High-efficiency dialysis for carbamazepine overdose

BACKGROUND: Carbamazepine intoxication is associated with seizures, coma, arrhythmias, and death. In acute intoxications, charcoal hemoperfusion enhances removal of the drug but is associated with thrombocytopenia, coagulopathy, hypothermia, and hypocalcemia. Alternatively, high-efficiency hemodialysis can be used without the side effects of charcoal hemoperfusion. CASE REPORT: We report an 18-month-old comatose, convulsing child with plasma carbamazepine 27 microg/mL treated with high efficiency hemodialysis. Therapeutic carbamazepine levels were obtained after 4.5 hours of high-efficiency hemodialysis. The patient developed no untoward side effects, improved clinically, and was subsequently discharged home without sequelae. We conclude that high-efficiency hemodialysis is a safe, effective alternative to charcoal hemoperfusion in the pediatric population.     

Status epilepticus after massive carbamazepine overdose

We report two patients who experienced status epilepticus after carbamazepine overdose. The first patient was an 18-year-old female with a history of epilepsy. She experienced 4 hour of persistent and prolonged seizures resistant to sodium amytal therapy. The status epilepticus ended with her death. The second patient was an 18-year-old male with a history of bipolar disorder. He experienced 5 hour of persistent and prolonged seizures that appeared to be resistant to diazepam, phenytoin, and phenobarbital. The seizures abated with the infusion of midazolam. This is a report of status epilepticus associated with wide complex tachycardia after carbamazepine overdose, which may be resistant to conventional therapy.     

Hypoglycemia - A rare complication of carbamazepine overdose

Carbamazepine overdose usually presents with neurological manifestations such as ataxia, seizures and altered sensorium or cardiac manifestations that include tachycardia, hypotension and ventricular extra-systoles. We report a patient with carbamazepine overdose who manifested recurrent hypoglycemia on the third and fourth day following ingestion that resolved with supportive therapy.KEY WORDS: Anti-epileptic, carbamazepine, complication, hypoglycemia, overdose     

Plasma levels of leptin and endogenous immune modulators during treatment with carbamazepine or lithium

Several psychopharmacological agents induce weight gain. Recent studies have suggested that the tumor necrosis factor- (TNF-) cytokine system is pathophysiologically involved. To assess whether carbamazepine and lithium, which have been reported to lead to weight gain, have effects on the circulating levels of cytokines, we measured plasma levels of TNF-, its soluble receptors sTNF-R p55 and p75, and leptin, as well as weight in 25 inpatients receiving lithium (n=10) or carbamazepine (n=15) weekly during the first 4 weeks of treatment. We found an increase in the body mass index and in TNF- and its soluble receptor levels, but not in leptin levels over the 4 weeks of treatment. These changes did not differ between treatment groups. Changes of weight during the first week of treatment, but no other parameter, strongly predicted weight change until endpoint. We conclude that the mood stabilizers carbamazepine and lithium have similar effects on the TNF- system and do not affect leptin levels.This revised version was published online in December 2004. An inadvertently included footnote to Table 1 was deleted.     

A fatal overdose of carbamazepine: case report and review of literature

Carbamazepine is a drug of choice for partial epilepsies, certain affective disorders and neuralgic pain syndromes. It has an excellent safety record; however, overdose can be dangerous. This article reports one of the very few fatalities from carbamazepine overdosage, in an individual with a peak carbamazepine level of 54 mg/L. Manifestations of this and other major carbamazepine overdoses reviewed from the literature were similar to those of tricyclic - anticholinergic overdose, with coma, hypotension, respiratory depression, cardiac arrhythmias, abnormal movements and seizures. Fatality from cardiovascular causes occurred despite decline of serum carbamazepine levels to the putatively non-toxic range, emphasizing the potential for delayed consequences of carbamazepine overdosage. Management should consist of vigorous gastric lavage and installation of activated charcoal, full supportive care in a monitored setting and consideration of early charcoal hemoperfusion, before the patient becomes hypotensive.     

Dissimilar effects of lithium and carbamazepine on erythrocyte lithium transport in vivo: clinical implications

The effect of lithium (Li) and carbamazepine (CBZ) on erythrocyte lithium transport in vivo was investigated in 28 patients with affective or schizoaffective illness (14 given Li and 14 given CBZ). In 12 of them, Li or CBZ were added to current psychotropic treatment. The activities of erythrocyte lithium-sodium countertransport (LSC), lithium-potassium cotransport (LPC) and passive lithium diffusion (PLD) were assayed before and after 28 days of treatment. The administration of Li caused a significant decrease of LPC as well as PLD activity. The administration of CBZ resulted in a significant increase of the activity of LPC system. No systematic relationship was observed between Li or CBZ-induced alterations in erythrocyte transport and changes in clinical state of patients. The possible clinical implications of the dissimilar effect of Li and CBZ on erythrocyte lithium transport are discussed.     

Influence of lithium on the anticonvulsant activity of carbamazepine

The present study was undertaken to see whether the recently reported synergism between lithium and carbamazepine (CBZ) in mania also extends against convulsions. The anti-convulsant effect of various doses of CBZ was assessed in albino rats pretreated with vehicle or lithium salt (0.54 mEg/kg/day, p.o. for 9 days). The animals were subjected to 3 tests: maximum electro shock seizures (MES); minimum electro convulsive thresholds (MET) and pentylenetetrazol (PTZ)-induced convulsions: abolition of hind limb extension after electro shock, increases in the MET for appearance of neck jerk and absence of convulsions for one hr after PTZ were taken as parameters of the anticonvulsive effect respectively. In the MES and MET tests lithum did not alter the anticonvulsive effect of CBZ. Lithium, however, potentiated the anticonvulsant effect of CBZ against PTZ-induced convulsions.     

The lithium concentration of the blood plasma in combined therapy with lithium carbonate and carbamazepine]

In view of the fact that therapy of affective psychoses with the combination of lithium carbonate with carbamazepine has been becoming ever common, the question arises about the influence of carbamazepine on plasma lithium concentration. On the material of 125 blood samples by using the method of dispersion analysis it was shown that carbamazepine exerts no effect on this parameter. Therefore when carbamazepine is added to lithium therapy it is not advisable to decrease lithium dose as it can result in a reduction of the therapeutic effect.     

Intravenous carbamazepine for the treatment of epilepsy

Introduction: Recently, an intravenous formulation of carbamazepine (CBZ) (sulphobutylether-7-beta-cyclodextrine carbamazepine, SBECD CBZ) has been developed and approved by the U.S. Food and Drug Administration. It is indicated as a short-term replacement therapy for oral CBZ formulations, when oral administration is temporarily not feasible and in adults with focal seizures with complex symptomatology as well as generalized tonic-clonic seizures and mixed seizure patterns.

Areas covered: This review focuses on the drug development, pharmacokinetics and pharmacodynamics of intravenous CBZ and provides a comprehensive overview of the studies assessing its clinical efficacy, tolerability and safety in adults with epilepsy.

Expert opinion: Intravenous CBZ has favorable pharmacokinetics and is well tolerated and safe when used as a short-term substitution for oral CBZ. Seizure control was unchanged after switching from oral to IV formulations. Overall, this new formulation represents a useful option to enhance continuity of care in adults with focal or generalized tonic-clonic seizures when oral CBZ administration is temporarily unfeasible. Further studies are needed to assess the efficacy and tolerability of IV CBZ used at larger doses (above 1600 mg/day), for a period longer than 7 days or for other indications not approved by FDA, such as prolonged convulsive seizures and status epilepticus.     

The effect of the introduction of safety packaging for carbamazepine on toxicity in overdose in adults

Background — Safety packaging has been shown to be effective in preventing childhood poisoning; however similar data for adults is lacking. In February 1993 the Australian packaging for carbamazepine was changed from bottles of tablets to blister packs. Objective — To assess whether there has been a change in the amount of carbamazepine taken per overdose or the severity of poisoning coinciding with this change. Design — Comparison of cohorts of patients presenting before and after repackaging. Setting — Newcastle, Australia. Subjects — Sixty-seven patients who ingested carbamazepine and presented to a general hospital which serves a well-defined geographic area. Main outcome measures — Number of tablets and total dose ingested, peak carbamazepine level, degree of sedation, need for intubation and the time in hospital and ventilated. Results — Significantly fewer tablets and a lesser amount was ingested by patients presenting after the repackaging. Though clinical measures were improved slightly after repackaging the differences did not reach statistical significance. Conclusions — Repackaging resulted in less carbamazepine reported to have been ingested in overdose. Clinical measures did not reflect the extent of this change. This may be due to effects of treatment or coingested drugs obscuring any difference or the reported differences may be due to a reporting bias associated with packaging. Repackaging is a promising means of reducing the severity of deliberate self poisoning but further study, including out of hospital mortality data, is required.     

Clinical pharmacokinetics of carbamazepine and its epoxy and hydroxy metabolites in humans after an overdose

In five cases of carbamazepine (CBZ) intoxication, the time curves of the plasma concentration and of the renal excretion rate of carbamazepine and its metabolites carbamazepine 10,11-epoxide (CBZ-epoxide) and trans-10,11-dihydro-10,11-dihydroxy-CBZ (CBZ-diol) were measured. Pseudo-steady-state or plateau-like plasma concentration-time curves were observed when doses of 12 or 18 g of CBZ were ingested. Hemoperfusion lowers the plasma concentration of CBZ and its metabolites by affecting the half-life. The effect of hemoperfusion is reduced by the continuous absorption from the gastrointestinal tract and redistribution from the tissues. The renal clearances of CBZ and of CBZ-epoxide are low (1 and 8 ml/min, respectively); both are flow dependent. The renal clearance of CBZ-diol is approximately 160-350 ml/min and is independent of the urine flow. Although urine stimulation increases the renal clearance of CBZ by 100%, the overall amount excreted increases only 1-2% of the dose. Protein binding of CBZ is approximately 80%, of CBZ-epoxide 50%, and of CBZ-diol 70%.     

Therapeutic concentrations of lithium and carbamazepine inhibit cGMP accumulation in human lymphocytes

Although a large variety of biochemical effects have been reported for lithium (Li) and carbamazepine (Cbm), the final molecular mechanism underlying their therapeutic efficacy for recurrent affective disorders is still unknown. The data presented here clearly indicate that therapeutic concentrations of both drugs inhibit sodium nitroprusside-induced accumulation of cGMP in human lymphocytes to about the same extent. The effect is not seen for other antidepressants, and shows pronounced interindividual variations in healthy volunteers. A similar effect of lithium and carbamazepine can also be demonstrated for the cGMP accumulation of central neurons using the model of dissociated cells of the mouse brain. The results are discussed in view of a common mechanism of action of both drugs. Furthermore, it is speculated that the individual sensitivity of the cGMP generating system of human lymphocytes to both drugs might be used to predict therapeutic response or nonresponse of the individual patient.     

Intravenous acetylcysteine for the treatment of acetaminophen overdose

Importance of the field: Acetaminophen is a leading cause of overdose-related hepatotoxicity. Although acetylcysteine prevents or minimizes acetaminophen-induced hepatotoxicity and reduces mortality, some patients presenting with complicated overdose scenarios (massive ingestions or combination or modified-release formulations) may develop toxicity despite administration of recommended dosage regimen.

Areas covered in this review: The article evaluates evidence regarding intravenous acetylcysteine's effectiveness in patients with acute overdoses who receive treatment within 10 h or > 10 h, patients with chronic supratherapeutic ingestions, and those with acetaminophen-induced fulminant hepatic failure. Intravenous and oral acetylcysteine are compared.

What the reader will gain: A one-size-fits-all approach towards acetylcysteine therapy provides suboptimal care in some patients. High-risk patients are identified. Specific discontinuation criteria are presented.

Take home message: The standard intravenous regimen will effectively treat most early-presenting uncomplicated overdoses. Acetylcysteine dosing should be individualized in patients with complicated presentations and in particular situations in which plasma acetaminophen concentrations may be persistently elevated at the end of the infusion or in late presenters. More studies are needed to evaluate the optimal intravenous dosage regimen and the role of oral acetylcysteine in these high-risk patients. Treatment decisions may be aided by consultation with a poison center and/or clinical toxicologist.     

Detoxication methods for bromureide poisoning

The efficiency of different detoxication methods for Carbromal intoxications was evaluated on bastard dogs using haemofiltration, haemodialysis and haemoperfusion with coated charcoal and polystyrene resins. Clearance rates and eliminated amounts of Carbromal and bromine were compared.Haemoperfusion is most effective in the elimination of Carbromal and haemodialysis for removal of bromide ions. Haemofiltration was least effective for both and should therefore not be used for the treatment of Carbromal intoxications.Presented in part on the 8. Gemeinsame Tagung der Deutschen und Österreichischen Gesellschaft für Internistische Intensivmedizin, München, Nov. 1976 und 9. Gemeinsame Tagung der Deutschen und Österreichischen Gesellschaft für Internistische Intensivmedizin, Linz, Sept. 1977