fluid overload and acute kidney injury kathleen d. liu february 18, 2014
TRANSCRIPT
Outline
• How much fluid is enough: what do we use to guide resuscitation?
• Fluid selection in the ICU• What are potential adverse consequences of
fluid overload itself?
What do we use to guide resuscitation?
• Physical Exam• Static monitors
– BP (MAP), CVP, PAOP or “wedge pressure”, TTE • Dynamic monitors
– Systolic pressure variation– Pulse pressure variation– Stroke volume variation/arterial pulse contour– Passive leg raise– Continuous TEE
• Metabolic monitors– Lactate, SVO2
Shippy et al, CCM 1984
What do we use to guide resuscitation?
• Physical Exam• Static monitors
– BP (MAP), CVP, PAOP or “wedge pressure”, TTE • Dynamic monitors
– Systolic pressure variation– Pulse pressure variation– Stroke volume variation/arterial pulse contour– Passive leg raise– Continuous TEE
• Metabolic monitors– Lactate, SVO2
Davison and Junker, CJASN 2008
Outline
• How much fluid is enough: what do we use to guide resuscitation?
• Fluid selection in the ICU: What fluids may be harmful to the kidney?– Hydroxyethyl starch– Chloride rich solutions (normal saline)
• What are potential adverse consequences of fluid overload itself?
Hydroxyethyl Starch• Prior studies have suggested increased rates of AKI
with HES
• CHEST: 7000 patients (Australia/NZ) randomized to receive 130/0.4 HES or saline
• Follow up to 90 days VISEP, NEJM 2008Myburgh et al, NEJM 2012
CHEST: Conclusions
• Largest study of HES in critically ill patients• No benefit and likely harm with HES• Caveats:
– Serum Cr, urine output that are used to define AKI may be affected by type of resuscitation fluid/changes in volume of distribution
– RRT should be less affected (though subjective); blinding helps
• Additional black box warning added by FDA in June 2013
Fluid selection and AKI: Chloride rich solutions
• Rationale: Hyperchloremia can lead to renal vasoconstriction with associated reductions in RBF
NaHCO3
NaAcetate
Dextrose
NH4Acetate
NaCl
NH4Cl
-50 -40 -30 -20 -10 0 10 20 30 40
% change in RBF (dogs)
Wilcox, JCI 1983
Impact of NS on renal function• Rationale: Compared to Plasmalyte, NS
resuscitation results in greater extracellular fluid volume and decreased renal perfusion
• Design: Crossover clinical trial of 12 healthy male volunteers– 2 L of either NS or Plasmalyte administered over 1h,
with 4h of followup; participants returned 7-10 days later for the 2nd half of the study
Chowdury et al, Annals Surg 2012
NS administration is associated with greater extracellular fluid expansion
Chowdury et al, Annals Surg 2012
What is the impact of chloride-rich fluids on the incidence of AKI?
• Pre/post study:0.9% NS Hartmann
solution4% gelatin Plasmalyte-1484% albumin 20% salt-
poor albumin
Yunos et al, JAMA 2012
Limitations
• Multiple interventions: unclear which component of intervention was associated with change in AKI
• Other temporal changes in care?
Yunos et al, JAMA 2012
Chloride rich solutions: Conclusions
• Results are intriguing and warrant repeating/study in other contexts
• With some exceptions, use balanced salt solutions rather than isotonic saline
Outline
• How much fluid is enough: what do we use to guide resuscitation?
• Fluid selection in the ICU• What are potential adverse consequences of
fluid overload itself?
Problems with observational studies of fluid balance
• Is increased mortality related to – Fluid itself?– Provider/process of care characteristics– Comorbidities associated with volume
overload (sepsis, hypotension)?– Lack of recognition of AKI?
Fluid overload is an independent risk factor for sepsis after AKI
Mehta et al, Intens Care Med, 2011
OR (95% CI)
Chronic kidney disease 0.40 (0.26-0.63)
Steroid therapy 1.93 (0.99-3.74)
Invasive procedure post-AKI 1.75 (1.15-2.66)
≥ 3 days of oliguria 3.40 (1.49-7.76)
Need for dialysis 1.58 (1.15-2.66)
SOFA score (per 1 point increase) 1.12 (1.04-1.20)
Fluid overload* 1.66 (1.05-2.64)
* 25% of AKI days with FO > 10% of body weight
What is the impact of fluid overload on antibiotic levels?
MIC
AUC/MIC
Peak/MIC
Time above MIC
Time
Con
cent
ratio
n
Concentration Dependency
Time Dependency
Antibiotic levels in patients on CRRT
• Prospective study of 52 patients receiving piperacillin/tazobactam on CRRT
• Patients received a mean of 8.6±1.5 g pip/tazo/24 hours (our standard dosing is 13.5 g/24 hours)
• Depending on what antibiotic breakpoint is used, up to 23% of cohort failed to achieve “adequate” antibiotic levels
Bauer et al, CJASN 2012
What is the impact of fluid management (diuretics) on AKI outcomes?
How does fluid balance impact AKI outcomes and ascertainment?
Impact of fluid balance on other organs: ALI and the FACTT trial
KIDNEY
FavorsDry
LUNG
CVP < 4PAOP < 8
MAP < 60Low flow by exam or CI <2.5
UOP < 0.5 ml/kg/h &
CVP or PAOP low
Furosemide
ARDS Network, N Engl J Med 2006
Impact of fluid balance on other organs: ALI and the FACTT trial
ARDS Network, N Engl J Med 2006
0 1 2 3 4 5 6 7
-2000
0
2000
4000
6000
8000
LiberalConservativeARMA 6 ml (1996-1999)
Study Day
ml o
f fl
uid
Fluid conservative approach has no impact on mortality
Liberal Conservative15
20
25
30
28.4 25.5
Mor
talit
y(%
)
P = 0.30
ARDS Network, N Engl J Med 2006
Fluid conservative approach increases the number of VFDs
Liberal
Conservative
0 2 4 6 8 10 12 14 16
12.09
14.55
P=0.0002
ARDS Network, N Engl J Med 2006
Dialysis to Day 60
Conservative Liberal P value
Patients (%) 10 14 0.06
Days 11.0 + 1.7 10.9 + 1.4 0.96
What is the impact of the fluid conservative approach on AKI?
ARDS Network, N Engl J Med 2006
Volume overload impacts AKI ascertainment: an underappreciated
problem in critically ill patients• The volume of distribution of Cr is total body
water• Volume overload therefore dilutes serum Cr
Cr
Cr
Cr
CrCr
Cr
CrCr
CrCr
CrCr
Cr
Cr
CrCr
And may mask AKI…
AKI incidence is higher with FC approach only before adjusting for fluid balance
Liu et al, CCM 2011
Renal Outcomes
Liberal Conservative
Not Adjusted Not Adjusted
AKIN Stage 1 253* 288*
AKIN Stage 2 54 69
AKIN Stage 3 75 75
AKI incidence is higher with FC approach only before adjusting for fluid balance
Liu et al, CCM 2011
Renal Outcomes
Liberal Conservative
Not Adjusted Adjusted Not Adjusted Adjusted
AKIN Stage 1 253* 328** 288* 290**
AKIN Stage 2 54 106 69 87
AKIN Stage 3 75 89 75 83
Patient Groupings
GROUP
AKIN Stage 1 AKI
PatientsBefore
Adjustment for Fluid Balance
&After
Adjustment for Fluid Balance
A NO & NO 328B NO & YES 131C YES & NO 54D YES & YES 487
Liu et al, CCM 2011
AKIN Stage 1: Groups and Outcomes: Mortality
A (-/-) B (-/+) C (+/-) D (+/+)0
5
10
15
20
25
30
35
40
Liu et al, CCM 2011
AKIN Stage 1: Groups and Outcomes: Mortality and VFDs
A (-/-) B (-/+) C (+/-) D (+/+)0
5
10
15
20
25
30
35
40
Liu et al, CCM 2011
Short timed creatinine clearance – a useful measurement in critically ill patients?
Pickering et al, Crit Care, 2012
Summary
• Fluid selection matters: avoid HES, await additional evidence with regards to use of NS versus balanced salt solutions
• Fluid overload is associated with adverse outcomes
• Fluid overload may affect:– Antibiotic levels– AKI ascertainment
“ The treatment of anuria should be conservative. If circulatory failure is present, appropriate steps should be taken to correct it. Otherwise, therapy is limited to the balanced maintenance of the patient until the kidneys have a chance to affect recovery…It is easy to expand the body fluids to such an extent as to produce dangerous pulmonary edema and perhaps to promote the formation of renal edema.”
-- Homer Smith, 1951
What is the impact of diuretic use and fluid balance on AKI?
FACTTN=1000
AKIN=306
No AKIN=794
Impact of post-AKI diuretic use and fluid balance
Grams et al, CJASN 2011