Bouchard et al: Fluid Accumulation in AKI (2005)

“Fluid overload is an independent risk factor for mortality in critically ill patients with acute kidney injury.”

Adapted from Bouchard J, et al.

1. Publication Details

Trial Title: Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury
Citation: Bouchard J, Soroko SB, Chertow GM, et al. Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int. 2009;76(4):422-427. DOI: 10.1038/ki.2009.159. Note: After a thorough search, the key study by Bouchard on this topic was published in 2009, not 2005. This summary is based on the 2009 publication.
Published: August 2009, in Kidney International
Author: Josée Bouchard, M.D.
Funding: National Institutes of Health (NIH) and others.

2. Keywords

Acute Kidney Injury (AKI), Fluid Overload, Fluid Balance, Mortality, Critical Care, Observational Study

3. The Clinical Question

In critically ill adult patients with acute kidney injury (AKI) (Population), is the degree of fluid accumulation (Intervention/Exposure) associated with 60-day mortality (Outcome)?

4. Background and Rationale

Existing Knowledge: Fluid resuscitation is a cornerstone of critical care, but excessive fluid administration can lead to fluid overload, causing tissue edema and organ dysfunction. The impact of fluid overload on outcomes specifically in patients with AKI was not well established.
Knowledge Gap: It was unclear if fluid accumulation was simply a marker of severe illness or an independent factor that directly contributed to worse outcomes in critically ill patients with AKI.
Proposed Hypothesis: The authors hypothesized that a higher degree of fluid accumulation would be independently associated with an increased risk of death in critically ill patients with AKI.

5. Study Design and Methods

Design: A prospective, multicenter, observational cohort study (used to identify risk factors and prognosis). This was a secondary analysis of the Program to Improve Care in Acute Renal Disease (PICARD) study.
Setting: 5 academic medical centers in the United States.
Trial Period: Data was collected from 1999 to 2001.
Population:
- Inclusion Criteria: Critically ill adult patients with AKI, defined by a rise in serum creatinine or the need for renal-replacement therapy (RRT).
- Exclusion Criteria: Included pre-existing end-stage renal disease.
Intervention: This was an observational study, so there was no assigned intervention. The exposure of interest was the percentage of fluid overload, calculated daily based on fluid balance and body weight.
Control: There was no control group; patients were stratified based on their degree of fluid overload.
Management Common to Both Groups: All aspects of patient care, including fluid management and the decision to initiate RRT, were at the discretion of the treating clinicians.
Power and Sample Size: As an observational study, a formal power calculation was not performed in the same way as for an RCT. The study included 618 patients from the PICARD cohort.
Outcomes:
- Primary Outcome: All-cause mortality at 60 days.
- Secondary Outcomes: Included recovery of kidney function.

6. Key Results

Enrollment and Baseline: 618 patients with AKI were included in the analysis. The median age was 61 years, and sepsis was the most common cause of AKI.
Trial Status: The analysis was completed as planned.
Primary Outcome: The degree of fluid overload was a strong and independent predictor of 60-day mortality. After adjusting for multiple other variables, patients with >10% fluid overload at the time of RRT initiation had a significantly higher risk of death compared to those with <10% fluid overload.
Secondary Outcomes: A higher degree of fluid overload was also independently associated with a lower probability of renal recovery among survivors.
Adverse Events: Not applicable in the same way as an interventional trial, but the study identified fluid overload itself as being associated with the adverse outcome of death.

7. Medical Statistics

Analysis Principle: The study used multivariable regression models to adjust for potential confounding variables.
Statistical Tests Used: The primary outcome was analyzed using a Cox proportional-hazards model.
Primary Outcome Analysis: The analysis aimed to determine the association between the degree of fluid overload and the risk of death over time.
Key Statistic(s) Reported: Adjusted Hazard Ratio (HR) for death for every 1% increase in fluid overload.
Interpretation of Key Statistic(s):
- Hazard Ratio (HR):
  - Calculation: The paper reports a complex statistical model, but the key finding was that >10% fluid overload was a significant predictor of mortality.
  - Clinical Meaning: For every 1% increase in fluid accumulation, the adjusted risk of death increased. Patients with >10% fluid overload had a substantially higher risk of death than those with less fluid accumulation.
Clinical Impact Measures: As this was an observational study showing association, not causation, NNT is not applicable.

8. Strengths of the Study

Study Design and Conduct: A well-conducted, prospective, multicenter observational study with detailed, daily data collection.
Generalizability: The inclusion of patients from five different academic centers increases the applicability of the findings.
Statistical Power: The large sample size provided adequate power to perform robust multivariable adjustments.
Patient-Centered Outcomes: The study focused on the important outcomes of mortality and recovery of kidney function.

9. Limitations and Weaknesses

Internal Validity (Bias): As an observational study, it can only show association, not causation. It is possible that sicker patients received more fluid (a phenomenon called confounding by indication), and that the severity of illness, not the fluid itself, was the true cause of the worse outcomes. The authors attempted to control for this with statistical adjustment, but residual confounding is still possible.
External Validity (Generalizability): The study was conducted in academic centers and the findings may not be fully generalizable to all ICU settings.
Other: The study does not provide guidance on how to best manage fluids to prevent overload, only that overload is associated with harm.

10. Conclusion of the Authors

The authors concluded that the degree of fluid accumulation is a strong and independent predictor of mortality and non-recovery of renal function in critically ill patients with AKI.

11. To Summarize

Impact on Current Practice: This was a landmark study that provided the first strong evidence that fluid overload is not just a marker of illness but is independently associated with harm in AKI. It was a major driver in shifting the clinical mindset from aggressive, protocolized fluid resuscitation towards a more conservative and individualized approach to fluid management.
Specific Recommendations:
- Patient Selection: For all critically ill adult patients, particularly those with or at risk for AKI.
- Actionable Intervention: The findings support a strategy of careful fluid stewardship, aiming to avoid excessive positive fluid balance.
What This Trial Does NOT Mean: This trial does NOT mean that fluid resuscitation is bad. It only suggests that the accumulation of fluid over time (fluid overload) is harmful. Early and adequate fluid resuscitation for shock remains a cornerstone of critical care.
Implementation Caveats: The key is to find the right balance: providing enough fluid to restore perfusion without causing harmful fluid overload. This requires careful and frequent reassessment of a patient’s fluid status.

12. Context and Related Studies

Building on Previous Evidence: The Bouchard et al. study (2009) provided high-quality evidence for a concept that was clinically suspected but not well-proven.
Influence on Subsequent Research: The findings of this study were a major impetus for the subsequent large randomized controlled trials on conservative versus liberal fluid strategies, such as the FACTT trial (2006) in ARDS and, more recently, the CLASSIC (2022) and CLOVERS (2023) trials in sepsis.

13. Unresolved Questions & Future Directions

Unresolved Questions: This observational study could not answer the key question of whether a specific strategy aimed at preventing or treating fluid overload would actually improve outcomes.
Future Directions: The entire field of research into conservative fluid strategies and de-resuscitation in the ICU can be seen as the future direction that followed from the pivotal findings of this and other similar observational studies.

14. External Links

Original Article: Bouchard et al. (2009) – Kidney International

15. Framework for Critical Appraisal

Clinical Question: The research question was highly relevant, addressing a very common clinical exposure (fluid administration) and its association with a critical outcome.
Methods: The prospective, multicenter cohort design was appropriate for the question. The use of detailed daily data collection and robust statistical adjustment for confounders is a major strength. The main limitation is the inherent risk of residual confounding that is present in all observational studies.
Results: The study reported a strong, consistent, and dose-dependent association between the degree of fluid overload and the risk of death.
Conclusions and Applicability: The authors’ conclusion is a fair and appropriate interpretation of their data. While not proving causation, this study provided powerful, hypothesis-generating evidence that has been highly influential in changing clinical practice towards a more cautious and thoughtful approach to fluid management in the ICU.

16. Disclaimer and Contact

This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.