Protocol for Early Goal-Directed Therapy (EGDT) in the Treatment of Severe Sepsis and Septic Shock

Inclusion criteria (patient must meet both 1 and 2):

1. Fulfillment of two of four criteria for the systemic inflammatory response syndrome (SIRS)

AND

2. Systolic blood pressure (SBP) no higher than 90 mm Hg (after a crystalloid-fluid challenge of 20 to 30 ml per kg of body weight over a 30-min period) OR Lactate concentration of 4 mmol/L or more (blood lactic acid)

Note: Criteria for a diagnosis of SIRS are Temp C greater than or equal to 38C or less than 36C, HR greater than 90 bpm, Resp. rate greater than 20 breaths/min or PaCO2 than 32 mm Hg, and WBC greater than 12,000 per mm3 or less than 4000 per mm3 or the presence of more than 10 percent immature bands. Fulfillment of two of four criteria is required for enrollement in the treatment protocol.

Exclusion criteria (Contraindications): Age of less than 18 years Pregnancy Acute cerebral vascular event Acute coronary syndrome Acute pulmonary edema Status asthmaticus Cardiac dysrhythmias (as a primary diagnosis) Contraindication to central venous catheterization Active gastrointestinal hemorrhage Seizure Drug overdose Burn injury Trauma Requirement for immediate surgery DNR-CC status (DNR-CCA is not an exclusion criteria) Advanced directives restricting implementation of the protocol

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Protocol Start

Intensive care unit.

Patient assigned to early goal-directed therapy (EGDT) must receive a central venous catheter capable of measuring central venous oxygen saturation (Edwards Lifesciences, Irvine, Calif.).

The catheter needs to be calibrated in-vitro, i.e. before placing in the vein. A nurse should connect the blue endpiece of the catheter to the monitor and calibrate the catheter according to the instructions.

A physician should place the catheter in a central vein. Access sites: Internal Jugular vein or Subclavian vein. Femoral access is not acceptable.

Catheter is placed using the standard Seldinger technique under sterile precautions. After placement the catheter must be connected to a computerized spectrophotometer for continuous monitoring.

The protocol is as follows:

A 500-ml bolus of crystalloid (normal saline) is given every 30 minutes to achieve a central venous pressure (CVP) of 8 to 12 mm Hg.

If the mean arterial pressure (MAP) is less than 65 mm Hg, vasopressors are given to maintain a MAP of at least 65 mm Hg.

If the MAP is greater than 90 mm Hg, vasodilators were given until it was 90 mm Hg or below.

If the central venous oxygen saturation (ScvO2) is less than 70 percent, red cells (PRBC) are transfused to achieve a hematocrit of at least 30 percent.

Dobutamine After the CVP, MAP, and hematocrit are thus optimized, if the ScvO2 is less than 70 percent, dobutamine administration is started at a dose of 2.5 mcg per kilogram of body weight per minute, a dose that is increased by 2.5 mcg per kilogram per minute every 30 minutes until the ScvO2 is 70 percent or higher or until a maximal dose of 20 mcg per kilogram per minute is given. Dobutamine is decreased in dose or discontinued if the MAP is less than 65 mm Hg or if the HR is above 120 bpm.

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OR

Levophed Levophed (norepinephrine) can be used as a pressor of choice instead of dobutamine. If the ScvO2 is less than 70 percent, Levophed administration is started at a dose of 2 mcg per minute, a dose that is increased by 2 mcg per minute every 30 minutes until the ScvO2 is 70 percent or higher or until a maximal dose of 20 mcg per minute is given. Levophed is decreased in dose or discontinued if the MAP is less than 65 mm Hg or if the HR is above 120 bpm.

To decrease oxygen consumption, patients in whom hemodynamic optimization could not be achieved should receive mechanical ventilation and sedatives.

Patient Monitoring

The patients' temperature, HR, urine output, BP, and CVP are measured continuously for the first 6 hours of treatment and assessed every 12 hours for 72 hours. Arterial and venous blood gas values (including central venous oxygen saturation measured by in vitro co-oximetry), lactate concentrations, and coagulation-related variables are measured at 3, 6, 12, 24, 36, 48, 60, and 72 hours.

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