[Clinical characteristics, diagnosis, and treatment of acute intoxication by baclofen].

For last few years in Russia and in the Armed Forces of RF is marked a growth of number of acute intoxications by GABA-agonists and by muscle relaxants, particularly by baclofen. Manifestations of intoxication by this specimen include cerebral and somatic-vegetal disorders, in grave cases of illness could evolve psychic excitement, delusions and coma. Treatment of baclofen intoxication compares of gastric lavage using a thick pathfinder, accompanied by insertion of adsorbent and apocathartic means, maintaining of impaired vital functions of body. Hereafter these injured patients should be hospitalized in a treatment institute, where exists a possibility of effectuating of reanimation and intensive care as well as extracorporal detoxication (hemosorption, hemodialysis).

A novel cause of intrathecal baclofen overdosage: lessons to be learnt.

CASE PRESENTATION: A serious intrathecal baclofen overdose occurred in a 45-year-old woman with primary progressive multiple sclerosis following a catheter dye study with concomitant change in baclofen concentration. The pump and catheter were emptied of baclofen 2000 microg/mL, refilled and primed with baclofen 1000 microg/mL. No correction was made for the ;dead space' between the reservoir and catheter access port, which contained baclofen 2000 microg/mL. Failure of the priming bolus to account for the residual baclofen concentration within the dead space resulted in a serious overdose.Action: Amendments are being made to both our local and the Medtronic protocols. CONCLUSION: We hope that by reporting this incident the risk of this potentially fatal error re-occurring is minimized.

Prolonged unconsciousness in a patient on automated peritoneal dialysis.

A 79-year-old man with end-stage renal disease treated by automated peritoneal dialysis was referred to the emergency department for altered consciousness. The first investigations, including toxicology screening, failed to reveal the precise etiology. The patient was treated for a possible seizure. After the progression of central nervous system depression with bradypnea, the patient was intubated and mechanically ventilated. It appeared later on that he had ingested by mistake one of his wife's medications, baclofen. Baclofen was detected in the blood sampled on admission at a level above the therapeutic range. Baclofen is mainly excreted by the kidney. A short-term administration of low-dose of baclofen is not effectively removed by peritoneal dialysis and may result in prolonged but reversible coma.

[EEG contribution to the diagnosis of baclofen overdose]. / Apport de l' EEG dans le diagnostic d'une intoxication au baclofène.

In a young woman presenting with severe coma, the EEG helped diagnosing baclofen overdose. In this patient, the first EEG showed continuous multifocal pseudoperiodic sharp waves. The diagnosis was confirmed by the plasma dosage providing an 8-fold increase above normal baclofen therapeutic range. Following symptomatic therapy, the patient improved within a few days and the EEG normalised. Few other drugs may be responsible for such EEG changes, namely lithium, cephalosporin, and bismuth. In such cases, EEG contribution to the diagnosis should not be ignored.

Local distribution and toxicity of prolonged hippocampal infusion of muscimol.

OBJECT: The activity of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, is reduced in the hippocampus in patients with complex partial seizures from mesial temporal sclerosis. To provide preliminary safety and distribution data on using convection-enhanced delivery of agents to treat complex partial seizures and to test the efficacy and safety of regional selective neuronal suppression, the authors infused muscimol, a GABA-A receptor agonist, directly into the hippocampus of nonhuman primates using an integrated catheter electrode. METHODS: Ten rhesus monkeys were divided into three groups: 1) use of catheter electrode alone (four monkeys); 2) infusion of escalating concentrations of muscimol followed by vehicle (three monkeys); and 3) infusion of vehicle and subsequent muscimol mixed with muscimol tracer (three monkeys). Infusions were begun 5 days after catheter electrode placement and continued for 5.6 days before switching to the other agent. Head magnetic resonance (MR) images and electroencephalography recordings were obtained before and during the infusions. Brain histological studies and quantitative autoradiography were performed. Neurological function was normal in controls and when muscimol concentrations were 0.125 mM or less, whereas higher concentrations (0.5 and 1 mM) produced reversible apathy and somnolence. Fluid distribution was demonstrated on MR images and muscimol distribution was demonstrated on autoradiographs throughout the hippocampus and adjacent white matter. CONCLUSIONS: Targeted modulation of neuronal activity is a reasonable research strategy for the investigation and treatment of medically intractable epilepsy.

Selected clinical aspects of acute intoxication with baclofen.

Baclofen is a lipophilic analogue of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in central nervous system. The aim of the study was to evaluate some clinical aspects of acute intoxication with baclofen. Fifty two patients (37 females and 15 males) aged from 14 to 58 (mean 30.6 +/- 13.7) years were analyzed. Patients were admitted to the Clinic of Internal Diseases and Acute Poisonings Medical University of Gdansk and the Centre of Acute Poisonings of Praski Hospital in Warszawa during the years 1996-2004 because of suicidal intoxication with baclofen. The doses of baclofen varied from 100 to 1500 (mean 444.8 +/- 317.8) mg. There were twenty eight patients (53.8%) in deep coma (III and IV grade of Matthew scale). Acute respiratory failure which required mechanical ventilation was observed in 18 cases (34.6%). Cardiac abnormalities included bradycardia (36.5%), hypertension (32.7%) and hypotension (3.8%). Toxic psychoses were observed in 6 cases (11.5%). The dosage of baclofen in patients with acute respiratory failure (ARF) was significantly higher than in patients without ARF. Treatment of patients with acute baclofen intoxication should take place in hospitals appropriately equipped which can provide artificial respiration.

[Acute intoxication with baclofen]. / Ostre zatrucia baklofenem.

UNLABELLED: Many authors have noticed an increase in suicidal intoxication with baclofen, a lipophilic analog of gamma-aminobutyric acid (GABA). Although morbidity and mortality is low in baclofen overdosage however may cause serious respiratory failure as also cardiac and neurological system disturbances. The aim of the study was to evaluate some clinical aspects of acute intoxication with baclofen. We analyzed 18 patients (8 females and 10 males) aged from 15 to 58 (mean 33+/-15.4) years. Patients were admitted to the Department of Toxicology in the years 1996-2003 because of suicidal intoxication with baclofen. Number of patients intoxicated with baclofen during the last four years of analysis was two times more than in the first four years. The doses of baclofen were from 150 to 1500 (mean 388) mg. There were twelve patients (66%) admitted to the Clinic in deep coma (III and IV grade of Matthew scale) with the hyporeflexia and low muscle tone. Acute respiratory failure which required mechanical ventilation (6 to 96--mean 53.2 hours) was observed in 10 cases (55.5%). Cardiac abnormalities included bradycardia (44.4%), hypertension (33.0%) and hypotension (5.5%). Toxic psychoses were observed in 6 cases (33.3%). Flumazenil administration had no impact on clinical advancement of coma. An increase in creatine kinase activity was observed in 12 patients (66.6%). CONCLUSIONS: There was no correlation between the dosage of baclofen and the clinical outcome. Baclofen poisoned patients should be admitted to hospitals with adequate medical equipment, especially respirators.

Baclofen overdose: drug experimentation in a group of adolescents.

BACKGROUND: Baclofen, a lipophilic analog of gamma-aminobutyric acid, is clinically used to control spasticity. We report a mass exposure to baclofen in adolescents seeking intoxication; toxicokinetic data are included. CASE SERIES: A group of adolescents became symptomatic after ingesting 3 to 30 20-mg tablets of baclofen during a party at a suburban Boys' Club. Several children were noted to be very lethargic by chaperones, ingestion was suspected, and paramedics were called. Some white tablets were found in a couch at the site of the party. The Massachusetts Poison Control Center was called, and the tablets were identified as baclofen (20 mg). Fourteen patients were taken to local hospitals; 9 required intubation. Eight adolescents were transferred to our institution. In these 8 patients, symptoms were noted within 1 to 2 hours after overdose. The most common clinical findings included coma (7), hypothermia (6), bradycardia (5), hypertension (4), and hyporeflexia (8). Mean length of mechanical ventilation was 40 hours. Three patients had unifocal premature ventricular contractions. Two patients had tonic-clonic seizures. A single dose of activated charcoal was given to all patients. Drugs administered included nifedipine (1), flumazenil (1), naloxone (1), lorazepam (2), and phosphenytion (2). All patients recovered and were discharged home within 5 days of ingestion. Serial serum baclofen levels were obtained in all intubated patients (range, 0.049 to 6.0; normal, 0.08 to .40 microgram/mL). Levels obtained 14 hours after ingestion showed a linear correlation with length of mechanical ventilation (R2 = 0.9863). Persistent symptoms were noted in some patients, despite nondetectable baclofen levels. Toxicologic screening for drugs of abuse was negative except in 2 patients with ethanol levels, both < 5 mg/dL. CONCLUSION: Baclofen overdose may result in coma, apnea, autonomic disturbances, cardiac conduction abnormalities, and seizures. Levels obtained shortly after overdose correlate with length of mechanical ventilation.