Doxapram HCl

 Action Increases depth of respirations (tidal volume) by stimulating respiratory center in CNS; respiratory rate may increase slightly. May elevate BP by increasing cardiac output. Respiratory depression from opiates is reversed without affecting pain relief.

 Indications Reversal of respiratory depression caused by anesthesia (other than muscle relaxants) or drug overdose; temporary measure for acute respiratory failure in patients with COPD who are not undergoing mechanical ventilation. Unlabeled use(s): Low doses of doxapram have been used in the treatment of apnea of prematurity when methylxanthines have failed.

 Contraindications Use in newborns (contains benzyl alcohol); seizures; muscle paresis; epilepsy or other convulsive states; flail chest; head injury; pneumothorax; acute asthma; pulmonary fibrosis; other conditions that restrict chest wall, respiratory muscles or alveolar expansion; severe hypertension; CVA.

 Route/Dosage

Anesthesia-induced Respiratory Depression

ADULTS: Bolus IV injection 0.5 to 1 mg/kg (single dose not to exceed 1.5 mg/kg). Can be given as multiple IV injections q 5 min (not to exceed total dose of 2 mg/kg). IV infusion Initial rate: 5 mg/min until satisfactory respiratory response is noted. Maintenance rate: 1 to 3 mg/min. Maximum total infusion dose is 4 mg/kg.

Drug-induced CNS Depression

ADULTS: Maximum daily dose is 3 g. Bolus IV injection Priming dose is 2 mg/kg. Repeat in 5 min. Depending on response, may give q 1 to 2 hr. Intermittent IV infusion Priming dose is 2 mg/kg. If respirations improve, give by IV infusion at 1 to 3 mg/min. Discontinue after 2 hr or if patient awakens.

Acute Hypercapnia from COPD

ADULTS: IV infusion 2 mg/ml with initial rate of 1 to 2 mg/min; may increase to maximum of 3 mg/min; discontinue after 2 hr.

 Interactions

Cyclopropane, enflurane, halothane: To prevent arrhythmias, wait ³ 10 min after stopping these anesthetics before giving doxapram. MAO inhibitors, sympathomimetics: Increased risk of hypertension. Muscle relaxants: Residual effects may be temporarily masked by doxapram. Incompatibilities: Do not add to or give with alkaline solutions such as aminophylline, thiopental or sodium bicarbonate.

 Lab Test Interferences None well documented.

 Adverse Reactions

CV: Arrhythmias; tachycardia; increased BP; tightness in chest; chest pain; phlebitis. CNS: Seizures; paresthesia; increased reflexes; disorientation; dizziness; involuntary movements. EENT: Mydriasis. GI: Nausea; vomiting; diarrhea; desire to defecate. GU: Urinary incontinence and retention; elevation of BUN. HEMA: Hemolysis (with rapid infusion). RESP Laryngospasm; bronchospasm; rebound hypoventilation; cough; hiccoughs; dyspnea. OTHER: Flushing; feelings of warmth; sweating.

 Precautions

Pregnancy: Category B. Lactation: Undetermined. Children: Safety and efficacy not established in children < 12 yr. Doxapram contains benzl alcohol, which has been associated with fatal “gasping syndrome” in premature infants. COPD patients: Do not increase infusion rate in severely ill patients; drug may increase work of breathing. Drug-induced CNS and respiratory depression: Used as adjunct to supportive care. Postanesthesia: Do not use as antidote for opiates or neuromuscular blockers.

 Administration/Storage

• Ensure that patent airway has been established before administration.
• Do not give in conjunction with mechanical ventilation.
• Have readily available oxygen, IV barbiturates (eg, Valium) and resuscitative equipment.
• Allow 10 min after administration of anesthetic before starting infusion.
• Rotate injection sites to avoid skin irritation.
• For intermittent infusion, dilute 250 mg in 250 ml of D5W, D10W or 0.9% normal saline for concentration of 1 mg/ml. Dilute 400 mg in 180 ml of IV fluid for 2 mg/ml concentration.
• Store at room temperature.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies. Note any history of seizure disorder.
• Assess BP, pulse, deep tendon reflexes, neurologic status, ECG and ABGs before infusion and q 30 min during infusion.
• Institute seizure precautions before administering drug.
• Assess for poststimulation respiratory depression for ³ 30 min to 1 hr after patient becomes alert.
• Monitor respiratory status. Position patient on side in slightly elevated position to prevent aspiration.
• Monitor BP and deep tendon reflexes to prevent overdosage.
• Monitor patient's CBC since rapid infusion can cause hemolysis.
• If ABGs deteriorate, notify physician immediately. Drug may need to be discontinued and mechanical ventilation started.
• Check infusion site regularly for extravasation, skin irritation and signs of thrombophlebitis.

 Patient/Family Education

• Instruct patient/family to notify physician immediately if shortness of breath worsens.