Incidence and impact of withdrawal of life-sustaining therapies in clinical trials of severe traumatic brain injury: A systematic review

Abstract

Background Most deaths following severe traumatic brain injury follow decisions to withdraw life-sustaining therapies. However, the incidence of the withdrawal of life-sustaining therapies and its potential impact on research data interpretation have been poorly characterized. The aim of this systematic review was to assess the reporting and the impact of withdrawal of life-sustaining therapies in randomized clinical trials of patients with severe traumatic brain injury. Methods We searched Medline, Embase, Cochrane Central, BIOSIS, and CINAHL databases and references of included trials. All randomized controlled trials published between January 2002 and August 2015 in the six highest impact journals in general medicine, critical care medicine, and neurocritical care (total of 18 journals) were considered for eligibility. Randomized controlled trials were included if they enrolled adult patients with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) and reported data on mortality. Our primary objective was to assess the proportion of trials reporting the withdrawal of life-sustaining therapies in a publication. Our secondary objectives were to describe the overall mortality rate, the proportion of deaths following the withdrawal of life-sustaining therapies, and to assess the impact of the withdrawal of life-sustaining therapies on trial results. Results From 5987 citations retrieved, we included 41 randomized trials (n = 16,364, ranging from 11 to 10,008 patients). Overall mortality was 23% (range = 3%-57%). Withdrawal of life-sustaining therapies was reported in 20% of trials (8/41, 932 patients in trials) and the crude number of deaths due to the withdrawal of life-sustaining therapies was reported in 17% of trials (7/41, 884 patients in trials). In these trials, 63% of deaths were associated with the withdrawal of life-sustaining therapies (105/168). An analysis carried out by imputing a 4% differential rate in instances of withdrawal of life-sustaining therapies between study groups yielded different results and conclusions in one third of the trials. Conclusion Data on the withdrawal of life-sustaining therapies are incompletely reported in randomized controlled trials of patients with severe traumatic brain injury. Given the high proportion of deaths due to the withdrawal of life-sustaining therapies in severe traumatic brain injury patients, and the potential of this medical decision to influence the results of clinical trials, instances of withdrawal of life-sustaining therapies should be systematically reported in clinical trials in this group of patients.

Peer Review #2 of "Early abolition of cough reflex predicts mortality in deeply sedated brain-injured patients (v0.1)"

“…Third, as the main cause of death was withdrawal of life-sustaining therapies, our study could have been exposed to the self-fulfilling prophecy bias. However, the proportion of WLST in our study was comparable to other reports (Leblanc et al, 2018). In addition, it is not a common clinical practice to base WLST solely on day 1 neurological examination.…”

Recovery from disorders of consciousness: mechanisms, prognosis and emerging therapies

“…Accurate prediction of poor outcome is important, as withdrawal of life-sustaining therapies is a leading cause of death for unconscious patients with acute brain injury 14 , 74 – 76 . Therefore, an inaccurate, overly pessimistic prediction could result in premature withdrawal of life-sustaining therapies, leading to death in patients who might have reached acceptable outcomes if given sufficient time to recover 12 , 13 . However, the process of determining poor outcome does not, by its converse, leave as its remainder those patients who will necessarily have a good outcome, or even recover consciousness.…”

Multicenter prospective study on predictors of short-term outcome in disorders of consciousness

“…(32 in VS/UWS, 45.0%; 20 in MCS, 28.2%) did not change their clinical diagnosis, and 11 patients in VS/UWS (15.5%) and 4 in MCS (5.6%) died. No patients died because of withdrawal of life-sustaining therapy27 ; death was due to severe medical complications (e.g., sepsis, acute respiratory distress, gastrointestinal bleeding, cardiac arrest) despite life-sustaining treatments. Among the 72 patients (50%) classified as improved, 20 in VS/UWS at baseline progressed to MCS…”