Use of Physostigmine for Cyclopentolate Overdose in an Infant

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Use of Physostigmine for Cyclopentolate Overdose in

an Infant

abstract

Topical application of eye drops may cause mild or severe adverse ocular or systemic effects. Children, particularly infants, are more prone to systemic adverse effects of topical eye drops because of their lower body mass and blood volume, immature metabolism, and immaturity of excretory, nervous, and cardiovascular systems. Early recognition of signs and symptoms of systemic toxicity is very impor-tant. Most of the signs and symptoms can resolve spontaneously; however, in severe cases, physostigmine treatment may be required. Respiratory distress is a rare adverse effect of cyclopentolate. We report an infant who developed respiratory distress after ocular in-stillation of cyclopentolate and was successfully treated with physo-stigmine. The beneﬁt of physostigmine use with close follow-up should be borne in mind in cases with a life-threatening cyclopentolate adverse effect.Pediatrics2012;130:e703–e705

AUTHORS:Oksan Derinoz, MD,a_{and Hamdi C. Emeksiz, MD}b a_{Departments of Pediatric Emergency Medicine, and}b_Pediatrics,

Gazi University Faculty of Medicine, Ankara, Turkey

KEY WORDS

cyclopentolate, ophthalmic solutions, physostigmine, respiratory distress

ABBREVIATIONS

PED—pediatric emergency department ROP—retinopathy of prematurity

www.pediatrics.org/cgi/doi/10.1542/peds.2011-3038 doi:10.1542/peds.2011-3038

Accepted for publication Mar 14, 2012

Address correspondence to Oksan Derinoz, MD, Gazi University, Faculty of Medicine, Department of Pediatric Emergency Medicine, Besevler, 06450, Ankara, Turkey. E-mail: oderinoz@gazi. edu.tr; [email protected]

FINANCIAL DISCLOSURE:The authors have indicated they have noﬁnancial relationships relevant to this article to disclose.

FUNDING:No external funding.

PEDIATRICS Volume 130, Number 3, September 2012 e703

CASE REPORT

at Viet Nam:AAP Sponsored on August 28, 2020 www.aappublications.org/news

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Cyclopentolate eye drops are commonly used for mydriasis during screening for retinopathy of prematurity (ROP).1 Topical application of these eye drops may cause severe adverse ocular or systemic adverse effects. Some of these effects can be life-threatening and re-quire immediate treatment.2 _{We report} an infant who developed respiratory distress after ocular instillation of cyclo-pentolate eye drops and was successfully treated with physostigmine.

CASE REPORT

The patient was born at 28 weeks’ gestation to a 20-year-old primiparous woman. She was born 1000 g by cae-sarean delivery as a twin spouse. Apgar score was obscure. Her neonatal problems included minimal lung dis-ease that required 1 month of mecha-nical ventilation. At 90 days of age (corrected postterm age of 12 days), she was transferred to our hospital for ROP examination. One drop 1% cyclo-pentolate was instilled 6 times in each eye at 5-minute intervals in our oph-thalmology department. Approximately 30 minutes later, she developed vomit-ing, cyanosis, and respiratory distress and was referred to our pediatric emergency department (PED).

In the PED, physical examination re-vealed mild cyanosis, abdominal dis-tention, and respiratory distress without

flushing and rash. Her respiration was irregular. Her abdomen was distended. Neurologic examination revealed no pathologicfinding except mydriasis. Her vital signs were as follows: fever, 40°C; respiratory rate, 68 breaths per minute; heart rate, 250 beats per minute, rhythm of sinus; systolic blood pres-sure, 70 mm Hg; and oxygen saturation, 90%. There was no evidence of sepsis (normal total white blood cell counts and C-reactive protein levels) on labo-ratory examination. The chest and ab-dominal x-ray showed diffuse pulmonary infiltration and diffuse bowel distension

with no radiologic evidence of necrotiz-ing enterocolitis. Blood gas test revealed respiratory acidosis. As her clinical sta-tus deteriorated progressively, she was intubated and ventilated with 100% ox-ygen, and immediately treated withﬂuid, antipyretics, and empirical antibiotics. The patient presented with clinical fea-tures of atropinization, which were at-tributed to cyclopentolate instillation. Therefore, administration of antidote treatment (i.e., physostigmine) was planned. She was transferred to the PICU for further follow-up. In the PICU, her vital signs were as follows: fever, 39°C; respiratory rate, 65 breaths per minute; heart rate, 210 beats per minute; blood pressure, 70/15 mm Hg; and oxygen saturation, 90%. While in the PICU she was still intubated and mechanically ventilated. Physo-stigmine infusion with a dose of 0.02 mg/kg over 10 minutes was given at the ninth hour of her hospital admission. Before physostigmine, her electrocar-diography was normal. The clinical symptoms resolved immediately after administration of physostigmine. The child awoke, opened her eyes at the end of the infusion, and her abdominal distention resolved completely on the following days. Her heart and respiratory rates decreased and her respiration became regular. Finally, she was extubated at the second day of PICU follow-up. She was discharged 8 days after admission to hospital.

DISCUSSION

Topical application of eye drops may cause serious ocular or systemic ad-verse effects. Systemic absorption of these drugs occurs primarily via nasal mucosa and conjunctiva, nasolacrimal duct, oropharynx, digestive system, and skin.2,3 _{The toxicity is dose-related.}2 Early recognition of systemic toxicity after eye drop instillation is important. Neonates are more susceptible than adults to the effects of systemic

absorption because of their lower body mass and blood volume, and their im-mature metabolic, excretion, and car-diovascular systems.4

Cyclopentolate is an anticholinergic agent whose topical administration to eyes causes mydriasis and cycloplegia.1,2 Its recommended maximum dose in an infant is 1 drop per day per eye of 0.5% solution.5_{Because of its} atropine-like actions via blocking acetylcholine receptors at postganglionic neuron, sys-temic adverse effects of cyclopentolate are similar to atropine. Dryness of the skin and mouth, dermalﬂushing, fever, irritability, abdominal distention, urinary retention, feeding intolerance, psychosis, ataxia, hallucinations, convulsion, coma, tachycardia with normal blood pressure, arrhythmia, and death can be observed after multiple instillations of the eye drop or accidental ingestion by infants, chil-dren, and patients with neurologic dis-orders (particularly Down syndrome).6 Most common adverse effects are cere-bellar dysfunction, hallucinations, psy-chosis, seizure, hypersensitivity, and anaphylactic reaction and transient paralytic ileus.1,2,6–9 _{These effects can} be reduced by preventive interventions, such as administering cyclopentolate at the lowest effective dose and/or phar-maceutical dilution of ophthalmic agent and/or applying digital pressure to the punctum for 1 to 2 minutes after drop administration.10 _{We observed} res-piratory distress in our patient as well; however, we were not sure whether this adverse effect was secondary to the di-rect or indidi-rect act of cyclopentolate. Cyclopentolate can cause vomiting and abdominal distention, which may lead to respiratory distress by aspiration of gastric contents. The underlying factors that precipitated the cyclopentolate ad-verse effect in our case were the use of a 1% solution, which is the only available form in Turkey, and administration of cyclopentolate over the recommended dose for an infant.

e704 DERINOZ and EMEKSIZ

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Although eye drop–related systemic toxicity and preventive interventions have been well documented, there is very little information in the literature about treatment of systemic toxicity. Systemic adverse effects generally im-prove spontaneously without sequelae at the end of 2 hours in adults and 4 to 6 hours in infants/children2_{; however,} severe toxicity should be treated with physostigmine.6

In our country, some antidotes, such as physostigmine, are not available in hospitals. In case of emergency, the Turkish Minister of Health is the only source for supplementation of this drug to hospitals. Therefore, our case was treated with physostigmine with a 9-hour delay after her admission. Eye drops–induced adverse effects usually

resolve within a few hours and antidote use is not generally required. Our patient’s clinical status did not improve until the time that we obtained the antidote; hence, she was treated with physostigmine. To our knowledge, our case is the youngest one in literature who was treated with physostigmine for a cyclopentolate-related overdose.

Physostigmine is a short-acting ace-tylcholinesterase inhibitor, which acts as an antidote of anticholinergic poi-soning. It slows the synaptic degrada-tion of acetylcholine, thus increasing its synaptic concentration and overcoming the postsynaptic blockade of anticho-linergic agents. The chemical proper-ties of the physostigmine facilitate its passing into the central nervous system and thus leads to recovery of all central

and peripheral anticholinergic symp-toms. Physostigmine infusion with a dose of 0.02 mg/kg (maximum of 0.5 mg/dose) over 3 minutes is recom-mended in infants/children. Impor-tantly, before infusion, conduction abnormalities (eg, PR, QRS, or QTc in-terval prolongation) should be checked on ECG.11

Cyclopentolate may cause respiratory distress because of its either direct or indirect effect in cases undergoing ROP examination. Therefore, physicians should be aware of its possible systemic adverse effects and can safely use physostigmine in severe cases and in infants, with close follow-up. In our opinion, availability of physostigmine should be sustained in ophthalmology clinics and PEDs.

REFERENCES

1. Lim DL, Batilando M, Rajadurai VS. Transient paralytic ileus following the use of cyclo-pentolate-phenylephrine eye drops during screening for retinopathy of prematurity. J Paediatr Child Health. 2003;39(4):318–320 2. Jones LW, Hodes DT. Possible allergic

reactions to cyclopentolate hydrochloride: case reports with literature review of uses and adverse reactions.Ophthalmic Physiol Opt. 1991;11(1):16–21

3. Alpay A, Ermis B, Ugurbas SC, Battal F, Sagdik HM. The local vasoconstriction of infant’s skin following instillation of myd-riatic eye drops. Eur J Clin Pharmacol. 2010;66(11):1161–1164

4. Patel AJ, Simon JW, Hodgetts DJ. Cycloplegic and mydriatic agents for routine ophthal-mologic examination: a survey of pediatric ophthalmologists.J AAPOS. 2004;8(3):274–277 5. Available at www.mdconsult.com/das/ pharm/body/334959483-97/1246850528/ full/1277. Accessed December 12, 2011 6. Labetoulle M, Frau E, Le Jeunne C. Systemic adverse effects of topical ocular treat-ments.Presse Med. 2005;34(8):589–595 7. Binkhorst RD, Weinstein GW, Baretz RM,

Clahane AC. Psychotic reaction induced by cyclopentolate (Cyclogyl). Results of pilot study and a double-blind study.Am J Oph-thalmol. 1963;55:1243–1245

8. Fitzgerald DA, Hanson RM, West C, Martin F, Brown J, Kilham HA. Seizures associated with 1% cyclopentolate eyedrops. J Pae-diatr Child Health. 1990;28:106–107 9. Tayman C, Mete E, Çatal F, Akca H.

Ana-phylactic reaction due to cyclopentolate in a 4-year-old child.J Investig Allergol Clin Immunol. 2010;20(4):347–348

10. Gray C. Systemic toxicity with topical oph-thalmic medications in children. Paediatr Perinat Drug Ther. 2006;7:23–29

11. Frascogna N. Physostigmine: is there a role for this antidote in pediatric poi-sonings? Curr Opin Pediatr. 2007;19(2): 201–205

CASE REPORT

PEDIATRICS Volume 130, Number 3, September 2012 e705

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DOI: 10.1542/peds.2011-3038 originally published online August 20, 2012;

2012;130;e703

Pediatrics

Oksan Derinoz and Hamdi C. Emeksiz

Use of Physostigmine for Cyclopentolate Overdose in an Infant

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DOI: 10.1542/peds.2011-3038 originally published online August 20, 2012;

2012;130;e703

Pediatrics

Oksan Derinoz and Hamdi C. Emeksiz

Use of Physostigmine for Cyclopentolate Overdose in an Infant

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