Cardiotoxic Medications

Transcription

1 Cardiotoxic Medications Dean Olsen, DO Faculty, New York City Poison Control Center Director Emergency Medicine Residency Nassau University Medical Center Assistant Professor Pharmacology, Toxicology New York College of Osteopathic Medicine

2 Disclosure! I have no financial or academic conflicts of interest.

3 Objectives! Review some common and interesting cardiovascular poisonings! Develop a treatment plan for each of these poisonings! Consider some aspects that make toxicologic cardiac arrest different from other causes 3

4 Final common pathway! Eventually all poisonings end one of two ways " Recovery " Death! Death is usually preceded by cardiac arrest! This lecture will not apply to all poisonings 4

5 Disclaimer! There is very little literature to guide us " RCT- none " Case series- few " Case reports- many- most bad! " Animal studies- Few! Much of this is based on theory, extrapolation and opinion 5

6 ABC! Do not forget excellent standard care " Acidosis, hypoxia, hypercarbia will not help you!! It is probably easier to prevent cardiac arrest than to treat it! Decontaminate but do not let it be your overriding thought 6

7 Peri-mortem Gestures! Lipid emulsion therapy " Used for bupivacaine toxicity " Lots of case reports and animal studies for other drugs " Mechanism " Lipid sink " Free fatty acid substrate " Increase viscosity " Dose: " 20% Lipid emulsion: 1.5 ml/kg then 0.25 ml/kg/min (may double) Methylene Blue " Nitrate scavenger " Causes vasoconstriction " May increase blood pressure " Dose: 1-2 mg/kg IV 7

8 Case 1! 27 Year old female! BIBEMS agitated diaphoretic found on the street! Witnesses report patient acting bizarre and agitated on street 8

9 Vital Signs! Blood pressure 180/110! Heart rate 170! Respirations 36! Temperature 103.9! Extremely agitated and diaphoretic 9

10 Emergency Department Course! Cardiac monitor, oxygen, IV access and blood drawn! Lorazepam 2mg IV! EKG obtained 10

11 Case 1 11

12 What is the cause?! Patient admits to cocaine use prior to being picked up by EMS! What is the treatment for this patients Arrhythmia? " Sodium bicarbonate 1-2meq/kg bolus 12

13 Sodium Channel Blockade 13

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15 Sodium Channel Blockers! Class 1A- Phase 0 " Quinidine " Procainamide " Disopyramide! Class 1B-Phase 4 " Lidocaine " Phenytoin " Mexiletine Moderate Dissociation Fast Dissociation! Class 1C- Phase 0-4 " Flecainide " Propafenone Prolonged Dissociation 15

16 Sodium Channel Blockers Potent! TCA! Cocaine! Quinidine! Propafenone! Mexiletine! Disopyramide! Chloroquine! Lidocaine! Procainamide! Flecanide! Citalopram! Venlafaxine Less Potent! Sedating H1 blockers! Carbamazepine! Cyclobenzaprine! Antipsychotics 16

17 Sodium Channel Blockade 17

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19 Sodium channel blockade 19

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21 Parker RB et al: Comparative effects of sodium bicarbonate and sodium chloride on reversing cocaine-induced changes in the electrocardiogram J Cardiovasc Pharmacol Dec;34(6):864-9! Dog model used! Randomized to treatment of NS vs NaHCO3! HaHCO3 superior in reversal of arrhythmia! Reversal of arrhythmia associated with reversal of acidosis 21

22 ! Literature review! Highlights the data on using NaHCO3 above Lidocaine in the treatment of cocaine induced wide complex tachycardia 22

23 Cocaine! Cocaine induced wide complex tachycardia " From sodium channel blockade (similar to TCA) " Sinus tachycardia that s aberrantly conducted " Usually associated with acidosis " Treatment: 1. Sodium bicarbonate 2. Lidocaine 3. Amiodarone? 4. Intralipid?? " Avoid # Type 1A antidysrhythmics # Beta blockers # Epinephrine 23

24 ! Lipid emulsion?? 24

25 Case 1! You treat the patient with 2 amps sodium bicarbonate and arrhythmia resolves. The patient is now in sinus tachycardia with ST segment elevation complaining of chest pain.! The treatments of choice are: A. Nitroglycerin, beta blocker, aspirin and referral to cath lab B. Nitroglycerin, aspirin and referral to cath lab C. Benzodiazepine, nitroglycerin, phentolamine D. Labetalol, nitroglycerin, aspirin, and referral to cath lab E. Do nothing she s young and cant be having and MI 25

26 Cocaine! Acute coronary syndrome associated with cocaine " Usually of vasospastic origin in younger patients " Treatment: 1. Benzodiazepines- titrate to sedation (may require large doses) 2. Nitroglycerin 3. Phentolamine " Avoid # Beta blockers (nonselective) 26

27 331 patients reviewed 151 received beta blockers Charts reviewed for adverse outcomes! In conclusion, administration of β-blockers to patients with cocaineassociated chest pain appears to be safe and may even be beneficial! This does not answer the real question! Problems " Retrospective chart review " Looked at patients with + tox screens only " Does not address why some got beta blockers and others did not " Vital signs not included " No pre/post beta blocker assessment " No pre and post beta blocker ecg s " Editorial failure 27

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29 Lange et al: Annals Internal Med, 1990 June 15; 112 (12) ! Randomized double blind placebo controlled study! Patients administered cocaine on cath table! Randomized to beta blocker vs placebo! Statistically significant decrease in coronary artery diameter 29

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35 Case 2! 47 year old female took an overdose in a suicide attempt! Patient arrives in the ED obtunded and has a witnessed generalized tonic-clonic seizure! Vitals P 140 BP 90/60 R 12 T 99.3! Skin: dry Pupils: 6mm not reactive; absent bowel sounds! An EKG is obtained 35

36 Case 2 36

37 Case 2! What is the most likely cause of this patients clinical condition? A. Cocaine B. TCA C. Digoxin D. Zoloft E. Anxiety! The patients parents bring in an empty bottle of amitriptyline 37

38 Case 2! The best initial treatment for this patent is? A. Procainamide B. Lidocaine C. Beta blocker D. Sodium bicarbonate 38

39 Tricyclic Antidepressants 39

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42 Tricyclic Antidepressants! Treatment " Arrhythmias " Sodium bicarbonate # 1-2 meq/kg IV bolus " Lidocaine / amiodarone? " Seizures " Benzodiazepines " Paralyze if needed " Intubate / Hyperventilate " ph

43 Tricyclic Antidepressants! What not to do " Procainamide " Quinidine " Dilantin " Beta blockers 43

44 ! Many xenobiotics can cause sodium channel blockade! Look for the characteristic EKG pattern! Sodium bicarbonate 44

45 Case 3! 35 year old male with altered mental status! HR 35 BP 50s systolic! Normal mental status! Skin cool, diaphoretic! No purposeful movement! EKG obtained 45

46 Case 3 46

47 Case 3! Patient found in vicinity of open bottles of atenolol and verapamil 47

48 Beta and Calcium Channel Blockers! 2 sets of problems that may or may not be inter-related! Bradycardia " Improved rate may not translate to improved perfusion " Many patients tolerate rates in the 30 s! Hypotension " Is it rate or contractility? 48

49 Beta and Calcium Channel Blockers! Hypotension associated with beta and calcium channel blockers " Drug induced cardiogenic shock " Ultimate problem is decrease in intracellular calcium " Switching of metabolism of myocardium from fatty acids to glucose for fuel 49

50 BETA-BLOCKER β1 Agonist 1 receptor 5 AMP ATP Adenylate cyclase G s protein Ca ++ PDE c-amp protein kinase A L-type voltagesensitive calcium channels Ca ++ Ca ++ Actin-myosin complex Myocardial Cell Sarcoplasmic reticulum Ca ++ CALCIUM CHANNEL BLOCKER 50

51 5 AMP ATP glucagon Adenylate cyclase G s protein catecholamines 1 receptor Calcium channel Ca ++ Ca ++ PDE Ca ++ c-amp protein kinase A Ca ++ Ca ++ Sarcoplasmic reticulum Ca ++ Ca ++ amrinone Actin-myosin complex High dose insulin and glucose Ca ++ 51

52 Beta and Calcium Channel Blockers! Treatment 1. Vasopressors 2. Calcium 3. Glucagon 4. High dose insulin therapy 5. Amrinone 6. Intralipid Therapy 7. Bypass, ECHMO or IABP 52

53 Beta and Calcium Channel Blockers! Vasopressors " High dose epinephrine " DA/Norepi/dobutamine/isoproterenol! Calcium chloride " No real upper limit " What is normal calcium when channels are blocked? " Use for both CCB and BB (Brimacombe) 53

54 Beta and Calcium Channel Blockers! IF BRADYCARDIC " Pacing- but may not improve BP! Glucagon " 5/10/15 mg boluses " Onset is minutes in animals " Faster onset reported in humans Stone CK 1, May WA, Carroll R., Treatment of verapamil overdose with glucagon in dogs. Ann Emerg Med Mar;25(3):

55 Euglycemic Insulin Therapy! Rational " Myocardial cells normally use primarily fatty acids for metabolism " Calcium channel blockers cause myocardial cells to become carbohydrate dependent " At the same time CCB s also inhibit the ability of myocardial cells to use these carbohydrates by inhibiting insulin release and increasing myocardial resistance to insulin " Decrease substrate delivery to myocardium through 55 decreased blood flow further worsens contractility

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57 ! Dose Euglycemic Insulin Therapy " 1u/kg bolus # Higher doses may be of benefit 57

58 Euglycemic Insulin " 1u/kg/h infusion Therapy " Dextrose infusion to keep serum glucose normal " Titrate drip as high as possible with keeping serum glucose normal 58

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60 Case 4! 16 year old male presents with history of taking grandmothers heart medication in suicide attempt! Presents with alteration in color perception confusion and vomiting! Intubated for agitation and confusion! HR 45 regular BP 120/70! ECG 60

61 Case 4 61

62 Case 3! Over the next 30 minutes the patient began to have multiform PVCs that degenerate to ventricular fibrillation! No response to defib x 3! Diagnosis and treatment? A. Calcium channel blocker OD; give pressors B. ACE inhibitor OD; standard ACLS C. Diuretic OD; give fluids and ACLS D. Digoxin OD; give Digibind 62

63 Cardiac Glycosides! Prior to Digibind survival following cardiac arrest was almost 0 (Bismuth) 63

64 ! In the multi-center study of Digibind survival for cardiac arrest patients was 54% " Most other causes result in 10% or less " The most treatable cause of arrest?? 64

65 Na-Ca Exchanger Na-K ATPase 3Na + 2K + K + Voltage sensitive potassium channel Ca ++ 3Na + Na + Voltage sensitive sodium channel Ca ++ Ca ++ Sarcoplasmic reticulum Actin-myosin complex Myocardial Repolarization L-type voltagesensitive calcium channel 65

66 Na-Ca Exchanger 3Na + Na-K ATPase 2K + K + Cardiac Glycosides Voltage sensitive potassium channel Ca ++ 3Na + Na + Voltage sensitive sodium channel Ca ++ Ca ++ Sarcoplasmic reticulum Actin-myosin complex Myocardial Repolarization L-type voltagesensitive calcium channel 66

67 Na-Ca Exchanger 3Na + Na-K ATPase 2K + K + Cardiac Glycosides Voltage sensitive potassium channel Ca ++ 3Na + Na + Ca ++ Voltage sensitive sodium channel Ca ++ Sarcoplasmic reticulum Actin-myosin complex Myocardial Repolarization L-type voltagesensitive calcium channel 67

68 Na-Ca Exchanger K+ K+ K+ Na-K ATPase K+ K+ Increased extracellular K+ K+ K+ Ca ++ Actin-myosin complex Ca++ Ca++ Sarcoplasmic Reticulum Ca++ Ca++ Ca++ Ca++ Ca++ K+ More Ca++ Available for contraction 68

69 Cardiac Glycosides! Additional Therapeutic Effects " Increased vagal tone " Decreased SA node firing " Decreased AV node conduction 69

70 Toxic Effects! Vagal stimulation " sinus bradycardia/arrest, PR prolongation, nodal blocks! Increased intracellular Ca++ $ automaticity " Increased resting membrane potential " Increased delayed after-depolarization's! Overall " Slowing of normal conduction " Increased atrial, AV node, and ventricular ectopy 70

71 Effect Of Digitalis OD On Resting Membrane Potential Phase 1 0mv Phase 2 Depolarization Threshold -65mv Phase 0 Phase 3-90mv Resting Membrane Potential Digitalis OD Myocardial Cell Action Potential Phase 4 71

72 Digoxin immune Fab! Treatment " Digibind " Antibody to digitalis " DO NOT PACE THESE PATIENTS!!!! Recommended dose : 20 vials in cardiac arrest " Equimolar neutralization is goal (not based on weight) " More may not be better " Not enough is bad " Case reports of patients responding to Digibind post cardiac arrest! Acute overdose 10 vials! Chronic overdose 5 vials 72

73 The ABG Comes Back The nurse comes in and tells you the ABG potassium is 7. How does this change your management? A. It does not B. Give Ca++ C. Give Bicarbonate D. Give insulin and D50 E. B, C and D 73

74 Potassium and Digoxin! Complex relationship! Hyperkalemia decreases digoxin toxicity " K+ and digoxin share a binding site " Early digoxin antidote = potassium! In acute overdose potassium us used as a prognostic indicator " High is bad (>5.5) " The cause of death is NOT hyperkalemia! Be careful using Ca ++ in these patients! Digoxin Fab is the treatment not Ca ++ 74

75 Electricity! Digoxin toxicity decreases fibrillation threshold! Normal digoxin levels do not appear to do this! Consider Digibind or antidysrhythmic before cardioversion 75

76 Summary! Cocaine ACS " Nitroglycerin " Benzodiazepines " Phentolamine! Cocaine arrhythmias " Sodium bicarbonate " Lidocaine " Amiodarone?! Avoid beta blockers and epinephrine 76

77 Summary! Calcium channel beta blockers " Pressors " Calcium " Glucagon " Insulin " Amrinone " Bypass, ECHMO or IABP! Digoxin " Digibind " Atropine, No pacing, antiarrhythmics 77

78 Questions? 78