In a 16-year-old taking diphenhydramine 50 mg daily and chlorpromazine 100 mg daily who presents with sinus tachycardia, how should I evaluate for sodium‑channel blockade and what is the recommended management?

Evaluation and Management of Sodium-Channel Blockade in a 16-Year-Old on Diphenhydramine and Chlorpromazine

Immediate ECG Assessment for Sodium-Channel Blockade

Obtain a 12-lead ECG immediately to evaluate for QRS prolongation (>100 ms), terminal R wave in aVR, and QT/QTc prolongation—these are the hallmark ECG findings of sodium-channel blockade from diphenhydramine and chlorpromazine. 1, 2

Key ECG Markers to Document:

• QRS duration: Baseline in adolescents is typically 65–80 ms; sodium-channel blockade causes widening to ≥100–130 ms 1, 3
• Terminal R wave in lead aVR: A positive deflection in aVR is a specific marker of sodium-channel toxicity 1
• QT/QTc interval: Prolongation beyond 500 ms indicates severe toxicity 2
• Heart rate: Sinus tachycardia (>100 bpm) is expected due to anticholinergic effects but does not exclude sodium-channel blockade 1, 3

Clinical Context:

Both diphenhydramine (50 mg daily) and chlorpromazine (100 mg daily) possess sodium-channel blocking properties 1, 4. Chlorpromazine demonstrates voltage-dependent sodium-channel blockade with greater affinity for inactivated channels, and this effect is potentiated at depolarized membrane potentials 4. The combination of these two agents creates additive risk for cardiotoxicity.

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Immediate Management Algorithm

Step 1: Stabilize and Monitor

• Continuous cardiac monitoring with telemetry to detect arrhythmia progression 5, 6
• Establish IV access and obtain baseline labs (electrolytes, complete blood count, thyroid function) 7, 6
• Assess hemodynamic stability: Check for hypotension, altered mental status, or signs of shock 5, 6

Step 2: Administer Sodium Bicarbonate if QRS ≥100 ms

If QRS duration is ≥100 ms or a terminal R wave in aVR is present, immediately administer IV sodium bicarbonate 1–2 mEq/kg as a bolus, followed by continuous infusion to maintain serum pH 7.45–7.55. 1, 8, 3

• Sodium bicarbonate reverses sodium-channel blockade by increasing extracellular sodium concentration and alkalinizing the serum, which reduces drug binding to the inactivated channel state 1, 3
• Repeat ECG every 15–30 minutes to document QRS narrowing; successful treatment typically shows QRS reduction within 30–60 minutes 1, 3

Step 3: Consider IV Lipid Emulsion for Refractory Cases

If QRS prolongation or hemodynamic instability persists despite sodium bicarbonate, administer 20% intravenous lipid emulsion (1.5 mL/kg bolus over 1 minute, followed by 0.25 mL/kg/min infusion). 2, 8

• Lipid emulsion acts as a "lipid sink" to sequester highly lipophilic drugs like diphenhydramine (octanol/water partition coefficient 3.3) 8
• Case reports demonstrate rapid QRS narrowing and hemodynamic improvement within minutes of lipid emulsion administration 2, 8

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Seizure Management

If seizures occur, administer IV benzodiazepines (lorazepam 0.1 mg/kg or midazolam 0.2 mg/kg) as first-line therapy. 1

• Diphenhydramine lowers seizure threshold through both anticholinergic effects and sodium-channel blockade 1
• Avoid phenytoin or other sodium-channel blocking antiepileptics, as they may worsen cardiotoxicity 1

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Ongoing Monitoring and Disposition

Monitor for Resolution:

• Serial ECGs every 2–4 hours until QRS duration normalizes and QTc <500 ms 1, 2
• Continuous telemetry for at least 24 hours after ECG normalization 2, 3
• Reassess mental status and anticholinergic signs (mydriasis, dry skin, urinary retention) 1

Disposition:

• ICU admission is mandatory for any patient with QRS >100 ms, hemodynamic instability, or seizures 2, 8, 3
• Cardiology consultation if arrhythmias persist or recur despite treatment 5

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Critical Pitfalls to Avoid

• Do not use Class Ia or Ic antiarrhythmics (procainamide, flecainide) for wide-complex tachycardia in this setting—they will worsen sodium-channel blockade 3
• Do not attempt cardioversion for sinus tachycardia with wide QRS; this rhythm is not a reentrant arrhythmia and will not respond to electrical therapy 5, 7
• Do not delay sodium bicarbonate while waiting for confirmatory drug levels; ECG findings alone justify empiric treatment 1, 3
• Do not overlook chlorpromazine's contribution: Its sodium-channel blocking potency is comparable to diphenhydramine and demonstrates marked use-dependent blockade 4

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Long-Term Medication Review

After acute stabilization, reassess the necessity of both diphenhydramine and chlorpromazine, as their combination poses ongoing risk for sodium-channel toxicity. 1, 4

• Consider alternative agents without sodium-channel blocking properties (e.g., second-generation antihistamines like cetirizine or loratadine for diphenhydramine; atypical antipsychotics for chlorpromazine) 1
• If continuation is unavoidable, obtain baseline and periodic ECGs to monitor for subclinical QRS widening 1, 2