Hospital outcomes and long-term survival after referral to a specialized weaning unit.

BACKGROUND.: Prolonged invasive mechanical ventilation (IMV) is a frequent challenge, and an increasing number of patients are transferred from intensive care units to long-term acute care hospitals or specialized weaning units. There are few published data for discharge home rates, use of noninvasive ventilation (NIV), or long-term survival. METHODS.: A case-note and database review was conducted of patients admitted to a UK national specialized weaning unit for weaning from IMV between 1992 and 2012. Patients were grouped into diagnostic categories according to the predominant cause of weaning failure. Weaning outcomes and long-term survival were assessed according to diagnostic group and mode of ventilation on discharge. RESULTS.: Four hundred and fifty-eight patients were transferred for weaning from IMV. Four hundred and seventeen (91%) survived to hospital discharge, of whom at least 343 (82%) were ultimately discharged to their own home. Three hundred and thirty (72%) weaned from IMV, of whom 142 weaned from all ventilation and 188 weaned to nocturnal NIV. Weaning success was highest for patients with chronic obstructive pulmonary disease and chest wall disorders. Median survival from unit discharge was 25 months (interquartile range 5-74), with the longest survival seen for patients discharged with nocturnal NIV [37 (12-81) months]. CONCLUSIONS.: These results confirm successful weaning outcomes for patients transferred to a specialized weaning and long-term ventilation service. In contrast to other service models, most patients achieved discharge to their own home.

Recessive mutations in the cancer gene Ataxia Telangiectasia Mutated (ATM), at a locus previously associated with metformin response, cause dysglycaemia and insulin resistance.

AIM: To investigate glucose and insulin metabolism in participants with ataxia telangiectasia in the absence of a diagnosis of diabetes. METHODS: A standard oral glucose tolerance test was performed in participants with ataxia telangiectasia (n = 10) and in a control cohort (n = 10). Serial glucose and insulin measurements were taken to permit cohort comparisons of glucose-insulin homeostasis and indices of insulin secretion and sensitivity. RESULTS: During the oral glucose tolerance test, the 2-h glucose (6.75 vs 4.93 mmol/l; P = 0.029), insulin concentrations (285.6 vs 148.5 pmol/l; P = 0.043), incremental area under the curve for glucose (314 vs 161 mmol/l/min; P = 0.036) and incremental area under the curve for insulin (37,720 vs 18,080 pmol/l/min; P = 0.03) were higher in participants with ataxia telangiectasia than in the controls. There were no significant differences between groups in fasting glucose, insulin concentrations or insulinogenic index measurement (0.94 vs 0.95; P = 0.95). The Matsuda index, reflecting whole-body insulin sensitivity, was lower in participants with ataxia telangiectasia (5.96 vs 11.03; P = 0.019) than in control subjects. CONCLUSIONS: Mutations in Ataxia Telangiectasia Mutated (ATM) that cause ataxia telangiectasia are associated with elevated glycaemia and low insulin sensitivity in participants without diabetes. This indicates a role of ATM in glucose and insulin metabolic pathways.

Cerebrospinal fluid hypocretin levels are normal in idiopathic REM sleep behaviour disorder.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is a common sleep disorder that can be associated with a number of neurodegenerative conditions as well as with narcolepsy. Current diagnostic criteria require overnight polysomnography, and there are no other biomarkers available. The control of REM sleep is complex with a putative on/off switch within the brainstem activated, amongst other things, by hypocretinergic pathways from the lateral hypothalamus. METHODS: Cerebrospinal fluid hypocretin levels were measured in five patients with idiopathic RBD. RESULTS: Hypocretin levels were between 254 and 450 pg/ml and therefore within the normal range of >100 pg/ml. CONCLUSION: Hypocretin levels in patients with idiopathic RBD are normal.

Why does gender influence survival in obstructive sleep apnoea?

The study aim was to compare the mortality risk of men and women diagnosed with obstructive sleep apnoea (OSA) and started on treatment with continuous positive airway pressure (CPAP). From August to December 2003 we reviewed the hospital records of patients who had started on CPAP for OSA between July 1995 and June 1998. Mortality rates were compared between men and women. Associations with mortality risk were determined using univariate and multivariate Cox's proportional hazards regression. The sample comprised 292 men and 47 women. Eight percent of the men and 23% of the women died (p=0.003). Univariate analysis showed increased mortality risk was associated with female sex, greater age when CPAP was started, a pre-treatment minimum nocturnal oxygen saturation (SpO(2)) <75%, a higher Charlson comorbidity index score and discontinuation of CPAP treatment. Female sex remained associated with increased mortality independent of age, minimum SpO(2) and CPAP use, but was not independent of the Charlson score. Women diagnosed with OSA and treated with CPAP demonstrated a 3.44 greater mortality risk than men, mostly due to greater comorbidity.

Vocal fold palsy due to plombage for tuberculosis.

A 67-year-old patient, who had previously undergone Lucite ball plombage for pulmonary tuberculosis, presented with a hoarse voice, intermittent stridor and breathlessness. Direct laryngoscopy confirmed a left vocal fold palsy. A left supraclavicular mass became apparent and a computerized tomograph (CT) scan showed that a Lucite ball had migrated into her supraclavicular fossa. Subsequently she developed left arm pain and weakness. The balls were removed surgically, following which her arm symptoms improved but her voice remained unchanged. Migration of implanted material should be considered when new symptoms appear in patients who have undergone plombage treatment.

Respiration during sleep in neuromuscular and thoracic cage disorders.

Many of the neuromuscular and thoracic cage disorders are associated with disorders of breathing during sleep. The abnormal mechanics of the chest wall impairs respiratory muscle function and this is compounded if there is underlying muscle weakness. Respiratory abnormalities appear during REM sleep before NREM or wakefulness. Central sleep apnoeas are characteristic, but obstructive apnoeas are also occur because of loss of tone in the upper airway dilator muscles. Arousals from sleep return the blood gases towards normal, but cause fragmentation of sleep, leading to daytime sleepiness. Ventilatory failure occurs particularly if the vital capacity is less than 1.0-1.5 litres or if the maximal inspiratory mouth pressure is less than 20-25cmH2O. Non invasive ventilation effectively prevents both central and obstructive apnoeas and improves the sleep architecture and daytime blood gases.

Increased ventilation with NiIPPV does not necessarily improve exercise capacity in COPD.

Evidence that noninvasive intermittent positive-pressure ventilation (NiIPPV) improves exercise capacity in chronic obstructive pulmonary disease (COPD) is limited. The effectiveness of different ventilators in this setting has not been studied. Three bilevel pressure support ventilators (Bipap S/T 30, Nippy2 and Vpap II ST), applied via a mouthpiece, were compared during submaximal treadmill exercise in eight subjects with COPD. Subjects walked to exhaustion with each of the ventilators and while breathing through the mouthpiece alone, in random order. In addition, four unencumbered walks were performed. The unencumbered distance (mean +/- SD) walked was 259 +/- 123 m. With the mouth-piece alone this decreased to 211 +/- 96 m and fell further to 145 +/- 76 m with NiIPPV. There was no difference between the brands of ventilator. At the break-point of exercise, significant increases were seen in tidal volume and minute ventilation in the ventilator walks compared with the mouthpiece alone. Noninvasive intermittent positive-pressure ventilation increased ventilation but did not improve exercise capacity in the subjects in this study. No significant differences were seen between the ventilators. The effectiveness of this technique and the optimal method of assistance require further clarification.

An overnight comparison of two ventilators used in the treatment of chronic respiratory failure.

Differences between bilevel ventilators used for noninvasive intermittent positive pressure ventilation (NIPPV) have been demonstrated during bench testing. However, there are no clinical studies comparing these machines. The authors have previously shown that the Quantum pressure support ventilator and Sullivan variable positive airway pressure II ST differ in performance during bench testing. To examine the clinical significance of this, these two machines were compared in the overnight treatment of subjects with chronic respiratory failure. Ten clinically-stable subjects with thoracic scoliosis were recruited. The subjects were already established on NIPPV, but none were using either of the ventilators to be tested. After familiarisation, the patients used the two ventilators in random order on consecutive nights. Peripheral oxygen saturation and transcutaneous carbon dioxide tension (Pt,CO2) were measured continuously, and sleep was recorded using polysomnography. There were no significant differences in arterial oxygen saturation, Pt,CO2 or sleep duration and quality between the two nights. Despite previously illustrated variation in laboratory performance, no differences were seen between the two ventilators when comparing overnight gas exchange and sleep in vivo. Further study is required to evaluate the significance of the differences found during bench testing in the clinical setting.

Noninvasive ventilation for chest wall and neuromuscular disorders.

Neuromuscular and chest wall disorders are individually uncommon but together form an important group of conditions that can lead to chronic ventilatory failure. This is best recognised in scoliosis, kyphosis, following a thoracoplasty, in muscular dystrophies, such as Duchenne muscular dystrophy (DMD), and myotonic dystrophy, after poliomyelitis and with motor neurone disease (amyotrophic lateral sclerosis). If bulbar function is impaired, tracheostomy ventilation may be required, but in other situations, noninvasive ventilation is preferable. Positive pressure techniques using nasal and face masks are usually the first choice, but negative pressure ventilation is an alternative. There are no randomised-controlled trials regarding the indications for initiating noninvasive ventilation, but this is usually provided if there are symptoms due to nocturnal hypoventilation or right heart failure in the presence of a raised carbon dioxide tension in arterial blood (Pa,CO2) either at night or, more usually, in the daytime as well. There is no evidence that "prophylactic" ventilatory support is of benefit if this is provided before ventilatory failure has appeared. Careful selection of patients is required, especially in the presence of progressive neuromuscular disorders such as DMD and motor neurone disease. There are no randomised-controlled trials concerning the outcome of noninvasive ventilation in these conditions, but studies have shown an improved quality of life, physical activity and haemodynamics, normalisation of blood gases and slight improvement in other physiological measures, such as the vital capacity and maximal mouth pressures. Survival in chest wall disorders is approximately 90% at 1 yr and 80% at 5 yrs, and similar figures have been obtained in nonprogressive neuromuscular conditions. If, however, the underlying disorder is deteriorating, particularly if it involves the bulbar muscles, it may limit survival despite the provision of adequate noninvasive ventilatory support.

Narcolepsy and psychopathology: is there an association?

BACKGROUND: It is widely believed that patients with narcolepsy show high rates of associated psychiatric disturbance, especially schizophrenia and depression. However, surveys have produced conflicting findings and have not addressed the potential confounding effects of stimulant drug treatment. METHOD: Forty-five patients with narcolepsy attending a sleep disorder clinic and 50 matched normal controls underwent structured psychiatric interview. Using a 'lifetime' approach, psychiatric symptoms and diagnoses were established for both groups. RESULTS: Four of the narcolepsy patients but none of the controls had experienced psychotic symptoms. All four patients were taking amphetamines, and the symptoms resolved when the dose was lowered or treatment was changed to modafinil. The lifetime frequency of various depressive syndromes did not differ significantly between the groups. CONCLUSIONS: Contrary to previous claims this study found little to suggest that narcolepsy is associated with schizophrenia. Nor, despite its serious social and occupational consequences, does narcolepsy appear to be associated with an increased frequency of diagnosable depressive disorders.

Effect of manually assisted cough and mechanical insufflation on cough flow of normal subjects, patients with chronic obstructive pulmonary disease (COPD), and patients with respiratory muscle weakness.

BACKGROUND: It has been suggested that cough effectiveness can be improved by assisted techniques. The effects of manually assisted cough and mechanical insufflation on cough flow physiology are reported in this study. METHODS: The physiological actions and patient self-assessment of manually assisted cough and mechanical insufflation were investigated in 29 subjects (nine normal subjects, eight patients with chronic obstructive pulmonary disease (COPD), four subjects with respiratory muscle weakness (RMW) with scoliosis, and eight subjects with RMW without scoliosis). RESULTS: The peak cough expiratory flow rate and cough expiratory volume were not improved by manually assisted cough and mechanical insufflation alone or in combination in normal subjects. The median increase in peak cough expiratory flow in subjects with RMW without scoliosis with manually assisted cough alone or in combination with mechanical insufflation of 84 l/min (95% confidence interval (CI) 19 to 122) and 144 l/min (95% CI 14 to 195), respectively, reflects improvement in the expulsive phase of coughing by these techniques. Manually assisted cough and mechanical insufflation in combination raised peak expiratory flow rate more than either technique alone in this group. The abnormal chest shape in scoliotic subjects and the fixed inspiratory pressure used made effective manually assisted cough and mechanical insufflation difficult in this group and no improvements were found. In patients with COPD manually assisted cough alone and in combination with mechanical insufflation decreased peak expiratory flow rate by 144 l/min (95% CI 25 to 259) and 135 l/min (95% CI 30 to 312), respectively. CONCLUSIONS: Manually assisted cough and mechanical insufflation should be considered to assist expectoration of secretions in patients with RMW without scoliosis but not in those with scoliosis.

Functional differences in bi-level pressure preset ventilators.

The performance of four bilevel positive pressure preset ventilators was compared. The ventilators tested were; BiPAP ST30 (Respironics); Nippy2 (B + D Electrical); Quantum PSV (Healthdyne); and Sullivan VPAP H ST (Resmed). A patient simulator was used to determine the sensitivity of the triggering mechanisms and the responses to a leak within the patient circuit, and to changes in patient effort. Significant differences (p <0.05) between the devices were seen in the trigger delay time and inspiratory trigger pressure. When a leak was introduced into the patient circuit, the fall in tidal volume (VT) was less than ten per cent for each ventilator. The addition of patient effort produced a number of changes in the ventilation delivered. Patient efforts of 0.25 s induced a variable fall in VT. An increase in VT was seen with some ventilators with patient efforts of 1 s but the effect was variable. Trigger failures and subsequent falls in minute volume were seen with the BiPAP and the Nippy2 at the highest respiratory frequency. Differences in the responses of the ventilators are demonstrated that may influence the selection of a ventilator, particularly in the treatment of breathless patients with ventilatory failure.

Health-related quality of life in narcolepsy.

Narcolepsy is a chronic sleep disorder characterised by symptoms of excessive daytime sleepiness and cataplexy. The aim of this study was to describe the health-related quality of life of people with narcolepsy residing in the UK. The study comprised a postal survey of 500 members of the UK narcolepsy patient association, which included amongst other questions the UK Short Form 36 (SF-36), the Beck Depression Inventory (BDI), and the Ullanlinna Narcolepsy Scale (UNS). A total of 305 questionnaires were included in the final analysis. The results showed that the subjects had significantly lower median scores on all eight domains of the SF-36 than normative data, and scored particularly poorly for the domains of role physical, energy/vitality, and social functioning. The BDI indicated that 56.9% of subjects had some degree of depression. In addition, many individuals described limitations on their education, home, work and social life caused by their symptoms. There was little difference between the groups receiving different types of medication. This study is the largest of its type in the UK, although the limitations of using a sample from a patient association have been recognised. The results are consistent with studies of narcolepsy in other countries in demonstrating the extensive impact of this disorder on health-related quality of life.