Adverse systemic effects from pledgets of topical ocular phenylephrine 10%

doi:10.1016/S0002-9394(02)01591-X

American Journal of Ophthalmology

Volume 134, Issue 4, October 2002, Pages 624-625

https://doi.org/10.1016/S0002-9394(02)01591-X Get rights and content

Abstract

PURPOSE: To report 11 cases of adverse systemic reactions to topical ocular application of phenylephrine 10% in pledget form and to discourage this method of treatment for hemostasis in laser assisted in-situ keratomileusis (LASIK) surgery and other ophthalmic uses.

DESIGN: Observational case series.

METHODS: The literature, reports provided to the spontaneous reporting system of the United States Food and Drug Administration and the National Registry of Drug-Induced Ocular Side Effects (Casey Eye Institute, Portland, Oregon) were reviewed. Age, sex, duration of therapy, other drugs the patient was taking, and systemic reactions are provided in the series of 11 cases with adverse systemic reactions.

RESULTS: Eleven cases of adverse systemic reactions to topical ocular phenylephrine 10% applied in pledget form occurred in 8 male and 3 female patients with an age range from 1 to 76 years. All cases occurred after a single exposure, most patients noted systemic effects within minutes of phenylephrine application, and the adverse systemic reactions included severe hypertension, pulmonary edema, cardiac arrhythmia, cardiac arrest, and subarachnoid hemorrhage.

CONCLUSIONS: We recommend ophthalmologists not use this method of phenylephrine application and believe it is contraindicated in ophthalmic surgery, especially when other medications may be used.

References (5)

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There are more references available in the full text version of this article.

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Shams, Jafari, and Mansfield reported a case of ventricular fibrillation in a patient undergoing cataract surgery when using a 2.5% solution of intracameral phenylephrine.38 Although there are numerous case reports of cardiovascular complications when using 10% topical phenylephrine in ophthalmic procedures in the literature,3,14,21 to our knowledge, no further instances of systemic complications associated with intracameral phenylephrine have been reported. Fraunfelder and Scafidi reviewed the complications after using 10% phenylephrine formulation topically and reported 15 cases of myocardial infarction and 11 deaths.13
Intracameral phenylephrine is commonly used in ophthalmic surgery as an alternative or supplement to mydriatic eye drops; hence, the importance of an evidence-based understanding of its risk-benefit profile is vital. We performed a comprehensive search in the PubMed, Google Scholar, and Cochrane databases for published studies and case reports relating to the use of intracameral phenylephrine. Articles from 1958 to 2021 with the following keywords were used: “intracameral phenylephrine,” “intracameral mydriatics,” “phenylephrine,” “pupil dilation,” “complications.” Intracameral phenylephrine was first used in 2003 as an alternative to topical mydriatics. Since then, it is being increasingly used with a variety of benefits, including rapid onset of mydriasis, and cost-effectiveness. There are various case reports, however, of ocular and systemic complications associated with intracameral phenylephrine such as generation of free radicals, toxic anterior segment syndrome, inconsistent pupillary dilation during surgery, and ventricular fibrillation. Alternatives to intracameral phenylephrine such as iris hooks, a Malyugin ring, intracameral epinephrine, and intracameral tropicamide were compared with intracameral phenylephrine. Intracameral phenylephrine appears to have a good safety profile.
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Drug delivery to the eye is a complex process. Ocular toxicology is dependent on the concentration of the drug, frequency of application, speed of removal, and whether the drug reaches sensitive cells such as the corneal endothelium, lens epithelium, or macula in toxic concentrations. Of equal importance is the vehicle for delivery and the pH, buffering systems, and preservatives necessary for optimum drug delivery. Topical ocular administration is the most commonly used method of drug delivery to the eye. This method concentrates the pharmacologic activity of the drug on/in the eye while limiting systemic reactions. Preservatives are important parts of topical ocular medications, not only to prolong shelf life but also to disrupt the corneal and conjunctival epithelium to allow greater drug penetration. There are many vehicles for topical ocular medication delivery including aqueous solutions, suspensions, ointments, pledgets, and injections. Toxicity responses may involve the anterior segment, ciliary body, lens, posterior segment, elevation of intraocular pressure, neurologic disorders, eyelashes, eyebrows, and orbit. This chapter includes instructions on how to apply topical ocular medication to yourself and someone else.
Cardiac, Vascular, and Renal Drugs
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This book is intended as a guide to help the clinician determine where a visual problem is a drug-induced ocular side effect. We continually review spontaneous case reports from the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization, the Food and Drug Administration, and the world literature. We have attempted to classify a suspected adverse event with our impression to causality (i.e. certain, probable, unlikely, conditional/unclassified). This chapter discusses cardiac, vascular, and renal drugs including drugs used to treat migraine, antianginal drugs, antiarrythmic drugs, antihypertensive drugs, bronchodilators, diuretics, osmotics, peripheral vasodilators, and vasopressors.
Anesthesia for Ophthalmic Surgery
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Our own worst enemy: Pharmacologic mechanisms of hypertension
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It is available as an oral, nasal, or ophthalmic decongestant over-the-counter, an injectable vasopressor for shock or hypotension, and an eye drop for mydriasis in ophthalmologic procedures. There have been case reports of hypertension, myocardial infarctions, cerebrovascular accident, subarachnoid hemorrhages, and even cardiac arrest because of the use of topical phenylephrine 10% for ocular surgeries.46,47 At least one of these cases could be attributed to an inadvertent overdose; however, increases in blood pressure have been reported in up to 2% of patients who received topical phenylephrine 10%.46
Drug-induced hypertension is often an unrecognized cause of resistant or secondary hypertension. It is defined as hypertension resulting from the unintended effect of a drug or from a drug's antagonistic effect on antihypertensive medications. The main mechanisms of drug-induced hypertension, when categorized broadly, include volume retention and sympathomimetic effects. These mechanisms along with management strategies will be further discussed in this article.
Intracerebral hemorrhage associated with oral phenylephrine use: A case report and review of the literature
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Weisberg15 reported a case of ICH 30 minutes following PHE topical administration (1 drop of 2.5% in each eye). Systemic effects of topical ocular PHE (10%) have been reported to include severe hypertension, “cerebrovascular accident”, severe headache, tonic convulsion, and SAH among others (cardiac arrhythmias/arrest) and can occur after a single exposure within minutes.20 One case of stroke after intracorporeal injection was also reported.
Prior reports have linked both ischemic and hemorrhagic stroke to use of sympathomimetic drugs including phenylephrine. The purpose of this study is to describe the first case, to our knowledge of intracerebral hemorrhage (ICH) after oral use of phenylephrine and to systematically review the literature on phenylephrine and acute stroke.
A case report and review of the literature.
A 59-year-old female presented with thunderclap headache, right hemiparesis, aphasia, and left gaze deviation. Head computed tomography (CT) showed a left frontal ICH with intraventricular and subarachnoid extension. She had no significant past medical history. For the previous 30 days, the patient was taking multiple common cold remedies containing phenylephrine to treat sinusitis. CT and magnetic resonance angiography showed no causative vascular abnormality. Catheter cerebral angiography supported reversible cerebral vasoconstriction syndrome (RCVS). Phenylephrine was determined to be the most likely etiology for her hemorrhage. A review of the literature, found 7 cases describing phenylephrine use with acute stroke occurrence: female, 5 of 7 (71%); route of administration, nasal (n = 3), ophthalmic (n = 2), intravenous (n = 1), intracorporeal injection (n = 1). Stroke types were subarachnoid hemorrhage (n = 5), ICH (n = 4), and ischemic (n = 1). One case reported RCVS after phenylephrine use.
It is scientifically plausible that phenylephrine may cause strokes, consistent with the pharmacologic properties and adverse event profiles of similar amphetamine-like sympathomimetics. As RCVS has been well described in association with over-the-counter sympathomimetics, a likely, although not definitive, causal relationship between phenylephrine and ICH is proposed.

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^☆: Supported in part by an unrestricted grant from Research to Prevent Blindness, New York, New York.

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Brief reportAdverse systemic effects from pledgets of topical ocular phenylephrine 10%☆

Abstract

Am J Ophthalmol

Am J Ophthalmol

Brief report
Adverse systemic effects from pledgets of topical ocular phenylephrine 10%☆