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Caffeine

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Dose and administration

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  Loading Dose Maintenance dose
IV 20 mg/kg/dose over 30 minutes 5 mg/kg/dose every 24hrs1,2,3 
Oral 20 mg/kg/dose - give with feed 5 mg/kg/dose
Additional information Maintenance dose can be increased to 10mg/kg/dose every 24 hours if apnoeas persist. 
Maintenance dose given at 0600 hrs.
If loading dose given before 2200 hrs, start maintenance at 0600 next day. 
If loading dose given after 2200 hrs, miss the next 0600 hr dose and give a day later at 0600hrs (i.e. between 24 to 32 hours after the loading dose).  

Note: Caffeine Citrate 20mg/ml is equivalent to Caffeine Base 10mg/ml

Indications

  1. Apnoea of prematurity 
  2. Respiratory stimulation to assist extubation - other doses have been used 

Contraindications and precautions

  • Known hypersensitivity to caffeine 
  • Caution in very immature infants 
  • Caution in neonates with liver and/or gastrointestinal tract disease 
  • Caution in neonates with fits or tachyarrhythmia 

Clinical pharmacology

Caffeine is a member of the group of chemically related alkaloids known as methylxanthines. Almost all organ systems can be influenced by the methylxanthines, although the predominant site of activity involves the central nervous system and the cardiovascular system. Three major cellular actions of the methylxanthines have been suggested: translocation of intracellular calcium, increasing accumulation of cyclic nucleotides (particularly cyclic 3'S' AMP), and blockage of receptors for adenosine.

Pharmacological effects of caffeine include: stimulation of medullary respiratory centres, generalised enhancement of CNS cellular response to stimulation, increased heart rate, decreased peripheral vascular resistance, increased cerebral vascular resistance, smooth muscle relaxation, skeletal muscle stimulation, stimulation of gastrointestinal secretions, and diuresis. Caffeine may increase diaphragmatic contractility. The pharmacological mechanisms proposed for the alteration of neonatal apnoea include: increased sensitivity of medullary respiratory centre to CO2, increased afferent nerve traffic to brain stem, increased catecholamine response, stimulation of central inspiratory drive, improved skeletal muscle contraction, improved metabolic homeostasis, and improved oxygenation via increased cardiac output and decreased hypoxaemic episodes. Caffeine, when compared to theophyllines with equal efficacy, has fewer side effects. Caffeine has a wider therapeutic to toxic ratio and is administered once a day because of its long half-life. Serious problems are rare and only occur in large overdose but would include neurological abnormalities such as tremor, seizures and hypertension, cardiac abnormalities such as tachyarrhythmias. Side effects are rare at levels <400μmol/ml.

Oral administration results in very good bioavailability. There is little evidence that food delays absorption of caffeine. Caffeine is metabolised by the liver cytochrome oxygenase system which is induced by phenobarbitone and phenytoin. Levels may be increased by enzyme inhibitors such as cimetidine.

Possible adverse effects

  • Failure to gain weight
  • Hyperglycaemia, hypoglycaemia3
  • Gastrointestinal disturbances (nausea, vomiting, abdominal distension)
  • Irritability, sleeplessness, jitteriness
  • Cardiac arrhythmias, tachycardia, rarely bradycardia, hypertension3
  • Diuresis and dehydration
  • Tachypnoea
  • Hyperreflexia, seizures
  • Necrotising enterocolitis2

Special considerations

  1. Half-life very long (t½>100hrs). A baby will need respiratory monitoring for several days after discontinuing.
  2. Rapid infusion of caffeine citrate may precipitate cardiac arrhythmias.
  3. Routine levels are not necessary on stable babies. Serum levels should be obtained if toxicity is suspected or if a baby continues to have apnoea and has not previously had an optimal level documented. Levels should not be checked within 6 hours of previous dose. Order levels the day before assay is to be done and do at 0830 hours. Therapeutic range is: 50 - 180 micromol/litre; levels > 260 micromol/litre are considered toxic . Note that the assay is not very accurate and has a coefficient of variation of 15%.
  4. Treatment of serious caffeine toxicity: activated charcoal 1 gm/kg as a slurry by gavage tube every 2-4 hours. Avoid sorbitol-containing preparations - they may cause osmotic diarrhoea.
  5. If infant is on phenobarbitone clearance of caffeine citrate is increased, therefore decrease dose interval from 24 hourly to 12-18 hourly

Management of Caffeine Citrate administration

Description

IV preparation Labelled as Caffeine Citrate Injection 20 mg/ml (equivalent to caffeine base 10 mg/ml).
Oral preparation Labelled as Caffeine Citrate Injection 20 mg/ml (equivalent to caffeine base 10 mg/ml).
Prescription Loading dose is charted on stat page of prescription chart in mg/dose.
Maintenance doses are charted on the prescription chart in mg/dose.

Administration

Slow IV infusion
1 Filter during administration with a 0.22 micron Pall filter.
2 Administer loading dose by slow IV infusion over 30 minutes using a syringe pump.
3 Administer maintenance dose over 15 minutes.
4 Compatible with sodium chloride 0.9%, glucose 5%, glucose 10%.
5 Incompatible with aciclovir and frusemide. Do not mix with other drugs, IV solutions unless checked beforehand with Pharmacy. Do not mix with blood or blood products.
6 Do NOT mix with Parenteral Nutrition solutions.
7 Flush tubing with sodium chloride 0.9% before and after administration.
Oral
1 Administer with feeds. Absorption is delayed but not decreased by feeds.

No information on IM administration.

Nursing considerations

  1. Observe IV site for signs of extravasation.
  2. Assess for signs of adverse effects.
  3. Initial treatment should be monitored by a cardiorespiratory monitor and a pulse oximeter. Once stable, discuss apnoea monitoring with doctor.
  4. Monitor apex beat, rate and rhythm regularly. Apex beat must be taken immediately prior to administration (preferably an undisturbed rate). If the apex beat is > 180/minute withhold medication and notify doctor / NS-ANP immediately. Dose may then be administered if requested by doctor/NS-ANP.
  5. Monitor respiratory rate, quality and effort.
  6. Monitor incidence of apnoea. Continue apnoea monitoring for several days after stopping caffeine.
  7. Monitor for glycosuria.
  8. May be administered orally once the baby is tolerating 50% of full oral feed volumes.

Storage

  • Ampoule unopened - at room temperature. Discard after use. DO NOT REFRIGERATE
  • Oral - discard 1 day after opening. DO NOT REFRIGERATE

References

  1. Trissel LA. Handbook on Injectable Drugs. American Society of Health-System Pharmacists (ASHP) 16th Edition.
  2. Phelps SJ, Hak EB, Crill CM, editors. Teddy bear book: Pediatric injectable drugs. 8th ed. Bethesda, MD: American Society of Heath-System Pharmacists; 2007.
  3. Martin, J, Managing editor. BNF for children 2010-2011. London: BMJ Group, Pharmaceutical Press & RCPCH Publications Ltd; 2010.
  4. Hey, E, editor. Neonatal formulary. 5th ed. Oxford: Blackwell Publishing; 2007
  5. Young TE, Mangum B, editors. Neofax: A manual of drugs used in neonatal care. 18th ed. Raleigh, North Carolina, USA: Acorn Publishing; 2005.

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Document Control

  • Date last published: 03 August 2011
  • Document type: Drug Dosage Guideline
  • Services responsible: Neonatology, ADHB Pharmacy
  • Owner: Newborn Services Clinical Practice Committee
  • Editor: Sarah Bellhouse
  • Review frequency: 2 years