Background
Post‐operative pain treatment with ketamine has been demonstrated to have post‐operative opioid‐sparing and anti‐hyperalgesic effects. However, evidence regarding the beneficial and harmful effects and the optimal dose and timing of perioperative treatment with ketamine for patients undergoing spinal surgery is unclear. The objective of this systematic review is to assess the analgesic, serious and non‐serious adverse effects of perioperative pain treatment with ketamine for patients undergoing spinal surgery.

Methods
This protocol for a systematic review is written according to The Preferred Reporting Items for Systematic Review and Meta‐Analysis Protocols guidelines. We will search Embase, CENTRAL, PubMed, WHO’s ICTRP, EU Clinical Trial Register and ClinicalTrials.gov to identify relevant randomised clinical trials. We will include all randomised clinical trials assessing perioperative ketamine treatment versus placebo or no intervention for patients undergoing spinal surgery. Two authors will independently screen trials for inclusion using Covidence, extract data and assess risk of bias using Cochrane's RoB tool. We will analyse data using Review Manager and Trial Sequential Analysis. Meta‐analysis will be performed according to the Cochrane guidelines and results will be validated according to the eight‐step procedure suggested by Jakobsen et al. We will present our primary findings in a ‘summary of findings’ table. We will evaluate the overall certainty of evidence using the GRADE approach.

Discussion
This systematic review will assess the beneficial and harmful effects of perioperative pain treatment with ketamine for patients undergoing spinal surgery and have the potential to inform best practice and advance research.