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191 Morphine Premedication for Intubation in Preterm Infants - A Pharmacokinetic and Pharmacogenetic Report
  1. E Norman1,
  2. L Elens2,
  3. M Anderssson3,
  4. O Beck3,
  5. R van Shaik2,
  6. A Rane3,
  7. V Fellman1,4
  1. 1Department of Pediatrics, Lund University and Skåne University Hospital Lund, Lund, Sweden
  2. 2Department of Clinical Chemistry, Erasmus MC, Rotterdam, Netherlands Antilles
  3. 3Division of Clinical Pharmacology, Lab Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
  4. 4Children’s Hospital, University of Helsinki, Helsinki, Finland

Abstract

Background and aims Morphine is used in preterm infants, but data are scars on pharmacokinetics (PK), pharmacodynamics (PD) and pharmacogenetics (PG). We aimed to study PK and PD/PG relation of morphine in infants included in a RCT comparing morphine with short-acting analgosedation as premedication for intubation.

Methods 17 preterm infants with a median (IQR) gestational age of 26.6 (25.1–28.7) w, birth weight 924 (721–1240) g and postnatal age 136 (17.5–322) h were randomized to receive morphine (0.3 mg/kg).

Blood samples for morphine, M6G and M3G concentrations were collected before administration, 20 min, 6 and 24 h after intubation. DNA was isolated from salivary swabs to genotype 18 polymorphisms in 12 genes using Taqman assays. Pain assessment (ALPS-0 and EDIN scales) was performed and additional morphine boluses were offered accordingly. The morphine level/pain score relation and the genotype influence on time to achieve a low pain score was calculated.

Results In infants receiving no additional doses, clearance was 1.5–3.3 ml/kg/min in 5 infants of 5–34 h and 9.9 in one infant of 332 h postnatal age.

Both morphine and morphine+M6G/5 correlated with mean ALPS-0 score at 6h (p=0.02 and 0.04) and 24 h (p=0.01 and 0.02). The COMT rs4680G>A (Val158Met) SNP was significantly correlated with time to reach the lowest pain score. COMT rs4680A patients experienced a faster response to opioids compared to rs4680GG patients in both groups (p=0.001 and p=0.072).

Conclusions Morphine clearance is dependent on postnatal age in premature infants. Genotyping would improve individual dosing of opioids during NICU-care.

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