Printable list of all renal failure and dialysis SAQs

College Answer

Likely mechanisms include pre-renal, renal and post-renal causes.

Pre-renal renal failure includes hypovolaemia (inadequate resuscitation), hypotension (inadequate perfusion pressure compared to his normal BP, ? hypertensive), and impaired cardiac output (myocardial depression, myocardial ischaemia/infarction, arrhythmias).

Renal mechanisms include toxins (circulating, nephrotoxic drugs [eg. aminoglycosides]) and microcirculatory failure (sepsis and inflammatory response) with medullary ischaemia, tubular obstruction and vasoconstriction (acute tubular necrosis).

Post-renal mechanisms include increased intra-abdominal pressure, ureteric obstruction and catheter problems (unrecognised, resulting in obstruction).

Discussion

Again, this is a question where the candidate is expected to demonstrate a systematic approach to the evaluation of renal failure.

In that, the question closely resembles Question 16 from the first paper of 2004, except in 2004 the patient was suffering from pneumonia and the candidate had to evalue their oliguria.

Given the differences between the two questions, the answer from 2004 is appropriately modified and reproduced below.

2) Discriminate between renal success and renal failure.

• Oliguria may be the manifestation of normal volume conservation mechanisms:
  • History will suggest decreased fluid intake
    • Vasopressin use may also be an obvious clue
  • Examination will demonstrate features of dehydration
  • Biochemistry will show an increased urea/creatinine ratio
  • Urinalysis will reveal concentrated urine with low urinary sodium
• Such oliguria will also respond to fluid boluses.
• Oliguria in the presence of normal or increased fluid balance suggests a failure of normal renal excretory function.
• Hypovolemia and dehydration may also be associated with renal failure; a failure to respond to fluid boluses can be an indication that pre-renal failure has developed. Oliguria of normal renal fluid conservation in hpovolemia is a continuum with the oliguria of renal failure due to renal hypoperfusion, and these categories may overlap.

Likely mechanisms of renal failure in a patient with multi-organ system failure and septic shock

• Pre-renal causes
  • Poor renal perfusion due to
    • decreased cardiac output
    • hypovolemia
    • septic shock with uncontrolled hypotension
    • abdominal compartment syndrome
    • renal arterial disease
    • renal venous thrombosis

• Intrarenal causes
  • ATN due to proloned renal hypoperfusion
  • Microvascular thrombotic damage due to DIC of sepsis
  • Nephrotoxic agents eg. gentamicin, IV contrast
  • Rhabdomyolysis
  • Autoimmune glomerulonephritis, eg. post-streptococcal glomerulonephritis or Goodpasture's syndrome (these are less likely)
  • Direct cytokine-associated nephrotoxicity of sepsis

• Post-renal causes
  • Obstruction of the urinary tract:
    • Ureteric obstruction by calculi or infection
    • Ureteric stenosis due to prior radiotherapy
    • Ureteric or bladder injury perioperatively
    • Uretheral obstruction by kinked or malpositioned IDC.

References

Schrier, Robert W., and Wei Wang. "Acute renal failure and sepsis." New England Journal of Medicine 351.2 (2004): 159-169.

Wan, Li, et al. "The pathogenesis of septic acute renal failure." Current opinion in critical care 9.6 (2003): 496-502.

College Answer

In this man, indications for renal replacement therapy/dialysis would include:
Uncontrolled electrolyte disturbances (eg. hyperkalaemia, hypernatraemia); uncontrolled metabolic acidosis (pH criteria depend on ventilatory response); uraemia (traditionally > 35 mmol/L, or ? creatinine  >  0.6  mmol/L);  complications  of  uraemia  (eg.  encephalopathy,  pericarditis);  fluid overload unresponsive to diuretics. Some units would consider early intervention (unproven) with specific techniques to minimise the inflammatory response to sepsis.

Discussion

This question closely resembles Question 8 from the second paper of 2005; "Outline  the clinical scenarios  in which you would consider  instituting dialysis in the critically ill.". In order to simplify revision, I reproduce the answer below:

Renal Indications

• Oliguria with volume overload
  • Oliguria is relative; urine output may be high and still inadequate in clearing the fluid.
• Uremia with symptoms
• Hyperkalemia ( K+ over 6.0)
• Metabolic acidosis due to renal failure or lactate (pH < 7.2)

Non-renal Indications​

• Removal of dialysable toxins, i.e. ones which aren’t very lipophilic or protein-bound
  • Lithium
  • Methanol
  • Ethylene glycol
  • Salicylates
  • Theophylline
  • Valproate
  • Pretty much any drug with a volume of distribution less than 0.5L/kg
  • If a toxin is equally well cleared by hemodialysis and hemoperfusion, then hemodialysis is preferred, because it will also correct any underlying acid-base disturbance.
• Removal of contrast agent
  • More relevant with old-school high-osmolar contrast
• Clearance of cytokines to decrease severity of sepsis
  • Still controversial. May be of use in patients with renal failure and sepsis.
  • No evidence that it helps in patients with sepsis who don’t have renal failure.
• 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
  • Hypercalcemia refractory to bishosphonates

References

College Answer

Available techniques (not limited to the candidates unit) include intermittent haemodialysis, peritoneal dialysis, and the variants contained within continuous renal replacement therapy (CRRT). Intermittent Haemo-Dialysis (IHD; solute clearance = diffusion): quick control, less ICU staff involvement (?  cost  implications), minimise  exposure  to  anticoagulation BUT  haemodynamic instability, potentially dramatic fluid and electrolyte shifts, exposure to extracorporeal circuit and filter membrane, vascular access problems, poor control between dialyses, timing dependent on dialysis staff.

Peritoneal dialysis (PD; solute clearance = convection): continuous control of fluids, avoids vascular access problems, gentle technique, cheap, does not require electricity/machinery/renal unit, timing only dependent on ICU staff BUT requires intact peritoneum, fluid dwelling may impair respiratory function, peritoneal access problems (especially infection), potential inability to control severe uraemia and electrolyte disturbances, hyperglycaemia.

Continuous Renal Replacement Therapy (CRRT; solute clearance = mixture of convection and diffusion): continuous control of fluids and electrolytes (and ? other substances), easily titratable (changing fluid replacement and arterial flow rate or gradient for ultrafiltrate), greater haemodynamic stability (compared with IHD), timing only dependent on ICU staff BUT complex, vascular access problems, usually requires anticoagulation, exposure to extracorporeal circuit and filter membrane.

Specific subtypes of CRRT should be discussed, including:

Continuous Arterio-Venous Haemofiltration (CAVH; solute clearance = convection): simple, can do without pump, electrolyte balance determined by replacement fluid BUT requires arterial access, arterial flow rates and ultrafiltrate flow limit clearance.

Continuous Veno-Venous Haemofiltration (CVVH; solute clearance = convection): avoids arterial access problems, blood flow rate controlled by pump, good clearance of middle molecules, electrolyte balance determined by replacement fluid BUT requires pump and large bore venous access

Continuous Veno-Venous Haemo-Dia-Filtration (CVVHDF; solute clearance = convection and diffusion): increased solute clearance (dependent on dialysate flow), flow rates controlled by pump, electrolyte balance determined by replacement fluid and dialsysate BUT less efficient clearance of middle molecules, still requires pump and large bore venous access.

Discussion

This question would benefit from a tabulated answer.

But firstly, to answer the last question - in this patient CVVHDF would be an appropriate therapy, as heis likely to be hemodynamically unstable, and may not tolerate SLEDD. As hemodynamic stability is reestablished SLEDD can be commenced as a means of intermittently correcting uraemia and fluid overload. The other presented options are either outdated (CAVH, really?) or inappropriate (IHD).

As for the main part of the question; it asks the candidate to compare advantages disadvantages and mechanisms for all available dialytic therapies. In more conservative questions (eg. Question 19 from the second paper of 2008, or Question 10 from the first paper of 2011) only a small selection of modalities is selected for discussion, which would make for a sensibly brief answer. The extensive tabulated answers from these questions will not be repeated here.

Instead, links are offered:

• Comparison of CVVHF, SLED and IHD
• Comparison of CVVHD, IHD and SCUF

The college answer to this question also incorporates peritoneal dialysis, CAVH, and separates into CVVHF from CVVHDF.

Thus, below is a table which compares the modalities which are missing from the tables linked above.

References

D'Intini, Vincent, et al. "Renal replacement therapy in acute renal failure." Best Practice & research clinical anaesthesiology 18.1 (2004): 145-157.

O'Reilly, Philip, and Ashita Tolwani. "Renal Replacement Therapy III: IHD, CRRT, SLED." Critical care clinics 21.2 (2005): 367-378.

Wei, S. S., W. T. Lee, and K. T. Woo. "Slow continuous ultrafiltration (SCUF)--the safe and efficient treatment for patients with cardiac failure and fluid overload." Singapore medical journal 36.3 (1995): 276-277.

Kanno, Yoshihiko, and Hiromichi Suzuki. "Selection of modality in continuous renal replacement therapy." (2010): 167-172. -This seems to be an entire issue of Contributions to Nephrology
(Vol. 166) by Claudio Ronco.

College Answer

(e)       Outline the means by which you would maximise urea clearance and filter life when using CVVHDF.

Urea clearance depends on ultrafiltrate flow rate (clearance by convection proportional to flow rate) and dialysate (countercurrent) flow rate (clearance proportional to flow rate). Increasing clearance would therefore be obtained by increasing either flow rates. Other factors include the use of filters with larger membrane surface areas, the use of predilution (ie. prefilter position for replacement fluid) if ultrafiltration rate is significant, and changing filter if it is failing. Independent factors that may prevent filter fibre loss (ie. prolong filter life) include adequate anticoagulation, priming with albumin, filter coating with anticoagulants, the use of predilution (decreasing oncotic pressure and haematocrit), and avoidance of large negative transmembrane pressures.

Discussion

I can proudly say that my diagram of the CVVHDF circuit is better than the college diagram.

Question (e) is unfairly broad.

There are numerous methods for prolonging circuit lifespan. The answer to Question 4 from the second paper of 2010 contains a massive table titled "Methods of Prolonging the CVVHDF Filter Lifespan", and I will not repeat it here.

The clearance of urea however is a unique question. Judging by the college answer, they were really asking "what strategies exist to increase the removal of solutes by dialysis?"

• Diffusive clearance depends on the following factors:
  • Membrane surface area
  • Concentration gradient of the specific solute
  • Blood flow rate (up to a point)
  • Countercurrent dialysate flow rate
  • Size of the molecule (smaller molecules like urea diffuse more easily)
  • Protein and RBC binding of the solute (urea also needs to diffuse out of RBC intracellular fluid)
• Convective clearance depends on the following factors:
  • Ultrafiltrate flow rate, which in turn is dependent upon transmembrane pressure
  • Porosity of the membrate (more relevant for larger molecules)

Urea is a small highly water soluble molecule, and thus is is easily removed by diffusion as well as convection. Thus, in order to improve the clearance of urea, one may perform the following manoeuvres:

• Use a filter with a larger surface area
• Increase the blood flow rate
• Increase the dialsyate flow rate
• Increase the rate of ultrafiltration
• Change the replacement fluid to pre-dilution, in order to improve the elution of urea from the RBC intracellular fluid
• Ensure that the filter lifespan is maximised, to increase the total duration of the dialysis session.

References

For a definitive treatment of all of this, you ought to pay homage to the gigantic and all-encompassing "Critical Care Nephrology" by Ronco Bellomo and Kellum (2009).

There is also extra stuff is from the Ronco et al article "The haemodialysis system: basic mechanisms of water and solute transport in extracorporeal renal replacement therapies" in Nephrol Dial Transplant ( 1998) 13 [Suppl 6 ]: 3–9.

Finally, the Gambro and Fresenius websites have been an excellent source of information.

College Answer

Aetiology: consider trauma and muscle compression (including immobility), exertional rhabdomyolysis (eg. heat stroke, grand mal seizures), drugs and toxins (via coma/immobility, agitation/hyperthermia,  myotoxins eg. HMG-CoA reductase inhibitors,   myonecrosis secondary to non-depolarising neuromuscular blockers), infections, inflammatory myopathies (eg. polymyositis), electrolyte abnormalities (esp. hypokalaemia and hypophosphataemia), hyperthermia (eg. malignant hyperpyrexia and neuroleptic malignant syndrome), metabolic myopathies.

Presentation:  Consider  history  of exertion,  fitting,  drug  exposure  (including  illicit),  immobility, family history, and previous episodes.   Patient may complain of painful or weak muscles, and pigmented urine. Investigations reveal markedly elevated muscle enzymes (especially CK), acute oliguric renal failure, and electrolyte abnormalities (hyperkalaemia, hyperphosphataemia, hypocalcaemia, hyperuricaemia and metabolic acidosis).

Principles of management: consider general supportive care, adequate fluid resuscitation, forced alkaline diuresis (including mannitol), specific treatment of underlying cause (eg. dantrolene, phosphate replacement, cooling, removal of precipitants, treatment of infection, fasciotomies etc), and correction of electrolyte abnormalities.

Discussion

Somebody at the college loves rhabdomyolysis. This question is virtually identical to Question 16 from the first paper of 2008 and Question 4 from the first paper of 2004.  It also vaguely resembles Question 26.3 from the second paper of 2013.

It is delightful to have a fellowship exam question start with "Please". Basic courtesy goes a long way.

References

College Answer

The definition of high volume haemofiltration and its potential role in Intensive Care patients is unclear.  Purported benefits include clearance of “bad” cytokines/mediators, with improvement in cardiovascular function and even mortality.  More aggressive dailysis may have some survival advantages (Ronco et al Lancet 2000).  Though, in this large prospective RCT, there was no further benefit demonstrated when increasing the ultrafiltration rate > 35ml/hr/kg (ie. approx 2000 mL/hr).

No adequately powered studies assessing other benefits, especially in those without renal failure have been published.  Additional risks of the use of higher volumes are largely centre dependent, but certainly include potential problems with fluid and electrolyte balance.

Discussion

Rimmele and Kellum have a nice article from 2012 summarising the key points of this practice.

The evidence base for high volume haemofiltration is also discussed in the Required Reading chapters.

By a certain sort of extension, one can relate this to the evidence base regarding the optimal dose of dialysis.

One should approach a "critically evaluate" question systematically.

Thus:

Rationale

• Proinflammatory mediators contribute to the pathogenesis of multi-organ system failure in systemic inflammatory states
• Modification of their activity should have a beneficial effect on the progression of MOSF
• Removal of such mediators from the circulation might be an effective means of decreasing their influence
• These proinflammatory molecules are largely water-soluble, which means they can be removed by CVVHDF.
• Ultrafiltration is the ideal means of removing such molecules because their size (5kDa-60kDa) makes them sub-optimal candidates for removal by countercurrent diffusion in dialysis.

Advantages

• Potential benefit in removing inflammatory mediators, thus decreasing the severity of MSOF
• High volume ultrafiltration decreases the intravascular concentration of these molecules rapidly, resulting in a rapid redistribution of these mediators from the interstitial fluid and into the intravascular compartment (from which they can be removed)
• Increasing the concentration gradient in this way should increase the rate of diffusional cytokine removal from infected tissues, leading to decreased leucocyte migratio into those tissues, and thus decreasing the inflammatory damage to those tissues
• Hemofiltration membranes also have some adsorptive properties, allowing the fixation of molecules of a size greater than the membrane cutoff.
• High ultrafiltration rates may increase the exposure of more membrane sites by increasing transmembrane pressure.

Disadvantages

• High ultrafiltration rates will also remove more of the "useful" middle molecules, including the following:
  • Anti-inflammatory mediators
  • Water-soluble vitamins
  • Amino-acids and other nutrients
• High ultrafiltration rates will also remove large volumes of fluid, requiring large volumes of replacement fluid: this can result in undesirably large changes in electrolyte concentration
• The exposure of cellular blood components to the filter membrane at high pressure may result in greater rates of hemolysis and platelet depletion
• High transmembrane pressures increase the risk of membrane rupture and circuit failure
• High-volume ultrafiltration by CVVHDF is highly labour-intensive in the crude physical sense (eg. a dialysis dose of 120ml/kg/hr equates to "8 litre exchanges" in a 70kg patient, which means the nurse looking after the patient has to carry 8 L of effluent away each hour, returning with 8 litres of prepared replacement fluid).

Evidence

• Small early cohort studies had demonstrated an improvement in survival and hemodynamic performance with doses around 100ml/kg/hr, in patients with sepsis, pancreatitis, and SIRS due to post-cardiac arrest global ischaemia.
• The IVOIRE study (2013) compared doses of 75ml/kg/hr with 35ml/kg/hr. They found no benefit in either primary or secondary otucomes, and were forced to conclude that this therapy "cannot be recommended for septic shock complicated by AKI".
• A recent (2014) meta-analysis of high volume hemofiltration in patients with sepsis-associated AKI identified four RCTs, finding no evidence of benefit in primary or secondary outcomes, and attributing a greater frequency of wild electrolyte derangement to the high-volume group.

Summary for practice

• The available evidence does not support the use of high volume hemofiltration in systemic inflammatory states.

References

Bellomo, Rinaldo, Ian Baldwin, and C. Ronco. "High-volume hemofiltration." (2004): 375-382.

Rimmelé, Thomas, and John A. Kellum. "High-volume hemofiltration in the intensive care unit: a blood purification therapy." Anesthesiology 116.6 (2012): 1377-1387.

Honore, P. M., J. Jamez, and M. Wauthier. "Very high volume hemofiltration: A comprehensive review." Proceedings from the International Symposium on Critical Care Nephrology (ISCCN). Melbourne, Australia, Australasian Medical Pub Co. 2001.This is not available even as an abstract, anywhere!

Clark, Edward, et al. "High-volume hemofiltration for septic acute kidney injury: a systematic review and meta-analysis." Critical Care 18.1 (2014): R7.

Joannes-Boyau, Olivier, et al. "High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial." Intensive care medicine 39.9 (2013): 1535-1546.

Laurent, Ivan, et al. "High-Volume Hemofiltration After Out-of-Hospital Cardiac ArrestA Randomized Study." Journal of the American College of Cardiology46.3 (2005): 432-437.

Wang, Hao, et al. "Clinical effects of continuous high volume hemofiltration on severe acute pancreatitis complicated with multiple organ dysfunction syndrome." World Journal of Gastroenterology 9.9 (2003): 2096-2099.

Honore, Patrick M., et al. "Prospective evaluation of short-term, high-volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock." Critical care medicine 28.11 (2000): 3581-3587.

College Answer

Dialytic techniques in the critically ill are becoming more widely used.  Traditional indications used for acute renal failure, are concerns about fluid overload (actual or to facilitate nutritional support), hyperkalaemia or other uncontrolled electrolyte disorders, metabolic acidosis, hyponatraemia, uraemic symptoms or elevated urea (e.g. 30 mmol/L).  As complications associated with techniques have been minimised, dialysis is often initiated earlier (anticipatory, oliguria, lower urea), and for non-renal indications (including sepsis or septic shock).   Dialysis or haemofiltration (e.g. with charcoal filter) can be used to increase the clearance of toxic products from the circulation (e.g. lithium, theophylline, myoglobin). Newer related extracorporeal techniques have also been developed to support liver dysfunction.

Discussion

This question is identical to Question 8 from the second paper of 2005.

References

College Answer

Rhabdomyolysis indicates muscle necrosis and release of intracellular constituents into the circulation. Causes of severe rhabdomyolysis (in this case implying Intensive Care management) include trauma (especially with compression injuries), extreme exertion (e.g. marathon or uncontrolled seizures), immobilisation for prolonged periods, Malignant Hyperpyrexia and Neurolept Malignant syndrome. Rare causes include metabolic myopathies and metabolic/endocrine abnormalities. Management includes confirmation of diagnosis (relevant history; marked elevation of  CK,  hyperkalaemia,  hyperphosphataemia,  hypocalcaemia,  hyperuricaemia,  and  acute  renal failure with metabolic acidosis [and/or lactic acidosis]), specific treatment for any underlying cause (e.g. fasciotomies for compartment syndromes, dantrolene and remove exposure to precipitant for MH, anti-seizure drugs and/or paralysis [as last resort] for status epilepticus), adequate fluid resuscitation (e.g. with isotonic saline), maintenance of an alkaline diuresis (e.g. use of mannitol), careful monitoring and treatment of metabolic disturbances, management of associated disorders (especially with multiple trauma or drug overdose) and consideration of renal replacement therapy.

Discussion

This question is virtually identical to Question 16 from the first paper of 2008, and vaguely resembles Question 26.3 from the second paper of 2013.

References

College Answer

Oliguria in the critically ill may well be an appropriate physiological response to relative volume depletion and circulating stress hormones (including ADH). In that scenario, there would be no evidence of renal failure per se (eg. increase in serum creatinine, decreased creatinine clearance), appropriate urinary concentration would occur (elevated urinary specific gravity and osmolality andlow urinary sodium <20 mmol/L), and an increase in urine output would be expected with fluid loading and/or diuretic administration. If instead signs/investigations suggest renal failure is developing, this would be traditionally divided into pre-renal, renal and post-renal causes. History (e.g. deliberate fluid restriction, associated medical conditions, past history of abdominal surgery, muscle damage, administration of nephrotoxic drugs [e.g. NSAIDs] etc.) and examination (confirmation of diagnosis [e.g. palpation, catheterisation, bladder scan], dehydrated, abdominal distension with increased intra-abdominal pressure, blocked/misplaced urinary catheter, etc.) will obviously help in the diagnosis. Urinalysis is also helpful (e.g. granular or epithelial cell casts with acute tubular necrosis, active sediment with glomerulonephritis, heavy proteinuria with nephritic syndrome.  Further  monitoring  may  be  required  if  the  haemodynamic  status  is  considered inadequate, and specific investigations to assess renal blood flow or exclude obstruction may be clinically indicated.

Specific treatment will depend on the cause (e.g. optimise pre-renal state with hydration and/or haemodynamic  supports,  adequate  treatment  of  infection,  relieve  obstruction,  remove nephrotoxins), but in general there are no specific therapies that have been demonstrated to improve long-term outcome. Treatment options that could be considered include diuretics to enhance urine output, alkalinisation of urine for rhabdomyolysis, and CRRT rather than intermittent haemodialysis if indications for dialysis have been met.

Discussion

An excellent article on evaluation of oliguria in the ICU is presented by RN Sladen.

A systematic aproach to oliguria is summarised elsewhere.

Briefly, an approach to this specific scenario would resemble the following:

1) Confirm oliguria.

• Exclude IDC malposition or kinking

2) Discriminate between renal success and renal failure.

• Oliguria may be the manifestation of normal volume conservation mechanisms:
  • History will suggest decreased fluid intake
    • Vasopressin use may also be an obvious clue
  • Examination will demonstrate features of dehydration
  • Biochemistry will show an increased urea/creatinine ratio
  • Urinalysis will reveal concentrated urine with low urinary sodium
• Such oliguria will also respond to fluid boluses.
• Oliguria in the presence of normal or increased fluid balance suggests a failure of normal renal excretory function.
• Hypovolemia and dehydration may also be associated with renal failure; a failure to respond to fluid boluses can be an indication that pre-renal failure has developed. Oliguria of normal renal fluid conservation in hpovolemia is a continuum with the oliguria of renal failure due to renal hypoperfusion, and these categories may overlap.

3) Discriminate between causes of renal failure

• Pre-renal causes
  • History and examination may suggest CCF, cirrhosis, renal artery stenosis, and so on.
  • Haemodynamic parameters may suggest decreased cardiac output and decreased renal perfusion
  • Hypovolemia due to dehydration may be supported by the serum biochemistry
  • Imaging of the renal vasculature may reveal stenosis or renal vein thrombosis
  • Urinalysis in this case should reveal no specific findings
  • Non-specific management would consist of optimising hemodynamic performance to improve renal perfusion.
  • Specific management would be dependent on the specific aetiology.
• Intrarenal causes
  • History would reveal trauma, infection, or the use of nephrotoxic agents.
  • Examination may confirm a source of sepsis
  • Biochemistry may demonstrate hypoprotinaemia (in nephrotic syndrome), a raised CK (rhabdomyolysis) or metabolic acidosis.
  • Specific biochemistry (ASOT) may reveal post-streptococcal glomerulonephritis as the cause of renal failure. Similarly, anti-GBM antibodies may confirm Goodpasture's syndrome.
  • Urinalysis is useful:
    • Muddy brown casts may suggest ATN
    • Proteinuria may suggest nephrotic syndrome
    • Red cell fragments may suggest glomerulonephritis
  • Non-specific management would consist of optimising hemodynamic performance to improve renal perfusion.
  • Specific management would be dependent on the specific aetiology, be it forced diuresis for rhabdomyolysis or high-dose steroids for Goodpasture's.
• Post-renal causes
  • One must consider an obstruction of the urinary tract:
    • Ureteric obstruction by calculi or infection
    • Ureteric stenosis due to prior radiotherapy
    • Ureteric or bladder injury
    • Urethral obstruction by kinked or malpositioned IDC.
  • Management would be specifically targeted to relieve the obstruction, and would depend on the nature and location of the obstruction. The range includes percutaneous nephrostomy, ureteric stenting, ureteric diversion, or simply reinserting the IDC.

References

Sladen, Robert N. "Oliguria in the ICU: systematic approach to diagnosis and treatment." Anesthesiology Clinics of North America 18.4 (2000): 739-752. This article is perfect for this question, but is not available as free full-text.

Lesko, Janene, and James R. Johnston. "Oliguria." AACN Advanced Critical Care 8.3 (1997): 459-468.

Dujovny, Nadav. "Oliguria." Common Surgical Diseases. Springer New York, 2008. 367-369.

Zaloga, Gary P., and Steven S. Hughes. "Oliguria in patients with normal renal function." Anesthesiology 72.4 (1990): 598-602.

College Answer

Plasmapheresis is used for a wide variety of conditions but predominantly immunologic, neurologic or haemopoietic diseases.   It is used to remove large molecules unable to be removed by less expensive techniques (eg. autoantibodies, immune complexes etc.), that are thought sufficiently toxic to require immediate removal. Replacement for plasma removal is either using large volumes of plasma (eg. especially in Thrombotic Thrombocytopenic Purpura [TTP]) and/or albumin. Plasmapheresis is associated with a variety of potential problems including those related to the procedure (eg. hypotension, dyspnoea, dilutional coagulopathy, immuno-suppresssion and infection), the replacement fluid (eg. hypocalcaemia, metabolic alkalosis), and the access catheters (eg. mechanical and infective).

Adverse reactions are more common using plasma as a replacement fluid (including paraesthesia, muscle cramps, and allergic reactions).  These risks must be balanced against any potential/purported advantages.

The  American  Association  of  Blood  Banks  (AABB)  and  the  American  Society  For Apheresis have published acceptable evidence based indications (Smith Transfusion 2003). Category I indications are defined as “conditions where plasmapheresis is standard and acceptable, either as primary therapy or as a first-line adjunct to other initial therapies. Efficacy is based on controlled or well-designed clinical trials or a broad base of published experience”.  Relevant Category one conditions in ICU include: Guillain-Barre and Acute and chronic inflammatory demyelinating polyradiculoneuropathy, Anti-GBM disease (Goodpasture’s syndrome), TTP and post-transfusion purpura.

Discussion

Plasmapheresis is discussed in the answer to Question 21 from the first paper of 2013, and in even greater detail in Question 14 from the first paper of 2010. Between these two answers, the advantages and disadvantages of plasma exchange are well covered.

References

College Answer

This patient is at high risk (baseline renal impairment, diabetes, manipulation of aorta, and requirement for intravenous contrast).

Potential causes of deterioration with Endoluminal grafts  are  multiple.    Specific factors  include:  they require radiographic evaluation (ie. contrast administration), involve arterial catheter insertion and aortic manipulation (ie. particulate [including cholesterol] emboli), the patients develop a post-operative inflammatory response, and they may be associated with problems with deployment (eg. occlusion of accessory renal artery, or complications that may be associated with haemodynamic compromise, &/or reoperation).

No specific studies have looked at  endovascular grafts. Prevention of  intravenous dye related renal dysfunction has been studied (mainly in coronary angiography). Factors shown to be potentially of benefit include volume expansion (in particular with 154 m/eq/L sodium bicarbonate [Merten 2004 JAMA]), the use of N-acetylcysteine orally (or IV) [Alonso 2004Am J Kidney Dis], the use of lower doses of low osmolal and iso-osmolal non-ionic dyes, and the avoidance of closely spaced studies. Other standard preventative measures include avoidance of volume depletion and nephrotoxins.   The role of mannitol, dopamine, loop diuretics and haemofiltration is uncertain.

Discussion

The patient in question is at risk of renal failure post procedure; however, endoluminal repair is associated with a greatly decreased risk of renal failure (OR ~ 0.42) and progression to dialysis (OR ~ 0.3).

The reasons for renal failure in such a patient include the following:

• Occlusion of renal artery by graft
• Damage to renal artery by procedure
• Atheromatous embolism into the renal circulation
• Renal ischaemia due to poor perioperative perfusion
• ATN due to rhabdomyolysis
• Nephrotoxicity due to contrast.

Of these factors, the first three are within the control of the surgeon to a great extent, and the "anaesthetic colleague" has little control over them. However, the "coallgue" can protect the patient from pre-renal causes of renal failure by ensuring good cardiac output and adequate blood pressure is maintained thoughout the procedure, and by paying careful attention to the periprocedure urine output.

Rhabdomyolysis is also an unpredictable complication, and all one can sensibly do is be careful in selecting which femoral artery one decides to access, and monitoring limb perfusion intraoperatively.

The last point - contrast-induced nephrotoxicity - is where the answering candidate will really earn their marks. This part of the question closely resembles Question 12 from the first paper of 2009, "Critically evaluate strategies that have been used in the prevention of acute kidney injury (AKI) associated with the administration of iodinated  radio contrast medium." A large and reasonably comprehensive table ("Protective Strategies against Contrast-Induced Nephropathy") is also presented in Required Reading section. In brief, the accepted strategies are as follows:

• Early identification of patients with risk factors
• Use of nonionic contrast media
• Use of a smaller volume of contrast media
• N-acetylcysteine
• Pre and post-hydration
• Sodium bicarbonate
• Statins (possibly)
• Prophylactic CVVHDF

References

Wald, Ron, et al. "Acute renal failure after endovascular vs open repair of abdominal aortic aneurysm." Journal of vascular surgery 43.3 (2006): 460-466.

Mehran, R., and E. Nikolsky. "Contrast-induced nephropathy: definition, epidemiology, and patients at risk." Kidney International 69 (2006): S11-S15.

Kelly, Aine M., et al. "Meta-analysis: effectiveness of drugs for preventing contrast-induced nephropathy." Annals of internal medicine 148.4 (2008): 284-294.

College Answer

Dialytic techniques in the critically ill are becoming more widely used. Traditional indications used for acute renal failure, are concerns about fluid overload (actual or to facilitate nutritional support), hyperkalaemia or other uncontrolled electrolyte disorders, metabolic acidosis, hyponatraemia, uraemic symptoms or elevated urea (e.g. 30 mmol/L). As complications associated with techniques have been minimised, dialysis is often initiated earlier (anticipatory, oliguria, lower urea), and even for non-renal indications (including sepsis or septic shock). Dialysis or haemofiltration (e.g. with charcoal filter) can be used to increase the clearance of toxic products from the circulation (e.g. lithium, theophylline, myoglobin). Newer related extracorporeal techniques have also been developed to support liver dysfunction.

Discussion

The question really asks "what are the indications for dialysis"?

A good resource for information about this topic is adqi.org, home of the Acute Dialysis Quality Initiative. Particularly, their "reports" section contains a series of recommendations for commencement of dialysis in AKI. Most of these recommendations are based on expert opinion rather than strong evidence.

In summary, the indications for dialysis are as follows:

Renal Indications

• Oliguria with volume overload
• Oliguria is relative; urine output may be high and still inadequate in clearing the fluid.
• Uremia with symptoms
• Hyperkalemia ( K+ over 6.0)
• Metabolic acidosis due to renal failure or lactate (pH < 7.2)

Non-renal Indications

• Removal of dialysable toxins, i.e. ones which aren’t very lipophilic or protein-bound
  • Lithium
  • Methanol
  • Ethylene glycol
  • Salicylates
  • Theophylline
  • Valproate
  • Pretty much any drug with a volume of distribution less than 0.5L/kg
  • If a toxin is equally well cleared by hemodialysis and hemoperfusion, then hemodialysis is preferred, because it will also correct any underlying acid-base disturbance.
• ​Removal of contrast agent
  • More relevant with old-school high-osmolar contrast
• Clearance of cytokines to decrease severity of sepsis
  • Still controversial. May be of use in patients with renal failure and sepsis.
  • No evidence that it helps in patients with sepsis who don’t have renal failure.
• 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
  • Hypercalcemia refractory to bishosphonates

Timing of dialysis

Guided by expert opinion and the IDEAL trial of 2010 (no mortality difference between early and late dialysis groups)

The current (2011) guidelines suggest the following:

• Start when the GFR has fallen to below 15ml/min
• Definitely start before the GFR falls to below 6ml/min
• Symptomatic uremia
• Inability to control fluid balance
• Inability to control blood pressure
• Progressive deterioration in nutritional status
• Diabetics may benefit from an earlier start

References

Cooper, Bruce A., et al. "A randomized, controlled trial of early versus late initiation of dialysis." New England Journal of Medicine 363.7 (2010): 609-619.

Tattersall, James, et al. "When to start dialysis: updated guidance following publication of the Initiating Dialysis Early and Late (IDEAL) study." Nephrology dialysis transplantation (2011): gfr168.

College Answer

Non pharmacological measures to consider include checking the integrity of the 
catheter, avoiding kinking of the catheter and predilution.

Discussion

This question vaguely resembles Question 4 from the second paper of 2010. While asking more specifically about HITS, it is answered by a huge table titled "Methods of Prolonging the CVVHDF Filter Lifespan". That table is well suited to answering this question, and I will reproduce it here.

References

Lewis, P. J., and C. T. Dollery. "Clinical pharmacology and potential of prostacyclin." British medical bulletin 39.3 (1983): 281-284.

Fiaccadori, Enrico, et al. "Continuous haemofiltration in acute renal failure with prostacyclin as the sole anti-haemostatic agent." Intensive care medicine 28.5 (2002): 586-593.

Han, Sang Jin, et al. "Use of nafamostat mesilate as an anticoagulant during extracorporeal membrane oxygenation." Journal of Korean medical science26.7 (2011): 945-950.

Hu, Z. J., et al. "Time course of activated coagulation time at various sites during continuous haemodiafiltration using nafamostat mesilate." Intensive care medicine 25.5 (1999): 524-527.

Akizawa, T., et al. "Nafamostat mesilate: a regional anticoagulant for hemodialysis in patients at high risk for bleeding." Nephron 64.3 (1993): 376-381.

Wester, J. P., et al. "Low-dose fondaparinux in suspected heparin-induced thrombocytopenia in the critically ill." Neth J Med 65.3 (2007): 101-108.

Mahieu, Elien, et al. "Anticoagulation With Fondaparinux for Hemodiafiltration in Patients With Heparin‐Induced Thrombocytopenia: Dose‐Finding Study and Safety Evaluation." Artificial organs 37.5 (2013): 482-487.

Morabito, Santo, et al. "Continuous renal replacement therapies: anticoagulation in the critically ill at high risk of bleeding." Journal of nephrology16.4 (2003): 566-571.

Tan, H. K., I. Baldwin, and R. Bellomo. "Continuous veno-venous hemofiltration without anticoagulation in high-risk patients." Intensive care medicine 26.11 (2000): 1652-1657.

Tolwani, Ashita J., and Keith M. Wille. "THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Anticoagulation for Continuous Renal Replacement Therapy." Seminars in dialysis. Vol. 22. No. 2. Blackwell Publishing Ltd, 2009.

Davies, H. T., et al. "A randomized comparative crossover study to assess the affect on circuit life of varying pre-dilution volume associated with CVVH and CVVHDF." The International journal of artificial organs 31.3 (2008): 221-227.

Davenport, Andrew. "Pre-dilution or post-dilution fluid replacement for continuous veno-venous hemofiltration: that is the question." Nephron Clinical Practice 94.4 (2004): c83-c84.

Davies, Hugh, and Gavin Leslie. "Maintaining the CRRT circuit: non-anticoagulant alternatives." Australian Critical Care 19.4 (2006): 133-138.

Reeves, John H., et al. "A controlled trial of low-molecular-weight heparin (dalteparin) versus unfractionated heparin as anticoagulant during continuous venovenous hemodialysis with filtration." Critical care medicine 27.10 (1999): 2224-2228.

Jeffrey, R. F., et al. "Anticoagulation with low molecular weight heparin (Fragmin) during continuous hemodialysis in the intensive care unit." Artificial organs 17.8 (1993): 717-720.

Wilkieson, Trevor J., et al. "Low-intensity adjusted-dose warfarin for the prevention of hemodialysis catheter failure: a randomized, controlled trial."Clinical Journal of the American Society of Nephrology 6.5 (2011): 1018-1024.

Teraoka, Satoshi, et al. "Heparin-free hemodialysis with an oral anti-platelet agent." ASAIO journal 38.3 (1992): M560-M563.

De Pont, Anne-Cornelie JM, et al. "Pharmacokinetics and pharmacodynamics of danaparoid during continuous venovenous hemofiltration: a pilot study."Critical Care 11.5 (2007): R102.

Haase, Michael, et al. "Use of fondaparinux (ARIXTRA®) in a dialysis patient with symptomatic heparin-induced thrombocytopaenia type II." Nephrology Dialysis Transplantation 20.2 (2005): 444-446.

Ho, Grace, et al. "Use of fondaparinux for circuit patency in hemodialysis patients." American Journal of Kidney Diseases 61.3 (2013): 525-526.

College Answer

a) List 5 likely causes of deterioration in renal function.

1.  Hypovolemia
2.  Abdominal compartment syndrome
3.  Renal artery trauma
4.  Low output state from myocardial dysfunction from cross clamping and

5.  peri-op ischemia
6.  Use of contrast
7.   Post op bleeding
8.  Ischemic rhabdomyolysis
9.  Nephrotoxic drugs

b) What is the likely cause of this plasma biochemistry?

Rhabdomyolysis from lower limb ischemia

Discussion

a) List 5 likely causes of deterioration in renal function.

Why has this patient's creatinine doubled?

There could be various reasons.

One may divide the answer by pathophysiological criteria (pre-renal, renal and post-renal) or one may organise them by aetiology. The following structures are suggested:

Answer organised by pathophysiology:

• Pre-renal
  • Hypovolemia due to blood loss
  • Hypotension due to distributive shock, eg. sepsis
  • Cardiac failure
  • Renal vascular damage
  • Abdominal compartment syndrome
• Renal
  • ATN due to prolonged aortic cross-clamp time
  • Nephrotoxicity due to drugs, eg. gentamicin or metformin
  • Contrast-induced nephropathy
  • ATN due to rhabodomyolysis
• Post-renal
  • Intraoperative ureteric or bladder injury
  • kinked or malpositioned IDC

Answer organised by aetiology:

• Vascular and cardiac causes
  • Renal vascular damage
  • Abdominal compartment syndrome
  • ATN due to prolonged aortic cross-clamp time
  • Cardiac failure with low cardiac output
• Infectious causes
  • Septic shock due to bacterial translocation from the gut during a period of ischaemia, or from ischaemic bowel due to atheromatous emboli
• Drug-related causes
  • Nephrotoxicity due to drugs, eg. gentamicin or metformin
  • Contrast-induced nephropathy
• Traumatic causes
  • Hypovolemia due to blood loss
  • Rhabdomyolysis

b) What is the likely cause of this plasma biochemistry?

Well, its clearly rhabdomyolysis (LDH and AST are enzymes which leak out of ischaemic muscle).

The question about rhabdomyolysis following AAA repair was truncated and reused as Question 6.2 in the second paper of 2012, where one might find a more detailed discussion of this complication.

References

Dattilo, Jeffery B., et al. "Clinical failures of endovascular abdominal aortic aneurysm repair: incidence, causes, and management." Journal of vascular surgery 35.6 (2002): 1137-1144.

Vanholder, Raymond, et al. "Rhabdomyolysis." Journal of the American Society of Nephrology 11.8 (2000): 1553-1561.

Bosch, Xavier, Esteban Poch, and Josep M. Grau. "Rhabdomyolysis and acute kidney injury." New England Journal of Medicine 361.1 (2009): 62-72.

Woodrow, G., A. M. Brownjohn, and J. H. Turney. "The clinical and biochemical features of acute renal failure due to rhabdomyolysis." Renal failure 17.4 (1995): 467-474.

Miller III, C. C., et al. "Serum myoglobin and renal morbidity and mortality following thoracic and thoraco-abdominal aortic repair: does rhabdomyolysis play a role?." European Journal of Vascular and Endovascular Surgery 37.4 (2009): 388-394

Safi, Hazim J., et al. "Predictive factors for acute renal failure in thoracic and thoracoabdominal aortic aneurysm surgery." Journal of vascular surgery 24.3 (1996): 338-345.

College Answer

a) Diffusion: is the movement of solutes from one compartment to another along a concentration gradient. Diffusion is the principal mode of solute clearance during dialysis. Convection is the movement of solute across a semipermeable membrane in conjunction with significant amounts of ultrafiltration of water (solvent drag). Convection is the principal mode of solute clearance during ultrafiltration.

b) Filtration fraction is the fraction of plasma that is removed from blood during hemofiltration. The optimal filtration fraction at a hematocrit of 30% is of the order of 20-25%. A higher filtration fraction can lead to hemoconcentration in the filter increasing the risk of filter clotting. The sieving coefficient is the ratio of the concentration of solutes in the ultrafiltrate to that of plasma. A high sieving coefficient is desirable for middle molecules but undesirable for albumin sized molecules.

Discussion

The nomenclature of CRRT is discussed in greater detail in the Required Reading section, as well as in this excellent LITFL summary.

Diffusion: the transport of solute across a membrane, along a concentration gradient. The correct definition is "the net movement of a substance from a region of high concentration to a region of low concentration". This is how small molecules are cleared during haemodialysis.

Convection: the transport of a solute across a membrane along with solvent (by "solvent drag"). The correct definition is "the collective movement of molecules within fluids".  

This is how small and middle molecules are cleared during haemofiltration

Filtration fraction is the volume of plasma removed from the dialysed blood by ultrafiltration. The correct phrase is "the ratio of ultrafiltration rate to plasma water flow rate".

According to the college answer, the ideal filtration fraction at a hematocrit of 30% is 20-25%.

Sieving coefficient is the ratio of a solute in the ultrafiltrate in comparison to its concentration in the plasma which returns to the patient. The correct phrase is "a measure of equilibration between the concentrations of two mass transfer streams". The sieving coefficient describes the efficiency of solute removal by ultrafiltration, and depends upon the properties of the membrane and on the rate of ultrafiltration.

References

O'Reilly, Philip, and Ashita Tolwani. "Renal Replacement Therapy III: IHD, CRRT, SLED." Critical care clinics 21.2 (2005): 367-378.

College Answer

Discussion

The college answer is difficult to improve upon.

One can only attempt to add explanations to the brief responses we have been supplied.

Some additional indices can be excavated from Chapter 61 of Critical Care Nephrology, and these are included in the table below.

References

UpToDate have an excellent summary of this topic for the paying customer.

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.

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

College Answer

A)        Dehydration
B)        GIT bleed
C)        Steroid therapy

Discussion

This question is almost identical to Question 6.3 from the second paper of 2012. In this version, the college increased the urea to 40mmol/L, and asked for only three differentials.  Differentials listed in the chapter concerned with uraemia are reproduced below to simplify revision.

References

College Answer

a) List the possible causes of renal impairment in this patient?

Pre-renal
Hypoperfusion due to hypovolemia, sepsis/vasodilation/Ileus 
Myocardial dysfunction/silent infarct in Diabetic

Renal

Pre-existing diabetic renal dysfunction
Possible drug toxicity eg metformin or contrast load

Post Renal
Obstruction
Surgical mal-adventure
Abdominal compartment syndrome

B) What initial interventions, monitoring and investigations would you perform on admission of the patient to ICU

Interventions 
Assess airway, breathing, circulation while receiving handover
Flush catheter
Assess for signs of hypovolaemia and fluid challenge prn
Stop all nephrotoxins
Check intra-abdominal pressure

Monitoring 
invasive blood pressure monitoring
Measure preload -CVP
Consider cardiac output monitoring/echocardiogram

Investigations 
CXR, ECG
Check gentamicin level if this has been administered ? CBC, coags and troponin, ELFT
Ultrasound kidneys (probably not if CT was done and no evidence obstruction)

Discussion

The first part of this question is a straightforward exercise in generating differentials.

Using a familiar framework, this list might resemble the following:

Vascular causes:

• Renal artery/vein damage intraoperatively
• Abdominal compartment syndrome causing decreased renal perfusion

Infectious causes:

• Sepsis-associated kidney injury
• Hypotension due to septic shock resulting in ATN

Drug-related causes:

• Nephrotoxins, such as antibiotics or CT contrast

Traumatic causes:

• Damage to the ureters or bladder perforation

If one wishes to increase the breath of one's differentials, one may peruse the tabulated causes of acute renal failure in the Required Reading section.

b) is a "discuss your investigations and management" question. Though it may not seem so from the model answer, I expect the college were looking for a structured response. Thus:

A) - secure airway and confrim ETT position

B) - ensure ventilation supports adequate respiratory compensation for the metabolic acidosis, and adequate oxygenation to support normal organ function

- Ensure PEEP is adequate to sustain oxygenation in the face of increased intra-abdominal pressure, but not so high as to impair the venous return from the abdominal organs.

C) - Ensure adequate organ perfusion by the careful use of vasopressors and inotropes

D) - Protect the patient from hyperglycaemia with monitoring and the use of insulin;

- strongly consider using sedating agents which do not rely on renal clearance

E) - Correct electrolyte abnormalities and investigate for toxic drug levels eg. gentamicin

F) - Ensure optimal hydration and consider renal replacement therapy to clear toxic drugs and to correct uremia and acid-base status

- Investigate the integrity of the renal tract and renal vessel patency by ultrasound

G) - Consider the relevance of nutrition in this patient, and commence TPN if a prolonged ileus is anticipated

H) - Ensure a normal haemoglobin (70-90g/L)

I) - Tailor antibiotic dosing to decreased glomerular filtration, and avoid nephrotoxic agents.

A more generic approach to the oligoanuric patient is presented in the Required Reading section.

References

Mindell, Joseph A., and Glenn M. Chertow. "A practical approach to acute renal failure." Medical Clinics of North America 81.3 (1997): 731-748.

Sladen, Robert N. "Oliguria in the ICU: systematic approach to diagnosis and treatment." Anesthesiology Clinics of North America 18.4 (2000): 739-752.

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

College Answer

Aetiology: consider trauma and muscle compression (including immobility), exertional rhabdomyolysis (eg. heat stroke, grand mal seizures), drugs and toxins (via coma/immobility, agitation/hyperthermia, myotoxins eg. HMG-CoA reductase inhibitors, myonecrosis secondary to non-depolarising neuromuscular blockers), infections, inflammatory  myopathies  (eg.  polymyositis),  electrolyte  abnormalities  (esp. hypokalaemia and hypophosphataemia), hyperthermia (eg. malignant hyperpyrexia and neuroleptic malignant syndrome), metabolic myopathies.

Presentation: Consider history of exertion, fitting, drug exposure (including illicit), immobility, family history, and previous episodes.  Patient may complain of painful or weak muscles, and pigmented urine. Investigations reveal markedly elevated muscle enzymes (especially CK), acute oliguric renal failure, and electrolyte abnormalities (hyperkalaemia, hyperphosphataemia, hypocalcaemia, hyperuricaemia and metabolic acidosis).

Principles of management: consider general supportive care, adequate fluid resuscitation, forced alkaline diuresis (including mannitol), specific treatment of underlying cause (eg. dantrolene, phosphate replacement, cooling, removal of precipitants, treatment of infection, fasciotomies etc), and correction of electrolyte abnormalities.

Discussion

The causes of rhabdomyolysis are discussed in Question 26.3 from the second paper of 2013.

A more extensive discussion of rhabdomyolysis can be found among the Required Reading summaries.

To simplify revision, I reproduce the list of differentials below:

Causes of rhabdomyolysis

• Vascular - muscle ischaemia, eg. ischaemic limb, or myocardial infarction
• Infectious - eg. necrotising fasciitis
• Neoplastic, eg. sarcoma
• Drug-related, eg. due to MDMA or statins, or due to neuroleptic-malignant syndrome
• Congenital, eg. some sort of congenital myopathy
• Autoimmune, eg polymyositis or dermatomyositis
• Traumatic, eg. crush injury, blast injury, compartment syndrome, immobilityetc
• Environmental, eg. hyperthermic injury, "heat stroke"
• Endocrine, eg. hyperthyroidism or phaeochromocytoma

Manifestations of rhabdomyolysis

• Historical features: Trauma, seizures, immobility, drug exposure
• Symptoms:- muscle pain, decreased mobility, weakness, tea-coloured urine
• Signs: Muscle compartment swelling, tenderness, weakness, fever
• Biochemistry: Elevated CK, AST, LDH, urinary myoglobin; renal dysfunction and electrolyte abnormalities (particularly hyperkalemia, hypocalcemia, hyperphosphataemia, hyperuricemia, lactic acidosis)
• Imaging: CT or MRI evidence of muscle oedema; ultrasound evidence of decreased compartment perfusion

Management of rhabdomyolysis

A recent meta-analysis of management strategies for rhabdomyolysis has presented the following conclusions:

• Commence IV fluids within 6 hours - as early as possible
• Aim for a urine output greater than 300ml/hr
• Use of sodium bicarbonate is only indicated to correct systemic acidosis
• Use of mannitol is only indicated if urine output >300ml/hr cannot be maintained

Dialysis may be commenced to improve the removal of myoglobin, if a high-permeability membrane filter is available. Even if it is not, standard CVVHDF seems to decrease the risk of renal injury.

References

Holt, S., and K. Moore. "Pathogenesis and treatment of renal dysfunction in rhabdomyolysis." Intensive care medicine 27.5 (2001): 803-811.

Vanholder, Raymond, et al. "Rhabdomyolysis." Journal of the American Society of Nephrology 11.8 (2000): 1553-1561.

Bosch, Xavier, Esteban Poch, and Josep M. Grau. "Rhabdomyolysis and acute kidney injury." New England Journal of Medicine 361.1 (2009): 62-72.

Allison, Ronald C., and D. Lawrence Bedsole. "The other medical causes of rhabdomyolysis." The American journal of the medical sciences 326.2 (2003): 79-88.

Brown, Carlos VR, et al. "Preventing renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a difference?." Journal of Trauma-Injury, Infection, and Critical Care 56.6 (2004): 1191-1196.

Scharman, Elizabeth J., and William G. Troutman. "Prevention of kidney injury following rhabdomyolysis: a systematic review." Annals of Pharmacotherapy47.1 (2013): 90-105.

Sorrentino, Sajoscha A., et al. "High permeability dialysis membrane allows effective removal of myoglobin in acute kidney injury resulting from rhabdomyolysis." Critical care medicine 39.1 (2011): 184-186.

Tang, Wanxin, et al. "Renal protective effects of early continuous venovenous hemofiltration in rhabdomyolysis: improved renal mitochondrial dysfunction and inhibited apoptosis." Artificial organs 37.4 (2013): 390-400.

College Answer

Discussion

CVVHDF, IHD and SCUF are discussed in this fashion in Question 10 from the first paper of 2011.

Thus, the same table can be reproduced here, mutatis mutandis.

An even more expansive table of comparison between all conceivable RRT modalities is available in the Required reading section.

References

D'Intini, Vincent, et al. "Renal replacement therapy in acute renal failure." Best Practice & research clinical anaesthesiology 18.1 (2004): 145-157.

O'Reilly, Philip, and Ashita Tolwani. "Renal Replacement Therapy III: IHD, CRRT, SLED." Critical care clinics 21.2 (2005): 367-378.

Wei, S. S., W. T. Lee, and K. T. Woo. "Slow continuous ultrafiltration (SCUF)--the safe and efficient treatment for patients with cardiac failure and fluid overload." Singapore medical journal 36.3 (1995): 276-277.

Kanno, Yoshihiko, and Hiromichi Suzuki. "Selection of modality in continuous renal replacement therapy." (2010): 167-172. -This seems to be an entire issue of Contributions to Nephrology (Vol. 166) by Claudio Ronco.

College Answer

Advs:
- Flush for filter and prolong filter life by reducing clotting in filter
- May increase urea clearance by elution from red cells

Discussion

This question asks the candidate to identify a pre-dilution fluid replacement strategy from a MS Word clip-art diagram, and then to list its advantages. The two replacement fluid techniques are compared in a summary chapter from the Required Reading section. There is also a whole big thing on this topic in the Renal section from the Primary Exam revision section. 

In brief, the "advs" of the pre-dilution fluid replacement strategy are as follows:

• 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 minimise, or even completely 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.

References

Mariano, Filippo. "Continuous Renal Replacement Therapy (CRRT) in Intensive Care." Practical Issues in Anesthesia and Intensive Care 2013. Springer Milan, 2014. 131-144.

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.

College Answer

Causes

Insufficient flow noted in the venous access limb (afferent).

Obstruction along the venous access limb from the lumen in the vein to the pump

Measures

Check line for obvious kinks/obstructions

Check position on x-ray if relevant (subclavian or IJ line)

Reposition line and ensure no clot.

Consider flushing line

Consider replacing line/ site esp if the low access flow state cannot be resolved.

Discussion

This question closely resembles Question 12 (specifically, section 12.3) from the first paper of 2009.

The image granted to us by the college is fairly unambiguous.

There is a big red sign saying "Low Access Pressure".

To simplify revision, I will reproduce the answer to Question 12.3 below:

First, one should check the access side of the circuit, beginning with the patient:

• Patient position - is it appropriate? Are they agitated?
• The vas cath is of poor design (i.e. you should have inserted a short widebore vas cath, with a circular lumen crossection)
• Vas cath up against the wall of a vessel
• Vas cath is kinked
• Vas cath tip is getting clotted
• 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).

The general approach to troubleshooting the CRRT circuit is summarised in a chapter from the Required Reading section.

References

The Gambro PRISMA Systems Operator's Manual is a wealth of information. However, it is very long.

This excellent nursing resource from Nepean ICU by Keren Mowbray is both succinct and complete.

So is this one (also from Nepean, by Alison Bradshaw - but it appears to be in Comic Sans)

Ricci, Zaccaria, Ian Baldwin, and Claudio Ronco. "Alarms and troubleshooting."Continuous Renal Replacement Therapy (2009): 15.

Carson, Rachel C., Mercedeh Kiaii, and Jennifer M. MacRae. "Urea clearance in dysfunctional catheters is improved by reversing the line position despite increased access recirculation." American journal of kidney diseases 45.5 (2005): 883-890.

College Answer

Answer:
Intravascular hemolysis
Rupture of filter membrane

Discussion

Its difficult to find a reference for this. The appearance is clearly that of blood, or at least haemoglobin. How did this happen?

Well; its one of the following possibilities:

• The filter membrane ruptured, releasing blood into the effluent
• There is a massive intravascular haemolysis
• The patient has recently received a dose of hydroxycobalamin, which tends to discolour all body fluids, and which will cause the blood detector in the dialysis machine to alarm.

References

Sutter, Mark, et al. "Hemodialysis complications of hydroxocobalamin: a case report." Journal of Medical Toxicology 6.2 (2010): 165-167.

College Answer

•     Increasing the rate of the dialysate flow
•     Increasing the rate of blood flow
•     Change composition of dialysate fluid to increase the concentration gradient
•    Increasing the surface area of the membrane
•    Replacement fluid to go post dilution

Discussion

This is another one of those "how would you increase the efficiency of dialysis" questions. This patient is underdialysed - on the grounds that the urea and creatinine have hardly changed after 24 hours of CVVHDF.

There are many things one can do to improve the rate of solute removal:

• Increase the blood flow rate
• Increase the dialysate flow rate
• Increase the ultrafiltration rate
• Increase the replacement fluid rate
• Use some proportion of pre-dilution replacement fluid to elute more urea out of red cells and allow longer circuit lifespans (thus potentially increasing total daily clearance by virtue of having a longer uninterrupted session)
• Use post-dilution replacement to increase the efficiency of middle molecule clearance (i.e. increase the filtration fraction up to the acceptable maximum, 0.25-0.30)
• Change the composition of the dialysate to improve the concentration gradient (hardly relevant here because conventionally there is no urea in the dialysate anyway, but yes - one can adjust the concentration of potassium and bicarbonate)
• Change to a filter with a greater surface area
• Change to a filter with higher membrane porosity, if middle molecule clearance (eg. endotoxin) is your main concern

The general strategies to increase solute clearance in CRRT are discussed in a summary chapter from the Required Reading section. Some combination of pre and post dilution would be ideal here. In short, you would increase the dialysate flow rate, as well as increasing the pre-dilution volume (to elute urea, if you believe in that sort of thing- it seems to be something inferred (eg. by Brunet et al, 1999) from the different clearance rates of urea, creatinine and urate when comparing pre-dilution to post-dilution.) With the increased pre-dilution volume, you are able to increase your ultrafiltration rate significantly (thus removing lots of middle molecules) up to some safe maximum of filtration fraction. The addition of a large volume of clean post-filter replacement fluid finishes the process by diluting the remaining solutes on the way back to the patient's circulation.   

References

John, Stefan, and Kai-Uwe Eckardt. "Renal replacement strategies in the ICU."CHEST Journal 132.4 (2007): 1379-1388.

Brunet, Sylvain, et al. "Diffusive and convective solute clearances during continuous renal replacement therapy at various dialysate and ultrafiltration flow rates." American journal of kidney diseases 34.3 (1999): 486-492.

College Answer

 General
°     Identify high risk patients-baseline renal impairment, other organ failure e.g. circulatory, age, diabetes, hypovolemia, myeloma. Multiple risks factors in the one patient are additive for AKI/dialysis dependence following contrast.

°     Review need for imaging in every patient-consider alternative imaging methods USS, MRI ( without gadolinium) and non contrast CT

Contrast Media

Type : - Use of iso-osmolar or lower osmolality contrasts associated with lower risk of nephrotoxicity – supported by double blind trials and meta-analysis

Volume :- contrast volume is an independent predictor of contrast induced AKI- avoid repetitive closely spaced studies.

Route: - The risk is greater if given intra arterially as opposed to IV.

Volume expansion  Volume expansion has a well established role in the prevention of contrast induced AKI. 0.9 % saline probably preferable to 0.45% saline (Mueller; Arch Int Med: 2002). Most pronounced in diabetics and larger volumes

IV Bicarbonate  Alkalisation may protect against free radical injury.
Merten (JAMA, 2004) The REMEDIAL trial also demonstrated a benefit of bicarbonate when combined with N-Acetylcysteine (NAC)
Recent trials dispute the use of bicarbonate. Brar, (JAMA 2008) included 353 patients undergoing coronary angiograms. Patients received either isotonic saline or bicarbonate. There was no difference in the primary outcome which was a 25% decrease in GFR on days 1 to 4 following angiography.

Candidates were not expected to provide specific details of authors and journal names

D- Pharmacologic
Many agents have been examined. NAC most effective, although not clearly proven
because of considerable heterogeneity exists in the studies examined and effect on clinical outcome (other than minor changes in serum creatine levels) remains unknown.

E- Dialysis and hemofiltration
Contrast medium is removed by dialysis. Both hemofiltration and dialysis have been studied. Marenzi (NEJM 2003) examined 114 patients with a mean creatinine of 265 umol/l who required coronary intervention. They were then randomised to either isotonic saline or hemofiltration begun 4-8 hours prior and resumed for 18-24 hours after. Those in the hemofiltration group had significantly lower rates of serum creatinine elevation, requirement for dialysis and one year mortality. The applicability of these findings to clinical practice is unclear. The high cost and need for prolonged ICU care will limit the utility of these techniques.

Candidates were not expected to provide specific details of authors and journal names

Discussion

This question would benefit from a tabulated answer.

Drug therapies for contrast-induced nephropathy are well presented in this review article from 2008.

Prophylaxis strategies are discussed in this 2006 paper from JAMA.

For some nice raw biochemistry of contrast media, one cannot look past this gem from Biomed Research International (2014)

As for the risk factors for contrast-induced nephropathy, they are well summarised in an article from Kidney International (2006) which within it contains a table closely resembling the one below:

References

​UpToDate has an excellent article on this, for the paying public.

Mehran, R., and E. Nikolsky. "Contrast-induced nephropathy: definition, epidemiology, and patients at risk." Kidney International 69 (2006): S11-S15.

Kelly, Aine M., et al. "Meta-analysis: effectiveness of drugs for preventing contrast-induced nephropathy." Annals of internal medicine 148.4 (2008): 284-294.

Minsinger, Kristopher D., et al. "Meta-analysis of the effect of automated contrast injection devices versus manual injection and contrast volume on risk of contrast-induced nephropathy." The American journal of cardiology 113.1 (2014): 49-53.

Solomon, Richard. "Contrast Media: Are There Differences in Nephrotoxicity among Contrast Media?." BioMed research international 2014 (2014).

Thayssen, Per, et al. "Prevention of Contrast-Induced Nephropathy With N-Acetylcysteine or Sodium Bicarbonate in Patients With ST-Segment–Myocardial Infarction A Prospective, Randomized, Open-Labeled Trial."Circulation: Cardiovascular Interventions 7.2 (2014): 216-224.

Sadat, Umar. "N-acetylcysteine in contrast-induced acute kidney injury: clinical use against principles of evidence-based clinical medicine!." Expert review of cardiovascular therapy 12.1 (2014): 1-3.

Mahmoodi, Khalil, et al. "The efficacy of hydration with normal saline versus hydration with sodium bicarbonate in the prevention of contrast-induced nephropathy." Heart Views 15.2 (2014): 33.

Wu, Mei-Yi, et al. "The effectiveness of N-acetylcysteine in preventing contrast-induced nephropathy in patients undergoing contrast-enhanced computed tomography: a meta-analysis of randomized controlled trials." International urology and nephrology 45.5 (2013): 1309-1318.

Albabtain, Monirah A., et al. "Efficacy of Ascorbic Acid, N‐Acetylcysteine, or Combination of Both on Top of Saline Hydration versus Saline Hydration Alone on Prevention of Contrast‐Induced Nephropathy: A Prospective Randomized Study." Journal of interventional cardiology 26.1 (2013): 90-96.

Solomon, Richard, et al. "Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents." New England Journal of Medicine 331.21 (1994): 1416-1420.

Dussol, Bertrand, et al. "A randomized trial of saline hydration to prevent contrast nephropathy in chronic renal failure patients." Nephrology Dialysis Transplantation 21.8 (2006): 2120-2126.

Weinstein, J-M., S. Heyman, and M. Brezis. "Potential deleterious effect of furosemide in radiocontrast nephropathy." Nephron 62.4 (1992): 413-415.

Navaneethan, Sankar D., et al. "Sodium bicarbonate therapy for prevention of contrast-induced nephropathy: a systematic review and meta-analysis."American Journal of Kidney Diseases 53.4 (2009): 617-627.

Kunadian, Vijayalakshmi, et al. "Sodium bicarbonate for the prevention of contrast induced nephropathy: a meta-analysis of published clinical trials."European journal of radiology 79.1 (2011): 48-55.

Mahmoodi, Khalil, et al. "The efficacy of hydration with normal saline versus hydration with sodium bicarbonate in the prevention of contrast-induced nephropathy." Heart Views 15.2 (2014): 33.

Saint-Laurent, Qc. "Consensus Guidelines for the Prevention of Contrast Induced Nephropathy."Canadian Association of Radiologists, 1740 Côte-Vertu, Saint-Laurent, Qc

Barbieri, Lucia, et al. "The role of statins in the prevention of contrast induced nephropathy: a meta-analysis of 8 randomized trials." Journal of thrombosis and thrombolysis (2014): 1-10.

Kapadia, Carl Behram, et al. "EFFICACY OF SHORT TERM, HIGH DOSE STATINS FOR PREVENTING CONTRAST-INDUCED ACUTE KIDNEY INJURY IN PATIENTS UNDERGOING CORONARY ANGIOGRAPHY AND/OR PERCUTANEOUS CORONARY INTERVENTION: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS." Journal of the American College of Cardiology 63.12_S (2014).

Spargias, Konstantinos, et al. "Ascorbic acid prevents contrast-mediated nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention." Circulation 110.18 (2004): 2837-2842.

College Answer

Creatinine Clearance: 
•    Gives estimation of Glomerular Filtration Rate (GFR).
•    Requires timed urine collection (usually 24 hours)
•    Accuracy  may  be limited  due to creatinine  secretion,  thus  overestimating
GFR, and incomplete urine collection.
•    Assumes steady state in GFR, which may not be the case in acute renal failure.
•    Determining exact GFR is rarely clinically necessary.

Serum Creatinine: 
•    Simple to measure and widely available.
•    Specific for renal function.
•    Indicator of GFR based upon constant production from muscle creatine and relatively constant renal excretion rate.
•    Production may be increased by trauma, fever or immobilisation.
•    Decreased in individuals with small stature cachexia, reduced muscle mass
(eg muscle disease, amputations)
•    Decreased  production  may  occur  in  liver  disease  because  of  decreased hepatic conversion of creatine to creatinine, decreased dietary protein intake, muscle wasting and increased renal tubular secretion of creatinine.
•    May be influenced by volume of distribution changes in critically ill patients

Urea:

•    Simple to measure and widely available
•    Not specific for renal function
•    May  be  affected  by liver  disease,  protein  intake,  catabolic  state,  volume status,  upper  gastrointestinal  bleeding,  and  drug  therapy  –  eg corticosteroids.

Urine Output: 
•    Simple to measure and universally available.
•    More sensitive to changes in renal function than biomarkers
•    Non-specific  –  can  have  normal  urine  output  despite  severe  acute  renal failure

Novel Biomarkers: 
•    Include a plasma panel (NGAL and cystatin C) and urine panel (NGAL, IL-8 and KIM-1)
•    Represent sequential biomarkers and so have potential for timing the initial insult and assessing the duration of AKI and for predicting overall prognosis
•    May also distinguish between various types and pathogeneses of AKI
•    Potential for high sensitivity and specificity
•    So far only tested in small studies and limited clinical situations and need further validation

Discussion

This question would benefit from a tabulated answer.

A good resource for novel biomarkers is this systematic review in Nature.

This table is reproduced without any substantial alteration in the Required Reading section on renal injury biomarkers.

References

Parikh, Chirag R., et al. "Urinary interleukin-18 is a marker of human acute tubular necrosis." American Journal of Kidney Diseases 43.3 (2004): 405-414.

Devarajan, Peasad. "Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of kidney disease." Scandinavian Journal of Clinical & Laboratory Investigation 68.S241 (2008): 89-94.

Bennett, Michael, et al. "Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study." CLINICAL JOURNAL-AMERICAN SOCIETY OF NEPHROLOGY 3.3 (2008): 665.

Herget-Rosenthal, Stefan, et al. "Early detection of acute renal failure by serum cystatin C." Kidney international 66.3 (2004): 1115-1122.

Royakkers, Annick ANM, et al. "Serum and urine cystatin C are poor biomarkers for acute kidney injury and renal replacement therapy." Intensive care medicine 37.3 (2011): 493-501.

Coca, S. G., et al. "Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review." Kidney international 73.9 (2007): 1008-1016.

Shemesh, Ovadia, et al. "Limitations of creatinine as a filtration marker in glomerulopathic patients." Kidney Int 28.5 (1985): 830-838.

Waikar, Sushrut S., and Joseph V. Bonventre. "Creatinine kinetics and the definition of acute kidney injury." Journal of the American Society of Nephrology20.3 (2009): 672-679.

Bellomo, Rinaldo, et al. "Acute renal failure–definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group." Critical care 8.4 (2004): R204.

Cockcroft, Donald W., and M. Henry Gault. "Prediction of creatinine clearance from serum creatinine." Nephron 16.1 (1976): 31-41.

Han, Won K., et al. "Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury." Kidney international 62.1 (2002): 237-244.

College Answer

12.1.   In reference to the above results, what does the raised creatine kinase indicate and how would this affect the kidney?

Rhabdomyolysis secondary to crush injury

Direct injury from myoglobin (direct tubular toxicity/obstruction)  and other haem related compounds and indirectly via hypovolaemia/shock (pre renal).

12.2.   You  initiate  CVVHDF  in  this  patient.  Following  24  hours  of  renal  replacement therapy,   you  become   concerned   that  you  are  not  achieving   optimal  solute clearance.

The dialysis settings are as given:

•    Blood Flow: 80 mls/min
•    Replacement fluid (post filter): 1000 mls/hr
•    Dialysate fluid: 1000 mls/hr
•    Effluent flow: 2000 mls/hr
•    Fluid removal: zero

(a)      What  changes  would  you  make  to  these  settings  so  as  to  enhance  solute clearance?

Increase   blood  flow,  replacement   fluid,  dialysate   and  effluent   flows,   and  change replacement fluid to be pre filter

12.3.   An alarm has sounded on the dialysis machine. Access pressures are high. How would you respond to this problem?

Check and manipulate vascular access
•    Malposition   (catheter   tip,   sucking   against   vessel   wall)and   kinking
(subclavian )
•    Change in patient position- side/supine/sitting
•    Site of catheter- e.g. sitting up –femoral access problems
•    Type of catheter-geometry, length, diameter
•    Negative intra thoracic pressure - high intra abdominal pressures
•    Hypovolemic patient –poor flow
•    Catheter occlusion / thrombosis

12.4.   Briefly outline the relationship between dose of dialysis and outcome

Candidates were not expected to list all of the literature but an understanding that this remains a controversial area- credit was given if they quoted relevant studies

Although  several  clinical  trials  have suggested  an improvement  in survival  with higher doses  of  CRRT  results  have  not  been  consistent  across  all  studies.  To  date  five randomised trials have assessed the relationship between intensity of CRRT in terms of effluent flow rate and outcomes of acute kidney injury.

•    Ronco (Lancet 2000) and Saudan (Kid Int 2006) found that lower doses around 20
-25ml kg hr were inferior in terms of survival to higher effluent flows of around 35 to
45 mls kg hr.
•    Two other studies Bouman (Crit Care Med 2002) and Tolwani (J Am Soc Nephrol,
2008) however found no difference in survival with higher effluent rates.
•    The latest study (NEJM 2008, VA/HIH acute renal failure Trial Network  or ATN study) found that mortality at 60 days was no different between two intensity arms. In the less intensive arm both IHD and SLED were used as standard practice of thrice per week and CVVHDF effluent flow at 20 mls kg hr. In the more intensive arm IHD and or SLED were used six times per week and CVVHDF at an effluent flow rate of 35ml kg hr.
•    The ANZICS CTG RENAL study just completed (25 v 40 ml kg hr). No difference in mortality between the two groups, a higher incidence of hypophosphatemia in the higher dose group.

Discussion

12.1.   In reference to the above results, what does the raised creatine kinase indicate and how would this affect the kidney?

Yes, a high CK indicates rhabdomyolysis, which is supported by the history. There are multiple mechanisms which lead to acute kidney injury in this scenario, which are well described in this excellent article:

• Tubular obstruction by precipitating myoglobin
• Free-radical-mediated injury due to generation of hydroxyl radicals by Fe²⁺
• Lipid peroxidation by hydroxyl radicals and duirectly by haem, leading to tubular membrane dysfunction
• Renal vasoconstriction - possibly due to nitric oxide scavenging by myoglobin
• Decreased renal blood flow due to shock in trauma

Broadly, the mechanisms of kidney injury due to rhabdomyolysis are discussed in greater detail in the Required Reading section. The answer to this question doe not require a great deal of detail, but there is a great deal of detail to discuss, and so I will continue to refer to the summary notes (where some moderate amount of detail is available).

12.2.   You  initiate  CVVHDF  in  this  patient.  Following  24  hours  of  renal  replacement therapy,   you  become   concerned   that  you  are  not  achieving   optimal  solute clearance.

The dialysis settings are as given:

•    Blood Flow: 80 mls/min
•    Replacement fluid (post filter): 1000 mls/hr
•    Dialysate fluid: 1000 mls/hr
•    Effluent flow: 2000 mls/hr
•    Fluid removal: zero

What  changes  would  you  make  to  these  settings  so  as  to  enhance  solute clearance?

The college has presented us with a slightly deranged dialysis prescription.

• The blood flow rate is too low; it should be 100-200ml/min
• The replacement fluid should be given pre-filter (though this actually decreases the rate of solute removal, it may improve the efficiency of the overall strategy by allowing a longer circuit lifespan).
• The flow rates of the dialysate fluid and effluent can be increased; this will result in greater solute removal by diffusion.
• One can also target a net fluid removal goal (say, 50-100ml/hr) to increase the removal of solute by convection

Generally speaking, strategies used to enhance solute clearance are discussed in greater detail in the Required Reading section.

12.3.   An alarm has sounded on the dialysis machine. Access pressures are high. How would you respond to this problem?

Low. The access pressure alarm should be low.  Yes, the access line has a pressure sensor, and that sensor does have a default high pressure alarm interrupt,  but it trips only if the pressure exceeds 300 mmHg (according to this helpful Prismaflex operator's manual). There is no natural scenario where directly accessing the patient's bloodstream would result in this sort of venous access pressure, even when dialysing from an ECMO circuit. In short, we should assume the college examiners meant the access pressures are low. 

An extremely low access pressure alarm suggests that the pump is sucking too hard. This is usually the result of some sort of obstruction to the flow of blood out of the patient.

Thus, one should check the access side of the circuit, beginning with the patient:

• Patient position - is it appropriate? Are they agitated?
• The vas cath is of poor design (i.e. you should have inserted a short widebore vas cath, with a circular lumen crossection)
• Vas cath up against the wall of a vessel
• Vas cath is kinked
• Vas cath tip is getting clotted
• 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 pressureventilation, 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).

One might even try to reverse the circuit limbs; even though this will result in some degree of recirculation, it does not appear to hamper the clearance of urea.

Troubleshooting of the dialysis circuit is covered in more detail in the Required Reading section.

Additionally, one can review this excellent nursing resource from Nepean ICU, by Keren Mowbray.

Lastly, Claudio Ronco has co-authored a nice textbook chapter on this topic.

12.4.   Briefly outline the relationship between dose of dialysis and outcome.Candidates were not expected to list all of the literature but an understanding that this remains a controversial area- credit was given if they quoted relevant studies.

This question makes reference to the following "relevant studies":

• Ronco (2000)
• Saudan (2006)
• Bouman (2002)
• Tolwani (2008)
• VA/NIH (2008)
• RENAL study (2009)

A meta-analysis which arrived in the wake of the last two papers confirmed in 2010 that "higher intensity RRT does not reduce mortality rates or improve renal recovery among patients with AKI". It seems 20-25ml/kg/hr is at least as good as 40ml/kg hr.

This finding has been confirmed by recent data in septic patients.

It seems beyond a certain dose, renal replacement therapy removes as many useful molecules as it does toxins, and the benefit from escalating the dose deteriorates.

References

Holt, S., and K. Moore. "Pathogenesis and treatment of renal dysfunction in rhabdomyolysis." Intensive care medicine 27.5 (2001): 803-811.

Ricci, Zaccaria, Ian Baldwin, and Claudio Ronco. "Alarms and troubleshooting."Continuous Renal Replacement Therapy (2009): 15.

Ronco, Claudio, et al. "Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial." The Lancet 356.9223 (2000): 26-30.

Saudan, P., et al. "Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure." Kidney international 70.7 (2006): 1312-1317.

Bouman, Catherine SC, et al. "Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: a prospective, randomized trial." Critical care medicine 30.10 (2002): 2205-2211.

Tolwani, Ashita J., et al. "Standard versus high-dose CVVHDF for ICU-related acute renal failure." Journal of the American Society of Nephrology 19.6 (2008): 1233-1238.

VA/NIH Acute Renal Failure Trial Network. "Intensity of renal support in critically ill patients with acute kidney injury." The New England journal of medicine359.1 (2008): 7.

Bellomo, R., et al. "Intensity of continuous renal-replacement therapy in critically ill patients." The New England journal of medicine 361.17 (2009): 1627-1638.

Jun, Min, et al. "Intensities of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis." Clinical Journal of the American Society of Nephrology 5.6 (2010): 956-963.

Zhang, Ping, et al. "Effect of the intensity of continuous renal replacement therapy in patients with sepsis and acute kidney injury: a single-center randomized clinical trial." Nephrology Dialysis Transplantation 27.3 (2012): 967-973.

Carson, Rachel C., Mercedeh Kiaii, and Jennifer M. MacRae. "Urea clearance in dysfunctional catheters is improved by reversing the line position despite increased access recirculation." American journal of kidney diseases 45.5 (2005): 883-890.

College Answer

With respect to plasma exchange therapy:

(a)        What are the physical principles of plasma exchange therapy?

•    Separation of plasma from blood cells by centrifugation or membrane filtration
•    Reinfusion  of  cells  plus  autologous  plasma  or  another  replacement  solution  eg albumin
•    Removes large molecular weight substances

(b)        What substances can plasma exchange effectively remove?

•    Pathogenic auto-antibodies
•    Immune complexes
•     Cryoglobulins
•    Myeloma light chains
•     Endotoxin
•    Cholesterol-containing lipoproteins /triglycerides

(c)        List 5 acute conditions where therapeutic plasma exchange is indicated.

Myasthenic Crisis
•    Goodpasture’s Syndrome with pulmonary haemorrhage
•    Hyperviscosity syndromes o   Cryoglobulinaemia o Paraproteinaemia 
o Waldenstrom’s Macroglobulinaemia 
•    Wegener’s Granulomatosis with pulmonary haemorrhage
•    Guillain-Barre Syndrome/Acute Inflammatory Demyelinating Polyradiculopathy
•    Antiphospholipid Antibody Syndrome
•    HELLP syndrome
•    Multiple sclerosis
•    HIV-related neuropathy
•     SLE
•     Pemphigus
•    Paraneoplastic syndromes
•    Rapidly progressive glomerulonephritis
•    Renal transplant rejection
•    Coagulation inhibitors
•    Auto-immune haemolytic anaemia
•     DIC
•    Overwhelming sepsis syndromes eg meningococcaemia
•    Reye’s syndrome
•    Paraquat poisoning

(d)        List     4     common     complications     of     this     therapy,     excluding     catheter-related complications

•    Hypotension due to excess fluid removal +/ inadequate volume replacement
•    Citrate-induced hypocalcaemia
•    Anaphylactic/transfusion reactions to fresh frozen plasma replacement solution
•    Coagulation  abnormalities  due  to removal  of  clotting  factors  not  replaced  when albumin replacement used.
•    Removal of useful immunoglobulins and complement which can in theory lead to an immunodeficient state.
•    Drug  removal  –  especially  drugs  with  high  protein-binding  and  low  volume  of distribution.  Potentials  in the diseases  in which  therapeutic  plasma  exchange  is used are cyclophosphamide and azathioprine.
•     Hypothermia
•    Pyrogenic reactions

•     Anaemia
•     Thrombocytopenia
•     Hepatitis

•     Vasovagal reactions

Discussion

This college answer is an excellent concise overview of what is expected from the college fellows. Note the extensive lists. The candidates were not expected to generate this many indications or complications; the right number of anything from the college list would have earned marks. One can do little in the discussion of such a well-answered question, except provide references for more detailed reading.

Thus; most of the question can be answered after reading Jeffrey L. Winters' 2012 article fromHematology. Additionally, our very own college examiners have put a whole chapter on this technique into Oh's Manual (Chapter 97, pp. 993).

a) Principles of plasmapheresis

• Plasmapheresis may refer to a variety of procedures, all involving the therapeutic separation of blood into components.
• Separation of blood into cellular and fluid components offers the opportunity to discard or modify those components. 
• This separation is usually accomplished by means of either a centrifuge or by the less frequently used method of porous membrane filtration.
• Unlike dialysis or haemofiltration, there is no size barrier: plasmapheresis removes the whole plasma with molecules of all sizes.
• Some blood components are then reinfused into the patient with or without modification, and the rest may be discarded or stored.
• If plasma is being removed,  volume is replaced with 4% albumin or FFP.

   Characteristics of a disease process which make plasmapheresis an effective option:

1. The disease has to be caused by some circulating factor, i.e. it has to be present in the blood
2. That factor has to have a sufficiently long plasma half-life, such that "turning off" the process of its production will still result in significant amounts of it persisting in the bloodstream.

b) Blood components removed by plasmapheresis

Undesirable blood components:

• Antibodies
• Immune complexes
• Abnormal plasma proteins, eg. myeloma light chains
• Immunoglobulins

• Protein-bound drugs
• Monoclonal antibody drugs, eg. rituximab
• Immune complexes
• Cryoglobulins
• Myeloma light chains
• Bacterial endotoxin
• High molecular weight toxins, eg. animal venom
• Cholesterol-containing lipoproteins /triglycerides
• Abnormal cells (eg. leukaemia blasts, excess RBCs or platelets)

Desirable blood components which you'd rather keep:

• Antithrombin
• Pseudocholinesterases and plasma esterases
• Useful antibodies, including monoclonal biological agents
• Useful medications
• Nutrients, eg. glucose, amino acids, water-soluble vitamins
• Diagnostically interesting antibodies (i.e. for serology)

c) Indications for urgent plasmapheresis

Urgent plasma exchange:

• TTP
• Catastrophic antiphospholipid syndrome
• Hyperviscosity syndrome (eg. myeloma)
• Guillain-Barre syndrome
• Myasthenia gravis
• Acute fulminant hepatitis with encephalopathy
• Amanita phalloides poisoning

Less urgent plasma exchange:

• Erythrodermic cutaneous T-cell lymphoma
• Wegeners granulomatosis
• Goodpasture's syndrome
• Eaton-Lambert syndrome
• Babesiosis
• Autoimmune haemolytic anaemia
• Cryoglobulinaemia
• Dermatomyositis/polymyositis
• Hemolytic uremic syndrome
• Familial hypercholesterolaemia
• Focal segmental glomerulosclerosis
• Paraproteinaemic polyneuropathy
• Antibody-mediated renal transplant rejection
• Fulminant Wilson's disease.

One should note that in their list of indications, the college noted some Grade II, III and IV recommendations, such as:

• HELLP syndrome
• Multiple sclerosis
• HIV-related neuropathy
• Pemphigus
• Coagulation inhibitors
• DIC
• Overwhelming sepsis syndromes eg meningococcaemia
• Reye’s syndrome
• Paraquat poisoning

d) Complications of plasmapheresis

• Due to vascular access
  • all the complications of large CVAD insertion: CLABSI, bleeding, vessel damage, etc etc
• Due to the circuit exposure
  • Low fibrinogen and coagulopathy
  • Haemolysis and thrombocytopenia
  • Hypothermia
  • Complement activation
• Due to anticoagulation
  • Paraesthesia due to hypocalcemia (due to regional citrate anticoagulation)
  • Bleeding complications
  • HITS
• Due to the replacement fluid
  • Urticaria
  • Febrile reaction to blood products
  • Anaphylaxis
• Due to the unavoidable removal of useful blood components
  • Loss of useful drugs
  • Immunosuppression
  • Anaphylaxis
  • Hypothermia
• Due to volume loss
  • Hypotension
  • Vasovagal syncope
  • Nausea and vomiting

References

McLeod, Bruce C. "Therapeutic apheresis: use of human serum albumin, fresh frozen plasma and cryosupernatant plasma in therapeutic plasma exchange."Best Practice & Research Clinical Haematology 19.1 (2006): 157-167.

Reimann, P. M., and P. D. Mason. "Plasmapheresis: technique and complications." Intensive care medicine 16.1 (1990): 3-10.

Winters, Jeffrey L. "Plasma exchange: concepts, mechanisms, and an overview of the American Society for Apheresis guidelines." ASH Education Program Book 2012.1 (2012): 7-12.

Oh's Manual: Chapter 97 (pp. 993)  Therapeutic  plasma  exchange  and  intravenous  immunoglobulin  therapy  by Ian  Kerridge,  David  Collins  and  James  P  Isbister.

Szczepiorkowski, Zbigniew M., et al. "Guidelines on the use of therapeutic apheresis in clinical practice—Evidence‐based approach from the apheresis applications committee of the American Society for Apheresis." Journal of clinical apheresis 25.3 (2010): 83-177.

Russi, Gianpaolo, and Piero Marson. "Urgent plasma exchange: how, where and when." Blood Transfusion 9.4 (2011): 356.

College Answer

No Anticoagulant +/- Saline Flushes (50-100ml every hour)

* Ensure good wide bore access, high flow rates, consider predilution
Advantage: 
Minimizes bleeding risk, but consumption of platelets and factors by membrane
(theoretical)

Disadvantage: 
Shortened filter life / increased time off dialysis

Regional citrate 
Advantage: 
Provides good regional anticoagulation
Pre-mix solutions and protocols for use have simplified process
Disadvantage 
Labor intensive,
Requires diligent monitoring of serum sodium, ionized calcium, and bicarbonate
Requires infusion of calcium outside the circuit (access issues) Large sodium load occurs when trisodium citrate used
May cause alkalosis
Special diasylate required: hyponatraemic, without buffer, Ca free
Not appropriate in liver failure

Prostacycline and Analogues 
Advantages 
Reduced bleeding risk
Disadvantages 
Shorter filter life
Hypotension

Direct thrombin Inhibitors: Hirudin / Lepirudin / Argatroban

Advantages:

Linear relationship between levels and APTT (<100s) for Hirudin

Disadvantages 
Renal clearance, accumulation in renal failure (Hirudin, Lepirudin) Hepatic metabolism, accumulation in liver disease (Argatroban) No antagonist
Argatroban falsely raises INR / PT Expense

Other agents Danaparoid Limited availability
Risk of cross-reactivity with heparin-induced antibodies

Serine Protease inhibitors (nafamostat) 
limited experience, massive cost

Fondaparinux 
Not readily available
Limited evidence supporting its use

Warfarin  /NSAIDS

Discussion

Thus question would have benefited from a tabulated answer.

In the table below, I have included heparin, for completeness. However one would be well-advised to omit heparin from their answer in the exam.

If one were to review only one resource for this answer, one would be satisfied by this article from Tolwani and Wille.

This table is reproduced with minimal changes in the Required Reading section on this topic.

References

Lewis, P. J., and C. T. Dollery. "Clinical pharmacology and potential of prostacyclin." British medical bulletin 39.3 (1983): 281-284.

Fiaccadori, Enrico, et al. "Continuous haemofiltration in acute renal failure with prostacyclin as the sole anti-haemostatic agent." Intensive care medicine 28.5 (2002): 586-593.

Han, Sang Jin, et al. "Use of nafamostat mesilate as an anticoagulant during extracorporeal membrane oxygenation." Journal of Korean medical science26.7 (2011): 945-950.

Hu, Z. J., et al. "Time course of activated coagulation time at various sites during continuous haemodiafiltration using nafamostat mesilate." Intensive care medicine 25.5 (1999): 524-527.

Akizawa, T., et al. "Nafamostat mesilate: a regional anticoagulant for hemodialysis in patients at high risk for bleeding." Nephron 64.3 (1993): 376-381.

Wester, J. P., et al. "Low-dose fondaparinux in suspected heparin-induced thrombocytopenia in the critically ill." Neth J Med 65.3 (2007): 101-108.

Mahieu, Elien, et al. "Anticoagulation With Fondaparinux for Hemodiafiltration in Patients With Heparin‐Induced Thrombocytopenia: Dose‐Finding Study and Safety Evaluation." Artificial organs 37.5 (2013): 482-487.

Morabito, Santo, et al. "Continuous renal replacement therapies: anticoagulation in the critically ill at high risk of bleeding." Journal of nephrology16.4 (2003): 566-571.

Tan, H. K., I. Baldwin, and R. Bellomo. "Continuous veno-venous hemofiltration without anticoagulation in high-risk patients." Intensive care medicine 26.11 (2000): 1652-1657.

Tolwani, Ashita J., and Keith M. Wille. "THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Anticoagulation for Continuous Renal Replacement Therapy." Seminars in dialysis. Vol. 22. No. 2. Blackwell Publishing Ltd, 2009.

Davies, H. T., et al. "A randomized comparative crossover study to assess the affect on circuit life of varying pre-dilution volume associated with CVVH and CVVHDF." The International journal of artificial organs 31.3 (2008): 221-227.

Davenport, Andrew. "Pre-dilution or post-dilution fluid replacement for continuous veno-venous hemofiltration: that is the question." Nephron Clinical Practice 94.4 (2004): c83-c84.

Davies, Hugh, and Gavin Leslie. "Maintaining the CRRT circuit: non-anticoagulant alternatives." Australian Critical Care 19.4 (2006): 133-138.

Reeves, John H., et al. "A controlled trial of low-molecular-weight heparin (dalteparin) versus unfractionated heparin as anticoagulant during continuous venovenous hemodialysis with filtration." Critical care medicine 27.10 (1999): 2224-2228.

Jeffrey, R. F., et al. "Anticoagulation with low molecular weight heparin (Fragmin) during continuous hemodialysis in the intensive care unit." Artificial organs 17.8 (1993): 717-720.

Wilkieson, Trevor J., et al. "Low-intensity adjusted-dose warfarin for the prevention of hemodialysis catheter failure: a randomized, controlled trial."Clinical Journal of the American Society of Nephrology 6.5 (2011): 1018-1024.

Teraoka, Satoshi, et al. "Heparin-free hemodialysis with an oral anti-platelet agent." ASAIO journal 38.3 (1992): M560-M563.

De Pont, Anne-Cornelie JM, et al. "Pharmacokinetics and pharmacodynamics of danaparoid during continuous venovenous hemofiltration: a pilot study."Critical Care 11.5 (2007): R102.

Haase, Michael, et al. "Use of fondaparinux (ARIXTRA®) in a dialysis patient with symptomatic heparin-induced thrombocytopaenia type II." Nephrology Dialysis Transplantation 20.2 (2005): 444-446.

Ho, Grace, et al. "Use of fondaparinux for circuit patency in hemodialysis patients." American Journal of Kidney Diseases 61.3 (2013): 525-526.

College Answer

Renal:
•    Low/no urine output
Metabolic and Endocrine:
•     Associated
o   Hyperkalaemia
o   Abnormal Ca++
o   Hyperphosphataemia
Need for dialysis determines fluid prescribing, feeding and any protein restriction
Cardiovascular:
•    Hypertension very common
•    Atherosclerosis common
•    Pericarditis common
Respiratory:
•    Prone to pulmonary oedema
Neurological:
•    Dialysis disequilibrium
Polyneuropathy and myopathy
Skin:
•    Fragile skin
Haematological:
•     Anaemia
•    Platelet dysfunction
Gastrointestinal:
•    Impaired gastrointestinal motility
•    Increased risk of bleeding related to gastric ulceration
Immunological:
•    Increased risk of infection
Pharmacological:
•    Altered clearance of medications that have predominant renal excretion
Vascular access:
•    Fistulas used for dialysis may complicate CVC and arterial access

Discussion

The college answer to this question is a systematic approach which the clever candidate will model. All one can do is rearrange the college response into a different frame.

B) Respiratory considerations:

• Tendency towards pulmonary oedema

C) Cardiovascular considerations:

• These chronically hypertensive patients may require higher MAP to perfus their organs
• They are prone to pericardial effusions
• The myocardium may be hypertrophied
• Atheromatous disease is amplified; coronary artery disease will likely be present

D) Pharmacokinetics are affected:

• Renally cleared substances will persist until the next dialysis session
• Renally cleared metabolites will also have a persisting effect
• Volume of distribution is increased

Neurological function can be impaired by high urea

E) Electrolyte and acid-base balance will be disturbed:

• High potassium
• High phosphate
• Accumulation of non-volatile acids (sulfate, urate, etc)

F) Fluid balance will be disturbed:

• Inability to produce urine makes the patient more likely to develop fluid overload
• Dialysis disequilibrium syndrome may develop

G) Nutrition is affected:

• Low-protein diets are usually required to decrease the rate of urea production.
• Albumin may be low (eg. with nephrotic syndrome) which decreases its positive antioxidant and scavenging effect.

H) There may be anaemia due to decreased EPO synthesis.

I) There may be immune dysfunction and increased risk of infection.

References

Arulkumaran, N., N. M. P. Annear, and M. Singer. "Patients with end-stage renal disease admitted to the intensive care unit: systematic review." British journal of anaesthesia 110.1 (2013): 13-20.

Szamosfalvi, Balazs, and Jerry Yee. "Considerations in the critically ill ESRD patient." Advances in chronic kidney disease 20.1 (2013): 102-109.

College Answer

Discussion

This tabulated college answer is an excellent model, and can be easily left unmodified as a tool of fellowship exam revision.

If one were prone to reinventing wheels, one would reorganise the table in the following manner:

An even larger, (barely readable) table comparing all previously examined RRT modalities is also available in the Required Reading section.

References

D'Intini, Vincent, et al. "Renal replacement therapy in acute renal failure." Best Practice & research clinical anaesthesiology 18.1 (2004): 145-157.

O'Reilly, Philip, and Ashita Tolwani. "Renal Replacement Therapy III: IHD, CRRT, SLED." Critical care clinics 21.2 (2005): 367-378.

Wei, S. S., W. T. Lee, and K. T. Woo. "Slow continuous ultrafiltration (SCUF)--the safe and efficient treatment for patients with cardiac failure and fluid overload." Singapore medical journal 36.3 (1995): 276-277.

Kanno, Yoshihiko, and Hiromichi Suzuki. "Selection of modality in continuous renal replacement therapy." (2010): 167-172. -This seems to be an entire issue of Contributions to Nephrology
(Vol. 166) by Claudio Ronco.

College Answer

a) List the likely mechanisms for this patient's renal failure
Likely mechanisms include pre-renal, renal and post-renal causes

Pre-renal:
Hypovolaemia (inadequate resuscitation)
Hypotension (inadequate perfusion pressure compared to his normal BP despite inotropes)
Impaired cardiac output (septic cardiomyopathy, myocardial ischaemia/infarction, dysrhythmias)

Renal:
Toxins (eg nephrotoxic drugs – need to specify gentamicin / NSAIDs / contast for CT)
Microcirculatory failure (sepsis and inflammatory response) with medullary ischaemia, tubular
obstruction and vasoconstriction (acute tubular necrosis)

Post-renal:
Raised intra-abdominal pressure
Unrecognised catheter problems

b) What would be your indications for renal dialysis in this man?
Uncontrolled electrolyte disturbances (hyperkalaemia, hypernatraemia)
Uncontrolled metabolic acidosis
Uraemia 30-35 mmol/l (optimal timing not known, uncontrolled studies suggest early CRRT better
than late, candidate should have his/her own threshold level)
Fluid overload unresponsive to diuretics
Early intervention to minimise inflammatory response in sepsis may be considered but is unproven

c) Outline the means by which you would maximise urea clearance when using CVVHDF
Urea clearance depends on ultrafiltrate flow rate and dialysate flow rate so clearance enhanced by
increasing blood flow rate and/or dialysate flow rate
Use of filters with larger membrane surface areas
Use of predilution
Changing filter if failing
Maximising time on CRRT by ensuring good vascular access, optimising filter life and limiting/rationalising time out of the ICU for imaging, surgery etc

Discussion

This dialysis question assesses the candidate's understanding of the mechanims of solute clearance during CVVHDF.

Part a) is reasonably simple, and requires one to regurgitate the standard renal failure triad (pre-renal, renal, post-renal causes). The salient feature of the answer is the college's demand for specific nephrotoxic agents.

A big table of causes of renal failure is available in the Required Reading section.

Part b) is also reasonably simple, and requires one to recall the indications for dialysis. Bellomo (in Oh's Manual) suggests the following criteria:

The salient feature is the colleges' demand that the candidate have their own threshold for how much urea is too much. Also, cytokine clearance to reduce the severity of sepsis is mentioned, but it would be wise to write that the evidence for it is lacking.

Part c) requires some thinking. Solute clearance with CVVHDF is maximised by increasing the dialysate flow rate, the ultrafiltration rate, and the increase in membrane surface area. Maximising filter life and maximising time on CRRT by optimising access are practical considerations worth mentioning.

General strategies to improve solute clearance are listed in the Required Reading section.

A summary box available in that chapter is reproduced below, to simplify revision.

References

For a definitive treatment of all of this, you ought to pay homage to the gigantic and all-encompassing "Critical Care Nephrology" by Ronco Bellomo and Kellum (2009).

There is also extra stuff is from the Ronco et al article "The haemodialysis system: basic mechanisms of water and solute transport in extracorporeal renal replacement therapies" in Nephrol Dial Transplant ( 1998) 13 [Suppl 6 ]: 3–9.

I have tried to explore the argument of pre vs post dilution in my notes.

Finally, the Gambro and Fresenius websites have been an excellent source of information.

College Answer

AKI can be defined as an abrupt (1 to 7 days) and sustained (more than 24 hours) decrease in kidney function. The ADQI formulated the RIFLE criteria to allow for AKI to be objectively and uniformly defined.

The implication of this classification is that a progression down the RIFLE criteria is associated with a higher length of stay in ICU and Hospital and is associated with a higher mortality.

The limitations of this classification relate to it’s dependence on measuring urine output and creatinine which is confounded by the following:-

1. Accuracy of urine output measures.
2. Urine output affected by the use of diuretics.
3. Baseline creatinine may be affected by the patients concurrent health problem eg it may be falsely high purely because the patient was dehydrated on admission.
4. It is uncertain how well balanced urine output and creatinine are even though they have been given an equal weighting.

Discussion

This question refers to the 2004 formulation of the RIFLE criteria by the ADQI.

 This is a system of classification which was supposed to step in and define the seveirty of renal failure, at a time when there were over 30 different disagreeing definitions. Its real use is in predicting mortality, and it helps decisionmaking in which mortality statistics play a role.

The Acute Dialysis Quality Initiative formulated this classification. Our very own Ronco, Bellomo and Kellum published this thing in 2004. And of course, its varios advantages and disadvantages have been picked apart in the literature reviews, not the least of which comes from Life In The Fast Lane. ADQI themselves have also addressed the limitations of their system.

The table itself is quoted in the college answer:

Major complaints against this system are elaborated upon elsewhere.

In brief:

• The system classifies renal failure once it has already become established.
• The criteria are unbalanced: GFR and urine criteria for the same class (R) have different outcomes, but have been given equal weighting.
• Urine criteria rely on impractical 6th and 12th hour measurements.
• Urine output criteria are altered by diuretics, DI, etc.
• Urine output measurements may be inaccurate.
• Creatinine levels may be affected by factors which do not affect outcome.
• The criteria for creatinine rely on the availability of baseline values.
• Nobody seems to agree on what the definiton of "baseline" is, anyway.
• The "Risk" criteria for creatinine may not be sensitive enough.
• The criteria require true GFR, rather than an estimated GFR.

• The criteria make no attempt to distinguish between different aetiologies.

The greatest criticism of this system would come from the front lines of critical care, where the definitions and their prognostic value play little role. Sure, they have some utility in epidemiology, but at the bedside there is no way to apply these criteria to make management decisions. The fact that only 2% of the candidates passed this question is telling. Cold pragmatic bastards, they never saw a point in studying something they all viewed as a research tool.

References

Bellomo, Rinaldo, et al. "Acute renal failure–definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group." Critical care 8.4 (2004): R204.

Cruz, Dinna N., Zaccaria Ricci, and Claudio Ronco. "Clinical review: RIFLE and AKIN–time for reappraisal." Critical care 13.3 (2009): 211.

College Answer

Rhabdomyolysis from lower limb ischaemia

Discussion

The elevated LDH (which is non-specific) and AST (which leaks from dying muscle) are characteristic of rhabdomyolysis. This is a well-recognised complication of AAA repair, although it is typically a complication of open repair. However, this endovascular repair was apparently unusually prolonged, and thus one can assume that the surgeon had a catheter in at least one of the femoral arteries for a while, occupying much of the lumen. In this context, a period of limb ischaemia could have occurred. Other potential explanations could include trashed legs due to a shower of atheroma, or ischaemia of lumbar paraspinal muscles.

An alternative explanation is hepatic ischaemia from some sort of intraoperative injury, but this is less likely given the normal bilirubin and totally normal GGT and ALT, as well as the fact that typically endovascular repair tends to spare the hepatic circulation.

References

Vanholder, Raymond, et al. "Rhabdomyolysis." Journal of the American Society of Nephrology 11.8 (2000): 1553-1561.

Bosch, Xavier, Esteban Poch, and Josep M. Grau. "Rhabdomyolysis and acute kidney injury." New England Journal of Medicine 361.1 (2009): 62-72.

Woodrow, G., A. M. Brownjohn, and J. H. Turney. "The clinical and biochemical features of acute renal failure due to rhabdomyolysis." Renal failure 17.4 (1995): 467-474.

Ferreira, José, et al. "Lumbar paraspinal rhabdomyolysis and compartment syndrome after abdominal aortic aneurysm repair." Journal of vascular surgery37.1 (2003): 198-201.

Miller III, C. C., et al. "Serum myoglobin and renal morbidity and mortality following thoracic and thoraco-abdominal aortic repair: does rhabdomyolysis play a role?." European Journal of Vascular and Endovascular Surgery 37.4 (2009): 388-394.

College Answer

• Dehydration
• Steroid therapy or Cushings 
• GI bleed
• Protein catabolism 
• Decreased muscle mass
• Ruptured bladder

Discussion

No history is given. Only naked blood results. This goes far to confirm the age-old impression of ICU as a specialty which is essentially a biochemical spectator sport.

Anyway. This patient has a high urea and high creatinine, with a mildly elevated potassium (though still within the normal range) and hypernatremia.

The most apparent problem is the uraemia, and thus the candidate would be expected to produce a list of differentials for an elevated urea. This hypothesis is confirmed by the college answer. To the sensible and comprehensive list of differentials which they have offered us, I will also add a few unusual differentials.

• Upper GI bleed
• Dehydration
• Protein catabolism
• Corticosteroid therapy (which increases protein catabolism)
• Tetracycline therapy
• High protein diet
• Urea therapy (for intracranial hypertension or SIADH, but who does that any more? )
• Mannitol
• Diabetes insipidus

(more differentials are listed in the chapter concerned with uraemia)

Interestingly, bladder rupture is offered as a cause of these findings; it is indeed known to be a cause of biochemical features consistent with renal failure. The urea and creatinine excreted in the urine is reabsorbed via the lining of the peritoneum, meaning that the urea "recirculates" and keeps rising. However, according to the linked article, typically a ruptured bladder gives rise to hyponatremia rather than hypernatremia.

References

Vanholder, Raymond, et al. "Rhabdomyolysis." Journal of the American Society of Nephrology 11.8 (2000): 1553-1561.

Heyns, C. F., and P. D. Rimington. "Intraperitoneal rupture of the bladder causing the biochemical features of renal failure." British journal of urology 60.3 (1987): 217-222.

Pumphrey, C. W., and E. R. Beck. "Raised blood urea concentration indicates considerable blood loss in acute upper gastrointestinal haemorrhage." British medical journal 280.6213 (1980): 527.

WISE, BURTON L. "Hyperosmolarity (hypernatremia) and azotemia induced by the administration of urea." AMA Archives of Neurology 2.2 (1960): 160-162.

Pierrakos, Charalampos, et al. "Urea for treatment of acute SIADH in patients with subarachnoid hemorrhage: a single-center experience." Annals of intensive care 2.1 (2012): 1-7.

Yilmaz, K., et al. "Evaluation of laboratory tests in dehydrated children with acute gastroenteritis." Journal of paediatrics and child health 38.3 (2002): 226-228.

Adrogué, Horacio J., and Nicolaos E. Madias. "Hypernatremia." New England Journal of Medicine 342.20 (2000): 1493-1499.

SHILS, MAURICE E. "Renal disease and the metabolic effects of tetracycline."Annals of internal medicine 58.3 (1963): 389-408.

Thomas, David R., et al. "Understanding clinical dehydration and its treatment."Journal of the American Medical Directors Association 9.5 (2008): 292-301.

Walser, Mackenzie, and Leonard J. Bodenlos. "Urea metabolism in man."Journal of Clinical Investigation 38.9 (1959): 1617.

Simmons, Patricia S., et al. "Increased proteolysis. An effect of increases in plasma cortisol within the physiologic range." Journal of Clinical Investigation73.2 (1984): 412.

College Answer

a)

Forms a calcium – citrate complex which drops the serum ionized calcium level. Calcium is necessary for IX ® IXa, X ® Xa and PT ® thrombin.

b)

Citrate complexed with calcium is partially removed by the filter, but some enters the circulation. Citrate is largely metabolized in the liver, entering the tricarboxylic acid pathway (Krebs cycle) generating NADH. Also generates bicarbonate (at a rate of 3 bicarb per 1 citrate).

c)

2 sorts of problems:

First (most commonly described), due to inadequate calcium replacement, are those of low ionized calcium, i.e. chilliness, anxiety, perioral paraesthesias, carpopedal spasm, tetany, QT prolongation and arrhythmias. Associated with metabolic alkalosis from citrate metabolism, and possibly with sodium overload from the hypertonic sodium citrate.

Secondly (less common), due to citrate load in excess of hepatic ability to metabolise it, i.e. accumulation of citrate-calcium complex. Metabolic acidosis with high anion gap from citrate; raised ratio of total to ionized calcium from complexed calcium in circulation (normal total:ionized ratio 1.9-2.2:1, toxic ratio > 2.5:1.

d)

Hypocalcaemia Liver failure

Low cardiac output (i.e. poor hepatic perfusion)

e)

Prostacyclin (PGI2) Argatroban Danaparoid Bivalirudin Fondaparinux Lepirudin

Discussion

Summaries exist, covering some of these topics:

• Citrate anticoagulation for the dialysis circuit
• Citrate toxicity due to citrate anticoagulation

What is the mechanism by which citrate provides anticoagulation?

Citrate is a calcium chelator, and by robbing the clotting cascade of its ionised calcium it disables the steps of the cascade in which calcium plays a role (many people dont realise that calcium used to be Factor IV). The following are clotting cascade proteins which require calcium to function:

• • Factor VIIa
  • Factor IXa
  • Factor X
  • Factors Xa
  • Factor II (prothrombin)

So, 2, 7 9 and 10. Same as the Vitamin K-dependent factors.

What is the metabolic fate of the citrate?

The words "metabolic fate" are music to my ears.

In brief, citrate - in the course of its metabolism via the Krebs cycle - removes 3 H⁺ ions from the body, which has the equivalent effect of adding 3 HCO₃^- molecules. Thus, it is generally said that "citrate generates three bicarbonate molecules". It is true - its metabolism is the equivalent of buffering, and in excess citrate can cause a metabolic alkalosis. Thankfully, some of the citrate ends up being removed by the dialysis circuit, as it is a very small molecule.

What are the features of citrate toxicity?

Citrate toxicity - or rather, its biochemical features - is touched upon in the answer to Question 3.3 from the second paper of 2013.

In brief, the main features of citrate toxicity are as follows:

• High anion gap metabolic acidosis
• Potentially, also a metabolic alkalosis
• Low ionised calcium
• Normal total calcium (thus, a high total to ionised calcium ratio)
• Coagulopathy

What conditions may increase the risk of citrate toxicity?

• Liver disease (unable to metabolise the lactate)
• Coagulopathy (requirement for regional anticoagulation of the CRRT circuit)
• HITTS (or any other contraindication to the use of heparin)
• Hypocalcemia
• Decreased hepatic blood flow (eg. in sepsis or other shock states)

Citrate is mainly metabolised in the liver.

What alternative(s) to citrate could you use in a patient with severe HITS?

The list offered by the college is hardly all-inclusive:

• Prostacyclin (PGI2)
• Argatroban
• Danaparoid
• Bivalirudin
• Fondaparinux
• Lepirudin

One might also mention using higher flow rates and pre-dilution as non-pharmacological means of increasing filter lifespan. In general, a massive list of strategies used to improve filter lifespan is also available somewhere around here, and it contains many options which don't involve citrate.

References

Oudemans-van Straaten, Heleen M., et al. "Citrate anticoagulation for continuous venovenous hemofiltration*." Critical care medicine 37.2 (2009): 545-552.

Tolwani, Ashita J., et al. "Simplified citrate anticoagulation for continuous renal replacement therapy." Kidney international 60.1 (2001): 370-374.

Bakker, Andries J., et al. "Detection of citrate overdose in critically ill patients on citrate-anticoagulated venovenous haemofiltration: use of ionised and total/ionised calcium." Clinical Chemical Laboratory Medicine 44.8 (2006): 962-966.

Uhl, L., et al. "Unexpected citrate toxicity and severe hypocalcemia during apheresis." Transfusion 37.10 (1997): 1063-1065.

Webb, A. R., et al. "Maintaining blood flow in the extracorporeal circuit: haemostasis and anticoagulation." Intensive care medicine 21.1 (1995): 84-93.

Mikaelsson, M. E. "The Role of Calcium in Coagulation and Anticoagulation."Coagulation and Blood Transfusion. Springer US, 1991. 29-37.

Mycielska, Maria E., et al. "Citrate transport and metabolism in mammalian cells." Bioessays 31.1 (2009): 10-20.

Kramer, Ludwig, et al. "Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients." Critical care medicine 31.10 (2003): 2450-2455.

College Answer

Ensure good wide bore access, high flow rates, consider predilution. 

No Anticoagulant +/- Saline Flushes (50 – 100 mL every hour) 

Advantage: 
 Minimizes bleeding risk. 

Disadvantage: 
 Shortened filter life / increased time off dialysis. 
 Alternative systemic anti-coagulant required for treatment of underlying HITTS. 

Regional citrate 
Advantage: 
 Provides good regional anticoagulation. 
 Pre-mix solutions and protocols for use have simplified process. 
Disadvantage: 
 Requires diligent monitoring of serum sodium, ionized calcium, and bicarbonate. 
 Requires infusion of calcium outside the circuit (access issues). 
 Large sodium load occurs when trisodium citrate used. 
 May cause alkalosis. 
 Special diasylate required: hyponatraemic, without buffer, Ca free. 
 Not appropriate in liver failure. 
 Alternative systemic anti-coagulant required for treatment of underlying HITTS. 

Prostacycline and Analogues 
Advantages 
 Reduced bleeding risk. 
Disadvantages 
 Shorter filter life. 
 Hypotension. 
 Alternative systemic anti-coagulant required for treatment of underlying HITTS. 

Direct thrombin Inhibitors: Bivalirudin / Hirudin / Lepirudin / Argatroban 
Advantages: 
 Linear relationship between levels and APTT (< 100s) for Hirudin. 
Disadvantages 
 Renal clearance, accumulation in renal failure (Bivalirudin, Hirudin, Lepirudin) Hepatic 
metabolism, accumulation in liver disease (Argatroban) No antagonist. 
 Argatroban falsely raises INR / PT. 
 Expense. 

Other agents 
Danaparoid 
 Limited availability 
 Risk of cross-reactivity with heparin-induced antibodies 
 Hard to monitor

Discussion

This question closely resembles several others. Past paper questions on this topic have included Question 4 from the second paper of 2010 and Question 17 from the first paper of 2007. The answer to such questions would benefit from a tabulated answer. A massive table, which acts as a reference for all such questions, can be found in the Required Reading summary on the Strategies to prolong the lifespan of the dialysis circuit. 

The major issue to remember in answering such questions is that all these fancy regional anticoagulant strategies do nothing about the need for systemic anticoagulation in HITTS.

References

College Answer

a)
Extracorporeal blood purification process to-

•  remove large molecular weight components of the plasma including antibodies, immune complexes, cryoglobulins, myeloma light chains as examples.
• Removal is by centrifugation of blood into components. Non plasma components are returned to patient, plasma is discarded.
• volume removed is replaced by colloid solutions such as plasma products (FFP), or albumin solutions. In some conditions whereby coagulation or immune factors are deficient then FFP replacement provides an additional therapeutic benefit.

b)
To justify therapeutic plasmaphoresis the substances removed should
A) have a sufficiently long T1/2 such that this process results in more rapid removal than other
endogenous clearance (e.g. suppression of macromolecule production),
B) Be key ‘toxic’ factor in the pathogenesis of the disease

c)
Immunoproliferative diseases with monoclonal immunoglobulins
 Hyperviscosity syndrome
 Cryoglobulinaemia
 Renal failure in multiple myeloma
 Autoimmune diseases due to autoantibodies or immune complexes
 Goodpasture’s syndrome
 Myasthenia gravis
 Guillain–Barre´ syndrome
 Chronic inflammatory demyelinating polyneuropathy (CIDP)
 Stiff-man syndrome
 Systemic lupus erythematosus
 Fulminant antiphospholipid syndrome
 Thrombotic thrombocytopenic purpura
 Haemolytic uraemic syndrome
 Rapidly progressive glomerulonephritis
 Coagulation inhibitors
 Autoimmune haemolytic anaemia
 Pemphigus
 Paraneoplastic syndromes
Conditions in which replacement of plasma may be beneficial _ removal of toxins
 Disseminated intravascular coagulation
 Overwhelming sepsis syndromes (e.g. meningococcaemia)
Conditions in which the mechanisms are unknown
 Reye’s syndrome
Removal of protein-bound or large molecular weight toxins
 Paraquat poisoning
 ?Envenomation

d)

a. Complications related to vascular access

i. Catheter-related sepsis

b. Complications related to extracorporeal circuits

i. Hypotension/loss of blood/thrombocytopenia

c. Complications related to exchange fluid

i. More common with FFP (vs Albumin)

ii. Transfusion reactions

iii. Allergic reactions

d. Complications related to anticoagulation

i. Citrate (hypocalcaemia)
ii. Heparin (bleeding, thrombocytopenia)

Discussion

Though worded slightly differently, this question is nearly identical to Question 14 from the second paper of 2010. That time, the college did not ask for the pre-requisites for effectiveness, just a list of potentially removable substances.

a) Principles of plasmapheresis

• Plasmapheresis may refer to a variety of procedures, all involving the therapeutic separation of blood into components.
• Separation of blood into cellular and fluid components offers the opportunity to discard or modify those components. 
• This separation is usually accomplished by means of either a centrifuge or by the less frequently used method of porous membrane filtration.
• Unlike dialysis or haemofiltration, there is no size barrier: plasmapheresis removes the whole plasma with molecules of all sizes.
• Some blood components are then reinfused into the patient with or without modification, and the rest may be discarded or stored.
• If plasma is being removed,  volume is replaced with 4% albumin or FFP.

b) Characteristics of a disease process which make plasmapheresis an effective option:

1. The disease has to be caused by some circulating factor, i.e. it has to be present in the blood
2. That factor has to have a sufficiently long plasma half-life, such that "turning off" the process of its production will still result in significant amounts of it persisting in the bloodstream.

c) Indications for urgent plasmapheresis 

The full list can be seen in this guidelines statement: Zbigniew et al, 2010

Urgent plasma exchange:

• TTP
• Catastrophic antiphospholipid syndrome
• Hyperviscosity syndrome (eg. myeloma)
• Guillain-Barre syndrome
• Myasthenia gravis
• Acute fulminant hepatitis with encephalopathy
• Amanita phalloides poisoning

Less urgent plasma exchange:

• Erythrodermic cutaneous T-cell lymphoma
• Wegeners granulomatosis
• Goodpasture's syndrome
• Eaton-Lambert syndrome
• Babesiosis
• Autoimmune haemolytic anaemia
• Cryoglobulinaemia
• Dermatomyositis/polymyositis
• Hemolytic uremic syndrome
• Familial hypercholesterolaemia
• Focal segmental glomerulosclerosis
• Paraproteinaemic polyneuropathy
• Antibody-mediated renal transplant rejection
• Fulminant Wilson's disease.

One should note that in their list of indications, the college noted some Grade II, III and IV recommendations, such as:

• HELLP syndrome
• Multiple sclerosis
• HIV-related neuropathy
• Pemphigus
• Coagulation inhibitors
• DIC
• Overwhelming sepsis syndromes eg meningococcaemia
• Reye’s syndrome
• Paraquat poisoning

d) Complications of plasmapheresis

• Due to vascular access
  • all the complications of large CVAD insertion: CLABSI, bleeding, vessel damage, etc etc
• Due to the circuit exposure
  • Low fibrinogen and coagulopathy
  • Haemolysis and thrombocytopenia
  • Hypothermia
  • Complement activation
• Due to anticoagulation
  • Paraesthesia due to hypocalcemia (due to regional citrate anticoagulation)
  • Bleeding complications
  • HITS
• Due to the replacement fluid
  • Urticaria
  • Febrile reaction to blood products
  • Anaphylaxis
• Due to the unavoidable removal of useful blood components
  • Loss of useful drugs
  • Immunosuppression
  • Anaphylaxis
  • Hypothermia
  • Loss of useful blood proteins (albumin, globulins)
• Due to volume loss
  • Hypotension
  • Vasovagal syncope
  • Nausea and vomiting

References

McLeod, Bruce C. "Therapeutic apheresis: use of human serum albumin, fresh frozen plasma and cryosupernatant plasma in therapeutic plasma exchange."Best Practice & Research Clinical Haematology 19.1 (2006): 157-167.

Reimann, P. M., and P. D. Mason. "Plasmapheresis: technique and complications." Intensive care medicine 16.1 (1990): 3-10.

Winters, Jeffrey L. "Plasma exchange: concepts, mechanisms, and an overview of the American Society for Apheresis guidelines." ASH Education Program Book 2012.1 (2012): 7-12.

Oh's Manual: Chapter 97 (pp. 993)  Therapeutic  plasma  exchange  and  intravenous  immunoglobulin  therapy  by Ian  Kerridge,  David  Collins  and  James  P  Isbister.

Szczepiorkowski, Zbigniew M., et al. "Guidelines on the use of therapeutic apheresis in clinical practice—Evidence‐based approach from the apheresis applications committee of the American Society for Apheresis." Journal of clinical apheresis 25.3 (2010): 83-177.

Russi, Gianpaolo, and Piero Marson. "Urgent plasma exchange: how, where and when." Blood Transfusion 9.4 (2011): 356.

Weinstein, Robert. "Basic principles of therapeutic blood exchange." Apheresis: principles and practice (2003): 295-320.

College Answer

a)
Diagram expected to be appropriately labelled and depict access and return lines, filter, dialysate, effluent and replacement fluid and include sites of pressure measurement and pumps

b)
(i)
Dialysis dose is equivalent to the effluent rate in ml/kg/hour.
Effluent rate = ultrafiltration rate for haemofiltration (CVVH)
= dialysis rate for haemodialysis (CVVHD)
= ultrafiltration rate + dialysis rate for haemodiafiltration (CVVHDF)
Dialysis doses (effluent rates) greater than 25 ml/kg/hr have not been shown to improve outcome but
it is reasonable to run at higher rates to compensate for downtime when the circuit has clotted or
been taken down to allow for patient transfer/treatment

(ii)
Transmembrane pressure (TMP) = (Filter pressure + Return pressure) / 2 –
(Effluent pressure)
High TMPs with normal return pressures indicate a problem with the filter. High TMPs with high
return pressures indicate a problem with the return line +/- the filter
Different filter membrane properties can produce different ultrafiltration rates for the same TMP.
Filters that are highly permeable to water (high flux membranes) allow more water to cross the
membrane for a given TMP.

(iii)
Sieving coefficient (SC) = Ultrafiltrate concentration / Blood concentration
SC is a measure of how effectively a substance is removed through the filter.
SC = 0 means the substance is not filtered at all e.g. protein sized molecules
SC = 1 means the substance is completely filtered e.g. urea, creatinine
SC depends on solute molecule size, protein binding and filter porousness

(iv)
Filtration fraction = Ultrafiltration rate / Blood flow rate* and should  0.25
* Strictly plasma flow rate (blood pump rate x 1 – Hct)
I.e. fraction of plasma that is removed from blood during filtration
Higher filtration fractions predispose to filter clotting through haemoconcentration.

 

Discussion

A diagram which could " to be appropriately labelled and depict access and return lines, filter, dialysate, effluent and replacement fluid and include sites of pressure measurement and pumps" exists on this site, and is reproduced here:

Because this diagram was not produced by Gambro or Fresenius, one should not hang their reputation on its accuracy. Also, an omission has been pointed out by the readers - blood warmers do not appear on the diagram. The position of blood warming coils on this device is in two usual places: on goes on the dialysate circuit before the dialysate pump, and the other goes on the blood circuit at the very end of the return line, after the pressure gauge.

The definitions and their relevance to CRRT:

Dialysis dose

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), or the sum of ultrafiltration rate and dialysis rate for CVVHDF

Relevance to CRRT:

• Prescribed dose is the effluent rate
• No benefit in outcomes with doses in excess of 25ml/kg/hr
• Practically, higher doses may be necessary to compensate for circuit downtime

Transmembrane pressure

Definition

Transmembrane pressure (TMP) = (P_F + P_R) / 2 – P_E

Where

P_F = Filter pressure

P_R = Return pressure

P_E = Effluent pressure

Relevance to CRRT:

• High TMP with normal return pressure suggests there is a filter problem
• High TMP with high return pressure suggests either the filter or the return line are the problem
• At any given TMP, the actual ultrafiltration rate will vary for membranes with different permeabilities

Sieving coefficient

Definition

Sieving coefficient (SC) = Ultrafiltrate concentration / Blood concentration

Relevance to CRRT:

• The sieving coefficient of any given molecule determines the success of its removal by CVVHDF
• SC depends on numerous factors, and is different for each molecule.
• Some of its determinants include:
  • Molecule size of the solute
  • Protein binding of the solute
  • Charge of the solute and of the filter membrane
  • Size and number of pores in the filter membrane

Filtration fraction

Definition

Filtration fraction = Ultrafiltration rate / Blood flow rate

more accurately:

Filtration fraction = Ultrafiltration rate / (blood pump rate × (1 – Haematocrit))

Relevance to CRRT:

• The filtration fraction is literally the fraction of plasma which is removed from blood during haemofiltration
• The ideal filtration fraction at a haematocrit of 0.30 is around 0.25
• Anything higher than this increases the risk of filter failure due to haemoconcentration.
• A higher TMP increases the filtration fraction
• A higher blood oncotic pressure decreases the filtration fraction

References

Bellomo, Rinaldo, and Claudio Ronco. "Nomenclature for continuous renal replacement therapies." Critical Care Nephrology. Springer Netherlands, 1998. 1169-1176.

Locatelli, Francesco, et al. "Dialysis dose and frequency." Nephrology Dialysis Transplantation 20.2 (2005): 285-296.

Claure-Del Granado, Rolando, et al. "Effluent volume in continuous renal replacement therapy overestimates the delivered dose of dialysis." Clinical Journal of the American Society of Nephrology 6.3 (2011): 467-475.

Clark, William R., et al. "Dose determinants in continuous renal replacement therapy." Artificial organs 27.9 (2003): 815-820.

College Answer

a)

Forms a calcium – citrate complex which drops the serum ionized calcium level. Calcium is necessary for IX → IXa, X → Xa and PT → thrombin.

b)

Citrate complexed with calcium is partially removed by the filter, but some enters the circulation. Citrate is largely metabolized in the liver, entering the tricarboxylic acid pathway (Krebs cycle) generating NADH. Also generates bicarbonate (at a rate of 3 bicarb per 1 citrate).

c)

2 sorts of problems.

First (most commonly described), due to inadequate calcium replac ement, are those of low ionized calcium, i.e. chilliness, anxiety, perioral paraesthesiae, carpopedal spasm, tetany, QT prolongation and arrhythmias. Associated with metabolic alkalosis from citrate metabolism, and possibly with sodium overload from the hy pertonic sodium citrate.

Secondly (less common), due to citrate load in excess of hepatic ability to metabolise it, i.e. accumulation of citrate - calcium complex. Metabolic acidosis with high anion gap from citrate; raised ratio of total to ionized calcium from complexed calcium in circulation (normal total:ionized ratio 1.9 - 2.2:1, toxic ratio > 2.5:1.

d)

Hypocalcaemia
Liver failure
Low cardiac output (i.e. poor hepatic perfusion)

e)

At least 3 classes or 4 drug names for full marks
Prostacyclin (PGI ₂ )
Argatroban
Danaparoid
Bivalirudin
Fondaparinux
Lepirudin
No anticoagulation

Discussion

This question is identical to Question 29 from the first paper of 2013.

References

College Answer

Additional Examiners’ Comments:

Candidates’ knowledge and understanding of a core topic was overall poor. Some candidates were not able to describe the mechanisms involved. Many described CVVHDF rather than CVVHF

Discussion

The college answer is of a surprisingly high quality. Little can be done to improve on it, except to furnish the points with references. And to rearrange the table, to make it look like a different table.

Some footnotes of interest:

* The college answer makes much of the improved clearance of middle molecules by CVVH, but in actual fact  all molecules  are cleared better by this modality. An excellent comparison, almost purpose-made for this SAQ, comes from Liao et al (2003). The authors found that clearance of small solutes by CVVH  was 8% better than by SLED, and 60% better than by IHD. This can be illustrated using graphs which were stolen shamelessly from the Liao paper. For large and middle molecules, CVVH is even better - twice as effective as SLED and four times as effective as IHD. This is mainly because the therapy is sustained continuously.

** Though the college answer presents intermittent haemodialysis as a technique purely dependent on diffusion, in practice this is not the case, even though it's called "haemodialysis".   Some ultrafiltration needs to occur in order to control the fluid balance, and this is the norm for maintenance dialysis - that's why people discuss the "dry weight" of chronic IHD patients. In case this baremetal fact needs to be varnished with peer-reviewed literature, one could pull out just about anything from the Am J Kid Dis  or Nephrology and Transplantation. Literally anything. Here's a 2016 study by Assimon et al correlating ultrafiltration rate to mortality, for example. For interests' sake, its worth noting that in that study the average ultrafiltration rate was about 6.6ml/hr/kr, or about 1.8L total fluid removal after a 4hr session for an average 70kg patient. Since probably the late 1980s straight HD has been replaced by HDF (haemodiafiltration), because the latter was a significant improvement. Canaud et al (1989) described it as "the new standard". 

*** The college suggests that fluid management is inherently more "flexible" in CVVH. This is an interesting statement. An article by Murugan (2016) also suggests that CVVH and CRRT in general allows more precision in the control of fluid balance. Practically, it is difficult to determine how the same 100ml/hr fluid removal by SLED or IHD is any less easy or less flexible. Arguably, it is actually easier to achieve a high negative fluid balance with SLED or IHD because the nurses do not need to laboriously exchange full bags of effluent. The main "flexibility"is really the ability to run the circuit continuously, which means you remove as much fluid as you want - you just need to keep it running for longer.

References

Assimon, Magdalene M., et al. "Ultrafiltration rate and mortality in maintenance hemodialysis patients." American Journal of Kidney Diseases 68.6 (2016): 911-922.

Jean, Guillaume, et al. "Online-haemodiafiltration vs. conventional haemodialysis: a cross-over study." BMC nephrology 16.1 (2015): 70.

Canaud, B., et al. "Hemodiafiltration with on-line production of bicarbonate infusate." Improvements in Dialysis Therapy. Vol. 74. Karger Publishers, 1989. 91-100.

Liao, Zhijie, et al. "Kinetic comparison of different acute dialysis therapies." Artificial organs 27.9 (2003): 802-807.

Murugan, Raghavan, et al. "Precision fluid management in continuous renal replacement therapy." Blood purification 42.3 (2016): 266-278.

O'Reilly, Philip, and Ashita Tolwani. "Renal replacement therapy iii: IHD, CRRT, SLED." Critical care clinics 21.2 (2005): 367-378.

College Answer

Discussion

The influence of end-stage renal failure on the management of critically ill patients  has also been asked about in Question 1 from the first paper of 2011.The college's model answer was so good, that I have reproduced it here.

Issues specific to ESRD raised in this article include:

• The central veins draining the access arm with the fistula should be protected from venous
  catheters
• Diet should be potassium- and phosphate-restricted
• An AV fistula should not be accessed for CRRT or SLEDD, because the sessions are long and the risk of needle dislodgement and lifethreatening haemorrhage is thus greatly increased.
• In terms of small solute clearance, there is no need to change the dose of dialysis in critically ill ESRD patients when compared to their regular maintenance dose.
• Hypotonic and hypertonic fluids should be avoided

References

Clermont, Gilles, et al. "Renal failure in the ICU: comparison of the impact of acute renal failure and end-stage renal disease on ICU outcomes." Kidney international 62.3 (2002): 986-996.

Szamosfalvi, Balazs, and Jerry Yee. "Considerations in the critically ill ESRD patient." Advances in chronic kidney disease 20.1 (2013): 102-109.

Arulkumaran, N., N. M. P. Annear, and M. Singer. "Patients with end-stage renal disease admitted to the intensive care unit: systematic review." British journal of anaesthesia 110.1 (2013): 13-20.

Thompson, Stephanie, and Neesh Pannu. "Renal replacement therapy in the end-stage renal disease patient with critical illness." Blood purification 34.2 (2012): 132-137.

College answer

Allergic / Acute Interstitial nephritis secondary to antibiotic use.      

Discussion

The eosinophils. They are high.

Everything else is normal.

It could be nothing else. The cellulitis, presumably it got flucloxacillin - and then the cillin caused an interstitial nephritis, as they tend to do. 

References

Perazella, Mark A., and Glen S. Markowitz. "Drug-induced acute interstitial nephritis." Nature Reviews Nephrology 6.8 (2010): 461-470.

College answer

a)    Outline how the renal dysfunction will influence antimicrobial dosing:           
 
•    Vancomycin: High dosing on Day 1 may be required to ensure adequate distribution. Dose adjustments made on trough levels. Consider Vancomycin infusion with steady state levels of 20-25 to maximise duration above MIC. 
•    Ciprofloxacin: Reduce frequency and maintain dose 
•    Metronidazole: No change 
 
Consider Therapeutic Drug Monitoring (TDM) where available- e.g. Vancomycin, Ciprofloxacin.  
      
b)    Outline possible strategies to minimise the risk of further renal injury from the CT: 
•    Review indication for CT and need for contrast  
Consider progressing straight to surgery without CT if indicated by clinical condition   • CT without contrast an option. 
•    If decision that contrast vital – lowest reasonable volume and isosmolar contrast (specifically avoid high osmolar contrast). Water contrast if ischaemic bowel a consideration  
•    Ensure euvolaemic, no real evidence for bicarbonate, weak evidence for N-acetylcysteine  
•    Correct other factors contributing to renal injury – adequate renal perfusion, stop nephrotoxics, monitor drug levels, monitor intra-abdominal pressures 
 
c)    List the factors that would influence your decision to start renal replacement therapy in this case:           
Traditional indications for renal replacement therapy in AKI include: 
•    Refractory fluid overload 
•    Hyperkalaemia (plasma potassium concentration >6.5 mmol/L) or rapidly rising potassium levels 
•    Signs of uraemia, such as pericarditis, neuropathy, or an otherwise unexplained decline in mental status 
•    Severe metabolic acidosis (pH <7.1) 
•    Toxin elimination (IV contrast in this case) 

However, there are limitations to restricting to these traditional indications in the critically ill patient, i.e. 
o    AKI part of MODS and negative influence of fluid overload on other organs – lungs and brain 
o    Ongoing fluid input exacerbates fluid overload– nutrition, vasoactives, antibiotics- so may need CRRT purely to achieve appropriate fluid balance. 
o    Acid-base and biochemical abnormalities poorly tolerated in critical illness 
 
Additional Examiners‟ Comments: 
In general, many candidates were not familiar with dosing of vancomycin, and ciprofloxacin. Many candidates did not address the strategy of reconsidering the need for contrast or alternatives. With respect to part (c), many candidates could not provide adequate detail and overall the answers were brief and superficial.  
 

Discussion

a)

Antibiotic dosing in renal failure is discussed in full elsewhere. Broadly speaking, such questions fall into the trap of testing nothing of particular use to the intensivist fellow: consider, the information asked for here is available rapidly, and in greater detail, from a number of smartphone-accessible resources. Surely, the merits of committing to memory some vast lists of antibiotic pharmacokinetics data are not yet apparent, but they will be - when the power fails and the telco companies are brought down by communist neutron bombs. The post-apocalypse intensivist will have to rely heavily on memorised material. Until then, let me access the Sanford guide on my phone to dose-adjust these antibiotics.

For this trick, we will plug a hypothetical weight of 70kg into a similarly widely-available Cockcroft-Gault calculator. Without guessing a height, the calculator spits out a creatinine clearance rate of 19.5ml/min. Wherever possible, IV recommendations were used here (the patient is probably not eating, what with the new anastomosis and all).

Ciprofloxacin: For a creatinine clearance of less than 30ml/min, the SG recommends:

• Keep the dose the same (400mg IV)
• Interval-adjust to one daily dose, instead of q12h.

Metronidazole, for a creatinine clearance of 10-50ml/min

• No adjustment neccessary (keep it 7.5mg/kg q6h)
  (once the CrCl gets to under 10ml/hr, interval-adjust to q12h dosing)

Vancomycin, for a creatinine clearance of 10-50ml/min

• Dose-decrease to 15mg/kg (normally, 13-30mg/kg)
• Interval-adjust to a range between daily dosing and giving one dose every 3-4 days (to be guided by daily levels is probably thebest advice)

b)

Prevention of contrast-induced nephropathy is discussed more completely in another chapter. A huge table is available there, full of stratgies (both currently well-loved and non-discredited). Instead of replicating that huge table here, the key strategies hich are applicable in this situation are listed below.

• Use of nonionic contrast media
• Use of a smaller volume of contrast media
• N-acetylcysteine
• Pre and post-hydration
• Sodium bicarbonate
• Prophylactic CVVHDF

c)

Timing of renal replacement therapy really could benefit from a "critically evaluate" sort of question, but in this case the college just wanted a list of factors. These must surely be the conventional indications for haemodialysis:

• Oliguria (less than 200ml in 12 hours) - (tick, he already has this)
• 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 (i.e. the contrast)

However, this question was valued 40% of the marks, so the college may have wanted us to say something more clever about the current controversy in early vs deferred dialysis.

References

College answer

a) The results indicate rhabdomyolysis.
The history is suggestive of muscle ischaemia from the prolonged duration of surgery and 
likely immobilization. The classic biochemical picture of hyperkalaemia, hyperphosphatemia, 
hypocalcaemia, high aspartate aminotransferase (AST), AKI with reduced Urea:Creatinine 
make rhabdomyolysis an important diagnosis to exclude. Other differentials causing an acute 
kidney injury are unlikely.

b) CK levels
• ECG
• Urine for myoglobin
• Serum lactate dehydrogenase (LDH)

c)
• Treat the cause; muscle debridement / fasciotomy if indicated
• Ensure adequate hydration – you need generous amounts of fluid aiming for urine output 1ml/kg/h
• Consider urinary alkalization with bicarbonate to keep pH > 6.5 (although there is limited 
evidence above fluid alone)
• Treat hyperkalaemia along conventional lines
• CRRT if remains oliguric, increasing U and Cr

d)
• Statins
• SSRIs
• Drugs of abuse: cocaine, amphetamines, heroin, LSD, ‘ Ecstasy’

Discussion

It's clearly rhabdomyolysis. "Give rationale for your answer", they ask. Well:

• History suggests prolonged immobility (12hr operation)
• Clinically, the urine is dark. They did not go as far as to actually describe it using terms like "tea-coloured" but the hint is strong enough.
• Biochemically, there are classical electrolyte abnormalities associated with rhabdomyolysis:
  • Hyperkalemia
  • Hypocalcemia
  • Hyperphosphataemia
• The elevated AST suggests some muscle breakdown
• The other LFTs and bilirubin are normal, suggesting a non-hepatic source for the AST.

Some other weirdness is also apparent:

•  The albumin: it is a bit low. Why? Surely the hypoalbuminaemia of critical illness could not have started already, eight hours after the operation? More likely, the albumin is low because of dilution by the inevitable six or so litres of crystalloid which this guy would have got intraoperatively. Additionally, head and neck cancer comes with some additional baggage (heavy smoker, alcoholic) which promotes sub-optimal nutrition- in fact one might make the argument that a normal albumin level might be unexpected.
• The sodium: it is a bit low. No reason is given for this in the college answer. There are several possible ways to interpret this. If one had an unshakeable faith in the college one might be tempted to believe that every parameter of this biochemistry panel was carefully calculated to elicit some sort of response in the exam candidate. Alternatively, one might hold the view that the lazy examiners threw some numbers together without thinking too hard about it. Finally, the SAQ might be based on an actual case, and the sodium abnormality reflects the tendency of real-world patient data to neglect the principles of SAQ design. In either case, the low sodium begs for some explanation from a person diligently dissecting this biochemistry problem. A handy explanation is the inevitable ADH release associated with surgery, and the water retention associated therewith. Other explanations are possible (exogenous water excess, CCF, hypothyroidism etc) but these are more far-fetched. SIADH due to nicotine, or a paraneoplastic syndrome associated with a squamous cell carcinoma, are also reasonable differentials.
• The platelets: they are raised. This can be explained by the stereotypical response to trauma (and a 12-hour head and neck procedure qualifies as trauma). Valade et al (2005) found that the platelet count rises in about 20% of trauma patients, and peaks usually by day 4. Interestingly (and appropriately for a stress response) it is associated with improved mortality. 

List other useful investigations? To really confirm the crap out of it, you'd order the following series of tests:

• CK level
• Urinary myoglobin
• Urate level
• Lactate

The college also recommend an ECG, because potassium.

A recent meta-analysis of management strategies for rhabdomyolysis has presented the following conclusions:

• Commence IV fluids within 6 hours - as early as possible
• Aim for a urine output greater than 300ml/hr
• Use of sodium bicarbonate is only indicated to correct systemic acidosis. There is no evidence for any benefit in rhabdomyolysis-induced AKI except for some uncontrolled case series, which does not stop people from recommending it anyway. It appears in the 2010 college answer, which pre-dates the 2013 meta-analysis. The savvy trainee seeking to remain in the good books with examiners who use forced alkaline diuresis will want to mention this therapy in their answer, with the caveat that it is may not be helpful, but is also probably not harmful.
• Use of mannitol is only indicated if urine output >300ml/hr cannot be maintained
• Actually removing the dead muscle is also helpful.

Dialysis may be commenced to improve the removal of myoglobin, if a high-permeability membrane filter is available. Even if it is not, standard CVVHDF seems to decrease the risk of renal injury.

Drugs associated with rhabdomyolysis:

• Antipsychotics (neuroleptic-malignant syndrome)
• SSRIs (serotonin syndrome)
• Statins
• Alcohol
• Cocaine
• MDMA (though the college had decided to throw about with its vulgar street name)
• Volatile anaesthetics (malignant hyperthermia)
• Propofol infusion syndrome
• Imatinib, sunatinib (tyrosine kinase inhibitors)
• Daptomycin (Hohenegger, 2012)
• Suxamethonium by way of malignant hyperthermia

References

College answer

    a) Risk factors for CIN: (any 6)                                         
1.    Age > 75 years 
2.    Pre-existing kidney disease (creatinine > 120 umol/L) 
3.    Diabetes Mellitus  
4.    Congestive Heart Failure 
5.    Liver Cirrhosis 
6.    Nephrotic Syndrome 
7.    Peripheral Vascular Disease 
8.    Dehydration or prior diuretic use, especially frusemide 
9.    Multiple Myeloma 
10.    Use of 1st generation hyperosmolal ionic contrast agents 
11.    High dose of IV contrast 
12.    Treatment with nephrotoxic agents, such as NSAIDs, aminoglycosides, amphotericin & cyclosporine A 
 
b)  
•    Use nonionic low-osmolal agents/avoid high osmolal agents 
•    Use lower doses of contrast and avoid repetitive, closely spaced studies (e.g. <48 hours apart).  
•    Avoid volume depletion and NSAIDs  
•    For patients at high risk, in the absence of contraindications to volume expansion, intravenous fluids prior to and continued for several hours after contrast administration. While no placebocontrolled studies have proven a benefit of prophylactic intravenous fluid in these risk groups, indirect data support its use. 
•    Either isotonic bicarbonate or isotonic saline may be used, preference for isotonic saline since less expensive and no risk of compounding errors. There are no commercially available isotonic sodium bicarbonate solutions available. Rate e.g.1 mL/kg/hour for 6 to 12 hours preprocedure, intraprocedure, and for 6 to 12 hours post procedure.  
•    For at-risk patients, acetylcysteine may be administered the day before and the day of the procedure, based upon its potential for benefit, low toxicity and cost. Although data are conflicting, acetylcysteine may be warranted based on some studies showing a benefit. If acetylcysteine is administered, a preferred dose is 1200 mg orally twice daily rather than 600 mg twice daily the day before and the day of the procedure.  
•    (No role for mannitol or other diuretics prophylactically. However, diuretics may be used to treat volume overload if present 
•    Prophylactic hemofiltration or hemodialysis after contrast exposure to prevent contrast nephropathy is not recommended 
•    Avoidance of contrast, alternative imaging modalities. 
 

Discussion

Risk factors for contrast-induced nephropathy can be divided into modifiable and non-modifiable:

Preventative strategies "that have been used" can be presented in a massive table:

References

College answer

a) 
Iv haemolysis 
 
b) 
Incompatible transfusion 
Medications 
DIC/ sepsis 
Massive transfusion 
Pre-existing  hereditary conditions e.g. G6PD deficiency, spherocytosis etc. 
 

Discussion

The question is very similar to Question 5.3 from the first paper of 2009, and though the college uses a different image for this version, the two photographs are so nearly identical that the author was compelled to re-use the image from 2009. Essentially, both pictures show a full effluent bag which is filled with a translucent red fluid, uniformly red. This is in contrast to a picture of circuit rupture, which looks a little different: because of the fact that whole erythrocytes have made it into the effluent, the fluid separates into layers (the erythrocytes sediment at the bottom). Free haemoglobin, in contrast, would remain suspended for much longer, though conceivably if the bag were left neglected somewhere, then it too would probably separate into layers over time. 

Anyway:

a)

• The haemoglobin is low
• The haptoglobin is low, suggesting that it has been depleted by free haemoglobin molecules
• The reticulocyte count is high, suggesting that the bone marrow is so busy producing new erythrocytes that normal quality control processes are suspended
• The bicarbonate is a little bit high, suggesting that perhaps the CRRT has finished a sustained long run, or that citrate was used to anticoagulate it.
• Creatinine and urea are both normalised, which supports the assertion made above (considering that this patient supposedly came in with acute anuric renal failure)
• The calcium is somewhat low, which could be the consequence of the high phosphate
• CK is normal, which is meaningful, because the other possible explanation for the colour of the dialysate is a leak of intracellular myoglobin.
• LDH is high, suggesting that some sort of cell lysis is taking place. LDH is not unique to red cells and would also rise if any tissue is damaged enough for cell membrane rupture to occur (for example, it was at one stage proposed as a cardiac injury biomarker).

b) Question 5.3 from the first paper of 2009 only asked for two causes, and the pass rate was 39%. Clearly that was too easy.  The possible explanations are:

• The filter membrane ruptured, releasing blood into the effluent (though as discussed above, this usually gives a somewhat different expensive cocktail-like appearance)
• There is a massive intravascular haemolysis (that's the most likely explanation given the biochemistry findings)
• The patient has received some drugs which discolour body fluids:
  •  Hydroxycobalamin, which tends to discolour all body fluids, and which will cause the blood detector in the dialysis machine to alarm (Cheungpasitporn et al, 2017)
  • Rifampicin
  • Phenytoin
  • Methyldopa

References

College answer

• Crush/pressure injury
• Drug/Toxins
• Hyperthermia
• Prolonged status
• Inflammatory myopathies
• Infective – viral, bacterial myositis
• Neuroleptic malignant syndrome

Discussion

So; the abnormalities seen are:

• Hypernatremia (trivial)
• Hyperkalemia
• Hyperchloraemia 
• Acidosis 
• Anion gap 22 (delta ratio = 2.0)
• High creatinine and urea
• Low calcium
• High phosphate
• High magnesium
• High AST but otherwise trivial LFT derangement
• Massive CK elevation

Thus, this is probably some sort of rhabodmyolysis. The anion gap can be interpreted as lactate. In generral the features expected with rhabodomyolysis are an elevated CK, AST, LDH, urinary myoglobin, renal dysfunction and electrolyte abnormalities (particularly hyperkalemia, hypocalcemia, hyperphosphataemia, hyperuricemia, lactic acidosis). DIC may also be present.

Five possible causes of this are asked for. Numerous causes of rhabdomyolysis are listed in the appropriate chapter; of these, the following are the most relevant to the presentation (young man, missing for a day, found obtunded):

• Alcohol intoxication
• Recreational drugs (eg. MDMA)
• Serotonin syndrome or neuroleptic malignant syndrome
• Seizures
• Head trauma with prolonged prostration, +/- compartment syndrome
• Heat stroke

References

College answer

Type of RRT: 
Intermittent Hemodialysis likely to be associated with rapid fluid and solute shifts with increase in cerebral oedema and ICP – avoid. 
CRRT better choice 

Higher threshold for commencement in the context of raised ICP. 
Risk of rebound intracranial hypertension if dialysate/replacement fluid sodium concentration is lower than plasma – consider using high sodium containing fluids 
 
Consider using filtration rather than dialysis if possible to minimise fluid & solute shifts and rebound increase in cerebral oedema 
 
Risk of hypotension when starting circuit and reduction in CPP: Start with small volume exchanges, ensure patient is not hypovolaemic prior, have vasopressor ready 
 
Risk of circuit anticoagulation in traumatic brain injury leading to intracranial haemorrhage. Consider no anticoagulation, or strategies that only anticoagulate circuit – e.g. citrate 
 
Consider placement of dialysis catheter – avoid jugular veins as risk of obstruction of venous outflow and haematoma 
 
Use of RRT may affect temperature management 
 
Examiner Comments: 
 
Candidates scored higher marks if they demonstrated sound knowledge of how parameters on the renal replacement prescription could be altered to improve safety for the patient. 
 

Discussion

There is plenty of literature to support this answer, and to make it somewhat more organised. Andrew Davenport published an excellent review article in 2007. He also published another excellent review article in 2008 to describe a practical approach to the issues involved. Both reviews are updates of an article he published in 2001. A slightly more recent experiment by Yeh et al (2016) focuses on the prevention of ICP fluctuations during RRT by modifying the IHD protocol. Recommendations from these studies can be summarised as follows:

References

College answer

a)

Either pre-or post-filter replacement fluid acceptable

Effluent pressure monitor not required

b)

Statement that this is a venous access problem

• Check patient: hypovolaemic? Potentially give volume
• Check settings: is blood flow excessive?
• Check proximal limb of circuit: kinking or clots?
• Access catheter: check for kinking due to insertion angle (replace) or clotting (try aspirating and flushing). Try withdrawing catheter slightly. Consider replacing catheter (different site, larger bore, longer catheter in femoral site, end-hole catheter instead of side hole)
• If all else fails try reversing lines

c)

Imminent clotting of the filter 

 Examiners Comments:

 This was answered well by most candidates.

Discussion

a)

It is pleasing to see the college offer some positive remarks to the candidates, a downtrodden species generally accused of having serious knowledge gaps. This time, they did well. It is equally pleasing to see the college offer a reasonable-looking diagram in their model answer. This one is not as easy to track down as some of the other Google images they used (it only appears in this presentation, although it very likely has some other source). As the official college diagram, it is superior to the locally available non-peer-reviewed options, and should be viewed as the Definitive CVVH Diagram for the purposes of exam revision.

b)

The pressure are:

                       Access pressure:        -240 mmHg* (-50 to -150 mmHg)

                       Pre-Filter pressure    46 mmHg*      (100 to 250 mmHg)

                       Return pressure:        38 mmHg*      (50 to 150 mmHg)

This is just short of the values which in the Prismaflex machines give a "Access Pressure Extremely Negative" alarm (-250 mmHg). The following troubleshooting section is lazily cut-and-pasted from the chapter on the troubleshooting of the dialysis circuit:

Causes of low access pressure

• 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).

Troubleshooting:

• 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.

c)

The pressure we are  presented with:

Access pressure: -110 mmHg    (-50 to -150 mmHg)

Pre-Filter pressure. 450 mmHg*   (100 to 250 mmHg)

Return pressure: 40 mmHg*     (50 to 150 mmHg)

The extremely high pre-filter pressure and the unusually low return pressure suggests that the filter is clotting. This would generate a "Filter Pressure Extremely Positive" alarm.

Causes of high filter pressure

• Filter pressure tends to rise gradually over the course of the dialysis session, as the filter becomes clogged with filth. This is part of the natural filter degradation.
• If it rises suddenly, there are few options as to why:
  • The line from the pressure gauge to the filter has become kinked or clamped
  • An embolus of clot or something has become lodged in the abovementioned line
  • You set the pre-dilution replacement solution flow rate too high

Troubleshooting:

• Check the circuit:
  • Ensure the line going into the filter is free from kinks.
  • Make sure there is no embarrassing clamp anywhere.
  • Assure yourself that the pre-dilution replacement fluid flow rate is appropriate
• Admit defeat
  • The filter has clotted. Get another one.

References

College answer

a) Ruptured bladder

Examiners Comments: 
 
Generally, these questions were answered well. Those candidates that failed, missed all or part of the question or misinterpreted what was being asked, reiterating how important it is to read the question and understand what is required before starting to answer. 
 

Discussion

The salient features of history are:

• Pelvis fracture
• Haemodynamic stability
• Previous good health

The biochemical abnormalities are:

• High creatinine
• High urea

The relevant negative features are:

• Normal acid-base balance
• Normal phosphate

All of these (but mainly the apparent "renal failure" and otherwise normal patient story)  suggest bladder rupture due to pelvic injuries, a well-described bit of exotica from the Journal of Urological Oddities. One good article is Heyns & Rimington (1987) who reported on a series of 20 such patients. The best description of the biochemistry involved is offered by Wystrychowski (1996), who described "uroperitoneum" as resulting in a "reverse autodialysis " of urine. Other associated features are usually haematuria, "ascites", acidosis hyponatremia and a raised potassium, which in this case all appear to be normal. The scenario is in fact not completely realistic because all of the features of renal failure should be present; in human trauma victims and in experimental bovine models there is usually significant acidosis, which is usually a normal anion gap variety. For instance, in this case report from Pintar & Wilke (1998) the bicarbonate was 13 mmol/L and potassium was 7.5 mmol/L. 

References

College answer

Access related complications: 
     CVL risks: insertion complications/infection/disconnection/blood loss/air embolism 
 Fistula complications: stenosis, varices, shunt, infection, steal syndrome

Peritoneal dialysis: peritonitis 
               Insertion complications: bowel perforation 
               Pleural effusions and respiratory compromise 
               Ileus 
Haemodynamic changes –vasodilation, hypercirculation, pericardial effusion, cardiomyopathy Anaemia 
Thrombocytopaenia 
Osmolality shifts-     dialysis disequilibrium 
Cellular activation;  Thromocytopaenia, leukocytosis Nutrient losses 
Peptides and protein loss: albumin, cytokines, hormones 
Electrolyte changes:      hypo/hyperkalaemia,     hypo/hypernatraemia,     hypomagnesaemia, hypophosphataemia., hypocalcaemia 
Increased risk of infections/impaired immunity 
Side effects of anticoagulation:     Heparin-bleeding, hypocalcaemia 
          Citrate-citrate lock, hypocalcaemia  
Mobility impairment/Lifestyle 
Hypothermia 
Adjustment of drug doses  
Muscle cramps 
Amyloidosis 
 

Discussion

This answer would benefit from a tabulated format, or indeed from any attempt at structure whatsoever. Without a model, one may try to compile a list of complications for all haemodialysis modalities, separate from a list of complications which are unique to each modality, and all of them separate from the complications of peritoneal dialysis which is a completely different animal. Then, within each modality, one might organise the complications by system. This cumbersome attempt is offered below.

References

College answer

References

Jones, Sarah L., et al. "Loop diuretic therapy in the critically ill: a survey." Critical Care and Resuscitation 17.3 (2015): 223.

Joannidis, Michael, Sebastian J. Klein, and Marlies Ostermann. "10 myths about frusemide." (2019): 545-548.

Rimmelé, Thomas, et al. "Use of loop diuretics in the critically ill." Cardiorenal Syndromes in Critical Care. Vol. 165. Karger Publishers, 2010. 219-225.

Shen, Yanfei, Weimin Zhang, and Yong Shen. "Early diuretic use and mortality in critically ill patients with vasopressor support: a propensity score-matching analysis." Critical Care23.1 (2019): 9.

Morgan, D. B., and C. Davidson. "Hypokalaemia and diuretics: an analysis of publications." Br Med J 280.6218 (1980): 905-908.

Mushiyakh, Yelena, et al. "Treatment and pathogenesis of acute hyperkalemia." Journal of community hospital internal medicine perspectives 1.4 (2012): 7372.

Rastogi, Shiva, et al. "Hyperkalemic renal tubular acidosis: effect of furosemide in humans and in rats." Kidney international 28.5 (1985): 801-807.

Droller, Michael J., Rein Saral, and George Santos. "Prevention of cyclophosphamide-induced hemorrhagic cystitis." Urology 20.3 (1982): 256-258.

Levi, T. M., et al. "Furosemide is associated with acute kidney injury in critically ill patients." Brazilian Journal of Medical and Biological Research 45.9 (2012): 827-833.

Wigand, M. E., and A. Heidland. "Ototoxic side-effects of high doses of frusemide in patients with uraemia." Postgraduate medical journal 47 (1971): 54.

Baldwin, Kathleen A., Cynthia E. Budzinski, and Craig J. Shapiro. "Acute sensorineural hearing loss: furosemide ototoxicity revisited." Hospital Pharmacy 43.12 (2008): 982-988.

Hansbrough, J. Randall, H. James Wedner, and David D. Chaplin. "Anaphylaxis to intravenous furosemide." Journal of allergy and clinical immunology 80.4 (1987): 538-541.

Kahn, Andrew M. "Effect of diuretics on the renal handling of urate." Seminars in nephrology. Vol. 8. No. 3. 1988.

Oh, T. E. "Frusemide and lithium toxicity." Anaesthesia and intensive care 5.1 (1977): 60-62.

Saffer, Daisy, and Alec Coppen. "Frusemide: A safe diuretic during lithium therapy?." Journal of affective disorders 5.4 (1983): 289-292.

Lameijer, W. "Accelerated Renal Elimination of Thallium in the Rat Due to Treatment with Furosemide or Potassium Ions." Mechanism of Toxic Action on Some Target Organs. Springer, Berlin, Heidelberg, 1979. 365-366.

Hazelhoff, María H., et al. "Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug resistance-associated protein 2 (Mrp2) with furosemide." Toxicology Research 4.5 (2015): 1324-1332.

Grissom, C. "High-altitude diseases (HACE/HAPE)." Respiratory emergencies. London: Hodder Arnold (2006): 253-267.

Cruz, Dinna N. "Cardiorenal syndrome in critical care: the acute cardiorenal and renocardiac syndromes." Advances in chronic kidney disease 20.1 (2013): 56-66.

Yancy, Clyde W., et al. "2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines." Journal of the American College of Cardiology 62.16 (2013): e147-e239.

Wilson, John R., et al. "Effect of diuresis on the performance of the failing left ventricle in man." The American journal of medicine 70.2 (1981): 234-239.

Faris, Rajaa F., et al. "Diuretics for heart failure." Cochrane Database of Systematic Reviews 2 (2012).

Ronco, Claudio, et al. "Cardiorenal syndrome." Journal of the American College of Cardiology 52.19 (2008): 1527-1539.

Lee, Joon, et al. "Association between fluid balance and survival in critically ill patients." Journal of internal medicine277.4 (2015): 468-477.

Shen, Yanfei, Xinmei Huang, and Weimin Zhang. "Association between fluid intake and mortality in critically ill patients with negative fluid balance: a retrospective cohort study." Critical Care 21.1 (2017): 104.

Boyd, John H., et al. "Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality." Critical care medicine39.2 (2011): 259-265.

Shen, Yanfei, Weimin Zhang, and Yong Shen. "Early diuretic use and mortality in critically ill patients with vasopressor support: a propensity score-matching analysis." Critical Care23.1 (2019): 9.

Ho, K. M., and B. M. Power. "Benefits and risks of furosemide in acute kidney injury." Anaesthesia 65.3 (2010): 283-293.

Rewa, O. G., et al. "The furosemide stress test for prediction of worsening acute kidney injury in critically ill patients: A multicenter, prospective, observational study." Journal of critical care 52 (2019): 109-114.

Jhund, Pardeep S., John JV McMurray, and Andrew P. Davie. "The acute vascular effects of frusemide in heart failure." British journal of clinical pharmacology 50.1 (2000): 9-13.

Dikshit, Krishna, et al. "Renal and extrarenal hemodynamic effects of furosemide in congestive heart failure after acute myocardial infarction." New England Journal of Medicine288.21 (1973): 1087-1090.

García-Pagán, Juan Carlos, et al. "Influence of pharmacological agents on portal hemodynamics: basis for its use in the treatment of portal hypertension." Seminars in liver disease. Vol. 19. No. 04. © 1999 by Thieme Medical Publishers, Inc., 1999.

Grill, Vivian, and T. John Martin. "Hypercalcemia of malignancy." Reviews in Endocrine and Metabolic Disorders1.4 (2000): 253-263.

Suki, Wadi N., et al. "Acute treatment of hypercalcemia with furosemide." New England Journal of Medicine 283.16 (1970): 836-840.

Kondo, Cláudia Seiko, et al. "Effects of intravenous furosemide on mucociliary transport and rheological properties of patients under mechanical ventilation." Critical Care 6.1 (2001): 81.

Felker, G. Michael, et al. "Diuretic strategies in patients with acute decompensated heart failure." New England Journal of Medicine 364.9 (2011): 797-805.

Bove, Tiziana, et al. "Intermittent furosemide administration in patients with or at risk for acute kidney injury: meta-analysis of randomized trials." PloS one 13.4 (2018): e0196088.

Sarai, Michael, and Aaron M. Tejani. "Loop diuretics for patients receiving blood transfusions." Cochrane Database of Systematic Reviews 2 (2015).

Joannidis, Michael, et al. "Prevention of acute kidney injury and protection of renal function in the intensive care unit: update 2017." Intensive care medicine 43.6 (2017): 730-749.

Bagshaw, Sean M., et al. "The effect of low-dose furosemide in critically ill patients with early acute kidney injury: a pilot randomized blinded controlled trial (the SPARK study)." Journal of critical care 42 (2017): 138-146.

Llorens, Pere, et al. "Clinical effects and safety of different strategies for administering intravenous diuretics in acutely decompensated heart failure: a randomised clinical trial." Emerg Med J 31.9 (2014): 706-713.

van der Voort, Peter HJ, et al. "Furosemide does not improve renal recovery after hemofiltration for acute renal failure in critically ill patients: a double blind randomized controlled trial." Critical care medicine 37.2 (2009): 533-538.

College answer

List the specific factors that may contribute to a high serum creatinine value in this patient. (3 Marks)
Pre-existing elevation of serum creatinine:
Diabetic Nephropathy Hypertensive Nephrosclerosis Renal Artery Stenosis

Acute elevation of serum creatinine Pre-renal factors
Hypotension, hypoperfusion
Prolonged aortic clamp time, surgical ligation renal artery Intra-abdominal hypertension
Cholesterol Embolism Renal factors
Radio-contrast Nephrotoxic drugs Rhabdomyolysis Sepsis
Post renal factors
Occlusion of both ureters - rare

What factors would influence your decision whether to start RRT in this patient? (7 marks)
Several factors would influence this decision
 
General condition of the patient including volume status

Baseline renal function and its likely trajectory

Other factors

If the patient is clinically stable, the current biochemistry would support a watch and wait approach. The serum creatinine value of 391 umol/L does put the patient in KDIGO stage 3 (or RIFLE ‘F’), which could be past the point when early RRT can be considered. The rate of rise of creatinine, urine output and its course (increasing or decreasing) and preoperative creatine will give an idea of the likelihood of renal recovery. If the patient was unstable, or had evidence of compromise from volume overload then early initiation of RRT could be considered.
Other factors might include – preoperative dialysis dependence
A requirement to remove the effects of sedative drugs to allow prognostication (perhaps in the setting of a cardiac arrest for example) might be another consideration.

Examiners Comments:

Candidates who tailored their answer to the specific patient in the question scored well, in contrast to those who simply listed generic indications for dialysis.

Discussion

"specific factors that may contribute to a high serum creatinine" basically means "likely causes of deterioration in renal function", just as it did in Question 24 from the first paper of 2007.  

Answer organised by pathophysiology:

• Pre-renal
  • Hypovolemia due to blood loss
  • Hypotension due to distributive shock, eg. sepsis
  • Cardiac failure
  • Renal vascular damage
  • Abdominal compartment syndrome
• Renal
  • ATN due to prolonged aortic cross-clamp time
  • Nephrotoxicity due to drugs, eg. gentamicin or metformin
  • Contrast-induced nephropathy
  • ATN due to rhabodomyolysis
• Post-renal
  • Intraoperative ureteric or bladder injury
  • kinked or malpositioned IDC