Sepsis and the Systemic Inflammatory Response Syndrome

Outline
1. Definitions and Diagnostic Criteria
2. Pathophysiology 3. Prognosis 4. Treatment 5. Example Cases

and tachypnea. and is generally manifested as a combination of vital sign abnormalities including fever or hypothermia. tachycardia. that may or may not be due to infection.What is SIRS? The systemic inflammatory response syndrome is systemic level of acute inflammation. .

Sepsis – SIRS which is secondary to infection.Definitions Severe SIRS – SIRS in which at least 1 major organ system has failed. Severe Sepsis – Severe SIRS which is secondary to infection. . Septic Shock – Severe sepsis resulting in hypotensive cardiovascular failure.

in the absence of intrinsic heart disease) WBC > 10.000/mm3 or >10% band forms on differential .3° or <36.000/mm3 or <4.0° C Tachypnea (RR>20 or MV>10L) Tachycardia (HR>90.Criteria for SIRS Requires 2 of the following 4 features to be present: Temp >38.

0.000-100.5 x control.30 & lactate > 1.5mL/kg/hr) or renal failure Hyperbilirubinemia Coagulopathy (platelets < 80. plus 1 of the following: Altered mental status SBP<90mmHg or fall of >40mmHg from baseline Impaired gas exchange (PaO2/FiO2 ratio<200-250) Metabolic acidosis (pH<7.000/mm3. INR >2.5 x upper limit of normal) Oliguria (<0.Criteria for Severe SIRS Must meet criteria for SIRS. or elevated fibrin degredation products) . PTT >1.

et al. 2nd ed. Critical Care Medicine. . 1997.Relationship Between SIRS and Sepsis Adapted from: Marini JJ.

Risk Factors for SIRS/Sepsis Extremes of age Indwelling lines/catheters Immunocompromised states Malnutrition Alcoholism Malignancy Diabetes Cirrhosis Male sex Genetic predisposition? .

with massive. uncontrolled release of proinflammatory mediators. .Pathophysiology Although inflammation is essential to host response against infection. SIRS results from a dysregulation of the normal response.

Pathophysiology Vasodilation: Activation of ATP-sensitive K+ channels in the vascular smooth muscle Increased synthesis of NO as a result of increased levels of the enzyme. inducible NO synthase Deficiency of vasopressin Intravascular Volume Depletion: Increased capillary permeability leading to thirdspacing of fluid Concurrent volume loss from vomiting or diarrhea .

with each additional organ failure raising the mortality rate by 15%. Mortality is roughly linearly related to the number of organ failures.Prognosis Overall mortality from SIRS/sepsis in the U. Hypothermia is one of the worst prognostic signs. . Patients presenting with SIRS and hypothermia have an overall mortality of ~80%. is approximately 20%.S.

glycemic control.Treatment Fluid Resuscitation Vasopressors Antibiotics Eradication of infection Ventilatory support. nutrition . steroids. activated protein C.

Treatment (Fluid Resuscitation) Rapid. length of stay. Although resuscitation with colloid will necessitate less overall volume of fluid. large volume infusions are generally indicated in all patients with septic shock. with an average requirement of 4-6L. . Some patients require up to 10L of crystalloid in the first 24 hours. or survival. there is no difference between patients treated with colloid versus crystalloid in the development of pulmonary edema.

A goal MAP should be 60-65mmHg. and skin perfusion are better variables to use in monitoring adequate perfusion. . mental status.Treatment (Vasopressors) These are second line agents in the treatment of septic shock (after volume resuscitation). although urine output.

In general. therapy should include two effective agents from different classes. for example. taking into consideration the likely source of infection. a beta-lactam and an aminoglycoside .Treatment (Antibiotics) Empiric antibiotic therapy should be instituted immediately after appropriate cultures have been drawn.

Treatment (Mechanical Ventilation) Nearly all patients with septic shock require supplemental oxygen. and approximately 80% require mechanical ventilation. Use of mechanical ventilation not only may improve oxygenation. but the necessary sedation +/.paralysis may improve organ perfusion by diverting blood flow away from the diaphragm. .

APC has been found to not be cost effective in those patients with APACHE II scores <25 or in those with relatively low life-expectancy even in the event of survival from sespis.Treatment (Activated Protein C) The PROWESS trial showed that patients who received a 96hr infusion of APC within 24 hours of presentation had a statistically lower 28-day mortality rate (25% vs. 31%). Treatment was of greater benefit in the most acutely ill patients (APACHE II score ≥ 25). .

345:1368-77.) . 31% to 47%. in which patients receiving this goaldirected therapy had improved in-hospital mortality compared to those with “standard” therapy.Protocol for Early Goal Directed Therapy in Septic Shock (Adapted from NEJM 2001.

6. She is currently complaining of some chills and a sensation of thirst. Her past medical history is significant for diabetes. Her vitals on exam: T=38. BP=128/65. but the remainder of her exam is otherwise normal. and COPD. RR=16. She is mildly diaphoretic.Case 1 An 82 year old nursing home resident is brought to the ER by ambulance for an intermittent fever that has lasted about 36 hours. hypertension. O2 sat=94% on RA. HR=95. .

HR=137. On exam. His vitals on presentation: T=39. He has crackles at the right lung base. He has had recent admissions to the hospital for alcohol withdrawal. His abdomen is benign. a 2/6 systolic murmur at the right upper sternal border.5. BP=114/40. RR=18. however he has a severe cellulitis with underlying fluctuance beneath his right forearm. O2 sat=96% on RA.Case 2 A 45 year old homeless IV drug user is brought to the ER by a friend because “he looked really sick today and wasn’t making any sense”. he appears both acutely and chronically ill. and is lethargic and only oriented to self. and is known to have early cirrhosis without a history of encephalopathy. .

Upon admission. BP=125/50. he is tremulous. However. RR=34. when the nursing assistant went in to take his vitals. The patient is currently complaining of shortness of breath and states that he feels “terrible”. O2 sat=85% on 4L. and given morphine prn for pain control. made NPO. His abdomen is moderately tender in the epigastric region. His vitals at this time: T=36. . but without peritoneal signs. you are called to attend to a cross-cover patient on a non-monitored bed – a 56 year old alcoholic admitted yesterday for alcoholic pancreatitis. you were told he had “mild pancreatitis” and that there “is nothing to do”. During sign-out. Upon exam. she found him to be in mild to moderate respiratory distress and “looking bad”. HR=140. His lungs have diffuse crackles bilaterally.Case 3 As the on-call intern. he was placed on D5 ½NS at 125cc/hr.5. but alert and oriented.

HR=135. . O2 sat=84% on RA.5. She became stuck in traffic on the way to the hospital. His abdomen appears mildly tender diffusely. His vitals upon arrival: T=40. BP=76/30. he appears cachectic and acutely ill. He is lethargic and is mumbling incoherently. Cardiac exam is significant only for a regular tachycardia. and during the 60 minute trip he has become confused and “sweaty”. His lung exam is significant for moderate bilateral crackles. RR=34. The remainder of the exam is unremarkable. On exam. but without peritoneal signs.Case 4 A 67 year old man with metastatic colon cancer is brought to the ER by his wife because he developed a “high fever” and was “just not looking very well” for the past day.

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