High‐frequency ventilation versus conventional ventilation for treatment of acute lung injury and acute respiratory distress syndrome

Sachin Sud; Maneesh Sud; Jan O Friedrich; Hannah Wunsch; Maureen O Meade; Niall D Ferguson; Neill KJ Adhikari

doi:10.1002/14651858.CD004085.pub3

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Figure 1

Study flow diagram.

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Figure 2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Figure 3

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Figure 4

Forest plot of comparison: 1 Mortality, outcome: 1.1 Hospital or 30‐day mortality.

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Figure 5

Forest plot of comparison: 2 Adverse events, outcome: 2.1 Treatment failure (intractable hypoxia, hypotension, acidosis, hypercapnoea requiring discontinuation of study intervention).

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Analysis 1.1

Comparison 1 Mortality, Outcome 1 Hospital or 30‐day Mortality.

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Analysis 1.2

Comparison 1 Mortality, Outcome 2 Hospital or 30‐day Mortality (Bollen 2005 patients lost to follow‐up excluded).

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Analysis 1.3

Comparison 1 Mortality, Outcome 3 Hospital or 30‐day mortality: Adult versus paediatric trials.

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Analysis 1.4

Comparison 1 Mortality, Outcome 4 Hospital or 30‐day Mortality: Low risk of bias versus unclear risk of bias.

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Analysis 1.5

Comparison 1 Mortality, Outcome 5 Hospital or 30‐day Mortality: Lung protective ventilation mandatory vs. not mandatory.

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Analysis 2.1

Comparison 2 Adverse events, Outcome 1 Treatment Failure (Intractable Hypoxia, Hypotension, Acidosis, Hypercapnea requiring discontinuation of study intervention).

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Analysis 2.2

Comparison 2 Adverse events, Outcome 2 Barotrauma.

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Analysis 2.3

Comparison 2 Adverse events, Outcome 3 Hypotension.

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Analysis 2.4

Comparison 2 Adverse events, Outcome 4 Hypotension (Shah and Mentzelopoulos included).

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Analysis 2.5

Comparison 2 Adverse events, Outcome 5 ETT Obstruction.

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Analysis 3.1

Comparison 3 Ventilator dependency, Outcome 1 Duration of Mechanical Ventilation.

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Comparison 4 Physiological endpoints (ratio of means), Outcome 1 PaO2/FiO2 (Ratio of Means).

Analysis 4.1

Comparison 4 Physiological endpoints (ratio of means), Outcome 1 PaO₂/FiO₂ (Ratio of Means).

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Analysis 4.2

Comparison 4 Physiological endpoints (ratio of means), Outcome 2 Oxygenation Index (Ratio of Means).

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Comparison 4 Physiological endpoints (ratio of means), Outcome 3 PaCO2 (Ratio of Means).

Analysis 4.3

Comparison 4 Physiological endpoints (ratio of means), Outcome 3 PaCO₂ (Ratio of Means).

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Analysis 4.4

Comparison 4 Physiological endpoints (ratio of means), Outcome 4 Mean Airway Pressure (Ratio of Means).

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Summary of findings for the main comparison. HFO compared to conventional mechanical ventilation for ALI and ARDS

HFO compared to conventional mechanical ventilation for ALI and ARDS
Patient or population: patients with ALI and ARDS Settings: Critical care units Intervention: High frequency oscillation Comparison: Conventional mechanical 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
	Conventional mechanical ventilation	High Frequency Oscillation
Hospital (or 30 day) mortality	Typical risk¹		RR 0.77 (0.61 to 0.98)	365 (6 studies)	⊕⊕⊕⊝ moderate^2,3
	443 per 1000	341 per 1000 (270 to 434)
6 month mortality	589 per 1000⁴	465 per 1000 (342 to 636)	RR 0.79 (0.58 to 1.08)	148 (1 study)	⊕⊕⊝⊝ low³
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.
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 The basis of the assumed risk is a systematic review and meta‐analysis of the mortality in patients with ARDS (Phua 2009). ² The risk of bias was low in four studies, and unclear in two studies due to incomplete outcome data. In three studies control group ventilation used higher tidal volumes then currently recommended. ³ We downgraded the quality of evidence due to imprecision because of small numbers of patients and outcome events, resulting in wide confidence intervals which might include both appreciable and negligible benefit (serious limitations), or appreciable benefit and possible harm (very serious limitations). ⁴ The basis of the assumed risk is the control group risk.

Summary of findings for the main comparison. HFO compared to conventional mechanical ventilation for ALI and ARDS

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Comparison 1. Mortality

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Hospital or 30‐day Mortality Show forest plot	6	365	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.61, 0.98]

2 Hospital or 30‐day Mortality (Bollen 2005 patients lost to follow‐up excluded) Show forest plot	6	362	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.61, 0.98]

3 Hospital or 30‐day mortality: Adult versus paediatric trials Show forest plot	6	365	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.61, 0.98]

3.1 Adult Trials	4	291	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.58, 1.02]
3.2 Paediatric Trials	2	74	Risk Ratio (M‐H, Random, 95% CI)	0.80 [0.44, 1.43]
4 Hospital or 30‐day Mortality: Low risk of bias versus unclear risk of bias Show forest plot	6	365	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.61, 0.98]

4.1 Low Risk of Bias Trials (free of selection, reporting, and attrition bias)	4	246	Risk Ratio (M‐H, Random, 95% CI)	0.70 [0.53, 0.92]
4.2 Unclear Risk of Bias Trials (possible selection, reporting or attrition bias)	2	119	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.65, 1.66]
5 Hospital or 30‐day Mortality: Lung protective ventilation mandatory vs. not mandatory Show forest plot	6	365	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.61, 0.98]

5.1 Lung Protective Ventilation Not Mandatory	3	267	Risk Ratio (M‐H, Random, 95% CI)	0.84 [0.61, 1.16]
5.2 Lung Protective Ventilation Mandatory	3	98	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.44, 1.03]

Comparison 1. Mortality

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Comparison 2. Adverse events

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Treatment Failure (Intractable Hypoxia, Hypotension, Acidosis, Hypercapnea requiring discontinuation of study intervention) Show forest plot	5	337	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.46, 0.99]

2 Barotrauma Show forest plot	6	365	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.37, 1.22]

3 Hypotension Show forest plot	3	267	Risk Ratio (M‐H, Random, 95% CI)	1.54 [0.34, 7.02]

4 Hypotension (Shah and Mentzelopoulos included) Show forest plot	5	349	Risk Ratio (M‐H, Random, 95% CI)	1.46 [0.77, 2.76]

5 ETT Obstruction Show forest plot	4		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Comparison 2. Adverse events

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Comparison 3. Ventilator dependency

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Duration of Mechanical Ventilation Show forest plot	4	276	Mean Difference (IV, Random, 95% CI)	‐0.75 [‐5.36, 3.85]

Comparison 3. Ventilator dependency

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Comparison 4. Physiological endpoints (ratio of means)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 PaO₂/FiO₂ (Ratio of Means) Show forest plot	7		Ratio of Means (Random, 95% CI)	Subtotals only

1.1 Day 1	7	323	Ratio of Means (Random, 95% CI)	1.24 [1.10, 1.40]
1.2 Day 2	5	262	Ratio of Means (Random, 95% CI)	1.16 [0.97, 1.37]
1.3 Day 3	5	228	Ratio of Means (Random, 95% CI)	1.17 [1.02, 1.35]
2 Oxygenation Index (Ratio of Means) Show forest plot	7		Ratio of Means (Random, 95% CI)	Subtotals only

2.1 Day 1	7	352	Ratio of Means (Random, 95% CI)	1.11 [0.97, 1.26]
2.2 Day 2	6	306	Ratio of Means (Random, 95% CI)	1.07 [0.92, 1.24]
2.3 Day 3	6	266	Ratio of Means (Random, 95% CI)	1.07 [0.88, 1.29]
3 PaCO₂ (Ratio of Means) Show forest plot	8		Ratio of Means (Random, 95% CI)	Subtotals only

3.1 Day 1	8	386	Ratio of Means (Random, 95% CI)	0.91 [0.78, 1.07]
3.2 Day 2	6	310	Ratio of Means (Random, 95% CI)	0.87 [0.72, 1.06]
3.3 Day 3	6	267	Ratio of Means (Random, 95% CI)	0.98 [0.84, 1.14]
4 Mean Airway Pressure (Ratio of Means) Show forest plot	8		Ratio of Means (Random, 95% CI)	Subtotals only

4.1 Day 1	8	389	Ratio of Means (Random, 95% CI)	1.33 [1.27, 1.40]
4.2 Day 2	6	309	Ratio of Means (Random, 95% CI)	1.26 [1.16, 1.37]
4.3 Day 3	6	274	Ratio of Means (Random, 95% CI)	1.22 [1.07, 1.39]

Comparison 4. Physiological endpoints (ratio of means)

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