CRRT in ICU

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CRRT in ICU
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Overview

• Introduction
• CRRT
• CRRT in ICU
• Indications
• Clinical studies
• ATN, RENAL
• RRT in ICU Preference
• Prescription
• Complications
• Self assessment
• Status of issues
• Conclusions

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Introduction
In the past, the interaction between nephrology
and intensive care was minimal
Today, there is continuous interaction with
several moments of high interaction due to common
patients and complex syndromes
Contrib Nephrol. Basel, Karger, 2010 (166)13
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Introduction (Contd)
Classification of blood purification in critical
care (BPCC) technology
PMX polymyxin- B immobilized fiber PMMA
polymethylmethacrylate PAN polyacrylonitrile
PEPA polyether polymer alloy
Contrib Nephrol. Basel, Karger, 2010(166)1120
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Introduction (Contd)
The calcification of terminology of blood
purification in critical care
HDF hemodiafiltration
Contrib Nephrol. Basel, Karger, 2010(166)1120
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Introduction (Contd)

• Continuous Blood Purification
• Blood purification initiated with the intention
  of continuing it for 24 h/day is defined as
  continuous blood purification, even if it has not
  been sustained for 24 h due to unavoidable
  circumstances
• When it is performed, the methods and
  circumstances of its implementation
• Hemofilter, blood flow (QB),
• Dialysis fluid flow (QD)
• Substitution fluid flow and filtration rate (QF)
  must be recorded

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CRRT

• CRRT technology
• The first CRRT treatments were performed using
  circuits driven by arterial blood pressure
• However, it is in the form of roller-pumped,
  venovenous therapy that CRRT became a mature
  technology
• CRRT originatedand remains widely practicedin
  the form of continuous hemofiltration

Nat. Rev. Nephrol. 20106521529.
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Nomenclature
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CRRT in ICU

• As a continuous therapy, CRRT can be rapidly
  tailored to changes in a patients clinical
  condition during critical illness

Nat. Rev. Nephrol. 20106521529.
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CRRT in ICU (Contd)

• These perceived advantages have contributed to
  the widespread uptake of CRRT as the first-choice
  RRT in ICUs throughout Australia, Japan and
  Europe
• In these regions, CRRT is usually initiated,
  prescribed and managed within the ICU, with RRT
  being integrated with other aspects of the
  management of critical illness

Nat. Rev. Nephrol. 20106521529.
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CRRT in ICU (Contd)
Blood purification treatments performed at the
ICU in Chiba University Hospital (19812008) in
Japan
Contrib Nephrol. Basel, Karger, 2010(166)2130
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CRRT in ICU (Contd)

• In north america, however, traditional structures
  of ICU management favor an open-ICU approach
• Within this model, RRT is usually prescribed by a
  nephrologist in the ICU and is initiated by a
  dialysis nurse
• In this environment, IHD has the advantage of
  requiring only daily or alternate-day attendance
  by the renal team
• Conversely, the relative labor costs of providing
  CRRT are increased, an effect that is compounded
  by the larger fixed costs and higher consumable
  requirements of CRRT
• These logistic factors have led to a preference
  for IHD over CRRT being maintained in ICUs that
  use the north american model,
• aAstance further justified by the lack of
  compelling evidence from controlled trials in
  favor of CRRT

Nat. Rev. Nephrol. 20106521529.
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CRRT in ICU (Contd)

• Two large multicenter, randomized controlled
  trials,
• The veterans affairs/ national institutes of
  Health acute renal Failure trial network (ATN)
  study and
• The randomized evaluation of normal versus
  augmented level replacement therapy (RENAL)
  trial,
• have now, however, examined the use of RRT in the
  ICU and provided a more consistent set of
  clinical data with which to answer questions
  concerning the clinical application of CRRT

Nat. Rev. Nephrol. 20106521529.
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CRRT in ICU Indications
Acute blood purification in critical care
currently performed in Japan
Contrib Nephrol. Basel, Karger, 2010(166)4753
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CRRT in ICU Indications

• 1 Acute kidney injury with
• Fluid overload (refractory to diuretics)
• Hyperkalemia (K gt 6.5)
• Severe metabolic acidosis (pH lt 7.1)
• Rapidly climbing urea/creatinine (or urea gt
  30mmol/l)
• Symptomatic uraemia encephalopathy,
  pericarditis, bleeding, nausea, pruritus
• Oliguria/anuria

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CRRT in ICU Indications

• 2 Overdose with a dialyzable drug or toxin
• Some drugs are removed by RRT
• As a general rule, drugs are cleared by RRT if
  they are water-soluble and not highly
  protein-bound

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CRRT in ICU Indications

• 3. Severe sepsis
• There has been recent interest in the potential
  for haemofiltration to remove inflammatory
  mediators in patients with severe sepsis/septic
  shock.
• A number of small studies (with 25 subjects or
  less) have suggested that high volume
  haemofiltration (40-85ml.kg-1.hr-1) may reduce
  vasopressor requirements and possibly improve
  survival in patients with septic shock
  irrespective of whether they have an AKI
• However, strong recommendations cannot be made
  about the role of RRT in this area until larger,
  well designed trials address the issue

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Mechanism

• Mechanism of solute removal
• Filtration (convection) versus dialysis
  (diffusion)

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Mechanism (Contd)
Schematic representation of CVVH and CVVHDF
circuits
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Mechanism (Contd)
The arrangement of a haemofiltration and a
haemodiafiltration circuit
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(No Transcript)
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CRRT in ICU

• Clinical studies of CRRT in the ICU
• The diversity of clinical approaches to the
  treatment of AKI in the ICU is illustrated by the
  results of the BEST Kidney study,
• The only multinational epidemiological study of
  RRT practice in the ICU
• Study documented the treatment of AKI in 1,738
  patients in 54 ICUs on five continents

Nat. Rev. Nephrol. 20106521529.
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CRRT in ICU (Contd)

• BEST study results
• CRRT was the most common choice of initial RRT
  treatment, with 80 of patients on CRRT
• IHD use was mostly restricted to ICUs in north
  and south America, where it was used as initial
  therapy in 3040 of patients, while, by
  contrast,
• CRRT is used first in 100 of ICUs in Australia
• Among patients receiving CRRT, however, marked
  variation in the modality, intensity, timing and
  threshold of use was observed,
• Making it difficult to compare outcomes between
  patients on CRRT and those on IHD

Nat. Rev. Nephrol. 20106521529.
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CRRT in ICU (Contd)
Nat. Rev. Nephrol. 20106521529.
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CRRT in ICU (Contd)

• Timing of CRRT
• Dose or intensity of CRRT

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CRRT in ICU (Contd)

• The ATN and RENAL trials
• Important to recognize that these studies
  differed in methodology and patient
  characteristics and that
• Any comments made from their comparison can only
  be regarded as inferential
• However, as the trials enrolled comparable
  patient populations (all patients were critically
  ill, all had been admitted to an ICU, and mean
  APACHE scores were equivalent at randomization),
• The marked discrepancies in outcomes in the two
  trials demand examination, even if any
  conclusions might be seen as controversial

Nat. Rev. Nephrol. 20106521529.
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Nat. Rev. Nephrol. 20106521529.
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CRRT in ICU (Contd)

• Both the ATN and RENAL studies failed to detect
  any survival benefit from more-intensive RRT
• In addition, no significant differences in
  mortality rates were observed between
  high-intensity and low-intensity treatment in
  pre-specified subgroups in either study

Nat. Rev. Nephrol. 20106521529.
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CRRT in ICU (Contd)

• ATN and RENAL studies
• These results provide definitive evidence to
  recommend that escalation of CRRT intensity to
  beyond conventional doses of 25 ml/kg per hour is
  not beneficial for unselected ICU patients with
  AKI

Nat. Rev. Nephrol. 20106521529.
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CRRT in ICU (Contd)

• RENAL study
• The results suggest that initial use of CRRT
  might be associated with greater recovery of
  independent renal function compared with use of
  IHD,
• but confirmation of this hypothesis in a
  prospective, multicenter, randomized controlled
  trial would be required for a strong
  recommendation for CRRT on this basis alone
• Disadvantages of CRRT include its
• Higher cost and the
• Need for greater use of anticoagulation therapy
  (compared to intermittent therapy)

Nat. Rev. Nephrol. 20106521529.
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CRRT in ICU (Contd)

• Authors of review in Nature reviews nephrology
  (2010) states
• Despite a lack of formal evidence, however, in
  our opinion the clinical argument for use of CRRT
  in patients with hemo dynamic instability does
  seem to be largely won
• Although our preference for the use of CRRT in
  critical illness may be influenced by the fact
  that we practice in Australian and UK
  environents,
• Even the ATN investigators in the US did not feel
  that they had sufficient equipoise to assign hemo
  dynamically unstable patients to IHD in their
  trial

Nat. Rev. Nephrol. 20106521529.
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CRRT in ICU (Contd)

• This decision is an important point because it
  implies that, in a large group of veterans
  affairs and other academic hospitals in the US,
• clinicians felt that patients receiving
  vasopressor therapy should receive CRRT in
  preference to IHD
• In the ATN trial, such patients formed the
  majority of individuals with AKI in the ICU
• If facilities and training are required to
  provide CRRT for the majority of patients
  requiring RRT, the economic arguments against
  extending use of CRRT to other patients become
  less important

Nat. Rev. Nephrol. 20106521529.
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CRRT in ICU (Contd)

• Dose of CRRT
• The ATN and RENAL studies have now established an
  upper limit of intensity for CRRT
• Given the likelihood of a doseresponse
  relationship at treatment intensities lt20 ml/kg
  per hour, delivery of doses lower than this seems
  to be undesirable
• Clinicians should prescribe CRRT on the basis of
  patient body weight to the established effluent
  flow rate target of 2025 ml/kg per hour

Nat. Rev. Nephrol. 20106521529.
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CRRT in ICU (Contd)

• Dose of CRRT (Contd)
• Equally importantly, both the ATN study and the
  RENAL study demonstrated that
• The prescribed dose is 1015 less than the
  delivered dose in these patients, presumably
  owing to treatment downtime
• Thus, if clinicians wish to avoid delivering a
  dose lt20 ml/kg per hour, they need to make
  appropriate adjustments to their prescription

Nat. Rev. Nephrol. 20106521529.
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RRT in ICU Preference

• Decision about which technique to use depends on
• 1. What we want to remove from the plasma

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RRT in ICU Preference (Contd)

• 2. The patients cardiovascular status
• CRRT causes less rapid fluid shifts and is the
  preferred option if there is any degree of
  cardiovascular instability.
• 3. The availability of resources
• CRRT is more labour intensive and more expensive
  than IHD
• Availability of equipment may dictate the form of
  RRT

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RRT in ICU Preference (Contd)

• 4. The clinicians experience
• It is wise to use a form of RRT that is familiar
  to all the staff involved
• 5. Other specific clinical considerations
• Convective modes of RRT may be beneficial if the
  patient has septic shock
• CRRT can aid feeding regimes by improving fluid
  management
• CRRT may be associated with better cerebral
  perfusion in patients with an acute brain injury
  or fulminant hepatic failure

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Prescription of CRRT

• A typical prescription for a 75kg patient
  requiring CRRT for an AKI would be as follows
• Anticoagulation
• Unfractionated Heparin 5,000 IU bolus followed
  by a pre-filter infusion at 500 IU.hr.-1
• Aim to anticoagulate filter but ensure APTTRlt2

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Prescription of CRRT (Contd)

• Fluid balance over 24 hours
• Aim for an even balance if the patient is
  euvolaemic
• Aim for the appropriate negative balance if the
  patient is fluid overloaded (lt1500ml/24hrs)
• Type of Replacement fluid/Dialysate
• Use solutions without potassium if serum
  potassium is high but switch to potassium
  containing solutions as serum potassium
  normalises
• Use a bicarbonate-based buffer rather than a
  lactate-based buffer if there are concerns about
  lactate metabolism or if serum lactategt8mmol.l.-1
  Note- An intravenous bicarbonate infusion may be
  required if a lactate-based buffer is used

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Prescription of CRRT (Contd)

• Exchange rate/treatment dose
• 1500ml.hr.-1 (75kg x 20ml.kg.-1hr-1)
• The treatment dose is usually prescribed as an
  hourly exchange rate which is the desired
  hourly flow rate adjusted for the patients
  weight
• In the case of CVVH, the exchange rate simply
  represents the ultrafiltration rate whereas in
• CVVHDF it represents a combination of the
  ultrafiltration rate and the dialysate flow rate
• In CVVHDF, the ratio of ultrafiltration to
  dialysate flow is often set at 11 but it can be
  altered to put the emphasis on either the
  dialysis or filtration component

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Prescription of CRRT (Contd)
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CRRT Complications

• Complications related to the vascath (including
  line-related sepsis)
• Haemodynamic instability
• Air emboli
• Platelet consumption
• Blood loss
• Electrolyte imbalances
• Hypothermia
• Effects of anticoagulation (bleeding or specific
  side-effects of the anticoagulant used e.g.
  heparin induced thrombocytopenia)

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Self Assessment - 1

• Which of the following statements comparing
  Dialysis with Filtration are true
• A Dialysis depends on diffusion whereas
  filtration depends on convection
• B Filtration is more effective than dialysis at
  removing small molecules
• C Filtration in more effective than dialysis at
  removing cytokines
• D Dialysis is not as effective as Filtration at
  removing water

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Self Assessment - 1 Answers

• Which of the following statements comparing
  Dialysis with Filtration are true
• A Dialysis depends on diffusion whereas
  filtration depends on convection - True
• B Filtration is more effective than dialysis at
  removing small molecules - False
• C Filtration in more effective than dialysis at
  removing cytokines - True
• D Dialysis is not as effective as Filtration at
  removing water - True

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Self Assessment - 2

• Which of the following statements are true
  regarding the differences between CRRT and IHD
• A CRRT is more cost effective than IHD
• B IHD is preferable to CRRT in patients who are
  cardiovascularly unstable
• C IHD offers an overall survival benefit when
  compared with CRRT
• D CRRT is preferable to IHD in patients with a
  coexistent acute brain injury

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Self Assessment 2 Answers

• Which of the following statements are true
  regarding the differences between CRRT and IHD
• A CRRT is more cost effective than IHD - False
• B IHD is preferable to CRRT in patients who are
  cardiovascularly unstable - False
• C IHD offers an overall survival benefit when
  compared with CRRT - False
• D CRRT is preferable to IHD in patients with a
  coexistent acute brain injury - True

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Self Assessment - 3

• Are the following statements regarding RRT True
  or False
• A Poor vascular access often contributes to the
  clotting of a filter
• B RRT has an established role in septic shock
  with normal renal function
• C Protein bound drugs are not easily removed by
  CRRT/IHD
• D The hospital mortality of patients with AKI on
  RRT is approx 60

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Self Assessment - 3 Answers

• Are the following statements regarding RRT True
  or False
• A Poor vascular access often contributes to the
  clotting of a filter - True
• B RRT has an established role in septic shock
  with normal renal function - False
• C Protein bound drugs are not easily removed by
  CRRT/IHD - True
• D The hospital mortality of patients with AKI on
  RRT is approx 60 - True

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CRRT in ICU Status of issues
Nat. Rev. Nephrol. 20106521529.
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Conclusions

• Much practice variation continues to exist in the
  provision of CRRT in the ICU
• Two large prospective, multicenter, randomized
  controlled trials (ATN and RENAL) have now
  addressed the appropriate intensity of CRRT, but
  many questions remain regarding the
• Timing of therapy,
• Role of intermittent dialysis in the ICU and the
• Effect of therapy choice on renal recovery

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Conclusions (Contd)

• Further examination of the results from these two
  studies may shed light on some of these issues
  and might guide the conception of future clinical
  trials
• Devising prescriptive guidelines for the
  management of all aspects of this complex and
  costly therapy that are widely applicable to
  differing clinical environments worldwide is
  likely to remain difficult

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Any Questions?
Thank You!