Prepared by

SHOCK & MANAGEMENT OF SEPSIS - Dr Khalilah, Dr Faizuddin

Supervised by
- Dr Zet
 INTRODUCTION
Sepsis continues to be a major cause of mortality and morbidity throughout the world.
The annual incidence of severe sepsis was approximately 3.0 cases per 1,000 of the
population.
In the United States alone, the incidence of severe sepsis will see an annual increase
of 1.5% which may be attributable to an increasing ageing population. (1)

1. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in
the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29:1303-
10.
 INTRODUCTION CONT
Malaysia is not immune from the global burden of sepsis. In 2008, severe sepsis was
the second leading cause of death in the Malaysian Ministry of Health hospitals. (2)
To date, there have been no local studies on the implementation or challenges in
applying EGDT in emergency departments (ED) until 2009 by UKMMC with a
conclusion that EGDT can be implemented in ED Malaysia with current resources and
expertise.

2. Health Facts 2008. Health Informatics Centre. Planning and Development Division. Ministry of Health
Malaysia [Online]. 2009 May 1
Shock is an acute clinical state characterized by inadequate cellular
perfusion leading to cellular damage and failure of major organ
systems
DEFINITION BY AMERICAN COLLEGE OF CHEST PHYSICIANS/SOCIETY OF CR ITICAL
CARE MEDICINE

3. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference, Levy MM et al., Crit. Care
Med. 2003, 31(4): 1250-1256)
CAUSES
Most common is bacterial infection, mainly Gram ve organisms
Gram ve: E. Coli, Klebsiella, Enterobacter
Gram +ve: Streptococci, Staph, Pneumococcus

Viruses, fungi and parasites often in immunocompromised

PATHOGENESIS
Infection triggers pro inflammatory response that results in peripheral vasodilation,
endothelial cell activation, increased vascular permeability and microthrombi
formation within microcirculation.
Initially, body will respond with increased cardiac output to compensate for
peripheral vasodilation (reduced SVR). MAP=COxSVR
As sepsis progresses, endothelial dysfunction results significant extravasation of fluid
and loss of intravascular volume. As a result, perfusion falls and clinical signs may be
indistinguishable from other types of shock.
PATHOPHYSIOLOGY
The manifestations of septic shock and the development of multi-organ failure (MOF)
are due largely to the pathophysiological effects of cytokines which are released as
part of the host immune response.
Although the host immune response and the release of cytokines are primarily for the
protection against microbes, uncontrolled release of these cytokines can have marked
deleterious effects on the body.
Sepsis has been described as the immune system gone haywire.
CYTOKINES
The cytokines include the interleukins, interferons, colony stimulating factors, tumour
necrosis factor and various growth factors.
The cytokines which are important in sepsis include tumour necrosis factor, Ill, IL6, IL8
and platelet-activating factor.
Both infection and injury can activate the cytokine cascade as well as the complement
coagulation and fibrinolytic systems of the body.
This results in shock, disseminated intravascular coagulation and fibrinolysis which are
the classical manifestations of sepsis.
NEUTROPHIL ACTIVATION
Neutrophil activation which results from the action of cytokines is believed to be an
important factor in the pathogenetic mechanism.
Activated neutrophils tend to form aggregates and become more adherent to
endothelial cells.
Neutrophil activation also results in production of free oxygen radicals. This and other
mechanisms lead to endothelial damage, injury to the microvasculature and
ischaemia.
Ischaemia leads to multi-organ failure. Ischaemia also results in the formation of
oxygen radicals when reperfusion occurs which further aggravates the endothelial
damage.
CLINICAL FEATURES
EARLY STAGE (compensated/warm shock)
Febrile
Shivering and malaise
Warm, dry and flushed skin
CRT <2s
Tachypneic
Rapid bounding pulse
Wide pulse pressure
CLINICAL FEATURES
LATE STAGE (decompensated/cold shock)
Altered sensorium
Cold clammy skin
CRT prolonged
Weak pulse
Hypothermia, hypotension
Oliguria
Narrow pulse pressure
Metabolic acidosis
INITIAL RESUSCITATION
Protocolized, quantitative resuscitation of patients with sepsis- induced tissue
hypoperfusion (defined in this document as hypotension persisting after initial fluid
challenge or blood lactate concentration 4 mmol/L) (grade 1C).
Goals during the first 6 hrs of resuscitation:
a) Central venous pressure (CVP) 812 mm Hg
b) Mean arterial pressure (MAP) 65 mm Hg
c) Urine output 0.5 mL/kg/hr
d) Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%,
respectively
In patients with elevated lactate levels targeting resuscitation to normalize lactate
(grade 2C).
 FLUID RESUSCITATION AND CVP MONITORING
Patients are usually fluid depleted absolute vs relative
Fluid resuscitation can help to reduce the global tissue hypoxia that is central to the
development of multiorgan dysfunction, by increasing the cardiac output and
improving oxygen delivery to the tissues (6)
Continued fluid challenges of 500-1000 ml of crystalloids or 300-500 ml of colloids
over 30minutes and repeated as appropriate.

Haupt M T, Gilbert E M, Carlson R W. Fluid loading increases oxygen consumption in septic patients with
lactic acidosis. Am Rev Respir Dis 1985. 131912916.916
 FLUID RESUSCITATION CONT
ultimate key to satisfactory fluid resuscitation ?
- clinical, urine output, CVP, peripheral perfusion

Crystalloid vs colloids ?
-In many recent studies, theres no apparent difference between
crystalloids and colloid
-no association with hospital/ICU mortality with type of fluid
administered during initial resuscitation (7)

7. McIntyre LA et al 2007 Canada

 FLUID RESUSCITATION CONT
Bottomline :

Both crystalloids and colloids can be used in the initial resuscitation of patients with
severe sepsis. The most current Surviving Sepsis Campaign guidelines recommend
giving fluid challenges of 1000ml of crystalloids or 300 500ml of colloids over
30mins to achieve a target CVP of 8mmH2o or more .(8)(9)

8. Dellinger RP et al. Surviving sepsis campaign: International guidelines for management of severe
sepsis and septic shock 2008. Critical Care Medicine 2008; 36(1); 296-327
9. Powell-Tuck J et al. British consensus guidelines on intravenous fluid therapy for adult surgical patients. GIFTASUP
2008
 MAP AND VASOPRESSORS
Even after adequate fluid resuscitation many patients remain hypotensive or have
inadequate tissue perfusion as a result of microvascular changes, myocardial
depression, vasodilatation and maldistribution of cardiac output (10)
MAP must be maintained at certain level even after adequate fluid resuscitation.

10. Beale R J, Hollenberg S M, Vincent J L. et al Vasopressor and inotropic support in septic shock: an
evidencebased review. Crit Care Med 2004. 32(Suppl)S455S465.S465.
 DOPAMINE VS NORADRENALINE
Dopamine has been commonly used as a first-line therapy for shock at many hospitals
for years
Dopamine has dose related effect-dopaminergic, beta 1, alpha 1.
Noradrenaline has effects on alpha 1, weaker beta 1 effect which is nullified by
reflex bradycardia in response to blood pressure hence the unchanged overall heart
rate
Choice of dopamine vs noradrenaline:
1. Noradrenaline might be preferred over dopamine as the first line vasopressor to
avoid cardiovascular adverse events
2. Dopamine is associated with more arrhythmic events.
 SCVO2 AND BLOOD TRANSFUSION
Scvo2 central venous oxygen saturation reflects tissue perfusion
 SCVO2 AND BLOOD TRANSFUSION

In the instance of the central venous oxygen saturation (ScvO2) was still below 70%
after adequate fluid and vasopressors, packed red cell transfusion will be given if
the hematocrit <30%.
DIAGNOSIS

Cultures as clinically appropriate before antimicrobial therapy if no significant

delay (> 45 mins) in the start of antimicrobial(s) (grade 1C).
At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be obtained
before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn
through each vascular access device, unless the device was recently (<48 hrs) inserted
(grade 1C).
Other source: sputum, urine, tissue abscess, CSF culture, peritoneal fluid, pleural fluid
wherever source of infection is suspected.
SOURCE CONTROL
A specific anatomical diagnosis of infection
requiring consideration for emergent source
control be sought and diagnosed or excluded
as rapidly as possible, and intervention be
undertaken for source control within the first
12 hr after the diagnosis is made, if feasible
(grade 1C).
ANTIMICROBIAL THERAPY
Administration of effective intravenous antimicrobials within the first hour of
recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade
1C) as the goal of therapy.
a) Initial empiric anti-infective therapy of one or more drugs that have activity
against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in
adequate concentrations into tissues presumed to be the source of sepsis (grade 1B).
b) Antimicrobial regimen should be reassessed daily for potential de-escalation
(grade 1B)
MECHANICAL VENTILATION OF SEPSIS-
INDUCED ARDS
Target a tidal volume of 6 mL/kg predicted body weight in patients with sepsis-
induced ARDS (grade 1A vs. 12 mL/kg).
Plateau pressures be measured in patients with ARDS and initial upper limit goal for
plateau pressures in a passively inflated lung be 30 cm H2O (grade 1B).
Positive end-expiratory pressure (PEEP) be applied to avoid alveolar collapse at
end expiration (atelectotrauma) (grade 1B).
That mechanically ventilated sepsis patients be maintained with the head of the bed
elevated to 30-45 degrees to limit aspiration risk and to prevent the development of
ventilator-associated pneumonia (grade 1B).
That a weaning protocol be in place and that mechanically ventilated patients with
severe sepsis undergo spontaneous breathing trials regularly to evaluate the ability
to discontinue mechanical ventilation when they satisfy the following criteria:
a) arousable;
b) hemodynamically stable (without vasopressor agents);
c) no new potentially serious conditions;
d) low ventilatory and end-expiratory pressure requirements; and
e) low Fio2 requirements which can be met safely delivered with a face mask or
nasal cannula.
If the spontaneous breathing trial is successful, consideration should be given for
extubation (grade 1A).
A conservative rather than liberal fluid strategy for patients with established sepsis-
induced ARDS who do not have evidence of tissue hypoperfusion (grade 1C).
In the absence of specific indications such as bronchospasm, not using beta 2-agonists
for treatment of sepsis-induced ARDS (grade 1B).
GLUCOSE CONTROL
A protocolized approach to blood glucose management in ICU patients with severe
sepsis commencing insulin dosing when 2 consecutive blood glucose levels are >180
mg/dL. This protocolized approach should target an upper blood glucose 180
mg/dL rather than an upper target blood glucose 110 mg/dL (grade 1A).
Blood glucose values be monitored every 12 hrs until glucose values and insulin
infusion rates are stable and then every 4 hrs thereafter (grade 1C).
Glucose levels obtained with point-of-care testing of capillary blood be interpreted
with caution, as such measurements may not accurately estimate arterial blood or
plasma glucose values (UG).
DEEP VEIN THROMBOSISPROPHYLAXIS
Patients with severe sepsis receive daily pharmacoprophylaxis against venous
thromboembolism (VTE) (grade 1B). This should be accomplished with daily
subcutaneous low-molecular weight heparin (LMWH) (grade 1B versus twice daily
UFH, grade 2C versus three times daily UFH).
If creatinine clearance is <30 mL/min, use dalteparin (grade 1A) or another form of
LMWH that has a low degree of renal metabolism (grade 2C) or UFH (grade 1A).
STRESS ULCER PROPHYLAXIS
Stress ulcer prophylaxis using H2 blocker or proton pump inhibitor be given to patients
with severe sepsis/septic shock who have bleeding risk factors (grade 1B).
SUMMARY
Fluid resuscitation and CVP monitoring
MAP maintenance and vasopressors
ScvO2 monitoring and blood
transfusion

+ Intravenous antibiotics administration

early