Effects of Dexmedetomidine on Postoperative Sleep Quality

In This Article

Abstract and Introduction

Abstract

Study Objectives: To assess the effect of dexmedetomidine (DEX) on postoperative sleep quality using polysomnography (PSG) to identify possible interventions for postoperative sleep disturbances.

Methods: An electronic search of PubMed/MEDLINE, EMBASE, Cochrane Library and Web of Science was conducted from database inception to November 20, 2022. Randomized controlled trials (RCTs) on the effect of DEX administration on postoperative sleep quality using PSG or its derivatives were included. No language restrictions were applied. The sleep efficiency index (SEI), arousal index (AI), percentages of stage N1, N2 and N3 of non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep were measured in our meta-analysis.

Results: Five studies, involving 381 participants were included. Administration of DEX significantly improved SEI, lowered AI, decreased the duration of stage N1 sleep and increased the duration of stage N2 sleep compared to placebo groups. There were no significant differences in the duration of stage N3 sleep and REM sleep. DEX administration lowered the postoperative Visual Analogue Scale (VAS) score and improved the Ramsay sedation score with no adverse effect on postoperative delirium (POD). However, high heterogeneity was observed in most of the primary and secondary outcomes.

Conclusions: Our study provides support for the perioperative administration of DEX to improve postoperative sleep quality. The optimal dosage and overall effect of DEX on postoperative sleep quality require further investigation using large-scale randomized controlled trials.

Introduction

Sleep disturbances, including sleep deprivation, disruption, and abnormal architecture, are prevalent in postoperative patients.^[1] Studies using polysomnography (PSG) have shown that the sleep pattern of patients is characterized by a disorganized circadian rhythm, prolonged sleep latency, fragmented sleep, decreased sleep efficiency, abnormally increased stages 1 and 2 of non-rapid eye movement (NREM) sleep (also called stage N1 and N2 sleep), decreased or absent stage 3 of NREM sleep (also called stage N3 sleep or slow-wave sleep) and rapid eye movement (REM) sleep.^[2,3] Postoperative sleep disturbances can result in significant adverse outcomes, including delirium, cardiovascular events, impaired immune function, prolonged mechanical ventilation, and postoperative physical and mental health decline.^[4–6] Therefore, interventions to improve postoperative sleep quality are attracting considerable attention from anesthesiologists.

Dexmedetomidine (DEX), an α-2 adrenergic agonist with high specificity, has been widely used as a sedative, anxiolytic, sympatholytic, and analgesic-sparing agent in clinics.^[7] Compared to gamma-aminobutyric acid (GABA) agonists, DEX more closely resembles natural NREM sleep.^[8,9] Several studies have reported favorable effects of DEX on sleep quality in patients after surgery or in the intensive care unit (ICU), as evaluated by objective tools, sleep questionnaires, or subjective assessments.^[10–14] However, no meta-analysis of randomized controlled trials (RCTs) has focused on the effect of DEX on sleep quality in postoperative patients, and the optimal dosage and overall effect of DEX remain unclear.

To summarize the available evidence and guide clinical practice, we conducted this systematic review and meta-analysis to evaluate the effects of DEX on postoperative sleep quality using PSG or its derivatives to identify possible interventions for postoperative sleep disturbance. We aimed to provide aggregated data and make a more validated conclusion regarding the administration of DEX to improve postoperative sleep.

Table 1. Baseline characteristics of included trials
First author, year of publication	Country	Type of surgery	Age range(yr)	Males(%)	Control group	No. randomized	No. in DEX group	No. in control group	ICU stay	DEX starting time	DEX dosage	Variables provided
Wu XH²⁰, 2016	China	Non-cardiac Surgery	≥ 65	57.9	Placebo	61	31	30	Yes	Postoperative	0.1 μg/kg/h, lasting 15 h	SEI, TST, AI, N1, N2, N3, REM
Chen ZC¹³, 2017	China	Abdominal hysterectomy	30–55	NR	Placebo	59	30	29	No	PCA	Continuous dose: 0.05 μg/kg/h Bolus dose: 0.05 μg/kg	SEI, AI, N1, N2, N3, REM, Ramsay, VAS
Jiang ZM¹⁸, 2018	China	Abdominal surgery	60–70	58.8	Placebo	97	Low dose group: 32 High dose group: 33	32	No	PCA	Low dose group: 0.072 μg/kg/h continuous dose, 0.024 μg/kg bolus dose High dose group: 0.144 μg/kg/h continuous dose, 0.048 μg/kg bolus dose	SEI, AI, N1, N2, N3, REM, VAS
Sun YM¹⁹, 2022	China	Non-cardiac surgery	≥ 18	51.4	Placebo	68	33	35	Yes	Postoperative	0.1–0.2 μg/kg/h, lasting 72 h	SEI, TST, AI, N1, N2, N3, REM
Wu Y¹⁴, 2022	China	Endoscopic sinus surgery	18–65	55	Placebo	96	48	48	No	Intraoperative	Loading dose: 0.5 μg/kg, continuous infusion: 0.2 μg/kg/h	SEI, AI, REM, Ramsay, VAS, PONV, POD

NR, not reported; PCA, patient controlled analgesia; SEI, sleep efficiency index; TST, total sleep time; AI, arousal index; N1, stage 1 of non-rapid eye movement sleep; N2, stage 2 of non-rapid eye movement sleep; N3, stage 3 of non-rapid eye movement sleep; REM, rapid eye movement sleep; VAS, visual analogue scale; PONV, postoperative nausea and vomiting; POD, postoperative delirium

Table 2. Subgroup analysis stratified by severity of illness
	Subgroup	Sample size		Weight (%)	MD with [95%CI]	Z	I ²(%)	P value
	Subgroup	DEX	Control	Weight (%)	MD with [95%CI]	Z	I ²(%)	P value
SEI	ICU	64	65	35.5	9.98 [3.48, 16.47]	3.01	0	0.003
SEI	Non-ICU	143	109	64.5	11.64 [-0.39, 23.66]	1.90	98	0.06
AI	ICU	64	65	21.9	-1.27 [-2.73, 0.18]	1.72	0	0.09
AI	Non-ICU	143	109	78.1	-2.51 [-4.17, -0.86]	2.98	96	0.003
N1	ICU	64	65	37.6	-8.09 [-14.93, -1.26]	2.32	0	0.02
N1	Non-ICU	95	61	62.4	-12.88 [-26.83, 1.08]	1.81	99	0.07
N2	ICU	64	65	24.4	7.21 [-7.88, 22.30]	0.94	39	0.35
N2	Non-ICU	95	61	75.6	17.82 [13.53, 22.12]	0.13	79	< 0.00001
N3	ICU	64	65	0	NE	NA	NA	NA
N3	Non-ICU	95	61	100	-2.09 [-7.51, 3.33]	0.76	92	0.45
REM	ICU	33	35	30.6	0 [-0.04, 0.04]	0	NA	1
REM	Non-ICU	143	109	69.4	-0.34 [-2.32, 1.64]	0.33	92	0.74

SEI, sleep efficiency index; AI, arousal index; N1, stage 1 of non-rapid eye movement sleep; N2, stage 2 of non-rapid eye movement sleep; N3, stage 3 of non-rapid eye movement sleep; REM, rapid eye movement sleep; MD, mean difference; CI, confidence interval; NE, not estimable; NA, not applicable