CRRT IN ACUTE KIDNEY INJURY

Dr Umut Selda BayrakçıYıldırım Beyazıt University, Ankara, Turkey

Acute renal failure is not a “cute” renal failure Druml W, 2004

The epidemiologic importance of AKI as a public health problem is underscored

because renal function can easily and practically indefinitely be replaced by modern renal replacement modalities, AKI presents a rather harmless complication

Despite the advances in the ability to provide dialysis to children, the out come of AKI remains surprisingly poor

MORTALITY in critically ill patients 53 % in the ATN trial 44.7 % in the RENAL trial

Even a small reduction in the renal function (0.3 mg/dl SCr increase) is a risk factor for morbidity and mortality in hospitalized patients. It is not a problem restricted to the kidneys It’s a systemic disease process

AKI exerts a fundamental impact On the course of diseaseThe evolution of associated complicationsPrognosis

Independently from the underlying disease

Patients with ARF, die not (only) with but (also) from AKI;

acute renal failure is not a “cute” renal failure but a dangerous condition.

Druml W, Intensive Care Med 2004, Bellomo R, et al. Lancet,2012, Hobson CE et al. Circulation 2009, Coca SG et al. Am J Kidney Dis 2009, Murugan R, Kellum JA. Nat Rev Nephrol 2011

Management of AKI

Largely supportive

Aimed preventing of life-threatening fluid or electrolyte complications

Avoiding or minimizing further renal injury

Providing appropriate nutrition to allow recovery from acute illness and renal dysfunction

Severe AKI or milder AKI in association with severe fluid overload or solute imbalance may require renal replacement therapy (RRT)

When RRT is indicated What is the OPTIMAL RRT modality

When to start?

Should clinicians wait for Frank anuria? Unequivocal signs of uremia? Fluid overload? Should treatment be indicated

proactively?

Are there reliable indices helping to choose RRT timing?

Absolute indications to start RRT

Uremic complications, for example encephalopathy, pericarditis, bleeding.

Serum urea at least 36 mmol/l (100 mg/dl).

K+ at least 6 mmol/l and/or ECG abnormalities.

Mg at least 4mmol/l and/or anuria/absent deep tendon reflexes.

Serum pH 7.15 or less.

Urine output less than 200 ml/12 h or anuria.

Diuretic-resistant organ edema (i.e. pulmonary edema) in the presence of AKI.

Acute Dialysis Quality Initiative (ADQI) workgroup,2001

When to start?

Not only the presence of AKI but also its severity should be assessed: pediatric RIFLE (Risk, Injury, Failure, Loss, End stage) Severe AKI and/or rapidly deteriorating kidney

function (towards “F” level) RRT initiation should be considered. Particularly if there was failure to respond to initial

therapy.

Critically ill patients with mild to moderate AKI (i.e. RIFLE category R/I): the most challenging Decision should be tailored dynamically

Sometimes we should consider RRT in earlier stages of

AKI:

Severe sepsis

Reduced renal reserve

Primary diagnoses associated with high catabolic rates

(septic shock, major trauma, burn, injury)

Gastrointestinal bleeding, rhabdomyolysis placing

considerable demand on kidney function

A positive fluid balance and overt clinical fluid overload

When RRT is indicated?

30 children Children with volume excess of 10% or less

improved survival 21 children on CRRT

Mean volume excess 16% survived Mean volume excess 33% did not survived

116 children with AKI, CRRT, 13 different center Mean volume excess 14% survived Mean volume excess 25% did not survived

Lane PH et al. Bone Marrow Transplant 1994, Goldstein et al Pediatrics 2001Goldstein et al. Kidney Int 2005

When RRT is indicated?

As soon as fluid overload occurs

unless there is excessive solute load

Reasonable TRESHOLD for initiation of RRT:

fluid overload of 15%

*BUN levels at initiation of RRT was not associated with survival

(increased in nonsurvivors)

Bunchman TE.Nature Clinical Practice 2008

When to start?

1847 ICU patients with AKI requiring RRT

Relationship between biochemical, physiological and comorbid factors at time of RRT start and ICU mortality

Independent risk factors for ICU mortality Mechanical ventilation Oligoanuria Serum urea Cardiovascular failure Failure to correct acidosis and development of more organ failure

within 48 hours of RR Survivors tended to have higher creatinine and lower urea levels at

the start of RTT YH Chou et al. Crit Care 2011.

Take home message-1

RRT should be recommended for AKI in critically ill

patients before organ failure and and metabolic

derangements have reached the slippery threshold

of irreversibility!!

Creatinine is not an ideal biomarker for decision on RRT timing

New biomarkers will hopefully improve the performance

of creatinine, urea and RIFLE

The message-2

The decision when to start RRT should be established case by case and guided by

Associated dysfunction of other organ systems

patients’ AKI severity

Urine output

Serum pH

locally available technics and devices

Stuivenberg Hospital Acute Renal Failure Project (SHARF)

RRT patients have higher mortality (43 vs 58%)

Longer ICU and hospital stay compared to patients treated with conservative approach

Elseviers MM et al. Crit Care

2010

Which is the best dialysis modality

The two most important factors that

influence choice of dialysis: The indication for dialysis Overall clinical status of the patients

*The decision will be based upon Specific patient characteristics Patients requirements/limitations The status of major organ systems

LOCAL EXPERTISE with specific dialysis techniques Facility experience Local resources

Should intermittent RRT or continuous RRT be used

No suitable powered randomized controlled trials

Results of present studies do not suggest a difference in patient survival

On the basis of patient survival all seem to be acceptable

State of the art Clinical status of the patient Intermittent HD requires careful use in patients

with impaired hemodynamic status

CVVH

Venovenous forms of CRRT is considered superior to other forms of CRRT because of Lover risk of hemorrhage Less frequent circuit clotting More predictable driving pressure through

the hemofilter

Advantages of CVVH

1. Continuous solute clearance and ultrafiltration

Gradual removal provided by hemofiltration

**Ideal modality for patients with cardiovascular instability

and hypotension

Continuous removal Fluid restriction is usually unnecessary

Freedom to provide large volumes of nutritional support,

drugs, blood products etc..

Advantages of CVVH

2. Specific metabolic advantage Wide variety of metabolic problems can be corrected easily

Severe metabolic acidosis Lactic acidosis Electrolyte abnormalities (s.a. hyperkalemia)

Superior control of uremia than intermittent HD It can also be adopted to gradually correct hyperosmolar

states

3. Less likely to lead to cerebral edema

4. Removal of mediators of inflammation

Modality Manual PD

Automated PD

İntermittent HD

Continious HF

Device Ultra Set (Y-set) Freedom cycler C3 Prisma

Manufacturer Baxter Fresenius Gambro Gambro

Cost per unit $6.95 $12,295.00 $18,000.00 $25,000.00

Cost of additional supplies

1.5% Dianeal $24.43/2 L

Pediatric tubing set $32.00 each 100HG dialyzer

$50.00 each;

M60 hemofilter set (filter and bloodlines)$160.00 each

Peritoneal dialysate as at left

pediatric bloodlines $11.40 each

Normocarb dialysate concentrate $20.00/3.0L

Cost of dialysis equipment (in U.S. dollars)

Flynn JT, Pediatr Nephrol 2002

WHICH IS THE BEST DIALYSIS MODALITY?

GUIDANCE FROM THE LITERATURE

1995: 42 children (following repair of congenital heart dis):

21 PD

21 HF; 9 CAVH, 12 CVVH

Survival: identical

Fluid removal, urea and creatinine clearance, and caloric

intake superior in HF

Fleming et al, J Thoracic Cardiovasc Surg, 1995

Adults: Because of limitations in clearance and difficulties in fluid removal PD is rarely used in ARFPediatrics: PD used to be the first choice; technical difficulties of HD in infants and young adults

1997: Comparison of HD and hemofiltration in pediatric ARF

122 children with ARF (retrospective)

58 HD

64 HF

Survival: 83% in HD, 48% in HF group

Higher percentage of children with primary renal dis in HD group

Higher percentage of patients with sepsis in HF group,

greater severity of illness in HF

Maxvold et al; Am J Kid Dis 1997

Comparison of 3 dialysis modality

279 children with ARF and/or inborn errors of metabolism (retrospective) 59 PD 140 HF 80 HD

Overall survival was 53% Variation in survival among modalities for certain

diagnoses

Comparison of 3 dialysis modality

ARF following bone marrow transplant %78 intermittent HD 33% PD 21% HF

ARF following repair of congenital heart disease 100% intermittent HD 33% PD 50% HF

Hemodynamic instability affect patient outcome predictive of modality choice

patients who were the most hemodynamically unstable were usually treated with either HF or PD whereas stable patients were usually treated with intermittent HD.

Bunchman TE, J Am Soc Nephrl, 1999, abstr

Limitations: Retrospective Single center study designs Small patient numbers Homogenous patient populations: results

couldn’t be generalized

Intermittent HD vs CRRT

Multicentre, prospective, randomized, controlled trial

316 adults, AKI patients

Mortality:

intermittent HD:62.5%

CRRT: 58.1%

Modality of RRT has no impact on the outcome in ICU

Rins RL et al. Nephrol Dial Transplant 2009

Single center, randomized, controlled trial (CONVINT)

252 adult AKI patients

Survival rate: 39.5% IHD

43.9% CVVH

No significant difference regarding mortality, renal outcome measures or survival

Schefold JC et al. Critical Care 2014

Intermittent HD vs CVVH

Multicenter, randomized and prospective

study (21 center, Hemodiafe Study Group)

Adults with multiorgan dysfunction syndrome

and AKI

Rate of survival did not differ between the

intermittent HD and CVVH

Vinsonneau C et al, The Lancet, 2006

Intermittent HD vs CVVH

ATN and RENAL studies suggest that CVVH might help with renal recovery

Meta-analysis studies reveals no difference in long term dialysis dependency

Ghahramani N et al. Nephrology 2008

Goal of dialysis Hemodynamic status

modality

Ultrafiltration Normotensivehypotensive

Intermittent HD (w isolated UF)Continuous HF or PD

Urea clearance Normotensivehypotensive

Intermittent HD or PDContinuous HF or PD

Treatment of hperkalemia

Either normotensiveor hypotensive

Intermittent HD

Correction of metabolic acidosis

Normotensivehypotensive

AnyContinuous HF or PD

Treatment of Hyperphosphatemia

Either normotensiveor hypotensive

Any; continuous hemofiltration possibly superior

Suggested modality choice in pediatric ARF

Flynn JT. Pediatr Nephrol 2002

RRT modality: conclusion

Few data available

regarding pediatric patients

Decision: empirical

Consider:

Underlying disease

Severity of illness

Advantages and

disadvantages of the

various modalities

available locally

Cost

Although survival was

somewhat the same/better

in intermittent HD group,

provision of HF most likely

contributed to the survival

of many patients who

might not survived had HF

not available

Maxvold NJ et al. Am J Kid Dis 1997 (abstr)

Conclusion

Combination

CRRT: early correction of hemodynamic

instability as long as multiorgan failure exist

Classic intermittent HD for long lasting-isolated

AKI

Rins RL et al. Nephrol Dial Transplant 2009

Dose of CVVH in AKI

Expression of how much dialysis should be prescribed in

order to achieve a certain level of blood cleansing

Dose relies on

Patient clinical picture (catabolic rate, muscle mass,

presence of pulmonary edema, fever, dysionemia etc.)

Solute to clear (water, urea, electrolytes, cytokines..)

The final desired blood level of the target solute

In CVVH (small solute) clearance is essentially considered

equal to UF rate

Optimal RRT dose in ICU: 2 multicenter clinical trialsCompare normal or less intensive renal support to intensive therapy

RENAL

1124 patients

25 ml/kg/h CVVHDF vs 40 ml/kg/h

N England J Med, 2009

VA/NIH ARF trial network (ATN)

study 1500 patients

20 ml/kg/h CVVHDF/ thrice weekly IHD vs 35 ml/kg/h/daily IHD

N England J Med, 2009

No benefit in outcomes by increases in intensity of RRT dose

Conclusion

Normal dose: 20-30 ml/kg/h for continuous therapy

Ricci Z, Ronco C. Current Opinion Critical Care, 2011

Overt underdialysis might be harmful in ICU!! Be careful about the discrepancy between

prescribed and delivered dose!!!

DOse REsponse Multicenter International Collaborative Initiative (DoReMi)

The difference between prescribed and delivered dose Relies on therapy downtime (the amount of time the

CRRT does not run in a 24 h period), clotting of the circuit, Vascular access problems Prescription errors

Crit Care 2009

When you prescribe 20-25 ml/kg/h during CRRT significant reduction indialysis dose delivery should be considered!

In practice you may need to over-prescribe RRT with 25% of safety margin

Recommendation: 30-35 ml/kg/h? Kellum JA, Ronco C Nat Rev Nephrol 2010Ricci Z, Ronco C. Curr Opin in Crit Care, 2011

Anticoagulation

Low dose heparin 10-20 IU/kg bolus 10-20 IU/kg/h continuous drip (target activated clotting

time: 180-200 s or partial tromboplastin time that is double the normal value)

Citrate anticoagulation

No anticoagulation

When to stop?

No randomized controlled trials addressing this issue

Observational studies have suggested that urine output can be used to predict successful cessation of CRRT

Spontaneous urine output >500 ml/day? (adult)

Uchino S et al. Crit Care Med 2009

Complications of CVVH

High cost

Technological complexity

Specialized nursing staff usually required

Hypothermia

Membrane bioincompatibility

Acid-base imbalance

Electrolyte imbalance

Removal of drugs and nutrients

Volume depletion

Common in both CVVH and IHD

Long-term outcomes

Mortality is high

At least 10% of children who survive AKI have evidence of Hyperfiltration Hypertension Microalbuminuria

Puts them at risk of long term progressive loss of kidney function

Long term follow-up is important!Early intervention with ACE inhibitors, angiotensin receptor blockers or other renoprotective therapies if necessary

Askenazi DJ et al. Kidney Int 2006

Firdevs Çalkanoğlu