Ovdi Dagan

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

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.

Risk factors for sternal wound infection in children undergoing cardiac surgery : a case-control study

SUMMARY Complex and prolonged cardiovascular operations are increasingly performed on young infants and children. The aims of this study were to define the incidence, causative bacterial pathogens and risk factors for sternal wound infections (SWIs) in infants and children undergoing cardiac surgery. The study group included all children who underwent cardiac surgery by median sternotomy at a tertiary paediatric centre from 1999 to 2003 and who were diagnosed with a postoperative SWI. Charts were reviewed for pre-, intra- and postoperative variables. The findings were compared with control patients operated on immediately before and after the cases and analysed by a stepwise logistic regression model. Of the 1821 children who underwent cardiac surgery, 49 (2.69%) had SWI; full data were available for 47. Twenty-nine (61.7%) had superficial wound infection and 18 (38.3%) deep wound infection. The main bacterial pathogens were Staphylococcus aureus in 14 patients (39%) and Pseudomonas aeruginosa in 12 (33%). Three variables emerged as significant independent risk factors for SWI: young age (odds ratio: 0.63; 95% confidence interval: 0.47-0.85; P<0.001 for each additional year), cyanotic heart disease (4.93; 1.98-12.3; P<0.001), and central venous catheter (CVC) dwell time (1.15; 1.06-1.24; P<0.001 for each additional day). Gram-negative infections were significantly associated with preoperative oxygen treatment (P=0.007) and prolonged urinary catheter dwell time (P=0.004). This study confirms younger age as risk factor for SWI and adds cyanotic heart disease and duration of CVC as new independent risk factors. Specific risks for Gram-negative infections are identified and should help to introduce new preventive strategies to decrease the incidence and severity of SWI.

Neuroimaging findings in neonates and infants from superior vena cava obstruction after cardiac operation

Abstract Background. Extraventricular obstructive hydrocephalus may develop after superior vena cava obstruction, an uncommon complication after cardiac surgery. Objective. To describe the neuroimaging findings in neonates and infants with superior vena cava thrombosis after cardiac surgery for congenital heart disease. Materials and methods. Between 1993 and 2001, 333 neonates and infants in our hospital underwent cardiac surgery, of whom 13 (3.9%) subsequently acquired superior vena cava syndrome. Eleven of these 13 children (7 boys, 4 girls) were evaluated by head ultrasound and computed tomography scans. Results. One child had normal findings on head ultrasound, and 10 children had extraventricular obstructive hydrocephalus (EVOH). In 6 children, aggravation of the hydrocephalus was noted up to 11.4 months after cardiac surgery; in 3 of them, the hydrocephalus was shunted to the peritoneum. One child had thrombosis of the dural sinuses, and 1 had hemorrhagic infarction. Two children died during follow-up. Conclusion. EVOH is a common complication of superior vena cava thrombosis, and head ultrasound should be performed in all neonates and infants with superior vena cava thrombosis after cardiac surgery. Long-term follow-up is needed, as the hydrocephalus may worsen even months after surgery.

Interleukin-8 secretion following cardiopulmonary bypass in children as a marker of early postoperative morbidity.

Background: Interleukin (IL)‐8, an 8 kDa peptide, is the first chemoattractant identified as being specific for neutrophils. Its possible association with early postoperative morbidity following cardiopulmonary bypass (CPB) in infants and children is unknown. This prospective cohort study sought possible roles of IL‐8 in the inflammatory response to CPB and investigated if changes in IL‐8 levels and clinical course and outcome were related.

Procalcitonin level as an aid for the diagnosis of bacterial infections following pediatric cardiac surgery

PURPOSE The aim of the present study was to determine if blood procalcitonin can serve as an aid to differentiate between bacterial and nonbacterial cause of fever in children after cardiac surgery. MATERIALS AND METHODS A nested case-control study of children who underwent open cardiac surgery in critical care units of fourth-level pediatric hospital was performed. Blood samples for procalcitonin level were collected 1 day before operation; 1 hour postoperation; on postoperative days 1, 2, and 5; and on the day of fever, when it occurred. RESULTS Of 665 children who underwent cardiac bypass surgery, 126 had a febrile episode postoperatively, 47 children with a proven bacterial infection and 79 without bacterial infection. Among the 68 children in whom fever developed within the first 5 postoperative days, procalcitonin level at fever day was significantly higher in those with bacterial infection (n = 16) than in those without infection (n = 52). Similarly, among the 58 children in whom fever developed after day 5 postoperation, a significant difference was found in procalcitonin level at fever day between those with (n = 31) and without (n = 27) bacterial infection. CONCLUSION During the critical early and late periods after cardiac surgery in children, procalcitonin level may help to differentiate patients with bacterial infection from patients in whom the fever is secondary to nonbacterial infectious causes.

Patterns and prognostic value of troponin, interleukin-6, and leptin after pediatric open-heart surgery

PURPOSE Leptin and interleukin-6 (IL-6) are inversely correlated and associated with decreased survival in critically ill patients. We investigated changes in leptin, IL-6, and troponin in children undergoing open-heart surgery, hypothesizing that IL-6 and troponin will increase after cardiopulmonary bypass (CPB) and will be negatively correlated with leptin. PATIENTS AND METHODS Serial blood samples were collected from 21 patients 24 hours before and up to 48 hours after surgery. RESULTS Leptin levels decreased by 50% during CPB (P < .001), then gradually increased, reaching baseline levels 12 hours after surgery. The IL-6 levels increased (P < .001) during CPB, peaking 2 hours after surgery and remaining slightly elevated at 24 hours after surgery (P < .001). Leptin and IL-6 were negatively correlated (R = -0.448, P < .001). Troponin levels increased during CPB (P < .001). Postoperative leptin and troponin were inversely correlated (r = -0.535, P < .001). Patients with modest elevations in troponin levels (<20 microg/L) had a shorter aortic clamp and CPB time (P < .01), lower IL-6 peak levels (P = .03), and shorter duration of ventilation and inotropic support compared with patients with peak troponin levels greater than 20 microg/L. CONCLUSIONS Lower leptin and higher IL-6 levels correlated with troponin, a marker of myocardial injury. Because leptin may have cardioprotective effects, the postoperative drop in its levels may further contribute to myocardial dysfunction.