Abstract
Phenylephrine 10% is used for pupillary dilatation and capillary decongestion. It had been advised to use a 2.5% concentration instead of 10% to guard against systemic reactions. Here, a case of severe systemic manifestation following conjuctival application of 2.5% phenylephrine is described.
A healthy adult was admitted for pterygium excision under ophthalmic blockade. Vital signs remained normal until a sponge soaked with phenylephrine 2.5% was applied over the excised pterygium to control bleeding. The patient developed bradycardia (heart rate of 30 bpm) and hypotension (pressure 80/40 mmHg), so intravenous atropine was given. This was followed by tachycardia (heart rate of 150 bpm) and hypertension (pressure 240/130 mmHg) and ECG showed ischaemic changes. Treatment included propofol, labetalol, frusamide, morphine and dexamethasone. The next day, a 12-lead ECG showed no ischaemic changes and the myocardial infarction screen was negative. Fundus examination showed no sign of papilloedema. This report emphasises that phenylephrine 2.5% is still dangerous, with unpredictable response.
BACKGROUND
Phenylephrine is a direct-acting sympathomimetic amine, which stimulates α-adrenergic receptors with minimal or no β-receptor effect. Traditionally topical phenylephrine 10% is used by ophthalmologists for pupillary dilatation and capillary decongestion.1 Systemic side effects after absorption of phenylephrine ranges from transient hypertension, angina, cardiac arrhythmias and syncope to fatal haemodynamic changes, subarachnoid haemorrhage, pulmonary oedema, myocardial infarction, left ventricular failure and death.2,3 It was therefore suggested that a concentration of 2.5% should be used because it is safer.3 We report a case of successful management of severe systemic manifestation following conjuctival application of 2.5% phenylephrine.
CASE PRESENTATION
A 36-year-old woman was admitted for pterygium excision under local anaesthesia. Medical history revealed that the patient was hypothyroid on replacement therapy (thyroxin 100 μg/day) with normal thyroid function tests.
A double injection peribulbar blockade was given, with a total of 16 ml of a mixture of lignocaine 2% and bupivacaine 0.5% without epinephrine, in a ratio of 2:3, respectively, together with 5 IU/ml hyalourindase. Vital signs remained within normal limits with a pulse of 60 bpm and blood pressure of 115/75 mmHg after the block. During surgery the surgeon noted that the pterygium was very vascular, and a 4×4 mm sponge soaked with phenylephrine hydrochloride 2.5% was applied over the excised area to control bleeding and improve visibility.
Within a few minutes the patient developed initial sinus bradycardia with a heart rate of 30 bpm and blood pressure 80/40 mmHg after the use of phenylephrine. Intravenous atropine 0.5 mg was given immediately, but the patient became restlessness and complained of severe headache. The next reading of blood pressure was 240/130 mmHg, and heart rate increased to 150 bpm. ECG showed ischaemic changes with ST segment depression.
In order to control her restlessness, a bolus dose of 50 mg of propofol was given intravenously which was supplemented to a total of 170 mg. Labetalol 5 mg increment was given up to a total of 75 mg to counter act the α effect of phenylephrine. Intravenous Morphine 8 mg and dexamethasone 8 mg, together with frusamide 40 mg were also given. The patient maintained consciousness with satisfactory tidal volume, respiratory rate and oxygen saturation throughout the event.
The patient gradually improved and recovered uneventfully apart from headache that resolved later in the night. The next day, a 12-lead ECG showed no residual ischaemic changes and the myocardial infarction screen was negative. The optic disc was normal with no sign of papilloedema. The patient was discharged home with no residual signs and symptoms.
INVESTIGATIONS
12-lead ECG.
Screening for myocardial infarction (MI), creatine phosphokinase (CK), creatine phosphokinase isoenzyme (CK-MB), troponin T.
TREATMENT
Atropine
Propofol
Labetalol
Morphine
Dexamethasone
Frusamide
OUTCOME AND FOLLOW-UP
Successful management with no residual complications.
DISCUSSION
The current report showed that β and α response could occur after topical conjuctival application of 2.5% phenylephrine. The cause of the exaggerated response to phenylephrine in this case could be attributed to the absorption of the drug through the open vessels during pterygium excision.
We observed a significant response within a few minutes of topical application; it had been described that the maximum plasma level of phenylephrine is usually achieved during the first 20 min following topical application, irrespective of the nature of the solution.4 It emphasises the importance of monitoring these patients closely for about 30 min following the administration of phenylephrine eye drops. The New York State Guideline recommends that initial dose of phenylephrine for adults should not exceed 0.5 mg (four drops of a 0.25% solution).3
The reports in the literature are conflicting and it is difficult to predict exactly what type of patient will have an abnormal response to phenylephrine. It has been reported that systemic side effects may be exaggerated in adult patients with idiopathic orthostatic hypotension.5 Symons and colleagues reported no significant change in the mean systolic and diastolic blood pressure in 126 patients receiving 10% phenylephrine drops.6 Malhotra et al in their study on 54 cases showed no difference in systemic cardiovascular effects of either the 2.5% or the 10% concentration.7 Consistent with our report, Fraunfelder et al pointed out that the 2.5% solution also has the potential to cause cardiovascular side effects.8 Macmillan and Barker described a case with severe bradycardia and hypertension following nasal back with phenylephrine for nasolacrimal duct surgery under general anaesthesia.9
Factors which increase absorption through the nasolacrimal system and the nasal mucosa are lid blinking, the lacrimal pump or gravity. Direct absorption may occur through the conjuctival blood vessels.10 Several methods had been described to reduce systemic absorption of topical phenylephrine. Salminen reported that digital pressure applied over the lacrimal sac reduces systemic absorption of conjuctival applied phenylephrine.11 Another approach is to reduce drop size while increasing concentration, which improves the therapeutic index of eye drops.12 Reducing eye drop volume, decreasing drug concentration and eyelid closure.13
In the management of this case we choose to use propofol because of it has a dual function as a sedative and peripheral vasodilator.14 It had been described by Macmillan and Barker9 that glycopyrrolate had a weak or no effect so we used atropine from the start. They also noted that Labetalol may increase the incidence of pulmonary oedema due to inability to compensate for the increased load especially following anticholinergics. In this case we used labetalol because of its rapid onset compared to the other available peripheral vasodilators, putting in mind that our patient was healthy, restless and complaining of severe headache.
We conclude that phenylephrine 2.5% is still dangerous, and the response could be unpredictable. We recommend that phenylephrine should be used with great care and attention should be given towards concentration and calculation of the total dose before local application of the drug.
LEARNING POINTS
Topical phenylephrine 2.5% should be used with cautioun.
Never exceed the recommended dose.
Patients should be monitored via ECG and blood pressure readings after drug application.
The attending anaesthesiologist should be aware of usage of the medication.
Footnotes
Competing interests: None.
Patient consent: Patient/guardian consent was obtained for publication.
REFERENCES
- 1.Fraunfelder FW, Fraunfelder FT, Jensvold B. Adverse systemic effects from pledgets of topical ocular phenylephrine 10%. Am J Ophthalmol 2002; 134: 624–5 [DOI] [PubMed] [Google Scholar]
- 2.Adler AG, McElwain GE, Merli GJ, et al. Systemic effect of eye drops. Arch Intern Med 1982; 142: 2293–4 [DOI] [PubMed] [Google Scholar]
- 3.Groudine SB, Hollinger I, Jones J, et al. New York State guidelines on the topical use of phenylephrine in the operating room. The Phenylephrine Advisory Committee. Anesthesiology 2000; 92: 859–64 [DOI] [PubMed] [Google Scholar]
- 4.Folk JC, Kumar V, Piper JG, et al. Aqueous vs viscous phenylephrine. II. Systemic absorption and cardiovascular effects. Arch Ophthalmol 1986; 104: 1189–91 [DOI] [PubMed] [Google Scholar]
- 5.Kumar V, Schoenwald RD, Barcellos WA, et al. Aqueous vs viscous phenylephrine. I. Mydriatic effects. Arch Ophthalmol 1986; 104: 1192–3 [DOI] [PubMed] [Google Scholar]
- 6.Symons RC, Walland MJ, Kaufman DV. A comparative study of the efficacy of 2.5% phenylephrine and 10% phenylephrine in pre-operative mydriasis for routine cataract surgery. Eye 1997; 11: 946–8 [DOI] [PubMed] [Google Scholar]
- 7.Malhotra R, Banerjee G, Brampton W, et al. Comparison of the cardiovascular effects of 2.5% phenylephrine and 10% phenylephrine during ophthalmic surgery. Eye 1998; 12: 973–5 [DOI] [PubMed] [Google Scholar]
- 8.Fraunfelder FT, Meyer SM. Possible cardiovascular effects secondary to topical ophthalmic 2.5% phenylepherine. Am J Ophthalmol 1985; 99: 362–3 [DOI] [PubMed] [Google Scholar]
- 9.Macmillan M, Barker K. Phenylephrine toxicity. Eur J Anaesthesiol 2008; 25: 426–7 [DOI] [PubMed] [Google Scholar]
- 10.Kumar V, Schoenwald RD, Chien DS, et al. Systemic absorption and cardiovascular effects of phenylepherine eyedrops. Am J Ophthalmol 1985; 99: 180–4 [DOI] [PubMed] [Google Scholar]
- 11.Salminen L. Review: systemic absorption of topically applied ocular drugs in humans. J Ocul Pharmacol 1990; 6: 243–9 [DOI] [PubMed] [Google Scholar]
- 12.Lynch MG, Brown RH, Goode SM, et al. Reduction of phenylephrine drop size in infants achieves equal dilation with decreased systemic absorption. Arch Ophthalmol 1987; 105: 1364–5 [DOI] [PubMed] [Google Scholar]
- 13.Baldwin FJ, Morley AP. Intraoperative pulmonary oedema in a child following systemic absorption of phenylephrine eyedrops. Br J Anaesth 2002; 88: 440–2 [DOI] [PubMed] [Google Scholar]
- 14.Gin T. Prevention of hypotension after propofol for rapid sequence intubation. Can J Anaesth 1996; 8: 877–8 [DOI] [PubMed] [Google Scholar]