Influence of alterations in forgoing life-sustaining treatment practices on a clinical sepsis trial

Objectives: To evaluate the timing of forgoing life-sustaining treatments in patients enrolled in a sepsis trial and to determine their influence on patient outcome and trial results. Design: Subset of patients in a prospective, randomized, double-blind, placebo-controlled study. Setting: Twenty-three academic medical centers. Patients. Enrolled patients who had life-sustaining therapies withheld or withdrawn. Measurements and Main Results: The number of patients, types of disorders and interventions, reasons, and timing of withholding and withdrawing life-sustaining treatments and their effect on mortality and trial results were assessed. Forgoing of life-sustaining therapies took place in 117 (22%) of 543 patients and occurred within 72 hrs of study drug administration in 38 (32%) patients. Withholding treatment (60%) was more common than withdrawing treatment (40%), but withdrawing treatment was more frequent (51%) than withholding treatment (20%) in the first 72 hrs of the trial (p < .01). Sixty-one (52%) patients had severe underlying disorders with a poor prognosis. The hospital mortality rate was 94% (of the 117 patients). The mean time (SEU) from withholding or withdrawing of treatment until death was 2.83 ± 0.57 and 0.32 ± 0.13 days, respectively (p < .001). Patients who had therapies forgone in the first 24, 48, and 72 hrs after receiving the study drug had higher mortality rates in the first 72 hrs (p < .01). Conclusions: A substantial number of patients enrolled in a sepsis trial had severe underlying diseases and had forgoing of therapies early in the course of the trial, which led to a higher early mortality rate. Enrollment of patients in clinical trials with severe underlying disorders with a high likelihood of having therapies forgone may bias the potential for showing the efficacy of new therapeutic modalities.