Does intrathecal fentanyl produce acute cross-tolerance to i.v. morphine?

Department of Anaesthetics, South Cleveland Hospital, Middlesbrough.
BJA British Journal of Anaesthesia (Impact Factor: 4.85). 04/1997; 78(3):311-3. DOI: 10.1093/bja/78.3.311
Source: PubMed

ABSTRACT We have examined the hypothesis that intrathecal fentanyl at operation can increase postoperative i.v. morphine requirements. We studied 60 patients undergoing Caesarean section. All received intrathecal 0.5% plain bupivacaine 2 ml combined with either fentanyl 0.5 ml (25 micrograms) (group F) (n = 30) or normal saline 0.5 ml (group S) (n = 30). In addition, 10 ml of an extradural solution (fentanyl 1 ml (50 micrograms) combined with 0.5% bupivacaine 9 ml) was administered after delivery. Extradural solution was only given before delivery if the intrathecal injection failed to produce a block above T6 or the patient required further analgesia. Postoperative analgesia was provided with i.v. morphine patient-controlled analgesia. At operation, intrathecal fentanyl reduced the need to administer extradural solution before delivery, increased the anaesthetist's satisfaction with analgesia and reduced nausea, but increased pruritus. Up to 6 h after delivery there was no difference in postoperative morphine requirements or pain scores. Between 6 h and 23 h there was a 63% increase in morphine requirements in group F. We consider the most likely explanation for this finding to be that intrathecal fentanyl induced acute spinal opioid tolerance.

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Available from: David W Cooper, Apr 24, 2014
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    • "A small number of clinical studies have looked at AOT and OIH in the setting of acute perioperative opioid exposure. A series of studies in patients undergoing surgery suggested that exposure to a high rather than to a low intraoperative opioid dose was associated with the increased opioid consumption and/or pain in the postoperative period (Cooper et al., 1997; Chia et al., 1999; Guignard et al., 2000; Joly et al., 2005). A feasible explanation for these findings is either the development of acute tolerance on the rescue opioids for controlling the postoperative pain or a possible OIH in patients exposed to a high intraoperative opioid dose (Angst and Clark, 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.
    Frontiers in Pharmacology 05/2014; 5(article 108):108. DOI:10.3389/fphar.2014.00108 · 3.80 Impact Factor
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    • "However, a placebo-controlled follow-up study using a similar experimental paradigm did not detect evidence for the development of acute tolerance [19]. A series of studies in patients undergoing surgery suggested that exposure to a high rather than to a low intraoperative opioid dose was associated with increased pain and/or opioid consumption in the postoperative period [7] [10] [18] [24]. A possible explanation for these findings is the development of acute tolerance in patients exposed to a high intraoperative opioid dose. "
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    ABSTRACT: It is widely accepted that chronic opioid therapy is associated with the development of pharmacological tolerance. More controversial is the question as to whether acute opioid administration can result in "acute tolerance." The aim of this double-blind, placebo-controlled study in thirty-six healthy human volunteers was to examine whether a 3-h intravenous infusion delivering two different but clinically relevant doses of the mu-opioid receptor agonist remifentanil would result in tolerance to analgesic, respiratory depressant and/or sedative opioid effects. The blood remifentanil concentration versus opioid effect relationship was determined before and after the 3-h infusion. Tolerance was inferred if the potency of remifentanil was significantly lower after the 3-h infusion. Opioid analgesia was assessed with the aid of the cold pressor test and models of electrical and heat pain. Respiratory depression was assessed by measuring arterial pCO2 and minute ventilation. Subjective sedation scores were assessed on a visual analogue scale. Mixed effects modeling was used to relate the steady-state blood remifentanil concentration to each pharmacodynamic assessment. Neither dose of remifentanil produced detectable tolerance to any of the measured opioid effects following a 3-h infusion. The study was adequately powered to detect a decrease in potency of 5-24% for analgesia, 20-48% for respiratory depression, and 32% for sedative effects. These results suggest that short-term administration of clinically useful doses of remifentanil is not associated with the development of significant tolerance to analgesic, respiratory depressant, or sedative opioid effects.
    Pain 02/2009; 142(1-2):17-26. DOI:10.1016/j.pain.2008.11.001 · 5.21 Impact Factor
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    • "Of greater clinical import, however, the present data (Fig 4) confirm evidence (Li et al., 2001; Rivat et al., 2002) that this so-called (Colpaert, 1996) 2nd order hyperalgesia also occurs with ongoing pain; in fact, the same 0.63 mg/kg remifentanil injection in normal rats produced no detectable hyperalgesia in the Randall- Selitto assay (Fig. 1). Pretreatment with fentanyl in addition to bupivacaine in women undergoing Caesarian section reduced the analgesic requirement before delivery, but increased it between 6 and 23 h later (Cooper et al., 1997). Also, in patients undergoing major abdominal surgery, the intra-operative use of a high as opposed to a low dose of fentanyl or remifentanil increased postoperative pain intensity and patient-controlled opioid consumption (Chia et al., 1999; Guignard et al., 2000). "
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    ABSTRACT: F 13640 is a newly discovered high-efficacy 5-HT(1A) receptor agonist that produces exceptional analgesia in animal models of tonic and chronic, nociceptive and neuropathic pains by novel molecular and neuroadaptive mechanisms. Here we examined the effects of F 13640 and remifentanil (0.63 mg/kg with either compound) when injected i.p. either before or 15 min after rats underwent orthopedic surgery. Surgery consisted of the drilling of a hole in the calcaneus bone and of an incision of the skin, fascia and plantar muscle of one foot. During surgery, the concentration of volatile isoflurane was progressively incremented depending on the animal's response to surgical maneuvers. Other experiments examined the dose-dependent effects of F 13640 (0.04 to 0.63 mg/kg) on surgical pain as well as on the Minimum Alveolar Concentration of isoflurane. Both F 13640 and remifentanil markedly reduced the intra-operative isoflurane requirement. F 13640 also reduced measures of postoperative pain (i.e., paw elevation and flexion). With these postoperative measures, remifentanil produced short-lived analgesia followed by hyperalgesia. F 13640 significantly reduced both surgical pain and the isoflurane Minimum Alveolar Concentration from 0.16 mg/kg onward. F 13640 produced powerful intra- and postoperative analgesia in rats undergoing orthopedic surgery. Unlike the opioid, remifentanil, F 13640 caused no hyperalgesia with ongoing postoperative pain, and should remain effective with protracted postoperative use.
    European Journal of Pharmacology 11/2005; 523(1-3):29-39. DOI:10.1016/j.ejphar.2005.09.003 · 2.53 Impact Factor
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