Viva 8

You have admitted a haemodynamically unstable septic patient with acute renal failure and the following biochemistry:


On Admission

Na (mmol/L)

135 – 145


K (mmol/L)

3.5 – 4.5


Urea (mmol/L)

3 – 8


Creatinine (umol/L)

50 – 100


Phosphate (mmol/L)

0.7 – 1.4


Lactate (mmol/L)

0.2 - 2


Will you dialyse this patient? Why, or why not?

The original viva from the college didn't give you a choice about CRRT, and was more interested in the choice of filter:

You have decided to initiate CVVHDF in a septic patient with acute renal failure and the following biochemistry:

Please choose the filter that you will use in a CVVHDF circuit for this patient? Name some advantages of the filter you have chosen?

The rest of the questions focused on circuit set up, discussion of pre-dilution, choice of dialysate, trouble shooting various alarms and interpretation of raised urea creatinine ratio.

Of course this viva relies heavily on a situation where the trainee walks into a room and finds the examiner sitting there, surrounded by different filters. This is not something that's likely to happen in the average viva practice group environment, at which these confabulated non-canonical vivas are aimed. Ergo, the author has taken extensive liberties with the original format. The trainee is given the option of not dialysing the patient, to see how they justify their position.

So, if they recommend early RRT, the following supporting rationale is valid:

  • Renal failure results in the accumulation of uraemic toxins
  • The damage done by this accumulation is dose-dependent, i.e. there is no "critical" value beyond which the urea suddenly becomes toxic: it is toxic all the time, and the more of it there is the worse the patient's condition
  • Ergo, the early removal of such toxins should benefit the patient 
  • For many patients the need for future dialysis is apparent (i.e. you know you're going to dialyse them at some point) and it would make no sense to wait for "symptomatic" uraemia.
  • Delaying therapy is unlikely to have any immediate benefit as you have not treated anything.
  • Medical therapies for managing complications of acute renal failure are not benign, for instance causing deafness (frusemide), bowel obstruction (cation exchange resins) and increased CO2(bicarbonate).

If they decide to wait and watch:

  • Renal replacement therapy is not benign: there are well-documented complications.
  • A proportion of patients with severe acute kidney injury never go on to require RRT
  • The safety of careful medical management is greater than the safety of careful RRT
  • Specifically, the patient may not require central venous catheterisation, sparing them the risks of large vessel access, catheter-related blood stream infection, puncture site haematoma and air embolism.
  • Renal replacement therapy is not cheap.
  • Most complications of acute renal failure are such that require relatively inexpensive and easily administered solutions, eg. calcium gluconate, sodum bicarbonate, frusemide, and so on.
  • The cost of RRT is not only in equipment but also in manpower and maintenance.
  • If spontaneous renal recovery is not achieved because RRT has caused some sort of "dialysis-induced renal injury", one may add the cost of more prolonged (potentially, life-long) dialysis.
  • Renal replacement therapy is not a "cure" for acute renal failure, it is merely a support strategy.
  • RRT may even cause a delay in renal recovery
  • Some of the retained toxins of uraemia may have some opportunistic benefit, eg. urea may act as an osmotic diuretic (i.e. in the presence of a high urea the urine output may be greater).
What is the evidence regarding the timing of renal replacement therapy in sepsis?
  • AKIKI trial by Gaudry et al (2016):
    • n= 620.
    • Of the delayed group, only 51% received dialysis - the rest scraped through without it.
    • Fewer catheter-associated infections in the delayed group.
    • Mortality between groups did not differ significantly (48.5% vs 49%), nor was there any increase in the length of ICU stay. BUT:
    • 50% of the patients had IHD instead of CRRT, even though they all required vasopressors (well, 85% did)
  • ELAIN trial by Zarbock et al, 2016):
    • n=230
    • Early RRT was found to reduce mortality, BUT:
    • Almost 50% were cardiac surgical patients
    • Not specific to sepsis
    • Fragility index of 3
  • Meta-analysis (Luo et al, 2017)
    • n=9698 patients (5408 "critically ill")
    • Early RRT decreased mortality only in the critically ill group
  • STARRT-AKI trial: currently enrolling
What are your standard absolute indications to start dialysis?
  • Oliguria (less than 200ml in 12 hours)
  • Anuria (0-50ml in 12 hours)
  • Urea over 35 mmol/L
  • Creatinine over 400mmol/L
  • Potassium over 6.5mmol/L
  • Refractory pulmonary oedema
  • Metabolic acidosis with pH less than 7.10
  • Hypernatremia over 160mmol/L
  • Hyponatremia under 110 mmol/L
  • Temperature over 40°C
  • Complications of uraemia: encephalopathy, pericarditis, myopathy or neuropathy
  • Overdose with a dialysable toxin
What are the consequences and clinical manifestations of uraemia?
Clinical Manifestations of Uraemia


  • Pericardial rub
  • Pericardial effusion


  • Mixed metabolic acidosis
  • Uraemic foetor
  • Pruritis
  • "Uraemic frost"
  • Nail atrophy
  • Sallow skin colouration and melanosis


  • Uraemic encephalopathy
  • Peripheral neuropathy


  • Improved glycaemic control in diabetics


  • Nausea
  • Vomiting


  • Platelet dysfunction
How would you interpret the ratio of urea to creatinine in this patient? 
  • The ratio is calculated from US units, rather than the usual units.
    In the US, your creatinine is not 500μmol/L, its 0.5mmol/L. Urea remains in mmol/L. 
    Thus, in this patient, the ratio is 50/0.55, i.e. 90.
    • Anything above 100 is considered abnormal (ie. too much urea and not enough creatinine).
    • Greater than 100 =  prerenal ARF
    • Less than 100 = ATN
  • So, you'd have to come to the conclusion that this patient is probably not going to improve remarkably with rehydration. However,  Bagshaw Langenberg and Bellomo (2006), were very critical of all these biochemical indices, concluding that "the scientific basis for the use of urinary biochemistry, indices, and microscopy in patients with septic ARF is weak". 
What other biochemical indices could you use to classify the cause of this renal failure as pre-renal or intra-renal?

This is identical to Question 25 from the second paper of 2007:

A Comparison of Findings in Pre-Renal and Intra-Renal Failure

Intra-renal Failure

Pre-renal failure

Urine osmolality

Less than 400-450 mOsm/kg: concentrating ability is lost

More than 450-500 mOsm/kg: concentrated urine is being passed.

This demonstrated that concentrating capacity is preserved,
which is unlikely in ATN.

Urine sodium

High in ATN (>40 meq/L) due in part to the tubular injury. Injured tubules cannot concentrate urine or appropriately reabsorb sodium.

Low in prerenal disease (<20 meq/L) in a (sometimes) appropriate attempt to conserve sodium. Pre-renal failure may also include various low-output or decreased renal blood flow states such as cirrhosis and CCF. 

Urea/ creatinine ratio

Normal in ATN

May be greater. In dehydration, urea is disproportionately elevated (indicating a loss of total body water).

The ratio is calculated from US units, rather than the usual units. In the US, your creatinine is not 500μmol/L, its 0.5mmol/L. Urea remains in mmol/L. Thus, urea/creatinine gives you the ratio. Anything above 100 is considered abnormal (ie. too much urea and not enough creatinine).

Urine/serum creatinine ratio

More than 40

Less than 20

Urine/serum osmolality

More than 1.0

More than 1.5

Fractional excretion of urea

More than 25%

Less than 25%

Fractional excreton of sodium

More than 2% (demonstrating a failure of sodium resorption)

Less than 1% (demonstrating a tendency to conserve sodium, as if in a state of hypovolemia)

Urine microscopy


  • muddy brown granular casts
  • epithelial cell casts
  • free epithelial cells
  • Nothing, or hyaline casts (which are non-specific)
Let's say you decided to commence RRT. Which modality will you use, and why?

The candidate should be allowed to ramble for a period.

What are the main methods of solute clearance by dialysis?
  • Diffusion
  • Convection
What is the definition of convective clearance?
  • "Convection is bulk-flow of solute across a semi-permeable membrane together with a solvent in a manner that is dependent on transmembrane pressure and membrane characteristics."  - ADQI
What determines convective clearance of a solute?

This equation describes Jc, the convective flux:

convective flux equation

Thus, the important elements are

  • sieving coefficient
  • solute concentration in plasma water
  • Ultrafiltration rate

The sieving coefficient is  ":the ratio of a specific solute concentration in the ultrafiltrate (removed only by a convective mechanism), divided by the mean plasma concentration in the filter."


  • Convection is less dependent on molecule size than diffusion
  • Small and middle molecules are equally likely to get convected across the membrane by solvent drag
  • There is still a size barrier, usually around 3000-5000Da
  • The porosity of the membrane is important as this determines the size barrier
  • The ultrafiltration rate is also of importance
What is the dose of dialysis you would prescribe, and why?
  • 25ml/kg/hr is the accepted dose of CRRT.
  • The RENAL group of investigators concluded that "increasing the intensity of continuous renal-replacement therapy from 25 to 40 ml of effluent flow per kilogram per hour does not reduce mortality or the rate of dependence on dialysis among critically ill patients".
How do you define the dose of dialysis?
  • Theoretically:
    • Definition of "dose" in CRRT is volume of blood "purified."
    • Measure of "dose" in CRRT: clearance rate of a representative marker solute.
  • Practically:
    • Dialysis dose is equivalent to the effluent rate in ml/kg/hour.
    • Effluent rate is the ultrafiltration rate for haemofiltration (CVVH).
    • In CVVHDF, in practical terms, the "volume of blood purified" dose of dialysis is essentially the effluent flow rate (i.e. the combination of dialysate and ultrafiltrate flow rates).
Will you use pre or post filter dilution? And why?
A Comparison of Pre-dilution and Post-dilution in CRRT
  Pre-dilution Post-dilution
  • Ultrafiltration rate is not limited by the blood flow rate (one can simply give more pre-dilution fluid if one wants more ultrafiltration to occur)
  • Elution of urea from RBCs is enhanced (urea migrates out of them into the diluted plasma)
  • Filter life is increased, as the haematocrit throughout the filter remains reasonably low
  • One may even avoid the need for circuit anticoagulation
  • With increased filter lifespan, one may achieve a higher solute clearance over the whole (longer) session, even though hourly solute clearance may be decreased.
  • Clearance of solute is directly related to ultrafiltration rate.
  • A higher solute clearance rate is produced
  • A smaller volume of replacement fluid is required (why is this an advantage? Perhaps, cost.)
  • Filter lifespan can remain unaffected if protected by adequate anticoagulation
  • Solute concentrations are decreased, and thus the concentration gradients are decreased in the countercurrent filter: the result is a decreased rate of solute clearance
  • A larger amount of predilution fluid is required
  • The rate of ultrafiltration is limited by the blood flow rate: you cannot order too much fluid removal, because otherwise the end-filter haematocrit will be too high. (This is why a smaller volume of replacement fluid is required!)
  • Because ultrafiltration rate is limited by filtration fraction (anything beyond 25% is too much), one may not achieve the desired "optimal" dose of 25ml/kg/hr with the normal blood flow rates of CRRT.
  • Filter life may be degraded by high end-filter haematocrit
The patient has a past history of HITS. What are the options for anticoagulating the circuit?
  • Reversible
  • Effective
  • Pre-mix solutions have simplified this process; protocols exist to guide the inexperienced
  • Cumbersome protocol; greatly increased workload
  • Requires frequent monitoring:
    • Sodium
    • Calcium
    • Bicarbonate (or pH)
  • If you are using trisodium citrate, you end up giving a massive amount of sodium
  • Acidosis may result due to excess citrate
  • Alkalosis may result when that citrate is metabolised
  • In hepatic failure, this is contraindicated (as citrate is metabolised mainly by the liver)
  • Special calcium-free hyponatraemic and bufferless dialysate is required
  • If the patient has HITTS, they will still require some sort of systemic anticoagulation
  • Risk of toxicity
    • High anion gap metabolic acidosis
    • Ionised hypocalcemia
Direct thrombin inhibitors:
Hirudin / Lepirudin
Bivalirudin / Argatroban
  • Alternative to heparin in HIT
  • Argatroban has a short halflife and is metabolised by the liver
  • There is a predictable near-linear relationship between hirudin levels and APTT
  • Expensive
  • Hirudin, lepirudin and bivalirudin are renally excreted; halflife will be prolonged
  • Argobatran is metabolised by the liver - halflife will be prolonged in liver failure
  • Argatroban falsely raises PT and INR.
  • All these molecules are too large to be removed by CRRT membranes, and will accumulate.
  • No reversal agent
Heparinoids (Danaparoid)
  • Expensive
  • Cross-reactivity with heparin/platelet antibodies (in 5%)
  • Long half life (48 hrs)
  • No reversal agent
  • Higher risk of bleeding than with heparin
Xa inhibitors: Fondaparinux
  • Renally cleared; may accumulate in high doses
  • Long halflife (15-20hrs)
  • No reversal agent
Serine protease inhibitors: Nafamostat
  • Suppresses neutrophil activity and may cause agranulocytosis
  • May cause increased bilirubin levels
  • Clearance relies on serum esterases, which may be decreased in chronic liver disease
  • May decrease protein C activity, leading to paradoxically increased circuit clotting
  • May cause anaphylaxis
  • May cause hyperkalemia
Prostacyclin (PGI2)
  • Very short half life (90 seconds)
  • Probably safe
  • Decreases platelet consumption in the circuit
  • Can be used together with heparin for a combined effect, as a "heparin-sparing" agent.
  • Hypotension from vasodilation
  • Ridicuously expensive
  • If the patient has HITTS, they will still require some sort of systemic anticoagulation
After a couple of hours, the machine issues this alarm: "WARNING: Access Extremely Negative". What could be the cause of this? What would you do about it?


  • The vas cath is kinked
  • The line is kinked
  • The vas cath is sucking against a vessel wall
  • The vas cath has become occluded with clot
  • The vas cath is of poor design (i.e. you should have inserted a short widebore vas cath, with a circular lumen crossection)
  • The blood flow to the vas cath is poor:
    • The patient is hypovolemic
    • There is increased intrathoracic or intraabdominal pressure, decreasing venous flow past the catheter tip
    • The patient is breathing without positive pressure ventilation, and is hyperventilating (deep panicked breaths create a strongly negative intrathoracic pressure during inspiration, which pulls blood in the opposite direction, out of the vas cath).


  • Check the circuit:
    • Start from the machine and work along the circuit, checking for kinks
    • Check the vascath for kinks; ensure it has not become dislodged
    • Obviously, unkink the kinked bits.
    • Try to gently rotate the vas cath, if possible. Some positions may be better than others.
    • Pause dialysis and aspirate the vas cath lumens, trying to suck out the clot (if there is one)
  • Check the patient
    • An agitated patient who is constantly repositioning themselves will play havoc with the access pressure. Encourage their cooperation.
    • Ensure there is enough venous blood (i.e. consider the possibility that there is hypovolemia)
    • Ensure the respiratory pattern is not responsible (for intrathoracic catheter tips and spontaneously breathing patients)
  • Admit defeat
    • First, just press "continue"*. Whatever the phenomenon was, it may have passed.
      *This rarely works.
    • You may have to resort to decreasing the blood flow rate. This will decrease the solute clearance somewhat, but at least the machine will stop alarming.
    • If nothing is working, one may find that swapping the access and return lumens can help. However, even if this does work, the recirculation will be massive (much of the returned blood will get sucked into the circuit again). Conventional wisdom holds that this is a useless strategy. You may as well not be dialysing at all, they say. However, a study by Carson et al (2005) suggests that reversing the lumens does not appear to hamper the clearance of urea.Still, in most circumstances, it is still better to resite the vas cath.
After another few hours, the machine alarms "WARNING: High Transmembrane Pressure". What is the definition of transmembrane pressure?

"Transmembrane pressure is the hydrostatic pressure gradient across the membrane. This is the driving force that causes ultrafiltration."

What is the formula used to calculate transmembrane pressure?

Thus, TMP is the effluent pressure subtracted from the average of the pressures in the blood side of the circuit (which are the filter pressure and the return pressure). TMP tends to rise gradually over the course of the dialysis session, as the filter becomes clogged with filth.

What are contraindications to the use of citrate?
  • Liver disease
  • Decreased hepatic blood flow
  • Severe shock (thus, decreased muscle perfusion- as muscle is a secondary site of citrate metabolism)
What are features of citrate toxicity? 

The cardinal features of citrate toxicity are:

  • High anion gap metabolic acidosis OR metabolic alkalosis
  • Low ionised calcium with a high (or normal) total calcium

Disclaimer: the viva stem above may be an original CICM stem, acquired from their publicly available past papers. Or, perhaps it is a slightly altered version of the original CICM stem. Or, it is a completely original viva stem, concocted by the monstrously amoral author of Deranged Physiology for nothing more than his own personal amusement. In either case, because the college do not make the main viva text or marking criteria available, almost everything here has been confabulated. It might sound like a plausible viva and it could be used for the purpose of practice, but all should be aware that it does not represent the "true" canonical CICM viva station. 


Gaudry, Stéphane, et al. "Initiation strategies for renal replacement therapy according to severity and septic shock: a post-hoc analysis of the AKIKI trial." D24. CRITICAL CARE: THE OTHER HALF OF THE ICU-UPDATE IN MANAGEMENT OF NON-PULMONARY CRITICAL CARE. American Thoracic Society, 2017. A7136-A7136.

Luo, Kaiping, et al. "The optimal time of initiation of renal replacement therapy in acute kidney injury: A meta-analysis." Oncotarget 8.40 (2017): 68795.

Wald, Ron, Martin Gallagher, and Sean M. Bagshaw. "Shedding new light on an old dilemma: two trials examining the timing of renal replacement therapy initiation in acute kidney injury." American Journal of Kidney Diseases 69.1 (2017): 14-17.

Sanjay Subramanian, John A. Kellum, and Claudio Ronco "Oliguria" in: Critical Care Nephrologyby Ronco, Bellomo and Kellum (2009) pp. 341

Crook, Martin. Case Presentations in Chemical Pathology. Elsevier, 2013.

Bagshaw, Sean M., Christoph Langenberg, and Rinaldo Bellomo. "Urinary biochemistry and microscopy in septic acute renal failure: a systematic review."American journal of kidney diseases 48.5 (2006): 695-705.

Vaara, Suvi T., et al. "Timing of RRT based on the presence of conventional indications." Clinical Journal of the American Society of Nephrology 9.9 (2014): 1577-1585.

Wierstra, Benjamin T., et al. "The impact of “early” versus “late” initiation of renal replacement therapy in critical care patients with acute kidney injury: a systematic review and evidence synthesis." Critical Care 20.1 (2016): 1.

Gaudry, Stéphane, et al. "Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit.New England Journal of Medicine (2016).

Seabra, Victor F., et al. "Timing of renal replacement therapy initiation in acute renal failure: a meta-analysis." American Journal of Kidney Diseases 52.2 (2008): 272-284.

Kleinknecht, Dieter, et al. "Uremic and non-uremic complications in acute renal failure: Evaluation of early and frequent dialysis on prognosis." Kidney international 1.3 (1972): 190-196.

Egal, Mohamud, et al. "Targeting Oliguria Reversal in Goal-Directed Hemodynamic Management Does Not Reduce Renal Dysfunction in Perioperative and Critically Ill Patients: A Systematic Review and Meta-Analysis." Anesthesia & Analgesia 122.1 (2016): 173-185.

Ahmed, U. S., H. I. Iqbal, and S. R. Akbar. "Furosemide in Acute Kidney Injury–A Vexed Issue."Austin J Nephrol Hypertens 1.5 (2014): 1026.

Zarbock, Alexander, et al. "Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury: the ELAIN randomized clinical trial."JAMA 315.20 (2016): 2190-2199.

Zhongping Huang, Jeffrey J. Letteri, Claudio Ronco, Dayong Gao, and William R. Clark "Predilution and Postdilution Reinfusion Techniques"; in: Critical Care Nephrology by Ronco, Bellomo and Kellum (2009) pp. 1370

Ronco, C., et al. "The haemodialysis system: basic mechanisms of water and solute transport in extracorporeal renal replacement therapies." Nephrology Dialysis Transplantation 13.suppl 6 (1998): 3-9.

Uchino, Shigehiko, et al. "Pre-dilution vs. post-dilution during continuous veno-venous hemofiltration: impact on filter life and azotemic control." Nephron Clinical Practice 94.4 (2004): c94-c98.

Nurmohamed, Shaikh A., et al. "Predilution versus postdilution continuous venovenous hemofiltration: no effect on filter life and azotemic control in critically ill patients on heparin." ASAIO Journal 57.1 (2011): 48-52.