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Biomedical subjects

M H Kryger

Publications and source records attributed to M H Kryger.

At least 19 recordsLinked to original sources

Short technical note: quantification of periodic breathing: preliminary studies.

Although the apnea/hypopnea index is the most widely used measure of breathing pattern abnormality during sleep, this index gives no information about the strength of the oscillation in the breathing pattern, its periodicity or its regularity. Such information may be required in research studies involving breathing patterns and how they are affected by interventions. We are exploring spectral analytic methods to determine two normalized indices, the periodicity index and the modified modulation index, to examine periodic breathing for all-night sleep studies. These methods are automatic and require no user interaction. Data were obtained from 11 heart failure patients who slept for a total of 21 nights in the sleep laboratory. Because individual patients had a marked regularity of their Cheyne-Stokes respiration during sleep, one would expect an extremely high correlation between the traditional measures of breathing pattern abnormality and these spectral analytic techniques. Indeed we found that there was an extremely high correlation between the periodicity index and the modulation index and the traditional measures of apnea/hypopnea index and the proportion of the night with periodic breathing (p less than 0.02 in all cases). When the breathing pattern was irregular but still with many apneas there was a discrepancy between the apnea index and the indices of periodicity. These techniques are still preliminary and future studies will determine their limitations in other patient populations and where the pattern is unstable.

Adult

Nasal CPAP reduces gastroesophageal reflux in obstructive sleep apnea syndrome.

Anecdotal reports suggest that obstructive sleep apnea syndrome (OSAS) patients may suffer from frequent nocturnal gastroesophageal reflux (GER) and that nasal continuous positive airway pressure may be an effective form of antireflux therapy in this population. To confirm these clinical impressions, we performed two consecutive days of 24-h esophageal pH monitoring, nocturnal esophageal pressure recording, and polysomnography on six OSAS patients complaining of regular nocturnal GER. On night one, the patients were untreated. Five of six subjects had abnormal amounts of nocturnal GER. Arousal, movement and swallowing were more frequent (p less than 0.043) and nadir intrathoracic pressure lower (p less than 0.005) in the 30 s prior to precipitous drops in esophageal pH (greater than or equal to 2 pH units) than during random control periods. A direct association between obstructive apneas and GER was not identified. On night two, nasal CPAP was administered and successfully treated apnea in five of six subjects. In these patients, there was also dramatic reduction in GER frequency and duration on CPAP. The mean percentage of time pH less than 4 dropped from 6.3 +/- 2.1 to 0.1 +/- 0.1 percent (p less than 0.025). We believe that OSAS may predispose to nocturnal GER by lowering intrathoracic pressure and increasing arousal and movement frequency. Nasal CPAP can correct these predisposing factors and reduce GER.

Adult

Management of obstructive sleep apnea.

Although the indications for treatment of obstructive sleep apnea are controversial, there is general agreement that treatment is warranted in patients with a combined apnea and hypopnea frequency of 20 events per hour of sleep. General therapeutic measures include abstinence from alcohol and weight loss in obese patients. A minority of patients with specific abnormalities of the nose, pharynx, or jaw may require surgical management. In the absence of specific upper airway abnormalities, the most effective treatment is nasal continuous positive airway pressure or, if necessary, bilevel positive airway pressure during sleep. The role of uvulopalatopharyngoplasty remains controversial, due in part to the reported variability in long-term efficacy of this procedure. Drug therapy may be effective in selected patients.

Humans

Subjective versus objective evaluation of hypnotic efficacy: experience with zolpidem.

There is little published literature on the correlation between subjective and objective efficacy of hypnotics. We wanted to determine whether there was a correlation between the patient's subjective evaluation of the efficacy of the hypnotic with the polysomnographic (PSG) findings. We studied 16 patients with chronic insomnia (sleep latency, greater than or equal to 30 minutes; total sleep time, greater than 240 but less than 420 minutes) for 11 nights who took placebos on nights 1 and 2, zolpidem (imidazopyridine) on nights 3-9 and placebo on nights 10 and 11. Patients completed a questionnaire each morning following PSG, which evaluated subjective sleep quality, sleep latency and total sleep time. These data were compared to PSG findings to answer specific questions about sleep latency reduction, efficacy of the hypnotic after a week's use, sleep quality after discontinuing the drug, and any correlation between subjective and objective measures. PSG findings indicated a shortened sleep latency, increased total sleep time, decreased total wake time and increased sleep efficiency when patients ingested zolpidem 30 minutes before bedtime. We found that after 7 nights (nights 3-9) the drug was still effective in reducing sleep latency and increasing total sleep time. Upon withdrawal (nights 10 and 11) sleep returned to baseline (nights 1 and 2). Subjectively, the patients confirmed those findings on the questionnaire, as well as a subjective reduction in the number of awakenings and, interestingly, a subjective increase in the time spent awake after sleep. Many of the objective variables we examined correlated highly with the subjective variables. While on zolpidem, subjects believed and were objectively shown to have a decreased sleep latency, increased total sleep time and decreased time awake before persistent sleep, although they tended to overestimate sleep latency and time spent awake before persistent sleep and underestimated total sleep time. Although the correlation between objective and subjective measures was high for the group, in individual patients there was an impressive difference between the two, and the highest coefficient of variation between a subjective and objective measures was 0.453. No correlations were found with subjective measures of refreshing quality of sleep, decrease in number of awakenings, how sleepy patients felt in the morning or their ability to concentrate in the morning. Thus, we believe the PSG remains the keystone in the evaluation of hypnotic efficacy.

Adult

Central sleep apnoea in congenital muscular dystrophy.

Sleep-disordered breathing may occur in a wide variety of neuromuscular syndromes, and may present with diverse, often isolated, symptoms or findings such as excessive daytime sleepiness, pulmonary hypertension, congestive heart failure, morning headaches, or hypoxia-induced nocturnal seizures. The authors report two sisters with congenital muscular dystrophy in whom central sleep apnoea resulted in the isolated symptom of nocturnal seizures in one, and morning headaches in the other. Review of the literature reveals that sleep-disordered breathing may be common in neuromuscular disorders, and may often be present when clinical weakness is mild, and insufficient to result in diurnal respiratory dysfunction.

Adult

Sleep in postpolio syndrome.

Post-polio patients may develop additional neuromuscular and respiratory symptoms decades after the acute attack, the post-polio syndrome. We hypothesize some post-polio symptoms may be due to breathing disorders occurring during sleep. We performed polysomnography on 13 post-polio patients: group 1 (five patients) were those already on ventilatory assistance (rocking beds) and group 2 (eight patients), those without any assistance. Patients requiring new treatment were then evaluated on nasal CPAP or nasal mask ventilation. Group 1 patients, on rocking beds, demonstrated consistently poor sleep quality with decreased total sleep time, sleep efficiency, percentage stage 2, slow wave sleep, rapid eye movement sleep and an increase in the number of arousals and percentage stage 1 sleep. Respiratory abnormalities were also present and in all cases caused significant O2 desaturation. These patients did not respond to CPAP with the rocking bed. Repeat night-time polysomnography on nasal mask ventilation demonstrated an improvement in sleep structure and gas exchange. Three group 2 patients, (group 2a) had sleep within normal limits. The five remaining (group 2b) had poor sleep quality that was similar to but not as disrupted as group 1 patients. All but one patient demonstrated obstructive or mixed apnea and were treated effectively with nasal CPAP. One patient required nasal mask ventilation (due to mixed apnea and marked hypoventilation) to which there was a dramatic response. These patients demonstrated improved sleep quality and an improvement in daytime symptomatology. Sleep studies should be performed on post-polio patients with excessive daytime sleepiness and respiratory complaints. Those with obstructive and mixed apnea can often be treated with nasal CPAP. Those with hypoventilation syndrome and sleep apnea attributable to sleepiness and respiratory complaints. Those with obstructive and mixed apnea can often be treated with nasal CPAP. Those with hypoventilation syndrome and sleep apnea attributable to respiratory muscle weakness can be treated with nasal mask ventilation. Individuals already on respiratory assistance such as rocking beds who have features of respiratory failure can also be treated effectively with long-term nasal mechanical ventilation.

Adult

The entrainment of low frequency breathing periodicity.

It has been predicted by mathematical models of the respiratory control system that the delay between the lung and the respiratory controller may determine the cycle time found in periodic breathing. We examined cycle time of periodic breathing and circulation time in 11 patients known to have circulation delay due to heart failure. We did not find a significant relationship between the amount of periodic breathing and circulation delay, but found a very high correlation between circulation delay and the cycle time of periodic breathing (r2 = 0.825; p = 0.0001).

Blood Circulation

The effect of oxygen on respiration and sleep in patients with congestive heart failure.

STUDY OBJECTIVE: To determine the effect of supplemental oxygen on Cheyne-Stokes respiration, nocturnal oxygen saturation (SaO2), and sleep in male patients with severe, stable congestive heart failure. DESIGN: Randomized, single-blind, placebo-controlled crossover study. SETTING: Patients referred from outpatient cardiology clinics of two teaching hospitals. PATIENTS: Sequential sample of nine outpatients with severe, stable congestive heart failure. INTERVENTIONS: For each patient, sleep studies (after an adaptation night) from two consecutive randomized nights were compared; one study was done while the patient breathed compressed air and the other while the patient breathed oxygen (O2). Compressed air and oxygen were both administered through nasal cannulae at 2 to 3 L/min. MEASUREMENTS AND MAIN RESULTS: Cheyne-Stokes respiration, defined as periodic breathing with apnea or hypopnea, was found in all patients. Low-flow oxygen significantly reduced the duration of Cheyne-Stokes respiration (50.7% +/- 12.0% to 24.2% +/- 5.4% total sleep time), mainly during stage 1 NREM (non-rapid eye movement) sleep (21.3% +/- 7.1% to 6.7% +/- 2.3% total sleep time) with no significant change during stage 2 sleep, slow-wave sleep, or REM (rapid eye movement) sleep. Although patients had normal SaO2 (96.0% +/- 1.7%) while awake, severe sleep hypoxemia was common; breathing oxygen reduced the amount of time that SaO2 was less than 90% from 22.3% +/- 8.0% to 2.41% +/- 1.93% of total sleep time. Sleep, disrupted to a variable extent in all patients, improved with oxygen therapy: There was an increase in total sleep time from 275.3 min +/- 36.6 to 324.6 min +/- 23.3; a reduction in the proportion of stage 1 sleep (27.6% +/- 5.8% total sleep time to 15.2% +/- 2.6% total sleep time); and a reduction in the number of arousals (30.4/h +/- 8.0 to 13.8/h +/- 1.9). The apnea-hypopnea index was reduced from 30.0 +/- 4.7 to 18.9 +/- 2.4 with oxygen breathing. CONCLUSION: In severe, stable congestive heart failure, nocturnal oxygen therapy reduces Cheyne-Stokes respiration, corrects hypoxemia, and consolidates sleep by reducing arousals caused by the hyperpneic phase of Cheyne-Stokes respiration. Correction of nocturnal hypoxemia and sleep disruption may improve the clinical status of these patients.

Adult

The effect of L-tryptophan on daytime sleep latency in normals: correlation with blood levels.

L-Tryptophan, an essential amino acid, is readily converted to serotonin, which is thought to be important for expression of slow wave sleep and possibly rapid eye movement (REM) sleep. A vast but often confusing literature exists on L-tryptophan effects on inducing, maintaining, or altering sleep. In this study we measured the effects of L-tryptophan on objective (multiple sleep latency) and subjective [Stanford Sleepiness Scale (SSS)] measures of sleepiness and examined their relationship to blood L-tryptophan levels. Ten healthy volunteers (eight men and two women; mean +/- SD age 34 +/- 10 years) received placebo or 1.2 or 2.4 g or L-tryptophan on separate days in random double-blind fashion. Sleep latency and SSS were measured initially and at 60 and 120 min after ingestion. Blood and urine were collected at regular intervals. Compared with placebo both L-tryptophan doses reduced sleep latency at 1 h, with the reduction persisting at 2 h for the 2.4-g dose only (p less than 0.05). There was a positive correlation between subjective and objective sleepiness measures but only with the 2.4-g dose (rs = 0.76, p less than 0.01). There was a highly significant correlation between blood L-tryptophan and sleep latency at 0, 60, and 120 min in all subjects for all drug conditions (r = 0.276, df = 79, p = 0.013). Very small amounts of free L-tryptophan or its metabolites were found in the urine, with the exception of kynurenic acid. We conclude that L-tryptophan consistently reduced sleep latency in normals and that this correlates with blood levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Heart rate response to breath-hold, valsalva and Mueller maneuvers in obstructive sleep apnea.

We wished to assess the role of increased vagal tone and arterial oxygen saturation (SaO2) as determinants of HR response to voluntary respiratory maneuvers in OSAS. The changes in HR and SaO2 during breath-hold (B), Valsalva (V) and Mueller (M) maneuvers were determined in nine male subjects with OSAS while breathing RA or O2. Oxygen saturation was significantly lower breathing RA than O2 at the end of B (92.6 +/- 1.6 vs 97.2 +/- 0.8 percent), V (92.9 +/- 1.3 vs 95.2 +/- 1.7 percent), and M (92.7 +/- 1.2 vs 95.3 +/- 1.9 percent). Despite this, there was no significant difference between the HR change while breathing RA and O2 during B (12 +/- 18 vs 7 +/- 15 beats/minute), V (-2 +/- 12 vs -5 +/- 17 beats/minute), and M (5 +/- 16 vs 1 +/- 8 beats/minute). The change in HR was not related to the duration of B, V, or M or to the mouth pressure generated during V and M. In order to determine if awake HR response to the maneuvers reflected HR response to obstructive apnea, we examined the relationship between the HR response to B, V, and M during wakefulness and the response to obstructive apnea of similar duration while asleep. A significant correlation was found between the HR response to obstructive sleep apnea during sleep and the response to awake B (r = 0.67, p less than 0.001), V (r = 0.51, p less than 0.05), and M (r = 0.75, p less than 0.001). We conclude that in OSAS, increased vagal tone is a major determinant of HR response to voluntary respiratory maneuvers, that bradycardia can occur in the absence of hypoxemia, and that HR response to these maneuvers, especially to M, during wakefulness predicts HR response to obstructive apnea while asleep.

Adult

Respiration and abnormal sleep in patients with congestive heart failure.

We investigated the interaction between respiration and sleep in ten male outpatients with severe, stable, maximally treated congestive heart failure (CHF). Cheyne-Stokes respiration (CSR), defined as periodic breathing with apnea or hypopnea, was found in all patients with a mean duration of 120 +/- 87 minutes [50.2 +/- 34.4 percent total sleep time (TST)]. The CSR was found predominantly during stage 1 (20.6 +/- 6.7 percent TST) and stage 2 (25.8 +/- 6 percent TST) NREM sleep and occurred rarely during slow wave sleep (SWS) (1.6 +/- 1 percent TST) and REM sleep (1.6 +/- 0.5 percent TST). All apneas and hypopneas were central. Despite normal awake arterial oxygenation (SaO2) (96.1 +/- 1.6 percent), significant, severe hypoxemia was found during sleep in seven patients with SaO2 less than 90 percent for 9 to 59 percent TST (mean +/- SD, 23 +/- 23 percent TST), and this was significantly related to the duration of CSR (r = 0.66, p less than 0.05). The mean minimum SaO2 for sleep stage was lowest during stage 1 (82.1 percent +/- 2.6 percent) and stage 2 (78.9 percent +/- 2.8 percent) NREM sleep, intermediate during REM sleep (84.5 percent +/- 1.8 percent) and highest during SWS (87.6 percent +/- 2.7 percent). Sleep was disrupted to a variable extent in all patients with a short mean TST (287 +/- 106 minutes), a high proportion of stage 1 sleep (26 +/- 19 percent TST), virtual absence of SWS (5 +/- 7 percent TST) which was found in only four patients, and a high number of sleep stage changes (30 +/- 27/hour) and arousals (28 +/- 25/hour). Arousals occurred predominantly during stage 1 (17 +/- 20/hour) and stage 2 (10 +/- 7/hour) NREM sleep and the majority immediately followed the hyperpneic phase of CSR. The amount of CSR (percent TST) was inversely related to the length of TST (r = -0.73, p less than 0.05), and directly related to the number of sleep stage changes (r = 0.79, p less than 0.01) and the number of arousals (r = 0.66, p less than 0.05). We conclude that in severe, stable CHF, CSR occurs predominantly during light sleep, that despite normal awake arterial oxygen saturation, significant hypoxemia may develop during sleep due to CSR, and that sleep is unstable and disrupted due to frequent arousals caused by the hyperpneic phase of CSR. These sequelae of CSR may be important determinants of the clinical status and outcome of patients with severe CHF.

Adult

Sleep apnea and body position during sleep.

In patients with obstructive sleep apnea, it is believed that body position influences apnea frequency. Sleeping in the lateral decubitus position often results in significantly fewer apneas, and some have recommended sleeping on the side as the major treatment intervention. Previous studies, although calculating apnea-hypopnea index (AHI) for supine and lateral decubitus positions, have not taken sleep stage into account. To examine the effect of both sleep stage and body position on apnea duration (AD) and frequency, we determined AHI and AD in all spontaneous body positions during rapid eye movement (REM) and non-REM (NREM) sleep by reviewing videotapes and polysomnograms from 11 overnight studies of 7 obese patients with severe sleep apnea. Consistent with previous work, AD was significantly longer in REM then in NREM (32.5 +/- 2.3 s versus 23.5 +/- 1.9 s; p less than 0.05). This difference persisted when adjusting for body position. AHI was greater on the back than on the sides (84.4 +/- 4.9/h versus 73.6 +/- 7.5/h, p less than 0.05), but after accounting for sleep stage, this difference remained only for NREM (103 +/- 4.8/h versus 80.3 +/- 9.2/h, p less than 0.05) and not for REM (83.6 +/- 5.3/h versus 71.1 +/- 4.2/h, p NS). Although reduced, AHI on the sides still remained clinically very high. Body position changed frequently throughout the night, but some patients spent little or no time on their back. We conclude that AD is longer in REM than NREM, regardless of position, and AHI is higher on the back only in NREM. As AHI remains very high on the sides, favoring the lateral decubitus position may not be as beneficial as previously thought in very obese patients. Less obese patients are more likely to benefit by position changes.

Adult

Identification and quantification of apneas by computer-based analysis of oxygen saturation.

Manual detection and quantitation of apneas from an all-night polysomnogram is very time-consuming. Because SaO2 changes with virtually every apnea event, we reasoned that by identifying cyclical SaO2 changes, we could calculate (1) an apnea-hypopnea index that would correlate very well with the manually derived apnea-hypopnea index, and (2) the duration of apnea-hypopnea events. We developed a computer algorithm to scan and detect dips in SaO2 data digitally stored as a time series by computer throughout overnight studies. Desaturations detected by computer were compared with the events detected manually in 9 all-night polysomnograms from 6 patients with typical obstructive sleep apnea. Events detected by one method but not the other were subsequently verified to determine the overall number of apnea-hypopnea events present and to determine false positive and false negative rates for the 2 methods of detection. The total number of apneas was 4,008. Both methods agreed on 3,639 of them. Of 77 manually recorded apneas not detected by computer, 24 were subsequently discounted (manual false positives, 24 of 4,007 = 0.6%) and 53 confirmed (computer false negatives, 1.32%). Of 358 events not detected manually, 316 were confirmed (manual false negatives, 7.9%) and 42 discounted (computer false positives, 1.1%). Using the final manual scoring as the reference, the computer program detected apneas with a sensitivity of 97.9%, and the predictive value of a computer-detected event was 90.8%. For event duration, a regression was performed on 3,623 matched apneas-hypopnea events, giving a coefficient of r = 0.9431, p less than 10(-6).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Mortality and apnea index in obstructive sleep apnea. Experience in 385 male patients.

Although obstructive sleep apnea (OSA) has been studied in detail for over a decade, the mortality of this disorder is unclear. We calculated cumulative survival in 385 male OSA patients. We found that those with an apnea index (AI) greater than 20 had a much greater mortality than those with AI = less than 20. The probability of cumulative eight-year survival was .96 +/- 0.02 (SE) for AI = less than 20 vs. 63 +/- 0.17 for AI greater than 20 (p less than .05). This difference in mortality related to AI was particularly true in the patients less than 50 years of age in whom mortality from other causes is not common. None of the patients treated with tracheostomy or nasal CPAP died. Eight of the patients treated with uvulopalatopharyngoplasty (UPPP) died and the cumulative survival of the UPPP-alone treated group was not different from the survival curve of untreated OSA patients with an apnea index of greater than 20. We conclude that OSA patients with an apnea index of greater than 20 have a greater mortality than those below 20 and that UPPP patients be restudied after therapy. If the latter patients are found not to have marked amelioration of their AI, then they should be treated by nasal CPAP or tracheostomy.

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