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Question No. 3
Q: In the absence of emergency indications what are the advantages and disadvantages with early and late timing of RRT initiation?
Answer No. 3
Early Initiation
- May confer benefit, in particular in circumstances in which there is a perception that recovery from AKI is not imminent
- Can theoretically facilitate more rapid correction of electrolyte and acid-base derangements and control of uraemia and mitigate fluid accumulation
- Would prevent the occurrence of overt complications of AKI
- May limit worsening of non-renal organ dysfunction (potential kidney-organ interactions)
- Will result in initiation of RRT in a significant portion of patients who may have regained renal function with conservative management
Late Initiation
- Has not been shown to lead to worse outcomes than early initiation
- Prevents complications of RRT in subset of patients that did not require it:
- Insertion of dialysis catheters
- Exposure to extracorporeal circuits
- Clearance of nutrients and medication
- Iatrogenic haemodynamic instability
- Reduces healthcare costs by limiting bedside workload and resource utilisation
Question No. 4
Q: What is the evidence in regard to early or late initiation of RRT?
Answer No. 4
Intervention
Population
Conclusion
- Early vs. Late initiation of RRT
- Early: Within 8 hours of meeting KDIGO stage 2 AKI
- Late: Within 12 hours of meeting KDIGO stage 3 AKI or emergency indication
- 231 patients with AKI and either severe sepsis or requiring catecholamine infusion
- Early group showed significantly lower mortality at 90 days (39.3% vs. 54.7%, p=0.03)
- Early vs. Late initiation of RRT
- Early: Immediately upon meeting KDIGO stage 3 AKI criteria
- Late: If oliguric 72 hours after meeting KDIGO stage 3 AKI criteria or emergency indications
- 620 patients with AKI requiring mechanical ventilation or catecholamine infusion
- No difference in mortality between early and late group (48.5% vs 49.7%, p=0.79)
- In delayed group 49% did not require RRT
- Early vs. Late initiation of RRT
- Early: within 12-hours of meeting failure by RIFLE criteria
- Late: after 48-hours of meeting failure by RIFLE criteria if no renal recovery or emergency indications
- 488 patients with severe AKI and septic shock
- No difference in mortality between early and late group (58% vs 54%, p=0.38)
- In delayed group:
- 38% did not require RRT
- 17% met indications for emergency RRT
Question No. 5
Q: What factors should be taken into account when determining whether initiation of RRT is appropriate for a patient in AKI?
Answer No. 5
- In the absence of emergency indications:
- Current evidence does not firmly confirm advantages of either an early or late initiation of RRT
- Most evidence supports the use of a “wait and see” attitude without leading to worse outcomes
- Patient should be considered as a whole (Table adapted from Macedo et al):
Severity of Illness & Trajectory
- AKI severity and trend
- Severity of electrolyte and acid base disorder
- Fluid balance and symptoms of overload
- Presence of other organ dysfunction impacted by AKI / fluid overload
Necessity of RRT
- Likelihood of early recovery of kidney function without RRT
- Underlying comorbidities impacted by AKI / fluid overload
- Associated acute organ dysfunction
Risks of RRT
- Vascular access
- Haemodynamic instability
- Infection
- Clearance of trace elements / vitamins / drugs
- Immobilisation
Other Factors
- Patient and family wishes
- Overall goals of care
- Availability of machines and nursing staff
- Healthcare costs
Question No. 6
Q: What are the basic components of CRRT that need prescribing in ICU?
Answer No. 6
Component
Choice
Blood Flow Rate
- Blood flow rates are typically slower than in intermittent dialysis (150-200mL/min)
- Generally, the faster the flow, the more efficient the dialysis.
Dialysate or Replacement Fluid Composition
- The specific fluid is based on the metabolic parameters of the patient, including the patient’s acid-base status and serum potassium concentration
- Typical flow rates range from 500mL/min to 800mL/min
Replacement Fluid Pre/Post Dilution Ratio
- The proportion of replacement fluid delivered before or after the filter
- Typically started with 30% pre- and 70% post-dilution
Effluent Rate (Dose)
- Dosing is weight based and is typically prescribed at a dose ranging from 20 mL/kg/hr to 35 mL/kg/hr
Fluid Removal Goal
- This is the amount of fluid to be removed from the patient over the course of the session
- Determined by clinical assessment of the patient’s volume status.
Anticoagulation
- Clotting within the dialysis circuit can result in significant blood loss
- Heparin is typically used unless the patient has a contraindication
- An alternative to heparin anticoagulation often used with CRRT is regional citrate anticoagulation, in which citrate is administered to chelate calcium, a critical cofactor in the clotting cascade
Question No. 7
Q: What effect do changes in the blood flow rate have?
Answer No. 7
Advantages
Disadvantages
High Blood Flows
- A lower filtration fraction required thus reducing the risk of filter clotting
- Easier to match ultrafiltration rates and therefore fluid removal targets
- Increased risk of haemodynamic instability
- Increased risk of hypothermia or haemolysis
- Requires well-functioning access to prevent high suction pressures developing
Low Blood Flows
- Reduced haemodynamic instability
- Reduced risk of filter related complications
- Lower suction pressures needed to achieve flow rates
- Increased risk of filter clotting due to high filtration fractions
- More challenging to meet fluid removal targets
Question No. 8
Q: What evidence exists to determine the optimum ‘dose’ of CRRT?
Answer No. 8
Intervention
Population
Conclusion
- Early vs. Late initiation of RRT
- Early: Within 8 hours of meeting KDIGO stage 2 AKI
- Late: Within 12 hours of meeting KDIGO stage 3 AKI or emergency indication
- 231 patients with AKI and either severe sepsis or requiring catecholamine infusion
- Early group showed significantly lower mortality at 90 days (39.3% vs. 54.7%, p=0.03)
- Early vs. Late initiation of RRT
- Early: Immediately upon meeting KDIGO stage 3 AKI criteria
- Late: If oliguric 72 hours after meeting KDIGO stage 3 AKI criteria or emergency indications
- 620 patients with AKI requiring mechanical ventilation or catecholamine infusion
- No difference in mortality between early and late group (48.5% vs 49.7%, p=0.79)
- In delayed group 49% did not require RRT
- Early vs. Late initiation of RRT
- Early: within 12-hours of meeting failure by RIFLE criteria
- Late: after 48-hours of meeting failure by RIFLE criteria if no renal recovery or emergency indications
- 488 patients with severe AKI and septic shock
- No difference in mortality between early and late group (58% vs 54%, p=0.38)
- In delayed group:
- 38% did not require RRT
- 17% met indications for emergency RRT
Question No. 9
Q: What is difference between prescribed and delivered dose? What dose should be prescribed?
Answer No. 9
- There may be a significant difference between the prescribed ‘dose’ and that which is actually delivered – estimated using clearance equations to be 73% in practice
- Due to a number of factors:
- Treatment downtime due to filter clotting
- Technical problems such as boor blood flow and recirculation
- Reduced filter efficacy over time
- Effects of pre-dilution
- It is recommended that a dose of at least 35 ml/kg/h (post-dilution) is prescribed for CRRT
- This ensures that an adequate dose of CRRT is delivered despite downtimes and other limiting factors
Question No. 10
Q: Why has a higher dose not shown to improve outcomes?
Answer No. 10
- Increasing the dose may cause loss of essential molecules and thus affect outcome:
- Antibiotics – many significantly cleared by RRT
- Amino acids and proteins
- Micronutrients (vitamins, selenium, folic acid)
Question No. 11
Q: What is the replacement fluid and what is it composed of?
Answer No. 11
- Replacement fluid is given to replace the fraction of fluid which has been produced as effluent
- The addition of fluid dilutes the concentration of solutes in excess in the plasma
- The addition of solutes in the fluid can increase the concentration of solutes that are deplete in the plasma
- They consist of a balanced salt solution with a molecule used to buffer acid – commonly either lactate or bicarbonate
- Individual components vary but should contain:
- Sodium 140 mmol/l
- Chloride 108–112 mmol/l
- Potassium 0–4 mmol/l
- Calcium 1.5–1.75 mmol/l
- Magnesium 0.5–0.75 mmol/l
Question No. 12
Q: Does the buffer make a difference?
Answer No. 12
- There is no conclusive evidence of a benefit on survival or renal outcome with either bicarbonate or renal outcomes
- Both types have advantages and disadvantages:
Bicarbonate Buffer
Lactate Buffer
- May result in better control of acidaemia
- May result in improved cardiovascular stability
- Unstable in solution, need to be prepared just prior to use
- More expensive
- Cheaper than bicarbonate buffer
- Longer shelf life
- Can result in rise in serum lactate:
- Lactate intolerance defined by rise in lactate >5 mmol/L
- Should be switched to bicarbonate buffer
Question No. 13
Q: Which factors effect the pharmacokinetics of drugs administered whilst patients are receiving RRT?
Answer No. 13
Drug Factors
- Protein binding:
- Highly protein bound drugs (e.g. warfarin, diazepam, propranolol and phenytoin) are only cleared by RRT in small amounts
- Molecular weight:
- Larger molecules cleared less effectively by diffusive therapies
Therapy Factors
- Timing of RRT:
- Drugs given between sessions will not be cleared until the subsequent session
- Dose of RRT:
- Reduced flow rates / shorter sessions will decrease clearance of drugs
- Membrane permeability
Patient Factors
- Residual GFR and urine production
- Hypoalbuminaemia
Question No. 14
Q: How should drugs be dosed during RRT?
Answer No. 14
- Dosing during RRT can be challenging given the numerous factors needed to be accounted for:
- Should not simply be dosed for reduced GFR
- Nomograms developed for use in stable patients on IHD can result in significant under-dosing
- Drug levels should be measured to aid dosing whenever possible
- In the absence of drug levels:
- ‘Bedside’ dosing guidelines should be used (e.g. ‘Renal Drug Handbook’)
- Expert pharmacist help should be sought when possible