Adrenal Function in Preterm Infants Undergoing Patent Ductus Arteriosus Ligation

Abstract

Background: Targeted milrinone treatment for low left ventricular output (LVO) reduces the incidence of acute cardiorespiratory instability following ligation of patent ductus arteriosus (PDA) in preterm infants. Despite this, some infants continue to experience postoperative deterioration. Adrenal insufficiency related to prematurity has been postulated as a possible mechanism. Objectives: To describe adrenal function in premature infants undergoing PDA ligation and to investigate its association with pre- and postoperative clinical and echocardiography-derived indices of disease severity. Methods: A retrospective cohort study was conducted over a 2-year period on infants who underwent PDA ligation and had preoperative adrenocorticotropic hormone (ACTH) stimulation. All infants were screened by echocardiography for low LVO at 1 h after surgery and treated with intravenous milrinone if LVO <200 ml/kg/min. The primary outcome evaluated was low LVO at 1 h after surgery. Secondary outcomes included hypotension and oxygenation and ventilation failure occurring within 24 h. Results: A total of 35 infants at a median gestation of 25.4 (24.5-26.4) weeks and weight at birth of 700 (600-810) g were included. Baseline median cortisol measured preoperatively was 202 (137-403) nmol/l. Following the ACTH stimulation test, 3 infants had cortisol ≤500 nmol/l while 15 had ≤750 nmol/l. There was no association seen between any cortisol value and low LVO postoperatively. Post-ACTH cortisol ≤750 nmol/l was significantly associated with hypotension (p = 0.03) and oxygenation (p = 0.04) and ventilation (p = 0.008) failure. Receiver-operator characteristic curve showed a high predictive value of post-ACTH cortisol for all clinical outcomes. Conclusions: Post-ACTH cortisol (≤750 nmol/l) may be associated with clinical indices of postoperative cardiorespiratory instability. Relative adrenal insufficiency may play a role in the etiology of post-PDA ligation hemodynamic and respiratory instability.

Catecholamine-resistant hypotension and myocardial performance following patent ductus arteriosus ligation

“…Prior studies have noted that myocardial performance appears to be impaired (decreased LVO, decreased SF, and increased MPI) following PDA ligation (5, 6, 8, 9). Our findings are consistent with the prior reports, and support the hypothesis that impaired myocardial performance may contribute to the development of postoperative hypotension.…”

“…Combinations of dopamine and dobutamine could be used. Milrinone was not used to treat post-ligation hypotension (however, at one study site (7 infants), a milrinone infusion was started shortly after ligation as part of an institutional protocol designed to prevent postoperative hypotension (8, 9). …”

“…Although measurements of myocardial performance, made shortly (1–2 hours) after ligation, have not been found to have a strong association with the development of post-ligation hypotension (5, 10, 12), indices of impaired myocardial performance, at 6–8 hours after the operation (closer to the time of clinical deterioration), appear to have a much stronger relationship (6). Prophylactic treatment with milrinone, starting shortly after ligation, has been reported to reduce the incidence of cardiorespiratory instability; however, despite early milrinone treatment, some infants continue to develop post-ligation catecholamine-resistant hypotension (8, 9). To date, no studies have examined the relationship between indices of myocardial performance during the postoperative period and the incidence of catecholamine-resistant hypotension.…”

Relationship of Salivary and Plasma Cortisol Levels in Preterm Infants: Results of a Prospective Observational Study and Systematic Review of the Literature

“…The assessment of hypothalamic-pituitary-adrenal function in very preterm infants is important as immaturity of the hypothalamic-pituitary-adrenal axis can lead to inadequate adrenal function in the face of acute illness [1,2] and corticosteroid therapy may influence adrenal function. For the purpose of cortisol measurement in preterm infants, easily available and workable methods are needed, ideally not inducing pain and stress to this vulnerable population [3] .…”

Hypotension following Patent Ductus Arteriosus Ligation: The Role of Adrenal Hormones

“…Retrospective studies have not identified differences in the surgical, anesthetic, or intraoperative fluid management among the infants who develop postoperative hypotension (1, 4). Indices of impaired myocardial performance are often observed prior to the development of hypotension (5–8), and prophylactic administration of milrinone, begun shortly after the surgery, appears to reduce the incidence of postoperative cardiorespiratory instability. However, some infants continue to develop post-ligation hypotension despite early treatment of low ventricular output with milrinone (7, 8).…”