Influence of alterations in foregoing life-sustaining treatment practices on a clinical sepsis trial. The HA-1A Sepsis Study Group.
OBJECTIVE
To evaluate the timing of foregoing life-sustaining treatments in patients enrolled in a sepsis trial and to determine their influence on patient outcome and trial results.


METHODS
Subset of patients in a prospective, randomized, double-blind, placebo-controlled study.


METHODS
Twenty-three academic medical centers.


METHODS
Enrolled patients who had life-sustaining therapies withheld or withdrawn.


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. Foregoing 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 (SEM) 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 foregone 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 foregoing 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 foregone may bias the potential for showing the efficacy of new therapeutic modalities.
Sprung
C L
CL
Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Hebrew University of Jerusalem, Israel.
Eidelman
L A
LA
Pizov
R
R
Fisher
C J
CJ
Ziegler
E J
EJ
Sadoff
J C
JC
Straube
R C
RC
McCloskey
R V
RV
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015982:Bias; D003657:Decision Making; D004311:Double-Blind Method; D005066:Euthanasia, Passive; D017052:Hospital Mortality; D006801:Humans; D008020:Life Support Care; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011379:Prognosis; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D018805:Sepsis / Q000401:mortality / Q000628:therapy*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C068069:nebacumab