SAMIR EL ANSARY

DefinitionsSepsis = suspected or proven infection

and some of the following:General VariablesInflammatory VariablesHemodynamic VariablesOrgan Dysfunction VariablesTissue Perfusion Variables

Sepsis VariablesGeneral InflammatoryFeverHypothermiaTachycardiaAltered Mental StatusEdemaHyperglycemia

LeukocytosisLeukopeniaNormal WBC with > 10

% immature formsC-reactive protein > 2

SDProcalcitonin > 2 SD

Sepsis VariablesHemodynamic Organ DysfunctionSBP <90MAP < 70SBP decrease > 40

Tissue PerfusionLactate > 1MottlingDecreased Capillary

Refill

P/F < 300UO < .5 ml/kg for 2

hours despite volume resuscitation

Cr increase > .5INR > 1.5IleusPlt < 100 KBili > 4

Severe Sepsis DefinitionSepsis induced organ dysfunction, hypoperfusion,

or hypotensionHypotensionElevated Lactic AcidOliguriaALI with P/F < 250 without pneumoniaALI with P/F < 200with pneumonia

Cr > 2Bili > 2Plt < 100KINR > 1.5

Septic Shock

Sepsis-induced hypotension that persists despite adequate fluid resuscitation

*All definitions cited from “Surviving Sepsis Campaign” published in Critical Care Medicine Feb 2013

SepsisSepsisInfectionInfection Severe Severe SepsisSepsis

Septic Septic ShockShock

Sepsis associated with any of the single organ dysfunctions is defined as severe sepsis, Although not shown here, severe sepsis

with two or more organs out is MODS. Severe sepsis with hypotension refractory to resuscitation is septic shock.

Deaths/Year

More people die in one year in North America from severe sepsis than from breast cancer, lung cancer, and colon cancer combined

More than 751,000 cases of severe sepsis in US annually. Increasing 1.5 % per annum, 1 mil/yr 2020 projection

Source control is most vital factor

Adequate resuscitation or re-established perfusion in 6 hours

Appropriate antibiotic therapy within 1 hr of hypotension

Determinants of Mortality

InterventionsEarly Goal Directed Therapy

(EGDT)Anti-microbialsSteroidsGlucose ControlLung Protective Ventilation

%

EGDT ResuscitationBegin at onset of hypotension or

lactate >4Do not delay while awaiting ICU

admissionInitial bolus is 30 ml/kg

crystalloid

Or mixed venous greater than or equ to 65%; Dobut infusion to max 20 microgr/kg/minute.

Early goal-directed resuscitation has been shown to The consensus panel judged use of central venous and

mixed venous oxygen saturation targets to be equivalent.

Either intermittent or continuous measurements of oxygen saturation were judged to be acceptable. Studies of patients with shock indicate that mixed venous oxygen saturation runs 5–7% lower than

central venous oxygen saturation (Scvo2)

EGDTInitial Resuscitation targets

CVP 8-12 (12-15 if mechanically ventilated)Mean arterial pressure ≥65Urine output ≥ 0.5 ml/kg/hourCentral venous oxygen saturation ≥ 65%If venous oxygen target still not achieved:

trial of fluid or transfuse PRBCs to HCT ≥30% and/or start dobutamine infusion

EGDT Outcomes

EGDT Cost23% reduction in hospital costMean reduction of 4 days per

hospital admissionCost per life savedReduction in hospital charges

What to Use?

Guideline: Colloid or crystalloid may be

usedUse of either 4 percent albumin or normal saline for fluid

resuscitation results in similar outcomes at 28 days.

EGDT (and we mean EARLY)

Adequate initial fluid resuscitation (AIFR) groupAdministration of an initial fluid bolus of ≥ 20

mL/kg prior to and achievement of a central venous pressure of ≥ 8 mm Hg within 6 h after the onset of therapy with a vasopressor

Conservative late fluid management (CLFM) Even-to-negative fluid balance measured on at least

2 consecutive days during the first 7 days after septic shock onset

Mean daily fluid balance days 1 through 7

NONSURVIVOR

S

SURVIVORS

VasopressorsMean arterial pressure (MAP)

maintained ≥ 65First choice: norepinephrine or

epinephrineVasopressin 0.03 units/min may be

added

Inotropes

Dobutamine infusion for suspected myocardial dysfunction suggested by elevated cardiac filling pressures and low cardiac output

Recommend against a strategy to increase cardiac index to supranormal levels

InterventionsEarly Goal Directed Therapy (EGDT)

Anti-microbialsSteroidsGlucose Control

AntimicrobialsBegin therapy within the first hour of recognizing

severe sepsis or septic shockBroad spectrum: one or more agents against likely

bacterial or fungal pathogensConsider combination therapy for potentially

resistant gram negative pathogensConsider combination therapy in neutropenic

patientsNarrow coverage when culture data available

InterventionsEarly Goal Directed Therapy

(EGDT)Anti-microbialsSteroidsGlucose Control

Steroid GuidelinesThe ACTH stimulation test should not be used to

identify the subset of adults with septic shock who should receive hydrocortisone.

Do not use corticosteroids in the treatment of sepsis in the absence of shock.

Corticosteroid therapy may be weaned when vasopressors are no longer required.

Recommended: hydrocortisone 50 mg iv q 6 hours

Also most cortisol assays measure total and free cortisol, while free is likely the pertinent

measurement. The corticol assays may over or underestimate the

the actual cortisol level since the relationship between free and total cortisol depends on serum

protein concentration.Dex can lead to profound and prolonged supression of the adrenal axis and along with no ACTH test, no

need for dex.

InterventionsEarly Goal Directed Therapy

(EGDT)Anti-microbialsSteroidsGlucose Control

Glucose ControversyLeuven protocol: 80-110Cardiac-surgical ICUReduced ICU LOSLess organ dysfunctionHypoglycemia 6.2%Decreased Mortality

3.4% ARR all patients9.4% ARR LOS >5 days

Leuven protocol: 80-110Medical ICU Reduced ICU LOSLess ventilator daysLess acute renal injuryHypoglycemia 18%Mortality difference

Overall: no difference LOS > 3 days: mortality↓

Glucose Control Guidelines

Patients with severe sepsis and hyperglycemia in the ICU should receive intravenous insulin.

Use validated protocol for insulin dose adjustment with a target glucose <180.

All patients on intravenous insulin receive a glucose calorie source.

Resuscitation “Bundles”Severe Sepsis 3 Hour Bundle

RecognitionFluid ResuscitationAntimicrobial TherapyOxygen Delivery

Severe Sepsis 6 Hour BundleLow-dose Steroids Glucose ControlLung Protective Ventilation

GOOD LUCK

SAMIR EL ANSARY