Elisabeth Norman

Early single-channel aEEG/EEG predicts outcome in very preterm infants

Aim:  To characterize early amplitude‐integrated electroencephalogram (aEEG) and single‐channel EEG (aEEG/EEG) in very preterm (VPT) infants for prediction of long‐term outcome.

Lower stress responses after newborn individualized developmental care and assessment program care during eye screening examinations for retinopathy of prematurity: A randomized study

OBJECTIVE. Screening examination for retinopathy of prematurity is distressing and painful. The aim of the present study was to investigate whether a Newborn Individualized Developmental Care and Assessment Program intervention during a retinopathy of prematurity examination results in less adverse behavioral, pain, and stress responses as compared with standard care. METHODS. The first 2 eye examinations in 36 preterm infants were evaluated. The infants were randomly assigned at the first eye examination to receive either Newborn Individualized Developmental Care and Assessment Program care or standard care. At the second examination, crossover of subject assignment was performed. The assessments included behavioral responses; recordings of heart rate, respiration, and oxygenation; pain scores (premature infant pain profile); and salivary cortisol at defined time points up to 4 hours after the eye examination. The nursing support given during the eye examinations (intervention score) were scored using predefined criteria. RESULTS. Altogether, 68 examinations were evaluated. Newborn Individualized Developmental Care and Assessment Program care was associated with better behavioral scores during the examination but there was no difference in heart rate, respiratory rate, oxygenation, or premature infant pain profile score between the 2 care strategies before or after the eye examination. Salivary cortisol increased from baseline to 30 minutes after the eye examination independent of care strategy and decreased significantly between 30 and 60 minutes when infants were subjected to Newborn Individualized Developmental Care and Assessment Program care but not after standard care. During the study period the intervention score for standard care increased and approached the score for Newborn Individualized Developmental Care and Assessment Program care at the later eye examinations. CONCLUSION. A Newborn Individualized Developmental Care and Assessment Program-based intervention during eye examination does not decrease pain responses but results in faster recovery, as measured by lower salivary cortisol 60 minutes after the examination. The differences were seen despite the influence from the Newborn Individualized Developmental Care and Assessment Program intervention on the standard care treatment that occurred during the study period.

Reversibility of acute intermediate phase bilirubin encephalopathy

Aim:  To show the potential for reversing acute intermediate to advanced phase bilirubin encephalopathy.

Premedication for intubation with morphine causes prolonged depression of electrocortical background activity in preterm infants

Background:Sedative and analgesic medications are used in critically ill newborns, but little is known about their effects on electrocortical activity in preterm infants. We hypothesized that morphine might induce prolonged neurodepression, independent of blood pressure, as compared with rapid sequence induction/intubation(RSI).Methods:Of 34 infants enrolled in a randomized controlled trial (RCT) comparing RSI (including thiopental 2–3 mg/kg and remifentantil 1 mcg/kg) with morphine (0.3 mg/kg) as premedication for intubation, 28 infants (n = 14 + 14; median gestational age 26.1 wk and postnatal age 138 h) had continuous two-channel amplitude-integrated electroencephalogram (aEEG/EEG) and blood pressure monitoring during 24 h after the intubation. Thirteen infants not receiving any additional medication constituted the primary study group. Visual and quantitative analyses of aEEG/EEG and blood pressure were performed in 3-h epochs.Results:RSI was associated with aEEG/EEG depression lasting <3 h. Morphine premedication resulted in aEEG/EEG depression with more discontinuous background and less developed cyclicity for 24 h, and during the first 9 h, interburst intervals (IBI) were significantly increased as compared with those of RSI treatment. The difference was not related to blood pressure.Conclusion:Premedication with morphine is associated with prolonged aEEG/EEG depression independent of blood pressure changes and may not be optimal for short procedures.

Development and psychometric properties of the Swedish ALPS-Neo pain and stress assessment scale for newborn infants

To validate and evaluate the psychometric properties of the ALPS‐Neo, a new pain assessment scale created for the continuous evaluation of pain and stress in preterm and sick term infants.

Effect of UGT2B7-900G>A (-842G>A; rs7438135) on morphine glucuronidation in preterm newborns: Results from a pilot cohort

AIM Assess association between UGT2B7 polymorphism -900G>A (rs7438135, also known as -842G>A) with morphine kinetics in preterm newborns undergoing mechanical ventilation. MATERIALS & METHODS Thirty-four infants were enrolled in a randomized clinical trial and allocated to rapid sequence intubation with remifentanil (1 µg/kg) or morphine (0.3 mg/kg). The latter group was included in our study. RESULTS Morphine plasma concentrations at 20 min post intubation were associated with postnatal age (p=0.017) and UGT2B7 -900G>A (p=0.036). UGT2B7 -900A allele carriers (n=13) had lower morphine levels compared with UGT2B7 -900G/G patients (n=2). Morphine-3-glucuronide and morphine-6-glucuronide plasma concentrations were only found to be associated with gestational and postnatal age. However, -900A allele carriers had a higher morphine-3-glucuronide:morphine metabolic ratio compared with patients genotyped as -900G/G (p=0.005), as determined by linear regression. CONCLUSION Our small pilot study illustrates that in addition to gestational and postnatal age, the UGT2B7 -900G>A polymorphism significantly alters morphine pharmacokinetics in preterm infants.

Thiopental pharmacokinetics in newborn infants: a case report of overdose

Thiopental may be used for sedation before intubation in newborn infants. A boy, born at 33 weeks of gestation (gw); birth weight 2435 g, was prescribed thiopental 3 mg/kg before intubation. He developed temporary hypotension and oxygen desaturation, and remained unconscious for longer than expected with a suppressed electroencephalography for 48 h. Serum thiopental concentration was 82, 59, 42 and 32 μmol/L after 20 min and 6, 24 and 68 h respectively. Serum concentrations from five newborn infants at the same time points after intubation with the same thiopental dose were used as reference values, and indicated a 10‐fold overdose in the index case. The cause of the overdose could not be identified. The infant recovered; cerebral magnetic resonance imaging at the age of 42 gw and psychomotor development at 2 years were normal. These results show that thiopental concentrations are variable in neonates and there is a high risk of dosage error as no specific paediatric formulation is available.

Thiopentone elimination in newborn infants: exploring Michaelis-Menten kinetics.

Background: Thiopentone elimination has been described using Michaelis–Menten pharmacokinetics in adults after prolonged infusion or overdose, but there are few reports of elimination in neonates.

Genetic Predisposition to Poor Opioid Response in Preterm Infants : Impact of KCNJ6 and COMT Polymorphisms on Pain Relief after Endotracheal Intubation

Background: Single-nucleotide polymorphisms in genes involved in pain control might predispose to exaggerated sensitivity or difference in opioid analgesic effect. The relevance of the KCNJ6 -1250G>A (rs6517442, c.-1787G>A) and the catecholamine-O-methyltransferase (COMT) c.472G>A (rs4680, Val158Met) single-nucleotide polymorphisms were studied in preterm infants needing intubation and randomized to a premedication strategy including remifentanil (n = 17) or morphine (n = 17). Methods: Pain was scored with Astrid Lindgren and Lund Childrens Hospital Pain Assessment Scale every 30 minutes for 6 hours. The pain relief provided by the opioids was compared between the different KCNJ6 and COMT genotypes. Results: Infants homozygous for the KCNJ6 -1250A allele had an increased duration after intubation to achieve a score indicating no pain compared with infants with the A/G or G/G genotypes (182 ± 30, 109 ± 29, and 60 ± 21 minutes, respectively; Logrank = 7.5, P = 0.006). Similarly, the duration was increased in individuals with the COMT Val/Val alleles compared with Val/Met and Met/Met (285 ± 37, 137 ± 25, and 63 ± 15 minutes, respectively; Logrank = 14.4, P = 0.0021). Cox proportional hazards analysis confirmed that the variation in both genes was independently associated with susceptibility to respond to therapy. Conclusion: We conclude that the KCNJ6 -1250A and COMT 158Val alleles are predisposing preterm newborns to diminished opioid-induced pain relief.

Placental transfer and pharmacokinetics of thiopentone in newborn infants

Background and Objectives Thiopentone, a short-acting barbiturate, has been introduced as premedication for intubation in newborn infants. The objectives of this study were to assess the pharmacokinetics of thiopentone in newborn infants, and to unravel whether placental transfer of the drug should be taken into account if administered to infants exposed to it during delivery. Methods Plasma concentrations were assessed with high-pressure liquid chromatography in samples from delivering mothers (n=27) receiving a median dose of 5.5 mg/kg (range 3.8–7.7) thiopentone for Caesarean section in gestational week 37.6 (range 25.7–41.4) and from corresponding umbilical cord blood (n=28). In infants (n=30) born at 35.4 weeks gestation (range 27.9–42.0) undergoing surgery at a median postnatal age of 24.5 h (range 4–521), repeated blood levels were assessed after administering a dose of 3 mg/kg thiopentone on clinical indication before intubation (seven samples per infant from 5 min to 48 h after administration). Results The umbilical/maternal concentration ratio was 0.7, the mean concentration of thiopentone was 55.7 µmol/l (SD±15.3) in mothers and 39.3 µmol/l (SD±12.5) in venous cord blood. In newborn infants undergoing surgery, the terminal half-life of thiopentone was 8 h (interquartile range (IQR) 2.5–10.8), and clearance 0.092 l/min per kg/postnatal age in days (IQR 0.02–0.1). Conclusions Thiopentone might be used as premedication for short-lasting intubation after birth, for example, for surfactant administration. During the first 4 h after birth the dose needs to be adjusted for maternal dosage as well as for the weight of the infant.