DOX-a-pram

Therapeutic Classification: central nervous system stimulants

• Used in carefully selected short-term situations with other supportive measures to treat postoperative patients with respiratory depression secondary to anesthesia.
• Prevention of acute hypercapnea during administration of oxygen to patients with acute respiratory insufficiency due to COPD (short-term only — less than 2 hr).
• Treatment of mild-to-moderate respiratory and CNS depression due to drug overdosage.

• In low doses, stimulates breathing by activating carotid receptors.
• Larger doses directly stimulate the respiratory center in medulla as well as produce generalized CNS stimulation.

• Transient increase in tidal volume, small increase in respiratory rate. Oxygenation is not increased.

Absorption: Administered IV only; results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Rapidly metabolized; metabolites mostly excreted by the kidneys.

Half-life: 2.4–4 hr.

(increases in minute volume)

Contraindicated in:

• Hypersensitivity
• Patients on mechanical ventilation
• Head trauma
• Seizures
• Flail chest
• Pulmonary embolism
• Pneumothorax
• Pulmonary fibrosis
• Acute asthma
• Extreme dyspnea
• Cardiovascular or cerebrovascular disease
• Pedi: Newborns (contains benzyl alcohol).

Use Cautiously in:

• Patients with a history of asthma or arrhythmias
• Hyperthyroidism
• Pheochromocytoma
• Serious uncorrected metabolic disorders
• Hepatic or renal impairment
• OB: Lactation: Pedi: Pregnancy, lactation, or children <12 yr (safety not established).

CV: hypertension, T-wave inversion, arrhythmias, changes in heart rate, chest pain.

Derm: flushing, pruritus, sweating.

EENT: gagging, mydriasis.

GI: diarrhea, nausea, vomiting.

GU: urinary retention, albuminuria, perineal/genital burning sensation, spontaneous voiding.

Hemat: hemolysis.

Local: phlebitis.

MS: muscle spasticity, involuntary movement, skeletal muscle hyperactivity.

Neuro: apprehension, disorientation, dizziness, generalized clonus, headache, paresthesia, positive bilateral Babinski’s sign , SEIZURES.

Resp: bronchospasm, cough, dyspnea, hiccups, LARYNGOSPASM, rebound hypoventilation, tachypnea.
Misc: fever.

Drug-Drug:

• Pressor effects may be ↑ by concurrent use of adrenergic amines (sympathomimetics) or MAO inhibitors.
• May mask residual effects of skeletal muscle relaxants. Initial release of epinephrine caused by doxapram may cause adverse reactions when given concurrently with anesthetics known to sensitize the myocardium to the effects of cathecholamines (wait 10 minutes following discontinuation of anthesthetic to administer doxapram).
• Concurrent use with aminophylline or theophylline may worsen skeletal muscle hyperactivity.

Respiratory Depression following Anesthesia

• IV (Adults): Intermittent injection–0.5–1 mg/kg (not to exceed 1.5 mg/kg) initially; may repeat every 5 min to a total of 2 mg/kg. Infusion: Initiate at 5 mg/min until response is obtained; then decrease infusion rate to 1–3 mg/min (total dose by infusion method should not exceed 4 mg/kg).

Drug-Induced CNS Depression

• IV (Adults): Intermittent injection– Give priming dose of 1–2 mg/kg; repeat in 5 min. May repeat at 1–2–hr intervals until sustained consciousness or total of 3 g/24 hr given. Infusion: Give priming dose of 1–2 mg/kg by direct injection; repeat in 5 min. If no response, continue supportive measures for 1–2 hr and repeat priming dose. If some respiratory stimulation occurs, initiate infusion at 1–3 mg/min. Discontinue infusion if patient begins to awaken or after 2 hr. Infusion may be restarted (along with priming dose) after rest interval of 30–120 min. Do not exceed 3 g/24 hr.

Acute Hypercapnea Secondary to COPD

• IV (Adults): Infusion– 1–2 mg/min (up to 3 mg/min). Should not be used for more than 2 hr.

• Injection: 20 mg/mL;

• Because of narrow margin of safety and indications for use, patient must be monitored constantly when receiving doxapram and until patient is fully alert for 30–60 min.
• Monitor respiratory status (rate and depth of respirations) and ABGs. Ensure that patient has patent airway and is adequately oxygenated. Relapse of respiratory depression may occur if CNS depressant has long duration of action. Position patient on side, with head of bed elevated to encourage maximal chest expansion and to prevent aspiration.
• Monitor neurologic status (level of consciousness and deep tendon reflexes). Notify health care professional if reflexes become hyperactive or if spasticity occurs.
• Monitor vital signs, ECG, and hemodynamic parameters. May cause tachycardia, hypertension, increased cardiac output, or increased pulmonary artery pressure. Report significant change in hemodynamic parameters, arrhythmias, or chest pain. Patients with COPD may be at increased risk for arrhythmias because of hypoxia. Discontinue infusion if sudden hypotension, dyspnea, or arrhythmia occur.
• Inspect infusion site. May cause thrombophlebitis (erythema, swelling, and pain or skin irritation).

• Monitor ABGs prior to and every 30 min during therapy. Notify health care professional immediately if ABGs deteriorate. May order cessation of drug, intubation, and mechanical ventilation.
  • Monitor hemoglobin, hematocrit, and leukocyte count. Rapid infusion may cause hemolysis.
  • May cause ↑ BUN and proteinuria.

• Toxicity is manifested by severe hypertension, tachycardia, and hyperactive reflexes or seizures. Infusion should be stopped immediately. Seizures may be controlled with diazepam or a short-acting barbiturate. Resuscitative equipment should be available at all times.

IV Administration:

• Administer undiluted. Administer over 5 min.
• Intermittent Infusion: For patients with respiratory depression, following anesthesia or drug-induced CNS depression, dilute 250 mg in 250 mL of D5W, D10W, or 0.9% NaCl. Concentration will be 1 mg/mL.
  • For patients with acute hypercapnea secondary to COPD, dilute 400 mg in 180 mL of D5W, D10W, or 0.9% NaCl. 2 mg/mL.
• Rate: Doses vary with patient's condition (see Route and Dosage section).
  • Administer via infusion pump to ensure accurate dosage.
• Y-Site Compatibility:
  • ampicillin
  • caffeine citrate
  • calcium chloride
  • calcium gluconate
  • cefazolin
  • ceftazidime
  • erythromycin
  • fentanyl
  • gentamicin
  • heparin
  • insulin
  • metoclopramide
  • metronidazole
  • oxacillin
  • phenobarbital
  • vancomycin
• Y-Site Incompatibility:
  • clindamycin
.

• Instruct patient to notify health care professional immediately if shortness of breath worsens.

• Treatment of postoperative respiratory depression not associated with skeletal muscle relaxants.
• Treatment of respiratory and CNS depression due to drug overdosage.
• Prevention of acute respiratory insufficiency in patients with COPD. Doxapram is not used often because of its narrow margin of safety.

Dopram