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HW on Capnography • DUE 3-25 instead of 18th • Write a paper on the use and indications of capnography monitoring. What is it’s benefits? Is there evidence to support it’s use? Find a scientific/scholarly article backing up your argument 1 • Preload-After load= Stroke Volume • Stroke Volume + HR = Cardiac Output • (SV a product of inotropy/contraction), (HR product of chronotropy/conduction) • Cardiac output X CaO2 = DO2 • (CaO2 determined primarily by Hb and ability of O2 to bind with it) • Oxygen consumption (VO2)= C(a-v) CO • CvO2 determined by amount of O2 left in venous blood after tissue consumption • Tissue Perfusion/Oxygenation dependent on all of the factors listed above (SV, HR, EDV, ESV, Inotropy, Chronotropy, Hb, PaO2, effective V/Q matching) 2 Clinical Pharmacology Objectives • Know basic ACLS drugs and usage • Understand drugs, doses, and routes of administration during cardiovascular emergencies • Learn to integrate basic drug pharmacology into ACLS algorithms © 2011 American Heart Association. Do not edit. 3 Drugs • Epinephrine • Vasopressin • Amiodarone • Lidocaine • Magnesium • Atropine • Dopamine • Adenosine • Oxygen • Aspirin • Nitroglycerin • Morphine • Fibrinolytics 4 Priorities for Drug Administration First—CPR and Early Defibrillation Then drug administration: 1. Intravenous 2. Intraosseous 3. Endotracheal 5 Drug Administration Secondary FYI Guidelines 2010: During cardiac arrest, high-quality CPR and early defibrillation are of primary importance, and drug administration is of secondary importance. Few drugs used in the treatment of cardiac arrest are supported by strong evidence. After provision of CPR and early defibrillation, rescuers can establish IV access, consider drug therapy, and insert an advanced airway. 6 ETT route • Although endotracheal administration of some resuscitation drugs is possible, IV or IO drug administration is preferred because it will provide more predictable drug delivery and pharmacologic effect. If IV and IO access cannot be established, some resuscitation drugs may be administered by the endotracheal route. 7 ETT Route • Administration of resuscitation drugs into the trachea, however, results in lower blood concentrations than the same dose given intravascularly. Furthermore, recent animal studies suggest that the lower epinephrine concentrations achieved when the drug is delivered by the endotracheal route may produce transient adrenergic effects. These effects can be detrimental, causing hypotension, lower coronary artery perfusion pressure and flow, and reduced potential for return of spontaneous circulation (ROSC). 8 Intraosseous Infusion • Drug delivery similar to central venous access possible • Average access time <2 minutes • Any drug given IV can be given IO 9 IO Route • IO cannulation provides access to a noncollapsible venous plexus, enabling drug delivery similar to that achieved by central venous access. Two prospective trials, in children and adults, and other studies documented that IO access is safe and effective for fluid resuscitation, drug delivery, and blood sampling for laboratory evaluation and is attainable in all age 10 groups Mechanisms of Drug Actions Sympathetic Nervous System • Autonomic Nervous System Sympathetic Dilates pupil Decreases salivation Constricts blood vessels Accelerates heartbeat Parasympathetic Relaxes airways Stimulates secretion of epinephrine and norepinephrine 11 Autonomic nervous system • key component that regulates the cardiovascular system and other organs. The sympathetic nervous system is the “fight/flight” part of this system, preparing the individual for stress. In certain pathological conditions, the administration of agents such as epinephrine stimulates the system, increasing heart rate and blood pressure. In other conditions drugs used to block this system are important for the treatment of certain diseases and symptoms, such as angina. 12 Mechanisms of Drug Actions Parasympathetic Nervous System • Autonomic Nervous System Constricts pupil Constricts airways Sympathetic Parasympathetic Slows heartbeat Stimulates intestine activity 13 Autonomic nervous system The parasympathetic nervous system is the “opposite” part of this system, slowing body functions and organ responses. In certain arrhythmias and pathological conditions, the administration of agents such as atropine stimulates the system, decreasing heart rate and terminating arrhythmias under the influence of the vagus nerve. 14 Mechanisms of Drug Actions • Receptor Stimulation – α-Receptors – β-Receptors – Dopaminergic Receptors Drug or agonist Receptor Physiologic response • Heart rate • Vasoconstriction 15 A physiologic stimulus or response interacts at a receptor site and causes a response, such as an increase in heart rate or slowing of a conduction stimulus. Drugs can be used to mimic an agonist or response or to block it. Adrenergic receptors in the body regulate cardiac, vascular, bronchiolar, and gastrointestinal smooth muscle tone. The major classes of adrenergic receptors are • α-Adrenergic (α1 and α2) receptors • β-Adrenergic (β1 and β2) receptors • Dopaminergic (DA) receptors 16 • Albuterol/Xopenex/Serevent/Racemic Epi/Foradil/Brovana • These are our sympathomimic bronchodilators, they are synthetic variations of the catecholamine Epinephrine that specialize on the Beta 2 • Minor Beta 1 side effects • Beta 2 receptors when stimulated cause bronchodilation • Beta 1 when stimulated increase the HR 17 Mechanisms of Drug Actions Reproduced from Lange RA. N Engl J Med. 2001 © Massachusetts Medical Society 18 • This is an example showing how norepinephrine serves as a neurotransmitter. Norepinephrine is made and stored in granules that are released and stimulate receptors on smooth muscle cells, causing muscle stimulation and contraction. In the case of blood vessels, smooth muscle constriction increases peripheral resistance and elevates blood pressure. Cocaine can block reuptake of norepinephrine and cause hypertension or hypertensive crisis. 19 Mechanisms of Drug Actions Receptor Stimulation Constricts blood vessels • α-Receptors Accelerates heartbeat 20 α-Adrenergic receptors predominantly regulate vascular smooth muscle tone. When α-adrenergic agonists stimulate vascular α-receptors, vasoconstriction occurs. α-Adrenergic receptors are also located in myocardial muscle cells, and stimulation of these receptors increases cardiac chronotropic (heart rate) function. For clinical purposes think in terms of one type of α-receptor, and think of vasoconstriction as the response to stimulation of α-receptors. The potency of the major α-adrenergic agonists (catecholamines) is as follows: • Norepinephrine++++ • Epinephrine+++ • Isoproterenol++ • Phenylephrine+ 21 Mechanisms of Drug Actions Accelerates heartbeat and contractility 1 Dilates blood vessels 2 Relaxes airways 2 Receptor Stimulation • -Receptors (1 and 2) 22 There are several types of β-adrenergic receptors. β1 and β2 are the most important: • β1-Adrenergic receptors are the β-adrenergic receptors of the heart. They concentrate in the sinus node and ventricles. β1-Receptors are excitatory. When agonists stimulate these receptors, the heart responds with an increase in rate plus an increase in strength of contractility. • β2-Adrenergic receptors are the β-adrenergic receptors of the rest of the body. These receptors in the periphery are counterregulatory. They oppose α-adrenergic vasoconstriction, leading to vasodilation. 23 Mechanisms of Drug Actions Accelerates heartbeat Receptor Stimulation • Dopaminergic Receptors (dosedependent effects) Constricts blood vessels Stimulates secretion of epinephrine and norepinephrine Vasodilates Renal Splanchnic Vasculature 24 • Dopamine: Chronotropic, and a vasoconstrictor • Vasopressor: Vasoconstrictor only • Epinephrine/nore pinephrine: inotropic/chronot ropic and vasoconstrictor 25 • Dopaminergic receptors are located in smooth muscle cells in the cerebral, coronary, renal, and splanchnic vascular beds. Dopaminergic receptors are also present in proximal renal tubular cells and in the pituitary gland. Activation of dopaminergic receptors in the smooth muscle cells results in cerebral, coronary, renal, and splanchnic vasodilation. Activation of the dopaminergic cells in the proximal renal tubular cells results in inhibition of sodium ion reabsorption from tubular fluid, so renal sodium excretion increases. Activation of pituitary dopaminergic receptors modulates thyroid and prolactin hormone release. The most significant effect of dopaminergic receptor activation is increased blood flow to the cerebral, coronary, renal, and splanchnic circulations. 26 Dose-Dependent and ReceptorDependent Drug Effects 27 • The interaction of a drug with receptors is complex. It varies from person to person, and it is further influenced by disease states, drug dose, drug distribution, receptors, and whether the patient is in cardiac arrest. 28 Note that most vasoactive drugs affect several types of adrenergic receptors (β1, β2, α, and DA). The receptors are affected with varying degrees of what is called receptor selectivity (the binding affinity of agonists for one type of receptor over another). Other factors that contribute to the net effect of these drugs include • Pharmacokinetics (affected by all processes that influence drug diffusion, distribution, and uptake) • Receptor density (a variety of clinical conditions influence the number of receptors present on the cell surface) and function (may be affected by activation of other receptors and other body processes) • Parasympathetic nervous system • Vasoactive platelet-mediated products such as thromboxane A2 and prostacyclin • Endothelial function (dysfunction may cause paradoxical responses to vasodilating stimuli) • Loss of vasodilating substances such as endothelium relaxing 29 factor Clinical Correlation You have delivered 1 shock from a defibrillator and immediately resumed CPR with chest compressions. Two minutes later you call for a rhythm check and see this rhythm: What is your next drug action? 30 When CPR and shocks have been ineffective in terminating VF, a vasopressor is used to increase peripheral vasoconstriction and elevate aortic diastolic pressure and therefore coronary perfusion pressure in an attempt to facilitate defibrillation. 31 Persistent or Recurrent VF/VT Immediately resume CPR with compressions Prepare to administer •Epinephrine 1 mg IV/IO push, repeat every 3 to 5 minutes or •Vasopressin 40 units IV/IO, in place of first or second dose epinephrine 32 Vasopressors in Persistent VF Epinephrine 1 mg IV/IO push, repeat every 3 to 5 minutes or Vasopressin 40 units IV/IO may be substituted for first or second dose epinephrine Central Aortic Pressure Coronary Perfusion Pressure 33 • Peripheral vasoconstriction increases coronary perfusion pressure, which determines blood flow during cardiac arrest. Experimental studies have shown that coronary perfusion and aortic diastolic pressure correlate with resuscitation success. 34 Epinephrine • Epinephrine is a naturally occurring catecholamine with both - and adrenergic agonist activity • Administer 1 mg (10 mL 1:10 000 IV bolus) every 3 to 5 minutes during cardiac arrest • Stimulation of -adrenergic receptors increases peripheral vasoconstriction and as a result increases coronary and cerebral blood flow 35 Epinephrine • The beneficial effects of epinephrine during cardiac arrest come from its α-adrenergic effects. – Stimulation of α-adrenergic receptors during CPR increases myocardial and cerebral blood flow. – During resuscitation epinephrine increases peripheral vasoconstriction and improves coronary artery perfusion pressure. – Epinephrine produces significant renal vasoconstriction even at very low doses, causing decreased renal blood flow and urine output. • Epinephrine makes ventricular fibrillation (VF) more responsive to direct-current shock. • Both beneficial and toxic physiologic effects of epinephrine administration during CPR have been shown in animal and human studies. Although epinephrine has been used universally in resuscitation, there is a paucity of evidence to show that it improves outcome in humans. 36 Epinephrine Stimulation of -adrenergic receptors • Increases heart rate, contractility, and conduction velocity • Increases conduction through the atrioventricular node • Decreases the ventricular muscle refractory period: these latter effects may increase the likelihood of arrhythmias 37 Epinephrine • • • Epinephrine produces β-adrenergic effects of increased heart rate, contractility, and conduction velocity. It increases heart rate by increasing the spontaneous depolarization rate of the sinoatrial node. It increases conduction through the atrioventricular node and decreases the ventricular muscle refractory period. These latter effects may increase the likelihood of arrhythmias. Epinephrine does increase coronary artery blood flow, but the β-adrenergic effects of epinephrine increase myocardial work and reduce subendocardial perfusion, so the net effect is a greater increase in oxygen demand than oxygen delivery to the myocardium. Epinephrine makes ventricular fibrillation (VF) more responsive to direct-current shock. Both beneficial and toxic physiologic effects of epinephrine administration during CPR have been shown in animal and human studies. Although epinephrine has been used universally in resuscitation, there is a paucity of evidence to show that it improves outcome in humans. 38 Epinephrine in Cardiac Arrest • Epinephrine may be administered IV/IO • Endotracheal administration provides uncertain doses • Remember to flush with 20 mL of fluid and elevate the arm or leg Special Considerations Cautions—Contraindications • High doses can cause arrhythmias • High doses do not improve survival and may contribute to postresuscitation myocardial dysfunction 39 Vasopressin • A naturally occurring hormone, also known as antidiuretic hormone (ADH) • Causes vasoconstriction by directly stimulating smooth muscle receptors • Causes no increase in myocardial oxygen consumption during CPR— no -receptor activity Clinical studies have shown vasopressin equivalent to epinephrine for treatment of cardiac arrest 40 Vasopressin • Vasopressin can be substituted for the first or second dose of epinephrine • Give 40 units IV/IO bolus Coronary perfusion pressure Vital organ blood flow Median frequency VF Cerebral oxygen delivery 41 Vasopressin There is no evidence on • The value of repeated vasopressin doses or • The best approach after administration of a single dose of vasopressin • no difference in outcomes (ROSC, survival to discharge, or neurologic outcome) with vasopressin (40 units IV) versus epinephrine (1 mg) 42 Clinical Correlation You have delivered a shock from a defibrillator and administered a vasopressor. Two minutes later you call for a rhythm check and see this rhythm: What is your next drug action? 43 Persistent or Recurrent VF/VT Following Shocks, Vasopressor Immediately resume CPR with compressions Consider and prepare to administer •Amiodarone 300 mg IV/IO push (Class IIb) or •Lidocaine 1 to 1.5 mg/kg (Class IIb) 44 IV amiodarone can be considered for the first-line treatment of VF or pulseless VT unresponsive to shock delivery, CPR, and a vasopressor. Lidocaine is an alternative antiarrhythmic of longstanding and widespread familiarity with fewer immediate side effects than may be encountered with other antiarrhythmics. Lidocaine, however, has no proven short-term or long-term efficacy in cardiac arrest. Lidocaine should be considered an alternative treatment to amiodarone (Class IIb, LOE B). 45 Antiarrhythmic Agents • Amiodarone • Lidocaine • Magnesium 46 Amiodarone IV amiodarone affects sodium, potassium, and calcium channels as well as - and -adrenergic blocking properties. It can be considered for the treatment of VF or pulseless VT unresponsive to shock delivery, CPR, and a vasopressor. 47 Arrhythmias— Antiarrhythmic Rx Basic Mechanisms of Action • Disturbed Automaticity • Reentry • Disturbed Conduction 48 Disturbed Automaticity. • This may involve a speeding up or slowing down of areas of automaticity such as the sinus node (sinus tachycardia or sinus bradycardia), the atrioventricular (AV) node, or the myocardium. • Abnormal beats (more appropriately called depolarizations rather than beats or contractions) may arise through this mechanism from the atria, the AV junction, or the ventricles. Abnormal rhythms, such as atrial or ventricular tachycardia, may also occur. 49 Disturbed Conduction • Conduction may be either too rapid (as in Wolff-Parkinson-White syndrome) or too slow (as in atrioventricular block). 50 Combinations of Disturbed Automaticity and Disturbed Conduction • Two examples are –A premature atrial contraction (disturbed automaticity) plus first-degree AV block (disturbed conduction) –Atrial flutter (disturbed automaticity) with 3:1 or higher grades of AV block (disturbed conduction) 51 Mechanism PVCs DELAYED CONDUCTION REENTRY IRRITABLE FOCUS Unidirectional Block Purkinje Fiber Reentry Muscle Fiber • Some forms of ventricular tachycardia are initiated by a PVC and sustained by a mechanism called unidirectional block, a circus rhythm similar to other arrhythmias using 2 pathways with different refractory characteristics to propagate the arrhythmia. This is also one method by which antiarrhythmic agents work—by altering refractory periods or converting unidirectional block to bidirectional block. A rapidly firing automatic focus is another mechanism for VT. Amiodarone Cardiac Arrest Dose—300 mg IV/IO Repeat Once—150 mg IV/IO Amiodarone is approved for • Refractory ventricular fibrillation during cardiac arrest • Recurrent ventricular fibrillation • Recurrent hemodynamically unstable ventricular tachycardia 54 Key Studies—Amiodarone ARREST Trial, Kudenchuk 1999 Patient group n Amiodarone 246 Placebo 258 Survival to admission Odds ratio for admission Survival to discharge 44% 1.6 13.4% 34% (P = .03) 1.0 (P = .02) 13.2% (P = NS) Kudenchuk PJ. N Engl J Med. 1999 55 ARREST Trial Return of Spontaneous Circulation (ROSC) 70 60 50 % 40 30 20 10 0 64% 41% ROSC 38% 33% No ROSC Amiodarone Placebo Kudenchuk PJ. N Engl J Med. 1999 56 ARREST Trial Survival to Hospital Admission 60 50 40 %30 20 10 0 44% 34% All 49% 39% VF/VT Amiodarone 17% 12% Asys/PEA Placebo Kudenchuk PJ. N Engl J Med. 1999 57 Key Studies—Amiodarone ALIVE Trial, Dorian 2002 Patient group n Survival to admission Survival to discharge Amiodarone 180 22.8% 5% Lidocaine 167 12.0% (P = .009) 3% (P = .34) Amiodarone 5 mg/kg vs lidocaine 1.5 mg/kg Dorian P. N Engl J Med. 2002 58 ALIVE Trial Survival to Hospital Admission % of pts 25 Lidocaine (n = 167) IV Amiodarone (n = 180) 20 15 10 5 0 12% 23% All patients P = .009 14% 25% VF or VT P = .03 59 Dorian P. N Engl J Med. 2002 Amiodarone Special Considerations Cautions—Contraindications • Because of the • For other uses, seek potentially lifeexpert consultation threatening side effects • Complex doseand difficulties dependent side effects associated with managing its use, amiodarone is prescribed in ACLS for only life-threatening arrhythmias 60 Lidocaine Initial Dose—1 to 1.5 mg/kg IV Repeat Dose—0.5 to 0.75 mg/kg IV every 5 to 10 minutes Maximum—3 mg/kg • Alternative to amiodarone in cardiac arrest from VF/VT • Can be used in stable monomorphic VT • Remember to search for and correct underlying causes of VT: - Ischemia - Electrolyte abnormality - Hypoxia - Proarrhythmia (other drugs) 61 Lidocaine • Prophylactic use in acute coronary syndromes is contraindicated • Reduce dose in the elderly and those with poor cardiac output, heart failure, and liver dysfunction Special Considerations Cautions—Contraindications • Discontinue immediately if signs of toxicity develop • Toxicity includes altered mental status, drowsiness, confusion, disorientation, ringing in ears • Serious side effects can include focal and grand mal seizures 62 Lidocaine Metabolism Hepatic Failure and CHF 63 Magnesium Cardiac Arrest Dose—1 to 2 g over 5 to 20 minutes Torsades—1 to 2 g IV/IO over 5 to 60 minutes • Recommended in cardiac arrest if torsades de pointes is present— especially if baseline QT interval prolongation is known to be present • Also recommended if hypomagnesemia is suspected • Not routinely indicated for acute coronary syndromes 64 Magnesium • Magnesium is required for proper function of the membrane pump in cardiac cells • Magnesium depletion causes cardiac cell depolarization • Torsades de pointes may occur and persist Special Considerations Cautions—Contraindications • Avoid rapid administration because hypotension may occur • Use with caution if renal failure is present • Not routinely indicated in acute myocardial infarction 65 Agents to Control Rate • Atropine • Dopamine Infusion • Epinephrine Infusion • Adenosine 66 Agents to Control Rate • Many new cardiovascular agents for the control of rate and rhythm are available to the healthcare provider. The provider must understand the clinical pharmacology of these drugs in order to select the proper drug and avoid serious complications in emergency settings. Knowledge of side effects and interactions with other drugs is important because many drugs reduce the efficacy of other therapies and add to unwanted effects, such as atrioventricular (AV) nodal depression. 67 Atropine Dose—0.5 mg bolus Repeat every 3 to 5 min as needed Maximum 3 mg • First drug for symptomatic bradycardia • May be beneficial in AV nodal blocks • Do not rely on atropine for infranodal blocks • Atropine is useful when blockade of the parasympathetic nervous system can increase rate or improve 68 AV conduction. • Atropine sulfate reverses cholinergic-mediated decreases in heart rate and should be considered a temporizing measure while awaiting a transcutaneous pacemaker for those patients. Atropine is useful for treating symptomatic sinus bradycardia and may be beneficial for any type of AV block at the nodal level. Do not rely on atropine for infranodal blocks (not likely to be effective for type II second-degree or third-degree AV block or a block in non-nodal tissue). After 1 or 2 doses of atropine with no response, move to pacing, epinephrine infusion, or a dopamine infusion as a second-line treatment. • The recommended atropine dose for bradycardia is 0.5 mg IV every 3 to 5 minutes to a total dose of 3 mg. Doses of atropine sulfate of less than 0.5 mg may paradoxically result in further slowing of the heart rate. Atropine administration should not delay implementation of external pacing for patients with poor perfusion. • Use atropine cautiously in the presence of acute coronary ischemia or myocardial infarction; increased heart rate may worsen ischemia or increase the zone of infarction. • Atropine may be used with caution and appropriate monitoring following cardiac transplantation. It will likely be ineffective because the transplanted heart lacks vagal innervation. One small, uncontrolled study documented paradoxical slowing of the heart rate and highdegree AV block when atropine was administered to patients after 69 cardiac transplantation. Atropine Special Considerations Cautions—Contraindications • Use with caution in • Use 0.5 mg the presence of incremental doses in cardiac ischemia the presence of • Do not rely on ischemia atropine for • Repeat every 3 to 5 infranodal blocks minutes as needed to (not likely to be a maximum of 3 mg effective for type II second-degree or third-degree AV block or a block in non-nodal tissue)70 Atropine • Excessive doses of atropine can cause an anticholinergic syndrome of delirium, tachycardia, coma, flushed and hot skin, ataxia, and blurred vision. Administration of atropine in doses of less than 0.5 mg can produce a paradoxical bradycardia owing to the central or peripheral parasympathomimetic effects of low doses in adults. • This effect can precipitate VF. • When repeated doses of atropine are required, restrict the total cumulative dose to the 3 mg (0.04 mg/kg) associated with full parasympathetic blockade. 71 Dopamine Infusion for Rate Bradycardia—2 to 10 mcg/kg per min Hypotension—2 to 20 mcg/kg per min • If bradycardia is unresponsive to atropine, a chronotropic (heart rate) agent can be given by infusion or pacing • Dopamine is also used at higher doses for blood pressure control in hypotension (inotropic agent) 72 Review: Blood Pressure = Cardiac Output Peripheral Vascular Resistance Cardiac Output = Heart Rate Stroke Volume Stroke Volume = EDV - ESV 73 Dopamine • Activates dopaminergic receptors and causes vasodilation in GI and renal vasculature • Ensure that adequate preload (volume) is present or hypotension may occur at low doses Special Considerations Cautions—Contraindications Remember: Blood Pressure = Cardiac Output Peripheral Vascular Resistance Cardiac Output = Heart Rate Stroke Volume 74 Dopamine low-dose dopamine may cause vasodilation and blood pressure may fall if patients do not have adequate filling pressures. • This may be accentuated in patients who have a bradycardia because heart rate may not increase to compensate for the fall in cardiac output due to a decrease in venous return. 75 Dopamine Special Considerations Cautions—Contraindications • May increase heart • Tissue necrosis may occur if rate and exacerbate interstitial tachyarrhythmia extravasation occurs • Nausea and vomiting are • Inactivated in common side alkaline solutions effects (bicarbonate) 76 Epinephrine Infusion for Rate 2 to 10 mcg per minute • If bradycardia is unresponsive to atropine, a chronotropic (heart rate) agent can be given by infusion or pacing • Epinephrine is initiated at 2 mcg per minute and titrated to patient response 77 Epinephrine Special Considerations Cautions—Contraindications • Epinephrine is also used in cardiac arrest at higher doses: 1 mg every 3 to 5 minutes IV/IO • Dosing higher than 10 mcg per minute can cause vasoconstriction • Raising blood pressure and increasing heart rate can cause myocardial ischemia • High doses can cause angina, arrhythmias 78 Adenosine 6 mg IV bolus 12 mg IV bolus 12 mg IV bolus • Endogenous purine nucleotide • Depresses sinus and AV nodal activity • Indicated for stable narrowcomplex supraventricular tachycardias unresponsive to vagal maneuvers Adenosine • Terminates reentry rhythms, not indicated for ventricular or pre-excited arrhythmias 79 Adenosine • • SVT does not respond to vagal maneuvers, give 6 mg of IV adenosine as a rapid IV push (Class I). Give adenosine rapidly over 1 to 3 seconds through a large (eg, antecubital) vein, followed by a 20 mL saline flush and elevation of the arm. If the rate does not convert within 1 to 2 minutes, give a 12 mg bolus. Give a second 12 mg bolus if the rate fails to convert within 1 to 2 minutes after the first 12 mg bolus. Amiodarone can achieve nearly 100% efficacy in the inhibition of induced sustained reentrant SVT. Adenosine is safe and effective in pregnancy. Adenosine, however, does have several important drug interactions. Larger doses may be required for patients with a significant blood level of theophylline, caffeine, or theobromine. The initial dose should be reduced to 3 mg in patients taking dipyrimadole or carbamazepine, in those with transplanted hearts, or if given by central venous access. Side effects with adenosine are common but transient; flushing, dyspnea, and chest pain are 80 the most frequently observed. Adenosine Special Considerations Cautions—Contraindications • Administer rapid IV push (1 to 3 seconds) with flush • Initial bolus of 6 mg • May repeat if no response with 12 mg dose twice • Transient periods of bradycardia and PVCs common after conversion • Higher doses may be required in patients taking theophylline or caffeine • Transient side effects include chest discomfort, flushing, nausea • Safe in pregnancy • Reduction of the initial dose (to 3 mg) may be required in patients receiving dipyrimadole or carbamazepine and those with central vein administration 81 Electrical Cardioversion Immediate electrical cardioversion is indicated for a patient with serious signs and symptoms related to a tachycardia 82 Synchronized Cardioversion Procedure: 1. Attach monitor leads to patient 2. Apply conductive material to paddles if not using hands-free defibrillation pads 3. Turn on defibrillator 83 Synchronized Cardioversion Procedure (cont’d): 4. Turn on synchronization mode 5. Verify synchronization signal on monitor screen 6. Select energy level 7. Place defibrillator pads or paddles on chest and apply pressure (if necessary) 8. Charge defibrillator 84 Synchronized Cardioversion Procedure (cont’d): 9. “CLEAR!” –Check yourself –Check patient –Check bed/stretcher –Check flow of oxygen 10. Press button(s) until discharge occurs 85 Cardioversion Energy Recommendations Biphasic Waveform • Atrial Fibrillation • Atrial Flutter & SVT • Monomorphic VT 120-200 J Initial 50-100 J Initial 100 J Initial • Increase the energy dose in a stepwise fashion for any subsequent cardioversion attempts • Use manufacturer-recommended doses 86 Cardioversion Energy Recommendations Monophasic Waveform • Atrial Fibrillation • Atrial Flutter & SVT • Monomorphic, Unstable With Pulse 200 J 200 J 100 J • Polymorphic or Pulseless VT—Treat as VF with high-energy unsynchronized defibrillation doses (Do not use low energy—high likelihood of causing VF in unsynchronized mode) 87 Synchronized Cardioversion Premedicate with both a sedative and an analgesic if appropriate. For example: • Sedatives ─ Diazepam ─ Midazolam ─ Etomidate • Analgesics ─ Fentanyl ─ Morphine ─ Hydromorphone 88 Reperfusion Therapy and ACS Adjuncts • Oxygen • Aspirin • Nitroglycerin • Morphine 89 Immediate General Treatment • Oxygen (if needed) • Aspirin 160 to 325 mg • Nitroglycerin SL or spray • Morphine IV (if pain not relieved with nitroglycerin) 90 Oxygen in ACS • Administer to patients who have an oxygen saturation <94% or respiratory compromise • If needed, initiate at 2 to 4 L/min with nasal cannula • Maintain O2 saturation ≥94% 91 Oxygen Use in Acute Coronary Syndromes Why? • Increases supply of oxygen to ischemic tissue When? • When O2 saturation <94% or respiratory compromise How? • Start with nasal cannula at 2 to 4 L/min Watch Out! • Rarely COPD patients with hypoxic ventilatory drive will hypoventilate 92 Platelet Role in ACS Adhesion Recruitment and Activation Aggregation FIBRIN RUPTURED PLAQUE X PAF X HEPARIN ASA GP IIb-IIIa GP IIb-IIIa CLOPIDOGREL PRASUGREL TICAGRELOR X GP IIb-IIIa 93 • Rupture of an atherosclerotic plaque results in exposure of the subendothelial matrix substrates, triggering adhesion of platelets to the area of disruption. Other platelet stimuli, such as thrombin, serotonin (5-HT), and collagen, activate platelets to secrete adenosine diphosphate (ADP) and thromboxane A2 (TxA2), further amplifying activation and thrombin generation. • Acute coronary syndromes typically are initiated by rupture of the thin fibrous cap over the lipid-laden intracoronary plaque. 94 Antiplatelet Agents • Blocks receptors on platelets X • Blocked receptors cannot attach to fibrinogen X • Fibrinogen cannot aggregate platelets to platelets 95 Platelet Receptor Blockade Thromboxane A2 Thrombin PLATELET HEPARIN ASPIRIN GP IIb-IIIa Platelet Receptor Fibrinogen GP IIb-IIIa PLATELET Clot Formation • As the activated platelets aggregate and cross-link, they develop high affinity for prothrombin and fibrinogen in the blood. • Prothrombin, one of the essential clotting factors, is converted by the activated platelets (among other activators) to thrombin. • Thrombin, in turn, acts to convert fibrinogen to fibrin. As fibrin concentrations increase, the fibrin begins to form fibrin strands. • The fibrin strands give substance and structure to a growing fibrin matrix. This matrix continues to attract activated platelets and soon entraps passing red blood cells Aspirin and Clopidogrel Indications: ACS examples • STEMI • NSTEMI • Unstable angina managed medically • UA undergoing PCI 98 Aspirin in ACS 160 to 325 mg, chewed • Administer to all patients with suspected ischemic pain • 2 - 4 “baby” aspirin can be given to facilitate chewing • Do not use enteric (coated) preparations • May be administered by rectal suppository 99 Aspirin: Actions • Actions – Blocks formation of thromboxane A2 (thromboxane A2 causes platelets to aggregate and arteries to constrict) • These actions will reduce – Overall mortality from AMI – Nonfatal reinfarction – Nonfatal stroke 100 Aspirin: Indications, Dose • Indications—As soon as possible! − Standard therapy for all patients with new pain/discomfort suggestive of ACS − Give within minutes of arrival • Dose: 160 to 325 mg taken as soon as possible 101 Aspirin: Precautions • Relatively contraindicated in patients with active peptic ulcer disease or asthma • Contraindicated in patients with known aspirin hypersensitivity • Bleeding disorders • Severe hepatic disease 102 Nitroglycerin • Administer to all patients with suspected ischemic pain unless contraindicated • Remember to reassess and repeat vital signs between doses • Up to 3 sublingual or spray doses may be given at 5-minute intervals • IV initiated for specific indications 103 Nitroglycerin: Actions • 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 104 IV Nitroglycerin—STEMI: Indications • First 24 to 48 hours in patients with STEMI and one or more of the following: – Recurrent ischemic chest pain – LV failure (acute pulmonary edema or CHF) – Elevated BP (especially with signs of LV failure) – Large anterior infarction – Persistent ischemia • Administration does not interfere with other agents known to decrease mortality (ACE-I) 105 Nitroglycerin: Dose • Sublingual: 0.3 to 0.4 mg; repeat every 5 minutes • Spray inhaler: 1 to 2 metered doses at 5-minute intervals • Maximum of 3 sprays within 15 minutes • IV infusion: 12.5 to 25 mcg bolus, 10 to 20 mcg/min infusion, titrated 106 Nitroglycerin: Precautions • Contraindicated if systolic BP <90 mm Hg • Contraindicated 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 107 Precautions • Recent phosphodiesterase inhibitor. If the patient has erectile dysfunction and has taken a phosphodiesterase inhibitor within the previous 24 hours (48 hours for tadalafil), nitrates may cause severe hypotension refractory to vasopressor agents. • Hypotension, bradycardia, or tachycardia. Avoid use of nitroglycerin in patients with hypotension (systolic BP <90 mm Hg), extreme bradycardia (<50 bpm), or tachycardia (heart rate >100 bpm). 108 Morphine Sulfate • Administer to all patients with suspected ischemic pain unresponsive to oxygen and nitrates • Remember to reassess and repeat vital signs between doses • Initial dose is 2 to 4 mg IV over 1 to 5 minutes • Administer slowly and only titrate to effect 109 Morphine • Produces CNS analgesia, which reduces the toxic effects of neurohumoral activation, catecholamine release, and heightened myocardial oxygen demand • Produces venodilation, which reduces LV preload and oxygen requirements • Decreases systemic vascular resistance, thereby reducing LV afterload • Helps redistribute blood volume in patients with acute pulmonary edema 110 Morphine Sulfate: Actions • To reduce pain of ischemia • To reduce anxiety • To reduce extension of ischemia by reducing oxygen demands 111 Morphine Sulfate: Indications • Continuing pain unresponsive to nitrates • Evidence of vascular congestion (acute pulmonary edema) • Systolic blood pressure >90 mm Hg • No hypovolemia 112 Morphine Sulfate: Precautions • Drop in blood pressure, especially in patients with – Volume depletion – Increased systemic resistance – RV infarction • Depression of ventilation • Nausea and vomiting (common) • Bradycardia • Itching and bronchospasm (uncommon) 113 Fibrinolytic Therapy • Breaks up the fibrin network that binds clots together • Indications: ST elevation in 2 or more contiguous leads or new LBBB – Threshold values: J-point elevation of 2 mm in V2 and V3* and 1 mm in all other leads – Time of symptom onset must be <12 hours – Caution: fibrinolytics can cause death from brain hemorrhage • Agents differ in their mechanism of action, ease of preparation and administration, cost, need for heparin • 3 agents currently available: alteplase (tPA, Activase), reteplase (Retavase), tenecteplase (TNKase) *2.5 mm in men <40 years; 1.5 mm in all women 114 Adjunctive Agents—ACS • -Receptor blocking agents • Clopidogrel • Heparin • ACE inhibitors and ARBs • Statins 115 Advanced Adjunctive Agents—ACS The use of ACS adjunctive agents is NOT routine • Timing and dose may depend on the patient, selection of treatment strategy, and a careful consideration of risk-benefit 116 -Blockers Mechanism of action • Blocks catecholamines from binding to -adrenergic receptors • Reduces HR, BP, myocardial contractility • Decreases AV nodal conduction • Decreases incidence of primary VF 117 -Blockers Absolute Contraindications • Severe CHF • SBP <100 mm Hg • Acute asthma (bronchospasm) • Second- or thirddegree AV block Cautions • • • • • Mild/moderate CHF HR <60 bpm History of asthma IDDM Severe peripheral vascular disease 118 Heparin • Mechanism of action – Indirect thrombin inhibitor (with AT III) • Indications – PCI or CABG – With fibrin-specific lytics – High risk for systemic emboli Conditions with high risk for systemic emboli, such as large anterior MI, atrial fibrillation, or LV thrombus 119 ACE Inhibitors • Mechanism of action – Reduces BP by inhibiting angiotensinconverting enzyme (ACE) – Alters post-AMI LV remodeling by inhibiting tissue ACE – Lowers peripheral vascular resistance by vasodilatation – Reduces mortality and CHF from AMI 120 Pharmacology QUESTIONS? 121