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Anaesthesia
Protocol
Pharmacotherapy for improving postoperative sleep quality: a protocol for a systematic review and network meta-analysis
  1. Di Yang1,2,
  2. Lei Yang1,
  3. Qian Li1,
  4. Yunxia Zuo1
  1. 1Department of Anaesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
  2. 2Department of Anaesthesiology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
  1. Correspondence to Dr Yunxia Zuo; zuoyunxia{at}scu.edu.cn; Dr Lei Yang; yanglei.wcha{at}scu.edu.cn

Abstract

Introduction Improving the quality of sleep may promote enhanced recovery in surgical patients. In addition to controversial or conflicting study conclusions, the current clinical studies on pharmacotherapy for improving postoperative sleep quality are mostly limited to evaluating the effect of a specific drug or supplement compared with placebo, and they lack comparisons between drugs or supplements. Therefore, we plan to conduct a systematic review and network meta-analysis to compare the efficacy of different drugs or supplements for improving postoperative sleep quality.

Methods and analysis We will search the MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CNKI and Wanfang databases from the dates of their inception to December 2022. We will only include randomised controlled trials, irrespective of language and publication status. The primary outcome is postoperative sleep quality assessed by any validated tools or polysomnography. We will assess the quality of all included trials according to version 2 of the Cochrane risk-of-bias tool for randomised trials. We will use the GeMTC package of R software to perform direct and indirect comparisons via a Bayesian framework using a random-effects model. We will use the Confidence in Network Meta-Analysis approach to evaluate the quality of evidence.

Ethics and dissemination Ethical approval is not required for this protocol because we will only be pooling published data. We plan to submit our review to academic conferences and peer-reviewed academic journals.

PROSPERO registration number CRD42022356508.

  • Adult anaesthesia
  • SLEEP MEDICINE
  • Adult surgery
  • Sleep medicine
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2022-069724

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    STRENGTHS AND LIMITATIONS OF THIS STUDY

    • Our study will comprehensively evaluate the effect of pharmacotherapy on improvement of postoperative sleep quality.

    • Three major databases (MEDLINE, Embase and Cochrane Central Register of Controlled Trials) and Chinese literature databases will be comprehensively searched, with no language restrictions.

    • We will assess the quality of included trials on the basis of version 2.0 of the risk-of-bias tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions.

    • We will use the Confidence in Network Meta-Analysis approach to evaluate the quality of evidence.

    • Despite planning a subgroup analysis, the potential heterogeneity between studies, such as the effect of different types of surgery on the results, cannot be completely eliminated.

    Introduction

    Sleep disturbance refers to the abnormal time, rhythm, cycle or pattern of sleep, which affects the quality of sleep during the night. The incidence of perioperative sleep disturbance varies from 37.9% to 88.1%, and symptoms may even last up to 1 year after surgery in some patients.1–5 Sleep disturbance, which is one of the most common aspects of severe postoperative discomfort,6 is associated with delayed recovery,7 postoperative pain,8 postoperative cognitive dysfunction,9 inflammatory response10 and cardiac complications.11 Therefore, improving the quality of sleep may promote the enhanced recovery of surgical patients.12

    Postoperative pain is believed to be one of the main causes of sleep disturbance.12 However, why sleep disturbance still occurs in patients with adequate analgesia is difficult to explain.13 This finding suggests that postoperative sleep disturbance may not only be associated with pain, but also with other factors (eg, sex, anxiety, comorbidity, anaesthesia techniques, anaesthesia drugs and postoperative complications),14–17 and the underlying mechanisms of postoperative sleep disturbance are complex. In addition to non-pharmacological therapy, such as relaxation therapy and improving the sleep environment,18 pharmacotherapy is also an important aspect of improving postoperative sleep quality.12 Some clinical studies have found that drugs or supplements with different mechanisms can improve postoperative sleep quality. These drugs or supplements include the following: melatonin, which is a pineal hormone agent19; zolpidem, which is a short-acting non-benzodiazepine compound of the imidazopyridine class20; midazolam, which is a benzodiazepine21; dexmedetomidine, which is a selective alpha-2 adrenoceptor agonist22; tramadol, which is an opioid agonist23; lidocaine, which is a local anaesthetic24; and magnesium, which is a mineral and electrolyte.25 However, there are divergent conclusions regarding zolpidem, melatonin and lidocaine regarding the improvement of sleep.25–27 In addition to these controversial study conclusions, the current clinical studies on pharmacotherapy for improving postoperative sleep quality have mostly been limited to evaluations of the effects of a specific drug or supplement compared with placebo, and they are lacking in comparisons between them.28 29 Consequently, clinicians have difficulty in choosing the most suitable and effective drug or supplement to improve postoperative sleep quality.

    Therefore, we plan to conduct a systematic review and network meta-analysis to compare the efficacy of different drugs or supplements for improving postoperative sleep quality.

    Methods and analysis

    This protocol (CRD42022356508) was registered in the International Prospective Register of Systematic Reviews.30 We reported this protocol in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines.31

    Patient and public involvement

    Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

    Data sources and searches

    We will search the following databases via OVID: MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. We will also search the Chinese databases CNKI and Wanfang. All databases will be searched from their dates of inception to December 2022. No language restrictions will be applied to the search strategy. The original keywords used for this search will include the postoperative period, perioperative period, sleep, sleep disturbance, sleep disorders and sleep quality. Full details of the original search strategy are shown in online supplemental table 1. We will search for conference papers by SCOPUS, limiting ‘source type’ to ‘conference proceeding’. We will also search for ongoing trials by ClinicalTrials.gov and the Chinese Clinical Trial Registry. In the available studies, we will reassess any subject terms or free-text terms for postoperative sleep quality that have not been used. We will add newly identified terms to the final modified search strategy. The final search strategy will be reported in our review.

    Eligibility criteria

    Types of study

    We will only include randomised controlled trials, irrespective of the language or publication status. Conference abstracts will also be included if sufficient data are available.

    Types of participants

    We will include studies of adult patients who underwent any surgical procedures and were administered any drugs or supplements aiming to improve postoperative sleep quality.

    Types of interventions

    We will include studies using any of the following interventions:

    • Melatonin

    • Dexmedetomidine

    • Zolpidem

    • Tramadol

    • Lidocaine

    • Midazolam

    • Any other drugs or supplements to improve postoperative sleep quality

    Types of comparisons

    We will compare different interventions with each other and with placebo.

    Types of outcomes

    The primary outcome is postoperative sleep quality assessed by any validated tools, such as the Pittsburgh Sleep Quality Index,32 Richards-Campbell Sleep Questionnaire,33 General Sleep Disturbance Scale34 and Epworth Sleepiness Scale,35 or polysomnography.

    The secondary outcomes are as follows: treatment-related adverse effects; quality of life assessed by the Quality of Recovery 15-item Questionnaire,36 the Medical Outcomes Study 36-Item Short Form,37 the Health-Related Quality of Life Scale38 or any other validated tools; postoperative pain intensity assessed by the Visual Analogue Scale or analgesics consumption; risk of mental disturbance, such as anxiety, depression and stress; and the length of hospital stay.

    Study selection

    Two investigators (DY and LY) will independently review and screen all of the titles and abstracts for eligibility and complete the study selection form (online supplemental table 2). If the information for eligibility is insufficient, we will retrieve the full text. Any disagreements will be resolved by consulting with a third author (QL). Finally, we will list all of the eligible trials in the eligible trials form (online supplemental table 3).

    Data extraction and quality assessment

    We will obtain the full-text versions of all eligible trials for data extraction. Two investigators (DY and LY) will independently extract the data from studies into an electronic data extraction form (online supplemental table 4). A third investigator will verify the data and integrate them into the final version of the data extraction form.

    Two investigators (DY and LY) will independently assess the quality of all included trials on the basis of version 2.0 of the Cochrane risk-of-bias tool for randomised trials (RoB 2), as described in the Cochrane Handbook for Systematic Reviews of Interventions.39 The assessment of the RoB 2 will include the following five domains: bias arising from the randomisation process; bias due to deviations from intended interventions; bias due to missing outcome data; bias in measurement of the outcome and bias in selection of the reported result. One of the three risk-of-bias judgements (low risk of bias, some concerns or high risk of bias) will be assigned to each domain. Any disagreements will be resolved by discussion. We will report a risk-of-bias table and a risk-of-bias summary figure in the review process.

    Statistical analysis

    We will calculate the risk ratios with 95% CIs for dichotomous data, and mean differences with 95% CIs for continuous data. We will calculate the standardised mean difference with the 95% CI in the case of outcomes with continuous data in different scales.

    We will use the GeMTC package of R software to perform direct and indirect comparisons via a Bayesian framework using a random-effects model. Network graphs and ranking probabilities will be generated and presented. We will perform a sensitivity analysis by using different imputation methods (low risk of bias studies and large sample size studies) and different statistical methods (including a fixed-effects model). We will generate a funnel plot to assess the publication bias if more than nine studies are included in the meta-analysis.40

    We will use the Χ2 test and I2 statistic to describe heterogeneity. We will consider significant statistical heterogeneity when the p value is <0.05, and substantial heterogeneity will be considered when the I2 statistic is >50%. We will investigate the clinical heterogeneity by a subgroup analysis when there is significant statistical heterogeneity. Subgroup analyses will be performed on the basis of age, disease, surgical type and anaesthesia techniques. Transitivity will be considered between study results when there are similar patients’ characteristics, interventions, outcomes and study design. We will use the node-splitting method to evaluate the inconsistency if there are three or more nodes in the loop. A p value of >0.05 will indicate that the difference between direct and indirect comparisons was not statistically significant. We will use directly compared results as the estimated effect size when there are inconsistencies in the study results.

    Assessing the quality of evidence

    We will use the Confidence in Network Meta-Analysis approach to evaluate the quality of evidence. This approach covers the following six domains: (1) within-study bias, (2) reporting bias, (3) indirectness, (4) imprecision, (5) heterogeneity and (6) incoherence.41

    Ethics and dissemination

    Ethics approval is not required for this protocol because we will only pool published data. We plan to submit our review to academic conferences and peer-reviewed academic journals.

    Ethics statements

    Patient consent for publication

    Acknowledgments

    We thank John Daniel from Liwen Bianji (Edanz) (www.liwenbianji.cn) for editing the English text of a draft of this manuscript.

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    Supplementary materials

    Footnotes

    • Contributors DY, LY, QL and YZ conceived and designed the study. LY developed the search strategy. DY, QL and YZ drafted the manuscript. All authors approved on submitting the article for publication.

    • Funding This study was supported by a research grant from the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD20005) and Key Research and Development Program of Science and Technology Department of Sichuan Province (no. 2023YFS0139)

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.