Therapeutic drug monitoring for caffeine in preterm neonates: an unnecessary exercise?

Objective: Our goal was to determine the value of measuring plasma caffeine levels in preterm neonates treated with caffeine for apnea. We evaluated plasma concentrations of caffeine attained in preterm neonates at standard doses, at varying postconceptual ages, with renal or hepatic dysfunction and when there was clinical lack of efficacy. We hypothesized that measurement of plasma caffeine concentrations during apnea therapy is not clinically helpful.

Patients/methods: An observational study was conducted at Hutzel Women's Hospital between January 2000 and September 2005. Preterm neonates who were being treated with caffeine and who had a plasma caffeine level measured on at least 1 occasion were included.

Results: A total of 231 caffeine blood levels were obtained from 101 preterm neonates with a median gestation of 28 weeks (range: 23-32 weeks) and birth weight of 1030 g (range: 540-2150 g). The caffeine citrate dose used ranged form 2.5 to 10.9 mg/kg (median: 5 mg/kg), and the levels ranged from 3.0 to 23.8 mg/L. Levels were between 5.1 and 20 mg/L in 94.8%, <5 mg/L in 2.1%, and >20 mg/L in 3.1%. Levels in the 5.1 to 20 mg/L range were attained on 91.3% of occasions when there was concomitant renal dysfunction (n = 23) and in all cases of hepatic dysfunction (n = 13). The median (25th, 75th quartiles) levels drawn for lack of efficacy (14.1 [10.2, 8.3] mg/L; n = 94) were comparable to those obtained for routine monitoring (13.7 [11, 9] mg/L; n = 107).

Conclusions: A majority of preterm neonates attain plasma caffeine levels between 5 and 20 mg/L, independent of gestation. This observation held even for the small number of subjects with elevated blood urea nitrogen, serum creatinine, or liver enzyme levels. Therapeutic drug monitoring is not necessary when caffeine is used for the treatment of apnea of prematurity in neonates.