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SOE 037: Renal Replacement Therapy 2

Introduction

You are called to see a 68-year-old man is 2 days post-operative following a femoral endarterectomy for an acutely ischaemic limb. He has developed rhabdomyolysis with morning bloods demonstrating an elevated creatine kinase (23,482 U) and an elevated creatinine (349 Umol/L)…

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Case Information

A blood gas shows:

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Question No. 3

Q: Can you describe the findings from the blood gas?

Answer No. 3

Summary
Summary
Summary

There is a profound high anion-gap metabolic acidosis with partial respiratory compensation

There is a profound high anion-gap metabolic acidosis with partial respiratory compensation

There is a profound high anion-gap metabolic acidosis with partial respiratory compensation

Description
Description
Description

Acid-Base Status

1. Primary Disorder
  • The primary disorder is a metabolic acidosis with a BE of -14.

Acid-Base Status

2. Compensation & Secondary Disorder
  • There is partial respiratory compensation
  • The measured (3.4 kPa) and expected (3.5 kPa) are similar so a secondary respiratory disorder is not suggested

Acid-Base Status

3. Assessment of Metabolic Acidosis
  • The anion gap is 24 mmol/L indicating the presence of a HAGMA
  • The delta ratio is 0.85 indicating an isolated HAGMA

Acid-Base Status

4. Assessment of HAGMA
  • Osmolarities not provided

Acid-Base Status

5. Assessment of NAGMA
  • Not applicable

Oxygen Status

6. Assessment of oxygenation
  • There is slight impairment of oxygenation with P/F ratio of 46.25

Oxygen Status

7. Assessment of oxygen carriage
  • Co-oximetry values not provided

Question No. 4

Q: Other than metabolic acidosis what are the indications for renal replacement therapy?

Answer No. 4

Renal Indications

Emergency Indications

  • Metabolic
    • ↑ K+ (>6.5 mmol/L)
    • ↑ urea (>40 mmol/L)
    • Uraemia with symptoms:
      • Pericarditis
      • Encephalopathy
  • Refractory pulmonary oedema
  • Metabolic Acidaemia due to renal failure (pH<7.15)
  • Oligo-anuria(<200ml/24 hours)

Non-Emergency Indications

  • Acheivement of homeostasis in AKI unresponsive to conservative management
    • Acid-base balance
    • Solutes
    • Fluid
Non-Renal Indications
  • Removal of dialysable toxins
  • Removal of contrast agent (Less relevant with newer contrast agents)
  • Clearance of cytokines to decrease severity of sepsis (controversial)
  • Control of body temperature (an extracorporeal circuit can help control hypo or hyperthermia which is resistant to other methods of control)
  • Control of otherwise uncontrollable electrolytes:
    • ↑ Ca+ refractory to pamidronate
    • Sodium abnormalities resistant to treatment

Question No. 5

Q: Can you draw the key components required to perform renal replacement therapy?

Answer No. 5

Basic anatomy of the continuous renal replacement therapy circuit

Question No. 6

Q: How does the circuit differ for haemodialysis and haemofiltration?

Answer No. 6

Haemodialysis
Haemofiltration
Haemodiafiltration
SCUF

Question No. 7

Q: What variables are controlled through the circuit that influence its function?

Answer No. 7

Fluid flows occuring through the basic renal replacement therapy circuit
Blood Flow Rate
Blood Flow Rate
Qb
  • The rate of blood flow from the patient towards the filter
  • Blood flow rates are typically slower than in intermittent dialysis, ranging from 150-200mL/min
Ultrafiltrate Rate
Ultrafiltrate Rate
Quf
  • The rate at which ultrafiltrate is produced by hydrostatic pressure across the membrane during convective therapies
  • It is influenced by the blood flow rate and the filtration fraction
Dialysate Flow Rate
Dialysate Flow Rate
Qd
  • The flow rate of dialysis fluid in dialytic therapies
  • Standard flow rates range from 8-50 mL/min
Effluent Rate
(Dose)
Effluent Rate
(Dose)
Qef
  • The effluent flow rate is the equivalent to ultrafiltration rate Quf in continuous haemofiltration, Qd in continuous haemodialysis, and both Quf & Qd in continuous hemodiafiltration
  • It is analogous to the ‘dose’ in continuous therapies
  • Dosing is weight-based and is typically prescribed at a dose ranging from 20 mL/kg/hr to 35 mL/kg/hr
Substitution Fluid Rate
Substitution Fluid Rate
Qs
  • Techniques in which produce a volume of ultrafiltrate require replacement of this fluid with a substitute fluid to prevent significant loss of volume.
  • The rate of substitution fluid describes the rate at which this replacement fluid is added to the plasma
Net Ultrafiltrate Rate
Net Ultrafiltrate Rate
Qnet
  • Represents the overall rate of fluid removal
  • It is the difference between the total effluent removed (Qef) minus the volume of replacement therapy
  • The fluid removal rate can be tailored by the machine to meet the total removal goal of the patient

Question No. 8

Q: What determines the clearance in CRRT? How is the effluent rate determined?

Answer No. 8

  • Clearance describes the volume of blood that is cleared of a substance per unit of time
  • The determinant of clearance in CRRT depends upon the mechanisms that are being utilised
    • In continuous haemofiltration:
      • A volume of ultrafiltrate is produced following the passage of the pressurised plasma over the membrane
      • Clearance is of a solute determined by the:
        • Rate at which ultrafiltrate is produced (Quf)
        • Sieving coefficient of the filter membranes (determined by the ratio of solute concentrations in the ultrafiltrate)
      • Most small molecules have a sieving coefficient of 1, meaning they pass freely through the membrane (though this is less true of middle molecules)
      • Therefore, the clearance is analogous to the ultrafiltrate production rate (Quf)
    • In continuous haemodialysis:
      • The concentration gradient across the membrane determines clearance
      •  The gradient is affected by the dialysate flow rate (Qd) and the blood flow rate (Qb)
      • Qd is much slower than Qb, and the dialysate becomes fully saturated.
      • Therefore, the dialysate rate (Qd) becomes the rate-limiting factor for solute removal and is analogous to clearance
    • Overall consequently, clearance is equivalent to the combination of the ultrafiltration rate (Quf) and dialysate (Qd), which is termed the effluent rate (Qef)
    • This is often discussed in terms of the ‘dose’ of a continuous replacement therapy which is given
  • In ultrafiltration, the effluent rate is determined by the flow of plasma into the membrane and the fraction of this which is filtered out as effluent (known as the filtration fraction)
  • To maintain a constant effluent rate:
    • At low blood flows a large filtration fraction is required
    • At high flows, a small filtration fraction can be used
  • The renal replacement circuits have inbuilt algorithms to deliver a desired effluent flow rate based upon the blood flow from the patient

Question No. 9

Q: What is the optimal dose of CRRT in AKI?

Answer No. 9

  • Adequate clearance, and how this influences outcome is not clear:
    • Current research suggests that a rate of 20-25ml/kg is adequate
    • Higher rates of clearance (35-40ml/kg) confer no benefit
    • Higher rates may need to be prescribed to ensure minimum desired clearance is met
  • High volume hemofiltration may be of benefit in:
    • Rhabdomyolysis
    • Clearance of ammonia and lactate
    • Pancreatitis (experimental)
    • Clearance of cytokines (experimental)
Optimum 'dose' range of continuous renal replacement therapy

Question No. 10

Q: What evidence exists to determine the optimum ‘dose’ of CRRT? 

Answer No. 10

Intervention
Population
Conclusion

RCT: ELAIN


Zarbock et al
JAMA (2016)

View Paper
  • 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)
The Bottom Line Review

RCT: AKIKI


Gaudry et al
NEJM (2016)

View Paper
  • 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
The Bottom Line Review

RCT: IDEAL-ICU


Barbar et al
NEJM (2018)

View Paper
  • 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
    The Bottom Line Review

Question No. 11

Q: What is difference between prescribed and delivered dose? What dose should be prescribed?

Answer No. 11

  • 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. 12

Q: What is the prognosis of patients requiring RRT in ICU?

Answer No. 12

  • Mortality remains high in critically ill patients
    • Mortality around – 45-60% in studies
    • RRT withheld in around 20% of patients
  • Of those that survive to ICU discharge:
    • If no chronic renal impairments prior to admission:
      • Long-term RRT required in 2-11%
      • CKD in 44%
    • If chronic renal impairment prior to admission:
      • Long-term RRT required in up to 55%

Question No. 13

Q: What are the complications of RRT?

Answer No. 13

Access Related
  • Failure to obtain access
  • Damage to vessels and surrounding structures
    • Risk of venous stenosis
    Pneumothorax / haemothorax
  • Haemorrhage
  • Infection
  • Air Embolism
  • Pain
Anticoagulation Related
  • Bleeding
  • Heparin induced thrombocytopenia
  • Hypocalcaemia with citrate
Filtration Related
  • Hypotension and haemodynamic instability:
    • Common on initiation of renal replacement as the circuit often takes 200-300 ml of blood
    • Usually responds to a fluid bolus
    Anaemia (up to 300ml of blood can be lost in clotted filter)
  • Removal of solutes:
    • Electrolyte imbalance
    • Trace elements and amino acids
    • Therapeutic drugs
    Hypothermia
  • Metabolic abnormalities
  • Reaction to filter membrane and anaphylaxis
  • Rising lactate:
    • Inability to metabolise lactate in the filter fluid to bicarbonate
    • Switch to filter fluid with bicarbonate buffer
    Immobility

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