title: Effects of hydroxyethyl starch in subgroups of patients with severe sepsis: exploratory post-hoc analyses of a randomised trial.
abstract: OBJECTIVE
  It has been speculated that certain subgroups of sepsis patients may benefit from treatment with hydroxyethyl starch (HES) 130/0.42, specifically in the earlier resuscitation of patients with more severely impaired circulation.
  
  
  METHODS
  This was a post-hoc, subgroup analysis of all 798 patients with severe sepsis randomised in the 6S trial according to time from ICU admission to randomisation, surgery and fluids given prior to randomisation and markers of shock at randomisation. Intervention effects estimated as risk ratios were analysed between the HES versus Ringer's acetate groups to detect subgroup heterogeneity of the effects on 90-day mortality. Multiple logistic regression was used to adjust for risk factors.
  
  
  RESULTS
  Most baseline characteristics were comparable between the HES and Ringer's acetate groups in the different subgroups. There was no heterogeneity in the intervention effect on 90-day mortality in the following subgroups: randomisation earlier than 4 h after ICU admission versus later (test of interaction P = 0.85), surgery versus no surgery (P = 0.42), colloids given versus not given (P = 0.57), <2 l of crystalloids given prior to randomisation vs. >2 l (P = 0.88) or plasma lactate >4 mmol/l versus <4 mmol/l (P = 0.54), hypotension versus no hypotension (P = 0.32) or use of vasopressor or inotropic agents at randomisation versus no use (P = 0.10).
  
  
  CONCLUSIONS
  The increased 90-day mortality observed in patients with severe sepsis resuscitated with HES 130/0.42 did not appear to depend on time course, surgery or fluids given prior to randomisation or on markers of shock at randomisation. As the analyses were planned post hoc and their power is reduced, the results should be interpreted with caution.
authors.affiliation: Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, 2100, Copenhagen, Denmark.
authors.forename: Rasmus G
authors.initials: RG
authors.lastname: Müller
authors.forename: Nicolai
authors.initials: N
authors.lastname: Haase
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
authors.forename: Anders
authors.initials: A
authors.lastname: Perner
mesh_terms: D000368:Aged; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use*; D007362:Intensive Care Units; D007552:Isotonic Solutions / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012151:Resuscitation; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; C028570:Ringer's acetate
references.citation: N Engl J Med. 2001 Nov 8;345(19):1368-77
references.pmid: 11794169
references.citation: Intensive Care Med. 2012 Mar;38(3):345-58
references.pmid: 22270471
references.citation: Trials. 2011 Jan 27;12:24
references.pmid: 21269526
references.citation: Intensive Care Med. 2013 Mar;39(3):345-64
references.pmid: 23291735
references.citation: Acta Anaesthesiol Scand. 2013 Jul;57(6):809
references.pmid: 23593998
references.citation: Crit Care. 2013 Jul 26;17(4):R166
references.pmid: 23890518
references.citation: Intensive Care Med. 2013 Apr;39(4):558-68
references.pmid: 23407978
references.citation: Intensive Care Med. 2013 May;39(5):811-22
references.pmid: 23430019
references.citation: Crit Care. 2012 May 24;16(3):R94
references.pmid: 22624531
references.citation: JAMA. 1993 Dec 22-29;270(24):2957-63
references.pmid: 8254858
references.citation: Curr Opin Anaesthesiol. 2013 Jun;26(3):253-60
references.pmid: 23492982
references.citation: Anesth Analg. 2013 Jan;116(1):35-48
references.pmid: 23115254
references.citation: N Engl J Med. 2012 Sep 27;367(13):1266-7; author reply 1267
references.pmid: 23013091
references.citation: N Engl J Med. 2012 Sep 27;367(13):1265-6; author reply 1267
references.pmid: 23013089
references.citation: Swiss Med Wkly. 2013 Jan 21;143:w13747
references.pmid: 23348833
references.citation: Anesth Analg. 2011 Mar;112(3):635-45
references.pmid: 21304149
references.citation: Intensive Care Med. 2011 Jan;37(1):86-96
references.pmid: 20924555
references.citation: BMJ. 2013 Feb 15;346:f839
references.pmid: 23418281
references.citation: N Engl J Med. 2012 Sep 27;367(13):1265; author reply 1267
references.pmid: 23013088
references.citation: Intensive Care Med. 2013 Feb;39(2):165-228
references.pmid: 23361625
references.citation: Crit Care Med. 1998 Nov;26(11):1793-800
references.pmid: 9824069
references.citation: Cochrane Database Syst Rev. 2013 Feb 28;(2):CD000567
references.pmid: 23450531
references.citation: Intensive Care Med. 2008 Jan;34(1):17-60
references.pmid: 18058085
references.citation: N Engl J Med. 2012 Nov 15;367(20):1901-11
references.pmid: 23075127
references.citation: Crit Care. 2012 Feb 29;16(1):R34
references.pmid: 22377234
references.citation: Crit Care. 2010;14(5):R185
references.pmid: 20950434
references.citation: Acta Anaesthesiol Scand. 2013 Jul;57(6):729-36
references.pmid: 23550716
references.citation: N Engl J Med. 2012 Jul 12;367(2):124-34
references.pmid: 22738085
references.citation: JAMA. 2013 Feb 20;309(7):678-88
references.pmid: 23423413
references.citation: N Engl J Med. 2012 Sep 27;367(13):1266; author reply 1267
references.pmid: 23013090