Editorials

Non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease

Between a fifth and a third of patients admitted to hospital with hypercapnic respiratory failure secondary to acute exacerbation of chronic obstructive pulmonary disease will die in hospital, despite selective use of mechanical ventilation. ^{1 2 3 4 5 6 7 8 9 10 11 12 13} In severe chronic obstructive pulmonary disease, hyperinflation places the respiratory muscles at a mechanical disadvantage and they function close to their maximum capacity.^{14 15} During acute exacerbations, elastic and resistive loads on the respiratory muscles increase and may lead to ventilatory failure. The ensuing tissue acidosis further impairs respiratory muscle function, producing a vicious cycle.¹⁶ Thus a logical approach is to assist the compromised "respiratory muscle pump".

Non-invasive positive pressure ventilation (NIPPV) employs a nasal or full face mask to administer ventilatory support from a flow generator and is established in the treatment of patients with a variety of chronic hypoventilatory syndromes. A role in acute exacerbation of chronic obstructive pulmonary disease (COPD) was suggested by early open and case control studies^{9 10 11} and has recently been confirmed by three randomised controlled trials (see 1).^{5 6 7}

Bott et al randomised 60 patients with exacerbations of chronic obstructive pulmonary disease to either standard treatment (antibiotics, bronchodilators, corticosteroids, respiratory stimulants, and oxygen) or standard treatment plus non-invasive ventilation on a medical ward.⁵ Nine of the 30 patients receiving standard treatment died in contrast to only one of the 26 who accepted non-invasive ventilation (relative risk 0.13, 95% CI 0.02-0.95). (Of the four who did not receive ventilation, two died.) Four patients who failed to respond to standard treatment were offered non-invasive ventilation, though three required intubation.

Brochard et al selected 85 patients with incipient acute respiratory failure from a pool of 275 and treated 42 with standard therapy and 43 with additional non-invasive ventilation.⁶ Patients were excluded if they needed immediate intubation, had heart failure, pneumonia, asthma, or sepsis, or were postoperative. In the standard treatment group, 74% were intubated and 29% died compared with 26% (p<0.001) and 9% (p=0.02) respectively in the ventilated group. Furthermore, life threatening complications were more frequent in the standard treatment group and hospital stay was longer (see 1)⁶

In a well matched group of patients, Kramer et al found a significant reduction in the need for intubation in patients treated with non-invasive ventilation (one of 11) over those receiving standard treatment (eight of 12).⁷ Mortality was lower than in the other studies and may reflect sample size, the intensive care setting, or longer duration of ventilation.

Although these studies seem conclusive, they could not be blind since "sham" ventilation is not feasible. Significant placebo effect and bias in management may have influenced the outcome. In two of the studies, investigators making clinical management decisions were unaware of which treatment arm a patient was in until ventilation was started,^{5 6} and in the third the decision to intubate was not made by the investigators.⁷ The lack of a clear protocol for establishing the need for intubation is therefore a weakness in two of the studies since it allows management bias, and although Brochard et al clearly specified criteria for intubation, they were complex.⁶ In two studies significant reductions in breathlessness scores and respiratory rate were found in the ventilated groups.^{5 7} However, breathlessness was measured by visual analogue scale rather than validated questionnaire. One recent controlled study has shown no beneficial effect of non-invasive ventilation given twice a day for three hours, but patients were less severely affected than in other studies since all recovered without the need for mechanical ventilation.¹⁷

Both the initial response to non-invasive ventilation and the severity of the ventilatory failure at presentation are important predictors of success. Ambrosino et al found that at one hour the blood pH was lower and PaCO2 higher in patients in whom non-invasive ventilation would be unsuccessful. Rapid improvement in pH and respiratory rate in the first hour of non-invasive ventilation has been shown to be an important predictor of success.^{5 17} Reversing the vicious cycle of ventilatory failure and acidosis is likely to be easier at an earlier stage since the level of assistance required may be less both in terms of time using the ventilator and magnitude of pressure support. Furthermore, other consequences of hypoventilation, such as mucus retention, are less likely. Thus non-invasive ventilation should be instituted at an early stage when the pH falls below 7.35 ^{5 6} and the respiratory rate exceeds 30 breaths per minute. If there is no improvement in these parameters in the first one to two hours, intubation should be considered.^{5 18} Two studies have shown that the more severe the episode of ventilatory failure (indicated by the degree of acidosis) the smaller the chances of success.^{6 8} Non-invasive ventilation cannot be recommended for patients who require immediate intubation because none of the controlled trials included such patients. The duration of ventilation will depend on need and tolerance, but in two controlled trials a mean of only six to eight hours per day was efficacious.^{5 6}

Which health professionals should initiate non-invasive ventilation is not clear, but the list may include pulmonary function technicians, physiotherapists, nurses, and junior medical staff, depending on local interest and expertise. Nursing staff under medical guidance should probably play a major role, especially as a 24 hour service is required. Earlier reports that non-invasive ventilation was time consuming for nursing staff¹³ have not been confirmed.^{5 7}

A trial of non-invasive ventilation should be considered early in the course of acute respiratory failure secondary to exacerbation of chronic obstructive pulmonary disease as a means of avoiding intubation and reducing hospital stay and mortality.

David R Baldwin, Consultant physician,^a Martin B Allen, Consultant physician ^b

^a Department of Respiratory Medicine, Nottingham City Hospital, Nottingham NG5 1PB, ^b Sleep and Ventilation Centre, Department of Respiratory Medicine, City General Hospital, Stoke on Trent ST4 6QG

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