Dexmedetomidine for hyperactive delirium at the end of life: An open-label single arm pilot study with dose escalation in adult patients admitted to an inpatient palliative care unit

Abstract

Background:

Terminal delirium, specifically the hyperactive delirium subtype at the end of life, is common in palliative care patients. Standard care often involves sedation to alleviate distress. The alpha₂-adrenoreceptor agonist dexmedetomidine may have promise in terminal delirium, due to its properties of decreasing delirium and permitting rousable sedation.

Aim:

This study aimed to describe the effect of dexmedetomidine on delirium and sedation, when delivered via continuous subcutaneous infusion (CSCI) in patients with terminal delirium.

Design:

The trial was prospectively registered in the ANZCTR database (ACTRN12618000658213) and conducted in accordance with CONSORT (pilot study extension). Twenty-two adult patients were treated with a CSCI of dexmedetomidine with a two-tier dose schedule, low and high dose. Delirium severity was measured by the Memorial Delirium Assessment Scale (MDAS, target <13), and sedation by the Richmond Agitation-Sedation Scale, Palliative Version (RASS-PAL, target −1 to −3).

Results:

All patients had a response to dexmedetomidine as measured by decrease in MDAS after initiation; 59% required escalation to high dose to maintain control of delirium. All responses to high dose were sustained. RASS-PAL scores showed significant variability, however mean scores remained within target range on both doses, and the majority of patients were rousable. Fifty percent of patients treated crossed over to standard care; no patients who crossed over were experiencing moderate-severe delirium. Predominant reason for crossover was family request for deeper sedation.

Conclusion:

Dexmedetomidine shows potential for the management of terminal delirium with improved interactivity. Further research is needed to determine efficacy compared to current standard care.

Keywords

Delirium terminal care pilot projects conscious sedation hypnotics and sedatives dexmedetomidine

Get full access to this article

View all access options for this article.

References

Lawlor

Gagnon

Mancini

, et al. Occurrence, causes, and outcome of delirium in patients with advanced cancer. Arch Intern Med 2000; 160(6): 786–810.

Candy

Jackson

Jones

, et al. Drug therapy for delirium in terminally ill adult patients. Cochrane Database Syst Rev 2012; 11: CD004770.

Cherny

Radbruch

and The Board of the European Association for Palliative Care. European Association for Palliative Care (EAPC) recommended framework for the use of sedation in palliative care. Palliat Med 2009; 23(7): 581–593.

Dietz

Schmitz

Lampey

, et al. Evidence for the use of Levomepromazine for symptom control in the palliative care setting: a systematic review. BMC Palliat Care [Internet] 2013; 12(1): 2

Afonso

Reis

Dexmedetomidine: current role in anesthesia and intensive care. Braz J Anesthesiol 2012; 62(1): 118–133.

Jakob

Ruokonen

Grounds

, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 2012; 307(11): 1151–1160.

Cavallazzi

Saad

Marik

PE.

Delirium in the ICU: an overview. Ann Intensive Care 2012; 2(1): 49–51.

Carrasco

Baeza

Cabré

, et al. Dexmedetomidine for the treatment of hyperactive delirium refractory to haloperidol in nonintubated ICU patients: a nonrandomized controlled trial. Crit Care Med 2016; 44(7): 1295–1306.

Parker

King

Hughes

CG.

Dexmedetomidine for the treatment of hyperactive delirium refractory to haloperidol in non-intubated patients. J Thorac Dis 2016; 8(7): E596–E598.

10.

Tang

Xia

Dexmedetomidine in perioperative acute pain management: a non-opioid adjuvant analgesic. J Pain Res 2017; 10: 1899–1904.

11.

Prommer

Review article: dexmedetomidine: does it have potential in palliative medicine?

Am J Hosp Palliat Care 2011; 28(4): 276–283.

12.

Gertler

Brown

Mitchell

, et al. Dexmedetomidine: a novel sedative-analgesic agent. Proc (Bayl Univ Med Cent) 2001; 14(1): 13–21.

13.

Jin

Liang

Chen

, et al. Dexmedetomidine prevent postoperative nausea and vomiting on patients during general anesthesia: a PRISMA-compliant meta analysis of randomized controlled trials. Medicine (Baltimore) 2017; 96(1): e5770.

14.

Meng

Z-T

X-H

, et al. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet 2016; 388(10054): 1893–1902.

15.

Hilliard

Brown

Mitchinson

A case report of dexmedetomidine used to treat intractable pain and delirium in a tertiary palliative care unit. Palliat Med 2015; 29(3): 278–281.

16.

Soares

LGL

Naylor

Martins

, et al. Dexmedetomidine: a new option for intractable distress in the dying. J Pain Symptom Manage 2002; 24(1): 6–8.

17.

Hamatani

Nakai

Nakamura

, et al. Survey of palliative sedation at end of life in terminally ill heart failure patients– a single-center experience of 5-year follow-up. Circ J. 2019; 83(7): 1607–1611.

18.

Hofherr

Abrahm

Rickerson

Dexmedetomidine: a novel strategy for patients with intractable pain, opioid-induced hyperalgesia, or delirium at the end of life. J Palliat Med 2020; 23(11): 1515–1517.

19.

Uusalo

Al-Ramahi

Tilli

, et al. Subcutaneously administered dexmedetomidine is efficiently absorbed and is associated with attenuated cardiovascular effects in healthy volunteers. Eur J Clin Pharmacol 2018; 74(8): 1047–1054.

20.

Gabriel

Intravenous versus subcutaneous access for palliative care patients. Br J Nurs 2014; 23(2): S20–S22.

21.

Kamath

Wiesner

Malinchoc

, et al. A model to predict survival in patients with end-stage liver disease. Hepatology 2001; 33(2): 464–470.

22.

Association AP. Diagnostic and statistical manual of mental disorders (DSM-IV). 4th ed. Am Psychiatric Assoc; 1994.

23.

Breitbart

Rosenfeld

Roth

, et al. The memorial delirium assessment scale. J Pain Symptom Manage 1997; 13(3): 128–137.

24.

Leonard

Nekolaichuk

Meagher

, et al. Practical assessment of delirium in palliative care. J Pain Symptom Manage 2014; 48(2): 176–190.

25.

Bush

Grassau

Yarmo

MN.

The Richmond Agitation–Sedation Scale modified for palliative care inpatients (RASS-PAL): a pilot study exploring validity and feasibility in clinical practice. BMC Palliat Care 2014; 13(1): 17.

26.

Health USDO, Services H. Common terminology criteria for adverse events (CTCAE). 2017;(5). https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf (accessed 15 July 2020).

27.

Beller

van Driel

McGregor

, et al. Palliative pharmacological sedation for terminally ill adults. Cochrane Database Syst Rev 2015; 1(1): CD010206.

28.

Hui

Frisbee-Hume

Wilson

, et al. Effect of lorazepam with haloperidol vs haloperidol alone on agitated delirium in patients with advanced cancer receiving palliative care. JAMA 2017; 318(11): 1047–1056.

29.

Hayhurst

Pandharipande

Hughes

CG.

Intensive care unit delirium: a review of diagnosis, prevention, and treatment. Anesthesiology 2016; 125(6): 1229–1241.

30.

Barbato

Barclay

Potter

, et al. Correlation between observational scales of sedation and comfort and bispectral index scores. J Pain Symptom Manage 2017; 54(2): 186–193.

31.

Agar

Lawlor

Quinn

, et al. Efficacy of oral risperidone, haloperidol, or placebo for symptoms of delirium among patients in palliative care. JAMA Intern Med 2017; 177(1): 34.

32.

Lawlor

Nekolaichuk

Gagnon

, et al. Clinical utility, factor analysis, and further validation of the memorial delirium assessment scale in patients with advanced cancer. Cancer 2000; 88(12): 2859–2867.

33.

Mercadante

Intravaia

Villari

, et al. Controlled sedation for refractory symptoms in dying patients. J Pain Symptom Manage 2009; 37(5): 771–779.

34.

McIver

Walsh

Nelson

The use of chlorpromazine for symptom control in dying cancer patients. J Pain Symptom Manage 1994; 9(5): 341–345.

35.

Liang

Zhou

Feng

J-J

, et al. Efficacy of dexmedetomidine on postoperative nausea and vomiting: a meta-analysis of randomized controlled trials. Int J Clin Exp Med 2015; 8(8): 12113–12134.

36.

Abrahm

JL.

Patient and family requests for hastened death. Hematology Am Soc Hematol Educ Program 2008; 2008: 475–480.

37.

Heijltjes

van Thiel

Rietjens

, et al. Changing practices in the use of continuous sedation at the end of life. A systematic review of the literature. J Pain Symptom Manage 2020; 60(4): 828–846.

38.

Monforte-Royo

Villavicencio-Chávez

Tomás-Sábado

, et al. What lies behind the wish to hasten death? A systematic review and meta-ethnography from the perspective of patients. PLoS One Public Library Sci 2012; 7(5): 1–16.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.02 MB