Blok VII Emergency &Trauma ,FK UMI

Treatment of Shock
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

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
Vicious cycle

Maldistribution of
Blood Flow

Cellular Perfusion
 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

TLR, toll-like receptors; NF-κB , nuclear factor κB; iNOS, inducible nitric oxide synthase.

Russell JA. N Engl J Med 2006;355:1699-713

 Procoagulant Response in Sepsis

TFPI, tissue factor–pathway inhibitor; PAI-1, plasminogen-activator inhibitor 1

Russell JA. N Engl J Med 2006;355:1699-713

 Kaplan–Meier 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.

Bernard GR et al. N Engl J Med 2001;344:699-709.

 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

o2 + substrate

Cellular Dysfunction

Multiple Organ Failure

Harrison’s Principles of Internal Medicine 15th ed, p. 222
1 Pathogenesis of
Hypovolemic
3 Shock

6 4 2
Hypoxemia, Oxygen Saturation and Clinical Monitoring
Extracellular and Vascular Fluid Compartment
 Catecholamines

Brenner GM, Stevens CW. Pharmacology p. 74, 2006

 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