01Approach to the Critical Patient/attcp57

Immediate stabilization

›Resuscitation priorities

›Airway assessment and protection

›GCS < 8 or inability to protect airway: proceed to RSI

›Pre-oxygenate before intubation

›Suction available for vomiting risk

›Vascular access

›Two large-bore peripheral IVs

›Central venous access for vasopressors and calcium chloride

›Arterial line for continuous blood pressure monitoring and titration

›Continuous monitoring

›Cardiac monitor and telemetry

›Pulse oximetry

›Capnography if intubated

Hemodynamic targets and escalation

›Hemodynamic goals

›MAP >= 65 mmHg

›Titrate vasopressors to target

›Norepinephrine first-line vasopressor

›Heart rate target >= 50 bpm

›Bradycardia < 50 bpm with hypotension triggers immediate escalation

›Transcutaneous pacing on standby

›Lactate clearance target

›Repeat lactate every 1 to 2 hours

›Downtrending lactate confirms perfusion improvement

›Escalation triggers

›Refractory hypotension despite calcium plus HDI plus vasopressors

›Escalate HDI rate

02History/hx71

Ingestion details

›Agent identification

›Specific CCB agent name

›Dihydropyridine: amlodipine, nifedipine, felodipine

›Nondihydropyridine: verapamil, diltiazem

›Formulation type

›Immediate-release: peak toxicity within 1 to 2 hours

›Sustained-release: peak toxicity delayed up to 12 to 24 hours

›Estimated dose and number of tablets

›Pill count comparison to prescribed supply

›Pharmacy records if available

›Time of ingestion

›Critical for decontamination eligibility

›Sustained-release: window for decontamination extends

Circumstances and co-ingestants

›Intent and context

›Intentional self-harm

›Suicidal ideation and plan

›Prior attempts

›Accidental or therapeutic error

›Pediatric exploratory ingestion

›Dose confusion in elderly patient

›Witnessed vs unwitnessed

›EMS report and scene information

›Suicide note

›Co-ingestants of concern

›Beta-blockers

›Synergistic cardiovascular depression

03Physical Exam/exam58

Vitals and hemodynamic snapshot

›Primary vital signs

›Blood pressure

›Hypotension hallmark of significant toxicity

›SBP < 90 mmHg triggers immediate intervention

›Heart rate

›Bradycardia with nondihydropyridines

›Reflex tachycardia possible early with amlodipine

›Respiratory rate

›Tachypnea from metabolic acidosis or pulmonary edema

›Respiratory depression in severe CNS involvement

›Temperature

›Hypothermia in severe shock states

›Fever suggests infection co-morbidity

›Oxygen saturation

›Pulmonary edema from cardiogenic shock

Cardiovascular exam

›Cardiac assessment

›Pulse character

›Weak thready pulse in cardiogenic shock

›Bounding pulse possible in pure vasodilatory shock

›Capillary refill

›Delayed > 2 seconds indicates poor perfusion

›Peripheral mottling

›Jugular venous distension

›Elevated JVP suggests cardiogenic pattern

›Flat JVP suggests vasodilatory or hypovolemic pattern

›Auscultation

04Differential Diagnosis/ddx41

Life-threatening mimics

›Cardiovascular toxicology

›Beta-blocker overdose

›ICD-10 T44.7

›Key differentiator: hypoglycemia in beta-blocker vs hyperglycemia in CCB

›Propranolol causes QRS widening and seizures

›Sotalol causes QT prolongation

›Digoxin toxicity

›ICD-10 T46.0

›Bradycardia and AV block with hyperkalemia

›Digoxin level diagnostic

›Tricyclic antidepressant overdose

›QRS widening > 120 ms differentiates

›Sodium bicarbonate responsive

›Cardiovascular emergencies

›Acute myocardial infarction with cardiogenic shock

›ICD-10 I21.9

›ECG and troponin differentiation

›STEMI pattern absent in CCB toxicity

›High-grade AV block from structural cause

›Ischemic or degenerative conduction disease

›No ingestion history

›Aortic dissection with cardiac tamponade

›Hypotension with bradycardia overlap

›POCUS and CT differentiation

Other toxicologic mimics

›Autonomic toxidromes

›Clonidine or central alpha-agonist overdose

05Laboratory Tests/lt62

Core metabolic and toxicology labs

›Point-of-care glucose

›Hyperglycemia characteristic of CCB toxicity

›Peak glucose > 16.7 mmol/l predicts severe toxicity

›Percentage increase from baseline > 71% also predicts severity

›Better severity predictor than hemodynamic parameters alone

›Serial glucose monitoring during HDI therapy

›Every 30 minutes during HDI initiation

›Every 60 minutes once stable

›Electrolytes and renal function

›Potassium

›Hypokalemia common during HDI therapy

›Monitor every 60 minutes during HDI

›Supplement to maintain >= 3.0 mmol/l

›Calcium

›Ionized calcium target up to 2x normal during therapy

›Monitor every 30 to 60 minutes during calcium infusion

›Sodium and bicarbonate

›Metabolic acidosis severity assessment

›Anion gap calculation

›Renal function

›Acute kidney injury from hypoperfusion

›Does not significantly alter CCB pharmacokinetics

›Toxicology co-ingestion screen

›Acetaminophen level

›Routine in all intentional overdoses

›Treatment decision threshold 150 mg/l at 4 hours on nomogram

›Salicylate level

06Diagnostic Tests/dt73

Scoring Systems

›CCB toxicity severity stratification

›No validated universal scoring system exists for CCB toxicity

›Severity based on clinical and laboratory parameters

›Mild: asymptomatic or mild hypotension responsive to fluids

›Moderate: hypotension requiring vasopressors, symptomatic bradycardia

›Severe: refractory shock, cardiac arrest, multi-organ failure

›Hyperglycemia as severity marker

›Peak glucose > 16.7 mmol/l predicts severe toxicity

›Percentage increase > 71% from baseline predicts severity

›Correlates better with outcomes than hemodynamic parameters alone

›Lactate as severity marker

›Lactate >= 4 mmol/l indicates shock state

›pH < 7.1 predicts poor outcome on VA-ECMO

›Bradycardia assessment framework

›ACC/AHA/HRS 2018 Bradycardia Guideline algorithm applicable

›Hemodynamically significant bradycardia triggers immediate intervention

›Drug-specific antidote pathway incorporated

›Pacing consideration for refractory bradydysrhythmias

MRI

›MRI role in CCB toxicity

›No primary role in acute CCB poisoning management

›Hemodynamic instability precludes MRI

›CT and POCUS preferred for acute assessment

›Potential delayed use

›Brain MRI for hypoxic-ischemic injury assessment after cardiac arrest

›Prognostication in post-resuscitation care

›Contraindications in acute setting

07Disposition/dispo46

ICU admission indications

›Mandatory ICU admission criteria

›All symptomatic CCB poisoning

›Hypotension, bradycardia, or AV block present

›Ongoing vasopressor or antidotal therapy requirement

›Intentional overdose with sustained-release formulation

›Delayed peak toxicity up to 12 to 24 hours

›Continuous telemetry mandatory

›Hemodynamic instability at any point

›Even if initially responding to treatment

›Relapse common with sustained-release agents

›ICU-level care requirements

›Continuous cardiac monitoring and telemetry

›Progressive AV block detection

›Dysrhythmia recognition

›Invasive hemodynamic monitoring

›Arterial line for vasopressor titration

›Central venous access

›HDI therapy monitoring infrastructure

›Glucose and potassium every 30 to 60 minutes

›Dextrose infusion co-administration

Observation criteria

›Extended observation indications

›Asymptomatic after sustained-release CCB ingestion

›Minimum 24-hour observation

›Serial ECGs and vital signs

›Do not discharge early

›Asymptomatic after immediate-release CCB ingestion

08Treatment/t105

GI decontamination

›Activated charcoal

›Activated charcoal 1 g/kg IV (max 50 to 100 g)

›Administer up to 6 hours post-ingestion per Clinical Toxicology Recommendations Collaborative 2026

›Sustained-release formulations: extend window beyond 6 hours if ongoing absorption suspected

›Additional dose may be appropriate for verapamil specifically

›Contraindicated if unprotected airway or hemodynamically unstable

›Preconditions for safe administration

›Intact or secured airway

›No bowel obstruction

›Cooperative patient or NGT administration

›Whole-bowel irrigation

›Polyethylene glycol solution 1.5 to 2 L/hr in adults via NGT

›Indicated for sustained-release formulations presenting > 2 hours post-ingestion

›Continue until rectal effluent clear

›Contraindicated if hemodynamically unstable or unprotected airway

›Contraindicated if bowel ileus present

First-line antidotes

›Calcium therapy

›Calcium gluconate 10% solution

›60 mL (6 g) IV over 10 to 20 minutes via peripheral line

›Repeat dosing every 15 to 30 minutes as needed

›Target ionized calcium up to 2x normal

›Preferred peripherally due to tissue safety

›Calcium chloride 10% solution

›20 mL (2 g) IV over 10 to 20 minutes via central line

›Three times more elemental calcium than gluconate

›Central line required to avoid tissue necrosis

›Monitoring during calcium infusion

›Ionized calcium level every 30 to 60 minutes

›ECG monitoring for hypercalcemia signs

›High-dose insulin euglycemia therapy (HDI)

›Insulin bolus

›Regular insulin 1 unit/kg IV bolus

›Administer with dextrose 50% 50 mL unless glucose > 16.7 mmol/l

›Class IIa recommendation per AHA 2025 guidelines

›Insulin infusion

›Start at 0.5 to 1 unit/kg/hr

›Escalate every 15 to 30 minutes based on response

›No established ceiling; doses up to 10 units/kg/hr reported in refractory cases

›Expert consensus supports early high-dose initiation before vasopressors

›Dextrose co-infusion

›D10W at 100 to 250 mL/hr; titrate to maintain glucose 6 to 10 mmol/l

›D25W or D50W bolus for hypoglycemia treatment

›Glucose monitoring every 30 minutes during titration

›Potassium monitoring

›Potassium every 60 minutes during HDI

›Supplement to maintain >= 3.0 mmol/l

›Hypokalemia is the most common HDI complication

›Caution with pure vasodilatory shock (amlodipine)

›HDI is a vasodilator and may worsen purely vasodilatory physiology

›Use when cardiogenic component suspected or confirmed by POCUS

›Atropine

›Atropine 0.5 to 1 mg IV for symptomatic bradycardia

›May repeat to total 3 mg

›Treatment failures common; do not rely on atropine alone

›Bridge only while definitive therapy initiated

Vasopressors

›Norepinephrine

›Norepinephrine first-line vasopressor for hypotension

›Start 0.1 to 0.2 mcg/kg/min IV

›Titrate to MAP >= 65 mmHg

›Doses up to 100 mcg/min reported in severe CCB toxicity

›Mechanism

›Alpha-1 and beta-1 adrenergic agonist

›Increases vascular resistance and cardiac output

›Epinephrine

›Alternative to norepinephrine or adjunct

›Start 0.1 mcg/kg/min IV

›Titrate to hemodynamic response

›Beta-1 stimulation may augment chronotropy and inotropy

Second-line and refractory therapies

›Methylene blue

›Methylene blue 1 to 2 mg/kg IV over 15 minutes

›Indicated for refractory vasodilatory shock especially amlodipine toxicity

›Mechanism: inhibits nitric oxide-mediated vasodilation

›Responses mixed and may be transient

›Repeat dosing may be needed

›Contraindicated in G6PD deficiency

›Glucagon

›Glucagon 3 to 10 mg IV bolus

›Follow with 3 to 5 mg/hr infusion

›cAMP-independent positive chronotropic and inotropic effects

›Tachyphylaxis common with prolonged use

›Vomiting is a frequent side effect: ensure airway protection

›Electrical pacing

›Transcutaneous pacing for hemodynamically significant bradydysrhythmias

›Bridge to transvenous pacing if stable capture achieved

›Not always effective with complete AV nodal blockade

›Capture thresholds may be elevated

›Transvenous pacing

›More reliable capture than transcutaneous

›Cardiology consultation for placement

›VA-ECMO

›Venoarterial ECMO for refractory cardiogenic shock

›Survival rates up to 77% reported in CCB toxicity

›Activate ECMO team early before cardiac arrest

›pH < 7.1 associated with increased ECMO mortality

›Expert consensus: ECMO preferred over ILE as salvage

Intralipid emulsion (ILE)

›ILE role and limitations

›20% lipid emulsion 1.5 mL/kg IV bolus

›Follow with 0.25 mL/kg/min for 30 to 60 minutes

›Only as last resort in cardiac arrest or peri-arrest

›Not recommended routinely per AHA 2025 and expert consensus

›Risks and concerns

›May increase GI absorption of lipophilic drugs and worsen poisoning

›Associated with abrupt cardiac arrest in some reports

›Interference with ECMO circuit

›Role is limited to peri-arrest when ECMO unavailable

09Special Populations/sp52

Pregnancy

›Pregnancy-specific considerations

›CCB toxicity risk in pregnancy

›Same pharmacologic mechanisms apply

›Fetal bradycardia and placental hypoperfusion risk

›Urgent obstetric consultation for viable gestation

›Resuscitation priorities

›Maternal stabilization is primary

›Fetal monitoring when gestation viable

›Left lateral decubitus positioning to relieve aortocaval compression

›Medication safety

›Calcium therapy: safe in pregnancy, crosses placenta minimally

›HDI: monitor fetal glucose indirectly via maternal levels

›Vasopressors: norepinephrine preferred over dopamine

›Methylene blue: limited data; use if maternal hemodynamics critical

›GI decontamination

›Activated charcoal: consider if airway protected

›Whole-bowel irrigation: use with caution given uterine pressure

Geriatric

›Older adult vulnerabilities

›Pharmacokinetic changes

›Reduced hepatic blood flow slows CCB metabolism

›Increased volume of distribution prolongs toxicity

›Lower therapeutic index due to baseline cardiac disease

›Baseline conduction disease

›Lower threshold for complete heart block

›Pacemaker consideration lower bar

›Pre-existing sick sinus syndrome or AV nodal disease

10Background/b77

Epidemiology

›Incidence and burden

›CCBs are a leading cause of poisoning mortality reported to poison centers

›Cardiovascular drug class with highest overdose fatality rate

›Amlodipine is now the most common CCB involved in poisoning

›Sustained-release formulations account for disproportionate mortality

›Demographics

›Intentional self-harm accounts for most severe cases

›Pediatric accidental exposures are high-risk due to low lethal dose

›Elderly patients at risk for therapeutic misadventure

›Outcomes

›Mortality highest with verapamil ingestion

›VA-ECMO survival rates up to 77% in refractory cases

›pH < 7.1 on ECMO associated with increased mortality

Pathophysiology

›Mechanism of toxicity

›L-type calcium channel blockade

›Inhibits voltage-gated calcium channels in cardiac and smooth muscle

›Calcium entry blocked in SA node, AV node, and myocardium

›Smooth muscle relaxation causes systemic vasodilation

›Cardiac effects

›Negative inotropy: reduced myocardial contractility

›Negative chronotropy: reduced SA node automaticity

›Negative dromotropy: slowed AV nodal conduction

›Cardiogenic shock and complete heart block in severe toxicity

›Vascular effects

›Systemic vasodilation

›Amlodipine: nitric oxide-mediated vasodilation is dominant mechanism

›Vasodilatory shock with initially preserved cardiac output

›Metabolic derangement

›Calcium channel blockade impairs insulin secretion from pancreatic beta cells

›Hyperglycemia is a direct pharmacologic effect

›Shift to free fatty acid utilization from glucose in myocardium

›High-dose insulin reverses this metabolic derangement

›Agent-specific patterns

›Verapamil

›Most potent cardiac depressant; highest CCB mortality

›Prominent bradycardia, AV block, and negative inotropy

›Diltiazem

›Intermediate cardiac and vascular effects

›Both bradycardia and hypotension

›Amlodipine

›Profound vasodilatory shock dominant

›Initial reflex tachycardia before progressive deterioration

›Very long half-life (30 to 50 hours); prolonged toxicity

Therapeutic Considerations

›High-dose insulin rationale

›Metabolic substrate restoration

›Reverses CCB-induced shift from glucose to free fatty acid utilization

›Cardiomyocytes preferentially use glucose during stress

›HDI restores glucose uptake and ATP production

›Evidence base

›Expert consensus and observational data support early use

›Some experts recommend HDI before vasopressors/inotropes

›No RCT but observational evidence demonstrates benefit

›AHA 2025 Class IIa recommendation for HDI in CCB toxicity

›Calcium therapy rationale

›Competitive antagonism of CCB at L-type channels

›Increases extracellular calcium concentration

›Partially overcomes channel blockade

›Target ionized calcium up to 2x normal for greater effect

›Effect may be incomplete in severe toxicity

›Methylene blue rationale

›Nitric oxide pathway inhibition

›Blocks guanylate cyclase activation

›Reduces cGMP-mediated vasodilation

›Particularly relevant for amlodipine toxicity

›ECMO as bridge

›Mechanical circulatory support

›Provides time for drug metabolism and elimination

›CCBs are hepatically metabolized; ECMO bridges to natural clearance

›No antidote that reverses toxicity directly; supportive care is treatment

›Drugs to avoid or use cautiously

›Intralipid emulsion routine use not recommended

›May worsen GI absorption of lipophilic agents

›Reserve for cardiac arrest/peri-arrest when ECMO unavailable

›Physostigmine not indicated

›No benefit in CCB toxicity

›HDI caution in pure vasodilatory shock without cardiogenic component

›POCUS to guide decision

11Patient Discharge Instructions/pdi32

copy discharge instructions

›Calcium channel blocker overdose recovery instructions

›You were treated for a calcium channel blocker medication overdose

›These medications affect your heart rate and blood pressure

›You were monitored closely and received treatments to stabilize your heart

›Activity and rest

›Rest at home for the next 24 to 48 hours

›Avoid strenuous physical activity until cleared by your doctor

›Medications

›Do not take your blood pressure or heart medications unless directed by your doctor

›A doctor will review and adjust your medication list before you leave

›Warning signs: return to the emergency room immediately if you experience

›Dizziness, lightheadedness, or fainting

›May indicate low blood pressure or slow heart rate returning

›Palpitations or feeling your heart beating slowly or irregularly

›Chest pain or pressure

›Shortness of breath

›Confusion, extreme sleepiness, or difficulty waking

›Nausea or vomiting that prevents you from taking medications

›Any recurrence of symptoms you had when you came to the hospital

›Follow-up appointments

›See your primary care doctor within 1 week

›Medication review and safe prescribing discussion

›Blood pressure and heart rate check

›Cardiology follow-up within 1 to 2 weeks if heart rhythm problems were detected

›Mental health follow-up if this was an intentional overdose

›Keep all scheduled mental health appointments

›Contact your mental health team or crisis line if you feel unsafe

12References/r35

Guidelines and key sources

›Primary guidelines

›AHA 2025 Guidelines for CPR and Emergency Cardiovascular Care Part 10

›Cao D et al. Circulation 2025

›AHA 2025 recommendations for calcium, HDI, vasopressors, methylene blue, ILE, and ECMO in CCB toxicity

›AHA 2023 Focused Update on Cardiac Arrest and Life-Threatening Toxicity

›Lavonas EJ et al. Circulation 2023

›Updated antidote recommendations and toxicologic cardiac arrest management

›Expert Consensus Recommendations for CCB Poisoning Management

›St-Onge M et al. Critical Care Medicine 2017

›Stepwise treatment framework and decontamination guidance

›ACC/AHA/HRS 2018 Bradycardia and Cardiac Conduction Delay Guideline

›Kusumoto FM et al. Heart Rhythm 2019

›Acute bradycardia management algorithm applicable to CCB toxicity

›Key studies and reviews

›Simpson MD, Cole JB. Current Opinion in Critical Care 2024

›Epidemiology of CCB poisoning and management implications

›Amlodipine as dominant agent; hyperglycemia severity markers

›Graudins A, Lee HM, Druda D. British Journal of Clinical Pharmacology 2016

›Antidotes and adjunct therapies for CCB and beta-blocker overdose

›Levine M et al. Critical Care Medicine 2007

›Hyperglycemia assessment after diltiazem or verapamil overdose

›Peak glucose > 16.7 mmol/l as severity predictor

›Megarbane B. British Journal of Clinical Pharmacology 2023

›HDI before vasopressors and inotropes in CCB toxicity: expert position

›Suarez F, Koyfman A, Long B. Journal of Emergency Medicine 2026

›Pearls and pitfalls for emergency clinicians in CCB and beta-blocker toxicity

›Hoegberg LCG et al. Clinical Toxicology 2026

Evidence & Review

Evidence & Review