Analgesic Effect of Intraoperative Intravenous S-Ketamine in Opioid-Naïve Patients After Major Lumbar Fusion Surgery Is Temporary and Not Dose-Dependent: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Abstract

Background: Severe pain often accompanies major spine surgery. Opioids are the cornerstone of postoperative pain management but their use can be limited by numerous side effects. Several studies claim that adjuvant treatment with intravenous (IV) ketamine reduces opioid consumption and pain after back surgery. However, the exact role of ketamine for this indication is yet to be elucidated. We compared 2 different doses of S-ketamine with placebo on postoperative analgesic consumption, pain, and adverse events in adult, opioid-naïve patients after lumbar fusion surgery. METHODS: One hundred ninety-eight opioid-naïve patients undergoing lumbar spinal fusion surgery were recruited to this double-blind trial and randomly assigned into 3 study groups: Group C (placebo) received a preincisional IV bolus of saline (sodium chloride [NaCl] 0.9%) followed by an intraoperative IV infusion of NaCl 0.9%. Both groups K2 and K10 received a preincisional IV bolus of S-ketamine (0.5 mg/kg); in group K2, this was followed by an intraoperative IV infusion of S-ketamine (0.12 mg/kg/h), while in group K10, it was followed by an intraoperative IV infusion of S-ketamine (0.6 mg/kg/h). Postoperative analgesia was achieved by an IV patient-controlled analgesia (IV PCA) device delivering oxycodone. The primary end point was cumulative oxycodone consumption at 48 hours after surgery. The secondary end points included postoperative pain up to 2 years after surgery, adverse events, and level of sedation and confusion in the immediate postoperative period. RESULTS: The median [interquartile range (IQR)] cumulative oxycodone consumption at 48 hours was 154.5 [120] mg for group K2, 160 [109] mg for group K10, and 178.5 [176] mg for group C. The estimated difference was −24 mg between group K2 and group C (97.5% confidence interval [CI], −73.8 to 31.5; P = .170) and −18.5 mg between group K10 and C (97.5% CI, 78.5–29.5; P = .458). There were no significant differences between groups. Postoperative pain scores were significantly lower in both ketamine treatment groups at the fourth postoperative hour but not later during the 2-year study period. The higher ketamine dose was associated with more sedation. Otherwise, differences in the occurrence of adverse events between study groups were nonsignificant. CONCLUSIONS: Neither a 0.12 nor a 0.6 mg/kg/h infusion of intraoperative IV S-ketamine was superior to the placebo in reducing oxycodone consumption at 48 hours after lumbar fusion surgery in an opioid-naïve adult study population. Future studies should assess ketamine’s feasibility in specific study populations who most benefit from reduced opioid consumption.

S-ketamine in patient-controlled analgesia reduces opioid consumption in a dose-dependent manner after major lumbar fusion surgery: A randomized, double-blind, placebo-controlled clinical trial

“…This oxycodone:S-ketamine ratio is also well tolerated. As previous studies have mainly focused on intraoperative administration, even showing no analgesic effect of intraoperative S-ketamine in opioid-naïve patients [ 38 ], this finding adds new data to the feasibility of adjunct S-ketamine with oxycodone for postoperative pain management after major lumbar spinal fusion surgery.…”

Postoperative pain treatment after spinal fusion surgery: a systematic review with meta-analyses and trial sequential analyses

“…For subgroup analyses, we identified 5 groups, which included 3 or more trials: nonsteroidal anti-inflammatory drugs (NSAIDs), 3 , 55 , 59 , 62 , 71 epidural analgesia, 2 , 7 , 21 , 32 , 60 ketamine infusion, 1 , 5 , 24 , 41 , 53 , 64 , 66 local infiltration analgesia, 6 , 22 , 44 , 61 and intrathecal (i.t.) morphine.…”

“…Six trials reported on PONV. 1,5,41,53,64,66 The meta-analysis found no significant difference between groups, RR 0.99 (95% CI: 0.76–1.28) with low heterogeneity I 2 = 12% (Appendix 5, available at http://links.lww.com/PR9/A157). The quality of evidence (GRADE) was very low (Table 2).…”

Sleep Well and Recover Faster with Less Pain—A Narrative Review on Sleep in the Perioperative Period

“…A very recent RCT on perioperative ketamine concluded that most of the 189 patients in the study complained of disturbed sleep on the night following surgery. However, there were no significant differences between the ketamine and placebo groups [ 57 ], neither were there significant differences between the groups regarding hallucinations or confusion, and no patients reported vivid dreams or nightmares.…”