Noninvasive ventilation practice patterns for acute respiratory failure in canadian tertiary care centres : A descriptive analysis

1Department of Medicine, Kingston General Hospital, Queen’s University, Kingston, Ontario; 2Department of Critical Care, Fraser Health and Division of Critical Care, University of British Columbia, Vancouver, British Columbia; 3Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, and Interdepartmental Division of Critical Care Medicine, University of Toronto; 4Interdepartmental Division of Critical Care Medicine, the Keenan Research Centre and the Li Ka Shing Knowledge Institute, St. Michael’s Hospital; 5Department of Medicine and Interdepartmental Division of Critical Care Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario; 6Department of Critical Care Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia; 7Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta; 8Lawrence S Bloomberg Faculty of Nursing, University of Toronto, Toronto, Ontario; 9Division of Critical Care Medicine, University of British Columbia, Vancouver, British Columbia; 10Department of Critical Care Medicine, University of Calgary, Calgary; 11Division of Critical Care Medicine, University of Alberta, Edmonton, Alberta Correspondence: Dr John Muscedere, Department of Medicine, Queens University, Kingston General Hospital, 76 Stuart Street, Kingston, Ontario K7L 2V7. Telephone 613-549-6666 ext 4642, e-mail muscedej@kgh.kari.net In the past two decades, there has been increased interest in the use of noninvasive ventilation (NIV) as a treatment for acute respiratory failure (1-3). NIV can provide ventilatory support with similar physiological benefits as invasive mechanical ventilation, including reduced work of breathing and improved gas exchange (4). NIV has advantages including the need for less sedation, reduced risk for ventilator-associated pneumonia, and shorter durations of ventilation and intensive care unit (ICU) stay (5). Consequently, the use of NIV has increased internationally (6) within ICUs, emergency departments (EDs) (7,8) and postanesthetic care units (9), as well as medical wards and palliative care units (10,11). However, the frequency of NIV use varies among sites and countries (1,2,12-17), and may be underutilized in some diagnoses (18). The quality of evidence supporting the use of NIV in various etiologies of acute respiratory failure varies. A recent Canadian clinical practice guideline (19) highlighted the varying strength of evidence to GC Digby, SP Keenan, CM Parker, et al. Noninvasive ventilation practice patterns for acute respiratory failure in Canadian tertiary care centres: A descriptive analysis. Can Respir J 2015;22(6):331-340.

support the use of NIV.Firm guidelines could not be proposed for the use of NIV in the setting of community-acquired pneumonia, chest trauma and immunosuppressed patients.
We hypothesized that there is significant practice variation among Canadian institutions in NIV use for acute respiratory failure.To evaluate this hypothesis, we conducted a multicentre, prospective study of NIV utilization in Canadian acute care settings.The primary objective of the present study was to describe practice variation in NIV use among participating Canadian hospitals.

METHODS
An interdisciplinary group of Canadian clinicians (respiratory therapists, intensivists and a registered nurse) (see Appendix 1 for participating institutions) was assembled.In addition, a standardized data collection form was developed and a respiratory therapist champion was identified at each site.All adult (>16 years of age) patients treated with NIV for acute respiratory failure of any etiology during a fourweek period at each hospital between February and August 2011 were included.Data were collected on patients located anywhere in the hospital: in the ED, ICU, coronary care unit (CCU ), high-acuity unit (HAU, including step-up or step-down units), ward (nonmonitored, defined as the lack of capacity for continuous electroencephalogram or oxygen saturation monitoring) or other.The timing of data collection periods varied among participating sites depending on local research ethics board approval processes and site capabilities.Approval was obtained from each local research ethics board; the need for informed consent was waived at each site.
The times and locations of NIV initiation and discontinuation were recorded.Also collected were data pertaining to patient characteristics, including age, sex, Glasgow Coma Scale (GCS) scores and arterial blood gas at the time of NIV initiation, goals of care (full code, do not resuscitate [DNR], no resuscitation in case of cardiac arrest, allowance for intubation), do not intubate [DNI], no intubation), indication for initiation of NIV (selected from a list of 17 indications), specialty of the physician ordering NIV (ED, ICU, respirology, other) and initial settings for NIV use.Patients were followed until NIV was discontinued and the reason for discontinuation was recorded (patient improvement, intubation or death), as well as survival status for the hospital admission.For patients with multiple NIV applications (ie, separate NIV initiations), only the index case was used in the analyses.
Data were entered into a central database REDCAP Version 3.3.0(20) by a single research coordinator.All analyses were performed using SAS version 9.3 (SAS Institute Inc, USA).Categorical variables are reported as counts and percentages, while continuous variables are reported as means and SDs.Continuous and categorical variables were analyzed using the Mann-Whitney and Fisher's exact tests, respectively.
Practice variation in NIV utilization was explored among sites by comparing the most common indications for NIV use; specialty of ordering physician; location of NIV initiation and discontinuation; NIV modes, interfaces and settings used; overall clinical outcomes including rates of intubation and hospital survival; and intubation and survival rates in patients with DNR and DNI orders.Between-site variation of specific NIV practices and outcomes were assessed using Fisher's exact test.NIV modes, interfaces, settings and clinical outcomes specific to DNR/DNI orders were not formally tested due to insufficient sample size.
Logistic regression analysis, with site as a random effect, was used to examine independent associations between intubation or mortality (in two separate multivariate models) and selected predictors.The following predictors were selected a priori based on investigator opinion: age, sex, GCS, pH, code status, pulmonary edema, chronic obstructive pulmonary disease (COPD), pneumonia, postextubation respiratory failure, site and location of NIV initiation.Patients with a code status of DNI were excluded from the intubation logistic regression analysis and only patients for whom intubation was a possible outcome were included.

Descriptive analysis
Patient and institutional characteristics: Eleven tertiary care universityaffiliated centres participated in the study.Institutional characteristics are presented in Table 1.A total of 337 NIV initiations were recorded; five patients received treatment with NIV on two separate occasions, and one received NIV on three separate occasions, resulting in 330 unique patients for analysis, with a mean (± SD) of 30.0±12.1 patients per centre (range 11 to 51 patients per centre).In the remainder of the analyses, only the 330 index NIV initiations were included.Patient characteristics are presented in Table 2. Most patients had a GCS of 15, while 21 (6.4%) had a GCS <10 and nine (2.7%) had a GCS <8.Resuscitation status was available for 319 (96.7%) patients, of which 225 (68.2%) were 'full code', 76 (23.0%) were DNR and 18 (5.4%)were DNI.Indication for NIV initiation: Of the 330 unique patients, 271 (82.1%) had a single indication for NIV initiation, 52 (15.8%) had two indications (eg, COPD and pneumonia) and three (0.9%) had three indications (eg, COPD, asthma and pulmonary edema).Pulmonary edema (n=104 [31.5%]) and COPD (n=99 [30.0%]) were the most common reasons for NIV initiation, followed by pneumonia (n=52 [15.8%]) and postextubation respiratory failure (n=30 [9.1%]) (Figure 1).The least commonly selected reasons for NIV use (≤6 patients per category) included altered level of consciousness, asthma, chronic alveolar hypoventilation, pleural effusion, pulmonary fibrosis, weaning and neuromuscular weakness; these categories were subsequently collapsed into one category termed 'miscellaneous' to simplify data reporting.'Other' was selected as the indication for NIV initiation for 23 (7.0%) patients, and the reasons listed included: obesity, rib fractures, sepsis, possible obstructive sleep apnea or was not indicated.
Significant variability (P<0.001)among sites was noted regarding the physician ordering NIV, with ED physicians ordering 9.1% to 62.5% of NIV initiations and respirologists ordering 0% to 25.6% of NIV initiations (Appendix 1).Also observed was significant variation (P<0.001)among sites in the location of NIV initiation with initiations on the wards ranging from 0% to 29.2% and, in HAUs, ranging from 0% to 25.5% (Appendix 1).Location of NIV discontinuation also varied significantly (P<0.001) according to site.NIV modes, interfaces and humidification: Bilevel noninvasive positive pressure ventilation (including pressure support ventilation) was the most common mode (305 patients [92.4%]) (Appendix 2).The mean expiratory positive airway pressure, positive end-expiratory pressure or continuous positive airway pressure was 8.6±11.8cmH 2 O, while the mean inspiratory (pressure support; above expiratory positive airway pressure/ positive end-expiratory pressure) was 10.4±5.5 cmH 2 O.Most patients (321 [97.3%]) used an oronasal or full-face interface (Appendix 3).Heated humidification was used for most patients (217 [65.8%]), a heat and moisture exchanger was used in only 14 (4.2%) and no humidification for 93 (28.2%) patients.

Clinical outcomes
Clinical outcomes according to site: Of the 328 patients for whom an intubation outcome was reported (310 of which were eligible for intubation based on code status), 69 (21.0%) were intubated (22.3% of patients eligible for intubation) (Figure 2).The number of patients who survived to hospital discharge was 239 (72.4%), while 90 died (27.4%); no data were available for one patient (0.3%).Although intubation rates varied among sites from 10.3% to 45.5%, the difference was not statistically significant (P=0.29).Mortality varied significantly among sites (P=0.006),ranging from 6.7% to 54.5% (Appendix 4).

Clinical outcomes according to indication for NIV initiation:
Intubation rates according to indication for NIV were: 15.9% for pulmonary edema, 15.7% for COPD, 30.8% for pneumonia and 26.7% for postextubation respiratory failure.Mortality rates according to indication were: 21.7% for pulmonary edema, 17.1% for COPD, 38.5% for pneumonia and 30.0%for postextubation respiratory failure.However, indication for NIV was not a significant predictor of either intubation or mortality (Appendixes 5 and 6).Clinical outcomes according to code status: Of 224 patients who were full code, 65 (29.0%) were intubated and 41 (18.3%) died.Of the patients who died, 18 (43.9%)had been intubated.Of 76 patients who were DNR, three (3.9%) were intubated and 36 (47.4%) died.Of 18 patients who were DNI, none were intubated and 10 (55.6%) died.Although all sites used NIV for DNR patients, only five sites used NIV for patients who were DNI.Outcomes for patients according to code status in are presented in Figure 3. NIV was used for palliation (ie, for comfort in a patient not expected to survive) in 18 (5.3%)patients, five of whom survived to hospital discharge.

Predictors of intubation and mortality:
In univariate analysis (Appendix 5), the patient characteristics that differed between intubated and nonintubated patients were age (older patients less likely to be intubated), GCS and DNR status.DNI patients were excluded because intubation was not a possible outcome for these patients and is confirmed by the fact that none of the DNI patients were intubated.In the multivariate model, the only independent predictor of intubation was DNR status.Patients with a DNR status were 0.11 (95% CI 0.03 to 0.37) times as likely to be intubated compared with patients with full code status (Appendix 7).
Nonsurvivors tended to be older with lower GCS and were more likely to have: DNR/DNI status, pneumonia, respiratory failure 'not otherwise specified', and to have NIV initiated in the ICU, CCU or HAU (Appendix 6).In multivariate analysis DNR/DNI status and NIV initiation in the ICU, CCU or HAU were independent predictors

DISCUSSION
In the present study, we found significant site variability among 11 Canadian tertiary care centres in indications for NIV, specialty of ordering physician, location of NIV initiation, level of pressure support at the time of NIV initiation and use of humidification.

Use of NIV and associated outcomes
There is strong evidence to support the use of NIV in COPD exacerbation (3,21,22) and cardiogenic pulmonary edema (3,(22)(23)(24)(25), and it has been suggested that NIV should be the first option for ventilatory support for patients with these diagnoses (19).In our study, COPD exacerbation and pulmonary edema were the two most common diagnoses for which NIV was initiated.We found that the use of NIV in patients with these indications was associated with relatively fewer intubations and lower mortality compared with other indications for NIV, though indication for NIV did not prove to be a significant variable in multivariate analysis.Rates of NIV failure requiring intubation or resulting in mortality were comparable to other reports (26).In particular, the higher rate of intubation in patients receiving NIV for respiratory failure secondary to pneumonia, compared with lower rates for pulmonary edema and COPD, is consistent with the lack of evidence in support of NIV use in this setting (19).The use of NIV for the indication of pneumonia, although not well supported by existing evidence, requires further investigation; possible reasons include lack of awareness of evidence, coexisting COPD or pulmonary edema, or temporization while other investigations were performed or response to therapy was assessed.
Growing evidence supports the use of NIV to facilitate weaning and extubation in patients with hypercapneic acute respiratory failure (27)(28)(29).There is also evidence for the use of NIV in improving respiratory outcomes postoperatively, including reduction in pulmonary morbidity, mortality, hypoxemia and length of stay (30)(31)(32)(33)(34)(35), for allowing early liberation from the ventilator (36), and for avoiding reintubation following planned extubation (37,38), although evidence for the latter is conflicting (39,40).We found that postextubation respiratory failure, postextubation support (extubation directly to NIV) and postoperative respiratory failure together accounted for approximately 16% of all NIV initiations, although significant variability among sites was observed.We found that NIV was used for indications such as community-acquired pneumonia, asthma and pulmonary fibrosis, for which there is no evidence to support its use.
As the indications for NIV have expanded, it has become a means of providing respiratory support to patients who are not candidates for intubation (41).Approximately 30% of the patients in our study had a code status of DNR (23.6%) or DNI (5.8%).This varies from the 44% of patients with a DNR or DNI code status in an American study of NIV practices by Ozsancak Ugurlu et al (26), with the majority of the difference attributed to a greater proportion of DNI patients (21.3%) in their study.Interestingly, in our study, fewer than one-half of the sites used NIV in patients that were DNI, indicating marked practice variation in use of NIV in patients with an alternative code status.Also of note was that only a very small percentage of DNR patients were intubated despite allowance for intubation with this code status.Finally, our finding that five of 18 patients for whom NIV was used for palliation survived to hospital discharge suggests that NIV may play a role in reversing respiratory failure in certain patients who are near the end of life.

Location of NIV initiation and prescribing physicians
NIV use has spread to areas outside of the ICU and is now more frequently seen in the ED (7,8) and postoperative recovery rooms (9), as   well as medical wards and palliative care units (10,11).Our study confirms the common use of NIV outside of the ICU setting across Canadian centres.In fact, not only was the ED the most common location for NIV initiation, it was the location for one-half of all NIV initiations and over one-third of NIV discontinuations.Even so, this trend was not observed at all sites, because NIV initiation in the ED occurred in <20% of cases at two sites.This variability was similarly observed in NIV prescribing practices of physicians across sites.While respirologists were less likely to be the initial prescriber of NIV in our study compared with a recent European survey ( 14), these differences can be attributed to organizational differences among regions, with respirologists in Europe less likely to work in ICUs and more likely to initiate NIV preventively on pulmonary wards and in different patient populations (14).Finally, HAU and wards represented the minority of sites for NIV use, and there was, once again, significant variability among sites.Together, these findings support the concept of a changing environment for NIV use with marked geographical variability (9)(10)(11).

NIV interfaces and settings
Consistent with the findings from other recent studies, the most common interface used in Canadian centres was overwhelmingly an oronasal (full-face) mask ( 14) and the most common mode of NIV was bilevel positive airway pressure (pressure support ventilation) ( 26), with only a few sites choosing continuous positive airway pressure as an initial mode.However, clinically relevant variation existed in NIV settings, particularly in initial inspiratory pressure and humidification of air, recognizing that inspiratory pressure, in particular, is likely to be titrated according to patient response and final inspiratory pressure settings were not analyzed.Our finding of heated humidification or heat moisture exchanger use in 70% of patients is slightly higher than that of a recent European analysis finding use in approximately 55% (14).These variations in practice among sites require further investigation and may, in part, be attributable to insufficient evidence to provide clear guidelines at this time (42).

Strengths and limitations
The present study had several strengths.Its multicentre and national scope enabled geographical comparisons in variability of NIV use that has not been previously demonstrated in Canada.The observational nature of the present study enabled it to proceed without patient consent, thereby minimizing inclusion bias.Furthermore, the prospective analysis of serial patients with no exclusion criteria, along with the use of a standardized data collection form, ensured that we collected data from a representative cohort.Finally, our well-defined a priori analyses ensure validity.
Our study had limitations.Notwithstanding the number of participating centres, the sample size is relatively small and limited to three provinces, with few patients per site.Because the present analysis was designed as a feasibility study, a four-week data collection period was arbitrarily chosen.However, data representing four weeks may not accurately represent local practices, and the variability in time of year studied (four weeks between February and August) may have led to perceived variation in frequency of presenting problems (eg, pneumonia) among centres.Although we found that mortality varied among centres, this should be interpreted cautiously because other factors, such as timing of data collection, severity of illness and small sample size, may account for this.We did not account for a measure of severity of illness in the model.Additionally, we only collected data from patients receiving NIV and, therefore, cannot comment on patients who were intubated without a trial of NIV.We are unable to assess whether there are patients who were not included in our data collection.Furthermore, there were multiple data collectors involved, and this may account for some of the variability in collected data.For example, it was common for more than one indication for NIV to be entered on the data collection form.Based on the number of 'other' diagnoses selected, the underlying diagnosis may not have always been clear to data collectors, and given that these were recorded at the time of NIV initiation, these may not reflect the final diagnosis.
In terms of generalizability of findings, our study involves a number of Canadian tertiary care academic centres from across the country; however, given recent data showing higher overall use of NIV in nonteaching hospitals ( 26), these results may not be representative of nonteaching hospitals and non-Canadian institutions.Furthermore, site comparison analysis may be affected by differing numbers of ICU beds and patients triaged, which was not taken into consideration and may limit generalizability of the data.

CONCLUSIONS
The present study demonstrates variability in NIV use among Canadian tertiary care centres.The reasons for this were not explored in the present study and may be due to a lack of knowledge of available evidence, lack of familiarity with existing clinical practice guidelines or a paucity of evidence in some diagnostic categories.Our findings need to be confirmed in a larger study with more diverse centres to explore reasons for variability.Further research is required to assess the impact of practice variation on outcomes and to guide quality improvement initiatives.

ACKNOWLEDGEMENTS:
Author contributions: SK, CP, TS, KB, SM, JR, DK, LR, MA, LB, CD and DE made contributions to research design, acquisition of data from participating institutions and revising the paper critically.GD, SK and JM substantially contributed to data analysis and interpretation, drafting of the paper and preparing revised versions for submission.We would also like to acknowledge the following RTs and research coordinators who assisted in data collection: Elizabeth Rohrs and Jason Zurba (Royal Columbian Hospital), Kory Klashinsky (Surrey Memorial Hospital), Kerri Porretta (St Michael's Hospital), Sandi Ellis and Brooke Thompson (Sunnybrook), Vagia Campbell and John Traill (Mount Sinai Hospital), Jennifer Barchard (Grey Nuns Hospital), Derry Thibealut (Kingston General Hospital), Patricia Thompson (Royal Alexandra Hospital), Lynda Lazosky (St Paul's Hospital), Renee Sholes, Kristopher Jolin (Peter Lougheed/Foot Hills), and Corrie Irwin and Denis Foster (Vancouver General Hospital).

FUNDING:
Funding included an unrestricted grant from Philips/ Respironics to support clinical practice guideline development with this study representing the first step toward a guideline implementation project to establish baseline utilization.Philips/Respironics had no role in the design or conduct of the study, nor in the interpretation of the results or preparation of the manuscript.

8 )
Data presented as n (%), presented as percentage of patients with a given indication for NIV.The percentages may not add to 100% because only the four most common indications are presented and some patients may have more than one indication.The overall P value comparing the distribution of indication by site using only the first indication per patient yielded a Fisher's exact test of <0.001.COPD Chronic obstructive pulmonary disease; RF Respiratory failure

Figure 3 )
Figure 3) Clinical outcomes according to code status.DNR Do not resuscitate; DNI Do not intubate

TABLe 1 institutional characteristics Site unique study patients NiV events* Total acute beds Critical care beds High acuity unit beds Cardiac critical care beds
Data presented as n unless otherwise specified.Data *Only index noninvasive ventilation (NIV) event is included in subsequent analysisFigure 1) Although only index noninvasive ventilation (NIV) initiations are reported in the bar graph and corresponding counts, the total number of indications (n=384) is higher than the number of patients (n=330) because some patients had multiple indications for their index NIV initiation.The asterisks denote the seven NIV re-initiations that have been excluded from the analysis.COPD Chronic obstructive pulmonary disease; Misc Miscellaneous (least commonly selected categories, including altered level of consciousness, asthma, chronic alveolar hypoventilation, pleural effusion, pulmonary fibrosis, weaning and neuromuscular weakness); NOS Not otherwise specified; Other Selected category by respiratory therapists with reasons listed including: obesity, rib fractures, sepsis, possible obstructive sleep apnea or was otherwise not indicated; RF Respiratory failure presented as mean ± SD or n (%).Only data for unique patientsare presented (n=330) as acquired at time of noninvasive ventilation initiation.*58.7% of patients had a Glasgow Coma Scale score of 15.HCO 3 Bicarbonate; PaCO 2 Partial pressure of carbon dioxide; PaO 2 Partial pressure of oxygen of mortality after adjusting for age, sex, pH, GCS, pulmonary edema, COPD, pneumonia, post-extubation respiratory failure and site (Appendix 8).

NiV) interface and humidification according to site
Data presented as n (%).HME Heat moisture exchanger Data presented as n (%) or mean ± SD.BiPAP Bilevel positive airway pressure; CCU Cardiac care unit; HAU High acuity unit; ICU Intensive care unit; NIV Noninvasive ventilation; NOS Not otherwise specified; PaCO 2 Partial pressure of carbon dioxide; PaO 2 Partial pressure of oxygen; PSV Pressure support ventilation Data presented as n (%) unless otherwise specified.BiPAP Bilevel positive airway pressure; CCU Cardiac care unit; ICU Intensive care unit; NIV Noninvasive ventilation; NOS Not otherwise specified; PaCO 2 Partial pressure of carbon dioxide; PaO 2 Partial pressure of oxygen; PSV Pressure support ventilation; Resp Respirology