Non‐invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The objective of this review is to determine the effect of NPPV in patients with acute exacerbations of asthma with respect to mortality, tracheal intubation, changes in blood gases, and hospital length of stay.
Background
Non‐invasive positive pressure ventilation (NPPV) has been suggested as an alternative treatment option for patients admitted to hospital with hypercapnic respiratory failure secondary to acute exacerbation of chronic obstructive pulmonary disease (COPD) (Bott 1993; Foglio 1992; Kramer 1995; Meduri 1989). Traditionally, patients who do not respond to conventional treatment are invasively mechanically ventilated; this involves sedation, intubation, attachment to a ventilator and transfer to the intensive care unit (ICU). Most patients do recover with tracheal intubation and assisted ventilation; however, these treatments are associated with high morbidity and there may be considerable difficulties weaning this patient group from ventilation (Brochard 1994; Esteban 1995). In addition, although intubation and mechanical ventilation is common practice, complications can result from the intubation process (damage to local tissue, drug interactions, side‐effects to procedures) and during the course of ventilation (ventilator associated pneumonia, pneumothorax and sinusitis) (Fagon 1993). Prolonged stays in ICU are therefore not uncommon.
NPPV employs a full facial or nasal mask that administers ventilatory support from a flow generator. NPPV enhances ventilation by unloading fatigued ventilatory muscles and its use has been established in the treatment of patients with a variety of chronic hypoventilatory syndromes (Moloney 1999). NPPV has the advantage that it can be applied intermittently for short periods, which may be sufficient to reverse the ventilatory failure. Moreover, sedation is not required allowing the patient to eat, drink and talk also permitting participation in decisions about their own care. Finally, the incidence of nosocomial pneumonia with NPPV use is lower than in intubated patients (Nourdine 1999; Guerin 1997; Kramer 1999). Over the last decade NPPV has been increasingly used as an adjunct therapy in the management of acute exacerbations of COPD, congestive heart failure and other conditions. NPPV has been successfully used to treat patients with COPD who are prone to exacerbations of respiratory failure. A recent systematic review of trials in patients with COPD has shown significant reductions in mortality, need for intubation, complications, treatment failure, length of hospital stay with rapid improvements in blood gases and respiratory rate (Ram 2003).
Although, NPPV has been shown to be effective in COPD patients with acute respiratory failure, its role in patients with acute respiratory failure following an exacerbation of asthma is uncertain. In some ways the pathophysiologic condition of acute respiratory failure in asthma is similar to that of acute respiratory failure in COPD. Therefore, there is reason to believe that NPPV may also be successful in patients with asthma. Unfortunately, only a few reports with have described the use of NPPV in patients with respiratory failure due to exacerbations of asthma (Meduri 1991; Benhamou 1992; Thys 1999; Soma 2002) with conflicting results.
Objectives
The objective of this review is to determine the effect of NPPV in patients with acute exacerbations of asthma with respect to mortality, tracheal intubation, changes in blood gases, and hospital length of stay.
Methods
Criteria for considering studies for this review
Types of studies
Studies will only be included if they are randomised controlled clinical trials.
Types of participants
Only studies of adult patients with severe acute asthma as the primary reason for admission to hospital will be included in this review. All patients would have a diagnosis of asthma using internationally accepted criteria (e.g. British Thoracic Society, American Thoracic Society) and hypercapnia (baseline or admission PCO2 > 6 kPa or 45mmHg). Studies including patients with features of COPD will be excluded unless data is provided separately for patients with asthma in studies recruiting both COPD and asthma patients.
Types of interventions
Studies will be included if the intervention was standard medical care (SMC) for the management of acute exacerbation of asthma plus NPPV applied through a nasal or facemask compared to SMC alone. Studies will not be excluded because of additional, standard therapy such as supplemental oxygen, antibiotics, bronchodilators, or steroids.
Treatment in the control group could include any form of standard therapy for the maagement of acute exacerbations of asthma, but which did not involve NPPV.
The following types of trials will not be considered for inclusion; patients with a primary diagnosis of pneumonia, weaning studies, patients with other underlying pathologies and studies where continuous positive airway pressure (CPAP) or endotracheal intubation preceded enrolment of patients into the trial.
Types of outcome measures
Primary outcome measure:
-
Mortality during the hospital admission
-
Tracheal intubation
Secondary outcome measures:
-
Arterial blood gases and pH
-
Respiratory rate
-
Length of hospital stay
-
Length of ITU/ICU stay
-
Symptom score (e.g. Borg scores, VAS)
-
Treatment failure (the combination of mortality, intubation and intolerance to the allocated treatment)
-
Complications
Search methods for identification of studies
An initial search will be carried out using CENTRAL with the following search terms: Asthma AND acute AND (nasal OR mechanical OR non‐invasive or non invasive or positive pressure OR intermittent positive pressure OR airway* pressure OR pressure‐controlled OR volume‐controlled AND ventilat*) OR positive pressure OR bi‐level positive pressure OR ventilation support OR NIPPV OR NPPV OR NIV
In order to reduced the chance of missing potential studies, seperate and additional searches will also be carried out on MEDLINE, EMBASE, CINAHL, Science Citation, web based clinical trials databases (e.g ClinTrials.gov), 20 key journals with web sites will also be searched as well as major respiratory conference proceedings (e.g. American Thoracic Society, British Thoracic Society, European Respiratory Society). Companies that manufacture ventilators will also be conrtacted for potential as well as researchers working in the area.
Following this, the bibliographies of each RCT obtained (and any review articles) will be searched for additional RCTs. Authors of identified RCTs will be contacted for other published, unpublished or ongoing studies.
Data collection and analysis
STUDY QUALITY GRADING:
The methodological quality of the included trials will be assessed independently by two reviewers with particular emphasis on the allocation concealment (Schulz 1995), which will be ranked using the Cochrane approach:
Grade A: Adequate concealment
Grade B: Uncertain
Grade C: Clearly inadequate concealment
Grade D: Not used
DATA EXTRACTION
Data will be extracted independently by two reviewers. Unpublished data will be requested from the primary authors when necessary. A standard form will be used that will describe the following: characteristics of the study (design, methods of randomisation, withdrawals / dropouts); participants (age, gender); intervention (type of NPPV, timing and duration of therapy, co‐interventions); control (agent and dose); outcomes (types of outcome measures, timing of outcomes, adverse events); and results. This data will then be entered into Review Manager 4.2 (RevMan) by a third party who will also identify and resolve dissimilarities.
STATISTICAL CONSIDERATIONS:
Data from all trials will be analysed using RevMan 4.2. For continuous variables, a weighted mean difference (WMD) or standardised mean difference (SMD) and 95% confidence interval (95%CI) will be calculated for each study. All similar studies will be pooled using WMD or SMD with their 95%CIs. For dichotomous variables relative risk (RR) with 95%CI will be calculated. Number needed to treat (NNT) will be calculated using the formula; NNT = 1/ [CER * (1 ‐ RR)], (where CER = control event rate and RR = relative risk).
SENSITIVITY ANALYSIS:
Heterogeneity among pooled estimates will be tested using the DerSimonian and Laird method; p < 0.05 will be considered statistically significant. Results will be reported using the fixed effect model where there is no statistically significant heterogeneity. If there is sufficient number of studies for a particular outcome that has significant heterogeneity, this would be investigated based on study quality, duration of NPPV, time to initiation of NPPV, type of NPPV and type of mask used to administer NPPV.
SUBGROUPS ANALYSIS:
If there are sufficient included studies subgroups would be based on baseline or admission pH (below 7.30 or between 7.35 ‐ 7.30) and the location of the study within the hospital (ICU or respiratory ward).
