From the Guidelines
High dose phenylephrine is generally considered to be greater than 500 mg/ml when administered as an intracavernous injection. Phenylephrine is a selective alpha-1 adrenergic receptor agonist that causes vasoconstriction and increases blood pressure. According to the American Urological Association guideline on the management of priapism 1, phenylephrine should be diluted with normal saline to a concentration of 100 to 500 mg/ml for intracavernous injections in adult patients.
- Key points to consider when administering high dose phenylephrine include:
- Close monitoring for potential adverse effects such as excessive hypertension, reflex bradycardia, decreased cardiac output, tissue ischemia, and end-organ damage
- Administration in a controlled setting with continuous hemodynamic monitoring
- Regular reassessment of the need for high dose therapy and attempts to wean the medication once the patient stabilizes
- Consideration of alternative treatments or additional vasopressors if high doses are required for an extended period It is essential to note that lower concentrations in smaller volumes should be used in children and patients with severe cardiovascular disease, as recommended by the guideline 1.
From the FDA Drug Label
10 OVERDOSAGE Overdose of phenylephrine hydrochloride can cause a rapid rise in blood pressure.
The FDA drug label does not answer the question.
From the Research
Definition of High-Dose Phenylnephrine
- The definition of high-dose phenylephrine is not strictly defined, but it can be inferred from various studies that doses above 100-200 micrograms/min are considered high 2.
- In one study, phenylephrine was administered at doses up to 360 micrograms/min in a patient with septic shock, with no detrimental effects on perfusion of vital organs and tissues 2.
- Another study used phenylephrine infusion at 15-20 micrograms/min, which is considered a relatively low dose, and was able to increase cardiac output in preload-dependent patients 3.
Clinical Applications of High-Dose Phenylnephrine
- High-dose phenylephrine has been used in the treatment of delayed ischemic deficits after subarachnoid hemorrhage, with no significant increase in systemic toxicity 4.
- It has also been used in the hemodynamic support of septic shock, with improvements in mean arterial pressure, cardiac output, and oxygen transport parameters 2.
- The use of high-dose phenylephrine requires close monitoring of patients, particularly those with underlying cardiac disease, to minimize the risk of adverse effects 4, 2.
Pharmacokinetics and Safety of Phenylnephrine
- The pharmacokinetics of phenylephrine have been studied in healthy volunteers, with maximum plasma concentrations and total systemic exposure increasing disproportionally with increasing dose 5.
- The safety and cardiovascular tolerability of phenylephrine have been evaluated in several studies, with no significant adverse effects reported at doses up to 30 mg 5, 6.
- However, the use of high-dose phenylephrine requires careful selection of patients and close monitoring of hemodynamic parameters to minimize the risk of adverse effects 6, 2.