[Proposal for a systematic analysis of polygraphy or polysomnography for identifying and scoring abnormal events occurring during non-invasive ventilation]. / Proposition pour une analyse systématique de la polygraphie et de la polysomnographie afin d'identifier les évènements anormaux survenant pendant la ventilation non invasive.

Non-invasive ventilation (NIV) is recognised as an effective treatment for chronic hypercapnic respiratory failure. Monitoring NIV during sleep may be preferable to daytime assessment. This paper reports the findings of an international consensus group, which systematically analysed nocturnal polygraphic or polysomnographic tracings recorded with either volume-cycled or pressure-cycled ventilators. A systematic description of nocturnal respiratory events, which occur during NIV, is proposed: leaks, obstruction at different levels of the upper airway (glottis and/or pharynx), with or without decrease of respiratory drive and asynchrony.

Proposal for a systematic analysis of polygraphy or polysomnography for identifying and scoring abnormal events occurring during non-invasive ventilation.

Non-invasive ventilation (NIV) is recognised as an effective treatment for chronic hypercapnic respiratory failure. Monitoring NIV during sleep may be preferable to daytime assessment. This paper reports the findings of an international consensus group which systematically analysed nocturnal polygraphic or polysomnographic tracings recorded with either volume-cycled or pressure-cycled ventilators. A systematic description of nocturnal respiratory events which occur during NIV is proposed: leaks, obstruction at different levels of the upper airway (glottis and/or pharynx), with or without decrease of respiratory drive and asynchrony.

[Treatment of obstructive sleep apnea syndrome with mandibular advancement appliances]. / Traitement du syndrome d'apnées obstructives du sommeil par les orthèses d'avancement mandibulaire.

Mandibular advancement device provide a therapeutic option for obstructive sleep apnea syndrome (OSAS). Clinical improvement has been proven in the different available studies, mainly on nocturnal respiratory events and quality of sleep. Less snoring have been noted by bed partners and objective studies have demonstrated a decrease in snoring frequency and intensity. The effects of these appliances on upper airways resistance syndrome is not yet well documented. The significant clinical improvement is secondary to the decrease in the occurrence of apneas and hypopneas. Polysomnographic improvement criteria with an apnea hypopnea index less than 10 per hour has been noted in certain cases, although no improvement or even worsening was noted in other cases. Sleep architecture has also changed in these patients, with a decrease in the time spent in stages 1 and 2, and an increase in the time spent in stages 3, 4 and rapid eye movement sleep. Micro-arousals are also reduced in number. Somnolence and loss of attention are improved; these have been evaluated subjectively or by a well known and approved somnolence scale. In some cases a test for vigilance was done. Our results are identical to those published in the different studies concerning respiratory events and sleep architecture.

[Outcome of adult patients with cystic fibrosis admitted to intensive care with respiratory failure: the role of non-invasive ventilation]. / Devenir des adultes mucoviscidosiques admis en réanimation pour décompensation respiratoire.

Recourse to mechanical ventilation may prove necessary in adult patients with cystic fibrosis who have reached the stage of severe respiratory insufficiency. We report the experience of an intensive care service using non-invasive ventilation (NIV) as the first step in the management of acute respiratory failure in these patients. The records of 16 patients with cystic fibrosis presenting with acute respiratory failure and treated with NIV were analysed retrospectively. The characteristics of the group were: mean age 26.9 +/- 9.5 years; mean FEV1 21.5 +/- 10.4% predicted; mean body mass index 16.8 +/- 2.1; mean Pa CO(2) on admission 66 +/- 15 mm Hg. The mean duration of NIV in the ICU was 10 +/- 7 days. Eight patients (50%) died after having been intubated on account of failure of NIV. The eight survivors were discharged home with long-term NIV (mean duration 235 +/- 158 days). Six of them have received a lung transplant. The mode of onset of respiratory failure was an important prognostic factor: a rapid onset (<7 days) was invariably associated with death, on the other hand a gradual deterioration (> 7 days) was noted in the eight patients able to leave the ICU. In conclusion NIV may be regarded as the treatment of choice in patients with cystic fibrosis admitted to ICU with respiratory failure. In the case of persistent hypercapnia after the acute episode long-term NIV may keep them stable while awaiting lung transplantation.

Solution-mediated phase transformation of anhydrous to dihydrate carbamazepine and the effect of lattice disorder.

This paper describes the kinetics of the solution-mediated phase transformation of the anhydrous monoclinic polymorph of carbamazepine (CBZ(A)) to the dihydrate crystal form (CBZ(D)). Monitoring both solution concentration and solid phase composition identified the steps and mechanisms that control the kinetic processes, and regulate the concentration of drug achieved during dissolution of the metastable solid phase, CBZ(A). The results show that the kinetics and the rate-controlling step for the transformation depend on grinding and storage conditions of CBZ(A). Grinding CBZ(A) shortened the transformation times and changed the rate-controlling step from crystallization of CBZ(D) to dissolution of CBZ(A). Grinding may cause various degrees of disorder in the form of lattice defects and/or amorphous regions. These disordered regions promote the anhydrous to dihydrate transformation by facilitating the surface nucleation of CBZ(D) on freshly ground CBZ(A) and on amorphous CBZ. The concentration-time profiles revealed aging effects on the solution-mediated transformation of ground CBZ(A) that were undetectable by diffraction and thermal analysis. These results have significant consequences on the concentration-time profiles of active pharmaceutical ingredients during dissolution of metastable solid phases, crystalline or amorphous.

Outcome of patients with idiopathic pulmonary fibrosis admitted to the ICU for respiratory failure.

STUDY OBJECTIVES: To analyze the outcome of acute respiratory failure (ARF) in patients with idiopathic pulmonary fibrosis (IPF), and to evaluate the benefits of invasive and noninvasive mechanical ventilation (MV). DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Fifteen consecutive patients with IPF referred to the ICU for ARF between January 1989 and June 1998. MEASUREMENTS AND RESULTS: Fifteen patients (mean +/- SD age, 64 +/- 10 years) were included. Eight patients had clinical, functional, and radiologic features of IPF, and the remaining seven patients also had biopsy specimen-proven IPF. The mean duration between diagnosis of IPF and admission to the ICU was 26.5 +/- 28 months. At the time of ICU admission, mean arterial blood gas levels were as follows: PaO(2)/fraction of inspired oxygen, 113 +/- 95; pH, 7.32 +/- 0.10; and PaCO(2), 55 +/- 21 mm Hg. All patients received MV; 12 patients required tracheal intubation, either at the time of ICU admission (n = 10) or after failure of noninvasive ventilation (NIV; n = 2); and 3 patients only received NIV. Three of the five patients receiving NIV died of respiratory failure. Eleven patients died in the ICU, either from hypoxemia (n = 8) or from septic shock (n = 3). Four patients were discharged alive from the ICU, and two of them died shortly thereafter. CONCLUSION: The outcome of patients with IPF referred to the ICU for ARF was very poor and not improved by MV. Without a clearly identified reversible cause of ARF, these patients should not benefit from admission to the ICU.

[Mandibular advancement orthoses used in the treatment of obstructive sleep apnea syndrome]. / Orthèses d'avancement mandibulaire utilisées comme traitement du syndrome d'apnée obstructive du sommeil.

Mandibular advancement devices represent a therapeutic option for obstructive sleep apnea syndrome (OSAS). Clinical improvement has been proven in the different available studies, mainly on nocturnal respiratory events and quality of sleep. Less snoring have been noted by bed partners and objective studies have demonstrated decrease in snoring frequency and intensity. The effect of these ortheses on upper airways resistance syndrome is not yet well documented. The significant clinical improvement is secondary to the decrease in the occurrence of apneas and hypopneas. Polysomnographic improvement criteria with an apnea hypopnea index less than 10 per hour has been noted in certain cases. Although no improvement or even worsening was noted in other cases. Sleep architecture has also changed in these patients, with a decrease in the time spent in stages 1 and 2, and an increase in the time spent in stages 3 and 4 and rapid eye movement sleep. Micro-arousals are also decreased in number certainly with the decrease in the occurrence of respiratory events. Somnolence and loss of attention are improved; these have been evaluated subjectively or by a well known and approved somnolence scale. In some cases a test for vigilance was done.

Principles of mandibular advancement device applied to the therapeutic of snoring and sleep apnea syndrome.

Mandibular advancement device (MAD) represents a therapeutic option for simple snoring to obstructive sleep apnea syndrome (OSAS). The different available studies report an improvement either on nocturnal respiratory events or on the quality of sleep. The decrease in the intensity of snoring is confirmed by the patient's partner and by objective studies. For the time being the effects of these mandibular advancement devices on the upper airway resistance syndrome has not yet been well documented. The significant clinical improvement is secondary to the decrease in apnea hypopnea index (AHI). A polysomnographically proved cure has been reported with AHI < 10/h. Sleep architecture is also improved with wearing MAD demonstrating a decrease in the time passed in stage 1 sleep and an increase in slow wave sleep and rapid eye movement sleep (REM). A decrease in microarousals index has been shown. Daytime vigilance disorders are subjectively and objectively less remarkable. Then MAD can be beneficial for mild to moderate SAOS.

Nocturnal hypoventilation in chronic respiratory failure (CRF) due to neuromuscular disease.

Decrease of respiratory muscle capacities in neuromuscular disease can lead to chronic respiratory failure with permanent alveolar hypoventilation. Respiratory centers elaborate a strategy of breathing dedicated to prevent overt respiratory muscles fatigue. This strategy may worsen chronic hypercapnia. During sleep, ventilation decreases because a lessening in respiratory centers function. During NREM sleep hypoventilation is only an exacerbation of what is seen during wakefulness. During REM sleep, atonia worsens much more hypoventilation particularly when diaphragmatic function is impaired. The effects of atonia are amplified by a very low reactivity of respiratory centers. Nocturnal mechanical ventilation improves nocturnal hypoventilation and daytime arterial blood gases (ABG). Mechanism of improvement in ABG and how nocturnal hypoventilation and diurnal hypoventilation interact, are still a matter of debate.

[Mandibular advancement orthotic for treatment of obstructive sleep apnea]. / Orthèses d'avancement mandibulaire utilisées comme traitement du syndrome d'apnée obstructive du sommeil.

Mandibular advancement devices represent a therapeutic option for obstructive sleep apnea syndrome (OSAS). Clinical improvement has been proved in the different available studies, mainly on nocturnal respiratory events and quality of sleep. Less snoring have been noted by bed partners and objective studies have demonstrated decrease in snoring frequency and intensity. The effect of these ortheses on upper airways resistance syndrome is not yet well documented. The significant clinical improvement is secondary to the decrease in the occurrence of apneas and hypopneas. Polysomnographic improvement criteria with an apnea hypopnea index less than 10 per hour has been noted in certain cases. Although no improvement or even worsening was noted in other cases. Sleep architecture has also changed in these patients, with a decrease in the time spent in stages 1 and 2, and an increase in the time spent in stages 3 and 4 and rapid eye movement sleep. Microarousals are also decreased in number certainly with the decrease in the occurrence of respiratory events. Somnolence and loss of attention are improved; these have been evaluated subjectively or by a well known and approved somnolence scale. In some cases a test for vigilance was done.

Effects of prone position on alveolar recruitment and oxygenation in acute lung injury.

OBJECTIVE: To investigate the effects of prone position (PP) on alveolar recruitment and oxygenation in acute respiratory failure. DESIGN: Prospective physiologic study. SETTING: Medical ICU two in a university hospital. PATIENTS: Twelve adult patients intubated and mechanically ventilated with medical primary acute lung injury/adult respiratory distress syndrome (ALI/ARDS) in whom PP was indicated. MEASUREMENTS AND RESULTS: We constructed the static inflation volume-pressure curves (V-P) of the respiratory system in the 12 patients and differentiated between lung and chest wall in ten of them. We determined the difference between end-expiratory lung volume on positive end-expiratory pressure (PEEP) and relaxation volume of the respiratory system on zero PEEP (delta FRC). The recruited alveolar volume was computed as the delta FRC times the ratio of static elastance of the respiratory system to the lung. These measurements together with arterial blood gases determination were made in supine position (SP1), after 1 h of PP and after 1 h of supine repositioning (SP2) at the same level of PEEP. The PaO2/FIO2 ratio improved from SP1 to PP (136 +/- 17 vs 204 +/- 24 mm Hg; p < 0.01). An PP-induced alveolar recruitment was found in five patients. The change in oxygenation correlated to the recruited volume. The static elastance of the chest wall decreased from 4.62 +/- 0.99 cmH2O/l in SP1 to 6.26 +/- 0.54 cmH2O/l in PP (p < 0.05) without any correlation to the change in oxygenation. CONCLUSIONS: Alveolar recruitment may be a mechanism of oxygenation improvement in some patients with acute hypoxemic respiratory failure. No correlation was found between change in oxygenation and chest wall elastic properties.

Sleep fragmentation in kyphoscoliotic individuals with alveolar hypoventilation treated by NIPPV.

Intermittent positive pressure ventilation (IPPV) delivered via nasal access can normalize alveolar ventilation for individuals with chronic alveolar hypoventilation (CAH) due to neuromuscular disease, spinal cord injury, or skeletal deformity. The purpose of this study was to evaluate the effect of nasal IPPV (NIPPV) air leakage-associated oxyhemoglobin desaturations (dSATs) on the sleep efficiency of kyphoscoliotic individuals with severe pretreatment nocturnal dSATs. Only individuals using nocturnal NIPPV without supplemental oxygen therapy were studied. Seven such individuals were able to maintain PaO2 greater than 60 mm Hg without supplemental oxygen therapy (five had been using oxygen therapy in the pretreatment period), had fewer hospitalizations, and had improvements in symptoms, arterial blood gas values, and nocturnal oxyhemoglobin saturation (SAT) by nocturnal NIPPV. This occurred despite polysomnographically observed sleep disruption and sleep stage changes associated with frequent transient dSATs and massive insufflation leakage. Arousals and dSATs were most frequent during rapid eye movement (REM) sleep with the latter occurring at a frequency of 10/h. The dSATs resulted in brief arousals or lightening of sleep stage 76% of the time. With or without arousal, central nervous system mediated reflex muscular activity occurred to diminish leak and normalize SAT. We conclude that the effectiveness of nocturnal NIPPV is dependent in part on central mediated muscular activity.

Side effects of nasal continuous positive airway pressure in sleep apnea syndrome. Study of 193 patients in two French sleep centers.

Nasal continuous positive airway pressure (N-CPAP) is now the treatment of choice for patients with sleep apnea syndrome (SAS). Side effects and adverse reactions have been described with this device. We have therefore systematically studied side effects of N-CPAP in 193 patients recruited consecutively from two French sleep centers (Lyon and Grenoble). Patients were followed up with repeated polysomnography, clinical assessment, and a formal questionnaire about subjective benefits and side effects of treatment. The patients (mean age, 59 +/- 12 years) were obese (body mass index, 32 +/- 7 kg/m2) and had been using N-CPAP for 19 +/- 17 months for moderate to severe SAS (respiratory disturbance index [RDI] = 53 +/- 25/h). The clinical presentation was the same in the two sleep centers. Fifty percent of the patients complained of at least one side effect due to the nasal mask (allergy to the face, air leaks, abrasions of the ridge of the nose). Using individually molded masks, the patients exhibited fewer abrasions of the bridge of the nose (p < 0.01) and had red eyes every morning in only 9% of cases vs 24% for the patients using industrial silicone nasal masks (p < 0.025). Patients with silicone nasal masks also had more allergic reaction to the face (13% vs 5%), but this difference did not reach significance. Dry nose or mouth in the morning affected 65% of the patients. Sneezing and nasal drip were present in more than 35% of the subjects and nasal congestion in 25%. When the patients were separated in two groups, whether or not using a humidifier, no difference was found for any of the side effects described. The clinical presentation as to the clinical benefits obtained from N-CPAP were different when comparing mild vs moderate-to-severe SAS. However, no differences were shown in the two subgroups regarding the side effects due to the nasal mask. The discomfort of the N-CPAP apparatus in terms of noise was described more frequently in the subgroup with mild SAS. We did not observe any correlation between the side effects and the level of pressure used during N-CPAP. The rate of compliance remains high with a daily use of 6.5 +/- 3 h, with 88% of the patients using their device every night. This could be explained by the clinical benefit obtained: only 1% of the patients had no subjective benefit induced by their therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Nasal intermittent positive pressure ventilation. Long-term follow-up in patients with severe chronic respiratory insufficiency.

Prior studies have shown that nasal intermittent positive pressure ventilation (NIPPV) can improve arterial blood gas values, prevent symptoms resulting from alveolar hypoventilation, and decrease hospitalization in patients with chronic respiratory failure. Most studies have involved small samples of patients followed up for a limited time. This study reviews our experience during 5 years use of NIPPV in 276 patients with kyphoscoliosis, posttuberculosis sequelae, Duchenne-type muscular dystrophy, COPD, and bronchiectasis followed up for > or = 3 years while receiving NIPPV. Outcomes were compared for patients who survived short term eg, died or converted to management with a tracheostomy and intermittent positive ventilation (TIPPV) during year 1 or year 2 on a regimen of NIPPV and long term, eg, survived more > or = 2 years on a regimen of NIPPV. The most favorable outcome was achieved by patients with kyphoscoliosis and posttuberculosis sequelae with improvement in PaO2 and PaCO2 (p < 0.0001) and a reduction in days of hospitalization for respiratory illness (p < 0.0001) for > or = 2 years while receiving NIPPV. Patients with Duchenne-type muscular dystrophy also had fewer hospital days during NIPPV (p < 0.003) but only 9 of 16 patients (56 percent) continued using NIPPV for the duration of followup. Benefit was also more short term for patients with COPD and bronchiectasis. NIPPV can sustain improvement in gas exchange, while reducing hospitalization for substantial periods of time. NIPPV can be an attractive and effective alternative to other methods of assisted ventilation such as TIPPV.

Sleep apnea syndrome and end-stage renal disease. Cure after renal transplantation.

We report two patients undergoing maintenance hemodialysis who presented with sleep apnea syndrome (SAS). The first patient is a 36-year-old man with a terminal Berger's glomerulopathy and associated obstructive sleep apnea syndrome (OSAS) (apnea-hypopnea index [AHI] = 80). He was receiving home hemodialysis and was treated by nasal continuous positive airway pressure (CPAP). After successful renal transplantation, his symptoms completely disappeared, and control polysomnography greatly improved (AHI = 9). The second patient had hypokalemic nephropathy with severe, uncontrolled hypertension and hypertensive myocardiopathy. He was receiving home dialysis and showed a central sleep apnea syndrome with an AHI of 51. He also was successfully treated by nasal CPAP. After renal transplantation, his sleep improved, insomnia disappeared, and polysomnography showed great improvement (AHI = 5). We discuss the role of periodic breathing related to end-stage renal disease associated metabolic abnormalities, as a pathogenetic factor of these SASs. Respiratory correction of chronic metabolic acidosis, "uremic toxins," "middle molecules," and hemodialysis are all evoked as etiologic factors and their own roles are discussed.

[Chronic respiratory insufficiency. Non-invasive long-term ventilation methods]. / Insuffisance respiratoire chronique. Méthodes non invasives de ventilation au long cours.

The techniques of non-invasive ventilation have reappeared in force as an assortment of therapeutic techniques since the end of the 1980's. At the same time there was a transient renewed interest in perithoracic ventilation favouring the use of new methods of connection to the patient (e.g. poncho). The principal feature has been the use of intermittent positive pressure ventilation by the nasal route, which rapidly became essential for home therapy in patients with chronic restrictive respiratory failure notably in those secondary to thoracic deformation and to neuromuscular pathology. The concept of resting the respiratory muscles has been the basis for techniques of ventilatory assistance and in part the nasal route has now replaced home ventilation using a tracheotomy. Also in certain types of acute respiratory failure, nasal ventilation widely preferred over endotracheal ventilation.

[Bronchiolo-alveolar carcinoma complicating myasthenia treated by azathioprine]. / Carcinome bronchiolo-alvéolaire compliquant une myasthénie traitée par azathioprine.

We report a case of broncho-alveolar carcinoma (CBA) in a man of 64 who had been treated with azathioprine for severe myasthenia gravis. The myasthenia was characterized by predominant involvement of the respiratory muscles, by resistance to anticholinesterase and by association with a thymoma without improvement after thymectomy. The CBA was associated with alveolar haemorrhage (HA) confirmed by lung biopsy and also by an infection due to Mycobacterium chelonae. The occurrence of HA in an immunodepressed patient is often due to an infection, notably aspergillosis. The role of CBA and the mycobacterial infections in the pathogenesis of HA is discussed. The use of azathioprine may lead to the occurrence of cancers, notably lung cancers, and also to haemopoietic neoplasia when doses of greater than 50 grams are used. We think that azathioprine may have contributed to the genesis of CBA in our patients.