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Raghavan Murugan, MD, MS, FRCPAssociate Professor of Critical Care Medicine, andClinical & Translational ScienceCore Faculty, Center for Critical Care Nephrology & CRISMA CenterUniversity of Pittsburgh School of Medicine
Fluid Balance and Long-Term
Outcomes in Critical Illness
Disclosure
• Grant from Bard Inc. – Intensity of monitoring of renal function
in critically ill patients
Background• Fluid balance (FB) is frequently disrupted in
critically ill patients with acute kidney injury (AKI)
• Positive FB prevalent in up to 40% of ICU patients
• Negative FB prevalent in up to 50% of patients
• However, association between exposure to FB and long term outcomes is unclear
Lowell et. al., Crit Care Med 1990Vaara et. al., Crit Care 2012Bellomo et. al., Crit Care Med 2012
Positive Fluid Balance• Previous studies that have examined
association between positive FB and outcomes – Conflicting results– Indication bias– Compared patients with only negative
FB– Examined only short term outcomes– Included patients for propensity to fluid
overload (e.g., Heart failure)
Negative Fluid Balance• Negative FB is thought to be
associated with improved survival– Compared patients to positive FB– Biologic plausibility – Short term outcomes
Bellomo et. al., Crit Care Med 2012
Conceptual Model
Murugan R and Kellum JA. CCM 2012
Positive Fluid Balance and Outcome
Prowle, J.R. et al; Nat Rev Neprol 2010
Hypothesis• Among critically ill patients, positive
FB, compared with even FB, is associated with increased 1-year mortality
• Negative FB, compared with even FB, is associated with lower 1-year mortality
• Among patients receiving RRT, positive and negative FB would be associated with impaired renal recovery
Methods• HIDenIC Dataset
– Adults admitted to 8 different UPMC ICUs between July, 2000 and October, 2008
• Mortality data from SSDMF and dialysis data from USRDS
• *FB = Cumulative daily fluid input – output X 100 Hospital admission weight• Propensity score was created to account for
indication bias for fluid use• AKI was defined using the KDIGO criteria
* Slewiski et. al., Intensive Care Medicine 2011
Methods• Propensity matched case-control
study to examine positive FB and mortality
• Grays model to estimate risk-adjusted hazard ratios of positive and negative FB
• Logistic regression model to estimate risk-adjusted OR for renal recovery
Study Population
Definition of Positive, Negative, and Even FB
• Positive FB: > 5%– 4.9%
• Even FB: 0-4% – 13.3%
• Negative FB: < 0%– 81.8%
Age, yrs, median (IQR) 60 (47-73) 65 (51-77) 65 (51-78) <0.001
BMI, kg/m2 median (IQR)
26.8 (23.4 - 31.2)
27.1 (23.6 - 31.6)
24.6 (21.3 - 28.7)
<0.001
Co-morbiditiesHistory of hypertension 2410(22.1) 432(24.3) 176(27) 0.0028History of vascular disease
721 (6.6) 140(7.9) 56(8.6) 0.0305
History of malignant neoplasms
361(3.3) 84(4.7) 42(6.4) <0.001
Multiple comorbidities 2951(27) 553(31) 268(41) <0.001Clinical CharacteristicsSurgical admission 7127 (65.2) 1047 (58.8) 410 (62.8) <0.001Vasopressors a 2622 (24) 396 (22.3) 193 (29.6) <0.001Mechanical Ventilation a 7136 (65.3) 995 (55.9) 393 (60.2) <0.001Sepsis a 1508 (13.8) 246 (13.8) 117 (17.9) 0.0128Apache III score mean (SD)
62.8 (26.2) 65.6 (29.2) 72.3 (29.9) <0.001
Fluids in 1st 24hrs,L/day, median (IQR)
3.4 (2.4 - 5) 3.54 (2.5 - 5.3)
4.4 (3 - 7) <0.001
Average daily fluid balance, L/day median
-0.9 (-1.4 to -0.5) 0.3 (0.1 - 0.6) 1 (0.5 - 1.7) <0.001
Baseline serum creatinine
0.81 (0.7 - 1.01) 0.84 (0.7 - 1.02)
0.82 (0.7 - 1.03)
0.0032
AKI within 24hrs of ICU 3110 (28.4 ) 686 (38.5) 260 (40) <0.001
Characteristic Negative(N=10,925)
Even(N=1,780)
Positive(N=653)
P Value
Key Baseline Characteristics
Crude Outcomes by Fluid BalanceCharacteristic Negative
(N=10,925)Even
(N=1,780)Positive(N=653)
P Value
Length of hospital stay (days, median, interquartile range)
15 (9-25) 11 (7-19) 17 (10-28) <0.001
All AKI 8741 (80) 1527 (85.7) 597 (91.4) <0.001
KDIGO Stage 1 2255 (20.6) 252 (14.2) 75 (11.5)<0.001
KDIGO Stage 2 4707 (43.1) 748 (42) 229 (35.1)
KDIGO Stage 3 1779 (16.3) 527 (29.6) 293 (44.9)
RRT requirement 362 (3.3) 229 (12.9) 128 (19.6) <0.001
Hospital mortality 1158 (10.6) 310 (17.4) 194 (29.7) <0.001
1 year mortality 2728 (25) 569 (32) 302 (46.3) <0.001
1 year renal recovery*
96 (26.5) 72 (31.4) 42 (32.8) 0.2695
* Defined as alive and independent of RRT in the RRT subgroup
Outcomes in the Propensity Matched Cohort
Characteristic
N (%)
Controls (<5% FB) (n = 1366)
Cases (>=5% FB) (n = 480)
P value
Length of hospital stay (days, median, interquartile range) 17 (10-30) 17 (10-28) 0.7111
AKI during hospitalization (KDIGO criteria)
Stage 1 179 (13.1) 58 (12.1) 0.0983
Stage 2 508 (37.2) 161 (33.5)
Stage 3 544 (39.8) 222 (46.3)
RRT requirement 171 (12.5) 104 (21.7) <0.001
Hospital Mortality 265 (19.4) 146 (30.4) <0.001
1 year Mortality 503 (36.8) 229 (47.7) <0.001
1 year Renal Recovery 41 (3) 32 (6.67) 0.216
Fluid Balance and Mortality
Mor
talit
y (%
)
Days from ICU admission
Positive
Even
Log Rank P <0.001
Controls (< 5%)
Days from ICU admission
Mor
talit
y (%
) Cases (> 5%)
Log Rank P <0.001
Negative
Negative vs Even FB on Mortality
Adjusted for age, sex, race, surgical admission, comorbidity, malignancy, baseline creatinine, BMI, mechanical ventilation, vasopressor use, sepsis, hypotensive index, APACHE III, AKI severity, oliguria
Adjusted Hazard Ratio Range = 0.60 – 1.32, P <0.001
Positive vs. Even FB on Mortality
Adjusted Hazard Ratio Range= 1.24 – 1.41, P =0.003
Adjusted for age, sex, race, surgical admission, comorbidity, malignancy, baseline creatinine, BMI, mechanical ventilation, vasopressor use, sepsis, hypotensive index, APACHE III, AKI severity, oliguria
Positive vs. Negative FB on Mortality
Adjusted for age, sex, race, surgical admission, comorbidity, malignancy, baseline creatinine, BMI, mechanical ventilation, vasopressor use, sepsis, hypotensive index, APACHE III, AKI severity, oliguria
Adjusted Hazard Ratio Range= 1.16 – 1.80, P <0.001
Fluid Balance and Renal Recovery and Mortality in
RRT SubgroupPopulation Characteristic
Adjusted Odds Ratio (95% CI) *
Renal Recovery Mortality
RRT population (n= 719)Positive vs Even FB 0.89 (0.50 – 1.59) 1.27 (0.74 – 2.17)
Negative vs Even FB 0.61 (0.39 – 0.97) 1.54 (1.02 – 2.35)
1 year survivors (n=252)
Positive vs Even FB 1.81 (0.48 – 6.86)
Negative vs Even FB 0.95 (0.36 – 2.49)
*Models adjusted for age, sex, race, reference estimated glomerular filtration rate, surgery, comorbidities,
oliguria, modality and timing of RRT, Apache III score, vasopressors, mechanical ventilation, suspected sepsis, and hypotensive index.
Conclusions• Positive, compared with even and
negative FB, is associated with increased 1 year mortality
• Negative, compared with even FB, has variable association with 1 year mortality
• Among patients receiving RRT, negative and positive FB were not associated with renal recovery
Acknowledgements
Vikram Balakumar, MD Florentina Sileanu, MS John Kellum, MD
Visit us at ccm.pitt.edu/center-critical-care-nephrology-team
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