Haldol - Hospice Matters
Its frequent use in delirium occurs despite little evidence of the effect of antipsychotics on the untreated course of delirium. A consecutive cohort of participants from 14 centers across four countries who had haloperidol commenced for delirium were recruited.
Data were collected at three time points: Investigators were also able to report clinical harms at any time up to 14 days after it was commenced. Of the participants included, the average dose was 2. Seven participants had their medication ceased due to harms 2 for somnolence and 2 for rigidity. Overall, 1 in 3 participants gained net clinical benefit at 10 days.
D elirium is a common and distressing symptom for many patients and families as the end of life approaches 1 , 2 and if no reversible factors are present, is an indicator of poor prognosis. Haloperidol is a butyrophenone derivative and dopamine antagonist. Although open label studies or randomized trials comparing two antipsychotics have shown improvement of delirium scores over time, 2 this may relate to the natural history of delirium, which is to resolve over time as precipitants are treated and reversed.
The three studies 6 — 8 with placebo arms have methodological problems inadequately powered, inadequate allocation concealment. Current international guidelines suggest targeted use of antipsychotics for severe behavioral disturbance in delirium with cautious dosing and close monitoring. This method of rapid reporting allows immediate and short-term net clinical effects benefits and harms to be systematically studied during routine care.
By aggregating data from a large number of centers each of whom have provided data from a small number of consecutive participants who were commenced on haloperidol for delirium as part of routine clinical care, the evidence base of the real-world net effectiveness of this medication can be established.
This process minimizes the work involved for individual clinicians, and represents a wide range of clinical settings and service delivery models. The aim of this study was to describe the net clinical effect i. All participating sites received ethical waivers as the work falls under quality assurance, quality improvement, performance monitoring, clinical audit study type or approval for low risk research depending on each site's Human Research Ethic Committee's assessment of this work.
The study methods have been described in detail previously. Participants were consecutive patients at participating clinical sites started on haloperidol as part of routine clinical care for delirium. Data were recorded at three set time points: The NCI criteria for delirium ask the clinician to rate overall severity of the symptoms but also impact on activities of daily living and other impacts such as threats of harm to self or others; Table 2.
This approach was chosen as the intention was to quantify the degree of impact from a symptom perspective and to align the assessment approaches of benefits and harms. A further 42 were dead by day 10 and a further 10 people by day Harms were attributed to haloperidol if the criteria for NCI CTCAE were greater than a baseline measurement at or before day 10 for that individual participant.
This is a questionnaire designed to determine the attribution of an adverse drug reaction being due to the drug itself rather than other factors.
Univariable logistic regression model for each outcome on key clinical and demographic parameters was undertaken, clustering over site to account for correlated readings. Additionally, logistic regression was performed for each outcome on each pair of key parameters and their product term to identify possible subgroups that were associated with outcomes.
We used multiple imputation to account for missing data, with 20 resamples drawn. No adjustment was made for multiple comparisons as the results are considered to be hypothesis generating. A p value less than 0. The clinical and demographic data of the study subjects are shown in Table 1.
The majority of participants had cancer. Participants received an average of 2. At 48 hours, 10 people had died and overall benefit was reported in 42 of participants Table 3 , Figs. At the end of the study, a total of 52 people had died and 55 of 67 were still on regular haloperidol.
A total of 14 of 57 participants Seven participants had their medication ceased for harms of whom two had somnolence and two had rigidity. In the logistic regression analyses, the Karnofsky score moderated the relationship between Charlson Comorbidity Index CCI and benefit from haloperidol.
The higher the Karnofsky score the stronger the association between worsening comorbidity higher CCI and poorer response. All other univariable and interaction analyses did not contain terms that were significant.
Approximately 1 in 3 participants experienced benefit at 48 hours. Approximately 1 in 15 participants stopped haloperidol due to harms, 4 of which were graded 4.
The participants were mostly elderly mean age, 73 years and of poor physical functional status mean AKPS They had multiple comorbidities CCI mean 5. Despite this clinical setting, haloperidol was relatively well tolerated in the immediate and short term. Of those with a documented harm, few were treated by a reduction in the dose or cessation of the medication. However the findings of this study are consistent with systematic reviews. An important change to the first of these pharmacovigilance studies 12 was that harm was measured at baseline in addition to T 1 and T 2 and only worsening over baseline is reported.
This study addresses only immediate and short-term harms. Harms of prolonged haloperidol administration such as some of the extrapyramidal effects will not be detected. Consistency of interpretation and measurement is a challenge for multicenter studies. This study also relies on clinicians recognizing delirium and utilizing a rating scale that only quantifies symptoms and some clinical impacts; rather than a detailed delirium scale with established psychometric properties.
NCI CTCAE is conceived as a high-level screening tool for a wide range of symptoms and data are not available on its correlation with diagnostic tools for delirium. A project officer provided continuing e-mail updates and an information stream about the study to provide a central point of liaison for participating sites Australia, New Zealand, Canada, and the United Kingdom.
This study demonstrates that when haloperidol is used for delirium, where the mean dose was 2. Thanks go to all the clinicians and the clinical units who have contributed to this program, Mr. Zac Vandersman and Ms. National Center for Biotechnology Information , U. Journal of Palliative Medicine. Find articles by Gregory B. Find articles by Meera Agar M. Find articles by Stephen J. Find articles by Jane Phillips. Find articles by Caroline Litster.
Find articles by Natasha Michael. Find articles by Matthew Doogue. Debra Rowett 9 Repatriation General Hospital. Daw Park, Adelaide, Australia.
Find articles by Debra Rowett. Find articles by David C. Accepted Jun Copyright , Mary Ann Liebert, Inc. This article has been cited by other articles in PMC. Method A consecutive cohort of participants from 14 centers across four countries who had haloperidol commenced for delirium were recruited. Results Of the participants included, the average dose was 2.
Conclusion Overall, 1 in 3 participants gained net clinical benefit at 10 days. Introduction D elirium is a common and distressing symptom for many patients and families as the end of life approaches 1 , 2 and if no reversible factors are present, is an indicator of poor prognosis. Methods The aim of this study was to describe the net clinical effect i.
Baseline Clinical and Demographic Data. Open in a separate window. Hospitalization indicated; 4, Life-threatening consequences; threats of self harm or harm to others; hospitalization indicated; 5, Death.
Statistical methods Univariable logistic regression model for each outcome on key clinical and demographic parameters was undertaken, clustering over site to account for correlated readings. Results The clinical and demographic data of the study subjects are shown in Table 1. Response at 48 hours to haloperidol for delirium in a palliatve care population. Net Clinical Effects Individual Patients.
Discussion Approximately 1 in 3 participants experienced benefit at 48 hours. Limitations This study addresses only immediate and short-term harms. Acknowledgments Thanks go to all the clinicians and the clinical units who have contributed to this program, Mr.
Author Disclosure Statement No competing financial interests exist. Delirium issues in palliative care settings. Evidence-based treatment of delirium in patients with cancer.
Efficacy of haloperidol in the treatment of nausea and vomiting in the palliative patient: J Pain Symptom Manage. A perspective on the management of delirium in terminally ill patients on a palliative care unit. Haloperidol in palliative care. A prospective random control study comparison of olanzapine and haloperidol in senile delirium. Phillips B, et al.
A randomized controlled trial of quetiapine versus placebo in the treatment of delirium.