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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
The ACCP/SCCM consensus conference committee. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992.
Widespread inflammatory response Two or more of the following
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. 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. Chest 1992. . Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis.
Brief Pathophysiology Proinflammatory response to infection – Mediators TNF Alpha. IL-1. IL-6 Complement system (C5 alpha) Bacterial factors – Endotoxin. bacterial cell wall products. bacterial toxins Immunosuppressive .
Curr Opin Crit Care 2004.10:354-363) .Time-course of inflammatory response during sepsis (modified from Management of Severe Sepsis and Septic Shock.
348:138-150) . N Engl J Med 2003.(Modified from The Pathophysiology and Treatment of Sepsis.
Cellular dysfunction Cellular hypoxia – – – Reduced surface area for diffusion Reduction in RBC deformability Impaired utilization of oxygen by mitochondria Vasodilation (nitric oxide) Vascular permeability Circulatory system dysregulation – – .
PEEP >7. 50% increase in Cr.5ml/cc/kg/hr.3. high lactate Hepatic: LFTs >2x normal GI: Bacterial overgrowth and translocation .Acute Organ Dysfunction Neuro: altered mental status Respiratory: Mechanical ventilation? (PF ratio <250. acute dialysis Heme: Platelets <100.000 or PT/PTT elevated Metabolic: pH <7.5) CV: Pressors? SBP<90 or MAP<70 despite fluids Renal: UO <0.
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 .
– – – – Sphygmomanometer unreliable Arterial catheter CVP Mixed Venous O2 sat . unable to protect airway Breathing: Respiratory failure Circulation: Restoration of blood pressure to levels which perfuse core organs.Resuscitation Airway: AMS.
Restoration of tissue perfusion Causes of poor tissue perfusion – – – Interventions – Volume infusion Leaky vessels Decreased vascular tone Myocardial depression Intravenous fluids PRBCs – – Vasopressors Inotropes .
. Critical Care Medicine 1999 Administered in well-defined.Intravenous Fluids Practice parameters for hemodynamic support of sepsis in adult patient in sepsis . Crystalloid: No evidence to recommend one over the other. tissue perfusion. rapidly infused boluses Continued until blood pressure. and oxygen delivery acceptable or presence of pulmonary edema Colloid vs. Task Force of the ACCCM/SCCM.
Cardiogenic pulmonary edema. Dopamine. Epinephrine. Norepinephrine.Vasopressors Second-line agents Hypotensive despite fluid resuscitation. or elevated wedge pressure (>18) Vascoconstrictors – Phenylephrine. Vasopressin .
103(6):1826-31 .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 vs norepinephrine Observational studies suggest Norepinephrine as first line agent for fluid refractory hypotension Martin et al Chest 1993.
Critical Care Medicine 2001 VP given to 16 septic patients with refractory hypotension.(infusion rates of 0. Circulation 1997. VP infusion improved MAP and SVR – Current recs are to consider with refractory hypotension despite adequate fluid resuscitation and high-dose conventional vasopressors.Vasopressors Vasopressin – – Limited data. studies suggest may be useful in vasodilatory shock Vasopressin deficiency contributes to the vasodilation of septic shock. 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.04 units per min) .01-0.
Divert gut. etc Remove infectious source – .Eradicate infectious source Empiric broad spectrum antibiotics – – ASAP after blood cultures collected Modify as culture results dictate Remove catheter. Drain abscess/fluid collections.
+/-Dobutamine. Exclusion Criteria: Age<18. . pulmonary edema. If MAP >90 vasodilators given until <90. or sepsis syndrome.5%).5% vs. immediate surgery. Treatment: In ER 500 ml crystalloid given q 30 min to achieve CVP 8-12 mmHg. septic shock. NEJM. 2001 Study design: Prospective. randomized study in urban emergency department enrolling 263 patients Inclusion Criteria: Adults severe sepsis. Pressors given to achieve MAP >65. status asthmaticus. seizure. immunosupressed. uncured cancer. Higher mean ScvO2. trauma. lower lactate. DNR. drug OD.Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. GIB. burns. SBP<90 (after fluid bolus) or lactate>4. Nov 8. arrhythmia. lower base deficit and a higher pH. 46. SIRS. ACS. Results: Improved in-hospital mortality (30. transfused to Hct of 30. pregnancy. If ScvO2<70. acute CVA. Lower APACHE scores.
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 May be difficult to interpret Detection of tissue hypoxia--Lactate – Treatment of tissue hypoxia – – – – Maximize arterial oxygen content Keep SaO2 >97% Augment cardiac output Support hematocrit .
thrombin Diffuse endovascular injury. multiorgan dysfunction and death. – TNF-alpha.Activated protein C Known inflammatory and procoagulant host responses to infection. . IL-6. modulates the inflammatory response reduced levels of protein C found in majority of patients with sepsis and are associated with increased risk of death. IL-1. Activated Protein C – – anticoagulant.
double-blind.Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis.0% p=0.06) . placebo-controlled. NEJM 2001. 28 day mortality significantly lower in the APC group – 24. 30.690 patients with severe sepsis.8% Trend towards increased bleeding (3.7 vs. 96 hour infusion of recombinant APC or placebo beginning within 24 hours of presentation. multicenter trial enrolling 1.5 vs/ 2. Randomized.
Activated Protein C Guidelines .
controlled trials of pharmacologic doses of glucocorticoids in sepsis/septic shock Steroid controversy in sepsis and septic shock: A meta-analysis. randomized. Critical Care Medicine 1995 – – Glucocorticoids offer no benefit Positive findings reported in 1/10 trials .Glucocorticoids Ten prospective.
and hyperpigmentation not specific enough in ICU setting . weakness. hyperkalemia.Revisiting Steroids… Adrenal Insufficiency – – – – 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.
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.95. p=0. 95% CI 0. p=0.47-0.02) Withdraw of pressors: 57% vs 40% (Hazards ratio 1. double-blind.Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. Conclusion: 7 day treatment with steroids beneficial in patients with sepsis and adrenal insufficiency.67. randomized. parallel-group trial performed in 19 French ICUs.001) No difference in adverse outcomes.84. 2002 Placebo-controlled.292.91. Results: Corticosteroids vs. 95% CI 1. . Placebo – – – Deaths: 53% vs 63%(Hazards ratio 0. JAMA Aug 21.
JAMA Aug 21. 2002 .Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.
Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. 2002 . JAMA Aug 21.
Glucose Control 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) .
cardiac output Identify and eradicate infection APC in patients with severe sepsis Consider corticosteroids Glucose Control . oxygen saturation.Summary Ensure tissue perfusion: resuscitate early with liberal IVF. Ensure tissue oxygenation: oxygen content. pressors and inotropes.
) .Septic Shock Algorithm Example (modified from Septic Shock. Lancet 2005.365:63-78.
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