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ORIGINAL ARTICLE
Is non-invasive ventilation safe in acute severe asthma? MICHAEL PALLIN, MARK HEW AND MATTHEW T. NAUGHTON Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, Victoria, Australia
ABSTRACT Background and objective: The effect of non-invasive ventilation (NIV) in acute severe asthma is unclear and there are concerns regarding its safety. Methods: We undertook a 5-year case–control review of mortality and morbidity associated with NIV use in acute severe asthma and compared this with asthma requiring invasive mechanical ventilation (IMV) and a control group with less severe asthma without ventilatory support. Results: Eight hundred seventy-three patients had acute severe asthma of whom 30 were treated with NIV, 17 with IMV and 90 served as controls. The mean duration of NIV was 9.5 ± 7.3 h with inspiratory positive airway pressure and expiratory positive airway pressure of 11.9 ± 1.4 and 5.8 ± 1.2 cmH2O respectively. Mortality was zero in the NIV and control groups, compared with 41% in the IMV group. None of the NIV or control groups required escalation to invasive ventilation. There were no instances of haemodynamic compromise in the NIV or control groups. Length of hospital stay was 121 ± 96 h in the NIV group and similar to the severe IMV group (136 ± 99 h, P > 0.05) and significantly longer than the control group (42 ± 40 h, P < 0.05). Conclusions: NIV can be safely used in acute severe asthma although further work is needed to delineate the precise patient selection process. Key words: asthma, mechanical ventilation, morbidity, mortality, non-invasive ventilation. Abbreviations: COPD, chronic obstructive pulmonary disease; EPAP, expiratory positive airway pressure; IMV, invasive mechanical ventilation; IPAP, inspiratory positive airway pressure; NIV, non-invasive ventilation; PEEP, positive end-expiratory pressure.
INTRODUCTION Although mortality rates due to asthma have declined over the past 3 decades1 with improved medical manCorrespondence: Michael Pallin, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Post Office box 315, Prahran, Vic. 3181, Australia. Email: pallinm@ gmail.com Received 18 July 2014; invited to revise 30 August 2014; revised 10 September 2014; accepted 11 September 2014 (Associate Editor: Amanda Piper). © 2014 Asian Pacific Society of Respirology
SUMMARY AT A GLANCE The role of non-invasive ventilation in acute asthma is not well described and there are concerns about its safety. Over a 5-year period, noninvasive ventilation was used without significant complications in patients with moderate acute severe asthma.
agement,2,3 asthma still causes 1 in every 250 deaths.4 Acute exacerbations of asthma requiring hospital admission are associated with a mortality of between 0.4% and 0.9%.5,6 However, in the setting of a severe exacerbation necessitating intensive care unit admission, often with invasive mechanical ventilation (IMV), mortality may approach 10%.2 Despite standard care in the management of acute asthma,7 some patients fail to improve and require endotracheal intubation for IMV. Although lifesaving in dire circumstances, IMV should also be used with caution, as it is associated with significant complications in asthmatics. Mortality is estimated to be three times as high in those patients receiving IMV compared with non-ventilated asthmatics;8 barotrauma occurs in 2–6% of patients;9,10 ventilator-associated pneumonia may occur as often as 7%;9,10 generalized, including respiratory muscle weakness occurs in up to 13% of patients9 and intensive care unit/hospital length of stay is also prolonged in those who receive IMV during an acute asthma presentation.8–10 Non-invasive ventilation (NIV) has proven benefits in preventing IMV in acute exacerbations of chronic obstructive pulmonary disease (COPD), acute pulmonary oedema and pulmonary infiltrates in immunocompromised patients, as well as the weaning of extubated COPD patients.11 There is also a good physiological basis to support the use of NIV in acute asthma;12 however, its use in the routine hospital setting remains somewhat controversial. Several single-centre studies have shown benefits in several physiological parameters.13–18 However, there are no large randomized controlled trials of NIV use in acute severe asthma with meaningful clinical outcomes such as treatment failure necessitating escalation to IMV, or mortality.12 Concern also exists regarding the possibility of barotrauma or haemodynamic Respirology (2014) doi: 10.1111/resp.12428
2 compromise secondary to runaway increases in dynamic hyperinflation that may be seen with the use of externally applied positive end-expiratory pressure (PEEP).19 The aims of the current study were to describe the experience of NIV utilization in the setting of acute severe asthma. In particular, we aimed to characterize our patient cohort, describe NIV use and evaluate relevant outcomes, including endotracheal intubation for IMV, morbidity and mortality over a 5-year period.
METHODS Data source and patient cohort The Alfred Hospital is a 450-bed tertiary metropolitan hospital serving a population of approximately 750 000 people. It sees 25 000 patients through its emergency department annually and has greater than 20 years experience in delivering acute and long-term NIV. The Alfred Health Information Service database was used to search for hospital admissions of >24 h duration where asthma was the principal diagnosis over a 5-year period between 1 July 2008 and 30 June 2013. Patient data were retrieved from the Alfred Hospital’s electronic medical records. Subjects were included in the analysis if they were ≥18 years with a pre-existing diagnosis of asthma. A diagnosis of asthma was considered to be established if the patient had attended the respiratory clinic in the Alfred Hospital and had a diagnosis of asthma made with complimentary spirometry studies, or if a diagnosis had been made with treatment implemented by a medical practitioner. Subjects were excluded from the analysis if there was significant coexistent illness contributing to the initial presentation, or if NIV or continuous positive airway pressure was used for co-existent chronic conditions. Patients were stratified according to whether they required ventilatory support, either NIV or IMV. In addition, each of the NIV patients were matched to three asthmatic controls who did not require ventilatory support, matched for age, gender and body mass index (BMI). The study received ethical approval from the Alfred Health Office of Ethics and Research Governance (Project Number: 38/14). Baseline measurements Patient demographics included age, gender, BMI, smoking status and co-morbid medical conditions. Spirometry measurements were recorded, if available, during disease stability within 1 year of hospital admission, either before or after the acute presentation, depending on availability. Physiological variables, including respiratory rate, objective work of breathing assessment (based on ability to speak in words, phrases or full sentences), heart rate (HR) and blood pressure (BP) immediately prior to initiation of NIV or IMV were recorded. For patients who did not receive ventilatory support, these variables were selected at the point of highest documented respiratory rate. Arterial blood gas (ABG) values were recorded. The ABG samples used for analysis were those taken before and closest to the point of NIV impleRespirology (2014)
M Pallin et al.
mentation, or during the initial emergency department work-up of those who did not require NIV support. ABGs were interpreted using the Copenhagen approach.20 The data pertaining to NIV use included the setting of NIV implementation, mode of NIV utilized, maximum pressures employed, and duration of NIV therapy.
Non-invasive ventilation The decision to commence NIV was based on the presence of increased work of breathing and/or respiratory acidosis, and was at the discretion of the senior treating physician. Treatment was either commenced in the emergency department or in the intensive care unit by experienced staff. The routine practice at our institution is to commence NIV using conservative inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP) (typically IPAP of 10–12 cmH2O and EPAP of 4–6 cmH2O). NIV was delivered via the BiPAP Vision or Synchrony (Philips Respironics Inc, Murrysville, PA, USA). Pressure support was then titrated as required to achieve clinically noticeable improvement in respiratory rate and/or PaCO2. Increases in EPAP were considered if upper airway collapse or difficulties in oxygenation persisted; however, caution was exercised due to concerns regarding further uncontrolled increases in end-expiratory lung volume with higher levels. The decision to discontinue NIV was again made at the discretion of the senior treating physician based on improvement in the patient’s clinical condition, the development of NIV-related complications or if the mode of treatment was not suitably tolerated. Outcome measures Primary outcomes evaluated were death and necessity to escalate to IMV. Secondary outcomes evaluated were length of stay (both intensive care unit and hospital) and instances of NIV-induced cardiovascular compromise or barotrauma. Cardiovascular compromise was considered to have occurred if a fall in blood pressure during NIV implementation had necessitated discontinuation of NIV or the initiation of vasoactive medication. Statistical analysis Comparisons of baseline patient characteristics and outcomes were made using one-way analysis of variance with multiple comparisons for continuous variables, and Fisher’s exact test for categorical data. This analysis was performed on data from all three groups (non-ventilated, NIV and IMV). Comparisons of physiological variables and acid–base status were made between the no ventilation group and the NIV group using the two-tailed t-test for continuous variables and Fisher’s exact test for categorical variables. Continuous variables are presented as mean ± standard deviation and categorical variables are summarized as percentages. Analysis was performed using Graphpad Prism version 6.0d (GraphPad Software, Inc., La Jolla, CA, USA). © 2014 Asian Pacific Society of Respirology
3
Non-invasive ventilation in acute asthma Table 1 Patient characteristics
Age (years) BMI (kg/m2) Female Current smoker
Control (n = 90)
NIV (n = 30)
40.7 (18.2) 27.5 (7.2) 54 (60) 20 (22.2)
36.5 (14.5) 28.4 (5.5) 20 (66.7) 9 (30)
IMV (n = 17) 39.5 (14.8) 31.6 (6.3) 7 (41.2) 10 (58.8)*
Spirometry
FEV1 (%-predicted) FEV1 (L)
n = 47 (52.2%)
n = 20 (66.7%)
75.6 (21.0) 2.25 (0.84)
80.0 (19.4) 2.56 (0.85)
n = 6 (35.3%) 81.7 (18.2) 2.94 (0.89)
Comorbidities Other respiratory Gastrointestinal Endocrine Cardiovascular Oncological Rheumatologic Neurological Haematological Psychiatric Recreational drug use
4 (4.4) 8 (8.9) 11 (12.2) 10 (11.1) 3 (3.3) 13 (14.4) 3 (3.3) 1 (1.1) 10 (11.1) 4 (4.4)
2 (6.7) 0 5 (16.7) 2 (6.7) 0 0** 0 0 9 (30.0)** 3 (10.0)
0 0 3 (17.6) 1 (5.9) 1 (5.9) 0 1 (5.9) 1 (5.9) 4 (23.5) 5 (29.4)*
* P < 0.05 for comparisons between no ventilation and IMV groups; ** P < 0.05 for comparisons between control and NIV groups. Continuous variables presented as means (SD) and categorical variables presented as numbers (percentage of whole). FEV1, forced expiratory volume in 1 s; IMV, invasive mechanical ventilation; NIV, non-invasive ventilation.
RESULTS Over the 5-year period studied, there were 1501 asthmatic patients admitted to the hospital, for whom asthma was the primary diagnosis in 873 individuals needing admission for >24 h. Of this cohort, 30 patients were identified in whom NIV was used in the management of acute asthma. In addition, there were 17 patients with acute asthma requiring IMV. Baseline characteristics of the three groups are displayed in Table 1 and data relating to NIV implementation is presented in Table 2. The majority of patients managed with IMV (15 of 17) had experienced a cardiorespiratory arrest in the community, and were intubated by paramedics at the scene. As a consequence, there is a lack of relevant physiological and acid–base data available prior to IMV, and comparisons of these variables have thus been limited to the control and NIV group. Table 3 summarizes the physiological variables observed immediately before NIV commencement or at highest documented respiratory rate for the control group. Those who required acute management with NIV demonstrated greater work of breathing as evidenced by a significantly higher respiratory rate and percentage of patients who were able to speak in words only. Patients requiring NIV had significantly higher systolic blood pressure, diastolic blood pressure and heart rate immediately prior to NIV commencement than the control group. Acid–base status during the acute presentation is presented in Table 4. There was greater acid–base © 2014 Asian Pacific Society of Respirology
Table 2
NIV implementation data
Setting of initial NIV implementation Emergency Department Intensive Care Unit Respiratory Ward Setting of NIV utilization throughout hospital stay Emergency Department Intensive Care Unit Respiratory Ward Mode utilized BPAP CPAP Maximum BPAP pressures utilized IPAP (cmH2O) EPAP (cmH2O) NIV Duration (Hours)
24 (80) 5 (16.7) 1 (3.3)
24 (80) 15 (50) 5 (16.7) 30 (100) 3 (10) 11.9 (1.4) 5.8 (1.2) 9.46 (7.33)
Continuous variables presented as means (SD) and categorical variables presented as numbers (percentage of whole). BPAP, bilevel positive airway pressure; CPAP, continuous positive airway pressure; EPAP, expiratory positive airway pressure; IPAP, inspiratory positive airway pressure.
derangement in the patients requiring NIV, which was manifest by more frequent metabolic acidosis without full respiratory compensation, and acute respiratory acidosis. Table 5 illustrates observed changes in physiological parameters following commencement of NIV. Respirology (2014)
4
M Pallin et al.
Table 3
Physiological variables and work of breathing assessment
Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Heart rate (bpm) Respiratory rate (brpm)
Control (n = 90)
NIV (n = 30)
133.9 (17.1) 75.2 (12.9) 102.9 (23.6) 23.5 (5.2)
155.9 (22.1)*** 82.6 (17.4)* 119.8 (15.9)** 33.0 (9.4)***
Work of breathing assessment n = 73 (81.1%) Speaks in words Speaks in phrases Speaks in full sentences
n = 18 (60%)
6 (8.2) 17 (23.3) 50 (68.5)
9 (50.0)** 8 (44.4) 1 (5.6)***
For comparisons between no ventilation and NIV groups, * P < 0.05, ** P < 0.001 and *** P < 0.0001. Continuous variables presented as means (SD) and categorical variables presented as numbers (percentage of whole). NIV, non-invasive ventilation.
Table 4
Acid-base status Control (n = 90)
Arterial blood gas available pH PaCO2 (mm Hg) PaO2 (mm Hg) Bicarbonate (mmol/L)
31 (34.4) 7.441 (0.051) 34.0 (6.6) 96.1 (43.3) 22.3 (4.1)
NIV (n = 30) 29 (96.7)*** 7.365 (0.057) 39.14 (10.6)* 138.3 (82.1)* 21.5 (4.1)
Arterial blood gas interpretation Normal Respiratory alkalosis Fully compensated respiratory acidosis Fully compensated metabolic acidosis Partially compensated metabolic acidosis Acute respiratory acidosis
13 (41.9) 2 (6.5) 1 (3.2)
3 (10.3)* 0 0
11 (35.5)
5 (17.2)
3 (9.7)
11 (37.9)*
1 (3.2)
10 (34.5)*
For comparisons between no ventilation and NIV groups, * P < 0.05 and *** P < 0.0001. Arterial blood gas values either immediately prior to NIV commencement or during initial assessment if not requiring ventilator support. Continuous variables presented as means (SD) and categorical variables presented as numbers (percentage of whole). NIV, non-invasive ventilation.
Significant decreases in systolic and diastolic blood pressure were observed shortly after NIV initiation with a concomitant reduction in respiratory rate and heart rate. During the course of the period studied, there were no deaths in either the control or NIV groups (Table 6). There were no instances where escalation from NIV to IMV was necessary. There were also no episodes of barotrauma or haemodynamic instability while receiving NIV. Patients who received NIV, as Respirology (2014)
expected, were admitted to the intensive care unit with significantly greater frequency and required longer hospital admissions than the control group.
DISCUSSION During the study period, patients who received NIV had two key characteristics. Firstly, they were relatively young with a near-normal FEV1 at baseline, consistent with classic reversible airflow obstruction. Secondly, they presented with increased work of breathing and significant acid–base disturbance, consistent with a severe acute asthma attack. In patients with these characteristics, NIV was utilized safely in the emergency department and the intensive care unit without any deaths or instances requiring escalation to IMV. Reassuringly there were no complications related to NIV implementation, specifically haemodynamic compromise or pulmonary barotrauma. Length of hospital stay was longer in those patients who required NIV than controls; however, this is not surprising given that they represented a more severe cohort at acute presentation. NIV likely provides physiological support in acute asthma by several different mechanisms. Firstly, the use of EPAP helps offset intrinsic PEEP generated as a consequence of dynamic hyperinflation. This means that smaller negative changes in intra-pleural pressure are required to initiate air movement from the central to distal airways and work of breathing therefore improves.21 Secondly, the application of EPAP has a direct bronchodilation effect on the airways that reduces resistance and facilitates improved expiratory airflow.17,22 Thirdly, ventilation–perfusion relationships can be improved using EPAP by recruiting lung units that have become obstructed due to airway secretions or through assisting in the clearance of distal secretions by aiding the collateral ventilation of obstructed units.23 Fourthly, the use of pressure support or IPAP augments tidal volume and further reduces work of breathing.24 Lastly, NIV may maximize the effects of nebulized bronchodilator medica© 2014 Asian Pacific Society of Respirology
5
Non-invasive ventilation in acute asthma Table 5 Physiological variables before and during NIV treatment
Respiratory rate (brpm) SBP (mm Hg) DBP (mm Hg) HR (bpm)
Prior to commencing NIV
Minimum reading during NIV treatment
P value
Time to minimum (h)
33.0 (9.4) 155.9 (22.1) 82.6 (17.4) 119.8 (15.9)
22.1 (8.5) 128.4 (14.9) 67.9 (13.2) 97.6 (18.8)
ORIGINAL ARTICLE
Is non-invasive ventilation safe in acute severe asthma? MICHAEL PALLIN, MARK HEW AND MATTHEW T. NAUGHTON Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, Victoria, Australia
ABSTRACT Background and objective: The effect of non-invasive ventilation (NIV) in acute severe asthma is unclear and there are concerns regarding its safety. Methods: We undertook a 5-year case–control review of mortality and morbidity associated with NIV use in acute severe asthma and compared this with asthma requiring invasive mechanical ventilation (IMV) and a control group with less severe asthma without ventilatory support. Results: Eight hundred seventy-three patients had acute severe asthma of whom 30 were treated with NIV, 17 with IMV and 90 served as controls. The mean duration of NIV was 9.5 ± 7.3 h with inspiratory positive airway pressure and expiratory positive airway pressure of 11.9 ± 1.4 and 5.8 ± 1.2 cmH2O respectively. Mortality was zero in the NIV and control groups, compared with 41% in the IMV group. None of the NIV or control groups required escalation to invasive ventilation. There were no instances of haemodynamic compromise in the NIV or control groups. Length of hospital stay was 121 ± 96 h in the NIV group and similar to the severe IMV group (136 ± 99 h, P > 0.05) and significantly longer than the control group (42 ± 40 h, P < 0.05). Conclusions: NIV can be safely used in acute severe asthma although further work is needed to delineate the precise patient selection process. Key words: asthma, mechanical ventilation, morbidity, mortality, non-invasive ventilation. Abbreviations: COPD, chronic obstructive pulmonary disease; EPAP, expiratory positive airway pressure; IMV, invasive mechanical ventilation; IPAP, inspiratory positive airway pressure; NIV, non-invasive ventilation; PEEP, positive end-expiratory pressure.
INTRODUCTION Although mortality rates due to asthma have declined over the past 3 decades1 with improved medical manCorrespondence: Michael Pallin, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Post Office box 315, Prahran, Vic. 3181, Australia. Email: pallinm@ gmail.com Received 18 July 2014; invited to revise 30 August 2014; revised 10 September 2014; accepted 11 September 2014 (Associate Editor: Amanda Piper). © 2014 Asian Pacific Society of Respirology
SUMMARY AT A GLANCE The role of non-invasive ventilation in acute asthma is not well described and there are concerns about its safety. Over a 5-year period, noninvasive ventilation was used without significant complications in patients with moderate acute severe asthma.
agement,2,3 asthma still causes 1 in every 250 deaths.4 Acute exacerbations of asthma requiring hospital admission are associated with a mortality of between 0.4% and 0.9%.5,6 However, in the setting of a severe exacerbation necessitating intensive care unit admission, often with invasive mechanical ventilation (IMV), mortality may approach 10%.2 Despite standard care in the management of acute asthma,7 some patients fail to improve and require endotracheal intubation for IMV. Although lifesaving in dire circumstances, IMV should also be used with caution, as it is associated with significant complications in asthmatics. Mortality is estimated to be three times as high in those patients receiving IMV compared with non-ventilated asthmatics;8 barotrauma occurs in 2–6% of patients;9,10 ventilator-associated pneumonia may occur as often as 7%;9,10 generalized, including respiratory muscle weakness occurs in up to 13% of patients9 and intensive care unit/hospital length of stay is also prolonged in those who receive IMV during an acute asthma presentation.8–10 Non-invasive ventilation (NIV) has proven benefits in preventing IMV in acute exacerbations of chronic obstructive pulmonary disease (COPD), acute pulmonary oedema and pulmonary infiltrates in immunocompromised patients, as well as the weaning of extubated COPD patients.11 There is also a good physiological basis to support the use of NIV in acute asthma;12 however, its use in the routine hospital setting remains somewhat controversial. Several single-centre studies have shown benefits in several physiological parameters.13–18 However, there are no large randomized controlled trials of NIV use in acute severe asthma with meaningful clinical outcomes such as treatment failure necessitating escalation to IMV, or mortality.12 Concern also exists regarding the possibility of barotrauma or haemodynamic Respirology (2014) doi: 10.1111/resp.12428
2 compromise secondary to runaway increases in dynamic hyperinflation that may be seen with the use of externally applied positive end-expiratory pressure (PEEP).19 The aims of the current study were to describe the experience of NIV utilization in the setting of acute severe asthma. In particular, we aimed to characterize our patient cohort, describe NIV use and evaluate relevant outcomes, including endotracheal intubation for IMV, morbidity and mortality over a 5-year period.
METHODS Data source and patient cohort The Alfred Hospital is a 450-bed tertiary metropolitan hospital serving a population of approximately 750 000 people. It sees 25 000 patients through its emergency department annually and has greater than 20 years experience in delivering acute and long-term NIV. The Alfred Health Information Service database was used to search for hospital admissions of >24 h duration where asthma was the principal diagnosis over a 5-year period between 1 July 2008 and 30 June 2013. Patient data were retrieved from the Alfred Hospital’s electronic medical records. Subjects were included in the analysis if they were ≥18 years with a pre-existing diagnosis of asthma. A diagnosis of asthma was considered to be established if the patient had attended the respiratory clinic in the Alfred Hospital and had a diagnosis of asthma made with complimentary spirometry studies, or if a diagnosis had been made with treatment implemented by a medical practitioner. Subjects were excluded from the analysis if there was significant coexistent illness contributing to the initial presentation, or if NIV or continuous positive airway pressure was used for co-existent chronic conditions. Patients were stratified according to whether they required ventilatory support, either NIV or IMV. In addition, each of the NIV patients were matched to three asthmatic controls who did not require ventilatory support, matched for age, gender and body mass index (BMI). The study received ethical approval from the Alfred Health Office of Ethics and Research Governance (Project Number: 38/14). Baseline measurements Patient demographics included age, gender, BMI, smoking status and co-morbid medical conditions. Spirometry measurements were recorded, if available, during disease stability within 1 year of hospital admission, either before or after the acute presentation, depending on availability. Physiological variables, including respiratory rate, objective work of breathing assessment (based on ability to speak in words, phrases or full sentences), heart rate (HR) and blood pressure (BP) immediately prior to initiation of NIV or IMV were recorded. For patients who did not receive ventilatory support, these variables were selected at the point of highest documented respiratory rate. Arterial blood gas (ABG) values were recorded. The ABG samples used for analysis were those taken before and closest to the point of NIV impleRespirology (2014)
M Pallin et al.
mentation, or during the initial emergency department work-up of those who did not require NIV support. ABGs were interpreted using the Copenhagen approach.20 The data pertaining to NIV use included the setting of NIV implementation, mode of NIV utilized, maximum pressures employed, and duration of NIV therapy.
Non-invasive ventilation The decision to commence NIV was based on the presence of increased work of breathing and/or respiratory acidosis, and was at the discretion of the senior treating physician. Treatment was either commenced in the emergency department or in the intensive care unit by experienced staff. The routine practice at our institution is to commence NIV using conservative inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP) (typically IPAP of 10–12 cmH2O and EPAP of 4–6 cmH2O). NIV was delivered via the BiPAP Vision or Synchrony (Philips Respironics Inc, Murrysville, PA, USA). Pressure support was then titrated as required to achieve clinically noticeable improvement in respiratory rate and/or PaCO2. Increases in EPAP were considered if upper airway collapse or difficulties in oxygenation persisted; however, caution was exercised due to concerns regarding further uncontrolled increases in end-expiratory lung volume with higher levels. The decision to discontinue NIV was again made at the discretion of the senior treating physician based on improvement in the patient’s clinical condition, the development of NIV-related complications or if the mode of treatment was not suitably tolerated. Outcome measures Primary outcomes evaluated were death and necessity to escalate to IMV. Secondary outcomes evaluated were length of stay (both intensive care unit and hospital) and instances of NIV-induced cardiovascular compromise or barotrauma. Cardiovascular compromise was considered to have occurred if a fall in blood pressure during NIV implementation had necessitated discontinuation of NIV or the initiation of vasoactive medication. Statistical analysis Comparisons of baseline patient characteristics and outcomes were made using one-way analysis of variance with multiple comparisons for continuous variables, and Fisher’s exact test for categorical data. This analysis was performed on data from all three groups (non-ventilated, NIV and IMV). Comparisons of physiological variables and acid–base status were made between the no ventilation group and the NIV group using the two-tailed t-test for continuous variables and Fisher’s exact test for categorical variables. Continuous variables are presented as mean ± standard deviation and categorical variables are summarized as percentages. Analysis was performed using Graphpad Prism version 6.0d (GraphPad Software, Inc., La Jolla, CA, USA). © 2014 Asian Pacific Society of Respirology
3
Non-invasive ventilation in acute asthma Table 1 Patient characteristics
Age (years) BMI (kg/m2) Female Current smoker
Control (n = 90)
NIV (n = 30)
40.7 (18.2) 27.5 (7.2) 54 (60) 20 (22.2)
36.5 (14.5) 28.4 (5.5) 20 (66.7) 9 (30)
IMV (n = 17) 39.5 (14.8) 31.6 (6.3) 7 (41.2) 10 (58.8)*
Spirometry
FEV1 (%-predicted) FEV1 (L)
n = 47 (52.2%)
n = 20 (66.7%)
75.6 (21.0) 2.25 (0.84)
80.0 (19.4) 2.56 (0.85)
n = 6 (35.3%) 81.7 (18.2) 2.94 (0.89)
Comorbidities Other respiratory Gastrointestinal Endocrine Cardiovascular Oncological Rheumatologic Neurological Haematological Psychiatric Recreational drug use
4 (4.4) 8 (8.9) 11 (12.2) 10 (11.1) 3 (3.3) 13 (14.4) 3 (3.3) 1 (1.1) 10 (11.1) 4 (4.4)
2 (6.7) 0 5 (16.7) 2 (6.7) 0 0** 0 0 9 (30.0)** 3 (10.0)
0 0 3 (17.6) 1 (5.9) 1 (5.9) 0 1 (5.9) 1 (5.9) 4 (23.5) 5 (29.4)*
* P < 0.05 for comparisons between no ventilation and IMV groups; ** P < 0.05 for comparisons between control and NIV groups. Continuous variables presented as means (SD) and categorical variables presented as numbers (percentage of whole). FEV1, forced expiratory volume in 1 s; IMV, invasive mechanical ventilation; NIV, non-invasive ventilation.
RESULTS Over the 5-year period studied, there were 1501 asthmatic patients admitted to the hospital, for whom asthma was the primary diagnosis in 873 individuals needing admission for >24 h. Of this cohort, 30 patients were identified in whom NIV was used in the management of acute asthma. In addition, there were 17 patients with acute asthma requiring IMV. Baseline characteristics of the three groups are displayed in Table 1 and data relating to NIV implementation is presented in Table 2. The majority of patients managed with IMV (15 of 17) had experienced a cardiorespiratory arrest in the community, and were intubated by paramedics at the scene. As a consequence, there is a lack of relevant physiological and acid–base data available prior to IMV, and comparisons of these variables have thus been limited to the control and NIV group. Table 3 summarizes the physiological variables observed immediately before NIV commencement or at highest documented respiratory rate for the control group. Those who required acute management with NIV demonstrated greater work of breathing as evidenced by a significantly higher respiratory rate and percentage of patients who were able to speak in words only. Patients requiring NIV had significantly higher systolic blood pressure, diastolic blood pressure and heart rate immediately prior to NIV commencement than the control group. Acid–base status during the acute presentation is presented in Table 4. There was greater acid–base © 2014 Asian Pacific Society of Respirology
Table 2
NIV implementation data
Setting of initial NIV implementation Emergency Department Intensive Care Unit Respiratory Ward Setting of NIV utilization throughout hospital stay Emergency Department Intensive Care Unit Respiratory Ward Mode utilized BPAP CPAP Maximum BPAP pressures utilized IPAP (cmH2O) EPAP (cmH2O) NIV Duration (Hours)
24 (80) 5 (16.7) 1 (3.3)
24 (80) 15 (50) 5 (16.7) 30 (100) 3 (10) 11.9 (1.4) 5.8 (1.2) 9.46 (7.33)
Continuous variables presented as means (SD) and categorical variables presented as numbers (percentage of whole). BPAP, bilevel positive airway pressure; CPAP, continuous positive airway pressure; EPAP, expiratory positive airway pressure; IPAP, inspiratory positive airway pressure.
derangement in the patients requiring NIV, which was manifest by more frequent metabolic acidosis without full respiratory compensation, and acute respiratory acidosis. Table 5 illustrates observed changes in physiological parameters following commencement of NIV. Respirology (2014)
4
M Pallin et al.
Table 3
Physiological variables and work of breathing assessment
Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Heart rate (bpm) Respiratory rate (brpm)
Control (n = 90)
NIV (n = 30)
133.9 (17.1) 75.2 (12.9) 102.9 (23.6) 23.5 (5.2)
155.9 (22.1)*** 82.6 (17.4)* 119.8 (15.9)** 33.0 (9.4)***
Work of breathing assessment n = 73 (81.1%) Speaks in words Speaks in phrases Speaks in full sentences
n = 18 (60%)
6 (8.2) 17 (23.3) 50 (68.5)
9 (50.0)** 8 (44.4) 1 (5.6)***
For comparisons between no ventilation and NIV groups, * P < 0.05, ** P < 0.001 and *** P < 0.0001. Continuous variables presented as means (SD) and categorical variables presented as numbers (percentage of whole). NIV, non-invasive ventilation.
Table 4
Acid-base status Control (n = 90)
Arterial blood gas available pH PaCO2 (mm Hg) PaO2 (mm Hg) Bicarbonate (mmol/L)
31 (34.4) 7.441 (0.051) 34.0 (6.6) 96.1 (43.3) 22.3 (4.1)
NIV (n = 30) 29 (96.7)*** 7.365 (0.057) 39.14 (10.6)* 138.3 (82.1)* 21.5 (4.1)
Arterial blood gas interpretation Normal Respiratory alkalosis Fully compensated respiratory acidosis Fully compensated metabolic acidosis Partially compensated metabolic acidosis Acute respiratory acidosis
13 (41.9) 2 (6.5) 1 (3.2)
3 (10.3)* 0 0
11 (35.5)
5 (17.2)
3 (9.7)
11 (37.9)*
1 (3.2)
10 (34.5)*
For comparisons between no ventilation and NIV groups, * P < 0.05 and *** P < 0.0001. Arterial blood gas values either immediately prior to NIV commencement or during initial assessment if not requiring ventilator support. Continuous variables presented as means (SD) and categorical variables presented as numbers (percentage of whole). NIV, non-invasive ventilation.
Significant decreases in systolic and diastolic blood pressure were observed shortly after NIV initiation with a concomitant reduction in respiratory rate and heart rate. During the course of the period studied, there were no deaths in either the control or NIV groups (Table 6). There were no instances where escalation from NIV to IMV was necessary. There were also no episodes of barotrauma or haemodynamic instability while receiving NIV. Patients who received NIV, as Respirology (2014)
expected, were admitted to the intensive care unit with significantly greater frequency and required longer hospital admissions than the control group.
DISCUSSION During the study period, patients who received NIV had two key characteristics. Firstly, they were relatively young with a near-normal FEV1 at baseline, consistent with classic reversible airflow obstruction. Secondly, they presented with increased work of breathing and significant acid–base disturbance, consistent with a severe acute asthma attack. In patients with these characteristics, NIV was utilized safely in the emergency department and the intensive care unit without any deaths or instances requiring escalation to IMV. Reassuringly there were no complications related to NIV implementation, specifically haemodynamic compromise or pulmonary barotrauma. Length of hospital stay was longer in those patients who required NIV than controls; however, this is not surprising given that they represented a more severe cohort at acute presentation. NIV likely provides physiological support in acute asthma by several different mechanisms. Firstly, the use of EPAP helps offset intrinsic PEEP generated as a consequence of dynamic hyperinflation. This means that smaller negative changes in intra-pleural pressure are required to initiate air movement from the central to distal airways and work of breathing therefore improves.21 Secondly, the application of EPAP has a direct bronchodilation effect on the airways that reduces resistance and facilitates improved expiratory airflow.17,22 Thirdly, ventilation–perfusion relationships can be improved using EPAP by recruiting lung units that have become obstructed due to airway secretions or through assisting in the clearance of distal secretions by aiding the collateral ventilation of obstructed units.23 Fourthly, the use of pressure support or IPAP augments tidal volume and further reduces work of breathing.24 Lastly, NIV may maximize the effects of nebulized bronchodilator medica© 2014 Asian Pacific Society of Respirology
5
Non-invasive ventilation in acute asthma Table 5 Physiological variables before and during NIV treatment
Respiratory rate (brpm) SBP (mm Hg) DBP (mm Hg) HR (bpm)
Prior to commencing NIV
Minimum reading during NIV treatment
P value
Time to minimum (h)
33.0 (9.4) 155.9 (22.1) 82.6 (17.4) 119.8 (15.9)
22.1 (8.5) 128.4 (14.9) 67.9 (13.2) 97.6 (18.8)
