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 especially lethal as they [[QT prolongation|prolong QT]], leading to dysrhythmias | *Agents with membrane-stabilizing activity (e.g. sodium channel blockade) are especially lethal as they [[QT prolongation|prolong QT]], leading to 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> | |||
*At toxic levels, beta-blockers will inhibit both beta-1 and beta-2 activity regardless for their affinity for specific receptors at therapeutic levels | |||
==Clinical Features== | ==Clinical Features== | ||
*Effects will typically be seen within 6 hours if ingestion with the exception of sotalol which can have a delayed and prolonged toxicity | |||
*Cardiac | *Cardiac | ||
**[[Bradycardia]] | **[[Bradycardia]] | ||
***Most common presenting sign | |||
**[[Hypotension]] | **[[Hypotension]] | ||
**Ventricular dysrhythmias | **[[Ventricular dysrhythmias]] | ||
*CNS | *CNS | ||
**Mental status | **[[Mental status changes]] | ||
***Delirium, coma | ***Delirium, coma | ||
**[[Seizure]] (esp with [[propranolol]]) | **[[Seizure]] (esp with [[propranolol]]) | ||
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**Bronchospasm (uncommon) | **Bronchospasm (uncommon) | ||
**[[Hypothermia]] | **[[Hypothermia]] | ||
**Brugada pattern of EKG with propanolol overdose | |||
**Sotalol has type III anti-arrhythmic that can lead to prolonged QT causing [[torsade de pointes]] and possibly [[ventricular fibrillation]] | |||
==Differential Diagnosis== | ==Differential Diagnosis== | ||
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**[[QT Prolongation]] | **[[QT Prolongation]] | ||
**Any bradydysrhythmia | **Any bradydysrhythmia | ||
**Obtain multiple ECGs over time to monitor any changes | |||
*Glucose | *Glucose | ||
*Chemistry | *Chemistry | ||
**Creatinine (esp with atenolol) | **Creatinine (esp with atenolol) | ||
*Continuous cardiac monitoring | |||
*Respiratory rate | |||
**Propranolol can induce central apnea | |||
==Management== | ==Management== | ||
#Adress airway, breathing, and circulation | |||
#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 | #*[[Atropine]] 0.5-1mg q3-5min up to 3mg | ||
#*Avoid atropine in wide-complex bradycardia and consider chronotropes such as [[epinephrine]], [[dobutamine]], [[dopamine]], [[isoproterenol]] | #*Avoid atropine in wide-complex bradycardia and consider chronotropes such as [[epinephrine]], [[dobutamine]], [[dopamine]], [[isoproterenol]] | ||
#*Consider [[transcutaneous pacing|transcutaneous]] vs [[transvenous pacing]] | #*Consider [[transcutaneous pacing|transcutaneous]] vs [[transvenous pacing]] | ||
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===[[Glucagon]]=== | ===[[Glucagon]]=== | ||
*Half-life is 20 min | *Acts independently of Beta-adrenergic receptors in cardiac tissue | ||
*Half-life is 20 min, thus, if effective, need to start drip quickly after bolus | |||
*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: 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> | ||
*Ped: 50mcg/kg | *Ped: 50mcg/kg | ||
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**Adult: 2-5 mg/hr | **Adult: 2-5 mg/hr | ||
**Ped: 70 mcg/kg/hr | **Ped: 70 mcg/kg/hr | ||
**Tachyphylaxis occurs quickly with glucagon so frequent monitoring of heart rate and blood pressure is necessary as the drip might need to be uptitrated | |||
*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> | *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 | **Continuous drip is usually limited by insufficient quantities from pharmacy | ||
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===Calcium=== | ===Calcium=== | ||
*Calcium gluconate 3g (30-60mL of 10% soln) | *Beta-antagonism decreases intracellular calcium leading to smooth muscle relaxation; supplementation may reverse hypotension by increasing intracellular calcium levels | ||
*Calcium chloride 1-3g IV bolus (10-20mL of 10% soln (requires large IV/central line) | *[[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] | **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 | **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 | **If effect in BP is seen can give as a drip at 10-50mg/kg/hr | ||
*Aim for calcium level of 14mg/dL and measure at least 30 minutes after administration | |||
===[[High dose insulin therapy| High-dose insulin and glucose]]=== | ===[[High dose insulin therapy| High-dose insulin and glucose]]=== | ||
*Takes 30- | *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 leading to increased cardiac output<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 0.5 gram/kg dextrose | *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 | *Regular insulin 1 Unit/kg/hr Drip, titrate infusion until hypotension is corrected or max 10u/kg/hr | ||
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**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 | ||
===Bicarbonate=== | |||
*Bolus if QRS is wide | |||
**Sodium channel blockade from propranolol | |||
===[[QT Prolongation]]=== | |||
*Magnesium if QT is prolonged | |||
**Sotalol known to prolong QT | |||
===[[Intralipid|Intralipid Therapy]]=== | ===[[Intralipid|Intralipid Therapy]]=== | ||
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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=== | ===[[ECMO]]=== | ||
*Consider VA ECMO for refractory cases | *Consider VA ECMO for refractory cases | ||
*Note that if ECMO is chosen, intralipids are avoided due to potential of clotting of the ECMO circuits | *Note that if ECMO is chosen, intralipids are avoided due to potential of clotting of the ECMO circuits | ||
===Sedation=== | ===Sedation=== | ||
*Consider [[ketamine]] as post-intubation sedation for hemodynamics | *Consider [[ketamine]] as post-intubation sedation for hemodynamics |
Revision as of 19:28, 20 November 2019
Background
- Coingestion with Calcium Channel Blockers, Tricyclic Antidepressants, and Antipsychotics increases mortality
- Agents with membrane-stabilizing activity (e.g. sodium channel blockade) are especially lethal as they prolong QT, leading to dysrhythmias
- Propranolol is particularly CNS toxic, as it is highly lipophilic and passes blood brain barrier freely, causing seizures and comatose state[1]
- At toxic levels, beta-blockers will inhibit both beta-1 and beta-2 activity regardless for their affinity for specific receptors at therapeutic levels
Clinical Features
- Effects will typically be seen within 6 hours if ingestion with the exception of sotalol which can have a delayed and prolonged toxicity
- Cardiac
- Bradycardia
- Most common presenting sign
- Hypotension
- Ventricular dysrhythmias
- Bradycardia
- CNS
- Mental status changes
- Delirium, coma
- Seizure (esp with propranolol)
- Mental status changes
- Other
- Hypoglycemia (interfere with gluconeogenesis and glycogenolysis; uncommon in adults)
- Helps to differentiate from Calcium Channel Blocker Toxicity
- Bronchospasm (uncommon)
- Hypothermia
- Brugada pattern of EKG with propanolol overdose
- Sotalol has type III anti-arrhythmic that can lead to prolonged QT causing torsade de pointes and possibly ventricular fibrillation
- Hypoglycemia (interfere with gluconeogenesis and glycogenolysis; uncommon in adults)
Differential Diagnosis
Symptomatic bradycardia
- Cardiac
- Inferior MI (involving RCA)
- Sick sinus syndrome
- Neurocardiogenic/reflex-mediated
- Increased ICP
- Vasovagal reflex
- Hypersensitive carotid sinus syndrome
- Intra-abdominal hemorrhage (i.e. ruptured ectopic)
- Metabolic/endocrine/environmental
- Hyperkalemia
- Hypothermia (Osborn waves on ECG)
- Hypothyroidism
- Hypoglycemia (neonates)
- Toxicologic
- Infectious/Postinfectious
- Other
Evaluation
- ECG
- PR prolongation
- Bradycardia
- QT Prolongation
- Any bradydysrhythmia
- Obtain multiple ECGs over time to monitor any changes
- Glucose
- Chemistry
- Creatinine (esp with atenolol)
- Continuous cardiac monitoring
- Respiratory rate
- Propranolol can induce central apnea
Management
- Adress airway, breathing, and circulation
- Consider activated charcoal if present within 2 hr of ingestion
- Symptomatic bradycardia
- Atropine 0.5-1mg q3-5min up to 3mg
- Avoid atropine in wide-complex bradycardia and consider chronotropes such as epinephrine, dobutamine, dopamine, isoproterenol
- Consider transcutaneous vs transvenous pacing
- Hypotension
- IV fluids
- Hypoglycemia
- If IV fluid and atropine are not sufficient then consider
Glucagon
- Acts independently of Beta-adrenergic receptors in cardiac tissue
- Half-life is 20 min, thus, if effective, need to start drip quickly after bolus
- 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
- Tachyphylaxis occurs quickly with glucagon so frequent monitoring of heart rate and blood pressure is necessary as the drip might need to be uptitrated
- 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
- Beta-antagonism decreases intracellular calcium leading to smooth muscle relaxation; supplementation may reverse hypotension by increasing intracellular calcium levels
- 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
- Aim for calcium level of 14mg/dL and measure at least 30 minutes after administration
High-dose insulin and glucose
- Takes 30-60 min for effect
- Augments myocardial contraction leading to increased cardiac output[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
Bicarbonate
- Bolus if QRS is wide
- Sodium channel blockade from propranolol
QT Prolongation
- Magnesium if QT is prolonged
- Sotalol known to prolong QT
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
- ↑ NIH. PROPRANOLOL HYDROCHLORIDE. https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+3176
- ↑ Kerns W. Management of beta-adrenergic blocker and calcium channel antagonist toxicity. Emerg Med Clin North Am. 2007;25(2):309-331. (Review)
- ↑ 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
- ↑ 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.
- ↑ High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning. Engebretsen KM et al. Clin Toxicol 2011;49:277-283
- ↑ 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
- ↑ Rothschild L, Bern S, Oswald, et al. Intravenous lipid emulsion in clinical toxicology. Scand J Trauma Resusc Emerg Med. 2010; 18:51.
- ↑ Cave, G. Intravenous Lipid Emulsion as Antidote Beyond Local Anesthetic Toxicity: A Systematic Review. 2009. 16(9)815–824