrossRefPubMedPubMedCentral

46.

Loisa P, Parviainen I, Tenhunen J et al (2007) Effect of mode of hydrocortisone administration on glycemic control in patients with septic shock: a prospective randomized trial. Crit Care 11:R21. https://doi.org/10.1186/cc5696 CrossRefPubMedPubMedCentral

47.

Lu N-F, Zheng R-Q, Lin H et al (2015) Improved sepsis bundles in the treatment of septic shock: a prospective clinical study. Am J Emerg Med 33:1045–1049. https://doi.org/10.1016/j.ajem.2015.04.031 CrossRefPubMed

48.

Lv Q, Gu X, Chen Q et al (2017) Early initiation of low-dose hydrocortisone treatment for septic shock in adults: a randomized clinical trial. Am J Emerg Med 35:1810–1814. https://doi.org/10.1016/j.ajem.2017.06.004 CrossRefPubMed

49.

McIntyre LA, Fergusson D, Cook DJ et al (2008) Fluid resuscitation in the management of early septic shock (FINESS): a randomized controlled feasibility trial. Can J Anaesth (J Can d’anesthésie) 55:819–826. https://doi.org/10.1007/bf03034053 CrossRef

50.

Memiş D, Kargi M, Sut N (2009) Effects of propofol and dexmedetomidine on indocyanine green elimination assessed with LIMON to patients with early septic shock: a pilot study. J Crit Care 24:603–608. https://doi.org/10.1016/j.jcrc.2008.10.005 CrossRefPubMed

51.

Merouani M, Guignard B, Vincent F et al (2008) Norepinephrine weaning in septic shock patients by closed loop control based on fuzzy logic. Crit Care 12:R155. https://doi.org/10.1186/cc7149 CrossRefPubMedPubMedCentral

52.

Morelli A, Lange M, Ertmer C et al (2007) Glibenclamide dose response in patients with septic shock: effects on norepinephrine requirements, cardiopulmonary performance, and global oxygen transport. Shock 28:530–535. https://doi.org/10.1097/shk.0b013e3180556a3c PubMed

53.

Morelli A, Ertmer C, Rehberg S et al (2009) Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study. Crit Care 13:R130. https://doi.org/10.1186/cc7990 CrossRefPubMedPubMedCentral

54.

Morelli A, Ertmer C, Rehberg S et al (2008) Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial. Crit Care 12:R143. https://doi.org/10.1186/cc7121 CrossRefPubMedPubMedCentral

55.

Morelli A, Ertmer C, Lange M et al (2008) Effects of short-term simultaneous infusion of dobutamine and terlipressin in patients with septic shock: the DOBUPRESS study. Br J Anaesth 100:494–503. https://doi.org/10.1093/bja/aen017 CrossRefPubMed

56.

Morelli A, Donati A, Ertmer C et al (2010) Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study. Crit Care 14:R232. https://doi.org/10.1186/cc9387 CrossRefPubMedPubMedCentral

57.

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. https://doi.org/10.1056/NEJMoa1500896 CrossRefPubMed

58.

Ngaosuwan K, Ounchokdee K, Chalermchai T (2017) Clinical outcomes of minimized hydrocortisone dosage of 100 mg/day on lower occurrence of hyperglycemia in septic shock patients. Shock. https://doi.org/10.1097/SHK.0000000000001061 PubMed

59.

Palizas F, Dubin A, Regueira T et al (2009) Gastric tonometry versus cardiac index as resuscitation goals in septic shock: a multicenter, randomized, controlled trial. Crit Care 13:R44. https://doi.org/10.1186/cc7767 CrossRefPubMedPubMedCentral

60.

Patel GP, Grahe JS, Sperry M et al (2010) Efficacy and safety of dopamine versus norepinephrine in the management of septic shock. Shock 33:375–380. https://doi.org/10.1097/SHK.0b013e3181c6ba6f CrossRefPubMed

61.

Payen DM, Guilhot J, Launey Y et al (2015) Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial. Intensive Care Med 41:975–984. https://doi.org/10.1007/s00134-015-3751-z CrossRefPubMedPubMedCentral

62.

Investigators ProCESS, Yealy DM, Kellum JA et al (2014) A randomized trial of protocol-based care for early septic shock. N Engl J Med 370:1683–1693. https://doi.org/10.1056/NEJMoa1401602 CrossRef

63.

Puskarich MA, Kline JA, Krabill V et al (2014) Preliminary safety and efficacy of l-carnitine infusion for the treatment of vasopressor-dependent septic shock: a randomized control trial. JPEN J Parenter Enter Nutr 38:736–743. https://doi.org/10.1177/0148607113495414 CrossRef

64.

Quenot J-P, Binquet C, Vinsonneau C et al (2015) Very high volume hemofiltration with the Cascade system in septic shock patients. Intensive Care Med 41:2111–2120. https://doi.org/10.1007/s00134-015-4056-y CrossRefPubMed

65.

Ranieri VM, Thompson BT, Barie PS et al (2012) Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 366:2055–2064. https://doi.org/10.1056/NEJMoa1202290 CrossRefPubMed

66.

Richard J-C, Bayle F, Bourdin G et al (2015) Preload dependence indices to titrate volume expansion during septic shock: a randomized controlled trial. Crit Care 19:5. https://doi.org/10.1186/s13054-014-0734-3 CrossRefPubMedPubMedCentral

67.

Russell JA, Vincent J-L, Kjølbye AL et al (2017) Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients. Crit Care 21:213. https://doi.org/10.1186/s13054-017-1798-7 CrossRefPubMedPubMedCentral

68.

Russell JA, Walley KR, Singer J et al (2008) Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 358:877–887. https://doi.org/10.1056/NEJMoa067373 CrossRefPubMed

69.

Schmoelz M, Schelling G, Dunker M, Irlbeck M (2006) Comparison of systemic and renal effects of dopexamine and dopamine in norepinephrine-treated septic shock. J Cardiothorac Vasc Anesth 20:173–178. https://doi.org/10.1053/j.jvca.2005.10.016 CrossRefPubMed

70.

Schortgen F, Clabault K, Katsahian S et al (2012) Fever control using external cooling in septic shock: a randomized controlled trial. Am J Respir Crit Care Med 185:1088–1095. https://doi.org/10.1164/rccm.201110-1820OC CrossRefPubMed

71.

Seguin P, Laviolle B, Guinet P et al (2006) Dopexamine and norepinephrine versus epinephrine on gastric perfusion in patients with septic shock: a randomized study [NCT00134212]. Crit Care 10:R32. https://doi.org/10.1186/cc4827 CrossRefPubMedPubMedCentral

72.

Shum HP, Leung YW, Lam SM et al (2014) Alteco endotoxin hemoadsorption in Gram-negative septic shock patients. Indian J Crit Care Med 18:783–788. https://doi.org/10.4103/0972-5229.146305 CrossRefPubMedPubMedCentral

73.

Singh RK, Agarwal V, Baronia AK et al (2017) The effects of atorvastatin on inflammatory responses and mortality in septic shock: a single-center, randomized controlled trial. Indian J Crit Care Med 21:646–654. https://doi.org/10.4103/ijccm.IJCCM_474_16 CrossRefPubMedPubMedCentral

74.

Sprung CL, Annane D, Keh D et al (2008) Hydrocortisone therapy for patients with septic shock. N Engl J Med 358:111–124. https://doi.org/10.1056/NEJMoa071366 CrossRefPubMed

75.

Stephens DP, Thomas JH, Higgins A et al (2008) Randomized, double-blind, placebo-controlled trial of granulocyte colony-stimulating factor in patients with septic shock. Crit Care Med 36:448–454. https://doi.org/10.1097/01.CCM.0B013E318161E480 CrossRefPubMed

76.

Torraco A, Carrozzo R, Piemonte F et al (2014) Effects of levosimendan on mitochondrial function in patients with septic shock: a randomized trial. Biochimie 102:166–173. https://doi.org/10.1016/j.biochi.2014.03.006 CrossRefPubMed

77.

Trof RJ, Beishuizen A, Cornet AD et al (2012) Volume-limited versus pressure-limited hemodynamic management in septic and nonseptic shock. Crit Care Med 40:1177–1185. https://doi.org/10.1097/CCM.0b013e31823bc5f9 CrossRefPubMed

78.

Trzeciak S, Glaspey LJ, Dellinger RP et al (2014) Randomized controlled trial of inhaled nitric oxide for the treatment of microcirculatory dysfunction in patients with sepsis. Crit Care Med 42:2482–2492. https://doi.org/10.1097/CCM.0000000000000549 CrossRefPubMed

79.

van Genderen ME, Engels N, van der Valk RJP et al (2015) Early peripheral perfusion-guided fluid therapy in patients with septic shock. Am J Respir Crit Care Med 191:477–480. https://doi.org/10.1164/rccm.201408-1575LE CrossRefPubMed

80.

van Haren FMP, Sleigh J, Boerma EC et al (2012) Hypertonic fluid administration in patients with septic shock: a prospective randomized controlled pilot study. Shock 37:268–275. https://doi.org/10.1097/SHK.0b013e31823f152f CrossRefPubMed

81.

Venkatesh B, Finfer S, Cohen J et al (2018) Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med NEJMoa1705835. https://doi.org/10.1056/nejmoa1705835

82.

Xu Q, Yan J, Cai G et al (2014) Effect of two volume responsiveness evaluation methods on fluid resuscitation and prognosis in septic shock patients. Chin Med J (Engl) 127:483–487. https://doi.org/10.3760/cma.j.issn.0366-6999.20131830

83.

Yu T, Peng X, Liu L et al (2015) Propofol increases preload dependency in septic shock patients. J Surg Res 193:849–855. https://doi.org/10.1016/j.jss.2014.08.050 CrossRefPubMed

84.

Zhou X, Liu D, Su L et al (2017) Use of stepwise lactate kinetics-oriented hemodynamic therapy could improve the clinical outcomes of patients with sepsis-associated hyperlactatemia. Crit Care 21:33. https://doi.org/10.1186/s13054-017-1617-1 CrossRefPubMedPubMedCentral

85.

Kaukonen K-M, Bailey M, Suzuki S et al (2014) Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA 311:1308–1316. https://doi.org/10.1001/jama.2014.2637 CrossRefPubMed

86.

Gaieski DF, Edwards JM, Kallan MJ, Carr BG (2013) Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med 41:1167–1174. https://doi.org/10.1097/CCM.0b013e31827c09f8 CrossRefPubMed

87.

Klein Klouwenberg PMC, Ong DSY, Bonten MJM, Cremer OL (2012) Classification of sepsis, severe sepsis and septic shock: the impact of minor variations in data capture and definition of SIRS criteria. Intensive Care Med 38:811–819. https://doi.org/10.1007/s00134-012-2549-5 CrossRefPubMed

88.

Féry-Lemonnier E, Landais P, Loirat P et al (1995) Evaluation of severity scoring systems in ICUs—translation, conversion and definition ambiguities as a source of inter-observer variability in Apache II, SAPS and OSF. Intensive Care Med 21:356–360. https://doi.org/10.1007/BF01705416 CrossRefPubMed

89.

Pettilä V, Hjortrup PB, Jakob SM et al (2016) Control groups in recent septic shock trials: a systematic review. Intensive Care Med 42:1912–1921. https://doi.org/10.1007/s00134-016-4444-y CrossRefPubMed

90.

Porter ME, Larsson S, Lee TH (2016) Standardizing patient outcomes measurement. N Engl J Med 374:504–506. https://doi.org/10.1056/NEJMp1511701 CrossRefPubMed

91.

Myles PS, Grocott MPW, Boney O et al (2016) Standardizing end points in perioperative trials: towards a core and extended outcome set. Br J Anaesth 116:586–589. https://doi.org/10.1093/bja/aew066 CrossRefPubMed

92.

Vincent J, Martin-Loeches I, Annane D (2016) What patient data should be collected in this randomized controlled trial in sepsis? Intensive Care Med 42:2011–2013. https://doi.org/10.1007/s00134-016-4560-8 CrossRefPubMed

93.

Investigators PRISM, Rowan KM, Angus DC et al (2017) Early, goal-directed therapy for septic shock—a patient-level meta-analysis. N Engl J Med 376:2223–2234. https://doi.org/10.1056/NEJMoa1701380 CrossRef

94.

Shankar-Hari M, Harrison DA, Rowan KM (2016) Differences in impact of definitional elements on mortality precludes international comparisons of sepsis epidemiology—a cohort study illustrating the need for standardized reporting. Crit Care Med 44:2223–2230. https://doi.org/10.1097/CCM.0000000000001876 CrossRefPubMed

95.

Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348:1546–1554. https://doi.org/10.1056/NEJMoa022139 CrossRefPubMed

96.

Ferreira FL, Bota DP, Bross A et al (2001) Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 286:1754–1758. https://doi.org/10.1001/jama.286.14.1754 CrossRefPubMed

97.

Minne L, Abu-Hanna A, de Jonge E (2008) Evaluation of SOFA-based models for predicting mortality in the ICU: a systematic review. Crit Care 12:R161. https://doi.org/10.1186/cc7160 CrossRefPubMedPubMedCentral

98.

Kempker JA, Martin GS (2016) Does sepsis case mix heterogeneity prevent outcome comparisons? Crit Care Med 44:2288–2289. https://doi.org/10.1097/CCM.0000000000001933 CrossRefPubMedPubMedCentral

Title: Unexplained mortality differences between septic shock trials: a systematic analysis of population characteristics and control-group mortality rates
Authors: Harm-Jan de Grooth
Jonne Postema
Stephan A. Loer
Jean-Jacques Parienti
Heleen M. Oudemans-van Straaten
Armand R. Girbes
Publication date: 01-03-2018
Publisher: Springer Berlin Heidelberg
Published in: Intensive Care Medicine / Issue 3/2018
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-018-5134-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Unexplained mortality differences between septic shock trials: a systematic analysis of population characteristics and control-group mortality rates

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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The top ten unknowns in paediatric mechanical ventilation

Correction to: Catheter retention as a consequence rather than a cause of unfavorable outcome in candidemia

What’s new: prevention of acute dialysis catheter-related infection

Suspended in time and space

Cardiac intensive care unit organisation in an economically less developed European country

Comparison of European ICU patients in 2012 (ICON) versus 2002 (SOAP)