Dialysis in the Critically Ill
Fellow’s conference
Cheryl Pirozzi, MD
February 15, 2012
www.pyroenergen.com/.../dialysis-treatment.jpg
Outline
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AKI in the ICU
Principles of RRT
Modes of RRT
Indications for RRT
Optimal timing: When to start and stop
Optimal modality: When to use what
Optimal dosing
RRT in specific clinical situations
Conclusions
AKI in the ICU
 AKI
is common in the ICU
Depending on definition of AKI, up to 5060% of patients in the ICU
 Up to 70% of these will require RRT
 Independent risk factor for mortality, 50 60% mortality in critically ill

Rondon-Berrios. Curr Opin Nephrol Hypertens. 2007 Mar;16(2):64-70.
Foot. Current Anaesthesia and Critical Care 2005; 16:321-329
•Miller's Anesthesia, 7th ed. 2009
AKI in the ICU
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Treatment of acute kidney injury (AKI) is
principally supportive -- renal replacement
therapy (RRT) indicated in patients with severe
kidney injury.
Goal: optimization of fluid & electrolyte balance
Multiple modalities of RRT :
 Intermittent hemodialysis (IHD),
 continuous renal replacement therapies
(CRRTs)
 hybrid therapies, ie sustained low-efficiency
dialysis (SLED)
Foot. Current Anaesthesia and Critical Care 2005; 16:321-329
Principles of dialysis
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Dialysis = diffusion =
passive movement of
solutes across a semipermeable membrane
down concentration
gradient
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Good for small molecules
(Ultra)filtration =
convection = solute +
fluid removal across semipermeable membrane
down a pressure gradient
(solvent drag)
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Better for removal of fluid
and medium-size molecules
Faber. Nursing in Critical Care 2009; 14: 4
Foot. Current Anaesthesia and Critical Care 2005; 16:321-329
Principles of dialysis
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Hemodialysis = solute passively diffuses down
concentration gradient
 Dialysate flows countercurrent to blood flow.
 Urea, creatinine, K move from blood to dialysate
 Ca and bicarb move from dialysate to blood.
Hemofiltration: uses hydrostatic pressure gradient to induce
filtration / convection plasma water + solutes across
membrane.
Hemodiafiltration: combination of dialysis and filtration.
•Miller's Anesthesia, 7th ed. 2009
•Foot. Current Anaesthesia and Critical Care 2005; 16:321-329
Modality of RRT
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Intermittent hemodialysis (IHD)
Continuous renal replacement therapy (CRRT)
Peritoneal dialysis
Hybrid therapies, like SLEDD
Intermittent hemodialysis (IHD)
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Oldest and most common technique
Primarily diffusive treatment: blood and dialysate
are circulated in countercurrent manner
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Also some fluid removal by ultrafiltration due to pressure
driving through circuit
Best for removal of small molecules
typically performed 4 hours 3x/wk or daily
Foot. Current Anaesthesia and Critical Care 2005; 16:321-329
•Miller's Anesthesia, 7th ed. 2009
Continuous RRT
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Introduced in 1980s
involve either dialysis (diffusion-based solute
removal) or filtration (convection-based solute
and water removal) treatments in a continuous
mode with slower rate of solute or fluid removal
CRRT includes continuous hemofiltration,
hemodialysis and hemodiafiltration, all of which
can be performed using arteriovenous or
venovenous extracorporeal circuits.
Continuous RRT
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Continuous venovenous hemofiltration (CVVH): Uses
blood pump to remove fluids/solutes by convection
Continuous venovenous hemodialysis (CVVHD): Uses
pump + dialysate run at low flow rate countercurrent
to blood flow
 Slower fluid removal but greater solute removal
Continuous venovenous hemodiafiltration (CVVHDF):
combines diffusion for small solute removal +
convection for large solutes
 Large volume filtered fluid → Requires
replacement fluid
 Most commonly used modality at the U
Continuous RRT
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Arteriovenous versions (CAVH, CAVHD and
CAVHDF) are similar to venovenous except use
AV access and systemic BP to run and blood
pump not required.
 Downsides: requires arterial cannulation (+
venous)
 Unreliable flow in pts with ↓ BP or severe PVD
 Requires more anticoagulation
 VV preferred due to lower risk, only one dual
lumen catheter, and faster/more reliable flow
Slow continuous ultrafiltration (SCUF):
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used for fluid removal in overloaded CHF patients
blood is driven through a highly permeable filter
in a venovenous mode to primarily remove
water, not solute.
The ultrafiltrate produced during membrane
transit is not replaced so it corresponds to the
fluid loss.
•Miller's Anesthesia, 7th ed. 2009
Peritoneal dialysis
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Least useful form of CRRT in the ICU
diffusive treatment: blood in capillaries of
peritoneal membrane exposed to dialysate in
abdomen
continuous or intermittent
Inefficient solute/volume clearance if unstable or
poor intestinal blood flow
Can’t use if intraabdominal pathology- risk of
peritonitis
Respiratory burden
Only two RCTs comparing to hemodialysis in AKI:
found inferior or no difference
Vanholder. Critical Care 2011;15:204
Foot. Current Anaesthesia and Critical Care 2005; 16:321-329
Sustained low-efficiency daily dialysis
(SLEDD)
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AKA Extended daily dialysis (EDD) or slow
continuous dialysis (SCD)
Hybrid therapy: IRRT at lower blood and
dialysate flows for prolonged times (Usually ≥ 5
hrs)
Uses conventional dialysis machines
Flexibility of duration and intensity
Major advantages: flexibility, reduced costs, low
or absent anticoagulation
Used at IMC but not U due to tech/nurse training
Anticoagulation
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CRRT requires continuous anticoagulation to
prevent clotting in the CRRT circuit
Tricky bcs ICU pts often at increased risk of
bleeding and hypercoagulable
Many options:
 Systemic anticoagulation with heparin (mst
common), LMWH, heparinoids, thrombin
antagonists
 Regional citrate anticoagulation (preferred)
 Other regional anticoagulation ie
heparin/protamine
Davenport. NDT Plus (2009) 2: 439–447
Regional citrate anticoagulation
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Citrate infused into the
blood at the start of the
circuit
provides anticoagulation by
chelating iCa++
Requires systemic Ca
infusion to replace Ca lost
with citrate
target extracorporeal blood
citrate 4–6 mmol/l, prefilter iCa++ <0.35 mmol/l
Davenport. NDT Plus (2009) 2: 439–447
Regional citrate anticoagulation
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Advantages of RCA for CRRT:
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avoids systemic anticoagulation (lower
bleeding risk) and heparin risks (HIT)
act as a buffer by conversion through to
bicarbonate
Disadvantages:
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potential metabolic complications: metabolic
acidosis/alkalosis, hypoCa, HyperNa, hypoMag
complex protocols-- q6h monitoring of Na, K,
Cl, iCa++, Mg, ABG, AG
More expensive
Davenport. NDT Plus (2009) 2: 439–447
Indications for RRT
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Acute management of life-threatening
complications of AKI:
A: Metabolic acidosis (pH less than 7.1)
E: Electrolytes -- Hyperkalemia (K >6.5 meq/L)
or rapidly rising K)
I: Ingestion -- Certain alcohol and drug
intoxications
O: Refractory fluid overload
U: Uremia, ie. pericarditis, neuropathy, decline in
mental status
Timing of initiation of RRT
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Unclear if earlier RRT is better
Theoretical benefits: may attenuate organ injury
from acidemia, uremia, fluid overload, and
systemic inflammation
Several non-randomized studies have reported
improved outcomes (incl survival), associated with
early RRT
One RCT: Bouman Crit Care Med. 2002;30(10):2205
106 ICU pts with UOP < 30 x 6 hrs and CrCl <20
assigned to early (≤ 12 hrs) high- or low- volume
CVVH, vs late (BUN 40 mmol/L, K 6.5 mmol/L or
severe pulmonary edema) low-volume CVVH→
Survival at 28 days and recovery of renal fcn
equivalent. However, underpowered
Timing of initiation of RRT
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Karvellas. A comparison of early versus late
initiation of renal replacement therapy in critically
ill patients with acute kidney injury. Critical Care
2011, 15:R72
Meta-analysis of 15 studies
Early RRT initiation associated
with ↓mortality (pooled OR
0.45)
However, significant
heterogeneity and bias
Some studies showed greater
renal recovery, ↓ duration RRT
and ICU length of stay
Timing of initiation of RRT
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Earlier initiation of RRT in critically ill patients
with AKI may have a beneficial impact on survival
and outcomes but data is insufficient
Many recommend initiation of RRT prior to the
development of advanced uremic symptoms, or
when the BUN reaches 80 - 100 mg/dL
No known threshold of fluid overload for initiating
RRT
Discontinuation of RRT
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Until “evidence of recovery of kidney
function”
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Improved UOP in oliguria
Decreasing creatinine
Creatinine clearance minimum 12 mL/min,
some say 20 mL/min
Continuous vs intermittent dialysis
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Ongoing debate
Theoretical benefits to both
At least 7 RCTs and 3 meta-analyses have not
demonstrated difference in outcome
 Eg Bagshaw Crit Care Med 2008, 36:610-617:
metaanalysis of 9 randomized trials: No effect
on mortality (OR 0.99) or recovery to RRT
independence (OR 0.76).
 suggestion that continuous RRT had fewer
episodes of hemodynamic instability and better
control of fluid balance
May be preferable in specific subpopulations
Vanholder et al. Pro/con debate: Continuous vs intermittent dialysis for acute kidney injury. Critical
Care 2011, 15:204
Pro-continuous RRT
? Theoretical advantage of more hemodynamic
stability allowing more adequate fluid removal
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Metaanalysis of 15 RCTs (Rabindranath Cochrane Rev
2007, 3): no difference between CRRT and IRRT in
haemodynamic instability or hypotension / escalation
of pressors, or mortality or RRT independence.
 Patients on CRRT had significantly higher MAP
However most trials excluded pts with major
hemodynamic issues
Some RCTs (but not all) show more negative fluid
balances with CRRT vs IRRT
Vanholder et al. Critical Care 2011, 15:204
Pro-continuous RRT
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? Better recovery of renal function due to
preserved hemodynamic stability
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All RCTs and meta-analyses have failed to show
superiority of CRRT in progression to CKD or RRT
dependence
? Improved solute removal due to longer dialysis
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Studies have been inconsistent in showing improved
clearance of creatinine and urea with CRRT
No evidence of improved removal of cytokines
Vanholder et al. Critical Care 2011, 15:204
Pro-continuous RRT
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Specific patient populations who may benefit
from CRRT
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Hemodynamic instability
Combined acute renal and hepatic failure
 Improved CV instability and intracranial pressure
Acute brain injury
 Decreased cerebral edema
Vanholder et al. Critical Care 2011, 15:204
Pro-intermittent RRT
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Practicality and flexibility
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Less expensive than CRRT (by about ½)
Fewer bleeding complications
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Uses same machines as chronic HD
Multiple pts per day
Easier to mobilize pts
CRRT requires continuous anticoagulation
Less filter clotting
Superior solute clearance, more rapid removal of
toxins (due to higher flows)
Vanholder et al. Critical Care 2011, 15:204
Pro-intermittent RRT
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Specific patient populations benefitting from
IRRT:
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High bleeding risk
 Ie. after recent surgery
Acute treatment of hyperkalemia, rhabdomyolysis,
poisoning, tumor lysis syndrome
Vanholder et al. Critical Care 2011, 15:204
Is SLEDD the answer?
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Hybrid therapy with flexibility of duration and
intensity
SLEDD vs CRRT
Major advantages: flexibility, reduced costs, low
or absent anticoagulation
Similar adequacy and hemodynamics
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One small study (16 pts) showed slightly higher acidosis
and lower BP (Baldwin 2007)
VA trial (Palevsky NEJM 2008) suggests similar
outcomes as CRRT and IRRT.
Vanholder et al. Critical Care 2011, 15:204
Optimal dosing
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Optimal intensity of RRT is controversial
VA/NIH Acute Renal Failure Trial Network. (NEJM
2008;359:7): RCT of 1124 critically ill pts with AKI
and sepsis or at least one organ failure to intensive
or less intensive renal-replacement therapy
Hemodynamically unstable pts received CRRT or
SLEDD, stable pts IRRT
Intensive RRT= IRRT or SLEDD 6x/wk or CRRT at
35 ml/kg/hr
Less intensive RRT= IRRT or SLEDD 3x/wk or CRRT
at 20 ml/kg/hr
Optimal dosing
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VA/NIH Acute Renal Failure Trial Network
No difference in mortality, recovery of kidney function, or
nonrenal organ failure
VA/NIH Acute Renal Failure Trial Network. NEJM 2008;359:7
Optimal dosing
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The RENAL Replacement Therapy Study
RCT of 1508 critically ill pts to CRRT of high vs low intensity
(40 vs 25 ml/kg/hr)
No difference in 90 d mortality or RRT independence
N Engl J Med. 2009 Oct 22;361(17):1627-38
Optimal dosing
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Recommended dosing:
IRRT: 3x/week
CRRT: delivered effluent flow rate of at least 20
mL/kg/hr
Up To Date.com
The role of RRT in different clinical
situations
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Sepsis and MODS
Congestive heart failure
•Miller's Anesthesia, 7th ed. 2009
RRT in sepsis/MODS
RRT has been proposed as a
“Extracorporeal blood purification therapy
(EBPT)” as adjuvant therapy for
sepsis/MODS for removal of harmful
inflammatory mediators or endotoxemia
 Some support from animal models and
small clinical studies
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Eg cytokines can be demonstrated in dialysis
effluent
•Miller's Anesthesia, 7th ed. 2009
Foot. Current Anaesthesia and Critical Care 2005; 16:321-329
RRT in sepsis/MODS
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Limited data, small studies:
Cole. Crit Care Med. 2002 Jan;30(1):100-6
 Phase II RCT of early CVVH x 48 h in 24 pts
with septic shock/MODS
 No ↓ in circulating cytokines and
anaphylatoxins or organ dysfunction
RRT in sepsis/MODS
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Limited data, small studies:
Boussekey et al. Intensive Care Med. 2008
Sep;34(9):1646-53
Pilot RCT of 20 pts with septic shock and ARF to
high volume hemofiltration [HVHF 65 ml/(kg h)]
vs low volume hemofiltration [LVHF 35 ml/(kg h).
HVHF decreased vasopressor requirement and
trend towards increase urine output but no effect
on survival, LOS, RRT, mech ventilation
RRT in sepsis/MODS
Overall, no good data showing improved
outcomes
 Insufficient evidence to support a role for
RRT as adjuvant therapy for septic shock
unless severe acute renal failure is
present.

Foot. Current Anaesthesia and Critical Care 2005; 16:321-329
RRT in congestive heart failure
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Slow continuous ultrafiltration (SCUF) effective
for fluid removal in decompensated CHF
UNLOAD trial (UF versus intravenous diuretics for
acute decompensated CHF):
 RCT 200 hypervolemic CHF pts to UF or
diuretics
 At 48 hrs, UF associated with improved weight
and fluid removal, and ↓ 90 d rehospitalization
and medical visits for CHF
•Costanzo et al J Am Coll Cardiol 2007; 49:675-683.
Conclusions
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AKI in the ICU is common and associated with
high mortality
The best time to initiate and stop RRT is
controversial
No good data that CRRT is better than IRRT in
the ICU, except for a few specific situations
 Consider CRRT if severely unstable pts, severe
volume overload, combined renal/hepatic
failure
 IRRT best if bleeding risk or acute
hyperkalemia/poisoning
 SLEDD is the most flexible
Conclusions
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More intense RRT dosing in the ICU does not
improve outcome
Insufficient evidence to support a role for RRT as
adjuvant therapy for septic shock unless severe
acute renal failure is present
Ultrafiltration is effective for fluid removal in CHF
References
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Miller: Miller's Anesthesia, 7th ed. 2009
Uchino S, Kellum JA, Bellomo R, et al: for the Beginning and Ending
Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute
renal failure in critically ill patients: A multinational, multicenter
study. JAMA 2005; 294:813-818.
Bouman CS, Oudemans-Van Straaten HM, Tijssen JG, Zandstra DF,
Kesecioglu J. Effects of early high-volume continuous venovenous
hemofiltration on survival and recovery of renal function in intensive care
patients with acute renal failure: a prospective, randomized trial. Crit Care
Med. 2002;30(10):2205.
Vanholder et al. Pro/con debate: Continuous vs intermittent dialysis for
acute kidney injury. Critical Care 2011, 15:204
Uchino S, Bellomo R, Morimatsu H, et al: Continuous renal replacement
therapy: A worldwide practice survey: The Beginning and Ending
Supportive Therapy for the Kidney (B.E.S.T. Kidney)
Investigators. Intensive Care Med 2007; 33:1563-1570.
Bagshaw SM, Berthiaume LR, Delaney A, Bellomo R: Continuous versus
intermittent renal replacement therapy for critically ill patients with acute
kidney injury: a meta-analysis. Crit Care Med 2008, 36:610-617.
Rabindranath K, Adams J, Macleod AM, Muirhead N: Intermittent versus
continuous renal replacement therapy for acute renal failure in adults.
Cochrane Database Syst Rev 2007, 3:CD003773.
References
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Palevsky PM, Zhang JH, O’Connor TZ, Chertow GM, Crowley ST,
Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RM, Smith MW,
Swanson KM; Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P:
Intensity of renal support in critically ill patients with acute kidney injury.
N Engl J Med 2008, 359:7-20.
RENAL Replacement Therapy Study Investigators, Bellomo R, Cass A, Cole
L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J,
Norton R, Scheinkestel C, Su S. Intensity of continuous renal-replacement
therapy in critically ill patients. N Engl J Med. 2009 Oct 22;361(17):162738.
Rondon-Berrios H, Palevsky PM. Treatment of acute kidney injury: an
update on the management of renal replacement therapy. Curr Opin
Nephrol Hypertens. 2007 Mar;16(2):64-70.
Palevsky P. Renal replacement therapy (dialysis) in acute kidney injury
(acute renal failure) in adults: Indications, timing, and dialysis dose.
UpToDate.com 2012
Boussekey N, Chiche A, Faure K, Devos P, Guery B, d'Escrivan T, Georges
H, Leroy O. A pilot randomized study comparing high and low volume
hemofiltration on vasopressor use in septic shock Intensive Care Med.
2008 Sep;34(9):1646-53.
Cole L, Bellomo R, Journois D, et al: High-volume hemofiltration in human
septic shock. Intensive Care Med 2001; 27:978-986.
Cole L, Bellomo R, Hart G, et al: A phase II randomized, controlled trial of
continuous hemofiltration in sepsis. Crit Care Med 2002; 30:100-106.
References
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Costanzo MR, Guglin M, Saltzberg MT, et al: for the UNLOAD Trial
Investigators: Ultrafiltration versus intravenous diuretics for patients
hospitalized for acute decompensated heart failure. J Am Coll
Cardiol 2007; 49:675-683.
Ronco C, Brendolan A, Lonnemann G, et al: A pilot study of coupled
plasma filtration with adsorption in septic shock. Crit Care
Med 2002; 30:1250-1255.
Carole L. Foot, John F. Fraser. So you need to start renal replacement
therapy on your ICU patient? Current Anaesthesia & Critical Care (2005)
16, 321–329
Peter Faber and Andrew A Klein. Acute kidney injury and renal
replacement therapy in the intensive care unit. Nursing in Critical Care
2009; 14: 4
Davenport A, Tolwani A. Citrate anticoagulation for continuous renal
replacement therapy (CRRT) in patients with acute kidney injury admitted
to the intensive care unit. NDT Plus (2009) 2: 439–447
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Surviving sepsis 2008:
D. Renal Replacement 1. We suggest that
continuous renal replacement therapies and
intermittent hemodialysis are equivalent in
patients with severe sepsis and acute renal
failure (grade 2B). 2. We suggest the use of
continuous therapies to facilitate management of
fluid balance in hemodynamically unstable septic
patients (grade 2D
AKI in the ICU

In BEST Kidney trial: multinational observational
trial of 29,269 ICU patients with AKI [oliguria
(UOP < 200/12h, azotemia (BUN > 30) or RRT]
 5.7% had AKI during their ICU stay
 4.3% treated with RRT
 47.5% due to septic shock
 30% had preadmission CKD
 Overall hospital mortality 60.3%. Of survivors,
13.8% dialysis dependent at discharge
 Independent risk factors for hospital mortality
included the use of vasopressors, mechanical
ventilation, septic shock, cardiogenic shock,
and hepatorenal syndrome.
•Uchino JAMA 2005; 294:813-818.
•Miller's Anesthesia, 7th ed. 2009