BACKGROUND: Albumin administration is suggested in patients with sepsis and septic shock who have received large volumes of crystalloids. Given lack of firm evidence, clinical practice variation may exist. To address this, we investigated if patient characteristics or trial site were associated with albumin use in septic shock. METHODS: We conducted a post-hoc study of the CLASSIC international, randomised clinical trial of fluid volumes in septic shock. Associations between selected baseline variables and trial site with albumin use during ICU stay were assessed in Cox models considering death, ICU discharge, and loss-to-follow-up as competing events. Baseline variables were first assessed individually, adjusted for treatment allocation (restrictive vs. standard IV fluid), and then adjusted for allocation and the other baseline variables. Site was assessed in a model adjusted for allocation and baseline variables. RESULTS: We analysed 1541 of 1554 patients randomised in CLASSIC (99.2%). During ICU stay, 36.3% of patients in the restrictive-fluid group and 52.6% in the standard-fluid group received albumin. Gastrointestinal focus of infection and higher doses of norepinephrine were most strongly associated with albumin use (subgroup with highest quartile of norepinephrine doses, hazard ratio (HR) 2.58, 95% CI 1.89 to 3.53). HRs for associations between site and albumin use ranged from 0.11 (95% CI 0.05 to 0.26) to 1.70 (95% CI 1.06 to 2.74); test for overall effect of site: p < .001. CONCLUSIONS: In adults with septic shock, gastrointestinal focus of infection and higher doses of norepinephrine at baseline were associated with albumin use, which also varied substantially between sites.

1st Department of Anaesthesiology and Intensive Therapy Medical University of Lublin Lublin Poland

Collaboration for Research in Intensive Care Copenhagen Denmark

Department of Anaesthesia and Intensive Care Medicine IRCCS Humanitas Research Hospital Rozzano Italy

Department of Anaesthesiology and Intensive Care Medicine Rikshospitalet Oslo University Hospital Norway

Department of Biomedical Sciences Humanitas University Pieve Emanuele Italy

Department of Cardiothoracic Anaesthesia and Intensive Care The Heart Centre Rigshospitalet University of Copenhagen Copenhagen Denmark

Department of Clinical Medicine University of Copenhagen Copenhagen Denmark

Department of Clinical Sciences Danderyd Hospital Karolinska Institutet Stockholm Sweden

Department of Intensive Care Guy's and St Thomas' Hospital London UK

Department of Intensive Care Medicine University Hospital Brussels Jette Belgium

Department of Intensive Care Rigshospitalet University of Copenhagen Copenhagen Denmark

Division of Emergencies and Critical Care Rikshospitalet Oslo University Hospital Norway

Medical Intensive Care Unit 1 Interni klinika Fakultni Nemocnice Plzen Czech Republic

Section of Biostatistics Department of Public Health University of Copenhagen Copenhagen Denmark

University of Bern Bern Switzerland

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Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47:1181-1247.

Vesteinsdottir E, Sigurdsson MI, Gottfredsson M, Blondal A, Karason S. Temporal trends in the epidemiology, management, and outcome of sepsis-a nationwide observational study. Acta Anaesthesiol Scand. 2022;66:497-506.

Lindén-Søndersø A, Jungner M, Spångfors M, et al. Survey of non-resuscitation fluids administered during septic shock: a multicenter prospective observational study. Ann Intensive Care. 2019;9:132.

Xu J, Cai H, Zheng X. Timing of vasopressin initiation and mortality in patients with septic shock: analysis of the MIMIC-III and MIMIC-IV databases. BMC Infect Dis. 2023;23:199.

Finfer S, Myburgh J, Bellomo R. Intravenous fluid therapy in critically ill adults. Nat Rev Nephrol. 2018;14:541-557.

Ellekjaer KL, Perner A, Jensen MM, Møller MH. Lactate versus acetate buffered intravenous crystalloid solutions: a scoping review. Br J Anaesth. 2020;125:693-703.

Caironi P, Tognoni G, Masson S, et al. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370:1-10.

Mårtensson J, Bihari S, Bannard-Smith J, et al. Small volume resuscitation with 20% albumin in intensive care: physiological effects: the SWIPE randomised clinical trial. Intensive Care Medicine. 2018;44:1797-1806.

Finfer S, McEvoy S, Bellomo R, et al. Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med. 2011;37:86-96.

Taylor C, Yang L, Finfer S, et al. An international comparison of the cost of fluid resuscitation therapies. Aust Crit Care. 2021;34:23-32.

Hoppe JD, Scriba PC, Klüter H. 5 Human Albumin. Transfus Med Hemotherapy. 2009;36:399-407.

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;350:2247-2256.

Caironi P, Tognoni G, Masson S, et al. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370:1412-1421.

Bellomo R, McEvoy S, Kai Lo S, et al. Effect of baseline serum albumin concentration on outcome of resuscitation with albumin or saline in patients in intensive care units: analysis of data from the saline versus albumin fluid evaluation (SAFE) study. BMJ. 2006;333:1044-1046.

Patel A, Laffan MA, Waheed U, Brett SJ. Randomised trials of human albumin for adults with sepsis: systematic review and meta-analysis with trial sequential analysis of all-cause mortality. BMJ. 2014;349:4561.

Lewis SR, Pritchard MW, Evans DJW, et al. Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database Syst Rev. 2018;8:CD000567.

Hammond NE, Taylor C, Finfer S, et al. Patterns of intravenous fluid resuscitation use in adult intensive care patients between 2007 and 2014: An international cross-sectional study. PLoS One. 2017;12:e0176292.

Zampieri FG, Bagshaw SM, Semler MW. Fluid therapy for critically ill adults with sepsis: a review. JAMA. 2023;329:1967-1980.

Meyhoff TS, Hjortrup PB, Wetterslev J, et al. Restriction of intravenous fluid in ICU patients with septic shock. N Engl J Med. 2022;386:2459-2470.

Meyhoff TS, Hjortrup PB, Møller MH, et al. Conservative versus Liberal fluid therapy in septic shock (CLASSIC) trial - protocol and statistical analysis plan. Acta Anaesthesiol Scand. 2019;63:1262-1271.

Meyhoff TS, Granholm A, Hjortrup PB, et al. Albumin administration in septic shock-protocol for post-hoc analyses of data from a multicentre RCT. Acta Anaesthesiol Scand. 2023;67:1128-1136.

Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61:344-349.

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.

Kjaer M-BN, Meyhoff TS, Sivapalan P, et al. Long-term effects of restriction of intravenous fluid in adult ICU patients with septic shock. Intensive Care Med. 2023;49:820-830.

Granholm A, Perner A, Krag M, et al. Development and internal validation of the simplified mortality score for the intensive care unit (SMS-ICU). Acta Anaesthesiol Scand. 2018;62:336-346.

Clark TG, Bradburn MJ, Love SB, Altman DG. Survival analysis part IV: further concepts and methods in survival analysis. Br J Cancer. 2003;89:781-786.

Beyersmann J, Allignol A, Schumacher M. Competing Risks and Multistate Models with R. Springer; 2012.

Bradburn MJ, Clark TG, Love SB, Altman DG. Survival analysis part III: multivariate data analysis-choosing a model and assessing its adequacy and fit. Br J Cancer. 2003;89:605-611.

Angeli P, Bernardi M, Villanueva C, et al. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406-460.

Runyon BA. Introduction to the revised American Association for the Study of Liver Diseases practice guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology (Baltimore, Md). 2013;57:1651-1653.

Hjortrup PB, Haase N, Wetterslev J, Perner A. Associations of hospital and patient characteristics with fluid resuscitation volumes in patients with severe sepsis: post hoc analyses of data from a multicentre randomised clinical trial. PLOS One. 2016;11:e0155767.

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;367:124-134.