Beta-blocker toxicity
(Redirected from Beta-Blocker Toxicity)
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 of 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
- Propranolol has sodium channel blockade activity leading to wide QRS[2]
- 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 with sotalol[3]
- Wide QRS with propanolol
- 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 [4] [5]
- 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[6]
- 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[7]
- 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[8]
- 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[9]
- IV 20% Intralipid at 1.5 mL/kg Bolus[10]
- 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
External Links
References
- ↑ NIH. PROPRANOLOL HYDROCHLORIDE. https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+3176
- ↑ Reith DM, Dawson AH, Epid D, Whyte IM, Buckley NA, Sayer GP. Relative toxicity of beta blockers in overdose. J Toxicol Clin Toxicol. 1996;34(3):273-278. doi:10.3109/15563659609013789
- ↑ Link MS, Foote CB, Sloan SB, Homoud MK, Wang PJ, Estes NA 3rd. Torsade de pointes and prolonged QT interval from surreptitious use of sotalol: use of drug levels in diagnosis. Chest. 1997;112(2):556-557. doi:10.1378/chest.112.2.556
- ↑ 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