This presentation includes approach to a patient admitting with calcium channel or beta blocker overdose. Toxic mechanism and clinical features are explained. Management is subdivided to Resuscitation, Risk assessment, supportive care & monitoring, investigations, decontamination, antidote and disposition. Antidotes explained are HEIT therapy, vasopressors, glucagon and lipid emulsion

1. CCB & BB
POISONING
Dr KTD Priyadarshani
Registrar in Emergency Medicine
Teaching Hospital Peradeniya
2023/03/28

2. CALCIUM CHANNEL
BLOCKERS

3. OVERVIEW
◦Severe CCB toxicity is highly lethal
◦Most lethal- Verapamil or Diltiazam
◦Good outcome with aggressive
treatment

4. TOXIC MECHANISM
Block opening of L type Ca Channel
◦ Cardiac toxicity
◦ Slowing of cardiac conduction (negative dromotropic)
◦ Reduced cardiac contraction force (negative inotropy)
◦ Sinus bradycardia ( negative chronotropic)
◦ Vascular dilatation
◦ Decreased afterload
◦ Systemic hypotension
◦ Coronary vasodilation
◦ Metabolic effects
◦ Inhibit insulin release
◦ Insulin resistance

5. CLINICAL FEATURES
◦ CVS
◦ Bradycardia, 1st degree heart block
◦ Hypotension
◦ Myocardial, non occlusive mesenteric
ischemia or stroke
◦ CNS
◦ Coma
◦ Seizures
◦ Cardiogenic pulmonary edema
◦ Metabolic
◦ Hyperglycemia
◦ Metabolic/lactic acidosis
◦ GI
◦ Bowel necrosis & ischemia

6. MANAGEMENT
RESUSCITATION
◦ A- Oxygen
◦ B- Early intubation
◦ C
◦ Fluid bolus 10-20 ml/kg crystalloid
◦ Arterial line
◦ Catecholamine infusion- Dopamine, Adrenaline or NE
◦ ECG

7. RISK ASSESSMENT
◦Drug – IR or ER
◦Co ingestion of BB or Digoxin
◦Elderly
◦Co morbidities

8. SUPPORTIVE CARE & MONITORING
◦ Invasive monitoring
◦ Atropine 0.6mg IV repeat up to 1.8 mg
◦ Often ineffective
◦ Calcium- Temporary measure to increase HR & BP
◦ Calcium gluconate 10% 60 ml or (0.6-1 ml/kg in children)
◦ calcium chloride 10% 20 ml IV over 15 min (0.2 ml/kg in children)
◦ Repeat boluses up to 3 times
◦ Consider infusion to keep Ca >2 mEq/L
◦ Ionised Ca every 30 min after & 1-2 hours
◦ Sodium bicarbonate for severe metabolic acidosis
◦ 50-100 mEq (0.5-1 mEq/kg in children)

9. INVESTIGATIONS
Bedside
◦ ECG- sinus bradycardia, varying degrees of AV block & slowing of intraventricular conduction, junctional &
ventricular escape rhythm
◦ ABG- lactatic acidosis+ high anion gap+low HCO3
◦ Blood sugar (hyperglycemia is a marker of severity)
Laboratory
◦ Serum Ca
◦ SE- hypokalemia
◦ S Creatinine
Imaging
◦ CXR- Pulmonary edema
◦ Echo- impaired contractility

10. DECONTAMINATION
◦ Gastric lavage- with in 1 hour
◦ Activated charcoal
◦ if <1 hr – for standard release or
◦ <4hr- for SR preparations
◦ Whole bowel irrigation if
◦ Patient is cooperative
◦ Present with in 4 hrs of ingestion of >10 tabs of Verapamil or Diltiazem SR
◦ No evidence of established toxicity

11. ANTIDOTE
◦ High dose insulin-euglycemic
therapy HEIT
◦ Vasoactive infusions
◦ IV lipid emulsion
◦ Cardiac pacing
◦ Circulatory support devices

12. ADRENERGIC AGENTS
◦ Agent with both alpha & beta agonist activity is useful
◦ Epinephrine or Norepinephrine- titrate to MAP 65mmHg
◦ But can use dopamine, vasopressin, dobutamine or isoproterenol as well
◦ When standard doses are inadequate, it is reasonable to use high doses or
multiple agents titrated to achieve a MAP >65 mmHg
◦ Consider Methylene blue if refractory vasoplegic
◦ Decrease cGMP formation
◦ Scavenge nitric oxide
◦ Inhibit nitric oxide synthesis- vasoconstriction

13. HEIT THERAPY
◦ Commence
◦ Glucose 25 g (50% 50 mL) IV bolus (if RBS <200 mg/dL)
◦ Short acting insulin 1 U/kg bolus to maximally saturate insulin receptors
◦ Continue
◦ Short acting insulin 0.5IU/kg/h & titrate every 30 min to a max 5 IU/kg/hr
◦ Dextrose 25g/h infusion titrated to maintain euglycemia (100-200mg/dL)
◦ Monitor
◦ Glucose- every 20 min for 1st hour, then every 1 h
◦ Potassium- replace only if <2.5 mmol/L & there is a source of potassium loss

14. Therapeutic end points
◦ Improvement in myocardial ejection fraction (>50%) increased BP (
SBP >90 mmHg in adults)
◦ Adequate heart rate (>60 bpm)
◦ Resolution of acidemia, euglycemia, adequate UOP (1-2 ml/kg/h)
◦ Reversal of cardiac conduction abnormalities (QRS interval <120 ms)
◦ Improved mentation
◦ Therapy is weaned off after withdrawal of other vasopressors, as
cardiotoxicity resolves.

15. GLUCAGON
◦ Bypass the beta receptor and stimulate cardiac activity via activation
of adenylate cyclase
◦ IV bolus 5mg in adult and 0.03 mg/kg in children given over 1-2 min
◦ A response is usually seen with in 15 min
◦ If no response – repeat a bolus
◦ If there is a hemodynamic improvement- maintenance infusion
5mg/kg/hr in adult 0.05 mg/kg/hr in children

16. IV LIPID EMULSION THERAPY
◦Create a pharmacological sink for fat soluble drugs, provide
fatty acid substrate for cardiac energy supply and improve
myocyte function by increasing intracellular calcium levels.
◦20% lipid emulsion 1.5ml/kg bolus over 2-3 minutes
followed by a 0.25 ml/Kg per min infusion
◦Can increase dose if blood pressure remain low
◦Upper limit- 10ml/kg over the initial 30 min

17. DISPOSITION
◦Clinical features – needs HDU/ICU care
◦Asymptomatic
◦ Cardiac monitoring for
◦ 4 hrs if standard release verapamil or Diltiazem
◦ 16 hrs if SR verapamil or Diltiazem
◦ Psychiatric assessment if possible

18. BETA BLOCKERS

19. OVERVIEW
◦ For treatment of various cardiovascular, neurogenic, endocrine,
ophthalmologic and psychiatric disorders
◦ Isolated overdose is usually benign
◦ Propranolol- sodium channel blocker- widen QRS
◦ Sotalol – block metabolic pathways, Potassium channel blocker-
prolong QT interval & torsade pointes

20. Toxic mechanism
◦ Competitive antagonist at 1
& 2 receptors
◦ Na channel blocker-
Propranolol
◦ Ventricular arrhythmia
◦ CNS direct toxicity
◦ K channel blockers- sotalol
◦ QT prolongation
◦ Risk of torsades de pointes

21. CLINICAL FEATURES
Onset by 4 hrs
◦ CVS
◦ Bradycardia – 60 bpm(sinus,
1st,2nd,3rd degree block, junctional or
ventricular),
◦ Hypotension
◦ Increased QRS (propanalol)
◦ Increased QTc (Sotalol)
◦ CNS
◦ Delirium, Coma
◦ Seizures (propanalol )
◦ Other
◦ Bronchospasm
◦ Pulmonary edema
◦ Hypokalemia
◦ Hypoglycemia

22. INVESTIGATIONS
Bedside
◦ ECG- serial monitoring
◦ Blood sugar
Laboratory
◦ SE
◦ RFT
Imaging
◦ Echo- impaired contractility

23. MANAGEMENT
RESUSCITATION – Propranolol- treat
like TCA overdose
◦ A- early intubation & ventilation
◦ B- hyperventilate (pH 7.5-7.55)
◦ C-
◦ Hypotension
◦ 20 ml/kg crystalloid
◦ NaHCO3 2mmol/kg until MAP>65
◦ Noradrenaline 0.15mg/kg
◦ Adrenaline 0.15 mg/kg
◦ Ventricular arrhythmia-
◦ Unlikely defibrillation will work
◦ Bicarbonate 2mmol/kg every 1-2 min to restore
perfusing rhythm
◦ Lidocaine 1.5 mg/kg IV- 3rd line when pH >7.5
◦ Type Ia (procainamide & amiodarone are
contraindicated
◦ Bradycardia & low BP-
◦ IV atropine 20 mcg/kg
◦ Glucagon 5-10 mg stat then 1-5 mg/hr
◦ Adrenaline infusion
◦ Isoprenaline 4 mcg/min IV infusion
◦ Torsades de pointes (sotalol)
◦ MgSO4 10 mmol IV over 15 min
◦ If HR <100 bpm- isoprenaline or overdrive pacing
◦ D-
◦ Seizure – IV Benzodiazapine

24. DECONTAMINATION
◦Activated charcoal- beneficial if given with in 1 hour

25. SUPPORTIVE MANAGEMENT
◦ Monitoring
◦ Cardiac Monitoring
◦ Monitor Blood pressure
◦ Invasive monitoring & central access

26. ANTIDOTE- HEIT THERAPY
◦ High dose insulin euglycemic therapy- as above

27. DISPOSITION
◦ Asymptomatic, normal ECG at 6 hours
◦ Medically cleared
◦ Clinical or ECG manifestations
◦ Admit to HDU or ICU

28. REFERENCES
◦ Tintinali Emergency Medicine- 9th Edition
◦ Life in the fast lane
◦ Murray L et al. Toxicology Handbook 3rd Edition. Elsevier Australia 2015. ISBN 9780729542241