Search

Severe traumatic brain injury (TBI) in childhood is associated with a high mortality and morbidity. Decompressive craniectomy has regained therapeutic interest during past years; however, treatment guidelines consider it a last resort treatment strategy for use only after failure of conservative therapy. We report on the clinical course of six children treated with decompressive craniectomy after TBI at a pediatric intensive care unit. The standard protocol of intensive care treatment included continuous intracranial pressure (ICP) monitoring, sedation and muscle relaxation, normothermia, mild hyperventilation and catecholamines to maintain an adequate cerebral perfusion pressure. Decompressive craniectomy including dura opening was initiated in cases of a sustained increase in ICP > 20 mmHg for > 30 min despite maximally intensified conservative therapy (optimized sedation and ventilation, barbiturates or mannitol). In all cases, the ICP normalized immediately after craniectomy. At discharge, three children were without disability, two children had a mild arm-focused hemiparesis (one with a verbal impairment), and one child had a spastic hemiparesis and verbal impairment. This spastic hemiparesis improved within 6 months follow-up (no motor deficit, increased muscle tone), and all others remained unchanged. These observational pilot data indicate feasibility and efficacy of decompressive craniectomy in malignant ICP rise secondary to TBI. Further controlled trials are necessary to evaluate the indication and standardization of early decompressive craniectomy as a 'second tier' standard therapy in pediatric severe head injury.

Summary We report an outbreak of sepsis from contaminated disinfectant in a neonatal and paediatric intensive-care unit. 28 infants were infected with Klebsiella oxytoca and basic measures to control the outbreak failed. The resistance of K oxytoca against the disinfectant was probably mediated by capsule formation, visible as mucoid colonies.

Increased Production of IL-6 and IL-8 in Neonatal Monocytes Analyzed by Flow Cytometric Single Cell Analysis: A Possible Mechanism Responsible for The High Letality in Neonatal Infection

Meconium aspiration syndrome (MAS) is still a condition associatedwith a high mortality, and many patients require extracorporeal membraneoxygenation (ECMO) as rescue therapy. Beneficial effects of surfactant andperflubron lavage have been reported. However, pure surfactant supplementationhas not been proven to be beneficial in the most severe forms of MAS. Thisstudy was performed to demonstrate an improvement in oxygenation in neonatestransferred for ECMO and fulfilling ECMO criteria with a saline lavage andsurfactant resupplementation. Twelve newborns with MAS [gestational age 36–40 weeks, mean birthweight 3200 g, age 4–16 h, oxygenation index (OI) > 40] transferred for ECMOtherapy were treated with saline lavage (5–10 cm3/kg body weight, aslong as green colored retrieval was observed) and resupplementation with bovinesurfactant (Alveofact, Boehringer, Ingelheim, Germany). The OI at admission and3 h after this procedure was compared using the t-test for pairedsamples. ECMO was available as rescue therapy at all times. The OI decreased from 49.4 (SD ± 13.3) to 27.4 (SD ± 7.3),P < 0.01. The decrease was sustained in nine patients, threepatients required ECMO and all patients survived. As MAS is a condition with parenchymal damage, pulmonaryhypertension and obstructive airway disease, no simple causative therapy ispossible. Surfactant application after removal of meconium by extensive lavageis feasible as long as 16 h after birth even in infants considered for ECMOtherapy; it might reduce the necessity of ECMO.

Background: Recently the resistance to activated protein C(APC-resistance) was identified to be the most common risk factor for deep vein thrombosis in the Caucasian population. Reports on a high frequency of APC-resistance in children and newborns with venous or arterial thrombembolism(Nowak-Gottl, Br J Hamatol 1996;92:992-8) and a high prevalence of thrombi within the large mesenteric artery branches in patients autopsied because of NEC (Ballance, J Pediatr 1990;117:S6-13), raising the question if APC-resistance is a risk factor for the development of neonatal necrotizing enterocolitis.

Introduction: In order to characterize differences in the pathophysiology of RDS in preterm infants compared with ARDS-like disease in newborns, we prospectively obtained TA (tracheal aspirates) from newborns requiring mechanical ventilation. Subjects and methods: TA were obtained within 48 h of intubation in 17 infants < 32 weeks of gestation(group 1; mean GA 29 ± 2.5 (SD) wks) and 14 newborns (group 2; mean GA 38 ± 3.2 (SD) wks). TA were cytocentrifuged and the cells were differentiated morphologically and immunocytologically (CD62L and CD11b). Total protein (TP), α2 -macroglobulin (α2-MG) and elastase-al-proteinase inhibitor complex (E-α1-PI) were analyzed and compared with controls requiring mechanical ventilation without underlying pulmonary diseases. Results: In both groups neutrophils and macrophages were found in TA, polymorphonuclear cells were positive for CD 62L and CD 11b. The table summarizes the results of the biochemical variables (mean ± SD): Conclusions: We demonstrated evidence for significant leukocyte endothelium-interactions as a consequence of granulocyte activation in the early course of both RDS and ARDS-like disease. Furthermore, significantly increased E-α1-PI concentrations in newborns ≥ 32 weeks suggest inflammatory mechanisms in ARDS-like disease. We conclude TA analyses might be helpful differentiating between both types of neonatal respiratory failure.

Background: Controversy still exits with respect to timing of surfactant administration in preterm infants at risk for or with manifest RDS. We therefore aimed to investigate in a multicenter trial whether early ( 2h following birth) surfactant administration would be superior. Subjects and methods: All infants with a gestational age from 27-32 weeks were enrolled stratified by center after prenatal parental informed consent. Early treatment with surfactant (100 mg/kg b.w. Alveofact® i.t.) was given to infants requiring intubation following birth, late treatment was given with an identical dosage to infants on mechanical ventilation with a FiO2 >0.4 between hours 2-6 following birth. The primary end point was the time on mechanical ventilation, secondary endpoints included mortality, BPD (28 days FiO2 >0.21 or mechanical ventilation), IVH >III/PVL. Sample size calculation revealed a total of 200 infants would have to be included to (α=0.05; β=0.80).Results: 236 infants were enrolled, 146 needed intubation and mechanical ventilation. Table 1 gives an overview on most relevant study data (intent-to-treat analysis).

Background: There are only scanty data on vancomycin(va) distribution to cerebrospinal fluid (CSF) in childhood. In order to characterize CSF distribution of va after intravenous administration, we prospectively investigated children with temporary external CSF-drainage. Subjects: In 7 children (age 1 month - 10 years), plasma and CSF-samples were taken simultaneously and va concentrations were measured(μg/ml; polarization fluorescence immunoassay; Abbott, Munich, F.R.G.).Interventions: Children were treated with i.v. va at doses in the range of 2 × 5 m/kg b.w. to 2 × 10 mg/kg b.w. per day, administered by within 60 minutes. Blood was drawn 1 h after the end of the infusions period, simultaneously CSF was aspirated from the drainage. Results: Median trough CSF va concentrations were 2.16μg/ml, mean corresponding plasma concentrations 2.72 μg/ml (n = 12 each), median peak CSF concentrations 2.5 μg/ml, median peak plasma concentrations 14.5 μg/ml (n = 4 each). All CSF cultures were sterile. Conclusion: Due to the outlined pharmacocinetic data, va may be considered for perioperative prophylaxis of CSF shunt infections.Table

Background: Both surfactant (SF) deficiency, anomalies in synthesis and inactivation are major pathophysiological features of neonatal RDS. We previously could show, that tracheal aspirates from preterm infants with RDS containing increased amounts of proteins exhibit abnormal surface properties in the pulsating bubble model (1).

Background: Lung surfactant, a complex composition of phospholipids, neutral lipids and various apoproteins is essential for lung function. In surfactant deficient neonates treatment was done successfully by endotracheal administration of either natural or artificial surfactant preparations. Alteration of the alveolo-capillary membrane may allow blood compounds, such as proteins and cells to interact with surfactant constituents and vice versa. The aim of our study was to investigate surfactant-related effects on PMN since these cells are major effector cells of the primary immune and inflammatory response, involved in pulmonary failure. Methods: PMN, isolated from citrated blood of 3 healthy volunteers were allowed to interact with different surfactant preparations for a time of 30 minutes. Cell activation, reflected by PMN degranulation was detected by measurements of elastase-activity in the supernatant. Results: While NAP-2-induced elastase release was suppressed about by 70% at concentrations of more than 1.0 mg/ml of natural preparations Survanta® and Curosurf®, the only artificial preparation Exosurf® showed slightly stimulating effects. Alveofact®, in contrast seems to combine both, activating and inhibiting properties, interfering with each other. If unstimulated, PMN were not affected by the surfactant preparations. Conclusion: NAP-2-induced activation of isolated PMN is modulated by surfactant. Clinical implications of preparation related effects have to be elucidated.

Acute lymphoblastic leukaemia (ALL) was diagnosed in a 36-year-old and treated with cytarabin, daunorubicin, doxorubicin and cytarabin, thioguanin, respectively, in an unrecognized pregnancy at conception and at about 35-37 days p.c., Amniocentesis at 16 weeks of gestation revealed a normal female karyotype. At delivery, brachycephaly, hypoplasia of supraorbital bony structures and hypotelorism were seen. Hypoplastic nasal root, bilateral choanal atresia and micrognathia caused hypoplasia of naso- and oropharynx. There was also bilateral aplasia of the radius and hypoplasia of the first ray of the hands. Internally, an atrial septal defect II could be demonstrated. The malformations detected are in accord with the timing of teratogenesis. Neurodevelopment is normal at the age of 8 months. Experience with the use of cytotoxic drugs in pregnancy has so far been limited to folate antagonists.

127 SECONDARY HYPERPARATHYROIDISM IN A PRETERM INFANT CAUSED BY HIGH PLASMA PROTEIN CONCENTRATION

Objective: Comparing high-dose (initial dose 100 mg/kg b.w., HD) with low-dose (initial dose 50 mg/kg b.w.) bovine surfactant given during hour 1 after birth. Patients and methods: Inclusion criteria: GA 24 - 29 weeks, b.w. 500-1500 g, need for intubation and ventilation, absence of congenital malformations and bacterial infections. Retreatment (max. cumulative dose 200 mg/kg b.w.) was permitted if the FiO2 was >0.4. Endpoinf. HD surfactant treatment improves oxygenation (paO2/FiO2) 2 h post treatment compared with LD treatment (sequential analysis, type I and II error 5 % each). Secondary end-points: air leaks, BPD (FiO2 >0.3 or mechanical ventilation at 28 days), IVH (grade II - IV), PDA, ROP (> grade III) and NEC. 41 infants (GA 27.3 weeks, b.w. 991 g) were randomized to HD treatment, 46 infants (GA 27.2 weeks, b.w. 959 g) to LD treatment. Results: Oxygenation was improved significantly in HD compared to LD treatment (paO2/FiO2 181 ± 119.7 versus 228.4 ± 112.3). Further outcome: HD versus LD infants: air leaks 15/33 %, BPD 24/39 %, IVH 24/35 %, PDA 32/37 %, ROP 10/13 %, NEC 0/2 %, death 15/13 %. Conclusion: HD versus LD bovine surfactant treatment in very premature infants significantly improved oxygenation. A tendency towards decreased incidence of pulmonary air-leaks was observed.

Digoxin steady state plasma concentrations (Css) and the corresponding serum creatinine concentrations were studied in 17 VLBW infants. Birth weight was in the range of 760-1 500 g (mean 1 068 g), gestational age ranged from 26 to 32 weeks (mean 28.7 weeks). Digoxin steady state plasma concentrations were found in the range of 0.5-6.5 ng/ml (mean 1.88 ng/ml) during maintenance therapy with 1.6-8.4 micrograms/kg BW/24 h (mean 4.4 micrograms/kg BW/24 h) given in two divided doses intravenously. No digoxin-like immunoreactive substance could be detected in the plasma of 18 infants (10 patients with a birth weight less than or equal to 1 500 g, 8 patients with a birth weight of 2 100-4 730 g) that were not treated with digoxin. The calculated digoxin clearance ranged from 0.38-4.03 ml/min/kg BW. Serum creatinine concentrations were found in the range of 35-274 mumol/l (0.4-3.1 mg/100 ml). A hyperbolic correlation may be derived from the digoxin clearance and the corresponding serum creatinine concentration. A linear relationship was observed between the dose normalized digoxin concentrations (y = Css/dose in 24 h) and the respective creatinine concentrations x (y = 0.52x-0.05; n = 17; s = 0.24; r = 0.86; p less than 0.01). According to this equation we suggest a dosing schedule for digoxin in VLBW infants with impaired renal function. Digoxin maintenance dose is derived from the digoxin target and the creatinine serum concentration. This dose recommendation proved reliable on four VLBW infants (birth weight 770-1 260 g) with decreased renal function.

Four neonates who presented with coma secondary to hyperammonaemia resulting in central respiratory failure were treated with peritoneal dialysis for between 16 and 120 hours. Underlying diseases were maple-syrup-urine disease, propionic acidaemia and citrullinaemia in two patients. Clinical improvement was observed in three patients within 16 to 72 hours after institution of peritoneal dialysis. Biochemical analysis revealed a rapid reduction in plasma concentrations of leucine, isoleucine and valine as well as their alpha-keto-analogues in the infant suffering from maple-syrup-urine disease. Correction of ammonia, glycine, alanine and propionic acid concentrations was observed in the infant with propionic acidaemia 24–72 hours after institution of peritoneal dialysis. Severe hyperammonaemia (1000–2500 μmol/1) in two infants with citrullinaemia before peritoneal dialysis was treated successfully in one infant; whereas the second infant showed no clinical improvement despite amelioration of biochemical parameters. Glucose-absorption from peritoneal dialysis solution was in the range of 216–441 mg/kg/h.

Intrauterine bone mineral accretion can be achieved in VLBW infants when Ca and P are administered in sufficient quantities to result in an urinary excretion of both elements(1). We observed three ELBW infants (650g/26weeks; 780/26; 580/27) who developed serial rib fractures and general severe bone demineralization inspite of an individual Ca/P supplementation monitored by urine Ca/P concentrations(1). Retrospective comparison of all Ca and P concentrations in simultaneously taken plasma and urine samples showed P-excretion at low plasma P concentrations (1.1-1.9 μM), i.e. an DTPR. Renal threshold for P was 2.4-2.8 μM in age-matched controlls. Demineralization was a result of renal P wasting. In one severely growth retarded infant who was born after recording silent CTG this tubular defect was present shortly after birth. Two infants developed DTPR during combined antibiotic treatment for sepsis. Fosfomycin was suspected to have impaired tubular function. Conclusion: DTPR causes severe bone demineralization in preterm infants and interferes with monitoring the P supplementation by measuring urinary P concentrations. (l)Assessment of Ca and P requirements and prevention of osteopenia in VLBW infants. Pediatr. Res. 20:1050(1986).

CONTROLLED MULTICENTER CLINICAL TRIAL OF BOVINE SURFACTANT (SF-RI 1) FOR PREVENTION RESPIRATORY DISTRESS SYNDROME IN VERY PREMATURE INFANTS