Non-invasive ventilation for acute respiratory disease

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1 Published Online March 31, 2005 Non-invasive ventilation for acute respiratory disease M. W. Elliott St James s University Hospital, Beckett Street, Leeds LS9 7TF, UK Non-invasive ventilation (NIV) has been shown to be effective in acute respiratory failure of various aetiologies in different health care systems and ward settings. It should be seen as complementary to invasive ventilation and primarily a means of preventing some patients from deteriorating to the point at which intubation is needed. Generally it is best initiated early before assisted ventilation is mandatory, although it has been shown to be effective even in very sick patients. Important benfits include the avoidance of endotracheal-tube-associated infections, which carry an important morbidity and mortality, and a reduction in health care costs. The most important ingredient for an acute NIV service is a well-trained enthusiastic ward team. Introduction Accepted: February 14, 2005 Correspondence to: M. W. Elliott, St James s University Hospital, Beckett Street, Leeds LS9 7TF, UK. mwelliott@doctors.org.uk Non-invasive ventilation (NIV) is well established in the management of acute respiratory failure, particularly resulting from acute exacerbations of chronic obstructive pulmonary disease (COPD), but also from hypoxaemic respiratory failure, community-acquired pneumonia and cardiogenic pulmonary oedema and after solid organ transplants. Its use in these settings has been assessed in many randomized controlled trials. It has also been used perioperatively, in the elderly and in patients with do not intubate orders. When NIV fails or is not deemed appropriate from the outset and there is subsequently difficulty in liberating the patient from invasive ventilation there may also be a role in weaning. 1 This article will focus on acute exacerbations of COPD, hypoxaemic respiratory failure and cardiogenic pulmonary oedema, and will provide practical guidelines. Those who require more details, particularly those wishing to start an NIV service, for whom further reading and training are vital, are directed to a number of books and review articles British Medical Bulletin 2004; 72: DOI: /bmb/ldh042 The Author Published by Oxford University Press on behalf of The British Council. All rights reserved. For permissions, please journals.permissions@oupjournals.org

2 M. W. Elliott In-hospital use of NIV The model of hospital care differs from country to country and it is important from the outset to be clear what is meant by the different terms used. For the purposes of this article the following definitions are used. In an intensive care unit (ICU) there is continuous monitoring of vital signs with a high nurse-to-patient ratio maintained round the clock. A general ward takes unselected emergency admissions and, although most will have a particular specialty interest, it is likely that, because of the unpredictability of demand, patients with a variety of conditions and degrees of severity will be cared for in the same clinical area. Nurse staffing levels will vary, but the intensity of nursing input will be much lower than on the ICU, particularly at night. A high dependency unit (HDU) also involves continuous monitoring in a specified clinical area with a nurse-to-patient ratio between those of the ICU and the general ward, but closer to the former. In countries which have few ICU beds, nurses on general wards will be more experienced in looking after sicker patients. These issues are important when extrapolating results obtained in one health care system to another. Acute exacerbations of COPD Patients with acute exacerbations of COPD form the largest single group of those treated successfully using NIV techniques 8, but success has been reported in many other conditions. The respiratory muscle pump in patients with severe COPD is often functioning close to the point at which it can no longer maintain effective ventilation. There are excessive elastic and resistive loads on it, because of hyperinflation and airways obstruction, respectively, and reduced capacity because of the adverse effect of hyperinflation on the configuration of the respiratory muscles, causing them to operate at a mechanical disadvantage. In addition the presence of intrinsic positive end-expiratory pressure (PEEP) causes an inspiratory threshold load. In an acute exacerbation, when the load on the respiratory muscle pump becomes excessive, effective ventilation can no longer be maintained, worsening hypoxia, hypercapnia and, most importantly, acidosis. Acidosis is particularly deleterious to muscle function and the capacity of the respiratory muscle pump is further reduced. It was previously considered that respiratory muscle function may also be compromised by the development of muscle fatigue, because of the increased load, but recent data have established that, at least in the strictest sense, this is not so. 9 A vicious circle develops of worsening acidosis causing further impairment of respiratory muscle function, which in turn has an adverse effect on ph and arterial blood gas tensions. 84 British Medical Bulletin 2004;72

3 NIV for acute respiratory disease When NIV was applied in the ICU 10 13, the most striking finding was a reduction in the need for endotracheal intubation and mechanical ventilation, which in the largest study translated into improved survival, reduced complication rates, and reduced length of both ICU and hospital stay. 10 These studies showed that NIV is feasible in acute exacerbations of COPD and that the prevention of endotracheal intubation is advantageous. Because paralysis and sedation are not needed with NIV, ventilation outside the ICU is an option. Given the considerable pressure on ICU beds in most countries, the high costs, and the distress experienced by some patients during admission to the ICU, this is an attractive option. NIV can be instituted at an earlier stage in the natural history of the exacerbation before mechanical ventilation would normally be considered necessary. There have been a number of prospective randomized controlled studies of NIV outside the ICU either on general wards or in accident and emergency departments NIV was instituted at a higher ph than that reported in the ICU studies and most failed to show any significant advantage of NIV when analysed on an intention-to-treat basis. However, in one study 14 a significant survival benefit was seen (9/30 vs. 1/26) when those unable to tolerate NIV were excluded. These studies were all relatively small and may have lacked sufficient statistical power to show a difference in the need for intubation and mortality, given that most patients with a mild exacerbation of COPD (defined by the degree of acidosis) would not be expected to need endotracheal intubation and mechanical ventilation anyway. 21 In a large (n=236) multicentre randomized controlled trial of NIV in acute exacerbations of COPD on general respiratory wards in 13 centres in the UK 19 treatment failure, a surrogate for the need for intubation defined by a priori criteria, was reduced from 27% to 15% by NIV. In-hospital mortality was reduced from 20% to 10%. Subgroup analysis suggested that the outcome in patients with ph <7.30 after initial treatment was inferior to that in the studies performed in the ICU. NIV was applied by the usual ward staff, most of whom had had little or no previous experience, using a bilevel device in spontaneous mode according to a simple protocol. This study suggests that, with adequate staff training, NIV can be applied with benefit outside the ICU and that the early (ph <7.35 on admission to the ward) introduction of NIV on a general ward results in a better outcome than providing no ventilatory support for acidotic patients outside the ICU. The results in the more severely affected patients (ph <7.30 after initial management) were not as good as those seen in the ICU studies, suggesting that this simple approach is not appropriate in these patients and that they are best managed in a higher dependency setting with a more sophisticated ventilator individually adjusted to their requirements. It is striking that in some studies NIV was administered for only a relatively short period (mean 7.6 h and 6 h daily) 10,14 or at very modest levels British Medical Bulletin 2004;72 85

4 M. W. Elliott for a longer period. 11 It appears that even short periods of NIV are usually sufficient to break the vicious circle produced by acidosis while other therapies take effect upon the precipitating cause. When acidosis cannot be improved, the downward spiral continues and other measures, usually intubation, must be instituted unless contraindicated on other grounds. The majority of studies excluded patients deemed to need intubation and mechanical ventilation. However Conti et al. 22 reported a prospective randomized controlled trial of NIV vs. immediate endotracheal intubation and mechanical ventilation in patients with an exacerbation of COPD. Not surprisingly, their patients were sicker than those reported in previous studies, as evidenced by the mean ph of 7.2, compared with 7.27 in the study by Brochard et al. 10 and 7.32 in the study by Plant et al. 19. In these sicker patients, they showed that NIV was no worse than endotracheal intubation and mechanical ventilation. In those who could be managed successfully with NIV there was an advantage not only in the short term but also in the year after hospital discharge in terms of a reduction in the need for hospital admission and de novo long-term oxygen therapy. This confirms the findings of two previous studies comparing NIV patients with historical controls who had been invasively ventilated. 23,24. The increased need for de novo chronic oxygen therapy in the invasively ventilated group may reflect additional lung damage, perhaps a consequence of the increased risk of lung infection. The intubation rate of 52% in the NIV group in the study by Conti et al. 22 was higher than in other randomized controlled trials, which is not surprising given that these were a sicker group of patients. However, it does reinforce the view that NIV is best instituted early. 25 Some patients were excluded from the study, in particular those intubated prior to transfer to the ICU or those with respiratory arrest or pauses, psychomotor agitation requiring sedation, heart rate below 60 beats/min or systolic blood pressure below 80 mmhg. The key message from this study is that in all but the sickest patients with an exacerbation of COPD there is little to be lost, and much to be gained, by a trial of NIV. Predicting the outcome from NIV in acute COPD Data available at the time NIV is initiated and after a short period can predict the likelihood of success or failure with a reasonable degree of precision. The severity of acidosis at baseline emerges as an important predictor; although NIV is less likely to be effective when patients are more acidotic, 10,26 this should not preclude a trial of NIV as the mode of ventilatory support of first choice because the benefits of NIV compared with intubation and mechanical ventilation are greater. 10,22 The tolerance 86 British Medical Bulletin 2004;72

5 NIV for acute respiratory disease Table 1 Indications for and predictors of success of NIV COPD NIV indicated when: ph <7.35 PaCO 2 > 6 kpa Respiratory rate >24 bpm After allowing time to evaluate the effect of standard medical therapy (in all but the most severely ill) NIV more likely to be successful if: Milder acidosis at baseline Absence of comorbidities No confusion Good mask fit Tolerance of NIV Improvement in ph with NIV Fall in respiratory rate with NIV Hypoxaemic respiratory failure Respiratory distress Respiratory rate >30 bpm Pao 2 /Fio 2 ratio >200 mmhg Failure of NIV Failure of non-invasive A different interface (i.e. an endotracheal tube) may be advantageous Failure of ventilation : initial ventilation through a non-invasive interface is succesful, but subsequently gas exchange deteriorates despite good interface fit and tolerance Change of interface less likely to be beneficial. of NIV and the change in arterial blood gas tensions, particularly ph, and respiratory rate in the early hours are reasonable predictors of the subsequent outcome 10,14,26,27. NIV is less likely to be successful if there are associated complications or if the patient s premorbid condition is poor. 28,29 Late failure after initially successful NIV is a bad prognostic factor, 29 with over half the patients dying even with invasive ventilation. This is more likely in patients with severe acidosis, poor functional status and complications. A clear distinction needs to be made between failure of non-invasive (i.e. a problem with the interface. which may be solved by using different interface, such as an endotracheal tube) and failure of ventilation (i.e. no problem with the interface but despite this an inability to maintain effective ventilation, when invasive ventilation probably has little to offer) (Table 1). NIV for hypoxaemic respiratory failure NIV has been used in patients with hypoxaemic (i.e. not hypercapnic) respiratory failure due to a variety of different conditions (e.g. acute respiratory distress sydrome, pneumonia, aspiration, trauma, the immunocompromised with lung infiltrates) and again the picture emerges British Medical Bulletin 2004;72 87

6 M. W. Elliott that most is to be gained when it is instituted early. There is no reason in principle why NIV could not be attempted in most patients requiring ventilatory support for whatever indication (see below for contraindications). However, there are issues around the maximum fractional inspired oxygen concentration that can be achieved, particularly with ventilators primarily designed for home use, and the degree of ventilator dependence. Patients may be adequately oxygenated while receiving NIV but if they come off it, even for a short period, catastrophic hypoxia may ensue. Antonelli et al. 30 compared intubation and conventional mechanical ventilation with NIV in patients with acute hypoxic respiratory failure of a variety of different aetiologies. Post hoc subgroup analysis of patients with simplified acute physiological scores of <16 and those of 16 showed that patients in the latter group had similar outcomes irrespective of the type of ventilation. However, NIV was superior to conventional mechanical ventilation in patients with a simplified acute physiological score <16. One problem with studies of this type is that the outcome from ICU is critically dependent upon the aetiology of the respiratory failure; small studies of patients with heterogeneous causes of respiratory failure lack sufficient power to determine confidently the effectiveness of the intervention. Hilbert et al. 33 conducted a prospective randomized controlled trial of NIV compared with standard treatment with supplemental oxygen and no ventilatory support in 52 immunosuppressed patients with pulmonary infiltrates and fever. Each group of 26 patients included 15 patients with haematological malignancy and neutropenia. Patients were recruited at an early stage of hypoxaemic respiratory failure. NIV (for at least 45 min) was alternated every 3 h with periods of spontaneous breathing with supplemental oxygen. Fewer patients in the NIV group required endotracheal intubation (12 vs. 20), had serious complications (13 vs. 21), died in the ICU (10 vs. 18) or died in hospital (13 vs. 21). The reason why relatively short periods of assisted ventilation should have been effective is interesting and open to speculation. Possible reasons include redistribution of extravascular fluid, alveolar recruitment and re-expansion of atelectatic lung, as well as the beneficial effects of pressure support on work of breathing, helping to maintain an adequate tidal volume and possibly allowing respiratory muscle recovery during periods of muscle unloading when on NIV. This study is in keeping with other studies in suggesting that early NIV can prevent intubation and therefore is best introduced early. The criteria on which patients were recruited to the study provide a useful starting point (Table 1) and NIV should now be strongly considered in such patients, provided that there are no contraindications. Continuous positive airway pressure (CPAP) has somesimilar physiological effects, is easier and cheaper to deliver and has been used in a 88 British Medical Bulletin 2004;72

7 NIV for acute respiratory disease variety of studies. However, in the only prospective randomized trial of CPAP versus standard therapy published to date there was no improvement in outcome (intubation rate and survival), although CPAP did result in a more rapid physiological improvement. 34 A higher number of adverse events occurred with CPAP treatment (18 vs. 6). A number of patients in the CPAP group had cardiorespiratory arrests; the improvement in physiological parameters may engender a false sense of security, with patients having improved oxygenation etc. while using non-invasive CPAP, but if it is discontinued, even for a short period for drinking etc., oxygen saturation may fall catastrophically. Therefore current data favour NIV as the non-invasive mode of ventilatory support of choice, but the same caveat regarding the potential for sudden deterioration should be made. Cardiogenic pulmonary oedema Positive pressure has been shown to improve oxygenation, increase cardiac output and reduce the work of breathing. Several studies have evaluated the use of CPAP in acute cardiogenic pulmonary oedema, and others have evaluated the use of bilevel positive airway pressure. Collectively, the available data suggests that CPAP is effective in terms of reduction in intubation rate and that there is a trend towards reduced mortality. 35 NIV may be advantageous in patients with significant hypercapnia; 36 the findings of an early study that NIV appeared to increase the rate of myocardial infarction compared with CPAP 37 has not been borne out by further studies. In the enthusiasm to apply NIV it is vital that standard drug treatment is not forgotten; in particular, high doses of nitrates have shown to be important in improving outcome. 38,39 Why is NIV preferable to invasive ventilation? A reduction in complications, particularly infections, is a consistent feature of NIV. 10,30,40,41. In intubated patients there is a 1% risk per day of developing pneumonia. This complication of invasive ventilation is associated with a longer ICU stay, increased costs and a worse outcome. The reduction in nosocomial infections is probably the most important advantage of avoiding endotracheal intubation by using NIV. This benefit is seen in the real world 42 as well as in the setting of a clinical trial; in a 3-week observational survey of 42 French ICUs the incidence of both nosocomial pneumonia (10% vs. 19%), and mortality (22% vs. 41%) was lower in NIV patients than in those with endotracheal intubation. This may reflect the fact that less severely unwell patients were British Medical Bulletin 2004;72 89

8 M. W. Elliott treated with NIV. In addition, NIV has been shown to be cost effective in the ICU setting. 43 If it can be performed outside the ICU, there are even greater savings to be made. 44,45 Contraindications There are no absolute contraindications to NIV, although a number have been suggested. 26 These include coma or confusion, inability to protect the airway, severe acidosis at presentation, significant comorbidity, vomiting, obstructed bowel, haemodynamic instability (two studies have shown only small changes in cardiac output when NIV is initiated but haemodynamic collapse comparable to that often seen when patients are intubated is very rare), radiological evidence of consolidation, and orofacial abnormalities which interfere with the mask face interface. In part, these contraindications have been determined by the fact that they were exclusion criteria for the controlled trials. Therefore it is more correct to state that NIV is not proven in these circumstances rather than that it is contraindicated. Whether NIV should be attempted must depend on individual circumstances. For instance, if invasive ventilation is not considered appropriate, but NIV would be acceptable, there is nothing to be lost by a trial of NIV and there are no contraindications in this situation. NIV may not be appropriate in well-documented endstage disease or when several comorbidities are present. Nursing/technical requirements for NIV in acutely ill patients Whether NIV should be performed on an ICU, an HDU or a general ward will depend upon many factors (Table 2). Nurses, physiotherapists or respiratory therapists may be the primary caregivers, and this will depend upon local availability, enthusiasm and expertise. Patients who cannot sustain ventilation for more than a minute or two when acutely unwell require continuous observation, and it would not be appropriate Table 2 Factors to be considered in deciding whether NIV should be performed on an ICU or on a general ward Severity of respiratory failure Significant comorbidity Likelihood of success of NIV (see Table 1) Will the patient be intubated if NIV fails? Patient s nursing requirements Ward staffing levels, expertise, and experience 90 British Medical Bulletin 2004;72

9 NIV for acute respiratory disease to ventilate these patients on a general ward unless a nurse is in constant attendance. Patients with this severity of ventilatory failure are often confused and usually require high inflation pressures. Continuous observation is needed to ensure that the patient does not remove the mask and that leaks are minimized. Even if the patient does not remove the mask there is a tendency for the Velcro straps of the headgear to work loose gradually at high pressures and for mask leaks to develop. As the clinical situation changes, ventilator settings may need to be adjusted. If the decision is made for ventilation to be performed on a general ward, it is very important that sufficient nursing or technical staff are available to give the patient, if not continuous, at least very frequent attention. NIV is unlikely to be successful on a ward with low nurse-to-patient ratios and other ill patients requiring considerable input. Because many patients, particularly those with COPD, breathe through their mouths when dyspnoeic, a full facemask is usually required acutely and occasionally the use of a mouth piece may be helpful. Once tolerating NIV and symptomatically improved this can be changed to a nasal mask. Newer interfaces are constantly becoming available and may be suitable for some patients. 46 Having established an adequate mask fit, it is essential to achieve and maintain adequate ventilation as soon as possible, as failure will often result in non-compliance with NIV. Oxygen saturation should be constantly monitored by pulse oximetry. Arterial blood gas tensions should be checked after min and ventilator settings adjusted as necessary; gas tensions should then be rechecked. Oxygen entrainment into the ventilator circuit is often needed to maintain adequate levels of arterial oxygen saturation, typically judged to be 90%, but importantly high levels are not needed as these patients are acclimatized to hypoxia. The addition of oxygen even during NIV may still occasionally cause worsening hypercapnia, probably by increasing the ratio of dead space to tidal volume, 47 and arterial blood gas tensions should be checked approximately 1 h after any change in oxygen flow rate. A ventilator with an oxygen blender should be used for patients with severe hypoxaemia, as it is not possible to deliver a high Fio 2 when oxygen is added to the ventilator circuit because of the diluting effect of high airflow through the circuit as a consequence of leaks. Problems encountered with masks are outlined in Table 3. Humidification NIV can cause an excess loss of water vapour, leading to thickened and tenacious secretions as well as the discomfort associated with a dry nose or mouth. In addition, increased nasal resistance has been described with CPAP leading to increased mouth leak, and there is no reason to British Medical Bulletin 2004;72 91

10 M. W. Elliott Table 3 Common problems associated with masks Pressure sores on bridge of nose due to prolonged use, excessive mask pressure, or bad fit Skin irritation due to excessive mask pressure, allergy to mask material, or lack of mask cleaning Corneal irritation due to leaks into the eyes Nasal and buccal mucosal irritation and dryness, particularly when there is mask leak Claustrophobia (particularly with full facemasks) Gastric distension (particularly with full facemasks) Increased risk of aspiration (particularly with full facemasks) Difficulty wearing spectacles (an issue during the recovery phase) believe that this will not also be a problem with NIV, particularly when pressure-cycled systems with high inspiratory flow rates are used. 48 Therefore adequate fluid intake and humidification is vital. Although eating and drinking help to keep the mouth moist, when this is not possible regular mouth care is an important comfort for the patient. Saliva stimulants such as pineapple juice or chunks are useful, as are artificial saliva sprays and water-based lubricating gels to keep the mouth moist. The lips can be protected with a soft petroleum gel such as Vaseline. The prevention of mouth leaks minimizes flow and improves the efficacy of ventilation as well as helping to prevent mouth dryness. Humidification of the inspired gas must be considered for some mask-ventilated patients, and is mandatory for those patients with a tracheostomy. It can be achieved using a heat and moisture exchange filter, a waterbath humidifier or regular nebulized saline. A waterbath humidifier with a heated wire circuit is ideal but expensive. Heat and moisture exchange filters trap the moisture in the exhaled air and return it in the next breath. However there are disadvantages. As the filter becomes saturated with water and secretions, the resistance to gas flow increases. This may be particularly important with a pressure-cycled ventilator in which the gas flow received by the patient falls off as the resistance of the heat and moisture exchange filter increases. With both volume- and pressure-cycled machines the effort required to trigger a breath in the assist mode may increase. To minimize these problems, heat and moisture exchange filters should be changed at least daily. Heat and moisture exchange filters have to be fitted between the patient and the exhale port in the ventilator circuit, increasing the dead space, which reduces effective ventilation. Intermittent nebulization of saline is an alternative which can be used to supplement the use of heat and moisture exchange filters. Nutrition Breathless patients may find it difficult to eat, and this is further compromised if they are unable to remove the mask for sufficient time to 92 British Medical Bulletin 2004;72

11 NIV for acute respiratory disease masticate food. Liquid supplements are an alternative but nasogastric feeding may be more appropriate, particularly acutely, and oral medication can be given easily. Fine-bore feeding tubes do not significantly affect mask fit. The patient should not lie flat when being tube fed to reduce the risk of aspiration. Inhaled drugs Inhaled drugs can be administered during NIV by adding a nebulizer to the circuit. This can be done by using a T-piece positioned as close as possible to the patient, ideally between the exhale valve and the patient to prevent fall out and loss of the drug, although this does increase the dead space. Most nebulizers are suitable, but a nebulizer that is able to work at varying angles is useful as often the ventilator circuit is unsupported, leaving the nebulizer to function on its side. In addition, aerosols can be administered into the ventilator circuit using metered dose inhalers and spacer devices. 49 Ideally, patients should receive their inhaled drugs off the ventilator, but this is obviously not possible if the patient is ventilator dependent in which case nebulization during NIV can be used. Physiotherapy Physiotherapy can be performed during NIV; indeed, it is sometimes more effective because the patient is less breathless and better able to cooperate. 7 However physiotherapists require specific training. Starting NIV on a ward for the first time Nursing and technical staff should be adequately prepared and the necessary equipment must be available before NIV is first tried. Ideally, equipment as outlined above should be available, but this will often not be practical and, indeed, too much variety may cause confusion. Minimum requirements are outlined in Table 4. Staff should use the equipment on each other in a non-clinical setting and practise the theoretical knowledge and skills before using them on real patients. Two or three enthusiastic staff are a real boon, as they will often carry the rest of the team with them. Nurses with previous experience of the ICU or NIV are particularly useful since they will be confident with ventilators. An experienced practitioner should be available 24 h a day to help sort out problems until staff are able to solve them themselves. As experience is gained, different types of ventilator, new British Medical Bulletin 2004;72 93

12 M. W. Elliott Table 4 Basic needs for an acute NIV service A simple ventilator: pressure-cycled machines are usually simple, compensate for moderate leaks, and are generally better tolerated by patients A supply of circuits already made up A range of mask sizes, both nasal and full face, and head gear. A minimum of two of each should always be available If the mask does not have an integral exhalation port one must be inserted into the ventilator circuit Connectors to allow customization of ventilator circuits (e.g. for entrainment of oxygen) Facility for cleaning masks, circuits, and headgear to an acceptable standard Trained competent staff. Issues to be addressed: Understanding of the rationale for assisted ventilation Mask and headgear fitting techniques Ventilator circuit assembly Theory of operation and adjusting ventilation to achieve desired outcome Cleaning and general maintenance The ability to recognize problems and act accordingly masks etc. can be added, widening the range of patients who can be successfully ventilated non-invasively. Conclusion NIV can be used with success in respiratory failure of various aetiologies, particularly acute exacerbations of COPD. It should be seen primarily as a means of avoiding the need for endotracheal intubation. There are few contraindications and usually little to be lost by a trial of NIV provided that there is a clear strategy of how to monitor progress and when to switch to invasive ventilation if the patient is not progressing satisfactorily. It is effective and cost effective and can be used in a wide variety of settings. When starting an NIV service, it should be kept as simple as possible and should begin with less severely ill patients. As expertise and confidence grow, more sophisticated equipment can be introduced and sicker patients treated. Training and education of the whole team doctors, nurses and therapists is key. References 1 Ferrer M, Bernadich O, Nava S, Torres A (2002) Noninvasive ventilation after intubation and mechanical ventilation. Eur Respir J, 19, Mehta S, Hill NS (2001) Noninvasive ventilation. Am J Respir Crit Care Med, 163, British Thoracic Society Standards of Care Committee (2002) Non-invasive ventilation in acute respiratory failure. Thorax, 57, Brochard L, Mancebo J, Elliott MW (2002) Noninvasive ventilation for acute respiratory failure. Eur Respir J, 19, Elliott MW, Confalonieri M, Nava S (2002) Where to perform noninvasive ventilation? Eur Respir J, 19, British Medical Bulletin 2004;72

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