Oxygen therapy in the pre‐hospital setting for people suffering from an acute exacerbation of chronic obstructive pulmonary disease
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To determine the effect of different oxygen therapies in the pre‐hospital setting (prior to casualty/emergency department) on outcome for patients with acute exacerbations of COPD.
Background
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in the developed world. Currently ranked as the fourth most common worldwide cause of death amongst those over the age of 45 years (Murray 1997). The disease is characterised by acute deteriorations in the patient's condition, termed exacerbations. which are often associated with the development of respiratory failure.
As a result of the disease process, this group of patients are predisposed to developing alveolar hypoventilation. This in turn causes an elevation of the partial pressure of arterial carbon dioxide (PaCO2), known as hypercarbia, and a reduction in partial pressure of arterial oxygen (PaO2), known as hypoxaemia. The combination of a PaO2 below 60 and PaCO2 above 45 is referred to as hypoventilatory (hypercapnic) respiratory failure, and is associated with a poor outcome in acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Impairment of gas exchange and the development of respiratory failure may be precipitated by a variety of factors, one of which is the administration of oxygen at high concentrations. In this group of patients, the administration of high inspired concentrations of oxygen may precipitate worsening of respiratory function, leading to further elevation of arterial carbon dioxide concentration.
Supplemental oxygen therapy in the emergency situation has traditionally been administered using "high‐flow" oxygen. This approach has been adopted on the basis that the population as a whole are at greater risk from failure to correct oxygenation than from its excessive administration. Indeed, people with AECOPD, oxygen driven nebulizers via mask at flows of 6‐8 L/min will often be used to achieve nebulization of bronchodilator. This approach has been brought into question. A recent retrospective study by Denniston et al found that the administration of an inspired oxygen concentration above 28% was associated with a 14% in‐hospital mortality, compared to a 2% in‐hospital mortality for those administered a concentration of oxygen less that 28% (Denniston 2002). This raised questions about the optimal delivery of oxygen to people with COPD in the pre‐hospital setting.
Objectives
To determine the effect of different oxygen therapies in the pre‐hospital setting (prior to casualty/emergency department) on outcome for patients with acute exacerbations of COPD.
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials comparing oxygen therapy at different concentrations or oxygen therapy versus placebo in the pre‐hospital setting for treatment of acute exacerbations of COPD. Other treatment interventions e.g. bronchodilators, corticosteroids should be standardised as far a possible for both intervention arms. Studies of acute asthma will be excluded.
Types of participants
Adults with an acute exacerbation of chronic obstructive pulmonary disease requiring medical or paramedical assistance in the pre‐hospital setting. The definition of an acute exacerbation will include any combination of an increase in breathlessness, sputum volume, sputum purulence, cough or wheeze and common cold symptoms. Subjects will be people with spirometric evidence of airflow obstruction (FEV1/FVC <0.7) plus smoking history of greater than 10 pack history years or use of standard definition e.g. GOLD.
Types of interventions
High fractional inspired oxygen concentration (FIO2) (>28%) oxygen therapy VERSUS placebo or low fractional inspired oxygen concentration (FIO2) (≤ 28%) oxygen therapy
Types of outcome measures
Primary outcome measure:
Mortality from Respiratory Causes
Secondary outcome measures:
All causes mortality
Dyspnoea score
Atrial blood gas measurements (ABG)
Duration of hospitalisation
Admission to ICU
Mental status score
Consciousness score (e.g. GCS)
Invasive ventilation
Non invasive ventilation
Lung function
Illness score e.g.. APACHE
Search methods for identification of studies
The search will be carried out using the Cochrane Airways Group Specialised Register, CENTRAL, MEDLINE, EMBASE and CINAHL. The following search will be used in CENTRAL and adapted for MEDLINE, EMBASE and CINAHL:
#1. PULMONARY DISEASE CHRONIC OBSTRUCTIVE explode tree 1 (MeSH)
#2. (lung* or respirat* or pulmonar* or airway* or airflow*)
#3. BRONCHITIS CHRONIC explode tree 3 (MeSH)
#4. PULMONARY EMPHYSEMA explode tree 1 (MeSH)
#5. (chronic* near obstruct*)
#6. (#2 and #5)
#7. bronchiti*
#8. emphysema*
#9. (copd or coad or cobd)
#10. (#1 or #3 or #4 or #6 or #7 or #8 or #9)
#11. EMERGENCY MEDICAL SERVICES explode tree 1 (MeSH)
#12. emergenc*
#13. emergicent*
#14. emergi‐cent*
#15. prehospital*
#16. pre‐hospital*
#17. hospital*
#18. ambulance*
#19. (patient* near transport*)
#20. EMERGENCY TREATMENT explode tree 1 (MeSH)
#21. first‐aid*
#22. (first next aid*)
#23. (#11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22)
#24. OXYGEN INHALATION THERAPY explode tree 1 (MeSH)
#25. RESPIRATORY THERAPY explode tree 1 (MeSH)
#26. OXYGEN single term (MeSH)
#27. oxygen*
#28. (inhal* near therap*)
#29. (respirat* near therap*)
#30. (nasal next cannula)
#31. (nasal next prong*)
#32. nrm
#33. hudson*
#34. venture*
#35. mask*
#36. (#24 or #25 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33 or #34 or #35)
#37. (#10 and #23 and #36)
All records in the Airways Group Register coded as 'COPD' will be searched with the terms:
(emergenc* or emergicent* or emergi‐cent* or prehospital* or pre‐hospital* or hospital* or ambulance* or (patient* and transport*) or first‐aid* or "first aid*") AND (oxygen* or ((inhal* or respiratory*) and therap*) or "nasal cannula*" or "nasal prong*" or NRM or venture* or Hudson* or mask*)
Reference lists from studies selected by electronic searching will be handsearched to identify other related articles. In addition, members of Cochrane Airways Group and experts in this field will be contacted for further trial and other unpublished materials.
Data collection and analysis
All potentially relevant trials will be assessed by at least two individuals who will independently select trials for inclusion in this review. All trials entered will be scored according to the adequacy of allocation concealment using the following grading system:
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Grade A ‐ Adequate concealment
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Grade B ‐ Unclear concealment
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Grade C ‐ Obviously not adequate concealment
Each study will be assessed using a 0‐5 scale based upon the method described by ( Jadad 1996) and summarised as follows:
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Was the study described as randomised (1= yes; 0= no)?
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Was the study described as being double blind (1= yes; 0= no)?
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Was there a description of withdrawals and dropouts (1= yes; 0= no)?
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Was the method of randomisation well described and appropriate (1= yes; 0= no)?
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Was the method of double blinding well described and appropriate (1= yes; 0= no)?
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Deduct 1 point if methods for randomisation or blinding were inappropriate.
Inter ‐ rater reliability will be measured using simple agreement, kappa and weighted kappa statistics.
In addition, each study will be assessed for the reliability of the diagnosis of COPD using the criteria:
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Was the age of subjects over 45 years?
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Was the smoking history greater than 10 pack years?
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Were subjects with a previous physician diagnosis of asthma excluded?
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Was there evidence of fixed airflow obstruction?
Two members of the review team will independently assess the titles and abstracts of all identified citations. Decisions of the two reviewers will be recorded (order or reject) and then compared. Any disagreements will be resolved by consensus with close attention to the inclusion/exclusion criteria. Two reviewers will evaluate the full text of all potentially eligible papers and make a decision whether to include or exclude each study according to the inclusion and exclusion criteria specified above. Any disagreements will be resolved by consensus with close attention to the inclusion/exclusion criteria. All studies that do not fulfil all of the criteria will be excluded and their bibliographic details listed, with the reason for exclusion. A third reviewer will resolve any discrepancies if the two reviewers disagree.
Data Extraction
Data for the trials will be extracted by one of the reviewers and sent to the authors for verification. For those studies where verification could not be obtained, a second independent reviewer will be used. A third reviewer will resolve any discrepancies if the two reviewers disagree. Bibliographic details such as author, journal, year of publication and language, will be registered. To obtain missing information, we will contact authors of primary studies. All trials will be combined using Review Manager (version 4.2).
Method of Analysis and Synthesis
Forest plots will be used to compare results across the trials.
For continuous variables the results of individual studies willl be combined as fixed effects weighted mean difference (WMD), with 95% confidence intervals (CI). Standardised mean difference (SMD), with 95% confidence intervals (CI) will be used if different scales of measurement had been used for an outcome. The SMD is a statistic which expresses the difference in means between treatment groups in units of the pooled standard deviation. For dichotomous outcomes, the odds ratio (OR) with 95% confidence interval, will be calculated, and compared with the Risk Ratio (RR) and Risk Difference (RD). For time‐to‐event outcomes such as log hazard ratios, the fixed effects generic inverse variance outcome will be used to combine results. This method gives a weighted average of the effect estimates of separate studies (Deek 2004). Number Needed to Treat will be calculated from the pooled Odds Ratio and its confidence interval, using the baseline risk in the control group.
An assessment of possible heterogeneity in which the null hypothesis is that all studies are evaluating the same effect will be carried out for pooled effects using a Breslow‐Day test of heterogeneity and a P value >0.05 considered to indicate significant differences between studies. An approach known as the I2 will be used to describe the percentage of total variation across studies that is due to heterogeneity rather than chance (Higgins 2003). A value >50% may be considered substantial heterogeneity. In the assessment of heterogeneity, possible causes arising from study design will be considered.
Bias
Attempts will be made to obtain data from intention‐to‐treat and per‐protocol populations. Sensitivity analysis will be carried out in relation to study quality.
Funnel plots will be used to investigate publication bias.
