Fergus Leahy

Ventilatory response to 100% and 15% O2 during wakefulness and sleep in preterm infants

To examine the ventilatory response to 100% and 15% O2 during wakefulness and sleep, we studied eleven preterm infants birthweight 1770 +/- 102 g; gestational age 32 +/- 1 weeks; postnatal age 31 +/- 5 days) on two occasions each. Wakefulness (W) was present around feeding time and was defined by open eyes for more than 2 min plus presence of purposeful movements. Rapid eye movement (REM) and non-rapid eye movement (N-REM) sleep were defined using electroencephalogram (EEG), electrooculogram (EOG), electrocardiogram (ECG), and body movements. During 100% O2 breathing, immediate (30 s) decreases of 28, 39 and 37% followed by late (5 min) increases in ventilation (Ve) of 42, 49 and 27% were observed during W, REM and N-REM sleep (P greater than 0.05 between states). PaCO2 decreased significantly towards the end of 5 min of breathing 100% O2 in W, REM and N-REM sleep (P greater than 0.05). Average duration of apnea following sudden administration of 100% O2 was 8.5, 11.1 and 8.8 s during W, REM and N-REM sleep (P greater than 0.05 between states). During inhalation of 15% O2, there was a late decrease in ventilation of 19 and 23% during wakefulness and REM sleep, and a sustained increase in Ve of 17% during N-REM sleep (P less than 0.05). PaCO2 at the end of hypoxia (5 min) was significantly decreased in N-REM sleep only (P less than 0.05). We suggest that (i) peripheral chemoreceptor activity is qualitatively intact during W and sleep, as reflected by (a) the immediate changes in Ve during inhalation of high and low O2, and (b) apnea following administration of 100% O2. (ii) The late decrease in ventilation with hypoxia is absent in N-REM sleep.

Response to cold air hyperventilation in normal and in asthmatic children

To assess the sensitivity of isocapnic hyperventilation with cold air in detecting airway hyperreactivity in asthmatic children, we studied 13 asthmatic patients (mean age 11.1 years) and 10 normal children. Cold air challenge consisted of 4 minutes of moderate hyperventilation plus another 4 minutes of maximal hyperventilation, both with subfreezing air (-16 degrees to -18 degrees C). Exercise and IHCA tests were done within 5 days and in random sequence. Mean (+/- SE) maximal % delta FEV1 after IHCA was 27 +/- 5.1% in the asthmatic children vs 4.5 +/- 1.2% in the normal subjects (P less than 0.01), even though there were no significant differences in the maximal minute ventilation equivalent between the two groups. Mean maximal % delta FEV1 after exercise was 31.7 +/- 5.6 in the asthmatic group. There was no difference in the sensitivity of the exercise and IHCA tests to detect bronchospasm in asthmatic children. Airway obstruction after IHCA was sharp and brief: maximal at 3 minutes after challenge, and back to 10% of baseline after 11 minutes. In seven asthmatic children the refractoriness to cold air and exercise was studied by repeating each test within 30 minutes; all seven showed significant refractoriness to exercise, and six showed no refractoriness to IHCA. We conclude that exercise and cold air-induced bronchospasm have different physiologic mechanisms, and that cold air testing can be used as a routine challenge to identify airway hyperreactivity in children.

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.

Chemical control of respiratory frequency and tidal volume during sleep in preterm infants.

During a given sleep state, respiration changes from periodic to regular and vice-versa. Because such spontaneous changes occur without changes in electro-encephalogram (EEG), electro-oculogram (EOG), electro-cardiogram (ECG) or body movements, we hypothesized that they are induced by chemical stimuli such as CO2. To test this hypothesis we examined 12 preterm infants in whom spontaneous changes in respiratory pattern were allowed to occur within the same sleep state, and infants in whom such changes were induced by inhalation of 0.3% to 1.2% CO2. Using a nosepiece and a screen flowmeter we measured the respiratory pattern, VE, f, VT, TI, TE, Ttot, VT/TI, TI/Ttot and PACO2. In REM sleep, spontaneous changes from periodic to regular were associated with increase in VE from 0.466 (mean) to 0.530 L/min (P less than 0.5) and CO2 induced changes accompanied by an increase in VE from 0.416 to 0.571 L/min (P less than 0.05). Similarly in N-REM sleep, VE increased from 0.385 to 0.445 L/min (P less than 0.05) during CO2 induced changes, and from 0.420 to 0.454 L/min (P less than 0.05) during CO2 induced changes, and from 0.420 to 0.454 L/min (P less than 0.05) during CO2 induced changes. Increased VE produced both spontaneously or by CO2 administration was associated with decreased VT, decreased Ttot, decreased VT/TI and slight increase in PACO2. We suggest that changes in respiratory pattern occurring within the same sleep state are chemically mediated.

Desquamative Interstitial Pneumonia Responsive to Chloroquine

described by Liet~aw~ c>t al.’ Pathologically, the two characteristic features of I)IP are the proliferation of cells lining the alveolar spaces and the presence of desquamated cells packing the alveolar spaces. The cells lir7ir~f; the spaces are type II alveolar cells, and those iying free in the spaces are chiefly of macrophage origin. There are case reports of the development of fibrosing alvealitis some years after lung biopsy had revealed DIP.&dquo;’ DIP tends to have a better prognosis than most interstitial pneumonias because it is generatly more responsive to steroids,’ but cases unrest~ar~sive to steroid or cytotoxic therapy have been reported in children. We report an infant who was unresponsive to steroids alone, but responded to a combination of chlaracluirle and steroid initially, and later to chloroquine alone.

Cranial blood volume changes during mechanical ventilation and spontaneous breathing in newborn infants

We derived a noninvasive method to compare changes in cranial blood volume during mechanical ventilation with changes occurring during spontaneous breathing in newborn infants. In ten infants receiving mechanical ventilation, cranial blood volume increased during inspiration by a mean of 8.3%. We found a consistent relationship between clinical estimation of lung compliance and the amount of cranial volume expansion. During spontaneous breathing in ten infants cranial blood volume decreased during inspiration by a mean of 5.8%. The findings indicate the need for careful monitoring during periods of rapid changes in lung compliance.

Effect of lung inflation on ventilation and various phases of the respiratory cycle in preterm infants.

The effect of sudden and sustained lung inflation on inspiratory time (Ti), expiratory time (Te) and duration of apnea, as a translation of the Hering-Breuer reflex, has not been systematically analyzed in preterm infants. To examine such effects, 10 infants (body weight 1,550 +/- 110 g; gestational age 31 +/- 1 weeks) were studied. Lung inflation was obtained by applying negative pressure around the chest using a negative pressure incubator. After a control period, lung volume functional residual capacity was increased by an average of 14, 23, 34 and 53%. During lung inflation, Ti, Te, total respiratory cycle duration, incidence and duration of apnea increased. Minute ventilation decreased due to a decrease in frequency. Tidal volume decreased but not significantly. Inspiratory and expiratory flows decreased. These results (1) confirm the presence of the Hering-Breuer reflex in preterm infants, as reflected by increased Te and appearance of apnea during lung inflation; and (2) show that contrary to expectations, Ti increased significantly with lung inflation.

1138 QUANTITATIVE NON-INVASIVE METHOD OF MEASURING CEREBRAL BLOOD FLOW (CBF) IN THE NEWBORN

We devised a quantitative method to estimate CBF based on the principle of jugular occlusion. With gentle and short compression of both jugular veins there is an increase in head circumference (OFC) which reflects CBF. To make measurements quantitative we differentiated regression of OFC on skull volume: Y=59.1 (X) -1,608, where Y = skull volume and X = OFC. The formula obtained was CBF=355/Y.dx/dt in ml/100g/min. Method entails measurement of (1)OFC, using a mercury strain gauge. Change in OFC is measured as a slope when jugular veins are compressed. (2)Skull volume, using polystyrene cast of the infants skull filled with water, and volume measured. Comparing values to autopsy brain weights it is accurate within ±4%. (3)Monitoring intracranial venous and arterial flow by Dopplers taped over superior sagittal sinus and nearby artery. When veins are completely occluded flow stops. Alveolar CO2(PACO2) is simultaneously recorded. When values from complete occlusions and no interference with arterial flow are taken, results are reproducible. In 8 preterm infants (G.A. 34wk ±2 S.D.; B.W. 1.8kg ±.6 S.D.; age 9.4 days ±7.9 S.D.)the mean CBF was 67.1 ±13.6 S.E. ml/100g/min. The values are similar to those reported previously using the N2O method. During administration of 2% to 3% CO2, CBF increased to 97 ±24.1 S.E. Mean PACO2 increased from 38.7 ±1.2 to 43.4 ±1.1 S.E.,therefore the increase in CBF per mmHg PACO2 was 6.9 ml/100g/min. The 10% increase in CBF is double that reported for adults. We suggest that CBF in preterm infants is more sensitive to changes in PACO2 than adults.

NON-INVASIVE MONITORING OF ARTERIAL 02 SATURATION IN NEWBORN INFANTS

Ear oximetry is a simple non-invasive method for measurement of arterial O2 saturation (SaO2) in adults and older children. To evaluate the practicability and accuracy of ear oximetry in newborn infants, we have measured SaO2 in 12 newborns, ages 2.1 days ± 1 (SD) using Biox II-A oximeter and its small ear probe. 15 SaO2 measurements were done during mechanical ventilation (for HMD, diaphragmatic hernia, sepsis) and compared to actual (CO-OX) and calculated SaO2 from simultaneously obtained arterial blood. Blood pressure was in normal range at the time of study. Bilirubin and Hb levels were noted. There was excellent correlation between SaO2 measured by ear oximetry and CO-OX values (n=12; r=0.987) and calculated SaO2 (n=13; r=0.989)(range: 43-99%). SaO2 measured on the scrotum correlated equally well to CO-OX SaO2 (n=6; r=0.979). Bilirubin and Hb levels had no effect on differences between the various SaO2 measurement methods. Ear oximetry is an accurate and practical method for monitoring SaO2 especially in chronic hypoxemia situations during the neonatal period. Transcutaneous PO2 monitoring will be preferred for preterm infants at risk of hyperoxia. However ear oximetry has the advantages of easier application of the probe with less risk of skin burns, and thus longer continuous monitoring of SaO2 in hypoxemic newborn infants.

1223 THE EFFECTS OF LUNG INFLATION ON THE VARIOUS PHASES OF THE RESPIRATORY CYCLE IN PRETERM INFANTS

Traditionally the Hering-Breuer reflex has been assessed by the presence and length of apnea and/or prolongation of expiratory time (Te) during sustained lung inflation. In recent years a decrease in inspiratory time (Ti) during lung inflation has also been suggested as an indicator of the inflation reflex. Both Te and Ti have not been analyzed systematically in neonates with stratified increase in lung volume. We decided, therefore, to examine the effects of sudden and sustained lung inflation on Ti, Te , and duration of apnea in preterm infants. Ten babies (G.A. 31±1 wk; B.W. 1500±110g) were studied. Lung inflation was obtained by applying negative pressure around the chest using a negative pressure incubator. Response time of the system was less than .3 sec. After a control period, we increased lung volume (FRC) by 15%, 25%, 35%, and 60%. We measured Ti, Te, apnea and FRC before and during lung inflation. We found a significant increase in Ti, Te, and duration of apnea with an increase in FRC by as little as 15% (p<0.01). These results suggest: 1)preterm infants show significant increase in Te and duration of apnea during sustained lung inflation indicating potent Hering-Breuer reflex; 2)contrary to expectations, Ti increased significantly with lung inflation. We speculate that changes in Ti and Te during lung inflation are not exclusively vagal dependent and may reflect changes in chest wall reflexes or in respiratory muscle performance.