Predicting Unacceptable Pain in Cardiac Surgery Patients Receiving Morphine Maintenance and Rescue Doses: A Model-Based Pharmacokinetic-Pharmacodynamic Analysis
Autor: | Catherijne A. J. Knibbe, Dick Tibboel, Sebastiaan C. Goulooze, P. Välitalo, Mohammed A A Saleh, Ron H.N. van Schaik, Elke H. J. Krekels, Sabine J.G.M. Ahlers, Eric P.A. van Dongen, Thomas Hankemeier |
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Přispěvatelé: | Clinical Chemistry |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
medicine.medical_specialty Analgesic Risk Assessment Drug Administration Schedule Pharmacokinetics Risk Factors Interquartile range Humans Pain Management Medicine Cardiac Surgical Procedures Aged Pain Postoperative Morphine business.industry Middle Aged Models Theoretical Confidence interval NONMEM Cardiac surgery Analgesics Opioid Treatment Outcome Anesthesiology and Pain Medicine Anesthesia Pharmacodynamics Female business medicine.drug |
Zdroj: | Anesthesia and Analgesia, 132(3), 726-734. Lippincott Williams & Wilkins |
ISSN: | 0003-2999 |
Popis: | BACKGROUND: Optimal analgesic treatment following cardiac surgery is crucial for both patient comfort and successful postoperative recovery. While knowledge of both the pharmacokinetics and pharmacodynamics of analgesics is required to predict optimal drug dosing, models quantifying the pharmacodynamics are scarce. Here, we quantify the pharmacodynamics of morphine by modeling the need for rescue morphine to treat unacceptable pain in 118 patients after cardiac surgery. METHODS: The rescue morphine event data were analyzed with repeated time-to-event (RTTE) modeling using NONMEM. Postoperative pain titration protocol consisted of continuous morphine infusions (median duration 20.5 hours) with paracetamol 4 times daily and rescue morphine in case of unacceptable pain (numerical rating scale ≥4). RESULTS: Patients had a median age of 73 years (interquartile range [IQR]: 63-77) and median bodyweight of 80 kg (IQR: 72-90 kg). Most patients (55%) required at least 1 rescue morphine dose. The hazard for rescue morphine following cardiac surgery was found to be significantly influenced by time after surgery, a day/night cycle with a peak at 23:00 (95% confidence interval [CI], 19:35-02:03) each day, and an effect of morphine concentration with 50% hazard reduction at 9.3 ng·mL-1(95% CI, 6.7-16). CONCLUSIONS: The pharmacodynamics of morphine after cardiac surgery was successfully quantified using RTTE modeling. Future studies can be used to expand the model to better predict morphine's pharmacodynamics on the individual level and to include the pharmacodynamics of other analgesics so that improved postoperative pain treatment protocols can be developed. |
Databáze: | OpenAIRE |
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