Orion Cardiology, PLLC : Effect of Xenobiotics on the EKG

Friday, May 9, 2025

Effect of Xenobiotics on the EKG

ECG Manifestations & Treatment of Major Xenobiotic Overdoses

Quick-reference for critical-care & toxicology settings.
Always consult a poison center / medical toxicologist; consider ECMO for refractory shock.

Xenobiotic Class (common agents)	Key ECG Findings	Electrophysiologic Mechanism	First-Line Treatment	Escalation / Adjuncts
Sodium channel blockers TCAs, quinidine, flecainide, cocaine, diphenhydramine	QRS > 100 ms (often > 160 ms) Dominant R or R′ in aVR > 3 mm / R : S > 0.7 Right-axis deviation, QT prolongation, VT/VF	Fast Na⁺ channel blockade → slowed phase 0 depolarization & conduction	IV sodium bicarbonate 1–2 mEq/kg bolus → infusion (target pH 7.45-7.55)	Hypertonic saline if acidemic Lidocaine, lipid emulsion Vasopressors, Mg, mechanical pacing / ECMO
Potassium channel blockers Sotalol, amiodarone, dofetilide, some antihistamines/macrolides	Marked QTc prolongation Polymorphic VT / torsades de pointes Bradyarrhythmias	Delayed repolarization via K⁺ channel inhibition	IV magnesium sulfate 2 g (repeat PRN) Replete K⁺ (>4.5 mmol/L)	Overdrive pacing 90-110 bpm / isoproterenol Lipid emulsion (lipophilic agents) Hemodialysis for sotalol, defibrillation if unstable
Digoxin (cardiac glycosides)	Bradycardia, high-grade AV block Atrial tachycardia + 2:1 block Bidirectional VT, PVCs “Reverse-tick” ST sagging	Na⁺/K⁺-ATPase inhibition → ↑vagal tone & intracellular Ca²⁺; hyper-K	Digoxin-immune Fab (4–6 vials empiric, titrate)	Atropine, pacing Mg for ventricular arrhythmias Avoid Ca²⁺ in hyper-K unless life-threatening
Beta blockers Propranolol, atenolol, metoprolol, labetalol, sotalol*	Sinus bradycardia, AV block Propranolol: QRS widening (Na⁺ block) Hypotension, possible VT/VF	β-adrenergic blockade ± membrane-stabilizing Na⁺ block	IV glucagon 5-10 mg bolus → 1-10 mg/h High-dose insulin euglycemic therapy (1 U/kg bolus → 0.5-1 U/kg/h + dextrose)	Calcium salts, vasopressors Lipid emulsion, pacing, ECMO
Calcium channel blockers Verapamil, diltiazem, amlodipine, nifedipine	Bradycardia, AV block (non-DHP) Sinus tachy / minimal ECG change (DHP with vasoplegia) Hypotension, hyperglycemia	L-type Ca²⁺ channel inhibition → ↓nodal conduction & contractility	IV calcium chloride 10–20 mL 10% (or gluconate 30–60 mL) High-dose insulin euglycemic therapy (as above)	Vasopressors (epi/norepi), glucagon Lipid emulsion, methylene blue (refractory vasoplegia) ECMO for profound shock

*Sotalol exhibits both β-blockade & potassium-channel blockade.

High-Dose Insulin Euglycemic Therapy Protocol

For severe β-blocker or calcium-channel-blocker toxicity (and select refractory cardiogenic shock) in an ICU/ED with toxicology support.
Always consult a regional poison center and be prepared for rapid escalation (vasopressors, VA-ECMO).

1 · Indications

Persistent hypotension, bradycardia, or cardiogenic shock from β-blocker or Ca-channel-blocker overdose despite initial resuscitation.
Refractory hypoperfusion in mixed or unknown xenobiotic toxicity when NaHCO₃, calcium, vasopressors, and lipid emulsion have failed.

2 · Contra-Indications & Cautions

Relative: profound hyperglycemia (> 400 mg/dL), severe hypokalemia (< 3.0 mmol/L), DKA.
Absolute: true insulin allergy (extremely rare) or inability to monitor glucose/potassium frequently.

3 · Drug Preparation

Solution	Concentration	Comment
Regular insulin (Humulin® R / Novolin® R)	1 unit / mL (e.g. 100 U in 100 mL 0.9 % NaCl via syringe pump)	Prime tubing with 20 mL to saturate binding sites.
Dextrose 10 % (D10W)	Standard premix	Titrate to keep BG 100–150 mg/dL.
KCl replacement	10–20 mmol in 100 mL	Maintain K⁺ 4.0–4.5 mmol/L.

4 · Dosing Algorithm

IV Insulin Bolus： 1 unit / kg actual body weight (ABW).
— If BG < 200 mg/dL, give Dextrose 25 g (50 mL D50W) simultaneously.
Continuous Insulin Infusion： Start at 0.5–1 unit / kg / hr.
— Titrate q15–30 min by 0.5–1 unit / kg / hr to achieve:
- MAP > 65 mmHg or > baseline, AND/OR
- Cardiac index > 2.5 L ∙ min⁻¹ ∙ m⁻², AND/OR
- Lactate trending down > 10 % per hr.
Maximum commonly reported: 10 unit / kg / hr (rare case reports up to 16).
Dextrose Infusion： Start D10W at 0.5 g / kg / hr (≈ 5 mL / kg / hr).
— Adjust rate or supplement with D50W boluses to keep BG 100–150 mg/dL.
Potassium： Check q30 min for first 2 hr, then hourly.
— If < 3.5 mmol/L, give 20–40 mmol KCl IV over 1 hr.

5 · Monitoring Checklist

Blood glucose q15 min × 4, then q30 min × 2, then hourly when stable.
K⁺, Mg²⁺, Phos, iCa²⁺ q1 h for 4 h, then q2 h.
Arterial blood gas & lactate q1–2 h to track perfusion.
Continuous ECG & invasive BP (arterial line recommended).
Urine output q1 h; consider indwelling catheter.

6 · Troubleshooting

Problem	Action
Hypoglycemia (BG < 90 mg/dL)	50 mL D50W IV push; ↑ D10W rate; re-check BG in 5 min.
Hypo-K (< 3.0 mmol/L)	Hold insulin escalation; give 40 mmol KCl IV over 1 hr; resume when K > 3.0.
Volume overload	Switch to D20–30W via central line; judicious diuretics.
No hemodynamic response after 30 min at 2 U / kg / hr	Double rate every 15–30 min up to 10 U / kg / hr; add vasopressors, consider VA-ECMO.

7 · Weaning & Disposition

Begin taper when vasopressors off & stable for ≥ 2 hr.
↓ insulin rate by 50 % every 30 min while maintaining dextrose; stop when at 0.5 U / kg / hr and hemodynamics remain stable.
Continue dextrose for 1–2 hr after insulin discontinuation; monitor BG q15 min for rebound hypoglycemia.

8 · Sample Adult Order Set (70 kg)

• Regular insulin 70 U IV bolus now
• Start insulin infusion 70 U/hr (1 U/mL) via syringe pump
• Start D10W at 350 mL/hr (0.5 g/kg/hr) via peripheral line
• Titrate insulin by 35 U/hr q15 min to MAP ≥ 65 mmHg
• Check BG q15 min × 4, then q30 min × 2, then q1 hr
• Replace potassium to maintain 4–4.5 mmol/L

Remember： Insulin is an inotrope.
Its positive effects may take 20-30 minutes; be patient and avoid prematurely abandoning therapy.

Last updated May 2025 — Compiled by critical-care.tox

Orion Cardiology, PLLC