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The Influence of Furosemide on Fluid Balance and Intra-abdominal Pressure in Critically Ill Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01072071
Recruitment Status : Unknown
Verified February 2010 by Ziekenhuis Netwerk Antwerpen (ZNA).
Recruitment status was:  Recruiting
First Posted : February 19, 2010
Last Update Posted : February 22, 2010
Information provided by:
Ziekenhuis Netwerk Antwerpen (ZNA)

Brief Summary:
Intra-abdominal hypertension (IAH) is a frequent cause of organ dysfunction in critically ill patients. Secondary IAH is mainly caused by excessive fluid resuscitation.The World Society for the Abdominal Compartment Syndrome (WSACS) recommends using diuretics to remove excess fluids and decrease intra-abdominal pressure (IAP). However, critically ill patients may not tolerate negative fluid balance in the acute phase of their disease and the injured kidney may not respond to diuretics. The aim of this study is to evaluate the influence of furosemide on fluid balance, IAP and kidney function in critically ill patients.

Condition or disease Intervention/treatment Phase
Intra-Abdominal Hypertension Drug: furosemide Not Applicable

Detailed Description:

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have been shown to cause organ dysfunction and mortality in different populations of critically ill patients. According to consensus definitions published by the World Society for the Abdominal Compartment Syndrome (WSACS), secondary IAH is due to a disease process outside the abdominal cavity. It is mainly caused by massive fluid resuscitation leading to bowel and abdominal wall edema or increased intra-abdominal volume and decreased abdominal wall compliance. Large observational studies have shown that positive fluid balance is an independent risk factor for mortality. The development of secondary IAH may be one of the mechanisms involved in this phenomenon. This has lead to the hypothesis that prognosis may be improved by managing fluid overload and aiming for a negative fluid balance as soon as possible after the resuscitation phase of the disease.

Several authors have shown in case reports and small series that renal replacement therapy with ultrafiltration can be used successfully to remove excess fluid and lower intra-abdominal pressure (IAP), but renal replacement therapy is invasive and clinicians may be reluctant in considering this therapy in patients with preserved diuresis and kidney function. In an effort to achieve the same goal using a less invasive technique, the new medical management algorithm for IAH published by the WSACS recommends the use of judicious diuresis in order to achieve a negative fluid balance and a decrease in IAP.

However, the kidney is especially sensitive to the deleterious effects of IAH and may be unresponsive to diuretics in the presence of IAH. Also, ongoing inflammation and capillary leak may lead to relative hypovolemia and impaired response to diuretics.

We plan a multicenter study to evaluate the influence of furosemide on fluid balance and IAP in critically ill patients with secondary intra-abdominal hypertension and to document the effect on the function of other organ systems. The aim of this study is to evaluate the feasibility and the safety of the furosemide administration protocol and to provide preliminary data to allow for an adequate power calculation.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: The Influence of Furosemide on Fluid Balance and Intra-abdominal Pressure in Mechanically Ventilated Critically Ill Patients With Secondary Intra-abdominal Hypertension
Study Start Date : February 2010
Estimated Primary Completion Date : December 2011
Estimated Study Completion Date : March 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Furosemide

Arm Intervention/treatment
No Intervention: Control group
Patients will be receiving standard of care ICU treatment of their underlying disease according to internationally accepted guidelines and recommendations.
Experimental: Furosemide group
patients will be receiving standard of care ICU treatment of their underlying condition according to international guidelines and recommendations. In addition, furosemide will be administered in continuous infusion as per protocol in order to achieve a preset target diuresis that is adjusted according to haemodynamic tolerance.
Drug: furosemide

Loading dose: 0,5mg/kg Start continuous infusion at a dose of 0,1mg/kg/h and titrate according to diuretic response.

Target value for diuresis = (amount of fluids administered at inclusion/kg/h) + 0.5mL/kg/h If safety check is satisfactory: increase target diuresis with 1mL/kg/h per 4h to a maximum of (amount of fluids administered at inclusion/kg/h) + 2.5mL/kg/h Maximal dose of furosemide: 0.3mg/kg/h Safety check every 4h. Furosemide is administered for 24h. If safety checks are satisfactory, additional periods of 24 can be added up to a maximum of 72h.

Other Name: Lasix (Sanofi-Aventis)

Primary Outcome Measures :
  1. intra-abdominal pressure [ Time Frame: every 4 hours during furosemide administration and daily for 7 days ]

Secondary Outcome Measures :
  1. serum creatinine [ Time Frame: daily for 7 days ]
  2. need for renal replacement therapy [ Time Frame: daily for 7 days ]
  3. ICU mortality [ Time Frame: 3 months ]
  4. acid-base status [ Time Frame: daily for 7 days ]
  5. hospital and 28d mortality [ Time Frame: after 28 days and after 6 months ]
  6. duration of mechanical ventilation [ Time Frame: 3 months ]
  7. ICU length of stay [ Time Frame: 3 months ]
  8. vasopressor dose [ Time Frame: daily for 7 days ]
  9. fluid balance [ Time Frame: daily for 7 days ]
  10. SOFA score [ Time Frame: daily for 7 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adult (>18y)
  • Sedation (Richmond Agitation and Sedation Score RASS ≤ -3) and mechanical ventilation anticipated to last for at least an additional 72h
  • Indication for IAP monitoring according to the recommendations published by the WSACS
  • IAP ≥ 12mmHg (intravesical IAP measurement according to WSACS guidelines)
  • Absence of surgically treatable abdominal lesions
  • Presence of fluid overload

Exclusion Criteria:

  • Pregnancy or lactation
  • Assisted spontaneous breathing ventilator mode
  • Chronic diuretic therapy or on diuretics during inclusion
  • Contra-indication to bladder catheterization such as bladder surgery or genitourinary trauma
  • Known hypersensitivity to furosemide
  • Renal failure Acute Kidney Injury Network (AKIN) class 3
  • Patients requiring high dose vasopressors (norepinephrine >0.5µg/kg/min, dobutamine >10µg/kg/min or dopamine>10µg/kg/min, epinephrine>0.5µg/kg/min)
  • Intra-abdominal pressure (IAP) >25mmHg at study entry
  • DNR orders in effect (other than DNR 1 'no CPR' order)
  • Patient not expected to survive for 7 days
  • Advanced liver cirrhosis (see pharmaceutical information on furosemide)
  • paO2/FiO2 ratio of <100
  • oliguria <500mL/24h preceding inclusion

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01072071

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Contact: Inneke E De laet, MD +32476216120
Contact: Manu Malbrain, MD PhD +3232177399

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ZNA Stuivenberg Intensive Care Unit Recruiting
Antwerpen, Belgium, 2060
Contact: Inneke E De laet, MD    +32476216120   
Contact: Manu Malbrain, MD PhD    +3232177399   
Sponsors and Collaborators
Ziekenhuis Netwerk Antwerpen (ZNA)

Additional Information:
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Responsible Party: Inneke De laet MD, ZNA Stuivenberg, Intensive Care Unit Identifier: NCT01072071     History of Changes
Other Study ID Numbers: IDL2009/003
First Posted: February 19, 2010    Key Record Dates
Last Update Posted: February 22, 2010
Last Verified: February 2010
Keywords provided by Ziekenhuis Netwerk Antwerpen (ZNA):
abdominal compartment syndrome
intra-abdominal pressure
fluid balance
Additional relevant MeSH terms:
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Intra-Abdominal Hypertension
Vascular Diseases
Cardiovascular Diseases
Compartment Syndromes
Muscular Diseases
Musculoskeletal Diseases
Natriuretic Agents
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action