Cortisol in Critically Ill Patients… We Have No Clue!


How often have you assessed adrenocortical function in critical illness by measuring cortisol levels or performing an ACTH stimulation test? And how often have you been involved in discussions on whether these tests actually should be done?
Venkatesh et al. provide us now with an article on this topic, leaving us with that odd sort of feeling… little we know, much we do! These are the ten false beliefs about cortisol in critically ill patients:
1. A relative adrenal insufficiency (RAI) has been proposed to be associated with worse outcome in critically ill patients. In fact, multiple studies have demonstrated that the reverse is true: higher random cortisol values are associated with a greater mortality in septic shock

2. Total plasma cortisol levels fluctuate significantly. Therefore, the interpretation of a single random total cortisol measurement is problematic.

3. Measuring total plasma cortisol by immunoassays will show different results when same sample is analysed by different assays.

4. ACTH stimulation test: There is no consistent relationship between cortisol response and illness severity in critical illness. Even if RAI is suspected, subgroup analysis of randomised controlled trials of steroids in septic shock do not consistently report a benefit of steroids given.

5. A normal ACTH stimulation test does not out-rule a clinically significant adrenal insufficiency.

6. Total plasma cortisol concentrations do not reflect accurately the bioavailable fraction of plasma free cortisol (PFC).

7. Direct measurement of free cortisol is complex and mostly not available. And.. unfortunately, calculating PFC concentrations using the Coolen’s equation is unreliable in critical illness.

8. In critical illness it is difficult, if not even impossible, to assess the tissue adrenal response based on plasma cortisol levels.

9. Elevated plasma cortisol levels are not only due to an increased production but also to a reduction in cortisol clearance occurring in critical illness.

10. Treating critically ill patients with classical doses of hydrocortisone (50-100mg every 8h) may result in grossly supraphysiological levels of cortisol.
Got interested on some further background information? Read here:

Venkatesh et al. Intensive Care Med, January 2015


More Evidence Relieving the Defendant: IV Contrast Material itself Does Not Cause Acute Kidney Injury

Screen Shot 2015-10-25 at 11.41.22

It’s remains a residual concern for clinicians: The fear that intravenous iodinated contrast material used for medical imaging might cause acute kidney injury (AKI), more dialysis and even death. In fact, practice guidelines still tell us to be cautious to use IV contrast material in patients at risk for acute renal failure.

In March 2014 a review article in BioMed Research International came to the conclusion, that by reviewing more recent evidence this risk is almost nonexistent in patients with normal renal function. Even in patients with pre-existing renal insufficiency the risk of secondary contrast-induced AKI is probably much smaller than traditionally assumed.

Mc Donald et al. have now provided further evidence, that the risk associated with the administration of IV iodinated contrast material has been overstated. In this single-center retrospective study they looked at almost all CT scans from 2000-2010 and, using propensity score matching, created two large groups (approx. 10’000 patients each) to compare patients with enhances CT-scans to the ones without enhanced CT-scans. They were able to show that the rate of emergent dialysis and short-term mortality among the two groups were not significantly different. In fact the development of AKI was independent of contrast material administration.
Take home message:

– AKI is associated with worse overall short-term outcomes (dialysis, 30-day mortality), but these outcomes are independent of contrast material exposure.

The nephrotoxic risk associated with administration of intravenous iodinated contrast material appears to have been overstated.

Or short: If you have a good indication for an enhanced CT-scan: Go for it!
McDonald RJ et al. Radiology 2014 December OPEN ACCESS

Also worth looking at:

Davenport MS et al. Radiology 2013 April OPEN ACCESS

BIJC post: Iodinated Radiocontrast Agents can cause Kidney Injury… But not as much as we thought they would!

Eleftheria terrae… Will this Organism Change Our Clinical Work?

Screen Shot 2015-01-10 at 22.21.23

Just recently in 2014 the WHO has requested to develop a draft global action plan to combat emergent antimicrobial resistance (AMR). AMR is present in all parts of the world, new resistance mechanisms emerge and spread globally. And most importantly: Patients with infections by drug-resistant bacteria are generally at risk of worse clinical outcome and death.

On the background of this the recent publication in Nature by Ling et al. is remarkable as it might offer the key to a new antimicrobial weapon in the near future. Teixobactin is the name of a macrocylic peptide representing a new class of antibiotics. It appears to be potent bactericidal agent against a broad panel of bacterial pathogens, especially gram-positive bacteria including MRSA, enterococci and VRE as well as M. tuberculosis, C. difficile and Anthrax. Teixobactin inhibits cell wall synthesis and most remarkably showed no development of resistance so far.

Teixobactin is produced by E. terrae, a microorganism discovered in the soil of a grassy field in Maine. As mentioned in the article, these ‘uncultured’ bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics.

An interesting article, especially if you want to see what’s going on outside the hospital!
Ling LL et al. Nature 2015; doi:10.1038/nature14098

Excellent Review on IV Fluid Resuscitation for the End of the Year 2014

Screen Shot 2014-04-05 at 21.41.27

Again we have picked a review article looking at fluid resuscitation in the ICU. This article by Lira et al. in the Annals of Intensive Care looks at all the new literature available in regards of fluid therapy during resuscitation. Also review current recommendations and recent clinical evidence. This results in an excellent systematic review that leaves us with following conclusions:

– Currently no indications exist for the routine use of colloids over crystalloids

– In regards of current evidence (including the Albios trial), the cost and limited shelf time the use of albumin as a resuscitation fluid is not recommended

– The use of hydroxy-ethyl-starch (HES) during resuscitation should be avoided

– In light of the lack of evidence, and the theoretical potential for adverse effect, the suggestion is to avoid gelatine or dextran

– The use of 0.9% normal saline is associated with the development of hyperchloremic metabolic acidosis and increased risk of AKI in susceptible patients. Therefore balanced crystalloid solutions should be considered/ preferred

– Current literature supports the use of balanced crystalloid solutions (e.g. Hartmann’s solution, Ringer’s lactate) whenever possible

This makes things quite simple actually… but of course opinions differ!
Lira and Pinsky, Annals of Intensive Care Dec 2014, 4:38 OPEN ACCESS

Read here: The Albios trial