Article

Effect of sodium bicarbonate in the treatment of moderate to severe cyclic antidepressant overdose

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Abstract

The objective of this study was to characterize the effect of intravenous hypertonic sodium bicarbonate (NaHCO3) administration in patients with moderate-to-severe cyclic antidepressant (CA) overdose. We reviewed charts of all 91 patients given the diagnosis of CA overdose in the University of California Los Angeles (UCLA) Emergency Medicine Center (EMC), who either died in the EMC or were admitted to the medical intensive care unit (MICU), and who received NaHCO3 in the EMC between 1980 and 1988. Twenty-four other patients with the same EMC diagnosis were admitted to the MICU during this period but did not receive NaHCO3. The response of blood pressure, electrocardiographic parameters, and mental status to serum alkalinization with NaHCO3 were evaluated. Major morbidity and mortality were recorded for all patients. Hypotension was corrected within 1 hour in 20 of 21 (96%) patients, QRS prolongation corrected in 39 of 49 (80%), and mental status improved in 40 of 85 (47%). There was one death, in a patient who was moribund on arrival to the EMC. No complications were attributable to the administration of NaHCO3. NaHCO3 seems to improve hypotension and normalize QRS duration rapidly in most patients treated, and improve mental status changes in almost one half. Serum alkalinization with NaHCO3, in conjunction with appropriate supportive care, seems to limit major morbidity and mortality effectively in patients with serious CA overdose.

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... 13,14,17 There is also a surprising lack of clinical studies demonstrating clinical benefit and resolution of ECG effects from alkalinisation therapy. 13,18 We hypothesised that utilisation of both NaHCO 3 and mechanical ventilation (dual therapy) is the optimal strategy to narrow QRS. Thus, our primary objective was to quantify the effects of NaHCO 3 and mechanical ventilation on serum pH and sodium concentration, and determine which treatment strategies are optimal for serum alkalinisation. ...
... Collected data included patient demographics, details of ingestion (including dose and timing of ingestion), serial blood gases (serum pH, sodium concentration and PCO 2 ), serial electrocardiograms (QRS interval), dose and timing of NaHCO 3 , and whether or not patients were mechanically ventilated. Since QRS > 100 ms is generally accepted as prognostic for seizures, arrhythmias and death, 9 and adapting from a prior observational study, 18 we defined widened QRS as >110 ms and a therapeutic response as narrowing of QRS with a decrease greater than 30 ms or to a total duration of <100 ms. We calculated the ratio of the dose of NaHCO 3 given (in mmol) in relation to the rise in serum sodium concentration (in mmol/L) observed within 6 hours following presentation. ...
Article
Aims: The objectives are to determine the effect of NaHCO3 and/or mechanical ventilation on the biochemical profile and serum alkalinisation in tricyclic antidepressant (TCA) poisoning and investigate the impact of effective alkalinisation therapy on the QRS interval in TCA poisoning. Methods: This was a retrospective review of TCA poisonings from three Australian toxicology units and a poisons information centre (Jan 2013-Jan 2019). We included patients with TCA toxicity who ingested>10mg/kg or had clinically significant toxicities consistent with TCA poisoning, and analysed patients' clinical, electrocardiogram and biochemical data. Results: Of 210 patients, 84 received NaHCO3 and ventilation (dual therapy), 12 NaHCO3 , 46 ventilation and 68 supportive care treatment. When compared with single/supportive groups, patients who received dual therapy had taken a significantly higher median dose of TCA(1.5g vs.1.3g,p<0.001), a longer median maximum QRS interval(124ms,IQR:108-138 vs.106ms, IQR:98-115, p<0.001) and were more likely to have seizures(14% vs.3%,p=0.006) and arrhythmias(17% vs.1%,p<0.001). The dual therapy group demonstrated greater increases in serum pH (median:0.11,IQR:0.04-0.17) compared to the single/supportive therapy group (median:0.03,IQR:-0.01-0.09)(p<0.001). A greater proportion of patients reached target pH 7.45-7.55 in the dual therapy group(59%) compared to the single/supportive therapy group(10%)(p<0.001). For each 100mmol bolus of NaHCO3 given, the median increase in serum sodium was 2.5mmol/L (IQR:1.5-4.0). QRS narrowing occurred twice as quickly in the dual therapy vs. single/supportive therapy group. Conclusions: A combination of NaHCO3 and mechanical ventilation was most effective in achieving serum alkalinisation and was associated with a more rapid narrowing of the QRS interval. We would advise the maximal dose of NaHCO3 should be <400 mmol(6 mmol/kg).
... Second, sodium bicarbonate increases the pH; a higher pH promotes dissociation of TCA from cardiac sodium channels and decreases TCA-induced blockade, primarily causing arrhythmias. [7,12] Third, TCAs are bound to protein in a pH-dependent fashion; in the higher pH range TCAs bind more easily to protein resulting in a lower pharmacologically active TCA concentration. Alkalinisation to a pH of 7.45-7.55 is advised until normalisation of the QRS interval, even in the absence of initial acidosis. ...
... Alkalinisation to a pH of 7.45-7.55 is advised until normalisation of the QRS interval, even in the absence of initial acidosis. [10,12] When the pH becomes >7.6 the risk of dysrhythmias increases. Metabolic and electrolyte disturbances need to be corrected. ...
Article
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Tricyclic antidepressant poisoning is a potentially lethal condition and treatment can be challenging. ECG findings are the most important risk stratification and should be used to guide subsequent therapy. Sodium bicarbonate is the main treatment along with activated charcoal. When high doses of a tricyclic antidepressant are ingested, the anticholinergic effect may be substantial. © 2016, Netherlands Society of Intensive Care. All rights reserved.
... The concentrations in the infusions were most often either 88 or 176 mEq/L and the rates were not specified. Of note, boluses were used without infusion in two of their patients [50]. Shannon et al. also recommend maintaining a sodium bicarbonate infusion to achieve an arterial blood pH of 7.45-7.55 ...
... Please see tables 1 and 2 for a summary of the agents and data presented in this section. Cocaine Case reports [6,7,55,56] C a n i n e [ 42,57] Cyclic antidepressants Case reports, retrospective series [19,50,58,59] Canine, rat, swine [41,[60][61][62][63] Canine Purkinje fibers, human atrial myocytes [64] Diphenhydramine Case report [2,65] Flecainide Case reports [8,66] ...
Article
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.
... The tricyclic antidepressants were analyzed in Cobas 6000 e501 (Roche Dignostics) by the homogeneous enzyme immunoassay technique. The analysis is since the drug present in the sample and the drug marked with the enzyme glucose-6-phosphate dehydrogenase (G6FDH) compete for the conjugation sites of the antibodies [10][11][12][13][14][15][16]. ...
... This will allow more AT to bind to proteins and thereby becoming pharmacologically inactive. In this case, the return of the patient from severely poisoned to a more stable state is caused by the changes in pH [16,26,45] rather than the effect of CAC-HP treatment. ...
Article
Coated Activated Charcoal Hemoperfusion (CAC-HP) does not reduce the plasma concentration in amitriptyline (AT)-poisoned pigs. The aim of this non-blinded, randomised, controlled animal trial was to determine if CAC-HP reduces the pathological ECG changes caused by AT poisoning. Fourteen female Danish Land Race pigs (mean weight 27.7 kg, range 20-35 kg (CAC-HP) and 24.4 kg, range 18-30 kg (control group, CG), n=7 in each group were included. After randomisation, the pigs were anaesthetised and intravenously poisoned with AT. The intervention group underwent 4 hr of CAC-HP plus standard care (oral activated charcoal). Intervention was compared to standard care alone. From each pig, a 12-lead ECG and haemodynamic variables were obtained at baseline, at full AT loading dose, before and during CAC-HP. Baseline ECG variables (RR, PR, QRS, QTc, QTp, QTe, TpTe, and TpTe/QT) for lead II, v2 and v5 were not significantly different (F=0.035 to 0.297, p-values 0.421 to 0.919). Differences within groups over time and between groups were tested by ANOVA repeated measures. For all variables, the time-plus-group level of significance revealed a p-value >0.05. Severe cardiovascular dysrhythmias occurred in both groups with 3 in the CAC-HP group versus 1 incident with premature death in the CG. The attenuating effect of CAC-HP to orally instilled activated charcoal alone on AT-induced ECG alterations did not differ significantly. We conclude that the use of modern CAC-HP as an adjunctive treatment modality in AT-poisoned pigs is inadequate.
... The scientific data on the use of sodium bicarbonate in the management of TCA toxicity is predominantly originated from animal studies, case reports, and case series [32,33]. Sodium bicarbonate is commonly administered as 8.4% solution 1-2 mEq/kg (see Table 1) in cases of TCA associated ECG abnormalities (such as QRS prolongation > 100 msec), hemodynamic compromise, and malignant ventricular arrhythmias [34][35][36]. ...
Article
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Adverse reactions to commonly prescribed medications and to substances of abuse may result in severe toxicity associated with increased morbidity and mortality. According to the Center for Disease Control, in 2013, at least 2113 human fatalities attributed to poisonings occurred in the United States of America. In this article, we review the data regarding the impact of systemic sodium bicarbonate administration in the management of certain poisonings including sodium channel blocker toxicities, salicylate overdose, and ingestion of some toxic alcohols and in various pharmacological toxicities. Based on the available literature and empiric experience, the administration of sodium bicarbonate appears to be beneficial in the management of a patient with the above-mentioned toxidromes. However, most of the available evidence originates from case reports, case series, and expert consensus recommendations. The potential mechanisms of sodium bicarbonate include high sodium load and the development of metabolic alkalosis with resultant decreased tissue penetration of the toxic substance with subsequent increased urinary excretion. While receiving sodium bicarbonate, patients must be monitored for the development of associated side effects including electrolyte abnormalities, the progression of metabolic alkalosis, volume overload, worsening respiratory status, and/or worsening metabolic acidosis. Patients with oliguric/anuric renal failure and advanced decompensated heart failure should not receive sodium bicarbonate.
... After that, a continuous IV infusion of sodium bicarbonate will be started to maintain a blood pH 7.50-7.55 [41]. It is better to taper the bicarbonate therapy before discontinuing it after the clinical improvement of conscious level and improvement, but not necessarily normalization of abnormal ECG findings. ...
Article
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Background In Bangladesh, each emergency physician faces amitriptyline overdose nearly a day. An acute cardiovascular complication, one of the worst complications is mainly responsible for the mortality in tricyclic overdose. Recently, we managed ventricular tachycardia in a young female presented with an impaired consciousness 10 h after intentionally ingesting 2500 mg amitriptyline. Here, we report it, discuss how the electrocardiography is vital to acknowledge and predict it and its’ complications and also the recent update of the management of it. Case presentation A young married Bangladeshi-Bengali girl, 25-year-old, having a history of disharmony with her husband, came with an impaired consciousness after intentionally ingesting 2500 mg amitriptyline about 10 h before arrival. There was blood pressure 140/80 mmHg, heart rate 140 beats-per-min, temperature 103 °F, Glasgow coma scale 10/15, wide complex tachycardia with QRS duration of 178 ms in electrocardiography, blood pH 7.36. Initially, treated with 100 ml 8.4% sodium bicarbonate. After that, QRS duration came to 100 ms in electrocardiography within 10 min of infusion. To maintain the pH 7.50–7.55 over the next 24 h, the infusion of 8.4% sodium bicarbonate consisting of 125 ml dissolved in 375 ml normal saline was started and titrated according to the arterial blood gas analysis. Hence, a total dose of 600 mmol sodium bicarbonate was given over next 24 h. In addition to this, gave a 500 ml intravenous lipid emulsion over 2 h after 24 h of admission as she did not regain her consciousness completely. Afterward, she became conscious, though, in electrocardiography, ST/T wave abnormality persisted. So that, we tapered sodium bicarbonate infusion slowly and stopped it later. At the time of discharge, she was by heart rate 124/min, QRS duration 90 ms in electrocardiogram along with other normal vital signs. Conclusion Diagnosis of amitriptyline-induced ventricular tachycardia is difficult when there is no history of an overdose obtained. Nevertheless, it should be performed in the clinical background and classic electrocardiographic changes and wise utilization of sodium bicarbonate, intravenous lipid emulsion, and anti-arrhythmic drugs may save a life. Keywords: Tricyclic antidepressants Amitriptyline overdoses Amitriptyline-induced ventricular tachycardia Wide complex tachycardia
... After that, a continuous IV infusion of sodium bicarbonate will be started to maintain a blood pH 7.50-7.55 [41]. It is better to taper the bicarbonate therapy before discontinuing it after the clinical improvement of conscious level and improvement, but not necessarily normalization of abnormal ECG findings. ...
... Un bolus de 100 ml de salin hypertonique 3 % peut être réalisé et répété après 10 minutes si besoin. Si l'hypotension persiste, il est recommandé de démarrer un traitement avec du bicarbonate de sodium (1,2). Le traitement est à débuter en cas d'élargissement du QRS > 100 ms ou en cas d'arythmie ventriculaire. ...
Article
Full-text available
Poisoning with tricyclic antidepressants is common and can be life-threatening. The classic management is well known (chelating gastrointestinal, sodium bicarbonate, benzodiazepine, norepinephrine). A few years ago, a treatment with lipid emulsion, previously used in local anesthetics poisoning, has been successfully tested in tricyclic poisoning with cardiac arrest. We are currently unable to explain the exact mechanism of this treatment but it could have a place in the treatment of severe tricyclic poisoning with hemodynamic instability in addition to the conventional treatment.
... Un bolus de 100 ml de salin hypertonique 3 % peut être réalisé et répété après 10 minutes si besoin. Si l'hypotension persiste, il est recommandé de démarrer un traitement avec du bicarbonate de sodium (1,2). Le traitement est à débuter en cas d'élargissement du QRS > 100 ms ou en cas d'arythmie ventriculaire. ...
Article
Full-text available
L'intoxication aux antidépresseurs tricycliques n'est pas rare et peut engager le pronostic vital du patient. La prise en charge classique est bien connue (chélateurs gastro-intestinaux, bicarbonate de sodium, benzodiazépines, amines vasoactives). Il y a quelques années, un traitement par émul-sion lipidique, jusque-là utilisé dans les intoxications aux anes-thésiques locaux, a été testé avec succès dans les intoxications aux tricycliques en arrêt cardio-respiratoire. Nous sommes, actuellement, incapables d'expliquer le fonctionnement exact de ce traitement, mais il pourrait avoir une place dans la prise en charge des intoxications aux tricycliques avec instabilité hémodynamique échappant au traitement conventionnel. mots-clés : Intoxication – Tricyclique – Emulsion lipidique – Etat de choc How I tReat … a poIsonIng wItH tRIcyclIc antIdepRessants : potentIal Role of a tReatment wItH lIpId emulsIon summaRy : Poisoning with tricyclic antidepressants is common and can be life-threatening. The classic management is well known (chelating gastrointestinal, sodium bicarbonate, ben-zodiazepine, norepinephrine). A few years ago, a treatment with lipid emulsion, previously used in local anesthetics poisoning , has been successfully tested in tricyclic poisoning with cardiac arrest. We are currently unable to explain the exact mechanism of this treatment but it could have a place in the treatment of severe tricyclic poisoning with hemodynamic instability in addition to the conventional treatment.
... demonstrated an increase in systolic BP (>15 mm Hg or to >90 mm Hg) within 1 h in 20 of 21 patients and a narrowing of the QRS interval (by >0.03 s or to <0.11 s) within 30 min in 39 of 49 patients. 11 The mechanism by which sodium bicarbonate exerts this effect, however, is unclear. Alkalinisation increases protein binding of TCAs and consequently reduces the concentration of pharmacologically active free drug, which may cause toxicity. ...
Article
A 28-year-old woman was admitted in a comatose state following ingestion of 5 g of amitriptyline. On arrival, there was intermittent seizure activity and a broad complex tachycardia on the ECG. Immediate resuscitation included 8 mg lorazepam, 2 L crystalloid fluid, 100 mL 8.4% sodium bicarbonate, 2 g of magnesium sulphate and lipid emulsion infusion. Despite this, the broad complex tachycardia persisted with haemodynamic instability. The case was discussed with the National Poisons Information Service, which advised further 8.4% sodium bicarbonate to achieve serum alkalinisation. Following this, the QRS duration reduced and haemodynamic stability was achieved. Serum alkalinisation continued in the intensive treatment unit before the patient was successfully extubated on day 5 and discharged on day 7 with no neurological sequelae. To our knowledge, this case is the largest recorded overdose of amitriptyline to have survived to discharge. The importance of serum alkalinisation in the management of tricyclic antidepressant poisoning is highlighted.
... [304][305][306] Give sodium bicarbonate (1-2 mmol kg −1 ) for the treatment of tricyclic-induced ventricular arrhytmias. [307][308][309][310][311][312] While no study has investigated the optimal target arterial pH with bicarbonate therapy, a pH of 7.45-7.55 is recommended. 255,257 Administration of bicarbonate may resolve arrhythmias and reverse hypotension even in the absence of acidosis. ...
... [304][305][306] Give sodium bicarbonate (1-2 mmol kg −1 ) for the treatment of tricyclic-induced ventricular arrhytmias. [307][308][309][310][311][312] While no study has investigated the optimal target arterial pH with bicarbonate therapy, a pH of 7.45-7.55 is recommended. 255,257 Administration of bicarbonate may resolve arrhythmias and reverse hypotension even in the absence of acidosis. ...
... Evidence of sodium channel antagonist effects (QRS widening on a 12-lead ECG, seizure activity) can occur in poisoning with some BB agents, such as propranolol and labetalol. Treatment might need to include serum alkalinization with intravenous hypertonic sodium bicarbonate, as used in cyclic antidepressant poisoning [6]. The clinical effects of toxicity are summarized in Table 1. ...
Article
Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs may also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This may also be the case for some BBs. Peak toxicity may be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole bowel irrigation may mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings to improve myocardial contractility and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in treatment of vasodilatory shock. Optimising serum calcium concentration may confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which may limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock.
... tricyclic antidepressants, cocaine, IA and IC antiarrhythmics, or antipsychotic drugs) bicarbonate therapy can be used to lessen the degree of sodium channel blockade through increased extra-cellular sodium ( figure 4). 11,[75][76][77][78] Saline appears to be less effective than sodium bicarbonate because some QRS-prolonging drugs are proposed to have a pH-dependent binding to the sodium channels, with less extensive binding at higher pH. The recommended pH level with bicarbonate treatment is between 7.50 and 7.55. ...
Article
Many drugs can significantly inf luence cardiac repolarisation causing an increased duration of this repolarisation phase, challenging the repolarisation reserve. This may set the stage for life-threatening ventricular arrhythmias such as torsades de pointes (TdP). TdP generally occurs in conjunction with a prolonged QT interval (QT) on the electrocardiogram. The Dutch Poisons Information Centre (NVIC) often receives information requests about drugs that can influence the QT already at therapeutic dosages. Drug-induced QT prolongation is dose dependent and hence can be particularly pronounced in overdose situations. Also, additional risk factors for the development of life-threatening arrhythmias are often present in intoxicated patients. This review focuses on identification and management of drug-intoxicated patients who are at risk for a reduction in their repolarisation reserve, measured by their QT interval. The QT interval is strongly dependent on heart rate, which has led to the introduction of different methods to adjust the QT interval, i.e. the QTc. Bazett's formula, which has been used for decades, lacks accuracy concerning QTc calculation at higher and lower heart rates, situations often relevant when dealing with intoxicated patients. Additionally, we highlight drugs with QT-prolonging potential that are commonly associated with an overdose setting in the Netherlands. Finally, standard treatment options specifically pointed toward the intoxicated patient at risk of QT prolongation and TdP will be discussed.
... QRS duration can be shortened in experimental animals and in humans by administration of NaHCO 3 or NaCl boluses (299). Antipsychotic agents well known to produce marked QT prolongation and torsades de pointes include thioridazine and haloperidol. ...
... Tricyclic antidepressants commonly cause death when taken in overdose (Henry, 1997). Intravenous sodium bicarbonate has been the most frequently used management for tricyclic antidepressant toxicity (Hoffman et al., 1993;Koppel et al., 1992). Amitriptyline (AMI), a commonly used tricyclic antidepressant, is highly bound (91 -95%) to AAG in plasma (Borga et al., 1970(Borga et al., , 1969 and it has been suggested that the administration of exogenous a 1 -acid glycoprotein (AAG), an 'acute phase' protein, may reduce the severity of tricyclic antidepressant toxicity. ...
Article
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Tricyclic antidepressants in overdose cause toxicity marked by prolongation of the QRS interval of the electrocardiogram. These drugs are bound to α1-acid glycoprotein (AAG) with high affinity in plasma. Animal studies have shown that the administration of AAG shortens the QRS prolongation induced by tricyclic antidepressants. In order to clarify the pharmacological mechanism involved and to obtain clinically relevant evidence at the cellular level, whole-cell patch clamp techniques were performed in single guinea-pig ventricular myocytes to elicit the time and voltage-dependent fast sodium currents using both normal and modified physiological solutions. Cells stayed viable for much longer when they were placed in normal physiological solutions, providing sufficient recording time for consistently reproducible, clinically relevant toxicological results to be obtained. Amitriptyline (AMI) produced a concentration-dependent blockade of sodium currents with an approximate IC50 of 0.69 μM. AAG reversed this blockade in a concentration-dependent fashion at concentrations ranging from 3.2 to 12.8 μM. Using the same experimental conditions, AAG also reversed the blockade of sodium current by quinidine, a class I antiarrythmic drug. Albumin did not reverse the blockade of sodium channels by AMI. The results indicate that AAG is a potential antidote for tricyclic antidepressant overdose.
Article
Background: The 2010 Advanced Cardiac Life Support guidelines stated that routine sodium bicarbonate (SB) use for cardiac arrest patients was not recommended. However, SB administration during resuscitation is still common. Objectives: To evaluate the effect of SB on return of spontaneous circulation (ROSC) and survival-to-discharge rates in adult cardiac arrest patients. Methods: We searched Medline, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to December 2019. We included trials on nontraumatic adult patients after cardiac resuscitation and SB treatment vs. controls. Results: A meta-analysis was performed with six observational studies, including 18,406 adult cardiac arrest patients. There were no significant differences in the ROSC rate (odds ratio [OR] 1.185; 95% confidence interval [CI] 0.680-2.065) and survival-to-discharge rate (OR 0.296; 95% CI 0.066-1.323) between the SB and no-SB groups. In the subgroup analysis based on the year factor, there were no significant differences in the mortality rate in the After-2010 group. In the subgroup analysis based on the continent, the ROSC rate (OR 0.521; 95% CI 0.432-0.628) and survival-to-discharge rate (OR 0.102; 95% CI 0.066-0.156) were significantly lower in the North American group. Conclusions: SB use was not associated with improvement in ROSC or survival-to-discharge rates in cardiac resuscitation. In addition, mortality was significantly increased in the North American group with SB administration.
Article
Background Sodium bicarbonate therapy (SBT) is currently indicated for the management of a variety of acute drug poisonings. However, SBT effects on serum potassium concentrations may lead to delayed QTc prolongation (DQTP), and subsequent risk of adverse cardiovascular events (ACVE), including death. Emergency department (ED)–based studies evaluating associations between SBT and ACVE are limited; thus, we aimed to investigate the association between antidotal SBT, ECG changes, and ACVE.Methods This was a secondary data analysis of a consecutive cohort of ED patients with acute drug overdose over 3 years. Demographic and clinical data as well as SBT bolus dosage and infusion duration were collected, and outcomes were compared with an unmatched consecutive cohort of patients with potential indications for SBT but who did not receive SBT. The primary outcome was the occurrence of ACVE, and secondary outcomes were delayed QTc (Bazett) prolongation (DQTP), and death. Propensity score and multivariable adjusted analyses were conducted to evaluate associations between adverse outcomes and SBT administration. Planned subgroup analysis was performed for salicylates, wide QRS (> 100 ms), and acidosis (pH < 7.2).ResultsOut of 2365 patients screened, 369 patients had potential indications for SBT, of whom 31 (8.4%) actually received SBT. In adjusted analyses, SBT was found to be a significant predictor of ACVE (aOR 9.35, CI 3.6–24.1), DQTP (aOR 126.7, CI 9.8–1646.2), and death (aOR 11.9, CI 2.4–58.9). Using a propensity score model, SBT administration was associated with ACVE (OR 5.07, CI 1.8–14.0). Associations between SBT and ACVE were maintained in subgroup analyses of specific indications for sodium channel blockade (OR 21.03, CI 7.16–61.77) and metabolic acidosis (OR: 6.42, 95% CI: 1.20, 34.19).Conclusion In ED patients with acute drug overdose and potential indications for SBT, administration of SBT as part of routine clinical care was an independent, dose-dependent, predictor of ACVE, DQTP, and death. This study was not designed to determine whether the SBT or acute overdose itself was causative of ACVE; however, these data suggest that poisoned patients receiving antidotal SBT require close cardiovascular monitoring.
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Amitriptyline poisoning (AT) is a common poisoning, and AT possess the ability to promote life-threatening complications by its main action on the central nervous and cardiovascular systems. The pharmacokinetic properties might be altered at toxic levels compared to therapeutic levels. The effect of coated activated charcoal hemoperfusion (CAC-HP) on the accumulation of AT and its active metabolite nortriptyline (NT) in various tissues was studied in a non-blinded randomized controlled animal trial including 14 female Danish Land Race piglets. All piglets were poisoned with amitriptyline 7.5 mg/kg infused in 20 min, followed by orally instilled activated charcoal at 30 min after infusion cessation. The intervention group received 4 h of CAC-HP followed by a 1-h redistribution phase. At study cessation, the piglets were euthanized, and within 20 min, vitreous fluid, liver tissue, ventricle and septum of the heart, diaphragm and lipoic and brain tissues were collected. AT and NT tissue concentrations were quantified by UHPLC-MS/MS. A 4-h treatment with CAC-HP did not affect the tissue accumulation of AT in the selected organs when tested by Mann-Whitney U test (p values between 0.44 and 0.73). For NT concentrations, p values were between 0.13 and 1.00. Although not significant, an interesting finding was that data showed a tendency of increased tissue accumulation of AT and NT in the CAC-HP group compared with the control group. Coated activated charcoal hemoperfusion does not significantly alter the tissue concentration of AT and NT in the AT-poisoned piglet.
Article
Acute drug poisoning due to accidental or self-damaging overdoses is responsible for 5-10% of emergency medical interventions in Germany. The treatment of asymptomatic to life-threatening courses requires extensive expertise. On the basis of a selective literature search, this article gives an overview of selected clinically relevant, acute drug poisonings with regard to epidemiology, symptomatology, diagnostics, and therapy.Intoxications with psychotropic drugs are the most common drug intoxications. Poisoning with tricyclic antidepressants causes anticholinergic, central nervous, and cardiovascular symptoms. Less toxic are selective serotonin reuptake inhibitors (SSRIs); the intoxication may be characterized by serotonin syndrome. Malignant neuroleptic syndrome is a severe complication of neuroleptic poisoning.Poisoning with analgesics is clinically relevant due to its high availability. For paracetamol poisoning, intravenous acetylcysteine is available as an antidote. Hemodialysis may be indicated for severe salicylate intoxication. Poisoning with nonsteroidal anti-inflammatory drugs is usually only associated with mild signs of intoxication.Poisoning with cardiac drugs (β-blockers and calcium antagonists) can cause life-threatening cardiovascular events. In addition to symptomatic therapy, insulin glucose therapy also plays an important role.The majority of acute drug poisonings can be treated adequately by symptomatic and partly intensive care therapy - if necessary with the application of primary and secondary toxin elimination. Depending on the severity of the intoxication, pharmacology-specific therapy must be initiated.
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Zu den psychotropen Substanzen gehören die therapeutisch indizierten Psychopharmaka. Vergiftungen durch sie treten bei Suizidversuchen oder fehlerhafter Dosierung auf. Andere psychotrope Substanzen werden aufgrund ihrer stimulierenden oder halluzinogenen Wirkung eingenommen Sie haben oft ein starkes Suchtpotenzial und Vergiftungen sind in der Regel Folge akzidenteller Überdosierungen. Zur Behandlung stehen mit Flumazenil für die Benzodiazepinvergiftung und mit Naloxon für die Opiatüberdosierung spezifische Antagonisten zur Verfügung. Bei Vergiftung mit trizyklischen Antidepressiva wird Natriumbikarbonat gegeben, das auch bei einer Kardiotoxizität durch Intoxikationen mit Serotoninwiederaufnahmehemmern oder Neuroleptika wirksam ist. Torsades-de-Pointes-Tachykardien werden mit Defibrillation und Magnesium therapiert. Die Behandlung von Vergiftungen mit Stimulanzien und Halluzinogenen erfolgt symptomatisch. β‑Blocker sind bei Intoxikationen mit Kokain und Amphetaminderivaten zu vermeiden.
Chapter
The use of the cyclic antidepressants (CAs) in the treatment of major depression has decreased as newer and safer antidepressants have become available. Cyclic Antidepressants historically have been primarily used to treat major depression but are still prescribed for other psychiatric and medical conditions, such as chronic pain syndromes (e.g., fibromyalgia), peripheral neuropathy, nocturnal enuresis, migraine headache, selected drug withdrawal syndromes, and obsessive-compulsive, attention-deficit, panic and phobia, anxiety, and eating disorders [1, 2]. The CAs are associated with a low therapeutic index, potential severe cardiotoxicity in overdose, and a high frequency of adverse effects secondary to their nonspecific pharmacologic actions. Although CA use is less than it once was, the CAs remain on the 2014 American Association of Poison Control Centers’ list of Top 25 Categories of Substances associated with fatalities [1, 3].
Chapter
Physostigmine salicylate (Antilirium®) is a short-acting, lipid-soluble, nonselective, carbamate cholinesterase (ChE) inhibitor used to increase acetylcholine (ACh) concentrations at cholinergic receptors and most commonly employed in the treatment of anticholinergic-induced delirium. Physostigmine was the first known anticholinesterase used by humans. The native Efik people of West Africa used dried, ripened Calabar beans () containing the alkaloid physostigmine in their “trial by ordeal” [1, 2]. First described in 1840, the Old Calabar “trial by ordeal” required an accused individual to consume 1–20 Calabar beans in various fashions. If the individual vomited (and thus cleared the gastric bean burden), he was deemed innocent; if emesis did not occur, a cholinergic crisis followed by death was considered a guilty verdict. Predictably, very few accused survived their ordeal [1].
Chapter
Therapeutic administration of sodium bicarbonate (NaHCO3) has the ability to alter xenobiotic pharmacokinetic properties, pharmacodynamic profile, or both. Sodium bicarbonate is available generically as 4.2%, 7.5%, and 8.4% intravenous solutions in water. NaHCO3 is also available as a 500 milliliter (mL) 5% solution and as tablets; however, for purposes of this discussion, only the intravenous solution will be considered. The milliequivalent (mEq) and milliosmolar (mOsm) content of each percentage is included in Table 1 [1]. Due to its decreased osmolality, the 4.2% solution is often preferred for pediatric patients.
Chapter
Management of a critically ill patient with cardiovascular disturbances requires the clinician to consider that a cardiac toxin may be involved. This chapter emphasizes recognition of cardiac arrhythmias, conduction abnormalities, and specific electrocardiogram (ECG) findings that might suggest the involvement of a cardiovascular toxin. First, relevant cardiac physiology and the toxic mechanisms pertinent to poisonings and overdose are reviewed. Next, we describe a clinical approach to the recognition and management of patients with rate and rhythm disturbances from cardiovascular toxins. Lastly, we discuss some specific cardiovascular toxins that show how autonomic disturbances, membrane-depressant effects, triggered rhythms, and systemic influences produce the protean manifestations of a patient with cardiac poisoning.
Chapter
According to the National Poison Data System (NPDS) of the American Association of Poison Control Centers, in 2014 poisoning in children under the age of 20 accounted for 61% of calls to poison centers in the United States [1]. The proportion of those cases that required referral to a health care facility (HCF) varied. 12.7% of children ≤5 years and only 16.5% of children between 6 and 12 years were managed in an HCF compared to 61.1% of teenagers (13–19 years). The proportion of children described as having a “Major Effect” rose from 0.07% in the under 5 age group to 1.65% in teenagers. The fatality rate was highest in the teen group (0.05%), where more than one half of ingestions are intentional versus the under 5 age group (<0.002%) where 99.5% of exposures are unintentional. The number of pediatric deaths among cases reported to US poison centers was 88. These figures have remained consistent over the past several years.
Chapter
Antidysrhythmics achieve their therapeutic goals of rhythm control through blockade or antagonism of various cardiac channels or receptors. In the Vaughan Williams convention [1], which endures despite its limitations due to its simplicity and clinical applicability, class I antidysrhythmic agents block the cardiac sodium channel by intent. As highlighted by the Cardiac Arrhythmia Suppression Trials (CAST I and II) of encainide, flecainide, and the subsequently withdrawn moracizine, these agents have the potential to increase mortality even at therapeutic dosing [2]. Cardiac sodium channel blockade may be an “on target” effect of class I agents or antidysrhythmics from other Vaughan Williams classes or an “off target” effect of a host of agents from multiple pharmaceutical classes, including antibiotics, antiepileptic drugs; cyclic, selective serotonin reuptake inhibitor, and serotonin–norepinephrine reuptake inhibitor antidepressants; antihistamines; antipsychotics; amide and ester local anesthetics; mood stabilizers; and opioids (Tables 1 and 2). Of note, this sodium channel blockade may be identified by other terminology, e.g., the “membrane-stabilizing effects” of certain beta-adrenergic antagonists or eponymous “local anesthetic effects.”
Article
Poisonings remain a frequent source of morbidity and mortality in the pediatric age group. All pediatricians, whether in training or in practice, encounter these patients, yet toxicologic training is lacking in most pediatric residencies. Objectives After completing this article, readers should be able to: 1. Understand the epidemiology of pediatric poisonings and explain how developmental milestones influence behavior that may lead to a poisoning exposure. 2. Perform a focused toxicologic physical examination and describe the various toxidromes. 3. Explain the primary acid-base disturbance in salicylate toxicity. 4. Determine which patient requires treatment after acute acetaminophen ingestion. 5. Provide the differential diagnosis of an anion gap metabolic acidosis. 6. Identify which drugs can lead to QRS and QTc prolongation and the treatment for each abnormality. 7. Describe the toxicologic differential diagnosis for hypoglycemia and explain the physiologic reasons why pediatric patients are at increased risk for complications. © 2017 by the American Academy of Pediatrics. All rights reserved.
Article
Treating patients with psychiatric problems can present numerous challenges for clinicians. The deliberate self-ingestion of antidepressants is one such challenge frequently encountered in hospitals throughout the United States. This review focuses on 1) the classes of antidepressants, their pharmacologic properties, and some of the proposed mechanism(s) for antidepressant overdose-induced seizures; 2) the evidence for seizures caused by antidepressants in overdose; 3) management strategies for patients who have intentionally or unintentionally overdosed on an antidepressant, or who have experienced an antidepressant overdose-induced seizure.
Chapter
According to the National Poison Data System (NPDS) of the American Association of Poison Control Centers, in 2014 poisoning in children under the age of 20 accounted for 61 % of calls to poison centers in the United States [1]. The proportion of those cases that required referral to a health care facility (HCF) varied. 12.7 % of children ≤5 years and only 16.5 % of children between 6 and 12 years were managed in an HCF compared to 61.1 % of teenagers (13–19 years). The proportion of children described as having a “Major Effect” rose from 0.07 % in the under 5 age group to 1.65 % in teenagers. The fatality rate was highest in the teen group (0.05 %), where more than one half of ingestions are intentional versus the under 5 age group (<0.002 %) where 99.5 % of exposures are unintentional. The number of pediatric deaths among cases reported to US poison centers was 88. These figures have remained consistent over the past several years.
Chapter
The use of the cyclic antidepressants (CAs) in the treatment of major depression has decreased as newer and safer antidepressants have become available. Cyclic Antidepressants historically have been primarily used to treat major depression but are still prescribed for other psychiatric and medical conditions, such as chronic pain syndromes (e.g., fibromyalgia), peripheral neuropathy, nocturnal enuresis, migraine headache, selected drug withdrawal syndromes, and obsessive-compulsive, attention-deficit, panic and phobia, anxiety, and eating disorders [1, 2]. The CAs are associated with a low therapeutic index, potential severe cardiotoxicity in overdose, and a high frequency of adverse effects secondary to their nonspecific pharmacologic actions. Although CA use is less than it once was, the CAs remain on the 2014 American Association of Poison Control Centers’ list of Top 25 Categories of Substances associated with fatalities [1, 3].
Chapter
Physostigmine salicylate (Antilirium®) is a short-acting, lipid-soluble, nonselective, carbamate cholinesterase (ChE) inhibitor used to increase acetylcholine (ACh) concentrations at cholinergic receptors and most commonly employed in the treatment of anticholinergic-induced delirium. Physostigmine was the first known anticholinesterase used by humans. The native Efik people of West Africa used dried, ripened Calabar beans () containing the alkaloid physostigmine in their “trial by ordeal” [1, 2]. First described in 1840, the Old Calabar “trial by ordeal” required an accused individual to consume 1–20 Calabar beans in various fashions. If the individual vomited (and thus cleared the gastric bean burden), he was deemed innocent; if emesis did not occur, a cholinergic crisis followed by death was considered a guilty verdict. Predictably, very few accused survived their ordeal [1].
Chapter
Therapeutic administration of sodium bicarbonate (NaHCO3) has the ability to alter xenobiotic pharmacokinetic properties, pharmacodynamic profile, or both. Sodium bicarbonate is available generically as 4.2 %, 7.5 %, and 8.4 % intravenous solutions in water. NaHCO3 is also available as a 500 milliliter (mL) 5 % solution and as tablets; however, for purposes of this discussion, only the intravenous solution will be considered. The milliequivalent (mEq) and milliosmolar (mOsm) content of each percentage is included in Table 1 [1]. Due to its decreased osmolality, the 4.2 % solution is often preferred for pediatric patients.
Chapter
Management of a critically ill patient with cardiovascular disturbances requires the clinician to consider that a cardiac toxin may be involved. This chapter emphasizes recognition of cardiac arrhythmias, conduction abnormalities, and specific electrocardiogram (ECG) findings that might suggest the involvement of a cardiovascular toxin. First, relevant cardiac physiology and the toxic mechanisms pertinent to poisonings and overdose are reviewed. Next, we describe a clinical approach to the recognition and management of patients with rate and rhythm disturbances from cardiovascular toxins. Lastly, we discuss some specific cardiovascular toxins that show how autonomic disturbances, membrane-depressant effects, triggered rhythms, and systemic influences produce the protean manifestations of a patient with cardiac poisoning.
Chapter
Antidysrhythmics achieve their therapeutic goals of rhythm control through blockade or antagonism of various cardiac channels or receptors. In the Vaughan Williams convention [1], which endures despite its limitations due to its simplicity and clinical applicability, class I antidysrhythmic agents block the cardiac sodium channel by intent. As highlighted by the Cardiac Arrhythmia Suppression Trials (CAST I and II) of encainide, flecainide, and the subsequently withdrawn moracizine, these agents have the potential to increase mortality even at therapeutic dosing [2]. Cardiac sodium channel blockade may be an “on target” effect of class I agents or antidysrhythmics from other Vaughan Williams classes or an “off target” effect of a host of agents from multiple pharmaceutical classes, including antibiotics, antiepileptic drugs; cyclic, selective serotonin reuptake inhibitor, and serotonin–norepinephrine reuptake inhibitor antidepressants; antihistamines; antipsychotics; amide and ester local anesthetics; mood stabilizers; and opioids (Tables 1 and 2). Of note, this sodium channel blockade may be identified by other terminology, e.g., the “membrane-stabilizing effects” of certain beta-adrenergic antagonists or eponymous “local anesthetic effects.”
Article
Poisoning with impaired mental state is a frequent cause for hospital admission. The initial management includes assessment of vital functions and airway management followed by focussed diagnostics. Poison Emergency Centers can provide valuable assistance in acute intoxications. Clinically important agents causing mental state alterations include opiates, benzodiazepines, tricyclic antidepressants, alcohol, methanol and ethylene glycol, carbon monoxide and salicylates. Most important therapeutic measures comprise supportive care, decontamination or elimination. For certain toxins specific antidotes are available. In presence of severe intoxications and impaired vital functions, the patient should be transferred to the intensive care unit (ICU). © Georg Thieme Verlag KG Stuttgart · New York.
Chapter
This online resource is a case-based guide to challenging areas in emergency medicine, and covers the core and sub-specialty areas, in particular the often grey areas of intensive care and paediatric emergency medicine. Complex cases are comprehensively examined from a multidisciplinary perspective with detailed consideration given to management options and the contemporary evidence base behind these decisions. An effective revision aid for MCEM and FCEM and a reference during workplace-based assessments, Challenging Concepts in Emergency Medicine highlights critical information through the use of boxed features: 'Learning points', 'Clinical tips', 'Evidence base', and 'Future advances'. Each chapter has been reviewed by a national or international expert in the field and they have provided an 'Expert commentary', giving a unique insight into how today's opinion leaders confront and deal with the very same management challenges that all clinicians can potentially face on a daily basis.
Article
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Imipramine, a tricyclic antidepressant (TCA), is used for the treatment of non-polar depression and nocturnal enuresis in children in whom an organic pathology has been excluded, anxiety disorders, and neuropathic pain. Clinical toxicity following the treatment of TCAs, including imipramine, is well known. The anticholinergic effects initially present include a dry mouth, ileus, dilated pupils, urinary retention, and mild sinus tachycardia. The central nervous system toxicity includes delirium, agitation, restlessness, hallucinations, convulsions, and CNS depression or coma. However, the most life-threatening toxicity remains the development of cardiac dysrhythmias. Conduction delays such as QRS and corrected QT prolongation, wide QRS complex tachycardia, and the Brugada electrocardiographic pattern have been reported. Sodium bicarbonate decreases QRS widening and suppresses dysrhythmias by providing excess sodium to reverse the TCA-induced sodium-channel blockade and possibly by binding directly to the myocardium. There are no pediatric case reports on imipramine or other TCA associated toxicity in Korea. Here, we describe a patient who presented with convulsions, tachycardia with a wide QRS complex, a Brugada electrocardiographic pattern, and anuresis associated with an accidental overdose of imipramine and the outcome of treatment with sodium bicarbonate.
Article
During cyclic antidepressant poisoning, seizures occur in 10.7 ± 8% of cases Seizures are often multiple and noticed to occur early after the patient has been monitored. They are best heralded with the best sensitivity by ECG. Some patients experience severe postictal cardiovascular complications. The deleterious effects of cyclic antidepressant-induced seizures on the cardiovascular system are probably due to associated hypoxemia, acidosis and/or tachycardia. These pathophysiological factors are known to amplify directly or indirectly the cyclic antidepressant membrane-stabilizing effect. Concerning the prevention and treatment of seizures all remains to be studied: who, when and how? Can we reduce the seizures induced cardiovascular complications? These questions are important since the mortality rate due to this frequent intoxication is between 2 and 3%. Currently, we only can make propositions that are based on a review of literature.
Article
To review the most common drugs implicated in overdoses admitted to the intensive care unit focusing on antidotes and reversal agents used in their management. Poisonings and overdoses due to pharmaceutical agents result in more than 100 000 critical care unit admissions each year. Ingestion of toxic alcohols, calcium channel blockers, beta-adrenergic antagonists, benzodiazepines, opioids, acetaminophen, tricyclic antidepressants, and salicylates are associated with a high rate of morbidity and mortality. Reviewing the mechanism of toxicity due to specific agents along with the mechanism of action, dosing, and adverse effects of appropriate antidotes is important for the successful management of these patients within the critical care unit. Understanding the most prevalent overdoses and their management using reversal agents and antidotes is essential to the overall treatment of these critically ill patients.
Article
Full-text available
Significant advances in diagnosis and management of tricyclic antidepressant overdose have occurred in recent years. This article reviews epidemiologic, pharmacologic, and therapeutic information to provide a systematic approach to these potentially life-threatening overdoses. The tricyclics are discussed as a group, with individual drugs specified when established differences exist.
Article
Full-text available
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.
Article
Deaths from tricyclic antidepressant (TCA) overdose are usually due to arrhythmias and/or hypotension. Tricyclic antidepressant toxicity is due mainly to the quinidine-like actions of these drugs on cardiac tissues. Slowing of phase 0 depolarisation of the action potential results in slowing of conduction through the His-Purkinje system and myocardium. Slowed impulse conduction is responsible for QRS prolongation and atrioventricular block, and contributes to ventricular arrhythmias and hypotension. Therapies that improve conduction, e.g. hypertonic sodium bicarbonate, are useful in treating these toxic effects. Other mechanisms contributing to arrhythmias include abnormal repolarisation, impaired automaticity, cholinergic blockade and inhibition of neuronal catecholamine uptake. Toxicity may be worsened by acidaemia, hypotension or hyperthermia. Sinus tachycardia is due to the anticholinergic effects of the tricyclic antidepressants as well as blockade of neuronal catecholamine reuptake. Sinus tachycardia is generally well-tolerated and requires no therapy. Sinus tachycardia with QRS prolongation may be difficult to distinguish from ventricular tachycardia. Electrocardiograms obtained using oesophageal or atrial electrodes may be useful in determining the relationship of atrial and ventricular activity. Although QRS prolongation alone is not compromising, it is a marker for patients at highest risk of developing seizures, arrhythmias or hypotension. Ventricular tachycardia (monomorphic) is a consequence of impaired myocardial depolarisation and impulse conduction. Hypertonic sodium bicarbonate may partially correct impaired conduction and be of benefit in treating ventricular tachycardia. Since hypertonic sodium bicarbonate appears to act by increasing the extracellular sodium concentration as well as by increasing extracellular pH, hyperventilation may be less effective. Hypertonic sodium bicarbonate is of particular benefit in patients who are acidotic, since acidosis aggravates cardiac toxicity. However, administration of hypertonic sodium bicarbonate is beneficial even when blood pH is normal Lignocaine (lidocaine) may be useful in treating ventricular tachycardia but should be administered cautiously to avoid precipitating seizures. Ventricular bradyarrhythmias are due to impaired automaticity or depressed atrioventricular conduction and can be treated by placement of a temporary pacemaker, or with a chronotropic agent, e.g. isoprenaline (isoproterenol), with or without concomitant vasoconstrictors. Ventricular fibrillation is unusual with tricyclic antidepressant toxicity and often represents an agonal rhythm. Treatment is empirical; antiarrhythmic agents that impair conduction (type Ia or Ic) or repolarisation [type Ia or III (bretylium, amiodarone)] should be avoided. Hypotension may aggravate tricyclic antidepressant-induced arrhythmias by impairing myocardial perfusion or causing systemic acidosis. Hypotension should be treated with hypertonic sodium bicarbonate if cardiac contractility is impaired, and with fluids if cardiac filling pressure is low. Inotropic agents may worsen or precipitate tachyarrhythmias and should be reserved for refractory hypotension. Other factors that may aggravate arrhythmias, e.g. hyperthermia, hypoxaemia and electrolyte imbalance, should be corrected. Seizures, and the resulting acidaemia, should be treated promptly. The role of phenytoin (diphenylhydantoin) and haemoperfusion in treating arrhythmias due to tricyclic antidepressant overdose are unclear, and their routine clinical use is not supported.
Article
Tricyclic antidepressant overdosage may be complicated by cardiac arrhythmias, which were sometimes difficult to treat prior to the use of sodium bicarbonate. Experiments have been done with several antiarrhythmics in an attempt to define the optimum treatment. Sodium bicarbonate proved the most effective experimentally and this supports our clinical experience. Physostigmine is a useful second drug, having beneficial effects against arrhythmias and central nervous system manifestations of toxicity. Practolol, although reversing the arrhythmias, tends to cause hypotension. Other drugs tried were less effective.
Article
Sodium bicarbonate has modified or reversed arrhythmias due to tricyclic antidepressants in 11 children. It has proved to be the most clinically effective method of treatment of these arrhythmias in children, and reference is made to experimental studies which support this view.
Article
Following intravenous administration of physostigmine salicylate for tricyclic antidepressant poisoning in 21 patients, convulsions occurred in two patients, and severe cholinergic manifestations occurred in two others. Because of these untoward effects and the very short duration of its beneficial action, it is very doubtful that physostigmine has any place in the routine management of tricyclic antidepressant poisoning.
Article
This article has no abstract; the first 100 words appear below. THE total number of patients who present at emergency departments because of drug overdose is difficult to ascertain, but in many facilities it is inordinately high. In one urban hospital, for example, overdoses and other drug-related emergencies are responsible for 38 percent of visits to the emergency department.¹ Toxicologic emergencies may in fact constitute a public health crisis.¹ In 1990 the American Association of Poison Control Centers (AAPCC) documented 1,713,465 reports of human exposure to toxins that resulted in consultations with a poison center; 10 percent of these exposures were considered intentional.² These data do not include drug overdoses that . . . Source Information From the Colorado Emergency Medicine Research Center and the Division of Emergency Medicine and Trauma, Department of Surgery, University of Colorado Health Sciences Center, Denver. Address reprint requests to Dr. Kulig at the University of Colorado Health Sciences Center, Campus Box B215, 4200 E. Ninth Ave., Denver, CO 80262.
Article
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.
Article
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)
Article
Deaths from tricyclic antidepressant (TCA) overdose are usually due to arrhythmias and/or hypotension. Tricyclic antidepressant toxicity is due mainly to the quinidine-like actions of these drugs on cardiac tissues. Slowing of phase 0 depolarisation of the action potential results in slowing of conduction through the His-Purkinje system and myocardium. Slowed impulse conduction is responsible for QRS prolongation and atrioventricular block, and contributes to ventricular arrhythmias and hypotension. Therapies that improve conduction, e.g. hypertonic sodium bicarbonate, are useful in treating these toxic effects. Other mechanisms contributing to arrhythmias include abnormal repolarisation, impaired automaticity, cholinergic blockade and inhibition of neuronal catecholamine uptake. Toxicity may be worsened by acidaemia, hypotension or hyperthermia. Sinus tachycardia is due to the anticholinergic effects of the tricyclic antidepressants as well as blockade of neuronal catecholamine reuptake. Sinus tachycardia is generally well-tolerated and requires no therapy. Sinus tachycardia with QRS prolongation may be difficult to distinguish from ventricular tachycardia. Electrocardiograms obtained using oesophageal or atrial electrodes may be useful in determining the relationship of atrial and ventricular activity. Although QRS prolongation alone is not compromising, it is a marker for patients at highest risk of developing seizures, arrhythmias or hypotension. Ventricular tachycardia (monomorphic) is a consequence of impaired myocardial depolarisation and impulse conduction. Hypertonic sodium bicarbonate may partially correct impaired conduction and be of benefit in treating ventricular tachycardia. Since hypertonic sodium bicarbonate appears to act by increasing the extracellular sodium concentration as well as by increasing extracellular pH, hyperventilation may be less effective. Hypertonic sodium bicarbonate is of particular benefit in patients who are acidotic, since acidosis aggravates cardiac toxicity. However, administration of hypertonic sodium bicarbonate is beneficial even when blood pH is normal. Lignocaine (lidocaine) may be useful in treating ventricular tachycardia but should be administered cautiously to avoid precipitating seizures. Ventricular bradyarrhythmias are due to impaired automaticity or depressed atrioventricular conduction and can be treated by placement of a temporary pacemaker, or with a chronotropic agent, e.g. isoprenaline (isoproterenol), with or without concomitant vasoconstrictors.(ABSTRACT TRUNCATED AT 400 WORDS)
Article
Sodium bicarbonate has been successfully used clinically to treat arrhythmias induced by tricyclic antidepressant drugs (imipramine, amitriptyline, nortriptyline, dibenzepin). Experiments conducted on puppies showed that arrhythmias caused by amitriptyline disappear when acidosis is adequately treated. Plasma protein binding of amitriptyline increases as pH rises, reducing the unbound fraction of drug. This mechanism is an important factor in the antiarrhythmic action of sodium bicarbonate in tricyclic antidepressant overdosage.
Article
Alkalinization of the blood by administration of sodium bicarbonate or hyperventilation is widely recommended for treatment of cardiac toxicity due to tricyclic antidepressant overdose, yet its efficacy and mechanism of action are poorly defined. We studied the effects and possible mechanism of action of 1 M NaHCO3 on desipramine (DMI) toxicity in anesthetized, paralyzed rats. Administration of DMI (45 mg/kg i.p.) produced a mean increase in QRS duration of 142% and a mean decrease in mean arterial pressure of 46%. Treatments were administered i.v. 35 min after DMI and their effects were assessed 10 min later. NaHCO3 (1 M) at doses of 3 and 6 mEq/kg decreased mean QRS duration 15 +/- 5 and 24 +/- 6%, respectively (mean +/- S.D.) and was superior to no treatment (P less than .01). NaCl (1 M) was as effective as NaHCO3 in decreasing QRS duration, as was 1 M NaHCO3 supplemented with 48 mM KCl. Respiratory alkalosis and 10% mannitol did not decrease QRS duration. NaHCO3, NaCl and NaHCO3/KCl all produced comparable increases in mean arterial blood pressure. Respiratory alkalosis and mannitol did not increase mean arterial pressure, but did prevent the decline seen in control animals. Acidosis produced by ventilation with 10% CO2 exacerbated QRS prolongation due to DMI. In acidotic animals, NaHCO3 and NaCl were equally effective in reversing QRS prolongation and hypotension. Correction of respiratory acidosis by discontinuation of inhaled CO2 did not improve QRS duration or mean arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Amitriptyline intoxication can result in severe ventricular arrhythmias that may be refractory to medical management. The mechanisms of these arrhythmias are unclear, and their optimal management is problematic. We studied the cardiac effects of amitriptyline infusion in anesthetized and awake dogs. Amitriptyline significantly increased heart rate, QRS duration, and AH and HV intervals. The concentration-response curves for these effects were, however, quite different, with significant changes beginning at a concentration of 1.5 +/- 0.4 mg/L for heart rate, compared with 2.4 +/- 0.4 mg/L for QRS and HV intervals and 3.7 +/- 0.5 mg/L for the AH interval. Ventricular tachyarrhythmias developed after marked QRS widening had occurred, and appeared in all six awake dogs and five of the six anesthetized dogs studied. Sodium bicarbonate was given to seven animals with ventricular tachyarrhythmias, and it rapidly reversed the arrhythmia in all instances. The benefit from sodium bicarbonate could not be attributed to changes in serum potassium or amitriptyline concentrations. It may have been due to alkalinization or changes in serum sodium concentration. These experiments suggest that: (a) amitriptyline intoxication frequently produces ventricular tachyarrhythmias, if high enough drug concentrations are achieved; (b) these arrhythmias are associated with marked slowing of intraventricular conduction; and (c) sodium bicarbonate is effective therapy for amitriptyline-induced ventricular arrhythmia.
Article
The authors report a case of maprotiline self-poisoning, associated with cardiac arrhythmias and conduction abnormalities, in a 24-year-old woman.
Article
Fifty-three cases of drug overdose requiring admission to a medical intensive care unit were studied. Tricyclic antidepressants were used in nearly 50 per cent of these serious adult overdoses. Barbiturates were involved in only 20 per cent. This may reflect changing patterns of drug usage and emphasizes the potential danger of tricyclics, the use of which is widespread in the general medical community. Unintentional overdoses occurred most often in substance abusers, whereas intentional overdoses occurred in a wider range of psychiatric disorders. A quarter of drug overdoses were free of psychiatric disease. Patients found to have an obvious manipulative intent were as likely to have made medically serious attempts as those who did not.
Article
Physostigmine is a commonly used therapy for the anticholinergic manifestations of tricyclic antidepressant (TCA) overdose. We describe two patients with TCA toxicity who developed asystole following the administration of physostigmine to treat seizures.
Intoxication par l'imipramine avec insuffisance cardiaque aigue.
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