Analgesia and Sedation at Terminal Extubation: A Secondary Analysis From Death One Hour After Terminal Extubation Study Data*

Abstract

To describe the doses of opioids and benzodiazepines administered around the time of terminal extubation (TE) to children who died within 1 hour of TE and to identify their association with the time to death (TTD).DESIGN: Secondary analysis of data collected for the Death One Hour After Terminal Extubation study. SETTING: Nine U.S. hospitals. PATIENTS:Six hundred eighty patients between 0 and 21 years who died within 1 hour after TE (2010TE ( -2021. MEASUREMENTS AND MAIN RESULTS:Medications included total doses of opioids and benzodiazepines 24 hours before and 1 hour after TE. Correlations between drug doses and TTD in minutes were calculated, and multivariable linear regression performed to determine their association with TTD after adjusting for age, sex, last recorded oxygen saturation/Fio 2 ratio and Glasgow Coma Scale score, inotrope requirement in the last 24 hours, and use of muscle relaxants within 1 hour of TE. Median age of the study population was 2.1 years (interquartile range [IQR], 0.4-11.0 yr). The median TTD was 15 minutes (IQR, 8-23 min). Forty percent patients (278/680) received either opioids or benzodiazepines within 1 hour after TE, with the largest proportion receiving opioids only (23%, 159/680). Among patients who received medications, the median IV morphine equivalent within 1 hour after TE was 0.75 mg/kg/hr (IQR, 0.3-1.8 mg/kg/hr) (n = 263), and median lorazepam equivalent was 0.22 mg/kg/hr (IQR, 0.11-0.44 mg/ kg/hr) (n = 118). The median morphine equivalent and lorazepam equivalent rates after TE were 7.5-fold and 22-fold greater than the median pre-extubation rates, respectively. No significant direct correlation was observed between either opioid or benzodiazepine doses before or after TE and TTD. After adjusting for confounding variables, regression analysis also failed to show any association between drug dose and TTD. CONCLUSIONS:Children after TE are often prescribed opioids and benzodiazepines. For patients dying within 1 hour of TE, TTD is not associated with the dose of medication administered as part of comfort care.

Ventilator Weaning and Terminal Extubation: Withdrawal of Life-Sustaining Therapy in Children. Secondary Analysis of the Death One Hour After Terminal Extubation Study

“…Studies have investigated dosing of palliative analgosedation and potential impact on time to death after WLST (22, 23). Here, we investigated if the method of WLST was associated with a difference in the dosage of analgesia or sedative medications provided around the end of life.…”

Time of Death and Medication Dosing: Are We Asking the Right Questions?*

“…Despite these limitations, the strength here lies in the numbers. The study by Tripathi et al (7) represents the largest cohort in pediatrics to date examining an association between TTD and withdrawal of LST. Findings are consistent with other studies where escalating doses of sedatives or analgesic to dying patients is not associated with timing to death (6, 9, 10).…”

“…In this issue of Pediatric Critical Care Medicine , the Death One Hour After Terminal Extubation (DONATE) study group present a retrospective, multi-institutional secondary analysis of a larger study and attempts to understand association of time to death (TTD) from terminal extubation (TE) with doses of medication including opioids and benzodiazepines used around the time of TE (7). The aim of the primary DONATE study was to validate a previously developed model (8) on the prediction of cardiac death within 1 hour of TE.…”

“…The rule of double effect, with its long history in medical ethics and its emphasis on clinician intent, has largely stood up in the face of criticism (11). Yet, perhaps, the revisiting of this question in the study by Tripathi et al (7) represents a shift in social norms unveiling of a new generation of clinicians raising questions on previously held beliefs.…”

“…The study by Tripathi et al (7), therefore, might be examined for the possibility of demonstrating under-dosing of appropriate medications at the end-of-life after withdrawal of LST or at the very least ask the question of why so few patients required any analgesic or sedative medication. The authors do report, after all, that 60% of this cohort did not receive any medications following the withdrawal of a ventilator.…”