Prescribing Dialysis

So, you want to place a dialysis order. Your order will be related to your indications for dialysis. This page attempts to explain some of the key considerations that need to be taken into account.

This page does include some specifics to working in Eastern Health ICUs; in particular in Box Hill where a mixture of CRRT and SLEDD is conducted.

Types of RRT

CRRT (Continuous Renal Replacement Therapy)

• This is the primary RRT used in most ICUs. It is usually run over 24 hours at a time but does result in far less efficient clearance of solute than SLEDD or IHD (see below).
• There are various forms CRRT can take:
  • CVVH – Continuous veno-venous haemofiltration
    • Sole use of convection
    • Good for removal of large molecules
  • CVVHD – Continuous veno-venous haemodialysis
    • Sole use of diffusion
    • Good for removal of small – medium molecules
  • CVVHDF – Continuous veno-venous haemodiafiltration
    • This is a combination of diffusion and convection
  • SCUF – Slow Continuous Ultrafiltration
    • Fluid removal only (no solute clearance)
    • No replacement fluid or dialysate used
• Dosage of CRRT is typically around 25 – 30ml/kg/hr. Some units or clinical circumstances require high dose (35-50ml/kg/hr). This is split as some combination of dialysate flow and pre/post-dilution flow. This will be explained in more detail later.
• Presently, the Baxter Prismax is used for patients in Eastern Health requiring CRRT. Citrate anticoagulation is the preferred method to anticoagulate these patients.
• Typical clearance rates for CRRT are 20 -30 ml/min – around the creatinine clearance of a patient with stage 4 CKD
• Due to the low flow rates and gentle clearance this is the most well tolerated form of renal replacement therapy (other than peritoneal dialysis).
• Blood flow runs veno-venous via a permacath or vascath.
• Pre-mixed 5L bags of dialysate fluid need to be hung. This is the primary limiting factor to the dialysate and filtration rates that can be run by these machines.
  • For example, if a 100kg man is prescribed a dose of 100ml/kg/hr of RRT then 10L of dialysate fluid per hour would need to be hung. Over a 10 hour shift this would require changing bags every 30 minutes!

SLEDD (Slow, Low Efficiency Daily Dialysis)

• Typically you can get enough clearance from this form of RRT that we would only need to perform a “run” every 24 to 48 hours for 6-12 hours at a time (hence “Daily”). We can achieve clearance rates of 120ml/min via SLED, as good as a healthy set of kidneys (normal creatinine clearance being 125ml/min).
• Veno-venous via a permacath or vascath.
• The dialysate fluid for this form of RRT is pumped in from the wall, this allows high rates of dialysate flows without breaking the backs of those running the RRT.
  • The dialysate fluid comes from a reverse osmosis (RO) purification plant which separates water from its solutes by forcing it through a semi-permeable membrane.
  • Solutes are then added back to it in the concentrations required before running it through the circuit (e.g. sodium, potassium, bicarbonate).
  • The fluid from the RO is not sterilised – this is fine in theory as it will never come into contact with the patient’s blood as it is separated by a semi-permeable membrane, however the RO system does need to be taken offline for cleaning with a reasonable frequency (weekly, fortnightly) to avoid accumulation of contamination.
• The maximum length of time a SLEDD circuit will last is 12 hours as crystallization occurs within the filter due to bicarbonate and other factors necessitating a circuit change.
• If using SLEDD, then it is important to take note of the patients urea level, as the high clearance rates can lead to rapid reductions in serum urea levels.
  • We don’t want to remove urea too quickly as this can result in rapid changes in serum osmolarity that can lead to cerebral oedema.
    • Serum Osmolarity = (2 x [Na]) + [Ur] + [Glucose]

IHD (Intermittent Haemodialysis)

• This is the mode that long term dialysis patients receive. It is aggressive, in that all the clearance for the week that would usually be done by the kidneys needs to be done in 3 sessions which typically last 3 – 4 hours each. The clearance is far higher than CRRT and is higher than SLEDD.
• Such aggressive renal replacement therapy requires a haemodynamically stable patient, as the rapid fluid and solute shifts can result in significant instability.
• May be arterio-venous (via a fistula) or venous-venous (via a permacath or vascath).
• Routinely dialysate flows of 500ml/min and blood flows of 400ml/min are used to achieve high clearance rates.

RRT dose

• The “dose” of RRT is the effluent flow rate (or what leaves the machine). Depending on the type of dialysis received this would be the dialysate flow rate +/- filtration flow rate (+/- fluid removal rate although generally fluid removal is not included as it only makes up a small portion)
  • For CVVHDF then the effluent rate is 50% dialysate and 50% filtration
• The biggest difference between the types of RRT (CRRT vs. SLEDD vs. IHD) is the “dose”
  • CRRT is often conducted in critical care due to lack of dialysis infrastructure that allows for IHD, namely the systems to carry out reverse osmosis.
• The “dose” of RRT relates to the clearance effect of the RRT
  • a higher dose will have a higher corresponding clearance
  • clearance is the volume of blood “cleared” per unit time of a particular solute e.g. urea
• In the ICU literature comparing high dose and low dose RRT the numbers generally used are 25 – 30ml/kg/hr for low dose and 35-50ml/kg/hr for high dose RRT.
• The literature focuses on continuous renal replacement therapy (CRRT)
  • There is no evidence for routinely using high dose RRT
  • So a 100kg patient who receives CRRT admitted to a typical ICU will receive ~3000ml/hr (30mls/kg/hr) of RRT dosage as a combination of filtration and dialysis
• Intermittent haemodialysis (IHD) dosage can be as high as 500ml/min dialysate with the addition of some pre-dilution too, which is at least 30000ml/hr! This is why patients on intermittent haemodialysis only need to receive RRT 3x per week.
• Prescribed RRT dose is often not the same as delivered RRT dose due to interruptions (circuit alarms, changing of replacement solutions, clinical procedures etc)
  • For example, to achieve a delivered dose of 20-25mls/kg/hr, a dose of around 30mls/kg/hr may need to be prescribed

Blood flow

• A higher blood flow rate will result in higher clearance, however with higher blood flow rates comes higher pressures in the RRT machine. Nursing staff may interpret this as the filter “clotting” or “clagging”, another common cause of high pressures in the filter.
  • Solute clearance is also related to the effluent flow rate, or dose.
  • In CRRT the effluent flow rate is usually the limiting factor so this will dictate solute clearance.
• Typically we would use a blood flow rate of 200ml/min during SLEDD, it should be enough depending on your dialysate rate.
• Starting blood flow rates for CRRT on the Prismax are based on patient weight.
  • If < 70kg: 150 mls/min
  • If 70 – 100Kg: 200 mls/min
  • If > 100kg: 250 mls/min
• Higher blood flow rates may be used however a Permacath (14.5Fr) may be required to achieve such flows, due to the smaller lumen of the Dolphin vascaths we typically use (13.5Fr).
  • The Hagen-Poiseuille equation describes the determinants of resistance to flow of liquid in a tube, if the lumen radius increases by 20% the flow through it can be doubled.
  • Shorter lumen vascaths should be able to achieve higher flows as well, although if the tip does not sit in the large central SVC/IVC, flows may be limited by vessel size.
• If blood flow is too low (< 100 – 150 mls/min) then there is an increased risk of the filter loss due to blood stasis in the circuit.
  • Repeated circuit changes are a task that no one enjoys

Dialysate flow

• This is the D of your order
• Solute clearance occurs via diffusion
• Dialysate flows counter-current to the blood in the circuit to maximise concentration gradients
• For CRRT the blood flow should be >2x dialysate flow – this may only be 16 – 40mls/minute (16mls equates to 1L/hr). 20mls/kg/hr is an appropriate value to use.
  • Clearance is a balance between allowing saturation of the dialysate (slower flows allow maximal saturation) and the flow of “new” dialysate into the circuit to maintain concentration gradients (faster flows).
• For SLEDD dialysate flow rates are faster – typically we would use 100 – 300ml/min of dialysate flow
• Higher flows may be used in dialyzable drug overdoses such as metformin or ethylene glycol.
• It is important to note that clearance rates will only increase with increasing dialysate flows if blood flow increases too.
  • As discussed earlier, blood flow can be limited
  • If both blood flow and dialysate rate are both slow then the dialysate soon becomes saturated reducing clearance
    • Increasing the blood flow rate doesn’t produce an improvement in clearance as the saturated dialysate flow hasn’t changed.
    • Likewise increasing the dialysate flow won’t improve clearance as the blood present at the lower flow rates has already been cleared of solutes.
• High dialysate rates only really come into play for dialyzable toxins where we would aim for clearance higher than normal renal function.

Concentration gradients in dialysate

• Dialysate bags are often pre-made with certain concentrations of solutes; the concentrations available depend on the modality of RRT prescribed.
  • For example, for SLEDD at BHH, you need to decide on concentration gradients for sodium (129-154 mmol/L), potassium (2, 3, 4 mmol/L), bicarbonate (24-40mmol/L – a higher concentration may increase rate of crystal formation in filter)
  • For CRRT, sodium and potassium can be added to the bags depending on the patient’s clinical state
• The larger the concentration gradient between serum and dialysate, the faster the solutes will equilibrate.
  • For example, if I had a patient with a serum [potassium] of 7mmol/L, I might set the dialysate [potassium] at 3mmol/L which would result in a relatively rapid removal of potassium to achieve a safe serum [potassium].
  • If [Potassium] of 2mmol/L was used and dialysate flow high and the RRT treatment long enough, it may be possibly to bring the [potassium] between 2-3mmol/L which may be unwise.
  • Some centres have potassium free dialysate so a decision regarding how fast you need to reduce [potassium] against the risks of too low a [potassium] need to be evaluated.
• If your patient is hypo or hypernatraemic, you need to take care to not set the sodium concentration too high or too low so that you avoid rapid change in serum osmolarity
  • For example, if you “had” to give RRT to a patient with a [sodium] of 120mmol/L you would set the sodium concentration at 129mmol/L and check the [sodium] frequently during the treatment to avoid correcting it too fast.
• Temperature (34 – 39°C) is another important modifiable factor (e.g. ensuring not hypothermic if patient bleeding, or helping cool a patient post cardiac arrest). CRRT may also mask a febrile response in patients.

Filtration

• This is your F of your HDF order
• Filtration involves water being “pushed” across a membrane via an applied hydrostatic force – this removal of fluid is known as ultrafiltration.
• Convection (“solvent drag”) is the associated movement of molecules through a membrane with the fluid being removed during ultrafiltration.
  • This clears middle – large size molecules and clearance is independent of concentration gradients across the membrane
  • The higher the filtration rate, the higher the solute clearance
• Filtration Fraction is the amount of plasma removed as an ultrafiltrate
  • This should ideally be ~20-25%
  • If it is too high, then the resultant higher haematocrit can lead to the filter clotting, particularly when running replacement fluid “post dilution”.
• The plasma removed is replaced by a replacement fluid to prevent hypovolaemia
  • This may be added “pre-dilution” (where fluid is added to the blood coming from the patient prior to entry into the filter hence “pre”) or “post-dilution” (where fluid is added to the blood returning to the patient after the filter hence “post”).
  • Pre-dilution will result in a lower clearance rate from your filtration than post-dilution, this is due to the solutes being diluted in concentration prior to entering the filter.
  • Each unit will often have their determined split of pre and post dilution fluid, and this may vary if CVVHF or CVVHDF is used
    • For CVVH often ~30% pre dilution and 70% post dilution replacement is used.
  • The default “post-dilution” is 200mls/hr.

Fluid removal rate

• Fluid is removed via the process of filtration, as described above.
• It is important that fluid removal can lead to haemodynamic instability so, so if a patient is becoming more unstable then this rate may need to be slowed or fluid removal abandoned.
  • If a patient remains haemodynamically unstable whilst being filtered
• To work out fluid removal, firstly consider how oedematous/overweight with fluid your patient is, how long you’re going to run your filter for and divide to attain the fluid removal rate per hour.
  • Simplistically, if you want to remove 2L fluid:
    • If they are having 8 hours of RRT treatment the fluid removal rate will be 250mls/hour
    • If they are having CRRT (over 24 hours) this will be 83mls/hour.
• There are some caveats to fluid removal:
  • To attain a net deficit of 2L all the other fluid that your patient is receiving during and between RRT runs should be included.
    • For example, if patient is on feeds at 80ml/hr over 20 hours that is an additional 1600mls. Therefore the actual fluid removal is 450mls/hr off to get your 2L negative! And in this example the only fluid the patient is receiving is the feeds (and not lots of other infusions)
    • In SLED/IHD fluid boluses are given every 2 hours to improve filter life. In BHH ICU, every 2 hours the nursing staff will bolus 150mls of dialysate fluid through the filter, again in order to prevent “clagging”. In an 8 hour run this equates to 450mls or an additional 55mls/hr removal.

Anticoagulation

• Anticoagulation of RRT is a broad topic with many controversies.
• Essentially you there are three options:
  • Do nothing
    • To minimise risk of the filter clotting then adequate blood flow must be maintained and haemoconcentration within the filter should be minimised
  • Regional – anticoagulate the machine (e.g. Citrate or Heparin / Protamine)
  • Systemic – anticoagulate the machine and patient

Regional Citrate Anticoagulation

• The use of citrate is growing in popularity and is the first line modality for anticoagulation in Eastern Health’s CRRT circuits.
• Citrate chelates calcium which inhibits platelet aggregation and coagulation by inhibiting thrombin formation (requires an ionised calcium levels < 0.35 mmol/L)
• This citrate – calcium complex is removed by the filter
• A post filter calcium infusion is therefore required to keep ionised calcium (iCa) within the normal range and this rate can be adjusted depending on monitored ionised calcium levels.
  • Initial Calcium compensation depending on initial iCa value:
    • If iCa > 1.2 mmol/L: 90%
    • If iCa 1.0 – 1.2 mmol/L: 100%
    • If iCa < 1.0 mmol/L: 110%
    • If iCa initially under 1.1 mmol/L then 10mls of calcium gluconate should be given
• Any remaining citrate is metabolised by the liver, kidney and muscles into bicarbonate.
• Contraindications include severe fulminant hepatic failure (care needed in those liver failure or ischaemic hepatitis).
• Complications include:
  • Metabolic Alkalosis – if excess citrate is delivered and metabolised then the bicarbonate produced will lead to an alkalosis
    • If suspected, reduce blood flow (as this will reduce citrate flow as blood flow and citrate flow are dependent on one another) or increase dialysate rate
  • Citrate accumulation (if unable to metabolise citrate – difficult to predict but those with liver dysfunction at higher risk) then this can cause a high anion gap metabolic acidosis, decreasing iCa (hypocalcaemia symptoms) or a ratio of total calcium : iCa > 2.5.
    • If suspected then needs discussion with senior but can consider using an alternative anticoagulation method, reducing the citrate dose or increasing the dialysate (to lose more citrate-calcium complex)
  • Electrolyte abnormalities – hypo / hypercalcaemia, hypomagnesaemia, hypernatraemia (citrate often comes as trisodium citrate)
    • Hypocalcaemia can be treated by increasing the “calcium compensation” or if thought to be related to reduced citrate metabolism then reducing blood flow may also help.

Heparin

• Do not administer heparin to patients with confirmed or suspected Heparin-induced thrombotic thrombocytopaenia (HITTs)
• Heparin can either be used as a regional or systemic anticoagulation
• Regional use requires protamine to be added to the filter circuit post filter but before the patient return
  • This requires an increased workload with the monitoring of both filter and patient APTT
  • Also exposes patient to the known risks of protamine (e.g. anaphylaxis, pulmonary hypertension)
• LMWH can also be used for systemic anticoagulation but need to consider accumulation given renal clearance
• At BHH for SLEDD:
  • Typical rates of heparin infusion are 300-800 units/hr
  • Rates are both patient (lower or no heparin for bleeding patients) and consultant dependent
  • Some of the heparin will be removed by the filter, decreasing the amount of systemic anticoagulation the patient will receive
  • We generally do not check APTTs during the filter run, although you would if you were running CRRT.
  • It is generally thought to be safe to administer the patient’s usual DVT prophylaxis (enoxaparin) during or after an RRT run due to the low doses of heparin used and the removal of heparin by the filter.

References and Further Reading

Complications of regional citrate anticoagulation

How to prescribe and troubleshoot continuous renal replacement therapy

Author: Nick Ryan