Calcium channel blocker toxicity: Difference between revisions

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==Background==
==Background==
*Hemodialysis is ineffective
*[[Hemodialysis]] is ineffective
*Precipitous deterioration is common (esp w/ verapamil)
*Precipitous deterioration is common (esp with verapamil)
*Nifedipine can kill a child with a single pill
*[[Nifedipine]] can kill a child with a single pill
 
===2 Classes===
===2 Classes===
====Dihydropyridines====
====Dihydropyridines====
*Nifedipine, Amlodipine, Nicardipine
*[[Nifedipine]], [[Amlodipine]], [[Nicardipine]]
**Systemic vasodilation, mild effect on heart
**Systemic vasodilation, mild effect on heart
* Toxicity = Hypotension, reflex tachycardia
*Toxicity = [[Hypotension]], reflex [[tachycardia]]
*With higher doses of toxicity peripheral selectivity is lost
*With higher doses of toxicity peripheral selectivity is lost
**I.e. may see decreased inotrophy, bradycardia
**I.e. may see decreased inotropy, [[bradycardia]]


===Non-dihydropyridines (verapamil, diltiazem)===
====Non-dihydropyridines====
*[[Verapamil]], [[Diltiazem]]
*Stronger effect on heart, weak vasodilators
*Stronger effect on heart, weak vasodilators
*Toxicity = Bradycardia, decreased inotropy
*Toxicity = [[Bradycardia]], decreased inotropy


==Diagnosis==
==Clinical Features==
*Cardiovascular
*Cardiovascular
**Hypotension (any CCB overdose)
**[[Hypotension]] (any CCB overdose)
**Bradycardia (usually only seen with verapamil/dilt)
**[[Bradycardia]] (usually only seen with [[verapamil]]/[[diltiazem]])
**AV/sinus block
**[[AV block|AV/sinus block]]
**CHF
**[[CHF]]
*Pulmonary
*Pulmonary
**Respiratory depression
**[[Respiratory arrest|Respiratory depression]]
**Pulmonary edema
**[[Pulmonary edema]]
*GI
*GI
**Nausea/vomiting
**[[Nausea/vomiting]]
*Neurologic
*Neurologic
**Lethargy, confusion, coma
**[[Lethargy]], [[confusion]], [[coma]]
*Metabolic
*Metabolic
**Hyperglycemia (due to insulin resistance)
**[[Hyperglycemia]] (inhibits insulin release from pancreatic islet cells)
***Helps to differentiate from [[Beta-Blocker Toxicity]]


==Work-Up==
==Differential Diagnosis==
#ECG
{{Symptomatic bradycardia}}
##PR prolongation (varying degrees of AV block)
###AV block occurs more commonly with verapamil
##Bradydysrhythmia
#Glucose
#Chemistry
##Serum calcium is often normal


==DDx==
==Evaluation==
#Beta blockers
*[[ECG]]
##More likely to cause CNS changes
**PR prolongation (varying degrees of AV block)
##Hypoglycemia is more common
***[[AV block]] occurs more commonly with verapamil
#Digoxin
**[[Bradycardia|Bradyarrhythmia]]
##Nausea/vomiting is more common
*Glucose
#Clonidine
**[[hyperglycemia]], may help distinguish [[β-blocker toxicity]]
##Miosis, somnolence
*Chemistry
#Cholinergic agents
**Serum calcium is often normal
##SLUDGE
 
==Management==
''The majority of literature on calcium channel blocker overdose management is low-quality evidence and high-dose insulin and extracorporeal life support have the best evidence; other therapies such as include calcium, dopamine, norepinephrine, and lipid emulsion therapy may be beneficial but are poorly studied<ref>St-Onge M, et al. Treatment for calcium channel blocker poisoning: a systematic review. Clin Toxicol 2014 [http://informahealthcare.com/doi/pdf/10.3109/15563650.2014.965827 PDF]</ref>


== Treatment  ==
*Monotherapy only successful for trivial overdoses  
*Monotherapy only successful for trivial overdoses  


===GI decontamination===
*[[Charcoal]]
**1g/kg (max 50g) x1
**Consider if present within 1-2hr with delayed-release preparation
*Consider [[whole bowel irrigation]] if sustained or extended-release, esp if the drug is verapamil or diltiazem


''The majority of literature on calcium channel blocker overdose management is low-quality evidence and high-dose insulin and extracorporeal life support have the best evidence and other therapies such as include calcium, dopamine, norepinephrine, and lipid emulsion therapy may be beneficial but are poorly studied<ref>St-Onge M, et al. Treatment for calcium channel blocker poisoning: a systematic review. Clin Toxicol 2014 [http://informahealthcare.com/doi/pdf/10.3109/15563650.2014.965827 PDF]</ref>
===[[IV fluids]]===
*Initial 20cc/kg bolus especially if source of hypotension is undifferentiated and also possibly hypovolemic or due to [[Sepsis]]


===Charcoal===
===[[Atropine]]===
*1g/kg (max 50g) x1
*Adult: 0.5-1mg IV q2-3min to max of 3g
**Consider if present w/in 1-2hr w/ delayed-release preparation
*Ped: 0.02mg/kg (minimum is 0.1mg)
*Administer to anyone with symptomatic [[bradycardia]]


===High-dose insulin and glucose===
#Takes 30-60min for effect
#Glucose:
##Adult: 50mL of D50W
##Ped: 2.5mL/kg of D10
#Insulin bolus 1 unit/kg followed by 0.5units/kg/hr
##Titrate infusion until hypotension is corrected or max 2u/kg/hr
##Requires frequent glucose and K checks
#Potassium
##If &lt;3 administer 20mEq IV
===Calcium===
===Calcium===
*Avoid if digoxin toxicity is possible
''Avoid if [[digoxin toxicity]] is possible''
#Calcium gluconate 3g (30-60mL of 10% soln)  
*[[Calcium gluconate]] 3g (30-60mL of 10% soln)  
#Calcium chloride 1-3g IV bolus (10-20mL of 10% soln (requires large IV/central line)
*[[Calcium chloride]] 1-3g IV bolus (10-20mL of 10% soln (requires large IV/central line)
##Preferred over calcium gluconate because it provides triple the amount of calcium on a weight-to-weight basis <ref>Tintinalli's 7th Ed.</ref>
**Preferred over calcium gluconate because it provides triple the amount of calcium on a weight-to-weight basis <ref>Tintinalli's 7th Ed.</ref>
##Effects of calcium are transient
**Give Calcium 1g Q5min to titrate to BP effect
##Repeat dosing often required
**If effect in BP is seen can give as a drip at 10-50mg/kg/hr
###Alternatively, can be given as an infusion: 2-6g/hour
**can safely push serum Calcium levels to 15-18 or even low 20s if patient tolerates (double normal)


===Vasopressors===
===[[Glucagon]]===
#Norepinephrine is agent of choice
*5mg IV bolus q10min x 2
===Glucagon===
*will often cause severe [[nausea/vomiting]], give [[Zofran]] prior
#5mg IV bolus q10min x 2  
 
===Fluids===
===[[Vasopressors]]===
*Initial 20cc/kg bolus especially if source of hypotension is undifferentiated and also possibly hypovolemic or due to [[Sepsis]]
*[[Norepinephrine]] is agent of choice
===Atropine===
**Start at 2mcg/min, uptitrate rapidly, goal MAP 65mmHg
##Adult: 0.5-1mg IV q2-3min to max of 3g
 
##Ped: 0.02mg/kg (minimum is 0.1mg)
===[[High dose insulin therapy| High-dose insulin and glucose]]===
#Intravenous lipid emulsion (when standard treatment fails)
* Mechanism of Action: Insulin has a positive inotropic effect on the heart by improving metabolic support of cardiac tissues during hypotensive shock (cardiac tissues preferentially utilize fatty acid as an energy source during normal condition; under stressed conditions, cardiac tissues rely on glucose metabolism as their primary energy source). Some studies have also demonstrated that high doses of insulin can induce endothelial nitric oxide synthase activity and improve microvascular dysfunction by a vasodila- tory effect in cardiac and pulmonary vasculature
##1.5mL/kg of 20% lipid followed by 0.25mL/kg/minute
 
##Data show significant benefit in animals and case reports show promise in humans
*Takes 30-60min for effect
##If used, report on http://www.lipidrescue.org to contribute to the database
*[[Dextrose|Glucose]]:
**Adult: 50mL of D50W
**Ped: 2.5mL/kg of D10
*[[Insulin]] bolus 1 unit/kg given with 1amp of D50, then 0.5 – 1 unit/kg/hr continuous infusion
**Titrate infusion until hypotension is corrected or max 2u/kg/hr
**Titrate dextrose drip to avoid hypoglycemia
**initial glucose checks q15 minutes until blood sugar stability established
*[[Potassium]]
**If <3 administer 20mEq IV
 
===[[Intralipid|Intravenous lipid emulsion]]===
*1.5mL/kg bolus of 20% lipid followed by 0.25mL/kg/minute


==Disposition==
==Disposition==
*Admit all symptomatic pts
*Admit all symptomatic patients
*Admit all sustained-release ingestions
*Admit all sustained-release ingestions
*D/C if asymptomatic x 6-8hrs
*Discharge if asymptomatic x 6-8hrs


==See Also==
==See Also==
*[[Calcium Channel Blockers]]
*[[Calcium Channel Blockers]]


==Source==
==Video==
{{#widget:YouTube|id=twKMOXaH2dE}}
 
==References==
<references/>
<references/>


[[Category:Cards]]
[[Category:Cardiology]]
[[Category:Tox]]
[[Category:Toxicology]]
[[Category:Pharmacology]]

Revision as of 14:30, 19 October 2019

Background

  • Hemodialysis is ineffective
  • Precipitous deterioration is common (esp with verapamil)
  • Nifedipine can kill a child with a single pill

2 Classes

Dihydropyridines

Non-dihydropyridines

Clinical Features

Differential Diagnosis

Symptomatic bradycardia

Evaluation

Management

The majority of literature on calcium channel blocker overdose management is low-quality evidence and high-dose insulin and extracorporeal life support have the best evidence; other therapies such as include calcium, dopamine, norepinephrine, and lipid emulsion therapy may be beneficial but are poorly studied[1]

  • Monotherapy only successful for trivial overdoses

GI decontamination

  • Charcoal
    • 1g/kg (max 50g) x1
    • Consider if present within 1-2hr with delayed-release preparation
  • Consider whole bowel irrigation if sustained or extended-release, esp if the drug is verapamil or diltiazem

IV fluids

  • Initial 20cc/kg bolus especially if source of hypotension is undifferentiated and also possibly hypovolemic or due to Sepsis

Atropine

  • Adult: 0.5-1mg IV q2-3min to max of 3g
  • Ped: 0.02mg/kg (minimum is 0.1mg)
  • Administer to anyone with symptomatic bradycardia

Calcium

Avoid if digoxin toxicity is possible

  • Calcium gluconate 3g (30-60mL of 10% soln)
  • Calcium chloride 1-3g IV bolus (10-20mL of 10% soln (requires large IV/central line)
    • Preferred over calcium gluconate because it provides triple the amount of calcium on a weight-to-weight basis [2]
    • Give Calcium 1g Q5min to titrate to BP effect
    • If effect in BP is seen can give as a drip at 10-50mg/kg/hr
    • can safely push serum Calcium levels to 15-18 or even low 20s if patient tolerates (double normal)

Glucagon

Vasopressors

  • Norepinephrine is agent of choice
    • Start at 2mcg/min, uptitrate rapidly, goal MAP 65mmHg

High-dose insulin and glucose

  • Mechanism of Action: Insulin has a positive inotropic effect on the heart by improving metabolic support of cardiac tissues during hypotensive shock (cardiac tissues preferentially utilize fatty acid as an energy source during normal condition; under stressed conditions, cardiac tissues rely on glucose metabolism as their primary energy source). Some studies have also demonstrated that high doses of insulin can induce endothelial nitric oxide synthase activity and improve microvascular dysfunction by a vasodila- tory effect in cardiac and pulmonary vasculature
  • Takes 30-60min for effect
  • Glucose:
    • Adult: 50mL of D50W
    • Ped: 2.5mL/kg of D10
  • Insulin bolus 1 unit/kg given with 1amp of D50, then 0.5 – 1 unit/kg/hr continuous infusion
    • Titrate infusion until hypotension is corrected or max 2u/kg/hr
    • Titrate dextrose drip to avoid hypoglycemia
    • initial glucose checks q15 minutes until blood sugar stability established
  • Potassium
    • If <3 administer 20mEq IV

Intravenous lipid emulsion

  • 1.5mL/kg bolus of 20% lipid followed by 0.25mL/kg/minute

Disposition

  • Admit all symptomatic patients
  • Admit all sustained-release ingestions
  • Discharge if asymptomatic x 6-8hrs

See Also

Video

{{#widget:YouTube|id=twKMOXaH2dE}}

References

  1. ↑ St-Onge M, et al. Treatment for calcium channel blocker poisoning: a systematic review. Clin Toxicol 2014 PDF
  2. ↑ Tintinalli's 7th Ed.
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