Sepsis Revised

8/13/2019 Sepsis Revised

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Epidemiology of Sepsis

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


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DefinitionsThe ACCP/SCCM consensus conference committee. Definitions for sepsis and organ failure and

guidelines for the use of innovative therapies in sepsis. Chest 1992.

SIRS

Widespread inflammatory response

Two or more of the following

Temp>38 C90 bpm

Tachypnea RR>20 or hyperventilation PaCO2 12,00010% immature neutrophils.

Sepsis: SIRS + definitive source of infection

Severe Sepsis: Sepsis + organ dysfunction, hypoperfusion,or hypotension


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DefinitionsThe ACCP/SCCM consensus conference committee. Definitions for sepsis and organ failure and

guidelines for the use of innovative therapies in sepsis. Chest 1992.

Septic Shock:

Sepsis + hypotension despite fluids

Perfusion abnormalities

Lactic acidosis Oliguria

Acute AMS

Multiple Organ System Failure: Abnormal function of two

or more organs such that homeostasis cannot be achieved

without intervention.


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Brief Pathophysiology

Proinflammatory response to infection

Mediators

TNF Alpha, IL-1, IL-6Complement system (C5 alpha)

Bacterial factors

Endotoxin, bacterial cell wall products, bacterial toxins

Immunosuppressive


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Time-course of inflammatory response during sepsis(modified fromManagement of Severe Sepsis and Septic Shock. Curr Opin Crit Care 2004;10:354-363)


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(Modified from The Pathophysiology and Treatment of Sepsis. N Engl J Med 2003;348:138-150)


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Cellular dysfunction

Cellular hypoxia

Reduced surface area for diffusion

Reduction in RBC deformability Impaired utilization of oxygen by mitochondria

Circulatory system dysregulation

Vasodilation (nitric oxide) Vascular permeability


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Acute Organ Dysfunction

Neuro: altered mental status

Respiratory: Mechanical ventilation? (PF ratio 7.5)

CV: Pressors? SBP


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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 pressureto levels which perfuse core organs.

Sphygmomanometer unreliable

Arterial catheter

CVP

Mixed Venous O2 sat


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Restoration of tissue perfusion

Causes of poor tissue

perfusion

Leaky vessels

Decreased vascular

tone

Myocardial depression

Interventions

Volume infusion

Intravenous fluids

PRBCs

Vasopressors

Inotropes


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Intravenous FluidsPractice 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, tissueperfusion, and oxygen delivery acceptable

or presence of pulmonary edema

Colloid vs. Crystalloid: No evidence torecommend one over the other.


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Vasopressors

Second-line agents

Hypotensive despite fluid resuscitation,

Cardiogenic pulmonary edema, or elevated

wedge pressure (>18) Vascoconstrictors

Phenylephrine, Norepinephrine, Dopamine,

Epinephrine, Vasopressin


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Vasopressors

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 vsnorepinephrine

Observational studies suggest Norepinephrine as first line

agent for fluid refractory hypotension

Martin et al Chest1993;103(6):1826-31


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Vasopressors

Vasopressin Limited data, studies suggest may be useful in vasodilatory shock

Vasopressin deficiency contributes to the vasodilation of septicshock. Circulation 1997. VP levels low in septic shock

10 patients in septic shock and already receiving catecholamines with

improvement of hypotension and decreased need for catecholamines Hemodynamic and metabolic effects of low-dose VP infusions in

vasodilatory septic shock. Critical Care Medicine 2001 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 conventionalvasopressors.(infusion rates of 0.01-0.04 units per min)


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Eradicate infectious source

Empiric broad spectrum antibiotics

ASAP after blood cultures collected

Modify as culture results dictate Remove infectious source

Remove catheter, Drain abscess/fluid

collections, Divert gut, etc


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Early Goal-Directed Therapy in the Treatment of

Severe Sepsis and Septic Shock.NEJM. Nov 8, 2001

Study design: Prospective, randomized study in urban emergency

department enrolling 263 patients

Inclusion Criteria: Adults severe sepsis, septic shock, or sepsis syndrome.

SIRS. SBP4.

Exclusion Criteria: Age65. If MAP >90 vasodilators

given until


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Assuring adequate tissue oxygenation

Goal: Maintain oxygen delivery (DO2) at levels

that match tissue O2 needs (VO2)

Supratherapeutic oxygenation not consistently shown to

be effective

Detection of tissue hypoxia--Lactate

May be difficult to interpret

Treatment of tissue hypoxia Maximize arterial oxygen content

Keep SaO2 >97%

Augment cardiac output

Support hematocrit


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Activated protein C

Known inflammatory and procoagulant host responses to

infection.

TNF-alpha, IL-1, IL-6, thrombin

Diffuse endovascular injury, multiorgan dysfunction anddeath.

Activated Protein C

anticoagulant, modulates the inflammatory response

reduced levels of protein C found in majority of patients withsepsis and are associated with increased risk of death.


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Efficacy and Safety of Recombinant Human

Activated Protein C for Severe Sepsis. NEJM 2001.

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

24.7 vs. 30.8%

Trend towards increased bleeding(3.5 vs/ 2.0% p=0.06)


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Activated Protein C Guidelines


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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

Glucocorticoids offer no benefit

Positive findings reported in 1/10 trials


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Revisiting Steroids

Adrenal Insufficiency

25-40% of ICU patients with septic shock

Mortality is more than double that of patientswith normal adrenal responsiveness

Hypotension refractory to vasopressors

hyponatremia, hyperkalemia, weakness, and

hyperpigmentation not specific enough in ICU

setting


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Effect of treatment with low doses of hydrocortisone

and fludrocortisone on mortality in patients with

septic shock. JAMA Aug 21, 2002

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

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 1.29-2.84, p=0.001)

No difference in adverse outcomes.

Conclusion: 7 day treatment with steroids beneficial in patients with

sepsis and adrenal insufficiency.


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Glucose Control

Recs are to keep serum glucose levels < 150


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Nutrition

Start early

Route: preferably enteral

Nutritional support improves wound healingand decreases susceptibility to infection.

Nutritional support results in higher

lymphocyte counts and higher serumalbumin (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.)

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Sepsis Revised