Inotropes + vasopressors
Download as PPTX, PDF32 likes9,779 views
1) The document provides information on inotropes and vasopressors including their classification, sites of action, clinical effects, indications, and doses. It discusses catecholamines like adrenaline, noradrenaline, dopamine, and dobutamine. It also covers phosphodiesterase inhibitors, vasopressin, ephedrine, metaraminol, phenylephrine, methoxamine, and digoxin. 2) The document concludes with recommendations on first and second line vasopressor/inotropic agents for different clinical situations like septic shock, heart failure, cardiogenic shock, anaphylactic shock, and anesthesia-induced hypotension.
![Inotropes
Definition:
An inotrope is an agent that alters force of contraction of cardiac muscle without
affecting the pre or after load. E.g. +ve inotropes contractility
Classification
• Class 1 intracellular [ca], include:
• Ca ions
• Drugs cAMP - adrenoagonists, PDIs, Glucagon
• Drugs affecting Na-K ATPase - digoxin
Class 2 sensitivity actomyosin to Ca ions – Levosimendan
Class 3 Metabolic / endocrinological – T3](https://image.slidesharecdn.com/inotropespressorsteaching-150619032008-lva1-app6891/85/Inotropes-vasopressors-2-320.jpg)
![• e.g. aminophylline, enoximone, milrinone
• Prevent breakdown of cAMP by enzyme phosphodiesterase:
intracellular [Ca] in myocytes - augments catecholamines at 1 and 2
receptors.
• Actions: Inodilation, i.e. rate and force of contraction, peripheral
vasodilation in skeletal muscle, bronchodilation.
Indications
• Aminophylline: asthma, cardiac failure.
• Enoximone: cardiac surgery - patients failing to respond to dobutamine
Phosphodiesterase inhibitors](https://image.slidesharecdn.com/inotropespressorsteaching-150619032008-lva1-app6891/85/Inotropes-vasopressors-12-320.jpg)
Inotropes + vasopressors
- 1. Johnny Kenth – ST3 Anaesthesia, Royal Blackburn Hospital
- 2. Inotropes Definition: An inotrope is an agent that alters force of contraction of cardiac muscle without affecting the pre or after load. E.g. +ve inotropes contractility Classification • Class 1 intracellular [ca], include: • Ca ions • Drugs cAMP - adrenoagonists, PDIs, Glucagon • Drugs affecting Na-K ATPase - digoxin Class 2 sensitivity actomyosin to Ca ions – Levosimendan Class 3 Metabolic / endocrinological – T3
- 5. Site of action du Toit E et al. Heart 2001;86:81-87
- 6. Drug Alpha-1 Beta-1 Beta-2 Dopaminergic Predominant Clinical Effects Phenylephrine *** 0 0 0 SVR ↑ ↑, CO ↔/↑ Noreadrenaline *** ** 0 0 SVR ↑ ↑, CO ↔/↑ Adrenaline *** *** ** 0 CO ↑ ↑, SVR ↓ (low dose) SVR/↑ (higher dose) Dopamine (mcg/kg/min) 0.5 to 2 0 * 0 ** CO 5 to 10 * ** 0 ** CO ↑, SVR ↑ 10 to 20 ** ** 0 ** SVR ↑ ↑ Dobutamine 0/* *** ** 0 CO ↑, SVR ↓ Isoproterenol 0 *** *** 0 CO ↑, SVR ↓ *** Very Strong Effect, ** Moderate effect, * Weak effect, 0 No effect.
- 7. Actions Acts on 1, 2, + 1 receptors. • CVS: HR (chronotropic) + contractility (inotropic -force of contraction) CO; also +ve dromotropic, bathmotropic & -ve lusitropic SBP rises, but with low doses DBP may fall due to (2 vasodilation and increased blood flow through skeletal muscle beds (2). At higher doses = 1 mediated vasoconstrictor effects • RS: Bronchial smooth muscle is relaxed 2 = bronchodilation • Other: Adrenaline mobilises glucose from glycogen and raises blood sugar. Pupillary dilation (mydriasis) occurs. • Side effects Ventricular arrhythmias, hypertension. Care with halothane anaesthesia as arrhythmias may occur Adrenaline (Epinephrine) Prepare the body for a "fight or flight" response.
- 8. Site of action du Toit E et al. Heart 2001;86:81-87
- 9. • Noradrenaline Acts mainly on 1 receptors with few effects on receptors. BP by vasoconstriction. Less likely to cause tachycardia than adrenaline. Indications Septic shock where peripheral vasodilation may be causing hypotension. Cautions Acts by afterload and therefore not appropriate for use in patients in cardiogenic shock. Blood supply to kidneys and peripheries Dose - 0.01-1 mcg/kg/min • Dopamine Acts on D, 1, 2 and 1 receptors, depending on the dose administered. Actions Dose dependent 1-2mcg/kg/min - acts on D receptors usually UO 2-10mcg/kg/min - acts on receptors CO >10mcg/kg/min - additional effects on 1 receptors vasoconstrict.
- 10. • Dobutamine Acts on 1 & 2, with minimal action on 1 receptors. It CO and afterload (2 effects). Indications Cardiogenic shock. Dose 2-30mcg/kg/min • Dopexamine Acts on 2 and D receptors. CO and afterload. blood supply to kidneys and ? + GI tract. Dose 0.5-6mcg/kg/min • Salbutamol Acts on 2 receptors Actions Relaxes bronchial smooth muscle i.e. bronchodilation; HR Indications Severe acute asthma. Dose By infusion 5-20mcg/min. IV bolus 1- 5mcg/kg
- 11. Site of action du Toit E et al. Heart 2001;86:81-87
- 12. • e.g. aminophylline, enoximone, milrinone • Prevent breakdown of cAMP by enzyme phosphodiesterase: intracellular [Ca] in myocytes - augments catecholamines at 1 and 2 receptors. • Actions: Inodilation, i.e. rate and force of contraction, peripheral vasodilation in skeletal muscle, bronchodilation. Indications • Aminophylline: asthma, cardiac failure. • Enoximone: cardiac surgery - patients failing to respond to dobutamine Phosphodiesterase inhibitors
- 13. • Action : directly on 1 + 2 receptors, indirectly on 1 receptors via NA release. • Side effects May cause tachycardia and hypertension. Possible arrhythmias if used with halothane. C/I MAOs, SNRI • Indications Low blood pressure due to vasodilation e.g. following spinal or epidural anaesthesia and drug overdoses. Better vasopressor to use in pregnancy as it does not reduce placental blood flow. • Dose 3-10 mg boluses iv, repeat until effective. Maximum dose is 60mg. • Length of action 5-15 minutes, repeated doses less effective (i.e. it demonstrates tachyphylaxis) EPHEDRINE
- 14. • Metaraminol Acts directly on 1 receptors also causes some noradrenaline and adrenaline release. Actions MAP and CO. Less likely to cause a reflex bradycardia than methoxamine or phenylephrine. Dose - 0.5 1mg boluses iv, 2-10mg s/c or im, by infusion at 1-20mg/hr. • Phenylephrine Acts directly on 1 receptors. Action Hypertension and a reflex HR. Dose, 0.1-0.5mg iv, by infusion 0.1 – 1 mcg/kg/min • Methoxamine acts on 1 receptors. Actions. MAP + reflex HR, and therefore it is good for hypotension with tachycardia. Useful during spinal anaesthesia. Side effects May produce bradycardia Dose 2-4mg boluses IV. Other pressors:
- 15. Naturally occurring nonapetide hormone, produced in post hypothamalamus by PVN SON, stored + released post pituitary. Acts on V1, V2, V3 and OTR - GPCR V1: receptors are found on vascular smooth muscle of the systemic, splanchnic, renal, and coronary circulations vasoconstriction (Gq) V2: predominantly located in the distal tubule and collecting ducts of the kidney aquaporin chn water re-absorption Uses: • Sepsis: NA usage, VASST, as safe as NA, VANISH - • Cardiac Arrest: ? survival ( Krismer et al) Asystole: ? survival to ED adm, + discharge. (Wenzel et), no affect mortality. VASOPRESSIN
- 16. Direct: Inhibits cardiac Na-K ATPase: • Intracellular Na • Na / Ca exchange intracellular Ca • Ca release from SR actin-myosin cross linkage • contractile force Inirect: inhibits neuronal Na-K ATPase • Vagal activity PK • Long T1/2 needs LD • Renal clearence Large VD Digoxin
- 17. Clinical Application 1st Line Agent 2nd Line Agent Septic Shock Noradrenaline Adrenaline Dopamine Vasopressin Heart Failure Dopamine PDIs (Milrinone) Dobutamine + Norad Cardiogenic Shock Dobutamine Levosimendan +/- Norad SBP<80 PDIs Anaphylactic Shock Adrenaline Vasopressin Neurogenic Shock Norad Hypotension Anesthesia- induced Ephedrine / Metaraminol / Phenylephrine **Adrenaline Following CABG Epinephrine (Adrenalin)
- 18. 72 year-old woman with DM Type II, hypertension and Stage II CKD, recurrent UTIs, is transferred from a MAU. Her vitals upon arrival are as follows: Temp 39C, BP 70/45, Hr 140, RR 20, O2 Sat 95% 4L02 Lab findings: WCC 24, Cr 3.5, Lac 3.4, Positive Ur Dp, CRP 241 After adequate IVF resuscitation, pt continues to remain hypotensive MAP 40-50s + tachycardic HR 110-130s. What is the most appropriate 1st line vasopressor/inotropic agent? A. Adrenaline B. Dobutamine C. Noreadrenaline D. Dopamine
- 19. 64 year-old man with PMHx IHD; prev. MI and PCI (2004; drug- eluting stents), ischemic cardiomyopathy (EF 30-35%) with ICD (2007). ED 1/52 Hx progressively worsening SOB at rest, orthopnea and bilateral lower extremity oedema, after running out of all medications about 10 days ago. In ED, vitals: Temp 36.6 C, BP 88/48, Hr 75, RR 25, O2 Sat 91% on RA. CXR reveals vascular congestion and bilateral pleural effusion. Bedside ultrasound reveals significantly diminished EF. What is the most appropriate 1st line vasoactive agent? A. Adrenaline B. Dobutamine C. Noreadrenaline D. Dopamine
- 20. 76 year-old cachexic female with PMHx: COPD, HTN and Osteoporosis was initially admitted under medics for acute exac COPD. Had fall on ward # L-NOF. Underwent CNB-spinal anaesthesia. 15 mins post induction her BP was 64/44, P108, RR18, SpO2 99% RA. What is the most appropriate 1st line vasopressor/inotropic agent? A. Adrenaline B. Dobutamine C. Dopexamine D. Dopamine E. Metaradine
Editor's Notes
- #7: Phenylephrine (Neo) has purely Alpha-adrenergic agonist activity and therefore results in vasoconstriction with minimal cardiac inotropy or chronotropy. MAP is augmented by raising SVR. Norepi (Levo) acts both on Alpha-1 and Beta-1 adrenergic receptors, thus producing potent vasoconstriction as well as a less pronounced increase in CO. A reflex bradycardia ususally occurs in response to increased MAP, such that mild chronotropic effect is canceled out and HR remains unchanged. Most commonly used in septic shock. Epinephrine potent beta-1 adrenergic receptor and moderate beta-2 and alpha-1 adrenergic receptors. Epi is often used for treatment of anaphylaxis, as second line agent in septic shock. Dopamine is dose depended. At dose 1-2 mcg/kg/min, predominant effect on dopamine-1 receptors in renal, mesenteric, cerebral and coronary beds, resulting in selective vasodilation. At 5-10mcg/kg/min, stimulates beta-1 and increases CO. >10mcg/kg/min, alpha adrenergic receptors and produce vasoconstriction with increased SVR. Dobutamine is not a vasopressor but rather a inotrope that causes vasodilation – increasea inotropy and chronotropy and reduces LV filling pressure. Isoproterenol is also primarily an inotropic and chronotropic agent rather than a vasopressor. Beta-1 primary. Unlike Dobutamine, has prominent chronotropic effect. Utility limited to hypotensive patients, where hypotension results from bradycardia.
- #8: -Catecholeamines broken down : COMT central; MAO- central + periphery - NA – adren PNMT= Phenylethanolamine N-methyltransferase Chronotropic (Heart rate) · Dromotropic (Conduction velocity) Inotropic (Contractility) · Bathmotropic (Excitability) · Lusitropic (Relaxation) A dromotropic agent is one which affects the conduction speed in the AV node, and subsequently the rate of electrical impulses in the heart.
- #16: V3 = mainly in pituitary, cause acth relapse
- #17: V3 = mainly in pituitary, cause acth relapse
- #19: Answer - NORAD Pt is in septic shock secondary to UTI.
- #20: Answer: Dopamine Pt is in acute decompensated heart failure with pending cardiogenic shock. Dopamine can be used as first line agent to increase CO; however, in heart failure with cardiogenic shock, Dobutamine and norad are first line agents.
- #21: Metaradrine = metaraminol