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

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

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.

Keywords: Clinical trials; Heterogeneity; Machine learning; Meta-research; Methodology; Septic shock.

Conflict of interest statement

All authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Control-group mortality rates categorized by trial inclusion criteria. The diamonds represent the mean mortality rates and 95% confidence intervals. The 95% prediction intervals (dashed lines) represents the estimated between-trial variability in mortality rates after adjusting for random chance and sample size. I2 represents the proportion of between-trial variability that cannot be explained by chance. There were no significant differences in mean mortality rates between inclusion criteria. MAP mean arterial pressure, SBP systolic blood pressure
Fig. 2
Fig. 2
Heatmap of included trials (n = 65) and associated baseline characteristics, ranked by decreasing mortality rates. White tiles represent the mean value across trials, while red and blue tiles are indicative of higher and lower than average values, respectively. Gray tiles (N/A) are variables that were not reported. The 28-day mortality rate ranged between 13.8 and 84.6%, with a mean of 38.6%. APACHE Acute Physiology and Chronic Health Evaluation, SAPS Simplified Acute Physiology Score, SOFA Sequential Organ Failure Assessment score, MAP mean arterial pressure, CVP central venous pressure, CNS central nervous system. (Asterisk) Variables with a significant univariate association with 28-day mortality
Fig. 3
Fig. 3
Included trials ordered by predicted control group mortality rate (diamonds). The predicted mortality rates were based on a multivariate weighted random-effects regression model with baseline mean Sequential Organ Failure Assessment (SOFA) score, the proportion of patients on mechanical ventilation, and mean serum creatinine as significant independent variables. The squares and brackets are the observed control-group mortality rates with 95% confidence interval. The figure illustrates that the model explained (R2) 41% of the variability in mortality rates, with significant residual heterogeneity (P < 0.0001). The red dots are the reported a-priori expected mortality rates used for sample size calculations

References

    1. Bone RC, Balk RA, Cerra FB, et al. 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. 1992;101:1644–1655. doi: 10.1378/chest.101.6.1644.
    1. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Intensive Care Med. 2003;29:530–538. doi: 10.1007/s00134-003-1662-x.
    1. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3) JAMA. 2016;315:801–810. doi: 10.1001/jama.2016.0287.
    1. Dellinger RP, Carlet JM, Masur H, et al. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2004;30:536–555. doi: 10.1007/s00134-004-2398-y.
    1. Shankar-Hari M, Phillips GS, Levy ML, et al. 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. 2016;315:775–787. doi: 10.1001/jama.2016.0289.
    1. ARISE Investigators, ANZICS Clinical Trials Group. Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496–1506. doi: 10.1056/NEJMoa1404380.
    1. Morelli A, Ertmer C, Westphal M, et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA. 2013;310:1683–1691. doi: 10.1001/jama.2013.278477.
    1. Vincent J-L, Hall JB, Slutsky AS. Ten big mistakes in intensive care medicine. Intensive Care Med. 2015;41:505–507. doi: 10.1007/s00134-014-3570-7.
    1. Marshall JC. Why have clinical trials in sepsis failed? Trends Mol Med. 2014;20:195–203. doi: 10.1016/j.molmed.2014.01.007.
    1. Opal SM, Dellinger RP, Vincent J-L, et al. The next generation of sepsis clinical trial designs: what is next after the demise of recombinant human activated protein C? Crit Care Med. 2014;42:1714–1721. doi: 10.1097/CCM.0000000000000325.
    1. Harhay MO, Wagner J, Ratcliffe SJ, et al. Outcomes and statistical power in adult critical care randomized trials. Am J Respir Crit Care Med. 2014;189:1469–1478. doi: 10.1164/rccm.201401-0056CP.
    1. 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. . Accessed 3 Nov 2016
    1. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535. doi: 10.1136/bmj.b2535.
    1. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12. doi: 10.1016/0197-2456(95)00134-4.
    1. 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)
    1. IntHout J, Ioannidis JPA, Rovers MM, Goeman JJ. Plea for routinely presenting prediction intervals in meta-analysis. BMJ Open. 2016;6:e010247. doi: 10.1136/bmjopen-2015-010247.
    1. Breiman L, Friedman J, Olshen R, Stone C. Classification and regression trees. Boca Raton, Florida, USA: CRC Press; 1984.
    1. Atkinson EJ, Therneau TM. An introduction to recursive partitioning using the RPART routines. Rochester, Minnesota, USA: Mayo Found; 2017.
    1. Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010
    1. Van Buuren S, Groothuis-Oudshoorn K. mice: Multivariate imputation by chained equations in R. J Stat Softw. 2011;45:1–67. doi: 10.18637/jss.v045.i03.
    1. Therneau T, Atkinson B, Ripley B (2017) rpart: recursive partitioning and regression trees. R Packag. version 4.1-11
    1. Annane D, Vignon P, Renault A, et al. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet (London, England) 2007;370:676–684. doi: 10.1016/S0140-6736(07)61344-0.
    1. Annane D, Timsit J-F, Megarbane B, et al. Recombinant human activated protein C for adults with septic shock: a randomized controlled trial. Am J Respir Crit Care Med. 2013;187:1091–1097. doi: 10.1164/rccm.201211-2020OC.
    1. 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;370:1583–1593. doi: 10.1056/NEJMoa1312173.
    1. Bahloul M, Chaari A, Ben Mbarek MN, et al. Use of heptaminol hydrochloride for catecholamine weaning in septic shock. Am J Ther. 2012;19:e8–e17. doi: 10.1097/MJT.0b013e3181e9b630.
    1. Chakraborty A, Mathur S, Dhunna R. Comparison of norepinephrine and dopamine in the management of septic shock using impedance cardiography. Indian J Crit Care Med. 2007;11:186. doi: 10.4103/0972-5229.37713.
    1. Chen C, Kollef MH. Targeted fluid minimization following initial resuscitation in septic shock: a pilot study. Chest. 2015;148:1462–1469. doi: 10.1378/chest.15-1525.
    1. Cicarelli DD, Vieira JE, Benseñor FEM. Early dexamethasone treatment for septic shock patients: a prospective randomized clinical trial. São Paulo Med J (Rev Paul Med) 2007;125:237–241. doi: 10.1590/S1516-31802007000400009.
    1. COIITSS Study Investigators. Annane D, Cariou A, et al. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA. 2010;303:341–348. doi: 10.1001/jama.2010.2.
    1. Dong W, Zhang G, Qu F. Effects of Ringer’s sodium pyruvate solution on serum tumor necrosis factor-α and interleukin-6 upon septic shock. Pak J Med Sci. 2015;31:672–677.
    1. Donnino MW, Andersen LW, Chase M, et al. Randomized, double-blind, placebo-controlled trial of thiamine as a metabolic resuscitator in septic shock: a pilot study. Crit Care Med. 2016;44:360–367. doi: 10.1097/CCM.0000000000001572.
    1. Dubin A, Pozo MO, Casabella CA, et al. 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. 2010;25:659.e1–659.e8. doi: 10.1016/j.jcrc.2010.04.007.
    1. Forceville X, Laviolle B, Annane D, et al. Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study. Crit Care. 2007;11:R73. doi: 10.1186/cc5960.
    1. Garg M, Sen J, Goyal S, Chaudhry D. Comparative evaluation of central venous pressure and sonographic inferior vena cava variability in assessing fluid responsiveness in septic shock. Indian J Crit Care Med. 2016;20:708–713. doi: 10.4103/0972-5229.182205.
    1. Gordon AC, Mason AJ, Perkins GD, et al. The interaction of vasopressin and corticosteroids in septic shock: a pilot randomized controlled trial. Crit Care Med. 2014;42:1325–1333. doi: 10.1097/CCM.0000000000000212.
    1. Gordon AC, Mason AJ, Thirunavukkarasu N, et al. Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial. JAMA. 2016;316:509–518. doi: 10.1001/jama.2016.10485.
    1. Hajjej Z, Meddeb B, Sellami W, et al. Effects of levosimendan on cellular metabolic alterations in patients with septic shock: a randomized controlled pilot study. Shock. 2017;48:307–312. doi: 10.1097/SHK.0000000000000851.
    1. Hjortrup PB, Haase N, Bundgaard H, et al. Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial. Intensive Care Med. 2016;42:1695–1705. doi: 10.1007/s00134-016-4500-7.
    1. Huh JW, Choi H-S, Lim C-M, et al. Low-dose hydrocortisone treatment for patients with septic shock: a pilot study comparing 3 days with 7days. Respirology. 2011;16:1088–1095. doi: 10.1111/j.1440-1843.2011.02018.x.
    1. Hyvernat H, Barel R, Gentilhomme A, et al. Effects of increasing hydrocortisone to 300 mg per day in the treatment of septic shock: a pilot study. Shock. 2016;46:498–505. doi: 10.1097/SHK.0000000000000665.
    1. Juffermans NP, Vervloet MG, Daemen-Gubbels CRG, et al. A dose-finding study of methylene blue to inhibit nitric oxide actions in the hemodynamics of human septic shock. Nitric Oxide. 2010;22:275–280. doi: 10.1016/j.niox.2010.01.006.
    1. Li M-Q, Pan C-G, Wang X-M, et al. Effect of the shenfu injection combined with early goal-directed therapy on organ functions and outcomes of septic shock patients. Cell Biochem Biophys. 2015;72:807–812. doi: 10.1007/s12013-015-0537-4.
    1. Li Y, Zhang X, Lin P, et al. Effects of shenfu injection in the treatment of septic shock patients: a multicenter, controlled, randomized, open-label trial. Evid Based Complement Alternat Med. 2016;2016:2565169.
    1. Lin S-M, Huang C-D, Lin H-C, et al. A modified goal-directed protocol improves clinical outcomes in intensive care unit patients with septic shock: a randomized controlled trial. Shock. 2006;26:551–557. doi: 10.1097/01.shk.0000232271.09440.8f.
    1. Livigni S, Bertolini G, Rossi C, et al. Efficacy of coupled plasma filtration adsorption (CPFA) in patients with septic shock: a multicenter randomised controlled clinical trial. BMJ Open. 2014;4:e003536. doi: 10.1136/bmjopen-2013-003536.
    1. Loisa P, Parviainen I, Tenhunen J, et al. Effect of mode of hydrocortisone administration on glycemic control in patients with septic shock: a prospective randomized trial. Crit Care. 2007;11:R21. doi: 10.1186/cc5696.
    1. Lu N-F, Zheng R-Q, Lin H, et al. Improved sepsis bundles in the treatment of septic shock: a prospective clinical study. Am J Emerg Med. 2015;33:1045–1049. doi: 10.1016/j.ajem.2015.04.031.
    1. Lv Q, Gu X, Chen Q, et al. Early initiation of low-dose hydrocortisone treatment for septic shock in adults: a randomized clinical trial. Am J Emerg Med. 2017;35:1810–1814. doi: 10.1016/j.ajem.2017.06.004.
    1. McIntyre LA, Fergusson D, Cook DJ, et al. Fluid resuscitation in the management of early septic shock (FINESS): a randomized controlled feasibility trial. Can J Anaesth (J Can d’anesthésie) 2008;55:819–826. doi: 10.1007/BF03034053.
    1. Memiş D, Kargi M, Sut N. Effects of propofol and dexmedetomidine on indocyanine green elimination assessed with LIMON to patients with early septic shock: a pilot study. J Crit Care. 2009;24:603–608. doi: 10.1016/j.jcrc.2008.10.005.
    1. Merouani M, Guignard B, Vincent F, et al. Norepinephrine weaning in septic shock patients by closed loop control based on fuzzy logic. Crit Care. 2008;12:R155. doi: 10.1186/cc7149.
    1. Morelli A, Lange M, Ertmer C, et al. Glibenclamide dose response in patients with septic shock: effects on norepinephrine requirements, cardiopulmonary performance, and global oxygen transport. Shock. 2007;28:530–535.
    1. Morelli A, Ertmer C, Rehberg S, et al. Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study. Crit Care. 2009;13:R130. doi: 10.1186/cc7990.
    1. Morelli A, Ertmer C, Rehberg S, et al. Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial. Crit Care. 2008;12:R143. doi: 10.1186/cc7121.
    1. Morelli A, Ertmer C, Lange M, et al. Effects of short-term simultaneous infusion of dobutamine and terlipressin in patients with septic shock: the DOBUPRESS study. Br J Anaesth. 2008;100:494–503. doi: 10.1093/bja/aen017.
    1. Morelli A, Donati A, Ertmer C, et al. Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study. Crit Care. 2010;14:R232. doi: 10.1186/cc9387.
    1. Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372:1301–1311. doi: 10.1056/NEJMoa1500896.
    1. Ngaosuwan K, Ounchokdee K, Chalermchai T. Clinical outcomes of minimized hydrocortisone dosage of 100 mg/day on lower occurrence of hyperglycemia in septic shock patients. Shock. 2017
    1. Palizas F, Dubin A, Regueira T, et al. Gastric tonometry versus cardiac index as resuscitation goals in septic shock: a multicenter, randomized, controlled trial. Crit Care. 2009;13:R44. doi: 10.1186/cc7767.
    1. Patel GP, Grahe JS, Sperry M, et al. Efficacy and safety of dopamine versus norepinephrine in the management of septic shock. Shock. 2010;33:375–380. doi: 10.1097/SHK.0b013e3181c6ba6f.
    1. Payen DM, Guilhot J, Launey Y, et al. Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial. Intensive Care Med. 2015;41:975–984. doi: 10.1007/s00134-015-3751-z.
    1. Investigators ProCESS, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683–1693. doi: 10.1056/NEJMoa1401602.
    1. Puskarich MA, Kline JA, Krabill V, et al. 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. 2014;38:736–743. doi: 10.1177/0148607113495414.
    1. Quenot J-P, Binquet C, Vinsonneau C, et al. Very high volume hemofiltration with the Cascade system in septic shock patients. Intensive Care Med. 2015;41:2111–2120. doi: 10.1007/s00134-015-4056-y.
    1. Ranieri VM, Thompson BT, Barie PS, et al. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012;366:2055–2064. doi: 10.1056/NEJMoa1202290.
    1. Richard J-C, Bayle F, Bourdin G, et al. Preload dependence indices to titrate volume expansion during septic shock: a randomized controlled trial. Crit Care. 2015;19:5. doi: 10.1186/s13054-014-0734-3.
    1. Russell JA, Vincent J-L, Kjølbye AL, et al. 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. 2017;21:213. doi: 10.1186/s13054-017-1798-7.
    1. Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358:877–887. doi: 10.1056/NEJMoa067373.
    1. Schmoelz M, Schelling G, Dunker M, Irlbeck M. Comparison of systemic and renal effects of dopexamine and dopamine in norepinephrine-treated septic shock. J Cardiothorac Vasc Anesth. 2006;20:173–178. doi: 10.1053/j.jvca.2005.10.016.
    1. Schortgen F, Clabault K, Katsahian S, et al. Fever control using external cooling in septic shock: a randomized controlled trial. Am J Respir Crit Care Med. 2012;185:1088–1095. doi: 10.1164/rccm.201110-1820OC.
    1. Seguin P, Laviolle B, Guinet P, et al. Dopexamine and norepinephrine versus epinephrine on gastric perfusion in patients with septic shock: a randomized study [NCT00134212] Crit Care. 2006;10:R32. doi: 10.1186/cc4827.
    1. Shum HP, Leung YW, Lam SM, et al. Alteco endotoxin hemoadsorption in Gram-negative septic shock patients. Indian J Crit Care Med. 2014;18:783–788. doi: 10.4103/0972-5229.146305.
    1. Singh RK, Agarwal V, Baronia AK, et al. The effects of atorvastatin on inflammatory responses and mortality in septic shock: a single-center, randomized controlled trial. Indian J Crit Care Med. 2017;21:646–654. doi: 10.4103/ijccm.IJCCM_474_16.
    1. Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008;358:111–124. doi: 10.1056/NEJMoa071366.
    1. Stephens DP, Thomas JH, Higgins A, et al. Randomized, double-blind, placebo-controlled trial of granulocyte colony-stimulating factor in patients with septic shock. Crit Care Med. 2008;36:448–454. doi: 10.1097/01.CCM.0B013E318161E480.
    1. Torraco A, Carrozzo R, Piemonte F, et al. Effects of levosimendan on mitochondrial function in patients with septic shock: a randomized trial. Biochimie. 2014;102:166–173. doi: 10.1016/j.biochi.2014.03.006.
    1. Trof RJ, Beishuizen A, Cornet AD, et al. Volume-limited versus pressure-limited hemodynamic management in septic and nonseptic shock. Crit Care Med. 2012;40:1177–1185. doi: 10.1097/CCM.0b013e31823bc5f9.
    1. Trzeciak S, Glaspey LJ, Dellinger RP, et al. Randomized controlled trial of inhaled nitric oxide for the treatment of microcirculatory dysfunction in patients with sepsis. Crit Care Med. 2014;42:2482–2492. doi: 10.1097/CCM.0000000000000549.
    1. van Genderen ME, Engels N, van der Valk RJP, et al. Early peripheral perfusion-guided fluid therapy in patients with septic shock. Am J Respir Crit Care Med. 2015;191:477–480. doi: 10.1164/rccm.201408-1575LE.
    1. van Haren FMP, Sleigh J, Boerma EC, et al. Hypertonic fluid administration in patients with septic shock: a prospective randomized controlled pilot study. Shock. 2012;37:268–275. doi: 10.1097/SHK.0b013e31823f152f.
    1. Venkatesh B, Finfer S, Cohen J, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med NEJMoa1705835. 2018
    1. Xu Q, Yan J, Cai G, et al. Effect of two volume responsiveness evaluation methods on fluid resuscitation and prognosis in septic shock patients. Chin Med J (Engl) 2014;127:483–487.
    1. Yu T, Peng X, Liu L, et al. Propofol increases preload dependency in septic shock patients. J Surg Res. 2015;193:849–855. doi: 10.1016/j.jss.2014.08.050.
    1. Zhou X, Liu D, Su L, et al. Use of stepwise lactate kinetics-oriented hemodynamic therapy could improve the clinical outcomes of patients with sepsis-associated hyperlactatemia. Crit Care. 2017;21:33. doi: 10.1186/s13054-017-1617-1.
    1. Kaukonen K-M, Bailey M, Suzuki S, et al. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA. 2014;311:1308–1316. doi: 10.1001/jama.2014.2637.
    1. Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med. 2013;41:1167–1174. doi: 10.1097/CCM.0b013e31827c09f8.
    1. Klein Klouwenberg PMC, Ong DSY, Bonten MJM, Cremer OL. Classification of sepsis, severe sepsis and septic shock: the impact of minor variations in data capture and definition of SIRS criteria. Intensive Care Med. 2012;38:811–819. doi: 10.1007/s00134-012-2549-5.
    1. Féry-Lemonnier E, Landais P, Loirat P, et al. 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. 1995;21:356–360. doi: 10.1007/BF01705416.
    1. Pettilä V, Hjortrup PB, Jakob SM, et al. Control groups in recent septic shock trials: a systematic review. Intensive Care Med. 2016;42:1912–1921. doi: 10.1007/s00134-016-4444-y.
    1. Porter ME, Larsson S, Lee TH. Standardizing patient outcomes measurement. N Engl J Med. 2016;374:504–506. doi: 10.1056/NEJMp1511701.
    1. Myles PS, Grocott MPW, Boney O, et al. Standardizing end points in perioperative trials: towards a core and extended outcome set. Br J Anaesth. 2016;116:586–589. doi: 10.1093/bja/aew066.
    1. Vincent J, Martin-Loeches I, Annane D. What patient data should be collected in this randomized controlled trial in sepsis? Intensive Care Med. 2016;42:2011–2013. doi: 10.1007/s00134-016-4560-8.
    1. Investigators PRISM, Rowan KM, Angus DC, et al. Early, goal-directed therapy for septic shock—a patient-level meta-analysis. N Engl J Med. 2017;376:2223–2234. doi: 10.1056/NEJMoa1701380.
    1. Shankar-Hari M, Harrison DA, Rowan KM. 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. 2016;44:2223–2230. doi: 10.1097/CCM.0000000000001876.
    1. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348:1546–1554. doi: 10.1056/NEJMoa022139.
    1. Ferreira FL, Bota DP, Bross A, et al. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA. 2001;286:1754–1758. doi: 10.1001/jama.286.14.1754.
    1. Minne L, Abu-Hanna A, de Jonge E. Evaluation of SOFA-based models for predicting mortality in the ICU: a systematic review. Crit Care. 2008;12:R161. doi: 10.1186/cc7160.
    1. Kempker JA, Martin GS. Does sepsis case mix heterogeneity prevent outcome comparisons? Crit Care Med. 2016;44:2288–2289. doi: 10.1097/CCM.0000000000001933.

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