COPD, chronic obstructive pulmonary disease; CPAP, continuous positive airway pressure; ED, emergency department; ETI, endotracheal intubation; ICU, intensive-care unit; NIMV, non-invasive mechanical ventilation; ST, standard medical treatment.
demonstrated a significantly lower rate of endotracheal intubation (11 of 43 vs. 31 of 42), mortality (4 vs. 12) and shorter hospital stays (23 vs. 35 days) in patients on NIMV compared to those only on standard medical therapy. The complication rate, particularly for pneumonia, was much lower in the NIMV group (two vs. seven) and most of the excess of complications and mortality in the control group was attributed to intubation. These data suggest that NIMV may be superior to IMV, but importantly these were highly selected patients, with the majority (70%) of patients with COPD admitted to the ICUs during the study period being excluded from the study. The intubation rate in the control group was higher than that in some other studies, and it has been suggested that over zealous oxygen supplementation precipitated worsening hypercapnia in some patients . Kramer et al.  reported similar results with non-invasive pressure support ventilation in a mixed group of patients with acute respiratory failure, with a substantial reduction in the need for intubation, which was most marked in the subgroup with exacerbation of COPD (one of 11 patients on NIMV compared to eight of 12 controls). However, the mortality rate was no different (one of 16 vs. two of 15). Another study that used a conventional ICU ventilator to deliver pressure support with CPAP by a face mask also found a decreased need for intubation and decreased length of hospital stay in patients ventilated non-invasively, besides achieving significant physiological improvement .
However, not all studies have shown benefit from NIMV. Barbe et al. found no benefit from NIMV over conventional treatment . Patients received two sessions of NIMV, using pressure support, of 3h each for the first 3 days of their admission. None of the patients in either group required intubation or died. In a recent study of unselected patients with respiratory failure of different aetiologies, there was no difference between NIMV and standard medical treatment alone . However, there was a trend to an increased mortality in the NIMV group, which was attributed to a delay in intubation in the NIMV group (4 vs. 26 h). However, the study included only six patients with COPD (two in the NIMV and four in the control group) and the two groups were not well matched, particularly for aetiology of respiratory failure.
Studies performed in the ICU [26,55,56] show that NIMV is feasible and results in more rapid physiological improvement [26,55,56] and that the en-dotracheal intubation (ETI) rate is substantially reduced [55,56]. In the largest study , there was a reduction in mortality with NIMV. By contrast, studies performed outside the ICU (in the emergency room or on a general ward) [21,54,57] have failed to show an advantage for NIMV. A number of factors may explain this difference. Firstly, nurse staffing and doctor-to-patient ratios are likely to be less than those on the ICU, resulting in less time spent adapting the ventilator to the patient. However, physiological improvement was still seen in these studies, suggesting that, at least initially, effective ventilation was provided. In the study by Barbe et al. , no patient in either group required ETI or died; the mean pH was 7.33 and thus recovery in most patients was likely. Given the small number of patients studied, it is not surprising that no difference was seen between the two groups. Furthermore, NIMV was initiated in the emergency room before other medical therapies had been given time to work. In contrast, the patients treated on the ICU were more ill (more acidotic) and are likely to have failed to improve with initial treatment with bronchodilators, steroids, etc. A recent study has shown that 25% of acidotic patients will correct their pH into the normal range following medical treatment in the emergency room .
A multicentre randomized controlled trial of NIMV in 236 patients with acute exacerbations of COPD on general respiratory wards in 13 centres  has recently been reported. NIMV was administered with an unsophisticated ventilator and only the level of inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP) had to be adjusted by the usual ward staff according to a simple protocol. Patients were randomized to NIMV or conventional therapy if respiratory rate was > 23 breaths/min and pH between 7.25 and 7.35 inclusive on arrival on the ward, after a period had elapsed allowing time for treatment initiated in the emergency department to work. 'Treatment failure', a surrogate for the need for intubation, defined by a priori criteria, was reduced from 27% to 15% by NIMV (P< 0.05). Inhospital mortality was also reduced, from 20% to 10% (P < 0.05). Subgroup analysis [59,60] suggested that the outcome in patients with pH < 7.30 after initial treatment was inferior to that in the studies performed in the ICU, suggesting that the use of a very simple ventilator according to protocol on a general ward is only appropriate for those with milder exacerbations.
There is no direct comparison between invasive mechanical ventilation (IMV) and NIMV, and the two techniques should be viewed as complementary, with NIMV being regarded as a means of obviating the need for ETI rather than as a direct alternative. Some patients require intubation from the outset and others after a failed trial of NIMV. Patients with COPD may be difficult to wean from invasive mechanical ventilation , and NIMV has been used successfully in weaning [62,63]. A multicentre randomized controlled trial  in which 50 patients who failed a 2-h T-piece trial after 48h invasive mechanical ventilation were randomized to continued endotracheal intubation and weaning using pressure support or extubation onto NIMV, and a similar weaning strategy showed a clear advantage for NIMV. More patients were weaned (88% vs. 68%), and the duration of ventilation (10.2 ± 6.8 vs. 16.6± 11.8 days) and ICU stay (15.1 ±5.4 vs. 24.0± 13.7days) were reduced using NIMV. Ninety-two per cent of patients randomized to NIMV were alive at 60 days, compared with 72% who received continuing invasive mechanical ventilation. There were no episodes of pneumonia in the non-invasive group, but seven in the control group. Girault et al. , in a further randomized controlled trial involving 33 patients, showed a reduction in the duration of invasive mechanical ventilation (4.6 ± 1.9 vs. 7.7 ± 3.8days) and a reduced mean daily ventilatory support. However, the study found that there was an increased total duration (11.5 ± 5.2 vs. 3.5 ± 1.4days) of ventilatory support when the non-invasive approach was used. There was no difference in the percentage of patients successfully weaned, or in complication rates.
A proportion of patients weaned from invasive ventilation subsequently deteriorate and require further ventilatory support. Hilbert et al. reported 30 COPD patients who developed hypercapnic respiratory distress within 72 h of extubation . They were treated with mask bilevel pressure support ventilation. Only six of these 30 patients, compared with 20 of 30 historical controls, required reintubation. Although in-hospital mortality was not significantly different, the mean duration of ventilatory assistance and length of intensive-care stay related to the event were significantly shortened by non-invasive ventilation.
The use of other modes of non-invasive ventilation has been reported in patients with COPD exacerbation. In a retrospective uncontrolled study, 105 patients were successfully weaned, and 93 were eventually discharged from hospital after intermittent negative-pressure ventilation by means of an iron lung . Of these 105 patients, 62 were in coma and 43 had a deteriorating level of consciousness at presentation. All patients were initially ventilated continuously for 12-48 h and subsequently received intermittent daytime ventilation until weaned. Any subsequent exacerbation was also treated with negative-pressure ventilation. Survival was 92% and 37% at 1 and 5 years, respectively. A more recent study by the same group was carried out in 150 patients with hypoxic hypercapnic coma (including 79% patients with COPD) . Of the 74 patients with only exacerbation of COPD as cause of coma, treatment failed only in 19 (26%) patients, including 14 (19%) who died.
When should assisted ventilation be started? Is it appropriate in all patients with an exacerbation of COPD?
One of the theoretical advantages of NIMV is that it can be started at an earlier stage in the evolution of ventilatory failure, before invasive ventilation would normally be considered appropriate. It has been suggested that NIMV should be started when the pH is < 7.35 and the respiratory rate > 30 [69,70]. The data from the Yorkshire non-invasive ventilation (YONIV) trial  support these criteria, suggesting it be instituted at an even lower respiratory rate
(> 23 breaths/min), but after a period during which the effect of drug treatment, adjustment of oxygen therapy, etc. can be evaluated. Reversing ventila-tory failure is likely to be easier at an early stage, when theoretically lower pressures used for shorter periods may improve tolerance [69,70]. NIMV is less likely to be effective in patients with more severe physiological disturbances at the outset, suggesting that once decompensation has become well established, the cycle of deterioration may not be broken with the use of NIMV [55,71]. If NIMV does not improve pH and respiratory rate within the first hour or two, intubation should be considered [55,71,72]. Patients with high Acute Physiology and Chronic Health Evaluation (APACHE) II scores, an inability to minimize the amount of mouth leak (because of lack of teeth, secretions, or breathing pattern) or inability to coordinate with NIMV are poor candidates for NIMV . In another study, patients who failed on NIMV had a significantly higher incidence of pneumonia (38.5% vs. 8.7%), were underweight, had a greater level of neurological deterioration, a higher APACHE II score and reduced compliance with ventilation as assessed by the physician in charge, compared to those who were successfully treated . Although both groups had similar PaO2/FiO2 ratios, patients failing on NIMV had a significantly more abnormal PaCO2 and pH before starting NIMV. Only baseline pH was found by logistic regression analysis to be able to predict success or failure of NIMV (mean 7.28 in successful group, versus 7.22 in the failure group) with a sensitivity of 97% and specificity of 71%. Coma or confusion, upper gastrointestinal bleeding, high risk of aspiration, haemody-namic instability or uncontrolled arrhythmia have been suggested as contraindications to NIMV . This is primarily for theoretical reasons, as these patients have been excluded from previous studies, and not because there is any evidence that invasive mechanical ventilation (IMV) is superior in these situations.
The question of which patients should be intubated is difficult. Poor prognostic indicators for patients who are invasively ventilated are: admissions after cardiorespiratory arrest, previous therapy with long-term oral steroids, development of renal or cardiac failure in ICU and high APACHE II scores . However, clinical estimates of survival for the same patient may vary among physicians . Numerous authors have tried to find prediction models that could help in the clinical decision to invasively ventilate patients presenting with acute exacerbation of COPD. Kaelin et al. reported that a multivariate analysis including eight parameters (fever greater than 38°C, FEVj/forced vital capacity (FVC), age, leucocytosis, PaCO2 when the patient was stable, low-flow oxygen treatment and plasma protein) could differentiate between those likely to survive for more than 6 months with an accuracy of 78% . However, if the decision to intubate and ventilate had been based on this analysis, it would have denied ventilation to 23% of patients who even tually survived for more than 6 months. Stauffer et al.  also found that a multivariate analysis (including age, diagnosis and duration of mechanical ventilation) could not produce a predicted probability of survival for weaning, ICU discharge, hospital discharge or 1year post hospital discharge. Another study performed in patients requiring ventilation for more than 3 weeks found that PaCO2 and maximal inspiratory pressure (MIP) could predict weaning success or failure, but not the survival rate . However, this study found that survival to 2years in those not able to be weaned from the ventilator was very poor compared to those who were eventually weaned (22% vs. 68%). Other authors have found that patients requiring long-term home ventilation (either non-invasively or via tracheostomy) have survival periods no different from those requiring only long-term home oxygen, the mean survival being 3 years . Overall, it appears that predicting the successful long-term survival of patients being considered for invasive ventilation is imprecise, and any prediction model will misclassify a significant proportion of patients who are likely to survive after ventilation.
The decision to treat patients with severe COPD with mechanical ventilation was previously taken solely by physicians. However, the importance of patients and their families in decisions on instituting such life-sustaining treatments is now well recognized. It has been suggested that decisions regarding life-sustaining interventions should be made by patients educated concerning their disease and treatment options . Shared decision-making is increasingly recognized as an emerging trend in health care . However, this does not mean that the physician should always forfeit his opinion in favour of the patient's preference . The American Thoracic Society has outlined a physician's responsibilities in these situations as follows: firstly, to assess whether the patient has adequate decision-making capacity; secondly, to inform the patient regarding the diagnosis, prognosis, risks, benefits and consequences of the full range of available medical interventions; and thirdly, to provide a professional recommendation .
Often, discussions take place once patients have been brought to hospital for an exacerbation, when they are too ill to participate in the decision-making process, and physicians and family members end up taking the decisions on their behalf . Unfortunately, health-care decisions made for a patient frequently do not reflect the patient's own preferences . Physicians for their part consider the patient's quality of life, while taking decisions to provide or withhold life-sustaining treatment options. This involves interpretation of the patient's prior medical experience, the physician's attitudes about medical responsibilities/patient rights and estimates of the patient's survival time .
There are definite cultural differences in patient, family and physician attitudes regarding end-of-life medical-care decisions, and in some societies both physicians and family members may regard withholding or withdrawing life-sustaining treatment as abandonment or even killing [88,89]. In a study carried out by Sullivan et al. , physicians were in favour of prior discussions regarding life-sustaining treatment options, but felt that patients had difficulty in grasping such information and accepting it in a short time. Patient individuality and differing rates of progression of disease add to the difficulty in deciding the optimal time for such a discussion. The use of a living will by individuals with chronic illness is a common practice in some societies and is one way in which patients' views regarding life-sustaining treatments can be determined. Even within such societies, certain sections such as 'black, poorly educated, underinsured, or cognitively impaired' are less likely to prepare a living will . Furthermore, the decisions that patients make are strongly influenced by the way physicians present the options [83,91,92]. In practice, during a crisis several problems are encountered even in patients who have made a living will. They include delay in presenting the advanced directive, conflict between the dictates of the living will and the wishes of the person named in the durable power of attorney, and controversy among health-care providers as to when in the course of disease the spirit of the advanced directive has been met . The legal validity of such an advanced directive also needs to be considered in each country.
Current data suggest that for selected patients, the outcome with NIMV is certainly no worse than with IMV  and possibly better  and it should therefore be the first-line treatment for most patients. If the patient's wishes about the appropriateness of intervention are unknown, NIMV is less problematic than IMV, because patients can choose to discontinue NIMV subsequently, when they may be better able to make such decisions. Patients retain a higher degree of control over their own destiny than is possible when they have been intubated. It may also buy time for family members to accept that further intervention is not appropriate. Indeed, NIMV has been successfully used in patients refusing endotracheal intubation .
A strong case cannot be made on current evidence for denying ventilation, especially NIMV, to any patient presenting with acute respiratory failure due to COPD and requiring ventilatory support. At the same time, it has been aptly stated that 'We have this technology that can, in some cases, save lives and in others prolong dying; we have a greater responsibility to determine when that technology will be used' .
What is the cost of NIMV?
In an early report on the use of NIMV in six patients, Chevrolet et al. 
found that, particularly in patients with obstructive lung disease, the technique was very time-consuming for the nurses and the time was largely wasted, since all of the patients eventually had to be intubated. As with any new technique, there is a learning curve, and the same group have subsequently published more encouraging results . In the ICU, in which there are high nurse-to-patient ratios, any additional work associated with NIMV is unlikely to have a major effect, but the issue of medical and nursing time is very relevant if the technique is to be performed in the ward environment. Nurses and therapists will have responsibility for a much larger number of patients, and any extra work associated with NIMV may mean that other tasks and patients are neglected.
In a randomized controlled trial comparing standard treatment with or without NIMV in a general ward setting, Bott et al.  found no difference in nursing care requirements, recorded on a daily basis by asking the senior nurse to record the amount of care needed using a simple visual analogue scale. This may have underestimated the care requirements associated with NIMV, because ventilation was initiated and maintained by staff supernumerary to the normal ward complement. In another study, with more detailed analysis of nursing and therapist activity, Kramer et al.  found that the respiratory therapist spent more time with patients in the NIMV group compared to the standard treatment group in the first 8 h, but this difference did not reach statistical significance. The time required in the NIMV group dropped significantly in the second 8-h period. The time demands on the nurses did not differ in the two groups throughout the measurement period, and neither the respiratory therapist nor the nurses considered caring for patients on NIMV as being any more difficult than the control patients. Nava et al.  found that in the first 48 h of assisted ventilation, NIMV was no more time-consuming or demanding for staff than invasive mechanical ventilation. However, after the first few days of ventilation, NIMV was significantly less time-consuming for both medical and nursing personnel.
Since most studies report a shorter period of ventilation and ICU and hospital stay, it is has been suggested that NIMV should be cheaper than invasive mechanical ventilation [98,99]. However, patients treated with NIMV do incur substantial financial costs during their hospitalization . Nava et al.  found that the total cost per day was comparable for invasive and non-invasive ventilation, although NIMV was performed on a respiratory ICU. In the study by Kramer et al. , the total hospital charges were 37.6± 7.9 (in thousands of dollars) in patients receiving NIMV vs. 33.9 ± 6.9 in control patients not receiving NIMV, which was not statistically different . In a recent multicentre study from the UK, the incremental cost of NIMV per patient avoiding the 'need for intubation' was £2829. However, the incremental savings per death avoided were £4114, by way of decreased ICU usage, thus providing a strong economic argument for the use of NIMV .
How should NIMV be used and by whom? Is it viable in the ordinary district general hospital setting?
Although early experience of NIMV in COPD exacerbation came from the ICU [16,17] it has been shown to be effective in the non-ICU setting [18,54,59,102]. The successful application of NIMV is critically dependent on nursing, therapist and medical staff expertise, and it is vital that all staff involved be adequately trained in the technique. Expertise and skill retention will be facilitated by maximizing exposure of all staff to patients receiving NIMV. The expected throughput of patients is another factor to be considered in deciding on the best location for NIMV. In a recent study in the UK, it has been suggested that for the average general hospital, serving a population of 250000 and with a standardized mortality rate for COPD of 100, six patients per month with an acute exacerbation of COPD will require NIMV, assuming that ventilation is initiated in patients with a pH < 7.35 after initial treatment . This number excludes patients with other conditions requiring NIMV and those who require it later in their hospital stay, e.g. for weaning, etc. With relatively small numbers of patients per month, NIMV is best performed in a single-sex location, to facilitate staff training and to maximize throughput and skill retention. In areas with a higher prevalence of COPD or hospitals serving larger populations, an NIMV service could reasonably be provided in more than one location.
A proportion of patients will fail with NIMV, requiring intubation and invasive ventilation; it is important that personnel and the facility for intubation be rapidly available if needed, if the trend to increased mortality with NIMV, as reported by Wood et al., is to be avoided . It could be argued that for patients with a high likelihood of failing (e.g. severe acidosis, severe hyper-capnia, initiating event unlikely to be rapidly reversible, etc.) , NIMV should be initiated on the ICU and once stabilized the patient could be transferred to the ward normally providing NIMV.
In any discussion about the location of an NIMV service, it is important to note that the model of hospital care differs from country to country and that 'ICU', 'high-dependency unit' (HDU) and 'general ward' will have different levels of staffing, facilities for monitoring, etc. [103-105]. Care must therefore be taken in the extrapolation of results obtained in one environment to other hospitals and countries.
In summary, staff training and experience are more important than location, and adequate numbers of staff, skilled in NIMV, must be available throughout the 24-h period. Because of the demands of looking after these acutely ill patients, and to aid training and skill retention, NIMV is usually best carried out in one single-sex location, with one nurse responsible for no more than three to four patients in total.
Is there still a role for ventilatory stimulants?
In acute respiratory failure due to COPD, respiratory drive is usually high . Despite this, respiratory stimulants have been used in exacerbations of COPD and may obviate the need for intubation [2,107,108]. Of a number of respiratory stimulants (doxapram, ethamivan, amiphenazole, prethcamide and nikethamide), only doxapram produced a significant increase in minute volume , and it also increased sputum production. It is also the only respiratory stimulant licensed for use in the UK. In a double-blind cross-over trial in eight patients with an acute exacerbation of COPD on controlled oxygen therapy, three patients had a rise in PaCO2 on placebo, which was reversed with doxapram . A double-blind study compared 40 patients on a doxapram infusion with 38 patients on placebo over a 2-h period . There was a significantly higher pH and lower PaCO2 in the doxapram group at all time points. However, intubation and death rates were not affected. One patient on doxapram developed a psychosis. In a randomized controlled study, patients with exacerbation of COPD and type II respiratory failure, who were not improving on conventional treatment, received either non-invasive ventilation or doxapram . Both groups of patients had an improvement in PaO2, but the level was higher and the peak level was sustained at 4h only in the NIMV group. Similarly, PaCO2 decreased in both groups of patients, but was sustained at 4 h only in those on NIMV. In the early part of the study, three patients in the doxapram group died. Subsequently, the protocol was modified and two further patients deteriorating on doxapram received NIMV and survived to discharge. Another respiratory stimulant, almitrine, is effective in improving both PaO2 and PaCO2 levels when infused in COPD patients with chronic respiratory failure, by increasing ventilation and improving the ventilation-perfusion relationship . A comparison of almitrine 0.5mg/kg infusion with doxapram 1 mg/kg found that the former was significantly better in increasing PaO2 and decreasing PaCO2 in patients with chronic type II respiratory failure . However, a randomized controlled trial against placebo in acute exacerbations of COPD revealed no benefit from almitrine .
Respiratory stimulants in acute exacerbations of COPD have been shown to have a short-term physiological effect, but there are no data to show that this translates into an improved outcome. Such evidence as there is suggests that NIMV is superior to doxapram. Respiratory stimulants may have a role when NIMV is not available or not tolerated.
Patients with an acute exacerbation of COPD place a major burden on health services. There is now good evidence from a number of randomized controlled trials that there is a major role for NIMV and that it should be introduced early, if acidosis persists after initial therapy in the emergency room. NIMV should be considered as a means of avoiding intubation rather than as a substitute for invasive ventilation, and the two techniques should be viewed as complementary. With regard to location, successful NIMV has been reported in the ICU, respiratory ICU and on the ward; the best location will vary from hospital to hospital and is largely dependent on staff training and expertise. Most patients with COPD will die of their disease, and better data are needed to inform the decision-making process regarding the appropriate use of noninvasive and invasive ventilation in acute exacerbations of COPD, if unnecessary suffering and prolongation of the act of dying are to be avoided.
1 Martin TR, Lewis SW, Albert RK. The prognosis of patients with chronic obstructive pulmonary disease after hospitalization for acute respiratory failure. Chest 1982; 82: 310-14.
2 Jeffrey AA, Warren PM, Flenley DC. Acute hypercapnic respiratory failure in patients with chronic obstructive lung disease: risk factors and use of guidelines for management. Thorax 1992; 47: 34-40.
3 Connors AF Jr, Dawson NV, Thomas C et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators. Am J Respir Crit Care Med 1996; 155: 959-67.
4 Vestbo J, Prescott E, Lange P, Schnohr P, Jenson G. Vital prognosis after hospitalization for COPD: a study of a random population sample. Respir Med 1998; 92: 772-6.
5 Fuso L, Incalzi R, Pistelli R et al. Predicting mortality of patients hospitalized for acutely exacerbated chronic obstructive pulmonary disease. Am J Med 1995; 98: 272-7.
6 Anon JM, Garcia de Lorenzo A, Zarazaga A, Gomez-Tello V, Garrido G. Mechanical ventilation of patients on long-term oxygen therapy with acute exacerbation of chronic obstructive pulmonary disease: prognosis and cost-utility analysis. Intensive Care Med 1999; 25: 452-7.
7 Costello R, Deegan P, Fitzpatrick M, McNicholas WT. Reversible hypercapnia in chronic obstructive pulmonary disease: a distinct pattern of respiratory failure with a favorable prognosis. Am J Med 1997; 102: 239-44.
8 Schols AM, Slangen J, Volovics L, Wouters EF. Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 157: 1791-7.
9 Antonelli Incalzi R, Fuso L et al. Comorbidity contributes to predict mortality of patients with chronic obstructive pulmonary disease. Eur Respir J1997; 10: 2794-800.
10 Warren PM, Flenley DC, Millar JS, Avery A. Respiratory failure revisited: acute exacerbation of chronic bronchitis between 1961 and 68 and 1970-76. Lancet 1980; i: 467-70.
11 Kamat SR, Heera S, Potdar PV et al. Bombay experience in intensive respiratory care over 6 years. J Postgrad Med 1989; 35: 123-34.
12 Braghiroli A, Zaccaria S, Ioli F, Erbetta M, Donner CF. Pulmonary failure as a cause of death in COPD. Monaldi Arch Chest Dis 1997; 52: 170-5.
13 Seneff MG, Wagner DP, Wagner RP, Zimmerman JE, Knaus WA. Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease. JAMA 1995; 274: 1852-7.
14 Moran JL, Green JV, Homan SD, Leeson RJ, Leppard PI. Acute exacerbation of chronic obstructive pulmonary disease and mechanical ventilation: a reevaluation. Crit Care Med 1998; 26: 71-8.
15 Driver AG, McAlevy MT, Smith JL. Nutritional assessment of patients with chronic obstructive pulmonary disease and acute respiratory failure. Chest 1982;82:568-71.
16 Meduri GU, Conoscenti CC, Menashe P, Nair S. Noninvasive face mask ventilation in patients with acute respiratory failure. Chest 1989; 95: 865-70.
17 Brochard L, Isabey D, Piquet J et al. Reversal of acute exacerbations of chronic obstructive lung disease by inspiratory assistance with a face mask. N Engl J Med 1990; 323: 1523-30.
18 Elliott MW, Steven MH, Phillips GD, Branthwaite MA. Non-invasive mechanical ventilation for acute respiratory failure. BMJ 1990; 300: 358-60.
19 Pingleton SK. Complications of acute respiratory failure. Am Rev Respir Dis 1988; 137: 1463-93.
20 Ambrosino N. Noninvasive mechanical ventilation in acute respiratory failure. Eur Respir J1996; 9: 795-807.
21 Wood KA, Lewis L, Von Harz B, Kollef MH. The use of noninvasive positive pressure ventilation in the emergency department. Chest 1998; 113: 1339-46.
22 Chevrolet JC, Jolliet P, Abajo B, Toussi A, Louis M. Nasal positive pressure ventilation in patients with acute respiratory failure. Chest 1991; 100: 775-82.
23 Elliott MW, Aquilina R, Green M, Moxham J, Simonds AK. A comparison of different modes of noninvasive ventilatory support: effects on ventilation and inspiratory muscle effort. Anaesthesia 1994; 49: 279-83.
24 Girault C, Richard J, Chevron V et al. Comparative physiological effects of noninvasive assist-control and pressure support ventilation in acute hypercapnic respiratory failure. Chest 1997; 111: 1639-48.
25 Diaz O, Iglesia R, Ferrer M et al. Effects of noninvasive ventilation on pulmonary gas exchange and hemodynamics during acute hypercapnic exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997; 156: 1840-5.
26 Celikel T, Sungur M, Ceyhan B, Karakurt S. Comparison of noninvasive positive pressure ventilation with standard medical therapy in hypercapnic acute respiratory failure. Chest 1998; 114:1636-42.
27 Girault C, Richard JC, Chevron V et al. Comparative physiologic effects of noninvasive assist-control and pressure support ventilation in acute hypercapnic respiratory failure. Chest 1997; 111: 1639-48.
28 Cinnella G, Conti G, Lofaso F et al. Effects of assisted ventilation on the work of breathing: volume-controlled versus pressure-controlled ventilation. Am J Respir Crit Care Med 1996; 153: 1025-33.
29 Meecham Jones DJ, Wedzicha JA. Comparison of pressure and volume preset nasal ventilator systems in stable chronic respiratory failure. Eur Respir J 1993; 6: 1060-4.
30 Vitacca M, Rubini F, Foglio K, Scalvini S, Nava S, Ambrosino N. Non-invasive modalities of positive pressure ventilation improve the outcome of acute exacerbations in COLD patients. Intensive Care Med 1993; 19: 450-5.
31 Ambrosino N, Vitacca M, Polese G et al. Short-term effects of nasal proportional assist ventilation in patients with chronic hypercapnic respiratory insufficiency. Eur Respir J1997; 10: 2829-34.
32 Patrick W, Webster K, Ludwig L et al. Non-invasive positive-pressure ventilation in acute respiratory distress without prior respiratory failure. Am J Respir Crit Care Med 1996; 153: 1005-11.
33 Ranieri VM, Grasso S, Mascia L et al. Effects of proportional assist ventilation on inspiratory muscle effort in patients with chronic obstructive pulmonary disease and acute respiratory failure. Anesthesiology 1997; 86: 79-91.
34 Wrigge H, Golisch W, Zinserling J et al. Proportional assist versus pressure support ventilation: effects on breathing pattern and respiratory work of patients with chronic obstructive pulmonary disease. Intensive Care Med 1999; 25: 790-8.
35 Appendini L, Purro A, Gudjonsdottir M et al. Physiological response of ventilator-dependent patients with chronic obstructive pulmonary disease to proportional assist ventilation and continuous positive airway pressure. Am J Respir Crit Care Med 1999; 159: 1510-17.
36 Appendini L, Patessio A, Zanaboni S
et al. Physiologic effects of positive end-expiratory pressure and mask pressure support during exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1994; 149: 1069-76.
37 Ferguson GT, Gilmartin M. CO2 rebreathing during BiPAP ventilatory assistance. Am J Respir Crit Care Med 1995; 151: 1126-35.
38 Ambrosino N, Nava S, Torbicki A et al. Haemodynamic effects of pressure support and PEEP ventilation by nasal route in patients with stable chronic obstructive pulmonary disease. Thorax 1993; 48: 523-8.
39 de Lucas P, Tarancon C, Puente L, Rodriguez C, Tatay E, Monturiol JM. Nasal continuous positive airway pressure in patients with COPD in acute respiratory failure: a study of the immediate effects. Chest 1993; 104: 1694-7.
40 Dottorini M, Baglioni S, Eslami A, Todisco T, Fiorenzano G. N-CPAP in patients with COPD in acute respiratory failure. Chest 1995; 107: 585-6.
41 Miro AM, Shivaram U, Hertig I. Continuous positive airway pressure in COPD patients in acute hypercapnic respiratory failure. Chest 1993; 103: 266-8.
42 Meduri GU, Abou-Shala N, Fox RC
et al. Noninvasive face mask mechanical ventilation in patients with acute hypercapnic respiratory failure. Chest 1991; 100: 445-54.
43 Marino W. Intermittent volume cycled mechanical ventilation via nasal mask in patients with respiratory failure due to COPD. Chest 1991; 99: 681-4.
44 Benhamou D, Girault C, Faure C, Portier F, Muir JF. Nasal mask ventilation in acute respiratory failure. Chest 1992; 102: 912-17.
45 Fernandez R, Blanch L, Valles J, Baigorri
F, Artigas A. Pressure support ventilation via face mask in acute respiratory failure in hypercapnic COPD patients. Intensive Care Med 1993; 19: 456-61.
46 Conway JH, Hitchcock RA, Godfrey RC, Carroll MP. Nasal intermittent positive pressure ventilation in acute exacerbation of chronic obstructive pulmonary disease: a preliminary study. Respir Med 1993; 87: 387-94.
47 Confalonieri M, Aiolfi S, Gandola L et al. Severe exacerbation of chronic obstructive pulmonary disease treated with BiPAP by nasal mask. Respiration 1994; 61: 310-16.
48 Hilbert G, Gruson D, Gbikpi-Benissan
G, Cardinaud JP. Sequential use of noninvasive pressure support ventilation for acute exacerbations of COPD. Intensive Care Med 1997; 23: 955-61.
49 Confalonieri M, Parigi P, Scartabellati A et al. Noninvasive mechanical ventilation improves the immediate and long-term outcome of COPD patients with acute respiratory failure. Eur Respir J1996; 9: 422-30.
50 Vitacca M, Clini E, Rubini F et al. Non-invasive mechanical ventilation in severe chronic obstructive lung disease and acute respiratory failure: short-and long-term prognosis. Intensive Care Med 1996; 22: 94-100.
51 Shneerson JM. The changing role of mechanical ventilation in COPD. Eur Respir J1996; 9: 393-8.
52 Coakley JH, Nagendran K, Honavar M, Hinds CJ. Preliminary observations on the neuromuscular abnormalities in patients with organ failure and sepsis. Intensive Care Med 1993; 19:
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