Intermittent positive airway pressure by nasal mask as a treatment for respiratory insufficiency in a patient with syringomyelia.

We report a case of a 73-year-old woman with chronic respiratory failure in association with syringohydromyelia and sleep apnea. She was initially intubated and mechanically ventilated. Weaning from the ventilator was only successful after nasal intermittent positive airway pressure therapy was started. A normalization of arterial blood gas exchange could be achieved.

Continuous positive airway pressure and lung inflation in sleep apnea patients.

BACKGROUND: It was shown in normals that an important decrease in upper airway resistance can be obtained with continuous positive airway pressure (CPAP). It was suggested that lung inflation in patients with sleep apnea syndrome (SAS) could also be a mechanism of action of CPAP. OBJECTIVE: In the present study we wanted to evaluate the effects of nocturnal CPAP on the daytime lung function pattern in patients with SAS. METHODS: We measured arterial blood gases and possible changes in static lung volumes in 57 SAS patients (37 with normal lung function, 10 with COPD and 10 with restrictive lung disease) after at least one month of CPAP therapy. RESULTS: A significant increase in PaO(2) (from 79 to 84 mm Hg, p = 0.01) and a decrease in AaDO(2) (from 23 +/- 1 to 16 +/- 1, p < 0.01) was only observed in SAS patients with normal lung function. This improved gas exchange was parallelled by a small but non significant change in the FRC (from 96.5 +/- 3.2 to 105.4 +/- 3.7%pred, p = 0.07) and TLC (from 101.3 +/- 1.7 to 104.1 +/- 1.4%pred, p = 0.15). Similar changes in TLC and FRC were also observed in SAS patients with obstructive and restrictive lung disease. CONCLUSIONS: Chronic nocturnal CPAP therapy can improve daytime gas exchange and may influence lung inflation during the daytime. The small changes seem to be a functional effect but of no clinical relevance.

Influence of longterm CPAP therapy on CO(2) drive in patients with obstructive sleep apnea.

According to recent publications, the values of the hypercapnic ventilatory responses (HCVR) in normocapnic obstructive sleep apnea (OSA) patients are highly variable, but they are usually within the normal range. In our study, CPAP therapy during 1 month did not seem to influence the HCVR [Verbraecken, J., De Backer, W., Willemen, M., De Cock, W., Wittesaele, W., Van de Heyning, P., 1995. Respir. Physiol. 101, 279-287]. It is, however, not well studied whether long term (1 year) CPAP therapy can influence HCVR in normocapnic patients. Therefore, we evaluated the effect of 1 year CPAP therapy on CO(2) drive in 20 OSA patients. The slope of HCVR (SHCVR) changed from 2.35+/-0.21 L min(-1) mmHg(-1) (control) to 1.66+/-0.16 L min(-1) mm Hg(-1) (P=0.04), but the mean within subject coefficient of variation in repeated measurements of SHCVR in treated and untreated OSA patients was not statistically different. Pa(O(2)) increased from 72+/-2 mm Hg to 80+/-2 (1 year) mm Hg. We conclude that CPAP therapy improves daytime gas exchange in normocapnic OSA and may possibly decrease CO(2) drive (slope) after a treatment period of 1 year.

Two months follow up of auto-CPAP treatment in patients with obstructive sleep apnoea.

BACKGROUND: Continuous positive airway pressure (CPAP) with fixed mask pressure is the current standard treatment for obstructive sleep apnoea (OSA). Auto-CPAP devices apply at any time the minimally required pressure to normalise breathing and may improve patient comfort and compliance. We present an open descriptive study of auto-CPAP treatment at home in patients previously managed with conventional CPAP. METHODS: Fifteen patients with obstructive sleep apnoea (OSA), previously treated for at least one year with standard CPAP, were followed prospectively for a two month period on auto-CPAP. Outcome measures were both subjective evaluation by the patients and objective (polysomnographic) data obtained at one and two months of follow up. RESULTS: The Epworth sleepiness score did not change significantly between baseline and follow up after one and two months and no systematic changes in CPAP related side effects were reported. Compared with the baseline polysomnographic values without treatment, a significant improvement in both respiratory and sleep parameters was observed during auto-CPAP. These results were not significantly different from those obtained with standard CPAP. A significant correlation was found between the effective CPAP pressure (Peff) and the amount of time spent below Peff during auto-CPAP treatment (r = 0.6, p = 0.01). CONCLUSION: Long term auto-CPAP treatment in these patients with severe OSA appears to provide comparable efficacy to that of standard CPAP treatment.

Relationship between CO2 drive and characteristics of apneas in obstructive and central sleep apnea.

Previously we showed that CO2 drive is increased in patients with obstructive sleep apnea (OSA). In the present study we would like to evaluate a possible relationship between CO2 drive and characteristics of apneas in obstructive and central sleep apnea (CSA). We compared the hypercapnic ventilatory response (HCVR) between patients with OSA and CSA. HCVR was correlated with total event time and mean event duration in both groups. 17 normocapnic patients in each group and 14 controls were studied. The apnea patients were matched for apnea-hypopnea index, age, sex, and BMI. SHCVR (slope) tended to be higher in apnea patients than in controls without statistical significancy: controls 1.65 (0.16), CSA 2.17 (0.22), OSA 2.55 (0.35) (l/min per mmHg) (P = 0.13). A significant correlation was found between HCVR and event time in CSA (0.52, P = 0.04) and between HCVR and apnea mean duration in OSA (r = 0.52, P = 0.04). We conclude that while CO2 drive was not statistically increased in both apnea types, small changes can contribute to breathing instability and may increase the total event time (in CSA) but may also shorten the apnea duration (in OSA).

Central sleep apnea after interrupting longterm acetazolamide therapy.

One month administration of acetazolamide (ACET) (at sea level) improves periodic breathing and decreases the number of central apneas (CA) (De Backer et al., 1995 Am. J. Respir. Crit. Care Med. 151, 87-91) in nonhypercapnic central apnea syndrome. It remains unclear whether cessation of therapy would provoke recurrence of symptoms. In the present study we evaluated the number of CA after 1 and 6 months interruption of ACET therapy. Eight patients with central sleep apnea were included [central apnea index (CAI) > 5 or apnea and hypopnea index (AHI) > 10 and obstructive apnea index (OAI) < 5]. Polysomnography was repeated once after 1 month treatment (N2), after 1 month off treatment (N3) and after 6 months off treatment. CAI (25 +/- 10 at N1) decreased during N2 (4 +/- 2) and N3 (5 +/- 3) and remained low after N4 (3 +/- 1). However an increase in the number of obstructive apneas and central hypopneas could be observed together with a shift from central apnea to hypopnea after N4. Maybe ACET induces a long lasting resetting of the CO2 threshold which is still present after interruption of the therapy.

[Nasal CPAP in sleep-related respiration disorders: patient profile, therapy compliance and influence of gas exchange and lung function pattern]. / Nasale CPAP bij slaapgebonden ademhalingsstoornissen: patientenprofiel, therapietrouw en invloed op de gasuitwisseling en het longfunctiepatroon.

A survey performed in 100 CPAP users indicated that irritation of the face, a painful nose and nasal obstruction were among the most frequently mentioned complaints in chronic CPAP users. In 132 normocapnic SAS patients a significant improvement of PaO2 was shown, with a decrease of the alveolo-arterial oxygen difference. This improved gas exchange was parallelled by a significant increase in the FRC and TLC. Maybe a modulation in force of the respiratory muscles may be involved. These data were more pronounced in obstructive sleep apnea than in central sleep apnea. In 50 chronic CPAP users we could show a lower AHI immediately after CPAP withdrawal after a previous prolonged treatment. These findings may support the insufflation theory as a mechanism of action of CPAP. Traditionally, mechanical splinting of the upper airway has been considered as the dominant mechanism of action. Other mechanisms like changes in regulation of breathing and decrease of the pharyngeal edema may be involved as well.

Stress responses to tilting and odor stimulus in preterm neonates after intrauterine conditions associated with chronic stress.

The effect of conditions linked with chronic intrauterine stress (CIUSTR) on the function of the autonomic nervous system (ANS) has not yet been evaluated systematically in premature neonates. We hypothesized that intrauterine stress deranges the function of the ANS as assessed by the clinical responses to certain stimuli. Twenty-one premature neonates who had suffered from CIUSTR, such as maternal smoking, maternal hypertension, and intrauterine growth retardation (STR Group), and 30 neonates who had not suffered from those intrauterine conditions were studied (C Group). They were exposed to a 10-s postural change test and a 10-s odor test. Heart rate, respiratory rate, and noninvasive blood pressure were measured at 15 s, 30 s, and at 1, 2, 3, 4, and 5 min after the test. The overall reaction pattern after the postural change test was mainly sympathetic, and was more pronounced in the STR Group. After the odor test, the overall response was parasympathetic but less pronounced in the STR Group. We, therefore, speculate that neonates who suffer from conditions known to be associated with CIUSTR exhibit a higher adrenergic state with little reserve to counteract stressful situations that may make them more vulnerable.

Assessment of respiratory effort by means of strain gauges and esophageal pressure swings: a comparative study.

We characterized apneas by a quantitative method (esophageal pressure measurements) and by a qualitative method (strain gauges) at the same time in 22 patients with sleep-related breathing disorders. Detection of respiratory effort by strain gauges significantly overestimated the total number of central apneas in each patient. Despite this overestimation, none of the patients was wrongly diagnosed as having pure central sleep apnea syndrome. Strain gauges are sufficiently reliable for the characterization of apneas in most patients. When strain gauges reveal that most apneas are central in origin, verification by esophageal pressure measurements is recommended.

Influence of uvulopalatopharyngoplasty on alpha-EEG arousals in nonapnoeic snorers.

Arousals are more numerous in heavy snorers than in nonsnorers and might be a cause of excessive daytime sleepiness (EDS) in these patients. The present study investigated whether treatment of snoring by uvulopalatopharyngoplasty (UPPP) had an influence on sleep microstructure in nonapnoeic snorers. The polysomnographic records of 10 nonapnoeic snorers were reviewed retrospectively and arousals scored according to the American Sleep Disorders Association (ASDA) 3 s definition. Scores for snoring, EDS and polysomnographic data were compared before and after UPPP (mean (+/-SD) time interval 249 +/- 183 days). UPPP resulted in a subjective improvement of snoring and a significant decrease in the arousal index (mean 14.6, 95% confidence interval (95% CI) 8.5-20.8 vs mean 9.1, 95% CI 6.6-11.5) (p = 0.01). EDS and the amount of slow-wave sleep remained unchanged. Uvulopalatopharyngoplasty resulted in an improvement of subjective snoring and a significant decrease of arousals in nonapnoeic snorers. Although these data do not provide any insight into whether the improvement observed can be maintained on a long-term basis, uvulopalatopharyngoplasty can be considered as a useful treatment modality to reduce sleep fragmentation and snoring in nonapnoeic snorers.

Stress responses in preterm neonates after normal and at-risk pregnancies.

OBJECTIVE: To evaluate the autonomic response in preterm neonates born after an at-risk pregnancy. METHODOLOGY: Twenty-one preterm neonates (gestational age; GA) 29-37 weeks; bodyweight (BW): 720-2113 g; postnatal age: 2-126 days), born after at-risk pregnancies (stressed (STR) group), were compared to 30 preterm neonates (GA: 26-36 weeks; BW: 813-2380 g: postnatal age: 2-86 days) without any intrauterine risk factor (C group). A 10 s pain stimulus was given on the forefoot and heart rate, respiratory rate and blood pressure were measured at 15 and 30 s, at 1, 2, 3, 4 and 5 min. After 10 s ocular compression six cardiac variables were recorded. RESULTS: After the pain stimulus the STR-group had a significant increase of heart rate at 15 s and an increase of diastolic blood pressure at 30 s. In the C group a significant increase of heart rate at 15 s was recorded. For the respiratory rate both groups showed an initial depression (significant at 15 s in the C group) followed by an increase. The time to react to the ocular compression was significantly shorter in the STR-group than in the C-group and thus more parasympathetic. CONCLUSIONS: We hypothesize that the different sympathetic and parasympathetic reaction patterns of the vital parameters to triggers in the STR-group are due to chronic stress, pointing to an altered maturation of the two components of the autonomic nervous system after chronic intrauterine stress (CIUSTR).

Clinical defense response to cold and noise in preterm neonates after intrauterine conditions associated with chronic stress.

Threatening stimuli may trigger abnormal reaction patterns in animals and infants. We investigated whether chronic intrauterine stress influenced these reactions. The autonomic defense response to cold and noise in 21 preterm newborns who had suffered from chronic intrauterine stress, such as maternal smoking, maternal hypertension, and intrauterine growth retardation (STR-group) was compared with the response in 30 preterm newborns without such condition (C-group). An ice cube was applied to the forehead and a 90 dB bleeptone was presented to the ears. After the cold test the heart rate, systolic, diastolic, and mean blood pressure increased in both groups, but to a lesser extent in the STR-group: the heart rate increased more at 2 minutes in the C-group (p = 0.009), and the systolic blood pressure was higher in the C-group at 30 seconds (p = 0.007). The respiratory rate decreased in both groups. After the auditory stimulus, no significant difference in response between the two groups was seen for any of the parameters. The number of arousals between the two groups was similar for both tests; they uniformly resulted in increased heart and respiratory rates. The classic passive defense response was not observed in either group of preterm newborns. The observed reaction could be defined as a combination of a sympathetic, active fight-or-flight reaction and a parasympathetic passive freezing, or paralysis, reaction. The latter was less pronounced in the C-group. This may point to a change in the maturation of the autonomic nervous system after chronic intrauterine stress. It is speculated that this could make these infants more vulnerable in stressful situations.

Chronic CO2 drive in patients with obstructive sleep apnea and effect of CPAP.

Obstructive sleep apnea (OSA) can be associated with depressed hypercapnic ventilatory response (HCVR) (White D.P., N.J. Douglas, C.K. Pickett, C.W. Willich and J.V. Weil, Am. Rev. Respir. Dis 128:984-986, 1983), which might be responsible for aggravating the sleep-related breathing disorder (SRBD). The present study evaluated whether in patients with various types of sleep apnea a significant decrease in the HCVR could be found (COMPARATIVE STUDY). In a second part of the study chronic CPAP therapy (Continuous Positive Airway Pressure) was evaluated in relation to control of breathing (CPAP STUDY). In the comparative study a significant increase of the slope in the normocapnic OSA and overlap group could be seen. A depressed HCVR could only be observed in chronic hypercapnic OSA. In the CPAP-study it was shown that changes in the AHI after CPAP do not parallel the HCVR. We conclude that in eucapnic OSA patients CPAP therapy does not change CO2 drive. We believe that increased chemical CO2 drive can contribute to its pathogenesis.

Obstructive sleep hypopnea syndrome in a patient with Marfan syndrome treated with oxygen therapy.

A patient with Marfan's syndrome and obstructive sleep hypopnea syndrome is reported. She had complained about insomnia, tiredness and hypersomnolence lasting 2 years. A complete nightly polysomnography revealed 94 obstructive hypopneas (the hypopnea index was 12.85) and no obstructive apneas. Presumably an increased laxity of the pharyngeal wall was responsible for the phenomenon. A therapy with CPAP was started, but was not tolerated by the patient. Oxygen therapy on the other hand turned out to be effective and well tolerated.

Effects of bretazenil vs. zolpidem and placebo on experimentally induced sleep disturbance in healthy volunteers.

The effects of bretazenil 0.25 and 0.5 mg, a partial agonist at the benzodiazepine receptor, on sleep electroencephalogram (EEG), subjective sleep quality and morning psychomotor performance were compared to zolpidem 10 mg and placebo using noise as an experimental sleep disturbing factor in a single dose, double-blind, crossover study. Twelve healthy volunteers were subjected to prerecorded traffic noise with a mean sound level of 52 dB(A) during eight hours in bed. Significant effects of noise were found on sleep electroencephalogram (EEG) parameters (rapid eye movement [REM] sleep, stage 2 sleep and number of arousals), and subjective sleep quality assessments, but not on psychomotor performance (choice reaction time, digit span memory, and symbol digit substitution). Both drugs reduced the number of shifts between sleep stages and the number of arousals and increased REM sleep latency. Only after 0.5 mg bretazenil, stage 2 sleep increased and REM sleep decreased. Both doses of bretazenil significantly affected performance in the symbol digit substitution test. Sleep quality improved under drug treatments compared to placebo. The results suggest that experimental sleep disturbance can be a valuable tool in the investigation of potential sleep promoting compounds.

[The usefulness of an alternative EEG scoring system in obstructive sleep apnea]. / Het nut van een alternatief EEG scoringsysteem in obstructieve slaapapnea.

Careful analysis of the EEG in obstructive sleep apnea (OSA) patients according to the Rechtschaffen and Kales (R & K) criteria indicates that obstructive apneas (OA) are more frequently observed during stage 1 and 2 sleep than during slow wave sleep. However it is also obvious that OA can be recognised during R & K wakefulness stage (St W). The purpose of the present study was to see whether further partition of R & K St W could define a wakefulness stage during which no apneas occur. Ten patients with predominantly OSA were studied (OA-Index 20 +/- 5). Patients EEG were scored according to classic R & K and to modified criteria which further divided R & K St W. Three additional stages were defined (STW-a, STW-b, STW-c). The partitioning of STW of R & K allowed us to define a W-stage (STW-a) during which no apneas occur, and to identify alpha (STW-b) and drowsiness (STW-c) during which OA occur frequently.

Enumeration of T-lymphocytes and T-lymphocyte subsets in rheumatoid arthritis using monoclonal antibodies.

The number of T-lymphocytes and T-lymphocyte subsets was measured in peripheral blood of 51 patients with rheumatoid arthritis. T-lymphocytes were counted by E-rosette tests and by the immunogold staining method with OKT3.PAN monoclonal antibody. Helper and suppressor T-lymphocytes were determined by the immunogold staining method with OKT4.IND and OKT8.SUP monoclonal antibody. The relative and absolute numbers of T-lymphocytes and helper T-lymphocytes in peripheral blood of patients with RA did not differ significantly from those in the blood of healthy subjects. However, the relative and absolute numbers of suppressor T-cells were significantly lower in patients with RA than in healthy subjects. The decrease of suppressor T-cells in the blood of patients with RA dit not correlate with the activity of the disease nor the presence of the rheumatoid factor.

Modulation of immunity in multiple sclerosis: a double-blind levamisole-placebo controlled study in 85 patients.

Levamisole seems to regulate cell-mediated immunity by restoring T-cell function. Since a deficiency of T lymphocytes has been described by various authors in multiple sclerosis patients. Of the 85 patients involved in the trial, evaluation of functional and neurological scores was possible in 54 (32 with placebo and 22 with levamisole). The mean follow-up period was 2 years. This double-blind controlled study indicates that both neurological function and disability significantly deteriorated in the placebo-treated patients, but remained fairly stable in the levamisole-treated group. Since the difference between both groups was not significant, no levamisole effect was demonstrated on progression in multiple sclerosis. With the exception of one case of granulocytopenia (which had no clinical effect), no drug-related changes could be demonstrated. This contrasts with the general impression that this immunomodulator agent might be harmful to patients with multiple sclerosis. The fact that during this blind study both annual relapse rate and disability score remained more stable in treated patients with severe disability suggests that, while waiting for a more effective treatment, long-term levamisole therapy could be useful in patients with multiple sclerosis.