A mixture of alfentanil and morphine for rapid postoperative loading with opioid: theoretical basis and initial clinical investigation

Abstract

SummaryPharmacokinetic modelling of estimated central nervous system concentrations was used to devise the optimal mixture of morphine and alfentanil for the treatment of postoperative pain. Modelling revealed that an intravenous opioid pain protocol using an alfentanil2morphine mixture in the proportions 0.75 : 10 mg would provide a profile of analgesia of rapid onset, yet slow offset. The regimen was evaluated in 58 patients in the recovery ward who were randomly allocated to receive analgesia using pain protocols with either morphine or the mixture. Groups were well matched for age, weight and initial pain scores. The mean (SD) time to patient comfort was 27.6 (20.2) min for the mixture and 41.2 (18.6) min for morphine (p 0.01). Multiple regression analysis revealed that that initial pain score (p 0.009) and drug group (p 0.02), but not age, weight or gender were independent predictors of the time to comfort. Drug group was not a significant predictor of adverse effects. Postoperative pain and current dose regimens Despite the best efforts of anaesthetists, many patients still experience moderate to severe pain in the recovery room. This is frequently managed using intravenous opioids titrated to analgesic effect, and nurse-administered`pain protocols' involving repeated intravenous bolus doses of opioid given at fixed`lock-out periods' can be very effective in this setting [1,2].However, commonly used opioids, such as morphine and pethidine, have a relatively slow onset to peak effect even after intravenous bolus dose administration. When repeated doses are given during titration regimens, thè lock-out period' between doses must allow for at least some of the effect of each dose to be seen before another is given. This can result in considerable delays before adequate analgesia is achieved. Increasing the frequency of administration of boluses may speed the onset of analgesia, but will also increase the risk of accumulation [3] and adverse effects such as respiratory depression. Choosing an opioid with a more rapid onset, such as alfentanil, may provide more rapid onset of analgesia, but will result in a brief duration of effect.The aim of this study was therefore to explore the feasibility of a mixture of opioids to produce the features of rapid onset, yet slow offset.Kinetic and dynamic basis of a mixture of alfentanil and morphine The concepts used here arose from a recent review of the opioid pharmacokinetic literature by the authors [3]. A data set of kinetic parameters was compiled from the literature (with various assumptions) and used to simulate the time-course of blood and estimated central nervous system (CNS) concentrations of opioids in various settings. It was noted that, after intravenous bolus administration, the estimated CNS concentrations of opioids were delayed relative to their blood concentrations to different extents depending on their rate of q 2001 Blackwell Science Ltd 739

A double-blinded randomized evaluation of alfentanil and morphine vs fentanyl: analgesia and sleep trial (DREAMFAST)

“…Dosing in Group AM was based on a previous study which used pharmacokinetic modelling to determine the optimal ratio of alfentanil to morphine for analgesia and then tested this model in the postanaesthesia care unit (PACU). 9 Dosing in Group F was consistent with routine practice and standard protocols at both hospitals.…”

“…In the postoperative anaesthesia care unit, a combination of alfentanil and morphine has more rapid onset and a similar duration of effect, along with a comparable sideeffect profile, than does morphine alone. 9 In the first 24 h after Caesarean section, women reported that the opioid combination in PCA, compared with morphine alone, resulted in more rapid onset and greater efficacy after each bolus, with no difference in analgesia duration or overall patient satisfaction. 10 Combining opioids may produce both rapid onset analgesia with timely control of incident pain allowing return to sleep, and longer duration of effect, leading to consolidated periods of sleep with fewer pain-related awakenings.…”

A Randomized Double‐Blind Comparison of a Morphine–Fentanyl Combination vs. Morphine Alone for Patient‐Controlled Analgesia Following Bowel Surgery

“…There are only 2 studies looking at pure agonist opioid mixtures for PCA in the literatue 13,14 . The first study examined a combination of morphine and alfentanil for PCA use after caesarian section.…”

Stability and Compatibility of Alfentanil Hydrochloride and Morphine Sulfate in Polypropylene Syringes

“…Combination of morphine with the more rapidly, but shorter acting opioid, alfentanil, has been shown to improve analgesic profile and patient satisfaction with PCA in the postoperative setting. 1,2 The Acute Pain Service at the Royal Adelaide Hospital (RAH) developed a protocol to investigate a combination of morphine sulfate 0.8mg/mL and alfentanil hydrochloride 55mg/mL in a double-blind crossover comparison with morphine sulfate 1mg/mL in PCA for pain associated with dressings in burns patients. The RAH pharmacy department was approached to prepare and blind syringes of the trial medications.…”