Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.
BACKGROUND
Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis.


METHODS
In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization.


RESULTS
Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline.


CONCLUSIONS
Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.).
Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. anders.perner@rh.regionh.dk
Anders
A
Perner
Nicolai
N
Haase
Anne B
AB
Guttormsen
Jyrki
J
Tenhunen
Gudmundur
G
Klemenzson
Anders
A
Åneman
Kristian R
KR
Madsen
Morten H
MH
Møller
Jeanie M
JM
Elkjær
Lone M
LM
Poulsen
Asger
A
Bendtsen
Robert
R
Winding
Morten
M
Steensen
Pawel
P
Berezowicz
Peter
P
Søe-Jensen
Morten
M
Bestle
Kristian
K
Strand
Jørgen
J
Wiis
Jonathan O
JO
White
Klaus J
KJ
Thornberg
Lars
L
Quist
Jonas
J
Nielsen
Lasse H
LH
Andersen
Lars B
LB
Holst
Katrin
K
Thormar
Anne-Lene
AL
Kjældgaard
Maria L
ML
Fabritius
Frederik
F
Mondrup
Frank C
FC
Pott
Thea P
TP
Møller
Per
P
Winkel
Jørn
J
Wetterslev
D000368:Aged; D004311:Double-Blind Method; D005260:Female; D005440:Fluid Therapy / Q000009:adverse effects / Q000379:methods; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000009:adverse effects / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D007552:Isotonic Solutions / Q000009:adverse effects / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D017582:Renal Replacement Therapy; D018805:Sepsis / Q000150:complications / Q000401:mortality / Q000628:therapy*
D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; C028570:Ringer's acetate