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INOTROPES & VASOPRESSORS
Johnny Kenth – ST3 Anaesthesia, Royal Blackburn Hospital
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
Catecholamine Synthesis
Site of action
du Toit E et al. Heart 2001;86:81-87
Drug Alpha-1 Beta-1 Beta-2 Dopaminergic Predominant Clinical Effects
Phenylephrine *** 0 0 0 SVR ↑ ↑, CO ↔/↑
Noreadrenaline *** ** 0 0 SVR ↑ ↑, CO ↔/↑
Adrenaline *** *** ** 0CO ↑ ↑, 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.
ActionsActs on 1, 2, + 1 receptors.
• CVS: HR (chronotropic) + contractility (inotropic -force of contraction) CO; also +ve dromotropic, bathmotropic & -ve lusitropicSBP 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.
Site of action
du Toit E et al. Heart 2001;86:81-87
• NoradrenalineActs 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
• DopamineActs on D, 1, 2 and 1 receptors, depending on the dose
administered.Actions Dose dependent
1-2mcg/kg/min - acts on D receptors usually UO2-10mcg/kg/min - acts on receptors CO>10mcg/kg/min - additional effects on 1 receptors
vasoconstrict.
• DobutamineActs 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
• SalbutamolActs on 2 receptorsActions Relaxes bronchial smooth muscle i.e.
bronchodilation; HR Indications Severe acute asthma.Dose By infusion 5-20mcg/min. IV bolus 1- 5mcg/kg
Site of action
du Toit E et al. Heart 2001;86:81-87
• 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
• 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
• MetaraminolActs directly on 1 receptorsalso 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.
• PhenylephrineActs directly on 1 receptors.Action Hypertension and a reflex HR.Dose, 0.1-0.5mg iv, by infusion 0.1 – 1 mcg/kg/min
• Methoxamineacts on 1 receptors.Actions. MAP + reflex HR, and therefore it is good for
hypotension with tachycardia. Useful during spinal anaesthesia.Side effects May produce bradycardiaDose 2-4mg boluses IV.
Other pressors:
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
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
Clinical Application
1st Line Agent2nd 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 VasopressinNeurogenic Shock Norad
HypotensionAnesthesia-induced
Ephedrine / Metaraminol / Phenylephrine **Adrenaline
Following CABG Epinephrine (Adrenalin)
Clinical Scenario I
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. AdrenalineB. Dobutamine C. NoreadrenalineD. Dopamine
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. AdrenalineB. Dobutamine C. Noreadrenaline D. Dopamine
Clinical Scenario II
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. AdrenalineB. Dobutamine C. DopexamineD. DopamineE. Metaradine
Clinical Scenario III
THANK YOU FOR L
ISTENING