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

Differential Diagnosis

Symptomatic bradycardia

Evaluation

  • ECG
  • Glucose
  • Chemistry
    • Creatinine (esp with atenolol)
  • Continuous cardiac monitoring
  • Respiratory rate
    • Propranolol can induce central apnea

Management

  1. Adress airway, breathing, and circulation
  2. Consider activated charcoal if present within 2 hr of ingestion
  3. Symptomatic bradycardia
  4. Hypotension
    • IV fluids
  5. 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

  1. ↑ NIH. PROPRANOLOL HYDROCHLORIDE. https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+3176
  2. ↑ 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
  3. ↑ 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
  4. ↑ Kerns W. Management of beta-adrenergic blocker and calcium channel antagonist toxicity. Emerg Med Clin North Am. 2007;25(2):309-331. (Review)
  5. ↑ 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
  6. ↑ 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.
  7. ↑ High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning. Engebretsen KM et al. Clin Toxicol 2011;49:277-283
  8. ↑ 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
  9. ↑ Rothschild L, Bern S, Oswald, et al. Intravenous lipid emulsion in clinical toxicology. Scand J Trauma Resusc Emerg Med. 2010; 18:51.
  10. ↑ Cave, G. Intravenous Lipid Emulsion as Antidote Beyond Local Anesthetic Toxicity: A Systematic Review. 2009. 16(9)815–824
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