beta adrenergic blocker overdose

see also:

• beta blockers
• toxicology
• LITFL - massive propranolol overdose

• more rapid onset of life-threatening features than with digoxin OD:
  • life-threatening CNS/CVS effects may occur within 30min of ingestion & death by 80min
• much of the cardioselectivity is lost in OD thus features characteristic of all beta blockers in OD are:
  • bradycardia (~70%)
  • hypotension (~70%)
  • decreased level of consciousness (>55%)
  • respiratory failure (~40%)
  • hypoglycaemia (esp. children)
  • AV block
  • negative inotropy
  • bronchospasm (actually uncommon in OD)
  • mild hyperkalaemia (usually doesn't require Rx unless digoxin OD too)
• mortality higher with propranolol than the cardioselective beta blockers because:
  • lipophilic ⇒ enters CNS ⇒ obtundation, resp. depression, seizures
• seizures most probably result from combination of:
  • hypotension, hypoglycaemia, hypoxia & direct CNS toxicity
• membrane stabilising (quinidine-like effect, also shown by nadolol & acebutalol):
  • impairs SA & AV nodal function ⇒ bradycardia & AV block
  • depressed ventricular conduction ⇒ wide QRS & occas. ventricular dysrhythmias
  • ⇒ VT, torsades, VF as well as bradyarrhythmias of other beta blockers
• those with intrinsic sympathomimetic activity (pindolol carteolol) may cause sinus tachycardia
  • labetalol by blocking alpha receptors has an additional mechanism for causing hypotension

• oxygen, monitor, IV line, ECG
• consider activated charcoal if recent ingestion:
  • consider 4h administration if drug undergoes entero-hepatic circulation
• if slow release formulation, consider whole bowel irrigation
• use atropine prior to vagally-stimulating procedures (eg. intubation, gastric lavage)
• propranolol overdose is managed primarily as a tricyclic antidepressant overdose (as early life-threats are due to its sodium-channel blocking effects) and secondarily as a beta-blocker overdose.

• good CPR (cardioversion/defibrillation unlikely to help)
• call an expert on toxicological arrests ASAP if possible
• give boluses iv sodium bicarbonate 1-2mEq/kg every 1-2 minutes until return of perfusing rhythm
• intubate and hyperventilate
• give adrenaline as per usual cardiac arrest protocol
• avoid amiodarone
• consider 20% intralipid 100ml over 1 minute, repeat once or twice in 3-5 minute intervals if required, followed by an infusion
• keep doing CPR

• 1st line now should probably be High Insulin-Dextrose - Euglycaemia Therapy (HIET) as pig studies seem to show this is the only effective Rx.
• IV atropine 0.02mg/kg children (min. 0.15mg) or 0.6mg adults:
  • tends to wear off quickly or be ineffective
• IV glucagon:
  • half-life 20min
  • adults: 5-10mg bolus then infusion 2-5mg/hr
  • children: 0.05-0.1mg/kg bolus then 0.05-0.1mg/kg/hr infusion
  • NB. reconstitute in sterile water & dilute in 5% dextrose as its diluent phenol toxicity will eventually cause toxicity!!
• 20ml/kg crystalloid solution to expand blood volume prn
• if inadequate response, consider an inotrope with chronotropic activity at higher (perhaps 20x) than usual doses:
  • isoprenaline:
    • in rats, reverses bradycardia in 76% & hypotension in all
    • may need up to 200-1660ug/min
  • dopamine:
    • may need up to 1000ug/min
  • adrenaline / epinephrine:
    • may need up to 1300ug/min
  • noradrenaline / norepinephrine:
  • amrinone but has no chronotropic activity
• refractory cases of bradycardia require early pacing
• refractory cases of hypotension:
  • peripheral arterial line and pulmonary artery catheter
  • may require IABP or cardiopulmonary bypass as the relatively short half lives (hours) means that these temporarising measures may be useful, as long as end-organ damage has not already occurred from prolonged hypotension
  • High Insulin-Dextrose - Euglycaemia Therapy (HIET)
    • unproven benefit in beta-blocker overdose

• usually treat VF/VT as per ACLS guidelines, avoiding VW class Ia & Ic drugs, ie. use lignocaine, DC;
• treat torsade as usual:
  • over-drive pacing with isoprenaline or a pacemaker
  • magnesium sulphate

• check for & treat hypoglycaemia:
• obtunded children should receive empiric 1-2ml/kg 25% glucose
• 5% dextrose infusions generally have been sufficient to maintain euglycaemia, esp. if concomitant glucagon & catecholamines.
• treat seizures as per usual

• most have large Vd's & thus are not suitable for dialysis EXCEPTIONS are the hydrophilic ones with low protein binding & low Vd:
  • atenolol (Tenormin), nadolol, sotalol, timolol

• if remain completely asymptomatic for 6hrs post-ingestion implies minimal risk unless slow-release formulation used
• ⇒ can be discharged after psych. assessment with medical F/U in 24hrs
• if slow-release preparation ⇒ admit
• if hypotension, higher than 1st degree HB or haemodynamically significant arrhythmias ⇒ ICU