Introduction, History and Indications - Teaching for Nursing Personnel

1. CONTINUOUS RENAL
REPLACEMENT THERAPY
(CRRT) :
AN INTRODUCTION, HISTORY AND INDICATIONS
DR SHAIRIL RAHAYU RUSLAN
CLINICAL LECTURER
DEPARTMENT OF
ANESTHESIOLOGY
UNIVERSITY MALAYA MEDICAL
CENTRE

3. WHAT IS HAEMODIALYSIS?
“ AN EXTRACORPOREAL MEDICAL
PROCESS THAT INVOLVES REMOVAL OF
WASTES FROM THE BLOOD”

4. GREEK
ORIGIN;
DIALYSIS  DISSOLUTION
“dia”  through
“lysis”  loosening/splitting
1960s – Scribner proposed CAVHD

5. [DIFFUSION]
[ULTRAFILTRATION]
[EXTRACORPOREAL
CIRCUIT]

9. RENAL REPLACEMENT
THERAPY
INTERMITTENT
INTERMITTENT
HAEMODIALYSIS
PROLONGED
INTERMITTENT RRT
SLEDD
CONTINUOUS
PERITONEAL DIALYSIS
CONTINUOUS RENAL
REPLACEMENT THERAPY
CVVHD/CVVHDF

11. CONTINUOUS RENAL
REPLACEMENT THERAPY
CRRT
SCUF
SLEDD
CVVH
CVVHD
CVVHDF
TPE

12. TYPES OF CRRT
SCUF  Slow Continuous Ultrafitration
SLEDD  Sustained Low-Efficiency Daily
Dialysis
SLEDD-F  Sustained Low-Efficiency Daily
Diafiltration
CVVH  Continuous venovenous
haemofiltration
CVVHD  Continuous venovenous

13. SO A BIT OF HISTORY….
1977
DR PETER KRAMER first described CAVH
(continuous arterio-venous haemofiltration
• A vascath inserted into an artery
into a vein through a haemofilter
• Ultrafiltration controlled by
raising or lowering the drain bag
(Elliot, Aitken & Chaboyer, 2007)

14. CAVH CIRCUIT
(Elliot, Aitken & Chaboyer, 2007)

15. 1982 
BUT…
Good for plasma water removal and dissolved solutes clearance…
Good haemodynamics compared to IHD…
LIMITED SOLUTE CLEARANCE
THE NEED TO CATHETERISE AN ARTERY
(Elliot, Aitken & Chaboyer, 2007)

16. 1984… FIRST CAVH EVER!!

17. 1980’S  VENOVENOUS
TECHNIQUE

18. 1990’S

Fully automated dialysis
machines
Aquarius
Fresenius
Gambro Prismaflex

19. INTERMITTENT HAEMODIALYSIS
1. BRIEF INTERVALS
2. USUALLY 2-3 DAYS ONCE, OVER 3-
4 HOURS
3. APPROPRIATE ACCESS REQUIRED

20. INTERMITTENT
HAEMODIALYSIS
ADVANTAGE
S
Maximum
solute clearance
Best therapy for
hyperkalemia
Limited
anticoagulation
time
DISADVANTAGE
S
Haemodynamic
instability
Rapid fluid and
electrolyte shift
Specialised
personnel
Complex
equipment
Difficult in
small infants

22. CONTINUOUS RENAL
REPLACEMENT THERAPY
1. SAME PRINCIPLES AS
INTERMITTENT
HAEMODIALYSIS
2. PROLONGED, OVER MANY
HOURS (UP TO DAYS)
3. MORE APPROPRIATE IN THE
CRITICALLY ILL

23. DESCRIPTION IHD/SLEDD/PRRT CRRT
Water quality Subject to reverse
osmosis and dialysis
machine maintanence
Sterile
Average dialysate flow
rate
200-500ml/min 30-60ml/min
Duration Intermittent; 2-4
hours
Continuous
Solute removal Rapid & intermittent
Rebound effect
possible
Slow & continuous
Adaptable solute
removal
Solute removal efficacy Small molecules (eg Small & big molecules
DIFFERENCES BETWEEN IHD &
CRRT
Reference:
1.Liao et al. Kinetic Comparison of Different Acute Dialysis Therapies. Artif Organs 2003:27:802
2.Bouchard, J, et al: Fluid Accumulation, Survival and Recovery of Kidney Function in Critically Ill Patients with Acute Kidney Injury. International Society of Nephrology, 2009; KI, 76
422-427
3.Wald R et al. The Association Between Renal Replacement Therapy Modality and Long-Term Outcomes Among Critically Ill Adults With Acute Kidney Injury: A Retrospective
Cohort StudyCrit

25. WHY CRRT?

26. INDICATIONS FOR RRT
RENAL REPLACEMENT THERAPY
(excretory function only)
RENAL SUPPORT
THERAPY
Life threatening changes
• Fluid balance
• Electrolyte control
• Acid-base regulation
Initiate emergently • Immune modulation in
sepsis
• Volume balance in
multi-organ
dysfunction/failure
• Nutritional support
• Volume removal in
refractory congestive
heart failure
• Alleviate ARDS induces
respiratory acidosis
Patient’s medical
condition
• Haemodynamically
unstable
• Acute brain injury
• Generalised brain
oedema
• Increased intracranial
pressure
Preference to initiate with
CRRT
Reference:
1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Su
2: 1–138.
2.Kellum et al. 2010. Continuous Renal Replacement Therapy. New York, Oxford University Press.

27. COMPONENTS OF CRRT

28. COMPONENTS OF CRRT
Vascular catheter to connect
patient to the CRRT system
Filter, or “artificial kidney”

29. COMPONENTS OF CRRT

30. COMPONENTS OF CRRT
TRANSPORT MEDIUM FOR REMOVAL
OF WASTE PRODUCT FROM BLOOD
PROVIDE BUFFER FOR ONGOING ACID
PRODUCTION

31. COMPONENTS OF CRRT
Source : Baxter Prismaflex

35. RENAL •UFAKE
NON-
RENAL •TNT

36. RENAL
INDICATIO
NS FOR
CRRT
[UFAKE]
Uraemi
a
Fluid
overloa
d
Metaboli
c
Acidosis
Hyper
Kalemi
a

37. NON-
RENAL
INDICATIO
NS FOR
CRRT
[TNT]
Toxi
ns
Na
(sodiu
m)
Temperatur
e control
hypertherm
ia

38. INDICATIONS FOR CRRT
• Oliguria (200ml in 12 hours)
• Anuria (less than 50ml in 12 hours)
• Hyperkalaemia (Potassium >6.5 mmol/L)
• Severe acidaemia (pH 30 mmol/L)
• Significant organ oedema (lung or heart overload)
• Uraemic encephalopathy
• Uraemic pericarditis
• Uraemic neuropathy/myopathy
• Severe dysnatraemia (Sodium >160 or <115mmol/L)
• Hyperthermia
• Drug overdose with dialyzable toxin (Elliot, Aitken
& Chaboyer, 2007)

39. CONTROVERSIAL INDICATIONS
(Vanholder, Van Biesen, & Lameire, 2001)

40. CONTRAINDICATIONS OF CRRT
1. Appropriate for conventional intermittent
haemodialysis or SLEDD
2. Patient and/or family desire for palliative care only
3. Terminal disease with no reasonable expectations
for recovery
4. Irreversible liver failure in a patient who is not a
candidate for liver transplantation.
References :
1. Brochard L, Abroug F, Brenner M, et al. An Official ATS/ERS/ESICM/SCCM/SRLF Statement : Prevention and management of acute renal failure in the ICU
patient : An international consensus conference in intensive care medicine. Am J Resp Crit Care Med, 2010; 181: 1128-1155.
2. Kelly JA, Lameire N and the KDIGO Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney International, 2012; Vol 2, Supplement
1.

41. WHEN TO STOP CRRT?
1.Resolution of underlying cause
2.Fluid management amenable to other
treatment
3.Logistics, cost
4.Change in the direction of management

42. WHY RRT MAY BE BETTER
COMPARED TO OTHER
MODALITIES?
oAllow early removal of toxic substances i.e urea, non-volatile acids,
drug toxicity, illness-specific agents such as in sepsis.
oLimit risk and complications of alterative treatment i.e frusemide,
resonium, bicarbonate
oSlow, gentle and continuous
oRemoves small molecules (urea and creatinine) as well as larger
molecules (beta 2 macroglobulin & inflammatory mediators)
oMore control of electrolytes & acid-base balance
oRemoves large amounts of fluid and waste products over time

43. The End

44. AKIKI TRIAL
oAKIKI TRIAL – delaying rrt
o- 50% patients randomised to “delayed RRT” arm ended up with no
RRT at all and no difference in survival and LOS in ICU/hospital
o- reduction of exposure to complications of RRT, vascath insertion
oCost-reduction in terms of equipment, staffage, monitoring and
reduced workload
oRRT may contribute to delayed renal recovery, and may remove
beneficial substances (eg endogenous mediators, therapeutic drugs).

45. AKIKI trial (Gaudry et al, 2006)multi-center RCT (31 French ICUs)
n =620 critically ill adults with stage 3 AKI, as per the KDIGO criteria
Intervention: immediate RRT (early RRT)
Comparison: RRT initiation only when medically necessary (severe hyperkalemia, metabolic acidosis, pulmonary oedema,
or a blood urea nitrogen level greater than 112 mg/dL, or oliguria for more than 72 hours) (late RRT)
Outcomes:
 no difference in the primary outcome of 60-day mortality (48.5% vs 49.7% p-value of 0.79)
 no difference in secondary outcomes
 mortality at 30-days
 ICU length-of-stay
 long-term dialysis dependence
 ventilator-free days
 vasopressor-free days
 There were differences in:
 the proportion of patients that actually received RRT (98% in early RRT group versus 51% in the late RRT)
 how early patients experienced adequate urine production (defined as 1000 mL of urine in a 24-hour period
without the help of diuretics) (earlier in the late RRT group)
 the rate of catheter-related bloodstream infections (10% in early RRT vs 5% in late RRT)
Commentary and criticisms
 The type of RRT used was at the discretion of the treating physician and only 45% received CRRT, which is at odds with
standard Australasian ICU practice
 Most of the patients in the late RRT group (68%) were dialysed because of either oliguria for > 72 hours, or a BUN
greater than 112 mg/dL
 the majority were medical patients (80%, e.g. sepsis)
 Fragility index = “-18”
 the outcome is consistent with the pre-existing literature (see systematic review by Wierstra et al, 2016)

46. Evidence
Systematic review (Wierstra et al, 2016)
 Earlier meta-analyses suggested that “early” RRT improves survival in
critical illness, however, no survival benefit was seen in the subgroup of
higher quality trials (RCTs)
 Systematic review of 36 studies (7 RCTs, 10 prospective cohorts, and 19
retrospective cohorts)
 n = 1042 patients from 9 studies were considered to be of high quality and
were included for quantitative analysis
 No survival advantage was found with “early” RRT (OR 0.665; 95 % CI
0.384–1.153, p = 0.146)
 No survival difference in subgroup analysis of reason for ICU admission
(surgical/medical) or definition of “early” (time/biochemical)
 No significant differences were observed in ICU or hospital LOS
 Conclusion
 no difference in survival or ICU/ hospital LOS with early or late RRT
 AKIKI and ELAIN trials were published after this systematic review

47. ELAIN TRIALELAIN trial (Zarbock et al, 2016) single-center RCT from Germany
n = 231 critically ill adults with stage 2 AKI
Intervention: immediate RRT (early RRT)
Comparison: RRT initiation only when stage 3 KDIGO criteria were met
Outcomes:
 improved primary outcome of 90-day mortality in the early RRT group (39.3% versus 54.7%)
 secondary outcomes
 These favoured early RRT:
 duration of mechanical ventilation (median of 125.5h vs 181.0h).
 number of patients who still required RRT at 60-days (15.9% vs 23.7%)
 there was no difference in the recovery of renal function at 90-days (88.2% vs 85.2%) (secondary
outcome)
Commentary and criticisms
 all patients received CVVHDF and were only transferred to IHD or SLEDD if RRT was required for more
than 7 days
 the majority were surgical patients (47% were cardiac surgery)
 median time difference to initiation of dialysis between the immediate and delayed groups was 25.5
hours
 Fragility index = 3
 given the small trial size and that prior studies (see systematic review by Wierstra et al, 2016) the
large mortality difference seen is this trial is unlikely to be true

48. STARRT-AKI
This is a large pragmatic international multi-center
RCT, including ICUs in Australasia, that is currently
in progress comparing early versus delayed RRT
IDEAL-ICU
Another French multi-center RCT is also in progress
comparing early versus late RRT in the critically ill

49. DIALYSIS FOR TOXICITY
Lack of high level evidence for RRT in toxicology
Kellum et al (2016) advocated :
Intermittent haemodialysis for methanol, isopropanolol, ethylene glycol
Intermittent haemodialysis/CRRT/haemoperfusion for lithium, salicylate,
theophylline, valproic acid

50. REFERENCES AND LINKS
Bagshaw SM, Lamontagne F, Joannidis M, Wald R. When to start renal replacement therapy in critically ill patients with acute kidney injury: comment on
AKIKI and ELAIN. Critical care. 2016; 20(1):245. [pubmed]
Gaudry S,Hajage D, Schortgen F, et al. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016; 375(2):122-33.
[pubmed]
Kellum,JA, Bellomo R, Ronco C. Continuous Renal Replacement Therapy. Oxford University Press, 2016. [Google books]
Ghannoum M, Nolin TD, Lavergne V, et al. Blood purification in toxicology: nephrology’s ugly duckling. Advances in chronic kidney disease. 2011;
18(3):160-6. [pubmed] [article]
Wald R, Adhikari NK, Smith OM, et al; Canadian Critical Care Trials Group. Comparison of standard and accelerated initiation of renal replacement
therapy in acute kidney injury. Kidney Int. 2015;88(4):897-904. [pubmed]
Wierstra BT, Kadri S, Alomar S, et al. The impact of “early” versus “late” initiation of renal replacement therapy in critical care patients with acute kidney
injury: a systematic review and evidence synthesis. Critical care. 2016; 20(1):122. [pubmed]
Zarbock A, Kellum JA, Schmidt C, et al. Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute
Kidney Injury: The ELAIN Randomized Clinical Trial. JAMA. 2016;315(20):2190-9. [pubmed]
Web resources :
CC Nerd — The Case of the Afflicted Kidney by Rory Spiegel (2016)
EXTRIP workgroup
The Bottom Line — ELAIN trial (2016)
The Bottom Line — AKIKI trial (2016)
The Bottom Line — Editorial: Early vs Late Renal Replacement Therapy (2016)
Life in The Fast Lane – Indications, timing and patient selection for RRT (https://lifeinthefastlane.com/ccc/indications-timing-and-patient-selection-for-
rrt/) (2017)