Pharmacological interventions to improve sleep in hospitalised adults: a systematic review

Salmaan Kanji, Alexandru Mera, Brian Hutton, Lisa Burry, Erin Rosenberg, Erika MacDonald, Vanessa Luks, Salmaan Kanji, Alexandru Mera, Brian Hutton, Lisa Burry, Erin Rosenberg, Erika MacDonald, Vanessa Luks

Abstract

Objectives: Patients often suffer from disturbed sleep in hospital. Poor-quality sleep in hospitalised patients has been associated with significant morbidity and pharmacological sleep aids are often prescribed. The objective of this systematic review is to evaluate the comparative efficacy and safety of pharmacological interventions used for sleep in hospitalised patients.

Setting/participants: We searched MEDLINE, Embase, the Cochrane database and grey literature for prospective studies that evaluated sleep in hospitalised adults after a pharmacological intervention.

Primary and secondary outcome measures: Two reviewers assessed studies for inclusion and extracted data for efficacy outcomes, including sleep efficiency, sleep latency, sleep fragmentation and objectively measured sleep stage distribution. Risk of bias was assessed and meta-analyses were planned contingent upon homogeneity of the included studies.

Results: After screening 1920 citations, 15 studies involving 861 patients were included. Medications studied included benzodiazepines, nonbenzodiazepine sedatives, melatonin, propofol and dexmedetomidine. Five studies were deemed to be of high quality. Heterogeneity and variable outcome reporting precluded meta-analysis in most cases. No consistent trends with respect to sleep efficiency, quality or interruptions were observed identifying a drug or drug class as superior to another or no treatment. Benzodiazepines appeared to be better than no treatment with respect to sleep latency, but this was not consistently demonstrated across all studies. Sleep stage distribution shows that sleep in hospital is dominated by stages N1 and N2.

Conclusions: There is insufficient evidence to suggest that pharmacotherapy improves the quality or quantity of sleep in hospitalised patients suffering from poor sleep. No drug class or specific drug was identified as superior even when compared to placebo or no treatment. Although 15 studies were included, the quality of evidence was limited by their quality and size. Larger, better-designed trials in hospitalised adults are needed.

Keywords: CLINICAL PHARMACOLOGY; SLEEP MEDICINE.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Figures

Figure 1
Figure 1
Process of study identification and selection. *Prospective cohort studies not using polysomnography to measure sleep. RCT, randomised controlled trial.
Figure 2
Figure 2
Risk of bias for randomised controlled trials using the Cochrane risk of bias tool. Risk of bias assessed as low, moderate or high for each category.
Figure 3
Figure 3
Risk of bias for prospective cohort studies (NewCastle-Ottawa Scale).
Figure 4
Figure 4
Sleep efficiency: observed differences from randomised and non-randomised studies and from active and inactive controlled studies (7 studies and 188 patients). Sleep efficiency was defined as the number of hours spent asleep divided by the total hours of observation. In some studies, mean and SD values were estimated using an approached described in the Methods section. *, non-randomised study; iv, intravenous; NMBA, neuromuscular blocking agent.
Figure 5
Figure 5
Sleep fragmentation: observed differences from randomised and non-randomised studies and from active and inactive controlled studies (5 studies and 125 patients). Sleep fragmentation was defined as the number of arousals or awakenings per hour of sleep. In some studies, mean and SD values were estimated using an approached described in the Methods section. *, non-randomised study; iv, intravenous; NE, not estimable; NMBA, neuromuscular blocking agent; NR, not reported.
Figure 6
Figure 6
Sleep architecture: observed differences from randomised and non-randomised studies and from active and inactive controlled studies (4 studies and 59 patients). Sleep stage distribution defined as percentage of total sleep time patients spent in each stage. In some studies, mean and SD values were estimated using an approached described in the Methods section. *, non-randomised study; cont, continuous dosing; DEX, dexmedatomidine; int, intermittent dosing; iv, intravenous; LOR, lorazepam; MID, midazolam; NE, not estimable; NMBA, neuromuscular blocking agent; No Trt, no treatment; PRO, propafol.

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