A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients wit

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A randomized, controlled trial of furosemide with
or without albumin in hypoproteinemic patients
with acute lung injury

• Crit Care Med 2005 331681-1687
• Nov 20, 2006, Presented by ???

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Background

• Hypoproteinemia is one of the strongest
  independent predictor of the development of
  ALI/ARDS
• Negative fluid balance is associate with improved
  outcomes in critically ill patients
• Objective A prospective, randomized controlled
  trial involving hypoptoteinemic patients with
  ALI/ARDS, to study the role of colloid
  supplementation

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Materials Methods - Study Design

• 80 power, two-tailed a of 0.05,
• Primary outcome change in oxygenation (minimum
  20) over a 24-hour period
• Other variables net fluid balance (I/O, body
  weight), serum total protein, serum albumin,
  serum creatinine

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Materials Methods Patient Selection

• February 1999 to December 2002
• Screen all adult (gt18-year-old) ICUs within
• Grady Memorial Hospital
• Emory University Hospital (57)
• Crawford Long Hospital
• Vanderbilt University Hospital (43)

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Patient Selection

• Enrollment criteria
• the American-European Consensus Conference
  definition for ALI
• Serum total protein lt 6.0 g/dl,
• ongoing nutritional support
• mechanical ventilation for 24 hours
• Exclude for the hemodynamic instability
• gt2L iv fluid bolus or gt4unit of PRBC transfusion
• Vasopressor use

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Treatment protocol

• A random allocation with a computer-generated
  four-subject-block randomization list
• Study 25g of 25 human serum albumin iv Q8H for
  3 days (daily serum total protein 8.0g/dl) a
  loading dose of iv furosemide (20mg) a
  continuous infusion of furosemide (1mg/mL) for 3
  days
• Control 100ml normal saline

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• Furosemide continuous infusion
• Start 4mg/hr (3-5 mg/hr, according age and Cr )
• Titrate every 4 hours to achieve a net negative
  fluid balnace and daily weight loss of 1kg
• Masimum dose 10mg/hr
• Hold when SBP lt 90mmHg, Na 155 meg/L, K 2.5
  meq/L

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Data collection

• Demographic information prior medical
  conditions, etiology of lung injury, severity of
  illness (APACHE score), sequential organ failure
  assessment (SOFA) scores, and lung injury scores
• Sruty data vital signs, fluid balance ,
  hemodynamics, serum chemisties, ventilator
  parameters and oxygenation
• 30 days later (outcome) need of mechanical
  ventilation, shock, documented nosocomial
  infections, and death

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Statistical analysis

• Descriptive statistics mean
• An intent-to-treat basis
• A priori analyses clinical site, hospital
  service, cause of ALI, duration of ALI berore
  enrollment
• Comparisons unpaired students t-test or
  Mann-Whitney U test
• Multiple comparisons repeated-measures, Tukeys
  procedure
• Dichotomous variables, proportions chi-square
  statistic
• Univatiate linear regression

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Results characteristics
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Physiologic treatment effects

• Increase in total protein (1.5 g/dL vs 0.5 g/dL)
• Change in serum albumin (1.3 g/dL vs 0.3 g/dL)
• Similar temporal changes in calculated COP

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Cumulative fluid balance

• Cumulative fluid loss (net input/output at day 3
  -5480ml vs -1490ml)

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• Greater fluid-bolus administration in the control
  group(1050ml vs 275ml)
• Seven vs one patients not achieved a net fluid
  balance during the study period
• No significant change in electrolyte (Na, K,
  HCO3) or biochemical measures of organ
  dysfunction (BUN, Cr, platelets and AST, ALT)

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Changes in oxygenation
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Treatment-related changes
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Stratified analysis

• Changes in the primary outcome variable were not
  different from the four a priori strata clinical
  site, cause of ALI, hospital service and time to
  enrollment
• Sepsis-induced ALI patients had the greastest
  improvement in oxygenation at 24 hrs

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Regression models

• Oxygenation changes in treated patients were best
  predicted by changes in COP and fluid balance
• Treatment allocation to receive albumin with
  furosemide was a/w improved oxygenation
• No significant affect of group assignment on time
  to successful extubation

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Clnical outcomes

• Hypotension more in the control group
• SOFA score 0.6 vs 1.1
• Death 7 vs 9 (p0.52)
• Shock-free days (median number) 14 vs 7
• Ventilator-free days 5.5 vs 1 (difference 4.5
  days, 95 CI, -2.5 to 11.5 days)

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Discussion

• Hypoproteinemic ALI patients treated with the
  combination of albumin and furosemide have
  significantly greater improvements in oxygenation
• Reduce extravascular lung water while maintaining
  cardiovascular function
• Longer-term clinical outcomes?

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• Fluid restrictive treatment regiment to reduce
  the duration of MV and ICU stay for patients with
  pulmonary edema
• Addition of albumin to stabilize hemodynamics
• For well-defined niche populations
• Small number of enrolled patients

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Conclusion

• The combination of albumin an furosemide in
  therapy for hypoproteinemic ALI patinets improved
  oxygenation through mechanisms that require
  further examination
• Consistent trends toward improved duration of
  mechanical ventilation are apparent

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Thank you