Morphine and its metabolites after patient-controlled analgesia: Considerations for respiratory depression

Department of Anesthesia, Stanford University, H3580, 300 Pasteur Dr, Stanford, CA 94305-5640, USA.
Journal of clinical anesthesia (Impact Factor: 1.19). 03/2011; 23(2):102-6. DOI: 10.1016/j.jclinane.2010.08.002
Source: PubMed


To assess concentrations of morphine and its metabolites after patient-controlled analgesia (PCA).
Pilot pharmacokinetic study of morphine and pharmacokinetic simulation.
Post-anesthesia care room and ward of an academic teaching hospital.
10 ASA physical status I, II, and III postoperative surgical patients.
Patients received morphine via PCA by routine hospital protocols.
The population mean plasma and effect-site concentrations of morphine, morphine-6-glucuronide (M6G), and morphine-3-glucuronide (M3G) was simulated in 4 patient group scenarios: morphine PCA used alone, morphine PCA used with continuous background morphine infusion of 0.5 mg/hr, morphine PCA used with continuous background morphine infusion of 1.0 mg/hr, and morphine PCA used with continuous background morphine infusion of 2.0 mg/hr.
The 4 groups exhibited simulated peak morphine, M6G, and M3G effect-site concentrations at 8 to 24 hours post-infusion. The highest peak morphine, M6G, and M3G effect-site concentrations decreased in the following order by group: 2.0 mg/hr morphine infusion + PCA group, 1.0 mg/hr morphine infusion + PCA group, and 0.5. mg/hr morphine infusion + PCA group.
Patients receiving morphine PCA should be monitored closely from 8 to 24 hours postoperatively. Morphine PCA given with background infusion rates up to 1.0 mg/hr does not offer distinct pharmacokinetic advantages over morphine PCA alone. Morphine PCA with background infusion rate of 2.0 mg/hr is associated with the greatest risk of respiratory depression.

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Available from: David R Drover, Feb 11, 2015
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    • "Most of the previous studies that assessed the safety and efficacy of postoperative IV-PCA with background infusion were conducted in morphine-based regimens.13,14,15, 16 Morphine has been the most widely used opioid in IV-PCA for a long time, and several studies showed evidence of safe and effective background infusion rates of morphine.9,10,17,18 On the other hand, little is known about appropriate background infusion rates of fentanyl when used in postoperative IV-PCA. "
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    ABSTRACT: This analysis was done to investigate the optimal regimen for fentanyl-based intravenous patient-controlled analgesia (IV-PCA) by finding a safe and effective background infusion rate and assessing the effect of adding adjuvant drugs to the PCA regimen. Background infusion rate of fentanyl, type of adjuvant analgesic and/or antiemetic that was added to the IV-PCA, and patients that required rescue analgesics and/or antiemetics were retrospectively reviewed in 1827 patients who underwent laparoscopic abdominal surgery at a single tertiary hospital. Upon multivariate analysis, lower background infusion rates, younger age, and IV-PCA without adjuvant analgesics were identified as independent risk factors of rescue analgesic administration. Higher background infusion rates, female gender, and IV-PCA without additional 5HT₃ receptor blockers were identified as risk factors of rescue antiemetics administration. A background infusion rate of 0.38 μg/kg/hr [area under the curve (AUC) 0.638] or lower required rescue analgesics in general, whereas, addition of adjuvant analgesics decreased the rate to 0.37 μg/kg/hr (AUC 0.712) or lower. A background infusion rate of 0.36 μg/kg/hr (AUC 0.638) or higher was found to require rescue antiemetics in general, whereas, mixing antiemetics with IV-PCA increased the rate to 0.37 μg/kg/hr (AUC 0.651) or higher. Background infusion rates of fentanyl between 0.12 and 0.67 μg/kg/hr may safely be used without any serious side effects for IV-PCA. In order to approach the most reasonable background infusion rate for effective analgesia without increasing postoperative nausea and vomiting, adding an adjuvant analgesic and an antiemetic should always be considered.
    Yonsei medical journal 05/2014; 55(3):800-6. DOI:10.3349/ymj.2014.55.3.800 · 1.29 Impact Factor
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    • "Decreased analgesia observed following enteral absorption is due to first-pass metabolism that is absent following parenteral delivery. Hepatic metabolism results in morphine-3-glucuronide and morphine-6-glucuronide, and these metabolites are renally excreted.49 Analgesia is a consequence of μ opioid receptor agonism centrally and peripherally.48,50 "
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    08/2011; 2:145-162. DOI:10.2147/SAR.S12944
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    ABSTRACT: Opioids are widely used in treatment of acute and chronic pain patients, and today a lot of efforts are put into individualize these therapies. Physicians would like to reduce deaths, minimize side effects and prevent toxicity, but – nevertheless PCA could represent a solution – up to date it is not yet completely reliable. A sustaining pharmacokinetic approach gives significant contribution, in particular in treatment of special populations (e.g. infants, elderly, and patients with renal/liver failure), which have a unique opioids pharmacokinetic profile to be taken into account, in order to maximize analgesic efficacy and reduce the risk of adverse events.
    European Journal of Pain Supplements 11/2011; 5(S2):477. DOI:10.1016/j.eujps.2011.08.020
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