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

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ISTENING