Ventilatory responses after major surgery and high dependency care.

BACKGROUND: Disturbed breathing during sleep, with episodic upper airway obstruction, is frequent after major surgery. Ventilatory responses to hypercapnia and hypoxia during episodes of airway obstruction are difficult to investigate because the usual measure, that of ventilation, has been attenuated by the obstruction. We simulated the blood gas stimulus associated with obstruction to allow investigation of the responses. METHODS: To assess ventilatory responses, we studied 19 patients, mean age 59 (19-79), first at discharge from high dependency care after major abdominal surgery and then at surgical review, ~6 weeks later. Exhaled gas was analysed and inspired gas adjusted to simulate changes that would occur during airway obstruction. Changes in ventilation were measured over the following 45-70 s. Studies were done from air breathing if possible, and also from an increased inspired oxygen concentration. RESULTS: During simulated obstruction, hypercapnia developed similarly in all the test conditions. Arterial oxygen saturation decreased significantly more rapidly when the test was started from air breathing. The mean ventilatory response was 5.8 litre min(-2) starting from air breathing and 4.5 litre min(-2) with oxygen breathing. The values 6 weeks later were 5.9 and 4.3 litre min(-2), respectively (P=0.05, analysis of variance). There was no statistical difference between the responses starting from air and those on oxygen. CONCLUSIONS: After major surgery, ventilatory responses to hypercapnia and hypoxaemia associated with airway obstruction are small and do not improve after 6 weeks. With air breathing, arterial oxygen desaturation during simulated rebreathing is substantial.

The influence of ectopic heart beats in gated ventricular blood-pool studies.

Direct data collection from ventricular blood-pool studies were stored in frame mode in a computer and by means of a modified tape recorder, the blood-pool image and ECG were recorded on tape. At the end of the study the tape data were replayed into the computer. The ECG signal was passed through a trigger circuit that detected the R wave which was sampled by the computer once every msec. Contractions outside of the desired range could be rejected along with the subsequent contraction. Of seven patients whose calculated ejection fractions were changed by more than 0.03, all had frequent (one in 20) ectopic contractions. The distorted ventricular volume curves were effectively restructured by the constraining procedure, changing the end-systolic volume and EF. Computer modeling showed a linear relationship between the percent of ectopic contractions and the underestimate of ejection fraction. One ectopic beat in ten led to a 5% underestimate of EF.

Predictors of survival in patients with chronic obstructive pulmonary disease treated with long-term oxygen therapy.

Long-term oxygen is the only therapy that has been shown to improve survival in patients with chronic obstructive pulmonary disease. The aim of this study was to assess the predictors of survival in such patients treated with long-term oxygen therapy. We studied 179 patients who were assessed for long-term oxygen therapy in two Departments of Respiratory Medicine: in Warsaw and in Edinburgh. Those who died following the prescription of long-term oxygen therapy had a similar forced expiratory volume in the first second (FEV1) and arterial carbon dioxide tension, but a slightly lower arterial oxygen tensions (p less than 0.05) than those who survived (p less than 0.05). A small but significant fall in FEV1 and a rise in arterial carbon dioxide tension (p less than 0.05) occurred in both survivors and nonsurvivors after treatment with oxygen, but arterial oxygen tension breathing air continued to fall only in those who died (p less than 0.005). Only two variables were independent predictors of survival in patients with chronic obstructive pulmonary disease treated with long-term oxygen therapy. These were the arterial oxygen tension and the mean pulmonary arterial pressure (Ppa). However, when the calculation was made on patients with PaO2 less than or equal to 60 mm Hg (n = 154), then FEV1 and PaO2 but not Ppa were found to predict survival.

Influence of age and gender on upper airway resistance in NREM and REM sleep.

The prevalence of irregular breathing during sleep is age and gender dependent, but the reason for this is unknown. This study tested the hypothesis that older men have a greater sleep-related increase in respiratory resistance. In 48 healthy subjects, 12 in each of four groups of younger and older men and women, airway resistance was measured during wakefulness and sleep using a mask, pneumotachograph, and catheter-mounted pressure sensors. Total respiratory resistance and total "low-flow," and "high-flow" oropharyngeal resistance were analyzed from 170,000 breaths, high flow being at rates above 50% maximal inspiratory flow. High-flow oropharyngeal and total respiratory resistance increased during non-rapid eye movement (NREM) sleep in all groups but not low-flow resistance. Total respiratory resistance increased from 12 +/- 1.2 cmH(2)O. l(-1). s(-1) awake to 16.2 +/- 2.4 in NREM sleep in young men, from 22.8 +/- 3.6 to 33.6 +/- 5.4 in young women, from 18 +/- 3 to 34.8 +/- 4.8 in older men, and from 26.6. +/- 4.2 to 34.2 +/- 6 in older women. The percentage of change in total respiratory resistance from awake to NREM sleep was not different between age groups or genders. We conclude that there are no major age or gender differences in the changes in airway resistance with sleep in normal subjects.

In vivo neutrophil sequestration within lungs of humans is determined by in vitro "filterability".

Neutrophils are normally delayed in transit through the lung microcirculation, relative to the passage of erythrocytes. This sequestration contributes to a pulmonary pool of neutrophils that may relate to the relative inability of neutrophils to deform compared with erythrocytes when in transit in the pulmonary capillaries. A micropore membrane was used to model the human pulmonary microcirculation, in which cell deformability was measured as the pressure developed during filtration of the cells through the membrane at a constant flow. We demonstrated a significant correlation between in vitro deformability and in vivo lung sequestration of indium-111-labeled neutrophils in 10 normal subjects (r = 0.69, P less than 0.02). In eight patients with stable chronic obstructive pulmonary disease, this relationship was not significant (r = -0.2, P greater than 0.05). Furthermore, in a subject with microscopic pulmonary telangiectasia known to allow significant passage of 30-microns microspheres, neutrophils passed through the lungs without delay. Moreover, neutrophils from patients studied acutely with an exacerbation of chronic obstructive pulmonary disease were temporarily less deformable (P less than 0.01). These studies confirm that cell deformability is an important determinant of the normal neutrophil sequestration within the lungs. Changes in cell deformability may alter the extent of this sequestration.

Accuracy of respiratory inductive plethysmograph in measuring tidal volume during sleep.

Respiratory inductance plethysmography (RIP) has been widely used to measure ventilation during sleep, but its accuracy in this role has not been adequately tested. We have thus examined the accuracy of the RIP by comparing tidal volume measured with RIP with that measured by a pneumotachograph in eight unrestrained normal subjects during sleep. We have also studied the effect of posture on the accuracy of the RIP. In all sleep stages the correlation between RIP tidal volume measurements and expired volume showed relatively poor correlations (mean r = 0.49-0.60), and the bias of the measurements varied widely. Changes in posture altered the correlations between the two measurements, with no systematic differences between positions. When the subjects resumed a position, the 95% confidence intervals of tidal volume measurement did not overlap the original confidence limits in that posture on 13 of 25 occasions. This study shows that the RIP does not accurately measure tidal volume during sleep in unrestrained subjects and should only be used for semiquantitative assessment of ventilation during sleep.

A new method of analysing pulmonary quasi-static pressure-volume curves in normal subjects and in patients with chronic airflow obstruction.

1. Exponential analysis of lung pressure-volume curves is used to deal with the non-linearity of the pressure-volume relationship. A major problem of this procedure is to define the lower volume limit for exponential curve fitting. 2. In 12 healthy subjects and 24 patients with chronic airflow obstruction, a cubic function was fitted to the quasi-static pressure-volume curves to define an inflection point. 3. The exponential function of Colebatch et al. (Colebatch, H.J.H., Ng, C.K.Y. & Nikov, N.J. Applied Physiol. 1979; 46, 387-93) was then fitted to the data for volumes above the inflection point. 4. Exponential analysis with a cubic determination of an inflection point provides an objective way to describe the elastic properties of the human lungs in vivo.

Changes in chest wall compartment volumes on induction of anaesthesia with eltanolone, propofol and thiopentone.

Changes in the expiratory dimensions of the rib cage and abdomen on induction of anaesthesia with eltanolone, propofol and thiopentone were measured in 76 patients using respiratory inductance bands. Calibration of the respiratory inductance plethysmograph was by simultaneous flow measurement with a pneumotachograph. Movement of the vertebral column was restrained with a rigid mattress to allow volume change to be estimated more accurately from rib cage and abdominal dimensions. Rib cage volumes decreased by a median of 125 ml, while the median change in the abdominal compartment was 0. These findings suggest that a reduction in rib cage volume may contribute to the decrease in functional residual capacity after induction of anaesthesia, but that changes in the diaphragmatic-abdominal compartment are not important.

Spectral oscillations of RR intervals in sleep apnoea/hypopnoea syndrome patients.

A recent study has shown that daytime heart rate variability is reduced in obstructive sleep apnoea/hypopnoea syndrome (OSAHS) patients. In the present study, the hypothesis was that sympathovagal balance around apnoeas/hypopnoeas and nocturnal autonomic activity are altered in OSAHS patients. Frequency- and time-domain analyses of RR intervals were performed to monitor sympathovagal activity noninvasively. Fourteen untreated OSAHS patients and seven healthy subjects underwent overnight polysomnography. Low (LF) and total (TF) frequency power increased 2 min around the end of apnoeas/hypopnoeas (LF 229+/-38 ms2 TF 345+/-45 ms2) compared with undisturbed sleep (LF 106+/-18 ms2, TF 203+/-23 ms2). The increase in high frequency (HF) power was not significant. LF increase was proportionally higher than the HF increase (normalised LF (LFn) 67+/-1 units, normalised HF (HFn) 33+/-1 units) compared with undisturbed sleep (LFn 52+/-2 units, HFn 48+/-2 units). RR duration did not change around apnoeas/hypopnoeas (RR 904+/-28 ms). The LF and TF power increase was greater around arousal-inducing (LF 260+/-45 ms2 TF 390+/-65 ms2) compared with self-terminating (LF 161+/-31 ms2, TF 249+/-40 ms2) apnoeas/hypopnoeas; the LF and LFn increases were significant in both groups compared with undisturbed sleep and HF power differences were nonsignificant. RR intervals were longer around self-terminating apnoeas/hypopnoeas (RR 914+/-29 ms); the differences were not significant compared with undisturbed sleep. RR interval spectral power was not influenced by the event type. RR duration decreased (912+/-28 ms) and LF, HF and TF power increased (LF 111+/-16 ms2 , HF 62+/-6 ms , TF 173+/-21 ms2) across patients, compared with healthy controls (RR 1138+/-91 ms, LF 57+/-3 ms2, HF 35+/-3 ms2, TF 91+/-6 ms2). LFn and HFn did not change significantly. Sympathetic activity increases around apnoeas/hypopnoeas. The recurrent nocturnal fluctuations of sympathovagal balance and the overall increase of nocturnal autonomic activity may be of importance in the development of cardiovascular disease in sleep apnoea patients.

Electroencephalographic spectral analysis: detection of cortical activity changes in sleep apnoea patients.

There are no visible electroencephalographic (EEG) changes at the termination of some apnoeas and hypopnoeas. This study tests the hypothesis that cortical activity fluctuates at apnoea/hypopnoea termination, despite the lack of visible changes. To detect these changes, EEG spectral analysis was performed and centred around the end of apnoeas/hypopnoeas in 15 sleepy patients. Ten second windows were applied and comparisons were conducted between the normalised power of the same frequency bands before and after termination of each apnoea/hypopnoea. Comparisons were performed within patients between apnoeas/hypopnoeas and periods of undisturbed sleep as well as between patients and healthy subjects during sleep. Normalised theta power (4-8 Hz) decreased significantly at apnoea/hypopnoea termination. No significant changes were found between consecutive periods of undisturbed sleep across the 15 patients. During nonrapid eye movement sleep, changes were detected irrespective of arousal visibility. During rapid eye movement sleep, nonarousal apnoeas/hypopnoeas were not accompanied by any significant spectral power changes. Theta power was significantly lower across patients compared to healthy subjects (p=0.03) and was correlated to the apnoea/hypopnoea index (rho=0.6, p=0.008). The authors conclude that electroencephalographic spectral analysis improves detection of changes at apnoea/hypopnoea termination. Further validation is needed to determine whether it improves correlation between nocturnal measures and daytime symptoms.

The effect of nonvisible sleep fragmentation on daytime function.

Patients with sleep apnea/hypopnea syndrome (SAHS) suffer from impaired daytime function that correlates with hypoxemia and visible electroencephalographic (EEG) arousals. However, not all breathing irregularities during sleep terminate with visible EEG arousal. We hypothesized that sleep disturbance without visible EEG change may impair daytime function. Twelve normal subjects spent two pairs of 2 nights each in the laboratory. The first night of each pair was for acclimatization. On the second night, subjects either slept undisturbed or had sleep fragmented every minute to cause a transient increase in arterial blood pressure or increase in heart rate without visible EEG arousal. We tested daytime function after each study night. We presented 253 +/- 23 tones (mean +/- SD), 79 +/- 7% of which did not cause visible EEG arousals. Fragmentation did not alter total sleep time (undisturbed: 419 +/- 27 min; fragmented: 414 +/- 32 min; p = 0.5) or arousal frequency (undisturbed: 22 +/- 4/h; fragmented: 25 +/- 6/h; p = 0.4). Fragmentation reduced slow-wave sleep (undisturbed: 24 +/- 5%; fragmented: 20 +/- 4%; p < 0.01), mean sleep onset latency on the multiple sleep latency test (MSLT) (undisturbed: 8.0 +/- 3.1; fragmented: 6.2 +/- 2.1 min; p = 0.01) and the maintenance of wakefulness test (MWT) (undisturbed: 29.0 +/- 10.0 min; fragmented 25.7 +/- 9.7 min; p = 0.04). Fragmentation decreased hedonic tone at 7 A.M. (27 +/- 4, 25 +/- 6; p = 0.03). Nonvisible (autonomic) sleep fragmentation makes normal subjects sleepier and impairs their mood.

Extent of pulmonary emphysema in man and its relation to the loss of elastic recoil.

1. We assessed lung density, determined by computerized tomography, as a measure of emphysema and related this to lung function and measurement of the elastic recoil of the lung in normal subjects and patients with chronic obstructive lung disease. 2. We found a significant correlation between measurements of elastic recoil pressure at 90% of total lung capacity and both the forced expiratory volume in 1 s (r = 0.80, P less than 0.001) and the transfer factor for carbon monoxide (r = 0.70, P less than 0.001). Measurements of elastic recoil of the lung also correlated with lung density as measured by computerized tomography scanning (P less than 0.001). 3. Multiple regression analysis demonstrated a correlation between the density of the lowest fifth percentile of the computerized tomography lung-density histogram, and both the natural logarithm of the shape parameter of the pressure-volume curve (P less than 0.01), and the transfer factor for carbon monoxide (P less than 0.01). However, the mean computerized tomography lung density correlated, in addition, with the elastic recoil pressure of the lungs at 90% of total lung capacity (P less than 0.001). 4. Since the elastic recoil pressure correlates with computerized tomography lung density, and hence with emphysema, and since elastic recoil pressure also correlates with the forced expiratory volume in 1 s, these results suggest that loss of elastic recoil is one determinant of airflow limitation in patients with chronic obstructive lung disease.

Neutrophil retention in the lungs of patients with chronic obstructive pulmonary disease.

In order to study neutrophil traffic in the lungs of humans, we harvested autologous neutrophils and radiolabeled them with indium-111 prior to reinjection. The passage of these [111In]neutrophils through the pulmonary vasculature was compared with that of [99mTc]erythrocytes in normal elderly subjects and in patients with chronic obstructive pulmonary disease (COPD). Neutrophil sequestration within the lungs of seven normal subjects, 10 min after reinjection, correlated with local erythrocyte transit times in the lungs (tau = 0.72, p less than 0.001). This relationship was lost in patients with COPD. In seven patients studied during an acute exacerbation of COPD, neutrophil retention was higher during the first passage through the lungs (mean, 22.0 SD 14.1%) compared with 14 patients studied when their condition was stable (16.3 SD 3.4%, p less than 0.001), or to the normal elderly subjects (13.7 SD 7.0%, p less than 0.001). In addition, the subsequent rate of neutrophil washout from the lungs was slower in patients with acute COPD (1.93 SD 0.66 x 10(-3)s1) than in those with stable disease (3.08 SD 1.8 x 10(-3)s-1, p less than 0.02). Neutrophil retention in the lungs correlated inversely with the extent of emphysema, assessed quantitatively by CT scanning (tau = 0.68, p less than 0.05). Thus, patients presenting with acute exacerbations of COPD have an increased neutrophil burden in the pulmonary vasculature with the potential for increased lung proteolysis.

Detection of apnoeas, hypopnoeas and arousals by the AutoSet in the sleep apnoea/hypopnoea syndrome.

Limited sleep study systems are increasingly being used to diagnose the sleep apnoea/hypopnoea syndrome, but validation is essential and detection of arousal's desirable. One such system (AutoSet) was validated on an event-by-event basis, and the hypothesis that sudden large breaths detected by this system mark arousal from sleep was also examined. Twenty consecutive patients (apnoea/hypopnoea index (AHI) 39+/-6 (SEM)) underwent polysomnography (PSG), which included real-time signals of AutoSet (Version 3.03) scored events. PSG respiratory events were defined using airflow and thoracoabdominal movement and AutoSet events using nasal pressure. All apnoeas were scored by both systems, but 41% more hypopnoeas were scored on PSG and these were clinically significant, with 78% ending in cortical arousal. Twenty per cent of apnoeas and hypopnoeas scored by the AutoSet occurred during wakefulness. Large breaths, defined as a two-thirds increase in ventilation, marked 77% of respiratory-associated but only 9% of spontaneous arousals. Large breaths also marked 48% of "autonomic" arousals following respiratory events without visible electroencephalographic changes. Twenty-seven per cent of large breaths occurred during wakefulness. This study shows that the AutoSet and the standard polysomnographic approach differ in their detection of hypopnoeas. The AutoSet underdetected hypopnoeas during sleep, but also included some hypopnoeas occurring during wakefulness. Detection of large breaths may potentially be useful for identifying respiratory arousals. Detection of periods of wakefulness may improve the accuracy of the system.

Frequency and significance of increased upper airway resistance during sleep.

Previous studies have shown that episodes of inspiratory flow limitation can be clinically important. We have challenged the hypothesis that patients with the "upper airway resistance syndrome" have more episodes of inspiratory flow limitation, associated with greater swings in pleural pressure and more arousals from sleep than normal subjects. We thus studied eight symptomatic patients with UARS (ESS > 10, AHI < 15) and eight matched asymptomatic subjects. All had overnight polysomnography with recording of pleural pressure and airflow derived from nasal pressure. Events scored visually using nasal pressure were termed flow limitation events and those using both signals "resistive events." The patients with UARS had no more episodes of flow limitation or resistive events than the controls. However, pleural pressure swings at resistive event termination were significantly more negative in the patient group (-15 [IQR 9-19]; -11 [8-12] cm H(2)O; p = 0.02) and the number of cortical arousals associated with resistive events was higher in the patients (median, 10 [5-15]; 3 [1-9]/h slept; p = 0.02). This study confirms that patients with UARS have periods of increased upper airway resistance associated with significant sleep fragmentation. However, resistive events are also common in normal subjects, although these are associated with less negative pleural pressure swings and fewer arousals. Thus, the clinical significance of resistive events needs to be interpreted with caution.

Neck and total body fat deposition in nonobese and obese patients with sleep apnea compared with that in control subjects.

Around 50% of patients with the sleep apnea/hypopnea syndrome (SAHS) are not obese: body mass index (BMI) < 30 kg/m2. We hypothesized that local fat deposition around the upper airway may be different in nonobese patients with SAHS from that in normal subjects with the same body mass. We therefore examined the relationship between indices of general obesity; BMI, neck circumference (NC), and percentage total body fat with neck fat deposition measured by magnetic resonance imaging in three matched subject groups. Nine nonobese, nonsnoring control subjects (BMI, 25 SE 0.7 kg/m2; NC, 38.1 SE 0.5 cm; age, 37.5 SE 2.5 yr), nine nonobese patients with SAHS (BMI, 25.7 SE 0.4 kg/m2; NC, 39.8 SE 0.8 cm; age, 40 SE 4.2 yr), and nine obese patients with SAHS matched to the other groups for age (BMI, 34 SE 1.1 kg/m2; NC, 43.9 SE 0.6 cm; age, 40 SE 2.7 yr). Neck volume and fat content were assessed from the hard palate to the vocal cords using T1-weighted images. Percentage total body fat was 30 and 44% greater in nonobese and obese patients with SAHS, respectively, than in control subjects. Neck tissue volume was 10% greater in nonobese and 28% greater in obese patients with SAHS than in control subjects. The percentage of neck tissue volume attributed to fat was 27% greater in nonobese and 67% greater in obese patients with SAHS than in control subjects. The excess fat in both the nonobese and obese patients with SAHS compared with that in control subjects was localized to areas anterolateral to the upper airway, the differences were 52 and 88%, respectively. There were no significant differences between nonobese patients with SAHS and control subjects with respect to fat located in other areas of the neck; obese patients with SAHS had 42% more fat than control subjects (p < 0.05). We conclude that even relatively nonobese patients with SAHS have excess fat deposition, especially anterolateral to the upper airway when compared with control subjects with the same level of obesity assessed using BMI and NC. This may contribute to their predisposition to SAHS.

Computer measurement of dynamic compliance: technique and reproducibility in man.

A computer program was developed to calculate the frequency dependence of dynamic compliance (Cdyn) using continuous data analysis. Cdyn was measured repeatedly in eight normal human subjects over a 2-yr period. Comparison with Cdyn results measured manually showed that the computer program improved 10-fold the ratio of variance within subjects to between subjects of the compliance at specific frequencies, but there was only slight improvement in indices of the slope of the frequency dependence of compliance. We suggest that the absolute compliance at specific frequencies merits further consideration as a pathophysiological measurement and that, if the frequency dependence of compliance continues to be used, standardization of its calculation should be applied and the wide normal range should be more widely appreciated. Measurements of Cdyn in subjects breathing 80% helium-20% oxygen confirm that inertia is insignificant when breathing with tidal volumes of less than 500 ml and frequency of less than 1.5 Hz.

Effect of exercise and isoprenaline on left ventricular ejection fraction in patients with angina pectoris as assessed by radionuclide angiography.

The effect of supine leg exercise and an infusion of isoprenaline (2 micrograms/min) have been compared in 9 patients with angina pectoris and 8 normal control subjects. Left ventricular ejection fraction was measured by radionuclide angiography using the gated blood pool technique. The normal subjects increased their ejection fraction from 0.57 +/- 0.02 at rest to 0.71 +/- 0.02 during exercise, and 0.76 +/- 0.03 during isoprenaline infusion. In patients with angina pectoris, the resting ejection fraction of 0.47 +/- 0.04 decreased to 0.35 +/- 0.04 during exercise but increased to 0.63 +/- 0.06 during isoprenaline infusion. Our results suggest that the changes in ejection fraction probably depend on the changes in left ventricular segmental wall motion. When dyskinesia is increased, as with exercise, the ejection fraction declines, but when dyskinesia is unaffected or improved, as with isoprenaline, the ejection fraction increases.

Randomized placebo-controlled crossover trial of continuous positive airway pressure for mild sleep Apnea/Hypopnea syndrome.

The minimal disease severity at which patients with the sleep apnea/hypopnea syndrome (SAHS) gain benefit from treatment is not well characterized, although a pilot study of continuous positive airway pressure (CPAP) therapy showed daytime improvements in patients with 5 to 15 apneas + hypopneas per hour slept (AHI). We have thus performed a second, larger, randomized, placebo- controlled study in a prospective series of 34 patients (13 female) with mild SAHS (AHI 5 to 15) and daytime sleepiness. Patients spent 4 wk on CPAP treatment and 4 wk on an oral placebo, with randomization of treatment order, and daytime assessments on the last day of each treatment. Effective CPAP use averaged 2.8 +/- 2.1 h (mean +/- SD) per night. Compared with placebo, CPAP improved symptom score (p < 0.01), subjective (Epworth; p < 0.01) but not objective (maintenance of wakefulness test; p > 0.2) sleepiness, performances on 2 of 7 cognitive tasks (p < 0.02), depression score (p < 0.01), and five subscales of the SF-36 health/functional status questionnaire (p