Prone position for acute respiratory failure in adults
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The objectives of this review are to ascertain whether prone ventilation offers a mortality advantage when compared with traditional supine or semi‐recumbent ventilation in patients with severe acute respiratory failure requiring conventional invasive artificial ventilation.
We plan to undertake the following subgroup analyses to explore possible sources of heterogeneity.
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Duration of daily ventilation in the prone position (less than 18 hours/day versus 18 hours/day or more). As any benefit from prone ventilation may be a dose (time) related phenomenon, the daily duration of time in that position would appear potentially important.
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Duration of supine ventilation prior to randomization. Since ventilatory‐induced lung injury is relatively rapid in onset, identification of any randomized trials and outcomes where there was very limited exposure to supine ventilation prior to randomization should be identified.
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Outcome according to severity (oxygenation index /PaO2/FIO2 ratio/severity of illness score, e.g. Simplified Acute Physiology Score II (SAPS II)): more severe lung injury benefit from prone ventilation. This may be an important sub‐group to explore. SAPS II or similar scores may indirectly reflect the severity of inciting injury and also be relevant.
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Tidal volume (size of mechanical breath given to the patient) in relation to body weight has been shown to affect survival and outcomes between high tidal volume (more than 10 ml/kg), moderate tidal volumes (8‐10 ml/kg) and low tidal volumes (less than 8 ml/kg) will be explored if the data permit.
We will analyze studies of acute lung injury and ARDS separately from other causes of acute severe hypoxaemic respiratory failure if data allow.
Acute lung injury and ARDS have been further sub‐classified into pulmonary and extrapulmonary causes and may behave differently to ventilatory strategies. We will explore differences in outcomes in these subcategories if the collected data allow.
Background
Acute respiratory failure can arise from a number of diseases or disease processes, and is a common reason for admission to hospital. Patients with profound gas exchange abnormalities unresponsive to ward‐based strategies (such as oxygen therapy or continuous positive airways pressure (CPAP) for hypoxaemic respiratory failure, or non‐invasive ventilation for hypercapnic ventilatory failure) may be referred to intensive care units (ICUs) for further management. Patients whose problems are predominantly related to oxygenation will include those with pneumonia, pulmonary oedema, pulmonary aspiration pneumonitis, pulmonary thromboembolism and acute respiratory distress syndrome (ARDS). Patients with ventilatory failure and hypercapnia include patients with chronic obstructive pulmonary disease (COPD), those receiving central nervous system depressant drugs and patients with neuromuscular problems.
Patients with profound hypoxaemia present a significant challenge for their carers, in dealing with both the hypoxaemia and the underlying process(es). Although hypoxaemia often is not perceived as the ultimate cause of death in these patients, it does have deleterious effects (Strachan 2001). Avoidance of profound hypoxaemia is one of the goals of supportive therapy in ICU, and a variety of manoeuvres are employed to ameliorate hypoxaemia. These include applications of positive end‐expiratory pressure (PEEP), use of inverse ratio ventilation (IRV), alveolar recruitment manoeuvres, restrictive fluid administration strategies, inhaled pulmonary vasodilators such as nitric oxide (Adhikari 2007; ARDSnet 2006a) and prostacyclin, corticosteroids and mechanical ventilation in the prone position (ARDSnet 2006; Cranshaw 2002; Klein 2004; Mentzelopoulos 2005). All of these therapies have been shown to improve oxygenation (Adhikari 2004; Verbrugge 2006), but few interventions have demonstrated a mortality benefit in randomized controlled trials (Petrucci 2007). High frequency oscillation (HFO) and extra‐corporeal membrane oxygenation (ECMO) are other modalities undergoing clinical trials at present. Traditional mechanical ventilation , which is normally utilized in supine or semi‐recumbent patients, while ensuring short‐term survival, may also contribute to lung injury. Ventilator‐induced lung injury has been demonstrated both in experimental animal models and in human subjects, and thus mechanical ventilation can perpetuate or accentuate the original injury to lung as well as causing dysfunction of distant organs (Verbrugge 2006). These effects are known as barotrauma, volutrauma and biotrauma.
However, Chatte 1997 and others have showed that ventilation with the patient in the prone position could have salutary effects on oxygenation (Gattinoni 2001; Lindahl 2001). Studies in recent years, in humans as well as experimental animal models, have confirmed that use of the prone position is associated with improved oxygenation in the majority of subjects. More than 70% of patients with lung injury have clinical improvement in oxygenation with prone mechanical ventilation. In a retrospective multivariate analysis, the use of prone positioning was independently correlated with positive outcomes in patients with ARDS (Venet 2003). The mechanisms by which prone position improves gas exchange include alveolar recruitment, redistribution of ventilation towards dorsal areas that remain well perfused, homogenization of tidal volume distribution and possible improved postural drainage of secretions (Gattinoni 2006; Guerin 2006). Postural drainage has also been postulated to reduce ventilator‐associated pneumonia. The homogenization of tidal volume distribution may reduce tissue stress/strain and consequently reduce the well‐described injurious effects of mechanical ventilation, providing additional benefit over and above that of improved oxygenation (Mentzelopoulos 2005). Thus there are three phenomena which might improve survival for patients: reduced extent and duration of hypoxaemia; reduced propensity to ventilator‐induced lung injury; and reduced incidence of nosocomial or ventilator‐associated pneumonia. There are adverse effects associated with the prone position for ventilation, most notably: unplanned extubation and risk of an episode of potentially catastrophic hypoxaemia; bronchial intubation which will also worsen hypoxaemia and increased risk of barotrauma (e.g. pneumothorax); development of pressure sores; ocular complications; and intracranial hypertension which can compromise cerebral circulation.
Improved oxygenation with use of the prone position could allow additional time for lung reparative processes, and by reducing secondary lung infection or injury, has the potential to accelerate recovery and lessen mortality in acute respiratory failure in adults. Adverse effects and complications might reduce these potential benefits.
Objectives
The objectives of this review are to ascertain whether prone ventilation offers a mortality advantage when compared with traditional supine or semi‐recumbent ventilation in patients with severe acute respiratory failure requiring conventional invasive artificial ventilation.
We plan to undertake the following subgroup analyses to explore possible sources of heterogeneity.
-
Duration of daily ventilation in the prone position (less than 18 hours/day versus 18 hours/day or more). As any benefit from prone ventilation may be a dose (time) related phenomenon, the daily duration of time in that position would appear potentially important.
-
Duration of supine ventilation prior to randomization. Since ventilatory‐induced lung injury is relatively rapid in onset, identification of any randomized trials and outcomes where there was very limited exposure to supine ventilation prior to randomization should be identified.
-
Outcome according to severity (oxygenation index /PaO2/FIO2 ratio/severity of illness score, e.g. Simplified Acute Physiology Score II (SAPS II)): more severe lung injury benefit from prone ventilation. This may be an important sub‐group to explore. SAPS II or similar scores may indirectly reflect the severity of inciting injury and also be relevant.
-
Tidal volume (size of mechanical breath given to the patient) in relation to body weight has been shown to affect survival and outcomes between high tidal volume (more than 10 ml/kg), moderate tidal volumes (8‐10 ml/kg) and low tidal volumes (less than 8 ml/kg) will be explored if the data permit.
We will analyze studies of acute lung injury and ARDS separately from other causes of acute severe hypoxaemic respiratory failure if data allow.
Acute lung injury and ARDS have been further sub‐classified into pulmonary and extrapulmonary causes and may behave differently to ventilatory strategies. We will explore differences in outcomes in these subcategories if the collected data allow.
Methods
Criteria for considering studies for this review
Types of studies
We will include all randomized controlled trials comparing conventional modes of mechanical ventilation in the supine or semi‐recumbent position compared with mechanical ventilation in the prone position in adults with acute respiratory failure.
We will include unpublished studies and abstracts.
We will not impose a language restriction.
Types of participants
We will include studies on adults with critical illness in an ICU setting requiring conventional mechanical ventilation for acute severe respiratory failure.
We will exclude studies primarily investigating patients with chronic respiratory impairment, such as chronic obstructive pulmonary disease. The focus of this review is acute severe respiratory failure.
We will exclude studies on neonates or paediatric patients (i.e. less than 16 years). These have been covered separately in Cochrane Reviews (Balaguer 2006; Wells 2005).
Types of interventions
We will examine interventions comparing conventional methods of ventilation and adjuncts in the supine/semi‐recumbent (which may encompass lateral positioning as part of routine pressure care) versus prone positions.
We will exclude studies using primary positions other than supine/semi‐recumbent.
We will exclude rotational therapies of position with the prone position.
We will exclude conventional prone ventilation with other experimental modes of ventilations such a high frequency jet ventilation (HFJV) or high frequency oscillation (HFO).
Types of outcome measures
We will seek information on the following main outcomes.
1. Short‐term mortality (10‐30 day or ICU mortality).
2. Longer‐term mortality (> 30 day or hospital mortality).
We will also seek information on:
3. Rates of ventilator‐associated pneumonia.
4. Number of days on a ventilator.
5. Length of ICU stay.
6. Length of hospital stay.
7. Maximum improvement in oxygenation.
8. Adverse events.
9. Quality of life.
10. Economic outcomes.
Planned sub‐groups analyses
Duration of daily ventilation in the prone position (less than 18 hours/day versus 18 hours/day or more).
Duration of supine ventilation prior to randomization (less than 48 hours versus 48 hours or more).
Outcome according to severity (oxygenation index /PaO2/FIO2 ratio/severity of illness score, e.g. Simplified Acute Physiology Score II (SAPS II)).
Tidal volume ( less than eight versus 8‐10 versus more than 10 ml/kg).
We will analyse studies of acute lung injury and ARDS separately from other causes of acute severe hypoxaemic respiratory failure if data allow.
Acute lung injury and ARDS have been further sub‐classified into pulmonary and extrapulmonary causes and we will analyse them according to this classification if data allow.
We will use meta‐regression to explore heterogeneity between sub‐groups if we identify sufficient studies (Deeks 2008). Otherwise we will utilize the Q‐partitioning method (Deeks 2008).
Search methods for identification of studies
We will search the current issue of The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), OVID MEDLINE (1950 to date), EMBASE (1980 to date), CINAHL (1982 to date) and LILACS (1992 to date).
We will search OVID MEDLINE with the search terms found in Appendix 1. We will use the same search strategy to search for CENTRAL, EMBASE and CINAHL within OVID. We have provided the search terms for LILACS accessed through the Virtual Health Library in Appendix 2.
We will also search for studies by:
a. searching reference lists of previous trials and review articles;
b. searching books related to critical care and mechanical ventilation;
c. communicating with colleagues, particularly published trialists;
d. subject‐specific search in the following journals for published proceedings' abstracts of clinical trials:
American Journal of Respiratory and Critical Care Medicine, vols 167‐9, 2004 to date;
Critical Care, vols 7‐13, 2003 to date;
Critical Care Medicine, vols 31‐7, 2003 to date;
Intensive Care Medicine, vols 30‐35, 2003 to date.
We will search for relevant ongoing trials in specific web sites:
Data collection and analysis
Trial identification, selection and abstraction
Two authors (RB and DWN) will independently screen and classify all citations as potentially primary studies, review articles or other. Two authors (RB and DWN) will also examine all potential primary studies, and decide on their inclusion in the review. The third author (NRW) will resolve any disagreements. If pertinent data are not available for published studies, we will contact the authors for further information.These authors will also independently abstract data on methodology and outcomes from each study in duplicate and use the Cochrane Anaesthesia Review Group (CARG) to assess methodological quality. The third author (NRW) will resolve any disagreements.
Methodological quality assessment
We will judge study quality on the basis of:
1. method of randomization;
2. method of allocation concealment as follows:
A: low risk of bias: adequate allocation concealment (i.e. central randomizations, such as allocation by a central office unaware of subject characteristics); computer file that can be accessed only after the characteristics of an enrolled participant have been entered; or other description containing elements suggesting adequate concealment;
B: moderate risk of bias: unclear allocation concealment (the authors either do not report an allocation concealment approach at all, or report an approach that does not fall under category A);
C: high risk of bias: inadequate allocation concealment (such as alternation or reference to case numbers or dates of birth);
D: no allocation concealment used: any procedure that is entirely transparent before allocation (such as an open list of random numbers or other description that contained elements indicating no concealment of allocation);
3. blinding of treatment and outcome to assessors;
4. completeness of follow up.
We will discuss the impact of methodological quality on the results. We will perform a sensitivity analysis, either including or excluding the classes C and D from the meta‐analysis.
Statistics
We will review the data from included studies qualitatively and then, if possible, combine it quantitatively by population, intervention and outcome, using The Cochrane Collaboration's statistical software, Review Manager 5 (RevMan 5.0). We will base quantitative analyses of outcomes on intention‐to‐treat results. In case of substantial clinical heterogeneity, we will not pool the results to perform statistical analysis. We will perform a sensitivity analysis on the basis of trial quality.
We will measure heterogeneity by Higgins' test (I2 greater than 25% equals significant heterogeneity (Higgins 2003). We will use a fixed‐effect model if we find good homogeneity between studies, otherwise we will use a random‐effects model.
For dichotomous outcomes we will calculate risk ratio (RR), while we will use odds ratio (OR) when the outcome is very small. We will use standardized mean differences (SMD) or mean differences (MD) as appropriate for continuous outcomes.
We will use a funnel plot to assess the risk of reporting bias (Higgins 2008) .
