Beta-blocker toxicity: Difference between revisions

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==Background==
==Background==
*Coingestion with [[Calcium Channel Blockers]], [[Tricyclic Antidepressants]], and [[Antipsychotics]] increases mortality
*Coingestion with [[Calcium Channel Blockers]], [[Tricyclic Antidepressants]], and [[Antipsychotics]] increases mortality
*Agents with membrane-stabilizing activity are esp lethal
*Agents with membrane-stabilizing activity are especially lethal as they [[QT prolongation|prolong QT]], leading to dysrhythmias
**Prolongs QT > dysrhythmias
**[[Propranolol]]
***Propranolol
**[[Sotalol]]
***Sotalol
*[[Propranolol]] is particularly CNS toxic, as it is highly lipophilic and passes blood brain barrier freely, causing seizures and comatose state<ref>NIH. PROPRANOLOL HYDROCHLORIDE. https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+3176</ref>


==Diagnosis==
==Clinical Features==
*Cardiac
*Cardiac
**Bradycardia
**[[Bradycardia]]
**Hypotension
**[[Hypotension]]
**Ventricular dysrhythmias
**[[Ventricular dysrhythmias]]
*CNS
*CNS
**Mental status change
**[[Mental status changes]]
***Delirium, coma
***Delirium, coma
**Seizure (esp w/ propranolol)
**[[Seizure]] (esp with [[propranolol]])
*Other
*Other
**Hypoglycemia (uncommon in adults)
**[[Hypoglycemia]] (interfere with gluconeogenesis and glycogenolysis; uncommon in adults)
***Helps to differentiate from [[Calcium Channel Blocker Toxicity]]
**Bronchospasm (uncommon)
**Bronchospasm (uncommon)
**Hypothermia
**[[Hypothermia]]


==Work-Up==
==Differential Diagnosis==
#ECG
{{Symptomatic bradycardia}}
#*PR prolongation
#*Bradycardia
#*[[QT Prolongation]]
#*Any bradydysrhythmia
#Glucose
#Chemistry
#*Creatinine (esp with atenolol)


==Differential Diagnosis==
==Evaluation==
*Calcium-channel blockers
*[[ECG]]
**Unlikely to cause CNS changes
**PR prolongation
**Hyperglycemia is more common
**[[Bradycardia]]
*Digoxin
**[[QT Prolongation]]
**Nausea/vomiting is more common
**Any bradydysrhythmia
*Clonidine
*Glucose
**Miosis, somnolence
*Chemistry
*Cholinergic agents
**Creatinine (esp with atenolol)
**SLUDGE


== Management ==
==Management==
#Consider [[activated charcoal]] if present within 2 hr of ingestion  
#Consider [[activated charcoal]] if present within 2 hr of ingestion  
#[[Symptomatic bradycardia]]  
#[[Symptomatic bradycardia]]  
#*[[Atropine]] 0.5-1mg q3-5min up to 0.04mg/kg  
#*[[Atropine]] 0.5-1mg q3-5min up to 0.04mg/kg  
#*Avoid atropine in wide-complex bradycardia and consider chronotropes such as [[epinephrine]], [[dobutamine]], [[dopamine]], [[isoproterenol]]
#*Consider [[transcutaneous pacing|transcutaneous]] vs [[transvenous pacing]]
#Hypotension
#Hypotension
#*IV fluids  
#*IV fluids  
#[[Hypoglycemia]]  
#[[Hypoglycemia]]  
#*Adult - D50
#*Adult - [[D50W]]
#*Ped - 2.5mL/kg of D10
#*Ped - 2.5mL/kg of [[D10W]]


;If IV fluid and atropine are not sufficient then consider:  
;If IV fluid and [[atropine]] are not sufficient then consider:  


===[[Glucagon]]===
===[[Glucagon]]===
*Half-life is 20min
*Half-life is 20 min
*Consider concurrent administration of ondansetron (causes n/v)
*Adult: 5 mg IV bolus over one minute <ref>Kerns W. Management of beta-adrenergic blocker and calcium channel antagonist toxicity. Emerg Med Clin North Am. 2007;25(2):309-331. (Review)</ref> <ref>Bailey B (2003). Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review. Journal of toxicology. Clinical toxicology, 41 (5), 595-602 PMID: 14514004</ref>
*Adult: 5mg IV bolus over one minute <ref>Kerns W. Management of beta-adrenergic blocker and calcium channel antagonist toxicity. Emerg Med Clin North Am. 2007;25(2):309-331. (Review)</ref> <ref>Bailey B (2003). Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review. Journal of toxicology. Clinical toxicology, 41 (5), 595-602 PMID: 14514004</ref>
*Ped: 50mcg/kg  
*Ped: 50mcg/kg  
*Rebolus if no response after 10min
*Rebolus if no response after 10 min
*Effects persist for 10-15 min
*Effects persist for 10-15 min
*If effective start infusion at:  
*If effective start infusion at:  
**Adult: 2-5mg/hr  
**Adult: 2-5 mg/hr  
**Ped: 70mcg/kg/hr
**Ped: 70 mcg/kg/hr
*Routine treatment with glucagon is not suggested as a sole antidote<ref>Graudins A et al. Calcium channel antagonist and beta‐blocker overdose: antidotes and adjunct therapies. Br J Clin Pharmacol. 2016 Mar; 81(3): 453–461.</ref>
**Continuous drip is usually limited by insufficient quantities from pharmacy
**Consider concurrent administration of [[ondansetron]] (causes nausea and vomiting)
 
===Calcium===
*[[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


===High dose insulin and glucose===
===[[High dose insulin therapy| High-dose insulin and glucose]]===
*Takes 30-60 min for effect
*Augments myocardial contraction<ref>High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.  Engebretsen KM et al.  Clin Toxicol 2011;49:277-283</ref>
*Augments myocardial contraction<ref>High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.  Engebretsen KM et al.  Clin Toxicol 2011;49:277-283</ref>
*Regular Insulin 1 Unit/kg IV Bolus accompanied by 0.5g/kg dextrose
*Regular Insulin 1 Unit/kg IV Bolus accompanied by 0.5 gram/kg dextrose
*Regular insulin 1Unit/kg/hr Drip  
*Regular insulin 1 Unit/kg/hr Drip, titrate infusion until hypotension is corrected or max 10u/kg/hr
*D50W drip at 0.1-0.2gram/kg/hr
*D50W drip at 0.1-0.2 gram/kg/hr
*Initial glucose checks q15 minutes until blood sugar stability established
*Replace potassium and magnesium if necessary


===[[Vasopressors]]===
===[[Vasopressors]]===
*Consider to be added as adjunctive therapy to all other therapies.  Toxcity can also be manage vasopressors alone <ref>Levine M et al. Critical Care Management of Verapamil and Diltiazem Overdose with a Focus on Vasopressors: A 25-Year Experience at a Single Center.  Ann Emerg Med 2013 May 1</ref>
*Consider to be added as adjunctive therapy to all other therapies
*Epinephrine  
*Toxicity can also be managed with vasopressors alone<ref>Levine M et al. Critical Care Management of Verapamil and Diltiazem Overdose with a Focus on Vasopressors: A 25-Year Experience at a Single Center.  Ann Emerg Med 2013 May 1</ref>
*[[Epinephrine]]
**Adult: Start 1 mcg/min and titrate to MAP=60  
**Adult: Start 1 mcg/min and titrate to MAP=60  
**Ped: Start 0.1mcg/kg/min
**Ped: Start 0.1mcg/kg/min


===Intralipid Therapy===
===[[Intralipid|Intralipid Therapy]]===
''Draw all labs prior to infusionSupport as an antidote comes from animal studies and case reports''
'''''Draw all labs prior to infusion'''''
 
*Support as an antidote comes from animal studies and case reports<ref>Rothschild L, Bern S, Oswald, et al. Intravenous lipid emulsion in clinical toxicology. Scand J Trauma Resusc Emerg Med. 2010; 18:51.</ref>
*IV 20% [[Intralipid]] at 1.5 mL/kg Bolus<ref>Cave, G. Intravenous Lipid Emulsion as Antidote Beyond Local Anesthetic Toxicity: A Systematic Review. 2009.  16(9)815–824</ref>
*IV 20% [[Intralipid]] at 1.5 mL/kg Bolus<ref>Cave, G. Intravenous Lipid Emulsion as Antidote Beyond Local Anesthetic Toxicity: A Systematic Review. 2009.  16(9)815–824</ref>
**Bolus could be repeated 1-2 times if persistent asystole
**Bolus could be repeated 1-2 times if persistent asystole
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**Infusion rate could be increased if the BP declines
**Infusion rate could be increased if the BP declines


===Hemodialysis===  
===[[Hemodialysis]]===
*Only effective for Nadolol, sotalol, and atenolol
*Only effective for [[nadolol]], [[sotalol]], and [[atenolol]]
 
===[[ECMO]]===
*Consider VA ECMO for refractory cases
*Note that if ECMO is chosen, intralipids are avoided due to potential of clotting of the ECMO circuits
 
===Sedation===
*Consider [[ketamine]] as post-intubation sedation for hemodynamics


==Disposition==
==Disposition==
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*[[Beta blockers]]
*[[Beta blockers]]


==Source==
==References==
<references/>
<references/>


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

Revision as of 00:27, 2 September 2019

Background

Clinical Features

Differential Diagnosis

Symptomatic bradycardia

Evaluation

Management

  1. Consider activated charcoal if present within 2 hr of ingestion
  2. Symptomatic bradycardia
  3. Hypotension
    • IV fluids
  4. Hypoglycemia
If IV fluid and atropine are not sufficient then consider

Glucagon

  • Half-life is 20 min
  • Adult: 5 mg IV bolus over one minute [2] [3]
  • Ped: 50mcg/kg
  • Rebolus if no response after 10 min
  • Effects persist for 10-15 min
  • If effective start infusion at:
    • Adult: 2-5 mg/hr
    • Ped: 70 mcg/kg/hr
  • Routine treatment with glucagon is not suggested as a sole antidote[4]
    • Continuous drip is usually limited by insufficient quantities from pharmacy
    • Consider concurrent administration of ondansetron (causes nausea and vomiting)

Calcium

  • 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

High-dose insulin and glucose

  • Takes 30-60 min for effect
  • Augments myocardial contraction[5]
  • Regular Insulin 1 Unit/kg IV Bolus accompanied by 0.5 gram/kg dextrose
  • Regular insulin 1 Unit/kg/hr Drip, titrate infusion until hypotension is corrected or max 10u/kg/hr
  • D50W drip at 0.1-0.2 gram/kg/hr
  • Initial glucose checks q15 minutes until blood sugar stability established
  • Replace potassium and magnesium if necessary

Vasopressors

  • Consider to be added as adjunctive therapy to all other therapies
  • Toxicity can also be managed with vasopressors alone[6]
  • Epinephrine
    • Adult: Start 1 mcg/min and titrate to MAP=60
    • Ped: Start 0.1mcg/kg/min

Intralipid Therapy

Draw all labs prior to infusion

  • Support as an antidote comes from animal studies and case reports[7]
  • IV 20% Intralipid at 1.5 mL/kg Bolus[8]
    • Bolus could be repeated 1-2 times if persistent asystole
    • Followed by infusion of 0.25 mL/kg/min for 30-60 minutes or until hemodynamic stability achieved
  • if responsive to bolus initiate infusion at 0.25 mL/kg/min for 1hr (e.g. about 600 mL over 30 minutes in a 70kg adult)
    • Infusion rate could be increased if the BP declines

Hemodialysis

ECMO

  • Consider VA ECMO for refractory cases
  • Note that if ECMO is chosen, intralipids are avoided due to potential of clotting of the ECMO circuits

Sedation

  • Consider ketamine as post-intubation sedation for hemodynamics

Disposition

  • Admit all symptomatic patients
  • Admit all sotalol ingestions (long half-life)
  • Observe all others for ~ 6hr

See Also

References

  1. NIH. PROPRANOLOL HYDROCHLORIDE. https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+3176
  2. Kerns W. Management of beta-adrenergic blocker and calcium channel antagonist toxicity. Emerg Med Clin North Am. 2007;25(2):309-331. (Review)
  3. Bailey B (2003). Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review. Journal of toxicology. Clinical toxicology, 41 (5), 595-602 PMID: 14514004
  4. Graudins A et al. Calcium channel antagonist and beta‐blocker overdose: antidotes and adjunct therapies. Br J Clin Pharmacol. 2016 Mar; 81(3): 453–461.
  5. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning. Engebretsen KM et al. Clin Toxicol 2011;49:277-283
  6. Levine M et al. Critical Care Management of Verapamil and Diltiazem Overdose with a Focus on Vasopressors: A 25-Year Experience at a Single Center. Ann Emerg Med 2013 May 1
  7. Rothschild L, Bern S, Oswald, et al. Intravenous lipid emulsion in clinical toxicology. Scand J Trauma Resusc Emerg Med. 2010; 18:51.
  8. Cave, G. Intravenous Lipid Emulsion as Antidote Beyond Local Anesthetic Toxicity: A Systematic Review. 2009. 16(9)815–824