Question 12

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.

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.