Hypertonic Saline and Terlipressin for Sepsis-associated Hypotension

Phase 3TerminatedNCT01271114

Hospital General de Ciudad Real21 enrolled

Overview

In hypotensive septic patients with controlled source, an hemodynamic management protocol including hypertonic saline (HS)and terlipressin improves MOD (Multiple Organ Dysfunction) Score by at least 3 points compared to the use of physiologic saline and norepinephrine. The appropriate design for this trial would be factorial. For the time being, will consider de intervention as a whole unit for this pilot study. In the future an appropriately sized factorial multicentric study shall be necessary. Other goals of the pilot study: 1. HS restores preload parameters adequately 2. HS associated with terlipressin normalizes blood pressure in septic shock 3. HS associated with terlipressin maintains plasma sodium levels 130-155mEq/L 4. There is an inverse relationship between plasma sodium and procalcitonin levels 5. HS increases plasma levels of vasopressin (AVP) 6. HS rises levels of cortisol but not of adrenocorticotropic hormone (ACTH)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Septic Shock Sepsis-associated Hypotension

Interventions

Hypertonic Saline and TerlipressinDRUG

Hypertonic saline 3% 7mL/Kg (with a maximum 500 mL)triggered by either Systolic Volume Variation or Pulse Pressure Variation more than 10%; Terlipressin infusion (dilution 1mg in 100mL) triggered by MAP below 70 mmHg for a goal MAP above 70 mmHg

Normal saline and norepinephrineDRUG

Normal saline IV bolus 7mL/kg (with a maximum 500 mL)triggered by either Systolic Volume Variation or Pulse Pressure Variation above 10%; Norepinephrine drip (80 micrograms/mL) to keep MAP at least 70 mmHg

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Criteria of SIRS: at least 2 of 4: * Temperature \> 38 °c or \< 36 ° C * More than 90 bpm heart rate * Respiratory rate more than 20rpm or PaCO2 less than 32 mm Hg or patient in mechanical ventilation * Less than 4000/ mm³ or more than 12000/mm³, or more than 10% leukocyte bands (immature) * Septic source known demonstrated (or at least of high probability) and controlled (if it is controllable) * Hematocrit 25% or higher and/or hemoglobin 8 g/dL or higher. If necessary, transfuse RBCs to meet this criteria * MAP less than 70 mm Hg. Note there is no requirement for adequate preload evidence Exclusion Criteria: * Hypernatremia at base-line of 155 mEq/L or greater Hyponatremia at base-line less than 130mEq / L * Prior endocrine disease affecting to the adrenal-pituitary axis. * Intracranial Hypertension, brain tumor, seizures, head trauma * Coronary Artery Disease active over the past year; or evidence of "myocardium at risk" by exercise stress test, pharmacological or positive gammagraphy last year without intervention * Pregnancy * Liver disease Child C, End-Stage-Renal-Disease * Under the age of 18 * Patients with order "do not resuscitate" or with minimal chances to survive

Outcomes

Primary Outcomes

MOD (Multiple Organ Dysfunction) Score

Time frame: daily, as long as the patient stays in the ICU

Secondary Outcomes

Hypertonic Saline restores IV fluid response parameters (Pulse Pressure Variation or Systolic Volume Variation) adequately

Time frame: First 48 hours

Hypertonic Saline associated with terlipressin maintains plasma sodium levels 130-155mEq/L

Time frame: As long as Hypertonic saline plus terlipressin are in use and one week later

There is an inverse relationship between plasma sodium and plasma procalcitonin levels measured by a negative Pearson coefficient

Time frame: As long as the patient stays in the ICU

Hypertonic Saline associated with terlipressin normalizes blood pressure in septic shock