TY - JOUR
T1 - Neuroleptic strategies for terminal agitation in patients with cancer and delirium at an acute palliative care unit
T2 - a single-centre, double-blind, parallel-group, randomised trial
AU - Hui, David
AU - De La Rosa, Allison
AU - Wilson, Annie
AU - Nguyen, Thuc
AU - Wu, Jimin
AU - Delgado-Guay, Marvin
AU - Azhar, Ahsan
AU - Arthur, Joseph
AU - Epner, Daniel
AU - Haider, Ali
AU - De La Cruz, Maxine
AU - Heung, Yvonne
AU - Tanco, Kimberson
AU - Dalal, Shalini
AU - Reddy, Akhila
AU - Williams, Janet
AU - Amin, Sapna
AU - Armstrong, Terri S.
AU - Breitbart, William
AU - Bruera, Eduardo
N1 - Funding Information:
Full funding for this study was provided by the National Institute of Nursing Research. DH was supported in part by grants from the National Cancer Institute ( R01CA214960 ; R01CA225701 ; R01CA231471 ) and Helsinn. JWu was supported in part by the National Institutes of Health Cancer Centre Support Grant ( P30CA016672 ). MD-G was supported in part by a National Cancer Institute grant ( R01CA200867 ). WB was supported in part by grants from the National Institutes of Health ( R25CA190169 ; R01CA190636 ; R25CA190169 ). EB was supported in part by grants from the National Cancer Institute ( R01CA214960 ; R01CA225701 ; R01CA231471 ). TA is employed as a senior investigator at the National Cancer Institute. We thank all the patients, caregivers, and clinicians who participated in this study. We are grateful to Kenneth Hess, a biostatistician who was instrumental to the study design and died before completion of this study.
Funding Information:
This study was funded by the National Institute of Nursing Research (R21NR016736). The funder of this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all of the data and the final responsibility for the decision to submit for publication.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/7
Y1 - 2020/7
N2 - Background: The role of neuroleptics for terminal agitated delirium is controversial. We assessed the effect of three neuroleptic strategies on refractory agitation in patients with cancer with terminal delirium. Methods: In this single-centre, double-blind, parallel-group, randomised trial, patients with advanced cancer, aged at least 18 years, admitted to the palliative and supportive care unit at the University of Texas MD Anderson Cancer Center (Houston, TX, USA), with refractory agitation, despite low-dose haloperidol, were randomly assigned to receive intravenous haloperidol dose escalation at 2 mg every 4 h, neuroleptic rotation with chlorpromazine at 25 mg every 4 h, or combined haloperidol at 1 mg and chlorpromazine at 12·5 mg every 4 h, until death or discharge. Rescue doses identical to the scheduled doses were administered at inception, and then hourly as needed. Permuted block randomisation (block size six; 1:1:1) was done, stratified by baseline Richmond Agitation Sedation Scale (RASS) scores. Research staff, clinicians, patients, and caregivers were masked to group assignment. The primary outcome was change in RASS score from time 0 to 24 h. Comparisons among group were done by modified intention-to-treat analysis. This completed study is registered with ClinicalTrials.gov, NCT03021486. Findings: Between July 5, 2017, and July 1, 2019, 998 patients were screened for eligibility, with 68 being enrolled and randomly assigned to treatment; 45 received the masked study interventions (escalation n=15, rotation n=16, combination n=14). RASS score decreased significantly within 30 min and remained low at 24 h in the escalation group (n=10, mean RASS score change between 0 h and 24 h −3·6 [95% CI −5·0 to −2·2]), rotation group (n=11, −3·3 [–4·4 to −2·2]), and combination group (n=10, −3·0 [–4·6 to −1·4]), with no difference among groups (p=0·71). The most common serious toxicity was hypotension (escalation n=6 [40%], rotation n=5 [31%], combination n=3 [21%]); there were no treatment-related deaths. Interpretation: Our data provide preliminary evidence that the three strategies of neuroleptics might reduce agitation in patients with terminal agitation. These findings are in the context of the single-centre design, small sample size, and lack of a placebo-only group. Funding: National Institute of Nursing Research.
AB - Background: The role of neuroleptics for terminal agitated delirium is controversial. We assessed the effect of three neuroleptic strategies on refractory agitation in patients with cancer with terminal delirium. Methods: In this single-centre, double-blind, parallel-group, randomised trial, patients with advanced cancer, aged at least 18 years, admitted to the palliative and supportive care unit at the University of Texas MD Anderson Cancer Center (Houston, TX, USA), with refractory agitation, despite low-dose haloperidol, were randomly assigned to receive intravenous haloperidol dose escalation at 2 mg every 4 h, neuroleptic rotation with chlorpromazine at 25 mg every 4 h, or combined haloperidol at 1 mg and chlorpromazine at 12·5 mg every 4 h, until death or discharge. Rescue doses identical to the scheduled doses were administered at inception, and then hourly as needed. Permuted block randomisation (block size six; 1:1:1) was done, stratified by baseline Richmond Agitation Sedation Scale (RASS) scores. Research staff, clinicians, patients, and caregivers were masked to group assignment. The primary outcome was change in RASS score from time 0 to 24 h. Comparisons among group were done by modified intention-to-treat analysis. This completed study is registered with ClinicalTrials.gov, NCT03021486. Findings: Between July 5, 2017, and July 1, 2019, 998 patients were screened for eligibility, with 68 being enrolled and randomly assigned to treatment; 45 received the masked study interventions (escalation n=15, rotation n=16, combination n=14). RASS score decreased significantly within 30 min and remained low at 24 h in the escalation group (n=10, mean RASS score change between 0 h and 24 h −3·6 [95% CI −5·0 to −2·2]), rotation group (n=11, −3·3 [–4·4 to −2·2]), and combination group (n=10, −3·0 [–4·6 to −1·4]), with no difference among groups (p=0·71). The most common serious toxicity was hypotension (escalation n=6 [40%], rotation n=5 [31%], combination n=3 [21%]); there were no treatment-related deaths. Interpretation: Our data provide preliminary evidence that the three strategies of neuroleptics might reduce agitation in patients with terminal agitation. These findings are in the context of the single-centre design, small sample size, and lack of a placebo-only group. Funding: National Institute of Nursing Research.
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U2 - 10.1016/S1470-2045(20)30307-7
DO - 10.1016/S1470-2045(20)30307-7
M3 - Article
C2 - 32479786
AN - SCOPUS:85086408483
SN - 1470-2045
VL - 21
SP - 989
EP - 998
JO - The lancet oncology
JF - The lancet oncology
IS - 7
ER -