Você está na página 1de 3


Acta Paediatr Tw

Acute Intoxication of Lidocaine and Chlorpheniramine:

Report of One Case

A case of acute intoxication involving lidocaine and chlorpheniramine (an antihistamine) in a

13-month-old child after ingestion of a commercial topical agent is presented. The major toxic
reaction consisted of convulsion, coma, tachycardia, fever, and fatigue. This report shows that
parents and physicians should be made aware of the hazards of lidocaine and overdose of other
topical agents in infants and children. (Acta Paediatr Tw 2005; 46:385-7)
Key words: lidocaine, chlorpheniramine, intoxication



Over-the-counter drugs may be ingested by children

due to their accessibility. Consequently, children may
have chance to experience significant adverse effects and
toxicity, especially when supratherapeutic doses are
Lidocaine was developed in 1948.5 It has been used
as a local anesthetic agent, an antiarrythmic and a
component of topical anesthetic cream. Intoxication with
parenteral lidocaine occurs frequently,6 but intoxication
with oral lidocaine rarely occurs, with most cases
reported in children receiving very large doses relative
to body weight. 7
Chlorpheniramine is one of the most widely used
antihistamines. The number of antihistaminics now
available through commercial channels is legion. Their
toxicity is not widely recognized by the layman, so they
are often used indiscriminately. Most severe poisonings
have been due to the accidental ingestion of these drugs
by young children.
We report a case who had a severe systemic
intoxication caused by ingestion of a topical agent
containing lidocaine and chlorpheniramine. The purpose
of this report is to call attention to the potential hazard
of these products when ingested accidentally by children.

A 13-month-old boy, weighing 8.6 kg, was well until

about one hour before admission. His parents found that
he was ingesting a commercial topical agent, but neither
the time he began to do this nor the amount ingested
was clear. The container of the drug was almost empty
when found. Just about five minutes later he fell down
to the ground suddenly and appeared cyanotic and
developed a generalized tonic-clonic seizure. He was
brought to a local hospital for first aid, and then he was
transferred to our hospital. In our emergency room, he
had perioral cyanosis and was given oxygen by face mask.
An arterial blood sample had pH=7.056, PCO2=51.1 torr,
and PO2=55.5 torr. Because of persistent seizure and
desaturation, the patient was endotracheally intubated.
Five doses of diazepam (total 10 mg) and two doses of
phenobarbital (total 200 mg) intravenously were given
to control the seizures. Seizures stopped approximately
90 minutes after the onset.
A computed tomographic scan of the head, performed
without contrast, was normal. An electrocardiogram
showed sinus tachycardia with normal PR, QRS, and
QT intervals. Laboratory values included serum sodium
142 mEq/L, chloride 99.2 mEq/L, potassium 4.62 mEq/
L, bicarbonate 14.0 mmol/L, ALT 61 U/L, AST 31 U/

Department of Pediatrics, Tri-Service General Hospital and National Defense Medical Center1, Taipei, Taiwan;
Department of Pediatrics, Faculty of Pediatrics, College of Medicine, Kaohsiung Medical University 2 ;
Department of Pediatrics, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical
University3 , Taiwan.
Received: June 7, 2005. Revised: November 9, 2005. Accepted: December 30, 2005.
Address reprint requests to: Dr. Yi-Ming HUA, Department of Pediatrics, Tri-Service General Hospital, No. 325,
Sec. 2, Cheng-Kung Road, Taipei 114, Taiwan.
TEL : 886-2-8792-7025
FAX : 886-2-8792-7293
E-mail: guitar@ndmctsgh.edu.tw


Lidocaine and chlorpheniramine intoxication

L, urea nitrogen 16 mg/dl, and creatinine 0.6 mg/dl.

White blood cell count was 9,100/mm 3 with 65%
neutrophils. Serum calcium concentration was normal.
Cerebrospinal fluid contained no blood cells and CSF
biochemistry studies were all within normal limits. Blood
and CSF samples obtained for culture were sterile.
On transportation to our Pediatric Intensive Care Unit,
the child was tachypneic and febrile (body temperature
was 38.6). The Glasgow coma scale was E1VeM4.
Neurological examination showed no focal deficits.
Ventilatory assistance was provided, and his blood
pressure and heart rate was supported with fluids and
medications. Maintenance doses of phenobarbital were
given. The container of the ingested agent was brought
to us by the patients father on the second day; the
components of this agent are listed in the Table. Venous
blood obtained approximately 14 hours after the onset
of seizure had a lidocaine concentration of 1.16 mg/L;
serum salicylate concentration was less than 50 mg/L.
Approximately 36 hours after his seizure, the child
awoke and remained alert; however, he was too weak
to sit up and looked depressed initially. His endotracheal
tube was removed about 43 hours after he was intubated.
His symptoms improved with time, but he was still unable
to walk very stably. He was discharged on the 9th
hospital day. Two days after the discharge, an
electroencephalogram was performed which showed a
generalized abnormal background with theda and delta
slow rhythm compatible with generalized encephalopathy.
However, the patient has remained seizure-free after
discharge. A follow-up EEG was not obtained.

The agent our patient ingested is a common topical
preparation with the indications of eczema, insect bite

Vol. 46, No. 6, 2005

and sore muscles. It is easily available at the drugstores

and supermarkets. The composition of this agent is listed
in the Table. Except prednisolone, the others
components of this agent are rather toxic, with high
toxicity ratings. Ingestion of one bottle of this agent
can be fatal to a toddler due to high dosage of lidocaine
and chlorpheniramine maleate. Severe and even lethal
intoxications have been described after accidental
ingestion of lidocaine or antihistamine, respectively;
however, severe intoxication resulting from ingestion
of lidocaine and antihistamine simultaneously has not,
to our knowledge, yet been reported. Additionally,
camphor, methyl salicylate and menthol are all potentially
fatal. However, they may not be contributory to the
symptoms of our case due to relative small amount.
The ingested dosage of drugs was estimated by
pharmacokinetic calculations according to the serum
lidocaine concentration obtained 14 hours after the
ingestion as follows.
Topical cream of lidocaine is almost 100 percent
absorbed orally, but undergoes extensive first-pass
metabolism, which results in a low oral bioavailability
of approximately 35 percent and minimal systemic plasma
lidocaine concentrations.8 The elimination half-life is 3.
2 hours in infants.9 Since the onset and disposition of
lidocaine is rather fast, we used a one-compartment
model to estimate the initial ingested dose, although it
should be a two-compartment model. Based on this, the
estimated maximum serum concentration of lidocaine was
about 20 mg/L and the initial ingested amount of the
agent was about 18.5 gm. The ingested dosage of these
components was calculated as a table, and the ingested
amount of chlorpheniramine maleate and lidocaine were
potentially fatal.
Serum lidocaine concentrations above 5 mg/L are
considered to be toxic. The major toxic effects of
lidocaine involve the central nervous system. Early

Table. The Components of the Ingested Agent

Methyl salicylate

Each gm contains
ingested amount


dose (mg/kg)


10 mg
30 mg
5 mg
5 mg
5 mg

185 mg
555 mg
23 mg



*Numerical toxicity rating is based on Clinical Toxicology of Commercial Products, 5th edition, by Gosselin RE, Smith
RP, and Hodge HC. Baltimore, MD: Williams and Wilkins; 1984.
4 = very toxic, probable oral lethal dose: 50-500 mg/kg
5 = extremely toxic, probable oral lethal dose: 5-50 mg/kg
CTM = chlorpheniramine maleate

Acta Paediatr Tw


symptoms (at serum lidocaine concentrations of 5 to 10

mg/L) are dizziness, drowsiness, tinnitus, and perioral
paresthesia. More severe symptoms are disorientation,
delirium, convulsions, coma (at concentrations of 10
to 20 mg/L), and cardiorespiratory arrest (concentrations
above 20 mg/L).10 Cardiotoxic effects include depression
of autonomic activity and conduction disturbances
causing heart block, ventricular tachyarrhythmia, and
asystole.6 Pediatric cases of toxicity usually have been
associated with chronic administration, or with acute
oral administration of lidocaine 30-80 mg/kg.7
The range of toxicity of antihistamines is variable and
unpredictable. Clinical evaluation is more important than
attempting to determine the amount ingested or injected.
Serum concentrations are generally not useful for
monitoring therapy, but may be helpful in confirming
the diagnosis. Side effects such as dizziness, tinnitus,
lassitude, incoordination, fatigue, blurred vision,
diplopia, insomnia, dryness of the mouth, irritability,
and tremor are common.11 Therapeutic or slightly larger
doses can produce toxic reactions, especially in children.
In young children, central stimulation, convulsion,
and high fever appear to be the dominant signs, followed
by a profound cardiorespiratory depression with death
due to vascular collapse.13 In children, as few as 20-30
antihistamine capsules may be lethal, and 10-60 mg/kg
has produced serious poisonings and death in toddlers.

Labeling over-the-counter drugs in a unique way and

warning of their toxicity may help to decrease lifethreatening events such as this case. It also may help
emergency personnel and toxicologists in taking
immediate measures when such exposures occur. Parents
and physicians should be made aware of the hazards of
lidocaine and overdose of other topical agents in infants
and children.


1. Hon KL, Ho JK, Leung TF, Wong Y, Nelson EA, Fok TF.
Review of children hospitalised for ingestion and poisoning at a tertiary centre. Ann Acad Med Singapore 2005;
2. Wazaify M, Kennedy S, Hughes CM, McElnay JC. Prevalence of over-the-counter drug-related overdoses at
Accident and Emergency departments in Northern Irelanda retrospective evaluation. J Clin Pharm Ther 2005; 30:
3. Khosla U, Ruel KS, Hunt DP. Antihistamine-induced
rhabdomyolysis. South Med J 2003; 96:1023-6.
4. Gunn VL, Taha SH, Liebelt EL, Serwint JR. Toxicity of
over-the-counter cough and cold medications. Pediatrics
2001; 108:E52.
5. Ritchie JM, Greene NM. Local anesthetics. In: Gilman AG,
Goodman LS, Rall TW, et al, eds. The pharmacological
basis of therapeutics. 7th ed. New York: Macmillan, 1985:
6. Rademaker AW, Kellen J, Tam YK, Wyse DG. Character
of adverse effects of prophylactic lodocaine in the coronary care unit. Clin Pharmacol Ther 1986; 40:71-80.
7. Hess GP, Walson PD. Seizures secondary to oral viscous
lidocaine. Ann Emerg Med 1988; 17:725-7.
8. Boyes RN, Scott DB, Jebson PR, Godman MJ, Julian
DG. Pharmacokinetics of lidocaine in man. Clin pharmacol
Ther 1971; 12:105-16.
9. Taketomo CK, Hodding JH, Kraus DM. Pediatric Dosage
Handbook. 3rd ed. Hudson, OH: Lexi-Comp, Inc.; 1996:
10. Mather LE, Cousins MJ. Local anaesthetics and their
current clinical use. Drugs 1979; 18:185-205.
11. Dipalma J. Drills pharmacology in medicine. 3rd ed. New
York: McGraw-Hill Book Company, Inc.; 1965:780.
12. Wyngaarden JB, Saveng MH. Toxic effects of antihistamine drugs. JAMA 1951; 145:277-82.
13. Reyes-Faacang A, Wenzel JE. Antihistamine toxicity in
children. Clin Pediatr 1969; 8:297-9.
14. Duerfeldt TH. Acute Benadryl poisoning. Northwest
Med 1947; 46:781.
15. Matusuoka S, Sadanaga Y, Nishi Y, Takano M, Kinjo
K. A case of Chlortrimeton (chlorpheniramine) intoxication.
Clin Neurol 1962; 2:159-62.