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...

Hyperinsulinaemia/euglycaemia therapy (HIET) consists of the infusion of high-dose regular insulin (usually 0.5 to 1 IU/kg per hour) combined with glucose to maintain euglycaemia. HIET has been proposed as an adjunctive approach in the management of overdose of calcium-channel blockers (CCBs). Indeed, experimental data and clinical experience, although limited, suggest that it could be superior to conventional pharmacological treatments including calcium salts, adrenaline (epinephrine) or glucagon. This paper reviews the pathophysiological principles underlying HIET. Insulin administration seems to allow the switch of the cell metabolism from fatty acids to carbohydrates that is required in stress conditions, especially in the myocardium and vascular smooth muscle, resulting in an improvement in cardiac contractility and restored peripheral resistances. Studies in experimental verapamil poisoning in dogs have shown that HIET significantly improves metabolism, haemodynamics and survival in comparison with conventional therapies. Clinical experience currently consists only of a few isolated cases or short series in which the administration of HIET substantially improved cardiovascular conditions in life-threatening CCB poisonings, allowing the progressive discontinuation of vasoactive agents. While we await further well-designed clinical trials, some rational recommendations are made about the use of HIET in severe CBB overdose. Although the mechanism of action is less well understood in this condition, some experimental data suggesting a potential benefit of HIET in β-adrenergic blocker toxicity are discussed; clinical data are currently lacking. IntroductionHyperinsulinaemia/euglycaemia therapy (HIET) consists of the infusion of high-dose regular insulin (most commonly 0.5 to 1 IU/kg per hour). Of course, frequent blood glucose monitoring by bedside capillary testing is needed to minimise the likelihood of hypoglycaemia. Glucose infusion is adapted to maintain euglycaemia (6 to 8 mmol/l, or 110 to 150 mg/dl). Adults may require 15 to 30 g of glucose per hour (as glucose 10% or more), associated with potassium supplements to maintain normokalaemia.Pathophysiological bases, as well as experimental data and clinical observations, suggest that HIET might be useful in cases of severe overdose of calcium-channel blockers (CBBs). Conventional measures that consist of intravenous fluids, calcium salts, dopamine, dobutamine, noradrenaline (norepinephrine), phosphodiesterase inhibitors or glucagon often fail to improve the haemodynamic condition of the patient, so that more invasive procedures such as intra-aortic balloon counterpulsation or extracorporeal circulatory support may be needed [1][2][3]. Until now, HIET has mainly been used as a rescue therapy and as an alternative to invasive procedures. However, HIET seems to ensure a more favourable energetic balance in the myocardium than other conventional treatment. It has few side effects provided that glycaemia is frequently checked, and it uses only widely av...

External fixation of supracondylar fractures in children is a simple and versatile method that combines the advantages of traction and surgical fixation.

The major potential adverse effect of use of sulfonylurea agents (SUAs) is a hyperinsulinaemic state that causes hypoglycaemia. It may be observed during chronic therapeutic dosing, even with very low doses of a SUA, and especially in older patients. It may also result from accidental or intentional poisoning in both diabetic and nondiabetic patients. The traditional approach to SUA-induced hypoglycaemia includes administration of glucose, and glucagon or diazoxide in those who remain hypoglycaemic despite repeated or continuous glucose supplementation. However, these antidotal approaches are associated with several shortcomings, including further exacerbation of insulin release by glucose and glucagon, leading only to a temporary beneficial effect and later relapse into hypoglycaemia, as well as the adverse effects of both glucagon and diazoxide. Octreotide inhibits the secretion of several neuropeptides, including insulin, and has successfully been used to control life-threatening hypoglycaemia caused by insulinoma or persistent hyperinsulinaemic hypoglycaemia of infancy. Therefore, this agent should in theory also be useful to decrease glucose requirements and the number of hypoglycaemic episodes in patients with SUA-induced hypoglycaemia. This has apparently been confirmed by experimental data, one retrospective study based on chart review, and several anecdotal case reports. There is thus a need for further prospective studies, which should be adequately powered, randomized and controlled, to confirm the probable beneficial effect of octreotide in this setting. IntroductionAlthough the number of oral medications available to treat diabetes mellitus has increased, sulfonylurea agents (SUAs) remain a mainstay of therapy for hyperglycaemia in type 2 diabetes. The major potential adverse effect of use of SUA is a hyperinsulinaemic state that causes hypoglycaemia. It may be observed during chronic therapeutic dosing, even with very low doses of a SUA, and especially in older patients. It may also result from accidental or intentional poisoning in both diabetic and nondiabetic patients [1].The traditional approach to SUA-induced hypoglycaemia includes the administration of glucose, and glucagon or diazoxide in those who remain hypoglycaemic despite repeated or continuous glucose supplementation [2,3]. However, these antidotal approaches are associated with several shortcomings, including further exacerbation of insulin release by glucose and glucagon, leading only to a temporary beneficial effect and later relapse into hypoglycaemia [3], as well as the adverse effects of both glucagon and diazoxide [2,4]. Other measures that have been proposed include corticosteroids and urinary alkalinization to enhance urinary elimination of the SUA (e.g. chlorpropamide) [5], but their usefulness has not clearly been established.Octreotide inhibits the secretion of several neuropeptides, including insulin, and has been successfully used to control life-threatening hypoglycaemia caused by insulinoma [6,7] or persistent h...