Low CD8 T cells in neonates and infants prior to surgery, and health-care-associated infections: prospective observational study.

BACKGROUND: Major surgery suppresses the cell-mediated immune response in children and adults. Data on preoperative and postoperative T-cell counts in pediatric surgical patients and their relationship to health-care-associated infection (HAI) are not yet known. METHODS: A prospective observational study was carried out in a level III multidisciplinary neonatal and pediatric intensive care unit. Before and after, and in the first 3 days after surgery, lymphocyte subsets in peripheral blood were measured in 28 neonates and infants on flow cytometry. HAI were classified according to CDC/NHSN criteria. RESULTS: Six out of 28 neonates and infants (21.4%) developed HAI (group I-HAI), while 22 out of 28 (78.6%) remained infection free (group II-non-HAI). In group I with HAI, the preoperative median cytotoxic T-lymphocyte (CD8-T-cell) level was found to be below normal, and remained very low throughout the study period. In addition, the median and interquartile CD8 T-cell range (358 cells/µL; 304-424 cells/µL) were twice as low compared to group II without HAI (822 cells/µL; 522-933 cells/µL; P = 0.013). No differences were found between the two groups with regard to patient demographics and clinical data. CONCLUSION: Neonates and infants who underwent a major surgical procedure and who had a very low preoperative CD8 T-cell level, developed HAI postoperatively.

Detection of seizures with amplitude-integrated electroencephalography in a neonate treated with extracorporeal membrane oxygenation.

Infants with severe cardiorespiratory failure treated with extracorporeal membrane oxygenation are at risk of hypoxic-ischemic injury and infarction of the brain, intracranial hemorrhage, and seizures. Consequently, this can lead to adverse neurodevelopmental outcome. We present a neonate treated with veno-arterial extracorporeal membrane oxygenation due to diaphragmatic hernia. The infant's brain function was continuously monitored with amplitude-integrated electroencephalography. The child experienced clinical seizures and subclinical seizure discharges, detected by amplitude-integrated electroencephalography, permitting the opportunity to treat them and adjust the anticonvulsive treatment accordingly.

Interleukin-10, T-lymphocytes, and cardiac output in children after ventricular septal defect repair: a pilot study.

OBJECTIVE: To evaluate the acute inflammatory response and cardiac output in children after surgery for ventricular septal defect. DESIGN AND SETTING: Prospective, observational study in a level III multidisciplinary neonatal and pediatric intensive care unit. PATIENTS: Ten children undergoing open-heart surgery for ventricular septal defect. INTERVENTIONS: All children received methylprednisolone (30 mg/kg) in cardiopulmonary bypass (CPB) prime. MEASUREMENTS AND RESULTS: Before and after cardiopulmonary bypass, plasma interleukin-10 and tumor necrosis factor alpha were measured by enzyme-linked immunosorbent assay, and lymphocyte subsets in peripheral blood by flow cytometry. Relative values (post-/pre-CPB) of interleukin-10 and tumor necrosis factor alpha were calculated. The cardiac index (CI) was measured continuously beat-to-beat by a pulse contour analysis (PiCCO). Children above the cutoff value (median cardiac index value 3.0 l min(-1) m(-2)) were designated as the normal CI group and those below this value as the low CI group. In the normal CI group the relative values of interleukin-10 remained almost seven times higher than pre-CPB values at 24 h while in the low CI group they decreased almost to pre-CPB values. Furthermore, the normal CI group, but not the low CI group, exhibited more than threefold decrease in T-lymphocytes (lymphocyte T-cells, T-helper cells, and cytotoxic T-cells) 24 h after CPB. CONCLUSIONS: Children operated on for ventricular septal defect developed either a normal or low CI. The higher relative values of interleukin-10 and lower counts of lymphocyte T-cells, T-helper and cytotoxic T-cells differentiated the normal CI group from the low CI group at 24 h after cardiopulmonary bypass.

Phosphate metabolism in red blood cells of critically ill neonates.

Very few data exist on phosphate metabolism in critically ill neonates. Therefore we studied the incidence of hypophosphataemia, the intracellular metabolism of phosphate by measuring adenosine 5'-triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) in red blood cells, and excretion of phosphate in urine. The aims of the study were early detection of changes in phosphate metabolism as possible diagnostic markers of sepsis and defining the cause of hypophosphataemia.Neonates, treated in multidisciplinary paediatric intensive care unit (PICU), included in the study, were less than three days of age. Eighteen of them had respiratory distress syndrome (RDS) and 16 had microbiologically confirmed or clinical sepsis. The overall incidence of hypophosphataemia in critically ill neonates was over 80%, and was more common (88%) and more profound in those with sepsis than in those with RDS (79%). Therefore the septic neonates needed significantly larger amounts of phosphate to maintain normophosphataemia. In septic neonates ATP concentration in red blood cells was significantly lower than in neonates with RDS and controls, while the 2,3-DPG concentration was increased as a result of compensation. In septic neonates urinary losses of inorganic phosphate (Pi) were significantly higher than in neonates with RDS. Hypophosphataemia in critically ill neonates is at least partly due to higher urinary losses of phosphate.

lnterleukin-6 (IL-6) and soluble receptors for interleukin-2 (slL-2R) in the diagnosis of early severe infection in the critically ill newborns.

The aim of our study was to evaluate the diagnostic accuracy of serial determination of interleukin-6 (IL-6) and soluble receptors of interleukin-2 (sIL-2R) in the diagnosis of early infection in the critically ill newborns and compare it with the routinely used C-reactive protein (CRP). Fourty-six critically ill newborns (median age 8 h, range 1-96 h), treated at the multidisciplinary intensive care unit, Division for Paediatric Surgery and Intensive Care, University Medical Centre Ljubljana, were included in the study. Newborns were divided into three groups: group I microbiologically confirmed severe infection (n = 14), group II suspected but not confirmed infection (n = 12) and group III respiratory distress syndrome without laboratory signs of infection. Serum concentrations of IL-6, sIL-2R and CRP were determined on admission and at 12 and 24 h after admission. On admission the concentrations of IL-6 and sIL-2R were significantly higher in group I than in group III, but there was no difference between groups I and II. On admission area under receiver operating characteristic (ROC) curve for IL-6 was 0.756, for IL-2R 0.821 and for CRP 0.799. Repeated determination at 12 h improved diagnostic accuracy for sIL-R and CRP but not for IL-6.

Use of semi-quantitative and quantitative culture methods and typing for studying the epidemiology of central venous catheter-related infections in neonates on parenteral nutrition.

To study the epidemiology - especially the impact of contaminated stopcocks - on central venous catheter (CVC) infection and catheter-related sepsis (CRS), semi-quantitative (SQ) and quantitative (Q) culture methods and typing of coagulase-negative staphylococci (CNS) were employed in 49 neonates with clinical signs of sepsis while receiving parenteral nutrition in the paediatric intensive care unit. The patients were divided into two groups according to stopcock contamination: group A consisted of 18 patients (36%) with contaminated stopcocks and group B consisted of 31 patients (64%) with sterile stopcocks. Five specimens were obtained from each patient, in addition to that from the stopcock: a swab taken from the skin surrounding the catheter puncture site; the CVC tip; the intradermal segment (IDC); and samples of parenteral fluid and blood. A total of 294 specimens (392 sites) was cultured and micro-organisms were identified. All CNS isolated were typed by biotyping, antibiogram, plasmid analysis and pulsed-field gel electrophoresis (PFGE), and the discriminatory power of the typing methods was compared. The CVC tips were infected in 25 patients (51%); 15 (83%) in group A and 10 (32%) in group B. Sepsis was detected in 24 neonates (49%), 13 in group A and 11 in group B. This was catheter-related in 15 patients (63%), 12 in group A and 3 in group B. CNS were recovered from 13 (52%) of 25 infected CVCs, nine in group A and four in group B. Sixty-five CNS isolates were recovered from these patients and belonged to 14 biotypes, 22 antibiograms, 22 plasmid profiles and 26 PFGE types. Typing showed that in six of nine patients in group A, CNS of the same type were recovered from the catheter tip and the stopcock, in one patient the catheter tip and skin isolates were the same and in two others the catheter tip isolates were different from stopcock and skin isolates. In all four patients in group B, different CNS types were recovered from CVC tips and skin. Bacteraemia was caused by CNS in 14 patients (58%), six in group A and eight in group B. Typing confirmed that nine cases (six in group A and three in group B) were catheter-related but five were not. SQ and Q culture methods and typing, especially by PFGE, allowed the study to determine that bacteria from contaminated stopcocks were frequently the source of CVC infection and CRS.

Heart rate and leukocytes after air and ground transportation in artificially ventilated neonates: a prospective observational study.

OBJECTIVE: To evaluate the effect of interhospital air and ground transportation of artificially ventilated neonates on heart rate and peripheral blood leukocyte counts. DESIGN: Prospective, observational study. SETTING: Level III multidisciplinary Neonatal and Pediatric Intensive Care Unit. PATIENTS: Fifty-eight near-term artificially ventilated transported neonates between May 2006 and April 2007. INTERVENTIONS: Day-helicopter, day- and night-ground transportation. MEASUREMENTS AND RESULTS: Heart rate at retrieval, on admission to the ICU and 1 h later, and peripheral blood leukocyte counts on admission and 1 d later were compared. Fifteen neonates were transported by helicopter during the daytime (D-HEL), 20 by daytime ground and 23 by nighttime ground transportation (D-GROUND, N-GROUND). No differences in delivery mode, birth weight, gestational age, gender, primary diagnoses for transportation, response time and duration of transportation were found between the groups. Similarly, no differences in pH, pCO(2), blood pressure and skin temperature at retrieval and on admission to the ICU were found between the three groups. The mean heart rate at retrieval did not differ significantly, while on arrival in the ICU and 1 h later the D-GROUND group of patients showed a significantly higher mean heart rate compared to the D-HEL and N-GROUND groups. Moreover, leukocyte counts on arrival in the ICU showed significantly higher leukocyte counts in the D-GROUND group of patients compared to the D-HEL group of patients. CONCLUSIONS: These results demonstrate that there is an association between daytime ground transportation and higher heart rate and peripheral blood leukocytes.

Methylprednisolone, cortisol and the cell-mediated immune response in children after ventricular septal defect repair.

BACKGROUND: This study evaluated the effects of methylprednisolone on cortisol and cell-mediated immune response (T-lymphocytes and HLA-DR+ monocytes) in peripheral blood after open-heart surgery with cardiopulmonary bypass (CPB) for ventricular septal defect. METHODS: A prospective observational study was carried out in a tertiary multidisciplinary neonatal and paediatric intensive care unit. Ten children under 2 years of age received methylprednisolone succinate (30 mg/kg body weight) in CPB priming solutions before the CPB system was connected to the patient during surgery. Before and immediately after and at 24 and 96 h after the operation, T-lymphocytes and HLA-DR+ monocytes were measured by flow cytometry, and methylprednisolone, methylprednisolone succinate and cortisol in blood plasma were assayed by liquid chromatography-mass spectrometry. RESULTS: The children were divided into groups with normal cardiac index (CI) and low CI. No significant differences in methylprednisolone and cortisol concentrations before and after surgery were found between the two groups. The normal CI group exhibited more than a three-fold decrease in T-lymphocytes 24 h after surgery and a two-fold decrease in HLA-DR+ monocyte fluorescence immediately after surgery. CONCLUSIONS: Children with normal and low CI were differentiated by T-lymphocytes and HLA-DR+ monocytes. Since no differences in methylprednisolone exposure and cortisol plasma levels between the low-CI and normal-CI groups were found, it can be concluded that factors other than methylprednisolone must contribute to differences in the cell-mediated response.

Continuous renal replacement therapy and plasma exchange in newborns and infants.

The objective of our study was to present our experience in the treatment of small children with continuous renal replacement therapy (CRRT) and plasma exchange (PE). From March 1986 to April 2000, 21 critically ill children (14 newborns and 7 infants) with acute renal failure (ARF) and multiple organ failure were treated with CRRT and PE. In the newborn group, there were 8 males and 6 females, age 15.7 +/- 11.7 days, with body weights of 3,348 +/- 585 g. In the infant group, there were 4 males and 3 females, age 118 +/- 67 days, with body weights 5,186 +/- 734 g. The indications for the beginning of CRRT and/or PE were ARF with anuria and hyperhydration (17 patients), azotemia and anuria (1 patient), hemolytic uremic syndrome (1 patient), and hyperammonemia (2 patients). In all patients, peritoneal dialysis was considered inappropriate. PE and CRRT monitors were used, double lumen 5 Fr and 7 Fr hemodialysis catheters were the vascular access, low dose heparin and prostacyclin were anticoagulants, and lactate or bicarbonate buffered replacement solutions were used predilutionally. Side events were clotting within the extracorporeal circuit, catheter malfunction, serious hypotension (6 patients), and pulmonary edema (1 patient). Ten of 21 patients (47.6%) recovered renal function and 9 of 21 patients (42.9%) survived. Survivors had fewer failing organs (3.6 +/- 0.5) than nonsurvivors (4.8 +/- 0.9) (p = 0.0008). Pump driven CRRT and PE were feasible, efficient, and safe procedures in newborns and infants. Without CRRT, it is uncertain whether any of our patients would have the chance to survive.