Article

Development of Acute Opioid Tolerance During Infusion of Remifentanil for Pediatric Scoliosis Surgery

Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada
Anesthesia and analgesia (Impact Factor: 3.47). 06/2006; 102(6):1662-7. DOI: 10.1213/01.ane.0000216036.95705.c2
Source: PubMed

ABSTRACT

We tested the hypothesis that continuous intraoperative infusion of remifentanil is associated with the development of clinically relevant acute opioid tolerance in adolescents undergoing scoliosis surgery. Thirty adolescents were randomly assigned to receive an intraoperative analgesic regimen consisting of continuous remifentanil infusion or intermittent morphine alone. Postoperative analgesic consumption was assessed with a patient-controlled analgesia device that was used to self-administer morphine. Cumulative postoperative morphine consumption, pain scores, and sedation scores were recorded by a blinded investigator every hour for the first 4 h postoperatively and then every 4 h for a total of 24 h. Cumulative morphine consumption in the remifentanil group was significantly more than that in the morphine group at each time point in the initial 24 h after surgery (P < 0.0001). At 24 h after surgery, cumulative morphine consumption was 30% greater in the remifentanil group (1.65 +/- 0.41 mg/kg) than in the morphine group (1.27 +/- 0.32 mg/kg) (95% confidence interval for the difference, 0.11 to 0.65 mg/kg). Differences in pain and sedation scores were not statistically significant. These data suggest that intraoperative infusion of remifentanil is associated with the development of clinically relevant acute opioid tolerance in adolescents undergoing scoliosis surgery.

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Available from: Basem Naser, Mar 14, 2014
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    • "Joly et al. (2005), in their randomized , double-blind study, showed that intraoperative remifentanil of 0.4 μg/kg/min triggered the larger hyperalgesia as well as the larger morphine consumption for 48 postoperative hours, compared with remifentanil of 0.05 μg/kg/min. In prospective, randomized, double-blind study, they suggested that remifentanil of mean 0.28 μg/kg/min was associated with the development of clinically relevant AOT, in patients underwent the general anesthesia using propofol infusion (Crawford et al., 2006). Many authors showed that the OIH can develop differently for different types of pain such as transdermal electrical stimulation (Angst et al., 2003; Hood et al., 2003; Koppert et al., 2003a,b; Troster et al., 2006), cold pressor pain (Compton et al., 2003, 2004), and pressure-evoked pain (Luginbuhl et al., 2003). "
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    ABSTRACT: The use of opioids may seem to be a double-edged sword; they provide straight analgesic and antihyperalgesic effects initially, but subsequently are associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) that have been reported in experimental studies and clinical observations. It has been suggested that opioids can induce an acute tolerance and hyperalgesia in dose- and/or time-dependent manners even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management in clinical anesthesia and in the intensive care units because of its rapid onset and offset. We reviewed articles analyzing AOT and/or OIH by remifentanil and focused on the following issues: (1) evidence of remifentanil inducing AOT and/or OIH and (2) importance of AOT and/or OIH in considering the reduction of remifentanil dosage or adopting preventive modulations. Twenty-four experimental and clinical studies were identified using electronic searches of MEDLINE (PubMed, Ovid, Springer, and Elsevier). However, the development of AOT and OIH by remifentanil administration remains controversial. There is no sufficient evidence to support or refute the existence of OIH in humans.
    Full-text · Article · Mar 2015 · American journal of therapeutics
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    • "Joly et al. (2005), in their randomized, double-blind study, showed that intraoperative remifentanil of 0.4 μg/kg/min triggered the larger hyperalgesia as well as the larger morphine consumption for 48 postoperative hours, compared with remifentanil of 0.05 μg/kg/min. In prospective, randomized, double-blind study, they suggested that remifentanil of mean 0.28 μg/kg/min was associated with the development of clinically relevant AOT, in patients underwent the general anesthesia using propofol infusion (Crawford et al., 2006). "
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    ABSTRACT: Introduction The use of opioids has been increasing in operating room and intensive care unit to provide perioperative analgesia as well as stable hemodynamics. However, many authors have suggested that the use of opioids is associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) in experimental studies and clinical observations in dose and/or time dependent exposure even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management during anesthesia as well as in the intensive care units because of its rapid onset and offset. Objectives Search of the available literature to assess remifentanil AOT and OIH based on available published data. Methods We reviewed articles analyzing remifentanil AOT and OIH, and focused our literature search on evidence based information. Experimental and clinical studies were identified using electronic searches of Medline (PubMed, Ovid, Springer, and Elsevier, ClinicalKey). Results Our results showed that the development of remifentanil AOT and OIH is a clinically significant phenomenon requiring further research. Discussions and Conclusions AOT - defined as an increase in the required opioid dose to maintain adequate analgesia, and OIH - defined as decreased pain threshold, should be suspected with any unexplained pain report unassociated with the disease progression. The clinical significance of these findings was evaluated taking into account multiple methodological issues including the dose and duration of opioids administration, the different infusion mode, the co-administrated anesthetic drug’s effect, method assessing pain sensitivity, and the repetitive and potentially tissue damaging nature of the stimuli used to determine the threshold during opioid infusion. Future studies need to investigate the contribution of remifentanil induced hyperalgesia to chronic pain and the role of pharmacological modulation to reverse this process.
    Full-text · Article · May 2014 · Frontiers in Pharmacology
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    • "Remifentanil, a potent, ultra-short acting μ-opioid receptor agonist, has been gaining popularity in clinical anesthesia. In humans, there are several reports that intraoperative remifentanil can be associated with the development of AOT, which is evidenced by an increased post-operative opioid consumption [10,11]. In contrast, there are also negative reports that intraoperative remifentanil does not cause AOT [12,13]. "
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    ABSTRACT: Background Acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) are undesirable effects of opioids that have been reported in both animals and humans. However, the development of AOT and OIH in cases of potent, short-acting μ-opioid receptor agonist remifentanil administration remains controversial. It has been suggested that the emergence of AOT and OIH by remifentanil could be dose and infusion duration dependent, i.e., low dose and short infusions may lead to negative results. In this study, we determined whether AOT and OIH could be elicited by prolonged, continuous administration of remifentanil at maximally tolerable doses in C57BL/6 mice. Results The analgesic effects of continuously administered remifentanil [by short (1 h) and prolonged (4 h) intraperitoneal infusions] were studied. These experiments involved repeated measurements of thermal thresholds during remifentanil administration. Therefore, particular attention was paid to prevent cumulative tissue injury, which could mimic pronociceptive effects of remifentanil. To exclude the possibility of pseudoAOT during infusion, we used brief cooling of all ipsilateral hindpaws that exhibited analgesic response. Thermal thresholds remained steadily elevated over a 1-h period during continuous administration at infusion rates of 120, 180, and 240 mg/kg/h, which indicated no AOT development. To exclude the possibility of pseudoOIH after infusion, intact contralateral hindpaws were used for all postinfusion threshold measurements. Thermal thresholds at each infusion rate returned to the baseline values within 15 min after the termination of the administration. They did not decrease below the baseline values during 1 h following infusion, which indicated no OIH development. Similar threshold dynamics were also observed for thermal and mechanical testing modalities in animals infused at 120 mg/kg/h for 4 h as well as in animals with rapidly attained and maintained maximum analgesia for 3 h. Conclusions These results suggest that neither intra-infusion AOT nor postinfusion OIH develops in mice receiving continuous remifentanil when the possibility of cumulative tissue injury mimicking AOT or OIH is carefully avoided.
    Full-text · Article · Mar 2013 · Molecular Pain
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