Local anaesthesia in term- and preterm infants

Background: Local anaesthesia is known to be a safe and effective method for postoperative pain management in adults and children. This convenient method is however rarely used in term and preterm infants, despite its obvious benefits. This is due to lack of research and experience in the area. The free fraction of local anaesthetics is responsible for both toxicity and efficacy. Alpha-1-acid-glycoprotein (AAGP) has a high affinity for amide local anaesthetics, thus plasma levels of AAGP determine the free fraction of LA. This is why this glycoprotein is important when determining dosages of LA infusions. There are very few studies concerning AAGP in newborns and none in extremely preterm infants.

Aims: • To assess the safety and efficacy of local anaesthesia administered by wound catheter after major surgery in term- and preterm infants. • To investigate levels of alpha-1-acid-glycoprotein in new-borns after delivery, and their correlation to age and mode of delivery.

Methods: The studies were performed at departments of Neonatology and Paediatric Anaesthesia and Intensive care at Karolinska University Hospital. All patients were term and preterm newborn infants. In the first two studies blood was obtained postoperatively after major surgery from patients with wound catheters for determination of Levobupivacaine (LB) concentrations after intermittent (StudyI) or continuous (Study II) infusion with LB: The first study used a sampling protocol of six samples over a 24 hour period and the second study used four samples in 72 hours. Pain was assessed using validated pain scales and morphine consumption was registered. In Study III levels of AAGP was determined in blood sampled from umbilical arteries direct after delivery.

Results/Conclusions: Studies I and II. The studied infusion regimens with LB administered by wound catheters was associated with plasma levels of LB well below toxicity. We also noted good wound healing, low pain scores and reduced need for opioids compared to our normal clinical experience. Study III: This study suggest a significant correlation between increasing gestational age and increasing levels of AAGP in plasma. AAGP levels in plasma seem to correspond with increasing maturity of the new-born infant. Gender and birth weight did not seem to influence AAGP concentrations in plasma. Infants born vaginally had significantly higher levels of AAGP compared to those born with planned caesarean section. • Local anaesthesia by wound catheter administration in term- and preterm new-born infants is a safe method to use. • Gestational age and mode of delivery should be factors when determining dosage of local anaesthetics.

List of scientific papers

I. Plasma concentrations of levobupivacaine associated with two different intermittent wound infusion regimens following surgical ductus ligation in preterm infants. Anell-Olofsson M, Lönnqvist PA, Bitkover C, Lundeberg S, Larsson BA, Eksborg S, Bartocci M. Paediatr Anaesth. 2015; 25: 711-718.
https://doi.org/10.1111/pan.12634

II. Plasma levels of levobupivacaine during continuous infusion via a wound catheter after major surgery in newborn infants: an observational study. Krylborn J, Anell-Olofsson ME, Bitkover C, Lundeberg S, Bartocci M, Stiller C-O, Larsson BA. European journal of Anaesthesiology. 2015; 32: 851-856.
https://doi.org/10.1097/EJA.0000000000000317

III. Plasma concentrations of alpha-1-acid-glycoprotein in preterm and term infants at birth: Influence of mode of delivery and implications for the use of local anaesthesia. Anell-Olofsson M, Ahmadi S, Eksborg S, Lönnqvist PA, von Horn H, Bartocci M. Br J Anaeth. 2018.
https://doi.org/10.1016/j.bja.2018.01.034