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Pharmacokinetics during therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy: a literature review.

ABSTRACT:

Background

Neonatal hypoxic ischaemic encephalopathy due to perinatal asphyxia, can result in severe neurodevelopmental disability or mortality. Hypothermia is at present the only proven neuroprotective intervention. During hypothermia, the neonate may need a variety of drugs with their specific pharmacokinetic profile. The aim of this paper is to determine the effect that hypothermia for neonates suffering from hypoxic ischaemic encephalopathy has on the pharmacokinetics and to what extent dosing regimens need adjustments.

Method

A systematic search was performed on PubMed, Embase and Cochrane Library of literature (2000-2020) using a combination of the following search terms: therapeutic hypothermia, neonate, hypoxic ischemic encephalopathy and pharmacokinetics. Titles and abstracts were screened, and inclusion/exclusion criteria were applied. Finally, relevant full texts were read, and secondary inclusion was applied on the identified articles.

Results

A total of 380 articles were retrieved, and 34 articles included after application of inclusion/exclusion criteria and duplicate removal, two additional papers were included as suggested by the reviewers. Twelve out of 36 studies on 15 compounds demonstrated a significant decrease in clearance, be it that the extent differs between routes of elimination and compounds, most pronounced for renal elimination (phenobarbital no difference, midazolam metabolite -21%, lidocaine -24%; morphine -21% to -47%, gentamicin -25% to -35%, amikacin -40%) during hypothermia. The data as retrieved in literature were subsequent compared with the dosing regimen as stated in the Dutch paediatric formulary.

Conclusion

Depending on the drug-specific disposition characteristics, therapeutic hypothermia in neonates with hypoxic ischaemic encephalopathy affects pharmacokinetics.

SUBMITTER: Lutz IC

PROVIDER: S-EPMC7299043 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesTo determine whether parents cuddling infants during therapeutic hypothermia (TH) would affect cooling therapy, cardiorespiratory or neurophysiological measures. The secondary aim was to explore parent-infant bonding, maternal postnatal depression and breastfeeding.DesignProspective observational study.SettingTwo tertiary neonatal intensive care units (NICU).ParticipantsParents and their term-born infants (n=27) receiving TH and intensive care for neonatal hypoxic-ischaemic encephalopathy.InterventionsCuddling up to 2 hours during TH using a standard operating procedure developed in the study (CoolCuddle).Main outcome measuresMean difference in temperature, cardiorespiratory and neurophysiological variables before, during and after the cuddle. Secondary outcomes were parental bonding, maternal postnatal depression and breastfeeding.ResultsDuring 70 CoolCuddles (115 cumulative hours), there were measurable increases in rectal temperature (0.07°C (0.03 to 0.10)) and upper margin of amplitude-integrated electroencephalogram (1.80 µV (0.83 to 2.72)) and decreases in oxygen saturations (-0.57% (-1.08 to -0.05)) compared with the precuddle period. After the cuddle, there was an increase in end-tidal CO2 (0.25 kPa (95% CI 0.14 to 0.35)) and mean blood pressure (4.09 mm Hg (95% CI 0.96 to 7.21)) compared with the precuddle period. From discharge to 8 weeks postpartum, maternal postnatal depression declined (13 (56.5%) vs 5 (23.8%), p=0.007); breastfeeding rate differed (71% vs 50%, p=0.043), but was higher than national average at discharge (70% vs 54.6%) and mother-infant bonding (median (IQR): 3 (0-6) vs 3 (1-4)) remained stable.ConclusionIn this small study, CoolCuddle was associated with clinically non-significant, but measurable, changes in temperature, cardiorespiration and neurophysiology. No infant met the criteria to stop the cuddles or had any predefined adverse events. CoolCuddle may improve breastfeeding and requires investigation in different NICU settings.