CRRT in ICU

1. CRRT in ICU Dr.

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

3. Introduction

4. Introduction (Contd)

5. Introduction (Contd)

6. 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

7. 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 originated�and remains widely practiced�in the form of continuous hemofiltration

9. CRRT in ICU As a continuous therapy, CRRT can be rapidly tailored to changes in a patient�s clinical condition during critical illness

10. CRRT in ICU (Contd)

11. CRRT in ICU (Contd)

12. 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

13. 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

14. CRRT in ICU: Indications

15. CRRT in ICU: Indications 1 Acute kidney injury with Fluid overload (refractory to diuretics) Hyperkalemia (K+ > 6.5) Severe metabolic acidosis (pH < 7.1) Rapidly climbing urea/creatinine (or urea > 30mmol/l) Symptomatic uraemia: encephalopathy, pericarditis, bleeding, nausea, pruritus Oliguria/anuria

16. 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

17. 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

18. Mechanism Mechanism of solute removal: Filtration (convection) versus dialysis (diffusion)

19. Mechanism (Contd)

20. Mechanism (Contd)

22. 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

23. 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 30�40% 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

24. CRRT in ICU (Contd)

25. CRRT in ICU (Contd) Timing of CRRT Dose or intensity of CRRT

26. 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

28. 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

29. 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

30. 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)

31. 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

32. 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

33. 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 dose�response relationship at treatment intensities <20 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 20�25 ml/kg per hour

34. CRRT in ICU (Contd) Dose of CRRT (Contd) Equally importantly, both the ATN study and the RENAL study demonstrated that The prescribed dose is 10�15% less than the delivered dose in these patients, presumably owing to treatment downtime Thus, if clinicians wish to avoid delivering a dose <20 ml/kg per hour, they need to make appropriate adjustments to their prescription

35. RRT in ICU: Preference Decision about which technique to use depends on: 1. What we want to remove from the plasma

36. RRT in ICU: Preference (Contd) 2. The patient`s 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

37. RRT in ICU: Preference (Contd) 4. The clinician`s 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

38. 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 APTTR<2

39. 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 (<1500ml/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 lactate>8mmol.l.-1 [Note- An intravenous bicarbonate infusion may be required if a lactate-based buffer is used]

40. 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 patient`s 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 1:1 but it can be altered to put the emphasis on either the dialysis or filtration component

41. Prescription of CRRT (Contd)

42. 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)

43. 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

44. 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

45. 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

46. 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

47. 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%

48. 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

49. CRRT in ICU: Status of issues

50. 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

51. 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

52. Any Questions?