Randomised double‐blind comparison of morphine vs. a morphine–alfentanil combination for patient‐controlled analgesia

Kee, Warwick D. Ngan; Khaw, Kim S.; Wong, Eric

doi:10.1046/j.1365-2044.1999.00844.x

Cited by 16 publications

(3 citation statements)

References 14 publications

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“…The first study examined a combination of morphine and alfentanil for PCA use after caesarian section. It found that patients who received the combination reported faster onset of analgesia after a PCA bolus when compared with a morphine alone PCA group 13 . Similar to our study, this advantage was not reflected in the visual analog scale pain scores.…”

Section: Discussionsupporting

confidence: 86%

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

Friedman¹,

Katznelson

Phillips³

et al. 2008

Pain Practice

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An ideal patient-controlled analgesia (PCA) opioid would have both a rapid onset and a long duration of action, attributes, which are not available in currently existing opioids including morphine, the most widely used agent. A mixture of rapid onset and long-acting opioids may potentially achieve both these qualities. In a randomized, double-blind study, we compared a fentanyl-morphine combination with morphine alone for PCA, in 54 patients undergoing bowel surgery. The combination solution was prepared according to a 1:75 fentanyl to morphine potency ratio. The mixture contained fentanyl 13.33 mug/mL and morphine 1 mg/mL. The morphine alone solution contained 2 mg/mL. Patients were randomly allocated to one of the regimens and were then evaluated 4 times during the first 48 hours following surgery. Time to effect, visual analog pain scores, opioid consumption, demands, deliveries, and side effects on an opioid-related symptom distress scale were recorded. Groups were well matched for age, weight, and sex. There were no significant differences between groups in time to effect, PCA usage, pain scores or side effects other than the occurrence of nausea, which was lower for the combination group in 1 visit. Further studies are needed to explore the potential of different potency ratios and opioid combinations to achieve rapid and long-lasting pain control.

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Section: Discussionsupporting

confidence: 86%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Friedman¹,

Katznelson

Phillips³

et al. 2008

Pain Practice

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“…A recent study compared the efficacy of morphine alone and an alfentanil−morphine mixture in the setting of patient‐controlled analgesia (PCA), finding no difference in reported pain scores over a 24‐h period [7]. Although the timing of recording pain scores used would not be expected to be particularly sensitive at detecting onset of analgesia, patients in the mixture group reported that they felt that the onset of pain relief was ‘fast’ more frequently than those in the morphine alone group.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2001

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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

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

Sharley¹,

Burgess

2003

Pharmacy Practice and Res

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Aim: To establish the chemical stability and physical compatibility of alfentanil hydrochloride and morphine sulfate in polypropylene syringes for patient controlled analgesia at the Royal Adelaide Hospital. Method: A stability indicating high pressure liquid chromatography (HPLC) method was developed and validated. Concentrations of alfentanil hydrochloride and morphine sulfate stored in polypropylene syringes were measured over a sixmonth period. Sample syringes were stored under refrigeration (2‐8°C) and at room temperature (22±1°C). Visual inspection for macro particulate matter was undertaken using an Allen viewer. Stability was defined as maintaining at least 90% of the day zero concentration. Quality control standards were assayed on each study day to determine intra‐ and inter‐day precision and accuracy. Results: Morphine sulfate content remained at 99% of initial concentration after 182 days at both storage conditions. Alfentanil hydrochloride content remained at 100% of initial concentration after 182 days at both storage conditions. No particulate matter was visible in sample syringes throughout the study period. Conclusion: Alfentanil hydrochloride and morphine sulfate in polypropylene syringes are chemically stable and physically compatible for 180 days in the concentrations studied, when protected from light and stored either under refrigeration (2‐8°C) or room temperature (22±1°C). An expiry date of six months can be applied, facilitating efficient manufacturing and clinical evaluation in the management of acute pain.

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Randomised double‐blind comparison of morphine vs. a morphine–alfentanil combination for patient‐controlled analgesia

Cited by 16 publications

References 14 publications

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

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

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

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

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