Karsten Harms

Surfactant treatment of neonates with respiratory failure and group B streptococcal infection

Objective. Connatal pneumonia caused by group B streptococcal (GBS) infection may be associated with surfactant dysfunction. We investigated the effects of surfactant treatment in term and preterm neonates with GBS infection and respiratory failure, in comparison with corresponding data from a control population of noninfected infants treated with surfactant for respiratory distress syndrome (RDS). Design/Methods. The study comprised 118 infants with respiratory failure, clinical and/or laboratory signs of acute inflammatory disease, and GBS infection proven by culture results. They were recruited retrospectively from a database of patients treated with surfactant at 28 neonatology units participating in European multicenter trials (1987–1993) and prospectively from the same units in the following years. A nonrandomized control group of 236 noninfected infants was selected from the same database. The primary parameters evaluated were oxygen requirement, ventilator settings, and incidence of complications. Results. Median birth weight in the GBS study group was 1468 g (25th–75th percentiles: 1015–2170), and median gestational age was 30 (27–33) weeks. Thirty-one percent of the infants weighed >2000 g. Median age at surfactant treatment was 6 hours. The mean initial surfactant dose was 142 mg/kg (standard deviation: 53). Ninety of the infants were treated with Curosurf (Chiesi Farmaceutici, Parma, Italy), 13 with Survanta (Abboth GmbH, Wiesbaden, Germany), 12 with Alveofact (Dr Karl Thomae GmbH, Biberach, Germany), and 3 with Exosurf (Wellcome GmbH, Burgwedel, Germany). Within 1 hour of surfactant treatment, median fraction of inspiratory oxygen was reduced from .84 (25th–75th percentiles: .63–1.0) to .50 (.35–.80). The incidence of complications in the study group (mortality: 30%; pneumothorax: 16%; intracranial hemorrhage: 42%) was high, compared with infants with RDS. Conclusions. Surfactant therapy improves gas exchange in the majority of patients with GBS pneumonia. The response to surfactant is slower than in infants with RDS, and repeated surfactant doses are often needed. The mortality and morbidity are substantial, considering the relatively high mean birth weight of the treated infants.

Randomized, controlled trial of amoxicillin prophylaxis for prevention of catheter-related infections in newborn infants with central venous silicone elastomer catheters☆☆☆★

OBJECTIVE To clarify the effectiveness of amoxicillin prophylaxis in the prevention of catheter-related infections. METHOD We performed a randomized, controlled, sequential, prospective trial in newborn infants undergoing percutaneous central venous catheterization. RESULTS Seventy-five infants (median birth weight, 1240 gm; median age at catheter insertion, 3 days) received prophylactic amoxicillin (100 mg/kg per day); 73 infants in the control group (median birth weight, 1170 gm; median age, 2 days) received no routine prophylactic antibiotic treatment. No infant receiving amoxicillin had septicemia, whereas two infants (2.7%) in the control group did; suspected septicemia (positive clinical and laboratory findings but negative blood culture results) was found in 3 infants in the amoxicillin group and in 6 of the control group (not significantly). Bacterial contamination of the catheter tip at removal was significantly reduced in the amoxicillin group (13.3% vs 28.8% in control subjects; p < 0.05). Negligible differences were found in duration of catheterization (median, 15 days in both groups), or the number of thrombotic (9.3% vs 2.7% in control subjects) and other catheter-related complications between the groups. CONCLUSION A low incidence of catheter-related infections can be achieved in neonates with central venous catheters without using prophylaxis with an antibiotic.

Airway humidification in mechanically ventilated neonates and infants: A comparative study of a heat and moisture exchanger vs. a heated humidifier using a new fast-response capacitive humidity sensor

OBJECTIVE To study the efficiency of a heated humidifier and a heat and moisture exchanger in mechanically ventilated neonates and infants. DESIGN Prospective, controlled, clinical study. SETTING University pediatric intensive care unit. PATIENTS Forty neonates and infants who needed mechanical ventilation were enrolled in the study. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS A heat and moisture exchanger and active airway humidification were alternately used in the same patients to exclude interindividual differences in airway humidification. Airway humidity was measured by a new fast-response capacitive humidity sensor which measures airway humidity with an acquisition rate of 20 Hz throughout the respiratory cycle. The humidity sensor was placed at the endotracheal tube adapter. Measurements were done at the beginning and at the end of three consecutive sessions of passive, active, and again passive airway humidification, each session lasting 6 hrs. There was no significant difference between mean inspiratory airway humidity with the heated humidifier (33.8 +/- 2.9 mg/L) and with the heat and moisture exchanger (34.0 +/- 2.6 mg/L). Moreover, the mode of airway humidification did not significantly influence body temperature or PCO2. No serious side effects such as endotracheal tube occlusion were observed. CONCLUSIONS Passive airway humidification by a heat and moisture exchanger is effective in mechanically ventilated neonates and infants over a 6-hr period. However, the performance and safety of a heat and moisture exchanger in prolonged mechanical ventilation remain to be proven.

Early versus late surfactant replacement therapy in severe respiratory distress syndrome

Abstract26 preterm infants with severe respiratory distress syndrome (RDS) have been treated at different ages with a single dose of natural porcine surfactant (Curosurf, 200 mg/kg). Criteria for treatment included clinical and radiological signs of severe RDS (grade III–IV), requirement of artificial ventilation and an FiO2 ≥0.6. Nineteen neonates have been subjected to early treatment (2–15 h of age, mean birth weight SD: 1201 ± 387 g) and 7 patients to late treatment (> 15 h to 48 h of age, birth weight SD 1624 ± 649 g). Average FiO2 before treatment was 0.88 in early-treated patients and 0.8 in late-treated patients, age at treatment was 4.6 h and 36 h, respectively (median). Both early- and late-treated infants exhibited an improvement in oxygenation (more than twofold increase of the PaO2/FiO2 ratio) within 5 minutes after initiation of therapy. Average duration of intermittent pressure ventilation was 15 days in the early treatment group and 19 days in the late treatment group. Total exposition to >21% oxygen was 21 days in early-treated and 48 days in late-treated infants. Pneumothorax occurred in none of the patients. All early treated infants survived without signs of severe bronchopulmonary dysplasia (BPD>21%O2, >90 days plus radiological changes). However, two out of seven late-treated infants developed severe BPD; one patient died as a consequence of cardiopulmonary deterioration. Two patients in the early treatment group died of nonpulmonary complications. We conclude that surfactant replacement therapy should probably be initiated as soon as possible after manifestation of severe RDS.

28 RANDOMIZED EUROPEAN MULTICENTER TRIAL OF SURFACTANT REPLACEMENT IN NEONATAL RESPIRATORY DISTRESS SYNDROME (RDS): SINGLE VERSUS MULTIPLE DOSES OF CUROSURF

There is now convincing evidence that the severity of neonatal respiratory distress syndrome can be reduced by surfactant replacement therapy; however, the optimal therapeutic regimen has not been found. The aim of this randomized European Multicenter Trial “Single versus multiple doses” was to reduce the incidence of RDS-associated pulmonary complications as well as mortality in patients receiving multiple doses of surfactant. In this trial, preterm infants (birthweight 700-2000 g) with severe RDS requiring artificial ventilation with FiO2 ≥0.6 were randomized into two groups at an age of 2-15 h. Exclusion criteria have been recently published (Pediatrics 1988, 82, 683-691). Both groups received immediately after randomization the usual dose of Curosurf (200 mg/kg). In infants randomized to receive multiple treatment, two additional doses of Curosurf (100 mg/kg) were instilled into the airway at the age of 12 h and 24 h, provided that the patient still needed artificial ventilation with an FiO2 >0.21. Interim analysis (n=245) showed a reduction of pneumothorax incidence (17% vs. 8,3%); single vs. multiple doses; additionally, the incidence of BPD (17% vs. 10%) and mortality (23% vs. 14%) was reduced in multiple treated patients. Final data of approximately 300 patients included in this trial - which will be finished in april 1990 - will be presented.

NEUTROPHIL ELASTASE IN TRACHEAL ASPIRATES OF INFANTS WITH RESPIRATORY DISTRESS SYNDROME (RDS)

Neutrophil Elastase (E) seems to play an important role in the pathogenesis of chronic lung disease (CLD) in premature infants; acute effects of this neutral protease on neonatal pulmonary disease have not been evaluated. In this prospective study we have analyzed E and α1-Proteinase-activity (α1-PI) in tracheal aspirates of 140 neonates with severe RDS (FiO2 > 0.6, mechanical ventilation) during the first day of life; all infants were treated with natural porcine surfactant (Curosurf).Results: In 42 infants (30 % [group 1]) a considerable activity of E was detected (0.8 - 253 μg/mg albumin, range); in 98 neonates (70 % [group 2]), who had protective levels of α1-PI, no E was found. Characteristics and disease severity were identical in both groups. Gestational age: 29.3 ± 2.3 weeks (group 1); 29,7 ± 2,2 (group 2). Using logistic regression analysis, 28 day outcome data of both groups showed an increased incidence of pulmonary interstitial emphysema (PIE) in patients with E-activity in tracheal aspirates (31.7 % vs. 17.5 %, group 1 vs. group 2, p < 0.05). The incidence of pneumothorax, CLD and non-pulmonary complications was identical in both groups.We conclude that Elastase present in the bronchoalveolar space of infants with RDS is associated with an increased risk of PIE.

167 INFLUENCE OF CLINICAL FACTORS ON MORTALITY AND MORBIDITY IN INFANTS WITH SERVERE RESPIRATORY DISTRESS SYNODROME |[lpar]|RDS|[rpar]| FOLLOWING SURFACTANT REPLACEMENT THERAPY

In an international multicenter trial infants with clinical and radiological signs of severe RDS were randomized to receive either a single dose (n=176) or three subsequent doses (n=167) of a porcine natural surfactant (Curosurf). Using a logistic regression model the effects of therapy, birth weight, sex, and other clinical factors on survival and various outcome parameters were evaluated. Results: Mortality (13vs.21%, p<0.05) and the incidence of pneumothoraces (9vs. 18%, p<0.01) were significantly lower in the multiple-dose group. Low birth weight, hospital allocation, low Apgar and initial disease severity were associated with an increased mortality. Low birth weight, hypothermia (admission temperature <36°C) and acidosis (pH<7.25) prior to surfactant treatment could be identified as risk factors for the development of an intracranial hemorrhage. Conclusion: Mortality and the incidence of pneumothoraces were significantly reduced after multiple-dose treatment of severe RDS as compared to a single dose regimen. 28 day outcome in surfactant treated infants is influenced by various clinical factors.

Surfactant replacement in severe RDS: effects of perinatal acidosis on therapeutic response

Respiratory distress syndrome (RDS) is still a major cause of morbidity and mortality in the neonatal period. Apart from immaturity of the surfactant system there are numerous conditions that can put infants at risk of developing RDS. From the clinical point of view it is virtually impossible to differentiate between RDS based on primary surfactant deficiency and RDS triggered or aggravated by other clinical conditions. It seems that some patients that we consider to have neonatal RDS really suffer from adult RDS even in the neonatal period [1–4].

27 Activity of Elastase and |[alpha]|1-proteinase inhibitor in bronchial secretions of premature infants suffering from severe respiratory distress syndrome (RDS) treated with a natural porcine Surfactant (Curosurf)

Proteolytic enzymes, especially elastase (E) released from neutrophils, seem to play a role in the pathogenesis of bronchopulmonary dysplasia (BPD). In some trials the combined incidence of death and BPD was shown to be reduced after surfactant replacement therapy in severe RDS.In a prospective study we have analyzed activities and concentrations of free elastase (E), α1-proteinase inhibitor (α1,-PI) and the enzyme inhibitor complex (E-α1-PI) in bronchial secretions of 52 premature infants suffering from severe RDS following surfactant replacement therapy. Within a randomized trial “single versus multiple doses of surfactant (Curosurf)” the enzyme inhibitor potential of patients with severe RDS was analyzed during the first 10 days of life.Results in 28/52 infants free elastase (E) was found in bronchial secretions (concentrations 0,8 - 162 μg/mg albumin). In these patients no free activity of α1-PI could be detected, however, E α1-PI was identical in all patients. Elastase was present especially in bronchial secretions of immature and Low birth weight infants. 21/28 infants in whom free elastase was detected had an gestational age <30 weeks. No differences in concentrations of free elastase were found between premature infants who received a single dose and those who received 3 subsequent doses of surfactant.Conclusions In all 52 cases the enzyme inhibitor complex <E α1-PI) could be demonstrated. The was no correlation between the concentration of E α1-PI and the activity of free elastase. Multiple treatment did not influence the imbalance between the activity of the enzyme and activity of α1-PI. Ue need sore knowlegde about factors that might influence the influx of neutrophils and the consecutive release of elastase into the bronchoalveolar space.