Dr Ross Freebairn Hawke’s Bay N.Z.

Renal Replacement Therapy What, When, Why & How Much.

Oliguria

• urine output < 0.5 ml/kg/hr

Matter of perspective

• Heart stops – Cardiac arrest

• Breathing stops – Respiratory arrest

• Kidneys stop – Oliguria – Renal arrest

Acute renal failure

• failure of solute and (usually) water clearance

• common

• associated with increased mortality

Oliguria

• warning sign of impaired tissue perfusion

• leads to acute renal failure if not corrected

• 2 hours’ oliguria MUST be treated urgently

Pathophysiology • outer renal

medulla prone to ischaemia

Pathophysiology

• reduced renal blood flow worsens medullary ischaemia

• ischaemia causes structural changes and ultimately acute tubular necrosis

Management

• treatable factors • hypovolaemia and shock - resuscitate • infection - source control and antibiotics • nephrotoxic drugs - discontinue where

possible • abdominal compartment syndrome -

decompress • rhabdomyolysis - alkalinise, mannitol • hypercalcaemia • obstruction

Resuscitation

• correct hypovolaemia • volume repletion • CVP guidance using serial fluid challenges

• restore cardiac output • vasopressors/inotropes if other evidence of

tissue hypoperfusion • restore perfusion pressure

• may need MAP > 80 mm Hg if previously hypertensive

• volume repletion and vasopressors

Frusemide is NOT

a resuscitation fluid

Dopamine • inconsistent diuretic effect

• but this may cause dehydration • does not

• increase creatinine clearance • prevent acute renal failure

• does cause serious toxicity problems • tachyarrhythmias • exacerbates renal and mesenteric ischaemia • impaired immune function

• fundamentally not useful

Frusemide

• does • reduce juxtamedullary oxygen

consumption • has not been shown to

• improve creatinine clearance • affect survival either way

• disadvantages • of diuresis

• may be used but ONLY after adequate volume resuscitation

Established acute renal failure

Management of renal failure

• avoid volume overload –  input = previous hour’s output +20 ml – BUT do not withold nutrition

• treat complications • adjust drug doses • renal replacement therapy

Temporizing measures

• hyperkalaemia • insulin/dextrose, NaHCO3, β2 agonists

• severe acidosis • NaHCO3 infusion

• volume overload • GTN infusion if BP permits • frusemide if still passing urine

Indications for CRRT • Urgent

–  Severe ↑ K –  Severe metabolic

acidosis –  Severe pulmonary

oedema due to fluid overload

–  Uraemic pericarditis

•  Less urgent/definite –  Non-obstructive oliguria

>12 h –  Creatinine 2 x baseline –  Uraemic encephalopathy,

neuropathy or myopathy –  Progressive dysnatraemia –  Hyperthermia –  Significant oedema –  Requirement for large

volume transfusion in patients with/at risk of pulmonary oedema/ARDS

From: Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury:  The ELAIN Randomized Clinical TrialJAMA. 2016;315(20):2190-2199. doi:10.1001/jama.2016.5828

Mortality Probability Within 90 Days After Study Enrollment for Patients Receiving Early and Delayed Initiation of Renal Replacement Therapy (RRT)KDIGO indicates Kidney Disease: Improving Global Outcomes. In the delayed group, 18 patients received RRT without reaching KDIGO stage 3 (these patients had an absolute indication). The median (quartile 1 [Q1], quartile 3 [Q3]) duration of follow-up was 90 days (Q1, Q3: 90, 90) in the early group and 90 days (Q1, Q3: 90, 90) in the delayed group. The vertical ticks indicate censored cases.

Factors affecting RRT

Patient focused System Imposed Clinician Influenced

Comorbidity Health structure Indications (timing)

Kidney reserve ICU organization Prescription

Metabolic rate Resource /Costs Local Practice

Primary diagnosis Resource/ equipment Goals of therapy

Continuous venovenous haemodiafiltration--an audit demonstrating control of electrolytes with haemodynamic stability in the critically ill. Freebairn RC, Lipman J. S Afr J Surg. 1994 Jun;32(2):77-82

80

85

90

95

100

105

110

115

Heart rate MAP SBP CVP

Time 036hrs

Pump

Ultrafiltrate

Pump

Replacement fluid

Solute

Plasma protein

Replacement fluid

Ultrafiltrate

Blood

Haemofilter membrane

Replacement fluid

• Determines plasma electrolyte concentration

• Bicarbonate lost, needs to be replaced

Replacement fluid

• Bicarbonate replacement – Bicarbonate –  Lactate

• Metabolized to bicarbonate by liver (or not!)

• Risk of metabolic acidosis

Dialysate

Effluent

Dialysis fluid

•  Solutes will reach equilibrium •  Plasma electrolyte & bicarbonate

concentration will tend towards dialysis fluid concentration

Anticoagulation

• None • Heparin

– Unfractionated –  Low molecular weight

• Citrate • Prostacyclin • Systemic anticoagulation

Anticoagulation

• Avoid: – Active, recent bleeding evident – Baseline INR >2, APTT >60s, platelets

<60 • Relative contra-indications

–  Less severe coagulopathy/thrombocytopaenia

–  Surgery within 24 h

Summary

• Haemofiltration – convection • Haemodialysis – diffusion • Adjust dose (effluent rate) according

to patient’s needs, interuptions to treatment –  Starting point 25 ml/kg/h

• Consider need for anticoagulation • Caution when starting CRRT in

haemodynamically unstable patients

Outcome  with  IRRT  vs  CRRT  (3)  

Vinsonneau,  S  et  al.    Lancet  2006;  368:  379-­‐385  

Choice of RRT • 1218 patients CRRT or IRRT for ARF • 54 ICUs in 23 countries. • Multivariable logistic regression

–  choice of CRRT • Not independent predictor of

–  hospital survival –  dialysis-free hospital survival.

• But is predictor of dialysis independence at hospital discharge among survivors (OR: 3.333, 95% CI: 1.845 - 6.024, p<0.0001).

Uchino S et al Patient and kidney survival by dialysis modality in critically ill patients with acute kidney injury. Int J Artif Organs. 2007 Apr;30(4):281-92.

0

.2

.4

.6

.8

1

0 20 40 60 80 100

IRRT

CRRT

days

Recovery from Dialysis Dependence- BEST Re

cove

ry fr

om d

ialy

sis

depe

nden

ce

Uchino S et al Patient and kidney survival by dialysis modality in critically ill patients with acute kidney injury. Int J Artif Organs. 2007 Apr;30(4):281-92.

How much replacement and dialysate do you use?

100 90 80 70 60 50 40 30 20 10

0

Group 1(n=146)

( Uf = 20 ml/h/Kg) Group 2 (n=139) ( Uf = 35 ml/h/Kg)

Group 3 (n=140)

( Uf = 45 ml/h/Kg)

41 % 57 % 58 %

p < 0.001 p n..s.

p < 0.001

Sur

viva

l (%

)

Effects of different doses in CVVH on outcome of ARF - Ronco & Bellomo study. Lancet . july 00

Conclusions:

• An increased treatment dose from 20 ml/h/kg to 35 ml/h/kg significantly improved survival.

• A delivery of 45ml/kg/hr did not result in further benefit in terms of survival, but in the septic patient an improvement was observed.

Effects of different doses in CVVH on outcome of ARF - Ronco & Bellomo study. Lancet . july 00

High Volume 37 vs 70 ml/kg

Joannes-Boyau O et al High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial Intensive Care Med (2013) 39:1535–1546

• Blood Purification: It must work!!! • maybe, • possibly, • Unlikely, • No

Never let evidence get in the way of a good opinion

• The fact that an opinion has been widely held is no evidence whatever that it is not utterly absurd; indeed in view of the silliness of the majority of mankind, a widespread belief is more likely to be foolish than sensible.

Bertrand Russell, Marriage and Morals (1929)

Recommendation • Renal replacement therapy

– When • Acute renal Failure • Exogenous toxin removal (lithium) • Early may be better-Probably is !!!!

– Dose : • 35+ ml/kg/hr (averaged) • No evidence for high dose

– Mode : • Whatever works for you

–  Frusemide is not a resuscitation fluid