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Circulating leptin and the perioperative neuroendocrinological stress response after pediatric cardiac surgery

Modan-Moses, Dalit MD; Ehrlich, Sharon MD; Kanety, Hanna PhD; Dagan, Ovdi MD; Pariente, Clara MSc; Esrahi, Nicole MD; Lotan, Danny MD; Vishne, Tali MD; Barzilay, Zohar MD; Paret, Gideon MD


Objective  Leptin may be involved in the acute stress response, regulating inflammatory parameters of major importance after cardiopulmonary bypass (CPB) surgery. Critically ill patients demonstrated significant increases in leptin levels in response to stress-related cytokines (tumor necrosis factor, interleukin [IL]-1) and abolishment of the circadian rhythm of leptin secretion. We characterized the pattern of leptin secretion in the acute postoperative period in children undergoing cardiac surgery and compared the changes in leptin levels with concomitantly occurring changes in cortisol levels, IL-8, and clinical parameters.

Design  Investigative study.

Setting  University-affiliated tertiary care hospital.

Participants and Interventions  Twenty-nine consecutive patients, aged 6 days to 15 yrs, operated upon for the correction of congenital heart defects were studied. Surgery in 20 patients (group 1) involved conventional CPB techniques, and 9 (group 2) underwent closed-heart surgery. The time courses of leptin, cortisol, and IL-8 levels were determined. Serial blood samples were collected preoperatively, on termination of CPB, and at six time points postoperatively. Plasma was recovered immediately, aliquoted, and frozen at −70°C until use.

Measurements and Main Results  The leptin levels in group 1 decreased during CPB to 51% of baseline (p < .001), then gradually increased, reaching 120% of baseline levels at 12–18 hrs postoperatively (p < .001), returning to baseline levels at 24 hrs (p < .01). In patients undergoing closed-heart surgery (group 2), leptin levels displayed a pattern resembling the first group: they decreased during surgery to 71% of baseline levels (p = .002) and showed a tendency to return to baseline thereafter. All group 1 patients’ cortisol levels increased significantly during the first hour of surgery, then decreased, returning to baseline levels at 18–24 hrs postoperatively. There was a significant negative correlation between leptin and cortisol levels (r = −2.8, p < .01). In group 2, cortisol levels increased during and after surgery, peaking 4 hrs postoperatively and decreasing thereafter. IL-8 levels determined in 15 group 1 patients increased significantly during CPB, peaked at the end of surgery, and then decreased but remained slightly elevated even at 48 hrs postoperatively. There was a significant correlation between cortisol and IL-8 levels (r = 2.55, p < .05). Children with leukocytosis, tachycardia, and hypotension had lower leptin levels and less variation over time as opposed to those with an uncomplicated course.

Conclusions  CPB is associated with acute changes in circulating leptin levels. These changes parallel those in cortisol, demonstrating an inverse relationship between leptin and cortisol. Further studies of the prognostic and therapeutic roles of leptin after CPB should be investigated.

From the Department of Pediatric Intensive Care (DMM, SE, DL, TV, ZB, GP) and the Institute of Endocrinology (HK, CP), The Chaim Sheba Medical Center, and the Department of Pediatric Intensive Care, Schneider Medical Center (OD, NE), both affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

This study was a part of the requirements for graduation from the Sackler Medical School of Tel Aviv University, Tel Aviv, Israel (ES).

Address requests for reprints to: Gideon Paret, MD, The Department of Pediatric Intensive Care, Chaim Sheba Medical Center, Tel Hashomer 5262l, Israel. E-mail:

The results of the current study indicate that leptin may play a role in the inflammatory response after cardiopulmonary bypass.

© 2001 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins