Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial
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We assessed the effects of a protocol restricting resuscitation fluid vs. a standard care protocol after initial resuscitation in intensive care unit (ICU) patients with septic shock.
We randomised 151 adult patients with septic shock who had received initial fluid resuscitation in nine Scandinavian ICUs. In the fluid restriction group fluid boluses were permitted only if signs of severe hypoperfusion occurred, while in the standard care group fluid boluses were permitted as long as circulation continued to improve.
The co-primary outcome measures, resuscitation fluid volumes at day 5 and during ICU stay, were lower in the fluid restriction group than in the standard care group [mean differences −1.2 L (95 % confidence interval −2.0 to −0.4); p < 0.001 and −1.4 L (−2.4 to −0.4) respectively; p < 0.001]. Neither total fluid inputs and balances nor serious adverse reactions differed statistically significantly between the groups. Major protocol violations occurred in 27/75 patients in the fluid restriction group. Ischaemic events occurred in 3/75 in the fluid restriction group vs. 9/76 in the standard care group (odds ratio 0.32; 0.08–1.27; p = 0.11), worsening of acute kidney injury in 27/73 vs. 39/72 (0.46; 0.23–0.92; p = 0.03), and death by 90 days in 25/75 vs. 31/76 (0.71; 0.36–1.40; p = 0.32).
A protocol restricting resuscitation fluid successfully reduced volumes of resuscitation fluid compared with a standard care protocol in adult ICU patients with septic shock. The patient-centred outcomes all pointed towards benefit with fluid restriction, but our trial was not powered to show differences in these exploratory outcomes.
KeywordsCritical care Fluid therapy Intensive care Resuscitation Sepsis Septic Shock
The CLASSIC trial was funded by the Danish Medical Research Council (09-066938) and supported by Rigshospitalets Research Council, the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (the ACTA Foundation) and the Ehrenreich Foundation. The funders of the study had no influence on the design or conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. We are grateful to the clinical staff of doctors and nurses at the participating ICUs for their important contribution and to patients and relatives for their consent to participate.
The CLASSIC trial investigators
Management Committee: Peter B. Hjortrup, Anders Perner (Chair), Nicolai Haase and Jørn Wetterslev.
Trial site investigators (in Denmark unless otherwise specified): Rigshospitalet: P.B. Hjortrup, A. Perner, N. Haase, K.R. Uhre, L.H. Nislev, L. Russell, C. Claudius, U.G. Pedersen, M.B. Madsen, M.H. Møller, M. Ibsen, K. Thornberg, F. Sjövall, F. Mondrup, H.C. Thorsen-Meyer, L. Quist, L. Vestergaard, C. Lund, J. Wiis, R. Hein-Rasmussen, C.P. Holler, J.O. White, S. Asghar; Randers Hospital: H. Bundgaard, D. Flye, K. Knudsen, B. Hougaard; Aalborg Hospital: B.S. Rasmussen, S.L. Thomsen, S.N. Granum; Herning Hospital: R. Winding, S. Haubjerg, L. Friholdt, N. Dey, M. Nygaard; Holbæk Hospital: H.H. Bülow, J.M. Elkjær, A. Aaen, S. Grangaard, L. Christensen, M. Hjort, S. Larsen; Helsinki University Hospital, Finland: V. Pettilä, E. Wilkman, M. Valkonen, S. Sutinen, L. Pettilä; Holstebro Hospital: D. Lodahl, R.V.M. Andersen; Nordsjællands Hospital: R.E. Berthelsen, M. Bestle, S. Lauritzen, L. Valbjørn; Herlev Hospital: H. Christensen.
Compliance with ethical standards
Conflicts of interest
The Department of Intensive Care, Rigshospitalet receives research funds from CSL Behring, Switzerland, Fresenius Kabi, Germany, and Ferring Pharmaceuticals, Denmark.
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