Multicenter controlled clinical trial of high-frequency jet ventilation in preterm infants with uncomplicated respiratory distress syndrome.

OBJECTIVE: To test the hypothesis that high-frequency jet ventilation (HFJV) will reduce the incidence and/or severity of bronchopulmonary dysplasia (BPD) and acute airleak in premature infants who, despite surfactant administration, require mechanical ventilation for respiratory distress syndrome. DESIGN: Multicenter, randomized, controlled clinical trial of HFJV and conventional ventilation (CV). Patients were to remain on assigned therapy for 14 days or until extubation, whichever came first. Crossover from CV to HFJV was allowed if bilateral pulmonary interstitial emphysema or bronchopleural fistula developed. Patients could cross over to the other ventilatory mode if failure criteria were met. The optimal lung volume strategy was mandated for HFJV by protocol to provide alveolar recruitment and optimize lung volume and ventilation/perfusion matching, while minimizing pressure amplitude and O2 requirements. CV management was not controlled by protocol. SETTING: Eight tertiary neonatal intensive care units. PATIENTS: Preterm infants with birth weights between 700 and 1500 g and gestational age <36 weeks who required mechanical ventilation with FIO2 >0.30 at 2 to 12 hours after surfactant administration, received surfactant by 8 hours of age, were <20 hours old, and had been ventilated for <12 hours. Outcome Measures. Primary outcome variables were BPD at 28 days and 36 weeks of postconceptional age. Secondary outcome variables were survival, gas exchange, airway pressures, airleak, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and other nonpulmonary complications. RESULTS: A total of 130 patients were included in the final analysis; 65 were randomized to HFJV and 65 to CV. The groups were of comparable birth weight, gestational age, severity of illness, postnatal age, and other demographics. The incidence of BPD at 36 weeks of postconceptional age was significantly lower in babies randomized to HFJV compared with CV (20.0% vs 40.4%). The need for home oxygen was also significantly lower in infants receiving HFJV compared with CV (5.5% vs 23.1%). Survival, incidence of BPD at 28 days, retinopathy of prematurity, airleak, pulmonary hemorrhage, grade I-II IVH, and other complications were similar. In retrospect, it was noted that the traditional HFJV strategy emphasizing low airway pressures (HF-LO) rather than the prescribed optimal volume strategy (HF-OPT) was used in 29/65 HFJV infants. This presented a unique opportunity to examine the effects of different HFJV strategies on gas exchange, airway pressures, and outcomes. HF-OPT was defined as increase in positive end-expiratory pressure (PEEP) by >/=1 cm H2O from pre-HFJV baseline and/or use of PEEP of >/=7 cm H2O. Severe neuroimaging abnormalities (PVL and/or grade III-IV IVH) were not different between the CV and HFJV infants. However, there was a significantly lower incidence of severe IVH/PVL in HFJV infants treated with HF-OPT compared with CV and HF-LO. Oxygenation was similar between CV and HFJV groups as a whole, but HF-OPT infants had better oxygenation compared with the other two groups. There were no differences in PaCO2 between CV and HFJV, but the PaCO2 was lower for HF-LO compared with the other two groups. The peak inspiratory pressure and DeltaP (peak inspiratory pressure-PEEP) were lower for HFJV infants compared with CV infants. CONCLUSIONS: HFJV reduces the incidence of BPD at 36 weeks and the need for home oxygen in premature infants with uncomplicated RDS, but does not reduce the risk of acute airleak. There is no increase in adverse outcomes compared with CV. HF-OPT improves oxygenation, decreases exposure to hypocarbia, and reduces the risk of grade III-IV IVH and/or PVL.

Effects of Carbicarb and sodium bicarbonate on hypoxic lactic acidosis in newborn pigs.

BACKGROUND: Use of sodium bicarbonate (NaHCO3) may result in intracellular acidosis due to the generation of CO2. Carbicarb, has been reported to be superior to sodium bicarbonate (NaHCO3) because of lesser generation of CO2. The present study was designed to investigate whether Carbicarb or NaHCO3 is superior to normal saline in the treatment of hypoxic lactic acidosis. METHODS: Hypoxia was induced by ventilation with 8% O(2) in 30 piglets with fixed ventilation. When the pH fell to < 7.2, hypoxia was reversed by placing the animals in 21% O2 (experiment 1) or 100% O(2) (experiment 2) and either saline, Carbicarb or NaHCO3 were given. Data were collected for 120 minutes after therapy. RESULTS: In both experiment 1 (severe acidosis, pH < or = 7.1) and 2 (moderate acidosis, pH < or = 7.2) use of Carbicarb and NaHCO3 increased the arterial carbon dioxide tension (pCO2) significantly (p < 0.05). With moderate acidosis: 1) use of alkalinizing agents compared to saline resulted in an initial improvement in arterial pH at 1 minute, but thereafter, the differences were not statistically significant; and 2) there were no differences in hemodynamic variables and plasma lactic acid concentration between the three groups. CONCLUSIONS: The data demonstrate that 1) both Carbicarb and NaHCO3 significantly increase arterial pCO2; and 2) use of either alkalinizing agent in moderate acidosis does not alter the course of acidosis.

Length of postexercise assessment in the determination of exercise-induced bronchospasm.

Exercise challenges were performed on 397 middle and high school athletes to detect unrecognized exercise-induced bronchospasm. All challenges were completed by a standard treadmill protocol and spirometry was performed prior to exercise and at 1, 10, 20, and 30 minutes after completion of the treadmill regimen. Using FEV1 as the diagnostic standard, we compared the number of students who had initial decreases of > or = 10%, > or = 15%, or > or = 20% at each of the four postexercise spirometric evaluations. FEV1 thresholds of > or = 10%, > or = 15%, and > or = 20%, when analyzed, identified 187, 125, and 90 subjects respectively with a positive response. The majority of those with a positive response were identified soon after completion of the exercise provocation; however, a larger than expected number of athletes had their initial drop in FEV1 > or = 20 minutes after cessation of exercise. This represented 9% to 14% of the total number of responders to exercise challenge. Protocols for evaluation of exercise-induced bronchospasm may need to be designed to include data points up to or beyond 30 minutes after exercise to avoid missing the late appearance of bronchospasm.

Determination of rebreathing oxygen consumption and derivation of oxygen delivery in intubated mongrel dogs after phlebotomy and isoproterenol infusion.

This study attempted to determine the correlation between oxygen consumption (VO2), pulmonary-capillary blood flow (QEPC), and oxygen delivery (DO2) by rebreathing and invasive techniques obtained over a range of hemoglobin concentration and cardiac output. Twenty mongrel dogs were instrumented with central arterial and venous catheters to determine DO2 by thermodilution cardiac output and standard formulas. The animals were administered isoproterenol in doses that increased DO2 and subsequently were serially phlebotomized by 30%, 40%, and 50% to decrease DO2. All animals were studied using a rebreathing technique to determine noninvasively VO2, QEPC, and DO2. Sixteen dogs completed the experimental protocol. A correlation analysis was carried out for VO2, QEPC, and DO2 obtained by the rebreathing and invasive methods. Thermodilution cardiac output increased from 3.91 +/- 1.77 L/min at baseline to 8.19 +/- 2.50 L/min during isoproterenol infusion. Hemoglobin varied from 12.21 +/- 1.26 gm% at baseline to 5.21 +/- 1.36 g% at 50% phlebotomy. Over this range of conditions, significant correlations were obtained between rebreathing VO2 and invasive VO2 (r = 0.80, p < 0.0001), rebreathing QEPC and invasive QEPC (r = 0.79, p < 0.0001), and rebreathing DO2 and invasive DO2 (r = 0.82 p < 0.0001). These data demonstrate that the rebreathing technique can be used to monitor oxygen metabolism over wide ranges of DO2.

The value of screening for risk of exercise-induced asthma in high school athletes.

Exercise challenges were performed on 166 middle and high school student athletes (aged 12 to 18 years) to evaluate undiagnosed exercise-induced asthma (EIA). Seventy-three percent were male, 70% were white, and 30% were black. All students completed a questionnaire and were briefly interviewed to elicit risk factors for EIA. Resting spirometry, exercise treadmill provocation, and postexercise spirometry at 1, 10, 20, and 30 minutes were performed. Twenty-two students had reductions in FEV1 > or = 15% from baseline; 15 of these had FEV1 reductions > or = 20%. Of students considered at risk for EIA by history or baseline spirometry (N = 48, 29%) eight (17%) demonstrated EIA after exercise. Of students with no risk factors (N = 118, 71%), 14 (12%) demonstrated EIA after exercise, but would not have been identified without exercise challenge. The overall incidence of EIA was 12%, a rate that is consistent with previous studies of college and Olympic athletes. Sixty-four percent of students identified with EIA were not considered at risk by routine screening methods. History and spirometry alone may not be adequate as screening tools for EIA in adolescents.

Controlled trial of beclomethasone dipropionate by nebulization in oxygen- and ventilator-dependent infants.

Parenteral glucocorticoids have been shown to be effective in the treatment of oxygen- and ventilator-dependent bronchopulmonary dysplasia. We conducted a randomized, prospective study using a nebulized, water-soluble form of beclomethasone dipropionate for the treatment of infants with oxygen- and ventilator-dependent lung disease. Newborn infants with chest x-ray changes consistent with bronchopulmonary dysplasia at 14 days of age were randomly assigned, in a paired sequential fashion by birth weight, to treatment (beclomethasone) or placebo (saline solution) groups. Treatment included three nebulized doses of beclomethasone (50 micrograms) or saline solution per day for 28 days. Measured variables included tidal volume, total dynamic compliance, and airway resistance. Weight gain, gender, and incidence of infection during therapy were also recorded. Pulmonary functions were measured before initiation of therapy and weekly thereafter. Thirteen infants, seven in the saline solution group and six in the beclomethasone group, met study criteria and completed treatment. Infants treated with beclomethasone had reductions in airway resistance that were significant in weeks 2, 3, and 4 (p < 0.05, p < 0.02, and p < 0.001, respectively). Dynamic lung compliance increased at weeks 3 and 4 (p < 0.01 and p < 0.05, respectively). As expected, tidal volume increased with weight and time, but there were no significant differences between groups. There were no differences between the groups in weight gain, gender, or infection. This study demonstrates that beclomethasone by nebulization (1) reduced airway resistance in oxygen-dependent neonates with bronchopulmonary dysplasia, (2) improved dynamic lung compliance, as reported with parenterally administered glucocorticoids, and (3) produced no apparent increase in the incidence of infection.

Unrecognized exercise-induced bronchospasm in adolescent athletes.

OBJECTIVE--As part of their preparticipation physical examinations, 1241 middle and high school student athletes completed a questionnaire and were interviewed to elicit risk factors for unrecognized exercise-induced bronchospasm (EIB). Spirometry was then performed when the students were at rest. RESEARCH DESIGN--All participants completed a questionnaire, were interviewed, and underwent baseline testing to determine forced expiratory volume in 1 second (FEV1). SETTING--All testing was performed in a school setting. SELECTION PROCEDURES--Athletes known to have EIB who were receiving appropriate treatment (46 athletes [4%]) and athletes with no risk factors based on medical history and normal results of spirometry (847 athletes [68%]) were eliminated from further evaluation. Students with medical histories indicating risk of unrecognized EIB and students with abnormal results of spirometry were eligible for exercise challenge by standard treadmill protocol. MEASUREMENTS AND RESULTS--Of the 348 eligible students, 230 (66%) completed the exercise challenge. Sixty-six of the 230 students had greater than 15% reduction in FEV1, and 50 of the 66 students had greater than 20% reduction, representing a 29% occurrence of previously undiagnosed EIB in a population of students identified with screening to be at risk of unrecognized EIB. Of the 179 students identified to be at risk based on medical history only, 28% had EIB. Of 33 students with positive results of spirometry but no medical history that put them at risk, 15% had EIB. Of the 18 students with medical histories that put them at risk and positive results of spirometry, 61% had EIB. Including the subpopulation with reduction in FEV1 of greater than 15%, students shown to be at risk after screening, and students previously identified as having EIB, 145 students were identified as having EIB (12%). CONCLUSIONS--These data are in accord with results of previously reported studies of college and Olympic athletes. The data may have implications for more extensive screening in the adolescent population.

Evaluation of the SonoClot Analyzer for the measurement of platelet function in whole blood.

A viscoelastometer, the SonoClot Coagulation Analyzer, has been proposed for use in the evaluation of platelet function. The purpose of this study was to evaluate systematically this instrument when used with whole blood. Under laboratory conditions, the coefficient of variation (cv) of determinations of whole blood activated clotting time (ACT) on the instrument was approximately 7.0 percent. In contrast, the cv of measurements on whole blood related to the graphic events associated with clot formation ranged from 9.2 to 41.7 percent. Because of the large and variable cvs associated with these measurements of clotting, the SonoClot Analyzer cannot presently be recommended for use in studies designed to examine quantitatively the clotting function in whole blood.

Compliance, alveolar-arterial oxygen difference, and oxygenation index changes in patients managed with extracorporeal membrane oxygenation.

Eighteen patients with meconium aspiration syndrome who failed conventional management were treated with extracorporeal membrane oxygenation (ECMO) for reversible respiratory failure. Dynamic lung compliance measurements were made prior to, during, and after ECMO support. P(A-a)O2 and oxygenation index (OI) measurements were calculated prior to and after ECMO support. Lung compliance decreased significantly comparing before-ECMO to during-ECMO, and increased significantly comparing during- to after-ECMO, but not comparing before- to after-ECMO measurements. P(A-a)O2 and OI decreased significantly from before to after ECMO. The improvement in oxygenation allowing removal from ECMO does not appear to be related to improved pulmonary mechanics, but may rather be secondary to increased effective pulmonary capillary blood flow.

Impaired interferon-alpha enhancement of neonatal monocyte phagocytosis.

Monocyte phagocytic activity was tested in 10 healthy term newborns using a latex phagocytic assay. The baseline phagocytic activity in the cord blood monocytes (37.7 +/- 3.8%) was comparable to adult controls (38.5 +/- 9.4%). When enhanced with 1,000 U/ml of alpha-interferon, the phagocytic activity was lower in cord blood monocytes (40.5 +/- 3.4%) than in the adult controls (47.9 +/- 10.6%), but this difference reached statistical significance only when the cord blood monocytes were enhanced with 2,000 U/ml reaching 43.6 +/- 4.3% in cord blood monocytes, as compared to 54.6 +/- 9.6% in adult controls. These findings may explain an inherent functional deficiency in the neonatal mononuclear phagocytic system which may not be evident during the quiescent phase of monocyte/macrophage activity, but may become apparent during an infectious challenge.

Noninvasive determination of effective (nonshunted) pulmonary blood flow in normal and injured lungs.

PEEP is utilized in acute respiratory failure to decrease intrapulmonary shunting and improve oxygenation. Despite these beneficial effects, PEEP may adversely affect cardiac output, thus reducing oxygen delivery. To monitor some of the cardiopulmonary effects of PEEP, we utilized a noninvasive rebreathing technique to measure effective (nonshunted) pulmonary blood flow (Qepr) and compared the results to those measured by thermodilution (Qepi) in normal and oleic acid-injured canine lungs. Qepr was highly correlated with Qepi (r = .92, r2 = .85, p less than .001) despite large variations in PEEP before lung injury (0 to 15 cm H2O) and after lung injury (0 to 20 cm H2O). This close correlation was found even with wide ranges in cardiac output (1.01 to 6.45 L/min) and intrapulmonary shunt fractions (0.03 to 0.67). This technique may prove valuable as a noninvasive method by which to monitor and adjust PEEP therapy in patients with acute lung injury.

Response of pulmonary mechanics to terbutaline in patients with bronchopulmonary dysplasia.

Terbutaline was administered to eight ventilator-dependent infants with evolving bronchopulmonary dysplasia to determine the potential for reductions in airway resistance. The drug was administered by nebulization through the endotracheal tube. Pre-treatment and post-treatment pulmonary mechanics measurements were performed. Patients had reductions in inspiratory (-14%, p = NS), expiratory (-47%, p less than .05) and total (-24%, p = NS) resistances. Tidal volume increased 36% (p less than .01). This study demonstrates that nebulized terbutaline can improve pulmonary mechanics in ventilator-dependent infants with evolving bronchopulmonary dysplasia.

Bilateral absence of the ulna in twins as a manifestation of the split hand--split foot deformity.

Bilateral absence of the ulna and ulnar rays in twin female infants are described as a manifestation of the split hand--split foot deformity (ectrodactyly). Family history revealed the father had a unilateral split hand. Given the wide variability of expression of this disorder and the availability of prenatal diagnosis, there is a need for obstetricians and pediatricians to recognize parents with this malformation and appreciate the potential for severely affected offspring.

The teething virus.

A prospective study was carried out on 500 teething infants which demonstrated that a new infectious agent, the human teething virus, is responsible for the febrile response that accompanies the eruption of deciduous teeth. Speculations are made concerning whether or not primary care physicians will began prescribing amoxicillin instead of Jack Daniel's to treat teething infants and their parents.

Controlled trial of dexamethasone in respirator-dependent infants with bronchopulmonary dysplasia.

A randomized trial was conducted of dexamethasone therapy in infants with bronchopulmonary dysplasia who were dependent on respirators and were not progressing clinically despite conventional treatment. Babies were admitted to the study if they had a roentgenogram and clinical diagnosis of bronchopulmonary dysplasia, were 2 to 6 weeks in age, weighed less than 1,500 g, had made no progress in weaning for the preceding five days, and were free of sepsis, patent ductus arteriosus, and congenital heart disease, and had had no intravenous fat for at least 24 hours. After parental consent was obtained, infants were randomly assigned to control or treatment groups. The study hypothesis was that with steroid treatment, babies could be weaned from the respirator within 72 hours and would show a significant improvement in lung compliance within that time. Sequential analysis exceeded criterion (P less than .05) when seven consecutive untied pairs showed weaning with dexamethasone and failure to wean in control infants. Pulmonary compliance improved by 64% in the treated group and 5% in the control group (P less than .01). No significant intergroup differences were noted in mortality, length of hospital stay, sepsis, hypertension, hyperglycemia, or electrolyte abnormalities. Study design permits the conclusion that dexamethasone can produce substantial short-term improvement in lung function, often permitting rapid weaning from the respirator, but long-term efficacy and safety must be demonstrated by further investigations.

Use of the rebreathing method in the differential diagnosis of congenital heart disease and persistent fetal circulation.

The differential diagnosis of congenital heart disease from persistent fetal circulation is clinically difficult and cardiac catheterization is often needed. The development of a safe, new technique for use of the rebreathing method has allowed the determination of effective pulmonary blood flow, lung tissue volume, lung diffusion capacity and functional residual capacity in 7 critically ill, ventilator-dependent infants at the bedside. Analysis of the data revealed highly significant differences for lung tissue volume and diffusion capacity, a minimally significant difference for effective pulmonary blood flow and no difference for functional residual capacity between the groups. Use of this method allows not only attainment of clinically useful information but also permits better insight into the pathophysiology of the disease state.