Do-not-resuscitate orders in trauma patients may bias mortality-based effect estimates: an evaluation using the PROMMTT study

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. 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. 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. 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.