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Biomedical subjects

M H Kryger

Publications and source records attributed to M H Kryger.

At least 37 records · Page 2Linked to original sources

A familial awake movement disorder mimicking restless legs in a sleep apnea patient.

We report on a patient with sleep apnea and an unusual familial movement disorder. The movements were present only during wakefulness and nocturnal arousals caused by disordered breathing. A 27-year-old obese man was referred with sleep onset insomnia, symptoms suggesting restless legs syndrome, daytime sleepiness, loud snoring and awakening with choking sensations. He was proven to have obstructive sleep apnea (apnea hypopnea index = 60.6). He also had a daytime movement disorder that was characterized by almost continuous stereotypic tapping of one or both legs. The movements were suppressible and not associated with any unpleasant or abnormal leg sensation. Virtually identical movements were present in three generations of his family. The severity of the movements did not worsen late in the day or with supine posturing. The nocturnal movements, consisting of a visible shaking of one or both legs, occurred only during arousals secondary to the apnea, had a mean duration of 5.7 +/- 3.0 (standard deviation) seconds and could not be defined as periodic limb movements in sleep (PLMS). Successful treatment of apnea by nasal continuous positive airway pressure dramatically reduced the movements during sleep (from 88.2 to 1.9 per hour). The clinical significance and the mechanism of this movement disorder is unknown. We discuss the features inconsistent with restless legs syndrome and consider other possible phenomenology, including akathisia. We conclude that this patient may have a previously unreported familial movement disorder and in addition developed the sleep apnea syndrome related to obesity.

Adult↗

Medical treatment of sleep apnea.

Obstructive sleep apnea is a common disorder. Since 1981 the treatment of choice has shifted from tracheostomy or weight loss to uvulopalatopharyngoplasty and then to continuous positive airway pressure. This review encompasses the most recent literature, focusing mainly on current treatment options and other potential and experimental modes of therapy. We review in detail continuous positive airway pressure therapy, including unwanted effects; compliance and possible ways to improve it; and ways to deal with the difficult patient. We also review dental appliances, electrical stimulation, and potential hormonal and nicotine treatment.

Administration, Cutaneous↗

Irregular breathing during sleep in patients with panic disorder.

OBJECTIVE: The authors examined the nocturnal breathing patterns of patients with panic disorder to determine whether these individuals had respiratory irregularities at a time when anxiety was not manifest. METHOD: Respiratory polysomnography was conducted on 14 medication-free patients with panic disorder and 14 healthy comparison subjects. Semiautomated indices of ventilatory variability were calculated for representative 3-minute, artifact-free sleep samples, and manually scored indices of irregular breathing were rated (blind to diagnosis) for the entire last 2 nights of sleep. RESULTS: Patients with panic disorder had evidence of abnormal sleep breathing as indicated by increased irregularity in tidal volume during REM and an increased rate of microapneas (i.e., brief [5-10-second] pauses in breathing). A subgroup of patients (including some with recent sleep panic attacks) had indices of subtle disorders in breathing during sleep that were above the 95th percentile for the comparison subjects. CONCLUSIONS: These findings extend the observations in the awake state that patients with panic disorder breathe more irregularly than healthy comparison subjects. The irregularities may be attributable to altered brainstem sensitivity to CO2 or to other as yet unexplained factors. A possible relationship between irregular nocturnal breathing and sleep panic attacks is discussed.

Adult↗

CPAP titration for sleep apnea using a split-night protocol.

We studied 107 patients with sleep-disordered breathing to confirm the effectiveness of continuous positive airway pressure (CPAP) titration using a split-night protocol. Patients spent two consecutive nights in our laboratory with complete polysomnography. On the first night, we applied a split-night protocol; the first half of the night was used as a baseline (B), and after a diagnosis was made, CPAP was applied during the second half of the night (SN). On the second night (2N), patients spent the entire night on CPAP to confirm the effectiveness of CPAP treatment. The SN and 2N both revealed a significant reduction in arousal index (37.8 +/- 27.9 on B, 13.2 +/- 12.1 on SN, 11.4 +/- 8.0 on 2N, values are mean +/- SD, p < 0.001), apnea hypopnea index (AHI) (23.6 +/- 26.3/h on B, 3.0 +/- 3.7/h on SN, 2.4 +/- 2.6/h on 2N, p < 0.001), percent total sleep time below 90% SaO2 (21.0 +/- 27.2% on B, 8.2 +/- 13.8% on SN, 4.9 +/- 10.2% on 2N, p < 0.001), and percent total sleep time below 80% SaO2 (1.1 +/- 3.8% on B, 0.0 +/- 0.1% on SN, 0.1 +/- 0.5% on 2N, p < 0.001). There were no significant differences between the SN and the 2N for these measurements. Final CPAP pressure was significantly lower at the end of the SN when compared with the 2N (8.8 +/- 2.7 cm H2O on SN, vs 10.3 +/- 2.8 cm H2O on 2N, p < 0.001). When patients were divided into three groups (AHI < 20, n = 69; 20 < AHI < 40, n = 18; AHI > 40, n = 20), the final CPAP pressure was different only in the group with AHI < 20 (8.1 +/- 2.3 cm H2O on SN, 9.6 +/- 2.3 cm H2O on 2N, p < 0.001). We conclude that a split-night protocol may be sufficient to determine the effective CPAP pressure, especially in patients with an AHI > 20.

Female↗

The effects of posture change and continuous positive airway pressure on cardiac natriuretic peptides in congestive heart failure.

We studied changes in the peripheral plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in seven patients with congestive heart failure (CHF) during four 1-h protocols during which patients maintained either an upright or a supine posture with or without nasal continuous positive airway pressure therapy (N-CPAP) at a pressure of 10 cm H2O (FIO2 = 0.21). The mean plasma ANP concentration of patients increased significantly from baseline at the end of 1 h of recumbency (65.9 +/- 5.8 to 82.6 +/- 8.3 pg/mL (mean +/- standard error); p < 0.05). This increase was prevented by concomitant N-CPAP therapy (72.1 +/- 8.0 to 61.0 +/- 8.8 pg/mL; p = NS). The mean level of ANP decreased significantly (71.9 +/- 9.0 to 62.5 +/- 8.0 pg/mL; p < 0.05) while patients simply maintained an upright posture. A significant reduction was also observed when patients remained upright with accompanying N-CPAP (72.6 +/- 10.9 to 54.6 +/- 4.3 pg/mL; p < 0.05). There were no significant changes observed in the mean level of BNP for any of the protocols undertaken. We conclude that in patients with chronic CHF, (1) an increase in ANP concentration occurs with recumbency, and this can be prevented by N-CPAP therapy; (2) a decrease in ANP occurs with maintenance of an upright posture, and that this reduction may be augmented by N-CPAP; and (3) no net change in BNP concentration occurs with either posture change or N-CPAP.

Aged↗

Effect of inhaled 3% CO2 on Cheyne-Stokes respiration in congestive heart failure.

Cheyne-Stokes respiration (CSR) in severe stable congestive heart failure (CHF) may be associated with significant nocturnal arterial oxygen desaturation and sleep disruption. Previous investigations of inhaled CO2 in CSR have been uncontrolled and of short duration, sleep has not been monitored electroencephalographically, and most patients studied have had neurological disease with or without cardiac disease. The purpose of our study was to document the effects of inhaled CO2 on CSR in patients with severe stable CHF (left ventricular ejection fraction < 35% and NYHA class 3 or 4 dyspnea) in controlled all-night polysomnographic studies. Six patients were studied for 3 nights and days: adaptation, control and inhalation of CO2. These patients received a constant F1CO2 = 0.03 in air (with a 4-5 mm Hg increase in PaCO2) on night 3. This caused virtual abolition of CSR as reflected by CSR duration/total sleep time (62-2.2%; p = 0.0012) and CSR duration/nonrapid eye movement (NREM) sleep time (73-2.4%; p = 0.00064), and NREM apnea index was reduced from 33.5 to zero (p = 0.026). The apparatus used to accurately control F1CO2, however, was intrusive and some features of sleep structure such as sleep latency were adversely affected. We conclude that inhalation of CO2 with a constant F1CO2 = 0.03 virtually eradicates CSR in all-night polysomnographically monitored studies in patients with severe stable CHF. The clinical significance of these findings remains to be determined.

Administration, Inhalation↗

Acute effect of nasal CPAP on periodic limb movements associated with breathing disorders during sleep.

Sleep-disordered breathing is commonly associated with periodic limb movements (PLMS). Nasal continuous positive airway pressure (nCPAP) is the most widely used treatment for sleep-disordered breathing. However, it is not clear whether nCPAP treatment of apnea also has a systematic effect on PLMS. We studied 15 patients with sleep-disordered breathing and PLMS in a split-night protocol in order to confirm the acute effects of nCPAP on PLMS. Although the PLMS index (PLMSI) did not change statistically (baseline, 38.7 +/- 20.5; CPAP, 31.3 +/- 17.0; p = ns), the PLMS-related index (PLMS-ArI) decreased significantly on nCPAP (baseline, 17.8 +/- 10.1; CPAP, 9.2 +/- 5.7; p < 0.05). Whether the reduced PLMS-ArI is sustained with chronic nCPAP is unknown and a matter of future investigation.

Adult↗

Ventilatory instability in patients with congestive heart failure and nocturnal Cheyne-Stokes breathing.

Many of the factors that appear to cause Cheyne-Stokes Breathing (CSB) in sleeping patients with congestive heart failure (CHF) are present during wakefulness. We studied the stability of ventilatory pattern in nine awake CHF patients (left ventricular ejection fraction 9-48%) who demonstrated CSB only while asleep and compared results with 13 age-matched normals. The test involved brief (30-50-second) exposure to hypoxia (end-tidal PO2 = 55 Torr) followed by breathing pure oxygen. During hypoxia, ventilation increased about 40% above air breathing control in both groups, whereas end-tidal CO2 declined to 92% of control in both groups. During hyperoxia, however, breathing pattern differed between groups. In the normals, ventilation gradually declined to air-breathing levels and did not significantly undershoot. In the patients, ventilation dropped more rapidly to baseline and an overshoot was present with ventilation being 72% and air-breathing control at 45 seconds of hyperoxia. Circulatory delay was calculated from the time interval between alveolar hypoxia and in increase in ventilation, and when corrections for circulatory delay were applied to ventilation during hyperoxia the differences between groups increased in that the patients' ventilation was less than baseline immediately after the delay. In the normals, the gradual decline in hyperoxic ventilation probably represents the decay of short-term potentiation (STP) activated by hypoxic hyperventilation. Results in the patients were compatible with absence of such STP decay, but could also have been due to a reduction in ventilatory drive early in hyperoxia related to prolonged circulation times.(ABSTRACT TRUNCATED AT 250 WORDS)

Cheyne-Stokes Respiration↗

The effect of nasal CPAP on nocturnal reflux in patients with aperistaltic esophagus.

It has been shown that nasal continuous positive airway pressure (nasal CPAP) significantly reduces nocturnal reflux both in patients with sleep apnea and in patients without sleep apnea but consistent abnormal nocturnal reflux. The mechanism by which CPAP is thought to reduce reflux includes the elevation of the resting lower esophageal sphincter (LES) pressure. In this study, we tested the effect of nasal CPAP in two groups of patients with aperistaltic esophagus but with different resting LES pressure. Seven patients with scleroderma esophagus and six patients treated for achalasia were tested over a 48-h period. On the first night, the patients were untreated; on the second night, both groups received applied nasal CPAP at 8 cm H2O pressure. The percentage of time the pH < 4.0, the number of reflux events > 5 min, and the length of the longest reflux event were all significantly reduced in the patients with achalasia (p < 0.03), but not in the scleroderma group (p > 0.20). These results suggest that a residual resting LES pressure greater than that demonstrated by patients with scleroderma (> 10 mm Hg) may be necessary for nasal CPAP to affect nocturnal reflux.

Adult↗

Sleep in nondepressed patients with panic disorder: II. Polysomnographic assessment of sleep architecture and sleep continuity.

This study assessed the EEG sleep of 16 patients with panic disorder who did not currently meet criteria for major depression in comparison to 16 age-comparable healthy controls. Patients with panic disorder had remarkably normal sleep, with only a modest reduction in total sleep time (374 +/- 46 min vs. 399 +/- 36 min) and delta sleep (11.4 +/- 6.2% vs. 16.4 +/- 6.6%) noted. Contrary to expectation, impairment in sleep maintenance and continuity was not found in the patients with panic disorder. We conclude (a) sleep in non-depressed patients with panic disorder is fairly unremarkable, and does not resemble that classically described for depressed patients, and (b) excessive arousability is not a characteristic feature of sleep in panic disorder.

Adult↗

Effects of zolpidem and triazolam on sleep and respiration in mild to moderate chronic obstructive pulmonary disease.

Sleep problems and nocturnal arterial oxygen desaturation are common in patients with chronic obstructive pulmonary disease (COPD). Hence, the safety and efficacy of new hypnotic agents must be ascertained in this group of patients. We performed a double-blind, randomized, single-dose, placebo and active drug controlled, crossover study in 24 patients with insomnia (subjective sleep latency > 30 minutes and sleep duration 4-6 hours) and mild to moderate COPD (mean FEV1 61 +/- 12(SD)% predicted) in order to establish the effects of zolpidem 5 mg and 10 mg on sleep and respiration and to compare these effects with triazolam 0.25 mg. Arterial oxygen saturation for the entire night, by hour and stage, and the apnea-hypopnea index for the entire night were not significantly different with placebo and the various drug conditions. Total sleep time and sleep efficiency were increased over placebo by all three drug conditions. Triazolam was more effective than zolpidem 5 mg but not zolpidem 10 mg, and there was no significant difference between zolpidem 5 mg and zolpidem 10 mg. Zolpidem 10 mg and triazolam both reduced the number of awakenings (> 15 seconds duration) per hour of sleep. Although there was a trend for triazolam to be more efficacious than zolpidem 10 mg, no statistically significant difference was found for any objective or subjective sleep variable. Likewise, zolpidem 10 mg tended to be more efficacious than zolpidem 5 mg, but the difference was only significant in terms of perceived sleep quality and ease of falling asleep.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Benzodiazepines in congestive heart failure: effects of temazepam on arousability and Cheyne-Stokes respiration.

We studied seven male patients with moderate to severe congestive heart failure (CHF) [left ventricular ejection fraction (LVEF) = 22.4 +/- 6.7; mean +/- SD] in a double-blind crossover trial to determine the effects of temazepam 15 mg on arousability, sleep architecture, Cheyne-Stokes respiration (CSR) and nighttime oxygen saturation. Sleep architecture was not markedly improved with temazepam. There was no significant change in total sleep time (TST) (383.1 +/- 14.1 minutes to 396.6 +/- 15.4 minutes, p = ns) (mean +/- SE, placebo vs. temazepam) or total wake time (TWT) (96.9 +/- 14.0 vs. 81.4 +/- 14.0 minutes, p = ns). Sleep stage proportions did not change appreciably except for a reduction in stage 1 sleep (6.7 +/- 1.2% vs. 4.0 +/- 1.0%, p < 0.05). Microarousals per hour of sleep decreased with temazepam (21.1 +/- 2.7/hour vs. 13.9 +/- 2.1/hour placebo, p < 0.05), with the largest change occurring in stage 2 (24.9 +/- 5.4/hour vs. 15.0 +/- 3.1/hour, p < 0.05). Wake time during sleep (WDS) was reduced from 82.5 +/- 11.7 minutes to 54.5 +/- 9.4 minutes, p < 0.03. Daytime alertness was improved with temazepam as was indicated by an increase in mean latency to sleep [multiple sleep latency test (MSLT) = 7.1 +/- 2.4 vs. 5.7 +/- 2.0 minutes, p < 0.04) on days following treatment with temazepam. There was no significant change in CSR as a percentage of TST (38.7 +/- 13.6% vs. 32.5 +/- 11.8%, p = ns). However, the apnea/hypopnea index (AHI) (10% filter) was decreased in stage 1 (28.1 +/- 9.7/hour vs. 15.6 +/- 8.2/hour). Overnight oxygen saturation did not change with temazepam (95.1 +/- 0.6% both nights) and the percentage of TST spent below 90% oxygen saturation was minimal for both conditions (1.5 +/- 1.1% vs. 2.2 +/- 1.7%, p = ns). We conclude that CHF patients with CSR experience frequent arousals and that these arousals can be reduced with temazepam. There was an improvement in daytime somnolence. There was no worsening of nighttime oxygen saturation.

Aged↗

Nasal continuous positive airway pressure. A new treatment for nocturnal gastroesophageal reflux?

Nasal continuous positive airway pressure (CPAP) reduces nocturnal gastroesophageal reflux (GER) in obstructive sleep apnea syndrome (OSAS) patients. The primary objectives of our investigation were to determine if CPAP could reduce reflux in non-OSAS patients and, if so, by what mechanism. Esophageal pH was monitored for 48 h in six nocturnal reflux patients. During the first 24 h, basal reflux data were collected; the second night, nasal CPAP was administered (pressure = 8 cm H2O). Esophageal manometry was obtained in six healthy adult volunteers both on and off nasal CPAP (pressure = 8 cm H2O) to ascertain CPAP's effects on esophageal pressure and peristalsis. The six reflux patients experienced less nocturnal GER while on CPAP. The mean percent time esophageal pH < 4 was reduced from 27.7 +/- 10.0 to 5.8 +/- 2.6 (p < 0.004); the mean reflux duration dropped from 2.1 +/- 0.6 to 0.9 +/- 0.5 min (p < 0.03); and the mean duration of longest reflux improved from 84.3 +/- 32.6 to 13.8 +/- 6.9 min (p < 0.01). The CPAP raised the mean resting midesophageal pressure by 4.4 cm H2O (p < 0.01) and the mean resting lower esophageal pressure (LES) by 13.2 cm H2O (p < 0.02) in the healthy volunteers. Nasal CPAP effectively reduced nocturnal GER in six patients with nocturnal reflux. The antireflux activity of CPAP is likely due to passive elevation of intraesophageal pressure and possibly to reflex LES constriction.

Administration, Intranasal↗

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↗