Short Reports Cardiopulmonary arrest following administration of Cyclomydril eyedrops for outpatient retinopathy of prematurity screening Jung M. Lee, MD, Sylvia R. Kodsi, MD, Majida A. Gaffar, MD, and Steven E. Rubin, MD Eyedrops used for mydriasis and cycloplegia can be systemically absorbed, causing serious side effects, including oxygen desaturation, apnea, bradycardia, transient hypertension, delayed gastric emptying, and transient paralytic ileus. These effects can be more serious in infants because of their lower body mass and immature cardiovascular and nervous systems. We report a case of a 27week-old infant who suffered a cardiopulmonary arrest after the administration of only Cyclomydril eyedrops (Alcon Laboratories, Fort Worth, TX) during an outpatient retinopathy of prematurity examination.
Case Report
A
twin female born at 27 weeks’ gestational age weighing 1010 g presented at North Shore-LIJ Health Systems for a follow-up retinopathy of prematurity (ROP) screening examination at 41 weeks’ corrected gestational age, 10 days after being discharged from the hospital. The patient had previously received Cyclomydril drops as part of routine ROP examinations beginning at 30 weeks’ corrected gestational age and every 2 weeks thereafter while hospitalized. At each of these examinations, the patient had received 3 sets (1 drop per eye) of Cyclomydril (cyclopentolate hydrochloride 0.2%, phenylephrine hydrochloride 1%; Alcon Laboratories, Fort Worth, TX), each at 5- to 10-minute intervals, without complications. The patient’s medical history was significant for patent ductus arteriosus (PDA) ligation, atrial septal defect, and chronic lung disease. The latest ROP examination was performed on the day prior to PDA ligation. Three days later the patient was discharged on no medications or oxygen requirements. At her outpatient office examination, the pupils were dilated with Cyclomydril eyedrops. One of the senior
Author affiliations: North Shore-LIJ Health Systems, Hofstra North Shore-LIJ School of Medicine Submitted August 23, 2013. Revision accepted November 19, 2013. Correspondence: Sylvia R. Kodsi, MD, North Shore-LIJ Department of Ophthalmology, Hofstra North Shore-LIJ School of Medicine, 600 Northern Blvd, Suite 220, Great Neck, New York 11021 (email: [email protected]). J AAPOS 2014;18:183-184. Copyright Ó 2014 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2013.11.010
Journal of AAPOS
authors (SER) administered 3 sets of Cyclomydril at 5- to 10-minute intervals. Approximately 15 minutes after the third set of drops were given, the baby was found to be unresponsive, apneic, cyanotic, and pulseless. Cardiopulmonary resuscitation was administered and the patient was revived after 2-3 minutes. Emergency medical services arrived 5-10 minutes later, and the patient was taken to the emergency room. While in the emergency room, almost 3 hours after the first set of Cyclomydril eyedrops were administered, the patient experienced another episode of apnea and bradycardia, which resolved with stimulation. During her hospitalization, she was discovered to have new-onset pulmonary hypertension, thought to be related to the recent PDA ligation. Subsequent dilated ROP examinations at the hospital and in clinic were performed without incident using tropicamide 1% and phenylephrine 2.5% instead of Cyclomydril.
Discussion Cyclomydril is a combination of cyclopentolate 0.2% and phenylephrine 1%, which is frequently used for mydriasis of premature infants for ROP screening examinations. Cyclopentolate is an anticholinergic that blocks pupillary constriction and ciliary muscle contraction and also inhibits the sphincter pupillae muscle causing mydriasis and cycloplegia. Phenylephrine is an alpha-adrenergic agent that acts directly on the pupillary dilator fibers causing mydriasis but not cycloplegia.1 Phenylephrine is often used in addition to cyclopentolate to achieve greater mydriasis.2 Systemic absorption of topical ophthalmic medications has been known to produce side effects by the “first pass” effect. Typically, oral medications are absorbed by the gastrointestinal tract and metabolized by the liver during the first pass. In contrast, topical ophthalmic agents drain through the nasolacrimal duct system, and up to 80% of the drug is absorbed through the nasal mucosa and passes directly into the systemic circulation without hepatic filtering.3 In infants, low body mass and immature cardiovascular and nervous systems can increase the risk of toxicity.4 Adverse effects related to systemic absorption of mydriatic eyedrops are well documented. A transient rise in systolic and diastolic blood pressures and bradycardia have been noted with systemic absorption of phenylephrine. The side effects related to cyclopentolate include oxygen desaturation, apnea, feeding intolerance, delayed gastric emptying, transient paralytic ileus, tachycardia, seizures, and psychosis.1,2 Tropicamide, as an anticholinergic agent also, has a similar side effect profile as cyclopentolate, and therefore caution must be used with any of the mydriatic agents. The difference in acid dissociation constants between tropicamide and cyclopentolate allows a greater concentration of tropicamide to penetrate the corneal epithelium and may explain its faster onset of action and shorter duration.5
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Multiple reports describe adverse events during and following ROP screening, including oxygen desaturation, apnea, and bradycardia,6 calling into question the effect and stress of the actual examination on the neonate contributing to these events.1,4 One study showed a significant rise in heart rate (P 5 0.0272) and a significant decrease in oxygen saturation levels (P 5 0.0275) in 30 neonates immediately after the ROP examination.7 In addition, apnea and bradycardia of prematurity (ABP) is common and occurs in the majority of infants weighing \1,000 g at birth. By 36 weeks’ corrected gestational age, however, most infants outgrow ABP.6 Our patient was already 41 weeks old, with no known history of ABP; moreover, the cardiopulmonary arrest occurred prior to the ROP examination and only after administration of the eyedrops. This suggests that the Cyclomydril contributed to the cardiopulmonary arrest. Furthermore, cyclopentolate was the likely culprit given that phenylephrine would have mostly been cleared by the time the patient had a second event of apnea and bradycardia, almost 3 hours after the eyedrops were administered.8 This infant did have undiagnosed pulmonary hypertension, which probably contributed to her cardiopulmonary arrest. The effect of cyclopentolate or phenylephrine on infants with pulmonary hypertension has not been studied. The use of dilating eye drops for ROP screening has known risks. Punctal occlusion of the nasolacrimal duct after drop administration can reduce systemic absorption, although further research is necessary to determine its true effectiveness.1 Reducing the drop size may also be of benefit: research has shown that a smaller drop size is as effective at dilating pupils as a standard drop size.1,4 However, even with these modifications neonates may still experience episodes of apnea and bradycardia during screening. In the hospital setting the infants are in a carefully controlled and monitored environment with extensive support personnel. However in the outpatient office, this is not the case, so pediatric ophthalmologists should be equipped to handle this type of emergency, either personally or with ancillary services that are immediately available.
Literature Search PubMed was last searched on October 24, 2013, without date or language restriction, using the following keywords: cyclomydril, cyclopentolate, cyclogyl, tropicamide, and phenylephrine in combination with the following terms: 0.2%, complications, adverse effects, apnea, infant, pulmonary hypertension. References 1. Mitchell AJ, Green A, Jeffs DA, Roberson PK. Physiologic effects of retinopathy of prematurity screening examinations. Adv Neonatal Care 2011;11:291-7. 2. Lim DL, Batilando M, Rajadurai VS. Transient paralytic ileus following the use of cyclopentolate-phenylephrine eye drops during screening for retinopathy of prematurity. J Paediatr. Child Health 2003;39:318-20. 3. Shiuey Y, Eisenberg MJ. Cardiovascular effects of commonly used ophthalmic medications. Clin Cardiol 1996;19:5-8.
4. Wheatcroft S, Sharma A, McAllister J. Reduction in mydriatic drop size in premature infants. Br J Ophthalmol 1993;77:364-5. 5. Young TE. Pharmacology review: topical mydriatics: the adverse effects of screening examinations for retinopathy of prematurity. Neoreviews 2003;4:e163-6. 6. Wood MG, Kaufman LM. Apnea and bradycardia in two premature infants during routine outpatient retinopathy of prematurity screening. J AAPOS 2009;13:501-3. 7. Rush R, Rush S, Nicolau J, Chapman K, Naqvi M. Systemic manifestations in response to mydriasis and physical examination during screening for retinopathy of prematurity. Retina 2004;24:242-5. 8. Understanding phenylephrine metabolism, pharmacokinetics, bioavailability and activity. Briefing document for the Nonprescription Drugs Advisory Committee. Summit, NJ: Schering-Plough Corporation; December 14, 2007.
Early detection of recurrent primary iris stromal cyst using ultrasound biomicroscopy Pavel Pochop, MD, PhD, Gabriela Mahelkova, MD, PhD, Jirı Cendelın, MD, PhD, and Denisa Petruskova, MD Primary iris stromal cyst characteristically presents as a smooth, round, translucent mass in the anterior chamber. In small children it tends to grow rapidly and may be confused with intraocular malignancy. Management is difficult, and recurrences are frequent. We report 2 cases of primary iris stromal cyst in which recurrence was detected relatively early using ultrasound biomicroscopy and successfully managed with iridectomy.
Case 1
A
n 18-month-old girl with a 12-month history of growing iris lesion was referred to Department of Ophthalmology, 2nd Faculty of Medicine, Charles University, Prague, and Motol University Hospital. An examination of the left eye revealed a large, translucent cystic lesion on the inferomedial iris measuring 5 5 4 mm and distorting the pupil. Fine vessels covered the surface of the clear fluid-filled cyst (Figure 1A). The underlying iris
Author affiliations: Department of Ophtalmology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic Supported by the Ministry of Health, Czech Republic—conceptual development of research organization, University Hospital Motol, Prague, Czech Republic, 00064203. Submitted July 3, 2013. Revision accepted September 14, 2013. Correspondence: Pavel Pochop, MD, PhD, Department of Ophtalmology, University Hospital Motol, V Uvalu 84 15006, Prague 5, Czech Republic (email: pavel.pochop@gmail. com). J AAPOS 2014;18:184-186. Copyright Ó 2014 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2013.09.017
Journal of AAPOS
Case Report
A
twin female born at 27 weeks’ gestational age weighing 1010 g presented at North Shore-LIJ Health Systems for a follow-up retinopathy of prematurity (ROP) screening examination at 41 weeks’ corrected gestational age, 10 days after being discharged from the hospital. The patient had previously received Cyclomydril drops as part of routine ROP examinations beginning at 30 weeks’ corrected gestational age and every 2 weeks thereafter while hospitalized. At each of these examinations, the patient had received 3 sets (1 drop per eye) of Cyclomydril (cyclopentolate hydrochloride 0.2%, phenylephrine hydrochloride 1%; Alcon Laboratories, Fort Worth, TX), each at 5- to 10-minute intervals, without complications. The patient’s medical history was significant for patent ductus arteriosus (PDA) ligation, atrial septal defect, and chronic lung disease. The latest ROP examination was performed on the day prior to PDA ligation. Three days later the patient was discharged on no medications or oxygen requirements. At her outpatient office examination, the pupils were dilated with Cyclomydril eyedrops. One of the senior
Author affiliations: North Shore-LIJ Health Systems, Hofstra North Shore-LIJ School of Medicine Submitted August 23, 2013. Revision accepted November 19, 2013. Correspondence: Sylvia R. Kodsi, MD, North Shore-LIJ Department of Ophthalmology, Hofstra North Shore-LIJ School of Medicine, 600 Northern Blvd, Suite 220, Great Neck, New York 11021 (email: [email protected]). J AAPOS 2014;18:183-184. Copyright Ó 2014 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2013.11.010
Journal of AAPOS
authors (SER) administered 3 sets of Cyclomydril at 5- to 10-minute intervals. Approximately 15 minutes after the third set of drops were given, the baby was found to be unresponsive, apneic, cyanotic, and pulseless. Cardiopulmonary resuscitation was administered and the patient was revived after 2-3 minutes. Emergency medical services arrived 5-10 minutes later, and the patient was taken to the emergency room. While in the emergency room, almost 3 hours after the first set of Cyclomydril eyedrops were administered, the patient experienced another episode of apnea and bradycardia, which resolved with stimulation. During her hospitalization, she was discovered to have new-onset pulmonary hypertension, thought to be related to the recent PDA ligation. Subsequent dilated ROP examinations at the hospital and in clinic were performed without incident using tropicamide 1% and phenylephrine 2.5% instead of Cyclomydril.
Discussion Cyclomydril is a combination of cyclopentolate 0.2% and phenylephrine 1%, which is frequently used for mydriasis of premature infants for ROP screening examinations. Cyclopentolate is an anticholinergic that blocks pupillary constriction and ciliary muscle contraction and also inhibits the sphincter pupillae muscle causing mydriasis and cycloplegia. Phenylephrine is an alpha-adrenergic agent that acts directly on the pupillary dilator fibers causing mydriasis but not cycloplegia.1 Phenylephrine is often used in addition to cyclopentolate to achieve greater mydriasis.2 Systemic absorption of topical ophthalmic medications has been known to produce side effects by the “first pass” effect. Typically, oral medications are absorbed by the gastrointestinal tract and metabolized by the liver during the first pass. In contrast, topical ophthalmic agents drain through the nasolacrimal duct system, and up to 80% of the drug is absorbed through the nasal mucosa and passes directly into the systemic circulation without hepatic filtering.3 In infants, low body mass and immature cardiovascular and nervous systems can increase the risk of toxicity.4 Adverse effects related to systemic absorption of mydriatic eyedrops are well documented. A transient rise in systolic and diastolic blood pressures and bradycardia have been noted with systemic absorption of phenylephrine. The side effects related to cyclopentolate include oxygen desaturation, apnea, feeding intolerance, delayed gastric emptying, transient paralytic ileus, tachycardia, seizures, and psychosis.1,2 Tropicamide, as an anticholinergic agent also, has a similar side effect profile as cyclopentolate, and therefore caution must be used with any of the mydriatic agents. The difference in acid dissociation constants between tropicamide and cyclopentolate allows a greater concentration of tropicamide to penetrate the corneal epithelium and may explain its faster onset of action and shorter duration.5
183
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Volume 18 Number 2 / April 2014
Multiple reports describe adverse events during and following ROP screening, including oxygen desaturation, apnea, and bradycardia,6 calling into question the effect and stress of the actual examination on the neonate contributing to these events.1,4 One study showed a significant rise in heart rate (P 5 0.0272) and a significant decrease in oxygen saturation levels (P 5 0.0275) in 30 neonates immediately after the ROP examination.7 In addition, apnea and bradycardia of prematurity (ABP) is common and occurs in the majority of infants weighing \1,000 g at birth. By 36 weeks’ corrected gestational age, however, most infants outgrow ABP.6 Our patient was already 41 weeks old, with no known history of ABP; moreover, the cardiopulmonary arrest occurred prior to the ROP examination and only after administration of the eyedrops. This suggests that the Cyclomydril contributed to the cardiopulmonary arrest. Furthermore, cyclopentolate was the likely culprit given that phenylephrine would have mostly been cleared by the time the patient had a second event of apnea and bradycardia, almost 3 hours after the eyedrops were administered.8 This infant did have undiagnosed pulmonary hypertension, which probably contributed to her cardiopulmonary arrest. The effect of cyclopentolate or phenylephrine on infants with pulmonary hypertension has not been studied. The use of dilating eye drops for ROP screening has known risks. Punctal occlusion of the nasolacrimal duct after drop administration can reduce systemic absorption, although further research is necessary to determine its true effectiveness.1 Reducing the drop size may also be of benefit: research has shown that a smaller drop size is as effective at dilating pupils as a standard drop size.1,4 However, even with these modifications neonates may still experience episodes of apnea and bradycardia during screening. In the hospital setting the infants are in a carefully controlled and monitored environment with extensive support personnel. However in the outpatient office, this is not the case, so pediatric ophthalmologists should be equipped to handle this type of emergency, either personally or with ancillary services that are immediately available.
Literature Search PubMed was last searched on October 24, 2013, without date or language restriction, using the following keywords: cyclomydril, cyclopentolate, cyclogyl, tropicamide, and phenylephrine in combination with the following terms: 0.2%, complications, adverse effects, apnea, infant, pulmonary hypertension. References 1. Mitchell AJ, Green A, Jeffs DA, Roberson PK. Physiologic effects of retinopathy of prematurity screening examinations. Adv Neonatal Care 2011;11:291-7. 2. Lim DL, Batilando M, Rajadurai VS. Transient paralytic ileus following the use of cyclopentolate-phenylephrine eye drops during screening for retinopathy of prematurity. J Paediatr. Child Health 2003;39:318-20. 3. Shiuey Y, Eisenberg MJ. Cardiovascular effects of commonly used ophthalmic medications. Clin Cardiol 1996;19:5-8.
4. Wheatcroft S, Sharma A, McAllister J. Reduction in mydriatic drop size in premature infants. Br J Ophthalmol 1993;77:364-5. 5. Young TE. Pharmacology review: topical mydriatics: the adverse effects of screening examinations for retinopathy of prematurity. Neoreviews 2003;4:e163-6. 6. Wood MG, Kaufman LM. Apnea and bradycardia in two premature infants during routine outpatient retinopathy of prematurity screening. J AAPOS 2009;13:501-3. 7. Rush R, Rush S, Nicolau J, Chapman K, Naqvi M. Systemic manifestations in response to mydriasis and physical examination during screening for retinopathy of prematurity. Retina 2004;24:242-5. 8. Understanding phenylephrine metabolism, pharmacokinetics, bioavailability and activity. Briefing document for the Nonprescription Drugs Advisory Committee. Summit, NJ: Schering-Plough Corporation; December 14, 2007.
Early detection of recurrent primary iris stromal cyst using ultrasound biomicroscopy Pavel Pochop, MD, PhD, Gabriela Mahelkova, MD, PhD, Jirı Cendelın, MD, PhD, and Denisa Petruskova, MD Primary iris stromal cyst characteristically presents as a smooth, round, translucent mass in the anterior chamber. In small children it tends to grow rapidly and may be confused with intraocular malignancy. Management is difficult, and recurrences are frequent. We report 2 cases of primary iris stromal cyst in which recurrence was detected relatively early using ultrasound biomicroscopy and successfully managed with iridectomy.
Case 1
A
n 18-month-old girl with a 12-month history of growing iris lesion was referred to Department of Ophthalmology, 2nd Faculty of Medicine, Charles University, Prague, and Motol University Hospital. An examination of the left eye revealed a large, translucent cystic lesion on the inferomedial iris measuring 5 5 4 mm and distorting the pupil. Fine vessels covered the surface of the clear fluid-filled cyst (Figure 1A). The underlying iris
Author affiliations: Department of Ophtalmology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic Supported by the Ministry of Health, Czech Republic—conceptual development of research organization, University Hospital Motol, Prague, Czech Republic, 00064203. Submitted July 3, 2013. Revision accepted September 14, 2013. Correspondence: Pavel Pochop, MD, PhD, Department of Ophtalmology, University Hospital Motol, V Uvalu 84 15006, Prague 5, Czech Republic (email: pavel.pochop@gmail. com). J AAPOS 2014;18:184-186. Copyright Ó 2014 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2013.09.017
Journal of AAPOS
