Pre-emptive opioid sedation during therapeutic hypothermia
| Autor: | Anuj Vakharia, Vania Oliveira, Theodora Markati, Sudhin Thayyil, Phoebe Ivain, Josephine Mendoza, Paolo Montaldo, Seetha Shankaran |
|---|---|
| Přispěvatelé: | Medical Research Council (MRC), Health Education England (HEE) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Sedation Hypothermia Pediatrics Hypothermia induced Article Hypothermia Induced medicine Humans pain Morphine business.industry Cooling therapy Infant Newborn Obstetrics and Gynecology Neurointensive care General Medicine Analgesics Opioid Opioid Current practice Pediatrics Perinatology and Child Health Emergency medicine Hypoxia-Ischemia Brain opioid 1114 Paediatrics and Reproductive Medicine therapautic hypothermia medicine.symptom neonate Opioid analgesics business medicine.drug |
| Popis: | Morphine is commonly used in neonates with hypothermic ischemic encephalopathy (HIE) during therapeutic hypothermia to provide comfort and analgesia. However, pharmacokinetic data to support morphine dosing in this vulnerable population are lacking. A prospective, two-center, clinical pharmacokinetic study of morphine was conducted in 20 neonates (birthweight 1.82 – 5.3 kg) with HIE receiving hypothermia. Morphine dosing was per standard of care at each center. Morphine and glucuronide metabolites (morphine-3-glucuronide and morphine-6-gluronide) were measured via a validated dried blood spot LC-MS/MS assay. From the available concentration data (n=106 for morphine; n=106 for each metabolite), a population pharmacokinetic model was developed using nonlinear mixed-effects modeling (NONMEM). The clearance of morphine and glucuronide metabolites were best predicted by birthweight allometrically scaled using an exponent of 1.23. In addition, the clearance of each glucuronide metabolite was influenced by serum creatinine. No other significant predictors of clearance or volume of distribution were found. For a 3.5 kg neonate, morphine clearance was 0.77 L/h (CV 48%) and the steady-state volume of distribution was 8.0 L (CV 49%). Compared to previous studies in full-term newborns without HIE, morphine clearance was markedly lower. Dosing strategies customized for this vulnerable population will be needed. Applying the final population pharmacokinetic model, repeated Monte Carlo simulations (n=1000 per simulation) were performed to evaluate various morphine dosing strategies that optimized achievement of morphine concentrations between 10-40 ng/ml. An optimized morphine loading dose of 50 μg/kg followed by a continuous infusion of 5 μg/kg/h was predicted across birthweight. |
| Databáze: | OpenAIRE |
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