Interaction between postoperative shivering and hyperalgesia caused by high-dose remifentanil

Abstract

Background: High-dose remifentanil-based anesthesia is associated with opioid-induced hyperalgesia (OIH) and postanesthetic shivering (PAS). These effects can be prevented by N-methyl-d-aspartate (NMDA) receptor antagonists. This study aimed to investigate correlations between OIH and PAS caused by high-dose remifentanil and the effects of low-dose ketamine on OIH and PAS.

Methods: Seventy-five patients scheduled for single-port laparoscopic gynecologic surgery were randomly allocated into three groups, each of which received intraoperative remifentanil: group L at 0.1 µg/kg/min; group H at 0.3 µg/kg/min; and group HK at 0.3 µg/kg/min plus 0.25 mg/kg ketamine just before incision, followed by a continuous infusion of 5 µg/kg/min ketamine until skin closure.

Results: PAS, postoperative tactile pain threshold, and the extent of hyperalgesia in group H were significantly different (P < 0.05) than in the other two groups. PAS was significantly correlated with OIH, including mechanically evoked pain such as postoperative tactile pain threshold (r = -0.529, P = 0.01) (r = -0.458, P = 0.021) and the extent of hyperalgesia (r = 0.537, P = 0.002) (r = 0.384, P = 0.031), respectively, in group H and group HK. Notably, both groups were treated with high-dose remifentanil. Tympanic membrane temperature, time to first postoperative analgesic requirement, postoperative pain scores, analgesic consumption, and cumulative patient-controlled analgesia volume containing morphine were comparable in all three groups.

Conclusions: OIH, including the enhanced perception of pain, and PAS were both associated with high-dose remifentanil, were significantly correlated and were attenuated by a low dose of ketamine. This suggests that a common mechanism in part mediated through activation of the central glutamatergic system (e.g., NMDA receptors), underlies the two effects caused by high doses of remifentanil.

Keywords: Ketamine; Opioid-induced hyperalgesia; Postanesthetic shivering; Remifentanil.

Fig. 1

Schematic representation depicting mapping of the peri-incisional area for assessment of punctuate mechanical hyperalgesia.

Fig. 2

(A) Mechanically evoked pain tactile pain threshold before and 24 h after surgery. (B) Extent of hyperalgesia 24 h after surgery. Group L: 0.1 µg/kg/min remifentanil, Group H: 0.3 µg/kg/min, Group HK: 0.3 µg/kg/min remifentanil plus 0.25 mg/kg ketamine. ^*P < 0.05 vs preoperative values, ^†P < 0.05 vs other two groups.