Vasoactive Drugs
Transcript of Vasoactive Drugs
![Page 1: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/1.jpg)
Management of ShockRole of Inotropic & Vasoactive drugs
Dr. Waheed A. Radwan
Professor of Critical Care Medicine
Cairo University
![Page 2: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/2.jpg)
Glossary of terms
• Inotropes: agents that improve myocardial contractility and enhance stroke volume
• Pressors: agents that increase systemic vascular resistance and increase blood pressure
• Chronotropic: Increase heart rate
• Lusotropic: improve relaxation during diastole and decrease EDP in the ventricles
![Page 3: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/3.jpg)
CONTRACTILITY HEART RATE
PRELOAD AFTERLOAD
L/Min
CARDIACOUTPUT
(CI=CO/m²)
Determinants of Cardiac Output
![Page 4: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/4.jpg)
CARDIOVASCULAR MEDICATIONS
• From ICU standpoint, can be divided into two main groups:– Cardiac arrest medications– Cardiac medications via continuous infusions
• Many of the meds used during a cardiac arrest may also be given as continuous infusions.
![Page 5: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/5.jpg)
CARDIOVASCULAR MEDICATIONS
• Main actions of most of the following cardiovascular medications will be determined by the adrenergic effects of the medications.
• Can either be:– alpha-adrenergic– beta-adrenergic– dopaminergic
![Page 6: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/6.jpg)
ALPHA-ADRENERGIC MEDICATIONS
• Can be divided into:– Alpha1-adrenergic effects:
• Vascular smooth muscle contraction
– Alpha2-adrenergic effects:• Vascular smooth muscle relaxation--this is a very
mild effect only at low doses of an alpha-adrenergic agent like epinephrine.
![Page 7: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/7.jpg)
BETA-ADRENERGIC MEDICATIONS
• Can be divided into:– Beta1-adrenergic effects:
• Direct cardiac effects
– Inotropy (improved cardiac contractility)
– Chronotropy (increased heart rate)
– Beta2-adrenergic effects:• Vasodilation
• Bronchodilation
![Page 8: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/8.jpg)
CARDIAC MEDS VIA CONTINUOUS INFUSION
• Epinephrine
• Norepinephrine
• Dopamine
• Dobutamine
• Milrinone/Amrinone
• Sodium Nitroprusside
• Nitroglycerin
• Isoproterenol
![Page 9: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/9.jpg)
EPINEPHRINE
• Both an alpha- and beta-adrenergic agent• Therefore, indications for its use as a
continuous infusion are:– low cardiac output state
• beta effects will improve cardiac function• alpha effects may increase afterload and decrease
cardiac output
– septic shock• useful for both inotropy and vasoconstriction
![Page 10: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/10.jpg)
EPINEPHRINE
• Actions are dose dependent (mcg/kg/min):– 0.02-0.08 = mostly beta1 and beta2 stimulation.
• increased cardiac output
• mild vasodilation
– 0.1-2.0 = mix of beta1 and alpha1
• increase cardiac output
• increase SVR = vasoconstriction
– > 2.0 = mostly alpha1
• increase SVR, and may decrease CO by increasing afterload
![Page 11: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/11.jpg)
EPINEPHRINE
• Side effects include:
• Anxiety, tremors,palpitations
• Tachycardia and tachyarrhythmias
• Increased myocardial oxygen requirements and potential to cause ischemia
• Decreased splanchnic and hepatic circulation (elevation of AST and ALT)
• Anti-Insulin effects: lactic acidosis, hyperglycemia
![Page 12: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/12.jpg)
NOREPINEPHRINE
• Employed primarily for its alpha agonist effect - increases SVR (and B.P.) without significantly increasing C.O.
• Used in cases of low SVR and hypotension such as profound “warm shock” with a normal or high C.O. state
• Infusion rates titrated between 0.05 to 1 mcg/kg/min
![Page 13: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/13.jpg)
NOREPINEPHRINE
• In general, norepinephrine differs from epinephrine in that at doses used in clinical practice, the vasoconstriction outweighs any increase in cardiac output.
– i.e. norepinephrine usually increases blood pressure and SVR, often without increasing cardiac output.
![Page 14: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/14.jpg)
NOREPINEPHRINE
• Side Effects:
• Similar to those of Epinephrine
• Can compromise perfusion in extremities and may need to be combined with a vasodilator e.g. Dobutamine or Nipride
• More profound effect on sphlancnic circulation and myocardial oxygen consumption
![Page 15: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/15.jpg)
DOPAMINE
• Intermediate product in the enzymatic pathway leading to the production of norepinephrine; thus, it indirectly acts by releasing norepinephrine.
• Directly has alpha, beta and dopaminergic actions which are dose-dependent.
• Indications are based on the adrenergic actions desired.
![Page 16: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/16.jpg)
DOPAMINE
• Improve renal perfusion 2-5 mcg/kg/min
• Improve C.O. in mild to moderate Cardiogenic or Distributive Shock 5-10mcg/kg/min
• Post-resuscitation stabilization in patients with hypotension (in conjuction with fluid therapy) 10-20mcg/kg/min
![Page 17: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/17.jpg)
DOBUTAMINE
• Synthetic catecholamine with inotropic effect (increases stroke volume) and peripheral vasodilation (decreases afterload)
• Positive chronotropic effect (increases HR)
• Some lusotropic effect
• Overall, improves Cardiac Output by above beta-agonist acitivity
![Page 18: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/18.jpg)
DOBUTAMINE
• Major metabolite is 3-O-methyldobutamine, a potent inhibitor of alpha-adrenoceptors.– Therefore, vasodilation is possible secondary to
this metabolite.
• Usual starting infusion rate is 5 mcg/kg/min, with the dose being titrated to effect up to 20 mcg/kg/min.
![Page 19: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/19.jpg)
DOBUTAMINE
• Used in low C.O. states and CHF e.g. myocarditis, cardiomyopathy, myocardial infarction
• If BP adequate, can be combined with afterload reducer (Nipride or ACE inhibitor)
• In combination with Epi/Norepi in profound shock states to improve Cardiac Output and provide some peripheral vasodilatation
![Page 20: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/20.jpg)
MILRINONE/AMRINONE
• Belong to new class of agents “Bipyridines”
• Non-receptor mediated activity based on selective inhibition of Phosphodiesterase Type III enzyme resulting in cAMP accumulation in myocardium
• cAMP increases force of contraction and rate and extent of relaxation of myocardium
• Inotropic, vasodilator and lusotropic effect
![Page 21: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/21.jpg)
AMRINONE
• First generation agent - limited use now
• Long half-life (4.4 hours) with potential for prolonged hypotension after loading dose
• Associated with thrombocytopenia
• Dosage: Load with 0.75 mg/kg with infusion rate of 5-10 mcg/kg/min
• Milrinone is preferred drug from this group
![Page 22: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/22.jpg)
MILRINONE
• Increases CO by improving contractility, decreased SVR, PVR (?), lusotropic effect; decreased preload due to vasodilatation
• Unique in beneficial effects on RV function
• Half-life is 1-2 hours
• Load with 50 mcg/kg over 30 mins followed by 0.3 to 0.75 mcg/kg/min
• No increase in myocardial O2 requirement
![Page 23: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/23.jpg)
VASODILATORS
• Classified by site of action
• Venodilators: reduce preload - Nitroglycerin
• Arteriolar dilators: reduce afterload Minoxidil and Hydralazine
• Combined: act on both arterial and venous beds and reduce both pre- and afterload Sodium Nitroprusside (Nipride)
![Page 24: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/24.jpg)
NITROPRUSSIDE
• Vasodilator that acts directly on arterial and venous vascular smooth muscle.
• Indicated in hypertension and low cardiac output states with increased SVR.
• Also used in post-operative cardiac surgery to decrease afterload on an injured heart.
• Action is immediate; half-life is short; titratable action.
![Page 25: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/25.jpg)
NITROPRUSSIDE
• Toxicity is with cyanide, one of the metabolites of the breakdown of nipride.
• Severe, unexplained metabolic acidosis might suggest cyanide toxicity.
• Dose starts at 0.5 mcg/kg/min and titrate to 5 mcg/kg/min to desired effect. May go higher (up to 10 mcg/kg/min) for short periods of time.
![Page 26: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/26.jpg)
NITROGLYCERIN• Direct vasodilator as well, but the major
effect is as a venodilator with lesser effect on arterioles.
• Not as effective as nitroprusside in lowering blood pressure.
• Another potential benefit is relaxation of the coronary arteries, thus improving myocardial regional blood flow and myocardial oxygen demand.
![Page 27: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/27.jpg)
NITROGLYCERIN
• Used to improve myocardial perfusion following cardiac surgery
• Dose ranges from 0.5 to 8 mcg/kg/min. Typical dose is 2 mcg/kg/min for 24 to 48 hours post-operatively
• Methemoglobinemia is potential side effect
![Page 28: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/28.jpg)
ISOPROTERENOL
• Synthetic catecholamine
• Non-specific beta agonist with minimal alpha-adrenergic effects.
• Causes inotropy, chronotropy, and systemic and pulmonary vasodilatation.
• Indications: bradycardia, decreased cardiac output, bronchospasm (bronchodilator).
• No longer available in some markets
![Page 29: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/29.jpg)
ISOPROTERENOL
• Occasionally used to maintain heart rate following heart transplantation.
• Dose starts at 0.01 mcg/kg/min and is increased to 1.0 mcg/kg/min for desired effect.
![Page 30: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/30.jpg)
INHALED NITRIC OXIDE
• Selective Pulmonary vasodilator
• Dilates only pulmonary capillaries to alveoli participating in gas exchange
• Decreases intrapulmonary shunt and improves V/Q matching
• Rapidly inactivated by Hgb in pulm. cap. so no systemic side effects (eg hypotension)
![Page 31: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/31.jpg)
INHALED NITRIC OXIDE
• Potential for use in ARDS and Pulmonary Hypertension
• Currently only approved for use in neonatal Pulmonary Hypertension
• Expensive
• Special monitoring equipment required
• Dose: Concentration of 0.5-60 ppm in inhaled gas
![Page 32: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/32.jpg)
Additional considerations
• Mechanical ventilation and oxygen therapy (to conserve CO)
• Analgesia, anxiolysis and sedation
• Electrolyte homeostasis esp Ca and Mg
• Nutrition - avoid hypoglycemia
• Anemia is an “unconstitutional surcharge”
• Last but not the least: Maintain appropriate intravascular volume
![Page 33: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/33.jpg)
Selecting inotropic and vasopressor agents for specific hemodynamic disturbances in children
Hemodynamic pattern Normal Deceased Elevated
Blood pressure or SVR
Septic Shock Stroke index High Stroke Index low to N
None or dopamineDobutamine or dopamine
NorepinephrineDopamine or epinephrine
(or dobutamine plusnorephinephrine)
NoneDobutamine
plusnitroprusside
Cardiogenic shock Dobutamine or amrinoneor dopamine
Epinephrine or dopamine --
Myocardial dysfunction (complicating critical illness)
Dobutamine or dopamineor amrinone
Epinephrine or dopamine(or dobutamine plus
norepinephrine)
Dobutamineplus
nitroprusside
CHF Dobutamine or dopamineor amrinone
-- Dobutamineplus
nitroprusside
Bradycardia None Isoproterenol None
![Page 34: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/34.jpg)
CARDIAC ARREST MEDICATIONS
• Epinephrine
• Atropine
• Sodium Bicarbonate
• Calcium (Chloride or Gluconate)
• Lidocaine
![Page 35: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/35.jpg)
EPINEPHRINE
• Both an alpha- and beta-adrenergic agent
• During cardiac arrest, most think it has the greatest benefit by alpha-adrenergic actions, increasing afterload and thus diastolic blood pressure, leading to improved coronary artery perfusion.
![Page 36: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/36.jpg)
EPINEPHRINE
• Indications:– Cardiac arrest– Severe bronchospasm– Anaphylactic reactions
• Route of Administration– IV or IO– SQ or IM (for bronchospasm)– ET (cardiac arrest without IV or IO access)
![Page 37: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/37.jpg)
EPINEPHRINE
• Dosage:– initial (low) dose: 0.01 mg/kg
= 0.1 cc/kg of 1:10,000
– subsequent (high) doses: 0.1 mg/kg
= (0.1 cc/kg of 1:1,000)
![Page 38: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/38.jpg)
ATROPINE
• Parasympathetic (not an alpha- or beta-adrenergic) agent--acts by blocking cholinergic stimulation of the muscarinic receptors of the heart.
• Results in an increase in the sinus rate of the heart.
• Little effect on systemic vascular resistance or myocardial contractility.
![Page 39: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/39.jpg)
ATROPINE
• Indications:– Bradycardia– Second or third degree heart block– Asystole– Pulseless electrical activity (electrical
mechanical dissociation)
• Route of Administration– IV, IO, ET, SQ, IM, nebulization
![Page 40: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/40.jpg)
ATROPINE
• Dosage:– 10 to 20 mcg/kg– minimum dose is 0.1 mg--smaller doses may
cause reflex bradycardia (central stimulatory effect on the medullary vagal nuclei)
– maximum (adult) dose is 2 mg
![Page 41: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/41.jpg)
SODIUM BICARBONATE
• Use during CPR remains a controversial issue due to lack of evidence showing benefit from receiving bicarbonate.
• Elevates blood pH by binding with hydrogen to form water and CO2
• HCO-3 + H+ => H2CO3 => H2O + CO2
• Must have adequate ventilation to remove CO2 or respiratory acidosis will worsen
![Page 42: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/42.jpg)
SODIUM BICARBONATE
• Adverse effects of acidosis:– Cardiac
• Decrease contractility• Lower threshold for ventricular fibrillation• Decrease responsiveness to catecholamines
– Vascular• Decrease systemic vascular resistance• Decrease systemic vascular responsiveness to
catecholamines• Increase pulmonary vascular resistance
![Page 43: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/43.jpg)
SODIUM BICARBONATE
• Indications:– Pre-existing acidosis– Prolonged CPR (after 10 minutes)– Pulmonary hypertensive crisis– Hyperkalemia
• Route of administration: – IV, IO
• Dosage– 1-2 meq/kg/dose (1 meq/cc or 0.5 meq/cc)
![Page 44: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/44.jpg)
CALCIUM
• Current recommendations for the use of calcium during CPR are restricted to a few specific situations.
• Intracellular calcium plays an important role in the process of cell death, but no studies have shown that transient hypercalcemia worsens outcome after cardiac arrest.
![Page 45: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/45.jpg)
CALCIUM
• Adverse Effects of Hypocalcemia– Decreased myocardial contractility– Decreased systemic vascular resistance– Decreased catecholamine release– Decreased cardiovascular response to
catecholamines
![Page 46: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/46.jpg)
CALCIUM
• Indications:– Hypocalcemia
• Ionized hypocalcemia may result from severe alkalosis or after large transfusions of citrated blood products.
– Hyperkalemia– Hypermagnesemia– Calcium channel blocker overdose
![Page 47: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/47.jpg)
CALCIUM
• Route of administration:– IV, IO only– Calcium chloride--central venous line– Calcium gluconate--peripheral venous line
• Dosage:– Calcium chloride = 10-20 mg/kg– Calcium gluconate = 100-200 mg/kg
![Page 48: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/48.jpg)
LIDOCAINE
• Class 1B antiarrhythmic
• Decreases automaticity threshold and ventricular fibrillation threshold.
• Effective in terminating PVCs.
• Rarely used in pediatric arrests as ventricular tachycardia and ventricular fibrillation are not commonplace.
![Page 49: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/49.jpg)
LIDOCAINE
• Indications:– Ventricular Tachycardia– Ventricular Fibrillation– Frequent PVCs
• Route of Administration:– IV, IO, ET
• Dosage:– 1 mg/kg/dose (may need up to 2.5 mg/kg ET)
![Page 50: Vasoactive Drugs](https://reader035.fdocuments.in/reader035/viewer/2022062307/553e09864a79593c328b484a/html5/thumbnails/50.jpg)
ENDOTRACHEAL MEDICATIONS
• LEAN– Lidocaine– Epinephrine– Atropine– Naloxone (Narcan)