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Abstract. An 18-month-old male presented to the emergency department (ED) for evaluation of lethargy and apnea. Four hours before
presentation, the patient was found with an empty bottle of ibuprofen,
an ingestion of as much as 7.2 grams (600 mg/kg). The ED course was
remarkable for a 30-second tonicclonic seizure. Laboratory analysis
was notable for metabolic acidosis. Four-hour and 7.5-hour serum ibuprofen levels were 640 and 39 g/mL, respectively. Following treatment, the patient improved and was extubated the next morning.
While metabolic acidosis has been frequently described at doses exceeding 400 mg/kg, seizures occurring early in the course of ibuprofen
toxicity have been rarely noted. Key words: ibuprofen; poisoning; pediatrics. ACADEMIC EMERGENCY MEDICINE 2000; 7:821823
Elif E. Oker,
MD, Department of Emergency Medicine, University of Illinois at
Chicago, 1740 West Taylor Street, Suite
1600, Chicago, IL 60612. Fax: 312-9962727; e-mail: istanbul@msn.com
CASE REPORT
An 18-month-old, 12-kg male with
an unremarkable past medical history was brought to the emergency
department (ED) for evaluation of
lethargy. According to the parents,
the patient was found approximately four hours prior to presentation with an empty bottle of ibuprofen, and with pill fragments in
his mouth. The patient had two episodes of emesis; one spontaneous
and the other manually induced by
a grandparent. After a brief period
of relatively normal behavior, the
parents noted that the patient became limp and was not easily
aroused. The patient subsequently
became apneic, prompting the parents to bring him to the ED. The patients past medical history included
eczema and otitis media. His parents indicated that he was occasionally given pseudoephedrine but was
not given any in the last 24 hours.
Further, it was discovered that his
grandmother took lisinopril, for
which all tablets were accounted.
821
Later investigation indicated a potential ingestion of as much as 7.2
grams of ibuprofen (600 mg/kg).
On presentation to the ED, the
patient was lethargic. Vital signs
were temperature (rectal) 96.8F,
respiratory rate 16 breaths/min,
heart rate 123 beats/min, and blood
pressure 118/48 mm Hg. The patients vital signs remained in this
range throughout his ED course.
Physical exam was significant for an
intact gag reflex, reactive pupils (3
mm), and withdrawal from painful
stimuli. He received, in increments,
a total of 600 mL of normal saline
and 1 mg of naloxone without response. A short time later the patient sustained a 30-second tonic
clonic seizure, which resolved with
lorazepam 1 mg IV push. The patient then became apneic, requiring
endotracheal intubation. Subsequent lavage with a 12-Fr nasogastric tube and 300 mL of normal saline revealed small pill fragments.
Activated charcoal was then administered. A sodium bicarbonate bolus
of 12 mEq was administered, followed by an infusion of D5W and 24
mEq/L sodium bicarbonate at 90 mL
per hour, in light of the patients persistent acidosis.
Laboratory analysis was notable
for arterial blood gas pH of 7.20,
pCO2 of 39 torr, pO2 of 469 torr, and
HCO
3 of 15 mEq/L on 100% oxygen.
A second arterial blood gas, drawn
approximately one hour after the
first, demonstrated a pH of 7.29,
pCO2 of 30 torr, pO2 of 336 torr, and
HCO
3 of 14 mEq/L. Serum chemistry obtained during the same period
revealed Na 140 mEq/L, Cl 107
mEq/L, HCO
17 mEq/L, K 4.9
3
mEq/L, BUN 13 mg/dL, Cr 0.4 mg/
dL, and glucose 157 mg/dL. The
complete blood count was unremarkable, and serum salicylate, acetaminophen, and ethanol levels were
negative; urine toxicology screen
was negative for cocaine, phencyclidine, opiates, benzodiazepines, barbiturates, and cannabinoids. An
electrocardiogram demonstrated a
sinus rhythm without QRS prolongation. A four-hour serum ibuprofen
level was 640 g/mL.
The patient was then transferred
to a tertiary care childrens hospital. A blood gas obtained after
transfer demonstrated a pH of 7.26,
while concomitant serum chemistry
showed bicarbonate of 18.2 mEq/L
822
IBUPROFEN
DISCUSSION
Much of what is known about ibuprofen toxicity stems from cases of
adult poisoning.19 Our case illustrates that ibuprofen may cause significant toxicity in children. The
wide availability of this over-thecounter product in pediatric formulations makes this a particular concern in children.
The low toxic profile of ibuprofen
in the pediatric population is encouraging. A randomized clinical
trial of more than 84,000 febrile children demonstrated that at standard
doses, an ibuprofen-treated group
was not at increased risk for hospitalization for acute gastrointestinal
bleeding, acute renal failure, or anaphylaxis.10 A comparison of 10,134
cases of analgesic exposure demonstrated a relatively good safety profile of ibuprofen in pediatric overdose.6 Of the 1,003 cases involving
children, 80% of those with ibuprofen ingestion were managed at home
without adverse outcome. Only 0.4%
of the ibuprofen cases demonstrated
severe symptoms. Of the pediatric
patients with ingestions presenting
to a hospital, 70.4% were treated
and discharged.6
Symptoms of ibuprofen overdose
have ranged from mild gastrointestinal upset to metabolic acidosis and
seizures. Most symptoms occur
within the first four hours without
any delayed effects.1 Seizures in ibuprofen toxicity occur in less than
10% of cases.11 There is no known
difference in the incidence of seizures among pediatric and adult
populations. Linden and Townsend12
reported two patients, a 2-year-old
and a 15-month-old, who ingested
Oker
et al. IBUPROFEN TOXICITY
CONCLUSIONS
In general, pediatric ibuprofen toxicity results in mild gastrointestinal
and central nervous system symptoms that necessitate only supportive therapy. Most symptoms manifest within the first four hours
post-ingestion. Children who ingest
more than 400 mg/kg may develop
metabolic acidosis, electrolyte abnormalities, seizures, and coma, as
demonstrated in our case. Transient
renal insufficiency has also been reported. Even in these more severe
presentations, aggressive supportive
care and attention to the basic tenets of poison management usually
effect a successful outcome. A proposed ibuprofen nomogram has not
been shown to be predictive of clinical symptoms and outcome and
therefore is not clinically useful. Patients who ingest less than 200 mg/
kg do not require hospitalization.
References
1. Hall AH, Smolinske SC, Conrad FL,
et al. Ibuprofen overdose: 126 cases. Ann
Emerg Med. 1986; 15:130812.
2. Hall AH, Smolinske SC, Kulig KW, et
al. Ibuprofen overdose: a prospective
study. West J Med. 1988; 48:6536.
3. Halpern SM, Fitzpatrick R, Volans
GN. Ibuprofen toxicity. A review of adverse reactions and overdose. Adverse
Drug React Toxicol Rev. 1993; 12:107
28.
4. Smolinske SC, Hall AH, Vandenberg
S, et al. Toxic effects of nonsteroidal antiinflammatory drugs in overdose. Drug
Safety. 1990; 5:25274.
5. Seifert SA, Bronstein AC, McGuire T.
Massive ibuprofen ingestion with survival. Clin Toxicol. 2000; 38(1):557.
6. Veltri JC, Rollins DE. A comparison of
the frequency and severity of poisoning
cases for ingestion of acetaminophen, aspirin, and ibuprofen. Am J Emerg Med.
1988; 6:1047.
7. Perry SJ, Streete PJ, Volans GN. Ibuprofen overdose: the first two years of
over-the-counter sales. Hum Toxicol.
1987; 6:1738.
8. McElwee NE, Veltri JC, Bradford DC,
et al. A prospective, population-based
study of acute ibuprofen overdose: complications are rare and routine serum
levels not warranted. Ann Emerg Med.
1990; 19:65762.
9. Jenkinson ML, Fitzpatrick R, Streete
PJ, Volans GN. The relationship between
plasma ibuprofen concentrations and
toxicity in acute ibuprofen overdose.
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14. Kim J, Gazarian M, Verjee Z, Johnson D. Acute renal insufficiency in ibuprofen overdose. Pediatr Emerg Care.
1995; 11:1078.
15. Al-Harbi NN, Domrongkitchiporn S,
Lireman DS. Hypocalcemia and hypomagnesemia after ibuprofen overdose.
Ann Pharmacother. 1997; 31:4324.
REFLECTIONS
Trauma Room One
Her feet slightly dirty resting on
their heels, legs apart, and toes
pointed outward from the bottom of
the stretcher. Her young, naked
body only a slightly different hue
from the white sheet she lay upon.
Breasts never meant to be exposed
to the harsh lights of the trauma
room, exposed for anyone to see. Her
long, yellow hair blood-stained red.
A small hole with powder burns just
above the right ear, execution style.
A grief stricken respiratory therapist anxiously squeezed the bag.
Alarms sounded and console lights
blinked off their warnings. A man
in blue saidhomicidesuicide.
Someone whispered in my ear, I
have a 15-year-old daughter. So do
I, I remember answering. Two men
in scrubs casually discussed how the
police were having trouble identify-