Further controlled, randomized, and probably multicenter trials are required to better delineate the therapeutic and prophylactic roles of l-carnitine and the optimal regimen of administration in the management of VPA toxicity.
Pyridoxine (vitamin B6) is a co-factor in many enzymatic pathways involved in amino acid metabolism: the main biologically active form is pyridoxal 5-phosphate. Pyridoxine has been used as an antidote in acute intoxications, including isoniazid overdose, Gyromitra mushroom or false morrel (monomethylhydrazine) poisoning and hydrazine exposure. It is also recommended as a co-factor to improve the conversion of glyoxylic acid into glycine in ethylene glycol poisoning. Other indications are recommended by some sources (for example crimidine poisoning, zipeprol and theophylline-induced seizures, adjunct to d-penicillamine chelation), without significant supporting data. The value of pyridoxine or its congener metadoxine as an agent for hastening ethanol metabolism or improving vigilance in acute alcohol intoxication is controversial. This paper reviews the various indications of pyridoxine in clinical toxicology and the supporting literature. The potential adverse effects of excessive pyridoxine dosage will also be summarized.
431 AED = antiepileptic drug; CNS = central nervous system; CoA = coenzyme A; CPS = carbamyl phosphate synthase; GABA = γ-aminobutyric acid; NAGA = N-acetyl glutamic acid; NMDA = N-methyl-D-aspartate; PCT = palmityl carnitine transferase; VHE = VPA-induced hyperammonaemic encephalopathy; VHT = VPA-induced hepatotoxicity; VPA = valproic acid.Available online http://ccforum.com/content/9/5/431 AbstractValproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well tolerated, but rare serious complications may occur in some patients receiving VPA chronically, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity (VHT) and VPA-induced hyperammonaemic encephalopathy (VHE). Some data suggest that VHT and VHE may be promoted by carnitine deficiency. Acute VPA intoxication also occurs as a consequence of intentional or accidental overdose and its incidence is increasing, because of use of VPA in psychiatric disorders. Although it usually results in mild central nervous system depression, serious toxicity and even fatal cases have been reported. Several studies or isolated clinical observations have suggested the potential value of oral L-carnitine in reversing carnitine deficiency or preventing its development as well as some adverse effects due to VPA. Carnitine supplementation during VPA therapy in high-risk patients is now recommended by some scientific committees and textbooks, especially paediatricians. Lcarnitine therapy could also be valuable in those patients who develop VHT or VHE. A few isolated observations also suggest that L-carnitine may be useful in patients with coma or in preventing hepatic dysfunction after acute VPA overdose. However, these issues deserve further investigation in controlled, randomized and probably multicentre trials to evaluate the clinical value and the appropriate dosage of L-carnitine in each of these conditions. IntroductionValproic acid (VPA) is a broad-spectrum antiepileptic drug (AED) that has been used for more than 30 years and is effective in the treatment of many different types of partial and generalized epileptic seizure. It is also prescribed to treat bipolar and schizoaffective disorders, social phobias and neuropathic pain, as well as for prophylaxis or treatment of migraine headache. VPA is a branched chain carboxylic acid (2-propylpentanoic acid or di-n-propylacetic acid), with a chemical structure very similar to that of short chain fatty acids (Fig. 1) [1].It is usually well tolerated. Indeed, VPA has fewer common side effects than do other AEDs, especially on behaviour and cognitive functions. Moreover, its adverse effects can often be minimized by initiating the drug slowly. However, rare serious complications may occur in some patients receiving VPA chronically, including fatal haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity (VHT) and VPA-induced hyperammonaemic encephalopathy (VHE). Some data suggest that VHT and VHE may be promoted either by a pre-existing carnitine deficiency or...
Background: The choice of tetanus prophylaxis for patients with wounds depends on obtaining their vaccination history, which has been demonstrated to be unreliable. Use of a rapid immunoassay (Tétanos Quick Stick, the TQS), combined with knowledge of certain demographic characteristics, may improve the evaluation of tetanus immunity and thus help to avoid inadequate prophylactic measures and reduce costs. Objectives: To evaluate the contribution of the TQS in the choice of tetanus prophylaxis and to perform a costeffectiveness analysis. The final aim was to define the place of the TQS in a modified algorithm for assessment of tetanus immunity in the emergency department. Method: In this Belgian prospective, double-blind, multicentre study, 611 adult patients with a wound were included; 498 (81.5%) records were valid. The TQS test was performed by a nurse before the vaccination history was taken and the choice of prophylaxis was made, using the official algorithm (Belgian Superior Health Council), by a doctor who was unaware of the TQS result. Results: The prevalence of protective anti-tetanus immunity was 74.1%. Immunity was lower in older patients and in female patients. The TQS was a cost-effective tool for patients presenting with a tetanus-prone wound and considered from the vaccination history to be unprotected. Use of the TQS would have improved management in 56.9% (95% CI 47.7% to 65.7%) of patients by avoiding unnecessary treatments, leading to a reduction in the mean cost per patient (J10.58/patient with the TQS versus J11.34/patient without). The benefits of the TQS use were significantly greater in patients ,61 years old: unnecessary treatment would have been avoided in 76.9% (95% CI 65.8% to 85.4%) of cases and the mean cost per patient reduced to J8.31. Conclusion: In selected patients, the TQS is a cost-effective tool to evaluate tetanus immunity. An algorithm is proposed for ED assessment of tetanus immunity integrating age and the TQS result.
Lack of protective immunity against tetanus is frequent but poorly evaluated by history taking. Several demographic characteristics are good predictors of seroprotection. TQS could be a valuable tool in selected patients to improve tetanus prophylaxis in the emergency department.
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