Caffeine citrate: Is it a silver bullet in neonatology?
Caffeine citrate is one of the most prescribed drug in the present day NICU for apnea. Its efficacy, tolerability, wide therapeutic index and safety margin has made it the drug of choice among the methylxanthines.

Its therapeutic uses in apnea of prematurity, mechanical ventilation, bronchopulmonary dysplasia has made it a “silver bullet” in neonatology. However, there are still controversies surrounding this drug.

This review, published in the journal Pediatrics & Neonatology is aimed to update the reader about the basic pharmacology, current therapeutic uses, adverse effects, controversies as well as present and future research of caffeine.

Dosing and route:-
- Caffeine is available as caffeine citrate, which is available in both oral and injectable formulations. Earlier, caffeine was also available as an intramuscular injection of caffeine benzoate. However, in view of bilirubin displacement from the albumin binding sites in the neonates, this formulation has gone out of favor.

- The dose of caffeine base is half that of caffeine citrate. The most popular dosing of caffeine citrate is 20 mg/kg loading and 5 mg/kg of maintenance dose OD, given either as slow intravenous infusion over twenty to thirty minutes or as oral formulation.

- This standard dosing is known to achieve therapeutic level of eight to 20 mg/L in more than 70% of neonates.15 However, many studies have shown higher doses of caffeine to be more effective with negligible adverse effects.

- Loading dose of up to 50 mg/kg and maintenance dose of up to 20 mg/kg has been shown to be more effective in reducing apneic episodes and facilitating extubation in comparison to standard dose.

Pharmacologic actions:-
- Caffeine stimulates the respiratory center, sensitizing it to hypercapnia. This leads to increase in mean respiratory rate and tidal volume, improved pulmonary blood flow, better carbon dioxide sensitivity and enhanced diaphragmatic function and breathing pattern.

- It also acts as a central stimulant as well as a somnolytic agent. The adenosine blocking action of caffeine is also known to secondarily affect several other neurotransmitters in the brain like dopamine, serotonin, noradrenaline, acetylcholine, gamma-aminobutyric acid [GABA], etc.

- Caffeine stimulates the myocardium and increases heart rate, cardiac output, stroke volume as well as mean arterial blood pressure. In kidneys, caffeine increases glomerular filtration rate and produces diuresis.

- This is primarily mediated via its adenosine antagonistic activity in the kidneys. Caffeine also increases basal metabolic rate, enhances catecholamine secretion and alters glucose homeostasis.

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