Infantil delirium induced by cycloplegic eye drops

Abstract

Cyclopentolate 1% and tropicamide 1% eye drops are considered to be safe in the pediatric population for the fundus examination and treatment of ocular diseases. Although adverse reactions rarely occur, some of them can be life-threatening such as seizure, delirium, coma, arrhythmia, acute life-threatening event, and death. Here we report 15 months old boy who developed delirium after administration of ocular cyclopentolate 1% drops in both eyes during a routine examination for retinopathy of prematurity. Cyclopentolate is a parasympatholytic drug with actions similar to atropine. With ophthalmic administration of cyclopentolate, severe central nervous system effects and systemic reactions may occur. In order to minimize absorption following instill one or two drops of 1% solution, applying pressure to nasolacrimal sac for 2 to 3 min should be considered. In mild to moderate toxicity, benzodiazepines may be used to control central nervous system findings secondary to anticholinergic effects.

Introduction

Topical cycloplegic eye drops are primarily used during fundus examination and ocular surgery and refraction and in the treatment of ocular disease and examination of retinopathy of prematurity (ROP). ¹ In children, cyclopentolate 1% and tropicamide 1% eye drops are considered to be safe in children, as severe adverse reactions are rare. However, these adverse effects include irritability, flushing, dried skin, seizure, delirium, and even life-threatening events. ² We report a 15-month-old boy developed delirium following repeated administration of topical cyclopentolate 1% eye drops and was successfully treated with the benzodiazepine.

Case report

A 15-month-old boy was admitted to emergency department (ED) with agitation, irritability, intractable crying, and flushing. He was born at the 26th weeks of gestation with a weight of 860 g by cesarean section to a 24-year-old primiparous mother. Past medical history revealed that due to respiratory distress syndrome, mechanical ventilation was required for 8 weeks and discharged with a well clinical condition. Past medical history revealed that the present case had respiratory distress syndrome, mechanical ventilation was required for 8 weeks and discharged with a well clinical condition. At 15 months, he was screened for ROP control at ophthalmology department. On his examination, he received cyclopentolate 1% eye drops three times 5 min apart to dilate his pupils. Fifteen minutes after the third set of drops, the mother noticed that her son had agitation, flushing, and intractable crying. When he developed these symptoms, he transferred to the ED. Upon admission, he was mildly confused, had flushing and dry/warm skin, agitation, tremor and severe behavioral disturbances were also present. Pupils were mydriatic with no reflex. His heart rate was 154/min, respiratory rate 36/min, peripheral capillary oxygen saturation 96%, and body temperature 39.3°C. His clinical status became worse progressively. The first step of his management was the administration of rectal diazepam and intravenous fluid. Serum glucose level, blood count, biochemical markers, and blood gas analyses were normal. Delirium symptoms resolved immediately and uncontrolled shaking, jumping and movements his extremities were gradually decreased. His symptoms improved at 3 h of follow-up and he was discharged without any complaint. All the clinical effects present in our case occurred following administration of toxic dose cyclopentolate. Trauma history, seizure activity or abnormal neurological findings were not present. Since only single dose diazepam was successful for the patient brain CT was not performed. The verbal consent was taken from the patient’s parents.

Discussion

Since cyclopentolate has a shorter duration of mydriasis and cycloplegia than atropine, most ophthalmologists prefer to use for routine ophthalmologic examination. ³ Cyclopentolate, which is an anticholinergic ophthalmic solution, blocks the responses of the sphincter muscle of the iris and the stimulation of the ciliary body muscle achieving mydriasis and cycloplegia.^1,4 The use of cyclopentolate 1% and tropicamide 1% eye drops usually considered to be safe in children and FDA approved in pediatric patients (without any age limit) and adults. ⁵ Even with therapeutic use, parasympatholytic drug (atropine-like) toxicity may be occurred but is considered a rare event. ⁶ As expected, poisoning or overdose of cyclopentolate may produce central nervous system (CNS) stimulatory activity consisting of psychotic reactions, behavioral disturbances, irritability, disorientation, hallucinations, and tremor, which is more frequently observed in children than adults. These clinical effects may be explained by slower clearance and extended the half-life of cyclopentolate. Children have lower body mass, blood volume, and immature cardiovascular, metabolic, and excretion systems.^3,7 In addition, CNS-related adverse reactions are more common, as the brain-to-body volume ratio is higher in children with increased brain–blood permeability than adults. ³ Previously, two cases of grand mal seizures were reported in children. ⁸

Although the most documented adverse effect is neuropsychiatric, systemic adverse effects such as fever, dryness of skin, dermal flushing, sinus tachycardia, and arrhythmia were also reported.^2,4 There have been several reports of systemic toxicity after topical use of cyclopentolate eye drops. Toxicity is dose-related and clinical effects are typically seen within 15 and 60 min after instillation of the eye drop similar to our case. Half life of cyclopentolate is 111 min and complete recovery of accommodation usually takes 6–24 h.^9,10 In Bauer et al., ¹¹ the maximum dose of cyclopentolate as one drop in each eye once daily is 0.5% for infants. In the present case, following clinical effects can be explained by anticholinergic toxicity which is related to overdose of cyclopentolate use. The observed clinical effects in our case were dried skin, irritability, fever, flushing, sinus tachycardia, excitation, hyperactivity, and behavioral changes, which were indicating delirium. As a first step of his management rectal diazepam was administered. Previous reports demonstrate that most adverse effects decreased within 2 and 6 h without any sequelae. ¹² All clinical effects of the present case also decreased within 3 h of his admission.

Therapeutic dosages for pediatric population instill one or two drops of 1% solution in the eye and may be repeated 5–10 min later if needed. In infants to instill one drop of 0.5% solution and apply pressure to nasolacrimal sac for 2–3 min in order to minimize absorption should be considered. Applying that maneuver may decrease developing these clinical effects. All children received cyclopentolate should be closely monitored for adverse effects for at least 30 min following instillation. ¹¹ When these effects occurred in children and observed by the ophthalmologist, immediate referral to the ED is essential. In case of cyclopentolate induced CNS toxicity use of tropicamide 1% eye drops was recommended by our ophthalmology department. On his next fundi examination, tropicamide 1% was used and no adverse effects observed.

Physostigmine is indicated to reverse the severe CNS effects caused by clinical or toxic dosages of anticholinergic drugs. ¹² Since we could not use physostigmine due to non-availability, one dose diazepam was administered. Although toxicity was successfully managed by one dose diazepam, use of physostigmine should be kept in mind in case of more severe CNS effects.