Angiotensin II in Septic Shock

Neysa Azalia Efrimaisa

Satria Utama
Wahyu Budi Pratama

Supervisor:
dr. Fauzal Aswad, Sp.JP

Introduction
Systemic vasodilatation and arterial hypotension are landmarks
of septic shock

Norepinephrine, a strong -adrenergic agonist, is the standard

vasopressor to treat septic shock-induced hypotension

Adrenergic vasopressors have been associated with several

detrimental effects, including organ dysfunction and increased
mortality
In addition to its classical hemodynamic function of regulating
arterial blood pressure, angiotensin II plays a key role in several
biological processes, including cell growth, apoptosis,
inflammatory response, and coagulation.

Definition

Definitions used to describe the condition of septic patients

Bacteriemia

Presence of bacteria in blood (positive blood cultures)

Septicemia

Presence of microbes or their toxins in blood

SIRS

2 of these conditions: fever (oral temp. >380C) or hypothermia (<360C); tachypnea (>24
breath/min); tachycardia (heart rate > 90 beats/min); leukocytosis (> 12.000/L);
leukopenia (< 4.000/L) or > 10% bands; may have a noninfectious etiology
SIRS that has a proven or suspected microbial etiology

Sepsis
Severe
sepsis

= sepsis syndrome: sepsis with 0ne or more signs of organ dysfunction, e.g:
1. Cadiovascular: arterial systolic blood pressure 90mmHg or mean arterial pressure
70mmHg that respons to administration of intravenous fluid
2. Renal: urine output < 0,5mL/kg per hour for 1 h despite adequate fluid resuscitation
3. Respiratory: PaO2/FIO2 250 or, if the lung is the only dysfunction organ, 200
4. Hematologic: platelet count < 80.000/L or 50% decrease in platelet count from highest
value ercorded over previous 3 days
5. Unexplained metabolic acidosis: a pH 7,30 or a base deficit 5,0mEq/L and a plasma
lactate level > 1,5 times upper limit of normal for reporting lab
6. Adequate fluid resuscitation: pulmonary artery wedge pressure 12mmHg or CVP
8mmHg

Septic shock

Sepsis with hypotention (arterial blood pressure < 90mmHg systolic, or 40mmHg less than
patients normal blood pressure) for at least 1 h despite adequate fluid resuscitation; or
need for vasopressors to maintain systolic blood pressure 90mmHg or mean arterial
pressure 70mmHg

Refractory
septic shock

Septic shock that last for > 1 h and does not respond to fluid or pressor administration

Dysfunction of mor than one organ, requiring intervention to maintain homeostasis

MODS
Septic shock
BLOK : Kegawatdaruratan

Sepsis: A Complex Disease

This Venn diagram

provides a conceptual
framework to view
the relationships
between various
components
of sepsis.

The inflammatory
changes of sepsis are
tightly linked to
disturbed hemostasis.

Septic shock
BLOK : Kegawatdaruratan

(Bone RC et al. Chest. 1992;101:1644-55.

Opal SM et al. Crit Care Med. 2000;28:S81-2).

Etiologi
Microorganism and condition that may predispose to infection
Microorganism

Condition

Gram-negative bacteria:

Diabetes mellitus
Lymphoproliferative diseases
Cirrhosis of the lever
Burns
Invassive procedures or devices
Neutropenia
Indwelling urinary catheter
Diverticulitis, perforated viscus

Enterobacteriaceae, pseudomonads, Haemophillus

spp., other gram-negative bacteria

Gram-positive bacteria:
Staphylococcus aureus, coagulase-negative
staphylococcus, enterococci, Streptococcus
pneumoniae, other streptococci, other gram-positive
bacteria

Fungi
Polymicrobial
Classic pathogens:
Neisseria meningitidis, S. pneumoniae, H.
influenzae,
Septic
shock Streptococcus pyogenes

BLOK : Kegawatdaruratan

Intravascular catheter
Indwelling mechanical devices
Burns
Neutropenia
Intravenous drug use
Infection with superantigen-producing S.
pyogenes
Neutropenia
Broad-spectrum antimicrobial therapy

Pathogenesis

(Rosario, 2011)
Septic shock

Trigger (organism-derived, e.g. endotoxin)

Release of tumor necrosis factor / other proinflammatory cytokines
Inflammatory cascade
Hypothalamus
Fever
Tachycardia
Tachypnea

Capillary endothelial cell

Vessel wall

Neutrophil migration
Nitric oxide synthesis
Platelet adherence
DIC
Vasodilatation
Depletion of intravascular vol
Cellular hypoxia

Septic Death
shock
Organ
BLOK : Kegawatdaruratan

dysfunction/hypoperfusion

Hypotension

Renin Angiotensin System

The renin-angiotensin system in

sepsis
Unresuscitated septic shock is
characterized by marked :
hypovolemia,
extracellular fluid volume
depletion,
decreased cardiac output,
low arterial blood pressure, and
decreased systemic vascular
resistance.

Infusion of angiotensin II in septic

shock

During sepsis, the activity of plasma renin,

angiotensin I and angiotensin II are
increased. Despite the high angiotensin II
plasma levels, pronounced hypotension,
associated with a reduced vasopressor effect
of angiotensin II, has been reported.
Moreover, RAS activation contributes to
oxidative stress and endothelial dysfunction,
which
has
been
associated
with
development of kidney and pulmonary injury
and with the severity of organ dysfunction.
Data from experimental animal models have

Conclusion
The

RAS plays a key role in fluid and electrolyte

homeostasis, arterial blood pressure and blood flow
regulation.
A better understanding of its complex interactions
with other neuroendocrine regulating systems is
crucial for the development of new therapeutic options
to treat septic shock.
Angiotensin
II is a powerful vasopressor in
experimental septic shock, and has proved to be safe
in the tested settings.
Administration of angiotensin II as an alternative to
norepinephrine should be further evaluated in clinical
trials

THANK YOU
dr. Fauzal Aswad, Sp.JP