Role of adenosine in the hypoxic ventilatory response of the newborn piglet.

The role of intracerebral adenosine levels in the control of ventilatory response to hypoxia was explored in 15 spontaneously breathing intubated piglets, 1-5 days old, sedated with chloral hydrate. Respiration was recorded via by a pneumotachograph. In all animals exposed to hypoxia (12% O2) for 10 minutes. There was an initial increase in ventilation followed by a late decrease (the biphasic ventilatory response). Both intravenous caffeine citrate (20 mg/kg) and an FiCO2 of 0.05 separately abolished or attenuated the late ventilatory depression associated with hypoxia. In the same piglets, the administration of 10 micrograms dipyridamole, a competitive inhibitor of adenosine receptors, directly into the cerebral ventricles abolished the hyperventilatory response to hypoxia. Conversely, the use of 20 micrograms intraventricular 8-phenyltheophylline abolished the late ventilatory depression associated with hypoxia. Neither drug had a direct effect on ventilation at the time of injection. These results suggest that adenosine is a part of the diphasic ventilatory response to hypoxia.

Pulmonary impedance as an index of severity and mechanisms of neonatal lung disease.

The measurement of resistive and elastic components of the respiratory system in neonates has been used to define disease severity and the response to therapy. The lung resistance (RL) and dynamic lung compliance (CLdyn) partition the impediment to gas flow into two components, each of which may be altered independently. The concept of lung impedance (ZLdyn) is the combined effect of the elastic and resistive loads presented to the respiratory muscles, which determines the gas flow that will result from the pressures generated by the respiratory muscles. In a first order system where RL and CLdyn are single values (independent of volume or respiratory rate), ZLdyn is the vector sum of the reactive [1/2 pi fb x CLdyn)] and resistive (RL) components at the infant's breathing rate (fb), if the transpulmonary pressure (Ptp) generated by the respiratory muscles during spontaneous respiration can be modeled mathematically by a sinusoidal function. Furthermore, the phase angle (theta) between the impedance and the resistive component will represent the relative magnitude of the resistive and reactive components. The validity of this model can be establishing by comparing the calculated theta to the observed temporal difference (measured theta) between the Ptp and flow derived from the polygraph tracing. This hypothesis was tested in 10 spontaneously breathing neonates with lung disease of differing etiology and severity. No significant difference was found between the measured and calculated theta values (mean difference, 1.2 +/- 3.9 degrees).(ABSTRACT TRUNCATED AT 250 WORDS)

Weaning to extubation directly from high-frequency oscillatory ventilation in an infant with cystic lung disease and persistent air leak: a strategy for lung protection.

We report the successful weaning and extubation of an infant from a SensorMedics 3100A high-frequency oscillator without returning to conventional ventilation. A 7-week-old term infant with respiratory syncytial virus bronchiolitis complicated by cystic pulmonary lesions repeatedly failed attempts to return to conventional ventilation from high-frequency oscillatory ventilation (HFOV) for weaning, because of recurrent pneumothoraces. A computed tomography of the chest revealed multiple well defined cysts of various sizes involving both lungs. Therefore, weaning to extubation from HFOV was proposed as a way of preventing further air leak. The weaning strategy consisted of a technique we refer to as "sprinting." Using this method, the patient was successfully extubated directly from HFOV, with no complications. A follow-up computed tomography of the chest showed marked improvement in the size of the cystic lesions. The patient was discharged home with no need for home oxygen therapy.

Use of a 12 French double-lumen catheter in a newborn supported with extracorporeal membrane oxygenation.

We present the first report of clinical experience with a 12 French double-lumen cannula in a newborn supported with venovenous extracorporeal membrane oxygenation. This cannula was used because the internal jugular vein could not accommodate a 14F double-lumen catheter. This newborn was on bypass for 94 h, and the highest plasma free hemoglobin noted at the end of that period was 56 mg/dl. The infant was successfully weaned from extracorporeal membrane oxygenation and discharged home at 35 days of age. We suggest that this 12F catheter may be beneficial and deserves further evaluation.

Pharmacodynamic effects and pharmacokinetic profiles of keto-doxapram and doxapram in newborn lambs.

Keto-doxapram (keto-dox), an oxidative metabolite of doxapram, is a possible ventilatory stimulating agent. Our study characterizes its ventilatory properties, pharmacodynamic effects, and pharmacokinetic profile, and those of its parent compound, doxapram. Two groups of five awake, unsedated, newborn lambs (2- to 6-d old) received, respectively, i.v. infusions of keto-dox or doxapram (2.5 mg/kg) over a period of 1 min. Ventilatory parameters were continuously recorded before and for 1 h after the drug infusion. The pharmacokinetic profiles of both drugs were determined from blood samples collected serially before and after drug injection. Both drugs stimulated ventilation. Keto-dox increased baseline minute ventilation by 46 +/- 6.1% and 27.8 +/- 8.1% (p less than 0.002) at 1 and 5 min, respectively, an effect that decreased after 5 min of infusion. Doxapram increased minute ventilation by 57 +/- 9% (p less than 0.002) at 1 min, and by 48 +/- 7% at 5 min, but its effect lasted for 20 min after injection. Compared with the effects of keto-dox, this doxapram increase was significantly higher (p less than 0.02). Also, doxapram, but not keto-dox, caused an increase in systolic blood pressure (from 110 +/- 3.5 to 118 +/- 3.4 mm Hg at 10 min, p less than 0.01), as well as a change in neuro-behavior. Both drugs exhibited a biexponential decay curve, characterized by a short alpha and a longer beta t1/2, but keto-dox has a faster elimination rate.(ABSTRACT TRUNCATED AT 250 WORDS)