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. 2008 Jan;34(1):163-8.
doi: 10.1007/s00134-007-0836-3. Epub 2007 Aug 21.

One single dose of etomidate negatively influences adrenocortical performance for at least 24h in children with meningococcal sepsis

Marieke den Brinker  1 , Anita C S Hokken-Koelega, Jan A Hazelzet, Frank H de Jong, Wim C J Hop, Koen F M Joosten
Affiliations

One single dose of etomidate negatively influences adrenocortical performance for at least 24h in children with meningococcal sepsis

Marieke den Brinker et al. Intensive Care Med. 2008 Jan.

Abstract

Objective: To investigate the effect of one single bolus of etomidate used for intubation on adrenal function in children with meningococcal sepsis.

Design: Retrospective study conducted between 1997 and 2004.

Setting: University-affiliated paediatric intensive care unit (PICU).

Patients and participants: Sixty children admitted to the PICU with meningococcal sepsis, not treated with steroids.

Interventions: Adrenal hormone concentrations were determined as soon as possible after PICU admission, and after 12h and 24h. To assess disease severity, PRISM score and selected laboratory parameters were determined.

Measurements and main results: On admission, before blood was drawn, 23 children had been intubated with etomidate, 8 without etomidate and 29 were not intubated. Children who were intubated had significantly higher disease severity parameters than those not intubated, whereas none of these parameters significantly differed between children intubated with or without etomidate. Children who received etomidate had significantly lower cortisol, higher ACTH and higher 11-deoxycortisol levels than those who did not receive etomidate. Arterial glucose levels were significantly lower in children who were intubated with etomidate than in non-intubated children. When children were intubated with etomidate, cortisol levels were 3.2 times lower for comparable 11-deoxycortisol levels. Eight children died, seven of whom had received etomidate. Within 24h cortisol/ACTH and cortisol/11-deoxycortisol ratios increased significantly in children who received etomidate, but not in children who did not, resulting in comparable cortisol/ACTH ratios with still significantly lowered cortisol/11-deoxycortisol ratios 24h after admission.

Conclusions: Our data imply that even one single bolus of etomidate negatively influences adrenal function for at least 24h. It might therefore increase risk of death.

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Figures

Fig. 1
Fig. 1
A schematic representation of steroidogenesis in the human adrenal gland and the effect of etomidate. Etomidate inhibits 11β-hydroxylase (CYP11B1), 11β- and 18-hydroxylase (CYP11B2) and cholesterol side-chain cleavage enzyme system (CYP11A) (shaded) with decreasing effectiveness. Decreased CYP11B1 activity will lead to lower levels of cortisol and increased levels of the upstream precursor 11-deoxycortisol. Decreased CYP11B2 will lead to lower aldosterone and higher 11-deoxycorticosterone levels, whereas decreased CYP11A will lead to generally decreased steroidogenesis. 3β-HSD, 3β-hydroxysteroid-dehydrogenase; CYP21, 21-hydroxylase; CYP17, 17-hydroxylase and 17, 20-lyase
Fig. 2
Fig. 2
Relation between ACTH and arterial lactate levels, depending on etomidate use. After adjustment for arterial lactate levels, using ANCOVA, mean ACTH levels were 4.1 times higher in etomidate use ( p < 0.001). Children who received etomidate (•, continuous line) and children who did not receive etomidate (○, dotted line). Data of children intubated without etomidate or those not intubated were pooled, as they did not significantly differ
Fig. 3
Fig. 3
Relation between cortisol and 11-deoxycortisol levels, depending on etomidate use. After adjustment for 11-deoxycortisol levels, using ANCOVA, mean cortisol levels were 3.2 times lower in case of etomidate use ( p < 0.001). Children who received etomidate (•, continuous line) and children who did not receive etomidate (○, dotted line). Data of children intubated without etomidate or those not intubated were pooled, as they did not significantly differ
Fig. 4
Fig. 4
Cortisol/ACTH ratios (a), cortisol/11-deoxycortisol ratios (b) and cortisol levels (c) according to patients' actual etomidate use during the first 24 h after admission. The three profiles differed between the groups along time ( p < 0.001). Data shown are geometric means with standard errors. Children who received etomidate (•, continuous line) and children who did not receive etomidate (○, dotted line). Within-group difference between successive time point (a, p < 0.05). Between-group difference at time points (b, p < 0.05). Numbers alongside data-points indicate numbers of children
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Comment in

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