Common pitfalls in the use of hypertonic sodium bicarbonate for cardiac toxic drug poisonings.

BACKGROUND: Hypertonic sodium bicarbonate is advocated for the treatment of sodium channel blocker poisoning, but its efficacy varies amongst different sodium channel blockers. This Commentary addresses common pitfalls and appropriate usage of hypertonic sodium bicarbonate therapy in cardiotoxic drug poisonings. SODIUM BICARBONATE WORKS SYNERGISTICALLY WITH HYPERVENTILATION: Serum alkalinization is best achieved by the synergistic effect of hypertonic sodium bicarbonate and hyperventilation (PCO2 ∼ 30-35 mmHg [0.47-0.6 kPa]). This reduces the dose of sodium bicarbonate required to achieve serum alkalinization (pH ∼ 7.45-7.55) and avoids adverse effects from excessive doses of hypertonic sodium bicarbonate. VARIABILITY IN RESPONSE TO SODIUM BICARBONATE TREATMENT: Tricyclic antidepressant poisoning responds well to sodium bicarbonate therapy, but many other sodium channel blockers may not. For instance, drugs that block the intercellular gap junctions, such as bupropion, do not respond well to alkalinization. For sodium channel blocker poisonings in which the expected response is unknown, a bolus of 1-2 mmol/kg sodium bicarbonate can be used to assess the response to alkalinization. SODIUM BICARBONATE CAN EXACERBATE TOXICITY FROM DRUGS ACTING ON MULTIPLE CARDIAC CHANNELS: Hypertonic sodium bicarbonate can cause electrolyte abnormalities such as hypokalaemia and hypocalcaemia, leading to QT interval prolongation and torsade de pointes in poisonings with drugs that have mixed sodium and potassium cardiac channel properties, such as hydroxychloroquine and flecainide. THE GOAL FOR HYPERTONIC SODIUM BICARBONATE IS TO ACHIEVE THE ALKALINIZATION TARGET (∼PH 7.5), NOT COMPLETE CORRECTION OF QRS COMPLEX PROLONGATION: Excessive doses of hypertonic sodium bicarbonate commonly occur if it is administered until the QRS complex duration is < 100 ms. A prolonged QRS complex duration is not specific for sodium channel blocker toxicity. Some sodium channel blockers do not respond, and even when there is a response, it takes a few hours for the QRS complex duration to return completely to normal. In addition, QRS complex prolongation can be due to a rate-dependent bundle branch block. So, no further doses should be given after achieving serum alkalinization (pH ∼ 7.45-7.55). MAXIMAL DOSING FOR HYPERTONIC SODIUM BICARBONATE: A further strategy to avoid overdosing patients with hypertonic sodium bicarbonate is to set maximum doses. Exceeding 6 mmol/kg is likely to cause hypernatremia, fluid overload, metabolic alkalosis, and cerebral oedema in many patients and potentially be lethal. RECOMMENDATION FOR THE USE OF HYPERTONIC SODIUM BICARBONATE IN SODIUM CHANNEL BLOCKER POISONING: We propose that hypertonic sodium bicarbonate therapy be used in patients with sodium channel blocker poisoning who have clinically significant toxicities such as seizures, shock (systolic blood pressure < 90 mmHg, mean arterial pressure <65 mmHg) or ventricular dysrhythmia. We recommend initial bolus dosing of hypertonic sodium bicarbonate of 1-2 mmol/kg, which can be repeated if the patient remains unstable, up to a maximum dose of 6 mmol/kg. This is recommended to be administered in conjunction with mechanical ventilation and hyperventilation to achieve serum alkalinization (PCO2∼30-35 mmHg [4-4.7 kPa]) and a pH of ∼7.45-7.55. With repeated bolus doses of hypertonic sodium bicarbonate, it is imperative to monitor and correct potassium and sodium abnormalities and observe changes in serum pH and on the electrocardiogram. CONCLUSIONS: Hypertonic sodium bicarbonate is an effective antidote for certain sodium channel blocker poisonings, such as tricyclic antidepressants, and when used in appropriate dosing, it works synergistically with hyperventilation to achieve serum alkalinization and to reduce sodium channel blockade. However, there are many pitfalls that can lead to excessive sodium bicarbonate therapy and severe adverse effects.

Failure of Intracardiac Pacing After Fatal Propafenone Overdose: A Case Report.

BACKGROUND: Propafenone is a sodium-channel blocker, class IC antiarrhythmic drug, frequently used to manage supraventricular dysrhythmias, especially atrial fibrillation. We report a self mono-intoxication with propafenone. CASE REPORT: A 68-year-old woman presented with a decreased level of consciousness, hypotension, and electrocardiogram showing QRS widening with atrial asystole and extreme bradycardia < 20 beats/min. After initial stabilization with transcutaneous pacing, laboratory findings detected normal electrolyte ranges and metabolic acidosis, and her medical history revealed availability of propafenone due to paroxysmal atrial fibrillation and depressive syndrome, which led to the suspicion of intoxication. Despite intravenous sodium bicarbonate, calcium, norepinephrine, and aggressive fluid replacement (10% glucose with insulin), hemodynamic stability was not achieved. Temporary intracardiac pacing was implanted. However, even with multiple electrode positions, effective capture could not be achieved. At that time, transcutaneous pacing was also ineffective. Consequently, the patient died in refractory asystole due to complete myocardial nonexcitability. The concentration of 5270 ng/mL of propafenone was found in the blood at autopsy, using gas spectrometry-mass chromatography. It is the third highest reported propafenone lethal concentration and the first case in which the myocardial nonexcitability refractory to intracardiac pacing was seen despite normal electrode position in the right ventricle, with failure to achieve the patient's hemodynamic stability. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should be aware of possible propafenone ingestion causing toxicity, which is probably more frequent than previously described, especially because propafenone is widely available due to its use in managing atrial fibrillation, the most common arrhythmia nowadays.

A Literature Review of the Use of Sodium Bicarbonate for the Treatment of QRS Widening.

Sodium bicarbonate is a well-known antidote for tricyclic antidepressant (TCA) poisoning. It has been used for over half a century to treat toxin-induced sodium channel blockade as evidenced by QRS widening on the electrocardiogram (ECG). The purpose of this review is to describe the literature regarding electrophysiological mechanisms and clinical use of this antidote after poisoning by tricyclic antidepressants and other agents. This article will also address the literature supporting an increased serum sodium concentration, alkalemia, or the combination of both as the responsible mechanism(s) for sodium bicarbonate's antidotal properties. While sodium bicarbonate has been used as a treatment for cardiac sodium channel blockade for multiple other agents including citalopram, cocaine, flecainide, diphenhydramine, propoxyphene, and lamotrigine, it has uncertain efficacy with bupropion, propranolol, and taxine-containing plants.

Cardiac sodium channel blockade after an intentional ingestion of lacosamide, cyclobenzaprine, and levetiracetam: Case report.

CONTEXT: Lacosamide treats partial seizures by enhancing slow inactivation of voltage-gated sodium channels. The described cardiac toxicity of lacosamide in the literature to date includes atrioventricular blockade (PR prolongation), atrial flutter, atrial fibrillation, sinus pauses, ventricular tachycardia and a single cardiac arrest. We report a second case of cardiac arrest following an intentional lacosamide overdose. CASE DETAILS: A 16 year-old female with a seizure disorder was found unresponsive in pulseless ventricular tachycardia after intentionally ingesting 4.5 g (76 mg/kg) lacosamide, 120 mg (2 mg/kg) cyclobenzaprine and an unknown amount of levetiracetam. Exact time of ingestion was unknown. Her initial electrocardiogram (ECG) demonstrated sinus tachycardia at 139 beats per minute, QRS duration 112 ms, and terminal R-wave in lead aVR > 3 mm. Despite treatment with 150 mEq of sodium bicarbonate, she had persistent EKG findings eight hours after presentation. Her serum lacosamide concentration nine hours after presentation was elevated at 22.8 µg/mL, while serum cyclobenzaprine concentration was 16 ng/mL (therapeutic: 10-30 ng/mL), and serum levetiracetam concentration was 22.7 µg/mL (therapeutic: 12-46 µg/mL). On hospital day three, ECG demonstrated resolution of the terminal R-wave with QRS of 78 ms. The patient recovered without physical or neurologic sequelae. DISCUSSION: The patient's lacosamide, cyclobenzaprine and levetiracetam overdose was associated with QRS prolongation and terminal right axis deviation--suggesting sodium channel blockade as a likely etiology for her cardiac arrest. Cyclobenzaprine has potential for sodium channel blockade and ventricular dysrhythmias although cardiac toxicity due to cyclobenzaprine alone is rare. The combination of cyclobenzaprine with lacosamide may have resulted in cardiovascular collapse. In conclusion, overdose of lacosamide combined with therapeutic concentrations of sodium channel blocking xenobiotics may cause cardiac conduction delays and cardiac arrest.

Wide complex tachycardia in a pediatric diphenhydramine overdose treated with sodium bicarbonate.

INTRODUCTION: Diphenhydramine is an antihistamine commonly implicated in overdose. It has many pharmacologic effects, including sodium channel blockade. Overdoses in toddlers causing QRS prolongation are only rarely reported and never with effective use of sodium bicarbonate. We report a diphenhydramine overdose in a toddler with multiple markers of sodium channel blockade effectively treated with sodium bicarbonate. METHODS: A 13-month-old infant girl was brought in by the emergency medical service for a witnessed tonic-clonic seizure. Two hours previously, the child had been found with an open bottle of 25-mg diphenhydramine tablets, 24 of which were missing. Midazolam was administered with seizure resolution. Examination revealed 4-mm reactive pupils; nystagmus; warm, dry, flushed skin; and altered mental status. Initial electrocardiograms revealed sinus tachycardia at a rate of 180 beats per minute, a prolonged QRS of 130 milliseconds (from a baseline of 65 milliseconds), and a positive terminal R wave in aVR, which later resolved after sodium bicarbonate treatment. The patient was discharged home the following day with no sequelae. RESULTS AND DISCUSSION: Diphenhydramine toxicity is a common poisoning in children. Toxicity typically presents with signs and symptoms of the anticholinergic toxidrome. Diphenhydramine also has sodium channel-blocking properties, and this can be shown in the form of prolonged QRS and a terminal R wave in aVR. QRS prolongation and aVR abnormalities from diphenhydramine ingestion in a toddler have been reported, but effective use of sodium bicarbonate has not. CONCLUSIONS: Electrocardiographic finding consistent with sodium channel blockade should be recognized as a complication of pediatric diphenhydramine overdose, and they seem responsive to hypertonic sodium bicarbonate.

[Flecainide poisoning]. / Intoxicación por flecainida.

Flecainide is an antiarrhythmic drug that blocks sodium channels during phase 0 of cardiac action potential, delaying conduction and reducing contractility. Intoxication by this drug is rare. Onset of effect, which is rapid, takes the form of hypotension and cardiac arrhythmias; mortality is high. No antidote is available and management is based on the few cases that have been reported. The metabolism of flecainide is affected by both kidney and liver failure, which lead to accumulation of the drug. Flecainide should not be used in patients with such failure unless the potential benefits clearly outweigh the risks. If flecainide is prescribed, diligent clinical, electrocardiographic, and hemodynamic vigilance is imperative and plasma levels of the drug should be monitored. We report a case of flecainide poisoning in which the drug was prescribed to treat atrial fibrillation in a woman with resolving sepsis with renal and hepatic complications.

Management of sodium-channel blocker poisoning: the role of hypertonic sodium salts.

Sodium-channel blockers act by slowing sodium influx into myocytes through voltage gated channels. Many substances have sodium-channel blocking properties and many others show this effect when taken in overdose. Sodium-channel blocker poisoning, associated with a high death rate, is characterized by a variety of clinical presentation, depending on the pharmaceutical agent involved. Sodium bicarbonate or lactate, increasing serum pH and extracellular concentration of the ion, displace the drug from its receptor sites and can be used for the treatment of cardiac toxicity in the setting of sodium-channel blocker poisoning. In spite of this theoretical assumption, the role played by hypertonic sodium salts is not well elucidated and conflicting results have been reported. Authors review the pathophysiologic mechanisms of sodium-channel blocker poisoning and the evidences in literature concerning the efficacy of hypertonic sodium salts in the treatment of the related toxicity.

Paralytic shellfish poisoning: seafood safety and human health perspectives.

Paralytic shellfish poisoning (PSP) is the foodborne illness associated with the consumption of seafood products contaminated with the neurotoxins known collectively as saxitoxins (STXs). This family of neurotoxins binds to voltage-gated sodium channels, thereby attenuating action potentials by preventing the passage of sodium ions across the membrane. Symptoms include tingling, numbness, headaches, weakness and difficulty breathing. Medical treatment is to provide respiratory support, without which the prognosis can be fatal. To protect human health, seafood harvesting bans are in effect when toxins exceed a safe action level (typically 80 microg STX eq 100 g(-1) tissue). Though worldwide fatalities have occurred, successful management and monitoring programs have minimized PSP cases and associated deaths. Much is known about the toxin sources, primarily certain dinoflagellate species, and there is extensive information on toxin transfer to traditional vectors - filter-feeding molluscan bivalves. Non-traditional vectors, such as puffer fish and lobster, may also pose a risk. Rapid and reliable detection methods are critical for toxin monitoring in a wide range of matrices, and these methods must be appropriately validated for regulatory purposes. This paper highlights PSP seafood safety concerns, documented human cases, applied detection methods as well as monitoring and management strategies for preventing PSP-contaminated seafood products from entering the food supply.

Seafood intoxication by tetrodotoxin: first case in Europe.

BACKGROUND: Tetrodotoxin is considered the most lethal toxin in the marine environment. Prior cases of intoxication previously described correspond to consumption of tetrodotoxin in tropical or subtropical regions of Asia or the Pacific Islands. OBJECTIVES: We present the first European case of tetrodotoxin intoxication in a patient who ingested part of a trumpet shellfish (Charonia sauliae) from the Atlantic Ocean in Southern Europe. CASE REPORT: Our patient suffered general paralysis, including the respiratory muscles, a few minutes after the consumption of a few grams of C. sauliae. Intubation and mechanical ventilation were necessary for 52 h after the intoxication. The corresponding electrophysiologic studies showed complete non-excitability, with no recordable sensory or motor nerve conduction. We detected the presence of tetrodotoxin in the mollusk and the patient's blood and urine by means of high-performance liquid chromatography-mass spectrometry analysis technique. A previous bioassay showed extremely high quantities of the toxin in the mollusk. CONCLUSIONS: This case alerts us to the possibility of a very harmful biotoxin in European coastal waters. This now should be included in the differential diagnosis of similar cases in Europe, and we must be vigilant for its possible presence in Europe.

Tetrodotoxin--distribution and accumulation in aquatic organisms, and cases of human intoxication.

Many pufferfish of the family Tetraodontidae possess a potent neurotoxin, tetrodotoxin (TTX). In marine pufferfish species, toxicity is generally high in the liver and ovary, whereas in brackish water and freshwater species, toxicity is higher in the skin. In 1964, the toxin of the California newt was identified as TTX as well, and since then TTX has been detected in a variety of other organisms. TTX is produced primarily by marine bacteria, and pufferfish accumulate TTX via the food chain that begins with these bacteria. Consequently, pufferfish become non-toxic when they are fed TTX-free diets in an environment in which the invasion of TTX-bearing organisms is completely shut off. Although some researchers claim that the TTX of amphibians is endogenous, we believe that it also has an exogenous origin, i.e., from organisms consumed as food. TTX-bearing animals are equipped with a high tolerance to TTX, and thus retain or accumulate TTX possibly as a biologic defense substance. There have been many cases of human intoxication due to the ingestion of TTX-bearing pufferfish, mainly in Japan, China, and Taiwan, and several victims have died. Several cases of TTX intoxication due to the ingestion of small gastropods, including some lethal cases, were recently reported in China and Taiwan, revealing a serious public health issue.

Acute fatal poisoning with pilsicainide and atenolol.

A fatal case of intentional poisoning with two antiarrhythmic agents, pilsicainide, a pure sodium channel blocker, and atenolol, a selective beta1 blocker, is presented. A woman in her twenties was found dead at home and empty pill packages of pilsicainide, atenolol, and aspirin were found near by. Hesitation marks were found on the wrist, and strong fibrous degeneration was observed in the cardiomyocytes of the sinoatrial node. The blood concentrations of pilsicainide and atenolol were 7.83 and 4.94 microg/ml, respectively, both far above the reported therapeutic levels. According to these results, we concluded that death was due to cardiac arrhythmia caused by poisoning with pilsicainide and atenolol. This is the first report of fatal poisoning attributable to an overdose of the combination of these two antiarrhythmic drugs.

Electrocardiographic abnormalities associated with poisoning.

This article will review the cardiovascular toxicities of various medications, stressing the electrocardiographic presentation--both rhythm and morphological issues--and emphasizing recognition and management issues. Cardiovascular toxins are grouped into categories causing similar electrocardiographic effects, including the potassium efflux blockers, sodium channel blockers, sodium-potassium adenosine triphosphatase blockers (ie, digitalis compounds), calcium channel blockers, and beta-adrenergic blockers. This article reviews the various electrocardiographic abnormalities associated with these 5 classes of agents, ranging from morphological abnormalities and conduction blocks to brady- and tachyarrhythmias.