Meena Garg

Growth failure in bronchopulmonary dysplasia: Elevated metabolic rates and pulmonary mechanics

Growth failure is a major problem in infants with bronchopulmonary dysplasia (BPD), but the cause is unknown. We studied 13 infants with BPD but without other medical problems that could contribute to growth failure at 6 months corrected age. We measured resting oxygen consumption (Vo2), Pao2, airway resistance, specific airway conductance, and dynamic pulmonary compliance (Cdyn) by body plethysmography and growth. Growth failure was defined as height and weight less than the tenth percentile of the Babson growth curves. Vo2 in infants with growth failure and BPD was markedly elevated compared with that in control infants and infants with BPD and normal growth. Vo2 showed an inverse correlation with body weight in infants with BPD but not in control infants. Although Vo2 was inversely related to Cdyn, the total work of breathing only partially explained the increased metabolic demands of the growth failure group. We speculate that growth failure in infants with BPD is partially the result of increased metabolic demands from increased work of breathing but that other mechanisms may act to elevate the metabolic expenditure of these infants.

The impact of extracorporeal membrane support in the treatment of congenital diaphragmatic hernia

Neonates with congenital diaphragmatic hernia (CDH) treated by immediate surgical intervention and conventional ventilatory support have an overall poor survival. The potential of extracorporeal membrane oxygenation (ECMO) therapy to improve survival of infants with CDH remains controversial. Comparison was made in a single institutions pre-ECMO and post-ECMO survival statistics to establish efficacy of extracorporeal support for persistent pulmonary hypertension (PPH). This study was accomplished by stratifying patients by an oxygen index (OI). Sixty-eight patients were treated for CDH from 1977 to 1986 without ECMO. Fifty-eight patients underwent repair of CDH within the first 24 hours of life. Data could be retrieved for calculation of the OI in 46 patients. Nineteen patients developed an OI of 40 or greater; one survived (5%). Three of 27 patients with an OI less than 40 died (OIs = 34, 38, and 38). Thirty-one patients were treated from 1987 to 1989 and none were excluded from ECMO based on a minimum PO2. Fifteen had an OI less than 40 (range, 1 to 38), were treated conventionally, and 13 survived (87%). Sixteen patients had an OI greater than 40 and 13 qualified for ECMO. Nine of 13 survived (69%). Comparing pre-ECMO and post-ECMO survival for infants with an OI of 40 or greater (5% v 69%), there is a significant improvement in survival when ECMO is used (P less than .001). ECMO support offers a strong adjunct in management of neonates with CDH who develop PPH.

Low serum cortisol in term newborns with refractory hypotension.

OBJECTIVES:The aim of this study is to measure baseline serum cortisol levels and clinical response to glucocorticoid therapy in a group of term infants with refractory hypotension.STUDY DESIGN:Seven term newborns with refractory hypotension were included. Serum cortisol levels were drawn before initiation of glucocorticoid therapy and measured by either fluorescence polarization immunoassay or radioimmunoassay. Baseline blood pressures, heart rate, and inotropes doses were recorded at baseline, then 4, 8, 12, 24, 48, 72, and 96 hours after glucocorticoid therapy. Urine output and volume expanders the infants received were recorded 24 hours before and after glucocorticoid therapy. Dexamethasone was used at a starting dose of 0.2 mg/kg per day divided every 12 hours. The statistical analysis was done using analysis of variance with repeated measures and paired t-test.RESULTS:Serum cortisol levels of the infants ranged from 2.0 to 15.4 μg/dl. After initiation of glucocorticoid therapy, there was significant improvement of blood pressure. Vasopressors were rapidly weaned and discontinued within 72 hours. In three of seven infants, no volume expanders were required after initiation of steroids, and none needed volume expanders after 2 days. Urine output increased significantly within 24 hours. All infants survived.CONCLUSIONS:Glucocorticoids improved pressure and stabilized clinical conditions of a group of term newborns with refractory hypotension. Serum cortisol levels of these infants were relatively low. We speculate that a subset of critically ill term infants has relative adrenal insufficiency and glucocorticoid therapy may be essential.

Long-term pulmonary sequelae in children who were treated with extracorporeal membrane oxygenation for neonatal respiratory failure.

Objective. Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for neonates with intractable respiratory failure, but the long-term pulmonary outcome is unknown. Our aim was to investigate the long-term pulmonary sequelae of these children. Study Design. We studied 50 children at 11.1 ± 1.1 years (mean ± SD) who had been treated with neonatal ECMO for meconium aspiration syndrome (38%), sepsis (18%), sepsis with pneumonia (12%), congenital diaphragmatic hernia (12%), congenital heart disease (8%), persistent pulmonary hypertension of the newborn (6%), and respiratory distress syndrome (4%) and 27 healthy controls (10.8 ± 1.6 years). All subjects completed a respiratory questionnaire and performed pulmonary function and graded cardiopulmonary exercise testing. Results. Neonatal ECMO survivors had hyperinflation (median residual volume: 131%), airway obstruction (median forced expired volume in 1 second: 79%), lower oxygen saturation with exercise, and lower peak oxygen consumption than controls. The ECMO group achieved similar exercise minute ventilation to controls, with more rapid and shallow breathing. ECMO survivors had an increased frequency of exercise-induced bronchospasm. Those who required higher inspired oxygen tension and ventilator pressures after weaning from ECMO had lower forced expired volume in 1 second and oxygen saturation values. Conclusion. Neonatal ECMO survivors experience lung injury lasting into later childhood. Lung dysfunction correlates with the extent and duration of barotrauma and oxygen exposure as neonates.

Phospholipid and surfactant protein A concentrations in tracheal aspirates from infants requiring extracorporeal membrane oxygenation

To test the hypothesis that infants with severe respiratory failure and the need for extracorporeal membrane oxygenation (ECMO) are surfactant deficient, we measured the amount of surfactant phospholipids, disaturated phosphatidylcholine, surfactant protein A, and protein in tracheal aspirates from 22 infants, who received ECMO therapy for respiratory failure with meconium aspiration syndrome (n = 18) or pneumonia (n = 4). Tracheal suction material was obtained in a standardized way every 4 hours during the period of ECMO treatment and pooled for 24-hour periods. During ECMO, mean total phospholipid, disaturated phosphatidylcholine, and surfactant protein A values in tracheal aspirates increased and protein values decreased significantly, predominantly during the 72-hour period before infants were weaned from ECMO. Of the 22 infants, 14 had an increase in tracheal aspirate phospholipid values of more than 200% and were found to need a shorter period of ECMO support (p less than 0.005) and post-ECMO ventilatory support (p less than 0.025) than did the eight infants with stationary or only moderate increases in tracheal aspirate phospholipid values, three of whom had pneumonia. We conclude that infants with respiratory failure who require ECMO treatment often have surfactant deficiency. We speculate that surfactant treatment might decrease the need for or the duration of ECMO support.

Intratracheal pulmonary ventilation versus conventional mechanical ventilation in a rabbit model of surfactant deficiency.

ABSTRACT: Intratracheal pulmonary ventilation (ITPV) enhances the clearance of CO2 from dead space and lungs by a bias flow of gas administered in the distal trachea. ITPV flow is continuously administered through a separate catheter placed within an endotracheal tube (ETT). After exiting from catheters tip in the distal trachea, the flow of gas is redirected outward away from the lungs. We hypothesized that, compared with conventional mechanical ventilation (CMV), ITPV may increase minute CO2 clearance (Vco2), reduce the partial pressure of CO2 dioxide in arterial gas (Paco2), and reduce distal tracheal peak inspiratory pressure (dPIP). We induced surfactant deficiency in 15 adult rabbits by lung lavage with 10 mL/kg normal saline. Animals were ventilated through a double-lumen 4.0 ETT, inserted through a tracheotomy incision. dPIP, distal positive end expiratory pressure, and distal mean airway pressure were monitored, and the mean exhaled CO2 concentration was measured. For ventilator rates (respiratory rate) of 30, 45, and 70 breaths/min, the study included two phases: phase I compared CO2 clearance and Paco2 between ITPV and CMV using similar ventilatory pressures; phase II evaluated the effectiveness of ITPV in reducing dPIP and tidal volume (Vt), compared with CMV, while maintaining eucapnea. When comparing ITPV and CMV, the following results (mean ± SD) were achieved at respiratory rate of 30, 45, and 70 breaths/min, respectively. Phase I ITPV resulted in mean percent reduction of Paco2 by 31.4 ± 10%, 37.1 ± 9.7% and 38.3 ± 9%; mean percent increase in Vco2 by 61.3 ± 29%, 56 ± 23%, and 98 ± 40%, compared with CMV. Phase II ITPV resulted in mean percent reduction of dPIP by 35.5 ± 14%, 38 ± 10.8%, and 37.2 ± 13.7%, and mean percent reduction in Vt by 34.7 ± 12.9%, 36.4 ± 15%, and 52.7 ± 10.7%, compared with CMV. The changes in Paco2, Vco2 (phase I), and dPIP and Vt (phase II) were all significantly more than 25% (p < 0.05). Oxygenation and pH were not significantly different between ITPV and CMV. We conclude that, in a surfactant deficiency rabbit model, ITPV is an efficient mode of assisted ventilation that increases CO2 clearance and reduces ventilator pressures required for adequate ventilation. We speculate that ITPV can minimize lung barotrauma associated with mechanical ventilation.

Non-Radiographic Weaning of Mean Airway Pressure (MAP) during High Frequency Oscillatory Ventilation (HFOV) in Adult New Zealand Rabbits 1695

Non-Radiographic Weaning of Mean Airway Pressure (MAP) during High Frequency Oscillatory Ventilation (HFOV) in Adult New Zealand Rabbits 1695

Low Plasma Cortisol In Term Infants With Refractory Hypotension. 1076

Low levels of circulating plasma cortisol have been reported in extremely low birthweight infants (ELBW) with hypotension refractory to vasopressors and volume expansion (Pediatrics 1993; 92:715). This is thought to be related to adrenal immaturity and has been shown to respond to glucocorticoid therapy. Based on clinical observations we theorized that a subset of term infants might also be incapable of synthesizing/secreting adequate cortisol in response to prolonged stress. Serum cortisol levels were obtained prior to initiating steroid therapy in term infants with refractory hypotension. Five were identified who had significant hypocortisolemia (2.3, 3.3, 5.6, 9.1, 15.4 mcg/dl). All had required inotropes and repeated volume expansion to maintain adequate blood pressure and urine output. Birthweight was 2.4 to 3.5 kg, gestational age 38-41 weeks and age 1-5 days. Diagnoses were congenital diaphragmatic hernia (n=2), meconium aspiration syndrome, meconium peritonitis, and hypoplastic left heart syndrome. Four were on dopamine (5-20 mcg/kg/min) and dobutamine (4-15 mcg/kg/min) and one was on epinephrine. All had received between 20 and 94 cc/kg of 5% albumin and/or fresh frozen plasma in the 24 hours prior to measurement of plasma cortisol. Blood cultures were negative. Echocardiograms revealed normal systolic function. All five infants were treated with dexamethasone 0.2 mg/kg/day. Vasopressors were weaned rapidly and discontinued within 72 hours in 4/5 patients. In 2/5 no volume expanders were required after initiation of steroids; none needed volume after 3 days. Urine output improved from 1.6 to 5.2 cc/kg/hr. All five infants survived. We conclude that a subset of critically ill term infants with refractory hypotension lack the ability to mount either an immediate or a sustained glucocorticoid response to stress. Steroid therapy results in rapid improvement in blood pressure and urine output. Whether, as in ELBW infants, this is the result of developmental delay or is secondary to some other mechanism remains to be determined.

Reduction of respiratory system resistance of rabbits with surfactant deficiency using a novel ultra thin walled endotracheal tube

&NA; The ultra thin walled, two‐stage endotracheal tube (UTW‐TS‐ETT) is very flexible, nonkinking, and has a widened extralaryngeal portion. The UTW‐TS‐ETT has a greater ID/OD (internal diameter/outer diameter) ratio than a comparable standard endotracheal tube (ST‐ETT) because of its thinner wall: 0.2‐0.25 mm in UTW‐TS‐ETT, compared to 0.55‐0.8 mm in ST‐ETT. The authors hypothesized that in an animal model of lung disease, significant reductions in respiratory system resistance (Rrs) of 30‐40% would be achieved using the UTW‐TS‐ETT, compared to Rrs achieved with the comparable ST‐ETT. This study compared the pulmonary mechanics of rabbits (N = 17, body weight 3.4‐4.7 kg) before and after induction of surfactant deficiency, using either ST‐ETT (OD 4.9 mm, ID 3.5 mm) or UTW‐TS‐ETT (OD 5.0 mm, ID 4.6 mm). Animals were sedated, paralyzed, and ventilated by an ETT placed through a tracheotomy incision. Surfactant deficiency was induced by lavaging the lungs with normal saline (10 ml/kg). Pulmonary mechanics were measured on identical ventilator settings for each ETT used at baseline and at 45 min after lavage. Compared to ST‐ETT, UTW‐TS‐ETT reduced Rrs by 50.6 ± 8.7% in normal lungs (significantly more than 40%; p < 0.01), and by 41.47 ± 16.2% in surfactant deficient lungs (significantly more than 30%; p < 0.05). Tidal volume increased with UTW‐TS‐ETT in all animals but did not achieve statistical significance. The UTW‐TS‐ETT did not induce significant changes in respiratory system compliance, PaO2, PaCO2, or pH. It is concluded that UTW‐TS‐ETT significantly reduces Rrs in rabbits with either normal lungs or with surfactant deficient lungs. This novel ETT may be beneficial for ventilated patients with increased Rrs, by effecting a decrease in Rrs and thus reducing the work of breathing and improving ventilation efficiency. ASAIO Journal 1996;42:1000‐1005.

Effect of Infant Sleeping Position on Lung Function and Gas Exchange in Preterm Infants ♦ 1946

Effect of Infant Sleeping Position on Lung Function and Gas Exchange in Preterm Infants ♦ 1946