Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality.
BACKGROUND
Adequate adrenal function is pivotal to survive meningococcal sepsis.


OBJECTIVE
The objective of the study was to evaluate adrenocortical function in meningococcal disease.


METHODS
This was an observational cohort study.


METHODS
The study was conducted at a university-affiliated pediatric intensive care unit.


METHODS
Sixty children with meningococcal sepsis or septic shock participated in the study.


METHODS
The differences in adrenal function between nonsurvivors (n = 8), shock survivors (n = 43), and sepsis survivors (n = 9) on pediatric intensive care unit admission were measured.


RESULTS
Nonsurvivors had significantly lower median cortisol to ACTH ratio than shock survivors and sepsis survivors. Because cortisol binding globulin and albumin levels did not significantly differ among the groups, bioavailable cortisol levels were also significantly lower in nonsurvivors than sepsis survivors. Nonsurvivors had significantly lower cortisol to 11-deoxycortisol ratios but not lower 11-deoxycortisol to 17-hydroxyprogesterone ratios than survivors. Using multiple regression analysis, decreased cortisol to ACTH ratio was significantly related to higher IL-6 levels and intubation with etomidate (one single bolus), whereas decreased cortisol to 11-deoxycortisol ratio was significantly related only to intubation with etomidate. Aldosterone levels tended to be higher in nonsurvivors than shock survivors, whereas plasma renin activity did not significantly differ.


CONCLUSIONS
Our study shows that the most severely ill children with septic shock had signs of adrenal insufficiency. Bioavailable cortisol levels were not more informative on adrenal function than total cortisol levels. Besides disease severity, one single bolus of etomidate during intubation was related to decreased adrenal function and 11beta-hydroxylase activity. Decreased adrenal function was not related to decreased 21-hydroxylase activity. Based on our results, it seems of vital importance to take considerable caution using etomidate and consider combining its administration with glucocorticoids during intubation of children with septic shock.
Department of Pediatrics, Division of Endocrinology and Division of Pediatric Intensive Care, Erasmus Medical Center--Sophia Children's Hospital, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands. m.denbrinker@erasmusmc.nl
Marieke
M
den Brinker
Koen F M
KF
Joosten
Olivia
O
Liem
Frank H
FH
de Jong
Wim C J
WC
Hop
Jan A
JA
Hazelzet
Marije
M
van Dijk
Anita C S
AC
Hokken-Koelega
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000311:Adrenal Glands / Q000503:physiopathology*; D000309:Adrenal Insufficiency / Q000382:microbiology* / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000450:Aldosterone / Q000097:blood; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D003350:Cortodoxone / Q000097:blood; D005045:Etomidate / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D007223:Infant; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008589:Meningococcal Infections / Q000150:complications*; D012083:Renin / Q000097:blood; D012121:Respiration, Artificial; D012772:Shock, Septic / Q000097:blood / Q000382:microbiology / Q000401:mortality / Q000503:physiopathology; D014156:Transcortin / Q000378:metabolism
D006993:Hypnotics and Sedatives; D015850:Interleukin-6; D000450:Aldosterone; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D014156:Transcortin; D012083:Renin; D003350:Cortodoxone; D006854:Hydrocortisone; D005045:Etomidate