Hemodynamic Drugs

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Inotropes
Action
Ephedrine Indirect NE release Mild direct , 1, 2 Acts like small dose epinephrine 1, 2, 1, 2 agonist Dose dependent action 1-3mcg/min = 3-10mcg/min = and 10+ mcg/min = and 1, 1, 2, D1 agonist Indirect NE release 1-3g/kg/min = D1 3-10 = 1,2>D1 10+ = 1>, D Strong 1> 2 Weak 1 Inhibits Phosphodiesterase III Increases cAMP Doesnt act at receptors Increased contractility Decreased PVR/SVR Increases intracellular cAMP

HR

Con

Preload SVR/PVR BP

CO

Indications
Low SVR (esp if HR low) Low CO (esp if HR low) Transient cardiac depression Cardiac Arrest Anaphylaxis Cardiogenic shock Bronchospasm Reduced CO Hypotension Low CO Low SVR Renal Insufficiency? Low CO (esp with SVR) Right heart failure Stress Echocardiography Low CO (esp with SVR) Right heart failure Pulm HTN Supplement -agonists Reduced proarrhythmic effect Hypoglycemia -blocker toxicity Low CO Refractory CHF Hypocalcemia Hyperkalemia Hypotension from hypocalcemia, CCB, or protamine Anesthetic overdose Counter act hypermagnesemia Low CO Right heart failure Pulm HTN Supplement -agonists Reduced proarrhythmic effect

Use
5-10mg IV bolus 25-50mg IM Tachyphylaxis with repeat dosing 4mg/250ccNS = 16mcg/cc 2-10mcg IV bolus (Never more unless extremis) Infusion 2-20mcg/min (Central line) Arrest: 0.5-1.0mg IV bolus Monitor end-organ perfusion closely 200-400mg/250cc = 800-1600mcg/cc Infusion 2-20mcg/kg/min (Central line) Monitor end-organ perfusion (esp>10mcg/kg/min) 250mg/250cc = 1,000mcg/cc Infusion: 2-30mcg/kg/min Often used with other inotropes/vasopressors 25-75mcg/kg load over 10min (beware BP) Infusion: 0.375-0.75mcg/kg/min Reduce infusion in renal failure Bolus: 1-5mg IV slowly Infusion: 25-75mcg/min Rarely used because of multiple side-effects (N/V, tachycardia, hyperglycemia, hypokalemia, anaphylaxis) 10% Calcium Chloride 100mg/cc 200-1000mg slow IVP (prefer central line) Causes vein inflammation Dont use immediately after reperfusion Bolus: 6-24mcg/kg (10-20min) Infusion: 0.05-0.4mcg/kg/min (up to 24 hrs) Active metabolite with 80hr half-life Effects last 24-48hrs after infusion stopped

Epinephrine

-/ 1-3 -/ 3-10 10-20

-/ 10-20

Dopamine

-/ (in -blocked pts)

Var

/-/

Dobutamine

Var

Milrinone

-/

Var

Glucagon

Calcium Chloride

Free Ca ion

-/

Levosimendan

Calcium-sensitizing agent Binds to troponin C cAMP-independent Vascular dilation KATPase channels

-/

Var

Douglas C. Shook, MD Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Womens Hospital

Hemodynamic Drugs
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Vasoconstrictors
Drug
Phenylephrine

Action
1-agonist

HR
-/ (reflex )

Con
-

Preload SVR/PVR BP

CO
-/

Indication
Peripheral vasodilation Low SVR SVT (Reflex vagal stim) TET spell Peripheral vascular collapse Shock, vasoplegia SVR Need SVR with some Con Phenylephrine isnt working Alt to Epi in Cardiac arrest Secondline agent: Shock, vasoplegia, sepsis, SVR Pulm HTN with SVR? Physiologic dose with Milrinone To reduce Norepi dose Not a first-line agent Limited clinical trials and case reports SVR - Septic shock, SIRS Refractory post-CPB vasoplegia Dec Norepi requirements

Use
40mg/250ccNS = 160mcg/cc 10mg/250ccNS = 40mcg/cc 40-80mcg IV bolus Infusion on micro gtt Start infusion at 10mcg/min 8mg/250ccNS = 32mcg/cc 2-10mcg IV bolus (extremis only) Infusion 2-20mcg/min (Central line) Monitor end-organ perfusion closely Infusion: 0.01-0.04U/min (physiologic) Lower incidence of end-organ hypoperfusion Infusion: 0.04-0.1U/min (Pharm dose) Monitor end-organ perfusion closely Bolus: 40U IV for VF arrest

Norepinephrine

1, 2, 1 agonist Intense 1 and 2 constriction throughout dosing range Direct vasoconstriction via V1 receptors

Variable

-/ (SVR)

Vasopressin No action on or receptors

/?

Var

Methylene Blue

Complex mechanism Inhibits NO/cGMP Inhibits NO synthase

Bolus: 1.5-2.0mg/kg over 15-30min Infusion: 0.25-1.0mg/kg/hr Monitor end-organ perfusion

Vasodilators
Nitroglycerin Direct vasodilator cGMP production Venous>Arterial Excellent coronary effects (reflex ) (refle x) (High dose) / Myocardial ischemia Increase coronary perfusion Relieve coronary spasm Hypertension Arterial dilation (high dose) Pulmonary HTN CHF HTN, SVR Controlled hypotension SVR>Preload at lower doses 40-80mcg IV bolus Infusion 10-200mcg/min At infusions higher than 200mcg/min switch to SNP or at another agent. Tolerance if infused for long periods of time. Infusion 0.1-2.0mcg/kg/min Avoid doses greater than 2.0 (toxicity) Protect from light Continuous BP monitoring (A-line) Taper infusion gradually Use with caution in liver/kidney dysfunction

Nitroprusside

Direct vasodilator cGMP production Arterial=Venous

(reflex )

(refle x)

Douglas C. Shook, MD Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Womens Hospital

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Beta-Blockers
Drug
Propranolol Labetolol Metoprolol Esmolol Excellent during intubation/extubation

Action
1, 2 antagonist 1, 2, 1 antagonist Ratio of : = 1:7 1 antagonist 1 antagonist

Half-life (Hrs)
3.5-6.0 3-8 3-4 9 min

Elimination
Hepatic Hepatic Hepatic RBC esterase

IV Dose
0.5-1.0mg IV prn 5-10mg IV prn 1-5mg IV prn 0.25-0.5mg/kg IV prn Infusion 50-200mcg/kg/min

Action o HR decreased o Contractility decreased o SVR unchanged or increased o AV conduction decreased o Atrial refractory period increased o Automaticity decreased Indications o Rx hypertension o Arrhythmias o Myocardial ischemia and infarction o Reduce dynamic ventricular outflow obstruction o Synergism with nitroglycerin for treating MI o Reduce perioperative myocardial morbidity and mortality Monitor for o Severe bradyarrhythmias o Heart block o Bronchospasm o CHF with low EF o Withdrawal syndrome with abrupt discontinuation (Hypertension and Tachycardia) Treatment of toxicity o -agonists (possible large doses) o Pacing o Calcium, milrinone, glucagon, thyroid hormone Assessment of -blockade o Minimal or no increase HR with exercise
Douglas C. Shook, MD Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Womens Hospital

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Dont treat epinephrine reactions from local anesthesia injection (BP) with -blockers Cardiovascular collapse.

Douglas C. Shook, MD Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Womens Hospital

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Calcium Channel Blockers

Drug Verapamil Action Calcium Channel Blocker Half-life 3-10 hrs Elimination Hepatic IV Dose Vial 5mg/2cc 0.625-1.25mg IV prn (Low dose) Info Myocardial depression>Peripheral arterial vasodilation Use low doses with GA or unstable patients Rx: SVT, HTN, vasospasm, ischemia, LV outflow obstruction,

Effects o Peripheral arterial vasodilation o Venodilation is minimal o Coronary dilation o Depression of myocardial contractility (Verapamil>Diltiazem>Nicardipine) o Improving myocardial ischemia o Prolonging AV refractory period (Verapamil, Diltiazem) o Decreased sinus rate (Verapamil, Diltiazem) Indications o MI o HTN o LV outflow obstruction o Vasospasm o Migraine prophylaxis o Arrhythmias (Verapamil, Diltiazem) Toxicity o Give Calcium Chloride, -agonists, milrinone, pacing

Muscarinic Antagonist
Drug Atropine Action Blockade of Ach at muscarinic receptors Half-life Variable Elimination Renal>Hepatic IV Dose 0.4-1.0mg IV Info Dosing for bradycardia May exacerbate bradycardia with dose <0.4mg IV Rx: Bradyarrhythmias (asystole, HR<40bpm Pts with poor diastolic compliance cannot tolerate HR near 40

Adverse effects o Tachycardia o Sedation o Urinary retention o Increased intraocular pressure o Dry mouth
Douglas C. Shook, MD Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Womens Hospital

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o PVCs

Douglas C. Shook, MD Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Womens Hospital

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Important Tips
Drug Dosage Calculations and Infusions Drug errors one of the most common causes of accidental injury to patients. Always ask for help if you have not used a drug before. Drugs are given in mg, mcg, and units. Not all drugs are labeled in a uniform manner. o Example epinephrine in the standard drug kit. Epi Vial = 1:1000 = 1mg/cc Epi box = 1:10,000 = 100mcg/cc Both are very high concentrations Concentrations as ratios o 1:1000 = 1gm/1000mL = 1mg/mL o 1:10,000 = 0.1mg/mL = 100mcg/mL o 1:100,000 = 0.01mg/mL = 10mcg/mL o 1:200,000 = 0.005mg/mL = 5mcg/mL o 1:1,000,000 = 1g/million mL = 1mcg/ml Concentrations as percents o x% = Xg/dL = Xg/100mL = 10xXmg/mL o 2% Lidocaine = 20mg/mL Look at the label before mixing o Example epinephrine vs ephedrine o Dilution in 10cc yields very different effects for the patient. Standard concentrations used at BWH. o Phenylephrine 40mg/250cc (160mcg/cc) o Epinephrine 4mg/250cc (16mcg/cc) o Norepinephrine 8mg/250cc (32mcg/cc) Make sure to check the label and dilution when starting an infusion. Double check the infusion pump so the concentration you calculated equals the concentration shown on the pump. Double check that you are not infusing into an arterial catheter. o Maintain the yellow/white caps on the pressure catheters. Infusions should run at a constant rate. Dont bolus in the infusion catheter. Monitoring effect of Hemodynamic infusions Effect on BP (cuff or better a-line) o Cycle the cuff a couple of times after a bolus has been given. Pulmonary artery catheter Cardiac Output Echocardiography Organ perfusion (urine output, concentration, skin, labs, etc)

Douglas C. Shook, MD Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Womens Hospital

Hemodynamic Drugs
8 of 11 Patients on Reserpine, Tricyclic Antidepressants, and MAO inhibitors Reserpine o Depletes intraneuronal NE leading to denervation hypersensitivity o Indirect acting agents (ephedrine) show diminished effect. o Direct acting agents may produce exaggerated effects. TCAs and MAO inhibitors o These drugs increase the availability of NE at receptors. o Indirect acting agents show an exaggerated response (life threatening hypertension) o Use direct acting agents in these patients. Start with small doses. o The response is greatest in the first 14-21 days of treatment. o If a reaction does occur use a vasodilator.

Douglas C. Shook, MD Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Womens Hospital

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Appendix A
Classification of Receptors with Organ and Response
Receptor Beta-1 Organ Heart Response Increased HR Increased contractility Increased conduction velocity Automaticity Risk of arrhythmias Lipolysis Renin release Increased HR Increased Contractility Dilation Dilation Relaxation Renin release Gluconeogensis Insulin release Constriction (arterial and venous) Increase contractility Decrease HR Inhibit insulin secretion Relaxation Constriction of sphincters Inhibits NE, Ach, serotonin, dopamine, and substance P release (sedation, Dec BP, etc) Inhibits NE release (Neg feedback) Analgesia/Anesthesia sparing effect Vasoconstriction Dilation (renal, mesenteric) Inhibit NE release Dec HR Dec contractility Dec conduction velocity Constriction Secretion Contraction Relaxation of sphincters Secretion Contraction Relaxation of sphincter Contraction SNS stimulation
Douglas C. Shook, MD Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Womens Hospital

Beta-2

Adipose tissue Renal Heart (less potent) Vascular (Muscle) Bronchial Uterus Renal Liver Pancreas Vascular (less brain/heart) Heart (less potent) Pancreas Intestine/Bladder

Alpha-1

Alpha-2 Presynaptic Postsynaptic Dopamine-1 Dopamine-2 Muscarinic

CNS Peripheral CNS Peripheral Blood vessels Presynaptic Heart Bronchial Salivary Glands Intestine Bladder

Nicotinic

Neuromuscular Jxn Autonomic ganglia

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Appendix B

(Important Slides From Talk)

Douglas C. Shook, MD Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Womens Hospital

Hemodynamic Drugs
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Douglas C. Shook, MD Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Womens Hospital

Hemodynamic Drugs
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Douglas C. Shook, MD Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Womens Hospital