Atrial arrhythmia after newborn eye exam,to caffeine or not to caffeine?

1 Case 1

A baby born at 28 3/7 weeks of gestational age, triplet A of triplets born via C-section. She was intubated on day one; a dose of surfactant was given for respiratory distress syndrome, and she was supported by nasal continuous positive airway pressure (CPAP) until her age was 35 weeks of corrected gestation. She was also receiving caffeine for apnea of prematurity.

The cardiology team was consulted initially for bradycardias at day 22 of life that was persistent for a period of 48-hours. The neonatal intensive care unit (NICU) team was concerned since the bradycardia persisted with ranging ventricular rate of 70–80 bpm (Fig. 1). The patient was placed on CPAP of 5 cm H₂O. A Holter monitor was placed after EKG findings of intermittent junctional rhythm. The Holter study showed low minimum heart rate of 51 with rare periods of junctional rhythm, as well as isolated blocked premature atrial contractions (PACs). On the morning of the event, patient had an eye exam and was pretreated with phynilephrine 1% - cyclopentolate 0.2% eye drops. The bradycardias self-resolved the following day and no interventions were required. Infant continued to do well without any further arrhythmia.

At 38 days old, she had a second eye exam and subsequently began to develop episodes of bradycardias (pressure in the 80’s) with occasional tachycardia up to 180 bpm. At that time the baby was on CPAP of 5 and on room air. The baby was feeding 22 ml every two hours over 30 minutes and was still on caffeine. During that time, the EKG (Figs. 2 and 3) showed frequent PACs with different p-wave morphology. There was sinus rhythm alternating with PACs that were blocked with affected ventricular rate of 80. She remained well and hemodynamically stable with no change in oxygen saturation. No changes in feeding pattern and no apneas. No interventions were required, except discontinuation of caffeine and the PACs eventually self-resolved.

Later, she was transferred to a level 2 nursery in a different hospital and was noted to have two similar episodes of bradycardia with repeat eye exams. Cardiology was consulted, and no interventions were required and the event abated on its own. She was discharged home after establishing full oral feeds. The patient will have a follow-up Holter at six months of age.

2 Case 2

A 9 week old ex-26+1/7 week gestational age infant underwent routine screening for retinopathy of prematurity as part of preparation for transfer from a level 3 NICU to a regional level 2 nursery to take place on the following day. The patient’s clinical course had previously been relatively unremarkable, other than the respiratory distress syndrome treated with surfactant followed by one week of mechanical ventilation, and apnea of prematurity treated with caffeine citrate. The patient also had anemia of prematurity requiring two packed red blood cell transfusions, a right subependymal hemorrhage, and indomethacin was administered for a medium sized PDA. Echocardiogram revealed otherwise normal intracardiac anatomy and normal biventricular function. The patient’s current medications included domperidone 0.6 mg PO QID, omeprazole 2 mg PO daily, caffeine citrate 17 mg PO daily as well as iron and vitamins. On the day of transfer, the patient received cyclopentolate 0.5% and phenylephrine 2.5% ophthalmic drops, 2 drops in each eye for a second ophthalmologic examination. Approximately 12 hours later, the patient had ten episodes of atrial tachycardia lasting from seconds to a minute (the baseline heart rate was 180–200, maximum of 270) that were recorded on a rhythm strip (Fig. 4). A 12-lead ECG was done hours after the episodes, which showed normal sinus rhythm (Fig. 5). There were no significant oxygen desaturations or drops in blood pressure during the tachycardia episodes, which resolved spontaneously. Caffeine was held, domperidone was discontinued after the event, and omeprazole was briefly held and then reinstated. The patient’s transfer was delayed for approximately 72 hours for cardiac consultation and observation. Caffeine was restarted prior to discharge. The patient did not have any subsequent recognized episodes of supraventricular tachycardia (SVT) on follow up.

3 Discussion

Phenylephrine 1% and cyclopentolate 0.2% ophthalmic drops are used as mydryiatic agents for neonatal eye exam in screening for retinopathy of prematurity. Cyclopentolate is an anticholinergic agent that blocks pupillary constriction and ciliary constriction, whereas phenylephrine is an alpha-adrenergic agent that acts directly on the pupillary dilator fibers. In addition, caffeine is routinely used for treatment of apnea of prematurity.

Literature has shown some correlation between mydriatic eye drops and multiple systemic effects. Cyclopentolate is known to cause seizures, apnea, delayed gastric emptying, feeding intolerance and tachycardia [3–5, 10].

Cyclomydril eye drops have been linked to cardiopulmonary arrest requiring CPR [5]. Significant effects on the blood pressure have been associated with the administration of phenylephrine eye drops, which have some systemic absorption [4]. Phenylephrine 2.5% eye drops is also reported to cause local vasoconstriction of the skin around the eye [7]. Ileitis is another side effect reported in premature infants when cyclopentolate eye drops is administered [6]. Caffeine, on the other hand, has been reported to cause agitations, irritability, tachycardia, tachypnoea, diuresis, electrolyte abnormalities, and hyperglycemia in neonates [7–9].

In conclusion, premature infants are susceptible to toxicity from mydriatric agents, which may result in atrial arrhythmias (PACs, SVT and bradycardia). It is common to use caffeine and mydriatics, most often with no significant adverse effects; however, one should be aware of the potential side effects of these medications when used in combination. Based on our observations, we suggest that temporarily holding all drugs that may potentiate the autonomic nervous system, (e.g. caffeine) prior to the administration of mydiatric agents may avoid the possibility of atrial arrhythmias in susceptible infants (ex: those with prior episodes of arrhythmias with eye exam). Limited instillation and dose reduction is also prudent in premature infants and neonates to reduce the potential for toxicity.

Financial disclosures

Authors has received no financial conflicts of interest to disclose.