The Healthy Heart-Mind Trial: Randomized Controlled Trial of Melatonin for Prevention of Delirium

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Abstract

OBJECTIVES: Delirium is a serious medical condition with increased incidence in at-risk surgical populations. We sought to determine if melatonin use reduces the incidence of delirium in individuals undergoing major cardiac surgery. DESIGN: Randomized double-blind placebo-controlled clinical trial (two arms, 1:1 allocation, parallel design). SETTING: The trial took place in two metropolitan hospitals (public tertiary and private) in Perth, Western Australia. PARTICIPANTS: We recruited 210 adults aged 50 years or older who were due to undergo coronary artery bypass grafting or valve replacement surgery. INTERVENTION: Participants were randomly assigned (1:1) to 7 days of treatment with melatonin 3 mg at night or matching placebo, starting 2 days before the surgery. MEASUREMENTS: The primary outcome of interest was incident delirium within 7 days of surgery as assessed via daily clinical assessment that included the Confusion Assessment Method. Secondary outcomes of interest included duration and severity of delirium, length of hospital stay, cognitive function, and mood and anxiety symptoms at discharge and 3 months after the surgery. RESULTS: The groups were well balanced for demographic and clinical parameters. Forty-two participants developed delirium, but it was evenly distributed between the groups (melatonin 21/98, 21.4%; placebo 21/104, 20.2%; adjusted odds ratio [OR] =.78; 95% confidence interval [CI] =.35-1.75). The median duration of delirium was 3 (interquartile range [IQR] = 2-4) and 2 (IQR = 1-3) days for people treated with melatonin and placebo, respectively (z = −1.03; P =.304). A similar proportion of participants experienced severe episodes of delirium in each group (melatonin 9/21, 42.9% vs placebo 6/21, 28.6%; χ2 =.93; P =.334; adjusted OR = 1.98; 95% CI =.40-9.78). The groups did not differ in terms of length of stay, mood, anxiety, and cognitive performance. CONCLUSION: The findings of this randomized double-blind placebo-controlled trial do not support the prophylactic use of melatonin to prevent delirium after major cardiac surgery.

Original languageEnglish
JournalJournal of the American Geriatrics Society
DOIs
Publication statusE-pub ahead of print - 8 Oct 2019

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Delirium
Melatonin
Randomized Controlled Trials
Placebos
Length of Stay
Ambulatory Surgical Procedures
Thoracic Surgery
Anxiety
Odds Ratio
Confidence Intervals
Confusion
Western Australia
Urban Hospitals
Incidence
Controlled Clinical Trials
Coronary Artery Bypass
Cognition
Demography

Cite this

@article{45f0d63104f9408097d6df72e4a68656,
title = "The Healthy Heart-Mind Trial: Randomized Controlled Trial of Melatonin for Prevention of Delirium",
abstract = "OBJECTIVES: Delirium is a serious medical condition with increased incidence in at-risk surgical populations. We sought to determine if melatonin use reduces the incidence of delirium in individuals undergoing major cardiac surgery. DESIGN: Randomized double-blind placebo-controlled clinical trial (two arms, 1:1 allocation, parallel design). SETTING: The trial took place in two metropolitan hospitals (public tertiary and private) in Perth, Western Australia. PARTICIPANTS: We recruited 210 adults aged 50 years or older who were due to undergo coronary artery bypass grafting or valve replacement surgery. INTERVENTION: Participants were randomly assigned (1:1) to 7 days of treatment with melatonin 3 mg at night or matching placebo, starting 2 days before the surgery. MEASUREMENTS: The primary outcome of interest was incident delirium within 7 days of surgery as assessed via daily clinical assessment that included the Confusion Assessment Method. Secondary outcomes of interest included duration and severity of delirium, length of hospital stay, cognitive function, and mood and anxiety symptoms at discharge and 3 months after the surgery. RESULTS: The groups were well balanced for demographic and clinical parameters. Forty-two participants developed delirium, but it was evenly distributed between the groups (melatonin 21/98, 21.4{\%}; placebo 21/104, 20.2{\%}; adjusted odds ratio [OR] =.78; 95{\%} confidence interval [CI] =.35-1.75). The median duration of delirium was 3 (interquartile range [IQR] = 2-4) and 2 (IQR = 1-3) days for people treated with melatonin and placebo, respectively (z = −1.03; P =.304). A similar proportion of participants experienced severe episodes of delirium in each group (melatonin 9/21, 42.9{\%} vs placebo 6/21, 28.6{\%}; χ2 =.93; P =.334; adjusted OR = 1.98; 95{\%} CI =.40-9.78). The groups did not differ in terms of length of stay, mood, anxiety, and cognitive performance. CONCLUSION: The findings of this randomized double-blind placebo-controlled trial do not support the prophylactic use of melatonin to prevent delirium after major cardiac surgery.",
keywords = "cardiothoracic, delirium, melatonin, prevention, surgery",
author = "Ford, {Andrew H.} and Leon Flicker and Rachael Kelly and Hema Patel and Jurgen Passage and Bradley Wibrow and Matthew Anstey and Mark Edwards and Almeida, {Osvaldo P.}",
year = "2019",
month = "10",
day = "8",
doi = "10.1111/jgs.16162",
language = "English",
journal = "The American Geriatrics Society, Journal",
issn = "0002-8614",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - The Healthy Heart-Mind Trial

T2 - Randomized Controlled Trial of Melatonin for Prevention of Delirium

AU - Ford, Andrew H.

AU - Flicker, Leon

AU - Kelly, Rachael

AU - Patel, Hema

AU - Passage, Jurgen

AU - Wibrow, Bradley

AU - Anstey, Matthew

AU - Edwards, Mark

AU - Almeida, Osvaldo P.

PY - 2019/10/8

Y1 - 2019/10/8

N2 - OBJECTIVES: Delirium is a serious medical condition with increased incidence in at-risk surgical populations. We sought to determine if melatonin use reduces the incidence of delirium in individuals undergoing major cardiac surgery. DESIGN: Randomized double-blind placebo-controlled clinical trial (two arms, 1:1 allocation, parallel design). SETTING: The trial took place in two metropolitan hospitals (public tertiary and private) in Perth, Western Australia. PARTICIPANTS: We recruited 210 adults aged 50 years or older who were due to undergo coronary artery bypass grafting or valve replacement surgery. INTERVENTION: Participants were randomly assigned (1:1) to 7 days of treatment with melatonin 3 mg at night or matching placebo, starting 2 days before the surgery. MEASUREMENTS: The primary outcome of interest was incident delirium within 7 days of surgery as assessed via daily clinical assessment that included the Confusion Assessment Method. Secondary outcomes of interest included duration and severity of delirium, length of hospital stay, cognitive function, and mood and anxiety symptoms at discharge and 3 months after the surgery. RESULTS: The groups were well balanced for demographic and clinical parameters. Forty-two participants developed delirium, but it was evenly distributed between the groups (melatonin 21/98, 21.4%; placebo 21/104, 20.2%; adjusted odds ratio [OR] =.78; 95% confidence interval [CI] =.35-1.75). The median duration of delirium was 3 (interquartile range [IQR] = 2-4) and 2 (IQR = 1-3) days for people treated with melatonin and placebo, respectively (z = −1.03; P =.304). A similar proportion of participants experienced severe episodes of delirium in each group (melatonin 9/21, 42.9% vs placebo 6/21, 28.6%; χ2 =.93; P =.334; adjusted OR = 1.98; 95% CI =.40-9.78). The groups did not differ in terms of length of stay, mood, anxiety, and cognitive performance. CONCLUSION: The findings of this randomized double-blind placebo-controlled trial do not support the prophylactic use of melatonin to prevent delirium after major cardiac surgery.

AB - OBJECTIVES: Delirium is a serious medical condition with increased incidence in at-risk surgical populations. We sought to determine if melatonin use reduces the incidence of delirium in individuals undergoing major cardiac surgery. DESIGN: Randomized double-blind placebo-controlled clinical trial (two arms, 1:1 allocation, parallel design). SETTING: The trial took place in two metropolitan hospitals (public tertiary and private) in Perth, Western Australia. PARTICIPANTS: We recruited 210 adults aged 50 years or older who were due to undergo coronary artery bypass grafting or valve replacement surgery. INTERVENTION: Participants were randomly assigned (1:1) to 7 days of treatment with melatonin 3 mg at night or matching placebo, starting 2 days before the surgery. MEASUREMENTS: The primary outcome of interest was incident delirium within 7 days of surgery as assessed via daily clinical assessment that included the Confusion Assessment Method. Secondary outcomes of interest included duration and severity of delirium, length of hospital stay, cognitive function, and mood and anxiety symptoms at discharge and 3 months after the surgery. RESULTS: The groups were well balanced for demographic and clinical parameters. Forty-two participants developed delirium, but it was evenly distributed between the groups (melatonin 21/98, 21.4%; placebo 21/104, 20.2%; adjusted odds ratio [OR] =.78; 95% confidence interval [CI] =.35-1.75). The median duration of delirium was 3 (interquartile range [IQR] = 2-4) and 2 (IQR = 1-3) days for people treated with melatonin and placebo, respectively (z = −1.03; P =.304). A similar proportion of participants experienced severe episodes of delirium in each group (melatonin 9/21, 42.9% vs placebo 6/21, 28.6%; χ2 =.93; P =.334; adjusted OR = 1.98; 95% CI =.40-9.78). The groups did not differ in terms of length of stay, mood, anxiety, and cognitive performance. CONCLUSION: The findings of this randomized double-blind placebo-controlled trial do not support the prophylactic use of melatonin to prevent delirium after major cardiac surgery.

KW - cardiothoracic

KW - delirium

KW - melatonin

KW - prevention

KW - surgery

UR - http://www.scopus.com/inward/record.url?scp=85074586314&partnerID=8YFLogxK

U2 - 10.1111/jgs.16162

DO - 10.1111/jgs.16162

M3 - Article

JO - The American Geriatrics Society, Journal

JF - The American Geriatrics Society, Journal

SN - 0002-8614

ER -