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ACADEMIC EMERGENCY MEDICINE July 2000, Volume 7, Number 7

Serious Toxicity in a Young Child


Due to Ibuprofen
KER, MD, LUKE HERMANN, MD, CARL R. BAUM, MD,
ELIF E. O
KATHLEEN M. FENTZKE, MD, TODD SIGG, PHARMD,
JERROLD B. LEIKIN, MD

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

Ibuprofen is a commonly used overthe-counter nonsteroidal anti-inflammatory analgesic derived from


propionic acid. In general, overdoses
of ibuprofen result in mild effects.
These effects include abdominal
pain, nausea, vomiting, lethargy,
headache, tinnitus, and ataxia.1 Serious toxicity, including coma, apnea, metabolic acidosis, hypotension, bradycardia, and renal and
hepatic dysfunction, has been observed in ingestions of more than
400 mg/kg. Symptoms usually develop within four hours of ingestion.15 We describe a child who deFrom the Department of Emergency
Medicine, University of Illinois at Chicago (EEO); Department of Emergency
Medicine, Cook County Hospital (LH);
Department of Pediatrics, Northwestern
University Medical Center/Childrens
Memorial Hospital (KMF, CRB); Department of Internal Medicine, RushPresbyterian-St-Lukes
Medical
Center
(JBL); Toxikon Consortium (EEO, CRB,
JBL); and Illinois Poison Center (TS),
Chicago, Illinois.
Received November 11, 1999; revision received March 7, 2000; accepted March 8,
2000.
Address for correspondence and reprints:

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

veloped severe symptoms (seizure,


metabolic acidosis, apnea, and lethargy) after an ibuprofen ingestion of
up to 600 mg/kg. The symptoms resolved in approximately eight hours
with no long-term sequelae to date.

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.

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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

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IBUPROFEN

with an anion gap of 13. A computed


tomography (CT) scan of the brain
was normal. A second ibuprofen
level, drawn approximately 7.5
hours post-ingestion, returned at 39
g/mL. A follow-up CT scan of the
brain demonstrated a small area of
low attenuation adjacent to the left
basal ganglia. The patients mental status and acidosis improved
through the night, and extubation
was accomplished without difficulty
the following morning. The remainder of the patients hospitalization
was unremarkable and he was discharged two days later.

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

approximately 600 mg/kg and 560


mg/kg of ibuprofen, respectively.
Both children were lethargic and developed metabolic acidosis. Zuckerman and Uy13 described the case of
a 6-year-old who developed shock,
coma, and metabolic acidosis after
ingesting 6 g of ibuprofen.
In addition to metabolic acidosis,
acute renal insufficiency has been
reported in pediatric ibuprofen overdose. A 2-year-old developed a transient rise in serum creatinine that
peaked at 2.1 mg/dL after ingesting
640 mg/kg of ibuprofen.14 Al-Harbi et
al.15 described a 21-month-old who
developed metabolic acidosis, renal
failure, hypocalcemia, hypomagnesemia, and seizures after ingesting 8
g of ibuprofen.
The treatment of ibuprofen toxicity is largely supportive. There has
been some discussion in the literature regarding the utility of serum
ibuprofen levels and their correlation with clinical symptoms. Hall et
al.1 reported 88 pediatric ibuprofen
overdose patients. Seven percent
were symptomatic; two had severe
symptoms (seizures and apnea). Six
pediatric patients with isolated ibuprofen ingestions had detectable
ibuprofen levels. These ranged between 1 and 460 g/mL. Of these patients, only one was symptomatic.
This patient was described as lethargic and drowsy after an ingestion of 807 mg/kg, and a two-hour
ibuprofen level was 460 g/mL. The
authors found a statistically significant correlation with an ingestion
history of 440 mg/kg and the development of symptoms. Based on these
and additional data from adult overdoses, an ibuprofen nomogram was
proposed. McElwee et al.8 prospectively studied 329 cases of ibuprofen
overdose that included 135 pediatric
cases. The majority of patients in
this study were managed at home
without adverse outcome. The authors found no correlation between
symptoms and serum ibuprofen
level in 76 of 85 patients with reported levels. The utility of the ibuprofen nomogram has since been
called into question. Jenkinson et
al.9 compared 44 cases of ibuprofen
ingestions with known ingestion
times and plasma concentrations
with 17 matched cases from the literature. A model of symptomatic toxicity and ibuprofen plasma concen-

tration was developed but lacked


specificity and sensitivity. The authors could not confirm the clinical
utility of an ibuprofen nomogram.

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.

ACADEMIC EMERGENCY MEDICINE July 2000, Volume 7, Number 7

Hum Toxicol. 1988; 7:31924.


10. Lesko SM, Mitchell AA. An assessment of the safety of pediatric ibuprofen.
A practitioner-based randomized clinical
trial. JAMA. 1995; 273:92933.
11. Leikin JB, Paloucek FP. Poisoning
and Toxicology Compendium. Hudson,
OH: Lexi-Comp Inc., 1998, pp 3201.

12. Linden CH, Townsend PL. Clinical


and laboratory observations: metabolic
acidosis after acute ibuprofen overdosage. J Pediatr. 1987; 111:9225.
13. Zuckerman GB, Uy CC. Shock, metabolic acidosis and coma following ibuprofen overdose in a child. Ann Pharmacother. 1995; 29:86971.

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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-

ing the shooter, his face blown off


and cold on the sidewalk. Perfect
justice, they agreed.
A small crowd gathered as usual
outside the room, morbidly observing the drama. Eyes and conversation directed toward the naked body
of a 16-year-old with long blonde
hair. Others passed by quickly looking the other way, avoiding emotional involvement and blocking
bothersome images. In a few hours,
in the quiet of the night, phones
would ring in several homes
throughout the countryan early
Christmas for a select few. A heart
has been found, a kidney that
matches yours. A gift from the dead
to the dying.
With the drama over, the paperwork done, the room cleaned and no
trace left of the indescribable trag-

edy, I left the ED through the ambulance entrance. A short walk, a


short drive, then to bed for the
night. A group of high school students gathered just outside the ambulance bay. A tall, thin, slightly
built girl was weeping on the shoulders of a young man. Long blonde
hair to her waist, a halter top and
jeans. By all measures a beauty,
nearly the twin of the recent occupant of trauma room 1. If the dead
could speak, what would she say? So
physically mature, and yet so emotionally unprepared. Whatever happened to our children?
WALTER TED KUHN, MD
Department of Emergency Medicine
Medical College of Georgia
Augusta, Georgia

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