Doxapram
Doxapram is a centrally acting analeptic agent (CNS and respiratory stimulant). In veterinary medicine, it is primarily utilized to stimulate respiration during or after general anesthesia and to speed awakening. It is also uniquely valuable for the **assessment of laryngeal function** (e.g., diagnosing laryngeal paralysis) under light anesthesia, as it stimulates deep inspiratory efforts that make arytenoid cartilage movement easier to evaluate. > **Clinical Pearl:** Historically, doxapram was routinely administered (often sublingually or via the umbilical vein) to stimulate breathing in neonates following dystocia or C-section. **This use is now highly controversial.** Doxapram significantly increases myocardial and cerebral oxygen demand. In an already hypoxic neonate, this can be detrimental. Current neonatal resuscitation guidelines strongly emphasize clearing the airway, providing oxygen, and utilizing positive pressure ventilation (mechanical support) over the use of analeptic drugs.
Mecanismo: Doxapram is a generalized CNS stimulant. Its respiratory effects are primarily driven by: 1. **Direct stimulation** of the **medullary respiratory centers**. 2. **Reflex activation** of peripheral **carotid and aortic chemoreceptors**. This dual action leads to transient increases in tidal volume and respiratory rate. > **Mechanistic Note:** While doxapram increases respiratory effort, it simultaneously increases the overall work of breathing, metabolic rate, and carbon dioxide production. Consequently, it does not reliably improve arterial oxygenation, which is why it cannot replace mechanical ventilation in severely hypoxic patients.
Dosificación por especie
- Gas anesthesia recovery · 1.1 mg/kg IV · IV · May repeat in 15-20 minutes if necessary · Adjust dosage for depth of anesthesia, respiratory volume and rate.
- Barbiturate anesthesia recovery · 5.5-11 mg/kg IV · IV · May repeat in 15-20 minutes if necessary · Adjust dosage for depth of anesthesia, respiratory volume and rate.
- To initiate or stimulate respirations in neonates after caesarian section or dystocia · 1-2 drops (1-2 mg) SC or sublingually · SC/SL · Once · Depending on severity of respiratory crisis.
- To stimulate respiratory function in neonates · 0.1 mL (2 mg) IV (IM or SL also possible) · IV/IM/SL · Once · Most likely to be beneficial to increase efforts in neonates with low-frequency, gasping, erratic pattern of breathing after receiving oxygen therapy.
- Primary apnea in asphyxic calves when intubation and mechanical ventilation are not feasible · 2 mg/kg IV · IV · Once · Contraindicated in premature calves or other patients with clinical signs indicative of lung immaturity.
- Primary apnea in newborn calves · 2 mg/kg IV · IV · Once
- Halothane, methoxyflurane anesthesia recovery · 0.44 mg/kg IV · IV · May repeat in 15-20 minutes if necessary · Adjust dosage for depth of anesthesia, respiratory volume and rate. ARCI UCGFS Class 2 Drug.
- Chloral hydrate ± magnesium sulfate anesthesia recovery · 0.55 mg/kg IV · IV · May repeat in 15-20 minutes if necessary · Adjust dosage for depth of anesthesia, respiratory volume and rate. ARCI UCGFS Class 2 Drug.
Vías de administración
Contraindicaciones
- Patients receiving mechanical ventilation
- Hypersensitivity to doxapram
- Seizure disorders
- Head trauma or cerebrovascular accidents (CVA)
- Uncompensated heart failure
- Severe hypertension
- Respiratory failure secondary to neuromuscular disorders
- Airway obstruction
- Pulmonary embolism
- Pneumothorax
- Acute asthma
- Dyspnea
- Hypoxia not associated with hypercapnia
- Premature calves or patients with clinical signs of lung immaturity
Efectos adversos
- Hypertension
- Arrhythmias
- Tachycardia
- Seizures (at high doses)
- Hyperventilation leading to respiratory alkalosis
- Increased myocardial oxygen demand
- Reduced cerebral blood flow
- Skeletal muscle hyperactivity
Interacciones farmacológicas
- General Anesthetics (e.g., halothane, enflurane) · Doxapram may increase epinephrine release and sensitize the myocardium to catecholamines. Use should be delayed for ~10 minutes after discontinuing these anesthetics.
- Muscle Relaxants · Doxapram may mask the effects of muscle relaxant drugs.
- Sympathomimetic Agents · Additive pressor (blood pressure increasing) effects may occur.
Monitoreo
- Respiratory rate and effort
- Cardiac rate and rhythm
- Blood gases (if available and indicated)
- CNS level of excitation and reflexes
- Blood pressure (if indicated)
Sobredosis
The reported LD50 for IV administration in neonatal dogs and cats is approximately 75 mg/kg. **Clinical signs of overdosage include:** - Respiratory alkalosis - Hypertension - Skeletal muscle hyperactivity - Tachycardia - Generalized CNS excitation, including seizures **Treatment:** Treatment is primarily supportive. Drugs such as short-acting IV barbiturates may be used to help decrease CNS hyperactivity. Oxygen therapy may be necessary.
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