Biochemical tolerance during low dose propylene glycol exposure in neonates: A formulation-controlled evaluation

Renal (diuresis, creatinemia, sodium), metabolic (Base Excess, Anion Gap, lactate, bicarbonate) and hepatic (liver enzymes, bilirubinemia) indicators before, during and following iv paracetamol-PG exposure in neonates as included in the PARANEO (paracetamol in neonates) study (intra-individual trends, ANOVA) were collected and analysed. Comparison with observations collected in cases exposed to either iv phenobarbital-PG or iv paracetamol-mannitol (inter-individual comparison, Mann Whitney-U test) were made.PG exposure (median 34.1？mg/kg/24？h) did not affect postnatal renal, metabolic and hepatic adaptations in 60 cases exposed to paracetamol-PG. These indicators were similar when compared to 29 cases exposed to phenobarbital-PG or 172 cases exposed to paracetamol-mannitol.Based on observations in 89 neonates, low dose PG exposure was tolerated well. Studies on PG pharmacokinetics and its covariates are needed to estimate the upper level of PG tolerance in neonates.Propylene glycol (1,2 propanediol, PG) is a clear, colourless, odourless, water-soluble alcohol. Physically, it is similar to ethylene glycol but PG is claimed to be less toxic [1,2]. However, PG exposure can cause lactic acidosis, may result in an increase in Anion Gap or Osmolar Gap, hyponatremia or hepatic dysfunction. Other side effects such as hemolysis, mental status changes or renal toxicity (e.g. renal tubular acidosis, acute tubular necrosis resulting in increased serum creatinine and oliguria) were reported as manifestations of PG toxicity [1-3]. Most of these reports relate to continuous intravenous (iv) administration of benzodiazepines (e.g. lorazepam) containing PG as solvent in adult intensive care setting, resulting in PG exposure above 200？g/day or 2？g/kg/day [4].Based on the current evidence, PG toxicity relates to its accumulation, and therefore is driven by the extent of exposure and the individual elimination capacity [5]. Median PG clearance following exposure to 3–15？g PG/m2 in adul