Caffeine Levels Not Helpful

Natarajan G, Botica ML, Thomas R, et al. Therapeutic Drug Monitoring for Caffeine in Preterm Neonates: An Unnecessary Exercise? PEDIATRICS (May 2007); 119: 936-940. [Full text] [PDF]

OBJECTIVE. Our goal was to determine the value of measuringplasma caffeine levels in preterm neonates treated with caffeinefor apnea. We evaluated plasma concentrations of caffeine attainedin preterm neonates at standard doses, at varying postconceptualages, with renal or hepatic dysfunction and when there was clinicallack of efficacy. We hypothesized that measurement of plasmacaffeine concentrations during apnea therapy is not clinicallyhelpful.

PATIENTS/METHODS. An observational study was conducted at HutzelWomen's Hospital between January 2000 and September 2005. Pretermneonates who were being treated with caffeine and who had aplasma caffeine level measured on at least 1 occasion were included.

RESULTS. A total of 231 caffeine blood levels were obtainedfrom 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 form2.5 to 10.9 mg/kg (median: 5 mg/kg), and the levels ranged from3.0 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 5.1to 20 mg/L range were attained on 91.3% of occasions when there was concomitant renal dysfunction (n = 23) and in all casesof 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 caffeinelevels between 5 and 20 mg/L, independent of gestation. Thisobservation held even for the small number of subjects withelevated blood urea nitrogen, serum creatinine, or liver enzymelevels. Therapeutic drug monitoring is not necessary when caffeineis used for the treatment of apnea of prematurity in neonates.

Comments. There appears to be much variation in practice concerning the use and monitoring of caffeine for apnea of prematurity (see 7-034 for the results of a recent survey that we conducted on this topic). The present study takes a critical look at the usefulness of obtaining caffeine levels. In premature infants receiving usual maintenance doses of caffeine citrate (5-8 mg/kg/day), caffeine levels were found to be in therapeutic range (5-20) about 95% of the time, regardless of gestational age, renal dysfunction or hepatic dysfunction. Also, levels as low as 2.9 can be therapeutic for decreasing apnea. Levels as high as 69 have been documented without any untoward effects. I agree with the author’s conclusion: the routine monitoring of caffeine levels is unnecessary. ABK.

Currently, caffeine is in use more and more compared to Aminophylline. We should know about monitoring its level. Caffeine has much less side effects than Aminophylline. Also it has been shown by this study and many other studies that there is no need to do the levels. It is unnecessary to prick a neonate for the test which is not indicated. As indicated in the article that majority of preterm neonates attain levels in same range. So if the caffeine given in correct dose there is no need to do the levels.

You may add your own comments to the discussion of this topic by selecting : Submit Comments.