CHAPTER 3-64: PHENYLEPHRINE

INTRODUCTION

1. Pharmacology. Phenylephrine directly and preferentially stimulates alpha₁-adrenergic receptors, although at higher doses it may also stimulate alpha₂- and beta₁-adrenergic receptors. It is a potent vasoconstrictor with little inotropic or chronotropic effect. Thus, in poisonings it is used primarily as a vasopressor to increase systemic vascular resistance. The onset of action following intravenous administration is immediate, and the effect persists for 15–30 minutes after infusion has stopped.

2. Indications. Phenylephrine is used to increase blood pressure in patients with hypotension caused by vasodilation or low systemic vascular resistance. Phenylephrine may be particularly useful in patients with tachycardia or dysrhythmia that might otherwise be exacerbated by the use of beta-adrenergic agents. Volume resuscitation should be done before or during administration of phenylephrine.

3. Contraindications

   1. Uncorrected hypovolemia.

   2. Relatively contraindicated in patients with peripheral vascular disease accompanied by severe localized ischemia or thrombosis.

   3. Use with caution in patients with bradycardia or hyperthyroidism.

4. Adverse effects

   1. Hypertension.

   2. Decreased cardiac output.

   3. Reflex bradycardia.

   4. Decreased renal perfusion and reduced urine output.

   5. Decreased tissue perfusion, resulting in necrosis and/or lactic acidosis.

   6. Tissue necrosis after extravasation.

   7. Anxiety, restlessness, tremor, and headache.

   8. Anaphylaxis induced by bisulfite preservatives in patients with hypersensitivity to sulfites.

   9. Use in pregnancy. FDA Category C (indeterminate). This does not preclude its short-term use for a seriously symptomatic patient (Introduction).

5. Drug or laboratory interactions

   1. Enhanced pressor response may occur in the presence of atomoxetine, cocaine, or cyclic antidepressants owing to inhibition of neuronal norepinephrine reuptake.

   2. Enhanced pressor response may occur in patients taking monoamine oxidase inhibitors owing to increased norepinephrine stores in the nerve endings.

   3. Propranolol and other beta₂-adrenergic blockers may increase blood pressure owing to unopposed alpha-adrenergic stimulation.

   4. Chloral hydrate overdose, cyclopropane, and halogenated or aromatic hydrocarbon solvents and anesthetics may enhance myocardial sensitivity to the arrhythmogenic effects of phenylephrine. Risk may be with high doses of phenylephrine.

6. Dosage and method of administration

   1. Caution: Avoid extravasation. The intravenous infusion must be free-flowing, and the infused vein should be observed frequently for signs of infiltration (pallor, coldness, or induration).

      1. If extravasation occurs, immediately infiltrate the affected area with phentolamine, 5–10 mg in 10–15 mL of normal saline (children: 0.1-0.2 mg/kg; maximum, 10 mg) via a fine (25-27-gauge) hypodermic needle; improvement is evidenced by hyperemia and return to normal temperature.

      2. Alternatively, topical application of nitroglycerin paste and infiltration of terbutaline have been reported successful.

   2. Intravenous Dose. Start at 0.5 mcg/kg/min and titrate upward to desired effect. Usual dose range is 0.5–2 mcg/kg/min.

7. Formulations. Phenylephrine HCl solution must be protected from light and should not be used if it appears brown or contains a precipitate.

   1. For continuous IV infusion, stock solution of 10 mg (1 mL of 1% solution) should be added to 250 or 500 mL of 5% dextrose or normal saline to provide a 40 mcg/mL and 20 mcg/mL solution, respectively. Some institutions have also used concentrations of 60, 100, 160, and 200 mcg/mL. Note that stability information ...