Question 5

Created on Tue, 06/06/2017 - 00:57
Last updated on Wed, 05/02/2018 - 15:53
Pass rate: 72.5%
Highest mark: 8.3

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A 53-year-old male is admitted to the ICU post 12-hour head and neck surgery. He has no other significant past medical history and normal baseline renal function.

Eight hours post ICU admission he is increasingly oliguric with dark-coloured urine. His laboratory results are as follows:

Parameter

Patient Value

Adult Normal Range

Sodium

130 mmol/L•

134— 146

Potassium

6.5 mmol/L•L•

3.4 -5.0

Creatinine

320 umol/L*

45 - 90

Urea

15.0 mmol/L•

3.0 - 8.0

Ionised calcium

0.85 mmol/L•

1.10- 1.35

Phosphate

2.6 mmol/L•

0.8 - 1.5

Albumin

28 g/L•

35 - 50

Total bilirubin

20 mol/l_

< 26

Aspartate transferase

510 IU/L*

< 35

Alanine transferase

100 IU/L•

< 35

Alkaline phosphatase

110 IU/L*

30- 110

Haemoglobin

150 g/L

120 - 160

White Cell Count

20.0 x 10

4.3 - 10.8

Platelet count

400 x 10

150 - 350

Give the most likely cause for the above results AND the rationale for your answer.

(30% marks)

List       other useful investigations.    (10% marks)

Briefly outline your management of this condition.  (40% marks)

List four drugs that can cause this condition. (20% marks)

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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)
  • Cliniclaly, 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.
  • 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. 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. 
  • 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

The best shortcut for the time-poor exam candidate is this UpToDate article.

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

Shapiro, Mark L., Anthony Baldea, and Fred A. Luchette. "Rhabdomyolysis in the intensive care unit." Journal of intensive care medicine 27.6 (2012): 335-342.

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.

Ioannidis, Konstantinos, et al. "Safety and effectiveness of the combination acetazolamide and bicarbonates to induce alkaline diuresis in patients with rhabdomyolysis." European Journal of Hospital Pharmacy 22.6 (2015): 328-332.

Hohenegger, Martin. "Drug induced rhabdomyolysis." Current opinion in pharmacology 12.3 (2012): 335-339.

Valade, N., et al. "Thrombocytosis after trauma: incidence, aetiology, and clinical significance." British journal of anaesthesia 94.1 (2005): 18-23.