[Show abstract][Hide abstract] ABSTRACT: The pattern-recognition molecule M-ficolin is synthesized by monocytes and neutrophils. M-ficolin activates the complement system in a manner similar to mannan-binding lectin (MBL), but little is known about its role in host defense. Neonates are highly vulnerable to bacterial sepsis, in particular, due to their decreased phagocytic function.
M-ficolin cord blood concentration was positively correlated with the absolute phagocyte count (ρ 0.51, P < 0.001) and with immature/total neutrophil ratio (ρ 0.34, P < 0.001). When comparing infants with sepsis and controls, a high M-ficolin cord blood concentration (>1,000 ng/ml) was associated with early-onset sepsis (EOS) (multivariate odds ratio 10.92, 95% confidence interval 2.21-54.02, P = 0.003). Experimental exposure of phagocytes isolated from adult donors to Escherichia coli resulted in a significant time- and dose-dependent release of M-ficolin.
In conclusion, M-ficolin concentrations were related to circulating phagocytes and EOS. Our results indicate that bacterial sepsis can trigger M-ficolin release by phagocytes. Future studies should investigate whether M-ficolin may be used as a marker of neutrophil activation during invasive infections.
We investigated M-ficolin in 47 infants with culture-positive sepsis during the first 30 days of life (13 with EOS and in 94 matched controls. M-ficolin was measured in cord blood using time-resolved immunofluorometric assay (TRIFMA). Multivariate logistic regression was performed.
Pediatric Research 04/2012; 71(4 Pt 1):368-74. · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rapid bedside determination of cerebral blood pressure autoregulation (AR) may improve clinical utility. We tested the hypothesis that cerebral Hb oxygenation (HbDiff) and cerebral Hb volume (HbTotal) measured by near-infrared spectroscopy (NIRS) would correlate with cerebral blood flow (CBF) after single dose phenylephrine (PE). Critically ill patients requiring artificial ventilation and arterial lines were eligible. During rapid blood pressure rise induced by i.v. PE bolus, ΔHbDiff and ΔHbTotal were calculated by subtracting values at baseline (normotension) from values at peak blood pressure elevation (hypertension). With the aid of NIRS and bolus injection of indocyanine green, relative measures of CBF, called blood flow index (BFI), were determined during normotension and during hypertension. BFI during hypertension was expressed as percentage from BFI during normotension (BFI%). Autoregulation indices (ARIs) were calculated by dividing BFI%, ΔHbDiff, and ΔHbTotal by the concomitant change in blood pressure. In 24 patients (11 newborns and 13 children), significant correlations between BFI% and ΔHbDiff (or ΔHbTotal) were found. In addition, the associations between Hb-based ARI and BFI%-based ARI were significant with correlation coefficients of 0.73 (or 0.72). Rapid determination of dynamic AR with the aid of cerebral Hb signals and PE bolus seems to be reliable.
Pediatric Research 01/2011; 69(5 Pt 1):436-41. · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND. The incidence of bacterial sepsis during the neonatal period is high. Mannan-binding lectin (MBL), L-ficolin, and H-ficolin recognize microorganisms and activate the complement system via MBL-associated serine proteases (MASPs). This study investigated whether cord blood concentrations of the lectin pathway proteins are associated with neonatal sepsis. METHODS. This was a case-control study including 47 infants with culture-proven sepsis during the first month of life and 94 matched controls. MBL, L-ficolin, H-ficolin, MASP-2, and MASP-3 levels were measured in cord blood with use of enzyme-linked immunosorbent assay and time-resolved immunofluorometric assay. Multivariate logistic regression was performed. RESULTS. Infants with gram-positive sepsis had significantly lower H-ficolin cord blood concentrations than controls (multivariate odds ratio [OR], 4.00; 95% confidence interval [CI], 1.51-10.56; P = .005), whereas infants with gram-negative sepsis had lower MBL cord blood concentrations (OR, 2.99; 95% CI, 0.86-10.33; P = .084). When excluding patients with postoperative sepsis, multivariate analysis confirmed that low H-ficolin was associated with a significantly higher risk of gram-positive sepsis (OR, 3.71; 95% CI, 1.26-10.92; P = .017) and late-onset sepsis (OR, 3.14; 95% CI, 1.07-9.21; P = .037). In contrast, low MBL was associated with a significantly higher risk of gram-negative sepsis (OR, 4.39; 95% CI, 1.10-17.45; P = .036) and early-onset sepsis (OR, 3.87; 95% CI, 1.05-14.29; P = .042). The concentrations of all the lectin pathway proteins increased with gestational age (P < .01). CONCLUSIONS. These preliminary results indicate that low MBL concentrations are a susceptibility factor for gram-negative sepsis, and low H-ficolin concentrations indicate susceptibility to gram-positive sepsis. The decreased expression of lectin pathway proteins in neonates must be considered to be an additional form of neonatal immunodeficiency.
[Show abstract][Hide abstract] ABSTRACT: A patent arterial duct in pre-term neonates is frequent. Systemic complications consecutive to left-to-right shunting are well known but fatal myocardial ischaemia has not been described till now. The presented premature baby died from catecholamine refractory cardiogenic shock. Autoptic examination revealed acute ischaemic changes predominantly in the inner third of myocardium, speaking of coronary hypoperfusion due to a steal phenomenon secondary to the patent arterial duct.
Cardiology in the Young 03/2010; 20(1):108-10. · 0.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In a 9-year-old boy, bridging to transplantation was successful with an external biventricular device, the Berlin Heart Excor (Berlin Heart, Berlin, Germany), during a 7-month period. Main long-term complications consisted of infection and hypercoagulability with clotting inside the chambers necessitating six pump exchanges, but without thromboembolic events. This report reviews hemostasis monitoring and management of long-term mechanical circulatory support.
The Annals of thoracic surgery 05/2008; 85(4):1453-6. · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Disseminated adenoviral infection with hepatitis is rare in children undergoing standard chemotherapy. We report on a 3(1/2)-year-old male with fatal adenovirus hepatitis receiving maintenance chemotherapy for acute lymphoblastic leukemia (ALL). Adenoviral hepatitis was proven by histology, viral culture, and PCR in a liver biopsy. Quantitative real-time PCR in the peripheral blood showed adenoviral DNA copy number >10(9)/ml. Despite aggressive supportive care and antiviral treatment with cidofovir, the patient died rapidly due to fulminant liver failure. Diagnostic and treatment options for adenovirus infection remain unsatisfactory for these patients. We propose suggestions for diagnosis and therapy.
Pediatric Blood & Cancer 04/2008; 50(3):647-9. · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Severe respiratory distress syndrome (RDS) caused by surfactant deficiency is described not only in preterm infants but also in (near-) term babies after caesarean section (CS), especially when carried out before the onset of labour. The aim of the present study was to document the severity of this theoretically avoidable entity in order to improve obstetric and perinatal care.
All neonates admitted to the paediatric intensive care unit of the University Hospital of Bern between 1988 and 2000 with RDS on the basis of hyaline membrane disease (HMD) needing mechanical ventilation (MV) after CS and with a birthweight > or = 2500 g were analysed. HMD was diagnosed when respiratory distress and the typical radiological signs were present. Patients were grouped into elective CS before onset of labour and before rupture of membranes (group 1, n = 34) and patients delivered by emergency CS or CS after onset of labour or rupture of membranes (group 2, n = 22). Analysed indices for severity of illness were duration of stay in intensive care unit and MV, ventilation mode, worst oxygenation index (OI), presence of pulmonary air leak, and systemic hypotension.
Mean gestational age (GA) was 37 2/7 weeks in group 1 and 36 2/7 weeks in group 2; no patient had a GA of > or = 39 0/7 weeks. Duration of MV was 4.4 days in group 1 and 3.9 days in group 2. Thirteen patients (38%) of group 1 and 7 (32%) of group 2 had to be managed by rescue high-frequency ventilation. A total of 7 patients had an OI>40. Eight patients (24%) in group 1 and 4 (18%) in group 2 developed a pulmonary air leak. Fourteen neonates (41%) in group 1 had to be supported by catecholamines versus 5 (22%) in group 2. There was one death in group 1.
Severe RDS on the basis of HMD can also occur in near-term babies after CS; even a fatal outcome can not be excluded. The severity of illness in elective CS without labour may be quite high and is comparable to newborns delivered by CS (after onset of labour and/or rupture of the membranes) who were 1 week younger. No case of HMD was found in our population when CS was carried out after completion of 39 post-menstrual weeks of gestation.
Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology 06/2003; 133(19-20):283-8. · 1.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the feasibility and reproducibility of the blood flow index (BFI) method for measuring cerebral blood flow.
Prospective functional study in pediatric intensive care.
14 consecutive patients with median age of 2 months (range 1 days-11 years) requiring artificial ventilation, invasive arterial blood pressure monitoring, and central venous access.
The first passage of an intravenous indocyanine green (ICG) bolus through the cerebral vasculature was monitored by noninvasive near-infrared spectroscopy. BFI was calculated by dividing maximal ICG absorption change by rise time. Reproducibility was evaluated by six ICG injections at 5-min intervals.
Of all ICG injections 6% were canceled, and 4% were eliminated due to injection failures. Median BFI of 17 reproducibility determinations was 71 (range 12-213) and median coefficient of variation (CV) of BFI was 10% (4.9-18.5). The quantity of ICG bolus did not affect the CV (0.1 vs. 0.3 mg ICG/kg). Eight reproducibility tests in patients after cardiac surgery had smaller CV than the others, and the eight in newborns had higher CV than in older children. Patient parameters such as arterial blood pressure, endtidal CO(2), and percutaneous oxygen saturation were stable and showed CV below 2% during reproducibility determination.
The BFI method allows rapid and repeated measurements of CBF with good feasibility and reproducibility. As a relative but not absolute measure of CBF, BFI seems to be suited for clinical evaluation of intraindividual CBF changes during determination of cerebrovascular reactivities or during therapeutic interventions.
Intensive Care Medicine 03/2003; 29(2):196-200. · 5.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Noninvasive near-infrared spectroscopy (NIRS) continuously monitors changes in cerebral hemoglobin saturation (Hb(Diff) ) and content (Hb(Total)). It may allow visualization of the dynamic cerebral autoregulatory response to rapid blood pressure increases without relevant contamination of the NIRS signal from extracerebral hemoglobin.
Prospective cohort study.
Multidisciplinary pediatric intensive care unit.
Six consecutive children in coma due to severe encephalopathy (head trauma, five patients; mumps encephalitis, one patient) requiring artificial ventilation, invasive arterial blood, and intracranial pressure monitoring.
Frontotemporal recording of Hb(Diff) and Hb(Total) while rapidly elevating blood pressure by bolus injection of phenylephrine.
During an increase of blood pressure of 13 +/- 1 mm Hg with a "rise time" of 16 +/- 1 secs (mean of a total of 31 injections +/- sem), a significant linear correlation was found between Hb(Diff) and intracranial pressure signals (mean coefficient, 0.46 +/- 0.04) but not between Hb(Total) and intracranial pressure. Three response patterns were observed. First, Hb(Diff) and intracranial pressure reduction, corresponding with vasoconstriction and normal dynamic autoregulation (n = 3); second, Hb(Diff) and intracranial pressure increase, corresponding with persistent vasodilation and abolished autoregulation (n = 11); and third, transient Hb(Diff) and intracranial pressure increase followed by a decrease at peak blood pressure elevation, called impaired autoregulation (n = 15). In one patient with fatal brain swelling, phenylephrine testing showed no effect on NIRS signals (n = 2). Furthermore, there were significant correlations between 31 pooled interindividual pairs of Hb(Diff) changes with intracranial pressure changes (values at baseline averaged over 60 secs subtracted from values at peak blood pressure elevation averaged over 5 secs), with a correlation coefficient of .82 (p <.001).
NIRS represents a new and promising technique for bedside determination of dynamic cerebral autoregulation during acutely induced blood pressure rise. The significant correlations found between NIRS signals and intracranial pressure excluded relevant extracerebral contamination of the NIRS signals. In our patients with severe encephalopathy, dynamic autoregulation was in most instances not fully preserved.
Critical Care Medicine 10/2002; 30(9):2014-21. · 6.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hypothermia may be an ideal neuroprotective intervention in hypoxic-ischemic encephalopathy after perinatal asphyxia. The present study describes the long-term effects of prolonged resuscitative whole-body hypothermia initiated 2 h after hypoxic-ischemic injury on brain morphology and neuropsychological behavior in 7-d-old rats. After right common carotid artery ligation and exposure to hypoxia of 8% O(2) for 105 min, 10 animals were kept normothermic at 37 degrees C and 10 animals were cooled to 30 degrees C rectal temperature for 26 h, starting 2 h after the hypoxic-ischemic insult. All hypoxic-ischemic animals were gavage fed to guarantee long-term survival. Neuroprotection was evaluated by magnetic resonance imaging and behavioral testing. Hypothermia significantly reduced the final size of cerebral infarction by 23% at 6 wk after the insult. The most extended tissue rescue was found in the hippocampus (21%, p = 0.031), followed by the striatum (13%, p = 0.143) and the cortex (11%, p = 0.160). Cooling salvaged spatial memory deficits verified at 5 wk of recovery with Morris Water Maze test; whereas circling abnormalities after apomorphine injection and sensory motor dysfunctions on rotating treadmill improved, yet did not reach statistical significance. When compared with controls, hypoxic-ischemic animals performed worse in all behavioral tests. Hypothermia did not influence functional outcome in controls. Significant correlations between behavioral performance and corresponding regional brain volumes were found. We conclude that 26 h of mild to moderate resuscitative hypothermia leads not only to brain tissue rescue, but most important to long-lasting behavioral improvement throughout brain maturation despite severity of injury and delayed onset of cooling.
Pediatric Research 04/2002; 51(3):354-60. · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We hypothesized that creatine (Cr) supplementation would preserve energy metabolism and thus ameliorate the energy failure and the extent of brain edema seen after severe but transient cerebral hypoxia-ischemia (HI) in the neonatal rat model. Six-day-old (P6) rats received subcutaneous Cr monohydrate injections for 3 consecutive days (3 g/kg body weight/day), followed by 31P-magnetic resonance spectroscopy (MRS) at P9. In a second group, P4 rats received the same Cr dose as above for 3 days prior to unilateral common carotid artery ligation followed 1 h later by 100 min of hypoxia (8% O2) at P7. Rats were maintained at 37 degrees C rectal temperature until magnetic resonance imaging was performed 24 h after HI. Cr supplementation for 3 days significantly increased the energy potential, i.e. the ratio of phosphocreatine to beta-nucleotide triphosphate (PCr/betaNTP) and PCr/inorganic phosphate (PCr/Pi) as measured by 31P-MRS. Rats with hemispheric cerebral hypoxic-ischemic insult that had received Cr showed a significant reduction (25%) of the volume of edemic brain tissue compared with controls as calculated from diffusion-weighted images (DWI). Thus, prophylactic Cr supplementation demonstrated a significant neuroprotective effect 24 h after transient cerebral HI. We hypothesize that neuroprotection is probably due to the availability of a larger metabolic substrate pool leading to a reduction of the secondary energy failure because DWI has been reported to correlate with the PCr/Pi ratio in the acute phase of injury. Additional protection by Cr may be related to prevention of calcium overload, prevention of mitochondrial permeability transition pore opening and direct antioxidant effects.
[Show abstract][Hide abstract] ABSTRACT: Early postoperative arrhythmias frequently are a relevant problem in the early postoperative management after surgical intervention for congenital heart disease. Few data are available indicating risk factors for their occurrence. The hypothesis was tested that factors closely related to the surgical procedure itself were associated with a higher incidence of arrhythmias early in the postoperative course after repair of congenital heart disease.
All consecutive patients undergoing 1 of 3 well-defined surgical procedures were prospectively evaluated for the occurrence of arrhythmias during the entire postoperative hospital stay by means of continuous electrocardiographic monitoring in the intensive care unit and use of 24-hour Holter monitors. Patients examined were those undergoing transatrial closure of a ventricular septal defect, repair of complete atrioventricular canal, and tetralogy of Fallot. The relation between procedural variables and the occurrence of arrhythmias was independently evaluated for each of these 3 heart defects.
Early postoperative arrhythmias occurred in 30% of patients with ventricular septal defect (n = 75), 35% of patients with tetralogy of Fallot (n = 52), and 47% of patients with atrioventricular canal (n = 45). Patients with arrhythmias tended to be younger (significant only in the ventricular septal defect group). In all 3 patient groups, there was a significant correlation between incidence of arrhythmias and longer extracorporeal bypass time (P <.05) and longer aortic crossclamp time (P <.01), as well as with higher maximum postoperative troponin serum levels (P <.01). In patients with atrioventricular canal, there was a significant relation between hemodynamically incomplete surgical results and the occurrence of arrhythmias (P <.01).
The occurrence of early postoperative arrhythmias after repair of congenital heart disease was significantly associated with procedure-related risk factors in each of 3 independent patient groups undergoing well-defined surgical procedures.
Journal of Thoracic and Cardiovascular Surgery 02/2002; 123(2):258-62. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: Evaluation of occurrence, clinical course, necessity of treatment, and outcome of early postoperative cardiac arrhythmias after open-heart surgery. DESIGN: Prospective study. SETTING: Tertiary pediatric intensive care and pediatric cardiology unit. PATIENTS: All consecutive pediatric patients undergoing cardiac surgery on cardiopulmonary bypass were studied for the occurrence of cardiac arrhythmias during the whole perioperative hospital stay. Measurements: All patients had continuous electrocardiographic monitoring (with memory function) during the whole intensive care stay. A 24-hr Holter recording was done thereafter in patients with arrhythmias. RESULTS: Of 310 patients studied, 83 (27%) had postoperative arrhythmias. The occurrence rate was not different whether surgical access was by atriotomy or ventriculotomy (26% vs. 28%, respectively). Infants (39%) and cyanotic patients (36%) had a higher occurrence rate of arrhythmias (p <.05). Arrhythmias were more common after prolonged cardiopulmonary bypass time and with higher postoperative maximum troponin serum levels. In addition, patients with hemodynamically significant residual findings after correction had an increased occurrence rate of arrhythmias (18 of 43; 42%; p <.01). Of the 83 children with arrhythmias, 53 (64%) required specific antiarrhythmic treatment. The use of antiarrhythmic drugs was required in only 7 of these patients. Only one patient (1.2% of patients with arrhythmias) died from arrhythmia. No major complications resulting from arrhythmias occurred during the postoperative clinical course in the other patients. CONCLUSIONS: Although they occur frequently, postoperative arrhythmias after open-heart procedures in children are associated with low morbidity and mortality.
Pediatric Critical Care Medicine 07/2001; 2(3):217-222. · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hypoxic-ischaemic encephalopathy (HIE) is of major importance in neonatal and paediatric intensive care with regard to mortality and long-term morbidity. Our aim was to analyse our data in full-term neonates and children with special regard to withdrawal of life support and bad outcome.
All patients with HIE admitted to our unit from 1992-96 were analysed. Criteria for HIE were presence of a hypoxic insult followed by coma or altered consciousness with or without convulsions. Severity of HIE was assessed in neonates using Sarnat stages, and in children the duration of coma. In the majority of cases staging was completed with electrophysiological studies. Outcome was described using the Glasgow Outcome Scale. Bad outcome was defined as death, permanent vegetative state or severe disability, good outcome as moderate disability or good recovery.
In the neonatal group (n = 38) outcome was significantly associated with Sarnat stages, presence of convulsions, severely abnormal EEG, cardiovascular failure, and multiple organ dysfunction (MOD). A bad outcome was observed in 27 cases with 14 deaths and 13 survivors. Supportive treatment was withdrawn in 14 cases with 9 subsequent deaths. In the older age group (n = 45) outcome was related to persistent coma of 24-48 h, severely abnormal EEG, cardiovascular failure, liver dysfunction and MOD. A bad outcome was found in 36 cases with 33 deaths and 3 survivors. Supportive treatment was withdrawn in 15 instances, all followed by death.
Overall, neonates and older patients did not differ with regard to good or bad outcome. However, in the neonatal group there were significantly more survivors with bad outcome, either overall or after withdrawal of support. Possible explanations for this difference include variability of hypoxic insult, maturational and metabolic differences, and the more compliant neonatal skull, which prevents brainstem herniation.
Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology 06/2001; 131(19-20):267-72. · 1.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A neonatal case of severe, ventilator-dependent tracheobronchomalacia (TBM) is described. The extent of the malacic segment was determined by endoscopy and tracheobronchography. Additionally, relevant and ever increasing reversible peripheral airway obstruction was documented by measuring the mechanical properties of the respiratory system before and after salbutamol. With the combination of endoscopically guided aortopexy and salbutamol infusion, the infant was eventually weaned from mechanical ventilation at the age of 86 days. We speculate that in ventilator-dependent infants with severe TBM the determination of bronchodilator responsiveness may have clinical consequences.
Intensive Care Medicine 08/1999; 25(7):729-32. · 5.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our aim was to analyze, in a retrospective study, changes in acute respiratory distress syndrome (ARDS) within the same pediatric intensive care unit by using the same diagnostic criteria as published in 1982.
Fifteen patients (mean age 5.1 years, range 16 days-15 years) admitted between 1988 and 1994 fulfilling our former criteria for ARDS were included in the study.
The incidence of ARDS after the age of 7 days was 0.45% of all admissions between the age of 1 week and 16 years vs 1.79% in the former series of patients (p < 0.001). Thus, the yearly rate of ARDS decreased from 5.7 to 2.1 cases per year. Six patients suffered a chronic underlying disease vs none in 1982 (p < 0.01). Triggering of ARDS by infection/inflammation was present in 14/15 patients vs 7/20 in the first series (p < 0.001). Except for the nadir PaO2/FiO2 ratio (54 mmHg vs 97 mmHg, p < 0.01), and duration of FiO2 > or = 0.5 (204 h vs 39 h, p < 0.01) there was no statistically significant difference with regard to respiratory data. Incidence of multiple organ/system failure and numbers of failing organs/systems remained unchanged. Eight of 15 patients died in the actual series vs 8/20 in 1982 (not significant).
Compared to our former data, the incidence of ARDS has decreased. Although the number of patients with severe chronic disease has increased, mortality remains statistically unchanged. Infection/inflammation is currently the predominant event triggering ARDS. Judging by the PaO2/FiO2 ratio and duration of FiO2 > or = 0.5, pulmonary involvement is more severe. The number of failing organs/systems remains nearly twice as frequent in non-survivors compared to survivors.
Anales espanoles de pediatria 06/1999; 50(6):566-70.