The FDA-approved indication for intravenous (IV) phenylephrine hydrochloride is for increasing blood pressure in adults with clinically significant hypotension resulting primarily from vasodilation in such settings as septic shock or anesthesia. Phenylephrine HCL is also used over-the-counter in ophthalmic formulations to promote mydriasis and conjunctival blood vessel vasoconstriction, intranasal administration as a treatment for uncomplicated nasal congestion, and as an over-the-counter additive to topical hemorrhoid medications.[1] Phenylephrine is less commonly used off-label as an additive to neuraxial/peripheral nerve blockade, to treat priapism and other conditions where local vasoconstrictive effects and reduced blood flow are the desired effect. In the setting of IV administration, phenylephrine is a commonly used anesthetic vasopressor for patients with normal cardiac function and hypotension secondary to the vasodilatory effect of anesthetic medications or non-cardiac shock states.

Phenylephrine is primarily an alpha-1 adrenergic receptor agonist with minimal to no beta-adrenergic activity; therefore, it is ideal for elevating mean arterial pressure. It does so by causing venous and arterial vasoconstriction and increasing cardiac preload without having any significant direct effect on cardiac myocytes.[2] Hypotension during general and neuraxial anesthesia remains one of the most commonly encountered problems for the anesthetic provider and must be addressed rapidly to avoid prolonged hypoperfusion states.[3] During any given surgical procedure, blood pressure can vary considerably based upon the patient’s underlying pathology, the dosage of anesthetic medications, volume status, the degree of surgical stimulation, and the presence of other blood pressure modulating medications. Vasopressor medications with short onset, short duration of action, and predictable dose-dependent responses such as phenylephrine are ideal for treating hypotensive patients.

Phenylephrine has been shown to be effective in offsetting commonly encountered hypotension associated with spinal anesthetics (60% to 70%) in obstetric patients and has become the preferred vasopressor in this setting.[3] Phenylephrine is also used in the intensive care unit (ICU) environment to treat septic and neurogenic shock. With the advent of the surviving sepsis campaign, management of sepsis has undergone more scrutiny and a more standardized approach to septic shock states has been developed with norepinephrine as the vasopressor/inotrope of choice.

Although phenylephrine is not recommended as the initial treatment of septic shock, it is an acceptable therapy in the case of norepinephrine associated arrhythmias, known high cardiac output with hypotension, and as a salvage therapy when combined inotrope and vasopressor drugs when low-dose vasopressin has failed to achieve MAP target.[4] Neurogenic shock secondary to acute traumatic spinal cord injury can similarly produce a systemic vasodilatory state, often in the setting of preserved cardiac output. These injuries frequently require higher target mean arterial pressures (85 to 90 mm Hg) to maintain spinal cord perfusion and reduce secondary injury, making phenylephrine a reasonable and safe choice in the hemodynamic maintenance of these patients.[5]

Phenylephrine is a direct-acting sympathomimetic amine that functions as an alpha-1 adrenergic agonist. Its chemical structure is related to epinephrine and ephedrine and possesses potent vasoconstriction properties when given intravenously or applied directly to mucosal membranes. The overall effect of intravenous phenylephrine on cardiac output and end perfusion is likely more complex and variable based on bolus versus infusion dosing, volume status, baseline heart rate, autonomic tone, and cardiac pathology. These variations are attributable to the degree of venoconstriction which can temporarily increase preload, arterial constriction which will increase systemic vascular resistance and afterload, and the presence of reflex bradycardia leading to an overall mixed effect on cardiac output depending on the patient population.[6][7][8] Regarding ophthalmic administration, phenylephrine binds alpha-1 receptors that innervate the iris dilator muscle yielding smooth muscle contraction and subsequent dilation of the pupil which can assist in fundoscopic exams, exposure in certain surgeries, and treatment of various conditions.[9]

The most common routes of administration for phenylephrine include oral, topical, intravenous, intranasal, ophthalmic, and rectal. Less commonly, phenylephrine has been administered in the epidural space, as an adjunct to peripheral nerve blockade, in the intracavernous space, intramuscularly, and subcutaneously.[10][11] When administering phenylephrine intravenously, dosing is typically in 50 to 100 mcg aliquots and frequently requires redosing as it has a short onset of action (1 to 3 minutes) and short duration of action (5 to 20 minutes).[12] 

Additionally, phenylephrine dosing can be via weight-based or non-weight based infusion with typical dose ranges of 0.1 to 1.5 mcg/kg per minute.[13] Despite the classic teaching that all vasoactive medications require central venous access to avoid necrosis in the event of tissue extravasation, phenylephrine has demonstrated to be safe and effective when given through peripheral intravenous catheters when dilution, vein, and catheter selection, and frequent site inspection are appropriate.[14] 

Ophthalmic solutions of phenylephrine have a wide range of concentrations and additives depending on the desired effect.  Concentrations utilized by medical professionals generally come in doses of 1%, 2.5%, or 10%. The 1% formulations are often administered in combination with cyclopentolate 0.2% for dilated fundus and cycloplegic exams in newborns of less than three months. The 2.5% formulations are the most commonly used for dilated fundus exams in adults, children over three months, and as an aid in diagnosing conditions such as episcleritis. The 10% formulation is less commonly used (due to fear of systemic absorption) in dilated exams and to provide exposure during surgeries.

Over-the-counter (OTC) preparations of phenylephrine combination drops may come in concentrations as low as 0.12% and are marketed as a treatment of "red-eye" or uncomplicated conjunctivitis. Phenylephrine is available as an FDA-approved, over-the-counter decongestant in oral concentrations of up to 10 mg, nasal solutions typically ranging between 0.125% to  1% and are found as an additive in various OTC topical hemorrhoid creams.[15][16]

The most common adverse reactions include nausea, vomiting, headache, and nervousness in an awake patient. Because of phenylephrine’s sole alpha-receptor stimulation, it can cause baroreceptor-mediated reflex bradycardia. Clinicians should consider different classes of vasopressor medications in the bradycardic, hypotensive patient. In specific patient populations, primarily hypovolemic patients with cardiac dysfunction, phenylephrine can increase afterload more so than preload, causing decreased cardiac output and potentially an exacerbation of angina, heart failure, and pulmonary hypertension.[6]

There are no absolute contraindications to phenylephrine aside from hypersensitivity to the drug or any of its components. Phenylephrine contains sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity is unknown and probably low. Phenylephrine use requires caution in patients with a history of bradycardia, autonomic dysfunction, severe cardiac dysfunction, and hypovolemia.