Terlipressin in Septic Shock in Cirrhosis

• Refractory shock [ Time Frame: ICU admission ] [ Designated as safety issue: No ]
• Variceal bleeding [ Time Frame: ICU admission ] [ Designated as safety issue: No ]
• Hepatorenal syndrome [ Time Frame: Hospitalization ] [ Designated as safety issue: No ]

Septic shock is a frequent and severe complication in cirrhosis. Current mortality rate ranges between 50 and 80% of cases. Refractory shock, hepatorenal failure and variceal bleeding are the main causes of death of these patients. Terlipressin administration could prevent these complications and improve survival in this setting.

Aim: To evaluate the effects of terlipressin administration on hospital survival in cirrhotic patients with severe sepsis or septic shock.

Methods: Prospective, open labelled, controlled trial evaluating 72 cirrhotic patients with severe sepsis or septic shock who will be randomized to receive terlipressin plus alpha-adrenergic drugs or only alpha-adrenergic drugs at shock diagnosis. Patients will be submitted to continuous systemic hemodynamic monitoring (S. Ganz catheter or Vigileo). Changes in vasoactive systems and cytokines levels will be also evaluated.

• Liver Cirrhosis
• Septic Shock

• Drug: Terlipressin plus alpha adrenergic drugs
  Terlipressin 1, 1.5 and 2 mg/4h intravenously in patients with body weight < 50 kg, between 50 and 70 Kg and > 70 Kg respectively. Duration: until 24h after shock resolution.
  Other Name: Glypressin
• Drug: alpha adrenergic drugs (Dopamine and/or norepinephrine)
  Dopamine (1-20 µg/Kg/min) and/or norepinephrine (0.05-4 µg/Kg/min) until shock resolution

• Experimental: 1
  Terlipressin plus alpha adrenergic drugs
  Interventions:

  • Drug: Terlipressin plus alpha adrenergic drugs
  • Drug: alpha adrenergic drugs (Dopamine and/or norepinephrine)
• Active Comparator: 2
  Alpha adrenergic drugs
  Intervention: Drug: alpha adrenergic drugs (Dopamine and/or norepinephrine)

Inclusion Criteria:

1. Age between 18 and 80 years;
2. Diagnosis of cirrhosis based on histology or on clinical, laboratory and ultrasonographical data;
3. Diagnosis of septic shock based on the presence of data compatible with systemic inflammatory response syndrome, a mean arterial pressure below 60 mmHg during more than 1 hour despite adequate fluid resuscitation, and need for circulatory support with vasopressor drugs.

Exclusion Criteria:

1. More than 24 hours of evolution of the shock;
2. Cardiac index < 2,5 l/min;
3. History of HIV infection or clinically relevant pulmonary, renal or cardiac disease except for atrial fibrillation;
4. Pregnancy;
5. Advanced hepatocellular carcinoma (Milan criteria);
6. Previous history of transplantation;
7. Uncontrolled gastrointestinal bleeding.