A Comparison of Ketamine and Paracetamol for Preventing Remifentanil Induced Hyperalgesia in Patients Undergoing Total Abdominal Hysterectomy

Abstract

Background: The aim of this prospective, randomized, placebo-controlled study was to compare the effects of ketamine and paracetamol on preventing remifentanil induced hyperalgesia.Methods: Ninety patients undergoing total abdominal hysterectomy were randomly assigned to one of three groups to receive (I) either saline infusion; (II) 0.5 mg/kg ketamine iv bolus or (III) 1000 mg iv paracetamol infusion before induction of anesthesia. Until the skin closure, anesthesia was maintained with 0.4 µg/kg/min remifentanil infusion in all groups, additionally Group II received 5 µg/kg/min ketamine infusion. Pressure pain thresholds were measured the day before surgery during the preoperative visit for baseline measurements and repeated postoperatively at 24 and 48 hours (hrs). Pressure pain thresholds were established by digital algometer on three different peri- incisional regions for calculating mean pressure pain threshold values. The visual analogue scale (VAS), sedation scores, total morphine consumption and side effects were assessed postoperatively.Results: Demographic characteristics, duration of surgery and anesthesia were similar in the three groups. Pain thresholds at the incision region were significantly lower at 24 and 48 hrs postoperatively in Group I than the other Groups (p< 0.05). In Group І, pain thresholds were lower compared with preoperative baseline values. Thresholds in Group ІІ and Group ІІІ were higher compared with preoperative baseline values (p< 0.05) The VAS scores at all evaluation times were significantly higher in Group І when compared to Group ІІ and at 2, 4, 6 ,12 hrs were higher in Group I than Group ІІІ (p< 0.05). The morphine consumption was higher in Group ІІІ at 24 and 48 hrs postoperatively (p< 0.05).Conclusion: It was shown that ketamine and paracetamol were both effective in preventing remifentanil induced hyperalgesia.

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

“…Thus far, a host of animal studies have found that OIH is reversible by the NMDA receptor antagonists MK-801 [31,42,[160][161][162][163][164][165], ketamine, or traxoprodil [93]. Human studies have found similar results by adding adjuvant ketamine [46,54,88,166], as well as gabapentinoids such as pregabalin [49,55] or gabapentin [23], or the cyclooxygenase-2 inhibitor parecoxib [48,167], as reviewed in the subsequent sections. However, more recent research has shown that manipulating these substrates does not unequivocally resolve OIH.…”

“…While some studies suggest that OIH develops after chronic opioid use [41][42][43], both rodent [44,45] and human studies [46][47][48][49] have documented OIH within hours of acute opioid administration. Studies using shorter-acting opioids such as remifentanil, sufentanil, fentanyl, and morphine provide the most suspicion of OIH [49][50][51][52][53][54][55][56]; however, there is documentation of this phenomenon in patients receiving long-acting opioids (e.g., methadone or buprenorphine) as well [23,43,[57][58][59][60].…”

The efficacy of N-methyl-d-aspartate receptor antagonists on improving the postoperative pain intensity and satisfaction after remifentanil-based anesthesia in adults: a meta-analysis

“…In 8 trials, a perioperative use of ketamine was administered [11,[22][23][24][25][26][27][28]. In 5 trials, a preoperative bolus of magnesium sulfate was followed by a continuous infusion throughout surgery [29][30][31][32][33].…”

The influence of dexmedetomidine on remifentanil‑induced hyperalgesia and the sex differences

“…Many experimental studies have been published in this field. Some studies suggested that N-methyl-D-aspartate (NMDA) receptor antagonists such as ketamine may play a role as a useful adjuvant to reduce RIH (6)(7)(8). COX-2 inhibitor parecoxib which were also investigated as nonsteroidal anti-inflammatory drugs were often administered as premedication before surgery (9,10).…”