New Trends in Management of Severe Sepsis Dr. M. HELMI AFIFI (MBBCh, MSc, MD, DHA) Prof. of Anesthesia & Intensive Care Menoufiya Faculty of Medicine, Egypt
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Sepsis: common, lethal, and expensive • Major cause of morbidity and mortality worldwide • Kills ~ 1,400 people worldwide every day • 400 000 ICU admission /y in USA • Mortality rate 30–40%
• $50 billion per year in health care costs in USA
Angus DC et al, Crit Care Med 2001; 29[Suppl.]:S109 American Heart Association. Heart Disease and Stroke statistics 2006 Update
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Severe Sepsis: Comparative Incidence and Mortality Incidence
†National
Mortality
Center for Health Statistics, 2001. §American Cancer Society, 2001. *American Heart Association. 2000. ‡Angus DC et al. Crit Care Med 2001
Infection “A microbial phenomenon due to invasion of host tissue by microorganisms”
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Sepsis “ Systemic host response to invasive infection”
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"Except on few occasions, the patient appears to die from the body's response to infection rather than from it." Sir William Osler – 1904 The Evolution of Modern Medicine 6
Systemic Inflammatory Response Syndrome
(SIRS) ďƒ˜ Widespread inflammatory response to a variety of severe clinical insults Trauma
Burn INFECTION
Pancreatitis
Others
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Systemic Inflammatory Response Syndrome
(SIRS) Widespread inflammatory response to a variety of severe clinical insults Clinically recognized by the presence of two or more of the following: 1. 2. 3. 4.
Temperature >38°C or <36°C Heart rate > 90/min RR > 20/min or PaCO2 <32 mmHg WBC >12,000 cells/mm3, <4000 cells/mm3 8
Sepsis SIRS + Evidence of infection
INFECTION
SIRS
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Severe Sepsis Sepsis + Organ dysfunction
Infection
SIRS
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Acute Organ Dysfunction Altered Consciousness Confusion Psychosis
Tachycardia Hypotension CVP PAOP
Oliguria Anuria Creatinine
Tachypnea PaO2 <70 mm Hg SaO2 <90% PaO2/FiO2 300
Platelets PT/APTT Protein C D-dimer
Jaundice Enzymes Albumin PT Balk. Crit Care Clin 2000;16:337-52
Septic shock Sepsis + Hypotension despite adequate fluid resuscitation + Hypoperfusion 12
Septicemia Sepsis that has an infection in the bloodstream itself
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ACCP/SCCM Consensus Conference 1991 Definitions 1. Systemic Inflammatory Response Syndrome (SIRS) 2. Sepsis (SIRS + infection) 3. Severe Sepsis (sepsis + end-organ damage) 4. Septic Shock (severe sepsis + hypotension despite a fluid bolus) Bone RC, et al: Chest 1992; 101:1644 â&#x20AC;&#x201C;1655 Crit Care Med 1992; 20:864 14
Sepsis: Progressive Disease Infection
Microbiological Phenomenon
Sepsis
Infection + SIRS
Severe Sepsis
Sepsis + End-Organ Damage
Septic Shock
Severe Sepsis + Refractory Hypotension
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Sepsis: Pathophysiology
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Sepsis: A complex disease
Systemic Inflammation
Coagulation
Sepsis Impaired Fibrinolysis
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Hemostasis is unbalanced in severe sepsis Coagulation Inflammation
Fibrinolysis
Hemostasis
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Sepsis: Pathophysiology Micro-organism
Microbial Products Host Inflammatory Mediators Inflammation
Coagulation 19
Sepsis: Pathophysiology Final Common Pathway Endothelial Cell Injury & Microvascular Thrombosis
Hypoperfusion/Ischemia Acute Organ Dysfunction
Death 20
Surviving Sepsis Campaign
Crit Care Med 2008 Reprint Also published in Intensive Care Medicine (January 2008) 22
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Management of Severe Sepsis : Activated Protein C (Xigris)
Fluid resuscitation Early Antibiotics Goal-Directed Rx
Source control
Low Dose Steroids
Hemodynamic support Intensive Mechanical ventilation Insulin Tx Nutritional support Renal replacement Rx
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Initial Resuscitation • Fluid resuscitation as soon as sepsis suspected • Should not wait until ICU admission • Elevated lactate identifies tissue hypoperfusion in at-risk patients who are not hypotensive • Resuscitation goals: EGDT
Rivers et al. NEJM 2001;345:1368-77
Early goal-directed therapy in severe sepsis & septic shock SIRS Golden hours Sepsis
Severe Sepsis
Septic Shock
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From Dellinger RP. Cardiovascular management of septic shock. Crit Care Med 2003;31:946-955. 27
Early goal-directed therapy in severe sepsis & septic shock â&#x20AC;˘ Involves manipulation of cardiac preload, afterload, and contractility to achieve a balance between systemic oxygen delivery and oxygen demand
â&#x20AC;˘ Resuscitation end points: CVP, BP, venous oxygen saturation, arterial lactate concentration
N Engl J Med 2001;345:1368-77
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Protocol for Early Goal-Directed Therapy Central venous and arterial catheterization CVP 8 -12 mm Hg
MAP 65 and 90 mm Hg
ScvO2 70%
Crystalloid Colloid Vasoactive agents Transf. of RBC until Hct 30% Inotropic agents
Goals achieved Hospital admission
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Early Goal-Directed Therapy Results 28-day Mortality 60 50
49.2%
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P = 0.01* 33.3%
30 20 10 0
Standard Therapy n=133
EGDT n=130
Rivers E. N Engl J Med 2001;345:1368-77.
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Fluid Therapy • Colloid or crystolloid resuscitation is considered equal – Natural or artificial colloids (less peripheral edema) – Crystalloids (less cost)
• Fluid challenge over 30 min – 500-1000 ml crystalloid – 300–500 ml colloid
• Target CVP 8 mm Hg (12 mm Hg in mechanically ventilated patients) 32
Vasopressors • Norepinephrine or dopamine through a central catheter is the initial vasopressor of choice. – Failure of fluid resuscitation – During fluid resuscitation attempts
• Do not use low-dose dopamine for renal protection • In patients requiring vasopressors, place an arterial catheter as soon as possible 33
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Vasopressin and Septic Shock •• Decreases or eliminates requirements of traditional pressors • As a pure vasopressor, expected to decrease cardiac output • Consider in refractory shock despite high dose conventional vasopressors • 0.01-0.04 units/minute in adults 35
Inotropic Therapy • Consider dobutamine in patients with measured low cardiac output despite fluid resuscitation. • Continue to titrate vasopressor to mean arterial pressure of 65 mm Hg or greater. • Do not increase cardiac index to achieve an arbitrarily predefined elevated level of oxygen delivery. 36
Corticosteroids • IV hydrocortisone 200-300 mg/d for 7 days – recommended in patients with septic shock who, despite adequate fluid replacement, require pressors to maintain adequate BP – Decreased mortality in patients with relative adrenal insufficiency
Annane et al. JAMA 2002;288:862-71 Briegel et al. Crit Care Med 1999;27:723-32
Controversies and Future Directions 1. How generalizable is EGDT to other populations? 2. How cost-effective is EGDT? 3. How are time and resources utilized so that the EGDT protocol is accomplished? 4. Which components of EGDT actually make a difference in outcomes?
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Mortality Reduction • 2006 analysis of available randomized and observational data from 12 centers, totaling 1,298 patients, yielded similar results – Mortality was reduced from 44.8% in the control group to 24.5% in the EGDT group
for every 5 EGDT patients, one life was saved • This is better than aspirin + streptokinase for MI 5-week mortality (NNT=19) or tPA for acute ischemic stroke within 4.5 hours (NNT=15) CHEST 2006; 130; 1579-1595.
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EGDT decreases health care resource consumption â&#x20AC;˘ Decrease in vasopressor use, hospital and ICU LOS, and MV days
â&#x20AC;˘ With a long ED wait time for an ICU bed, there are few options other than making this an ED intervention
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Take home message
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Employ EGDT & Sepsis Bundles in the treatment of severe sepsis and septic shock • if you want to save lives, • save your institution money, • improve your department’s standing in the house of medicine
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Thank You