The perioperative combination of methadone and ketamine reduces post‐operative opioid usage compared with methadone alone

Background A synergy between ketamine and methadone ( ME ) to produce antinociception has been demonstrated in experimental neuropathy. We wanted to compare post‐operative opioid requirements in patients undergoing multilevel lumbar arthrodesis after the administration combined ME –ketamine ( MK ) or ME alone. Methods This was a randomised double‐blind study. During sevoflurane–remifentanil anaesthesia, 11 patients in each group received the following: ketamine bolus (0.5 mg/kg) after tracheal intubation, followed by an infusion of 2.5 μg/kg/min in the MK or saline bolus plus infusion in the ME group. Post‐operative analgesia – during 48 h – was provided by patient‐controlled analgesia ( PCA ), delivering bolus containing the following: ME 0.25 mg plus ketamine 0.5 mg in the MK group or ME 0.5 mg in the ME group. Lockout was 10 min, maximum of 3 boluses/h in both groups. Before closing the wound, all the patients received intravenous (i.v.) ME 0.1 mg/kg, dexketoprophen and paracetamol. Pain intensity was evaluated by a numerical rating scale ( NRS ), on arrival at recovery room ( RR ) and 24 and 48 h after surgery. In the RR , i.v. ME was administered until NRS was 3 when PCA was started. Dexketoprophen and paracetamol were administered 48 h. Results Remifentanil requirements were higher in the MK group ( P  = 0.004). Patients in the MK group received 70% less ME by PCA at 24 h ( MK vs. ME group, median and interquartile range) – 3.43 mg (1.9–6.5) vs. 15 mg (9.65–17.38) ( P < 0.001) – and at 48 h – 2 mg (0.5–3.63) vs. 9.5 mg (3.5–13.75) ( P  = 0.001). Patients in the MK group also attempted less doses, at 24 h: 19.5 (12.75–79.5) vs. 98 (41.5–137) ( P  = 0.043). Both groups had similar NRS values and comparable side effects. Conclusions Perioperative ketamine– ME combination significantly decreased opioid consumption by PCA .