Erika F Fernandez MD

1
Adrenal function in critically ill term newborn
infants

• Erika F Fernandez MD
• Assistant Professor
• Department of Pediatrics, Division of Neonatology

2
Background

• Many intubated late preterm and term newborns
  will receive fluid boluses vasopressors for
  hypotension
• The etiology of hypotension in
• many infants is unclear
• In other critically ill populations
• Hypotension and shock have
• been linked to
• relative adrenal insufficiency
• cortisol lt 15 mcg/dl acute stress
• Glucocorticoids have significantly ?
  mortality morbidity in large RCTs

Lamberts et al, NEJM 3371285, 1997
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Evidence for AI in term newborns Small
observational studies

• 10 infants with diaphragmatic hernia 79 of
  cortisol values lt7mcg/dl
• Pittinger and Sawin, J Pediatr Surg 35223, 2000
• 5 of 6 infants with hypotension refractory to
  vasopressors had cortisol values lt 10mcg/dl, BP
  improved in assoc. with dexamethasone
• Tantivit et al, J Perinatol 19352, 1999

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Prevalence of low cortisol values

• Retrospective chart review
• 35 weeks GA with cortisol values
• Critically ill
• Intubated, mechanically ventilated and on
  vasopressors for hypotension

BW (g) GA (weeks) Postnatal day Cortisol concentration, mcg/dl Number () with cortisol lt15 mcg/dl
Total, n32 Total, n32 3034 38 2 1 (03) 11.7 (527) 18 (56)
Treated with hydrocortisone n23 3045 38 2 1 (02) 7.5 (519) 15 (65)
Did not receive hydrocortisone n9 3004 38 3 1 (03.5) 23.5 (1230) 3 (33)
Fernandez and Watterberg et al, J Perinatol
25114, 2005
Data are mean _ SD or median (25-75) 3 infants
died (1 MAS, 1 HLHS, 1 CHD)
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Physiologic response to hydrocortisone

• Critically ill hypotensive infants treated w/
  hydrocortisone,
• Cortisol lt15mcg/dl (?)
• compared to
• Cortisol 15 mcg/dl (O)
• Cortisol lt15mcg/dl responded to HC with
• ? dopamine support
• ? heart rate
• ? volume expanders

Fernandez, Watterberg et al. J Perinatol 25114,
2005
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Prospective observational study of term and late
preterm critically ill newborns
Non-critically ill infants Critically ill infants Critically ill infants Critically ill infants
Non-critically ill infants All NOT receiving vasopressors Receiving vasopressors
Gestation (weeks) 38.1 38.1 36.2 38.8
Birth weight (g) 3240 3046 2612 3221
Postnatal age (days) 2 1-4 1 0-1 1 1-2 1 0-1
Baseline cortisol (mcg/dl) -- 4.6 10.9 4.5
ACTH-stimulated cortisol (mcg/dl) 34.2 41.0 40.9 45.3
Baseline cortisol lt 15 mcg/dl (n()) -- 26 (74) 6 (60) 20 (80)
ACTH pg/ml 11.9
Median 25-75 percentile P-value critically
ill infants not receiving vasopressors vs. those
receiving vasopressors P lt 0.05
Fernandez, Montman, Watterberg. 2008, unpublished
data
7
No correlation between measures of severity of
illness and cortisol values
Fernandez, Montman, Watterberg, 2008, unpublished
data
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Summary

• High incidence of Rx for hypotension in
  mechanically ventilated term and late preterm
  infants
• Transitional relative adrenal insufficiency
  appears to be associated with cardiovascular
  instability in this population
• Prospective observational data consistent with
  this hypothesis
• There are no randomized controlled trials of
  hydrocortisone for the treatment of hypotension
• Plan multicenter RCT of hydrocortisone for
  hypotension
• We have submitted a proposal for a multicenter
  observational study through NIH/NICHD/NRN (
  currently undergoing budget approval ) to collect
  baseline data for the final design of such as RCT

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Mentors and Collaborators

• Kristi Watterberg, MD Professor Pediatrics,
  Division of Neonatology, Mentor, Principal
  Investigator for Neonatal Research Network
  (NIH/NICHD/NRN)site at UNM
• Robin Ohls, MD, Professor Pediatrics, Division of
  Neonatology, Co-Principal Investigator for NRN
  site at UNM
• Rebecca Montman, RN, GCRC Research Nurse
• Conra Backstrom, RN, GCRC Research Nurse
• GCRC statistics, Ronald Schrader, PhD
• Administrative support, Green Carlson