Circulatory Failure and Inotropic Drugs

Circulatory Failure and Inotropic Drugs

Posted by Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


Inotropic treatment refers to intravenous vasopressor therapy with potent cardiovascular vasoactive drugs. The drugs commonly used are synthetic fast-acting catecholamines. These drugs are administered intravenously intermittently or in a continuous infusion via a CVL or a peripheral venous catheter (PVC). The treatment usually results, but not always in elevated blood pressure, increased heart volume and increased oxygen transport. The catecholamines activate α and β receptors i vital organs and peripheral vessels. Αlfa1 receptors are predominantly in peripheral blood vessels postsynaptically, β1 receptors are present in the heart, β2 receptors are found in the heart, blood vessels, uterus and respiratory tract. DA1 receptors are found primarily in splanchnicus and kidneys. Vasopressor drugs have short-term sympathomimetic effects on circulation with positive effects on blood pressure and oxygen delivery, but may in prolonged use damage vessels, extremities and vital organs such as the heart and kidneys. There is an increased risk of cardiac arrhythmias and ischemia but the risk depends on how the medication is used. Common vasopressors are dopamine, adrenaline, norepinephrine and dobutamine. Long-term use may present a risk of an exhausted heart with cardiac failure and increased risk of intestinal ischemia and peripheral ischemia. In case of moderate hypotension, short-acting drugs like ephedrine and phenylephrine should be used primarily, but if necessary for long-term effects, continuous infusion of more potent drugs is recommended.

Suggested treatment for hypotension that does not respond to initial fluid supply;

At low heart rate <90 bpm and low blood pressure: First-hand therapy Ephedrine 5-10 mg iv, secondary therapy Dopamine, 2-10 μg/kg/min dose after pulse and blood pressure response, third-hand therapy Epinephrine 0.1-1.0 mg iv, then in continuous infusion, 0.05-0.1-0.30 μg/kg/min as measured after pulse and blood pressure response.

At high heart rate> 90 beats/min and low blood pressure: First-hand therapy in addition to fluid therapy is Phenylephrine 0.1-0.2 mg i v. Secondary therapy is Dobutamine, 2-10-15 μg/kg/min alt. Norepinephrine which is dosed after pulse, blood pressure, CO and SvO2. Norepinephrine is given in a continuous infusion, 0.01-0.1- (0.5) μg/kg/min = 3-40 ml/h for 70 kg. Normal starting dose noradrenaline 0.05 μg/kg/min, is dosed after blood pressure. Norepinephrine may also be used as a first-aid kit in a severely ill patient, but should preferably not be given in peripheral venous canal due to risk of hemodynamic instability.

Physiological effects of Inotropic Drugs

Inotropic Agentα 1β 1β 2DA- 1SVRCOHRBP
Epinephrine (Adrenaline)+++++++++++
Norepinephrine (Noradrenaline)+++++++zero+/-↑↑
Dobutamine +++++++zero+/-
Dopamine +++++++++++
Ephedrine++++++zero
Phenylephrine+++zerozerozero+/-+/-
Isoprenalinezero++++++++zero
Levosimendan ----
Milrinone ---
Vasopressin----+/-↑↑
Vasopressor therapy in anesthesia induced hypotension
 Low blood pressure and low heart rateLow blood pressure and high heart rate
First choice medicationEphedrine 5-10 mg i v. intermittentlyPhenylefrine 0,1 mg i v. intermittently
Second choice medicationDopamin 2-10-15 μg/kg/minPhenylefrine in continuous infusion, 0,05-0,15 μg/kg/min
Third choice medicationEpinephrine 0,01-0,1-(0,5) μg/kg/minNorepinephrine in continuous infusion, 0.01-0.1- (0.5) μg /kg/min

 


Cardiac failure – Perioperative care

By Sven Erik Ricksten, Chief Physician, Professor of Anesthesia & Intensive Care.

Sahlgrenska University Hospital.

Updated 2020-09-02


Chronic heart failure

  • Prevalence ≈ 2%
  • > 75 years, prevalence ≈ 8%
  • Within 10-20 years, the prevalence has increased 2-3 times
  • Increased age
  • Today, more and more people survive acute myocardial infarction but experience heart failure

Chronic heart failure – clinical syndrome

  • Impaired ventricle (chamber) function
  • Increased pressure in the pulmonary circulation
  • Impaired physical capacity
  • Neuroendocrine activation
  • Reduced survival

Pathophysiology of cardiac failure

  • (MAP – CVP) = Cardiac Output  x  SVR
  • Cardiac Output = SV x HR
  • SV ↓ CO ↓

Pharmacological treatment

  • ACE inhibitors
  • Angiotensin II receptor blockers
  • ß-blockers (metoprolol, bisoprolol, carvedilol)
  • Aldosterone receptor antagonists
  • Diuretics
  • Digoxin

ACE inhibitor, angiotensin II rec. blockers

  • Reduces angiotensin II
  • Reduced catecholamines
  • Decreased aldosterone
  • Reduced ADH
  • Increases bradykinin
  • Increases NO
  • Increases MPGI2
  • Decreased production of tissue angiotensin II
  • Antiproliferative effect
  • Reduces remodeling

ß-blockers (metoprolol, bisoprolol, carvedilol)

  • Reduces MVO2
  • Increased glucose uptake
  • Improved energy utilization
  • Antiarrhythmic effect
  • Reduced Ca2+ leakage from SR
  • Antiapoptotic effect
  • Antioxidant

Aldosterone receptor antagonists

  • Decreased myocardial collagen
  • Lowers catecholamines
  • Improves the barore reflex
  • Improves endothelial function (NO)

Brain natriuretic peptide (B-type natriuretic peptide, BNP)

  • Decreased myocardial collagen
  • Lowers catecholamines
  • Improves the baroreceptor reflex
  • Improves endothelial function (NO)

Prognostic value of natriuretic peptides (BNP, NT-proBNP)

  • Preoperative increase in GDP/NT-proBNP increases risk of:
    • MACE (OR: 19.8)
    • Mortality (OR: 9.3)
    • Cardiac death (OR: 23.9)
    • “Cut-off” level?
  • Method
  • GDP/NT-proBNP in relation to other methods?

NT-proBNP (reference values)

  • < 400 ng/l heart failure unlikely
  • 400-900 ng/l possible heart failure
  • > 900 heart failure likely

Perioperative treatment

  • Identification of at-risk patient (EF, NT-proBNP, clinic)
  • Is the patient optimally treated for failure?
  • What do we do with the “failure medication” before surgery?

Pharmacological treatment

  • ACE inhibitors, angiotensin II receptor blockers
  • ß-blockers (metoprolol, bisoprolol, carvedilol)
  • Aldosterone receptor antagonists
  • Diuretics
  • Digoxin

Perioperative treatment

  • Identification of at-risk patient (EC, GDP, clinical picture)
  • Is the patient optimally treated for failure?
  • What do we do with the “failure medication before op.?
  • Choice of anesthesia technique (regional, general anesthesia?)

Surgery in the lower half of the body

Regional anesthesia for primary heart failure and heart failure secondary to:

  1. Aortic valve insufficiency
  2. Mitral valve insufficiency

Case report

  • 37-year-old woman with twin pregnancy in week 33. Looking for an emergency due to shortness of breath and bone swelling. Previously heart healthy.
  • BP: 110/60, HF: 120, SpO2 90%
  • Slight increase of CK-MB.
  • ECG: repol. interference.
  • Echo shows biventricular cardiac failure.
    • LVEF: 20% MI, TI grade 3/4.
  • Treatment is started with furosemide and nitroglycerin infusion
  • Decision on acute caesarian section. Anesthesia policy?

Induction of anesthesia for a patient with heart failure

  • Hypnotics:
    • Thiopentone
    • Midazolam
    • Ketamine
    • Propofol
  • Opiates (fentanyl)

Induction of anesthesia with propofol (2 mg/kg + 0.1 mg/kg/min) and its effects on muscle sympathetic (MSA), MAP and HR

Maintenance of anesthesia

  • TIVA (propofol, opiate)
  • Inhalation anesthesia

Intraoperative monitoring for heart failure

  • Invasive blood pressure
  • 2-3 lead ECG, ST trend
  • CVL
  • PA catheter?
  • TEE – in case of pronounced hemodynamic instability

Inotropic drugs

  • Epinephrine (Adrenaline)
  • Norepinephrine (Noradrenaline)
  • Isoprenaline
  • Dopamine
  • Dobutamine
  • Phosphodiesterase inhibitors
    • amrinone
    • milrinone
    • enoximone
  • Calcium sensitizer
    • levosimendane

Inotropic drugs

  • Norepinephrine (Noradrenaline)
  • Epinephrine (Adrenaline)
  • Dopamine
  • Dobutamine
  • Isoprenaline
  • Levosimendan
  • Milrinone

Recommendations

    • Identify high-risk patient
    • Insert arterial line, CVL (the day before)
  • Arterial pressure (MAP) and central venous saturation before induction
  • Link milrinone and norepinephrine (NA) to CVL
  • Use anesthesia techniques you are familiar with
  • Control MAP (65-75 mm Hg) with NA
  • Control central venous saturation (≈ 60-70%) with milrinone
  • Control volume supply according to CVP
  • Hemoglobin > 10 g/dl
  • Be two anesthesiologists at the start of anesthesia!

Diastolic heart failure

  • Myocardial relaxation
    • Active, energy-intensive process
    • Affected by ischemia and
    • Inotropic drugs
  • Passive filling
    • Extracardiac factors
    • Structural factors

Diastolic dysfunction

Definition:

  • Normal filling pressure gives too low filling of LV
  • Elevated filling pressure is required for adequate filling of LV
  • 40-50% of heart failure patients have isolated diastolic dysfunction

Isolated diastolic dysfunction

  • Hemodynamics as in systolic failure
  • LVEF is normal, LVEDV low
  • Left ventricle hypertrophy
  • Abnormal Mitral Doppler (E/A < 1)
  • Hypertension, aortic stenosis
  • Dynamic outflow obstruction of LV (functional aortic stenosis)

Treatment of outflow obstruction of left ventricle with SAM

  • Increase preload (“volume challenge”)
  • Avoid tachycardia
  • No inotropic agents
  • No vasodilator
  • In case of tachycardia, give ß-blockers
  • Monitor therapy with Eco-Doppler !!!

Pulmonary hypertension and right ventricular failure

Pulmonary circulation and right ventricle

Interaction between RV and LV (“ventricular interdependence”)

  • Change in pressure/volume in one ventricle directly affects pressure/volume in the other ventricle
  • Immediate power transmission between RV and LV
  • Joint muscle fibers, septum, pericardium
  • Diastolic and systolic interaction

Diastolic ventricular interaction at pressure/volume loading of RV (right ventricle)

  • Increased volume/distension of RV during diastole, septum displaced to the left
  • Reduces LV volume, i.e. reduced LV preload
  • LVs end-diastolic pressure (PCWP) increases
  • LV’s compliance decreases

Systolic ventricular interaction at pressure/volume loading of RV

  • During pressure/volume loading of the RV, a flattened septum is shifted from left to right in the systole
  • LV-assist more efficiently at a high system pressure
  • RV function deteriorates at a low system pressure (peripheral vasodilation)

Pulmonary hypertension

  • MPAP > 25 mmHg or SPAP > 55 mmHg
  • Right ventricular hypertrophy/failure

Classification

  • Primary, idiopathic pulmonary hypertension (sporadic, familial)
  • Related to collagenous vascular diseases (scleroderma, lupus, RA)
  • Portopulmonary hypertension
  • Pulmonary venous hypertension (LV failure, MI/MS, AS)
  • Pulmonary hypertension associated with lung disease
  • Pulmonary hypertension caused by thromboembolism

Anesthesiological aspects of pulmonary hypertension

Anesthesia for primary/secondary pulmonary hypertension and RV failure

  • Continue chronic medication for pulmonary hypertension (Ca2 + antagonists, sildenafil, ET antagonists, i.v. PGI2)
  • Intravenous PGI2 is switched to inhalation
  • Easy premedication
  • Insertion of PA catheter before induction (CVP, PA)

Anesthesia for primary/secondary pulmonary hypertension and RV failure

  • TIVA (propofol/opioid).
  • Avoid ketamine, N2O (increases PVR) and inhalants (negative inotropic effect)
  • TEE for monitoring HK function
  • Hypoxia and hypercapnia increase PVR
  • Regional anesthesia: unwanted pressure drop and RV failure
  • Noradrenaline for high SVR (MAP)
  • Inhalation NO, prostacyclin and/or milrinone (selective lowering of PVR)
  • In case of RV failure, i.v. milrinone + noradrenaline

 

Conclusions

  • The prevalence of chronic heart failure is constantly increasing
  • Understand the pathophysiology
  • Identify the patient at risk
  • Anesthesia technique less interesting
  • Adequate monitoring
  • Take the help of inotropic/vasoactive drugs
  • Do not forget the diagnosis of dynamic LV outflow obstruction in case of sudden and severe intraoperative cardiogenic shock
  • Noradrenaline + inhalation of vasodilators in pulmonary hypertension and RV failure

Inotropic and vasoactive drugs in treatment of heart failure

By Sven Erik Ricksten, Chief Physician, Professor of Anesthesia & Intensive Care.

Sahlgrenska University Hospital.

Updated 2020-09-02


Chronic heart failure

  • Prevalence ≈ 2%
  • > 75 years, prevalence ≈ 10%
  • Within 10-20 years, the prevalence has increased 2-3 times
  • Increased age
  • Today, more and more acute coronary syndrome survives

Inotropic treatment

  • Acute decompensation of a chronic heart failure (ICM, DCM)
    • hypotension
    • hypoperfusion
  • Acute coronary syndrome
    • widespread myocardial damage LV, RV
    • VSD, Papillary Muscle Rupture (MI)
  • “Myocardial stunning” after revascularization
  • Postoperative failure after cardiac surgery/transplantation
  • Septic shock – septic cardiomyopathy
  • Myocarditis
  • Postpartum cardiomyopathy
  • Right ventricular failure (pulmonary embolism, ARDS)

Inotropic drugs

  • Adrenaline
  • Noradrenaline
  • Isoprenaline
  • Dopamine
  • Dobutamine
  • Phosphodiesterase inhibitors
    • milrinone
  • Calcium sensitizers
    • levosimendan

Adrenaline

  • Dosage is given in ng/kg/min
    • 10-30 ng/kg/min: beta 1.2 stimulation
    • 30-100 ng/kg/min: alpha + beta stimulation
  • > 100 ng/kg/min: alpha stimulation
  • Tachycardia
  • Vasoconstriction
  • Arrhythmia

Noradrenaline

  • The beta-receptor stimulating effect is similar to that of adrenaline
  • Stimulates alpha receptors in low concentrations
  • Given at low SVR and hypotension
  • Sepsis and Systemic Inflammatory Response Syndrome (SIRS)
  • Minor tachycardia and arrhythmias compared to adrenaline

Isoprenaline

  • Beta-1, 2 stimulation only
  • Positive inotropic and chronotropic effect
  • Vasodilation and hypotension
  • Given in bradyarrhythmias and AV blocks

Dopamine

  • Dosage is given in µg/kg/min
    • 0.5-2.5 µg/kg/min: stimulates dopamine receptors
    • 1-10 μg/kg/min: beta-receptor stimulation
    • 5-10 µg/kg/min: alpha stimulation
  • Tachycardia, arrhythmia
  • Lowers SVR in low doses
  • Vasoconstriction, SVR and PCWP increase with increasing doses
  • Increased MVO2
  • Good for heart failure and hypotension

Dobutamine

  • Beta-1, 2 stimulation (d-dobutamine), SVR unchanged
  • Alpha stimulation (l-dobutamine), SVR unchanged
  • At higher doses the beta-2 effect dominates over alpha, MVO2 unchanged/increase ie SVR and PCWP decrease
  • Tachycardia, arrhythmias MVO2 unchanged/increase
  • 2-15 µg/kg/min

Limiting factors when using catecholamines

  • Down-regulation of beta and alpha receptors
  • Tolerance development
  • Tachycardia, arrhythmia
  • Does not increase survival in LV failure

Phosphodiesterase inhibitors (milrinone)

  • Minor increase in heart rate compared to dobutamine
  • Better vaso-venodilators compared to dobutamine
  • Additive effect to ß-stimulator
  • Does not increase MVO2
  • Less pronounced tachyphylaxis compared to ß-stimulators

Levosimendan

Levosimendan – hemodynamics

Calcium sensitizer and diastole

Levosimendan and diastolic function in the clinic

  • Patients (n = 23) with AVR due to aortic stenosis
  • Randomized postoperatively to:
    • placebo (n = 11)
    • levosimendan (0.1 and 0.2 µg/kg/min) (n = 12)
  • Left ventricular isovolumic relaxation time (IVRT)
  • Heart rate, filling pressure, arterial pressure were kept constant with pacing, colloid and phenylephrine

Inotropic and lusitropic effects of levosimendan vs. milrinon

  • Patients (n = 31) with AVR due to aortic stenosis
  • Randomized postoperatively to:
    • milrinone 0.4 and 0.8 µg / kg / min (n = 16)
    • levosimendan 0.1 and 0.2 µg / kg / min (n = 15)
  • Strain echocardiography (TEE):
    • LV strain (2-chamber, rear wall)
    • RV strain (4-chamber, free wall)
  • Strain rate systole (SR-S)
  • Strain rate early-diastole (SR-E)
  • Heart rate, filling pressure, arterial pressure were kept constant with pacing, colloid and phenylephrine

Inotropic and vasoactive drugs for cardiogenic shock

”At present there are no robust and convincing data to support a specific inotropic therapy as the best solution to reduce mortality in haemodynamically unstable patients with cardiogenic shock complicating AMI.”

Physiological effects of Inotropic Drugs

Inotropic Agentα 1β 1β 2DA- 1SVRCOHRBP
Epinephrine (Adrenaline)+++++++++++
Norepinephrine (Noradrenaline)+++++++zero+/-↑↑
Dobutamine +++++++zero+/-
Dopamine +++++++++++
Ephedrine++++++zero
Phenylephrine+++zerozerozero+/-+/-
Isoprenalinezero++++++++zero
Levosimendan ----
Milrinone ---
Vasopressin----+/-↑↑

Cochrane Database Syst Rev. 2014 Jan 2;1:CD009669. doi: 10.1002/14651858.CD009669.pub

Dopamine or norepinephrine as a vasopressor in cardiogenic shock?

Adrenalin or noradrenalin?

  • 57 patients with AMI + PCI and cardiogenic shock
  • Randomized to
    • adrenaline (n = 27)
    • noradrenaline (n = 30)
  • Target MAP 65-70 mmHg
  • Primary end-point: change in cardiac output over 72 hours
  • Safety end-point: refractory cardiogenic shock

Levosimendan vs dobutamine in cardiogenic shock

  • 22 patients with STEMI and PCI
  • Cardiogenic shock
  • Randomized to:
    • levosimendan (n = 11) 24 µg/kg + 0.1 µg/kg/min
    • dobutamine (n = 11) 5 µg/kg/min
  • No IABP

Levosimendan vs enoximon (phosphodiester inhibitors) in cardiogenic shock

  • Cardiogenic shock after PCI due to AMI
  • IABP
    • noradrenaline (≈0.25 µg/kg/min)
    • dobutamine (≈10 µg/kg/min)
  • Randomized to:
    • levosimendan (n = 16)
    • enoximone (n = 16)
  • End-point: 30-day mortality

Inotropic and vasoactive drugs in right ventricular failure

Right ventricular failure (RVF)

Cardiac causes

  • Coronary heart disease (RV infarction)
  • Valve diseases
  • Cardiomyopathy (ischemic, dilatative)
  • Cardiac surgery (CABG, AVR, MVR)
  • Heart transplant
  • Post-LVAD

Extracardiac causes

  • Pulmonary embolism
  • Lung diseases (COPD, ARDS)
  • Primary pulmonary hypertension
  • Sepsis
  • Lung transplantation
  • Post-thrombendarterectomy

Inhaled NO at RVF after posterior AMI

  • Thirteen patients with RV infarction and cardiogenic shock
  • Inhalation of NO (80 ppm)

Inhaled NO during heart transplantation and RVF

Inhalation of prostaglandins and milrinone – dosage

  • Prostacycline  (Flolan®): 10 µg/ml, 5-10 ml/h
  • Iloprost (Ilomedin®, Ventavis®): 10 µg/ml, 2.5-5 µg x 6-9
  • Treprostinil (Remodulin®): 30-50 µg x 4
  • Milrinone: 1 mg/ml, 5-10 ml/h

Renal effects of inodilators

Cardiac output increase gives increase in RBF affecting GFR?

Renal effects of milrinone

  • Patients undergoing cardiac surgery with normal preoperative renal function (n = 27)
  • Two groups:
    • severe heart failure after weaning from CPB requiring milrinone (n = 8)
    • no heart failure after CPB (n = 19)
  • Systemic hemodynamics (PAC)
  • Renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), renal oxygen extraction (RO2Ex)
  • Measurements: T0 = 30 ‘after CPB, T1 = 60’ after CPB

Renal effects of levosimendan?

”Effects of Levosimendan on Glomerular Filtration Rate, Renal Blood Flow, and Renal Oxygenation After Cardiac Surgery With Cardiopulmonary Bypass: A Randomized Placebo-Controlled Study”

Bragadottir et al Crit Care Med 2013;41:2328

  • Uncomplicated cardiac surgery, normal renal function
  • ICU, sedated, mechanically ventilated
  • Randomised to:
    • placebo, n = 15
    • levosimendan, n = 15, 12 µg/kg + 0.1 µg/kg/min
  • Systemic hemodynamics (PAC)
  • Renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR) renal oxygen consumption (RVO2), renal oxygen extraction
  • (RO2Ex), filtration fraction

“Differential effects of levosimendan and dobutamine on glomerular filtration rate in patients with heart failure and renal impairment: a randomized double-blind controlled trial”

Lannemyr et al J Am Heart Assoc 2018;e008455

  • Chronic heart failure (NYHA III-IV), LVEF < 40%
  • Renal impairment: GFR < 80 ml/min
  • Randomised to:
    • dobutamine 7.5 µg/kg/min (n=16)
    • levosimendan 12 µg/kg +0.1 µg/kg/min (n=16)
  • Central hemodynamics
  • Renal blood flow (RBF), GFR, renal oxygenation
  • Renal vein catheter, infusions clearance of PAH and 51Cr-EDTA

Conclusions

  • Inotropic therapy is indicated for heart failure associated with hypotension/hypoperfusion
  • Milrinone and levosimendan have similar haemodynamic effects
  • Milrinone and levosimendan are equipotent in terms of inotropic and lusitropic effects on both LV and RV
  • Noradrenaline is preferable to dopamine in cardiogenic shock
  • Levosimendan is the only inotropic meal that increases GFR

Argipressin

Argipressin is a synthetic analogue to pitressin. Argipressin causes systemic vasoconstriction, and thus elevated peripheral vascular tone with elevated blood pressure. It can also be administered locally and results in decreased bleeding in laparoscopic surgery of ectopic pregnancy and in myoma extirpation.

Indication: Reported hypotension due to vasoplegia (refractory hypotension). Treatment failure with other inotropic drugs at low peripheral vascular resistance.

Dosage: 2.4-4.8 E/hour (which usually becomes 6-12 ml/h)

Concentration: 20 U/ml. Dilution of Argipressin is done by diluting 1 ml of 1 ampoule (1 ml = 20 U) with 49 ml of Glucose 5% in a 50 ml syringe giving a concentration of 0.4 U/ml.

Side effects: Headache, flush, hypotension, pain in extremities, peripheral edema, blurred vision, nasal congestion, nightly sweating.

Caution: Caution in angina pectoris, cardiac decompensation, renal failure, poorly controlled hypertension, anaphylaxis or hypersensitivity to vasopressin.


Dobutamine (Dobutamin Hameln®)

Positive inotropic drug with weak vasodilating effect. Dobutamine is a synthetic, sympathomimetic amine. The positive inotropic effect is based primarily on the agonistic effect on the heart’s beta1-receptors, but also on the heart’s alpha-receptors.

Concentration: Standard solution 2 mg/ml.

Receptor activity: α1 +, β1 ++++, β2 ++, DA-1 zero.

Physiological effects: SVR ↓, CO ↑, HR ↑, BP +/-. Binds to and stimulates beta1 receptors in the heart. Provides increased contraction force.

Indication: Low cardiac output, low heart rate, cardiac failure, sepsis.

Dosage: 2-10-15 μg/kg/min = 5-40 ml/h for 70 kg.

Dose activity: <3 μg/kg/min – usually no effect on blood pressure or blood pressure drop, 5-10 μg/kg/min β1 effect, increased cardiac output >10 μg/kg/min – α1 effect. Increased heart rate.

Adverse reactions: Tachycardia, hypotension in hypovolemia.


Dopamine (Intropin®, Abbodop®, Giludop®)

Dopamine is a sympathomimetic catecholamine. The positive inotropic effect is based primarily on the agonistic effect on the heart’s beta1-receptors, but also on the heart’s alpha-receptors. Significant chronotropic effect.

Concentration: Standard solution 2 mg/ml

Receptor activity: α1 ++, β1 ++++, β2 ++, DA-1 +++

Indication: Refractory hypotension, low cardiac output, heart failure, oliguria, sepsis.

Dosage: 3-15 μg/kg/min = 7-40 ml/h for 70 kg.

Dose activity: <3 μg/kg/min – DA effect, 5-10 μg/kg/min β1 effect, increased heart rate, > 10 μg/kg/min – mostly α1 effect.

Adverse reactions: Tachycardia, arrhythmias, renal and intestinal hypoperfusion, mental symptoms, pituitary dysfunction.


Ephedrine

Ephedrine is a naturally occurring alkaloid. Ephedrine acts as a blood pressure enhancer through stimulation of adrenergic alpha and beta receptors. Ephedrine acts directly on the receptors, but mainly by releasing endogenous noradrenaline, which in turn affects the receptors. The positive inotropic effect is based primarily on the agonistic effect on the heart’s beta1 receptors, but also to some extent on the heart’s alpha1 receptors.

Receptor activity: α1 +, β1 +++, β2 ++, DA-1 zero.

Physiological effects: Slightly increased inotropy, chronotropy and blood pressure increase. Releases noradrenaline. Increased cardiac output (CO), increased blood pressure and mean arterial pressure. Increased SVR, decreased CO, increased HR, increased BP. Short-term effect for 5-15 minutes during intravenous administration. Slightly more prolonged effect after subcutaneous or intramuscular administration.

Indication: Temporary drop in blood pressure, vasodilation, bradycardia, blood pressure drop after spinal anesthesia and epidural anesthesia, blood pressure drop after anesthesia induction, bronchial asthma.

Adverse reactions: Tachycardia, extravasation, arrhythmias, atrial fibrillation, cardiovascular disease.

Concentration: Solution 50 mg/ml. The usual concentration is 5 mg/ml (diluted) or 50 mg/ml.

Dosage: 5-10 mg i v. Normal starting dose 5 mg i v, adjusted for blood pressure and pulse. 25-50 mg can be given i m. Intramuscular dose can be given at the same time as intravenous administration, e.g. 5 mg i v plus 25 mg intramuscularly associated with spinal anesthesia.

Dose activity: 5 – 10 mg usually produces moderate effect on blood pressure, with unchanged CO, > 10 mg also gives increased CO.


Epinephrine (Adrenaline)

Adrenaline is a sympathomimetic catecholamine. The positive inotropic effect is based primarily on the agonistic effect on the heart’s beta1-receptors, but also on the heart’s alpha1 receptors.

Concentration: Normal concentration is 0.05 mg/ml alt. 0.1 mg/ml for continuous infusion. For manual injections, 0.1 mg/ml or a “weak” solution at 0.01 mg/ml are common concentrations.

Receptor activity: α1 ++++, β1 ++++, β2 +++

Physiological effects: SVR ↑, CO ↑, HR ↑, BP ↑, bronchodilation

Indication: Circulatory shock, refractory hypotension, allergic shock, anaphylaxis, cardiac arrest, severe cardiac failure, cardiogenic shock, severe poisoning, severe bronchospasm, status asthmaticus, severe stridor.

Dosage: 0.05-0.1- (0.30) μg/kg/min = 3-40 ml/h for 70 kg. Normal starting dose 0.1 μg/kg/min, dose adjusted to blood pressure. Anaphylaxis/asthma: 0.3-0.5 mg i.m., CPR 1 mg i v. At established circulation but congestive heart failure 0.1 mg i.v. at a time. At circulation collapse 0.1-1.0 mg i v, titrate after blood pressure, avoid overdose.

Dosage activity: <0.05 μg/kg/min – usually moderate effect on blood pressure, 0.05-0.1 μg/kg/min β1 effect, increased cardiac output,> 0.1 μg/kg/min – mostly α1 effect

Adverse reactions: Tachycardia, arrhythmias, uncontrolled blood pressure increase.


Isoprenaline

Isoprenaline is a sympathomimetic amine. The positive inotropic effect is based primarily on the agonistic effect on the heart’s beta1 receptors and beta2 receptors, but also on the heart’s alpha1 receptors. Isoprenaline is vasodilatory with pronounced positive chronotropic effect.

Concentration: Standard concentration at 0.2 mg/ml.

Receptor activity: α1 zero, β1 ++++, β2 ++++, DA-1 zero. Positive chronotropic and inotropic effects on the heart. Potent vasodilation and increased heart rate. Increased cardiac output (CO), diastolic blood pressure and mean arterial pressure.

Physiological effects: Decreased SVR, CO ↑↑, HR ↑↑, decreased BP, bronchodilation.

Indication: Circulatory shock, bradycardia, AV block III, refractory hypotension, cardiac arrest, severe heart failure with low CO, cardiogenic shock, some severe poisoning.

Dosage: 0.01-0.15 μg/kg/min, 15-30 ml/h for 70 kg. Normal starting dose 0.05 μg/kg/min, adjusted for blood pressure.

Dosage activity: < 0.05 μg/kg/min – usually moderate effect on blood pressure, possibly blood pressure fall, increased CO, 0.05-0.1 μg/kg/min β1 effect, increased cardiac output, increased heart rate.

Adverse reactions: Tachycardia, blood pressure fall, arrhythmias.


Levosimendan (Simdax®)

Levosimendan enhances the calcium sensitivity of the contractile proteins through a calcium-dependent binding to cardiac troponin C. In addition, levosimendan opens ATP-sensitive potassium channels in vascular smooth muscle, resulting in vasodilation of systemic and coronary resistor vessels and systemic venous capacitor vessels.

Receptor activity: Calcium sensitizer in the myocardium.

Concentration: Solution at 2.5 mg/ml. Normal concentration at 0.025 mg/ml or 0.05 mg/ml.

Physiological effects: Increased contractile force, CO↑, HR↑, vasodilation, increased ejection fraction, hypotension, decreased SVR.

Indication: Circulatory shock, severe cardiac failure, cardiogenic shock, stunned myocardium.

Dosage: 6-12 μg/kg/min for 10 minutes followed by a continuous infusion at 0.1 μg/kg/min for 24 hours.  Normal starting dose at 6 μg/kg/min, adjusted for blood pressure.

Dosage activity: 0.05-2 μg/kg/min – usually moderate effect on blood pressure, blood pressure drop.

Contraindications: Reported hypotension, hypokalaemia, hypovolemia, tachycardia, left ventricular mechanical obstruction, Torsade de Pointes arrhythmias, renal impairment.

Adverse reactions: Tachycardia, blood pressure fall, headache, atrial fibrillation, ventricular extrasystoles, arrhythmias, hypokalaemia.


Milrinone (Corotrop®)

Milrinone is a bipyridine derivative with both positive inotropic and vasodilating effect, but with little chronotropic effect.

Receptor activity: Phosphodiesterase-III inhibitor.

Physiological effects: SVR↓, CO↑, HR↑, BP+/-. Provides increased cardiac contraction force and increased stroke volume, vascular dilator.

Indication: Severe cardiac failure, cardiogenic shock.

Concentration: Solution at 1 mg/ml. The usual concentration for continuous infusion is 0.1 mg/ml (100 μg/ml) alt. 0.15 mg/ml (150 μg/ml).

Dosage: Initially a slow (10 minute) intravenous injection of 50 μg/kg. Thereafter a continuous infusion of 0.37-0.75 μg/kg/min. Normal starting dose at 0.5 μg/kg/min, adjusted for blood pressure. In the vast majority of patients, hemodynamic improvement is noted within 5-15 minutes. Doses in the range of 0.375-0.50 μg/kg/min tend to maximize the initial improvement in cardiac output, while doses in the range of 0.50-0.75 μg/kg/min tend to maximize the improvement in the pre- and afterload parameters such as pulmonary capillary wedge (PCW) pressure, mean arterial pressure and systemic vessel resistance (SVR).

Dosage activity: <0.375 μg/kg/min – usually moderate effect on circulation, 0.5-0.75 μg/kg/min β1 effect, blood pressure increase, increased CO and EF.

Contraindications: Hypovolemia, obstructive aorta or pulmonary valve. In case of acute myocardial infarction observe caution.

Side effects: hypotension, increased cardiac oxygen consumption, tachycardia, VES, VT.


Norepinephrine (Noradrenaline)

Norepinephrine (Noradrenaline) is a sympathomimetic amine. The positive inotropic effect is based primarily on the agonistic effect on the heart’s beta1 receptors, but also on the heart’s alpha1 receptors.

Concentration: Normal concentration for continuous infusion at 0.1 mg/ml. “Double strength” 0.2 mg/ml. “Weak” strength 0.05 mg/ml. Receptor activity: α1 +++, β1 +++, β2 +. DA-1 zero. Physiological effects: SVR ↑, CO +/-, HR ↑, BP ↑↑,

Indication: Circulatory shock, refractory hypotension, sepsis, anaphylaxis, severe hypotension with vasodilation, cardiogenic shock, severe poisoning.

Side effects: Tachycardia, arrhythmias, renal and intestinal hypoperfusion, peripheral ischemia, intestinal ischemia, splanchnicus ischemia.

Dosage: 0.01-0.1- (0.5) μg/kg/min = 3-40 ml/h for 70 kg. Normal starting dose 0.05 μg/kg/min, adjusted for blood pressure.

Dosage activity: <0.05 μg/kg/min – usually moderate effect on blood pressure, 0.0-5 0.1 μg/kg/min β1 effect, blood pressure increase, > 0.1 μg/kg/min – α1 effect with blood pressure increase, vasoconstriction, tachycardia.

Contraindications: Hypertension, pronounced hypovolemia, hyperthyroidism, peripheral hypoxia, peripheral vasoconstriction, hyperadrenergic conditions.


Phenylephrine

Phenylephrine is a sympathomimetically substituted phenethylamine. Pure alpha receptor agonist. Provides vasoconstriction and blood pressure increase. Reduced cardiac output (CO), increased diastolic blood pressure and mean arterial pressure (MAP).

Receptor activity: α1 +++, β1 zero, β2 zero, DA-1 zero.

Physiological effects: Increased SVR, decreased CO, decreased HR, increased BP, reflective bradycardia.

Indication: Hypotension, vasodilation, drop in blood pressure after spinal anesthesia and epidural anesthesia.

Side effects: Bradycardia, cardiac failure, pulmonary edema.

Concentration: Standard solution 0.1 mg/ml. A common concentration is 0.1 mg/ml or (0.2 mg/ml). Also available in the concentration of 10.0 mg/ml that may be diluted.

Dosage: 0.1-0.2 mg i v. Normal starting dose 0.1 mg i v, adjusted for blood pressure. Phenylephrine is usually given in repeated bolus doses, but can also be given in continuous infusion at 0.1 mg/ml strength. The usual dose is 0.05-0.15 μg/kg/min = about 3 – 20 ml/h for 70 kg.

Dosage activity: < 0.3 mg: usually moderate effect on blood pressure, CO unchanged, > 0.5 mg reduced CO, vasoconstriction.


Vasopressin

Vasopressin is an antidiuretic hormone that regulates the resorption of water into the renal distal tubules. Regulates water balance, resulting in increased urinary osmolarity. Provides increased peripheral vasoconstriction and elevated blood pressure.

Concentration: Normal concentration for continuous infusion at 0.1 mg/ml. “Double strength” 0.2 mg/ml. Weak strength 0.05 mg/ml.

Receptor activity: V2 +++, α1 zero, β1 zero, β2 zero, DA-1 zero.

Physiological effects: SVR ↑, CO +/-, HR ↑, BP ↑↑.

Indication: Circulatory shock, refractory hypotension, sepsis, anaphylaxis, severe hypotension with vasodilation, cardiogenic shock, severe poisoning.

Side effects: Tachycardia, arrhythmias, renal and intestinal hypoperfusion, peripheral ischemia, intestinal ischemia, splanchnicus ischemia.

Dosage: 0.01-0.1- (0.5) μg/kg/min = 3-40 ml/h for 70 kg. Normal starting dose 0.05 μg/kg/min, adjusted for blood pressure.

Dosage activity: < 0.05 μg/kg/min – usually moderate effect on blood pressure, 0.0-5 0.1 μg/kg/min β1 effect, blood pressure increase,> 0.1 μg/kg/min – α1 effect , blood pressure increase, vasoconstriction, tachycardia.

Contraindications: Hypertension, hypovolemia, hyperthyroidism, peripheral hypoxia, peripheral vasoconstriction, hyperadrenergic conditions.