A 72-year-old male was admitted to ICU five days ago following primary resection and anastomosis of a perforated sigmoid diverticulum. He is receiving antibiotic treatment with ciprofloxacin, vancomycin and metronidazole.
Over the last 12 hours he has produced a total of 200 mis of urine, and his creatinine has doubled from baseline to a value of 300 µmol/L.
a) Outline how the renal dysfunction will influence antimicrobial dosing for the three antibiotics in use. (30% marks)
His abdomen becomes progressively distended, and he develops anuria and a metabolic acidosis. The surgical team requests a contrast CT scan.
b) Outline possible strategies to minimise the risk of further renal injury from the CT scan. (30% marks)
c) List the factors that would influence your decision to start renal replacement therapy in this case. (40% marks)
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.
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)
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
- Pre and post-hydration
- Sodium bicarbonate
- Prophylactic CVVHDF
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.
Chapter (pp. 540) 48 Renal replacement therapy, also by Rinaldo Bellomo
Interestingly, an article by Bellomo and Ronco from 1999 also contains a list of indications very similar to the one from Oh's, but with slightly different criteria (eg. a temp of 39.5°C, and a urea over 30mmol/L). Also, it contains some lovely black-and-white pictures of 1990s dialysis machines. One may note that in the ensuing decade, they have become subjected to hipster design pressures, developing unnecessarily aerodynamic curves and shiny touchscreens. Not all of us view this evolution of style as an improvement. Some still prefer to be surrounded by equipment which resembles the set of Alien.
Bellomo, R., and C. Ronco. "Renal replacement therapy in the intensive care unit." Intensive Care Med (1999) 25: 781±789