Does melatonin administration reduce the incidence of postoperative delirium in adults?: Systematic review and meta-analysis

Jonathan Barnes; Emma Sewart; Richard A Armstrong; Maria Pufulete; Robert Hinchliffe; Ben Gibbison; Ronelle Mouton

doi:10.1136/bmjopen-2022-069950

Does melatonin administration reduce the incidence of postoperative delirium in adults? Systematic review and meta-analysis

Jonathan Barnes^*, Emma Sewart, Richard A Armstrong, Maria Pufulete, Robert Hinchliffe, Ben Gibbison, Ronelle Mouton

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

4 Citations (Scopus)

Abstract

Postoperative delirium (POD) is common. It is associated with increased morbidity and mortality. Many cases may be preventable and melatonin offers promise as a preventative agent.

OBJECTIVE: This systematic review provides an up-to-date synthesis of the evidence on the effect of melatonin in preventing POD.

DESIGN: A systematic search of randomised controlled trials of melatonin in POD was run across multiple databases (EMBASE, MEDLINE, CINAHL, PsycINFO) and a clinical trials registry (ClinicalTrials.org) (1 January 1990 to 5 April 2022). Studies examining the effects of melatonin on POD incidence in adults are included. Risk of bias was assessed using the Cochrane risk of bias 2 tool.

OUTCOME MEASURES: The primary outcome is POD incidence. Secondary outcomes are POD duration and length of hospital stay. Data synthesis was undertaken using a random-effects meta-analysis and presented using forest plots. A summary of methodology and outcome measures in included studies is also presented.

RESULTS: Eleven studies, with 1244 patients from a range of surgical specialties were included. Seven studies used melatonin, in variable doses, and four used ramelteon. Eight different diagnostic tools were used to diagnose POD. Time points for assessment also varied. Six studies were assessed as low risk of bias and five as some concern. The combined OR of developing POD in the melatonin groups versus control was 0.41 (95% CI 0.21 to 0.80, p=0.01).

CONCLUSION: This review found that melatonin may reduce the incidence of POD in adults undergoing surgery. However, included studies displayed inconsistency in their methodology and outcome reporting. Further work to determine the optimum regime for melatonin administration, along with consensus of how best to evaluate results, would be beneficial.

PROSPERO REGISTRATION NUMBER: CRD42021285019.

Original language	English
Article number	e069950
Number of pages	8
Journal	BMJ Open
Volume	13
Issue number	3
DOIs	https://doi.org/10.1136/bmjopen-2022-069950
Publication status	Published - 29 Mar 2023

Bibliographical note

Funding Information:
This work was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. RAA and ES are NIHR Academic Clinical Fellows

Publisher Copyright:
© 2023 BMJ Publishing Group. All rights reserved.

Keywords

Humans
Adult
Melatonin/therapeutic use
Emergence Delirium
Incidence
Length of Stay

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Cite this

@article{8b891e62801b4264b8e0ad47aa5fc37f,

title = "Does melatonin administration reduce the incidence of postoperative delirium in adults?: Systematic review and meta-analysis",

abstract = "Postoperative delirium (POD) is common. It is associated with increased morbidity and mortality. Many cases may be preventable and melatonin offers promise as a preventative agent.OBJECTIVE: This systematic review provides an up-to-date synthesis of the evidence on the effect of melatonin in preventing POD.DESIGN: A systematic search of randomised controlled trials of melatonin in POD was run across multiple databases (EMBASE, MEDLINE, CINAHL, PsycINFO) and a clinical trials registry (ClinicalTrials.org) (1 January 1990 to 5 April 2022). Studies examining the effects of melatonin on POD incidence in adults are included. Risk of bias was assessed using the Cochrane risk of bias 2 tool.OUTCOME MEASURES: The primary outcome is POD incidence. Secondary outcomes are POD duration and length of hospital stay. Data synthesis was undertaken using a random-effects meta-analysis and presented using forest plots. A summary of methodology and outcome measures in included studies is also presented.RESULTS: Eleven studies, with 1244 patients from a range of surgical specialties were included. Seven studies used melatonin, in variable doses, and four used ramelteon. Eight different diagnostic tools were used to diagnose POD. Time points for assessment also varied. Six studies were assessed as low risk of bias and five as some concern. The combined OR of developing POD in the melatonin groups versus control was 0.41 (95% CI 0.21 to 0.80, p=0.01).CONCLUSION: This review found that melatonin may reduce the incidence of POD in adults undergoing surgery. However, included studies displayed inconsistency in their methodology and outcome reporting. Further work to determine the optimum regime for melatonin administration, along with consensus of how best to evaluate results, would be beneficial.PROSPERO REGISTRATION NUMBER: CRD42021285019.",

keywords = "Humans, Adult, Melatonin/therapeutic use, Emergence Delirium, Incidence, Length of Stay",

author = "Jonathan Barnes and Emma Sewart and Armstrong, {Richard A} and Maria Pufulete and Robert Hinchliffe and Ben Gibbison and Ronelle Mouton",

note = "Funding Information: This work was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. RAA and ES are NIHR Academic Clinical Fellows Publisher Copyright: {\textcopyright} 2023 BMJ Publishing Group. All rights reserved.",

year = "2023",

month = mar,

day = "29",

doi = "10.1136/bmjopen-2022-069950",

language = "English",

volume = "13",

journal = "BMJ Open",

issn = "2044-6055",

publisher = "BMJ Publishing Group",

number = "3",

}

TY - JOUR

T1 - Does melatonin administration reduce the incidence of postoperative delirium in adults?

T2 - Systematic review and meta-analysis

AU - Barnes, Jonathan

AU - Sewart, Emma

AU - Armstrong, Richard A

AU - Pufulete, Maria

AU - Hinchliffe, Robert

AU - Gibbison, Ben

AU - Mouton, Ronelle

N1 - Funding Information: This work was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. RAA and ES are NIHR Academic Clinical Fellows Publisher Copyright: © 2023 BMJ Publishing Group. All rights reserved.

PY - 2023/3/29

Y1 - 2023/3/29

N2 - Postoperative delirium (POD) is common. It is associated with increased morbidity and mortality. Many cases may be preventable and melatonin offers promise as a preventative agent.OBJECTIVE: This systematic review provides an up-to-date synthesis of the evidence on the effect of melatonin in preventing POD.DESIGN: A systematic search of randomised controlled trials of melatonin in POD was run across multiple databases (EMBASE, MEDLINE, CINAHL, PsycINFO) and a clinical trials registry (ClinicalTrials.org) (1 January 1990 to 5 April 2022). Studies examining the effects of melatonin on POD incidence in adults are included. Risk of bias was assessed using the Cochrane risk of bias 2 tool.OUTCOME MEASURES: The primary outcome is POD incidence. Secondary outcomes are POD duration and length of hospital stay. Data synthesis was undertaken using a random-effects meta-analysis and presented using forest plots. A summary of methodology and outcome measures in included studies is also presented.RESULTS: Eleven studies, with 1244 patients from a range of surgical specialties were included. Seven studies used melatonin, in variable doses, and four used ramelteon. Eight different diagnostic tools were used to diagnose POD. Time points for assessment also varied. Six studies were assessed as low risk of bias and five as some concern. The combined OR of developing POD in the melatonin groups versus control was 0.41 (95% CI 0.21 to 0.80, p=0.01).CONCLUSION: This review found that melatonin may reduce the incidence of POD in adults undergoing surgery. However, included studies displayed inconsistency in their methodology and outcome reporting. Further work to determine the optimum regime for melatonin administration, along with consensus of how best to evaluate results, would be beneficial.PROSPERO REGISTRATION NUMBER: CRD42021285019.

AB - Postoperative delirium (POD) is common. It is associated with increased morbidity and mortality. Many cases may be preventable and melatonin offers promise as a preventative agent.OBJECTIVE: This systematic review provides an up-to-date synthesis of the evidence on the effect of melatonin in preventing POD.DESIGN: A systematic search of randomised controlled trials of melatonin in POD was run across multiple databases (EMBASE, MEDLINE, CINAHL, PsycINFO) and a clinical trials registry (ClinicalTrials.org) (1 January 1990 to 5 April 2022). Studies examining the effects of melatonin on POD incidence in adults are included. Risk of bias was assessed using the Cochrane risk of bias 2 tool.OUTCOME MEASURES: The primary outcome is POD incidence. Secondary outcomes are POD duration and length of hospital stay. Data synthesis was undertaken using a random-effects meta-analysis and presented using forest plots. A summary of methodology and outcome measures in included studies is also presented.RESULTS: Eleven studies, with 1244 patients from a range of surgical specialties were included. Seven studies used melatonin, in variable doses, and four used ramelteon. Eight different diagnostic tools were used to diagnose POD. Time points for assessment also varied. Six studies were assessed as low risk of bias and five as some concern. The combined OR of developing POD in the melatonin groups versus control was 0.41 (95% CI 0.21 to 0.80, p=0.01).CONCLUSION: This review found that melatonin may reduce the incidence of POD in adults undergoing surgery. However, included studies displayed inconsistency in their methodology and outcome reporting. Further work to determine the optimum regime for melatonin administration, along with consensus of how best to evaluate results, would be beneficial.PROSPERO REGISTRATION NUMBER: CRD42021285019.

KW - Humans

KW - Adult

KW - Melatonin/therapeutic use

KW - Emergence Delirium

KW - Incidence

KW - Length of Stay

U2 - 10.1136/bmjopen-2022-069950

DO - 10.1136/bmjopen-2022-069950

M3 - Article (Academic Journal)

C2 - 36990485

SN - 2044-6055

VL - 13

JO - BMJ Open

JF - BMJ Open

IS - 3

M1 - e069950

ER -