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Abstract
Background and importance Apnoea of prematurity (AOP) is an alteration of the regulation of breathing and is very prevalent. The treatment of choice is caffeine but there is a lot of variability in its dosage, often using doses higher than recommended. Despite the wide safety range, pharmacokinetic monitoring may be necessary in certain cases.
Aim and objectives The goal was to establish the usefulness of saliva for monitoring serum caffeine levels non-invasively.
Material and methods This was a single centre, prospective, observational study. Premature patients admitted to the neonatology service between December 2017 and August 2018 being treated with caffeine for AOP were sequentially included on request for informed consent. Two paired samples of saliva–blood were collected per patient, at pre-dose time, taking advantage of routine blood withdrawals. Saliva was collected with cellulose sponges (Eyetec) in Eppendorf tubes and blood in dry tubes (Mini-collect). Salivary secretion stimulators were not used. The samples were centrifuged immediately after being collected and stored at −20°C. The determination was made by micro-extraction in solid phase in tube coupled to capillary liquid chromatography. We recorded date of birth, gestational age (GA), sex, weight, caffeine treatment regimen, renal function and concomitant drugs.
Results Forty-seven neonates were included, mean GA 27.8 (SD 2.36) weeks, birth weight 1.11±0.44 kg and 62% were male sex. Mean corrected GA on the day of determination was 31±2.7 weeks and weight was 1.85±0.45 kg. Administration was oral in 59% and intravenous in 41%. The mean concentration of caffeine in saliva was 16.35±9.21 and in serum 19.28±9.21 µg/mL. Serum and saliva concentrations showed a strong correlation (Pearson’s correlation=0.83, figure 1), which was higher with oral administration (0.90 vs 0.73 intravenous). Predictive model of linear regression of blood values was performed from saliva values. When comparing weight, GA, sex, caffeine dose (mg/kg) and concomitant drugs, no differences in correlation were observed through a multivariate analysis. No patient had kidney failure.
Correlation between serum and saliva (intravenous and oral) levels
Conclusion and relevance Saliva determination is a reliable and non-invasive method for monitoring caffeine levels in preterm children with AOP. Correlation was higher when caffeine was administered orally, probably due to greater clinical stability when oral medication is administered.
References and/or acknowledgements No conflict of interest.