Ward-based non-invasive ventilation for hypercapnic exacerbations of COPD: a real-life perspective

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1 Q J Med 2010; 103: doi: /qjmed/hcq063 Advance Access Publication 26 May 2010 Ward-based non-invasive ventilation for hypercapnic exacerbations of COPD: a real-life perspective K.M. MCLAUGHLIN 1, I.M. MURRAY 1, G. THAIN 2 and G.P. CURRIE 1 From the 1 Department of Respiratory Medicine and 2 Department of Physiotherapy, Aberdeen Royal Infirmary Aberdeen, Scotland, AB25 2ZN, UK Address correspondence to K.M. McLaughlin, Department of Respiratory Medicine, Aberdeen Royal Infirmary Aberdeen, Scotland, AB25 2ZN, UK. k.mclaughlin@nhs.net Received 23 November 2009 and in revised form 31 March 2010 Summary Background: Non-invasive ventilation (NIV) has revolutionized the management of hypercapnic exacerbations of chronic obstructive pulmonary disease (COPD). However, most published data have evaluated highly selected patients within the context of randomized controlled trials. Objective: We wished to evaluate the outcomes of ward-based NIV in real-life patients admitted to hospital with a hypercapnic exacerbation of COPD. Methods: Retrospective data (gender, age, baseline ph, PaCO 2 and values after 1 and 4 h of NIV, and outcomes) were evaluated for all patients receiving NIV in the respiratory unit of Aberdeen Royal Infirmary from January 2006 to December Data were analysed in three groups: as a whole, in those with baseline ph 7.25 and baseline ph <7.25. Introduction Chronic obstructive pulmonary disease (COPD) is a disabling and progressive lung disorder characterized by partially reversible airflow limitation. 1 It is a common cause of morbidity and mortality and is predicted to be the third leading cause of death worldwide by In a report by the British Lung Foundation, it was suggested that 3.7 million people in the UK may have COPD, despite only being currently diagnosed. 3 In the years ahead, these missing millions are likely to add Results: Data were available for all 392 patients commenced on ward-based NIV [45% male, mean age (range) 71 years (42 89)] with mean baseline ph of 7.24 and PaCO 2 of 10.1 kpa; respective values improved significantly (P <0.0001) following 1 and 4 h of NIV and treatment was considered successful in 66%. In those with baseline ph <7.25 and 7.25, the success rates of NIV were 58 and 72%, respectively. Conclusions: In hypercapnic exacerbations of COPD, ward-based NIV is useful in the real-life setting with physiological parameters improving after only a short treatment period, while two-thirds of all patients were discharged from hospital. Further data are required to help determine factors other than ph which influence the outcome of NIV. further burden to the already significant socio-economic impact of COPD, currently estimated at 1.5 billion per annum in the UK, predominantly attributable to in-patient care. 4 An exacerbation of COPD is defined as an acute sustained worsening of symptoms from a usual stable state which is beyond normal day to day variation. 5 Exacerbations have a negative impact upon physical and psychosocial well-being and are associated with increased mortality, 6 depression and anxiety, 7 more rapid decline in lung function 8 and increased likelihood of becoming housebound. 9! The Author Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please journals.permissions@oxfordjournals.org

2 506 K.M. McLaughlin et al. The mainstay of treatment for acute exacerbations includes controlled oxygen, bronchodilators, corticosteroids and antibiotics. 5 Non-invasive ventilation (NIV) has revolutionized the management of acute exacerbations of COPD and is usually indicated when hypercapnic respiratory failure is present (PaCO 2 6 kpa, ph <7.35). 10 Indeed, a recent report by Hosker et al. indicated that in almost 25% of emergency admissions with an exacerbation of COPD, an acidosis (ph <7.35) was present. 11 NIV has multiple advantages over invasive ventilatory support. For example it can be used in general wards and allows patients to eat, drink, communicate and maintain a physiological cough, and intermittent use can facilitate weaning. 10 The purpose of this article is to illustrate our own real-life retrospective data surrounding the use of NIV in a general ward environment. We feel it is important to do so as the vast majority of published evidence surrounding NIV use has evaluated highly selected patients within the stringent realms of randomized controlled trials. In other words, since strict criteria usually need fulfilled before entry into a clinical trial is possible (often resulting in exclusion of elderly patients and those with major co-morbidities, major electrolyte disturbance and more severe exacerbations), outcomes may not always be representative of everyday practice. Methods Data were gathered retrospectively from a password protected database for unselected patients commenced on ward-based NIV for respiratory failure due to an exacerbation of COPD; all had been admitted to the respiratory unit in Aberdeen Royal Infirmary between January 2006 and December 2009 inclusive. Demographics (age and gender), Table 1 ph and PaCO 2 at baseline, and after 1 and 4 h of NIV physiological variables (ph and PaCO 2 ) and outcomes (hospital discharge, inability to tolerate NIV, transfer to intensive care and death) were extracted for all patients. Data from patients were subsequently evaluated in three groups: as a whole, those with baseline ph 7.25 (in whom NIV is most widely studied and advocated) and in those with a more severe exacerbation characterized by baseline ph <7.25 (in whom the beneficial effects of NIV are less pronounced and less well studied). Data were then analysed using SPSS and a paired T-test performed to compare values at baseline to those at 1 h, and between 1 and 4 h. Results Over 4 years, 392 patients [45% male, mean age (range) 71 (42 89)] with hypercapnic exacerbations of COPD were treated with NIV after assessment by a respiratory specialist (consultant, registrar or staff grade). Data were available for all individuals with overall mean baseline ph and PaCO 2 shown in Table 1. Outcome of NIV Treatment success was defined as an initial improvement in physiological and clinical parameters allowing cessation of NIV, while failure was defined as clinical and/or physiological deterioration resulting in transfer to intensive care, patient inability to tolerate NIV or death. Adopting these criteria, NIV was successful in 259 patients overall (66%). Reasons for treatment failure were death (n = 115), transfer to intensive care (n = 13) and inability to tolerate NIV (n = 5). For patients with initial ph 7.25 (n = 228) and ph <7.25 (n = 164), outcomes are shown in Figures 1 and 2, respectively. All patients Prior to NIV 1 h post NIV 4 h post NIV n = 392 n = 344 n = 159 Mean ph * 7.33** Mean PaCO 2 (kpa) * 8.3** Patients with ph 7.25 n = 228 n = 202 n =95 Mean ph * 7.35** Mean PaCO 2 (kpa) * 8.4** Patients with ph <7.25 n = 164 n = 142 n =64 Mean ph * 7.30** Mean PaCO 2 (kpa) * 8.53** n denotes the number of patients who had an arterial blood gas performed at 1 and 4 h. *P <0.0001: significant improvement between 1 h and baseline values. **P <0.0001: significant improvement between 1 and 4 h values.

3 Ward-based NIV 507 ph 7.25, n=228 NIV therapy Success, n=164 Failure, n=64 Failed to tolerate NIV, n=5 Died, n=8 Discharged, n=156 Figure 1. Outcomes for patients with ph Arterial ph and PaCO 2 For all patients, those with initial 7.25 and ph <7.25, the mean ph and PaCO 2 prior to NIV, and 1 and 4 h later, are shown in Table 1. In all groups, a significant improvement (P <0.0001) in both ph and PaCO 2 occurred at 1 and 4 h. Discussion ph<7.25, n=164 Success, n=95 Failure, n=69 Died, n=1 Discharged, n=94 Figure 2. Outcomes for patients with ph <7.25. NIV therapy Our data have shown that in unselected patients with an exacerbation of COPD necessitating NIV, ICU transfer, n=7 Discharged, n=4 Died, n=3 ICU transfer, n=6 Discharged, n=5 Died, n=1 Ward based care, n=57 Discharged, n=3 Ward based care, n=63 Discharged, n=1 Died, n=54 Died, n=62 67% were ultimately discharged from hospital, while in those with a milder exacerbation (ph 7.25), this figure increased to 71%. In those with a more severe exacerbation, characterized by baseline ph <7.25, the hospital discharge rate was 61%. This in turn indicates that more severe exacerbations can be successfully treated with NIV, although suitability for intensive care admission should be assessed and clearly documented from the outset. Moreover, patients who fail to improve characterized by clinical deterioration and/ or lack of improvement in ph or respiratory rate

4 508 K.M. McLaughlin et al. after 1 h of NIV should not have admission to intensive care delayed where considered appropriate. Indeed, clinical trials suggest that more severe acidosis at onset (ph <7.30) is associated with greater likelihood of treatment failure. 12,13 This finding was succinctly highlighted by Keenan et al. who performed a systematic review and subgroup analysis of 15 randomized controlled trials of NIV for COPD exacerbations; patients with a more severe exacerbation (defined as ph <7.30) were more likely to require endotracheal intubation (ETI) and had higher mortality rates, than those with a less pronounced acidosis. 14 In the only other published study of real-life outcomes involving a large number of patients (n = 226) treated with NIV for hypercapnic exacerbations of COPD, an in-patient mortality of 16% was observed. 15 However, in this population, baseline median ph was higher than our own (7.28 vs. 7.24). Due to the retrospective nature of our data, the number of endpoints available was limited. Ten randomized controlled trials have compared ward-based NIV vs. usual medical care (UMC) for patients with hypercapnic exacerbations of COPD across a variety of endpoints (Table 2). 12,13,16 23 The primary endpoint in the majority (n = 9) of studies was need for ETI 12,13,16 21,23 while in one it was 30-day mortality. 22 Secondary endpoints included mortality, arterial ph, respiratory rate and mean length of stay. Four of the trials evaluating the need for ETI as the primary endpoint reported a significant reduction in ETI for patients treated with NIV compared with control. 13,16,18,23 For example, in one study of 75 randomized patients, 18 a significant (P = 0.04) reduction was observed in the number of patients meeting the criteria for ETI in Table 2 those treated with NIV compared to control: 14 vs. 34% respectively. Moreover, in a multi-centre trial in China (n = 342 individuals), 23 a significant reduction in need for ETI was found in patients treated with NIV vs. control (% vs. 15% respectively, P = 0.002). In our group of patients, the overall mortality rate was 33%, although it needs to be pointed out that patients were included in our analysis irrespective of co-morbidities, relative contra-indications to NIV, age or presence of electrolyte disturbance. Five trials of ward-based NIV have evaluated mortality as an endpoint, 13,19,20,22 of which three described a significant reduction with NIV vs. UMC. 13,20,22 For example, Plant et al. reported a mortality rate of 20% in controls compared with 10% in those receiving NIV (P = 0.05). 13 Avdeev et al. reported a reduction in mortality from 31 to 8% favouring NIV (P <0.05), 20 while Bott et al. report a significant reduction for patients receiving NIV compared with UMC (4 vs. 30%, respectively, P = ). 19 Our data evaluating 392 patients with baseline ph of 7.24 demonstrated significant improvements at 1 and 4 h (7.26 and 7.33, respectively). As a secondary endpoint, eight trials have evaluated changes in mean arterial ph between patients treated with NIV and UMC at various time intervals (1 72 h) after initiation of NIV. 12,13,16,18,20 23 In seven of these, significant improvements in mean arterial ph were observed for patients treated with NIV compared with UMC. 12,13,16,18,20,22,23 NIV can successfully be carried out in a number of settings 14 providing appropriately trained and experienced staff are available. In our hospital, we have developed a physiotherapist-led ward-based service with complementary input by medical Prospective randomized controlled trials comparing NIV on general wards with usual medical care in COPD Study NIV interface No. of subjects randomized Mean age (years) (NIV vs. UMC) Baseline ph (NIV vs. UMC) ETI/treatment failure, P-value (NIV vs. UMC) Carrera 18 Face mask vs vs vs. 34%, 0.04 CRG 23 Face mask vs vs vs. 15%, Keenan 17 Face or nasal mask vs vs vs. 7%, del Castillo 12 Face or nasal mask vs vs vs. 14%, NS Dikensoy 16 Face mask vs vs vs. 41%, <0.05 Plant 13 Face or nasal mask vs vs vs. 27%, <0.02 Bardi 19 Nasal mask vs vs vs. 14%, NS Avdeev 20 Face or nasal mask vs vs vs. 28%, 0.18 Barbe 21 Nasal mask vs. 65 NR 0 vs. 0, 1 Bott 22 Nasal mask 60 NR 7.35 vs NR ETI: endotracheal intubation; NR: no data reported; NS: non-significant difference; CRG: Collaborative Research Group.

5 Ward-based NIV 509 and nursing staff by which to deliver NIV. 24 However, physiotherapy involvement with NIV is highly variable and depends on local expertise, staffing and levels of interest. This was highlighted in a recent survey in the UK, where the majority (97%) of physiotherapists were involved with patients already receiving NIV, although only 68% actively assessed patients for its use and less than half (46%) were involved in initiating treatment. 25 Whether a physiotherapist-led NIV service is feasible in other hospitals remains to be seen, although with reduction in junior doctors working hours coupled with less time spent in sub-specialty areas, physiotherapists may be suitably placed to maintain one of the threads of continuity in patient care. As described above, current randomized controlled data evaluating the use of NIV in general wards for hypercapnic exacerbations of COPD, overwhelmingly support its use. Compared to standard treatment, these benefits amount to reductions in ETI rates, mortality and hospital stay, and improvements in physiological variables such as ph and respiratory rate. 12,13,16,23 Arguably, many of the other benefits of NIV may be explained by the avoidance of invasive mechanical ventilation and its linked complications such as ventilator acquired pneumonia, pulmonary barotrauma and slow weaning. Moreover, the recovery period following mechanical ventilation may be associated with problems such as critical illness polyneuropathy, hospital acquired infection and nutritional deficiencies, all of which lead to subsequent longer periods of rehabilitation and convalescence. When NIV is used on general wards for hypercapnic exacerbations of COPD, these benefits appear to be extrapolated into real-life as supported by our own data. 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