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2025 PACUPrep BCCCP Preparatory Course Management of Acute Overdoses – Cardiovascular Agents Diagnostic and Classification Strategies in Acute Overdoses

Lesson 58, Topic 2

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Diagnostic and Classification Strategies in Acute Overdoses

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Diagnostic and Classification Strategies in Acute Cardiovascular Overdoses

Objective

Apply diagnostic and classification criteria to assess a patient with acute cardiovascular agent overdose and guide initial management.

I. Clinical Manifestations

Early recognition of the characteristic cardiovascular, neurologic, and metabolic signs of cardiotoxic overdoses is critical for directing prompt and specific therapy.

1.1 Cardiovascular Signs: Bradycardia, Hypotension, Arrhythmias

Bradycardia: A heart rate below 60 bpm is a common finding in beta-blocker (BB) and calcium-channel blocker (CCB) overdose due to suppression of the sinoatrial node.
Hypotension: This results from a combination of negative inotropy (reduced contractility), vasodilation (especially with dihydropyridine CCBs), capillary leak, and central nervous system sedation.
Arrhythmias: While BB and CCB overdoses most often cause bradyarrhythmias and atrioventricular (AV) block, other agents like tricyclic antidepressants (TCAs) and some antipsychotics can produce QRS widening and life-threatening ventricular tachyarrhythmias.

Clinical Pearl: Differentiating Shock Etiology +

In CCB overdose, profound vasoplegia (low systemic vascular resistance) often exceeds direct myocardial depression. A bedside echocardiogram can rapidly differentiate this distributive shock state from primary pump failure, guiding the choice between vasopressors and inotropes.

1.2 Neurologic and Metabolic Findings: Altered Consciousness, Hypoglycemia

Altered mental status: This can arise from direct central effects of lipophilic drugs, cerebral hypoperfusion from shock, or the presence of co-ingestants like benzodiazepines.
Hypoglycemia: BBs inhibit hepatic gluconeogenesis and glycogenolysis. CCB overdose may cause initial hyperglycemia due to insulin release inhibition, followed by profound hypoglycemia as shock develops.
Electrolyte disturbances: Hyperkalemia is a classic finding in severe digoxin toxicity, while high-dose insulin therapy, a key antidote, can cause significant hypokalemia.

Clinical Pitfall: Masked Hypoglycemia +

The bradycardia caused by BB or CCB overdose blunts the typical sympathoadrenal (tachycardic) response to hypoglycemia. Therefore, clinicians must routinely measure serum glucose in these patients rather than relying on vital signs to detect this dangerous metabolic complication.

II. Laboratory Evaluation

Rapid laboratory panels and specific biomarkers are essential to stratify toxicity severity, identify metabolic derangements, and guide resuscitation efforts.

Key Laboratory Assessments in Cardiotoxic Overdose
Test	Clinical Significance	Therapeutic Goal / Note
Electrolytes & Glucose	Identifies hyperkalemia (digoxin), hypokalemia (HDI therapy), and hypoglycemia (BB/CCB).	Maintain normokalemia and euglycemia. Frequent monitoring is critical during antidote therapy.
Arterial Blood Gas (ABG)	Metabolic acidosis (elevated anion gap) reflects lactic acidosis from tissue hypoperfusion.	Monitor for worsening acidemia, which impairs catecholamine effectiveness and predicts poor outcomes.
Serum Lactate	A key marker of shock severity. Levels >4 mmol/L correlate with high mortality.	Target ≥10% clearance per hour as a marker of effective resuscitation.
Cardiac Biomarkers	Troponins and natriuretic peptides help distinguish primary myocardial injury from secondary demand ischemia.	The trend is more important than the absolute value for prognostication.
Specific Drug Levels	Quantitative assays for digoxin, TCAs, and some BBs can confirm exposure and guide specific antidotes.	Do not delay empiric therapy while awaiting results, as turnaround times can be long.

Editor’s Note: Limitations of Drug Levels +

While specific drug levels are useful when available, there is insufficient source material to provide detailed therapeutic ranges and optimal sampling times for many agents. A comprehensive approach would include typical peak levels, recommended time to sampling post-ingestion, and guidance on interpreting serial measurements. Clinical correlation remains paramount.

III. ECG Interpretation

The electrocardiogram (ECG) is a rapid, non-invasive tool that can identify specific ion channel blockade and arrhythmia risk, helping to tailor antidotal therapy.

3.1 QRS Duration: Thresholds and Prognostic Value

A QRS duration > 100 ms is a sensitive indicator of significant sodium channel blockade, commonly seen with TCAs and Class I antiarrhythmics.
A QRS duration > 160 ms is highly predictive of ventricular dysrhythmias and seizures, warranting immediate administration of sodium bicarbonate.

3.2 Conduction Abnormalities: AV Block and Bundle Branch Blocks

First-degree AV block (PR interval > 200 ms) is an early sign that may progress to higher-grade block.
Second- or third-degree (complete) AV block is a hallmark of severe BB/CCB overdose and may require temporary cardiac pacing.
A new bundle branch block suggests significant intraventricular conduction delay from drug toxicity rather than primary ischemia.

3.3 Dysrhythmias: Ventricular Tachycardia and Torsade de Pointes

Polymorphic ventricular tachycardia (Torsade de Pointes), resulting from QT interval prolongation, should be managed with magnesium sulfate 2 g IV over 10 minutes, regardless of the baseline serum magnesium level.

Clinical Pearl: QRS Duration in TCA Overdose +

In tricyclic antidepressant overdose, the QRS duration correlates more strongly with the risk of seizures than with hemodynamic collapse. This finding should guide proactive anticonvulsant therapy in addition to sodium bicarbonate administration.

IV. Imaging and Hemodynamic Monitoring

Echocardiography and invasive monitoring devices are crucial for refining the diagnosis of shock type and guiding the titration of advanced therapies.

4.1 Bedside Echocardiography

Function Assessment: Quickly assess left ventricular ejection fraction (LVEF) and end-diastolic volume to distinguish cardiogenic shock (poor contractility) from distributive shock (vasodilation).
Therapy Response: Serial echocardiograms can be used to evaluate for improvement in cardiac function during treatment with high-dose insulin or intravenous lipid emulsion therapy.

4.2 Invasive Monitoring

Arterial Line: Provides continuous, real-time mean arterial pressure (MAP) monitoring, which is essential for precise vasopressor titration.
Central Venous Pressure (CVP): Offers an estimation of preload. A pulmonary artery catheter may be considered for refractory shock to obtain comprehensive hemodynamics and assess candidacy for extracorporeal membrane oxygenation (ECMO).

Controversy: Routine Pulmonary Artery Catheter Use +

The routine use of pulmonary artery catheters in toxicologic shock is not universally endorsed. Concerns include the risk of infection and catheter-related complications, coupled with a lack of definitive data showing improved patient outcomes. Its use is typically reserved for complex, refractory cases where the additional hemodynamic data is deemed essential for management.

V. Classification and Severity Scoring

Using a mechanism-based classification and validated scoring systems helps stratify risk and informs the urgency of intervention.

5.1 Mechanism-Based Classification

Beta-Blockade: Toxicity primarily results from competitive inhibition of β₁-adrenergic receptors in the heart, leading to decreased heart rate and contractility.
Calcium-Channel Blockade: Toxicity results from inhibition of L-type calcium channels in cardiac nodal tissue and vascular smooth muscle, causing bradycardia, AV block, and vasodilation.
Sodium-Channel Blockade: “Membrane stabilizing activity” from agents like TCAs and some antiarrhythmics slows intracardiac conduction, leading to QRS widening and ventricular arrhythmias.

5.2 Poison Severity Score (PSS) and Risk Stratification

The PSS grades toxicity from 0 (none) to 3 (severe) based on clinical and lab findings. While simple, it is often supplemented by risk stratification algorithms that trigger specific actions. High-risk criteria that should prompt early, aggressive therapy include:

Heart Rate < 50 bpm
Systolic Blood Pressure < 90 mmHg
QRS Duration > 100 ms
Serum Lactate > 4 mmol/L

Meeting any of these criteria should trigger consideration for high-dose insulin, lipid emulsion therapy, and immediate transfer to an intensive care unit.

Clinical Pearl: Targeted Therapy +

Mechanism-based treatment algorithms outperform generic scoring systems in predicting response to targeted therapies. For example, understanding that BB/CCB toxicity is a state of “insulin resistance” explains why high-dose insulin is a cornerstone therapy for this specific receptor blockade.

VI. Clinical Pathways and Decision Algorithms

Structured pathways and decision algorithms expedite the administration of life-saving antidotes and ensure patients are managed at the appropriate level of care.

Figure 1: Simplified Antidote Pathways. This flowchart illustrates the tiered approach to managing beta-blocker and calcium-channel blocker overdoses. High-dose insulin is a key therapy for both. For persistent refractory shock, advanced therapies like intravenous lipid emulsion or ECMO should be considered.

6.2 Integration with ICU Admission Criteria

A patient’s requirement for any advanced therapy is a clear indication for ICU-level care. This includes:

Initiation of high-dose insulin euglycemia (HDIE) therapy.
Administration of intravenous lipid emulsion (ILE).
Need for multiple vasopressors or escalating doses.
Requirement for invasive hemodynamic monitoring or mechanical circulatory support (e.g., ECMO).

Clinical Pearl: Systems-Based Improvements +

Embedding these decision algorithms and treatment pathways into electronic health record order sets can significantly reduce the time to antidote administration. This systems-based approach has been shown to improve outcomes in time-sensitive cardiotoxic overdoses by standardizing care and reducing cognitive load on clinicians.

References

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