Non‐invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma

Wei Jie Lim; Redhuan Mohammed Akram; Kristin V Carson; Satya Mysore; Nadina A Labiszewski; Jadwiga A Wedzicha; Brian H Rowe; Brian J Smith

doi:10.1002/14651858.CD004360.pub4

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Figure 1

Study flow diagram.

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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1 NPPV versus usual care, Outcome 1 Mortality during hospital admission.

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Analysis 1.2

Comparison 1 NPPV versus usual care, Outcome 2 Endotracheal intubation.

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Analysis 1.3

Comparison 1 NPPV versus usual care, Outcome 3 Number of hospital admissions.

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Analysis 1.4

Comparison 1 NPPV versus usual care, Outcome 4 Length of ICU stay (hours).

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Analysis 1.5

Comparison 1 NPPV versus usual care, Outcome 5 Treatment failure.

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Analysis 1.6

Comparison 1 NPPV versus usual care, Outcome 6 PEF (L/minute).

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Analysis 1.7

Comparison 1 NPPV versus usual care, Outcome 7 PEF (% predicted).

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Analysis 1.8

Comparison 1 NPPV versus usual care, Outcome 8 FVC (% predicted).

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Analysis 1.9

Comparison 1 NPPV versus usual care, Outcome 9 FEV1 (% predicted).

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Analysis 1.10

Comparison 1 NPPV versus usual care, Outcome 10 FEV1 (litres).

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Analysis 1.11

Comparison 1 NPPV versus usual care, Outcome 11 FEF_25‐75% (% predicted).

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Analysis 1.12

Comparison 1 NPPV versus usual care, Outcome 12 ABG ‐ pH.

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Comparison 1 NPPV versus usual care, Outcome 13 ABG ‐ PaCO2 (mmHg).

Analysis 1.13

Comparison 1 NPPV versus usual care, Outcome 13 ABG ‐ PaCO₂ (mmHg).

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Comparison 1 NPPV versus usual care, Outcome 14 ABG ‐ PaO2/FiO2 (mmHg).

Analysis 1.14

Comparison 1 NPPV versus usual care, Outcome 14 ABG ‐ PaO₂/FiO₂ (mmHg).

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Analysis 1.15

Comparison 1 NPPV versus usual care, Outcome 15 Respiratory rate.

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Summary of findings for the main comparison. Non‐invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma

Non‐invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma
Patient or population: patients with asthma Settings: Intervention: non‐invasive positive pressure ventilation
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Non‐invasive positive pressure ventilation
Mortality Follow‐up: 30 days	See comment	See comment	Not estimable	86 (2 studies)	⊕⊝⊝⊝ very low^1,2,3	Not estimable
Endotracheal intubation Follow‐up: 30 days	See comment	See comment	RR 4.48 (0.23 to 89.13)	86 (2 studies)	⊕⊕⊝⊝ low^1,2	No events in control group
Length of hospital stay Follow‐up: 30 days	See comment	See comment	See comment	86 (2 studies)	⊕⊝⊝⊝ very low^1,2,3	Unable to pool data
Number of hospital admissions Follow‐up: 30 days	625 per 1000	175 per 1000 (56 to 525)	RR 0.28 (0.09 to 0.84)	33 (1 study)	⊕⊝⊝⊝ very low^2,3,4
FEV1 (% predicted) Percentage scale from: 1% to 150%. Follow‐up: 1 to 30 days	Mean FEV1 (% predicted) ranged across control groups from 35.51 L to 43.9 %	The mean FEV1 (% predicted) in the intervention groups was 14.02 % higher (7.73 to 20.32 higher)	MD 14.02 (7.73 to 20.32)	66 (2 studies)	⊕⊕⊝⊝ low^2,5
FVC (% predicted) Percentage scale from: 1% to 150%. Follow‐up: 1 to 30 days	Mean FVC (% predicted) ranged across control groups from 41.26 L to 58.1 %	The mean FVC (% predicted) in the intervention groups was 12.27 % higher (4.38 to 20.16 higher)	MD 12.27 (4.38 to 20.16)	66 (2 studies)	⊕⊕⊝⊝ low^2,5
Respiratory rate (breaths per minute). Scale from: 12 to 40. Follow‐up: 1 to 30 days	Mean respiratory rate ranged across control groups from 17.8 per minute to 23.3 per minute	Mean respiratory rate in the intervention groups was 1.42 breaths per minute higher (2.77 to 0.07 higher)	MD ‐1.42 (‐2.77 to ‐0.07)	146 (3 studies)	⊕⊕⊝⊝ low^2,5
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio; OR: odds ratio
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Soroksky 2003 had three areas of unclear risk whereas Gupta 2010 had a high risk for selective reporting ² Small sample size ³ Comparison of intervention not available ⁴ Unclear risk of bias for allocation sequence generation, allocation concealment and reporting of incomplete outcome data ⁵ Some studies had areas of unclear risk, being sequence generation, allocation concealment and selective reporting

Summary of findings for the main comparison. Non‐invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma

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Table 1. Summary of intervention effectiveness: secondary outcomes

Study ID/N‐values

Outcome results (comparing intervention to control):

Number of hospital admissions

Length of hospital stay

Length of ICU stay

Symptom scores

Treatment failure

Complications

Lung function tests

ABG

Respiratory rate

PEF

FVC

FEV1

FEF_25‐75%

PaCO₂

PaO₂/FiO₂

Brandao 2009

‐

Favours intervention

No evidence of effect

Favours intervention

‐

Favours intervention group a

Gupta 2010

‐

Favours intervention

‐

No evidence of effect

‐

No evidence of effect

‐

No evidence of effect

Soroksky 2003

Favours intervention

No evidence of effect

‐

No evidence of effect

‐

Favours Intervention

No evidence of effect

Favours Intervention

‐

No evidence of effect

Filho 2009

‐

1 patient deteriorated in control group and was withdrawn

‐

Favours intervention

Not reported

Favours intervention

‐

Favours intervention

De Miranda 2004

‐

No evidence of effect

‐

No evidence of effect

Table 1. Summary of intervention effectiveness: secondary outcomes

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Table 2. Narrative synthesis

Study ID/sub‐headings	Detailed synthesis of intervention effectiveness
Brandao 2009 Primary outcome:	There were no reported outcome measures for intubation or mortality
Brandao 2009 Secondary outcomes:	The number of hospital admissions, length of hospital stays, symptoms scores, ABG results and complications were not reported. Compared to the effect of nebulisation in the control group, intervention group a: (IPAP 15 cm H₂O and EPAP 5 cm H₂O), had significantly higher PEF (P = 0.04) and lower respiratory rate (P = 0.04); whereas intervention group b (IPAP 15 cm H₂O and EPAP 10 cm H₂O) had significantly higher PEF (P = 0.03), FVC (P = 0.03), FEV1 (P = 0.03) and FEF_25‐75% (P = 0.0001) with no evidence of effect for respiratory rate
Gupta 2010 Primary outcome:	The authors reported that there were no mortalities in any group. 2 patients in the intervention group were subsequently intubated. 4 patients in the control group were crossed over to receive the intervention, however, none were subsequently intubated
Gupta 2010 Secondary outcomes:	The median length of stay in hospital for the intervention group was 38 hours (interquartile range 24 to 48 hours) compared to 54 hours (interquartile range 48 to 72 hours) for the control group (P = 0.01). The median length of stay in the respiratory ICU was 10 hours (interquartile range 8 to 20 hours) for the intervention group compared to 24 hours (interquartile range 18 to 36 hours) in the control group (P = 0.01). 64% (16/25) of patients in the control group and 85.7% (24/28) of patients in the intervention group had a ≥ 50% improvement in FEV1 at 4 hours (P = 0.08). Time to disappearance of accessory muscle use was 2.3 (± 1.4) hours in the intervention group and 3.2 (± 1.7) hours in the control group (P = 0.06). The mean dose of inhaled salbutamol required during hospitalisation was 31.2 mg (± 14.5) in the NPPV group and 42.8 mg (± 10.4) in the control group (P = 0.008). This was significantly lower in the NPPV group. The mean dose of inhaled ipratropium required during hospitalisation was 5.2 mg (± 2.8) in the NPPV group and 7.6 mg (± 2.2) in the control group with a P value of 0.007. This was significantly lower in the NPPV group
Soroksky 2003 Primary outcome:	There were no reported outcome measures for intubation or mortality
Soroksky 2003 Secondary outcomes:	The number of hospital admissions was analysed on an intention‐to‐treat basis with 17.6% (3/17) participants in the intervention group and 62.5% (10/16) in the control group requiring hospitalisation (P = 0.0134). During follow‐up (1 month), only 1 patient in each group was re‐admitted to the emergency department and both were discharged after a short treatment without re‐hospitalisation. Average length of stay in the emergency department was 5.9 hours (± 1.3) for the intervention group and 5.6 hours (± 1.3) for the control (P = NS). There was an increase in FEV1 for the intervention group during the 3 hours of BPV treatment (mean ± SD; intervention: 56.1 ± 16.3; control: 42.3 ± 15.9; P = 0.03), which steadily increased for an additional hour after discontinuation of treatment (mean ± SD; intervention: 57.4 ± 17.7; control: 43.9 ± 16.7; P = 0.04). PEFR also increased in the intervention arm at both 3 and 4 hours post treatment (P = 0.03 and P = 0.04, respectively), and although FVC showed a similar improvement at 3 hours for the intervention arm (P = 0.03) this was not maintained at 4 hours post BPV administration (P = NS). Respiratory rate decreased significantly in the BPV group (41.3 ± 12.8%) compared to the control group (31 ± 11.4%) at 4 hours' follow‐up (P = 0.02). 2 patients in the intervention arm and 1 in the control arm could not tolerate the nasal mask and did not complete the 3‐hour protocol, subsequently they were withdrawn from the study
De Miranda 2004 Primary outcome:	There were no reported outcome measures for intubation or mortality
De Miranda 2004 Secondary outcomes:	Only PEF (measured in L/minute) and respiratory rate were reported. Both outcomes were reported to have statistically significant improvements in each of the 3 groups; however, comparisons between groups were not reported in the study. Outcomes reported were intervention group A mean PEF 293.80 (SD 82.12; P < 0.001) and mean respiratory rate 17.57 (SD 4.29; P < 0.001), intervention group B mean PEF 310.71 (SD 88.08; P < 0.001) and mean respiratory rate 16.66 (SD 3.19; P < 0.001), control group mean PEF 260.95 (SD 88.08; P < 0.001) and mean respiratory rate 17.80 (SD 4.06; P < 0.007)
Filho 2009 Primary outcome:	There were no reported outcome measures for intubation or mortality
Filho 2009 Secondary outcomes:	A reduction of respiratory rate (P = 0.001), TV (P = 0.01) and MV (P = 0.01), as well as a gain in FEV1 (P = 0.001), FVC (P = 0.001), PEF (P = 0.001) and IC (P = 0.01) in the intervention group compared to the control group were reported. However, no data were available from the published abstract for meta‐analysis
ABG: arterial blood gas; EPAP: expiratory positive airway pressure; FEF_25‐75%: forced expiratory fraction 25‐75%; FEV1: forced expiratory volume in one second; FVC: forced vital capacity; IC: inspiratory capacity; ICU: intensive care unit; IPAP: inspiratory positive airway pressure; MV: minute ventilation; NPPV: non‐invasive positive pressure ventilation; NS: not significant; PEF: peak expiratory flow; PEFR: peak expiratory flow rate; TV: tidal volume.

Table 2. Narrative synthesis

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Table 3. Summary of intervention effectiveness: primary outcomes

Study ID	Outcome results (comparing intervention to control)
	Mortality during hospital admission	Intubation
Brandao 2009	‐	‐
Gupta 2010	No evidence of effect	No evidence of effect
Soroksky 2003	No evidence of effect	No evidence of effect
Filho 2009	‐	‐
De Miranda 2004	‐	‐

Table 3. Summary of intervention effectiveness: primary outcomes

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Comparison 1. NPPV versus usual care

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality during hospital admission Show forest plot	2	86	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

1.1 ICU	1	53	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Ward	1	33	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Endotracheal intubation Show forest plot	2	86	Risk Ratio (M‐H, Fixed, 95% CI)	4.48 [0.23, 89.13]

2.1 ICU	1	53	Risk Ratio (M‐H, Fixed, 95% CI)	4.48 [0.23, 89.13]
2.2 Ward	1	33	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Number of hospital admissions Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Length of ICU stay (hours) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5 Treatment failure Show forest plot	2	86	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.21, 2.53]

6 PEF (L/minute) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

7 PEF (% predicted) Show forest plot	2	66	Mean Difference (IV, Fixed, 95% CI)	19.97 [15.01, 24.93]

8 FVC (% predicted) Show forest plot	2	66	Mean Difference (IV, Fixed, 95% CI)	12.27 [4.38, 20.16]

9 FEV1 (% predicted) Show forest plot	2	66	Mean Difference (IV, Fixed, 95% CI)	14.02 [7.73, 20.32]

10 FEV1 (litres) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

11 FEF_25‐75% (% predicted) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

12 ABG ‐ pH Show forest plot	1	53	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.03, 0.01]

13 ABG ‐ PaCO₂ (mmHg) Show forest plot	1	53	Mean Difference (IV, Fixed, 95% CI)	0.5 [‐2.83, 3.83]

14 ABG ‐ PaO₂/FiO₂ (mmHg) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

15 Respiratory rate Show forest plot	3	146	Mean Difference (IV, Fixed, 95% CI)	‐1.42 [‐2.77, ‐0.07]

15.1 ICU	1	53	Mean Difference (IV, Fixed, 95% CI)	‐1.60 [‐3.75, 0.55]
15.2 Ward	2	93	Mean Difference (IV, Fixed, 95% CI)	‐1.30 [‐3.04, 0.44]

Comparison 1. NPPV versus usual care

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