Doxapram

DOXAPRAM

Mechanism of Action

Doxapram (Dopram) is a peripheral and central nervous system stimulant. Selective activation of carotid chemoreceptors by low doses ofdoxapram stimulates hypoxic drive, producing an increase in tidal volume and a slight increase in respiratory rate. At larger doses, the central respira-tory centers in the medulla are stimulated.

Clinical Uses

Because doxapram mimics a low Pao₂, it may be useful in patients with chronic obstructive pulmo-nary disease who are dependent on hypoxic drive yet require supplemental oxygen. Drug-induced respiratory and central nervous system depression, including that seen immediately postoperatively, can be temporarily overcome. Doxapram is not a specific reversal agent, however, and should not replace stan-dard supportive therapy (mechanical ventilation). For example, doxapram will not reverse paralysis caused by muscle relaxants, although it may tran-siently mask respiratory failure. The most common cause of postoperative hypoventilation—airway obstruction—will not be alleviated by doxapram. For these reasons, many anesthesiologists believe that the usefulness of doxapram is very limited.

Side Effects

Stimulation of the central nervous system leads to a variety of possible side effects: changes in mental status (confusion, dizziness, seizures), cardiac abnor-malities (tachycardia, dysrhythmias, hypertension), and pulmonary dysfunction (wheezing, tachypnea). Vomiting and laryngospasm are of particular con-cern to the anesthesiologist in the postoperative period. Doxapram should not be used in patients with a history of epilepsy, cerebrovascular disease, acute head injury, coronary artery disease, hyperten-sion, or bronchial asthma.

Dosage

Bolus intravenous administration (0.5–1 mg/kg) results in transient increases in minute ventilation (the onset of action is 1 min; the duration of action is 5–12 min). Continuous intravenous infusions (1–3 mg/min) provide longer-lasting effects (the maximum dose is 4 mg/kg).

Drug Interactions

The sympathetic stimulation produced by doxa-pram may exaggerate the cardiovascular effects of monoamine oxidase inhibitors or adrenergic agents. Doxapram should probably not be used in patients awakening from halothane anesthesia, as halothane sensitizes the myocardium to catecholamines.