Victor Chernick

Effect of racemic epinephrine and salbutamol on clinical score and pulmonary mechanics in infants with bronchiolitis

To test the efficacy of a combined alpha- and beta-receptor agonist in acute bronchiolitis, we compared inhaled racemic epinephrine with salbutamol in a double-blind, crossover, randomized protocol. Twenty-four infants, 4.6 +/- 0.5 (mean +/- SEM) months of age, with their first episode of bronchiolitis were tested. After sedation with chloral hydrate, a clinical score and pulmonary mechanics measurements using simultaneous signals of airflow volume and transpulmonary pressure were recorded. After baseline measurements, infants received either nebulized salbutamol, 0.03 ml/kg, or racemic epinephrine, 0.1 ml/kg. Thirty minutes later, there was a significant decrease in clinical score after treatment with racemic epinephrine compared with the baseline score (p < 0.001); this difference was not present after salbutamol inhalation (p = 0.42). Only 13 patients had a decrease in clinical score after salbutamol therapy, in comparison with 20 infants treated with racemic epinephrine (p < 0.01). Both drug decreased respiratory rate, but the decrease was greater after the use of racemic epinephrine (p < 0.001). There was a significant decrease in inspiratory, expiratory, and total pulmonary resistance after treatment with racemic epinephrine compared with baseline values (p < 0.01) but no significant change after salbutamol inhalation. There was no significant correlation between the clinical score and pulmonary mechanics either at baseline or after drug treatment. We conclude that racemic epinephrine is superior to salbutamol in the treatment of infants with their first episode of acute bronchiolitis.

Unilateral hyperlucent lung syndrome inchildren

The clinical course and the results of laboratory investigations of 5 children withunilateral hyperlucent lung syndrome are presented. This syndrome appears to be an acquired disease that follows a viral bronchiolitis and pneumonitis in childhood. The adenovirus was a possible etiologic agent in 3 of the patients. The hyperlucent appearance of the lung was due to overdistention of alveoli plus a marked decrease in blood flow to the affected lung, which was smaller than normal. The ventilation of the affected side was diminished because of airway obstruction. Blood gas data obtained by selective catheterization of the pulmonary veins revealed a large intrapulmonary shunt on the affected side. Early in the course of the disease, the major branches of the pulmonary artery were not hypoplastic; it is suggested that the pulmonary artery hypoplasia, in part, results from a failure of growth on the affected side secondary to the bronchopulmonary pathology. Despite a major loss of functioning lung tissue, recurrent pulmonary infections and respiratory symptoms appeared to decrease with time.

Sleep, wakefulness and the monosynaptic reflex in fetal and newborn lambs

Abstract1.Electrocorticogram (ECoG), electromyogram (EMG) of the lateral rectus and antigravity muscles (neck and masseter) and breathing activity (FB) were monitored in chronically prepared fetal sheep of 125–140 days gestation and in newborn lambs up to 11 days postnatal age.2.Awake state (AW), non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM) were defined using standard criteria for ECoG, eye movements and postural muscle tone.3.The percentage of time the fetuses spent in each state was: NREM sleep 53%, REM sleep 41.4%, and AW 5.6%.4.Spontaneous intrauterine breathing activity occurred only during REM sleep, but 35% of REM sleep was not associated with FB.5.Gasps (isolated deep inspirations) appeared occasionally throughout the recording and were not related to any specific sleep state or wakefulness.6.In the fetus, the monosynaptic reflex (MSR) induced by direct electrical stimulation of the fibular nerve was enhanced by about 75% during REM sleep compared to NREM and AW. In the newborn lamb the adult pattern of suppression of MSR during REM sleep was not seen until several days after birth.

Effect of Feeding on the Chemical Control of Breathing in the Newborn Infant

Summary: To examine the influence of feeding on the chemical control of breathing in neonates, we studied the ventilatory response to 3% CO2 in air in nine bottle fed (BOT) and eight breast fed (BR) term infants during feeding while the infants were alert. Control responses were obtained either before or after feeding. VE, respiratory frequency, tidal volume, inspiratory time, expiratory time, and sum of inspiratory and expiratory time, VT/Ti, Ti/Ttot, PACO2 and slope (S) of CO2 response (liter/min/kg/mmHg) were determined. During 3% CO2 while resting BR had a lower VE, VT, VT/ Ti than BOT and S in BR was 40% of BOT (P < 0.05). During feeding and CO2 when compared to resting and CO2 there was no difference in either BR or BOT in VT/Ti but Ti/Ttot decreased in both groups. During feeding, S in BOT was reduced from 0.049 ± 0.012 (mean ± S.E.) to 0.013 ± 0.002 (74% reduction) and in BR from 0.020 ± 0.002 to 0.009 ± 0.002 (55%). Thus, behavioral activity (either BR or BOT) markedly depresses the ventilatory response to chemical stimuli (CO2). This modification is primarily related to changes in “effective” respiratory timing (Ti/Ttot) rather than mean inspiratory flow (VT/Ti).Speculation: This is the first demonstration in the newborn infant that behavioral activity (feeding) can override the usual ventilatory control mechanisms. The precise mechanism is unknown and requires further study.

Effects of Steroids on the Enzymatic Pathways of Lecithin Production in Fetal Rabbits

The present study was undertaken to study the effect of corticosteroids on lecithin production in fetal lung. Rabbit fetuses were injected intraperitoneally with hydrocortisone succinate at 24 days of gestation and sacrificed at 27 days. Lung DNA concentration was not changed, but evidence is presented to suggest that total lung DNA content was decreased by saline injection and by steroid injection. Minimum surface tension of pooled lungs was increased by control injections but was reduced to ‘normal’ levels by the steroids. Steroids caused no significant change in lung total phospholipid or lecithin contents. The specific activity of labelled choline, methionine and palmitate indicated increased incorporation of choline and palmitate into lung lecithin in steroid-injected fetuses. It is suggested that steroids accelerate fetal lung development by influencing the composition of surfactant at the alveolar surface.

Clinical trial of naloxone, in birth asphyxia+

To determine whether endogenous opiates play a role in the pathogenesis of perinatal asphyxia, a blinded clinical trial of naloxone, a competitive opiate receptor blocker, was undertaken in infants with low 1-minute Apgar scores. Of 85 infants with 1-minute Apgar score 0 to 3, 44 received an injection of naloxone (approximately 0.4 mg/kg) and 41 received saline solution. In 108 infants with 1-minute Apgar score 4 to 6, 54 received naloxone and 54 saline solution. In neither group was there a significant effect of naloxone on respiratory frequency or heart rate up to 30 minutes after injection, nor at 24 hours of age. In both groups active muscle tone of upper and lower limbs was increased by naloxone, a response that may not be beneficial in the face of inadequate oxygen delivery to vital organs. We conclude that naloxone at this dose had no readily apparent benefit in the resuscitation of the asphyxiated newborn infant.

Effect of a Soft Boston Orthosis on pulmonary mechanics in severe cerebral palsy.

Spinal braces such as the Soft Boston Orthosis (SBO) help stabilize scoliosis and improve sitting, positioning, and head control in individuals with cerebral palsy. However, their impact on pulmonary mechanics in this population has not been studied. We examined the effect of a Soft Boston Orthosis on the pulmonary mechanics and gas exchange in 12 children and young adults (5–23 years of age) with severe cerebral palsy. Pulmonary resistance, compliance, tidal volume, minute ventilation, work of breathing, oxygen saturation, and end‐tidal CO2 tension were measured with the subjects seated both with and without the orthosis and in the supine position without the orthosis.

Influence of sleep state on the response to hypercapnia in fetal lambs

The effect of sleep state on the respiratory response to hypercapnia was studied in 14 chronic fetal sheep, 125-140 days gestation. Fetal PaCO2 was raised by 11 to 34 Torr by gradually increasing the maternal FICO2 to 0.09. Fetal sleep state was monitored. Fetal breathing (FB) was analysed in terms of frequency (f), tracheal pressure (TP) and ventilation equivalent (VEq) = sigma TP /min. In 16 out of 17 experiments on apneic fetuses in NREM sleep, the fetuses switched to REM sleep and in 14 instances began to breathe within 2 1/2 min thereafter. The PaCO2 at which apneic fetuses started breathing was 54.8 +/- 8.4 Torr (mean +/- SD). In 4 out of 10 trials on breathing fetuses in REM sleep the fetuses switched to NREM sleep and stopped breathing before removal of the CO2 stimulus. During REM sleep hypercapnia stimulated FB by an increase in TP and by a reduction in the number and duration of apneic pauses. It is concluded that in the fetal lamb CO2 stimulates breathing only during REM sleep and that this stimulus is superimposed on the basic mechanism that stimulated spontaneous FB during this sleep state.

Acute bronchodilator response to a combination of beta-adrenergic and anticholinergic agents in patients with cystic fibrosis

Patients with cystic fibrosis had a better acute bronchodilator response to albuterol and ipratropium bromide than to either drug alone. Further studies of long-term efficacy and safety seem justified.

Sleep quality in children with asthma treated with theophylline or cromolyn sodium

The effect of theophylline and cromolyn sodium on sleep was studied in 10 children with asthma who were 10 to 17 years of age (mean 13.5 +/- 2.4 years). Theophylline or cromolyn sodium was taken for 14 days in a double-blind, crossover, placebo-controlled trial. Theophylline blood levels before sleep were 10.2 +/- 4 micrograms/ml during the theophylline period. There was no difference in pulmonary function between the two periods. Theophylline did not disrupt sleep as measured by sleep latency, total sleep time, sleep efficiency, movement time, microarousals, and arousals. Apneic episodes (greater than or equal to 10 seconds) were of central origin and less frequent during the theophylline period (p less than 0.05). Arterial oxygen desaturation (greater than 5% decrease from baseline saturation when awake) was less frequent during the theophylline treatment (p less than 0.05). We conclude that theophylline treatment of the childrens asthma did not disrupt sleep and appeared to have a protective effect in regard to apnea, hypopnea, and arterial oxygen saturation.