Clinical Trial: Stop Hypernatremia, Use Metolazone, for Aggressive, Controlled, Effective Diuresis

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Stop Hypernatremia, Use Metolazone for Aggressive, Controlled, Effective Diuresis

Brief Summary: Patients who are on mechanical ventilation in an intensive care unit often require diursis as part of their pre-extubation regimen. The drug of choice for diuresis has traditionally been furosemide. However, this drug cause hypernatremia (a rise in serum sodium) in a significant proportion of patients. Hypernatremia is traditionally treated by providing free water supplementation to the patient. This strategy creates a vicious and unproductive cycle of giving free water, and then diuresing it off. We propose a strategy for breaking this cycle by using a second diuretic-- metolazone-- which has a tendency to rid the body of more sodium, thereby minimizing hypernatremia.

Detailed Summary:

Mechanical ventilation is a mainstay of Intensive Care. Weaning from mechanical ventilation remains a significant issue in Intensive Care Unit (ICU) care worldwide. It is well established that a strategy of diuresis with negative fluid balance shortens the duration of mechanical ventilation in both acute lung injury and cardiogenic pulmonary edema patients. Despite publication of at least one formalized but complex evidence-based conservative fluid strategy, there is no practical, uniformly implemented protocol for setting or achieving volume status targets. The default approach at many hospitals involves using ad hoc doses (either intermittent or continuous) of a loop diuretic (usually furosemide) with instructions to monitor fluid balance and follow electrolytes in an attempt to reach arbitrary target volume diuresis. Moreover, there are barriers to achieving any particular target, including pre-existing renal failure/diuretic resistance, diuretic-induced creatinine elevation, acquired diuretic resistance, hypotension from volume loss, and electrolyte derangements including hypokalemia and hypernatremia. Strategies exist for preventing or treating the above complications but there is presently no accepted standard for preventing or treating diuretic-induced hypernatremia. In fact, the standard current intervention is to replace the free water deficit that may be induced by the loop diuretic, while simultaneously perpetuating the free water deficit by continuing to administer the causative loop diuretic. This approach is circular and does not effectuate the desired negative fluid balance. We will address the lack of an accepted prevention strategy using a randomized controlled clinical trial in ICU patients with the following specific aims:

  1. Conduct a randomized, pilot trial of standard versus metolazone supplemented diuresis in ICU patient
    Sponsor: Oregon Health and Science University

    Current Primary Outcome: Fluid balance [ Time Frame: 24, 36, 48, and 72 hours after either protocol is initiated ]

    Differences in fluid balance (total net liters negative from the time diuresis is initiated) between the study group and control group at the following intervals: 24, 36, 48, and 72 hours after either protocol is initiated.


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Serum sodium [ Time Frame: Continuous for 72 hours ]
      Number patients whose Na remains below 145 (meq/L) during the period of diuresis; versus the number of patients whose sodium exceeds 145 (meq/L) and require free water replacement.
    • Hyponatremia [ Time Frame: Continuous for up to 72 hours ]
      Number of patients who develop hyponatremia (Na < 136 meq/L)
    • Time to extubation [ Time Frame: Unitl the patient is actually extubated, undergoes tracheostomy, or expires. ]
      Time in hours from initiation of protocol to extubation (difference between study group and control group
    • Acute Kidney Injury [ Time Frame: Continuous for the first 72 hours ]
      Number of patients who develop acute kidney injury (increase in creatinine by more than 25%)


    Original Secondary Outcome: Same as current

    Information By: Oregon Health and Science University

    Dates:
    Date Received: June 1, 2012
    Date Started: June 2012
    Date Completion: June 2013
    Last Updated: June 26, 2012
    Last Verified: June 2012