Sepsis and the Systemic Sepsis and the Systemic Inflammatory Response SyndromeInflammatory Response Syndrome

M. Farid WajdiM. Farid WajdiFK Unram/RSUP Prop MataramFK Unram/RSUP Prop Mataram

OutlineOutline

1.1. Definitions and Diagnostic CriteriaDefinitions and Diagnostic Criteria2.2. EpidemiologyEpidemiology3.3. PathophysiologyPathophysiology4.4. TreatmentTreatment

What is SIRS?What is SIRS?

The systemic inflammatory response The systemic inflammatory response syndrome is systemic level of acute syndrome is systemic level of acute inflammation, and is generally manifested as inflammation, and is generally manifested as a combination of vital sign abnormalities a combination of vital sign abnormalities including fever or hypothermia, tachycardia, including fever or hypothermia, tachycardia, and tachypnea.and tachypnea.

Criteria for SIRSCriteria for SIRS

Requires 2 of the following 4 features to be Requires 2 of the following 4 features to be present:present:

Temp >38.3° or <36.0° CTemp >38.3° or <36.0° CTachypnea (RR>20 or MV>10L)Tachypnea (RR>20 or MV>10L)Tachycardia (HR>90, in the absence of Tachycardia (HR>90, in the absence of intrinsic heart disease)intrinsic heart disease)WBC > 10,000/mmWBC > 10,000/mm33 or <4,000/mm or <4,000/mm33 or or

>10% band forms on differential >10% band forms on differential

DefinitionsDefinitionsSystemic Inflammatory ResponseSystemic Inflammatory ResponseSyndrome (SIRS) :Syndrome (SIRS) :► Systemic inflammatory response to various Systemic inflammatory response to various

stresses.stresses.► Meets 2 or more of the following criteria :Meets 2 or more of the following criteria :

– Temperature of >38C/<36degree CTemperature of >38C/<36degree C– Heart rate of more than 90 beats/minHeart rate of more than 90 beats/min– RR >20 breaths/min or PaCo2 <32mmHgRR >20 breaths/min or PaCo2 <32mmHg– WBC >12,000/mm3 or <4000/mm3WBC >12,000/mm3 or <4000/mm3

DefinitionsDefinitionsSEPSIS :SEPSIS :► Evidence of SIRS accompanied by known or suspected Evidence of SIRS accompanied by known or suspected

infection.infection.

Severe SEPSIS :Severe SEPSIS :► Sepsis accompanied by hypoperfusion or organ Sepsis accompanied by hypoperfusion or organ

dysfunction.dysfunction.► Cardiovascular : Cardiovascular :

– SBP<90mmhg/MAP<70 for at least 1 hr despite SBP<90mmhg/MAP<70 for at least 1 hr despite adequate volume adequate volume resuscitation or the use of vasopressors to achieve the same goals.resuscitation or the use of vasopressors to achieve the same goals.

► Renal : Renal : – Urine output <0.5ml/kg/hr or Acute Renal Failure.Urine output <0.5ml/kg/hr or Acute Renal Failure.

► Pulmonary : Pulmonary : – PaO2/FiO2 <250if other organ dysfuncton is present or <200 if the PaO2/FiO2 <250if other organ dysfuncton is present or <200 if the

lungs is the only dysfunctional organ.lungs is the only dysfunctional organ.

DefinitionsDefinitionsSevere SEPSIS (contd) :Severe SEPSIS (contd) :► Gastrointestinal : Gastrointestinal :

– Hepatic dysfunction (hyperbilirubinemia,Elevated transaminasesHepatic dysfunction (hyperbilirubinemia,Elevated transaminases► CNS : CNS :

– Alteration in Mental status (delirium)Alteration in Mental status (delirium)► Hematologic : Hematologic :

– Platelet count of <80,000/mm3 or decreased by 50% over 3 Platelet count of <80,000/mm3 or decreased by 50% over 3 days/DICdays/DIC

► Metabolic : Metabolic : – PH<7.30 or base deficit >5.0mmol/LPH<7.30 or base deficit >5.0mmol/L– Plasma lactate >1.5 upper limit of normal.Plasma lactate >1.5 upper limit of normal.

Septic Shock :Septic Shock :► Severe Sepsis with persistent hypoperfusion or Severe Sepsis with persistent hypoperfusion or

hypotension despite adequate fluid resuscitationhypotension despite adequate fluid resuscitation

EpidemiologyEpidemiology

► Current estimates suggest that over 750,000 cases of Current estimates suggest that over 750,000 cases of Sepsis are diagnosed annually, resulting in more than Sepsis are diagnosed annually, resulting in more than 200,000 deaths.200,000 deaths.

► The incidence rate for Sepsis has been increasing over The incidence rate for Sepsis has been increasing over the past two decades, driving an increase in the number the past two decades, driving an increase in the number of deaths despite a decline in case-fatality rates.of deaths despite a decline in case-fatality rates.

► Sepsis is the tenth leading cause of death in the United Sepsis is the tenth leading cause of death in the United States and accounts for more than 17 billion dollars in States and accounts for more than 17 billion dollars in direct healthcare expenditures.direct healthcare expenditures.

► Risk factors include age > 65 years, male, non-whites. Risk factors include age > 65 years, male, non-whites. ► A primary site of infection cannot be established in 10% A primary site of infection cannot be established in 10%

of patients with severe Sepsis/SIRS.of patients with severe Sepsis/SIRS.

Epidemiology:Epidemiology:

Epidemiology : Mortality rateEpidemiology : Mortality rate

Epidemiology : Causative organismEpidemiology : Causative organism

Relationship Between SIRS and SepsisRelationship Between SIRS and Sepsis

Adapted from: Marini JJ, et al. Critical Care Medicine, 2nd ed. 1997.

Risk Factors for SIRS/SepsisRisk Factors for SIRS/SepsisExtremes of ageExtremes of ageIndwelling lines/cathetersIndwelling lines/cathetersImmunocompromised statesImmunocompromised statesMalnutritionMalnutritionAlcoholismAlcoholismMalignancy Malignancy DiabetesDiabetesCirrhosisCirrhosisMale sexMale sexGenetic predisposition? Genetic predisposition?

PathophysiologyPathophysiology

Although inflammation is essential to host response against infection, SIRS results from a dysregulation of the normal response, with massive, uncontrolled release of pro-inflammatory mediators.

PathophysiologyPathophysiologyVasodilation:Vasodilation:

Activation of ATP-sensitive KActivation of ATP-sensitive K++ channels in the channels in the vascular smooth musclevascular smooth muscleIncreased synthesis of NO as a result of increased Increased synthesis of NO as a result of increased levels of the enzyme, inducible NO synthaselevels of the enzyme, inducible NO synthaseDeficiency of vasopressin Deficiency of vasopressin

Intravascular Volume Depletion:Intravascular Volume Depletion:Increased capillary permeability leading to third-Increased capillary permeability leading to third-spacing of fluidspacing of fluidConcurrent volume loss from vomiting or diarrhea Concurrent volume loss from vomiting or diarrhea

TreatmentTreatment

Fluid ResuscitationFluid Resuscitation

VasopressorsVasopressorsAntibioticsAntibioticsEradication of infectionEradication of infection

Ventilatory support, activated protein C, Ventilatory support, activated protein C, steroids, glycemic control, nutritionsteroids, glycemic control, nutrition

TreatmentTreatment(Fluid Resuscitation)(Fluid Resuscitation)

Rapid, large volume infusions are generally Rapid, large volume infusions are generally indicated in all patients with septic shock. indicated in all patients with septic shock.

Some patients require up to 10L of crystalloid in Some patients require up to 10L of crystalloid in the first 24 hours, with an average requirement the first 24 hours, with an average requirement of 4-6L. of 4-6L.

Although resuscitation with colloid will Although resuscitation with colloid will necessitate less overall volume of fluid, there is necessitate less overall volume of fluid, there is no difference between patients treated with no difference between patients treated with colloid versus crystalloid in the development of colloid versus crystalloid in the development of pulmonary edema, length of stay, or survival. pulmonary edema, length of stay, or survival.

TreatmentTreatment(Vasopressors)(Vasopressors)

These are second line agents in the These are second line agents in the treatment of septic shock (after volume treatment of septic shock (after volume resuscitation). resuscitation).

A goal MAP should be 60-65mmHg, A goal MAP should be 60-65mmHg, although urine output, mental status, and although urine output, mental status, and skin perfusion are better variables to use skin perfusion are better variables to use in monitoring adequate perfusion. in monitoring adequate perfusion.

TreatmentTreatment(Antibiotics)(Antibiotics)

Empiric antibiotic therapy should be instituted Empiric antibiotic therapy should be instituted immediately after appropriate cultures have immediately after appropriate cultures have been drawn, taking into consideration the been drawn, taking into consideration the likely source of infection,likely source of infection,

In general, therapy should include two In general, therapy should include two effective agents from different classes, for effective agents from different classes, for example, a beta-lactam and an example, a beta-lactam and an aminoglycoside aminoglycoside

TreatmentTreatment(Mechanical Ventilation)(Mechanical Ventilation)

Nearly all patients with septic shock Nearly all patients with septic shock require supplemental oxygen, and require supplemental oxygen, and approximately 80% require mechanical approximately 80% require mechanical ventilation. ventilation.

Use of mechanical ventilation not only Use of mechanical ventilation not only may improve oxygenation, but the may improve oxygenation, but the necessary sedation +/- paralysis may necessary sedation +/- paralysis may improve organ perfusion by diverting blood improve organ perfusion by diverting blood flow away from the diaphragm. flow away from the diaphragm.

TreatmentTreatment(Activated Protein C)(Activated Protein C)

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

TerimakasihTerimakasih

Protocol for Early Goal Directed Therapy in Protocol for Early Goal Directed Therapy in

Septic ShockSeptic Shock

(Adapted from NEJM 2001; 345:1368-77, in which patients receiving this goal-directed therapy had im-proved in-hospital mortality compared to those with “standard” therapy, 31% to 47%.)