ACLS Pharmacology 1 Objectives To review and obtain a better understanding of medications used in ACLS – Indications & Actions (When & Why?) – Dosing (How?) – Contraindications & Precautions (Watch Out!) 2 3 Drug Classifications Class I: Recommendations – Excellent evidence provides support – Proven in both efficacy and safety Class II: Recommendations – Level I studies are absent, inconsistent or lack power – Available evidence is positive but may lack efficacy – No evidence of harm 4 Drug Classifications Class IIa Vs IIb – Class IIa recommendations have Higher level of available evidence Better critical assessments More consistency in results – Both are optional and acceptable, – IIa recommendations are probably useful – IIb recommendations are possibly helpful Less compelling evidence for efficacy 5 Drug Classifications Class III: Not recommended – Not acceptable or useful and may be harmful – Evidence is absent or unsatisfactory, or based on poor studies Indeterminate – Continuing area of research; no recommendation until further data is available 6 Oxygen Indications (When & Why?) – Any suspected cardiopulmonary emergency – Saturate hemoglobin with oxygen – Reduce anxiety & further damage – Note: Pulse oximetry should be monitored Universal Algorithm 7 Oxygen Dosing (How?) Device Flow Rate Oxygen % Nasal Prongs 1 to 6 lpm 24 to 44% Venturi Mask 4 to 8 lpm 24 to 40% Partial Rebreather Mask 6 to 10 lpm 35 to 60% 15 lpm up to 100% Bag Mask Universal Algorithm 8 Oxygen Precautions (Watch Out!) – Pulse oximetry inaccurate in: Low cardiac output Vasoconstriction Hypothermia – NEVER rely on pulse oximetry! Universal Algorithm 9 VF / Pulseless VT Case 3 10 VF / Pulseless VT • Epinephrine 1 mg IV push, repeat every 3 to 5 minutes or • Vasopressin 40 U IV, single dose, 1 time only Resume attempts to defibrillate 1 x 360 J (or equivalent biphasic) within 30 to 60 seconds Consider antiarrhythmics: • Amiodarone (llb for persistent or recurrent VF/pulseless VT) • Lidocaine (Indeterminate for persistent or recurrent VF/pulseless VT) • Magnesium (llb if known hypomagnesemic state) • Procainamide (Indeterminate for persistent VF/pulseless VT; llb for recurrent VF/pulseless VT) Resume attempts to defibrillate 11 Epinephrine Indications (When & Why?) – Increases: Heart rate Force of contraction Conduction velocity – Peripheral vasoconstriction – Bronchial dilation VF / Pulseless VT 12 Epinephrine Dosing (How?) – 1 mg IV push; may repeat every 3 to 5 minutes – May use higher doses (0.2 mg/kg) if lower dose is not effective – Endotracheal Route 2.0 to 2.5 mg diluted in 10 mL normal saline VF / Pulseless VT 13 Epinephrine Dosing (How?) – Alternative regimens for second dose (Class IIb) Intermediate: 2 to 5 mg IV push, every 3 to 5 minutes Escalating: 1 mg, 3 mg, 5 mg IV push, each dose 3 minutes apart High: 0.1 mg/kg IV push, every 3 to 5 minutes VF / Pulseless VT 14 Epinephrine Precautions (Watch Out!) – Raising blood pressure and increasing heart rate may cause myocardial ischemia, angina, and increased myocardial oxygen demand – Do not mix or give with alkaline solutions – Higher doses have not improved outcome & may cause myocardial dysfunction VF / Pulseless VT 15 Vasopressin Indications (When & Why?) – Used to “clamp” down on vessels – Improves perfusion of heart, lungs, and brain – No direct effects on heart VF / Pulseless VT 16 Vasopressin Dosing (How?) – One time dose of 40 units only – May be substituted for epinephrine – Not repeated at any time – May be given down the endotracheal tube DO NOT double the dose Dilute in 10 mL of NS VF / Pulseless VT 17 Vasopressin Precautions (Watch Out!) – May result in an initial increase in blood pressure immediately following return of pulse – May provoke cardiac ischemia VF / Pulseless VT 18 Amiodarone Indications (When & Why?) – Powerful antiarrhythmic with substantial toxicity, especially in the long term – Intravenous and oral behavior are quite different – Has effects on sodium & potassium VF / Pulseless VT 19 Amiodarone Dosing (How?) – Should be diluted in 20 to 30 mL of D5W 300 mg bolus after first Epinephrine dose Repeat doses at 150 mg VF / Pulseless VT 20 Amiodarone Precautions (Watch Out!) – May produce vasodilation & shock – May have negative inotropic effects – Terminal elimination Half-life lasts up to 40 days VF / Pulseless VT 21 Lidocaine Indications (When & Why?) – Depresses automaticity – Depresses excitability – Raises ventricular fibrillation threshold – Decreases ventricular irritability VF / Pulseless VT 22 Lidocaine Dosing (How?) – Initial dose: 1.0 to 1.5 mg/kg IV – For refractory VF may repeat 1.0 to 1.5 mg/kg IV in 3 to 5 minutes; maximum total dose, 3 mg/kg – A single dose of 1.5 mg/kg IV in cardiac arrest is acceptable – Endotracheal administration: 2 to 2.5 mg/kg diluted in 10 mL of NS VF / Pulseless VT 23 Lidocaine Dosing (How?) – Maintenance Infusion 2 to 4 mg/min 1000 mg / 250 mL D5W = 4 mg/mL – 15 mL/hr = 1 mg/min – 30 mL/hr = 2 mg/min – 45 mL/hr = 3 mg/min – 60 mL/hr = 4 mg/min VF / Pulseless VT 24 Lidocaine Precautions (Watch Out!) – Reduce maintenance dose (not loading dose) in presence of impaired liver function or left ventricular dysfunction – Discontinue infusion immediately if signs of toxicity develop VF / Pulseless VT 25 Magnesium Sulfate Indications (When & Why?) – Cardiac arrest associated with torsades de pointes or suspected hypomagnesemic state – Refractory VF – VF with history of ETOH abuse – Life-threatening ventricular arrhythmias due to digitalis toxicity, tricyclic overdose VF / Pulseless VT 26 Magnesium Sulfate Dosing (How?) – 1 to 2 g (2 to 4 mL of a 50% solution) diluted in 10 mL of D5W IV push VF / Pulseless VT 27 Magnesium Sulfate Precautions (Watch Out!) – Occasional fall in blood pressure with rapid administration – Use with caution if renal failure is present VF / Pulseless VT 28 Procainamide Indications (When & Why?) – Recurrent VF – Depresses automaticity – Depresses excitability – Raises ventricular fibrillation threshold – Decreases ventricular irritability VF / Pulseless VT 29 Procainamide Dosing (How?) – 20-30 mg/min IV infusion – May push at 50 mg/min in cardiac arrest – In refractory VF/VT, 100 mg IV push doses given every 5 minutes are acceptable – Maximum total dose: 17 mg/kg VF / Pulseless VT 30 Procainamide Dosing (How?) – Maintenance Infusion 1 to 4 mg/min 1000 mg / 250 mL of D5W = 4 mg/mL – 15 mL/hr = 1 mg/min – 30 mL/hr = 2 mg/min – 45 mL/hr = 3 mg/min – 60 mL/hr = 4 mg/min VF / Pulseless VT 31 Procainamide Precautions (Watch Out!) – If cardiac or renal dysfunction is present, reduce maximum total dose to 12 mg/kg and maintenance infusion to 1 to 2 mg/min – Remember Endpoints of Administration VF / Pulseless VT 32 PEA Case 4 33 PEA Review for most frequent causes • • • • • Hypovolemia Hypoxia Hydrogen ion—acidosis Hyper-/hypokalemia Hypothermia • • • • • Tablets (drug OD, accidents) Tamponade, cardiac Tension pneumothorax Thrombosis, coronary (ACS) Thrombosis, pulmonary (embolism) Epinephrine 1 mg IV push, repeat every 3 to 5 minutes Atropine 1 mg IV (if PEA rate is slow), repeat every 3 to 5 minutes as needed, to a total dose of 0.04 mg/kg 34 Epinephrine Indications (When & Why?) – Increases: Heart rate Force of contraction Conduction velocity – Peripheral vasoconstriction – Bronchial dilation Pulseless Electrical Activity 35 Epinephrine Dosing (How?) – 1 mg IV push; may repeat every 3 to 5 minutes – May use higher doses (0.2 mg/kg) if lower dose is not effective – Endotracheal Route 2.0 to 2.5 mg diluted in 10 mL normal saline Pulseless Electrical Activity 36 Epinephrine Precautions (Watch Out!) – Raising blood pressure and increasing heart rate may cause myocardial ischemia, angina, and increased myocardial oxygen demand – Do not mix or give with alkaline solutions – Higher doses have not improved outcome & may cause myocardial dysfunction Pulseless Electrical Activity 37 Atropine Sulfate Indications (When & Why?) – Should only be used for bradycardia Relative or Absolute – Used to increase heart rate Pulseless Electrical Activity 38 Atropine Sulfate Dosing (How?) – 1 mg IV push – Repeat every 3 to 5 minutes – May give via ET tube (2 to 2.5 mg) diluted in 10 mL of NS – Maximum Dose: 0.04 mg/kg Pulseless Electrical Activity 39 Atropine Sulfate Precautions (Watch Out!) – Increases myocardial oxygen demand – May result in unwanted tachycardia or dysrhythmia Pulseless Electrical Activity 40 Asystole Case 5 41 Asystole Transcutaneous pacing: If considered, perform immediately Epinephrine 1 mg IV push, repeat every 3 to 5 minutes Atropine 1 mg IV, repeat every 3 to 5 minutes up to a total of 0.04 mg/kg Asystole persists Withhold or cease resuscitation efforts? • Consider quality of resuscitation? • Atypical clinical features present? • Support for cease-efforts protocols in place? 42 Epinephrine Indications (When & Why?) – Increases: Heart rate Force of contraction Conduction velocity – Peripheral vasoconstriction – Bronchial dilation Asystole: The Silent Heart Algorithm 43 Epinephrine Dosing (How?) – 1 mg IV push; may repeat every 3 to 5 minutes – May use higher doses (0.2 mg/kg) if lower dose is not effective – Endotracheal Route 2.0 to 2.5 mg diluted in 10 mL normal saline Asystole: The Silent Heart Algorithm 44 Epinephrine Precautions (Watch Out!) – Raising blood pressure and increasing heart rate may cause myocardial ischemia, angina, and increased myocardial oxygen demand – Do not mix or give with alkaline solutions – Higher doses have not improved outcome & may cause myocardial dysfunction Asystole: The Silent Heart Algorithm 45 Atropine Sulfate Indications (When & Why?) – Used to increase heart rate Questionable absolute bradycardia Asystole: The Silent Heart Algorithm 46 Atropine Sulfate Dosing (How?) – 1 mg IV push – Repeat every 3 to 5 minutes – May give via ET tube (2 to 2.5 mg) diluted in 10 mL of NS – Maximum Dose: 0.04 mg/kg Asystole: The Silent Heart Algorithm 47 Atropine Sulfate Precautions (Watch Out!) – Increases myocardial oxygen demand Asystole: The Silent Heart Algorithm 48 Other Cardiac Arrest Drugs 49 Calcium Chloride Indications (When & Why?) – Known or suspected hyperkalemia (eg, renal failure) – Hypocalcemia (blood transfusions) – As an antidote for toxic effects of calcium channel blocker overdose – Prevent hypotension caused by calcium channel blockers administration Other Cardiac Arrest Drugs 50 Calcium Chloride Dosing (How?) – IV Slow Push 8 to 16 mg/kg (usually 5 to 10 mL) IV for hyperkalemia and calcium channel blocker overdose 2 to 4 mg/kg (usually 2 mL) IV for prophylactic pretreatment before IV calcium channel blockers Other Cardiac Arrest Drugs 51 Calcium Chloride Precautions (Watch Out!) – Do not use routinely in cardiac arrest – Do not mix with sodium bicarbonate Other Cardiac Arrest Drugs 52 Sodium Bicarbonate Indications (When & Why?) – Class I if known preexisting hyperkalemia – Class IIa if known preexisting bicarbonateresponsive acidosis – Class IIb if prolonged resuscitation with effective ventilation; upon return of spontaneous circulation – Class III (not useful or effective) in hypoxic lactic acidosis or hypercarbic acidosis (eg, cardiac arrest and CPR without intubation) Other Cardiac Arrest Drugs 53 Sodium Bicarbonate Dosing (How?) – 1 mEq/kg IV bolus – Repeat half this dose every 10 minutes thereafter – If rapidly available, use arterial blood gas analysis to guide bicarbonate therapy (calculated base deficits or bicarbonate concentration) Other Cardiac Arrest Drugs 54 Sodium Bicarbonate Precautions (Watch Out!) – Adequate ventilation and CPR, not bicarbonate, are the major "buffer agents" in cardiac arrest – Not recommended for routine use in cardiac arrest patients Other Cardiac Arrest Drugs 55 Acute Coronary Syndromes Case 6 56 57 Acute Coronary Syndromes Chest pain suggestive of ischemia Immediate assessment (<10 minutes) • Measure vital signs (automatic/standard BP cuff) • Measure oxygen saturation • Obtain IV access • Obtain 12-lead ECG (physician reviews) • Perform brief, targeted history and physical exam; focus on eligibility for fibrinolytic therapy • Obtain initial serum cardiac marker levels • Evaluate initial electrolyte and coagulation studies • Request, review portable chest x-ray (<30 minutes) Immediate general treatment • Oxygen at 4 L/min • Aspirin 160 to 325 mg • Nitroglycerin SL or spray • Morphine IV (if pain not relieved with nitroglycerin) Memory aid: “MONA” greets all patients (Morphine, Oxygen, Nitroglycerin, Aspirin) EMS personnel can perform immediate assessment and treatment (“MONA”), including initial 12-lead ECG and review for fibrinolytic therapy indications and contraindications. Assess initial 12-lead ECG 58 Aspirin Indications (When & Why?) – Administer to all patients with ACS, particularly reperfusion candidates Give as soon as possible – Blocks formation of thromboxane A2, which causes platelets to aggregate Acute Coronary Syndromes 59 Aspirin Dosing (How?) – 160 to 325 mg tablets Preferably chewed May use suppository – Higher doses may be harmful Acute Coronary Syndromes 60 Aspirin Precautions (Watch Out!) – Relatively contraindicated in patients with active ulcer disease or asthma Acute Coronary Syndromes 61 Nitroglycerine Indications (When & Why?) – Chest pain of suspected cardiac origin – Unstable angina – Complications of AMI, including congestive heart failure, left ventricular failure – Hypertensive crisis or urgency with chest pain Acute Coronary Syndromes 62 Nitroglycerin Indications (When & Why?) – Decreases pain of ischemia – Increases venous dilation – Decreases venous blood return to heart – Decreases preload and cardiac oxygen consumption – Dilates coronary arteries – Increases cardiac collateral flow Acute Coronary Syndromes 63 Nitroglycerine Dosing (How?) – Sublingual Route 0.3 to 0.4 mg; repeat every 5 minutes – Aerosol Spray Spray for 0.5 to 1.0 second at 5 minute intervals – IV Infusion Infuse at 10 to 20 µg/min Route of choice for emergencies Titrate to effect Acute Coronary Syndromes 64 Nitroglycerine Precautions (Watch Out!) – Use extreme caution if systolic BP <90 mm Hg – Use extreme caution in RV infarction – Suspect RV infarction with inferior ST changes – Limit BP drop to 10% if patient is normotensive – Limit BP drop to 30% if patient is hypertensive – Watch for headache, drop in BP, syncope, tachycardia – Tell patient to sit or lie down during administration Acute Coronary Syndromes 65 Morphine Sulfate Indications (When & Why?) – Chest pain and anxiety associated with AMI or cardiac ischemia – Acute cardiogenic pulmonary edema (if blood pressure is adequate) Acute Coronary Syndromes 66 Morphine Sulfate Indications (When & Why?) – To reduce pain of ischemia – To reduce anxiety – To reduce extension of ischemia by reducing oxygen demands Acute Coronary Syndromes 67 Morphine Sulfate Dosing (How?) – 1 to 3 mg IV (over 1 to 5 minutes) every 5 to 10 minutes as needed Acute Coronary Syndromes 68 Morphine Sulfate Precautions (Watch Out!) – Administer slowly and titrate to effect – May compromise respiration; therefore use with caution in acute pulmonary edema – Causes hypotension in volume-depleted patients Acute Coronary Syndromes 69 Acute Coronary Syndromes • ST elevation or new or presumably new LBBB: strongly suspicious for injury • ST-elevation AMI • ST depression or dynamic T-wave inversion: strongly suspicious for ischemia • High-risk unstable angina/ non–ST-elevation AMI • Nondiagnostic ECG: absence of changes in ST segment or T waves • Intermediate/low-risk unstable angina 70 ST Elevation 71 Recognition of AMI Know what to look for— – ST elevation >1 mm – 3 contiguous leads J point plus 0.04 second Know where to look – Refer to 2000 ECC Handbook PR baseline ST-segment deviation = 4.5 mm 72 ST Elevation Baseline Ischemia—tall or inverted T wave (infarct), ST segment may be depressed (angina) Injury—elevated ST segment, T wave may invert Infarction (Acute)—abnormal Q wave, ST segment may be elevated and T wave may be inverted Infarction (Age Unknown)—abnormal Q wave, ST segment and T wave returned to normal 73 Beta Blockers Indications (When & Why?) – To reduce myocardial ischemia and damage in AMI patients with elevated heart rates, blood pressure, or both – Blocks catecholamines from binding to ß-adrenergic receptors – Reduces HR, BP, myocardial contractility – Decreases AV nodal conduction – Decreases incidence of primary VF Acute Coronary Syndromes 74 Beta Blockers Dosing (How?) – Esmolol 0.5 mg/kg over 1 minute, followed by continuous infusion at 0.05 mg/kg/min Titrate to effect, Esmolol has a short half-life (<10 minutes) – Labetalol 10 mg labetalol IV push over 1 to 2 minutes May repeat or double labetalol every 10 minutes to a maximum dose of 150 mg, or give initial dose as a bolus, then start labetalol infusion 2 to 8 µg/min Acute Coronary Syndromes 75 Beta Blockers Dosing (How?) – Metoprolol 5 mg slow IV at 5-minute intervals to a total of 15 mg – Atenolol 5 mg slow IV (over 5 minutes) Wait 10 minutes, then give second dose of 5 mg slow IV (over 5 minutes) – Propranolol 1 to 3 mg slow IV. Do not exceed 1 mg/min Repeat after 2 minutes if necessary Acute Coronary Syndromes 76 Beta Blockers Precautions (Watch Out!) – Concurrent IV administration with IV calcium channel blocking agents like verapamil or diltiazem can cause severe hypotension – Avoid in bronchospastic diseases, cardiac failure, or severe abnormalities in cardiac conduction – Monitor cardiac and pulmonary status during administration – May cause myocardial depression Acute Coronary Syndromes 77 Heparin Indications (When & Why?) – For use in ACS patients with Non Q wave MI or unstable angina – Inhibits thrombin generation by factor Xa inhibition and also inhibit thrombin indirectly by formation of a complex with antithrombin III Acute Coronary Syndromes 78 Heparin Dosing (How?) – Initial bolus 60 IU/kg Maximum bolus: 4000 IU – Continue at 12 IU/kg/hr (maximum 1000 IU/hr for patients < 70 kg), round to the nearest 50 IU Acute Coronary Syndromes 79 Heparin Dosing (How?) – Adjust to maintain activated partial thromboplastin time (aPTT) 1.5 to 2.0 times the control values for 48 hours or angiography – Target range for aPTT after first 24 hours is between 50 & 70 seconds (may vary with laboratory) – Check aPTT at 6, 12, 18, and 24 hours – Follow Institutional Heparin Protocol Acute Coronary Syndromes 80 Heparin Precautions (Watch Out!) – Same contraindications as for fibrinolytic therapy: active bleeding; recent intracranial, intraspinal or eye surgery; severe hypertension; bleeding disorders; gastroinintestinal bleeding – DO NOT use if platelet count is below 100 000 Acute Coronary Syndromes 81 Glycoprotein IIb/IIIa Inhibitors Indications (When & Why?) – Inhibit the integrin glycoprotein IIb/IIIa receptor in the membrane of platelets, inhibiting platelet aggregation – Indicated for Acute Coronary Syndromes without ST segment elevation Acute Coronary Syndromes 82 Glycoprotein IIb/IIIa Inhibitors Indications (When & Why?) – Abciximab (ReoPro) Non Q wave MI or unstable angina with planned PCI within 24 hours Must use with heparin – Binds irreversibly with platelets – Platelet function recovery requires 48 hours Acute Coronary Syndromes 83 Glycoprotein IIb/IIIa Inhibitors Indications (When & Why?) – Eptifibitide (Integrilin) Non Q wave MI, unstable angina managed medically, and unstable angina / Non Q wave MI patients undergoing PCI Platelet function recovers within 4 to 8 hours after discontinuation Acute Coronary Syndromes 84 Glycoprotein IIb/IIIa Inhibitors Indications (When & Why?) – Tirofiban (Aggrastat) Non Q wave MI, unstable angina managed medically, and unstable angina / Non Q wave MI patients undergoing PCI Platelet function recovers within 4 to 8 hours after discontinuation Acute Coronary Syndromes 85 Glycoprotein IIb/IIIa Inhibitors Dosing (How?) – NOTE: Check package insert for current indications, doses, and duration of therapy. Optimal duration of therapy has NOT been established. Acute Coronary Syndromes 86 Glycoprotein IIb/IIIa Inhibitors Dosing (How?) – Abciximab (ReoPro) ACS with planned PCI within 24 hours – 0.25 mg/kg bolus (10 to 60 minutes before procedure), then 0.125 mcg/kg/min infusion PCI only – 0.25 mg/kg bolus – Then 10 mcg/min infusion Acute Coronary Syndromes 87 Glycoprotein IIb/IIIa Inhibitors Dosing (How?) – Eptifibitide (Integrilin) Acute Coronary Syndromes – 180 mcg/kg IV bolus, then 2 mcg/kg/min infusion PCI – 135 mcg/kg IV bolus, then begin 0.5 mcg/kg/min infusion, then repeat bolus in 10 minutes Acute Coronary Syndromes 88 Glycoprotein IIb/IIIa Inhibitors Dosing (How?) – Tirofiban (Aggrastat) Acute Coronary Syndromes or PCI – 0.4 mcg/kg/min infusion IV for 30 minutes – Then 0.1 mcg/kg/min infusion Acute Coronary Syndromes 89 Glycoprotein IIb/IIIa Inhibitors Precautions (Watch Out!) – Active internal bleeding or bleeding disorder within 30 days – History of intracranial hemorrhage or other bleeding – Surgical procedure or trauma within 1 month – Platelet count > 150 000/mm3 Acute Coronary Syndromes 90 PTCA 91 Fibrinolytics Indications (When & Why?) – For AMI in adults ST elevation or new or presumably new LBBB; strongly suspicious for injury Time of onset of symptoms < 12 hours Acute Coronary Syndromes 92 Fibrinolytics Indications (When & Why?) – For Acute Ischemic Stroke Sudden onset of focal neurologic deficits or alterations in consciousness Absence of subarachnoid or intracerebral hemorrhage Alteplase can be started in less than 3 hours of symptom onset Acute Coronary Syndromes 93 Fibrinolytics Dosing (How?) – For fibrinolytic use, all patients should have 2 peripheral IV lines 1 line exclusively for fibrinolytic administration Acute Coronary Syndromes 94 Fibrinolytics Dosing for AMI Patients (How?) – Alteplase, recombinant (tPA) Accelerated Infusion – 15 mg IV bolus – Then 0.75 mg/kg over the next 30 minutes Not to exceed 50 mg – Then 0.5 mg/kg over the next 60 minutes Not to exceed 35 mg 3 hour Infusion – Give 60 mg in the first hour (initial 6 to 10 mg is given as a bolus) – Then 20 mg/hour for 2 additional hours Acute Coronary Syndromes 95 Fibrinolytics Dosing for AMI Patients (How?) – Anistreplase (APSAC) Reconstitute 30 units in 50 mL of sterile water 30 units IV over 2 to 5 minutes – Reteplase, recombinant Give first 10 unit IV bolus over 2 minutes 30 minutes later give second 10 unit IV bolus over 2 minutes – Streptokinase 1.5 million IU in a 1 hour infusion – Tenecteplase (TNKase) Bolus 30 to 50 mg Acute Coronary Syndromes 96 Fibrinolytics Adjunctive Therapy for AMI Patients (How?) – 160 to 325 mg aspirin chewed as soon as possible – Begin heparin immediately and continue for 48 hours if alteplase or Retavase is used Acute Coronary Syndromes 97 Fibrinolytics Dosing for Acute Ischemic Stroke (How?) – Alteplase, recombinant (tPA) Give 0.9 mg/kg (maximum 90 mg) infused over 60 minutes – Give 10% of total dose as an initial IV bolus over 1 minute – Give the remaining 90% over the next 60 minutes – Alteplase is the only agent approved for use in Ischemic Stroke patients Acute Coronary Syndromes 98 Fibrinolytics Precautions (Watch Out!) – Specific Exclusion Criteria Active internal bleeding (except mensus) within 21 days History of CVA, intracranial, or intraspinal within 3 months Major trauma or serious injury within 14 days Aortic dissection Severe uncontrolled hypertension Acute Coronary Syndromes 99 Fibrinolytics Precautions (Watch Out!) – Specific Exclusion Criteria Known bleeding disorders Prolonged CPR with evidence of thoracic trauma Lumbar puncture within 7 days Recent arterial puncture at noncompressible site During the first 24 hours of fibrinolytic therapy for ischemic stroke, do not give aspirin or heparin Acute Coronary Syndromes 100 ACE Inhibitors Indications (When & Why?) – Reduce mortality & improve LV dysfunction in post AMI patients – Help prevent adverse LV remodeling, delay progression of heart failure, and decrease sudden death & recurrent MI Acute Coronary Syndromes 101 ACE Inhibitors Indications (When & Why?) – Suspected MI & ST elevation in 2 or more anterior leads – Hypertension – Clinical signs of AMI with LV dysfunction – LV ejection fraction <40% Acute Coronary Syndromes 102 ACE Inhibitors Indications (When & Why?) – Generally not started in the ED but within first 24 hours after: Fibrinolytic therapy has been completed Blood pressure has stabilized Acute Coronary Syndromes 103 ACE Inhibitors Dosing (How?) – Should start with low-dose oral administration (with possible IV doses for some preparations) and increase steadily to achieve a full dose within 24 to 48 hours Acute Coronary Syndromes 104 ACE Inhibitors Dosing (How?) – Enalapril 2.5 mg PO titrated to 20 mg BID IV dosing of 1.25 mg IV over 5 minutes, then 1.25 to 5 mg IV every six hours – Captopril Start with 6.25 mg PO Advance to 25 mg TID, then to 50 mg TID as tolerated Acute Coronary Syndromes 105 ACE Inhibitors Dosing (How?) – Lisinopril (AMI dose) 5 mg within 24 hours onset of symptoms 10 mg after 24 hours, then 10 mg after 48 hours, then 10 mg PO daily for six weeks – Ramipril Start with single dose of 2.5 mg PO Titrate to 5 mg PO BID as tolerated Acute Coronary Syndromes 106 ACE Inhibitors Precautions (Watch Out!) – Contraindicated in pregnancy – Contraindicated in angioedema – Reduce dose in renal failure – Avoid hypotension, especially following initial dose & in relative volume depletion Acute Coronary Syndromes 107 Bradycardias Case 7 108 Bradycardia Bradycardia • Slow (absolute bradycardia = rate <60 bpm) or • Relatively slow (rate less than expected relative to underlying condition or cause) Primary ABCD Survey • Assess ABCs • Secure airway noninvasively • Ensure monitor/defibrillator is available • • • • • • • • Secondary ABCD Survey Assess secondary ABCs (invasive airway management needed?) Oxygen–IV access–monitor–fluids Vital signs, pulse oximeter, monitor BP Obtain and review 12-lead ECG Obtain and review portable chest x-ray Problem-focused history Problem-focused physical examination Consider causes (differential diagnoses) 109 Bradycardia Serious signs or symptoms? Due to bradycardia? No Type II second-degree AV block or Third-degree AV block? No Observe Yes Intervention sequence • Atropine 0.5 to 1.0 mg • Transcutaneous pacing if available • Dopamine 5 to 20 µg/kg per minute • Epinephrine 2 to 10 µg/min • Isoproterenol 2 to 10 µg/min Yes • Prepare for transvenous pacer • If symptoms develop, use transcutaneous pacemaker until transvenous pacer placed 110 Atropine Sulfate Dosing (How?) – 0.5 to 1.0 mg IV every 3 to 5 minutes as needed – May give via ET tube (2 to 2.5 mg) diluted in 10 mL of NS – Maximum Dose: 0.04 mg/kg Bradycardias 112 Atropine Sulfate Precautions (Watch Out!) – Use with caution in presence of myocardial ischemia and hypoxia – Increases myocardial oxygen demand – Seldom effective for: Infranodal (type II) AV block Third-degree block (Class IIb) Bradycardias 113 Dopamine Indications (When & Why?) – Second drug for symptomatic bradycardia (after atropine) – Use for hypotension (systolic BP 70 to 100 mm Hg) with S/S of shock Bradycardias 114 Dopamine Dosing (How?) – IV Infusions (Titrate to Effect) – 200 mg / 250 mL of D5W = 800 µg /mL – 400 mg / 250 mL of D5W = 1600 µg /mL – 800 mg/ 250 mL of D5W = 3200 µg /mL Bradycardias 115 Dopamine Dosing (How?) – IV Infusions (Titrate to Effect) Dose “Renal Dose" – 1 to 5 µg/kg per minute Moderate Dose “Cardiac Dose" – 5 to 10 µg/kg per minute High Dose “Vasopressor Dose" – 10 to 20 µg/kg per minute Low Bradycardias 116 Dopamine Precautions (Watch Out!) – May use in patients with hypovolemia but only after volume replacement – May cause tachyarrhythmias, excessive vasoconstriction – DO NOT mix with sodium bicarbonate Bradycardias 117 Isoproterenol Indications (When & Why?) – Temporary control of bradycardia in heart transplant patients – Class IIb at low doses for symptomatic bradycardia – Heart Transplant Patients! Bradycardias 121 Isoproterenol Dosing (How?) – Infuse at 2 to 10 µg/min – Titrate to adequate heart rate Bradycardias 122 Isoproterenol Precautions (Watch Out!) – Increases myocardial oxygen requirements, which may increase myocardial ischemia – DO NOT administer with poison/druginduced shock Exception: Beta Blocker Poisoning Bradycardias 123 Stable Tachycardias Case 9 124 Diltiazem Indications (When & Why?) – To control ventricular rate in atrial fibrillation and atrial flutter – Use after adenosine to treat refractory PSVT in patients with narrow QRS complex and adequate blood pressure – As an alternative, use verapamil Stable Tachycardias 125 Diltiazem Dosing (How?) – Acute Rate Control 15 to 20 mg (0.25 mg/kg) IV over 2 minutes May repeat in 15 minutes at 20 to 25 mg (0.35 mg/kg) over 2 minutes – Maintenance Infusion 5 to 15 mg/hour, titrated to heart rate Stable Tachycardias 126 Diltiazem Precautions (Watch Out!) – Do not use calcium channel blockers for tachycardias of uncertain origin – Avoid calcium channel blockers in patients with Wolff-Parkinson-White syndrome, in patients with sick sinus syndrome, or in patients with AV block without a pacemaker – Expect blood pressure drop resulting from peripheral vasodilation – Concurrent IV administration with IV ß-blockers can cause severe hypotension Stable Tachycardias 127 Verapamil Indications (When & Why?) – Used as an alternative to diltiazem for ventricular rate control in atrial fibrillation and atrial flutter – Drug of second choice (after adenosine) to terminate PSVT with narrow QRS complex and adequate blood pressure Stable Tachycardias 128 Verapamil Dosing (How?) – 2.5 to 5.0 mg IV bolus over 1to 2 minutes – Second dose: 5 to 10 mg, if needed, in 15 to 30 minutes. Maximum dose: 30 mg – Older patients: Administer over 3 minutes Stable Tachycardias 129 Verapamil Precautions (Watch Out!) – Do not use calcium channel blockers for wide-QRS tachycardias of uncertain origin – Avoid calcium channel blockers in patients with Wolff-Parkinson-White syndrome and atrial fibrillation, sick sinus syndrome, or second- or third-degree AV block without pacemaker Stable Tachycardias 130 Verapamil Precautions (Watch Out!) – Expect blood pressure drop caused by peripheral vasodilation – IV calcium can restore blood pressure, and some experts recommend prophylactic calcium before giving calcium channel blockers – Concurrent IV administration with IV ßblockers may produce severe hypotension Stable Tachycardias 131 Adenosine Indications (When & Why?) – First drug for narrow-complex PSVT – May be used diagnostically (after lidocaine) in wide-complex tachycardias of uncertain type Stable Tachycardias 132 Adenosine Dose (How?) – IV Rapid Push – Initial bolus of 6 mg given rapidly over 1 to 3 seconds followed by normal saline bolus of 20 mL; then elevate the extremity – Repeat dose of 12 mg in 1 to 2 minutes if needed – A third dose of 12 mg may be given in 1 to 2 minutes if needed Stable Tachycardias 133 Adenosine Precautions (Watch Out!) – Transient side effects include: Facial Flushing Chest pain Brief periods of asystole or bradycardia – Less effective in patients taking theophyllines Stable Tachycardias 134 Beta Blockers Indications (When & Why?) – To convert to normal sinus rhythm or to slow ventricular response (or both) in supraventricular tachyarrhythmias (PSVT, atrial fibrillation, or atrial flutter) – ß-Blockers are second-line agents after adenosine, diltiazem, or digoxin Stable Tachycardias 135 Beta Blockers Dosing (How?) – Esmolol 0.5 mg/kg over 1 minute, followed by continuous infusion at 0.05 mg/kg/min Titrate to effect, Esmolol has a short half-life (<10 minutes) – Labetalol 10 mg labetalol IV push over 1 to 2 minutes May repeat or double labetalol every 10 minutes to a maximum dose of 150 mg, or give initial dose as a bolus, then start labetalol infusion 2 to 8 µg/min Stable Tachycardias 136 Beta Blockers Dosing (How?) – Metoprolol 5 mg slow IV at 5-minute intervals to a total of 15 mg – Atenolol 5 mg slow IV (over 5 minutes) Wait 10 minutes, then give second dose of 5 mg slow IV (over 5 minutes) – Propranolol 1 to 3 mg slow IV. Do not exceed 1 mg/min Repeat after 2 minutes if necessary Stable Tachycardias 137 Beta Blockers Precautions (Watch Out!) – Concurrent IV administration with IV calcium channel blocking agents like verapamil or diltiazem can cause severe hypotension – Avoid in bronchospastic diseases, cardiac failure, or severe abnormalities in cardiac conduction – Monitor cardiac and pulmonary status during administration – May cause myocardial depression Stable Tachycardias 138 Digoxin Indications (When & Why?) – To slow ventricular response in atrial fibrillation or atrial flutter – Third-line choice for PSVT Stable Tachycardias 139 Digoxin Dosing (How?) – IV Infusion Loading doses of 10 to 15 µg/kg provide therapeutic effect with minimum risk of toxic effects Maintenance dose is affected by body size and renal function Stable Tachycardias 140 Digoxin Precautions (Watch Out!) – Toxic effects are common and are frequently associated with serious arrhythmias – Avoid electrical cardioversion unless condition is life threatening Use lower current settings (10 to 20 Joules) Stable Tachycardias 141 Amiodarone Indications (When & Why?) – Powerful antiarrhythmic with substantial toxicity, especially in the long term – Intravenous and oral behavior are quite different Stable Tachycardias 142 Amiodarone Dosing (How?) – Stable Wide-Complex Tachycardias Rapid Infusion – 150 mg IV over 10 minutes (15 mg/min) – May repeat Slow Infusion – 360 mg IV over 6 hours (1 mg/min) Stable Tachycardias 143 Amiodarone Dosing (How?) – Maintenance Infusion 540 mg IV over 18 hours (0.5 mg/min) Stable Tachycardias 144 Amiodarone Precautions (Watch Out!) – May produce vasodilation & shock – May have negative inotropic effects – May prolong QT Interval DO NOT administer with other drugs that may prolong QT Interval (Procainamide) – Terminal elimination Half-life lasts up to 40 days Stable Tachycardias 145 Amiodarone Precautions (Watch Out!) – Contraindicated in: Second or third degree A-V block Severe bradycardia Pregnancy CHF Hypokalaemia Liver dysfunction Stable Tachycardias 146 Lidocaine Indications (When & Why?) – Depresses automaticity – Depresses excitability – Raises ventricular fibrillation threshold – Decreases ventricular irritability Stable Tachycardias 147 Lidocaine Dosing (How?) – For stable VT, wide-complex tachycardia of uncertain type, significant ectopy, use as follows: 1.0 to 1.5 mg/kg IV push Repeat 0.5 to 0.75 mg/kg every 5 to 10 minutes; maximum total dose, 3 mg/kg Stable Tachycardias 148 Magnesium Sulfate Indications (When & Why?) – Torsades de pointes with a pulse – Wide-complex tachycardia with history of ETOH abuse – Life-threatening ventricular arrhythmias due to digitalis toxicity, tricyclic overdose Stable Tachycardias 151 Magnesium Sulfate Dosing (How?) – Loading dose of 1 to 2 grams mixed in 50 to 100 mL of D5W IV push over 5 to 60 minutes Stable Tachycardias 152 Magnesium Sulfate Dosing (How?) – Maintenance Infusion 1 to 4 g/hour IV (titrate dose to control the torsades) Stable Tachycardias 153 Magnesium Sulfate Precautions (Watch Out!) – Occasional fall in blood pressure with rapid administration – Use with caution if renal failure is present Stable Tachycardias 154 Procainamide Indications (When & Why?) – Depresses automaticity – Depresses excitability – Raises ventricular fibrillation threshold – Decreases ventricular irritability – Atrial fibrillation with rapid rate in WolffParkinson-White syndrome Stable Tachycardias 155 Procainamide Dosing (How?) – Perfusing Arrhythmia 20 mg/min IV infusion until: – Hypotension develops – Arrhythmia is suppressed – QRS widens by >50% – Maximum dose of 17 mg/kg is reached In refractory VF/VT, 100 mg IV push doses given every 5 minutes are acceptable Stable Tachycardias 156 Procainamide Dosing (How?) – Maintenance Infusion 1 to 4 mg/min Stable Tachycardias 157 Procainamide Precautions (Watch Out!) – If cardiac or renal dysfunction is present, reduce maximum total dose to 12 mg/kg and maintenance infusion to 1 to 2 mg/min – Remember Endpoints of Administration Stable Tachycardias 158 Acute Ischemic Stroke Case 10 159 Acute Ischemic Stroke Suspected Stroke Detection Dispatch Delivery Door Immediate assessment: <10 minutes from arrival • Assess ABCs, vital signs • Provide oxygen by nasal cannula • Obtain IV access; obtain blood samples (CBC, electolytes, coagulation studies) • Check blood sugar; treat if indicated • Obtain 12-lead ECG, check for arrhythmias • Perform general neurological screening assessment • Alert Stroke Team: neurologist, radiologist, CT technician EMS assessments and actions Immediate assessments performed by EMS personnel include • Cincinnati Prehospital Stroke Scale (includes difficulty speaking, arm weakness, facial droop) • Los Angeles Prehospital Stroke Screen • Alert hospital to possible stroke patient • Rapid transport to hospital Immediate neurological assessment: <25 minutes from arrival • Review patient history • Establish onset (<3 hours required for fibrinolytics) • Perform physical examination • Perform neurological examination: Determine level of consciousness (Glasgow Coma Scale) Determine level of stroke severity (NIH Stroke Scale or Hunt and Hess Scale) • Order urgent noncontrast CT scan (door-to–CT scan performed: goal <25 minutes from arrival) • Read CT scan (door-to–CT read: goal <45 minutes from arrival) • Perform lateral cervical spine x-ray (if patient comatose/history of trauma) 160 Nitroprusside Indications (When & Why?) – Hypertensive crisis Acute Ischemic Stroke 161 Nitroprusside Dosing (How?) – Begin at 0.1 mcg/kg/min and titrate upward every 3 to 5 minutes to desired effect Up to 0.5 mcg/kg/min – Action occurs within 1 to 2 minutes Acute Ischemic Stroke 162 Nitroprusside Dosing Precautions (How?) – Use with an infusion pump; use hemodynamic monitoring for optimal safety – Cover drug reservoir with opaque material Acute Ischemic Stroke 163 Nitroprusside Precautions (Watch Out!) – Light-sensitive; therefore, wrap drug reservoir in aluminum foil – May cause hypotension and CO2 retention – May exacerbate intrapulmonary shunting – Other side effects include headaches, nausea, vomiting, and abdominal cramps Acute Ischemic Stroke 164 Drugs used in Overdoses 165 Calcium Chloride Indications (When & Why?) – As an antidote for toxic effects of calcium channel blocker overdose Drugs Used in Overdoses 166 Calcium Chloride Dosing (How?) – 8 to 16 mg/kg (usually 5 to 10 mL) IV for hyperkalemia and calcium channel blocker overdose Drugs Used in Overdoses 167 Calcium Chloride Precautions (Watch Out!) – Do not use routinely in cardiac arrest – Do not mix with sodium bicarbonate Drugs Used in Overdoses 168 Flumazenil Indications (When & Why?) – Reduce respiratory depression and sedative effects from pure benzodiazepine overdose Drugs Used in Overdoses 169 Flumazenil Dosing (How?) – First Dose 0.2 mg IV over 15 seconds – Second Dose 0.3 mg IV over 30 seconds – Third Dose 0.4 mg IV over 30 seconds – Maximum Dose 3 mg Drugs Used in Overdoses 170 Flumazenil Precautions (Watch Out!) – Effects may not outlast effects of benzodiazepines – Monitor for recurrent respiratory depression – DO NOT use in suspected tricyclic overdose – DO NOT use in seizure-prone patients – DO NOT use if unknown type overdose or mixed drug overdose with drugs known to cause seizures Drugs Used in Overdoses 171 Naloxone Hydrochloride Indications (When & Why?) – Respiratory and neurologic depression due to opiate intoxication unresponsive to oxygen and hyperventilation Drugs Used in Overdoses 172 Naloxone Hydrochloride Dosing (How?) – 0.4 to 2 mg IVP every 2 minutes – Use higher doses for complete narcotic reversal – Can administer up to 10 mg in a short time (10 minutes) Drugs Used in Overdoses 173 Naloxone Hydrochloride Precautions (Watch Out!) – May cause opiate withdrawal – Effects may not outlast effects of narcotics – Monitor for recurrent respiratory depression Drugs Used in Overdoses 174 Review of Infusions 175 Dobutamine Indications (When & Why?) – Consider for pump problems (congestive heart failure, pulmonary congestion) with systolic blood pressure of 70 to 100 mm Hg and no signs of shock – Increases Inotropy Review of Infusions 176 Dobutamine Dosing (How?) – Usual infusion rate is 2 to 20 µg/kg per minute – Titrate so heart rate does not increase by more than 10% of baseline – Hemodynamic monitoring is recommended for optimal use Review of Infusions 177 Dobutamine Precautions (Watch Out!) – Avoid when systolic blood pressure <100 mm Hg with signs of shock – May cause tachyarrhythmias, fluctuations in blood pressure, headache, and nausea – DO NOT mix with sodium bicarbonate Review of Infusions 178 Dopamine Indications (When & Why?) – Second drug for symptomatic bradycardia (after atropine) – Use for hypotension (systolic BP 70 to 100 mm Hg) with S/S of shock Review of Infusions 179 Dopamine Dosing (How?) – IV Infusions (Titrate to Effect) Dose “Renal Dose" – 1 to 5 µg/kg per minute Moderate Dose “Cardiac Dose" – 5 to 10 µg/kg per minute High Dose “Vasopressor Dose" – 10 to 20 µg/kg per minute Low Review of Infusions 180 Dopamine Precautions (Watch Out!) – May use in patients with hypovolemia but only after volume replacement – May cause tachyarrhythmias, excessive vasoconstriction – DO NOT mix with sodium bicarbonate Review of Infusions 181 Epinephrine Indications (When & Why?) – Symptomatic bradycardia: After atropine, dopamine, and transcutaneous pacing (Class IIb) Review of Infusions 182 Epinephrine Dosing (How?) – Profound Bradycardia 2 to 10 µg/min infusion (add 1 mg of 1:1000 to 500 mL normal saline; infuse at 1 to 5 mL/min) Review of Infusions 183 Epinephrine Precautions (Watch Out!) – Raising blood pressure and increasing heart rate may cause myocardial ischemia, angina, and increased myocardial oxygen demand – Do not mix or give with alkaline solutions – Higher doses have not improved outcome & may cause myocardial dysfunction Review of Infusions 184 Norepinephrine Indications (When & Why?) – For severe cardiogenic shock and hemodynamic significant hypotension (systolic blood pressure < 70 mm/Hg) with low total peripheral resistance – This is an agent of last resort for management of ischemic heart disease and shock Review of Infusions 185 Norepinephrine Dosing (How?) – 0.5 to 1 mcg/min titrated to improve blood pressure (up to 30 µg /min) – DO NOT administer is same IV line as alkaline infusions – Poison/drug-induced hypotension may higher doses to achieve adequate perfusion Review of Infusions 186 Norepinephrine Precautions (Watch Out!) – Increases myocardial oxygen requirements – May induce arrhythmias – Extravasation causes tissue necrosis Review of Infusions 187 Calculating mg/min dose X gtt factor = gtts/min Solution Concentration 2 mg X 60 gtt/mL 4 mg = 30 gtts/min Using a 60 gtt set: 30 gtt/min = 30 cc/hr 188 Calculating µg/kg/min dose X kg X gtt factor = cc/hr solution concentration 5 µg /min X 75 kg X 60 gtt/mL 1600 µg /cc = 18.75 cc/hr Using a 60 gtt set: 18.75 cc/hr = 18.75 gtts/min 189 Furosemide Indications (When & Why?) – For adjuvant therapy of acute pulmonary edema in patients with systolic blood pressure >90 to 100 mm Hg (without S/S of shock) – Hypertensive emergencies – Increased intracranial pressure 190 Furosemide Dosing (How?) – 20 to 40 mg slow IVP – If patient is taking at home, double their daily dose 191 Furosemide Precautions (Watch Out!) – Dehydration, hypovolemia, hypotension, hypokalemia, or other electrolyte imbalance may occur 192 Questions? 193