See also [[TCA overdose]], [[Local anaesthetic systemic toxicity]] See: [EMCrit - sodium channel blocker](https://emcrit.org/ibcc/nacb/) > [!key points] important considerations when giving HCO3 > - ventilation is important when giving bicarbonate therapy. HCO3 may paradoxically worsen the pH with ↑ pCO2. gently hyperventilate, aiming for low-normal pCO2 in most cases (pCO2 30-35 if TCA) > - the QRS often remains prolonged eg 120-140ms for 24-48 hours following severe TCA overdose, so do not aim for an unrealistic QRS target (eg 100-120) ms because this probably will never happen. > - furthermore, in [[Sodium channel blocker|sodium channel blocker toxicity]] due to non-TCA medications, the QRS prolongation *may not respond to HCO3* at all > - also, avoid treating a broad complex QRS that is not secondary to Na-channel toxicity but is actually pre-existing interventicular conduciton delay > - perform [[Blood gas]] analysis regularly to ensure target pH and pCO2 are met and iatrogenic harm is avoided. severe [[hypokalemia|hypo-k]] can be easy to miss # ECG - QRS prolongation (100ms predicts seizure in TCA; 160 predict arrhythmia) - QT prlongation - terminal R in aVR > 3mm - R/S ratio > 0.7 in aVR # Drugs - [[TCA overdose]] - propranolol - flecanide - lignocaine - [[Cocaine]] - [[lamotrigine overdose]] - [[Venlafaxine]] - hydroxchloroquine # Treatment - na-channel blockade --> 1mL/kg (1mmol/kg) [[HCO3 therapy|NaHCO3]] - works for TCA ECG, but ==may not fix other Na-channel blockers== - can [overdo HCO3](https://www5.austlii.edu.au/au/cases/act/ACTCD/2025/1.html); stop this treatment up to 3mmol/kg for non-TCA - consider pre-existing bundle branch block as cause for wide complex as well - ==for TCA, up to 6mmol/kg== - for non-TCA, up to 3mmol/kg to pH of 7.35-7.45 - **hyperventilate** patient to blow off CO2 from the HCO3 pCO2 30-35 (if TCA) or 35-40 if non-TCA - *** # further learning - why doesn’t phenytoin cause “typical” Na-channel blocking cardiac effects? > [!TLDR] > Phenytoin toxicity is more like lignocaine toxicity because it is class Ib and quickly dissociates from Na channels, while TCA is more like class IA toxicity (eg procainamide) because it prolongs QRS We know that some anti-epileptics like carbamazapine and lamotrigine cause arrhythmias like TCAs. So why doesn’t [phenytoin](x-devonthink-item://2F041FBD-FF1C-4E21-9CD5-5550C288F006?page=750), whose toxidrome is more CNS issues, or hypotension related to the propylene glycol in IV infusion given too quickly? This has to do with the specific sodium channel blocking effects of these drugs as class I antiarrhythmics. ![[Pasted image 20241016115409.png]] The term “sodium channel blocker” in this context generally refers to Ia or Ic agents with either class Ia or class Ic antiarrhythmic activity, which causes a slowing of phase-zero depolarization in cardiomyocytes (purple arrows above). To an extent, the variation between these agents might have something to do with the receptor dissociation kinetics. sodium channel blockers used as Class I antiarrhythmic bind only to the channel in the open or inactivated state, and dissociate from the binding site when the channel is resting during diastole. - **Class Ia**: intermediate dissociation kinetics, - **Class Ib**: fast dissociation kinetics, and - **Class Ic**: slow dissociation kinetics ![[88F25AF9-328F-486C-BA1F-D539F8325035.jpeg]] Note that Ib agents like [lignocaine](x-devonthink-item://2F041FBD-FF1C-4E21-9CD5-5550C288F006?page=1024) and phenytoin do not affect phase zero depolarization or prolong the QRS complex. lignocaine can actually reduce the action potential duration, making it *useful* in the treatment of arrhythmias caused by class Ia or class Ic intoxication. lignocaine’s ability to tighten up the QTc interval likewise makes it useful in the management of [[Torsades de Pointes]]. Among [[TCA overdose#mechanism|TCA’s]] other effects (alpha-blocking, anti-cholinergic), [TCAs also have effects similar to IA agents](x-devonthink-item://2F041FBD-FF1C-4E21-9CD5-5550C288F006?page=1071) prolonging phase 0 and elongating the QRS. [Class IA](x-devonthink-item://2F041FBD-FF1C-4E21-9CD5-5550C288F006?page=895&istart=2007&ilength=46&search=Management%20of%20Class%20IA%20Antidysrhythmic%20Toxicity) and [class Ic](x-devonthink-item://2F041FBD-FF1C-4E21-9CD5-5550C288F006?page=897&istart=3479&ilength=46&search=Management%20of%20Class%20IC%20Antidysrhythmic%20Toxicity) toxicity is often what is being treated during “sodium channel blocker cardiac toxicity.” Impaired depolarization within the ventricular conduction system slows the propagation of ventricular depolarization, which manifests as prolongation of the QRS complex on the electrocardiogram (ECG). The right bundle branch has a relatively longer refractory period, and it is *affected disproportionately* by xenobiotics that slow intraventricular conduction. This slowing of depolarization results in a rightward shift of the terminal 40 ms of the QRS axis and the right bundle branch block pattern that is noted on the ECG of patients who are exposed to or overdose with a TCA. In contrast, [lignocaine](x-devonthink-item://2F041FBD-FF1C-4E21-9CD5-5550C288F006?page=1024) or phenytoin have far more pronounced effects on neuro Na-channels (lignocaine needs ~10mcg/mL concentration to cause cardiac effects). ![[Pasted image 20241016110544.png]] All [[Local anaesthetic systemic toxicity|local anaesthetics]] directly produce a dose dependent decrease in cardiac contractility, with the effects roughly proportional to their peripheral anesthetic effect. To a certain extent, the ↓ cardio toxicity of lignocaine is a function of earlier recognition due to neuro effects presenting first. Although lidocaine and bupivacaine both block sodium channels in the open or inactivated states, lidocaine quickly dissociates from the channel at diastolic potentials, allowing rapid recovery from block during diastole (known as fast on–fast off kinetics). Therefore, sodium channel blockade with lidocaine is much more pronounced at rapid heart rates (accounting for the antidysrhythmic effects for ventricular tachycardia). In contrast, at high concentrations, bupivacaine rapidly binds to and slowly dissociates from sodium channels (fast on–slow off kinetics), with significant block accumulating at all physiologic heart rates. Accordingly, at heart rates of 60 to 150 beats/min, approximately 70 times more lidocaine is needed than bupivacaine to produce an equal effect on Vmax of the action potential. Enhanced conduction block in Purkinje fibers and ventricular muscle cells sets up a reentrant circuit responsible for the ventricular tachydysrhythmias induced by bupivacaine. **References:** - [deranged physiology - fast voltage-gated sodium channels ](https://derangedphysiology.com/main/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20011/fast-voltage-gated-sodium-channels-cardiac-muscle) - [deranged physiology - class I antiarrhythmic agents](https://derangedphysiology.com/main/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20966/class-i-antiarrhythmic-agents) - [deranged physiology - phenytoin](https://derangedphysiology.com/main/cicm-primary-exam/required-reading/nervous-system/Chapter%20234/phenytoin)