Thangaraj Abiramalatha 1,2 , Sumith Koshy Mathew 3 , Binu Susan Mathew 3 , Machilakath Panangandi Shabeer 1 , Geethanjali Arulappan 4 , Manish Kumar 1 , Visalakshi Jayaseelan 5 , Kurien Anil Kuruvilla 1 Show Affiliations »
Abstract
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OBJECTIVE: Adequate data on fentanyl pharmacokinetics in neonates are lacking. The study was performed to compare serum concentrations and clinical outcome between continuous infusion (CI) and intermittent bolus (IB) doses of fentanyl for analgesia and sedation in neonates . METHODS: In this open-label randomised controlled trial, neonates requiring 24-48 hours of mechanical ventilation and fentanyl administration were recruited . In CI regimen, 1 mcg/kg loading dose was followed by 1 mcg/kg/hour infusion. In IB regimen, 1mcg/kg/dose was administered every 4 hours.Maximum six blood samples were collected in 48 hours from each baby at prespecified time points for estimating serum fentanyl concentration. Secondary outcomes were pain scores (Neonatal Infant Pain Scale and Neonatal Pain, Agitation and Sedation Scale for acute and ongoing pain, respectively) and incidence of adverse effects of fentanyl . RESULTS: 100 neonates were recruited, 53 in CI and 47 in IB group . In CI regimen, median (IQR) serum fentanyl concentration was 0.42 (0.35, 0.46) to 0.61 (0.47, 0.89) ng/mL throughout the infusion period. In IB regimen, median (IQR) peak concentration ranged from 2.21 (1.82, 3.55) to 3.61 (2.91, 4.51) ng/mL and trough concentration 0.41 (0.33, 0.48) to 0.97 (0.56, 1.25) ng/mL for various doses.Median (IQR) peak concentration (Cmax, 3.06 (1.09, 4.50) vs 0.78 (0.49, 1.73) ng/mL; p<0.001) was significantly higher and area under concentration-time curve (AUC0-24, 19.6 (10.4, 33.5) vs 13.2 (10.8, 22.6) µg·hour /L; p=0.12) was higher (though not statistically significant) in IB than CI regimen. Pain scores and adverse effects were comparable between the two regimens. CONCLUSION: CI regimen of fentanyl produces steady serum concentrations, whereas IB regimen produces wide fluctuations in serum concentration with high-peak concentrations. A serum fentanyl concentration of 0.4-0.6 ng/mL produces adequate analgesia and sedation in neonates . TRIAL REGISTRATION NUMBER: CTRI/2014/11/005190. © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
RCT Entities: Population
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Outcomes
OBJECTIVE: Adequate data on fentanyl pharmacokinetics in neonates are lacking. The study was performed to compare serum concentrations and clinical outcome between continuous infusion (CI) and intermittent bolus (IB) doses of fentanyl for analgesia and sedation in neonates. METHODS: In this open-label randomised controlled trial, neonates requiring 24-48 hours of mechanical ventilation and fentanyl administration were recruited. In CI regimen, 1 mcg/kg loading dose was followed by 1 mcg/kg/hour infusion. In IB regimen, 1mcg/kg/dose was administered every 4 hours.Maximum six blood samples were collected in 48 hours from each baby at prespecified time points for estimating serum fentanyl concentration. Secondary outcomes were pain scores (Neonatal Infant Pain Scale and Neonatal Pain , Agitation and Sedation Scale for acute and ongoing pain , respectively) and incidence of adverse effects of fentanyl . RESULTS: 100 neonates were recruited, 53 in CI and 47 in IB group. In CI regimen, median (IQR) serum fentanyl concentration was 0.42 (0.35, 0.46) to 0.61 (0.47, 0.89) ng/mL throughout the infusion period. In IB regimen, median (IQR) peak concentration ranged from 2.21 (1.82, 3.55) to 3.61 (2.91, 4.51) ng/mL and trough concentration 0.41 (0.33, 0.48) to 0.97 (0.56, 1.25) ng/mL for various doses.Median (IQR) peak concentration (Cmax, 3.06 (1.09, 4.50) vs 0.78 (0.49, 1.73) ng/mL; p<0.001) was significantly higher and area under concentration-time curve (AUC0-24, 19.6 (10.4, 33.5) vs 13.2 (10.8, 22.6) µg·hour/L; p=0.12) was higher (though not statistically significant) in IB than CI regimen. Pain scores and adverse effects were comparable between the two regimens. CONCLUSION: CI regimen of fentanyl produces steady serum concentrations, whereas IB regimen produces wide fluctuations in serum concentration with high-peak concentrations. A serum fentanyl concentration of 0.4-0.6 ng/mL produces adequate analgesia and sedation in neonates. TRIAL REGISTRATION NUMBER: CTRI/2014/11/005190. © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
Entities: Chemical
Disease
Species
Keywords:
continuous infusion; fentanyl; intermittent bolus doses; neonate; pain score; pharmacokinetics
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Year: 2018
PMID： 30322973 DOI： 10.1136/archdischild-2018-315345
Source DB: PubMed Journal: Arch Dis Child Fetal Neonatal Ed ISSN： 1359-2998 Impact factor: 5.747