Experience of Remifentanil in Extremely Low-birth-weight Babies Undergoing Laparotomy

Premature babies experience pain and require adequate analgesia for any painful procedure. Fentanyl and morphine resulted in safe and effective anesthesia in the past; however, their pharmacokinetics may be impaired in preterm babies with multiorgan failure. Remifentanil, despite the absence of available pharmacokinetic data in preterm infants and few reports in newborns, demonstrated its advantages in children undergoing either major surgery or minor painful procedures and has been shown to be useful even in neonates, because its elimination is independent of organ function. We report two cases of babies born at 26 weeks’ and 27 weeks’ gestation, weighing 580g and 400g, respectively, undergoing laparotomy for necrotizing enterocolitis. Both received midazolam bolus and remifentanil infusion at high doses. This technique seems to be an advantageous alternative even in extremely low-birth-weight prematures. Furthermore, it becomes a technique of choice in these babies because the available ventilators are often not equipped with halogenated vaporizers. Particularly in intensive care, where there are no scavenger systems, it could allow to operate without moving out the preterm babies and avoiding stress and hypothermia

Disposition of Midazolam in Asphyxiated Neonates Receiving Therapeutic Hypothermia - A Pilot Study

Background: Moderate hypothermia has become an established therapy for asphyxiated neonates. Midazolam is a frequently used sedative for this indication, although it has never been investigated how therapeutic hypothermia and asphyxia influence midazolam metabolism in neonates. Patients and Methods: 9 asphyxiated newborns were treated with whole body hypothermia of 32-34 degrees C for 72 h and all of them received continuous midazolam infusion for sedation. Serum concentrations of midazolam and its metabolites 1-hydroxy-midazolam and 4-hydroxy-midazolam were measured during hypothermia and the rewarming period. Renal and hepatic parameters were assessed to take into account the influence of asphyxia related renal or hepatic impairment. Results: We found a high interindividual variability of serum midazolam concentrations in asphyxiated neonates with therapeutic hypothermia; median midazolam concentration was 369.3ng/ml (minimum 36.6; maximum 3218.6ng/ml). The population pharmacokinetic model revealed a midazolam clearance of 2.57ml/kg/min, comparable to midazolam clearances observed in normothermic critically ill neonates. However, midazolam clearance was significantly decreased in patients with asphyxia related renal and hepatic impairment. Conclusion: It seems that isolated hypothermia does not significantly influence midazolam metabolism. However, neonates with asphyxia related hepatic and renal impairment are at risk of generating unexpectedly high serum midazolam concentrations. In addition pronounced interindividual variability of midazolam metabolism may contribute to dangerously high midazolam concentrations

Remifentanil degradation in umbilical cord blood of preterm infants

ABSTRACT Background: No pharmacokinetic data about remifentanil in preterm infants exist, although remifentanil is increasingly used in this especially vulnerable subgroup of pediatric patients. Unfortunately, ethical restrictions in the volume of blood that can be withdrawn for kinetic sampling nearly prohibit pharmacokinetic studies in preterm infants. Methods: Because remifentanil is rapidly metabolized by nonspecific blood esterases, we collected umbilical cord serum of preterm and term infants to investigate whether the activity of nonspecific blood esterases depends on gestational age. Umbilical cord serum, buffer solution, ascorbic acid, and remifentanil were mixed in a glass vial placed in a shaking water bath at 37°C. Subsequently, serum samples were subjected to liquid chromatography-mass spectrometry-based analysis of remifentanil and its metabolite GR90291 after 0, 30, 60, 100, and 150 min. Results: We analyzed umbilical cord serum samples of 34 preterm infants (24 -36 gestational weeks) and six term infants. The degradation rates of remifentanil to its major metabolite GR90291 were comparable in preterm and term infants. The overall median degradation half-life of remifentanil was 143 Ϯ (interquartile range) 47 min (minimum, 76 min; maximum, 221min) without significant differences between very preterm infants (less than 28 gestational weeks