1)Department of Ophthalmology and Visual Neuroscience,
The University of Tokushima, School of Medicine, Tokushima,
Japan, and 2)Center for Maternity and Perinatal
Care, Tokushima University Hospital, Tokushima, Japan
Abstract: The patient was a low birth weight infant with
a history of renal failure. She was referred to our department
29 days after birth to undergo fundus examination. She experienced
renal failure after undergoing a mydriatic test and needed
medical treatment. Eyedrops containing phenylephrine were
instilled several times and additional drops were also instilled
during the fundal examination using an eyelid retractor,
therefore the blood concentration of the drug was elevated
sufficiently to contract the renal vessels, ultimately inducing
renal failure. The present case suggests that since the
use of mydriatic eyedrops in low birth weight infants could
induce renal failure, the following points should be considered
: 1) Mydriatic eyedrops should be used with caution by monitoring
mydriasis and avoiding excessive instillation ;2) After
instillation, the lacrimal region should be compressed to
prevent the flow of mydriatic drops to the nasolacrimal
canal ; and 3) Vital signs should be monitored to check
the onset of any adverse reactions for 12 hours after fundal
examination. J. Med. Invest. 50 : 203-206, 2003
Keywords:Renal failure, mydriatic drug, phenylephrine, retinopathy
of prematurity
INTRODUCTION
Due to recent advances in neonatal care, the chance of survival
for low birth weight infants has improved. However, the
prevalence of premature retinopathy has increased. The first
area of the retina affected by premature retinopathy is
the peripheral region, and fundal examination using a mydriatic
drug is therefore essential.
Systemic adverse reactions associated with the instillation
of mydriatic eyedrops include hypertension and bradycardia
(1, 2). However renal failure has not been reported previously.
This paper presents a case of premature retinopathy who
showed renal failure after mydriatic tests.
CASE REPORT
Patient : A 29-day-old female weighing 674g. History of
present illness : In May, 1999, super low birth weight twins(690g)
were delivered after 26 weeks and 3 days of gestation. The
patient was referred to our department29 days after birth
to undergo fundal examination. Past medical history:On days4and5after
birth, indomethacin sodium was administered intravenously
to treat patent ductus arteriosus, and then the patient
suffered acute renal failure. Family medical history :The
other twin, an older brother, was also a super low birth
weight infant, weighing 964g. Findings on initial examination:
Fundal examination was performed using a mydriatic eyedrop
(Mydrin-P®). A broad circumferential avascular zone
was observed in both eyes, and the patient was therefore
diagnosed as premature retinopathy. Course (Figure 1) :
On day 36, the patient was diagnosed as stage 1, following
the international classification for premature retinopathy.
On day 43, clinical staging therefore advanced to stage
2. The ocular fundi were difficult to examine clearly due
to poor mydriasis and hazy media.
On day 46, a thorough fundal examination was performed by
instilling more drops of a mydriatic drug (Mydrin-P®).
On the next day, urine volume decreased. On day 48, the
patient's general condition worsened and the number of apneic
episodes increased. Consequently, the patient was placed
on respiratory management by nasal continuous positive airway
pressure (NCPAP). Decreased urine volume was treated by
restricting water intake and administering a diuretic drug
and dopamine.
On day 50, further fundus examination was perfor-med. Mydrin-P®
was again used and additional drops were instilled during
the examination. On day 51,anuresis was confirmed and continuous
dopamine infusion was initiated following the diagnosis
of acute renal failure. A diuretic was administered intravenously
on several occasions. In addition, the patient was intubated
for artificial respiration management to avoid apnea. Since
the patient experienced renal failure after the instillation
of Mydrin-P®, excessive usage of the mydriatic drops
was suggested to be the cause. As a result, in subsequent
fundus examinations, the use of Mydrin-P® was restricted
and the pupil was allowed to dilate with time. The patient
did not experience further renal failure thereafter.
Several laser coagulation therapies improved clinical staging
of premature retinopathy to stage3.
DISCUSSION
Mydriatic eyedrops are normally used for routine fundus
examination. Mydriasis is essential for premature retinopathy
patients, since the periphery of the ocular fundus needs
to be examined. Mydriatic eyedrops are roughly divided into
two types : parasympathetic blockers and sympathetic stimulants.
The former directly or indirectly affects the pupillary
sphincter muscle, whereas the latter directly or indirectly
affects the pupil-lary dilator muscle.
Commonly used drugs for mydriasis include: trop-icamide,
atropine, cyclopentolate (parasympathetic blockers) and
phenylephrine (sympathetic stimulant). Mydrin-P®
is an eyedrop containing 0.5% tropicamide and 0.5% phenylephrine
hydrochloride. Since this is a fast-acting and long-lasting
drug, it is often utilized in mydriasis tests.
Tropicamide is a muscarinic antagonist that exerts little
effect on the circulatory system. Although mydriatic drugs
have been shown to cause adverse reactions in neonates and
low birth weight infants such as bradycardia, few cases
requiring special procedures have been re-ported (3). Phenylephrine
is a potent α1-adrenergic receptor stimulant that
acts on the cardiovascular system to increase blood pressure,
lower heart rate, and constrict blood vessels in such organs
as the kidney and the extremities to reduce blood flow (4,
5). Phen-ylephrine must therefore be administered with caution
to patients with heart diseases such as hypertension, coronary
disease or heart failure (6, 7).
Due to reports of bradycardia and apneic episodes, caution
should be exercised when using Mydrin-P®in low birth
weight infants by close monitoring and dilution of the drug
as necessary (8).
Caputo et al. instilled10% phenylephrine in six neon-ates,
for a total of three times with five minute intervals. They
reported increases in systolic pressure by 10mmHg to 26mmHg
and diastolic pressure by 2mmHg to 14mmHg, while the heart
rate decreased up to 20% in four neonates (1).
Rosales et al. instilled 2.5% phenylephrine and 0.5%tropicamide
in ten low birth weight infants, weighing less than 1600g,
for a total of three times with five minute intervals. An
increase of greater than 20% in systolic pressure was observed
in eight patients and an increase of greater than 50% was
observed in three of these eight patients (2). Compared
with adults, the effects of these drugs were reported to
be greater in neonates, especially low birth weight infants,
and due to immature cardiovascular and cerebrovascular systems,
increased blood pressure is more likely to induce adverse
reactions.
The development of the pupillary dilator muscle is incomplete
in neonates, and several instillations are therefore necessary
in dilating the pupil sufficiently(3). The tendency is that
the more severe the prematurity, the more difficult mydriasis
(9). In the present patient, the mydriatic drug was instilled
many times due to poor mydriasis. This caused the accumulation
of phenylephrine in the blood, constricting the renal vessels
and thus resulting in renal failure.
When a mydriatic eyedrop is instilled, it enters not only
the anterior chamber through the cornea, but also the blood
through the conjunctiva, and the nasal mucosa and gastrointestinal
tract through the nasolacrimal canal (10). On some mydriatic
drugs, about 80% of administered dose is absorbed by the
body (11). For example, under normal condition, 80% of timolol
instilled to rabbits is absorbed by the body. Therefore,
in order to increase the concentration of a mydriatic drug
in the eye by blocking the flow of the drug to the nasolacrimal
canal, compression of the lacrimal region and closure of
the eyelids are recommended. Whitson et al. instilled10%
phenylephrine and reported that blood concentration20minutes
after the instillation could be reduced by15-19% by closing
the eyelids for one minute (12). Most neonates will close
their eyes after instillation of a mydriatic drug, but in
the present patient, an eyelid retractor was used to instill
eyedrop containing phe-nylephrine. As the result, the flow
of this drug to the nasolacrimal canal was elevated, and
blood concentration of phenylephrine therefore became high
enough to cause renal failure.
Initially, we considered one possible explanation for the
renal failure as follows: The fundus examination is very
stressful for infants, and they sometimes experience apneic
episodes after undergoing ophthalmol-ogical examination.
To ensure sufficient cerebral blood flow after an apneic
episode, the diving reflex constricts peripheral blood vessels,
and this could lead to renal failure. However, assisted
ventilation reduced the number of apneic episodes in the
present patient when renal failure was exacerbated, thus
negating the potential role of this possibility as the onset
of renal failure.
The present patient was a low birth weight infant with a
history of renal failure. When eyedrops containing0.5% phenylephrine
were instilled several times to dilate the pupil and the
additional drops were instilled during the examination using
an eyelid retractor, the blood concentration of the drug
was elevated sufficiently to contract the renal vessels,
ultimately inducing renal failure.
To the best of our knowledge, renal failure following the
instillation of mydriatic eyedrops has not previously been
reported. The present case suggests that since the use of
mydriatic eyedrops in low birth weight infants could induce
renal failure, the following points should be borne in mind:1)
Mydriatic eyedrops should be used with the caution by monitoring
mydriasis and avoiding excessive instillation;2) After instillation,
the lacrimal region should be compressed to avoid the flow
of mydriatic drops to the nasolacrimal canal; and 3) Vital
signs should be monitored to check the onset of any adverse
reactions for 12 hours after fundal examination.
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