Prof. DR. dr. Hadyanto Lim, M.

Kes,SpFK,FESC,FIBA,FAHA
Department of Pharmacology and Molecular Sciences,
Faculty of Medicine, Methodist University of Indonesia - Medan
Molecular Biology Research,
Postgraduate School, University of Sumatra Utara - Medan



Blok VII Emergency &Trauma ,FK UMI
Treatment of Shock
February 27, 2012
Critical Care Patient
Singer M. Lancet 2007; 370: 636-637
Shock
A medical emergency characterized by
inadequate perfusion of vital organ, usually
because of a very low arterial blood pressure.

Accompanied by pallor, coldness and moistness
of the skin, collapse of superficial veins,
alteration of mental status.

Classification of Shock
Hypovolemic
Traumatic
Cardiogenic
- Intrinsic
- Compressive
Septic
- Hyperdynamic
- Hypodynamic
Neurogenic
Hypersensitivity - anaphylaxis, reaction to drugs

Pathogenesis of Shock
Irrespective of cause, the hypoperfusion-
induced imbalance between delivery of and
requirements for oxygen and substrate leads to
cellular dysfunction.

The cellular injury induces the production and
release of inflammatory mediators that further
compromise perfusion through functional and
structural changes within the microvasculature.
Concepts of Pathogenesis of Shock
Impaired perfusion
Cellular Injury
Maldistribution of
Blood Flow
Cellular Perfusion
Vicious cycle
Sepsis to Septic Shock
Sepsis associated with acute organ dysfunction,
results from a generalized inflammatory and
procoagulant response to an infection.

Septic shock is defined as severe sepsis with
hypotension, despite adequate fluid resuscitation.

Mortality rate ranging from 20% for sepsis to 50%
for septic shock.
Inflammatory Responses to Sepsis
Russell JA. N Engl J Med 2006;355:1699-713
TLR, toll-like receptors; NF-B , nuclear factor B; iNOS, inducible nitric oxide synthase.
Procoagulant Response in Sepsis
Russell JA. N Engl J Med 2006;355:1699-713
TFPI, tissue factorpathway inhibitor; PAI-1, plasminogen-activator inhibitor 1
Bernard GR et al. N Engl J Med 2001;344:699-709.
KaplanMeier Estimates of Survival among 850 Patients with Severe Sepsis in the
Drotrecogin Alfa Activated Group and 840 Patients with Severe Sepsis in the Placebo
Group.
Proposed Actions
of Activated
Protein C in
Modulating the
Systemic
Inflammatory,
Procoagulant,
and Fibrinolytic
Host Responses
to Infection
Bernard GR et al. N Engl J Med 2001;344:699-709.
Principle of Management of Shock
Imbalance
o
2
+ substrate

Cellular Dysfunction
Harrisons Principles of Internal Medicine 15
th
ed, p. 222
Multiple Organ Failure
Pathogenesis of
Hypovolemic
Shock
1
2
3
4 6
Hypoxemia, Oxygen Saturation and Clinical Monitoring
Extracellular and Vascular Fluid Compartment
Brenner GM, Stevens CW. Pharmacology p. 74, 2006
Catecholamines
Direct-Acting Adrenergic Receptor Agonist
Catecholamine :
- Norepinephine, Epinephrine, Dopamine
(Natural)
- Isoproterenol, Dobutamine (Synthetic)

Non-Cathecholamine :
- Phenylethylamines
- Imidazolines

Structures of catecholamine and non-catecholamine
Norepinephrine
Activation of
1
adrenergic receptor, producing
vasoconstriction and increases peripheral resistance.

Increases systolic and diastolic blood pressure.

Reflex bradycardia if BP increases sufficiently to
activate baroreceptor reflex.

Epinephrine
Increases the SBP, but can decrease the DBP.

Lower doses produce greater stimulation of
2

adrenergic receptors than
1
, thereby causing
vasodilation and decreasing diastolic BP.



Isoproterenol
Activates
1
and
2
-adrenergic receptors and
produces vasodilation and cardiac stimulation.

It usually lowers the diastolic and mean arterial
pressure, but it can increase systolic pressure by
increasing the heart rate and contractility.
Dobutamine
Increases myocardial contractility and stroke
volume while producing a smaller increase in heart
rate.
Increases cardiac output in persons with acute
heart failure.
Reduces vascular resistance by activating
2
-
adrenergic receptors, thereby decreasing cardiac
afterload, which contributes to an increased in
stroke volume and cardiac output.
Comparisons of cardiovascular effects of catecholamines