. 2016 Nov 24;5(1):199.

doi: 10.1186/s13643-016-0378-2.

Melatonin and melatonin agonists to prevent and treat delirium in critical illness: a systematic review protocol

Jennifer Foster^{1

2

3}, Lisa D Burry^{4

5}, Lehana Thabane^{6

7

8

9

10}, Karen Choong^{10

11}, Kusum Menon^{12

13

14}, Mark Duffett^{10

11}, Alexandra Cheung⁵, Melanie Guenette⁵, Timothy Chimunda^{15

16}, Louise Rose^{17

18

19

20

21}

Affiliations

¹ Department of Paediatrics, Schulich School of Medicine & Dentistry, Western University, London, Canada. jfoste56@uwo.ca.
² IWK Health Centre, Dalhousie University, 5850/5980 University Avenue, Halifax, NS, B3K 6R8, Canada. jfoste56@uwo.ca.
³ Division of Children's Health & Therapeutics, Children's Health Research Institute, London, Canada. jfoste56@uwo.ca.
⁴ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
⁵ Department of Pharmacy, Mount Sinai Hospital, 600 University Avenue, Room 18-377, Toronto, ON, M5G1X5, Canada.
⁶ Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
⁷ Biostatistics Unit, Centre for Evaluative Medicine, St. Joseph's Healthcare, Hamilton, ON, Canada.
⁸ Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada.
⁹ Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
¹⁰ Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
¹¹ Pediatric Critical Care Unit, McMaster Children's Hospital, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada.
¹² Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
¹³ Division of Critical Care, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
¹⁴ Departments of Pediatrics and Epidemiology and Community Medicine, University of Ottawa, Ottawa, ON, Canada.
¹⁵ Department of Anesthesia, University of Toronto, Toronto, ON, Canada.
¹⁶ School of Medicine, University of Queensland, Brisbane, QLD, 4072, Australia.
¹⁷ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
¹⁸ Evaluative Clinical Sciences, Trauma, Emergency & Critical Care Research Program, Sunnybrook Research Institute, Toronto, ON, Canada.
¹⁹ Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada.
²⁰ Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.
²¹ Provincial Centre of Weaning Excellence, Toronto East General Hospital, Toronto, ON, Canada.

PMID: 27881185
PMCID: PMC5122010
DOI: 10.1186/s13643-016-0378-2

Melatonin and melatonin agonists to prevent and treat delirium in critical illness: a systematic review protocol

Jennifer Foster et al. Syst Rev. 2016.

. 2016 Nov 24;5(1):199.

doi: 10.1186/s13643-016-0378-2.

Authors

Affiliations

¹ Department of Paediatrics, Schulich School of Medicine & Dentistry, Western University, London, Canada. jfoste56@uwo.ca.
² IWK Health Centre, Dalhousie University, 5850/5980 University Avenue, Halifax, NS, B3K 6R8, Canada. jfoste56@uwo.ca.
³ Division of Children's Health & Therapeutics, Children's Health Research Institute, London, Canada. jfoste56@uwo.ca.
⁴ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
⁵ Department of Pharmacy, Mount Sinai Hospital, 600 University Avenue, Room 18-377, Toronto, ON, M5G1X5, Canada.
⁶ Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
⁷ Biostatistics Unit, Centre for Evaluative Medicine, St. Joseph's Healthcare, Hamilton, ON, Canada.
⁸ Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada.
⁹ Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
¹⁰ Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
¹¹ Pediatric Critical Care Unit, McMaster Children's Hospital, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada.
¹² Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
¹³ Division of Critical Care, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
¹⁴ Departments of Pediatrics and Epidemiology and Community Medicine, University of Ottawa, Ottawa, ON, Canada.
¹⁵ Department of Anesthesia, University of Toronto, Toronto, ON, Canada.
¹⁶ School of Medicine, University of Queensland, Brisbane, QLD, 4072, Australia.
¹⁷ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
¹⁸ Evaluative Clinical Sciences, Trauma, Emergency & Critical Care Research Program, Sunnybrook Research Institute, Toronto, ON, Canada.
¹⁹ Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada.
²⁰ Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.
²¹ Provincial Centre of Weaning Excellence, Toronto East General Hospital, Toronto, ON, Canada.

PMID: 27881185
PMCID: PMC5122010
DOI: 10.1186/s13643-016-0378-2

Abstract

Background: Delirium is a syndrome characterized by acute fluctuations and alterations in attention and arousal. Critically ill patients are at particularly high risk, and those that develop delirium are more likely to experience poor clinical outcomes such as prolonged duration of ICU and hospital length of stay, and increased mortality. Melatonin and melatonin agonists (MMA) have the potential to decrease the incidence and severity of delirium through their hypnotic and sedative-sparing effects, thus improving health-related outcomes. The objective of this review is to synthesize the available evidence pertaining to the efficacy and safety of MMA for the prevention and treatment of ICU delirium.

Methods: We will search Ovid MEDLINE, Web of Science, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL to identify studies evaluating MMA in critically ill populations. We will also search http://apps.who.int/trialsearch for ongoing and unpublished studies and PROSPERO for registered reviews. We will not impose restrictions on language, date, or journal of publication. Authors will independently screen for eligible studies using pre-defined criteria; data extraction from eligible studies will be performed in duplicate. The Cochrane Risk of Bias Scale and the Newcastle-Ottawa Scale will be used to assess the risk of bias and quality of randomized and non-randomized studies, respectively. Our primary outcome of interest is delirium incidence, and secondary outcomes include duration of delirium, number of delirium- and coma-free days, use of physical and chemical (e.g., antipsychotics or benzodiazepines) restraints, duration of mechanical ventilation, ICU and hospital length of stay, mortality, long-term neurocognitive outcomes, hospital discharge disposition, and adverse events. We will use Review Manager (RevMan) to pool effect estimates from included studies. We will present results as relative risks with 95% confidence intervals for dichotomous outcomes and as mean differences, or standardized mean differences, for continuous outcomes.

Discussion: Current guidelines make no pharmacological recommendations for either the prevention or treatment of ICU delirium. This systematic review will synthesize the available evidence on the efficacy and safety of MMA for this purpose, thus potentially informing clinical decision-making and improving patient outcomes.

Systematic review registration: PROSPERO CRD42015024713.

Keywords: Delirium; Intensive care; Melatonin; Melatonin agonists; Prevention; Systematic review; Treatment.

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Becker JE, Smith JR, Hazen EP. Becker JE, et al. Psychosomatics. 2020 Sep-Oct;61(5):467-480. doi: 10.1016/j.psym.2020.04.015. Epub 2020 Apr 25. Psychosomatics. 2020. PMID: 32482345 Free PMC article. Review.
Evaluation of Melatonin Practices for Delirium in Pediatric Critically Ill Patients.
Laudone TW, Beck SD, Lahr HJ. Laudone TW, et al. J Pediatr Pharmacol Ther. 2021;26(4):361-365. doi: 10.5863/1551-6776-26.4.361. Epub 2021 May 19. J Pediatr Pharmacol Ther. 2021. PMID: 34035680 Free PMC article.
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Herling SF, Greve IE, Vasilevskis EE, Egerod I, Bekker Mortensen C, Møller AM, Svenningsen H, Thomsen T. Herling SF, et al. Cochrane Database Syst Rev. 2018 Nov 23;11(11):CD009783. doi: 10.1002/14651858.CD009783.pub2. Cochrane Database Syst Rev. 2018. PMID: 30484283 Free PMC article.
Pediatric Delirium: Evaluation, Management, and Special Considerations.
Malas N, Brahmbhatt K, McDermott C, Smith A, Ortiz-Aguayo R, Turkel S. Malas N, et al. Curr Psychiatry Rep. 2017 Aug 12;19(9):65. doi: 10.1007/s11920-017-0817-3. Curr Psychiatry Rep. 2017. PMID: 28801871 Review.
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Dludla PV, Nkambule BB, Dias SC, Johnson R. Dludla PV, et al. Syst Rev. 2017 May 12;6(1):96. doi: 10.1186/s13643-017-0493-8. Syst Rev. 2017. PMID: 28499416 Free PMC article.

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Melatonin and melatonin agonists to prevent and treat delirium in critical illness: a systematic review protocol

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Melatonin and melatonin agonists to prevent and treat delirium in critical illness: a systematic review protocol

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