Continuous Intravenous Infusion

• Start at 0.5mg/kg/hour and, if necessary, titrate upwards at increments of 0.5 mg/kg/hour to a usual maximum of 1.5 mg/kg/hour
• Review continuing use on a daily basis. There is some evidence that the effect may not be sustained.

Indications

• Apnoea of prematurity unresponsive to caffeine citrate (or aminophylline).

Contraindications and Precautions ^{1, 2, 3}

1. Seizures
2. Recent periventricular haemorrhage
3. Cerebral oedema
4. Severe hypertension
5. Cardiac failure
6. Hyperthyroidism

Precautions

• Impaired renal or hepatic function

Clinical Pharmacology ^{1, 2, 3, 4}

Doxapram is a respiratory stimulant, acting principally through the central respiratory centres in the medulla. Stimulation of peripheral carotid chemoreceptors may also contribute to the respiratory action. The resultant effect is an increase in tidal volume with an increase in respiratory rate. Doxapram has a quick onset and short duration of action. A release in catecholamines has been noted following the use of doxapram, leading to a pressor effect, attributed to an increase in cardiac output rather than a peripheral vasoconstriction.

Doxapram undergoes extensive hepatic metabolism, with very little free drug appearing in the urine.

Possible Adverse Effects ^{1, 2, 3, 7}

1. Hypertension is the most common adverse effect seen in preterm infants, and can even occur at low doses⁷.  Monitor blood pressure regularly.
2. QTc prolongation, 2nd degree heart block, arrhythmias.
3. Seizures (may be associated with high doses), irritability, flushing, sweating, involuntary movements, muscle spasm.
4. Respiratory distress
5. Vomiting, diarrhoea, urinary retention.
6. Extravasation may cause thrombophlebitis or skin irritation.

Drug Interactions ¹

1. Caffeine Citrate, aminophylline  -  possible increase in CNS stimulation.

Special Considerations ^{3, 6}

1. Do not use in conjunction with mechanical ventilation.
2. Monitor:
   • B.P. & pulse rate (sudden onset of hypotension or dyspnoea suggests that doxapram should be stopped)
   • Blood gases: consider ventilation if there is a deterioration in blood gas parameters without clinical improvement
3. Watch for accumulation if high doses are infused for more than 36 to 48 hours.
4. Signs of overdose are: excessive pressor effect, tachycardia, skeletal muscle hyperactivity (tremors), enhanced deep tendon reflexes.
5. Some preparations of doxapram contain benzyl alcohol as a preservative (e.g.Wyeth brand of Dopram®). Benzyl alcohol may cause significant metabolic and neurological disturbance in infants.
6. Doxapram is not licensed for use in children. There are limited trials evaluating its use in neonates for the treatment of apnoea.