Extrapyramidal Side Effects of Metoclopramide in a Child-A Case Report-Juniper Publishers
Juniper Publishers-Journal of Pediatrics
Abstract
Metoclopramide is antiemetic, antinauseant and
gastric prokynetic. European medicines agency (EMA) in July 2013 has
officially recommended a very restricted use of metoclopramide in
children, because of serious and common neurological side effects. A 3
years old boy was admitted to our pediatric department due to altered
consciousness, nausea, vomiting and dehydration. Day before he recived a
one oral and one intravenous dose of Reglan (metoclopramide).
Immidiately after admission he developed dramatic neurological symtoms
with face and extremity muscles spasms, trismus, ophistotonus and
extreme agitation. Neurological symptoms were present for about 3 hours,
with periodically withdrawal and worsening. He received only
symptomatic therapy and after 6 hours child was fully recovered and
without complaints. Despite repeated warnings about the possible
neurological side effects, metoclopramide continues to be used in
children for the treatment of nausea and vomiting. If the physician is
not familiar with these side effects of metoclopramide physician can
easily incorrectly interpret these symptoms and diagnose it as tetany,
convulsions, encephalitis, food poisoning, intoxication etc. Physicians
need to follow the recommendations about indications, dosage, drug forms
and way of administration of metoclopramide in children. Detailed
previous medical history and drug use history is necessary for avoiding
misdiagnosis, and for timely recognition and adequate treatment of
metoclopramide side effects in children.
Keywords: Metoclopramide; Extrapyramidal; Side Effects; Children
Introduction
Metoclopramide(chemicalname:
4-amino-5-chloro-N-2-diethylaminoethyl-2-methoxybenzamide hydrochloride
monohydrate) is antiemetic, antinauseant and gastric prokynetic. By
blocking dopamine (D2) receptors, and affecting 5HT-3 receptors as antagonist and 5HT-4
receptors as agonist, metoclopramide inhibits brain vomiting center,
accelerates gastric emptying and increases the resting tone of the lower
esophageal sphincter. Metoclopramid administred intravenously expresses
its effects after 1-3 minutes. The effect occurs 10-15 minutes after
intramuscular administration, and 15-20 minutes after oral dose.
Metabolism takes place in the liver, and about 80% of the drug is
excreted in the urine in the first 24 hours after intake. Half-life vary
from 2,5 to 6 hours. Dose of metoclopramide in children, if it must be
given, should not exceede 0,10-1,15 mg/kg/8h, or 0,5mg/kg,/day.
European medicines agency (EMA) in july 2013 has
officially recommended a changes to the use of metoclopramide in
children. The use of metoclopramide in children now is very resticted
because of serious and common neurological side effects, especially
extrapyramidal disorders (acute dystonia, rigidity,
hypokinesia/akinesia, dyskinesia, akathisia, tremor and paraesthesias,
neurloleptic malignant syndrome). Acute dystonia is most frequent side
effect in children. It includes tonic muscular contractions (face and
extremity muscles), trismus, oculogyric crisis, torticollis,
opisthotonus, pharyngeal muscle spasm or laryngospasm. Rigidity is
increased muscle tone and steady resistance to pasive movements of the
limbs. Tardive dyskinesia is characterized by involuntary choreiform
movements of the tongue, face, mouth and extremities. It is side effect
that appears more often in the elderly and can be permanent.
Akathisia is a subjective feeling of objective sign
of muscle unrest, particulary in the lower extremities. Patient has
difficulty to remaine lying and stay calm, and it can be misdiagnosed as
psychiatric disorder or encephalitis. Neuroleptic malignant syndrome is
rare but fatal complication. It is presented with hypertermia, skeletal
muscles hypertonicity, mental changes and autonomic instability. The
incidence of some of these side effects in children is 6 times higher
than in adults, and it can be up to 25%. Extrapyramidal disorders can
occur even at minimal dosage level, usually within 24-72 hours after
taking this medicine. Typical medical history and clinical signs are
sufficient for diagnosis. Other less frequent side affects of
metoclopramide are elevated prolactine levels, transient hypertension,
cardiac conduction disturbances, altered hepatic function test results,
methaemoglobinaemia,agranulocytosis etc. Dispite recomendations for
restriction of use
of metoclopramide in pediatric population, we often admitt child
with the information about prescribed or applied metocopramide
in emergency department. While pediatricians generally comply
with these recommendations, very often metoclopramide is
prescribed to the children by general practitioners and physicians
in emergency services [1-5].
Official recomendations of European medicines agency about
use of metoclopramide in children are:
Metoclopramide is officially contrainidcated in children under
1 year of age. In children and young over 1 year of age (and under
20 years) metoclopramide is restricted to following conditions
and only as second line therapy:
- Vomiting associated with radiation therapy, chemotherapy or postoperative nausea and vomiting.
- Assist in small bowel intubation.
Oral formulations of metoclopramide are associated
with overdose, and they are not recommended in children
and adolescents. If they are administred, patients should use
appropriately designed graduated oral syringe to ensure accuracy.
Intravenous administration should be as slow bolus over at
least 3 minutes. Metoclopramide should only be prescribed for
short-term use (up to 5 days) and maximum dose in 24 hours is
0,5 mg per kg body weight. Metoclopramide should not be used in
pregnancy if not clearly needed, and it is not recommended during
the first three months of pregnancy unless there are compelling
reasons to do so. Metoclopramide is excreted in human breast
milk and its use is not recommended in nursing mothers unless
the expected benefit outweighs the potential risk.
The use of metoclopramide is strictly contraindicated in
patients in whom increased gastrointestinal motility might be
dangerous, in patients with phaeochromocytoma, hypersensitivity
to metoclopramide, procaine, procainamide, patients with
porphyria or epilepsy.
Case Report
A 3 years old boy was admitted to our pediatric department
due to altered consciousness, nausea, vomiting and dehydration.
One day before admision started diarrhea and vomiting. A
morning before he recived a single adequate therapeutic oral dose
of Reglan (metoclopramide), and night before in the emergency
service with intravenous crystalloids he recived one adequate
therapeutic intravenous dose of Reglan. At the admission child
was exhaused, somnolent, and had signs of mild to moderate
dehydration. His vital signs were as following: arterial blood
pressure 90/60 mmHg, pulse 100/min, respiratory rate 20/min,
axillary temperature 37,5oC, capillary refilling 2-3 sec.
Immidiately
after admission he developed dramatic neurological symtoms
with face and extremity muscles spasms, trismus, ophistotonus and
extreme agitation. Child periodically complained of pain in the
arms and stomach. Laboratory testing was done and intravenous
rehydration with crystalloids was administred. In laboratory
results we found mild metabolic acidosis and mild hypokalaemia
which were not present in control laboratory testing after one
hour of rehydration and potassium substitution. Stool testing has
shown a positive result for Rota virus. Neurological symptoms
were present for about 3 hours, with periodically withdrawal and
worsening. Intravenous rehydration and electrolyte substitution
were continued and after 6 hours child was fully recovered and
without complaints. Control examination was performed after
two days, and finding was completely normal.
Discussion
Despite repeated warnings about the possible neurological
and other side effects, metoclopramide continues to be
used in children for the treatment of nausea and vomiting.
Metoclopramide is prescribed to the children most often by the
general practitioners and doctors in the emergency services. It is
the duty of pediatricians to inform these colleagues with whom
they cooperate about possible side effects of metoclopramide
in children. Neurological adverse effects of metoclopramide are
idiosyncratic and do not depend on dosage. They can appear even
at standard treatment dose, but they are more likely to appear
in overdoses and have cumulative effect with repeated use.
Possible explanation is that metoclopramide by blocking a specific
postsynaptic dopamine receptors in basal ganglia can produce
acute extrapyramidale reactions. Children, particulary females
are more susceptible. Fortunately, acute reactions are usually self
limited, respond well to the treatment and do not need any further
evaluation and follow-up . In children most frequent neurological
reactions are face and extremity muscle contractions, torticolis,
opisthotonus, oculogyric crises.
Patient and parents experience these sudden and rapidly
accelerated symptoms very dramaticly and should be, in case
of prescribing metoclopramide, warned in advance about the
possibility of developing these symptoms. If he is not familiar
with these side effects of metoclopramide physician can easily
incorrectly interpret these symptoms and diagnose it as tetany,
convulsions, encephalitis, food poisoning, intoxication etc.
Phyisicians in the first place need to take good previous medical
history, and history about drug use, and than recognise these side
effects and treat them properly. Recommended treatment in acute
phase is to secure airway in case of upper airway obstruction
because of pharyngeal muscle spasm or laryngospasm, then
apply oral, intravenously or intramuscular: Diphenhydramine
hydrochloride (1,25 mg/kg/dose, maximum 300 mg/day with
6 hour intervals), or benztropine mesylate (0,02-0,05 mg/kg/
dose, maximum 2 mg/kg/day and once or twice per day), or
biperiden lactate (0,04 mg/kg, maximum four doses with 30
minute intervals). Midazolam can be administred in patients with
convulsions, in common anticonvulsive doses.
Conclusion
Use of metoclopramide in the pediatric population should
be restricted to some specific conditions such as small bowel
intubation procedures, radiotherapy, chemotherapy and
postoperative period associated nausea and vomiting, and only
as a second line medication. Metoclopramide is contraindicated
in children under one year of age. Physicians need to follow
the recommendations about dosage, drug forms and way od
administration of metoclopramide in children. Detail previous
medical history and drug use history is necessary for avoiding
misdiagnosis, and for timely recognition and adequate treatment
of metoclopramide side effects in children.
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