The Effect of Recombinant Human Erythropoietin (rHuEPO) on Microcircualtory Alteration in Intensive Care Unit Patients With Severe Sepsis and Septic Shock

Recruitment Critical Care research coordinators and a Research Fellow will screen patients for severe sepsis and septic shock in the London Health Sciences Center-Critical Care Trauma Center (LHSC-CCTC). The patients who meet the inclusion criteria will be introduced to this study. Informed consent will be obtained from the patient or a family member or a substitute decision maker.

Inclusion Criteria:

• The patients must be 18 years old and over to be included in the study. They must meet criteria for sepsis defined as:40

  1. Two or more criteria for the systemic inflammatory response syndrome (SIRS):

     • heart rate greater than 90 beats per minute, or paced, or taking beta-blockers or the calcium channel blockers verapamil or diltiazem
     • respiratory rate greater than 20 breathes per minute, or a PaC02 less than 32 mmHg, or mechanically ventilated
     • temperature greater than 38 or less than 36 degrees Celsius
     • white blood cell count greater than 12 x 109/L or less than 4 x 109/L, or more than 10% bands on the differential.

  2. Suspected or confirmed source of infection

     And either one of the following definitions:

  3. Severe Sepsis: Sepsis with at least one organ dysfunction defined as urine output < 0.5 ml/kg/hr for 1 hour, PaO2/FiO2 < 250 (less than 200 if lung is the only dysfunctional organ), platelets < 80 x109/L or a 50% decrease from baseline in the past 3 days, or pH < 7.30 or lactate > 1.5 mmole/L upper normal with base deficit > 5
  4. Septic shock <48hrs: Persistent arterial hypotension with a systolic pressure < 90 mmHg or a MAP < 60 mmHg or a reduction of in systolic blood pressure > 40 mmHg from baseline, despite adequate fluid resuscitation in the absence of other cause for hypotension or requiring the administration of a pressor agent to maintain the above blood pressure.

Exclusion Criteria:

• Clinically apparent other forms of shock including cardiogenic, obstructive (massive pulmonary embolism, cardiac tamponade, tension pneumothorax) or hemorrhagic shock
• A known previous severe reaction to erythropoietin
• Uncontrolled hypertension (hypertensive urgency, hypertensive emergency and hypertensive encephalopathy)
• Myocardial infarction and/or stroke within one month
• Hypersensitivity reaction after previous rh-EPO use. Known sensitivity to products from mammalian cell cultures
• Previous history of deep venous thromboses or pulmonary embolism
• Burns
• Cirrhosis
• Traumatic brain injury
• Less than 18 years of age
• Family or patient not committed to aggressive care
• Currently enrolled in another related interventional study
• Any active cancer patients of any type and stage except for patients with basal and squamous cell skin cancers
• Patient weighing > 100 kg