Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis

Anders Perner; Nicolai Haase; Anne B Guttormsen; Jyrki Tenhunen; Gudmundur Klemenzson; Anders Åneman; Kristian R Madsen; Morten H Møller; Jeanie M Elkjær; Lone M Poulsen; Asger Bendtsen; Robert Winding; Morten Steensen; Pawel Berezowicz; Peter Søe-Jensen; Morten Bestle; Kristian Strand; Jørgen Wiis; Jonathan O White; Klaus J Thornberg; Lars Quist; Jonas Nielsen; Lasse H Andersen; Lars B Holst; Katrin Thormar; Anne-Lene Kjældgaard; Maria L Fabritius; Frederik Mondrup; Frank C Pott; Thea P Møller; Per Winkel; Jørn Wetterslev; 6S Trial Group

doi:10.1056/nejmoa1204242

Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis

Anders Perner, Nicolai Haase, Anne B Guttormsen, Jyrki Tenhunen, Gudmundur Klemenzson, Anders Åneman, Kristian R Madsen, Morten H Møller, Jeanie M Elkjær, Lone M Poulsen, Asger Bendtsen, Robert Winding, Morten Steensen, Pawel Berezowicz, Peter Søe-Jensen, Morten Bestle, Kristian Strand, Jørgen Wiis, Jonathan O White, Klaus J ThornbergLars Quist, Jonas Nielsen, Lasse H Andersen, Lars B Holst, Katrin Thormar, Anne-Lene Kjældgaard, Maria L Fabritius, Frederik Mondrup, Frank C Pott, Thea P Møller, Per Winkel, Jørn Wetterslev, 6S Trial Group

1231 Citations (Scopus)

Abstract

BACKGROUND: Hydroxyethyl starch (HES) 130/0.42 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.)

Original language	English
Journal	New England Journal of Medicine
Volume	367
Issue number	2
Pages (from-to)	124-34
Number of pages	11
ISSN	0028-4793
DOIs	https://doi.org/10.1056/nejmoa1204242
Publication status	Published - 12 Jul 2012

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Perner, A., Haase, N., Guttormsen, A. B., Tenhunen, J., Klemenzson, G., Åneman, A., Madsen, K. R., Møller, M. H., Elkjær, J. M., Poulsen, L. M., Bendtsen, A., Winding, R., Steensen, M., Berezowicz, P., Søe-Jensen, P., Bestle, M., Strand, K., Wiis, J., White, J. O., ... 6S Trial Group (2012). Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. New England Journal of Medicine, 367(2), 124-34. https://doi.org/10.1056/nejmoa1204242

Perner, A, Haase, N, Guttormsen, AB, Tenhunen, J, Klemenzson, G, Åneman, A, Madsen, KR, Møller, MH, Elkjær, JM, Poulsen, LM, Bendtsen, A, Winding, R, Steensen, M, Berezowicz, P, Søe-Jensen, P, Bestle, M, Strand, K, Wiis, J, White, JO, Thornberg, KJ, Quist, L, Nielsen, J, Andersen, LH, Holst, LB, Thormar, K, Kjældgaard, A-L, Fabritius, ML, Mondrup, F, Pott, FC, Møller, TP, Winkel, P, Wetterslev, J & 6S Trial Group 2012, 'Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis', New England Journal of Medicine, vol. 367, no. 2, pp. 124-34. https://doi.org/10.1056/nejmoa1204242

@article{a78d029dceaf45c2999e9b996a9d71fa,

title = "Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis",

abstract = "BACKGROUND: Hydroxyethyl starch (HES) 130/0.42 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.)",

author = "Anders Perner and Nicolai Haase and Guttormsen, {Anne B} and Jyrki Tenhunen and Gudmundur Klemenzson and Anders {\AA}neman and Madsen, {Kristian R} and M{\o}ller, {Morten H} and Elkj{\ae}r, {Jeanie M} and Poulsen, {Lone M} and Asger Bendtsen and Robert Winding and Morten Steensen and Pawel Berezowicz and Peter S{\o}e-Jensen and Morten Bestle and Kristian Strand and J{\o}rgen Wiis and White, {Jonathan O} and Thornberg, {Klaus J} and Lars Quist and Jonas Nielsen and Andersen, {Lasse H} and Holst, {Lars B} and Katrin Thormar and Anne-Lene Kj{\ae}ldgaard and Fabritius, {Maria L} and Frederik Mondrup and Pott, {Frank C} and M{\o}ller, {Thea P} and Per Winkel and J{\o}rn Wetterslev and Pott, {Frank Christian}",

year = "2012",

month = jul,

day = "12",

doi = "10.1056/nejmoa1204242",

language = "English",

volume = "367",

pages = "124--34",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "2",

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TY - JOUR

T1 - Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis

AU - Perner, Anders

AU - Haase, Nicolai

AU - Guttormsen, Anne B

AU - Tenhunen, Jyrki

AU - Klemenzson, Gudmundur

AU - Åneman, Anders

AU - Madsen, Kristian R

AU - Møller, Morten H

AU - Elkjær, Jeanie M

AU - Poulsen, Lone M

AU - Bendtsen, Asger

AU - Winding, Robert

AU - Steensen, Morten

AU - Berezowicz, Pawel

AU - Søe-Jensen, Peter

AU - Bestle, Morten

AU - Strand, Kristian

AU - Wiis, Jørgen

AU - White, Jonathan O

AU - Thornberg, Klaus J

AU - Quist, Lars

AU - Nielsen, Jonas

AU - Andersen, Lasse H

AU - Holst, Lars B

AU - Thormar, Katrin

AU - Kjældgaard, Anne-Lene

AU - Fabritius, Maria L

AU - Mondrup, Frederik

AU - Pott, Frank C

AU - Møller, Thea P

AU - Winkel, Per

AU - Wetterslev, Jørn

AU - 6S Trial Group

PY - 2012/7/12

Y1 - 2012/7/12

N2 - BACKGROUND: Hydroxyethyl starch (HES) 130/0.42 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.)

AB - BACKGROUND: Hydroxyethyl starch (HES) 130/0.42 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.)

U2 - 10.1056/nejmoa1204242

DO - 10.1056/nejmoa1204242

M3 - Journal article

C2 - 22738085

SN - 0028-4793

VL - 367

SP - 124

EP - 134

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 2

ER -

Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis

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