The analgesic effect of nefopam combined with low dose remifentanil in patients undergoing middle ear surgery under desflurane anesthesia: a randomized controlled trial / 대한마취과학회지

BACKGROUND: We investigated the effects of the combined administration of nefopam, a N-methyl-D-aspartate receptor antagonist and low dose remifentanil, on early postoperative pain and analgesic requirement. METHODS: Fifty patients scheduled to undergo mastoidectomy and tympanoplasty were randomized to be given either nefopam 40 mg mixed with normal saline 100 ml (Group N) or an equal amount of normal saline (Group C) before anesthesia induction. Anesthesia was maintained with 5-6 vol% desflurane and remifentanil 0.05-0.15 microg/kg/min during the surgery. Postoperative pain was controlled by titration of ketorolac in the postanesthesia care unit (PACU) and ward. We evaluated the intraoperative remifentanil dose, recovery profiles, ketorolac demand in the PACU and ward, numeric rating scale (NRS) for pain at time intervals of every 10 min for 1 h in the PACU, 6, 12, 18 and 24 h in a ward, as well as the time to first analgesic requirement in the PACU and ward. RESULTS: Ketorolac demand and NRS in the PACU were significantly lower in Group N than Group C (P = 0.002, P = 0.005, respectively). The time to first analgesic requirement in the PACU in Group N were significantly longer than Group C (P = 0.046). There were no significant differences in intraoperative remifentanil dose, ketorolac demand, NRS, and the time to first analgesic requirement in the ward between the groups. CONCLUSIONS: Nefopam administration combined with low dose remifentanil infusion reduces pain and analgesic consumption during the immediate postoperative period in patients undergoing middle ear surgery under desflurane anesthesia.

Magnesium Sulfate Attenuate Opioid Tolerance in Patients undergoing Major Abdominal Surgery

BACKGROUND: Magnesium is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. Magnesium is thought to be involved in opioid tolerance by way of inhibiting calcium entry into cells. METHODS: The patients were randomly assigned to three groups according to the anesthetic regimens: Group M received magnesium sulfate and Group C received saline intravenously under remifentanil-based anesthesia. Group S received saline intravenously under sevoflurane based anesthesia in place of remifentanil. The patients in the group M received 25% magnesium sulfate 50 mg/kg in 100 ml of saline, and those patients in groups C and S received an equal volume of saline before induction of anesthesia; this was followed by 10 mg/kg/h infusion of either magnesium sulfate (group M) or an equal volume of saline (groups C and S) until the end of surgery. Pain was assessed on a visual analog scale at 1, 6, 12, 24, and 36 hours after the operation. The time to the first postoperative analgesic requirement and the cumulative analgesic consumption were evaluated in the three groups. RESULTS: The visual analog scales for pain and the cumulative analgesic consumption were significantly greater in group C than in other groups. The time to first postoperative analgesic requirement was significantly shorter in group C than that in the other groups. There were no differences between group M and S for side effects. CONCLUSIONS: A relatively high dose and continuous remifentanil infusion is associated with clinically relevant evidence of acute opioid tolerance. NMDA-receptor antagonist, magnesium sulfate as an adjuvant analgesic prevents opioid tolerance in patients who are undergoing major abdominal surgery under high dose and continuous remifentanil infusion-based anesthesia.

A Double-blinded, Randomized, Placebo Controlled Study of the Effect a Small Dose of Ketamine has on Postoperative Pain of Sevoflurane-remifentanil Anesthesia / 대한마취과학회지

BACKGROUND: Remifentanil is a useful and relatively safe opioid, but acute tolerance to it frequently develops, as patients who have received remifentanil based anesthesia often suffer postoperative hyperalgesia.This study investigated whether a small dose of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, can attenuate postoperative pain suffered with remifentanil anesthesia. METHODS: 32 patients who were scheduled to undergo laparoscopic cholecystectomy were randomly assigned to two groups: a ketamine group (group K) and a control group (group C).All patients were given remifentanil by target controlled infusion (TCI) to the effect site (concentrations:4.0-6.0 ng/ml).Just before incision patients in group K received 0.15 mg/kg ketamine intravenously and patients in group C received the same volume, but only of normal saline.Pain scores measured by Numerical Rating Scale (NRS) and additional use of analgesics were immediately recorded by a blinded investigator at the post-anesthesia care unit (PACU) and general ward up to 24 hours after surgery. RESULTS: The average NRS scores upon arrival to PACU, 5, 10, 15 and 30 min in PACU, and 5 hours after discharge from PACU were significantly lower in group K than group C.The frequency of additional analgesics use was also significantly lower in group K. CONCLUSIONS: It is suggested that a small dose of ketamine attenuates the postoperative pain felt with remifentanil anesthesia. This finding also suggests that ketamine may decrease the possible acute tolerance developed with remifentanil anesthesia.

Effect of remifentanil on postoperative pain in gynecologic surgery with sevoflurane anesthesia / 대한마취과학회지

BACKGROUND: Rapid development of acute opioid tolerance and hyperalgesia is well established in animal studies and is more likely to occur with large doses of short-acting drugs. Several experimental and clinical studies of varied design that have been conducted in humans comparing remifentanil with other routinely used anesthetics or placebo preparations have produced conflicting results. The aim of this study was to investigate whether remifentanil had any impact on postoperative pain after gynecologic surgery. METHODS: Sixty patients undergoing gynecological surgery were randomly allocated into three groups (each n=20): N group with normal saline, L group with target-controlled infusion (TCI) of 1 ng/ml remifentanil, and H group with TCI of 3 ng/ml remifentanil. All patients were anesthetized with sevoflurane to maintain mean arterial pressure within 20% of basal values. Thirty minutes before the end of surgery, patients received morphine sulfate through a patient-controlled infusion device. Pain scores, sedation scores, and analgesic requirements were recorded for 48 hours postoperatively. RESULTS: The mean remifentanil infusion dose of the H group was significantly higher than that of the L group. The VAS scores of the L and H groups were significantly higher than those of the N group only at the postanesthetic care unit and not at the ward. CONCLUSIONS: Intraoperative use of remifentanil with sevoflurane may be related to increased postoperative pain during early postanesthetic period. Provision for effective preventive and therapeutic management strategies in case of intraoperative remifentanil use may be reasonable.

Opioid rotation to oral morphine in the treatment of cancer pain not responding to transdermal fentanyl escalation

<b>Purpose</b>; Transdermal fentanyl (TF) has less systemic adverse effects as compared to morphine. However, few patients with cancer related pain obtain insufficient analgesic response despite the dose escalation of TF. The aims of this study were to describe patients with poor analgesic response and to evaluate the efficacy of opioid rotation from TF to oral morphine. <b>Case reports</b>; We conducted a retrospective chart review and analyzed six patients managed with opioid rotation in detail. Before opioid rotation, an average dose of TF was 204μg/hr. A significant decrease in pain score was found in all patients who switched to oral morphine, and five patients were treated with the combination of TF and oral morphine. <b>Conclusion</b>; These results may indicate that patients who are treated with relative high dose TF (over 200μg/hr) tended to response to poor analgesic, and opioid rotation is beneficial to restore the analgesic effects. We speculate that this clinical phenomenon is associated with opioid tolerance.

Effects of ketamine on preventing the increase of postoperative morphine requirement induced by fentanyl / 中国临床药理学与治疗学

AIM: To observe the effects of ketamine on preventing the increase of postoperative morphine requirement induced by fentanyl.METHODS: Sixty women undergoing total abdominal hysterectomy by spinal anaesthesia were assigned to 4 groups consisting of placebo(normal saline,C),fentanyl(3 bolus of 1 ?g/kg,at 15 min intervals,F),ketamine(infusion of 15 ?g?kg-1?min-1 ketamine from the skin incision until 20 min before the end of the surgery,K),ketamine and fentanyl(infusion of 15 ?g?kg-1?min-1 ketamine from the skin incision until 20 min before the end of the surgery plus 3 bolus of 1 ?g/kg fentanyl,at 15-min intervals,FK).The cumulative morphine consumption,pain score,and adverse effects(nausea, vomiting,hallucination,dizziness and itching) were recorded at 1,3,6,12,24,48 h postoperatively.RESULTS: There were no significant differences in age,weight,duration of surgery and the post-operative sensory block time.The cumulative morphine consumption in group F was significantly higher than those in group C at 3,6,12 h postoperatively(P