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Sepsis, a systemic host response to the invasion of a pathogenic microorganism, may progress to severe sepsis, wherein the patient experiences acute dysfunction in at least one organ system, and further develop into septic shock if the patient cannot regain adequate systemic blood pressure and perfusion after adequate and appropriate fluid resuscitation. Further prospective study of the potential mortality benefit with combination norepinephrine and vasopressin in critically ill patients with septic shock needs to be performed. Our research will resolve this essential question and improve the scientific knowledge surrounding vasoactive medications in patients with septic shock.

Sepsis, a systemic host response to the invasion of a pathogenic microorganism, may progress to severe sepsis, wherein the patient experiences acute dysfunction in at least one organ system, and further develop into septic shock if the patient cannot regain adequate systemic blood pressure and perfusion after adequate and appropriate fluid resuscitation. The exact societal burden from severe sepsis and septic shock in difficult to quantify: millions of individuals in both industrialized and developing nations experience these syndromes each year, the best medical centers in the world have only achieved a 22% mortality rate for severe sepsis, and caregivers as well as patients endure a long-lasting impact from caring from loved ones who have survived severe sepsis. Recently, the impactful work performed by Rivers and colleagues that established early goal-directed therapy (EGDT) as the standard of care for patients with severe sepsis or septic shock has been compared to usual care in three international trials. The results of these trials suggest that usual care is as effective as EGDT, which necessitates new research be conducted into each component of EGDT to determine how and to what extent specific therapies are safe and effective. One key aspect of the provision of care to patients with septic shock is the time to initiation and choice of vasoactive agents. This study will investigate the use of norepinephrine and vasopressin versus norepinephrine alone as the initial vasoactive regimen in critically ill adult patients with septic shock.

Inclusion Criteria:

• Age ≥18 years (no maximum age)

• At least 2 of 4 systemic inflammatory response syndrome criteria:

  1. Fever (>38°C) or hypothermia (<36°C),
  2. Tachycardia (heart rate >90 bpm),
  3. Tachypnea (respiratory rate >20 breaths/min or partial pressure of carbon dioxide <4.3 kPa) or need for mechanical ventilation,
  4. Abnormal leucocyte count (>12000 cells/mm3, <4000 cells/mm3 or >10% immature (band) forms).

• Hypotension despite adequate intravenous fluid resuscitation (minimum 20 mL/kg within the previous 4 hours)

• Clinical suspicion for or confirmation of an infection

• Admitted or being admitted to the medical intensive care unit

Exclusion Criteria:

• End-stage renal disease requiring long-term dialysis
• Pregnant
• Not expected to be alive within 48 hours of enrollment
• Receipt of a continuous infusion of vasoactive medication(s) other than use for emergency stabilization of blood pressure (for less than 4 hours)
• Enrollment in another clinical trial within 30 days