Article

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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    • "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: 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.
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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.
    Full-text · Article · May 2014 · Frontiers in Pharmacology
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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.
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