sodium-bicarbonate and Cardiotoxicity

Ropivacaine has been described as a safer local anaesthetic (LA); however, serious cardiotoxic accidents have been reported. Intravenous-lipid-emulsion (ILE) therapy during LA intoxication seems to act as an antidote. Sodium bicarbonate is the standard treatment for sodium channel blocker drug toxicity. We compared both antidotes on the reversion of electrophysiologic toxicity induced by ropivacaine. Ropivacaine 5 mg kg

Topics: Anesthetics, Local; Animals; Antidotes; Cardiotoxicity; Fat Emulsions, Intravenous; Heart Rate; Lipids; Ropivacaine; Sodium Bicarbonate; Swine

Bupropion cardiotoxicity widens QRS complexes by inhibiting cardiac gap junctions. Sodium bicarbonate is the standard treatment for QRS widening from sodium channel blockade, but its effect on QRS widening in bupropion cardiotoxicity is not well-studied.. This is a retrospective cohort study of bupropion overdoses from 10 hospitals between January 2010 and June 2022. Patients with documented administration of sodium bicarbonate and QRS duration > 100 milliseconds on pre-bicarbonate electrocardiogram were included. Patients with no electrocardiogram within four hours of treatment or with baseline pre-overdose wide QRS and < 10 milliseconds widening from baseline were excluded. The primary outcome was a change in QRS duration between the pre-bicarbonate electrocardiogram and the first electrocardiogram after initial bicarbonate administration. Secondary outcomes included prevalence of post-bicarbonate QRS < 100 milliseconds, change in electrocardiogram intervals after total bicarbonate administration, and change in metabolic parameters and hemodynamics. Wilcoxon signed-rank testing was performed on the primary outcome. Linear regression modeling was performed to test for an association between change in QRS and bicarbonate dosing.. Thirteen patients were included for final analysis. The median age was 32 years, and 54% were male. Six patients developed seizures; one developed ventricular tachycardia, and four received vasopressors. The median QRS and QTc pre-bicarbonate were 116 and 495 milliseconds, respectively. The median change in QRS duration was -2.0 milliseconds, which was not statistically significant (. Sodium bicarbonate did not significantly decrease QRS duration in this small retrospective cohort of bupropion overdoses.

Topics: Adult; Bicarbonates; Bupropion; Cardiotoxicity; Drug Overdose; Electrocardiography; Female; Humans; Male; Retrospective Studies; Sodium Bicarbonate

Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Cardiotoxicity; Drug Overdose; Electrocardiography; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Predictive Value of Tests; Sodium Bicarbonate; Tachycardia, Ventricular

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

Tricyclic antidepressants (TCAs) are a major cause of fatal drug poisoning due to their cardiotoxicity. Alkalinization by sodium bicarbonate (NaHCO3) administration, the first-line therapy for TCA-induced cardiotoxicity, can occasionally yield insufficient efficacy in severe cases. Because most TCAs are highly lipophilic, lipid emulsion may be more effective than alkalinization. However, it remains to be determined whether lipid emulsion is more beneficial than alkalinization in reversing amitriptyline-induced cardiotoxicity.. Hemodynamic variables were recorded from in vivo guinea pig models and Langendorff-perfused hearts. Whole-cell patch-clamp experiments were conducted on enzymatically isolated ventricular cardiomyocytes to record fast sodium currents (INa). Lipid solutions were prepared using 20% Intralipid. The pH of the alkaline solution was set at 7.55. We assessed the effect of lipid emulsion on reversing amitriptyline-induced cardiotoxicity, in vivo and in vitro, compared to alkalinization. The data were evaluated by Student t test, 1-way repeated-measures analysis of variance, or analysis of covariance (covariate = amitriptyline concentration); we considered data statistically significant when P < .05.. In the in vivo model, intervention with lipids significantly reversed the amitriptyline-induced depression of mean arterial pressure and prolongation of QRS duration on electrocardiogram more than alkalinization (mean arterial pressure, mean difference [95% confidence interval]: 19.0 mm Hg [8.5-29.4]; QRS duration, mean difference [95% confidence interval] -12.0 milliseconds [-16.1 to -7.8]). In the Langendorff experiments, perfusion with 1% and 2% lipid solutions demonstrated significant recovery in left ventricular developed pressure (LVdevP), maximum change rate of increase of LVdevP (dP/dtmax) and rate-pressure product compared with alkaline solution (LVdevP [mm Hg], alkaline 57 ± 35, 1% lipid 94 ± 12, 2% lipid 110 ± 14; dP/dtmax [mm Hg/s], alkaline 748 ± 441, 1% lipid 1502 ± 334, 2% lipid 1753 ± 389; rate-pressure product [mm Hg·beats·minute], alkaline 11,214 ± 8272, 1% lipid 19,025 ± 8427, 2% lipid 25,261 ± 4803 with analysis of covariance). Furthermore, lipid solutions (0.5%-4%) resulted in greater recovery of hemodynamic parameters at 3 μM amitriptyline. Amitriptyline inhibited INa in a dose-dependent manner: the half-maximal inhibitory concentration (IC50) was 0.39 μM. The IC50 increased to 0.75 μM in the alkaline solution, 3.2 μM in 1% lipid solution, and 6.1 μM in 2% lipid solution. Furthermore, the lipid solution attenuated the use-dependent block of sodium channels by amitriptyline more than alkaline solution. On 30 consecutive pulses at 1 Hz, the current decreased to 50.1 ± 2.1, 60.3 ± 1.9, and 90.4% ± 1.8% in standard, alkaline, and 1% lipid solution, respectively. Even 0.5% lipid solution showed greater effects than the alkaline solution in all experiments.. Lipid emulsion significantly suppressed amitriptyline-induced INa, inhibition, which was likely related to the marked improvement in hemodynamic status observed in vivo and in isolated perfused hearts. These results suggest the superiority of lipid emulsion as the first-line therapy for TCA-induced cardiotoxicity compared to alkalinization therapy.

Topics: Acid-Base Equilibrium; Action Potentials; Alkalies; Amitriptyline; Animals; Arterial Pressure; Cardiotoxicity; Disease Models, Animal; Emulsions; Guinea Pigs; Heart Diseases; Heart Rate; Hydrogen-Ion Concentration; Infusions, Intravenous; Isolated Heart Preparation; Kinetics; Male; Myocytes, Cardiac; Phospholipids; Recovery of Function; Sodium; Sodium Bicarbonate; Soybean Oil; Ventricular Function, Left