(Received August 21, 1972; revision accepted for publication January 29, 1973.)
ADDRESS FOR REPRINTS: (J.M.B. ) Department of Pediatrics, St. Vincent’s Hospital and Medical Center of New York, 153 West 11th Street, New York, New York 10011.
PEDlAmics, Vol. 51, No. 6, June 1973
1032
SYSTEMIC
HYPERTENSION
FOLLOWING
OCULAR
ADMINISTRATION
OF
IO%
PHENYLEPHRINE
IN THE
NEONATE
Virginia Borromeo-McGrail, M.D., Joseph M. Bordiuk, M.D., and Hans Keitel, M.D.
From the Department of Pediatrics, St. Vincent’s Hospital and Medical Center of New York
ABSTRACT. The effect of ophthalmic instillation
of 10% phenylephrine on systemic blood pressure
in the neonate has not been previously evaluated, despite reports of adverse reactions. The effect of 10% and 23% phenylephrine eye drops in healthy
low birth weight neonates was compared in a
dou-ble-blind studs’. Blood pressure showed a rise of 12
to 16 mm Hg in systole and 10 to 14 mm Hg in
diastole following administration of 10% phenyl-ephrine. Blood pressure remained stable in infants receiving 23&% phenylephrine.
Consistent, although more variable, increases in
blood pressure were noted in eight low birth
weight infants given 10% phenylephrine eye drops
in a nonblind study. Complete mydriasis was
achieved with 24% phenylephrine as well as with
10%.
Neither concentration had an effect on pulse
or respiratory rates. Cutaneous administration of
either 10% or 2%% phenylephrmne to abdominal skin produced local blanching but no systemic effect.
To avoid potentially dangerous sequelae from
ia-trogenic hypertension, it is recommended that not
more than one drop of 23% phenylephrine in each eye be administered to neonates for mydriasis. Pe-diatrics, 51 : 1032, 1973, PHENYLEPHBINE
HYPER-TENSION, ADVERSE EFFECTS OF PHENYLEPHRZNE,
EYE DROPS, NEONATAL BLOOD PRESSURE, DOPPLER
BLOOD PRESSURE MEASUREMENT.
T
EN percent phenylephrine is amydri-atic widely used in newborn nurseries in preparation for fundoscopic examination. In 1956, McReynolds et a!.’ reported the
occurrence of hypertension and subarach-noid hemorrhage following application of a cotton pack soaked with 10% phenyleph-rine to a patient’s eye. Blood pressure rose
from 118/68 to 230/130 mm Hg. In spite of this potential danger, we have found no studies evaluating systemic blood pressure response to phenylephrine eye drops in the
neonate.
It is the purpose of this communication to
report the occurrence of significant
hyper-tension in low birth weight infants follow-ing ophthalmic instillation of 10% phenyl-ephrine.
METHODS
AND
MATERIALS
Studies were carried out on healthy, low birth weight infants under 1 month of age and weighing from 907 gm to 2,438 gm. Blood pressure was determined using the
Doppler method#{176} with the transducer placed over the brachial artery. The reli-ability of this method has been previously reported.2 The infants were studied while euthermic, asleep, in the supine position, and approximately one-half hour after feed-ing. Pulse and respiratory rates were
re-corded with standard monitors. All control blood pressures were normal.
Ophthalmic Instillation
A double-blind study was carried out in 12 low birth weight infants recording the blood pressure following ophthalmic ad-ministration of either 10% phenylephrine,
23% phenylephrine, or normal saline. In-fants were monitored in the control state until stable blood pressure, pulse, and re-spiratory rates were obtained. One drop of
ophthalmic solution identified by code was instilled in each eye by a nurse, and
re-0 Roche Arteriosonde 1010 Prototype.
I
#{176} _____E1:
lIIIIIIIIIII
-15 -10 -5 0 5 0 5 20 25 30 35 40 45 50 55 60
f MINUTES
Fic. 1. Systolic blood pressure 11, diastolic blood pressure I, pulse S, and respiratory rate A, peated blood pressure measurements were
obtained for approximately one hour. The physician performing the blood pressure
measurements did not know the
composi-tion of the instilled solution. The 10% phe-nylephrine group included three infants
and the 2%% phenylephrine group included four infants.
A separate group of eight low birth
weight infants was studied in an open trial
with 10% phenylephrine ophthalmic
instil-lation. In this study, the observer was
aware that 10% phenylephrine drops had been instifled. Other experimental condi-lions were identical to the double-blind
controlled study.
1033
Cutaneous Administration
In three 1- to 5-day-old infants varying concentrations of phenylephrine were
ap-plied to normal abdominal skin. The solu-tion used was identifiable by code. Blood pressure, pulse, and respiration were
moni-tored both before and after skin application of the coded solution.
RESULTS
Ophthalmic Instillation
Ocular instillation of physiologic saline or 2%% phenylephrine caused no alteration in blood pressure (Fig. 1 and Fig. 2) . The
in-fants in the blind study receiving 10%
1034
70
65
7 55
- Sc
45
::
:
---2) I I I I I I I I
-15 -10 -5 0 5 0 5 20 25 30 35 40 45 50 55 60 65
PHENEPHRlNE21/?0/ ( 9#{216}pINEACHEYE) MINUTES
FI(;. 2. Blood pressure following ophthalmic instillation of 23% phenylephrine. Symbols represent systolic and diastolic pressures of individual patients.
80
75
i 70
65
I
60a ss
50
0
4
4c
3!
3c
-I I
-15 -10 -5 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70
t
P1IENYLEPHRINElO#{176}/,(1 DROP INEACH EYE) MINUTESFic. 3. Blood pressure following ophthalmic instillation of 10% phenylephrine in double-blind study.
TABLE I
BLOOD PRESSURE FOLLOWING OPHTHALMIC
INSTILLATION OF 10% PHENYLEPHRINE6
6 Diastolic pressure on last patient not obtainable.
Patients 1, 2, and 3 were studied in double-blind
fashion. Patients 4 through 1 1 were studied in a
non-blind fashion.
1035
blood pressure ranging from 12 to 16 mm Hg systolic (18% to 25%) and 10 to 14 mm Hg diastolic (22% to 50%) (Fig. 3). The pulse and respiratory rates remained stable.
In the nonblind study, the blood pressure increase was variable and ranged from 6 to 22 mm Hg systolic (7% to 50%) and from
4 to 18 mm Hg diastolic (13% to 70%) (Table I). The increase in blood pressure with 10% phenylephrine was detected within 5 minutes and usually lasted 70 mlii-utes. Hypertension with 10%
phenyleph-rine was not related to size, age, or
nutri-tional state of the infant. All patients who received either 2%% or 10% phenylephrine
had full pupillary dilatation within 25 to 30 minutes. The time of onset and degree of dilatation was not related to the
concentra-lion of phenylephrine used.
Cutaneous Application
It was noted that all infants with
oph-thalmic instillation of phenylephrine devel-oped blanching of their eyelid skin. The blanching appeared between 10 and 15
minutes following application and persisted for at least 60 minutes. Application of either
10% or 23% phenylephrine to the abdomi-nal skin of three infants caused local blanching but there was no associated alter-ation of blood pressure, pulse or respiratory rate.
DISCUSSION
Phenylephrine is a sympathomimetic agent which acts primarily as an alpha ad-renergic stimulant. It is a powerful systemic vasoconstnctor but is almost completely lacking in chronotropic and inotropic car-diac activity. Cardiac irregularities are seen
only rarely, following large doses.4 The first ocular studies with phenyleph-rine were reported in 1936 by Heath.5 He demonstrated a mydriatic effect with a 1% solution. The effect was noted in approxi-mately ten minutes and lasted up to four
and one-half hours. Since that lime there have been several reports of adverse
sys-temic reactions following the use of the
Control
Blood Pressure 15’ 30’ 45’ 60’
Percent
Increase
Systolic
63 74 75 74 74 19.0
66 70 80 78 76 1.0
64 70 76 78 74 21.7
70 74 74 6.0
60 70 76 78 78 33.0
54 64 68 68 26.0
52 68 68 66 33.0
50 60 60 60 20.0
50 60 56 20.0
40 56 64 60 56 58.0
44 48 48 50 55 25.0
Diastolic
46 55 54 55 52 20.0
44 50 54 58 54 33.0
32 40 44 42 40 36.0 40 42 46 46 44 15.0
36 40 44 20.0
30 34 34 13.0
30 40 44 46.0
26 40 40 36 52.0 20 26 30 26 30 50.0
20 38 36 90.0
10% solution.1’6’7 Our studies demonstrated a significant and consistent rise in both sys-tolic and diastolic blood pressure in
neo-nates receiving 10% phenylephrine solu-lion. This rise may be detrimental to the low birth weight infant, especially the in-fant with intracranial bleeding, or the in-fant with a systemic to pulmonary shunt such as patent ductus arteriosus. It is not an uncommon practice in some nurseries to in-still 10% phenylephrine eye drops repeat-edly at ten-minute intervals until “maximal
in-stillation could cause a progressive increase in blood pressure. Thus, there would be a
definite potential of iatrogenic cerebral hemorrhage as reported by McReynolds if
10% phenylephrine were used repeatedly.
Two and one-half percent phenylephrine produced excellent persistent mydriasis without any evidence of systemic reaction.
This concentration appears to be both effective and safe.
Nachman and Esterly8 noted skin blanch-ing following local application of
phenyl-ephrine and suggested the possibility of an associated systemic response. We found that cutaneous application of small doses of phenylephrine caused no increase in
sys-temic blood pressure.
Our studies again emphasize the possibil-ity of a systemic reaction to drugs applied
for local effect. Reported toxicity due to ophthalmic atropine is of particular interest
in relation to our studies.9 Atropine, phenyl-ephrine and their cogeners may be given together with a resultant summation of
toxic effects.
SUMMARY
Systemic hypertension results from the
ocular instillation of 10% phenylephrine. However, Z%% phenylephrine eye drops did
not alter blood pressure, but were found to
be effective for mydriasis in the low birth weight infant. It is recommended that no
more than one drop of 23% phenylephnne be used in each eye to induce mydriasis in
the neonate.
REFERENCES
1. McReynolds, W. U., Havener, W. H., and
Hen-derson, J. W. : Hazards in the use of sympa-thomimetic drugs in ophthalmology. Arch.
Ophthal., 56: 176, 1956.
2. Hochberg, H. M. : Automatic ultrasonic blood pressure measurement in children : A feasibil-ity study. Curr. Thera. Res., 13:483, 1971.
3. Keitel, H., Bordiuk, J., and Borromeo-McGrail,
V. : Blood pressure measurement by
ultra-sound in the newborn, unpublished data.
4. Goodman, L. S., and Gilinan, A. : The
Pharma-cological Basis of Therapeutics, ed. 4. New
York: The Macmillan Company, 1970, p. 510.
5. Heath, P.: Neosynephrine hydrochloride; some
uses and effects in ophthalmology. Arch.
Ophthal., 16:839, 1936.
6. Lansche, R. K. : Systemic reactions to topical
epinephrine and phenylephrine. Amer. J.
Ophthal., 61:95, 1966.
7. Solosko, D., and Smith, R. B.: Hypertension
fol-lowing 10% phenylephrine ophthalmic. Anes-thesiology, 36: 187, 1972:
8. Nachman, R. L., and Esterly, N. B. : Increased
skin permeability in preterm infants. Pre-sented at meeting of Society for Pediatric Re-search, Atlantic City, New Jersey, 1971.
9. German, E., and Siddiqui, N. : Atropine toxicity
from eye drops. New Eng. J. Med., 282:689,
