Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.


BACKGROUND
NCT02079402.
Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Peter B
PB
Hjortrup
Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Nicolai
N
Haase
Department of Intensive Care, Randers Hospital, Randers, Denmark.
Helle
H
Bundgaard
Department of Intensive Care, Aalborg University Hospital, Aalborg, Denmark.
Simon L
SL
Thomsen
Department of Intensive Care, Herning Hospital, Herning, Denmark.
Robert
R
Winding
Department of Intensive Care, Helsinki University Hospital, Helsinki, Finland.
Ville
V
Pettilä
Department of Intensive Care, Holbæk Hospital, Holbæk, Denmark.
Anne
A
Aaen
Department of Intensive Care, Holstebro Hospital, Holstebro, Denmark.
David
D
Lodahl
Department of Intensive Care, Nordsjællands Hospital, Hillerød, Denmark.
Rasmus E
RE
Berthelsen
Department of Intensive Care, Herlev Hospital, Herlev Municipality, Denmark.
Henrik
H
Christensen
Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Martin B
MB
Madsen
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Per
P
Winkel
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Jørn
J
Wetterslev
Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. anders.perner@regionh.dk.|Centre for Research in Intensive Care, Copenhagen, Denmark. anders.perner@regionh.dk.
Anders
A
Perner
D000368:Aged; D001775:Blood Circulation / Q000502:physiology; D003422:Critical Care / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D005440:Fluid Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012151:Resuscitation / Q000379:methods*; D012772:Shock, Septic / Q000503:physiopathology / Q000628:therapy*; D014882:Water-Electrolyte Balance / Q000502:physiology*
Critical care; Fluid therapy; Intensive care; Resuscitation; Sepsis; Septic; Shock
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