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Programme in Critical Care University of Western Ontario London, Ontario, Canada SIRS, Sepsis, and...
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Transcript of Programme in Critical Care University of Western Ontario London, Ontario, Canada SIRS, Sepsis, and...
Programme in Critical CareUniversity of Western Ontario
London, Ontario, Canada
SIRS, Sepsis, and MODS
Claudio Martin, MSc, MD
Objectives
• To know definitions of SIRS, sepsis, septic shock, MODS
• To become familiar with the epidemiology of sepsis
• To learn basic pathophysiology (inflammation, cardiovascular physiology) of SIRS and sepsis
But first, a real case:
Case presentation
• 43-year-old male• Flu-like symptoms for 1
day• In ER
– Temp 39.5– Pulse 130– Blood pressure 70/30– Respirations 32– Petechial rash– Chest, CV, Abdominal
exam normal
Case presentation - 2
• Laboratory– pH 7.29, PaO2 82,
PaCO2 29• Investigations pending
– Blood, urine cultures• Orally intubated and
placed on mechanical ventilation
• Central venous catheter inserted– Cefotaxime 2 g iv– Normal saline 2 litres
initially, repeated• Admitted to ICU
Case presentation - 3
• In ICU:– Noradrenaline started to
support blood pressure– Additional fluid (saline
and pentastarch) given based on low CVP
– Pulmonary artery catheter inserted to aid further hemodynamic management
• Despite therapy patient remained anuric– Continuous venovenous
hemofiltration initiated
Case presentation - 4
• Early gram stain on blood revealed gram negative rods
• Patient started on:– Hydrocortisone 100 mg iv q8h– Recombinant activated protein C
24g/kg/hour for 96 hours– Enrolled in RCT (double-blind) of vasopressin
vs norepinephrine for BP support– Enteral nutrition via nasojejunal feeding tube– Prophylaxis for stress ulcers, deep venous
thromboses
Case Presentation - Resolution
• Patient gradually stabilized and improved with complete resolution of organ dysfunction over 5 days
• Final cultures confirmed diagnosis as meningococcemia
Infection: Part of a bigger picture
• Infection:– Presence of organisms in a
closed space or location where not normally found
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.Opal SM et al. Crit Care Med. 2000;28:S81-2.
Infection
SIRS: Systemic Inflammatory Response Syndrome
• SIRS: A clinical response arising from a nonspecific insult manifested by 2 of the following:– Temperature
38°C or 36°C– HR 90 beats/min– Respirations 20/min– WBC count
12,000/mL or 4,000/mL or >10% immature neutrophilsAdapted from: Bone RC et al. Chest. 1992;101:1644-55.
Opal SM et al. Crit Care Med. 2000;28:S81-2.
Sepsis: More Than Just Inflammation
• Sepsis:– Known or suspected
infection– SIRS criteria
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Severe Sepsis: Acute Organ Dysfunction
• Severe Sepsis = Sepsis with signs of acute organ dysfunction in any of the following systems: – Cardiovascular (septic
shock)– Renal– Respiratory– Hepatic– Hemostasis– CNS– Unexplained metabolic
acidosisAdapted from: Bone RC et al. Chest. 1992;101:1644-55.
Sepsis: A Complex Disease
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.Opal SM et al. Crit Care Med. 2000;28:S81-2.
Predisposition
• Pre-existing disease– Cardiac, Pulmonary, Renal– HIV
• Age (extremes of age) • Gender (males)• Genetics
– TNF polymorphisms (TNF promoter high secretor genotype)
Response
• Physiology– Heart rate– Respiration– Fever– Blood pressure– Cardiac output– WBC– Hyperglycemia
• Markers of Inflammation– TNF– IL-1– IL-6– Procalcitonin– PAF
Organ Dysfunction
• Lungs
• Kidneys
• CVS
• CNS
• PNS
• Coagulation
• GI
• Liver
• Endocrine
• Skeletal Muscle
Adult Respiratory Distress Syndrome Acute Tubular Necrosis Shock Metabolic encephalopathy Critical Illness Polyneuropathy Disseminated Intravascular Coagulopathy Gastroparesis and ileus Cholestasis Adrenal insufficiency Rhabdomyolysis
Specific therapy exists
Magnitude of the Problem
• Estimated 215,000 deaths from US 1995 data• High cost for management (ICU care,
diagnostic testing, drugs)– Estimated 20 day LOS; $22,000 cost
• Represents 9.3% of all deaths• Equals deaths after acute myocardial infarction
Sepsis: Defining a Disease Continuum
A clinical response arisingfrom a nonspecific insult, including 2 of the following:– Temperature ≥38oC or
≤36oC– HR ≥90 beats/min– Respirations ≥20/min– WBC count
≥12,000/mm3 or ≤4,000/mm3 or >10% immature neutrophils SIRS = systemic inflammatory response SIRS = systemic inflammatory response
syndrome.syndrome.
Bone et al. Bone et al. Chest.Chest. 1992;101:1644. 1992;101:1644.
SIRS with a presumed or confirmed infectious process
SepsisSepsisSIRSSIRSInfection/Infection/TraumaTrauma Severe SepsisSevere Sepsis
Sepsis: Defining a Disease Continuum
Bone et al. Bone et al. Chest.Chest. 1992;101:1644; Wheeler and Bernard. 1992;101:1644; Wheeler and Bernard. N Engl J MedN Engl J Med. 1999;340:207. . 1999;340:207.
SepsisSepsisSIRSSIRSInfection/Infection/TraumaTrauma Severe SepsisSevere Sepsis
• Sepsis with ≥1 sign of organ failure– Cardiovascular (refractory
hypotension)– Renal– Respiratory– Hepatic– Hematologic– CNS– Unexplained metabolic
acidosis
ShockShock
Epidemiology of SepsisThe International Cohort Study
SepsisSepsisInfectionInfection Severe Severe SepsisSepsis
Septic Septic ShockShock
18 28 24 30
35% mortality
8353 patients with LOS > 24h4277 infections (2696 on admission)
Percent of cases within each category
Alberti, Int Care Med 2002
Sources of SepsisThe International Cohort Study
Severe Severe SepsisSepsis
Septic Septic ShockShock
Respiratory 66 53
Abdomen 9 20
Bacteremia 14 16
Urinary 11 11
Multiple - -
Microbiology of SepsisThe International Cohort Study
Severe Severe SepsisSepsis
Septic Septic ShockShock
Gram-positive 44 40
Gram-negative 47 47
Fungal 9 13
Polymicrobial - -
Inadequate Resuscitation
Preoperative Illness
Trauma or Operation
Tissue Injury
optimal oxygen delivery and
support
Recovery
Excessive Inflammatory
Response
SIRS/MODS
Pathogenesis of SIRS/MODS
Homeostasis Is Unbalanced in Severe Sepsis
Carvalho AC, Freeman NJ. J Crit Illness. 1994;9:51-75; Kidokoro A et al. Shock. 1996;5:223-8; Vervloet MG et al. Semin Thromb Hemost. 1998;24:33-44.
Inadequate Resuscitation
Preoperative Illness
Trauma or Operation
Tissue Injury
optimal oxygen delivery and
support
Recovery
Excessive Inflammatory
Response
SIRS/MODS
Pathogenesis of SIRS/MODS
QO2 = Flow * O2 content
BP=CO * SVR
Intra Organ Distribution
regional distribution
Microcirculation
Cardiac Output
Intra Organ Distribution
regional distribution
Microcirculation
Regulation of oxygen delivery
Cardiac output
Normal Abnormal
Oxygen Consumption
III
NADH + H+
NAD+ADP + Pi
1/2 O2 + H+
ATP
I
H+ Cytc
H2O
H+
H+
H+ H+
Q IV
•Pyruvate Dehydrogenase (PDH) activity decreased
•Decreased delivery of Acetyl CoA to TCA cycle
•Mitochondrial dysfunction
Severe Sepsis: The Final Common Pathway
Endothelial Dysfunction and Microvascular Thrombosis
Hypoperfusion/Ischemia
Acute Organ Dysfunction (Severe Sepsis)
Death