William A. Whitelaw

Automated analysis of digital oximetry in the diagnosis of obstructive sleep apnoea

BACKGROUND The gold standard diagnostic test for obstructive sleep apnoea (OSA) is overnight polysomnography (PSG) which is costly in terms of time and money. Consequently, a number of alternatives to PSG have been proposed. Oximetry is appealing because of its widespread availability and ease of application. The diagnostic performance of an automated analysis algorithm based on falls and recovery of digitally recorded oxygen saturation was compared with PSG. METHODS Two hundred and forty six patients with suspected OSA were randomly selected for PSG and automated off line analysis of the digitally recorded oximeter signal. RESULTS The PSG derived apnoea hypopnoea index (AHI) and oximeter derived respiratory disturbance index (RDI) were highly correlated (R = 0.97). The mean (2SD) of the differences between AHI and RDI was 2.18 (12.34)/h. The sensitivity and specificity of the algorithm depended on the AHI and RDI criteria selected for OSA case designation. Using case designation criteria of 15/h for AHI and RDI, the sensitivity and specificity were 98% and 88%, respectively. If the PSG derived AHI included EEG based arousals as part of the hypopnoea definition, the mean (2SD) of the differences between RDI and AHI was –0.12 (15.62)/h and the sensitivity and specificity profile did not change significantly. CONCLUSIONS In a population of patients suspected of having OSA, off line automated analysis of the oximetry signal provides a close estimate of AHI as well as excellent diagnostic sensitivity and specificity for OSA.

Wave intensity analysis and the development of the reservoir–wave approach

The parameters of wave intensity analysis are calculated from incremental changes in pressure and velocity. While it is clear that forward- and backward-traveling waves induce incremental changes in pressure, not all incremental changes in pressure are due to waves; changes in pressure may also be due to changes in the volume of a compliant structure. When the left ventricular ejects blood rapidly into the aorta, aortic pressure increases, in part, because of the increase in aortic volume: aortic inflow is momentarily greater than aortic outflow. Therefore, to properly quantify the effects of forward or backward waves on arterial pressure and velocity (flow), the component of the incremental change in arterial pressure that is due only to this increase in arterial volume—and not, fundamentally, due to waves—first must be excluded. This component is the pressure generated by the filling and emptying of the reservoir, Otto Frank’s Windkessel.

Modafinil in obstructive sleep apnea-hypopnea syndrome: a pilot study in 6 patients.

We studied the effects of modafinil, a vigilance-enhancing drug, on excessive daytime sleepiness, memory, night sleep and respiration in 6 patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) using a double-blind random cross-over design with 24-hour polysomnography, verbal memory test and a 5-week sleep-wake diary kept by the patients. There were two 2-week treatment periods in which either modafinil or placebo was used; they were separated by a 1-week wash-out period. Our results show that modafinil reduces daytime sleep duration, lengthens the duration of subjective daytime vigilance and improves long-term memory in patients with OSAHS without modifying night sleep and respiration events.

Mechanisms of Sleep Apnea at Altitude

At altitude normal people often develop periodic breathing in sleep--regularly recurring periods of hyperpnea and apnea. This phenomenon is probably explained by instability of the negative feedback system for controlling ventilation. Such systems can be modeled by sets of differential equations that describe behavior of key components of the system and how they interact. Mathematical models of the breathing control system have increased in complexity and the accuracy with which they simulate human physiology. Recent papers by Zbigniew Topor et al. (5,6) describe a model with two separate feedback loops, one simulating peripheral and the other central chemoreceptor reflexes, as well as accurate representations of blood components, circulatory loops and brain blood flow. This model shows unstable breathing when one chemoreceptor loop has high gain while the other has low gain, but not when both have high gain. It also behaves in counter-intuitive way by becoming more stable when brain blood flow is reduced and unresponsive to blood, gas changes. Insights from such models may bring us closer to understanding high altitude periodic breathing.

Impaired ventilatory response to carbon dioxide in patients with chronic renal failure : implications for the intensive care unit

ObjectivesTo compare aspects of ventilatory control and the susceptibility to depressant drugs between patients with chronic renal failure and normal volunteers. DesignProspective, controlled study. SettingPulmonary function laboratory of a university hospital. PatientsSix patients with chronic renal failure requiring hemodialysis and ten normal, control subjects. InterventionsVentilatory responses to breathing CO2 were studied using a rebreathing method. The effects of triazolam (0.5 mg orally) and me peridine (1 mg/kg, subcutaneously) on these measurements were also studied. Measurements and Main ResultsDialysis patients showed definite impairment in the ventilatory response to CO2, which could not be accounted for by differences in respiratory mechanics, muscle strength, or acid-base status. Meperidine impaired ventilatory responses in control subjects and in renal patients, while triazolam had little effect on either group. The effect of the drugs was not proportionately greater in dialysis patients than in control subjects. ConclusionsChronic renal failure results in a poorly responsive ventilatory control system, which may make renal failure patients more difficult to wean from mechanical ventilation. The oretically, these patients may be more vulnerable to disturbances in blood gas homeostasis and subsequent respiratory arrest than other patients in an unmonitored environment. (Crit Care Med 1994; 22:413–419)

Volume loading reduces pulmonary vascular resistance in ventilated animals with acute lung injury: evaluation of RV afterload

During mechanical ventilation, increased pulmonary vascular resistance (PVR) may decrease right ventricular (RV) performance. We hypothesized that volume loading, by reducing PVR, and, therefore, RV afterload, can limit this effect. Deep anesthesia was induced in 16 mongrel dogs (8 oleic acid-induced acute lung injury and 8 controls). We measured ventricular pressures, dimensions, and stroke volumes during positive end-expiratory pressures of 0, 6, 12, and 18 cmH(2)O at three left ventricular (LV) end-diastolic pressures (5, 12, and 18 mmHg). Oleic acid infusion (0.07 ml/kg) increased PVR and reduced respiratory system compliance (P < 0.05). With positive end-expiratory pressure, PVR was greater at a lower LV end-diastolic pressure. Increased PVR was associated with a decreased transseptal pressure gradient, suggesting that leftward septal shift contributed to decreased LV preload, in addition to that caused by external constraint. Volume loading reduced PVR; this was associated with improved RV output and an increased transseptal pressure gradient, which suggests that rightward septal shift contributed to the increased LV preload. If PVR is used to reflect RV afterload, volume loading appeared to reduce PVR, thereby improving RV and LV performance. The improvement in cardiac output was also associated with reduced external constraint to LV filling; since calculated PVR is inversely related to cardiac output, increased LV output would reduce PVR. In conclusion, our results, which suggest that PVR is an independent determinant of cardiac performance, but is also dependent on cardiac output, improve our understanding of the hemodynamic effects of volume loading in acute lung injury.

Spike trains from single motor units in human parasternal intercostal muscles.

Recordings of single motor unit activity were obtained from parasternal intercostal muscles of normal humans during quiet breathing. Spike trains from 52 individual motor units were analyzed. All these units were low threshold ones, recruited at low inspired volumes and therefore at low tension thresholds. Mean frequency of firing at onset was 7.8 Hz and mean increase in frequency through the breath was 3.6 Hz. Onset and peak frequencies were positively correlated with inspiratory flow rate. Alternation of interspike intervals between long and short was found in the spike trains of 6 of 13 units tested and this occurred at frequencies of 6-12/s. Doublet discharges at the beginnings of spike trains were seen during voluntary neck flexion but never in quiet breathing or voluntary deep breaths. The pattern of activity in these human intercostal motor units was similar to that reported for low threshold, slow twitch units in other mammalian skeletal muscles, including respiratory muscles.

Agoraphobic avoidance and panic frequency as predictors of laboratory induced panic reactions

This study examined the importance of agoraphobic avoidance and frequency of panic as predictors of psychological and physiological responses of panic sufferers to a laboratory based provocation procedure. Psychophysiologic comparisons were made between 22 panic disorder patients and 15 controls, at baseline and across three periods of carbon dioxide gas inhalations (1, 3, 5%; balance oxygen). Subjective measures of anxiety, frightening cognitions and body sensations were obtained across the phases. Physiological measures of minute ventilation, breathing rate, tidal volume, end tidal CO2 and heart rate were also obtained. Between group comparisons revealed significant differences between the groups on the subjective measures with no significant differences occurring on the physiological measures. Within group analyses revealed that pre-session questionnaire measures of agoraphobia avoidance and panic frequency predicted the degree of anxiety, frightening sensations and cognitions during baseline and 5% CO2 inhalation. The results indicated that both self-reported agoraphobic avoidance and panic frequency are strong clinical predictors of psychological reactions of panic sufferers during laboratory provocation.

Differences between middle cerebral artery blood velocity waveforms of young and postmenopausal women.

Objective: We characterized middle cerebral artery (MCA) blood flow velocity waveforms measured by transcranial Doppler ultrasonography in premenopausal (26.6 ± 6.1 years, mean ± SD) and postmenopausal (54.0 ± 3.6 years) women, of whom six were receiving hormone therapy (PM-HT) and seven were not (PM-non-HT). We hypothesized that feature points on MCA waveforms are altered in postmenopausal women compared with those in young women. Design: A short protocol involved maintaining end-tidal PO2 at euoxia (88 mm Hg) and end-tidal PCO2 at 1.5 mm Hg above eucapnic values using a dynamic end-tidal forcing system. Doppler data for the velocity spectral outline (Vp) were collected every 10 ms, and velocity waveform analyses were done on a beat-by-beat basis. Waveform features were identified over each cardiac cycle, including the average Vp (VCYC), maximum acceleration (AMAX), and the ratio of the velocity at the reflected wave and the velocity at peak systole (VR:VMAX). Results: VCYC was unchanged between premenopausal and postmenopausal women (69.4 ± 9.6 and 67.5 ± 11.1 cm/s, respectively). AMAX was significantly higher (P = 0.007) in premenopausal women (987.9 ± 280.7 cm/s2) compared with postmenopausal women (743.1 ± 100.3). Conversely, VR:VMAX was significantly smaller (P < 0.001) in premenopausal women (0.90 ± 0.09) compared with postmenopausal women (1.11 ± 0.05). In postmenopausal women, the reflected wave is higher than the maximum velocity at peak systole, suggesting the presence of a shoulder in the MCA waveform. Conclusions: Further investigations are required to assess whether this waveform analysis can provide insight into pathophysiologic changes in cerebral hemodynamics with aging.

Sleep of the great

Both Lewis Carroll and William Shakespeare appear to have made clinical observations of sleep apnea syndromes long before they were discovered by medical science, and to have understood something about their physiological mechanisms. The somnolent dormouse in Alice in Wonderland indicates that his problem is one of sleep and breathing and is subject to modern treatment for obstructive apnea. Shakespeare in Henry IV presents a case of obstructive apnea along with a case of Cheyne-Stokes breathing and uses the plot of these history plays to explain by analogy the theoretical basis for periodic breathing.