What is what?
Inotrope
A substance that alters the force of muscular contraction (positive/negative)
Vasopressor
An agent producing vasoconstriction and a rise in blood pressure, usually understood to be systemic arterial pressure unless otherwise specified.
Vasodilator
An agent that causes dilation of the blood vessels
Chronotrope
A substance that alters the rate of a regularly recurring phenomenon such as the heartbeat (positive/negative)
Inodilator
An agent with both positive inotropic and vasodilator effects
Lusitrope
Relaxation functions of cardiac muscle and chambers
Dromotrope
Alteration in impulse conduction (positive/negative)
Shock
Shock is a clinical state which occurs when an imbalance between oxygen supply and demand results in the development of tissue hypoxemia NOT always hypotension NOT always reduced oxygen delivery
Shock
Physiologically Hypoxic
Low PaO2
Clinically Cardiogenic
Myocardial disease
Anaemic
Low haemoglobine level
Extracardiac Obstructive
Pulmonary embolus / tamponade
Stagnant
Low Cardiac output Maldistribution
Hypovolemic
Uncontrolled haemorrhage Excessive fluid loss
Histotoxic
Eg Cyanide poisening
Distributive
Sepsis
Initial priority
Maintain reasonable hemodynamics
Fluid resuscitation (How Much?)
Fluid responsiveness
Vasoactive Agents
Vasopressors
Raise Blood Pressure
Inotropes
Raise Cardiac Output
Most vasoactive agents have mixed effects Blood pressure blood flow perfussion Which cardiac output is adequate in shock (which shock) and how to measure it?
Vasoactive agents
Individual effects Mixed effects Overlapping effects Dose dependent effects
1-receptor 1-receptor 2-receptor Dopaminerg-receptor
Receptor specific
Alpha and beta adrenergic effects of vasoactive catecholamines. Adapted from Vincent, JL Critical Care Medicine in Churchill's Ready Reference, Vincent, JL, ed. (Churchill Livingstone Elsevier), 2009, pp 12-13.
Effects of vasoactive catecholamines on pressure and blood flow. Adapted from Vincent, JL Critical Care Medicine in Churchill's Ready Reference, Vincent, JL, ed. (Churchill Livingstone Elsevier), 2009, pp 12-13.
1-receptor
Vasoconstriction of arteries (inclusive coronary arteries) Vasoconstriction of veins
Other areas of smooth muscle contraction are:
Ureter, vas deferens, hair (arrector pili muscles), uterus (when pregnant), urethral sphincter, bronchioles, gastrointestinal tract
Glycogenolysis and gluconeogenesis from adipose tissue and liver Secretion from sweat glands Na+ reabsorption from kidney.
1-receptor
Increase cardiac output, by
positive chronotropic effect positive dromotropic effect positive inotropic effect
increasing the volume expelled with each beat (increased ejection fraction).
2-receptor
Dilate arteries to skeletal muscle
Glycogenolysis and gluconeogenesis Smooth muscle relaxation, e.g. in bronchi,GI tract (decreased motility).
Dopamine-Receptor
Dose dependent
< 5 g/kg/min: Dopamine receptors
Vasodilation in renal bed Vasodilation in mesenteric bed
Dopamine-Receptor
Vasopressors
The principles The choices
Norepinephrine Dopamine Epinephrine Phenylephrine Vasopressin
The Complications
Vasopressors
Endpoint = Arterial Pressure Minimal BP for autoregulation Below this pressure flow is directly dependent on pressure
Animal studies: MAP < 60 mmHg compromises
Coronary / Renal / Central nervous system vascular bed
Vasopressors
Principal use:
Vasodilatory shock: Sepsis
Other use
Cardiogenic shock
Coronary perfusion
Obstructive shock
Temporize Treat Life threatening hypotension
Hypovolemic shock
Temporize Treat Life threatening hypotension
Noradrenaline = Norepinephrine
Noradrenaline = Norepinephrine
Potent -adrenergic agonist with limited adrenergic agonist effects
Increase of MAP by vasoconstriction Small increase in SV and CO Filling pressures unchanged to modestly increased (1-3 mmHg)
Dopamine
Dopamine
Natural precursor of Noradrenaline and Adrenaline Dose dependent effects with overlap
< 5 g/kg/min: Dopamine receptors
Vasodilation in renal bed Vasodilation in mesenteric bed
Increase in MAP and CO due to an increase in SV and a lesser extent HR Renal dose of dopamine? (2 g/kg/min)
Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J, Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Lancet 2000;356:2139-43.
Dopamine or Noradrenaline
Dopamine or Noradrenaline
Adrenaline
Adrenaline
Potent - and -adrenergic agonist effects Increase MAP
Increase in CO Increase in peripheral vascular tone
Increase in heart rate (HR) + potential to induce tachyarrhythmias Induces Hypoglycemia Increase Lactate concentration
Adrenaline vs Noradrenaline
2 Studies NO DIFFERENCE IN
Time to hemodynamic succes Vasopressor withdrawel 28-day mortality ICU mortality Hospital mortality
Myburgh JA, Higgins A, Jovanovska A, Lipman J, Ramakrishnan N, Santamaria J. A comparison of epinephrine and norepinephrine in critically ill patients. Intensive care medicine 2008;34:2226-34. Annane D, Vignon P, Renault A, et al. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet 2007;370:676-84.
Phenylephrine
Phenylephrine
Selective 1-adrenergic agonist
Rapid onset Short duration Primary vascular effects
Vasopressine
Vasopressine
Synthesized in the hypothalamus and stored in the pituitary gland Released in response to
Decreased blood volume Decreased intravascular volume Increased plasma osmolality
Effects
Constricts vascular smooth muscle via V1 receptor Increase responsiveness to catecholamines Inhibition of vascular smooth muscle NO production K+ - ATP channels
Complications of vasopressors
Tachycardia and tachyarrhytmias Myocardial ischemia and infarction
Coronary artery constriction
Inotropes
The principles The choices
Dobutamine Phosphodiesterase inhibitors Levosimendan
Indicated in cardiogenic shock (other shocks less clear cut) increasing cardiac output to predetermined supranormal levels in all patients does not improve outcomes
Gattinoni L, Brazzi L, Pelosi P, et al. A trial of goal-oriented hemodynamic therapy in critically ill patients. New England Journal of Medicine 1995;333:1025-32.
The principles
Dobutamine
Predominant 1 adrenergic effects
Positive Inotropic Positive chronotropic
Initial agent of choice in septic shock with low CO and adequate filling pressure (small group)
Phosphodiesterase inhibitors
Increase intracellular cAMP independent of the receptor Inotropic effect Fewer chronotropic and arrhythmogenic effects One important note is the differential effects of increased cAMP in smooth muscle compared to cardiac muscle. Increased cAMP will promote relaxation in smooth muscle and hypotension Milrinone is a more potent pulmonary vasodilator than dobutamine, and so is often preferred in cases of predominant right heart failure
DA
Phenylephrine
Vasopressin Dopamine Dobutamine
++ 0 +++ 0 0 + +
0 0 0 0 0 +++ 0
Vasoactive Agents
Vasopressors
Raise Blood Pressure
Inotropes
Raise Cardiac Output
Sublingual circulation
Near infrared spectroscopy
Lactate
Hypoperfusion or cellular metabolism
Sublingual capnometry
References
Vincent, JL Critical Care Medicine in Churchill's Ready Reference, Vincent, JL, ed. (Churchill Livingstone Elsevier), 2009, pp 12-13. Hollenberg SM Vasoactive drugs in circulatory shock. . Am J Respir Crit Care Med. 2011 Apr 1;183(7):847-55. Epub 2010 Nov 19. Hollenberg SM, Ahrens TS, Annane D, et al. Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update. Crit Care Med 2004;32:1928-48. Dellinger RP, Carlet JM, Masur H, et al. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004;32:858-73. Van den Berghe G, de Zegher F. Anterior pituitary function during critical illness and dopamine treatment. Crit Care Med 1996;24:1580-90. Oberbeck R, Schmitz D, Wilsenack K, et al. Dopamine affects cellular immune functions during polymicrobial sepsis. Intensive care medicine 2006;32:731-9. Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J, Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Lancet 2000;356:2139-43.
References
De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010;362:779-89. Myburgh JA, Higgins A, Jovanovska A, Lipman J, Ramakrishnan N, Santamaria J. A comparison of epinephrine and norepinephrine in critically ill patients. Intensive care medicine 2008;34:2226-34. Annane D, Vignon P, Renault A, et al. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet 2007;370:676-84. Russell JA, Walley KR. VASST trial results. European Society of Intensive Care Medicine 2006. Gattinoni L, Brazzi L, Pelosi P, et al. A trial of goal-oriented hemodynamic therapy in critically ill patients. New England Journal of Medicine 1995;333:1025-32. Hollenberg SM, Parrillo JE. Acute Heart Failure and Shock in Cardiology, 3rd edition (Crawford MH, DeMarco J, Paulus WJ, eds), Mosby, Philadelphia, 2010, p. 964 Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77.