Calcium Channel Blocker and Beta Blocker Toxicity

Properties
Glucagon
High Dose Insulin
Euglycemia
Calcium Salts
Catecholamins
(epinephrine,
isoproterenol,
dopamine)
Dose
Peds: Initial: 50 mcg/kg IV
Adult: Initial: 3 to 5 mg IV
over 1-2 min
May start a glucagon
infusion based on response
dose/hr
LD: 1 u/kg regular insulin IV
MD: 1-10 u/kg/hr IV, max
10 units/kg/hr
PLUS Dextrose 10-50% @ 0.5
gm/kg/hr IV to maintain
euglycemia (BG goal 150-
250)
Adult: 1-3 gm IV
Peds: 60 mg/kg IV up to
3 gm
May repeat every 10-
20 minutes up to 9 gm
in adults and 180
mg/kg in peds
Usual doses; Titrated to
clinical effect with
hemodynamic
monitoring
Onset of Action
5-20 min
Tachyphylaxis after 12-24h
Delayed, 15-60 min
Mins, titrate to effect
Mins, titrate to effect
Adverse Effects
Emesis, hyperglycemia,
hypercalcemia,
Hypokalemia,
hypoglycemia
Vasoconstriction, renal
failure
Tachyarrhythmia,
hypertension, ischemia
Mechanism of
action
Bypasses inhibited beta
receptors, ↑ cAMP leading to
↑ chronotropy and inotropy
Inhibits Na+/Ca2+
antiporter, ↑ myocardial
Ca2+, ↑ carbohydrate
delivery to myocardium,
mild vasodilation ↑
perfusion
↑ Ca2+ concentration
gradient, ↓ the
negative inotropy,
impaired conduction,
and hypotension. No
effect on heart rate.
Providing ↑ adrenergic
activity at ⍺ + β
receptors
Comments
If full 10mg dose fails, start
drip at 10mg/hr because
glucagon will have
synergistic effects with
subsequent antidotes.
Patients may develop
tachyphylaxis.
Must administer with
dextrose source. Monitor
glucose every 15 min

Author, year
Design/ sample size
Intervention & Comparison
Outcome
Doepker, 2014
Case series:
Patient 1: PEA post-amlodipine,
verapamil, and metoprolol
ingestion
Patient 2: cardiogenic shock
post- amlodipine, simvastatin,
lisinopril, and metformin
ingestion
Both treated with:
Calcium, glucagon, vasopressors,
high-dose insulin, and IV lipid emulsion
Both initially treated with glucagon, calcium, and
vasopressors
Both had subsequent hemodynamic improvement,
resolution of shock, and full neurologic recovery
Holger, 2011
Case Series:
-
BB overdose, n=5
-
CCB overdose, n=2
-
BB + CCB overdose, n=2
-
Poly-drug, n=2
High-dose insulin + dextrose
AEs: Hypoglycemia in half of patients, hypokalemia
High-dose insulin therapy based on a 1-10 U/kg/h
dosing guideline appears to be effective in these
cardiotoxic overdoses
Page, 2009
Case Report:
Massive metoprolol overdose
(5 g)
1-2 u/kg regular insulin IV x4, then
insulin drip @ 10 u/kg
Additional therapies:
Atropine, Isoprenaline, Metaraminol,
0.9% Saline bolus
Improvement in heart rate and blood pressure
seen with addition of insulin + glucose.
Patient hemodynamically stable at hour 7.
Stellpflug, 2010
Case Report:
Cardiac arrest secondary to
intentional BB overdose
IV lipid emulsion and high-dose insulin
Care with intravenous lipid emulsions and insulin
therapy up to 21.8 u/kg/hr were utilized for
treatment. Patient survived to discharge with
baseline neurologic function
Love, 1998
Case Report:
Patients with symptomatic
bradycardia who failed
atropine after beta blocker
toxicity
N=9
Glucagon post atropine
Glucagon was effective in correcting
symptomatic bradycardia and hypotension in 8/9
patients.
Levine, 2013
Retrospective chart review:
48 patients with diltiazem and
verapamil overdoses
33 patients treated with vasopressors
8 patients treated with glucagon
and/or calcium
-
29/33 patients treated with vasopressors
survived without complication
o
3 patients had cardiac arrest
o

1.
Kerns II W, et al. Insulin improves survival in a canine model of acute beta-blocker
toxicity. Ann Emerg Med . 1997;29:748-757.
2.
Holger JS, et al. Insulin versus vasopressin and epinephrine to treat beta-blocker
toxicity. Clin Toxicol 2007;45:396-401.
3.
Holger JS, et al. High-dose insulin: a consecutive case series in toxin-induced
cardiogenic shock. Clin Toxicol. 2011;49:653-658.
4.
Page C, et al. The use of high-dose insulin-glucose euglycemia in beta-blocker
overdose: a case report. J Med Toxicol . 2009;5:139-143.
5.
Stellpflug SJ, et al. Intentional overdose with cardiac arrest treated with intravenous
fat emulsion and high-dose insulin. Clin Toxicol. 2010;48:227-229.
6.
Engebretsen KM, et al. High-dose insulin therapy in beta-blocker and calcium
channel-blocker poisoning. Clin Toxicol . 2011;49:277-283.
7.
Love JN, et al. A potential role for glucagon in the treatment of drug-induced
symptomatic bradycardia. Chest. 1998;114:323-326.
8.
Kerns II, W., 2007. Management of β-adrenergic blocker and calcium channel
antagonist toxicity. Emergency medicine clinics of North America, 25(2), pp.309-
331.
9.
Doepker B, Healy W, Cortez E, Adkins EJ. High-dose insulin and intravenous lipid
emulsion therapy for cardiogenic shock induced by intentional calcium-channel
blocker and beta-blocker overdose: a case series. The Journal of emergency
medicine. 2014 Apr 1;46(4):486-90.
10.
Meany CJ, Sare H, Hayes BD, Gonzales JP. Intravenous lipid emulsion in the
management of amlodipine overdose. Hosp Pharm. 2013:48(10):848-54.
11.
Lashari BH, Minalyan A, Khan W, Naglak M, Ward W. The use of high-dose insulin
infusion and lipid emulsion therapy in concurrent beta-blocker and calcium
channel blocker overdose. Cureus 10(11):e3534. DOI 10.7759/cureus.3534