Introduction Postoperative delirium (POD) is a significant complication in digestive surgery, potentially increasing hospital stays, costs, and mortality. Corticoids, such as dexamethasone and methylprednisolone, have been reported to reduce POD. However, the efficacy of hydrocortisone (HC) remains unexplored. This trial aims to evaluate HC’s effectiveness in preventing POD in surgical patients.

Methods and analysis A multicentre (three hospitals), randomized, blinded (patient-blinded, surgeon-blinded, anaesthesiologist-blinded, and monitor-blinded), placebo-controlled trial of HC for the prevention of POD in patients undergoing digestive surgery was started in June 2024. Patients undergoing digestive surgery are randomly assigned to the HC or placebo group. The stratification factors are age, sex, disease stage, and procedure type. Before skin incision, the participants in the HC group are administered 500 mg HC intravenously. The participants in the placebo group are administered the same volume of saline that is indistinguishable from the HC. The primary outcome is the presence of POD from postoperative Days 1 to 3, which is assessed using the Confusion Assessment Method-ICU (CAM-ICU). The secondary outcomes are changes in serum sodium levels, postoperative mortality, length of hospital stay, functional independence measures, and complications within 28 days. To date, 61 patients of a planned 180 have been enrolled in the study.

Ethics and dissemination This protocol was approved by the Nagoya University Clinical Research Review Board and was registered with the Japan Registry of Clinical Trials on 24 May 2024. The results of this trial will be disseminated through peer-reviewed journals.

Trial registration number jRCTs041240032

Strengths and limitations of this study

This randomized controlled trial (RCT) is the first study to answer the clinical question of whether the preoperative use of hydrocortisone (HC) in digestive surgery is beneficial.

A multicentre (three hospitals), double-blinded (patient-, surgeon-, anaesthesiologist-, and monitor-blinded) placebo-controlled RCT is the optimal study design for addressing the clinical question above.

A loading dose of HC (500 mg), which is simple and easy for anaesthesiologists to administer, is administered intravenously over 15–30 min just before surgery.

The study inclusion criteria are extensive, and the exclusion criteria are limited; therefore, this protocol will have broad applicability if the trial results are positive.

On the basis of previous data regarding postoperative delirium (POD) from the National Center for Geriatrics and Gerontology (NCGG), the necessary sample size is estimated to be 180 patients; however, the incidence of POD tends to vary widely among institutions, and the risk of underpowered statistics is not negligible.

The authors have declared no competing interest.

jRCTs041240032

This study did not receive any funding.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee/IRB of Nagoya University Hospital, National Center for Geriatrics and Gerontology and Tsushima City Hospital gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes