sodium-bicarbonate and Arrhythmias--Cardiac

Hyperkalemia is a common problem in both inpatients and outpatients. Many disease states (eg, chronic kidney disease) and medications may precipitate hyperkalemia. There are several drugs now available to treat hyperkalemia. Many of these drugs are relatively new. This review provides information regarding drug-induced causes of hyperkalemia and provides detailed information on the medications used to treat this problem.

Topics: Acute Disease; Administration, Intravenous; Adrenergic beta-Agonists; Arrhythmias, Cardiac; Calcium; Cation Exchange Resins; Chronic Disease; Electrocardiography; Glucose; Humans; Hyperkalemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Polymers; Polystyrenes; Potassium; Silicates; Sodium Bicarbonate; Sodium Potassium Chloride Symporter Inhibitors

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.

Topics: Action Potentials; Anti-Arrhythmia Agents; Antidepressive Agents, Tricyclic; Antidotes; Antimalarials; Arrhythmias, Cardiac; Drug Overdose; Heart Conduction System; Heart Rate; Humans; Risk Factors; Sodium Bicarbonate; Sodium Channel Blockers

Cocaine use is common in many areas of the world, particularly the United States and Western Europe. Toxicity following the use of cocaine is associated with a wide range of clinical features. In this review, we will focus on the cocaine-associated cardiac arrhythmias and, in particular, some of the controversies in their etiology and management. Cocaine can produce arrhythmias either through the production of myocardial ischemia or as a direct result of ion channel alterations. Excessive catecholamines, combined with sodium and potassium channel blockades, give rise to a wide variety of supra-ventricular and ventricular rhythms. The animal and human evidence for ion channel dysfunction is reviewed, and the effects of catecholamines are followed from the cardiac action potential to the development of arrhythmias. Finally, theoretical constructs are combined with existing evidence to develop a rational treatment strategy for patients with cocaine-induced cardiac arrhythmias. In particular, we review the evidence concerning the controversies relating to the use of lidocaine in comparison with sodium bicarbonate, in terms of QRS prolongation secondary to sodium channel blockade.

Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cocaine; Cocaine-Related Disorders; Humans; Lidocaine; Long QT Syndrome; Myocardium; Potassium Channels; Sodium Bicarbonate; Sodium Channels

Topics: Advanced Cardiac Life Support; Algorithms; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium; Cardiopulmonary Resuscitation; Child; Defibrillators; Drug Administration Routes; Electric Countershock; Glucose; Heart Arrest; Humans; Magnesium; Parents; Sodium Bicarbonate; Sweetening Agents; Vasoconstrictor Agents

Experimental studies suggest that both alkalinisation and sodium loading are effective in reducing cardiotoxicity independently. Species and experimental differences may explain why sodium bicarbonate appears to work by sodium loading in some studies and by a pH change in others. In the only case series, the administration of intravenous sodium bicarbonate to achieve a systemic pH of 7.5-7.55 reduced QRS prolongation, reversed hypotension (although colloid was also given) and improved mental status in patients with moderate to severe tricyclic antidepressant poisoning. This clinical study supports the use of sodium bicarbonate in the management of the cardiovascular complications of tricyclic antidepressant poisoning. However, the clinical indications and dosing recommendations remain to be clarified. Hypotension should be managed initially by administration of colloid or crystalloid solutions, guided by central venous pressure monitoring. Based on experimental and clinical studies, sodium bicarbonate should then be administered. If hypotension persists despite adequate filling pressure and sodium bicarbonate administration, inotropic support should be initiated. In a non-randomised controlled trial in rats, epinephrine resulted in a higher survival rate and was superior to norepinephrine both when the drugs were used alone or when epinephrine was used in combination with sodium bicarbonate. Sodium bicarbonate alone resulted in a modest increase in survival rate but this increased markedly when sodium bicarbonate was used with epinephrine or norepinephrine. Clinical studies suggest benefit from norepinephrine and dopamine; in an uncontrolled study the former appeared more effective. Glucagon has also been of benefit. Experimental studies suggest extracorporeal circulation membrane oxygenation is also of potential value. The immediate treatment of arrhythmias involves correcting hypoxia, electrolyte abnormalities, hypotension and acidosis. Administration of sodium bicarbonate may resolve arrhythmias even in the absence of acidosis and, only if this therapy fails, should conventional antiarrhythmic drugs be used. The class 1b agent phenytoin may reverse conduction defects and may be used for resistant ventricular tachycardia. There is also limited evidence for benefit from magnesium infusion. However, class 1a and 1c antiarrhythmic drugs should be avoided since they worsen sodium channel blockade, further slow conduction velocity and depress contractility.

Topics: Alkalosis, Respiratory; Anti-Arrhythmia Agents; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Humans; Hypotension; Poisoning; Sodium Bicarbonate

Sodium bicarbonate infusion is widely recommended in textbooks for patients who present with self-poisoning from tricyclic antidepressives. Cardiac conduction disorders could also be treated or prevented by means of such an infusion. The scientific basis for these recommendations was investigated by using Medline to search for publications about clinical studies that supported the use of sodium carbonate; 111 articles were scrutinized. Observational studies and case reports mention a rapid improvement in hypotension and cardiac arrhythmias following the administration of sodium bicarbonate. Results from animal experiments are contentious; it is not clear whether alkalinisation or the administration of extra sodium causes the effect. Randomized studies in patients have not been carried out. As the toxicity of sodium bicarbonate is low, and its potential benefit appears to be high, we recommend its use, despite the lack of scientific evidence. No recommendations concerning dosing, concentration and the length of the therapy can be provided on the basis of the literature.

Topics: Adult; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Drug Overdose; Female; Humans; Hypotension; Infusions, Intravenous; Retrospective Studies; Sodium Bicarbonate

Topics: Adult; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Clinical Trials as Topic; Drug Overdose; Emergency Medicine; Evidence-Based Medicine; Female; Humans; Injections, Intravenous; MEDLINE; Sodium Bicarbonate; Treatment Outcome; United Kingdom; United States

Topics: Animals; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Cardiovascular Diseases; Child, Preschool; Drug Overdose; Female; Humans; Hypertonic Solutions; Hypotension; Infant, Newborn; Sodium Bicarbonate

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bicarbonates; Child; Child, Preschool; Electrocardiography; Epinephrine; Heart Arrest; Humans; Infant; Infant, Newborn; Injections; Prognosis; Respiration, Artificial; Resuscitation; Sodium; Sodium Bicarbonate

Topics: Adult; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bicarbonates; Blood Circulation; Brain Ischemia; Cardiotonic Agents; Child; Electric Countershock; Heart Arrest; Heart Massage; Humans; Hypoxia, Brain; Infant, Newborn; Resuscitation; Sodium Bicarbonate; Ventricular Fibrillation

The use of contrast media during cardiac resynchronization therapy (CRT) devices implantation is associated with the risk of contrast-induced nephropathy (CIN). The aim of this study was to evaluate the possible beneficial role of periprocedural intravenous volume expansion with isotonic saline and sodium bicarbonate solution in patients who undergo CRT implantation. Eligible patients were randomly assigned in a 1:1 ratio to receive hydration plus one-sixth molar sodium bicarbonate (study group) or not (control group). Primary end point was CIN incidence. Secondary end points were (1) a combined end point of death, heart transplantation, or hospitalization for heart failure at 12 months, (2) incidence of death, and (3) the need for renal replacement therapy at 12 months. Final analysis was performed with 93 patients. In the hydration group CIN incidence was significantly reduced related to control group (0% vs 11%, p = 0.02). There was a trend to reduce the combined end point in hydration group (12.5% vs 22%, p = 0.14). Finally, CIN incidence was related to a higher 12 months mortality (25% vs 7%, p = 0.03). In conclusion, CIN incidence was 11% in a nonselected population of patients receiving a CRT device. CIN appearance could be reduced by using a hydration protocol based on sodium bicarbonate and isotonic saline.

Topics: Aged; Arrhythmias, Cardiac; Cardiac Resynchronization Therapy; Contrast Media; Female; Hospitalization; Humans; Kidney Diseases; Male; Middle Aged; Prospective Studies; Sodium Bicarbonate; Treatment Outcome

Flecainide is a 1C antidysrhythmic that is primarily used for ventricular tachycardia or premature ventricular contractions when other treatment is ineffective. It has a very narrow therapeutic window which may cause death in a double dose and requires inpatient initiation for cardiac monitoring. Despite established pharmacokinetic data from flecainide in therapeutic dosing, there is negligible data on flecainide toxicokinetics after an intentional overdose. Due to the inherent differences in pharmacokinetic and toxicokinetic principles, rarely can the peak effect or elimination half-life accurately be applied to the poisoned patient after an overdose. In overdose, flecainide can cause a variety of fatal dysrhythmias which may require sodium bicarbonate for stabilization but also may reduce the renal elimination of flecainide, meaning the life-saving treatment may prolong the time of toxicity.. We present a case of an acute ingestion of flecainide with a known time of ingestion and known amount of ingestion who experienced subsequent life-threatening effects which required endotracheal intubation, sodium bicarbonate, aggressive electrolyte repletion, and multiple days in an intensive care unit.. Serial serum and urine samples revealed a prolonged toxic serum concentration of flecainide.. These results demonstrate the change in elimination kinetics of flecainide in the setting of urinary alkalization which is evident through prolonged morphologic changes present on serial electrocardiograms.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Drug Overdose; Electrocardiography; Flecainide; Humans; Sodium Bicarbonate

Del Nido cardioplegia (DNC) has been proven safe and effective in pediatric patients. However, the use of DNC in adult undergoing cardiovascular surgery lacks support with substantial evidence. This study aimed to evaluate the efficacy of DNC as a cardioplegia of prophylaxis to ventricular arrhythmias associated to cardiovascular surgery in adult patients.. This study recruited nine hundred fifty-four patients who underwent cardiopulmonary bypass surgeries in Nanjing Hospital affiliated to Nanjing Medical University between January 2019 and December 2019. Among 954 patients, 324 patients were treated with DNC (DNC group), and 630 patients were treated with St. Thomas cardioplegia (STH group). The incidence of postoperative arrhythmia as well as other cardiovascular events relavant to the surgery were investigated in both groups.. In DNC group, the incidence of postoperative ventricular arrhythmias was lower (12.4% vs. 17.4%, P = 0.040), and the length of ICU stay was shorter (1.97 ± 1.49 vs. 2.26 ± 1.46, P = 0.004). Multivariate logistic regression demonstrated that the use of DNC helped to reduce the incidence of postoperative ventricular arrhythmias (adjusted odds ratio 0.475, 95% CI 0.266-0.825, P = 0.010). The propensity score-based analysis and subgroup analysis indicated that DNC has the same protecting effects towards myocardial in all kinds of cardiopulmonary bypass surgeries.. Del Nido cardioplegia may potentially reduce the incidence of postoperative ventricular arrhythmias, shorten the length of ICU stay and improve the overall outcome of the patients undergoing cardiovascular surgery.

Topics: Adult; Aged; Arrhythmias, Cardiac; Bicarbonates; Calcium Chloride; Cardiac Surgical Procedures; Cardioplegic Solutions; Cardiopulmonary Bypass; China; Electrolytes; Female; Heart Arrest, Induced; Humans; Incidence; Intensive Care Units; Length of Stay; Lidocaine; Magnesium; Magnesium Sulfate; Male; Mannitol; Middle Aged; Potassium Chloride; Retrospective Studies; Risk Assessment; Risk Factors; Sodium Bicarbonate; Sodium Chloride; Solutions; Time Factors; Treatment Outcome; Young Adult

Lacosamide is a third-generation antiepileptic drug. Its likely mechanism of action is via neuronal sodium channel blockade, via a unique manner compared with other antiepileptic drugs that block sodium channels. A paucity of information exists regarding lacosamide overdosage. Lacosamide overdosage is thought to cause QRS prolongation and seizures, due to its effect of sodium channel blockade. The potential efficacy of sodium bicarbonate to reverse the effects of lacosamide has not been well studied. Furthermore, prior reports of lacosamide toxicity have occurred in the setting of concomitant polypharmacy. Thus, the isolated toxic effects of the drug have not been well elucidated.. We report a case of a suspected, single-ingestion overdose on lacosamide. The patient developed signs of cardiotoxicity and seizure. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: After lacosamide overdosage, the emergency physician must be capable of acute management of subsequent lacosamide toxicity. Understanding the mechanisms of action causing toxicity due to this drug can help the clinician to anticipate the interventions that may be needed or useful to treat this potentially toxic ingestion.

Topics: Arrhythmias, Cardiac; Cardiotoxicity; Drug Overdose; Electrocardiography; Epilepsy; Female; Humans; Lacosamide; Middle Aged; Seizures; Sodium Bicarbonate

Bupivacaine cardiotoxicity mainly manifests as inhibition of the cardiac sodium channel, which slows conduction, particularly at the ventricular level. Experimental studies have demonstrated that intravenous lipid emulsions (ILEs) can reduce the cardiotoxic effects of bupivacaine, but the extent of these effects is controversial. Sodium bicarbonate (B) represents the standard treatment of toxicity related to sodium channel-blocking drugs. The aim of this study was to compare the effects of ILEs and B on the speed of recovery from bupivacaine-induced effects on the electrocardiographic parameters.. Bupivacaine 4 mg/kg was administered to 24 anesthetized pigs. Three minutes after delivering the bupivacaine bolus, the animals were given the following: ILE 1.5 mL/kg followed by 0.25 mL/kg/min (ILE group) and B 2 mEq/kg followed by 1 mEq/kg/h (B group). Controls (C group) were given saline solution, 50 mL followed by 1 mL/kg/h. Electrophysiological parameters were evaluated in sinus rhythm and during right ventricular pacing at several time intervals up to 30 minutes. Data were analyzed as the area under the curve (AUC) for the first 10 minutes (AUC10) or 30 minutes (AUC30).. Bupivacaine increased the sinus cycle length, PR interval, and QRS duration. AUC30 of the sinus rhythm QRS duration after antidote administration was significantly different among the 3 groups (P = .003). B group experienced faster recovery from intoxication than the C group (AUC10, P = .003; AUC30, P = .003) or the ILE group (AUC10, P = .018). During the first minute, 50% of the B group (versus 0% of the ILE and C groups) had recovered >30% of QRS duration (P = .011). The trend toward faster recovery in the ILE group than in the C group did not reach significance (AUC10, P = .23; AUC30, P = .06). Effects on the paced QRS duration at a rate of 150 bpm were more intense but with similar results (B versus C group: AUC10, P = .009; AUC30, P = .009; B versus ILE: AUC10, P = .015; AUC30, P = .024). The recovery process of the paced QRS tended to be slower for all antidotes.. In a closed-chest swine model, B was an effective treatment for electrophysiological alterations caused by established bupivacaine toxicity. At clinical doses, B ameliorated bupivacaine electrocardiographic toxicity faster than ILE. Use-dependent effects of bupivacaine are prominent and delay the effects of both antidotes, but B produces faster recovery than ILE.

Topics: Action Potentials; Anesthetics, Local; Animals; Antidotes; Arrhythmias, Cardiac; Bupivacaine; Cardiotoxicity; Disease Models, Animal; Fat Emulsions, Intravenous; Heart Conduction System; Heart Rate; Recovery of Function; Sodium Bicarbonate; Sus scrofa; Time Factors

Yew leaves poisoning is a rare life-threatening intoxication, whose diagnosis can be difficult. Initial symptoms are nausea, vomiting, abdominal pain, dizziness, tachycardia, muscle weakness, confusion, beginning within 1 hr from ingestion and followed by bradycardia, ventricular arrhythmias, ventricular fibrillation, severe hypotension, and death. Taxine-derived alkaloids are responsible for the toxicity of the yew leaves, blocking sodium and calcium channels, and causing conduction abnormalities. Because of lack of a specific antidote and limited efficacy of common antiarrhythmic drugs, prompt diagnosis, detoxification measures, and immediate hemodynamic support (also with transvenous cardiac stimulation) are essential.

Topics: Adrenergic alpha-Agonists; Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiopulmonary Resuscitation; Cephalotaxus; Charcoal; Electrocardiography; Female; Gastric Lavage; Heart Arrest; Humans; Magnesium Sulfate; Male; Middle Aged; Norepinephrine; Pacemaker, Artificial; Plant Extracts; Plant Leaves; Sodium Bicarbonate; Treatment Outcome

Loperamide, a non-prescription anti-diarrheal agent, is a peripheral mu-opioid receptor agonist that is excluded from the blood-brain barrier by p-glycoprotein at therapeutic doses. Overdoses of loperamide penetrate the central nervous system (CNS), leading to abuse. We report cardiac conduction abnormalities and dysrhythmias after ingestion of a recreational supra-therapeutic dose of loperamide confirmed with an elevated blood loperamide concentration.. A 48-year-old woman with a history of alcohol and benzodiazepine abuse presented to the emergency department (ED) with somnolence, weakness and slurred speech. She was taking 20 to 40 tablets of 2 mg loperamide 1-2 times/day for weeks along with clonazepam and whiskey. Vital signs were: blood pressure (BP), 124/90 mmHg; heart rate (HR), 88/min; respiratory rate(RR), 20/min; T, 36.9 °C; O2 saturation 100% on room air (RA). Glucose was 6.4 mmol/L. Electrocardiogram (ECG) had a ventricular rate of 58/min, QRS 164 ms, QT 582 ms with no discernable p-waves. Lactate was 3.5 mmol/L and potassium was 6.2 mEq/L. Labs were notable for an anion gap of 20 mEq/L, ethanol of 3.9 mmol/L, creatinine of 2.3 mg/dL and loperamide concentration of 210 ng/mL (average therapeutic plasma concentration 1.2 ng/mL). She became hypotensive, but responded to fluids. Following treatment for hyperkalemia with calcium, insulin, dextrose, and hypertonic sodium bicarbonate a repeat ECG had a ventricular rate of 66/min, QRS 156 ms, and QT 576 ms. Magnesium was given and pacer pads were placed. During the infusion of magnesium, her BP fell to 92/58 mmHg with a HR of 54/min, RR 14/min, O2 saturation of 97% on RA so the infusion was stopped. The ECG after the magnesium infusion had a ventricular rate of 51/min, QRS of 134 ms, and QT 614 ms. In the ICU she had multiple runs of non-sustained ventricular tachycardia that did not require therapy. Over the next 48 h she improved and was transferred to a floor bed. On day four of hospitalization the patient left against medical advice. At that time, her ECG showed sinus tachycardia with a heart rate 114/min, QRS 82 ms, QT 334 ms.. Loperamide produces both QRS and QT prolongation at supra-therapeutic dosing. A blood loperamide concentration of 210 ng/mL is among the highest concentrations reported. Supra-therapeutic dosing of loperamide is promoted on multiple drug-use websites and online forums as a treatment for opioid withdrawal, as well as for euphoric effects. With the current epidemic of prescription opioid abuse, toxicity related to loperamide, an opioid agonist that is readily available without a prescription is occurring more frequently. It is important for clinicians to be aware of the potentially life-threatening toxicity related to loperamide abuse in order to provide proper diagnosis, management and patient education.

Topics: Alcoholism; Arrhythmias, Cardiac; Benzodiazepines; Blood Pressure; Calcium; Central Nervous System; Clonazepam; Dose-Response Relationship, Drug; Drug Overdose; Electrocardiography; Emergency Service, Hospital; Female; Glucose; Heart Rate; Humans; Hyperkalemia; Insulin; Loperamide; Magnesium; Middle Aged; Respiratory Rate; Sodium Bicarbonate; Substance-Related Disorders

This case report describes the possible benefit of intravenous lipid emulsion in two patients surviving a severe intoxication with hydroxychloroquine in a dose that was previously considered to be lethal. The first case involves a 25-year-old female who ingested 17.5 grams of hydroxychloroquine, approximately one hour before presentation. An ECG showed QRS widening and the lab results showed hypokalaemia. She became unconscious, and developed hypotension and eventually apnoea. After intubation, supportive care consisted of norepinephrine and supplementation of potassium. Moreover, sodium bicarbonate and intravenous lipid emulsion were started to prevent cardiac toxicity. After these interventions, haemodynamic stability was established within a few hours. Although cardiomyopathy was confirmed, the patient recovered after two weeks. The second case concerns a 25-year-old male who took 5 grams of hydroxychloroquine. At presentation, two hours after intake, he showed QTc prolongation and hypokalaemia. The patient was treated with the usual supportive care and, although presentation to hospital was later, with intravenous lipid emulsion. Also this patient recovered. In conclusion, these cases show the benefit of supplemental intravenous lipid emulsion to prevent cardiac toxicity after a severe intoxication with hydroxychloroquine.

Topics: Adult; Arrhythmias, Cardiac; Chromatography, Liquid; Drug Overdose; Electrocardiography; Fat Emulsions, Intravenous; Female; Humans; Hydroxychloroquine; Hypokalemia; Hypotension; Male; Norepinephrine; Potassium Chloride; Sodium Bicarbonate; Suicide, Attempted; Tandem Mass Spectrometry; Vasoconstrictor Agents

We present an 18-month boy with imipramine poisoning to illustrate the neuro-cardiac toxic effects of this potentially deadly poison in children. The toddler ingested an unknown amount of imipramine from a non-childproof bottle which clearly labelled that the drug must be kept out of reach from children. He developed neurologic and cardiac symptoms. Electrocardiography (ECG) showed tachycardia and widened QRS. He was immediately treated with bicarbonate infusion and made an uneventful recovery. This is the youngest and only reported case of symptomatic imipramine ingestion in our locality. Imipramine has been surpassed by newer antidepressants for the treatment of depression in the past decade. Literature is searched to review the mortality rate in young children. Intensive care neuro-cardiac support contributes to the favorable outcome. Despite clear labelling of the bottle, carelessness on the part of the adult and the use of non-childproof bottle are definite preventable factor to such potentially fatal ingestion.

Topics: Accidents, Home; Adrenergic Uptake Inhibitors; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Drug Overdose; Electrocardiography; Heart Conduction System; Heart Rate; Humans; Imipramine; Infant; Infusions, Intravenous; Male; Neurotoxicity Syndromes; Sodium Bicarbonate; Tachycardia; Time Factors; Treatment Outcome

Flecainide is a class IC antidysrhythmic primarily indicated for ventricular dysrhythmias and supraventricular tachycardia (SVT). Class IC antidysrhythmic overdose has a reported mortality of 22%, and death results from dysrhythmias and cardiovascular collapse. We report a near-fatal flecainide overdose in an 18-day-old treated successfully with sodium bicarbonate.. An 18-day-old, 2 weeks premature, 4-kg boy developed persistently high heart rates (220-240 beats/min) and electrocardiographic changes consistent with SVT. There was minimal response to vagal maneuvers, adenosine, and esmolol, and a transthoracic echocardiogram showed no underlying structural abnormality. The patient was then started on flecainide 4 mg orally every 8 h (Q8h). After the fourth dose he developed lethargy, cold clammy skin, and a heart rate of 40 beats/min with no palpable pulse. The patient was given 0.1 mg of atropine intravenously, with an increase of the heart rate to 160 beats/min. The child's cardiac monitor revealed a wide-complex tachycardia with left bundle branch morphology, with associated pallor and poor capillary refill. Sodium bicarbonate was administered intravenously due to suspected flecainide toxicity. Approximately 5 min after intravenous administration of 10 mEq of 8.4% sodium bicarbonate twice, his rhythm converted to a narrow-complex tachycardia. A serum flecainide concentration was 1360 μg/L (therapeutic, 200-1000 μg/L) drawn 1 h before the cardiac arrest. It was later discovered that a twofold dosing error occurred: the patient received 8 mg Q8h instead of 4 mg Q8h for four doses.. Flecainide toxicity in children is rare, especially in neonates. It is important for clinicians to be able to identify and treat this uncommon poisoning.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Drug Overdose; Flecainide; Humans; Infant, Newborn; Male; Medication Errors; Sodium Bicarbonate; Treatment Outcome

Intoxication caused by propafenone is very rare, and there is no case reported before propafenone and captopril intoxication together. There are few case reports in the literature about intoxication with more than 6 g of propafenone. We present the clinical manifestation and successfully treatment of 9 g of propafenone and 1 g captopril intoxication in an 18-year-old female. An 18-year-old female was brought to the emergency department approximately half an hour after she committed suicide with 30 propafenone tablets, 300 mg each, and 20 captopril tablets, 50 mg each. Her fist electrocardiography (ECG) shows a chaotic ventricular rhythm with a prolonged QRS complex. After fluid and sodium bicarbonate infusion and permanent pacemaker implantation, sinus rhythm was achieved. This case, to our knowledge, is the first in that it describes the successful recovery of a patient who ingested extensively large doses of propafenone (9 g) and captopril (1 g), both of which are known to have severe cardiac side effects.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Captopril; Cardiopulmonary Resuscitation; Electrocardiography; Emergency Medical Services; Female; Fluid Therapy; Glasgow Coma Scale; Hemodynamics; Humans; Intubation, Gastrointestinal; Long QT Syndrome; Pacemaker, Artificial; Propafenone; Sodium Bicarbonate; Suicide, Attempted

A 23-month-old boy was brought to the emergency department of an adult and pediatric tertiary care center 1 hour after an inadvertent “double dose” of 120 mg flecainide (9.2 mg/kg). His electrocardiogram revealed sinus rhythm with a terminal R wave in aVR greater than 7 mm, a bifascicular block, and prolonged QRS and QTc intervals. A dramatic improvement in the bifascicular block and terminal R wave occurred after the administration of sodium bicarbonate. He was discharged after 36 hours with no complications. This case demonstrates that flecainide can cause significant cardiac conduction disturbances in doses much lower than previously described. All supratherapeutic ingestions should be assessed in hospital.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Electrocardiography; Emergency Service, Hospital; Flecainide; Heart; Humans; Infant; Male; Prescription Drug Misuse; Sodium Bicarbonate

Tricyclic antidepressant (TCA) morbitity is primarily due to cardiac arrhythmias and hypotension, which become more refractory to treatment as acidosis progresses (Ann Emerg Med. 1985;14:1-9; Clin Toxicol. 2007;45:203-233; Flomenbaum N, Goldfrank L, Hoffman R, et al. Goldfrank's toxicologic emergencies. 8th ed. McGraw-Hill Companies, Inc, 2006). Early recognition and aggressive treatment are necessary for patient survival.

Topics: Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Cyclohexanols; Desipramine; Drug Overdose; Electrocardiography; Female; Humans; Middle Aged; Sodium Bicarbonate; Venlafaxine Hydrochloride

Topics: Antiemetics; Arrhythmias, Cardiac; Drug Overdose; Electrocardiography; Humans; Indoles; Quinolizines; Sodium Bicarbonate; Sodium Channels

A 19-year-old woman was brought by ambulance to the emergency department (ED) from a police holding cell. Less than 3 hours earlier, the patient had been a passenger in a car stopped for a traffic violation. As the police officer approached the car, the patient was noted to hurriedly stuff 2 plastic bags containing a white powdery substance into her mouth. On questioning, it was reported that the packets contained cocaine. Less than an hour after being taken to the police station, the patient was witnessed to have a generalized seizure. What is the pharmacological basis of acute cocaine intoxication? What are the cardiovascular manifestations of acute cocaine intoxication? What is the basis for using sodium bicarbonate in cocaine-induced wide-complex dysrhythmias? What is the basis for the use of lidocaine in cocaine-induced wide-complex dysrhythmias? Is there any evidence for the use of amiodarone to treat cocaine-induced wide-complex dysrhythmias?

Topics: Amiodarone; Anti-Arrhythmia Agents; Anticonvulsants; Antidotes; Arrhythmias, Cardiac; Charcoal; Cocaine; Electrocardiography; Emergency Medical Services; Female; Heart Arrest; Humans; Lidocaine; Lorazepam; Pulse; Seizures; Sodium Bicarbonate; Sympathomimetics; Tachycardia, Ventricular; Young Adult

Topics: Adult; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Cardiology; Dothiepin; Electrocardiography; Female; Humans; Sodium Bicarbonate

Tricyclic antidepressant poisoning is often associated with significant cardiovascular and central nervous system toxicity. Effective treatment includes the use of appropriate gastric decontamination techniques, the administration of sodium bicarbonate, and meticulous supportive care. Tricylcic antidepressant toxicity typically lasts 24-48 hours following a significant overdose.. We describe a case of tricyclic antidepressant poisoning where significant clinical toxicity (QRS prolongation, metabolic acidosis) was observed for up to 4 days following ingestion of a modified-release preparation of amitriptyline. Successful patient recovery was associated with the use of multidose activated charcoal and repeated administration of intravenous sodium bicarbonate.. Clinicians should be aware of the potential for prolonged tricyclic toxicity in patients who have ingested modified-release amitriptyline in overdose. Gastric decontamination techniques such as multidose activated charcoal and whole bowel irrigation should be considered where there is evidence of ongoing tricyclic antidepressant absorption or clinical toxicity following ingestion of a modified-release preparation. These interventions may be indicated for prolonged periods (greater than 36 hours) post ingestion.

Topics: Acidosis; Adult; Amitriptyline; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Central Nervous System Diseases; Charcoal; Delayed-Action Preparations; Female; Humans; Injections, Intravenous; Poisoning; Sodium Bicarbonate; Treatment Outcome

Determination of arterial blood gas (ABG) values is essential in the evaluation of patients with TCA poisoning. The relationship between arterial and venous blood gas pH has not been established in TCA poisoning. In TCA poisoning, blood vessels vasodilatation due to antidepressant-induced alpha-blockade and also metabolic acidosis may lead to arterialization of venous blood, which in turn enhances the relationship between ABG and VBG parameters. Therefore this study was designed to evaluate the relationship between ABG and VBG pH values in TCA poisoned patients.. This prospective study was performed in the Poisoning Emergency Department of Noor Hospital, Isfahan, Iran. Samples for arterial and venous blood gas analysis were obtained during initial evaluation of TCA-poisoned patients and 30 min after treatment with sodium bicarbonate. The venous blood gas samples were collected with samples for other blood tests at the time of intravenous line insertion. Laboratory data were recorded on a database form initiated in the emergency department and analyzed by paired student t-test. The degree of agreement between the arterial and venous pH measurements was evaluated by Bland and Altman method.. Data from 50 TCA-poisoned patients were analyzed. There were significant differences between mean differences of ABG and VBG parameter values on the initial evaluation. There was also a relationship between arterial and venous pH on the initial evaluation.. In TCA poisoning, the peripheral venous pH measurement is a valid and reliable substitute for arterial pH.

Topics: Acid-Base Equilibrium; Acidosis; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Blood Gas Analysis; Data Interpretation, Statistical; Diagnostic Tests, Routine; Electrocardiography; Humans; Hydrogen-Ion Concentration; Hypotension; Injections, Intravenous; Patients; Sodium Bicarbonate

Topics: Arrhythmias, Cardiac; Diphenhydramine; Humans; Hypnotics and Sedatives; Respiration, Artificial; Sodium Bicarbonate

Diphenhydramine, a common ingredient in over-the-counter medications, is often taken in overdose. Toxicity is usually limited to anticholinergic symptoms. However, because diphenhydramine also exhibits type IA sodium channel blockade, cardiac toxicity is also possible. Although it would be expected that, like other type IA toxicities, diphenhydramine-induced cardiotoxicity could be responsive to hypertonic sodium bicarbonate, this finding is largely unappreciated. We describe 3 cases of diphenhydramine-induced cardiac toxicity that were responsive to bicarbonate.

Topics: Acetaminophen; Adult; Arrhythmias, Cardiac; Aspirin; Diphenhydramine; Drug Combinations; Fatal Outcome; Female; Humans; Hypertonic Solutions; Hypnotics and Sedatives; Infusions, Intravenous; Male; Methapyrilene; Nonprescription Drugs; Salicylamides; Sodium Bicarbonate; Suicide, Attempted; Treatment Outcome

To describe the clinical presentation of patients with cyclic antidepressant (CA) and use of sodium bicarbonate (NaHCO(3)) in the treatment of this overdose in the prehospital setting.. A three year retrospective observational review of records was performed using the San Diego County Quality Assurance Network database for prehospital providers. All adult patients who were treated with NaHCO(3) by paramedics for a CA overdose were included. Demographic data, presenting cardiovascular and neurological symptoms, paramedic treatments, and any changes in status were reviewed.. Twenty one patients were treated by paramedics with NaHCO(3) for CA overdose. Seventeen patients (80%) presented with mental status changes, including 11 presenting with a GCS<8. Seven of the 21 (33%) presented with a cardiac arrhythmia expected to possibly respond to NaHCO(3) treatment. Seven of the 21 (33%) were hypotensive, and five (24%) patients had reported seizure activity. Only 2 of the 21 patients (10%) treated with NaHCO(3) had recorded improvements after administration of the drug, while the other 19 remained stable without any deterioration. Sixteen of 21 patients (76%) were given NaHCO(3) for indications on standing order, while five patients were treated outside the standing order indications by base physician order with none of the five patients having any change in status ater treatment.. After prehospital NaHCO(3) use in patients with CA overdose, there were no complications reported, two patients improved in status and the others remained unchanged. Base hospital physician orders of NaHCO(3) for indications beyond the standing orders were not associated with changes in patient status.

Topics: Adult; Aged; Allied Health Personnel; Antidepressive Agents; Antidotes; Arrhythmias, Cardiac; California; Coma; Drug Overdose; Emergency Medical Services; Female; Humans; Male; Middle Aged; Retrospective Studies; Sodium Bicarbonate; Time Factors

Cocaine toxicity causes myocardial depression, malignant dysrhythmias, and sudden death, partially due to cocaine-related myocardial sodium channel blockade. Because of cocaine's ability to block cardiac sodium channels, sodium bicarbonate (NaHCO3) has been proposed as an antidote. The hypothesis of this study was that NaHCO3 would correct cocaine-induced conduction abnormalities and resultant hemodynamic compromise in an animal model simulating severe cocaine intoxication.. Prospective, controlled, experimental study in which 15 anesthetized dogs were given three successive boluses of cocaine (7 mg/kg) and then randomized to receive NaHCO3, 2 mEq/kg (n = 8) or placebo (n =7).. Arterial, left ventricular, and pulmonary artery pressures; cardiac output (CO); electrocardiogram (ECG); blood gases; and serum concentrations of cocaine were measured at baseline, at fixed time intervals after each bolus of cocaine, and then after administration of NaHCO3 or placebo. Statistical significance was determined by analysis of variance (ANOVA) for repeated measures.. Seven dogs experienced significant arrhythmias, including VT, pulseless electrical activity, and third-degree atrioventricular block; 2 of these dogs expired prior to receiving NaHCO3 and were excluded. Immediately after administering NaHCO3, QRS duration decreased by 30% (p < 0.001), returning to baseline more quickly than in the control group. This effect was associated with a brief 30% decrease in MAP (p = NS). After NaHCO3, CO increased 78% and remained increased for 5 min (p < 0.007). One dog converted from complete heart block to sinus rhythm shortly after NaHCO3 administration.. NaHCO3 improved ECG changes secondary to cocaine toxicity and improved myocardial function.

Topics: Animals; Antidotes; Arrhythmias, Cardiac; Blood Gas Analysis; Blood Pressure; Cardiac Output; Cocaine; Dogs; Electrocardiography; Electrophysiology; Heart Rate; Hemodynamics; Sodium Bicarbonate; Sodium Channel Blockers; Ventricular Function, Left

Severe acidemia (blood pH < 7.1 to 7.2) suppresses myocardial contractility, predisposes to cardiac arrhythmias, causes venoconstriction, and can decrease total peripheral vascular resistance and blood pressure, reduce hepatic blood flow, and impair oxygen delivery. These alterations in organ function can contribute to increased morbidity and mortality. Although it seemed logical to administer sodium bicarbonate to attenuate acidemia and therefore lessen the impact on cardiac function, the routine use of bicarbonate in the treatment of the most common causes of severe acidemia, diabetic ketoacidosis, lactic acidosis, and cardiac arrest, has been an issue of great controversy. Studies of animals and patients with these disorders have reported conflicting data on the benefits of bicarbonate, showing both beneficial and detrimental effects. Alternative alkalinizing agents, tris-hydroxymethyl aminomethane and Carbicarb, have shown some promise in studies of animals and humans, and reevaluation of these buffers in the treatment of severe acidemic states seems warranted. The potential value of base therapy in the treatment of severe acidemia remains an important issue, and further studies are required to determine which patients should be administered base therapy and what base should be used.

Topics: Acidosis; Acidosis, Lactic; Animals; Arrhythmias, Cardiac; Bicarbonates; Buffers; Calcium; Carbonates; Cardiac Output; Diabetic Ketoacidosis; Drug Combinations; Heart Arrest; Humans; Myocardial Contraction; Oxygen; Potassium; Sodium Bicarbonate; Tromethamine; Vascular Resistance; Water-Electrolyte Balance

Ethylene glycol toxicity has produced central nervous system abnormalities including coma, cerebral edema, and cranial nerve dysfunction.. A 26-year-old male developed widespread brainstem and midbrain dysfunction with corresponding cranial computed tomography findings after ingesting ethylene glycol. The computed tomography scan which was obtained 3 days after ethylene glycol ingestion showed low density areas in the basal ganglia, thalami, midbrain, and upper pons. The neurologic findings in our patient reflected dysfunction of all the areas of hypodensity on the cranial computed tomography scan. A magnetic resonance imaging of the brain obtained 24 days after ingestion revealed bilateral putamen necrosis. The patient's neurologic sequelae resolved over the following 4 months.

Topics: Acute Kidney Injury; Adult; Arrhythmias, Cardiac; Brain Diseases; Brain Edema; Brain Stem; Calcium Gluconate; Charcoal; Coma; Cranial Nerve Diseases; Ethanol; Ethylene Glycol; Humans; Male; Mesencephalon; Putamen; Pyridoxine; Renal Dialysis; Sodium Bicarbonate; Thiamine; Tomography, X-Ray Computed; Treatment Outcome

Severe cocaine toxicity causes acidemia and cardiac dysfunction. These manifestations are described in 4 patients who presented with seizures, psychomotor agitation, and cardiopulmonary arrest. Their initial laboratory values demonstrated acidemia and electrocardiographic findings that included a prolonged QRS complex and QTc duration and a rightward T40 ms axis deviation. Treatment of the patients with hyperventilation, sedation, active cooling, and sodium bicarbonate infusion led to the normalization of their blood pHs and reversal of their cardiac conduction disorders. Acidemia can contribute to cocaine cardiac disorders by promoting conduction delays, dysrhythmias, and depressed myocardial contractility. Good supportive care corrects the blood pH and cardiac conduction disorders and remains the major focus in the management of patients with cocaine toxicity.

Topics: Acid-Base Imbalance; Adult; Akathisia, Drug-Induced; Alkalies; Apnea; Arrhythmias, Cardiac; Cocaine; Cocaine-Related Disorders; Crack Cocaine; Electrocardiography; Heart; Heart Arrest; Humans; Hydrogen-Ion Concentration; Hypnotics and Sedatives; Hypothermia, Induced; Male; Myocardial Contraction; Narcotics; Respiration, Artificial; Seizures; Sodium Bicarbonate

Cardiac depression is the main adverse effect of severe tricyclic antidepressant poisoning. The aim of this study was to investigate whether treatment with epinephrine or norepinephrine increases survival as compared with standard treatment with sodium bicarbonate in experimental amitriptyline poisoning.. Nonrandomized, controlled intervention trial.. University laboratory.. Male, anesthetized, paralyzed, and mechanically ventilated Sprague-Dawley rats (n = 91).. Rats subjected to a 60-min infusion of amitriptyline (2 mg/kg/min) were treated with a continuous infusion of either epinephrine, norepinephrine, sodium bicarbonate, epinephrine plus sodium bicarbonate, norepinephrine plus sodium bicarbonate, or placebo.. Inotropic drug treatment was associated with an increased survival rate as compared with treatment with sodium bicarbonate and treatment with placebo. Epinephrine treatment was superior to norepinephrine. Additional treatment with sodium bicarbonate increased survival rate for each inotropic drug. Sodium bicarbonate and inotropic drug treatment independently increased the survival rate (p < .001 for both effects). No interaction between these two treatment effects was observed.. Both epinephrine and norepinephrine increased the survival rate in tricyclic antidepressant poisoning in rats. Sodium bicarbonate increased the survival rate independent of inotropic drug treatment. Furthermore, epinephrine was superior to norepinephrine when used both with and without sodium bicarbonate, and the most effective treatment was epinephrine plus sodium bicarbonate.

Topics: Amitriptyline; Animals; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Disease Models, Animal; Drug Combinations; Electrolytes; Epinephrine; Hemodynamics; Humans; Male; Norepinephrine; Poisoning; Rats; Rats, Sprague-Dawley; Sodium Bicarbonate; Survival Rate; Sympathomimetics

Topics: Arrhythmias, Cardiac; Humans; Sodium Bicarbonate

Hypotension is a major contributor to mortality in tricyclic antidepressant overdose. Recent data suggest that tricyclic antidepressants inhibit calcium influx in some tissues. This study addressed the potential role of calcium channel blockade in tricyclic antidepressant-induced hypotension.. Two interventions were studied that have been shown previously to improve blood pressure with calcium channel blocker overdose. CaCl2 and 4-aminopyridine. Anesthetized rats received the tricyclic antidepressant desipramine IP to produce hypotension, QRS prolongation, and bradycardia. Fifteen min later, animals received CaCl2, NaHCO3, or saline. In a second experiment, rats received tricyclic antidepressant desipramine IP followed in 15 min by 4-aminopyridine or saline.. NaHCO3 briefly (5 min) reversed hypotension and QRS prolongation. CaCl2 and 4-aminopyridine failed to improve blood pressure. The incidence of ventricular arrhythmias (p = 0.004) and seizures (p = 0.03) in the CaCl2 group was higher than the other groups.. The administration of CaCl2 or 4-aminopyridine did not reverse tricyclic antidepressant-induced hypotension in rats. CaCl2 therapy may possibly worsen both cardiovascular and central nervous system toxicity. These findings do not support a role for calcium channel inhibition in the pathogenesis of tricyclic antidepressant-induced hypotension.

Topics: 4-Aminopyridine; Animals; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Blood Pressure; Bradycardia; Calcium Channels; Calcium Chloride; Desipramine; Disease Models, Animal; Electrocardiography; Hypotension; Male; Rats; Saline Solution, Hypertonic; Sodium Bicarbonate

To review the data on pharmacology, pathophysiology and treatment of cocaine toxicity, with particular relevance to the heart and cardiovascular system.. Published epidemiology, laboratory and clinical studies on the pharmacology, electrophysiology and pathophysiology of cocaine toxicity and its treatment.. Cocaine toxicity-related morbidity and mortality are frequent due to the potent pharmacological effects of the drug as an indirect-acting sympathomimetic agent and its class I antiarrhythmic property paradoxically inducing pro-arrhythmia. The cardiac and cardiovascular toxic effects of cocaine include various degrees of myocardial ischemia, cardiac arrhythmias, cardiotoxicity, hypertensive effects, cerebrovascular effects and a hypercoagulable state. Treatment of cocaine toxicity must be based on the multiple factors leading to the toxicity. Sodium bicarbonate appears to have an important role in the acute setting with conduction abnormalities, seizures or acidosis. Unopposed alpha-stimulation provided by beta-blockade should be avoided. Central nervous system hyperexcitability should be treated with diazepam. The use of calcium antagonists appears logical.. Cocaine is an alkaloid with widespread illicit use. The rationale for treating acute cocaine intoxication has become clearer and more logical with increased knowledge of its mechanisms of action.

Topics: Arrhythmias, Cardiac; Cerebrovascular Disorders; Cocaine; Heart; Humans; Hypertension; Myocardial Ischemia; Sodium Bicarbonate

Propoxyphene overdose is known to cause widening of the QRS complex on ECG. We report a case of a 54-year-old female who ingested approximately 100 propoxyphene hydrochloride tablets in a suicide attempt. She developed a wide complex dysrhythmia which responded to sodium bicarbonate therapy. Propoxyphene-induced wide complex dysrhythmia responsive to sodium bicarbonate therapy has not been previously reported in the literature.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arrhythmias, Cardiac; Dextropropoxyphene; Drug Interactions; Electrocardiography; Female; Fluoxetine; Humans; Middle Aged; Sodium Bicarbonate

Topics: Adult; Arrhythmias, Cardiac; Bicarbonates; Electrocardiography; Female; Humans; Hyperkalemia; Male; Middle Aged; Sodium; Sodium Bicarbonate

This is a report of an intentionally administered overdose of dimenhydrinate to a 4 month-old infant who subsequently presented with status epilepticus, coma, and life threatening ventricular dysrhythmias. Initial toxicologic analysis of the serum by fluorescence polarization immunoassay was positive for tricyclic antidepressants. Repeat analysis of the serum at 6 hours post ingestion by gas chromatography mass spectrometry analysis defined diphenhydramine 4.8 micrograms/mL. The infant was managed with IV sodium bicarbonate as utilized in tricyclic antidepressant intoxication. The dysrhythmias resolved and the infant recovered without sequelae.

Topics: Arrhythmias, Cardiac; Bicarbonates; Child Abuse; Dimenhydrinate; Drug Overdose; Gas Chromatography-Mass Spectrometry; Heart; Humans; Infant; Male; Sodium; Sodium Bicarbonate; Status Epilepticus

Hypertonic (1M) sodium bicarbonate can partially reverse the cardiac toxicity of some Class IA antiarrhythmic agents, presumably by antagonizing sodium channel inhibition. We studied the effects of 1M sodium bicarbonate on toxicity due to the Class IC drug flecainide. Anesthetized rats received i.v. loading and maintenance doses of flecainide to produce QRS prolongation of 76% that was stable over the 60 min study period. 20 min after the start of the maintenance infusion, groups of 8 rats received an i.v. infusion of 1M sodium bicarbonate (6 meq/kg) or an equal volume of 0.9% saline. QRS prolongation was reduced by 1M sodium bicarbonate but not only 0.9% saline (% change -12.2 +/- 10.0 v. +3.0 +/- 2.7, p = 0.001). Expressed as a percent of the flecainide-induced QRS prolongation, bicarbonate reduced this prolongation by 26.5%. The improvement in QRS duration persisted until sacrifice 30 min later. Compared to controls, the bicarbonate group had a significantly higher blood pH (7.55 +/- 0.06 v. 7.44 +/- 0.05) and serum sodium concentration (149 +/- 5 v. 137 +/- 2 meq/l). Serum flecainide concentrations were similar. These data suggest that 1M sodium bicarbonate can partially reverse flecainide-induced conduction delay in rats. This effect may be due to changes in the extracellular pH and sodium concentration. 1M sodium bicarbonate may be useful in assessing the role of sodium channel inhibition in mediating the toxicity of flecainide or other Class IC drugs.

Topics: Animals; Arrhythmias, Cardiac; Bicarbonates; Blood Pressure; Electrocardiography; Flecainide; Heart; Hypertonic Solutions; Male; Rats; Sodium; Sodium Bicarbonate

Cyclic antidepressant overdose is a major cause of drug overdose deaths and morbidity in the United States. The cyclic antidepressants are prescribed widely by primary care physicians and psychiatrists, and accidental overdose in children is not uncommon. Children have exhibited toxic effects with relatively small amounts of cyclic antidepressants. The management of cyclic antidepressant overdose is difficult because of the complex effects on the cardiovascular and nervous systems. The pertinent pharmacology of cyclic antidepressants in therapeutic amounts and in overdose is reviewed in this article. The clinical manifestations of cyclic antidepressant overdose are described. A protocol for effective management of cyclic antidepressant overdose in children is proposed.

Topics: Absorption; Acetylcholine; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Autonomic Nervous System; Bicarbonates; Child; Child, Preschool; Female; Heart Conduction System; Humans; Hypotension; Infant; Ipecac; Male; Norepinephrine; Phenytoin; Physostigmine; Seizures; Sodium; Sodium Bicarbonate; Tissue Distribution

Reversing ventricular ectopy with plasma alkalinization following acute tricyclic antidepressant overdose is a recognized mode of therapy. The mechanism responsible for this effect is unclear. Changes in plasma protein binding of free drug, effects of the sodium ion on the myocardium, and alterations of plasma concentrations of alpha-1-acid glycoprotein may all interact to alter toxicity of tricyclics in overdose. An in vitro investigation using equilibrium dialysis was designed to examine the effect of altering plasma pH on percentage of free amitriptyline at clinical overdose plasma concentrations. A 1973 report on this effect lacked adequate controls and was faulty in experimental protocol. The current investigation used plasma concentrations typically present in amitriptyline overdose, a sensitive gas liquid chromatographic assay to detect total and free drug, and adequate control of plasma pH. The results of two separate experiments demonstrated a significant decrease in percentage of free amitriptyline of 20% over a pH range of 7.0-7.4 (P less than 0.05) and 42% over a pH range of 7.4-7.8 (P less than 0.05). The rate of change in slope in both experiments was not significantly different (P less than 0.01) indicating similar effects of pH change on plasma protein binding of amitriptyline within the two groups.

Topics: Amitriptyline; Arrhythmias, Cardiac; Bicarbonates; Chromatography, Gas; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Ions; Protein Binding; Sodium; Sodium Bicarbonate

Overdose with amitriptyline and other tricyclic antidepressants can result in ventricular conduction abnormalities as well as severe ventricular arrhythmias. The arrhythmogenic effects of these compounds may be attributed to their direct local anesthetic actions in blocking sodium channels in cardiac membranes. Thus tricyclic-induced ventricular arrhythmias usually do not respond well to therapy with standard Class I antiarrhythmic drugs that also have the same direct local anesthetic action and may potentiate the adverse effects of tricyclic antidepressants. Cardiac toxicity was produced in dogs by the administration of amitriptyline, both orally and IV. At serum concentrations less than 2,000 ng/mL, sinus tachycardia occurred with widened QRS complexes. At higher concentrations, QRS duration became more markedly prolonged and was followed by ventricular tachyarrhythmias. Occurrence of ventricular tachyarrhythmias was associated with QRS durations of more than 0.11 second. Sodium bicarbonate (18 to 36 mEq) administered IV over either 30 seconds or two minutes rapidly converted ventricular tachycardia to normal sinus rhythm. Conversion was associated with abbreviation of the QRS complex and was accompanied by a rise in both systolic and diastolic pressures. The duration of sodium bicarbonate effect paralleled the duration of the changes in arterial pH and plasma bicarbonate concentrations. In vitro studies in cardiac Purkinje fibers suggested that reversal of amitriptyline-induced cardiac membrane effects by sodium bicarbonate may be attributed not only to alkalinization but also to increased in extracellular sodium concentration, diminishing the local anesthetic action of amitriptyline and resulting in less sodium channel block.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amitriptyline; Animals; Arrhythmias, Cardiac; Bicarbonates; Dogs; Electrocardiography; Heart Conduction System; Propranolol; Sodium; Sodium Bicarbonate; Tachycardia

Topics: Arrhythmias, Cardiac; Atropine; Bicarbonates; Calcium Chloride; Epinephrine; Heart Arrest; Humans; Sodium; Sodium Bicarbonate

The beneficial hemodynamic effects of sodium bicarbonate as treatment for tricyclic antidepressant poisoning were investigated in an animal model. Seven adult dogs (17.5 to 20 kg) were poisoned by an intravenous infusion of amitriptyline. Toxicity was defined as a doubling of the initial QRS width. A continuous infusion was used to maintain toxicity for 30 minutes after which 44.5 mEq of sodium bicarbonate was administered intravenously. Five of the animals survived to completion of the experiment. Three of the surviving animals developed dysrhythmias. All dysrhythmias ceased within one minute of administration of sodium bicarbonate. An increase in mean blood pressure (P less than .05) and serum pH (P less than .05) and a decrease in mean QRS width (P less than .05) occurred following administration of sodium bicarbonate. The maintenance of toxicity for 30 minutes suggests that this model can be used for future studies of tricyclic antidepressant poisoning.

Topics: Amitriptyline; Animals; Arrhythmias, Cardiac; Bicarbonates; Blood Gas Analysis; Dogs; Electrocardiography; Heart Rate; Sodium; Sodium Bicarbonate

Topics: Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Bicarbonates; Humans; Kinetics; Sodium Bicarbonate

Sodium bicarbonate has been recommended for the treatment of arrhythmias induced by tricyclic antidepressants. It is unclear, however, whether this therapy is effective only in the presence of acidosis. A case is presented in which there was an immediate response to sodium bicarbonate in three episodes of ventricular tachycardia despite the presence of alkalosis on two of the three occasions. Given the poor response to conventional therapy of arrhythmias induced by tricyclic antidepressants the use of sodium bicarbonate may be reasonable even in the presence of alkalosis. However, in the presence of pre-existing respiratory or metabolic alkalosis, such therapy is not without risk, and it is suggested that it be reserved for life-threatening situations when the arrhythmia has failed to respond to hyperventilation or antiarrhythmics or both.

Topics: Adult; Alkalosis; Alkalosis, Respiratory; Arrhythmias, Cardiac; Bicarbonates; Electrocardiography; Female; Humans; Hydrogen-Ion Concentration; Imipramine; Sodium Bicarbonate

Topics: Adult; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Bicarbonates; Female; Humans; Hypotension; Sodium Bicarbonate

Enuresis is a common problem often treated effectively with imipramine hydrochloride. The usefulness of this therapy carries with it, however, the risk of accidental overdose by younger siblings of these enuretic patients. Traditional support measures are effective in the treatment of the mild to moderate overdose, while separate symptomatic treatment of seizures and cardiac arrhythmias is possible as outlined herein. Physostigmine offers a single alternate treatment which is effective in the full panorama of life-threatening manifestations of an imipramine overdose.

Topics: Adult; Arrhythmias, Cardiac; Bicarbonates; Child; Child, Preschool; Coma; Diazepam; Drug Administration Schedule; Enuresis; Humans; Hypotension; Imipramine; Phenobarbital; Physostigmine; Seizures; Sodium Bicarbonate

Topics: Arrhythmias, Cardiac; Bicarbonates; Cardiac Pacing, Artificial; Diagnosis, Differential; Electrocardiography; Emergencies; Epinephrine; Heart Ventricles; Humans; Sodium Bicarbonate; Tachycardia; Ventricular Fibrillation

Direct-air ventilation, external cardiac compression, and external defibrillation are established techniques for patients who unexpectedly develop cardiac arrest. The proper use of drugs can increase the incidence of successful resuscitation. Intracardiac adrenaline (epinephrine) acts as a powerful stimulant during cardiac standstill and, in addition, converts fine ventricular fibrillation to a coarser type, more responsive to electrical defibrillation. Routine use of intravenous sodium bicarbonate is recommended to combat the severe metabolic acidosis accompanying cardiac arrest. Lidocaine is particularly useful when ventricular fibrillation or ventricular tachycardia tends to recur. Analeptics are contraindicated, since they invariably increase oxygen requirements of already hypoxic cerebral tissues. The following acrostic is a useful mnemonic for recalling the details of the management of cardiac arrest in their proper order: A (Airway), B (Breathing), C (Circulation), D (Diagnosis of underlying cause), E (Epinephrine), F (Fibrillation), G (Glucose intravenously), pH (Sodium bicarbonate), I (Intensive care).

Topics: Acidosis; Arrhythmias, Cardiac; Bicarbonates; Brugada Syndrome; Cardiac Conduction System Disease; Critical Care; Drug Therapy; Electric Countershock; Epinephrine; Glucose; Heart Arrest; Heart Conduction System; Humans; Intensive Care Units; Lidocaine; Resuscitation; Sodium Bicarbonate; Tachycardia, Ventricular; Ventricular Fibrillation

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Carbon Dioxide; Cardiac Conduction System Disease; Heart Conduction System; Humans; Sodium Bicarbonate