Acute abdominal pain is a chief complaint in emergency departments and represents 7%–10% of emergency room (ER) visits. Acute appendicitis represents 15% of the causes of abdominal pain and 62% of the causes that require surgical treatment. Opioid analgesia has been evaluated in clinical trials, and they have determined it does not impact diagnostic accuracy. Despite evidence, withholding analgesia is still a common practice. Pain severely impacts quality of life and analgesia has become essential in humanised medicine. We aim to determine the safety and effectiveness of different opioid regimens for adult patients that present to the ER with acute suspected appendicitis.

We will search MEDLINE and Embase via Ovid, and the Cochrane Central Register of Controlled Trials without restrictions on the study publication date. Screening, extraction and risk of bias assessment will be performed in duplicate. We will use the Cochrane Risk of Bias Assessment Tool. We will perform both pairwise meta-analysis and network meta-analysis (NMA) if transitivity and coherence principles are met. Heterogeneity will be evaluated using the I² and ² and using the thresholds recommended by Cochrane. We will perform sensitivity analysis based on the pre-established potential effect modifiers, risk of bias and data that required transformation or imputation. Publication bias will be addressed by using funnel plots on a pairwise level. We will assess the strength of the body of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE) per outcome, and evidence from the NMA will be assessed using the GRADE approach for NMA.

Approval by an ethics committee is not required for this study since no personal information will be handled. Information will be disseminated by publication on a peer-reviewed journal.

CRD42024583804.