Effect of changes in lung volume on respiratory system compliance in newborn infants

Total respiratory system compliance (Crs) at volumes above the tidal volume (VT) was studied by use of the expiratory volume clamping (EVC) technique in 10 healthy sleeping unsedated newborn infants. Flow was measured with a pneumotachograph attached to a face mask and integrated to yield volume. Volume changes were confirmed by respiratory inductance plethysmography. Crs measured by EVC was compared with Crs during tidal breathing determined by the passive flow-volume (PFV) technique. Volume increases of approximately 75% VT were achieved with three to eight inspiratory efforts during expiratory occlusions. Crs above VT was consistently greater than during tidal breathing (P less than 0.0005). This increase in Crs likely reflects recruitment of lung units that are closed or atelectatic in the VT range. Within the VT range, Crs measured by PFV was compared with that obtained by the multiple-occlusion method (MO). PFV yielded greater values of Crs than MO (P less than 0.01). This may be due to braking of expiratory airflow after the release of an occlusion or nonlinearity of Crs. Thus both volume recruitment and airflow retardation may affect the measurement of Crs in unsedated newborn infants.     

Respiratory mechanics during halothane anesthesia and anesthesia-paralysis in humans

In six spontaneously breathing anesthetized subjects [halothane approximately 1 maximum anesthetic concentration (MAC), 70% N2O-30% O2], we measured flow (V), volume (V), and tracheal pressure (Ptr). With airway occluded at end-inspiration tidal volume (VT), we measured Ptr when the subjects relaxed the respiratory muscles. Dividing relaxed Ptr by VT, total respiratory system elastance (Ers) was obtained. With the subject still relaxed, the occlusion was released to obtain the V-V relationship during the ensuing relaxed expiration. Under these conditions, the expiratory driving pressure is V X Ers, and thus the pressure-flow relationship of the system can be obtained. By subtracting the flow resistance of equipment, the intrinsic respiratory flow resistance (Rrs) is obtained. Similar measurements were repeated during anesthesia-paralysis (succinylcholine). Ers averaged 23.9 +/- 4 (+/- SD) during anesthesia and 21 +/- 1.8 cmH2O X 1(-1) during anesthesia-paralysis. The corresponding values of intrinsic Rrs were 1.6 +/- 0.7 and 1.9 +/- 0.9 cmH2O X 1(-1) X s, respectively. These results indicate that Ers increases substantially during anesthesia, whereas Rrs remains within the normal limits. Muscle paralysis has no significant effect on Ers and Rrs. We also provide the first measurements of inspiratory muscle activity and related negative work during spontaneous expiration in anesthetized humans. These show that 36-74% of the elastic energy stored during inspiration is wasted in terms of negative inspiratory muscle work.     

Modalities of the hyperventilation of exercise in maximal triangular effort on the ergometry bicycle in 11-to-13-year-old boys

Tidal volume, respiratory frequency, ventilatory equivalent, mean inspiratory flow Vt/Ti, and respiratory timing Ti/Ttot were measured at each level of an incremental exercise in a group of 8 untrained boys. Breathing pattern of the child is characterized by a fast frequency and a small tidal volume. Ventilation at maximal exercise reaches 50% of adults mean value. For the same ventilation, Vt/Ti (when expressed in ml X mn-1 X kg-1) is higher in the child. That suggests a higher central inspiratory activity.     

Expiratory volume clamping: a new method to assess respiratory mechanics in sedated infants

During breathing under sedation via a two-way valve, airflow (V), volume (delta V), and airway pressure (P) were recorded in eight normal (N) infants, seven with reversible obstructive airway disease (ROAD), and seven with chronic lung disease (CLD). Intermittently, expiratory volume clamping (EVC) was applied, involving selective occlusion of the expiratory valve for three to five breaths. The latter produced cumulative increases in delta V that, due to progressive recruitment of the Hering-Breuer reflex, were accompanied by increasing expiratory plateaus in P (i.e., apneas). The resultant passive inflation delta V-P relationships were closely approximated by the expression: delta V = aP2 + bP + c, wherein a represented the pressure-related changes in chord compliance (Crs), b the Crs at P = 0, and c the difference between the dynamic end-expiratory and relaxation volumes of the respiratory system. Relative to N, the ROAD and CLD infants had significantly reduced weight-specific values of a/kg, their b/kg values were increased, whereas the c/kg measurements did not significantly vary. Moreover, for each subject we determined the net Crs/kg obtaining at P = 20 cmH2O (i.e., Crs20/kg), an estimate of the net deflation compliance; the passive respiratory time constant (tau rs) based on the slope of the expired delta V/V relationship; and the respiratory system conductance (Grs/kg). Relative to N, the mean Crs20/kg was significantly reduced only in the infants with CLD and, due to increases in tau rs, both patient groups depicted significantly diminished values of Grs/kg, suggesting the presence of airways obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory effects of naloxone

The respiratory effects of naloxone (200 micrograms X kg-1) on dogs, was studied measuring the parameters breath rate, inspiratory volume, breath minute volume, inspiratory time, total time of cycle, inspiratory volume/inspiratory time ratio, and inspiratory time/total time of cycle ratio. The statistical study was made by using the analysis of variance. Naloxone increases all the parameters studied as well as the response to CO2 while it decreases inspiratory time. The results suggest that there are opioid neurons in the respiratory centre. The blockade of the opioid receptors by naloxone almost explains the respiratory effects observed.     

Active and passive respiratory mechanics in anesthetized dogs

In six spontaneously breathing anesthetized dogs (pentobarbital sodium, 30 mg/kg) airflow, volume, and tracheal and esophageal pressures were measured. The active and passive mechanical properties of the total respiratory system, lung, and chest wall were calculated. The average passive values of respiratory system, lung, and chest wall elastances amounted to, respectively, 50.1, 32.3, and 17.7 cmH2O X l-1. Resistive pressure-vs.-flow relationships for the relaxed respiratory system, lung, and chest wall were also determined; a linear relationship was found for the former (the total passive intrinsic resistance averaged 4.1 cmH2O X l-1 X s), whereas power functions best described the others: the pulmonary pressure-flow relationship exhibited an upward concavity, which for the chest wall presented an upward convexity. The average active elastance and resistance of the respiratory system were, respectively, 64.0 cmH2O X l-1 and 5.4 cmH2O X l-1 X s. The greater active impedance reflects pressure losses due to force-length and force-velocity properties of the inspiratory muscles and those due to distortion of the respiratory system from its relaxed configuration.     

Respiratory mechanics during high-frequency oscillatory ventilation: a physical model and preterm infant study

Accurate mechanics measurements during high-frequency oscillatory ventilation (HFOV) facilitate optimizing ventilator support settings. Yet, these are influenced substantially by endotracheal tube (ETT) contributions, which may dominate when leaks around uncuffed ETT are present. We hypothesized that 1) the effective removal of ETT leaks may be confirmed via direct comparison of measured vs. model-predicted mean intratracheal pressure [mPtr (meas) vs. mPtr (pred)], and 2) reproducible respiratory system resistance (Rrs) and compliance (Crs) may be derived from no-leak oscillatory Ptr and proximal flow. With the use of ETT test-lung models, proximal airway opening (Pao) and distal (Ptr) pressures and flows were measured during slow-cuff inflations until leaks are removed. These were repeated for combinations of HFOV settings [frequency, mean airway pressure (Paw), oscillation amplitudes (ΔP), and inspiratory time (%t(I))] and varying test-lung Crs. Results showed that leaks around the ETT will 1) systematically reduce the effective distending pressures and lung-delivered oscillatory volumes, and 2) derived mechanical properties are increasingly nonphysiologic as leaks worsen. Mean pressures were systematically reduced along the ventilator circuit and ETT (Paw > Pao > Ptr), even for no-leak conditions. ETT size-specific regression models were then derived for predicting mPtr based on mean Pao (mPao), ΔP, %t(I), and frequency. Next, in 10 of 11 studied preterm infants (0.77 ± 0.24 kg), no-to-minimal leak was confirmed based on excellent agreement between mPtr (meas) and mPtr (pred), and consequently, their oscillatory respiratory mechanics were evaluated. Infant resistance at the proximal ETT (R(ETT); resistance airway opening = R(ETT) + Rrs; P < 0.001) and ETT inertance (P = 0.014) increased significantly with increasing ΔP (50%, 100%, and 150% baseline), whereas Rrs showed a modest, nonsignificant increase (P = 0.14), and Crs was essentially unchanged (P = 0.39). We conclude that verifying no-leak conditions is feasible by comparison of model-derived vs. distending mPtr (meas). This facilitated the reliable and accurate assessment of physiologic respiratory mechanical properties that can objectively guide ventilatory management of HFOV-treated preterm infants.     

Respiratory changes in thoracic muscle length during bronchoconstriction

The purpose of the present study was to assess the effects of bronchoconstriction on respiratory changes in length of the costal diaphragm and the parasternal intercostal muscles. Ten dogs were anesthetized with pentobarbital sodium and tracheostomized. Respiratory changes in muscle length were measured using sonomicrometry, and electromyograms were recorded with bipolar fine-wire electrodes. Administration of histamine aerosols increased pulmonary resistance from 6.4 to 14.5 cmH2O X l-1 X s, caused reductions in inspiratory and expiratory times, and decreased tidal volume. The peak and rate of rise of respiratory muscle electromyogram (EMG) activity increased significantly after histamine administration. Despite these increases, bronchoconstriction reduced diaphragm inspiratory shortening in 9 of 10 dogs and reduced intercostal muscle inspiratory shortening in 7 of 10 animals. The decreases in respiratory muscle tidal shortening were less than the reductions in tidal volume. The mean velocity of diaphragm and intercostal muscle inspiratory shortening increased after histamine administration but to a smaller extent than the rate of rise of EMG activity. This resulted in significant reductions in the ratio of respiratory muscle velocity of shortening to the rate of rise of EMG activity after bronchoconstriction for both the costal diaphragm and the parasternal intercostal muscles. Bronchoconstriction changed muscle end-expiratory length in most animals, but for the group of animals this was statistically significant only for the diaphragm. These results suggest that impairments of diaphragm and parasternal intercostal inspiratory shortening occur after bronchoconstriction; the mechanisms involved include an increased load, a shortening of inspiratory time, and for the diaphragm possibly a reduction in resting length.     

AMPA glutamate receptors and respiratory control in the developing rat: anatomic and pharmacological aspects

The developmental role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) glutamate receptors in respiratory regulation remains undefined. To study this issue, minute ventilation (V(E)) was measured in 5-, 10-, and 15-day-old intact freely behaving rat pups using whole body plethysmography during room air (RA), hypercapnic (5% CO(2)), and hypoxic (10% O(2)) conditions, both before and after administration of the non-N-methyl-D-aspartate (NMDA) receptor antagonist 1,2,3, 4-tetrahydro-6-nitro-2,3-dioxobenzo[f]quinoxaline-7-sulfonamide disodium (NBQX; 10 mg/kg ip). In all age groups, V(E) during RA was unaffected by NBQX, despite reductions in breathing frequency (f) induced by increases in both inspiratory and expiratory duration. During hypoxia and hypercapnia, V(E) increases were similar in both NBQX and control conditions in all age groups. However, tidal volume was greater and f lower after NBQX. To determine if AMPA receptor-positive neurons are recruited during hypoxia, immunostaining for AMPA receptor (GluR2/3) and c-fos colabeling was performed in caudal brain stem sections after exposing rat pups at postnatal ages 2, 5, 10, and 20 days, and adult rats to room air or 10% O(2) for 3 h. GluR2/3 expression increased with postnatal age in the nucleus of the solitary tract (NTS) and hypoglossal nucleus, whereas a biphasic pattern emerged for the nucleus ambiguus (NA). c-fos expression was enhanced by hypoxia at all postnatal ages in the NTS and NA and also demonstrated a clear maturational pattern. However, colocalization of GluR2/3 and c-fos was not affected by hypoxia. We conclude that AMPA glutamate receptor expression in the caudal brain stem is developmentally regulated. Furthermore, the role of non-NMDA receptors in respiratory control of conscious neonatal rats appears to be limited to modest, albeit significant, regulation of breathing pattern.     

Model analysis of respiratory responses to inspiratory resistive loads

Based on experimental inspiratory driving pressure waveforms and active respiratory impedance data of anesthetized cats, we made model predictions of the factors that determine the immediate (first loaded breath) intrinsic (i.e., nonneural) tidal volume compensation to added inspiratory resistive loads. The time course of driving pressure (P) was given by P = atb, where a is the pressure at 1 s from onset of inspiration and represents the intensity of neuromuscular drive, t is time, and b is a dimensionless index of the shape of the driving pressure wave. For a given value of active respiratory impedance, tidal volume compensation to added resistive loads increases with increasing inspiratory duration and decreasing value of b but is independent of a. Model predictions of load compensation are compared to experimental results.     

Development of CO2 sensitivity: effects of gestational age, postnatal age, and sleep state

To determine the independent effects of sleep state, gestational age, and postnatal age on eucapnic ventilation and steady-state CO2 sensitivity, nine premature (146 +/- 3 days) and eight full-term (168 +/- 2 days) monkeys, Macaca nemestrina, from accurately timed conceptions were studied serially over the first 3 wk of life. Minute volume (VE)/kg,tidal volume (VT)/kg, and respiratory frequency were quantitated during rapid-eye-movement sleep (REM) and nonrapid-eye-movement sleep (NREM)in room air and when animals were breathing varied concentrations of cO2 in 21% O2. Eucapnic VE/kg and CO2 sensitivity [(deltaVE/kg)/delta PaCO2] increased progressively with advancing postnatal age during NREM sleep in grouped term and premature animals. CO2 sensitivity was not significantly different between REM and NREM sleep except in full-term animals at the highest postconceptual age studied (189 +/- 2 days) when [(delta VE/kg)/delta PaCO2] was lower in REM sleep than in NREM sleep (209 +/- 54 vs. 301 +/- 71 ml.min-1.kg-1.Torr-1; P less than 0.05, paired-t test). Gestational age had no measurable effect on eucapnic ventilation or CO2 sensitivity. These results support the hypothesis that REM sleep-induced depression of CO2 sensitivity develops in the neonatal monkey with advancing postconceptual age.     

Contribution of central and reflex nervous activity to the rapid increase in pulmonary ventilation at the start of muscular exercise in man

To investigate the relative contributions of the central and peripheral neural drive to hyperventilation at the onset of muscular exercise, five volunteers were tested during the first ten breaths while performing both voluntary (VM) and passive (PM) ankle rotations with a frequency of 1 Hz and through an angle of 10 degrees. Resulting breathing patterns for the two movements were compared. Hypocapnic hyperventilation, found in both PM and VM, indicated its neural origin. Respiratory changes were higher in VM than in PM. In both experimental conditions, increases in ventilation (VE) depended more on respiratory frequency (f) than on tidal volume (VT). Moreover, increases in VT adapted, breath-by-breath, to values lower than the initial ones, while increases in f rose progressively. Expiratory time was reduced more than inspiratory time (TI); increases in inspiratory flow (VT/TI) depended to the same extent on changes in both TI and VT. Increases in expiratory tidal volume were initially higher than in inspiratory tidal volume, thereby producing a reduction in functional residual capacity. Because PM respiratory changes could be considered to be of nervous reflex origin only, the identical breathing patterns in PM and VM indicated that the hyperventilation found also in VM was mainly of reflex origin. The increase in VE was considered to be dependent on a greater stimulus from muscle proprioreceptors.     

Influence of tidal volume on respiratory compliance in anesthetized infants and young children

Recent studies have suggested a close association between total respiratory compliance (Crs) and tidal volume in anesthetized paralyzed infants who are being artificially ventilated. To investigate this further, the multiple occlusion technique was used to measure Crs in 20 anesthetized infants and young children (aged 1-25 mo) before elective surgery. Measurements were made after intubation 1) during spontaneous breathing (SB), 2) after administration of a non-depolarizing muscle relaxant with tidal volume and frequency mimicking that during SB, and 3) with the child still paralyzed but tidal volume approximately double that during SB. Compared with values obtained during SB, there was no significant change in Crs after paralysis when ventilation matched the child's own pattern (P greater than 0.2). When ventilated with the larger tidal volumes, the infants showed a highly significant increase in Crs (mean 62%, range 14-158%, P less than 0.0001). These results may have implications not only for studies performed during anesthesia but also when infants were monitored in the intensive care setting. Values of Crs obtained in ventilated infants may reflect both the mechanical behavior of the respiratory system and the pattern of ventilation at the time of measurement.     

Decay of inspiratory muscle pressure during expiration in conscious humans

In eight conscious spontaneously breathing adults we studied the decay of pressure developed by the inspiratory muscles during expiration (PmusI). PmusI was obtained according to the following equation: PmusI(t) = Ers X V(t) - Rrs X V(t), where V is volume and V is flow at any instant t during spontaneous expiration, and Ers and Rrs are, respectively, the passive elastance and resistance of the total respiratory system. Ers was determined with the relaxation method, and resistance with the interrupter method. All subjects showed marked braking of expiratory flow by PmusI. The mean time for PmusI to reduce to 50 and 0% amounted, respectively, to 23 and 79% of expiratory time. During expiration, 24-55% of the elastic energy stored during inspiration was used as resistive work and the remainder (45-76%) as negative work.     

Forced oscillatory impedance of the respiratory system at low frequencies

Respiratory mechanical impedances were determined during voluntary apnea in five healthy subjects, by means of 0.25- to 5-Hz pseudo/random oscillations applied at the mouth. The total respiratory impedance was partitioned into pulmonary (ZL) and chest wall components with the esophageal balloon technique; corrections were made for the upper airway shunt impedance and the compressibility of alveolar gas. Neglect of these shunt effects did not qualitatively alter the frequency dependence of impedances but led to underestimations in impedance, especially in the chest wall resistance (Rw), which decreased by 20-30% at higher frequencies. The total resistance (Rrs) was markedly frequency dependent, falling from 0.47 +/- 0.06 (SD) at 0.25 Hz to 0.17 +/- 0.01 at 1 Hz and 0.15 +/- 0.01 kPa X l-1 X s at 5 Hz. The changes in Rrs were caused by the frequency dependence of Rw almost exclusively between 0.25 and 2 Hz and in most part between 2 and 5 Hz. The effective total respiratory (Crs,e) and pulmonary compliance were computed with corrections for pulmonary inertance derived from three- and five-parameter model fittings of ZL. Crs,e decreased from the static value (1.03 +/- 0.18 l X kPa-1) to a level of approximately 0.35 l X kPa-1 at 2-3 Hz; this change was primarily caused by the frequency-dependent behavior of chest wall compliance.     

Changes in respiratory activity induced by mastication in humans.

We studied the influence of mastication on respiratory activity in nine healthy volunteers who were requested to masticate a 5-g chewing gum bolus at a spontaneous rate (SR) for 5 min and "at the maximum possible rate" (MPR) for 1 min. Significant increases in respiratory frequency were induced by SR mastication due to a decrease in both the inspiratory and expiratory time. Tidal volume displayed slight nonsignificant decreases, but minute ventilation and mean inspiratory flow significantly increased. The duty cycle (TI/TT) did not change significantly. Total airway resistance significantly increased. Both peak and rate of rise of the integrated electromyographic activity of inspiratory muscles presented marked increases, accompanied by the appearance of a low level of tonic muscular activity. Similar but more intense effects on respiratory activity were induced by MPR mastication; in addition, a significant decrease in tidal volume and a significant increase in TI/TT were observed. Rhythmic handgrip exercise performed at metabolic rates comparable to those attained during SR or MPR mastication induced similar changes in the drive and time components of the breathing pattern, although accompanied respectively by nonsignificant or significant increases in tidal volume. Furthermore, the frequency of SR mastication significantly entrained the respiratory rhythm. The results suggest that mastication-induced hyperpnea does not merely represent a ventilatory response to exercise but also reflects complex interactions between respiratory and nonrespiratory functions of the upper airway and chest wall muscles.     

Role of nitric oxide during hyperventilation-induced bronchoconstriction in the guinea pig.

Airway function is largely preserved during exercise or isocapnic hyperventilation in humans and guinea pigs despite likely changes in airway milieu during hyperpnea. It is only on cessation of a hyperpneic challenge that airway function deteriorates significantly. We tested the hypothesis that nitric oxide, a known bronchodilator that is produced in the lungs and bronchi, might be responsible for the relative bronchodilation observed during hyperventilation (HV) in guinea pigs. Three groups of anesthetized guinea pigs were given saline and three groups given 50 mg/kg N(G)-monomethyl-L-arginine (L-NMMA), a potent nitric oxide synthase inhibitor. Three isocapnic ventilation groups included normal ventilation [40 breaths/min, 6 ml/kg tidal volume (VT)], increased respiratory rate only (150 breaths/min, 6 ml/kg VT), and increased respiratory rate and increased volume (100 breaths/min, 8 ml/kg VT). L-NMMA reduced expired nitric oxide in all groups. Expired nitric oxide was slightly but significantly increased by HV in the saline groups. However, inhibition of nitric oxide production had no significant effect on rate of rise of respiratory system resistance (Rrs) during HV or on the larger rise in Rrs seen 6 min after HV. We conclude that nitric oxide synthase inhibition has no effect on changes in Rrs, either during or after HV in guinea pigs.     

Interrupter technique for measurement of respiratory mechanics in anesthetized cats

In six spontaneously breathing anesthetized cats (pentobarbital sodium, 35 mg/kg ip), airflow, changes in lung volume, and tracheal and esophageal pressures were measured. Airflow was interrupted by brief airway occlusions during relaxed expirations (elicited via the Breuer-Hering inflation reflex) and throughout spontaneous breaths. A plateau in tracheal pressure occurred throughout relaxed expirations and the latter part of spontaneous expirations indicating respiratory muscle relaxation. Measurement of tracheal pressure, immediately preceding airflow, and corresponding volume enabled determination of respiratory system elastance and flow resistance. These were partitioned into lung and chest wall components using esophageal pressure. Respiratory system elastance was constant over the tidal volume range, divided approximately equally between the lung and chest wall. While the passive pressure-flow relationship for the respiratory system was linear, those for the lung and chest wall were curvilinear. Volume dependence of chest wall flow resistance was demonstrated. During inspiratory interruptions, tracheal pressure increased progressively; initial tracheal pressure was estimated by backward extrapolation. Inspiratory flow resistance of the lung and total respiratory system were constant. Force-velocity properties of the contracting inspiratory muscles contributed little to overall active resistance.     

Effect of PEEP on the mechanics of the respiratory system in ARDS patients.

In patients with adult respiratory distress syndrome (ARDS) we studied the effect of positive end-expiratory pressure (PEEP) on respiratory mechanics. We used the technique of rapid airway occlusion during constant flow (V) inflation to partition the total respiratory system resistance (Rrs) into the interrupter resistance (Rint,rs) and the additional resistance (delta Rrs) due to viscoelastic pressure dissipations and time constant inequalities. We also measured static (Est,rs) and dynamic (Edyn,rs) elastance of the respiratory system. The procedure was carried out in nine ARDS patients at different inspiratory V and inflation volumes (delta V) at PEEP of 0, 5, 10, and 15 cmH2O. We found that during baseline ventilation (delta V = 0.7 liter and V = 1 l/s), Est,rs, Edyn,rs, and Rint,rs did not change significantly with PEEP, whereas delta Rrs and Rrs increased significantly only with PEEP of 15 cmH2O. The increase of delta Rrs and Rrs with PEEP was positively correlated with the concomitant changes in end-expiratory lung volume (P < 0.001). At all levels of PEEP, under iso-delta V conditions, delta Rrs decreased with increasing V, whereas at a fixed V, delta Rrs increased with increasing delta V. A four-parameter model of the respiratory system failed to fully describe respiratory dynamics in the ARDS patients, probably due to nonlinearities.     

Respiratory compliance during sedation, anesthesia, and paralysis in infants and young children

Although total respiratory compliance (Crs) has been shown to fall in adults on induction of halothane anesthesia, no successful paired studies have been reported in children. The multiple occlusion technique was used to measure Crs in 17 infants and young children during sedated sleep (CrsS) and shortly after, following induction of halothane anesthesia (CrsA). Crs fell in all but one infant after induction of anesthesia, with a mean fall of 34.7% (range 0-58%). This was accompanied by a reduction in tidal volume and increase in frequency in every case. In 7 of the 17 children, who were to be paralyzed for surgical purposes, Crs was also measured in this anesthetized-paralyzed state. When tidal volume administered during manual ventilation was similar to that observed during measurement of CrsA, Crs during this low-volume ventilation was similar to CrsA. When tidal volume was increased and Crs remeasured, there was a significant increase in every case, with the high-volume Crs within 10% of CrsS in all but one child, in whom there was a 31.4% increase with respect to CrsS. Changes in tidal volume accounted for approximately 50% of the variability in each state. These results demonstrate a highly significant fall in Crs in infants and young children after induction of halothane anesthesia. In addition it appears that this reduction in Crs can be reversed by paralyzing the child and manually ventilating with tidal volumes approximating those seen during sedation.