Sleep during and following critical illness: A narrative review

Table 5 Summary of randomised clinical trials assessing nocturnal melatonin as a pharmacological sleep aid

Ref.	Design	Patients	Intervention & control	Sedation	Outcome
Ibrahim et al[158], 2006	Single centre, double-blind, randomised trial	32 pts	I: Melatonin 4 mg; C: placebo; For ≥ 48 h	Infusions ceased for ≥ 12 h	No significant difference in total sleep time by modified SOT
Bourne et al[136], 2008	Single centre, double-blind, randomised trial	24 pts	I: Melatonin 10 mg; C: Placebo; For 4 nights	Ceased for ≥ 30 h	No significant difference in total RCSQ or sleep efficiency by BIS
Foreman et al[222], 2015	Single centre, pilot, randomised trial	12 pts	I: Melatonin 3 mg plus eye masks and headphonesC: Standard care; For 1-7 d	Propofol allowed. Opiates ceased > 24 h	Primary outcome not determined in 65% due to uninterpretable PSG
Mistraletti et al[221], 2015	Single centre, double-blind, randomised trial	82 pts	I: Melatonin 3+3 mg; C: Placebo; From day 3 of ICU until ICU discharge	Enteral hydroxyzine and lorazepam allowed	No significant difference in total sleep time by nurse observation
Gandolfi et al[224], 2020	Double centre, double-blind, randomised trial	203 pts	I: Melatonin 10 mg; C: Placebo For 7 d or until hospital discharge	As per treating clinician	Statistically improved total RCSQ, mean (SD): I: 61 (26) C: 70 (21) (P = 0.03); No significant difference in total sleep time by nurse observation
Wibrow et al[225], 2021	Multicentre (12), double blind, randomised, trial	841 pts	I: Melatonin 4 mg; C: Placebo; For 14 d or until ICU discharge	As per treating clinician	No significant difference in total RCSQ

BIS: Bispectral index; ICU: Intensive care unit; PSG: Polysomnography; RCSQ: Richards-Campbell Sleep Questionnaire; SOT: Sleep observation tool.