10/26/2015 HIGH DOSE INSULIN IN BETA BLOCKER AND CALCIUM CHANNEL BLOCKER OVERDOSE. Session # 5 C
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1 HIGH DOSE INSULIN IN BETA BLOCKER AND CALCIUM CHANNEL BLOCKER OVERDOSE Session # 5 C 1
2 TOM SCULLARD RN MSN CCRN CLINICAL CARE SUPERVISOR MEDICAL INTENSIVE CARE UNIT HENNEPIN COUNTY MEDICAL CENTER MINNEAPOLIS MINNESOTA 2
3 OBJECTIVES 1. Identify the cardiovascular effects of beta blocker and calcium channel blocker overdoses 2. Describe the proposed mechanism of high dose insulin use in beta blocker and calcium channel blocker overdose 3. Describe the role of the nurse when caring for the patient receiving high dose insulin therapy. OVERDOSE Intentional ingestion Unintentional ingestion Patient error Medication interaction Children 3
4 BETA BLOCKER & CALCIUM CHANNEL BLOCKER OVERDOSE Overdose is associated with a high incidence of morbidity and mortality due to cardiovascular toxicity including profound hypotension and conduction disturbances AMERICAN ASSOCIATION OF POISON CONTROL CENTERS NATIONAL POISON DATA SYSTEM beta blocker overdoses 5076 calcium channel blocker overdoses Fatalities beta blocker 13 calcium channel blocker 24 4
5 BETA BLOCKERS & CALCIUM CHANNEL BLOCKERS Beta Blockers 128 million prescriptions for β-blockers filled in th most commonly prescribed medication class Calcium channel blockers 98 million prescriptions filled in 2010 BETA BLOCKER USES Beta blockers are used for treating: Abnormal heart rhythm High blood pressure Heart failure Angina (heart pain) Tremor Pheochromocytoma Prevention of migraines 5
6 BETA BLOCKERS (BRAND NAMES CANADA) Apo-Atenolol (atenolol) Apo-Metoprolol (metoprolol) Apo-Propranolol (propranolol) Apo-Timol (timolol) Betaloc (metoprolol) Blocadren (timolol) Corgard (nadolol) Inderal (propranolol) Lopressor (metoprolol) Monitan (acebutolol) Novo-Atenol (atenolol) Novometoprol (metoprolol) Novo-Pindol (pindolol) Novo-Timol (timolol) Sectral (acebutolol) Sotacor (sotalol) Tenormin (atenolol) Trandate (labetalol) Trasicor (oxprenolol) Visken (pindolol) 6
7 CALCIUM CHANNEL BLOCKER USES Calcium channel blockers are approved for treating: High blood pressure Angina Abnormal heart rhythms (for example, atrial fibrillation, paroxysmal supraventricular tachycardia) Subarachnoid hemorrhage Raynaud's phenomenon Cardiomyopathy Migraine headaches 7
8 CALCIUM CHANNEL BLOCKERS (BRAND NAMES CANADA) Adalat (nifedipine), Apo-Diltiaz (diltiazem) Apo-Nifed (nifedipine) Apo-Verap (verapamil) Cardene (nicardipine) Cardizem (diltiazem) Cardizem SR (diltiazem) Isoptin (verapamil) Nimotop (nimodipine) Novo-Diltazem (diltiazem) Novo-Nifedin (nifedipine) Novo-Veramil (verapamil) Nu-Diltiaz (diltiazem) Nu-Nifed (nifedipine) Nu-Verap (verapamil) Plendil (felodipine) Renedil (felodipine) Sibelium (flunarizine) Syn-Diltiazem (diltiazem) Verelan (verapamil) CARDIAC MYOCTES Myocte: Type of cell found in muscle tissue Cardiac myoctes responsible for: Electrical impulses Contractility Exchange ions 8
9 BETA AND CALCIUM CHANNEL RECEPTORS What do they do? BETA RECEPTORS Beta 1 Primarily regulate myocardial tissue and affect the rate of contraction via impulse conduction Beta 2 smooth muscle tone and influence vascular and bronchiolar relaxation Beta 3 thought to primarily affect lypolysis and may have effects on cardiac inotropy 9
10 BETA RECEPTORS ACTION Beta receptors coupled with Gs protiens Activate adenylate cyclase Form camp from ATP activates camp dependent protein kinase (PK-A) Causes increase calcium into the cell Leads to increased release calcium by sarcoplasmic reticulum in the heart Increased contractility, heart rate BETA- BLOCKERS Beta-blockers selectively antagonize the effects of catecholamines at the beta-adrenergic receptor that are linked to G proteins 10
11 BETA BLOCKERS Beta-adrenergic antagonists competitively antagonize the effects of catecholamines at the beta-adrenergic receptor and blunt the chronotropic and inotropic response to catecholamines BETA BLOCKER OVERDOSE SYMPTOMS Hypotension Bradycardia Bronchospasms Cool extremities r/t vasoconstriction Beta 2 blockade and alpha -1 activity Low blood sugars? Inhibition of release of glucagon in the pancreas 11
12 CALCIUM CHANNELS Found on myocardial cells action potential generation in sinoatrial tissue initiates calcium release from intracellular storage which is needed for contraction Vascular smooth muscle cells Maintains tone β-islet cells of the pancreas CALCIUM CHANNELS Calcium enters open voltage-sensitive calcium channels to promote the release of calcium from the sarcoplasmic reticulum. The released calcium combines with troponin to cause muscle contraction via actin and myosin fibers 12
13 CALCIUM CHANNEL BLOCKER OVERDOSE Calcium channel blockers prevent the opening of the voltage-gated calcium channels and reduce calcium entry into cells during phase 2 of an action potential. CALCIUM CHANNEL BLOCKER OVERDOSE SYMPTOMS Hypotension Bradycardia Hyperglycemia Hypoinsulinemia Warm extremities (vasodilation) Conduction delays Metabolic Acidosis (poor perfusion) 13
14 BETA BLOCKER AND CALCIUM CHANNEL OVERDOSE In overdose, β-blockers and CCBs often have similar presentation and there is much overlap in treatment. Cardiotoxicity characterized by hypotension and bradycardia is the common clinical feature SIGNS AND SYMPTOMS Hyperglycemia Bronchospasm Cardiogenic shock Metabolic acidosis Pulmonary edema due to pre-capillary vasodilation and increased transcapillary hydrostatic pressure, Bowel infarction/ileus 14
15 BETA BLOCKER/ CALCIUM CHANNEL BLOCKER DRUG INDUCED SHOCK Heart preferred energy source Free Fatty Acids Stress Carbohydrate Increased glucose (glycogenolysis) Decreased insulin (pancreatic b-islet cell blockage) Lack of fuel for energy production Aerobic Anaerobic metabolism TREATMENT Airway Breathing Circulation Decontamination (Gastrointestinal) Gastric lavage Activated charcoal Whole bowel irrigation 15
16 TREATMENT Fluids Atropine Calcium Glucagon Pacing Adrenergic drugs dopamine, norepinephrine, epinephrine Insulin 16
17 INSULIN Case series Animal models INSULIN When to use Conventional therapies fail Fluids Atropine Calcium Glucagon Pacing Adrenergic drugs dopamine, norepinephrine, epinephrine 17
18 INSULIN Strong positive inotropic effect Increases uptake of carbohydrates The preferred fuel substrate of the heart under stressed conditions facilitates myocardial glucose delivery and cardiac contractility enhance cardiac contractility without increasing myocardial work, unlike cathecholamines Inhibits free fatty acid metabolism INSULIN Vasodilation of systemic, coronary, and pulmonary vasculature Improves local microcirculation aids systemic perfusion Accelerates oxidation of myocardial lactate and reversal of metabolic acidosis 18
19 INSULIN DOSING 1 unit/kg bolus dose ( regular insulin) continuous infusion unit/kg /hr 10 units/kg/hr Titrate to response (20-30 minutes) Heart rate 50 Systolic blood Pressure 100 INSULIN DOSING Onset of action = minutes? 2 hours Continue until hemodynamically stable Duration hemodynamic status 9-72 hours 19
20 DEXTROSE Dextrose bolus 0.5g/kg with initial insulin bolus if blood sugar < 400 mg/dl Infusion ml/hr of 10% solution Goal glucose mg/dl COMPLICATIONS OF HIGH DOSE INSULIN Hypoglycemia Supplemental glucose Hypokalemia Extracellular intracellular shift Monitor every hour while insulin titration Every 6 hours once stable Target
21 WEANING INSULIN Slow taper (2 units/kg/hr) q 30 minutes Stop Continue to monitor blood glucose for 24 hour after insulin discontinued NURSING CARE Frequent glucose monitoring minutes for the 1 st hour then hourly Insulin/dextrose titration Frequent labs 21
22 QUESTIONS References Doepker, B., Healy, W., Cortez, E., & Adkins, E. J. (2014). 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, 46(4), doi: Engebretsen, K. M., Kaczmarek, K. M., Morgan, J., & Holger, J. S. (2011). High dose insulin therapy in beta blocker and calcium channel blocker poisoning. Clinical Toxicology, 49, doi: / Kerns, W. (2007). Management of b adrenergic blocker and calcium channel antagonist toxicity. Emergency Medicine Clinics of North America, 25, doi: /j.emc Lheureux, P., Zahir, S., Gris, M., Derrey, N., & Penaloza, A. (2006). Bench to bedside review: Hyperinsulinaemia/euglycaemia. Critical Care, 10(3). Retrieved March 4, 2014, from Lyden AE, Cooper C, Park E (2014) Beta Blocker Overdose Treated with Extended Duration High Dose Insulin Therapy. J Pharmacol Clin Toxicol 2(1):1015. Mowry, J., Spyker, D., Cantilena, L., Bailey, E., Ford, M., (2013) annual report of the american association of poisoncontrol centers national poison data system (npds): 30th annual report. Clinical Toxicology, doi: / Shepard, G. (2006). Treatment of poisoning caused by β adrenergic. American Journal of Health System Pharmacy, 63, doi: /ajhp
23 References Woodward, C., Pourmand, A., & Mazer Amirshahi, M. (2014). High dose insulin therapy, an evidence based approach to beta blocker/calcium channel blocker toxicity. DARU Journal of Pharmaceutical Sciences, 22, 36. doi: /
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