Effect Of Small-dose Ketamine On Clinically Relevant Concentrations Of Remifentanil-induced Postoperative Hyperalgesia

Objective:To observe the effect of clinically relevant concentrations of remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Methods:Fourty patients aged 29-83 yr (ASA I-III) scheduled for abdominal surgery were randomly assigned to receive intraoperative low-dose ketamine(bolus dose of 0.5mg/Kg followed by continuous infusion of 5μg.kg-1.min-1) or an equal volume of saline during remifentanil/sevoflurane anesthesia.Then anesthesia was induced with midazolam 0.03mg/Kg, fentanyl 2μg/Kg, vecuronium 0.1mg/Kg and propofol 1-2mg/Kg, and patient-controlled intravenous analgesia (PCIA) with tramadol after operations. The index of hemodynamics and bispectral index of the electroencephalogram (BIS) were recorded at following time points:before induction,after induction,orotracheal intubation,piece,skin closure and extubation.The concentration of substance P (SP) was measured after entering the operating room,two hours after starting the surgery,12 and 24h postoperative. Pain scores,sedation scores and tramodal consumption in post anesthesia care unit (PACU) were recored. The total times that patients pressed the PCIA control key was observed in the first postoperative 24 h. Awakening time,extubation time and anesthetic-related complications were recorded as well. Results:Intraoperative hemodynamic responses at orotracheal intubation were more stable in KG group (P＜0.01). Verbal rating scales (VRS) in 15 minutes after extubation were lower in KG group (P<0.01); Ramsay sedation score were higher than CG group (P<0.01). The visual analog pain scores (VAS) during 20 postoperative hours were significantly greater in CG group (P<0.01). The concentration of SP at the time of 12 and 24 h postoperative, both two groups were higher than baseline values (P <0.01); compared with the same point of CG group, there were significant difference (P<0.01). Patients in CG group required tramadol for the first time earlier than in KG group (P<0.05); Tramadol comsumption in PACU were much more than KG group (P<0.01). The total times that patients pressed PCIA control key in KG group was less than CG group in the first postoperative 24h (P<0.01). Awakening time,extubation time and anesthetic-related complications were similar in each group. Conclusion:Intraoperative low-dose ketamine could lighten postoperative pain and sedation score,decrease tramadol consumption and the concentration of SP. These data suggest that small-dose ketamine could prevent clinically relevant concentrations of remifentanil-induced postoperative hyperalgesia; Intraoperative low-dose ketamine had no effect on awakening time,extubation time and anesthetic-related complications, which suggest that it could be safety compounded in general anesthesia.