ATYPICAL BACLOFEN TOXICITY PRESENTING FIRST WITH SEIZURE FOLLOWED BY COMA
Lookabill SK
1,2,3
| West KG
| Kerns WP
1
1,2
| Murphy CM
1,2
Carolinas Poison Center, Carolinas Medical Center, Charlotte, North Carolina | 2Carolinas Medical Center, Carolinas HealthCare System, Charlotte, North Carolina | 3University of North Carolina, Eshelman School of Pharmacy, Chapel Hill, North Carolina
1
BACKGROUND
CASE REPORT
• Significant baclofen toxicity often presents
with delirium followed by somnolence and
has been implicated in findings consistent
1
with brain death.
• 12-year-old, 76 kg female with a history of
pseudotumor cerebri, gastroesophageal
reflux disease, frequent migraine headaches,
and a history of optic neuritis was witnessed
to have vomiting and rapidly developed
seizure-like activity.
Baclofen, a GABAB agonist, is used in the treatment of muscle spasticity.
• Baclofen toxicity can present first with tonicclonic seizures followed by non-convulsive
status (NSE) epilepticus causing a persistent
coma-like state (Table 1).2,3
The following case report describes a baclofen
overdose in which the patient developed seizures prior to developing apparent central nervous system (CNS) depression.
Table 1
Clinical Findings in Baclofen Toxicity3
Neurologic
− impaired consciousness/
deep coma
− absent brain stem reflexes
− ataxia
− hypothermia
− seizures/nonconvulsive
status epilepticus
− disorders of the autonomic
nervous system
− psychiatric disorders
− sinus bradycardia/sinus
tachycardia/conduction
abnormalities
Cardiorespiratory
− arterial hypo- and hypertension
− respiratory depression
Gastrointestinal
Musculoskeletal
Ophthalmologic
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− nausea/vomiting/diarrhea
− muscle flaccidity
− rhabdomyolysis
− strong bilateral injections of
the conjunctivas, bilateral
lagophthalmos
− delayed reaction to light/
unreactive
− impaired vision/miosis/
mydriasis
CASE DISCUSSION
• Earlier in the day, she had reported suicidal
ideation through a text to a friend but
denied ingestion when confronted by an
adult.
• Medications the patient had access to include:
Patient’s Home
Medications
Medications Available
in the Home
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
gabapentin
magnesium
naratriptan
omeprazole
baclofen
clonazepam
fluoxetine
lacosamide
lamotrigine
levothyroxine
ondansetron
prochlorperazine
simvastatin
vitamin D
zonisamide
• The patient was treated with midazolam, fosphenytoin, and pyridoxine.
• She was extubated approximately 24 hours
after presentation and returned to her neurologic baseline on day 5.
• Workup for encephalitis and infectious etiologies was negative. Computed tomographic scan of the head demonstrated no
structural abnormalities.
• She was subsequently discharged on
zonisamide anticonvulsant therapy for a new
seizure disorder.
• Baclofen level drawn approximately 24 hours
after presentation was 160 ng/mL (reference:
100–400 ng/mL). Gabapentin, lacosamide,
lamotrigine, and zonisamide levels were undetectable. Six-panel immunoassay urine
drug screen was negative.
• The baclofen level returned after discharge.
After confirmation of baclofen ingestion, longterm seizure prophylaxis was discontinued.
Figure 1
• After intubation she experienced a generalized tonic-clonic seizure and was administered lorazepam 2 mg IV and levetiracetam
500 mg IV.
• Electroencephalogram (EEG) was “markedly
abnormal” and demonstrated continued seizure activity (Figure 1).
• Baclofen overdose can lead to a variety of clinical manifestations (Table 1).
3
• Symptoms commonly reported in cases of pediatric baclofen overdose include:
– Emesis
– Headache
– Unresponsiveness or coma
– Flaccidity
– Loss of deep tendon reflexes
• Seizures have been reported in baclofen toxicity including convulsive and
nonconvulsive seizures.
• In this case, vomiting and seizures were the first clinical signs of overdose.
• During treatment, it was difficult to discern if these seizures were organic
or toxin-induced as the patient’s mother insisted on an accurate baclofen
pill count.
• Her seizures proved difficult to treat and required benzodiazepines, multiple antiepileptic medications, and pyridoxine.
• Although the baclofen level appeared therapeutic, it was likely much
higher when she was having seizure activity.
– In therapeutic use, baclofen has a half-life of 3 to 6 hours.
– Baclofen demonstrates first-order elimination pharmacokinetics with a
potentially prolonged half-life after overdose; 8.6 hours in one report.6
– Her level was drawn greater than 24 hours after the time of ingestion.
• The baclofen laboratory result returned after patient discharge and the
antiepileptic medication was stopped.
• The patient remained unresponsive on arrival to the emergency department (ED) and
was intubated.
• Vital signs include:
– Blood pressure: 113/69 mmHg
– Heart rate: 67 bpm
– Respiratory rate: 14 breaths/min
– O2 saturation: 100%
– Temperature: 97°F
• Baclofen ingestions resulting in toxicity from drug abuse and suicide have
2–5
been reported in pediatric patients.
CONCLUSION
This case demonstrates seizure development prior to the onset of apparent CNS depression.
EEG DIAGNOSIS: Markedly abnormal, periodic EEG
with sharp discharges and occasional complex spike
discharges followed by relative or substantial electrodecrement every 2–3 seconds.
CLINICAL INTERPRETATION:
• The complex spikes followed by severe voltage attenuation is more suggestive of epileptic activity,
while other period sharp discharges are nonspecific.
• They may represent cortical dysfunction following
extensive seizure activity or they may represent a
burst-suppression pattern in the context of severe
cerebral dysfunction.
Prolonged coma-like state may be related to nonconvulsive status epilepticus.
EEG should be considered early in the hospital course to determine if
seizures are contributing to the patient’s altered mental status.
If seizures are present, treatment may require targeting of multiple
areas of the gamma-aminobutyric acid pathway.
REFERENCES
1.
Leung NY, Whyte IM, Isbister GK. Baclofen overdose: defining the spectrum of toxicity. Emerg Med Australas. 2006;18(1):77-82.
2.
Caron E, Morgan R, Wheless JW. An unusual cause of flaccid paralysis and coma: baclofen overdose. J Child Neurol. 2014;29(4):555-559.
3.
Weißhaar GF, Hoemberg M, Bender K, et al. Baclofen intoxication: a "fun drug" causing deep coma and nonconvulsive status epilepticus--a case report and review of the literature. Eur J Pediatr.
2012;171(10):1541-1547.
4.
Masi G, Mucci M, Liboni F, Ferrari A, Sicca F. Self-induced multiple comas with recreational baclofen overdoses in an adolescent girl. J Clin Psychopharmacol. 2013;33(6):830-832.
5.
Perry HE, Wright RO, Shannon MW, Woolf AD. Baclofen overdose: drug experimentation in a group of adolescents. Pediatrics. 1998;101(6):1045-1048.
6.
Gerkin R, Curry SC, Vance MV, Sankowski PW, Meinhart RD. First-order elimination kinetics following baclofen overdose. Ann Emerg Med. 1986;15(7):843-846.