On-call scenario 5: Sources

Last updated: Tuesday, November 26, 2019

You might have thought about sources such as these:

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You initially check the product SmPC which gives no specific advice on dosing in CVVH. It does state that ceftriaxone is eliminated mainly as unchanged drug: approximately 60% of the dose being excreted in the urine (almost exclusively by glomerular filtration), and the remainder via the biliary and intestinal tracts. The SmPC also states that in patients with renal or hepatic dysfunction, the pharmacokinetics of ceftriaxone are only minimally altered and the elimination half-life is only slightly increased. If kidney function alone is impaired, biliary elimination of ceftriaxone is increased; if liver function alone is impaired, renal elimination is increased. The licensed dose in severe infections is 2-4g daily given normally as a once daily dose, and the SmPC confirms that administration of cephalosporins may result in convulsions.

The Renal Drug Database advises that doses used in continuous arteriovenous/venovenous haemodialysis (CAV/VVHD) patients can be used in CVVH and continuous arteriovenous haemofiltration (CAVH) patients, bearing in mind that drug clearance in CAV/VVH might be lower. For CAV/VVHD the recommended dose is 2 g every 12–24 hours. Protein binding is 85-95%.

You are reassured by what you have found so far but are concerned about the relatively high degree of protein binding of ceftriaxone. 

You remember that drugs that are highly protein bound are less likely to be removed by haemofiltration. Now what would you do? You take a look at Martindale which doesn’t give any advice about dosing in haemofiltration. It does, however, mention that levels of ceftriaxone can be measured to assess whether dose adjustment is needed.

You think about ringing your critical care pharmacist at home but because of the time of night you try Embase first. This isn't a source that you will use very often when on-call, but do remember that it's there and that it might sometimes be your only source of information. Your search brings up a couple of papers, including a small clinical study.

Have a think about what you would do next. How would you advise the consultant?
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