Transcript Management of Septic Shock

Management of Septic Shock
Epidemiology of Sepsis
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751K cases annually in the United States and rising
Most common cause of death in non-coronary ICU
30% Mortality when shock present
Severe sepsis $22K/pt, $16 billion/year
Definitions
The ACCP/SCCM consensus conference committee. Definitions for sepsis and organ failure and
guidelines for the use of innovative therapies in sepsis. Chest 1992.
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SIRS
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Widespread inflammatory response
Two or more of the following
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Temp>38 C<36 C
Heart Rate >90 bpm
Tachypnea RR>20 or hyperventilation PaCO2 <32 mmHg
WBC >12,000<4000 or presence of >10% immature neutrophils.
Sepsis: SIRS + definitive source of infection
Severe Sepsis: Sepsis + organ dysfunction, hypoperfusion,
or hypotension
Definitions
The ACCP/SCCM consensus conference committee. Definitions for sepsis and organ failure and
guidelines for the use of innovative therapies in sepsis. Chest 1992.
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Septic Shock:
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Sepsis + hypotension despite fluids
Perfusion abnormalities
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Lactic acidosis
Oliguria
Acute AMS
Multiple Organ System Failure: Abnormal function of two
or more organs such that homeostasis cannot be achieved
without intervention.
Brief Pathophysiology
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Proinflammatory response to infection
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Mediators
 TNF Alpha,
IL-1, IL-6
 Complement system (C5 alpha)
 Bacterial factors
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Endotoxin, bacterial cell wall products, bacterial toxins
Immunosuppressive
Time-course of inflammatory response during sepsis
(modified from Management of Severe Sepsis and Septic Shock. Curr Opin Crit Care 2004;10:354-363)
(Modified from The Pathophysiology and Treatment of Sepsis. N Engl J Med 2003;348:138-150)
Cellular dysfunction
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Cellular hypoxia
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Reduced surface area for diffusion
Reduction in RBC deformability
Impaired utilization of oxygen by mitochondria
Circulatory system dysregulation
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Vasodilation (nitric oxide)
Vascular permeability
Acute Organ Dysfunction
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Neuro: altered mental status
Respiratory: Mechanical ventilation? (PF ratio <250, PEEP
>7.5)
CV: Pressors? SBP<90 or MAP<70 despite fluids
Renal: UO <0.5ml/cc/kg/hr, 50% increase in Cr, acute
dialysis
Heme: Platelets <100,000 or PT/PTT elevated
Metabolic: pH <7.3, high lactate
Hepatic: LFTs >2x normal
GI: Bacterial overgrowth and translocation
Management of Sepsis
Resuscitate: ABCs
 Restore tissue perfusion
 Identify and eradicate source of infection
 Assure adequate tissue oxygenation
 Activated Protein C
 Steroids
 Glucose Control
 Nutrition
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Resuscitation
Airway: AMS, unable to protect airway
 Breathing: Respiratory failure
 Circulation: Restoration of blood pressure
to levels which perfuse core organs.
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Sphygmomanometer unreliable
Arterial catheter
CVP
Mixed Venous O2 sat
Restoration of tissue perfusion
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Causes of poor tissue
perfusion
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Leaky vessels
Decreased vascular
tone
Myocardial depression
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Interventions
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Volume infusion
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Intravenous fluids
PRBCs
Vasopressors
Inotropes
Intravenous Fluids
Practice parameters for hemodynamic support of sepsis in adult patient in sepsis. Task Force of the
ACCCM/SCCM. Critical Care Medicine 1999
Administered in well-defined, rapidly
infused boluses
 Continued until blood pressure, tissue
perfusion, and oxygen delivery acceptable
or presence of pulmonary edema
 Colloid vs. Crystalloid: No evidence to
recommend one over the other.
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Vasopressors
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Second-line agents
Hypotensive despite fluid resuscitation,
Cardiogenic pulmonary edema, or elevated
wedge pressure (>18)
Vascoconstrictors
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Phenylephrine, Norepinephrine, Dopamine,
Epinephrine, Vasopressin
Vasopressors
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Catecholamines may modulate immune system
Epinephrine may decrease splanchnic perfusion and pH
Dopa and norepi have similar effects on renal function
Dopamine may result in greater splanchnic acidosis vs
norepinephrine
Observational studies suggest Norepinephrine as first line
agent for fluid refractory hypotension
Martin et al Chest 1993;103(6):1826-31
Vasopressors
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Vasopressin
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Limited data, studies suggest may be useful in vasodilatory shock
Vasopressin deficiency contributes to the vasodilation of septic
shock. Circulation 1997.
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Hemodynamic and metabolic effects of low-dose VP infusions in
vasodilatory septic shock. Critical Care Medicine 2001
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VP levels low in septic shock
10 patients in septic shock and already receiving catecholamines with
improvement of hypotension and decreased need for catecholamines
VP given to 16 septic patients with refractory hypotension.
VP infusion improved MAP and SVR
Current recs are to consider with refractory hypotension despite
adequate fluid resuscitation and high-dose conventional
vasopressors.(infusion rates of 0.01-0.04 units per min)
Eradicate infectious source
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Empiric broad spectrum antibiotics
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ASAP after blood cultures collected
Modify as culture results dictate
Remove infectious source
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Remove catheter, Drain abscess/fluid
collections, Divert gut, etc
Early Goal-Directed Therapy in the Treatment of
Severe Sepsis and Septic Shock. NEJM. Nov 8, 2001
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Study design: Prospective, randomized study in urban emergency
department enrolling 263 patients
Inclusion Criteria: Adults severe sepsis, septic shock, or sepsis syndrome.
SIRS. SBP<90 (after fluid bolus) or lactate>4.
Exclusion Criteria: Age<18, pregnancy, acute CVA, ACS, pulmonary
edema, status asthmaticus, arrhythmia, GIB, seizure, drug OD, burns,
trauma, immediate surgery, uncured cancer, immunosupressed, DNR.
Treatment: In ER 500 ml crystalloid given q 30 min to achieve CVP 8-12
mmHg. Pressors given to achieve MAP >65. If MAP >90 vasodilators
given until <90. If ScvO2<70, transfused to Hct of 30. +/-Dobutamine.
Results: Improved in-hospital mortality (30.5% vs. 46.5%). Higher mean
ScvO2, lower lactate, lower base deficit and a higher pH. Lower APACHE
scores.
Assuring adequate tissue oxygenation
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Goal: Maintain oxygen delivery (DO2) at levels
that match tissue O2 needs (VO2)
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Detection of tissue hypoxia--Lactate
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Supratherapeutic oxygenation not consistently shown to
be effective
May be difficult to interpret
Treatment of tissue hypoxia
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Maximize arterial oxygen content
Keep SaO2 >97%
Augment cardiac output
Support hematocrit
Activated protein C
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Known inflammatory and procoagulant host responses to
infection.
– TNF-alpha, IL-1, IL-6, thrombin
Diffuse endovascular injury, multiorgan dysfunction and
death.
Activated Protein C
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anticoagulant, modulates the inflammatory response
reduced levels of protein C found in majority of patients with
sepsis and are associated with increased risk of death.
Efficacy and Safety of Recombinant Human
Activated Protein C for Severe Sepsis. NEJM 2001.
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Randomized, double-blind,
placebo-controlled, multicenter
trial enrolling 1,690 patients with
severe sepsis.
96 hour infusion of recombinant
APC or placebo beginning within
24 hours of presentation.
28 day mortality significantly
lower in the APC group
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24.7 vs. 30.8%
Trend towards increased bleeding
(3.5 vs/ 2.0% p=0.06)
Activated Protein C Guidelines
Glucocorticoids
Ten prospective, randomized, controlled
trials of pharmacologic doses of
glucocorticoids in sepsis/septic shock
 Steroid controversy in sepsis and septic
shock: A meta-analysis. Critical Care
Medicine 1995
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Glucocorticoids offer no benefit
Positive findings reported in 1/10 trials
Revisiting Steroids…
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Adrenal Insufficiency
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25-40% of ICU patients with septic shock
Mortality is more than double that of patients
with normal adrenal responsiveness
Hypotension refractory to vasopressors
hyponatremia, hyperkalemia, weakness, and
hyperpigmentation not specific enough in ICU
setting
Effect of treatment with low doses of hydrocortisone
and fludrocortisone on mortality in patients with
septic shock. JAMA Aug 21, 2002
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Placebo-controlled, randomized, double-blind, parallel-group trial
performed in 19 French ICUs.
300 adults with severe sepsis who underwent corticotropin test were
randomly assigned to receive hydrocortisone and fludrocortisone or
placebo for 7 days.
Main outcome measure: 28 day survival in patients with abnormal
corticotropin test.
Results: Corticosteroids vs. Placebo
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Deaths: 53% vs 63%(Hazards ratio 0.67, 95% CI 0.47-0.95, p=0.02)
Withdraw of pressors: 57% vs 40% (Hazards ratio 1.91, 95% CI 1.292.84, p=0.001)
No difference in adverse outcomes.
Conclusion: 7 day treatment with steroids beneficial in patients with
sepsis and adrenal insufficiency.
Effect of treatment with low doses of hydrocortisone
and fludrocortisone on mortality in patients with
septic shock. JAMA Aug 21, 2002
Effect of treatment with low doses of hydrocortisone
and fludrocortisone on mortality in patients with
septic shock. JAMA Aug 21, 2002
Glucose Control
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Recs are to keep serum glucose levels < 150
Nutrition
Start early
 Route: preferably enteral
 Nutritional support improves wound healing
and decreases susceptibility to infection.
 Nutritional support results in higher
lymphocyte counts and higher serum
albumin (surrogate markers of immune
competency)
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Summary
Ensure tissue perfusion: resuscitate early
with liberal IVF, pressors and inotropes.
 Ensure tissue oxygenation: oxygen content,
oxygen saturation, cardiac output
 Identify and eradicate infection
 APC in patients with severe sepsis
 Consider corticosteroids
 Glucose Control
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Septic Shock Algorithm Example
(modified from Septic Shock. Lancet 2005;365:63-78.)