Impact of low-dose intrathecal morphine on orthopedic surgery: a protocol of a systematic review and meta-analysis of randomized controlled trials

ABSTRACT Introduction Patients undergoing orthopedic surgery usually suffer considerably from peri-operative pain and intrathecal morphine (ITM) has recently been used as an effective analgesic method. The intrathecal morphine dose achieving optimal analgesia for orthopedic surgery while minimizing side effects has not yet been determined. There is currently a lack of literature synthesis on the safety and effects of low-dose ITM on orthopedic surgery. Methods and analysis A thorough literature search will be performed on multiple electronic databases and trial registries until January 11 th 2022, and reference lists will be examined. Two independent reviewers will select studies, extract data and assess the risk of bias and quality of the included studies. We will select randomized controlled trials comparing low-dose ITM (<100μg) with high-dose ITM (<200μg) or placebo treatment or other comparatives. We will assess the risk of bias using the Cochrane risk of bias tool and Jadad score will be applied to assess the quality of each included trial. We will also use Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) to determine the confidence in effect estimates. Publication bias will be evaluated by visually inspecting funnel plots and Egger regression asymmetry test in estimations of more than 10 trials. Standard meta-analysis will be performed using R package meta. Ethics and dissemination The results of this systematic review and meta-analysis will be disseminated through peer-reviewed journal and related conferences. The data used in this meta-analysis will not contain individual patient data and ethical approval is therefore not required.