title: Do-not-resuscitate orders in trauma patients may bias mortality-based effect estimates: an evaluation using the PROMMTT study.
abstract: BACKGROUND
  The impact of do-not-resuscitate (DNR) orders has not been systematically evaluated in acute trauma research. We determined the frequency, timing, and impact on mortality-based effect estimates for patients with DNR orders in the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study.
  
  
  METHODS
  Trauma patients surviving at least 30 minutes and transfused one or greater unit of red blood cell within 6 hours of admission (n = 1,245) from 10 Level 1 centers were enrolled. We report descriptive statistics and results from survival analysis to compare the association of blood product transfusion ratios with outcome defined as mortality and as a composite, DNR, and death.
  
  
  RESULTS
  DNRs were reported for 95 patients (7.6%), with 94 in-hospital deaths. There were 172 deaths without DNRs. Of 90 known DNR order times, the median was 53 hours (interquartile range, 9-186 hours) after admission; the median DNR-to-death time was 10 hours (2-32 hours). DNRs were for comfort measures only (43%), no cardiopulmonary resuscitation (40%), and no intubation or cardiopulmonary resuscitation (16%). Compared with the 116 non-DNR deaths that occurred after the earliest DNR order (2 hours), the DNR decedents were significantly older with a less severe base deficit, fewer red blood cell and plasma transfusions, and a later median time of death (98 [21-230] hours vs. 17 [4-91] hours). In multivariable Cox models that accounted for time-varying blood product ratios, the associations were consistent, regardless of whether outcome was defined as mortality or the composite.
  
  
  CONCLUSIONS
  DNR orders were instituted after the 24-hour period of highest mortality risk and more often in older patients not in severe shock. Findings from the primary PROMMTT analyses of the impact of blood product ratios on survival did not materially change when the original mortality outcome was redefined as a composite of DNR or death. DNR orders are potentially an important mediating variable that should be systematically evaluated in trauma research.
authors.affiliation: Center for Translational Injury Research, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA. Charles.E.Wade@uth.tmc.edu
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wade
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: del Junco
authors.forename: Erin E
authors.initials: EE
authors.lastname: Fox
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Cotton
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Cohen
authors.forename: Peter
authors.initials: P
authors.lastname: Muskat
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schreiber
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Rahbar
authors.forename: R Michelle
authors.initials: RM
authors.lastname: Sauer
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Brasel
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Bulger
authors.forename: John G
authors.initials: JG
authors.lastname: Myers
authors.forename: Herb A
authors.initials: HA
authors.lastname: Phelan
authors.forename: Louis H
authors.initials: LH
authors.lastname: Alarcon
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
mesh_terms: D000328:Adult; D015982:Bias; D001803:Blood Transfusion / Q000379:methods*; D016009:Chi-Square Distribution; D005260:Female; D006470:Hemorrhage / Q000401:mortality / Q000628:therapy*; D017052:Hospital Mortality; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012151:Resuscitation / Q000379:methods; D016414:Resuscitation Orders; D018709:Statistics, Nonparametric; D015996:Survival Rate; D013997:Time Factors; D014193:Trauma Centers; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014947:Wounds and Injuries / Q000401:mortality / Q000628:therapy*