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Biomedical subjects

L Gortner

Publications and source records attributed to L Gortner.

At least 55 records · Page 3Linked to original sources

Early versus late surfactant treatment in preterm infants of 27 to 32 weeks' gestational age: a multicenter controlled clinical trial.

OBJECTIVE: To investigate whether early (<1 hour after birth) surfactant administration would be superior to late treatment (2-6 hours after birth) in preterm infants. STUDY DESIGN: Randomized controlled multicenter clinical trial. PATIENTS AND METHODS: Prenatal randomization of all infants of 27 to 32 weeks' gestational age stratified by center after parental informed consent. Early treatment: 100 mg/kg body weight bovine surfactant (SF-RI1, Alveofact; Dr K. Thomae, Biberach, Germany) to infants requiring intubation after birth. Late treatment: identical dosage to infants requiring intubation up to 6 hours of age with the fraction of inspired oxygen >0.4 at 2 to 6 hours after birth. Primary endpoint: the time on mechanical ventilation. Main secondary endpoints: mortality, bronchopulmonary dysplasia, intraventricular hemorrhage >/=grade III, and periventricular leukomalacia. Sample size calculation: at least 280 infants to prove superiority of either approach (alpha = 0.05; beta = 0.90). RESULTS: Enrollment of 317 infants, 154 randomized to early surfactant treatment, 163 to late surfactant treatment. Study infants (all following data intent-to-treat groups: early versus late surfactant) were similar with respect to: gestational age, 29.5 +/- 1.6 weeks versus 29.7 +/- 1.6 weeks; birth weight, 1227 +/- 367 g versus 1269 +/- 334 g; and the rate of prenatal corticosteroids, 79.9% versus 72.8%. Duration of mechanical ventilation: 3 days (0-8) versus 2 days (0-6) (median, interquartile); further outcome variables: death or bronchopulmonary dysplasia (day 28) 25.9% versus 23.9%, mortality 3.2% versus 1.8%, intraventricular hemorrhage >/=grade III 6.5% versus 3.7%, and periventricular leukomalacia 5.2% versus 5.5% not differing statistically. CONCLUSION: In preterm infants with a high rate of prenatal glucocorticoids, early surfactant administration was not found to be superior to late treatment in terms of relevant outcome variables.

Drug Administration Schedule↗

Demonstration of fetal coronary blood flow by Doppler ultrasound in relation to arterial and venous flow velocity waveforms and perinatal outcome--the 'heart-sparing effect'.

This longitudinal observational study evaluates the stage at which coronary flow can be visualized by color-coded and pulsed wave Doppler sonography in fetuses with normal cardiac anatomy. Fetal biometry, echocardiography and Doppler examination of the umbilical and middle cerebral arteries, ductus venosus, inferior vena cava and umbilical vein were performed in 109 cases. Fetuses were divided into five groups based on the Doppler examination of the umbilical artery, birth weight and the ability to visualize coronary blood flow. Coronary blood flow was identified in six of 55 fetuses with normal growth who had normal Doppler studies and perinatal outcome. In these, visualization of coronary blood flow was possible after 31 weeks' gestation at a median gestational age of 37 weeks. Coronary blood flow was also visualized in ten of 54 fetuses with severe intrauterine growth retardation and highly pathological flow velocity waveforms in all vessels soon after a significant increase of venous indices in the inferior vena cava and ductus venosus. In these cases, coronary blood flow was identified at a significantly earlier gestational age (median 27 weeks). These fetuses had a poor perinatal outcome (average birth weight less than 3rd centile, mortality rate 50%, significantly lower umbilical artery blood pH and Apgar scores after 1 and 5 min). Intrauterine fetal death occurred in five fetuses after a median of 3.5 days following visualization of coronary blood flow. Median coronary peak blood flow velocities in the right coronary artery were higher in intrauterine growth-retarded than appropriate-for-gestational-age fetuses.

Blood Flow Velocity↗

Comparison of vancomycin and teicoplanin for prophylaxis of sepsis with coagulase negative staphylococci (CONS) in very low birth weight (VLBW) infants.

A prospective randomized study was performed to evaluate the efficacy of a low dose (5 mg/kg/day bid) vancomycin compared with a low dose (5 mg/kg/day once daily) teicoplanin therapy to prevent CONS sepsis in VLBW-infants. All infants received this therapy after their 4th day of life or after an eventual therapy of early onset sepsis as long as an i.v. line was in place or 1500 g body weight. Twenty-seven infants were treated with vancomycin (birth weight 1103 +/- 286 g, gest. age 28.8 +/- 1.9 weeks), 28 with teicoplanin (birth weight 1133 +/- 226 g, gest. age 29.04 +/- 2.2 weeks). The infants were observed for clinical and laboratory signs of sepsis. On day 4 of therapy and every 3rd day during therapy serum creatinine levels, tracheal aspirates, stool cultures and vancomycin/teicoplanin peak and trough levels were obtained. We could not detect any case of blood culture positive sepsis and 1 case of suspected sepsis (neg. blood cultures) in both groups, as compared with a former CONS sepsis rate of 24% in our institution's VLBW infants without antibiotic prophylaxis. Nine patients in the vancomycin and five in the teicoplanin group had tracheal colonization with CONS. In both groups peak and trough levels of antibiotics were in the bactericidal range. Serum creatinine was not normal in both groups. We conclude that teicoplanin is preventing CONS sepsis as well is vancomycin. The minimal inhibitory concentrations of both antibiotics against grampositive isolates in units using this strategy have to be observed carefully to detect emerging resistance.

Anti-Bacterial Agents↗

Do cardiac output and serum lactate levels indicate blood transfusion requirements in anemia of prematurity?

BACKGROUND: Whether and when to transfuse in anemia of prematurity is highly controversial. Some authors suggest transfusions simply if the hemoglobin (Hb) level is below a defined normal range. Others propose the use of clinical or laboratory parameters in anemic patients to decide whether to transfuse or not. HYPOTHESIS: A decreasing amount of circulating Hb should cause a compensatory increase in cardiac output (CO) and an increase in arterial serum lactate. MATERIALS AND METHODS: In 56 anemic preterm infants (not in respiratory or hemodynamic failure) we analyzed CO after the first week of life using a Doppler sonographic method. At the same time serum lactate levels, Hb levels and oxygen saturation were registered. Nineteen of these patients were given transfusion when they demonstrated clinical signs of anemia by tachycardia > 180/min, tachypnea, retractions, apneas and centralization (group 2). The remaining 37 patients were not transfused (group 1). Serum lactate, CO, heart rate (HR), oxygen delivery, respiratory rate, capillary refill and Hb were analyzed in both groups and in group 2 before and 12-24 h after transfusion. Data between groups 1 and 2 and in group 2 before and after transfusion were compared. RESULTS: In the 56 patients studied no linear correlation between Hb and CO or between Hb and serum lactate was found. Nor could any correlation be demonstrated between the other variables studied. Examining the subgroups separately, a negative linear correlation was demonstrated between serum lactate and oxygen delivery in group 2. No other significant correlations were detected. However, when the pre- and post-transfusion data were compared in group 2 (increase of Hb from 9.45 (SD 3.44) to 12.5 (SD 3.8) g/100 ml), the CO decreased from 281.3 (SD 162.6) to 224 (SD 95.7) ml/kg per min (p < 0.01) and serum lactate decreased significantly from 3.23 mmol/l (SD 2.07) before to 1.71 (SD 0.83) after transfusion. Oxygen delivery was 35.8 (+/- 0.19) ml/kg per min group 1, 27.8 (+/- 0.05) pre- and 43.4 (+/- 0.07) post-transfusion in group 2 (p < 0.01). CONCLUSIONS: CO measurements and serum lactate levels add little information to the decision-making process for blood transfusions, as neither CO nor serum lactate levels correlate with HB levels in an otherwise asymptomatic population of preterm infants. In infants where the indication for blood transfusion is made based on traditionally accepted clinical criteria, serum lactate is an additional laboratory indicator of impaired oxygenation, as it correlates significantly with oxygen delivery. A significant lower oxygen delivery in patients in whom blood transfusion is indicated and an increase in oxygen induced by transfusion demonstrate the value of these criteria in identifying preterm infants who benefit from transfusion.

Anemia, Neonatal↗

Exhaled nitric oxide in childhood asthma.

UNLABELLED: Endogenous synthesis of nitric oxide (NO) and its presence in exhaled air was observed in various species including humans. Particularly high levels were found in adults with bronchial asthma, possibly because of the underlying pulmonary inflammatory activity. We studied oral and nasal exhaled NO by chemiluminescence in 47 children aged between 6 and 10 years. Thirty children had bronchial asthma, 17 were healthy controls. In asthmatic children oral exhaled NO was 13.4 +/- 1.4 parts per billion (ppb) (mean +/- SEM), nasal exhaled NO was 21.7 +/- 1.5 ppb. In healthy controls oral exhaled NO was 7.2 +/0 1.0 ppb, nasal exhaled NO was 18.2 +/- 22 ppb. Oral exhaled NO was significantly higher in asthmatic children compared to healthy controls (P = 0.0017). Nasal exhaled NO did not differ significantly in the two groups. There was a significant negative correlation between oral exhaled NO and forced expiratory volume in 1 s (FeV1). No significant correlation between oral or nasal exhaled NO and other markers of obstructive lung function impairment, oral minute ventilation, the body mass index and the presence of upper respiratory tract infection could be found. CONCLUSION: Children with bronchial asthma have significantly higher levels of orally exhaled nitric oxide than healthy controls.

Asthma↗

Fetal intracerebral hemorrhage in the second trimester: diagnosis by sonography and magnetic resonance imaging.

Germinal matrix intraventricular hemorrhage has rarely been observed in the fetus. In most cases the etiology is clear. We report one case of prenatal diagnosis of a periventricular hemorrhage of uncertain etiology in a fetus of 22 weeks' gestation. For confirmation of the ultrasound diagnosis, antenatal magnetic imaging was performed. A male child was delivered in good condition at 37 weeks by Cesarean section. Postnatal ultrasound examination showed a cystic lesion in the right frontal lobe (10 x 10 mm) connecting with the right lateral ventricle. The development of the child at 18 months of age has been normal without any neurological impairment.

Adult↗

In vitro modulation of induced neutrophil activation by different surfactant preparations.

Endotracheal surfactant administration has gained an important role in the treatment of respiratory failure. Polymorphonuclear neutrophil granulocyte (PMN) activation mediated by chemoattractants, such as interleukin-8 (IL-8), neutrophil-activating peptide-2 (NAP-2) and formylated bacterial oligopeptides, has been found to be involved in the pathophysiology of acute respiratory failure. We investigated potential modulating effects of commercial surfactant preparations (Exosurf, Alveofact, Curosurf and Survanta) on spontaneous and chemoattractant-induced PMN function. Isolated cytochalasin B (CytB)-treated PMNs from healthy adults were incubated with increasing concentrations of surfactant. The response of the cells was measured in terms of elastase release from the lysosomes within 30 min. The PMNs showed no direct activation by any of the surfactants tested. However, when cells were stimulated with suboptimal dosages of chemokines, such as IL-8 (2 nM) or NAP-2 (100 nM), or formyl-methionyl-leucyl-phenylalanine (fMLP) (50 nM), and co-incubated with increasing concentrations of surfactant (0.05-8 mg.mL-1) the release of elastase was markedly modulated depending on the surfactant preparation used. Whilst Exosurf and Alveofact showed only modest effects on the elastase release induced by all three mediators, Curosurf and Survanta markedly inhibited the cellular response in a dose-dependent manner. At concentrations above 1 mg.mL-1, Curosurf and Survanta decreased the IL-8-, NAP-2- and fMLP-induced elastase release by 83, 67 and 90%, and by 82, 75 and 80%, respectively. In conclusion, exogenous surfactant may modulate the inflammatory response of the airways by affecting the chemoattractant-induced polymorphonuclear neutrophil activation. Surfactant preparations with inhibiting properties on neutrophil activation may participate in the prevention of neutrophil-induced lung damage.

Adult↗

Treatment of severe non-neonatal ARDS in children with surfactant and nitric oxide in a "pre-ECMO"-situation.

The use of exogenous surfactant and nitric oxide in neonates has reduced the number of infants requiring ECMO. The purpose of this study was to demonstrate whether these two therapeutic options might reduce the number of over 28 days old children with severe ARDS requiring ECMO, without reducing changes of survival and morbidity. Over a 30 month period all non-neonatal ARDS patients transferred to our institution for ECMO evaluation were treated based on a study-algorithm. If they did not fulfill "fast entry criteria" (paO2 < 40 for more than 3 hrs.) we first tried different ventilation, vasodilatation, and hemodynamic strategies for max. 4 hrs. (inv. I/E ratio, HFOV, epoprostenol, high doses norepinephrine. If the OI did not decrease by < 10, 30-280 mg natural surfactant or 1-20 ppm nitric oxide were treatment options depending on the degree of pulmonary hypertension measured by echocardiography and by mixed venous saturation measurements. It was possible to use NO and surfactant sequentially. The patients had different etiologies of ARDS as near drowning, pneumonia, immunosuppression, and sepsis. If their OI did not decrease by 10 in 8 hrs. ECMO was installed. Nineteen patients were evaluated, 6 improved with conventional therapy, their OI decreased without a relapse (mean OI at begin of the study: 38). Six patients improved with surfactant therapy alone (mean OI: 54), 4 patients improved after surfactant and sequential NO-treatment, 3 patients were initially treated with NO, 1 sequentially with surfactant. One patient did not show any benefit from NO or surfactant and was put on ECMO. Three patients died (withdrawal of life support because of severe brain damage caused by the underlying disease). We could not observe any respiratory related failure. No patient had to be discharged on oxygen. A sophisticated treatment algorithm integrating different modern ARDS treatment options can reduce the number of patients requiring ECMO. We speculate however that these options can only be used effectively in centers involved in ARDS treatment quite frequently and that these centers have to provide ECMO as one of their therapeutic tools.

Administration, Inhalation↗

Teratogenic effects in a case of maternal treatment for acute myelocytic leukaemia--neonatal and infantile course.

Experience with the use of cytotoxic drugs in the first trimester of pregnancy is limited. We report on the clinical phenotype and infantile development of a girl born to a 36-year-old mother. Before recognition of pregnancy, the latter had been treated for acute myelocytic leukaemia receiving cytarabine, daunorubicin and doxorubicin at conception and cytarabine and thioguanine at about 35-37 days post conception. At delivery, there were severe brachycephaly, hypoplasia of the anterior cranial base and the midface as well as synostoses of both coronal and metopic sutures. Further findings included bilateral four-finger hands with hypoplastic thumbs and absent radii. This phenotype is reminiscent of the Baller-Gerold syndrome. The child, at present 15 months old, has had to undergo two operations for fronto-orbital advancement because of insufficient growth of the mid-face, nasal airway hypoplasia and increased intracranial pressure. Motor milestones are slightly retarded--neurodevelopment is otherwise normal. These findings are discussed in the context of the few previous reports and are particularly important for future genetic counselling.

Abnormalities, Drug-Induced↗

High-dose versus low-dose bovine surfactant treatment in very premature infants.

The aim of the study was to determine if high-dose bovine surfactant (Alveofact, initially 100 mg/kg birth weight) would improve oxygenation compared with low-dose surfactant (50 mg/kg birth weight) administered intratracheally within 1 h after birth. Inclusion criteria included gestational age 24-29 weeks and birth weight 500-1500 g, intubation and mechanical ventilation, absence of congenital malformations and bacterial infections. Retreatment was considered if the fraction of inspired oxygen (FiO2) was > 0.4 (dose 50 mg/kg birth weight). The primary endpoint was level of oxygenation (PaO2/FiO2) 2 h after treatment. The study design was a sequential analysis using a triangular test with alpha = 0.05 and 95% power to detect a 25% improvement in the endpoint. Oxygenation was improved significantly with high-dose (n = 42) compared to low-dose treatment (n = 48): 30.9 +/- 15.0 kPa (231.5 +/- 112.7 mmHg) versus 24.1 +/- 15.7 kPa (180.6 +/- 118.0 mmHg) (mean +/- SD). The survival rate was 83% in both groups and the incidence of pulmonary interstitial emphysema was 33% versus 14% with the high-dose treatment. We conclude that high-dose surfactant significantly improved oxygenation and reduced lung barotrauma. An initial dose greater than 50 mg/kg birth weight of surfactant is required for optimal acute response.

Dose-Response Relationship, Drug↗

Diagnosis and treatment of necrotizing enterocolitis. A retrospective evaluation of abdominal paracentesis and continuous postoperative lavage.

From 1980 to 1991, 70 preterm and 20 term infants suffering from necrotizing enterocolitis (NEC) were treated at the University of Ulm hospitals. NEC was primarily suspected from clinical signs. The diagnosis was established by plain abdominal X-rays, infection markers and abdominal paracentesis. Indication for surgery resulted from paracentesis, from radiologically proven perforation, from ileus symptoms and from rapid clinical deterioration; 44 preterm and 7 term infants underwent surgery. Bowel resections were performed in 5 of the term and in 16 of the preterm infants. An enterostomy was fashioned in 33 cases. Total necrosis of the gut was apparent in 8 infants. A continuous peritoneal lavage was performed in 34 babies. One term and 18 preterm babies, all with a birth weight less than 1000 g, died. This results in a NEC-related overall mortality of 19%.

Decision Support Techniques↗

Rapid increase of blood pressure in extremely low birth weight infants after a single dose of dexamethasone.

Blood pressure was retrospectively studied in all 22 extremely low birth weight infants (ELBW) (birth weight median 720 g, range 450-1020 g) who were admitted between July 1989 and October 1991 and received dexamethasone on days 2-25 (median 10) because of bronchopulmonary dysplasia or since lung function had not improved after installation of bovine surfactant. The average blood pressure during the 4 h before dexamethasone increased significantly (median individual increase 8 mmHg, P = 0.0005) until 8-12h thereafter. In addition to the lung disease, ten infants showed severe arterial hypotension with prolonged capillary refilling time ( > 3s) and oliguria and needed continuous infusion of epinephrine to increase blood pressure and urinary flow after treatment with colloids, dopamine and dobutamine had proved ineffective. Epinephrine infusion could be stopped in eight infants 8 h after dexamethasone administration. In ELBW infants blood pressure rose 8-12 h after a single dose of 0.25 mg/kg dexamethasone. In ELBW infants suffering from arterial hypotension who do not respond to infusion of colloids and catecholamines, dexamethasone may represent a new therapeutic tool.

Blood Pressure↗