Caffeine for apnea of prematurity

With the advent of Cafcit, a commercial preparation of caffeine citrate for intravenous administration, iv caffeine has replaced aminophylline as VUMC NICU’s methylxanthine of choice for the treatment of apnea of prematurity. Caffeine has a better side-effect profile and a wider therapeutic window than other methylxanthines.

Caffeine citrate (IV/PO)      Loading dose: 20 mg/kg x 1

                                          Maintenance dose: 5 mg/kg q 24 h

The first maintenance dose begins 24 hours after the loading dose.

Previously, our maintenance dose of po caffeine was 10 mg/kg/q 24 hours. Due to methylxanthines’ potential adverse effects on mesenteric blood flow/GI side effects, this dose has been reduced to match the iv maintenance dose. However, in infants with no evidence of adverse effects who continue to have symptomatic apnea of prematurity, the maintenance dose of po caffeine can be increased in 2.5 mg/kg increments up to 10 mg/kg q 24 hours if necessary.

Caffeine serum levels are not obtained routinely. Caffeine levels are performed off-site with a turn-around time of 2-3 days. However, caffeine levels can be obtained on a prn basis if a baby has symptoms of potential toxicity or if the infant continues to have persistent unexplained apnea despite an adequate dose of caffeine.

Therapeutic range: 4-20 mcg/mL

Symptoms of toxicity

• Unexplained tachycardia (HR > 180 bpm for > 10 minutes at rest)
• Unexplained seizure activity
• Excessive agitation lasting over 1 hour without identifiable precipitating factors
• Vomiting, especially bloody emesis

For these symptoms, withhold caffeine and consider obtaining a caffeine level to make a diagnosis.

Infants receiving both caffeine and cimetidine should have caffeine levels monitored due to potential drug interaction. Infants on low dose erythromycin do not need to have caffeine levels monitored. Infants simultaneously receiving caffeine and antimicrobial doses of erythromycin should be carefully observed for symptoms of toxicity.

References:

Steer PA, Henderson-Smart DJ. Caffeine versus theophylline for apnea in preterm infants. Cochrane Database of Systematic Reviews (2):CD000273, 2000. http://www.nichd.nih.gov/cochraneneonatal/Steer/Steer.HTM

Henderson-Smart DJ, Steer P. Methylxanthine treatment for apnea in preterm infants. . Cochrane Database of Systematic Reviews (2):CD000140, 2000.   http://www.nichd.nih.gov/cochraneneonatal/DHS1/DHS.HTM