Randomised crossover trial of telemonitoring in chronic respiratory patients (TeleCRAFT trial).

DESIGN: Randomised crossover trial with 6 months of standard best practice clinical care (control group) and 6 months with the addition of telemonitoring. PARTICIPANTS: 68 patients with chronic lung disease (38 with COPD; 30 with chronic respiratory failure due to other causes), who had a hospital admission for an exacerbation within 6 months of randomisation and either used long-term oxygen therapy or had an arterial oxygen saturation (SpO2) of <90% on air during the previous admission. Individuals received telemonitoring (second-generation system) via broadband link to a hospital-based care team. OUTCOME MEASURES: Primary outcome measure was time to first hospital admission for an acute exacerbation. Secondary outcome measures were hospital admissions, general practitioner (GP) consultations and home visits by nurses, quality of life measured by EuroQol-5D and hospital anxiety and depression (HAD) scale, and self-efficacy score (Stanford). RESULTS: Median (IQR) number of days to first admission showed no difference between the two groups­77 (114) telemonitoring, 77.5 (61) control ( p=0.189). Hospital admission rate at 6 months increased (0.63 telemonitoring vs 0.32 control p=0.026). Home visits increased during telemonitoring; GP consultations were unchanged. Self-efficacy fell, while HAD depression score improved marginally during telemonitoring. CONCLUSIONS: Telemonitoring added to standard care did not alter time to next acute hospital admission, increased hospital admissions and home visits overall, and did not improve quality of life in chronic respiratory patients. TRIAL REGISTRATION NUMBER: NCT02180919 (ClinicalTrials.gov).

Risk management protocol for gastrostomy and jejunostomy insertion in ventilator dependent infants.

Gastrostomy, gastrojejunostomy and anti-reflux surgery in infants and children who are chronically ventilator dependent are associated with significant risk of morbidity and mortality. We report outcomes of 22 high risk children who underwent these procedures at our centre. Pre-operative investigations included: overnight oxygen and carbon dioxide monitoring and subsequent optimisation of ventilatory support, echocardiography, video fluoroscopy, and assessment of gastroesophageal reflux. We carried out 24 procedures under general anaesthesia. Twenty-one children used ventilatory support pre-operatively. Median age of first surgical procedure was 18 months (range 3-180). Supplementary feeding was commenced in 20 children prior to procedure, median age 9 months (1-31). Median PICU length of stay was 1 (1-8) days. No children died in the post-operative period. Extubation was possible within 24h in 87% of cases. Complications included; atelectasis (n=2), ileus (n=2), abdominal distension (n=4) and loose stools (n=1). We conclude that, in this high risk cohort of ventilator dependent children with predominantly neuromuscular disorders, with careful assessment, operative intervention can be carried out under general anaesthesia, with the child being extubated early back onto their routine ventilatory support and aggressive airway clearance. Additionally this protocol can minimise post-operative complications and is associated with a good outcome in the majority.

Outcome of goal-directed non-invasive ventilation and mechanical insufflation/exsufflation in spinal muscular atrophy type I.

BACKGROUND: There are widely discrepant views on the respiratory management of infants with spinal muscular atrophy (SMA) type I. Typically, management is palliative. DESIGN: A descriptive study of interventions and investigations is reported that were offered to a cohort of 13 children with SMA type I referred to our centre. Interventions and investigations included sleep studies, provision of non-invasive positive pressure ventilation (NIPPV) for ventilatory support/dependency and for physiotherapy and the use of mechanical insufflation/exsufflation (MI-E). RESULTS: NIPPV was provided for the following indications: continuous positive airways pressure flow driver dependency (n=3), nocturnal hypoventilation (n=3), to enable successful extubation (n=2), in anticipation of respiratory decompensation (n=3), and oxygen dependency/decompensation (n=2). NIPPV and MI-E were used for successful protocol-led extubations (n=9) but not non protocol-led successes (n=3). NIPPV was essential for discharge home in patients with ventilatory dependency (n=7) and was used for palliation of respiratory symptoms (n=4). Chest wall shape improved with NIPPV. The parents of children who died (n=5) were positive about the use of these techniques. CONCLUSION: NIPPV can be used to facilitate discharge home, and MI-E is helpful in this group. This symptom and goal-directed approach can be used to inform medical decision making and to help parents make informed choices about the appropriateness of respiratory interventions in SMA type I.

Evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic influenza and other airborne infections.

BACKGROUND: Influenza viruses are thought to be spread by droplets, but the role of aerosol dissemination is unclear and has not been assessed by previous studies. Oxygen therapy, nebulised medication and ventilatory support are treatments used in clinical practice to treat influenzal infection are thought to generate droplets or aerosols. OBJECTIVES: Evaluation of the characteristics of droplet/aerosol dispersion around delivery systems during non-invasive ventilation (NIV), oxygen therapy, nebuliser treatment and chest physiotherapy by measuring droplet size, geographical distribution of droplets, decay in droplets over time after the interventions were discontinued. METHODS: Three groups were studied: (1) normal controls, (2) subjects with coryzal symptoms and (3) adult patients with chronic lung disease who were admitted to hospital with an infective exacerbation. Each group received oxygen therapy, NIV using a vented mask system and a modified circuit with non-vented mask and exhalation filter, and nebulised saline. The patient group had a period of standardised chest physiotherapy treatment. Droplet counts in mean diameter size ranges from 0.3 to > 10 µm were measured with an counter placed adjacent to the face and at a 1-m distance from the subject/patient, at the height of the nose/mouth of an average health-care worker. RESULTS: NIV using a vented mask produced droplets in the large size range (> 10 µm) in patients (p = 0.042) and coryzal subjects (p = 0.044) compared with baseline values, but not in normal controls (p = 0.379), but this increase in large droplets was not seen using the NIV circuit modification. Chest physiotherapy produced droplets predominantly of > 10 µm (p = 0.003), which, as with NIV droplet count in the patients, had fallen significantly by 1 m. Oxygen therapy did not increase droplet count in any size range. Nebulised saline delivered droplets in the small- and medium-size aerosol/droplet range, but did not increase large-size droplet count. CONCLUSIONS: NIV and chest physiotherapy are droplet (not aerosol)-generating procedures, producing droplets of > 10 µm in size. Due to their large mass, most fall out on to local surfaces within 1 m. The only device producing an aerosol was the nebuliser and the output profile is consistent with nebuliser characteristics rather than dissemination of large droplets from patients. These findings suggest that health-care workers providing NIV and chest physiotherapy, working within 1 m of an infected patient should have a higher level of respiratory protection, but that infection control measures designed to limit aerosol spread may have less relevance for these procedures. These results may have infection control implications for other airborne infections, such as severe acute respiratory syndrome and tuberculosis, as well as for pandemic influenza infection.

Analysis of home support and ventilator malfunction in 1,211 ventilator-dependent patients.

Risk management is an important aspect of home ventilation (HV). We examined the nature of calls to a home support helpline to identify patient/equipment problems and strategies to minimise risk for patients, healthcare teams and manufacturers. From 1,211 adult and paediatric patients with neuromuscular disease, chronic obstructive pulmonary disease or chest wall disease receiving HV, all calls to a dedicated respiratory support telephone hotline between January 1, 2006 and June 30, 2006 were analysed. 1,199 patients received noninvasive ventilation, 12 tracheostomy ventilation; 149 had two ventilators for 24-h ventilator dependency. There was a mean of 528 daytime calls per month and 14 calls a month at night. Following 188 calls, a home visit was performed; these identified a technical problem that could either be solved in the patient's home in 64% or required replacement or new parts in 22% of cases. In 25 calls in which no mechanical fault was identified, 13 patients were either found to be unwell or required hospital admission. Patients using HV have a substantial requirement for assistance, with most technical problems being resolved simply. Where no fault can be found during an equipment check, the patient themselves may be unwell and should receive early clinical evaluation. The patient may have mistaken clinical deterioration for an equipment problem.

Resolution of central sleep apnoea following implantation of a left ventricular assist device.

Central sleep apnoea (CSA) occurs in up to 40% of patients with chronic heart failure (CHF). It is thought to be a consequence of CHF and is associated with an accelerated decline in cardiac function, and increased morbidity and mortality. The optimal treatment of CSA remains unclear. Resolution of CSA has been reported after cardiac transplantation. We report the first case of resolution of CSA 10 months following implantation of a permanent Jarvik 2000 left ventricular assist device (LVAD). The correction of CSA after implantation of the LVAD was associated with improvements in symptoms, exercise capacity, renal function, and increased arterial carbon dioxide levels at rest during wakefulness and also reduction in brain natriuretic peptide.

Lives on the line? Ethics and practicalities of duty of care in pandemics and disasters.

Pandemics and acute emergencies raise pressing medical, ethical and organisational challenges. These include global governance, priority setting, triaging of patients, allocation of scarce resources and restricting individual liberty in the interests of public health. We will focus particularly on an issue of direct relevance to all respiratory team members, i.e. what is the duty of the healthcare worker to continue working in the face of personal risk, and draw lessons from guidelines, ethical considerations, past pandemics and evolving experience with H1N1 swine influenza.

Autotitrating versus standard noninvasive ventilation: a randomised crossover trial.

The aim of the present study was to compare the efficacy of automatic titration of noninvasive ventilation (NIV) with conventional NIV in stable neuromuscular and chest wall disorder patients established on long-term ventilatory support. In total, 20 neuromuscular and chest wall disease patients with nocturnal hypoventilation treated with long-term NIV completed a randomised crossover trial comparing two noninvasive pressure support ventilators: a standard bilevel ventilator (VPAP III) and a novel autotitrating bilevel ventilator (AutoVPAP). Baseline physiological measurements, overnight polysomnography and Holter monitoring were repeated at the end of each 1-month treatment period. Nocturnal oxygenation was comparable between the autotitrating device and standard ventilator, as were sleep efficiency, arousals and heart rate variability. However, there was a small significant increase in mean overnight transcutaneous carbon dioxide tension (median (interquartile range) 7.2 (6.7-7.7) versus 6.7 (6.1-7.0) kPa) and a decrease in percentage stage 1 sleep (mean+/-sd 16+/-9 versus 19+/-10%) on autotitrating NIV compared with conventional NIV. Autotitrating noninvasive ventilation using AutoVPAP produced comparable control of nocturnal oxygenation to standard nonivasive ventilation, without compromising sleep quality in stable neuromuscular and chest wall disease patients requiring long-term ventilatory support for nocturnal hypoventilation.

Congenital myasthenic syndromes in childhood: diagnostic and management challenges.

The Congenital Myasthenic Syndromes (CMS), a group of heterogeneous genetic disorders of neuromuscular transmission, are often misdiagnosed as congenital muscular dystrophy (CMD) or myopathies and present particular management problems. We present our experience of 46 children with CMS, referred to us between 1992-2007 with provisional diagnoses of congenital myopathy (22/46), CMS or limb-girdle myasthenia (9/46), central hypotonia or neurometabolic disease (5/46), myasthenia gravis (4/46), limb-girdle or congenital muscular dystrophy (4/46) and SMA (2/46). Diagnosis was often considerably delayed (up to 18y4 m), despite the early symptoms in most cases. Diagnostic clues in the neonates were feeding difficulties (29/46), hypotonia with or without limb weakness (21/46), ptosis (19/46), respiratory insufficiency (12/46), contractures (4/46) and stridor (6/46). Twenty-five children had delayed motor milestones. Fatigability developed in 43 and a variable degree of ptosis was eventually present in 40. Over the period of the study, the mainstay of EMG diagnosis evolved from repetitive nerve stimulation to stimulation single fibre EMG. The patients were studied by several different operators. 66 EMGs were performed in 40 children, 29 showed a neuromuscular junction abnormality, 7 were myopathic, 2 had possible neurogenic changes and 28 were normal or inconclusive. A repetitive CMAP was detected in only one of seven children with a COLQ mutation and neither of the two children with Slow Channel Syndrome mutations. Mutations have been identified so far in 32/46 children: 10 RAPSN, 7 COLQ, 6 CHRNE, 7 DOK7, 1 CHRNA1 and 1 CHAT. 24 of 25 muscle biopsies showed myopathic changes with fibre size variation; 14 had type-1 fibre predominance. Three cases showed small type-1 fibres resembling fibre type disproportion, and four showed core-like lesions. No specific myopathic features were associated with any of the genes. Twenty children responded to Pyridostigmine treatment alone, 11 to Pyridostigmine with either 3, 4 DAP or Ephedrine and five to Ephedrine alone. Twenty one children required acute or chronic respiratory support, with tracheostomy in 4 and nocturnal or emergency non-invasive ventilation in 9. Eight children had gastrostomy. Another 11 were underweight for height indicative of failure to thrive and required dietetic input. A high index of clinical suspicion, repeat EMG by an experienced electromyographer and, if necessary, a therapeutic trial of Pyridostigmine facilitates the diagnosis of CMS with subsequent molecular genetic confirmation. This guides rational therapy and multidisciplinary management, which may be crucial for survival, particularly in pedigrees where previous deaths have occurred in infancy.

A high prevalence of sleep disordered breathing in men with mild symptomatic chronic heart failure due to left ventricular systolic dysfunction.

BACKGROUND: Sleep disordered breathing (SDB) is common in severe chronic heart failure (CHF) and is associated with increased morbidity and mortality. The prevalence of SDB in mild symptomatic CHF is unknown. AIM: The aim of this study was to determine the prevalence and characteristics of SDB in male patients with NYHA class II symptoms of CHF. METHODS AND RESULTS: 55 male patients with mild symptomatic CHF underwent assessment of quality of life, echocardiography, cardiopulmonary exercise, chemoreflex testing and polysomnography. 53% of the patients had SDB. 38% had central sleep apnoea (CSA) and 15% had obstructive sleep apnoea. SDB patients had steeper VE/VCO(2) slope [median (inter-quartile range) 31.1 (28-37) vs. 28.1 (27-30) respectively; p=0.04], enhanced chemoreflexes to carbon dioxide during wakefulness [mean+/-sd: 2.4+/-1.6 vs. 1.5+/-0.7 %VE Max/mmHg CO(2) respectively; p=0.03], and significantly higher levels of brain natriuretic peptide and endothelin-1 compared to patients without SDB. No differences in left ventricular ejection fraction, percent predicted peak oxygen uptake, or symptoms of SDB were observed. CONCLUSIONS: A high prevalence of SDB was found in men with mild symptomatic CHF. Patients with SDB could not be differentiated by symptoms or by routine cardiac assessment making clinical diagnosis of SDB in CHF difficult.

UK physicians' attitudes and practices in long-term non-invasive ventilation of Duchenne Muscular Dystrophy.

Previous studies have shown that long-term non-invasive ventilation (NIV) is not always routinely offered by all physicians in Duchenne Muscular Dystrophy (DMD), despite evidence that this treatment improves quality of life and survival. This study examined UK physicians' practices related to respiratory follow-up and DMD ventilation. A mailed questionnaire was used. Thirty-eight of the 59 (64%) UK physicians identified via the Muscular Dystrophy Campaign (MDC) responded. Eighty-one per cent of respondents felt ethically obliged to discuss NIV with families while 13% believed that NIV results in poor quality of life. Forty-seven per cent of physicians discuss in-depth the use of NIV when the patient is in respiratory failure. Eighty-four ventilated DMD patients in the respondents' practice use NIV (via Bi-Pap Nasal mask). Nearly 66% of physicians do not consider the public cost to be an impediment to offering NIV, despite significant problems with resources' allocation in their area. While the majority of UK physicians have comparable attitudes and practices regarding NIV, the questionnaire highlighted that not all specialists were aware of the existence of consensus guidelines regarding respiratory monitoring. In addition, different practices of disclosure of life-prolonging ventilation options were used by different physicians. Seventy-one per cent of physicians wished for national consensus guidelines for different DMD age groups.

Adaptive servo-ventilation and deadspace: effects on central sleep apnoea.

Central Sleep Apnoea (CSA) occurs commonly in heart failure. Adaptive servo-ventilation (ASV) and deadspace (DS) have been shown in research settings to reverse CSA. The likely mechanism for this is the increase of PaCO(2) above the apnoeic threshold. However the role of increasing FiCO(2) on arousability remains unclear. To compare the effects of ASV and DS on sleep and breathing, in particular effects on Arousal Index (ArI), ten male patients with heart failure and CSA were studied during three nights with polysomnography plus measurements of PetCO(2). The order of the interventions control (C), ASV and DS was randomized. ASV and DS caused similar reductions in apnoea-hypopnoea index [(C) 30.0 +/- 6.6, (ASV) 14.0 +/- 3.8, (DS) 15.9 +/- 4.7 e h(-1); both P < 0.05]. However, DS was associated with decreased total sleep time compared with C (P < 0.02) and increased spontaneous ArI compared to C and ASV (both P < 0.01). Only DS was associated with increased DeltaPetCO(2) from resting wakefulness to eupnic sleep [(C) 2.1 +/- 0.9, (ASV) 1.3 +/- 1.0, (DS) 5.6 +/- 0.5 mmHg; P = 0.01]. ASV and DS both stabilized ventilation however DS application also increased sleep fragmentation with negative impacts on sleep architecture. We speculate that this effect is likely to be mediated by increased PetCO(2) and respiratory effort associated with DS application.

Symptom burden of sleep-disordered breathing in mild-to-moderate congestive heart failure patients.

The symptom burden resulting from sleep-disordered breathing (SDB) in patients with mild-to-moderate congestive heart failure (CHF) is unclear. The current authors monitored 24-h activity levels and compared subjective and objective measures of daytime sleepiness in 39 CHF patients, New York Heart Association class 2-3, on optimal medication. A total of 22 patients were classified as SDB (apnoea/hypopnoea index (AHI) median (range) 22.3 (16.6-100) events.h-1), and 17 as no SDB (NoSDB; AHI 3.7 (0-12.3) events.h-1). SDB was defined as AHI>or=15 events.h-1. Patients were assessed by 24-h activity monitoring (actigraphy) for a period of up to 14 days, a single objective sleepiness test (Oxford Sleep Resistance test) and Epworth Sleepiness Scale. The duration of daytime activity was significantly shorter in the SDB group compared with the NoSDB group. The SDB group also had increased time in bed and poorer sleep quality, as shown by the fragmentation index. Objectively the SDB group when compared with the NoSDB group were significantly sleepier, subjectively the groups did not differ. The amount of napping was similar for both groups. Despite the lack of subjective symptoms of daytime sleepiness, congestive heart failure patients with sleep-disordered breathing were objectively sleepier during the day and had reduced daytime activity with longer periods in bed and poorer sleep quality when compared with those without sleep-disordered breathing.

Can heart rate variation rule out sleep-disordered breathing in heart failure?

In patients with obstructive sleep apnoea (OSA), the very low frequency power spectral density index (VLFI) derived from analysis of heart rate correlates with the severity of obstructive apnoeas. VLFI is also associated with Cheyne-Stokes respiration/central sleep apnoea (CSR/CSA) in congestive heart failure (CHF). The present authors have tested the hypothesis that per cent VLFI, derived from a standard Holter ECG recording, can be used to detect the presence of OSA and CSR/CSA in patients with mild-to-moderate CHF. In total, 60 CHF patients underwent polysomnography with monitoring of heart rate. Data from 33 patients were analysed for per cent VLFI. Of the 60 patients, 27 were excluded due to atrial fibrillation, extensive pacing or frequent ventricular extra systoles. Receiver operator characteristic curves were constructed to establish the per cent VLFI that would optimally identify the presence or absence of sleep-disordered breathing. Using an apnoea-hypopnoea index>20 events.h-1 and setting the per cent VLFI at 2.23% yielded a sensitivity of 85%, specificity of 65%, positive predictive value of 61% and a negative predictive value of 87%. The latter increased to 100% when using an apnoea-hypopnoea cut-off of 30 events.h-1. In conclusion, these results suggest that spectral analysis of heart rate may be useful as a "rule-out test" for sleep-disordered breathing in patients with mild-to-moderate congestive heart failure.

Randomised controlled trial of non-invasive ventilation (NIV) for nocturnal hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia.

BACKGROUND: Long term non-invasive ventilation (NIV) reduces morbidity and mortality in patients with neuromuscular and chest wall disease with hypercapnic ventilatory failure, but preventive use has not produced benefit in normocapnic patients with Duchenne muscular dystrophy. Individuals with nocturnal hypercapnia but daytime normocapnia were randomised to a control group or nocturnal NIV to examine whether nocturnal hypoventilation is a valid indication for NIV. METHODS: Forty eight patients with congenital neuromuscular or chest wall disease aged 7-51 years and vital capacity<50% predicted underwent overnight respiratory monitoring. Twenty six with daytime normocapnia and nocturnal hypercapnia were randomised to either nocturnal NIV or to a control group without ventilatory support. NIV was started in the control group if patients fulfilled preset safety criteria. RESULTS: Peak nocturnal transcutaneous carbon dioxide tension (Tcco2) did not differ between the groups, but the mean (SD) percentage of the night during which Tcco2 was >6.5 kPa decreased in the NIV group (-57.7 (26.1)%) but not in controls (-11.75 (46.1)%; p=0.049, 95% CI -91.5 to -0.35). Mean (SD) arterial oxygen saturation increased in the NIV group (+2.97 (2.57)%) but not in controls (-1.12 (2.02)%; p=0.024, 95% CI 0.69 to 7.5). Nine of the 10 controls failed non-intervention by fulfilling criteria to initiate NIV after a mean (SD) of 8.3 (7.3) months. CONCLUSION: Patients with neuromuscular disease with nocturnal hypoventilation are likely to deteriorate with the development of daytime hypercapnia and/or progressive symptoms within 2 years and may benefit from the introduction of nocturnal NIV before daytime hypercapnia ensues.