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Re: Efficacy of intraoperative morphine
- Frederic Aubrun, Bruno Riou (13 March 2007)
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Efficacy of intraoperative morphine
- Hernán R. Muñoz, Luis I. Cortínez (19 December 2006)
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Frederic Aubrun, MD, PhD , Bruno Riou
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Efficacy of intraoperative morphine. Munoz HR et al. article ID: 98/1/124. I wish to thank Dr. Mùnoz et al. for their comments and offer the following response. Pico et al performed morphine titration in the operating room using an empirical variable: the respiratory rate.1They did not calculate the number of patients needed to decrease the level of pain or morphine consumption because they could not estimate the time to achieve pain relief in PACU using a peroperative morphine titration. With only 20 patients in each group, they recorded a wide range of intraoperative morphine dose to control pain in PACU. In our study protocol, we administered a fixed bolus of 0.15 mg.kg-1 morphine immediately before the end of the surgical procedure, at skin closure. This dose was based on previous results about morphine requirements in the immediate postoperative period.2-3 We could not control the “time variable”. The time between morphine or placebo administration and the end of surgery was 26 ± 21 vs 23 ± 16 min (NS) and the time between the arrival in PACU and the start of morphine titration was 32 ± 39 vs 29 ± 40 min (NS) and so there was a long delay for morphine to reach efficient concentrations. Moreover, there were no significant differences in both groups in the time between morphine/placebo administration and tracheal extubation (59 vs 63 min). In the same way, elimination half life of sufentanil is approximately 2.7 hrs4 and this opioid probably “pollutes” analgesic effect of morphine in the perioperative period. We think that a fixed dose of morphine is probably not adapted to all patients with moderate or severe predictable pain. Firstly, (severe) postoperative pain depends on pre- and peroperative predictive factors as the preoperative treatment or the dose of sufentanil. Secondly, we did not specifically assess the effect of a loading dose after moderate or major surgery. The type of surgery was heterogeneous and I agree with Dr. Mùnoz that the risk of over- or underdosage increases with a fixed dose of anticipated morphine analgesia. This remark applies also in emergency conditions with an inadequate control of moderate or severe pain after a fixed dose of morphine.5 Lastly, Dr. Munoz suggests that morphine is extremely slow to reach its maximal effect but it should be pointed out that most patients experienced complete pain relief during iv morphine administration after only 3-4 boluses, i.e. 15-20 min in our protocol,2-3 which do not represents a such long delay, particularly for complete pain relief. sincerely, Frédéric Aubrun, MD, PhD. 1- Pico L, Hernot S, Nègre I et al. Peroperative titration of morphine improves immediate postoperative analgesia after total hip arthroplasty. Can J Anaesth 2000; 47: 309-14. 2- Aubrun F, Langeron O, Quesnel C et al. Relationship between measurement of pain using visual analog score and morphine requirements during postoperative intravenous morphine titration. Anesthesiology 2003; 9: 1415 -21. 3- Aubrun F, Monsel S, Langeron O et al. Postoperative titration of intravenous morphine. Eur J Anaesthesiol 2001; 18: 159-65. 4- Monk JP, Beresford R, Ward A. Sufentanil: a review of its pharmacological properties and therapeutic uses. Drugs 1988; 36: 286-313. 5- Bijur PE, Kenny MK, Gallagher EJ. Intravenous morphine at 0.1 mg/kg is not effective for controlling severe acute pain in the majority of patients. Annals of Emergency Med 2005; 46: 362-7. Conflict of Interest:None declared |
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Hernán R. Muñoz Departamento de Anestesiología. Facultad de Medicina. Ponificia Universidad Católica de Chile, Luis I. Cortínez
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Editor- We have read with interest the study by Aubrun and colleages1 on the administration of intraoperative morphine during anaesthesia with isoflurane, nitrous oxide and sufentanil. The main findings were that the intraoperative loading dose of morphine slightly reduced (in a statistical but not clinically significant manner) the postoperative pain intensity and did not reduce the postoperative morphine consumption. Although the incidence of sedation in the post-anaesthesia care unit (PACU) was doubled in the group that received morphine, since it was not considered an opiate related adverse effect, intraoperative morphine was not associated with more adverse effects compared with placebo. Since we believe that postoperative sedation can be produced or enhanced by morphine, we think that the practical conclusion from Aubrun’s study can be that “intraoperative morphine does not reduce early postoperative pain but increases the rate of adverse effects”. But why is this so if some studies have shown that intraoperative morphine administration results in an improved control of pain with no more (or even less) adverse affects?2 3 The study by Pico and colleagues2 shifted the early postoperative morphine titration to the last stage of the intraoperative period during skin closure with patients breathing spontaneously. The aim of titration was to reduce the respiratory rate to 12 bpm. A wide range of intraoperative morphine (2 – 20 mg) was needed but these patients had an easier control of pain and less clinical respiratory depression in the PACU than control patients. In contrast, by giving a fixed dose of morphine in mg kg-1, as in Aubrun’s study, the risk of having either overdosed patients resulting in more adverse effects or underdosed patients resulting in suboptimal pain management, increases. An additional factor is the time for morphine to work. All recent experimental evidence in humans show that morphine is extremely slow to reach its maximal effect4-6 and in a clinical study we found that during remifentanil anaesthesia intraoperative morphine is more effective than placebo only when it is given more than 40 minutes before the end of surgery.3 Thus, more time for morphine to work is also an explanation for the results in the study by Pico and coworkers.2 In the study by Aubrun and colleagues the mean±SD time for morphine administration was 59±26 minutes before tracheal extubation and it was not a controlled variable. It would have been interesting to analyze the influence of both the time of morphine administration and the time of the last dose of sufentanil on the final effect of morphine. Hernán R. Muñoz Luis I. Cortínez Departamento de Anestesiología Facultad de Medicina Pontificia Universidad Católica de Chile e-mail: hmunoz@med.puc.cl 1. Aubrun F, Amour J, Rosenthal D, Coriat P, Riou B. Effects of a loading dose of morphine before i.v. morphine titration for postoperative pain relief: a randomized, double-blind, placebo-control study. Br J Anaesth 2007;98:124-30. 2. Pico L, Hernot S, Nègre I, Samii K, Fletcher D. Intraoperative titration of morphine improves immediate postoperative analgesia after total hip arthroplasty. Can J Anaesth 2000;47:309-14. 3. Muñoz HR, Guerrero ME, Brandes V, Cortínez LI. Effect of timing of morphine administration during remifentanil-based anaesthesia on early recovery from anaesthesia and postoperative pain. Br J Anaesth 2002;88:814 -8. 4. Coda B, Tanaka A, Jacobson RC, Donaldson G, Chapman CR. Hydromorphone analgesia after intravenous bolus administration. Pain 1997;71:41-8. 5. Sarton E, Olofsen E, Romberg R, den Hartigh J, Kest B, Nieuwenhuijs D, Burm A, Teppema L, Dahan A. Sex differences in morphine analgesia: an experimental study in healthy volunteers. Anesthesiology 2000;93:1245- 1254. 6. Dahan A, Romberg R, Teppema L, Sarton E, Bijl H, Olofsen E. Simultaneous measurement and integrated analysis of analgesia and respiration after an intravenous morphine infusion. Anesthesiology 2004;101:1201-9. Conflict of Interest:None declared |
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