Effect of high-dose glucocorticoids on persistent opioid use 3 to 12 months after primary total hip or knee arthroplasty. Protocol for a target trial emulation using observational data from Danish registries

Abstract

Background Persistent postsurgical pain and opioid use after primary total hip and knee arthroplasty (THA and TKA) have major consequences for the patient and for society. High-dose perioperative treatment with glucocorticoids reduces inflammation and acute pain, both of which are associated with persistent postsurgical pain. We therefore hypothesise that routine treatment with glucocorticoids reduces the number of patients with persistent opioid use.

Objective To determine if perioperative glucocorticoids for primary THA or TKA surgery, relative to no glucocorticoids, decreases the number of patients taking opioids in the period from 3 to 12 months after surgery.

Design Target trial emulation trial with data from Danish national registries.

Setting All departments of orthopaedic surgery in Denmark, from 1 January 2010 to 31 December 2020.

Participants Patients with primary osteoarthritis undergoing primary THA or TKA, excluding presurgical users of glucocorticoids or insulin because these patients do not always receive the intervention.

Intervention A single high-dose glucocorticoids (≥125 mg methylprednisolone or ≥24 mg dexamethasone) after induction of anaesthesia.

Comparator No glucocorticoids during surgery.

Allocation Patients operated at departments where treatment with high-dose glucocorticoids was standard of care at the time of surgery constitute the treatment arm, while patients operated at departments where high-dose glucocorticoids was not used serve as controls. Thus, all patients will be analysed according to their ‘allocation’, regardless of whether they received the treatment or not.

Main outcome measures The primary outcome is number of persistent opioid users, defined as patients who redeem a prescription within at least two of the last three quarters during the first postsurgical year. The primary safety outcome is number of days alive and out of hospital within 90 days after surgery.

Expectations These results will provide important evidence for or against the use of perioperative glucocorticoids in total hip and knee arthroplasty.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study did not receive any external funding.

Author Declarations

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:

The institutional review board of the Capitol Region of Denmark gave ethical approval for this work (reference P-2023-16) The Patient Files Team, Centre for Health, Capital Region of Denmark gave access to patient files (identifier R-23002069).

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

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