Original Article

Clinical efficacy of phentolamine in the treatment of feeding

intolerance in premature infants with low birth weight
Hongya Li1, Bin Li2, Xuehua Wen3
ABSTRACT
Objective: To discuss the clinical efficacy of phentolamine in the treatment of feeding intolerance in
premature infants with low birth weight.
Methods: Seventy-one low-birth-weight infants with feeding intolerance were randomly divided into the
phentolamine group and the erythromycin group (38 patients and 33 patients, respectively). The infants
were given basic treatment, such as gastric lavage, temporary fasting, nutritional support and abdominal
massage. The phentolamine group was intravenously pumped with phentolamine as the basis of basic
treatment, while the erythromycin group was given erythromycin as the basis of basic treatment. The time
for gastrointestinal symptoms to disappear, the time the basic standard was reached, the time parenteral
nutrition was used, the total time enteral feeding was implemented, the length of stay, and the increase in
physical indexes according to the corrected gestational age of 40 weeks of the two groups were compared.
Results: There was no significant difference between the phentolamine group and the erythromycin group
in vomiting disappearance time or the increase in physical indicators at the corrected gestational age
of 40 weeks (P>0.05), while the abdominal distension disappearance time, the time of restoration to
birth weight, the time to reach the basic standard, the total time of parenteral nutrition, the total time
of enteral feeding, and the length of stay in the phentolamine group were shorter than those in the
erythromycin group, with significant differences (P<0.05).
Conclusion: Phentolamine has a significant effect on alleviating symptoms and shortening the treatment
time while treating feeding intolerance in premature infants with low birth weight, without adverse events,
so it is worthy of clinical promotion.
KEYWORDS: Phentolamine; Feeding intolerance; Low birth weight infants; Premature infants.
doi: https://doi.org/10.12669/pjms.36.7.2633
How to cite this:
Li H, Li B, Wen X. Clinical efficacy of phentolamine in the treatment of feeding intolerance in premature infants with low birth
weight. Pak J Med Sci. 2020;36(7):1655-1658 doi: https://doi.org/10.12669/pjms.36.7.2633
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1.
2.
Hongya Li,
Bin Li,
INTRODUCTION
Department of Neonatology,
Maternal and Child Care Service Centre of Baoding, Feeding intolerance (FI) refers to a group of
Baoding, Hebei, 071000, P.R. China. clinical syndromes of intolerance to enteral nutrition
3. Xuehua Wen,
1,3: Department of Neonatology,
caused by gastrointestinal disturbance of newborns,
The First Central Hospital of Baoding, Baoding, but its etiology is currently still unclear. Due to the
Hebei, 071000, P.R. China.
immature development of various nerve reflexes
Correspondence: and the influence of gastrointestinal and swallowing
Dr. Bin Li, dysfunction, most premature infants have varying
Department of Neonatology, degrees of feeding intolerance, which affects their
Maternal and Child Care Service Centre of Baoding,
Baoding, Hebei, 071000, P.R. China. growth and development as well as quality of life.1
E-mail: [email protected] There is a high incidence of FI in premature infants,
* Received for Publication: April 4 2020
which may develop into life-threatening neonatal
* Corrected and Edited: August 15, 2020 necrotizing enterocolitis (NEC)2 and lead to poor
* Accepted for Publication: * September 18, 2020 psychological development.3 The conversion of

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 Hongya Li et al.

low-birth-weight premature infants from tube- and treatment in the Guidelines for the Management
feeding nutrition to full oral milk feeding is one of of Premature Infants: After the children developed
the criteria for premature infants to be discharged feeding intolerance, they were given gastric
from the hospital.4 Therefore, it has become a lavage, temporary milk ban, abdominal massage,
common concern of the medical staff in the neonatal supplementation of intestinal probiotics and other
intensive care unit to promote the safe and effective basic treatments. The phentolamine group was
oral feeding of premature infants as soon as given an intravenous infusion of phentolamine
possible. The intravenous infusion of phentolamine as the basis of basic treatment. The liquid
was used in this study to treat feeding intolerance configuration method was used: phentolamine (1.8
in premature infants, and good clinical efficacy was mg/kg) was added to a 10-ml 5% glucose injection
obtained. The experience is summarized as follows. for 10 h of continuous pumping once/day with a
pumping speed of 0.3 μg/(kg·min) for 3-5 days.
METHODS The erythromycin group was given erythromycin,
Seventy-one low-birth-weight premature infants 5 mg/kg, once daily as the basis of basic treatment,
aged less than 1.0 day who were admitted to the which was added to the 20-ml 10% glucose injection
Neonatology Department of Maternal and Child for 10 hour continuous pumping (1 mg/(kg·h), once
Care Service Center of Baoding and our hospital daily, 3-5 days). The intravenous nutrition support
from January 2015 to July 2018 were enrolled in for both groups was discontinued when total enteral
this study. nutrition was performed. During the study, daily
Inclusion criteria: 1500 g ≤ birth weight < 2500 changes in the infants were recorded, including
g, 224 d (32 weeks) ≤ gestational age < 258 d (37 basic vital signs, daily milk-taking volume, residual
weeks). The patients were randomly divided into milk volume, daily weight changes, and symptoms
the phentolamine group and erythromycin group of vomiting or abdominal distension. The following
(38 patients and 33 patients, respectively). There indexes were compared: (1) time of disappearance
was no significant difference between the two of gastrointestinal symptoms (vomiting and
groups in sex, gestational age or body weight before abdominal distension); (2) time to reach the basic
treatment (P >0.05; Table-I). standard [the time required for the amount of milk
Ethical Approval: The study was approved by fed orally after birth to reach 100 ml/(kg•d)]; (3) the
the Institutional Ethics Committee of Baoding time of total parenteral nutrition (TPN); (4) the time
First Hospital, and written informed consent was to reach total enteral nutrition (TEN); (5) the length
obtained from all participants. of stay; and (6) the increase in physical indexes
Diagnostic Criteria: First, surgical conditions, (body mass, body length and head circumference)
such as congenital gastrointestinal malformation, at the corrected gestational age of 40 weeks.
necrotizing enterocolitis and normal gastrointestinal Statistical Analysis: The SPSS 19.0 statistical
feeding, were excluded. The diagnostic criteria software package was used for analysis, with the
were as follows: (1) vomiting refers to vomiting measurement data with a normal distribution
≥3 times per day; (2) abdominal distension refers expressed as the mean ± standard deviation (x±s),
to a 24-h abdominal circumference increase of and the intergroup comparison was performed
≥1.5 cm, accompanied by visible peristalsis; (3) by the independent sample t test. P < 0.05 was
gastric retention refers to the storage of more than considered statistically significant.
1/3 of previous milk or coffee-ground or bile-like RESULTS
substances in the stomach.
Therapeutic methods: After admission to the The time to disappearance of vomiting
hospital, both groups of children were kept between the phentolamine treatment group and
warm and given total intravenous alimentation, the erythromycin group showed no significant
anti-infection treatment and other supportive
treatment to ensure water, electrolyte and acid- Table-I: Comparison of general information
base balance; when necessary, the intravenous between the two groups before treatment.
infusion of plasma and gamma globulin was Group Sex Body weight Gestational
performed for immunoenhancement, and CPAP (male/female) (g) age (d)
and mechanical ventilation therapy were used for
Phentolamine group 20/18 2032±258 246±8.5
respiratory failure. All treatment methods were
used in strict accordance with the rules of diagnosis Erythromycin group 17/16 2080±338 242±8.9

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 Phentolamine in the treatment of premature infants

Table-II. Comparison of indexes between the two groups after treatment ( ±s).
Group Disappearance Disappearance Recovery to Length Reached the Time of Time of
of vomiting of abdominal birth weight of stay basic standard TPN TEN
(d) distension (d) (d) (d) (d) (d) (d) (d)
Phentolamine group 4.0±1.8 3.2±1.3* 6.8±1.5* 13.3±3.9* 10.9±3.4* 11.6±3.8* 12.9±3.6*
Erythromycin group 3.7±2.0 3.2±1.9 8.6±1.8 20.7±9.6 17.6±11.1 17.6±11.6 22.1±12.5
T Value 0.28 5.15 4.06 50.1 24.3 29.1 42,8
P P>0.05 P<0.05 P<0.05 P<0.05 P<0.05 P<0.05 P<0.05
Note: compared with the erythromycin group, *P<0.05.

Table-III: Comparison of the increase in physical bleeding and necrotizing enterocolitis if severe. The
indexes between the two groups at the corrected length of stay will be longer, and long-term intra-
gestational age of 40 weeks ( ±s). venous hyperalimentation is required if there is no
Group Cases Body Body Head effective treatment, which may easily lead to com-
weight length circumference plications, such as cholestasis, bleeding and infec-
(g) (cm) (d) tion.6 Therefore, it is very important to adopt active
treatment methods to reduce feeding intolerance.
Phentolamine group 38 4.2±1.0 3.4±0.9 4.1±0.9
The non-drug clinical treatment methods for
Erythromycin group 33 3.2±1.1 2.6±1.0 3.0±1.1
feeding intolerance in premature infants usually
T value 0.01 3.67 1.59
include newborn touch, kangaroo nursing, non-
p P>0.05 P>0.05 P>0.05
nutritive sucking, establishment of a breast milk
bank, application of deeply hydrolyzed milk
difference (P >0.05), but the disappearance time powder, supplementation of intestinal probiotics,
of abdominal distension, the time of recovery to etc., and all of these methods have achieved good
birth weight, the length of stay, the time to reach efficacy.7-9 As a kind of drug therapy, erythromycin
basic standard, and the time of TPN and TEN has a pro-kinetic effect on the full digestive tract,
showed statistically significant differences in the which can enhance esophageal contraction,
erythromycin group (P < 0.05; Table-II). There was increase the pressure on the lower esophageal
no significant difference in body weight, body sphincter, enhance gastric antrum contraction
length or head circumference between the two and gallbladder contraction and promote colon
groups at the corrected gestational age of 40 weeks movement.10 Low-dose erythromycin is usually
(P >0.05; Table-III). used to treat neonatal feeding intolerance, which
DISCUSSION can activate the gastrointestinal motility receptor
to cause mild contraction of the digestive tract
In China, the rate of premature infants is high and improve feeding tolerance, thus shortening
and is exhibiting an obvious increasing trend as the the time of parenteral nutrition and achieving
number of second births of elderly parturient women early enteral feeding. In addition, the intravenous
and in vitro fertilization pregnancies increases.5 administration of erythromycin in the treatment of
The majority of premature infants are low-birth- feeding intolerance in premature infants has been
weight, very-low-birth-weight or extremely low- suggested in many studies11 and is widely applied
birth-weight infants. Low-birth-weight infants are in clinical work.
relatively mature in the development of various Nevertheless, the treatment of feeding
systems, and feeding is the prominent problem intolerance in premature infants with low-dose
of premature infants at this stage. Therefore, the erythromycin is the only drug option, so it is
feeding intolerance of low-birth-weight premature necessary to further explore a variety of drug
infants was selected as the topic for this study. treatment methods to achieve individualized
The central nervous system of premature infants treatment and address feeding intolerance in
is not fully developed, and its regulation of the oral premature infants at different gestational ages.
cavity, throat and airway is immature; therefore, Phentolamine, an α-receptor blocker, can
parenteral nutrition is generally needed to assist en- competitively block the binding of norepinephrine
teral nutrition for preterm infants. Feeding intoler- to the α receptor, thus relieving vasoconstriction.
ance is a common clinical complication among pre- Moreover, phentolamine can directly dilate
mature infants, which may cause gastrointestinal arterioles and bronchi and improve pulmonary

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 Hongya Li et al.

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Source of Funding: None. Authors’ Contributions:

Conflicts of Interest: None.
HL & BL: designed this study and prepared this
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