INSTITUTE OF CRITICAL CARE MEDICINE

INSTITUTE OF CRITICAL CARE MEDICINE
ROYAL CARE SUPER SPECIALITY HOSPITAL

DR. RAM E RAJAGOPALAN DR.M.N. SIVAKUMAR
ACKNOWLEDGEMENT DR. RAM E RAJAGOPALAN DR.M.N. SIVAKUMAR INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

CALCIUM CHANNEL BLOCKERS &
BETA BLOCKERS its the dose of a chemical or drug that determines if the chemical moiety is a therapeutic agent or it turns to be a poison Dr. S.LAKSHMIKANTHCHARAN MD.,IDCCM.,EDIC Consultant Intensivist, RCH, Neelambur

INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE
OVERVIEW Pharmacophysiology Overdose Clinical Manifestations Management INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

PROBLEM STATEMENT Poison-induced cardiogenic shock (PICS) is common Overdoses of beta-blockers (BBs) and calcium channel blockers (CCBs) account for over 65% of deaths from all cardiovascular medications. BB toxicity is the commonest cause of PICS in America CCB overdose is less frequent, but is the cardiovascular agent with the highest mortality rate in America, responsible for 48% of all deaths from cardiovascular agents. 2012 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 30th Annual Report. Mowry JB, Spyker DA, Cantilena LR Jr, Bailey JE, Ford M Clin Toxicol (Phila) Dec; 51(10): INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

PROBLEM STATEMENT The most commonly prescribed anti hypertensive drugs especially in India The ease of availability Management of patients following overdose of these drugs can be difficult INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

PHARMACOPHYSIOLOGY INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

TOXICOKINETICS OF CCB The Calcium Channel Different types – focus on L-type channel. A voltage - gated channel found in cardiac myocytes, pacemaker cells, vascular smooth muscle, and on beta islet cells in the pancreas. When the cell is depolarized, it allows for calcium influx and initiates different intracellular pathways. Smooth muscle - calcium binds directly to calmodulin  contraction. Pancreas - the calcium allows for exocytosis of insulin. Based on cell type INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

IN PACEMAKER CELLS IN CARDIAC MYOCYES In the pacemaker cells of the heart, slow calcium influx begins in phase 4 and is also responsible for phase 0 of the pacemaker action potential, which is further depolarization In myocytes, When the cell is depolarized, the L-type (L) calcium channel opens and calcium moves into the cytoplasm. This corresponds to phase 2, also known as the plateau phase, of the myocyte action potential. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

In myocytes, When the cell is depolarized  the L-type calcium channel opens calcium moves into the cytoplasm Calcium then binds the ryanodine receptor on the sarcoplasmic reticulum triggering a large calcium efflux from the SR into the cell Calcium bind troponin leads to contraction of the actin and myosin filiments INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

BLOCKAGE OF L-TYPE CHANNELS IN……
INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

SELECTED CHARACTERISTICS OF SOME CA+ CHANNEL BLOCKERS
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MECHANISM OF CARDIOTOXICITY IN CCB OVERDOSE
During stress cardiac myocytes switch from fatty acids to glucose for energy production  At high doses - decreased insulin decreases cardiac carbohydrate metabolism lack of fuel for aerobic energy production shift back to fatty acid oxidation within the cells which might not be adequate Impaired energy production negative inotropy and chronotropy profound shock and metabolic acidosis INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

TOXICOKINETICS OF BB The Beta-Receptor an adrenergic receptor the beta-1 receptor – In heart  Coupled to a stimulatory G protein Activates adenylate cyclase ATP to cAMP Stimulates protein kinase A Phosphorylate or activate, the L-type calcium channel PKA also phosphorylates phospholamban Increased intracellular calcium Increased inotropy and chronotropy. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

The beta-2 receptor : on vascular smooth muscle - vasodilation. In skeletal muscle glycogenolysis and potassium uptake In liver glycogenolysis and gluconeogenesis In lungs bronchodilation. The beta-3 receptor is involved in lipolysis, and is not significant INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

Some β-blockers may antagonize cardiac sodium channels, producing quinidine-like effects that will increase toxicity in overdose. β – blockers with Membrane stabilizing activity (MSA) (eg, propranolol, acebutolol) inhibit myocardial fast sodium channels, which can result in a widened QRS interval and may potentiate other dysrhythmias β - blockers with Intrinsic sympathomimetic activity (ISA) shows partial agonist effect at the beta receptor site, resulting in less bradycardia and hypotension. The protective effects of ISA do not completely prevent cardiovascular toxicity following overdose. Highly lipid soluble agents such as propranolol cross the BBB and can result in unwanted CNS effects. Greene Shepherd, Treatment of poisoning caused by β-adrenergic and calcium-channel blockers, American Journal of Health-System Pharmacy, Volume 63, Issue 19, 1 October 2006, Pages 1828–1835, INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

OVERDOSE Receptor selectivity is lost Effects not normally seen at therapeutic doses can occur. In overdose, β-blockers and CCBs often have similar presentation and there is much overlap in treatment. Cardiac toxicity: Negative inotropy - myocardial depression Negative chronotropy - sinus bradycardia Negative dromotropy - atrioventricular node blockade Effects on vascular sm ms tone: Decreased afterload Systemic hypotension Coronary vasodilation Cardiotoxicity characterized by Hypotension & Bradycardia . Any drug may be harmful if the dose is large enough. Determining an exact toxic dose for a given individual is difficult because of the variability in patient-specific factors such as age, genetics, health status, and other recently ingested substances. Such factors should be taken into account when establishing a toxic dose, with the realization that some patients will be outliers in either direction. To try to avoid problems with low-dose outliers, safety recommendations are generally set below the lowest dose rather than the mean dose reported to cause harm. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

Greene Shepherd, Treatment of poisoning caused by β-adrenergic and calcium-channel blockers, American Journal of Health-System Pharmacy, Volume 63, Issue 19, 1 October 2006, Pages 1828–1835, INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

Olson KR, Erdman AR, Woolf AD et al. Calcium channel blocker ingestion: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol . 2005; 43:797–822. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

CLINICAL PRESENTATION INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

CLINICAL PRESENTATION INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE
Time since ingestion and the severity of the overdose Asymptomatic decompensate rapidly. Obtunded or in cardiac arrest. Cardiovascular signs  Hypotension and bradycardia cardiogenic shock. Conduction disturbances  mild interval prolongation/ CHB Arrhythmias, QT prolongation and torsades de pointes may be encountered CNS  decreased or altered mental status, obtundation,coma and seizures. Metabolic findings - BB hypoglycemia CCB hyperglycemia. Depending on the time since ingestion and the severity of the overdose, the patient may appear clinically well on presentation. Some patients will never become symptomatic; however, others may decompensate rapidly, and all patients should be monitored closely initially. Patients may complain of dizziness or nausea. Seizures or syncope may occur. In the more severe cases, a patient can present obtunded or in cardiac arrest. The main clinical signs that will be encountered are cardiovascular. Hypotension and bradycardia are common and can be severe. They may occur simultaneously, or either can precede the other. Deterioration into cardiogenic shock is typical of severe toxicity. A variety of conduction disturbances may be seen, mainly in the form of a conduction delay. It can occur anywhere, and can be a mild interval prolongation or complete heart block. Arrhythmias, QT prolongation and torsades de pointes may be encountered with some of these medications CNS findings, as mentioned above, include decreased or altered mental status, obtundation, and coma. Seizures have been reported following beta-blocker overdose, especially propranolol, because it blocks sodium channels. There are metabolic findings associated with overdose. Beta-blocker toxicity can cause hypoglycemia that seems to occur more commonly in children, and significant hyperkalemia. In contrast, calcium channel blocker toxicity typically causes hyperglycemia. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

MANIFESTATIONS AND COMPLICATIONS OF BETA-BLOCKER OVERDOSE IN ORDER OF DECREASING FREQUENCY Excessive blockade of the β-receptors - bradycardia and hypotension. G protein responsible for converting ATP to cAMP is disabled, which results in less cytosolic calcium being available As β-selectivity is lost in overdose, even “β1-selective” agents can block β2 & β3-receptors and bring about bronchospasm and a reduction in inotropy. Lipophilicity is a good predictor of CNS depression in β-blocker overdose. Beta-blockers, such as atenolol, that have poor lipid solubility generally will not directly produce sedation. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

DIFFERENTIAL DIAGNOSIS INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE
The differential includes toxicity from these agents: Digoxin Imidazoline (e.g., clonidine) Opiate Sedative hypnotic Cholinergic toxicity. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

HISTORY The time of ingestion The specific name of the medication Co - ingestants The number of pills ingested The exact amount of drug in each tablet The formulation (i.e., immediate release vs. sustained release) Alcohol, or illicit drugs Patients who are on other cardioactive medication INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

INITIAL CARE & GASTRIC DECONTAMINATION
ABC Gastric lavage – Consider time since ingestion – Benefit outweigh risk? • Activated charcoal (1 gm/kg) if appropriate –within 60 minutes of ingestion( 2 hrs - SR preparations) – Patient is cooperative with intact airway – No good evidence for repeat doses Whole-bowel irrigation – Evidence for improved outcome is lacking – Has been advocated for sustained-release preparations – Polyethylene glycol solution, orally/ NG at 1 to 2 L/hour Many emergency physicians believe that all forms of gastric decontamination must be done within a specific time frame, such as only performing gastric lavage within one hour of overdose. However, absorption from the gastrointestinal tract may be delayed in the overdose setting, and gastrointestinal decontamination should be considered in all potentially life- threatening overdoses. While there are a myriad of therapeutic options, there is no pure antidote for calcium channel or beta-blocker toxicity. With significant morbidity and mortality possible, early aggressive management is key. Consequently, if the patient has ingested a potentially life-threatening dose of these medications, GI decontamination can be performed, even more than 1 hour after ingestion. In cases where orogastric lavage is believed to be ineffective or contraindicated, activated charcoal can be consideredA. In a human trial, volunteers took standard doses of verapamil and then took activated charcoal. The results showed that activated charcoal given immediately after ingestion decreased the amount absorbed (the area under the curve) for all formulations, while delayed activated charcoal was only able to decrease the area under the curve in a slow-release preparation.14 One case report details multiple diltiazem levels through treatment and chronicles multi-dose activated charcoal. There did not appear to be any significant reduction in the area under the curve.15 If the ingestion is serious and there are no contraindications, give activated charcoal. If the amount of drug ingested is known, the dose of activated charcoal is 10 times that dose up to a maximum of 50 g/dose. In adults, if the dose is unknown, give 1 g/kg; in children, the dose is 0.5 g/kg. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

INVESTIGATIONS 12 lead ECG Electrolytes BUN / Cr Digoxin level if concomitant toxicity suspected ABG Lactic acid Echocardiogram CXR INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

TREATMENT OF BETA BLOCKER POISONING
PHASE 1 – RESUSCITATION PHASE Boluses of atropine Glucagon Fluids PHASE 2 – STABILISATION PHASE Glucagon infusion High dose insulin – euglycemia Catecholamines Phosphodiesterase inhibitors Intravenous pacing PHASE 3 – SALVAGE THERAPY Hemodialysis Intralipid IABP ECMO INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

TREATMENT OF CCB POISONING
PHASE 1 – RESUSCITATION PHASE Isotonic iv fluids calcium (1D) PHASE 2 – STABILISATION PHASE Catecholamine infusion, invasive monitoring (1D) Intravenous calcium (1D) High dose insulin glucose infusion (1D) intravenous pacing (2D) PHASE 3 – SALVAGE THERAPY Lipid emulsion (2D) Cardiac supports- aortic balloon, ECMO (2D) CRITICAL CARE MEDICINE: MARCH VOLUME 45 INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

IV FLUIDS Expands intravascular volume and counteracts vasodilation to a certain extent Standard practice. In mild cases, this may be all that is needed to reverse toxicity Around 20 ml/kg crystalloids Pulmonary edema MOA EVIDENCES DOSE ADR standard practice to start with intravenous crystalloid fluid boluses for patients who are hypotensive if no contraindication (20 ml/kg). In mild cases, this may be all that is needed to reverse toxicity. Atropine for symptomatic bradycardia. By antagonism of muscarinic receptors, there may be less inhibition of adenylate cyclase in the heart, and therefore, more cAMP. Its efficacy is minimal, and it is unlikely to improve hemodynamics in patients with beta-blocker or calcium channel blocker overdose. Nevertheless, since it is readily available, there is little down side to its administration. The adult dose is mg IV repeated to maximum of 3 mg INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

CRYSTALLOIDS Caveat of using earlier versions of glucagon vs recombinant ones – up to 100 units of insulin in standard glucagon noted INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

ATROPINE ACLS By antagonism of muscarinic receptors, there may be less inhibition of adenylate cyclase in the heart causing more cAMP. For symptomatic bradycardia as per ACLS.Its efficacy is minimal, and it is unlikely to improve hemodynamics. Adult dose is mg IV repeated to maximum of 3 mg Not much MOA EVIDENCES DOSE ADR INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

VASOPRESSORS Activates alpha and beta receptors competes with beta-blockers In CCB pts, beta activation can provide some activation of the L-type channels, peripheral alpha-1-receptor activation causes vasoconstriction Standard practice for any hypotension not responding to fluids As patients are resistant to these drugs, the initial dose should be high and the infusion rates should be rapidly titrated to effect. Arrythmias, hyperlactatemia, limb ischemia, bowel ischemia MOA EVIDENCES DOSE ADR INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

VASOPRESSORS rare for one catecholamine to be equally effective against all toxic effects, so combinations of drugs are often used Epinephrine and norepinephrine activate both beta- and alpha-receptors. They compete with beta-blockers, and in calcium channel blocked patients, beta activation can provide some activation of the L-type channels, and also activate downstream channels to produce contraction and increase heart rate. Also, peripheral alpha-1-receptor activation causes vasoconstriction. Dopamine must be converted to epinephrine or norepinephrine to exert its clinical effects. When catecholamine stores have already been depleted by physiologic stress, this is less likely to be effective compared to giving epinephrine or norepinephrine. Isoproterenol - non-specific beta-adrenergic agonist. Overcoming the beta-blockade may induce more peripheral vasodilation via the beta-2 receptor. Without alpha effects, this can exacerbate hypotension. Dobutamine - specific for the beta-1 receptor and does not act peripherally. It may be more useful for beta-1-specific beta- blockers, like metoprolol, or in central acting calcium channel blockers, like diltiazem. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

IN A NUTSHELL Caveat of using earlier versions of glucagon vs recombinant ones – up to 100 units of insulin in standard glucagon noted INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

CALCIUM An attempt to raise serum calcium levels  it overcomes the blockade of the L-type channel by calcium channel blockers and the downstream effects of beta-blockade increases inotropy and stroke volume. Success of this therapy is inconsistent. Multiple case reports and animal studies show that calcium chloride infusion improves inotropy, hemodynamics but heart rate is unaffected. Bolus of calcium gluconate 10% 3 g (30 mL) or calcium chloride 10% 1 g (10 mL), repeated as needed. Maintain with infusion of mL/kg/hr 10% CaCl or mL/kg/hr calcium gluconate Do not exceed Ca++ level of 14 mg/dL or twice normal levels of ionized Ca Use central line for CaCl infusion to avoid tissue necrosis. Watch for arrhythmias with rapid infusion MOA EVIDENCES DOSE ADR Because deleterious effects on calcium transport may contribute to beta-blocker toxicity, IV calcium salts have been suggested for treating hypotension. calcium should be given cautiously and less aggressively than for cases of calcium channel blocker overdose. Howarth DM, Dawson AH, Smith AJ, et al. Calcium channel blocking drug overdose: An Australian series. Hum Exp Toxicol. 1994;13:161–166 Henry M, Kay MM, Viccellio P. Cardiogenic shock associated with calcium-channel and beta blockers: Reversal with intravenous calcium chloride. Am J Emerg Med. 1985;3:. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

GLUCAGON Activates adenylate cyclase, increasing cyclic AMP independently of the beta-adrenergic receptor. It increases inotropy and chronotropy in animal models. In animal models of CCB and BB poisoning, glucagon exerts its effect primarily as a positive chronotrope, with little or no effect on BP . A number of positive case reports have been reported in BB and CCB poisoning, but not as a sole agent. IV bolus of 50 mcg/kg (max 10 mg) over 1-2 minutes short (20-minute) half-life, infusion of 2 to 5 mg/hr started immediately diuted in 5% dextrose gastrointestinal (e.g. Nausea, Vomiting), mild hyperglycemia, hypokalemia, and allergic reactions. MOA EVIDENCES DOSE ADR Bailey B. Glucagon in beta‐blocker and calcium channel blocker overdoses: a systematic review. J Toxicol Clin Toxicol 2003; 41: 595–602. Kosinski EJ, Stein N, Malindzak GS, Boone E. Glucagon and propranolol (Inderal) toxicity. N Engl J Med 1971; 285: 1325–5. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

HIGH DOSE INSULIN EUGLYCEMIA (HDIE) THERAPY
Normally cardiac cells acquire energy via fatty acid oxidation, but need glucose in times of stress, such as toxin-induced cardiogenic shock. Insulin improves glucose utilization in the heart. Most effective treatment on literature There are no randomized controlled human trials. Human case reports with CCB shows improved survival, although in severe cases, other treatments should be used in conjunction. 1 u/kg bolus with a dextrose bolus of 0.5 g/kg  Infusion of 0.5 unit/kg/hr with a dextrose infusion of 0.5 g/kg/hr, which is titrated to effect. Hypoglycemia Hypokalemia Mild vasodilation No effect on heart rate MOA EVIDENCES DOSE ADR Espinoza TR, Bryant SM, Aks SE. Hyperinsulin therapy for calcium channel antagonist poisoning: a seven‐year retrospective study. Am J Ther 2013; 20: 29–31. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

RESCUE THERAPIES Transcutaneous or transvenous pacing (If HR < 40). Electrical capture is not always successful & if capture does occur BP is not always restored. Intralipid Phosphodiesterase inhibitors IABP Cardiopulmonary bypass ECMO Hemodialysis INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

INTRALIPID Forms a “lipid sink” around lipophilic drug molecules making them ineffective Fatty acids from the emulsion provide the myocardium with an energy source No human RCTs, few animal studies and multiple human case reports - appears to have contributed to recovery from cardiogenic shock or arrest. American College of Toxicologist usage suggestion 20 % Intralipid emulsion 1.5 ml/kg initial bolus ( rpt q3-5min in cardiac arrest) 0.25 ml/kg/min for 30 – 60 min Max – 8 mg/kg Anaphylactoid reaction Fat overload syndrome ( coagulopathy, jaundice and lipid accumulation in liver) MOA EVIDENCES DOSE ADR Anayphylaxis from Local anaesthetic toxicity Any lipophilic drug mopping – verapamil toxicity As these are case reports, and there may exist a bias against reporting or publishing negative outcomes, human case- control studies are needed to further elucidate the efficacy of IFE in beta-blocker and calcium channel blocker overdose. At this time, given the potential benefit and despite no human randomized controlled trials performed to date, IFE may be considered for patients who are failing other modalities or during cardiac arrest. Intravenous lipid emulsion in the management of amlodipine overdose.Meaney CJ, Sareh H, Hayes BD, Gonzales JP Hosp Pharm Nov; 48(10): INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

PHOSPHODIESTERASE INHIBITORS
Phosphodiesterase (PDE) inhibition leads to increased cAMP without activation of the beta-receptor. Animal studies show PDE inh improve inotropy with little effect on heart rate. When all other therapies are failing, a trial may be considered. Milrinone 50-mcg/kg IV bolus, then mcg/kg/min infusion. Amrinone 75-mcg/kg IV bolus, then mcg/kg/min infusion. Also have a vasodilating effect, and this may counteract their inotropic effects on blood pressure MOA EVIDENCES DOSE ADR Kollef MH. Labetalol overdose successfully treated with amrinone and alpha‐adrenergic receptor agonists. Chest 1994; 105: 626–7. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

EXTRACORPOREAL TREATMENT INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE
Invasive Procedures. Given the reversible nature of many poisonings, ECMO can allow time for drug redistribution and/or metabolism to a point where cardiac function in an otherwise healthy heart is restored. When other treatments fail, even when the patient is in cardiac arrest, there are case reports of using an IABP/ ECMO with success. If the patient is symptomatic following overdose, consult cardiology early, so that if the patient continues to deteriorate, these invasive procedures can be performed ECMO are not very effective in cases of refractory vasodilatory shock where cardiac output is already increased Baud FJ, Megarbane B, Deye N, Leprince P. Clinical review: aggressive management and extracorporeal support for drug‐induced cardiotoxicity. Crit Care 2007; 11: 207. Megarbane B, Deye N, Baud FJ. Extracorporeal Life‐Support for Acute Drug‐induced Cardiac Toxicity. In: Year Book of Intensive Care and Emergency Medicine, 1st edn. Berlin, Heidelberg: Springer, 2008; 179–89 INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

HAEMODIALYSIS Hemodialysis - useful in low lipid soluble & low protein binding beta blockers. Atenolol is < 5% protein bound so dialyzable along with nadolol, sotalol & acebutalol. Consider hemodialysis only when glucagon & other pharmacotherapy fails. CCB are highly protein bound so hemodialysis not useful. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

CONSENSUS RECOMMENDATIONS
Critical care medicine consensus recommendations highlighted the evidences available and their usefulness CRITICAL CARE MEDICINE: MARCH VOLUME 45 INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

SUMMARY OF COUNTER MEASURES
BB CCB Decontamination + IV Fluids Atropine - Inotropes ++ IV Calcium +++ IV Glucagon Insulin Glucose therapy Intravenous pacemaker _ Intralipid Aortic balloon pump ? ECMO INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

TAKE HOME MESSAGE Poisoning by β-blockers or CCBs usually produces hypotension and bradycardia, which may be refractory to standard resuscitation measures No ideal antidote Reversible over time, so give aggressive supportive care till the effect of drug wares off For cases of β-blocker poisoning where symptomatic bradycardia and hypotension are present, high-dose glucagon is considered the first-line antidote For cases of CCB poisoning where cardiotoxicity is evident, a combination of calcium and epinephrine should be used initially, reserving HDIE for refractory cases INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

PHONE A FRIEND ! National AIIMS- poison centre 24 X 7 National poison information centre Regional Centre – Amrita Dr.V.V.Pillai - Analytical toxicology laboratory Royalcare Super Speciality Hospital - Poison centre INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

REFERENCES 2016 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 34th Annual Report David D. Gummin, James B. Mowry, Daniel A. Spyker, Daniel E. Brooks, Michael O. Fraser & William Banner. An Evidence-based Approach to Beta-Blocker and Calcium Channel Blocker Toxicity | AHC Media: Continuing Medical Education Publishing Graudins A, Lee HM, Druda D. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies. Br J Clin Pharmacol. 2015;81(3):453–461. doi: /bcp.12763 St-Onge, P.-A. Dubé, S. Gosselin, C. Guimont, J. Godwin, P. M. Archambault, J.-M. Chauny, A. J. Frenette, M. Darveau, N. Le sage, J. Poitras, J. Provencher, D. N. Juurlink & R. Blais (2014) Treatment for calcium channel blocker poisoning: A systematic review, Clinical Toxicology, 52:9, Lashari B H, Minalyan A, Khan W, et al. (November 01, 2018) 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: /cureus.3534 St-Onge M, Anseeuw K, Cantrell FL, et al. Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults. Crit Care Med. 2017;45(3):e306–e315. INSTITUTE OF CRITICAL CARE MEDICINE, RCH, CBE

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