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The impact of intra-operative sufentanil dosing on post-operative pain, hyperalgesia and morphine consumption after cardiac surgery.

Journal European journal of pain (London, England)
Year 2013
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This article is included in 1 Systematic review Systematic reviews (1 reference)

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BACKGROUND: There is an ongoing debate whether opioids when used for intra-operative analgesia may enhance post-operative pain. We studied the effect of two different intra-operative dosings of sufentanil on post-operative morphine consumption, pain and hyperalgesia after cardiac anaesthesia. METHODS: Forty-two male patients (age: 48-74 years) undergoing first-time coronary artery bypass graft surgery were randomized to one of two groups receiving total intravenous anaesthesia with propofol and a target controlled infusion of sufentanil with a target of 0.4 ng/mL (group SL, n = 20) or 0.8 ng/mL (group SH, n = 22) plasma concentration. Post-operative morphine requirement in the first 48 h was assessed using patient-controlled analgesia (PCA). Pain rating during deep inspiration, and the extent of primary and secondary hyperalgesia near the sternotomy wound were assessed. RESULTS: The post-operative morphine requirements in the first 48 h were 0.68 ± 0.21 mg/kg in group SL and 0.96 ± 0.44 mg/kg in group SH (p < 0.05). In group SL, pain during deep inspiration was significantly lower on the first post-operative day (p < 0.05). Primary hyperalgesia had its maximum on the second and third post-operative day, without a difference between the two groups. The extent of secondary mechanical pinprick hyperalgesia was not different between the groups. DISCUSSION: Intra-operative dosing of sufentanil significantly influenced post-operative morphine consumption, pain and hyperalgesia. For cardiac anaesthesia in combination with propofol, a sufentanil target concentration of 0.4 ng/mL may be preferable.

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Antihyperalgesic effects of dexmedetomidine on high-dose remifentanil-induced hyperalgesia

Authors Lee C , Kim YD , Kim JN
Journal Korean journal of anesthesiology
Year 2013
Links Pubmed DOI PubMed Central

This article is included in 2 Systematic reviews Systematic reviews (2 references)

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Background: Dexmedetomidine is a highly selective α2 adrenergic agonist that has been shown to decrease the intensity of opioid-induced hyperalgesia (OIH). We aimed to investigate the antihyperalgesic effects of dexmedetomidine on high-dose remifentanil-induced hyperalgesia. Methods: Ninety American Society of Anesthesiologists physical status I-II patients undergoing laparoscopically assisted vaginal hysterectomy (LAVH) were randomly assigned to one of the following three groups, each of which received either dexmedetomidine (an initial dose of 1.0 μg/kg for 10 min, followed by a continuous infusion of 0.7 μg/kg/hr) or placebo saline 15 min before the induction of anesthesia and intraoperative remifentanil infusion: group C received a placebo and 0.05 μg/kg/min remifentanil; group RH received a placebo and 0.3 μg/kg/min remifentanil; and group DRH received dexmedetomidine and 0.3 μg/kg/min remifentanil. Results: The mechanical hyperalgesia threshold 24 hr after surgery was significantly lower in group RH than in the other two groups. Postoperative pain intensity using visual analog scale (VAS) and cumulative volume of a patient-controlled analgesia (PCA) containing morphine over 24 hr were significantly greater in group RH than in group DRH. The time to the first postoperative analgesic requirement was significantly shorter in group RH than in the other two groups. The desflurane requirement was significantly greater in group C than in the other groups. The frequency of hypotension and bradycardia was significantly higher, but shivering and postoperative nausea and vomiting were significantly lower in group DRH than in the other two groups. Conclusions: High-doses of remifentanil induced hyperalgesia, which presented a decreased mechanical hyperalgesia threshold, enhanced pain intensity, a shorter time to first postoperative analgesic requirement, and greater morphine consumption, but dexmedetomidine efficiently alleviated those symptoms. Dexmedetomidine may be a novel and effective treatment option for preventing or attenuating OIH. © the Korean Society of Anesthesiologists, 2013.

Primary study

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Intraoperative infusion of 0.6-0.9 µg·kg(-1)·min(-1) remifentanil induces acute tolerance in young children after laparoscopic ureteroneocystostomy.

Authors Kim SH , Lee MH , Seo H , Lee IG , Hong JY , Hwang JH
Journal Anesthesiology
Year 2013
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This article is included in 1 Systematic review Systematic reviews (1 reference)

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BACKGROUND: Intraoperative infusion of opioids has been associated with increased postoperative pain and analgesic requirements, but the development of tolerance in young children is less clear. This prospective, randomized, double-blinded study was designed to test the hypothesis that the intraoperative administration of remifentanil results in postoperative opioid tolerance in a dose-related manner in young children. METHODS: We enrolled 60 children (aged 1-5 yr) who were undergoing elective laparoscopic ureteroneocystostomy. Patients were randomized and received an intraoperative infusion of 0, 0.3, 0.6, or 0.9 µg·kg·min remifentanil. Postoperative pain was managed by a parent/nurse-controlled analgesia pump using fentanyl. The primary outcome included the total fentanyl consumptions at 24 and 48 h postsurgery. Secondary outcomes were the postoperative pain scores and adverse effects. RESULTS: The children who received 0.6 and 0.9 µg·kg·min remifentanil required more postoperative fentanyl than the children who received saline or 0.3 µg·kg·min remifentanil (all P < 0.001) for 24 h after surgery. The children who received 0.3-0.9 µg·kg·min intraoperative remifentanil reported higher pain scores at 1 h after surgery than the children who received saline (P = 0.002, P = 0.023, and P = 0.006, respectively). No significant intergroup differences in recovery variables were observed, but vomiting was more frequent in the 0.9 µg·kg·min remifentanil group than in the other groups (P = 0.027). CONCLUSIONS: The intraoperative use of 0.3 µg·kg·min remifentanil for approximately 3 h (range: 140-265 min) did not induce acute tolerance, but the administration of 0.6 and 0.9 µg·kg·min remifentanil to young children resulted in acute tolerance for 24 h after surgery in an apparently dose-related manner.

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Effect of oral pregabalin on opioid-induced hyperalgesia in patients undergoing laparo-endoscopic single-site urologic surgery

Authors Lee C , Lee HW , Kim JN
Journal Korean journal of anesthesiology
Year 2013
Links Pubmed DOI PubMed Central

This article is included in 7 Systematic reviews Systematic reviews (7 references)

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Background: Pregabalin is an antiepileptic drug that is effective for treating postoperative pain, neuropathic pain, anxiety, and hemodynamic instability. The aim of this study was to investigate the effect of a single preoperative dose of pregabalin in patients with opioid-induced hyperalgesia (OIH). Methods: Ninety ASA I-II patients undergoing laparoendoscopic single-site urologic surgery were randomly assigned to one of the following three groups that received either pregabalin or placebo 1 h before anesthesia and an intraoperative remifentanil infusion. Group plL received placebo and 0.05 μg/kg/min remifentanil, group plH received placebo and 0.3 μg/kg/min remifentanil, and group prH received 300 mg pregabalin plus 0.3 μg/kg/min remifentanil. The primary endpoint was pain intensity upon movement 1, 6, 12, and 24 h after surgery. Secondary endpoints were the area of hyperalgesia and mechanical hyperalgesia threshold 24 h after surgery, time to first postoperative analgesic requirement, and cumulative postoperative volume of morphine administered via a patient- controlled analgesia (PCA) pump over 24 h. Results: The time to first postoperative analgesic requirement in group plH was significantly shorter than that in group plL. The injected PCA volume was significantly greater in group plH than that in the other two groups. Postoperative pain intensity in group plH was significantly greater than that in the other two groups at 6, 12, and 24 h after surgery. The mechanical hyperalgesia threshold and the area of hyperalgesia around the surgical incision 24 h after surgery in group plH differed significantly from those in the other two groups, which were not significantly different. Adverse effects were comparable among groups. Conclusions: High-dose remifentanil induced hyperalgesia, including increased pain intensity, increased area of hyperalgesia, and decreased mechanical hyperalgesia threshold. These effects were attenuated by oral administration of a single preoperative dose of pregabalin (300 mg) in patients undergoing laparo-endoscopic single-site urologic surgery. © The Korean Society of Anesthesiologists, 2013.

Primary study

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Remifentanil used as adjuvant in general anesthesia for spinal fusion does not exhibit acute opioid tolerance

Authors Yeom JH , Kim KH , Chon MS , Byun J , Cho SY
Journal Korean journal of anesthesiology
Year 2012
Links Pubmed DOI PubMed Central

This article is included in 2 Systematic reviews Systematic reviews (2 references)

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Background: Although acute tolerance to opioids, especially to remifentanil, has been demonstrated consistently in animal studies, the results of clinical trials in humans are controversial. The aim of this study was to determine whether intraoperative infusions of remifentanil used as an adjuvant in general anesthesia result in acute tolerance, an event manifested by increased postoperative pain and a higher opioid requirement than usual. Methods: Sixty patients who underwent surgery under general anesthesia for spinal fusion were randomly assigned to receive sevoflurane-nitrous oxide-oxygen (group SO, n = 20), sevoflurane-remifentanil-nitrous oxide-oxygen (group SR, n = 20), or propofol-remifentanil-oxygen (group PR, n = 20) in a double-blinded manner. All patients within 1 hour after induction received PCA (fentanyl 0.4 μg/kg/ml and ondansetron 16 mg) administered intravenously at a basal infusion rate of 1 ml/h, after being intravenously injected with a loading dose of fentanyl (1 μg/kg). Data for fentanyl requirement, verbal Numerical Rating Scale (NRS) pain score at rest, and presence of nausea or vomiting were collected at 1, 24, and 48 hours after surgery. Results: We did not find any significant difference in postoperative PCA fentanyl requirements, NRS or side effects among the groups. Conclusions: Remifentanil as an adjuvant to sevoflurane or propofol in general anesthesia for adults having surgery for spinal fusion does not appear to cause acute opioid tolerance or hyperalgesia in patients. However, further studies are needed to elucidate whether sevoflurane and propofol exert a clinically significant effect on opioid-induced tolerance or hyperalgesia and whether this effect is related to the age of the patient, the dose and duration of remifentanil given and the intensity of pain experienced postoperatively. © the Korean Society of Anesthesiologists, 2012.

Primary study

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Intrathecal fentanyl added to bupivacaine and morphine for cesarean delivery may induce a subtle acute opioid tolerance

Journal International journal of obstetric anesthesia
Year 2012
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This article is included in 1 Systematic review Systematic reviews (1 reference)

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Background: Previous studies have demonstrated that the addition of intrathecal fentanyl to a spinal anesthetic for cesarean delivery improves intraoperative analgesia. However, intrathecal fentanyl may induce acute tolerance to opioids. The objective of this study was to investigate whether the addition of intrathecal fentanyl to spinal anesthesia with intrathecal morphine increases postoperative analgesic requirements and pain scores. Methods: In this randomized, double-blinded study, 40 women having elective cesarean delivery were enrolled. Patients received spinal anesthesia with hyperbaric bupivacaine 12 mg, morphine 200 μg, and fentanyl 0, 5, 10 or 25 μg. Each patient received intravenous patient-controlled analgesia morphine for 24 h postoperatively. Outcome measures included postoperative morphine usage and pain scores, as well as intraoperative pain, nausea, hypotension and vasopressor use. Results: Total morphine use over the 24-h post-spinal study period was similar among the study groups (P = 0.129). Postoperative pain scores were higher in patients receiving fentanyl 5, 10 and 25 μg compared to fentanyl 0 μg control group (P = 0.003). Conclusions: The study results suggest that intrathecal fentanyl may induce acute tolerance to intrathecal morphine. However, because there was no difference in postoperative analgesia requirement and the difference in pain scores was small, the clinical significance of this finding is uncertain. © 2011 Elsevier Ltd. All rights reserved.

Primary study

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The effects of magnesium sulfate infiltration on perioperative opioid consumption and opioid-induced hyperalgesia in patients undergoing robot-assisted laparoscopic prostatectomy with remifentanil-based anesthesia

Authors Lee C , Song YK , Jeong HM , Park SN
Journal Korean journal of anesthesiology
Year 2011
Links Pubmed DOI PubMed Central

This article is included in 2 Systematic reviews Systematic reviews (2 references)

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Background: Opioids not only exert an antinociceptive effect, but also modulate central N-methyl-D-aspartate (NMDA) receptors, resulting in hyperalgesia and acute opioid tolerance. This study was aimed to investigate the effect of the NMDA receptor antagonist, magnesium in preventing remifentanil-induced hyperalgesia. Methods: For this study, 75 patients scheduled for robot-assisted laparoscopic prostatectomy were randomly allocated into three groups of patients whose incision sites were infiltrated: Group M, with 25% magnesium sulfate 80 mg/kg; Group S, with the same volume of saline under remifentanil-based anesthesia, and Group D, with the same volume of saline under desflurane based anesthesia. All three groups were infiltrated into incision sites after pneumoperitoneum. Intraoperative evaluation included mean remifentanil dose, and postoperative evaluation included pain severity at time intervals of 30 min, 6, 12, 24 and 36 hours, time to first postoperative analgesic requirement, and analgesic dosage required during 24 hours. Results: Mean remifentanil doses during the intraoperative periods in group M were significantly lower than those in group S (P < 0.001). The time to first postoperative analgesic requirement in postoperative period in groups M and D was significantly longer than that in group S (P < 0.001). Visual analog scale scores for pain in groups M and D were significantly lower than those in group S for 12 hours after operation. Conclusions: A relatively high dose and continuous infusion of remifentanil were associated with opioid induced hyperalgesia. Wound infiltration with magnesium sulfate decreased opioid consumption and reduces opioid induced hyperalgesia. © the Korean Society of Anesthesiologists, 2011.

Primary study

Unclassified

Target-controlled dosing of remifentanil during cardiac surgery reduces postoperative hyperalgesia

Journal Journal of cardiothoracic and vascular anesthesia
Year 2011
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This article is included in 2 Systematic reviews Systematic reviews (2 references)

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Objective: One of the strategies to attenuate opioid-induced hyperalgesia (OIH) may be to decrease intraoperative doses of opioids by using target-controlled infusion (TCI). Design: Double-blind and randomized study. Setting: A single university hospital. Participants: Forty American Society of Anesthesiologists II to III patients scheduled for elective cardiac surgery. Interventions: patients were randomized to 1 of the 2 groups: 1 group received an infusion of intraoperative remifentanil using TCI (target: 7 ng/mL), and the 2nd one was given an intraoperative continuous infusion (CI) (0.3 μg/kg/min). The anesthestic protocol and postoperative pain management were the same in both groups. The extent of mechanical dynamic hyperalgesia on the middle line perpendicular to the wound was considered the primary endpoint. The secondary endpoints were other results of dynamic and punctuate hyperalgesia until postoperative day 7, visual analog scale (VAS) and verbal rating scale (VRS) scores, and total morphine consumption until postoperative day 2. Measurements and Main Results: Morphometric and demographic characteristics and duration of surgery were comparable in both groups. Intraoperative remifentanil consumption was greater in CI than in TCI group (5,329 [1,833] v 3,662 [1,160] μg, p = 0.003). During the first 44 hours, there were no differences in morphine consumption, VAS, and VRS. The extent of hyperalgesia was significantly lower on postoperative days 1, 2, and 4 in the TCI group than in the CI group on the 3 evaluated lines (p < 0.05). Punctuate hyperalgesia evaluating 3 different points was lower in the TCI than in the CI group from postoperative day 1 until postoperative day 7 (p < 0.05). Conclusions: The intraoperative decrease of opioid consumption when comparing the CI versus TCI mode of administration of remifentanil led to less OIH after cardiac surgery.

Primary study

Unclassified

The effects of intraoperative adenosine infusion on acute opioid tolerance and opioid induced hyperalgesia induced by remifentanil in adult patients undergoing tonsillectomy

Authors Lee C , Song YK , Lee JH , Ha SM
Journal The Korean journal of pain
Year 2011
Links Pubmed DOI PubMed Central

This article is included in 1 Systematic review Systematic reviews (1 reference)

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Background: Adenosine has been shown to have a wide spectrum of unique pain-relieving effects in various clinical situations. The aim of this study was to investigate the effects of intraoperative adenosine infusion on acute opioid tolerance and opioid induced hyperalgesia induced by remifentanil in adult patients undergoing tonsillectomy. Methods: For this study, ninety patients were randomly allocated into groups that receive either adenosine (adenosine group) or saline (remifentnail group) intravenously under remifentanil based anesthesia and saline (sevoflurane group) under sevoflurane anesthesia. The patients in adenosine group received adenosine at dose of 80 μg/kg/min, and those in remifentnail group and sevoflurane group received an equal volume of saline 10 minutes after the induction of anesthesia until the end of surgery. Intraoperative evaluation included time weighted mean remifentanil dose, and postoperative evaluations included degree of pain severity at 1, 6, 12, and 24 hours, time to first postoperative requirement, and analgesic dose required during 24 hours after operation. Results: Time weighted mean remifentanil dose during intraoperative period in adenosine group was significantly lower than that of remifentnail group (P = 0.00). The first postoperative analgesic were required earlier in remifentanil group than sevoflurane group or adenosine group (P = 0.00). Pethidine requirement during 24 hours in sevoflurane group and adenosine group was significantly lower than that of remifentnail group (P = 0.00). The visual analog scale scores for pain in sevoflurane group and adenosine group were significantly lower than those of remifentnail group for 12 hours after operation (P = 0.00). Incidence of hypotension (P = 0.024) and number of ephedrine administered (P = 0.011) in adenosine group were significantly higher than those of sevoflurane group. Conclusions: The above results suggest that intraoperative adenosine infusion prevent acute opioid tolerance and opioid induced hyperalgesia induced by remifentanil. © 2011 The Korean Pain Society.

Primary study

Unclassified

Magnesium sulfate prevents remifentanil-induced postoperative hyperalgesia in patients undergoing thyroidectomy.

Authors Song JW , Lee YW , Yoon KB , Park SJ , Shim YH
Journal Anesthesia and analgesia
Year 2011
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This article is included in 2 Systematic reviews Systematic reviews (2 references)

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BACKGROUND: In a randomized, double-blind, prospective study, we investigated whether an intraoperative high versus low dose of remifentanil increased postoperative hyperalgesia and whether magnesium can prevent remifentanil-induced hyperalgesia. METHODS: Ninety patients undergoing thyroidectomy were randomly assigned to 1 of 3 groups. Remifentanil was intraoperatively infused at 0.05 μg/kg/min (group LO) or 0.2 μg/kg/min (groups HI and HM). Patients in group HM received MgSO(4) 30 mg/kg at induction followed by an intraoperative infusion of 10 mg/kg/h. Mechanical pain thresholds on the forearm and periincisional area were assessed by von Frey filament the evening before surgery and postoperatively at 24 and 48 hours. Pain measured on a verbal numerical rating scale (VNRS) (0-10) and additional analgesics were recorded in the postanesthesia care unit postoperatively at 6, 24, and 48 hours. RESULTS: There was a significantly greater decrease in pain threshold on the periincisional area at 24 and 48 hours postoperatively in group HI, as compared with the other 2 groups. The 95% confidence intervals for the mean difference in pain thresholds on the periincisional area at 24 and 48 hours postoperatively were 0.31 to 1.11 and 0.36 to 1.14 for group HI versus group LO, 0.45 to 1.26 and 0.54 to 1.32 for group HI versus group HM (values are log(10) of force in milligrams). The change in pain threshold on the forearm was similar among the groups. Group HI had significantly higher VNRS scores (median [interquartile range], 3 [2-4]) than group LO (2 [1-3] and group HM (2 [1-3]) at 48 hours postoperatively. The 95% confidence intervals for median difference in VNRS score at 48 hours postoperatively were 1 to 2 for group HI versus group LO and 0 to 2 for group HI versus group HM. There were no significant differences in the number of patients who requested rescue analgesics in the postoperative anesthesia care unit and general ward during 48 hours postoperatively among the 3 groups. CONCLUSIONS: A relatively high dose of intraoperative remifentanil enhances periincisional hyperalgesia. Intraoperative MgSO(4) prevents remifentanil-induced hyperalgesia. However, hyperalgesia did not reach clinical relevance in terms of postoperative pain or analgesic consumption in patients undergoing thyroidectomy.