CD 007720

Corticosteroids for pneumonia (Review)
Chen Y, Li K, Pu H, Wu T
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2011, Issue 3 http://www.thecochranelibrary.com
Corticosteroids for pneumonia (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 7. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 8. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 9. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 Hydrocortisone versus placebo, Outcome 1 Mortality. . . . . . . . . . . . . Analysis 1.2. Comparison 1 Hydrocortisone versus placebo, Outcome 2 PaO2 :FIO2 improvement 100 from study entry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.3. Comparison 1 Hydrocortisone versus placebo, Outcome 3 PaO2 :FIO2 . . . . . . . . . . . . Analysis 1.4. Comparison 1 Hydrocortisone versus placebo, Outcome 4 Chest radiograph score. . . . . . . . Analysis 1.5. Comparison 1 Hydrocortisone versus placebo, Outcome 5 Improvement in chest radiograph score from day 1 to day 8. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.6. Comparison 1 Hydrocortisone versus placebo, Outcome 6 On mechanical ventilation. . . . . . . Analysis 1.7. Comparison 1 Hydrocortisone versus placebo, Outcome 7 Length of stay in the ICU. . . . . . . Analysis 2.1. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 1 Death. . . . . . . Analysis 2.2. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 2 Participants require to change the treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.3. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 3 Duration of treatment (number of participants to be treated more than two weeks). . . . . . . . . . . . . . . . . . . Analysis 2.4. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 4 Time to normalisation of spO2 (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.5. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 5 Length of hospital stay (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.6. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 6 Duration of IV antibiotics (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.7. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 7 Time to normalisation of body temperature (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.8. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 8 Time to normalisation of respiratory rate (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.9. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 9 Time to normalisation of C reactive protein (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.10. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 10 Time to normalisation of WBC (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1 1 2 2 3 3 4 7 8 9 11 13 14 15 16 16 17 17 18 18 21 35 37 37 38 38 39 39 40 40 41 42 43 43 44 44 45 45 46
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Analysis 3.1. Comparison 3 Budesonide (Pulmicort) plus antibiotics versus antibiotics only, Outcome 1 Time to clinical symptoms disappearing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.2. Comparison 3 Budesonide (Pulmicort) plus antibiotics versus antibiotics only, Outcome 2 Rate of relapse. Analysis 4.1. Comparison 4 Intravenous dexamethasone versus placebo, Outcome 1 Duration of mechanical ventilation. Analysis 4.2. Comparison 4 Intravenous dexamethasone versus placebo, Outcome 2 Duration of supplemental oxygen. Analysis 4.3. Comparison 4 Intravenous dexamethasone versus placebo, Outcome 3 Length of stay in the paediatric intensive care unit. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.4. Comparison 4 Intravenous dexamethasone versus placebo, Outcome 4 Length of stay in the hospital. . APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .
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[Intervention Review]
Corticosteroids for pneumonia

Yuanjing Chen2 , Ka Li3 , Hongshan Pu4 , Taixiang Wu1
1 Chinese Cochrane Centre, Chinese Clinical Trial Registry, Chinese Evidence-Based Medicine Centre, INCLEN Resource and Training
Centre, West China Hospital, Sichuan University, Chengdu, China. 2 Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China. 3 Department of Surgery III, West China Hospital, Sichuan University, Chengdu, China. 4 West China Hospital, Sichuan University, Chengdu, China Contact address: Taixiang Wu, Chinese Cochrane Centre, Chinese Clinical Trial Registry, Chinese Evidence-Based Medicine Centre, INCLEN Resource and Training Centre, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, 610041, China. txwutx@hotmail.com. Editorial group: Cochrane Acute Respiratory Infections Group. Publication status and date: New, published in Issue 3, 2011. Review content assessed as up-to-date: 30 December 2010. Citation: Chen Y, Li K, Pu H, Wu T. Corticosteroids for pneumonia. Cochrane Database of Systematic Reviews 2011, Issue 3. Art. No.: CD007720. DOI: 10.1002/14651858.CD007720.pub2. Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT Background Pneumonia is an acute inammation of the lungs and treatments differ depending on the type and severity. Corticosteroids can inuence immune regulation, carbohydrate metabolism, protein catabolism, electrolyte balance and stress response. However, the benets of corticosteroids for patients with pneumonia remains unclear. Objectives To assess the efcacy and safety of corticosteroids in the treatment of pneumonia. Search strategy We searched Cochrane Central Register of Controlled Clinical Trials (CENTRAL) (The Cochrane Library 2010, Issue 11) which contains the Cochrane Acute Respiratory Infections Groups Specialised Register, MEDLINE (1966 to December week 4, 2010), EMBASE (1974 to December 2010), the China National Knowledge Infrastructure (CNKI) (1978 to December 2010) and VIP (1986 to December 2010). Selection criteria Randomised controlled trials (RCTs) assessing the effectiveness of corticosteroids for pneumonia. Data collection and analysis Three review authors selected studies. We telephoned the trial authors to conrm the randomisation method used. We extracted and analysed the methodological details and data from the included studies. Main results We included six studies including 437 participants in the review. Two studies were of high methodological quality and three were of poor quality. All studies involved small numbers of participants. Two small studies provided weak evidence that corticosteroids did not signicantly reduce mortality (Peto odds ratio (OR) 0.26; 95% CI 0.05 to 1.37), but accelerated the resolution of symptoms or time to clinical stability, and decreased the rate of relapse of the disease. Steroids can improve the oxygenation and reduce the need for
Corticosteroids for pneumonia (Review) Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 1
mechanical ventilation in severe pneumonia. There was no signicant difference between treatment groups with regards to the time to discharge from the intensive care unit (ICU). There were insufcient data to report the time to pneumonia resolution and admission to ICU. Typical adverse events associated with corticosteroid therapy were infrequent. Authors conclusions In most patients with pneumonia, corticosteroids are generally benecial for accelerating the time to resolution of symptoms. However, evidence from the included studies was not strong enough to make any recommendations.
PLAIN LANGUAGE SUMMARY Corticosteroids for pneumonia Pneumonia is an acute respiratory disease that is usually caused by bacteria but it can also be caused by other infectious agents such as fungi, parasites and viruses. Corticosteroids can act as an anti-inammatory agent for patients with pneumonia but they can adversely suppress the immune system, which prevents the body from ghting the causative pathogens and results in a serious infection. The purpose of this review was to assess whether corticosteroids for pneumonia are benecial. We identied six trials (437 participants) and found that although the effects of corticosteroids vary depending on the type and severity of pneumonia, the overall effect is benecial for most patients. Corticosteroids did not signicantly reduce mortality compared to the placebo group. Arrhythmia, upper gastrointestinal bleeding and malignant hypertension may be related to corticosteroids. The evidence from this review is weak due to limitations of the included studies. Large trials with more patients are needed to provide robust evidence.
BACKGROUND
Description of the condition

Pneumonia is an acute inammation of the lungs caused by pathogens such as bacteria, viruses, mycoplasma, chlamydia, fungi and parasites. It is a common illness worldwide and is a major cause of death among all age groups. Symptoms include cough, sputum production, fever, chills, fatigue, shortness of breath, night sweats and pleuritic chest pain. Other symptoms may include loss of appetite, skin discolouration, nausea, vomiting, mood swings and joint pains or muscle aches (Hoare 2006). Chemotherapy or radiation therapy can also cause non-infective pneumonitis. Pneumonia can be divided into community-acquired pneumonia (CAP), nosocomial (hospital-acquired) pneumonia (HAP) and aspiration pneumonia. CAP is the most common type of pneumonia and occurs when one is infected by pathogens without being recently hospitalized. People of all ages can contract CAP and the most common causative agents are Streptococcus pneumoniae (S. pneumoniae), Mycoplasma pneumoniae (M. pneumoniae), Haemophilus inuenzae (H. inuenzae), viruses and atypical bacteria. The annual incidence of CAP in Europe and North America is 34 to 40 cases per 1000 in children (Ostapchuk 2004), six
per 1000 in the 18 to 59 year old population and 20 to 34 per 1000 in those aged 60 and older. It occurs three to four million times per year in the United States, accounting for about 500,000 hospitalizations annually (Plouffe 1996). Nosocomial pneumonia, also called hospital-acquired pneumonia (HAP), is dened as pneumonia occurring in the rst 48 hours after hospital admission (Leroy 2004). Approximately one-half of HAP cases occur in patients admitted to medical or surgical wards. The remaining episodes occur in patients admitted to intensive care units (ICUs) and are related to mechanical ventilation (Leroy 2004). Individuals with HAP usually have an underlying illness and have been exposed to bacteria, therefore it tends to be more serious than CAP (Gerald 2004). Aspiration pneumonia (or aspiration pneumonitis) comprises a small percentage of community-acquired and hospital-acquired pneumonia. Aspiration pneumonitis occurs rapidly and some cases may be associated with inhalation of a large volume of sterile acidic gastric contents or aspirating other foreign objects.
Description of the intervention

Many patients with pneumonia do not require hospitalization and
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usually recover fully with oral antibiotics, uids and rest. However, older people, people who have difculty in breathing, or those who have severe medical conditions are at greater risk (dEscrivan 2005) and may require corticosteroids (Garcia-Vidal 2007). The natural steroid cortisol is produced by the adrenal glands. Steroids, also known as corticosteroids, are a class of steroid hormones. Synthetic derivatives of the natural steroid include prednisone, prednisolone, methylprednisolone, betamethasone, dexamethasone, triamcinolone and hydrocortisone. It is possible to administer corticosteroids by inhalation, orally or intravenously.
2. Do corticosteroids shorten symptoms in mild pneumonia? 3. Is the occurrence of relative adrenal insufciency a possible rationale for using corticosteroids in pneumonia? 4. Are there any dose-effect relationships between corticosteroids and pneumonia?
METHODS
How the intervention might work

Corticosteroids inuence immune regulation and also effect carbohydrate metabolism, protein catabolism, electrolyte balance and stress response. They are used for treating inammatory diseases of the bowel (colitis), joints (arthritis), skin (dermatitis) and lungs (pneumonia or asthma). Corticosteroids act partly by inducing anti-inammatory genes which repress inammatory genes (Adcock 2000). A retrospective observational study suggests that systemic corticosteroids may reduce mortality in severe CAP cases (Garcia-Vidal 2007). However, corticosteroids have side effects, most of which are related to the dose and duration of therapy (Seale 1986). The side effects only manifest after a long period of high-dose usage and the most common are disturbance of metabolism, immune depression, prolonged healing, growth retardation in children, hirsutism, diabetes, Cushings Syndrome (also called hypercortisolism) and thinning of the bones (osteoporosis), particularly in women during and following menopause. In some cases they can cause emotional disturbances such as depression. Many of the adverse effects only occur over prolonged administration and most short-term adverse events are reversible when the drug is discontinued.
Criteria for considering studies for this review
Types of studies Randomised controlled trials (RCTs) assessing the effectiveness of corticosteroids for pneumonia.
Types of participants Participants of any age or sex with pneumonia. The diagnosis of pneumonia is usually made from taking a medical history, physical examination and a chest X-ray. Occasionally sputum cultures assist diagnosis. Diagnosis can be difcult, especially in HAP and pneumonia of immunocompromised people. Computerised tomography (CT) scanning of the lungs is sometimes used to make the diagnosis (Wipf 1999). We included people with pneumonia associated with chronic obstructive pulmonary disease (COPD) but excluded cases associated with immunosuppression, HIV, tuberculosis, acute schistosomiasis, fungal or parasitic infections, or chemotherapy and radiotherapy-associated lung changes.
Why it is important to do this review

The benets of corticosteroids for severe pneumonia remain unclear, although they are sometimes used in clinical practice. There is therefore a need to systematically review the effectiveness of corticosteroids for pneumonia.
Types of interventions Trials comparing the following. 1. Corticosteroids with antibiotics versus antibiotics alone. 2. Corticosteroids with antibiotics versus corticosteroids of a different dose with antibiotics.
OBJECTIVES
To assess the efcacy and safety of corticosteroids in the treatment of pneumonia. In particular, we aim to answer the following questions. 1. Do corticosteroids reduce mortality and the incidence of pneumonia complications such as severe sepsis or acute respiratory distress syndrome (ARDS) in severe pneumonia? Types of outcome measures
Primary outcomes
1. Mortality.
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Secondary outcomes
Search methods for identication of studies
1. Time to resolution of symptoms or time to clinical stability. Symptoms include fever, cough, positive chest X-ray, elevation of white blood cell count, difculty in breathing, etc. 2. Relapse of pneumonia. 3. Proportion of patients requiring either ventilatory or inotropic support, or both. 4. Rate of admission to intensive care unit (ICU). 5. Time to discharge from ICU. Adverse events Serious adverse events have been dened as any event that leads to death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or signicant disability, and any reported serious event that might jeopardise the patient or require an intervention to prevent it ( ICHEWG 1997). All other adverse events are not considered to be serious.
Electronic searches We searched the Cochrane Central Register of Controlled Clinical Trials (CENTRAL) (The Cochrane Library 2010, Issue 11) which contains the Cochrane Acute Respiratory Infections Groups Specialised Register, MEDLINE (1966 to December, 2010), EMBASE (1974 to December 2010), the China National Knowledge Infrastructure (CNKI) (1978 to December 2010) and VIP (1986 to December 2010). We used the following search strategy to search MEDLINE and CENTRAL. We combined the search strategy with the Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE: sensitivity- and precision-maximising version (2008 revision); Ovid format (Lefebvre 2009). We adapted the search strategy for EMBASE (see Appendix 1), the China National Knowledge Infrastructure and VIP (Figure 1).
Figure 1. Search strategy used in the Chinese databases
MEDLINE (Ovid)
1 exp Pneumonia/ 2 pneumon*.tw. 3 CAP.tw. 4 HAP.tw. 5 Respiratory Distress Syndrome, Adult/ 6 adult respiratory distress syndrome.tw. 7 acute respiratory distress syndrome.tw. 8 ARDS.tw. 9 or/1-8 10 exp Steroids/ 11 steroid*.tw,nm. 12 exp Adrenal Cortex Hormones/ 13 corticosteroid*.tw,nm. 14 prednisone.tw,nm. 15 prednisolone.tw,nm. 16 methylprednisolone.tw,nm. 17 betamethasone.tw,nm. 18 dexamethasone.tw,nm. 19 triamcinolone.tw,nm. 20 hydrocortisone.tw,nm. 21 or/10-20 22 9 and 21 Searching other resources We did not impose any language or publication restrictions. We searched the Chinese Journals Full Text Database (1979 to February 2010), Chinese Journals Full Text Database Century Journals (1979 to February 2010), Chinese Doctoral Degree Thesis Full Text Database (1979 to February 2010), Chinese Outstanding Master Degree Thesis Full Text Database (1979 to February 2010) and WANFANG Database (1993 to February 2010). We searched the WHO ICTRP Search Portal (http:// www.who.int/ictrp/network/en/index.html) for ongoing trials.
cluded those trials which had not developed a research protocol, or in which coin tossing or card shufing was used in the presence of the allocated participants, because there was high risk of selection bias. We recorded the trial ID, name and contact details of trialists, date of query to trialist, method of query (for example, telephone) and response of trialist for each trial, whether it was included or excluded. We recorded all of the information in an additional table.
Data extraction and management Three review authors (YC, KL, HP) independently extracted the methodological details and data from publications. Data for extraction included study title; design; study population size; duration; number of drop-outs, withdrawals and loss to follow up and participants analysed in the different treatment groups; inclusion and exclusion criteria; intervention (route and dosage); and outcomes (Higgins 2009). There was no disagreement among the review authors.
Assessment of risk of bias in included studies We assessed risk of bias using the following criteria described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2009) and Wu 2007, and we graded the quality of evidence using GRADEproler.
Randomisation process
Data collection and analysis
A - adequate sequence generation was reported using one of the following approaches: we considered a random numbers table or computer-generated random numbers; coin tossing; or shufing used for generating the allocation sequence before the trial as having a low risk of selection bias. B - does not specify one of the adequate methods outlined in (A) but only mentions random - we considered this to have a moderate risk of selection bias. C - we excluded other methods of allocation, for example quasirandomisation, that appeared to have a high risk of bias.
Selection of studies Four review authors (YC, KL, HP, TW) undertook the selection of studies. Two review authors (YC, HP) independently scanned the titles and abstracts of all the articles identied by the literature search. The same review authors independently assessed whether the trials met the inclusion criteria. We resolved disagreements by discussion. We contacted trial authors of the original reports to obtain further information if the search results contained insufcient information to make a decision about eligibility. We exAllocation concealment process
A - adequate measures to conceal allocation and the allocation sequences, such as central randomisation, and the use of sealed opaque envelopes - we considered this a low risk for selection bias. B - unclear: concealed allocation where the author does not report the allocation concealment method used - we considered this a moderate risk for selection bias.
C - inadequately-concealed allocation, where an approach was reported that does not fall into one of the categories in (A). D - does not conceal allocation. C and D can be considered as high risks for selection bias.
Dealing with missing data We assessed incomplete outcome data for potential bias from exclusions and attrition. 1. Low risk of bias: trials where few exclusions and attrition are noted and an intention-to-treat (ITT) analysis is possible. 2. Moderate risk of bias: trials which report the rate of exclusion, attrition or both to be about 10%, whatever ITT analysis is used. 3. High risk of bias: the rate of exclusion, attrition or both is higher than 15%, or wide differences in exclusions between groups, whatever ITT analysis is used. Assessment of heterogeneity We assessed clinical and methodological heterogeneity before pooling. If data were similar enough, we carried out an assessment for statistical heterogeneity using the Chi2 test with signicance being set at P < 0.1. We used the I2 statistic to estimate the total variation across studies. An I2 < 40% is not considered important in terms of heterogeneity, 30% to 60% represents moderate heterogeneity, 50% to 90% substantial heterogeneity and 75% to 100% represents considerable heterogeneity (Higgins 2009). Assessment of reporting biases We did not investigate potential publication bias by funnel plot (Egger 1997) due to only a few studies being included, although we assessed reporting bias according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008). 1. No - low risk of reporting bias: all of the outcomes were reported in detail. 2. Probably yes - moderate risk of reporting bias: at least one of the outcomes were mentioned but not in detail. 3. Yes - high risk of reporting bias: at least one of the outcomes were not reported. Data synthesis
Level of blinding
A - double-blinding: participants and results assessor were masked - we considered this a low risk for both performance and detection bias. B - single-blinding of results assessor - we considered this a moderate risk for both performance and detection bias. If single-blinding was performed for participants but not the results assessor, we considered the study as having a high risk of detection bias. C - we considered non-blinding as a high risk for both performance and detection bias. Use of blinding for mortality was not required.
Incomplete outcome data
Low risk of bias - we considered number of drop-outs or loss to follow less than 10% as low risk of bias due to incomplete outcome data. Moderate risk of bias - we considered this to be a rate of drop-out or loss to follow up between 10% and 15%. High risk of bias - number of drop-outs or loss to follow higher than 15%.
Selective reporting bias
We expected to assess selective reporting bias by comparing the protocol and published trial reports. However, we were unable to locate the protocol and so were unable to identify whether reporting bias existed or not.
Other potential sources of bias
We expected to address potential sources of bias, for example, different doses of corticosteroids, length of follow up, and characteristics of participants (for example, age, stage of disease). However, we did not nd any potential sources of bias in the included studies.
We carried out meta-analyses using the Review Manager 5 software program (RevMan 2008). We used a random-effects model for pooled data analysis. We did not combine results of trials with different comparator drugs. Subgroup analysis and investigation of heterogeneity We performed subgroup analyses based on different types of corticosteroids and different comparators (Higgins 2009). Sensitivity analysis We did not perform sensitivity analyses to test the robustness of the evidence because of the small number of included studies. However, we did test the following:
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Measures of treatment effect We expected both dichotomous and continuous data. We analysed different comparisons separately. We used the risk ratio (RR) with 95% condence intervals (CI) and control events rates for reporting dichotomous data. We expressed continuous data as mean differences (MD) with 95% CI.
1. excluded studies with inadequate concealment of allocation; 2. excluded studies in which the outcome evaluation was not blinded; and we 3. compared the difference between pooling analysis results by using a xed-effect model and a random-effects model because robust evidence should not be transposed by changing the effect model.
RESULTS
Description of studies
See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classication. We identied 50 controlled trials. Of these, we excluded 35 trials and 10 trials are awaiting for classication due to difcultly in retrieving the article or contacting the original trial authors. These data will be analysed when we update the review. The remaining six trials involving 437 participants met the inclusion criteria and were included in this review. Results of the search 125 relevant studies appeared in our search. Included studies Participants in the included studies were of any age or sex with pneumonia. Two trials (Cao 2007; van Woensel 2003) mainly focused on children, while the other four (Confalonieri 2005; Marik 1993; McHardy 1972; Mikami 2007) focused on adults or the elderly. One study was conducted in China (Cao 2007) with 120 children aged from three months to 14 years infected by M. pneumoniae. They were divided into four groups: 30 in the control group, 30 in the budesonide (Pulmicort) group, 30 in the clarityne (Loratadine tablets) group, and 30 in the thymosin or transfer factor (TF) injection group. The Confalonieri 2005 study involved 48 participants: 24 in the hydrocortisone infusion group and 24 in the placebo group. There were 30 patients in the Marik 1993 study: 14 in the hydrocortisone group and 16 in the placebo group. One hundred and twenty six participants were included in McHardy 1972 and were divided to four groups: 43 in group 1, 20 in group 2, 43 in group 3 and 20 in group 4. The Mikami 2007 study involved 31 patients: 15 received prednisolone intravenously for three days and 16 in the control group did not receive prednisolone. There were 82 participants in the van Woensel 2003 study: 37 in the steroid group (including 18 participants with bronchiolitis
and 17 with pneumonia) and 45 in the control group (including 21 participants with bronchiolitis and 22 with pneumonia). In all trials, the interventions were antibiotics with corticosteroids versus antibiotics with placebo or antibiotics alone. The corticosteroids included hydrocortisone (Confalonieri 2005; Marik 1993), prednisolone (McHardy 1972; Mikami 2007), budesonide (Cao 2007) and dexamethasone (van Woensel 2003). In Confalonieri 2005, hydrocortisone was given as an intravenous 200 mg loading bolus followed by an infusion (hydrocortisone 240 mg in 500 cc 0.9% saline) at a rate of 10 mg/hour for seven days and protocol-guided antibiotic treatment. In Marik 1993, the participants of the treatment group received 10 mg/kg of hydrocortisone intravenously 30 minutes prior to starting antibiotic therapy. In McHardy 1972, group 1 and group 3 received 1 g ampicillin daily and 2 g ampicillin daily, respectively; group 2 received 1 g ampicillin plus 20 mg prednisolone and group 4 received 2 g ampicillin plus 20 mg prednisolone, respectively. In Mikami 2007, the corticosteroids group received 40 mg of prednisolone intravenously for three days plus intravenous antibiotics within eight hours of hospital admission. This was then modied, based on culture results. In some of the studies, treatment of pneumonia with corticosteroids was just one part of the trial. In the study by Cao 2007 for example, the control group were given azithromycin or erythromycin for seven days, and in the budesonide (Pulmicort) group the participants also had budesonide (Pulmicort) inhalation 250 to 500 g/day for seven days in the control group. The study aimed to compare the effectiveness of budesonide and azithromycin and erythromycin for M. pneumonia in children. We only focused on the results of the effectiveness of budesonide. The van Woensel 2003 study looked at the effectiveness of corticosteroids for pneumonia and bronchiolitis. The trial medication was intravenous dexamethasone (0.15 mg/kg six-hourly for 48 hours) or placebo and had to have been started within 24 hours of mechanical ventilation. These trials mainly measured improvements in oxygenation (Confalonieri 2005), time to resolution of symptoms or time to clinical stability (Cao 2007; Confalonieri 2005; Mikami 2007) and the length of hospital stay or ICU stay (Marik 1993; Mikami 2007; van Woensel 2003). One study measured mortality (Marik 1993). The outcomes of each trial are noted in the Characteristics of included studies table.
Excluded studies Most of the excluded studies were retrospective. Some did not use random allocation and were excluded because the trial author refused to give details of the study. The reasons for exclusion can be found in the Characteristics of excluded studies table.
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Risk of bias in included studies

Two studies were of higher quality (Confalonieri 2005; van Woensel 2003) and four were of poorer quality (Cao 2007; Marik 1993; McHardy 1972; Mikami 2007). The summary of quality assessment can be found in Figure 2 and Figure 3. Figure 2. Risk of bias graph: review authors judgements about each risk of bias item presented as percentages across all included studies.
Figure 3. Risk of bias summary: review authors judgements about each risk of bias item for each included study.
Allocation All of the participants were randomly allocated. Randomisation methods for two studies (Confalonieri 2005; van Woensel 2003) involved generation in blocks of 10 for each participating site by a randomisation centre. The Cao 2007 study did not provide any information about the method of randomisation. We telephoned Dr. Cao who told us that the allocation sequence was generated by computer but we still judged the randomisation method as unclear and the allocation procedure was not concealed because the author mentioned that the participants were selected by sampling from
the in-patients. In Marik 1993, participants were randomized by a random number generator to receive either hydrocortisone or placebo. In McHardy 1972, the method of generating and concealing the allocation sequence was not mentioned. In Mikami 2007, the study did not reveal the details of the method of randomisation, it just mentioned that they divided the participants randomly but the allocation concealment in this trial was well done, because the investigators were not actively involved in the treatment of the participants and the physicians who took care of the participants were not informed of the outcome parameters.
In fact, most of the included trials performed adequate allocation concealment, either by sealed envelopes (Cao 2007; Confalonieri 2005) or by keeping the concealed randomisation list in a separate location (van Woensel 2003). However, in the trial by Marik 1993, allocation concealment was not clearly stated. Blinding There was no blinding in McHardy 1972 and Mikami 2007 as they were open-label trials. In Cao 2007, blinding was not clearly stated in the article, so we contacted the trial author and discovered that it was a single-blinded trial, because the doctor knew the treatment assignment while the participants did not. The other trials are double-blinded, placebo-controlled studies. Incomplete outcome data Incomplete outcome data was clearly stated in the included studies if they had drop-outs or losses to follow up (Confalonieri 2005; van Woensel 2003). There was no risk of attrition bias for the other four studies.
Improvement in oxygenation There are several ways to measure oxygenation, including as partial pressure of oxygen in arterial blood (PaO2 ), inspired oxygen concentration (FIO2 ) and saturation of blood oxygen (SpO2 ). In Confalonieri 2005, participants receiving hydrocortisone displayed signicantly greater improvement in PaO2 : FIO2 compared with placebo (mean difference (MD) 95.00; 95% CI 45.17 to 144.83) (Analysis 1.3) and signicantly more participants had PaO2 : FIO2 improvement 100 from study entry (RR 2.50, 95% CI 1.40 to 4.47) (Analysis 1.2). In Mikami 2007, the trialists detected the days to normalisation of SpO2 . However, participants receiving prednisolone did not display signicantly faster normalisation of SpO2 (MD -2.10; 95% CI -4.43 to 0.23) (Analysis 2.4).
Time to pneumonia resolution There were no reports of time to pneumonia resolution.
Time to resolution of symptoms or time to clinical stability Resolution of symptoms and clinical stability can be calculated as improvement in chest radiograph and normalisation of body temperature, respiratory rate, white blood cell (WBC) and C reactive protein. In Confalonieri 2005, participants receiving prednisolone displayed signicantly lower chest radiograph scores (MD -1.50; 95% CI -2.10 to -0.90) and signicantly higher improvement in chest radiograph scores from day 1 to day 8 (RR 4.20; 95% CI 1.91 to 9.21) (Analysis 1.4, Analysis 1.5). In McHardy 1972 the duration of treatment, change of treatment, resolution of temperature, clearance of pathogens from sputum or laryngeal swabs and maximum radiological clearance were reported. None of the outcomes identied important differences between ampicillin groups and ampicillin plus prednisolone groups (Analysis 2.2 and Analysis 2.3). In Mikami 2007, participants receiving prednisolone showed faster normalisation of body temperature (MD -3.60; 95% CI 6.28 to -0.92) (Analysis 2.7), respiratory rate (MD -3.40; 95% CI -5.52 to -1.28) (Analysis 2.8) and normalisation of C reactive protein (MD -4.10; 95% CI -7.15 to -1.05) (Analysis 2.9) compared to the placebo group. There was no signicant difference between prednisolone and placebo in terms of WBC (MD 2.00; 95% CI 0.61 to 4.61) (Analysis 2.10). The Cao 2007 study showed clinical symptoms disappearing faster in the budesonide treatment group than in the control group (MD -8.00; 95% CI -9.25 to -6.75) (Analysis 3.1).
Selective reporting There was no evidence of selective reporting. Other potential sources of bias This was not clearly stated in the included studies.
Effects of interventions
We collected data on the basis of corticosteroid treatment plus antibiotic therapy or antibiotics only. The corticosteroid treatment included hydrocortisone, prednisolone, budesonide and dexamethasone. The baseline characteristics were clearly stated in the studies and the groups were comparable with regards to sex and age distribution and severity of the disease, except for Cao 2007 and van Woensel 2003. In Cao 2007, there were 32 more boys than girls. In van Woensel 2003 the proportion of males was higher and patients were signicantly younger in the dexamethasone group than in the placebo group. Mortality In three studies participants receiving hydrocortisone or prednisolone displayed no statistically signicant differences compared with placebo (Peto odds ratio (OR) 0.26; 95% CI 0.05 to 1.37; and Peto OR1.41, 95% CI 0.39 to 5.04, respectively). One participant died in the hydrocortisone group and ve in the control group (Confalonieri 2005; Marik 1993) (Analysis 1.1), nine died in ampicillin alone groups and three in ampicillin plus prednisolone groups, respectively (McHardy 1972) (Analysis 2.1).
Relapse of the disease In Cao 2007, participants receiving budesonide showed a lower rate of relapse (MD -2.43; 95% CI -2.79 to -2.07) compared with the comparison group (Analysis 3.2).
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Proportion of patients requiring either ventilatory or inotropic support, or both Participants receiving hydrocortisone in two trials (Confalonieri 2005; Marik 1993) displayed less need for mechanical ventilation (RR 0.43; 95% CI 0.22 to 0.85) than participants receiving placebo (Analysis 1.6). In van Woensel 2003 the dexamethasone group had signicantly longer mechanical ventilation (MD 0.80; 95% CI 0.15 to 1.45) and duration of supplemental oxygen (MD 1.70; 95% CI 0.75 to 2.65) compared to the placebo group (Analysis 4.1 and Analysis 4.2). Rate of admission to intensive care unit (ICU) There were no reports of admissions to ICU. Time to discharge from ICU In Marik 1993, participants receiving hydrocortisone displayed no difference in length of stay in the ICU (MD -0.30; 95% CI 3.81 to 3.21) compared to the placebo group (Analysis 1.7). In van Woensel 2003 there was no difference between the dexamethasone group and the placebo group in terms of length of stay in the pediatric ICU (MD 0.20; 95% CI -0.50 to 0.90) (Analysis 4.3). Adverse events Arrhythmia (one case) and upper gastrointestinal bleeding (one case) were reported in Confalonieri 2005. One participant developed malignant hypertension three days after medication (van Woensel 2003). No other severe adverse events were reported.
DISCUSSION
Summary of main results

In statistical terms, corticosteroids did not signicantly reduce mortality in participants with pneumonia. However, there was obvious clinical value: in two small studies (Confalonieri 2005; Marik 1993) one participant the corticosteroid group died compared to ve deaths in the placebo group. Corticosteroids can accelerate the resolution of symptoms and clinical stability and reduce relapse rates of the disease. Improvement in oxygenation, need for ventilatory or inotropic support and time to discharge from the intensive care unit (ICU) differed between the studies, therefore subgroup analyses were necessary. There were no data, or insufcient data, to examine the time to pneumonia resolution and rate of admission to ICU. Typical adverse events associated with corticosteroid therapy were infrequent. The use of corticosteroids showed signicantly better oxygenation in terms of PaO2 :FIO2 and PaO2 , FIO2 improved in the
Confalonieri 2005 trial but it did not coincide with an improvement of SpO2 in the Mikami 2007 study. These differences can be attributed to the participants in these two studies: the Mikami 2007 study excluded severe and septic cases, while Confalonieri 2005 study participants had severe community-acquired pneumonia (CAP). In mild pneumonia the decrease in oxygenation is not obvious, thus improvement associated with corticosteroid use can be subtle in these cases. As a result, with respect to oxygenation, corticosteroids are only benecial for severe pneumonia. We should note that although the PaO2 and FIO2 appeared to be statistically signicantly better compared to receiving hydrocortisone with placebo (mean difference (MD) 95.00; 95% CI 45.17 to 144.83) its clinical importance is still doubtful. In Confalonieri 2005 and Marik 1993, the application of hydrocortisone also reduced the need for mechanical ventilation and length of stay in the ICU, while in van Woensel 2003 the need for mechanical ventilation and supplemental oxygen increased, as did the length of stay in ICU after using dexamethasone. Although the three studies focused on participants with severe pneumonia, the difference was that participants in the van Woensel 2003 study were respiratory syncytial virus (RSV) infected children, including both the bronchiolitis and pneumonia subgroups. RSV is a common cause of lower respiratory tract infection in infants and children. The results of the van Woensel 2003 trial showed that corticosteroids beneted the bronchiolitis subgroup only. In other participants with severe pneumonia, the reduced need for mechanical ventilation was related to oxygenation improvement and inammation relief from corticosteroids (Confalonieri 2005; Marik 1993). In Cao 2007, the main focus was M. pneumoniae in children; it detected the duration of clinical symptoms and the rate of relapse. The results of this study showed that the a corticosteroid (budesonide) can decrease the duration of clinical symptoms and the rate of relapse. Mycoplasma pneumoniae (M. pneumoniae) infection is a common cause of pneumonia, especially in children, accounting for 10% to 40% of all pneumonia in children and it is characterized by a long clinical course and repeated infection (Esposito 2001). M. pneumoniae is a superantigen which can activate the macrophages and induce secretion of cytokine, so the inammation response is intense. Corticosteroids can act as an anti-inammatory agent for children with M. pneumoniae. We would have liked to have answered three important questions: 1. whether the incidence of complications of pneumonia (such as severe sepsis or acute respiratory distress syndrome (ARDS)) could be reduced by corticosteroids; 2. whether the occurrence of relative adrenal insufciency is a possible rationale for using corticosteroids in pneumonia; and 3. whether there are any dose-effect relationships between corticosteroids and pneumonia?
Overall completeness and applicability of

11
evidence
On the whole, corticosteroids can improve clinical symptoms and reduce the rate of relapse of mild pneumonia. In severe pneumonia corticosteroids can improve oxygenation and clinical symptoms and reduce mechanical ventilation and length of stay in ICU. Further trials would help clarify the validity of the ndings of this review and could determine more clearly the role of corticosteroids in patients with pneumonia in comparison with other therapies.
Quality of the evidence
In general, the quality of the evidence is still weak (Figure 4; Figure 5; Figure 6; Figure 7; Figure 8; Figure 9) due to the fact that the results were taken from small, single studies. We collected the information by telephoning trial authors rather than relying on published articles. In addition, the blinding procedures were not adequate (Cao 2007). The Mikami 2007 study was an open-label study and the detailed method of randomisation was not clearly stated. Allocation concealment was not clear in Marik 1993 so there is also a risk of selection bias. The two other higher quality studies included only small numbers of participants (Confalonieri 2005; van Woensel 2003).
12
Figure 4.
13
Figure 5.
14
Figure 6.
15
Figure 7.
Figure 8.
16
Figure 9.
Potential biases in the review process

Some of the trials that we encountered claimed to be randomized controlled trials. We contacted the trial authors and found out that many of the studies were either retrospective or incorrect in their method of randomisation. We allocated studies where we could not contact the trial author or we could not nd the full text to Studies awaiting classication.
AUTHORS CONCLUSIONS Implications for practice

In patients with pneumonia, corticosteroids may relieve symptoms but the evidence is weak. In severe pneumonia, corticosteroids can also be used to improve oxygenation and reduce the use of mechanical ventilation. However, there is insufcient evidence to conrm whether they can reduce mortality and resolve pneumonia. We do not recommend the use of steroids for respiratory syncytial virus-infected children with pneumonia because there is no signicant benet for the patient. However, we do recommend corticosteroids for M. pneumoniae infected children because corticosteroids can signicantly relieve clinical symptoms and prevent relapse of the disease. Our included studies did not compare the effects of different doses of corticosteroids and so we are unable to make any recommendations with regards to the dosage of corticosteroids in clinical practice. Due to the limitations of the included
Agreements and disagreements with other studies or reviews

We were unable to nd other reviews or meta-analyses of corticosteroids for pneumonia, but a review of corticosteroid therapy for sepsis and related syndromes (Annane 2009) found that prolonged low-dose corticosteroid therapy could have a benecial effect on short-term mortality.
17
studies and the review process, the quality of evidence is low.
prolonged low-dose corticosteroid therapy can benet mortality or not.
Implications for research

More large clinical trials of corticosteroids for pneumonia are needed to enhance the body of evidence. These trials need to be designed for patients with severe pneumonia and patients with mild pneumonia, and children and adults, covering the different causes of pneumonia. We encourage trialists to measure changes in pneumonia resolution, symptom relief, oxygenation, length of stay in ICU and rate of admission to ICU. In the meantime, more data concerning adverse events need to be reported to guide our application of corticosteroids. Future studies should explore whether the occurrence of relative adrenal insufciency is a possible rationale for using corticosteroids in pneumonia or not, and whether
ACKNOWLEDGEMENTS
The review authors wish to thank Elizabeth Dooley (Managing Editor), Clare Dooley (Assistant Managing Editor) and Sarah Thorning (Trials Search Co-ordinator) of the Cochrane ARI Group. We would also like to thank the following people for commenting on the draft protocol: Anne Lyddiatt, Chanpen Choprapawon, Marco Confalonieri, Sree Nair and Allen Cheng; and Amanda Young, Marco Confalonieri, Robert Ware and Allen Cheng for commenting on the draft review.
REFERENCES
References to studies included in this review

Cao 2007 {published data only} Cao LF, Lu YM, Ma HG, Ma M. Budesonide inhaling auxiliary therapy after mycoplasma pneumoniae infection of children. International Journal of Respiration 2007;27(8):5679. Confalonieri 2005 {published data only} Confalonieri M, Urbino R, Potena A, Piattella M, Parigi P, Puccio G. Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomised study. American Journal of Respiratory and Critical Care Medicine 2005;171(3):2428. Marik 1993 {published data only} Marik P, Kraus P, Sribante J, Havlik I, Lipman J, Johnson DW. Hydrocortisone and tumour necrosis factor in severe communityacquired pneumonia. A randomised controlled study. Chest 1993; 104(2):38992. McHardy 1972 {published data only} McHardy VU, Schonell ME. Ampicillin dosage and use of prednisolone in treatment of pneumonia: co-operative controlled trial. British Medical Journal 1972;4(5840):56973. Mikami 2007 {published data only} Mikami K, Suzuki M, Kitagawa H, Kawakami M, Hirota N, Yamaguchi H. Efcacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalisation. Lung 2007;185(5):24955. van Woensel 2003 {published data only} van Woensel JB, van Aalderen WM, de Weerd W, Jansen NJ. Dexamethasone for treatment of patients mechanically ventilated for lower respiratory tract infection caused by respiratory syncytial virus. Thorax 2003;58(5):3837.
Cai 2007 {published data only} Cai JP, Chu JX. Clinical efciency of combivent combined with pulmicortin for treating children with broncho-pneumonia. Chinese Journal of Coal Industry Medicine 2007;10(7):764. Chen 2006 {published data only} Chen JY, Li SH, Chen YP, Zhang GL. A clinical observation of pulse methylprednisolone therapy on severe measles pneumonia in children. Chinese Pediatric Emergency Medicine 2006;13(6):5201. Chen 2006b {published data only} Chen SP. Observation of the effect of low-dose heparin atomisation inhalation for child pneumonia. Youjiang Medical 2006;34(2):151. Chen 2007 {published data only} Chen YL. The observation of the effect of ambroxol-assisted in treating infantile bronchial pneumonia. Modern Journal of Integrated Traditional Chinese and Western Medicine 2007;16(20): 2855. Chu 2009 {published data only} Chu WH, Wang L, Peng S. 34 cases of azithromycin combined with corticosteroids treating severe pneumonia in children. Chinese Journal of Practical Medicine 2009;36(3):83. Dai 2009 {published data only} Dai LJ. Therapeutic observation of large dose of methylprednisolone on severe pneumonia with pulmonary brosis. Heilongjiang Medical Science 2009;32(3):54. Fang 2003 {published data only} Fang F, Jiang QQ, Guo LF, Wang JY, Wei HX. Inhalation dexamethasone on course of pneumonia with coxsackie virus B infection. Journal of Chinese General Practice 2003;2:434. Feng 2001 {published data only} Feng L. 40 cases of ultrasonic spray treatment of ribavirin plus dexamethasone for pneumonia in infants. Chinese Medical Journal 2001;2(10):911. Finch 2002 {published data only} Finch R, Schurmann D, Collins O, Kubin R, McGivern J. Randomized controlled trial of sequential intravenous (i.v.) and oral
18
References to studies excluded from this review

Bai 2003 {published data only} Bai JP, Hua T, Xu BY, Chen JW, Liu SZ, Lin ZB. 105 cases of Pulmicort repulse for pneumonia. Journal of Applied Clinical Pediatrics 2003;18(3):2178.
moxioxacin compared with sequential i.v. and oral co-amoxiclav with or without clarithromycin in patients with communityacquired pneumonia requiring initial parenteral treatment. Antimicrobial Agents and Chemotherapy 2002;46(6):174654. Guan 2004 {published data only} Guan XP. Atomization inhalation of budisonide for pneumonia in children. Chinese Contemporary Medical Science 2004;3(5):26. Han 2003 {published data only} Han SH, Peng RA, Li SZ. The clinical observation of hydrocortisone combined with erythromycin in treating mycoplasma pneumonia. Metallurgical Industry of China Journal of Medicine 2003;20(2):103. Han 2007 {published data only} Han MZ. The clinical treatment and observation of budesonide inhalation compression on infantile pneumonia breathing. Journal of Practical Medical Techniques 2007;14(33):46556. He 2008 {published data only} He WX, Lian QP, Gao L, Niu GP. Observation on effect of tanreqing injection ultrasonic atomising inhalation therapy in children with acute pneumonia. Guide of Chinese Medicine 2008;6 (4):1101. Hong 2005 {published data only} Hong SX, Wang RQ, Zuo ZQ. Observation on effect of budesonide inhalation suspension nebulization to treat 59 cases of neonatal pneumonia. Theory and Practice of Medicine 2005;18(3):3234. Huang 2008 {published data only} Huang ZM, Yang ZK, Zhou M, Gong F, Zhang L. The application of budesonide in pneumonia of newborns. Chinese Modern Doctor 2008;46(16):134. Li 2006 {published data only} Li CE. Nursing and observation on effect of budesonide inhalation suspension nebulization to treat 29 cases of preterm infants pneumonia. Medicine World 2006;11:245. Marks 1972 {published data only} Marks MI, Chicoine L, Legere G, Hillman E. Adrenocorticosteroid treatment of hydrocarbon pneumonia in children - a cooperative study. Journal of Pediatrics 1972;81(2):3669. Mer 1998 {published data only} Mer M, Richards GA. Corticosteroids in life-threatening varicella pneumonia. Chest 1998;114(2):42631. Song 2005 {published data only} Song WH, Jiang WS, Huang XS, Huang J. The observation of effect of Pulmicort inhalation in treating children with asthmatic pneumonia. Journal of Clinical Pulmonary 2005;10(5):6323. Song 2008 {published data only} Song X, Wu CQ. Mucosolvan adjuvant treatment of inhalation pneumonia in infants and young children. Journal of Hangzhou Teachers College (Medical Edition) 2008;28(6):4057. Sun 2006 {published data only} Sun LH, Jiang XM, Kong CX. Ultrasonic spray treatment of neonatal pneumonia and nursing clinical observation. Contemporary Nurse 2006;5:612.
Tao 2008 {published data only} Tao F, Wang J, Zhang QF. Low doses of glucocorticoid in the assistance treatment of mycoplasmal pneumoniae lobar pneumonia in children. Journal of Tianjin Medical University 2008;14(2):334. Wang 2007 {published data only} Wang CP, Fang J, Liu YH, Wang HB. Methylprednisolone combined with high dose intravenous gamma globulin treatment of severe asthmatic pneumonia. Journal Gannan Medical University 2007;27(6):8501. Wong 2006 {published data only} Wong XY, Lin CW, Deng MH. The clinical observation of Mucosolvan intravenous treatment of infantile bronchopneumonia. Chinas Maternal and Child Health 2006;21(14):20101. Wu 2007 {published data only} Wu HT, Li JC. Hydrocortisone treatment of 44 cases of epidemic asthmatic pneumonia. Modern Journal of Integrated Traditional Chinese and Western Medicine 2007;16(25):3705. Wu 2009 {published data only} Wu CX. Auxilliary therapy of atomization inhalation of Pulmicort repulse for Mycoplasma pneumonia in children. Zhejiang Journal of Integrative Traditional Chinese and Western Medicine 2009;19(1): 112. Xie 2005 {published data only} Xie HN, Zhang DF. Clinical observation on the therapeutic effect of methylprednisolone on babies with pneumonia. China Tropical Medicine 2005;5(5):9641013. Zhang 2004 {published data only} Zhang YZ, Shi YX. Observation on effect of budesonide inhalation suspension nebulization to treat 39 cases of neonatal pneumonia. Theory and Practice of Medicine 2004;17(10):118990. Zhao 2008 {published data only} Zhao J. The nursing role of compressed air pumps adrenaline inhalation combined with dexamethasone on neonatal infectious pneumonia. Chinese Foreign Medical Treatment 2008;26:1167. Zheng 2008 {published and unpublished data} Zheng L, Huang LL, Zhang JF. Atomization inhalation of Mucosolvan, terbutalin and Pulmicort repulse. Modern Journal of Integrated Traditional Chinese and Western Medicine 2008;17(23): 36989.
References to studies awaiting assessment

Braun 1986 {published data only} Braun SR, Levin AB, Clark KL. Role of corticosteroids in the development of pneumonia in mechanically ventilated head-trauma victims. Critical Care Medicine 1986;14(3):198201. Chen 2003 {published data only} Chen lY. Supplementary therapy of inhalation of oxygen-driven neonatal pneumonia infection. Chinese Journal of Primary Medicine and Pharmacy 2003;10(12):37. Confalnonier 2006 {published data only} Confalonieri M, Trevisan R. Prolonged infusion of hydrocortisone in patients with severe community acquired pneumonia. Recent Progress in Medicine 2006;97(1):326.
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Dambrava 2006 {published data only} Dambrava P, Penarroja G, Aldabo I, Cano E. Are corticosteroids useful in community acquired pneumonia?. European Respiratory Journal 2006;28:531. Hatakeyama 1995 {published data only} Hatakeyama S, Tachibana A, Suzuki K, Okano H. Treatment of aspiration pneumonia with low-dose methylprednisolone and antibiotics. Japanese Journal of Thoracic Diseases 1998;33(1):516. Lee 1980 {published data only} Lee M, Sukumaran M, Berger HW, Reilly TA. Inuence of corticosteroid treatment on pulmonary function after recovery from aspiration of gastric contents. Mount Sinai Journal of Medicine 1980;47(4):3416. Li 2005 {published data only} Li Zhongdong. Treatment of 68 cases of pneumonia in children with atomization inhalation of Pulmicort repulse. Chengdu Medical Journal 2005;31(1):12. Li 2007 {published data only} Li JH. Clinical observation of atomization inhalation of Pulmicort repulse for bronchopneumonia in children. Journal of Shanxi Medical College for Continuing Education 2007;17(2):401. Liu 2008 {published data only} Liu L, Qiao HM, Zhang YF, Cheng HJ, Lu JR, Li YB. Clinical observation of adjuvant Pulmicort repulse for mycoplasma pneumonia in children. Maternal and Child Health Care of China 2008;23(13):18279. Lv 1991 {published data only} Lv A, Yan B. Treatment of 22 cases of pneumonia in children with auxiliary therapy of dexamethasone. Academic Journal of Weifang Medical College 1991;13(2):1389. Ma 2006 {published data only} Ma HG, Cao LF, Lu YM, Ma M. Observation on effect of budesonide suspension to adjuvant treat children with Mycoplasma pneumoniae infection. Journal of Clinical Pediatrics 2006;24(5): 4157. Soboleva 2000 {published data only} Soboleva LR, Laskin GM, Kyzyayv AI, Soboleva LG. Effectiveness of corticosteroid in patients with uncomplicated communityacquired pneumonia. European Respiratory Journal 2000;16(Suppl 31):140. Wang 2008 {published data only} Wang Y, Zhu Y, Zhang X, Zhao W. The clinical observation of short-term low-dose glucocorticoid in treating mycoplasma pneumonia. Chinas Maternal and Child Health 2008;23:4924.
dEscrivan 2005 dEscrivan T, Guery B. Prevention and treatment of aspiration pneumonia in intensive care units. Treatments in Respiratory Medicine 2005;4(5):31724. Egger 1997 Egger M, Davey Smith G, Schneider M, Minder C. Bias in metaanalysis detected by a simple graphical test. BMJ 1997;315:62934. Esposito 2001 Esposito S, Principi N. Asthma in children: are chlamydia or mycoplasma involved?. Paediatric Drug 2001;3:15968. Garcia-Vidal 2007 Garcia-Vidal C, Calbo E, Pascual V, Ferrer C, Quintana S, Garau J. Effects of systemic steroids in patients with severe communityacquired pneumonia. European Respiratory Journal 2007;30(5): 9516. Gerald 2004 Gerald L, Mandell JE, Bennett DR. Mandells Principles and Practices of Infection Diseases. 6th Edition. Vol. 4016, Churchill Livingstone, 2004. Higgins 2009 Higgins JPT, Altman DG. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 [updated September 2009]. The Cochrane Collaboration (available from www.cochrane-handbook.org). Chichester, UK: John Wiley & Sons, Ltd, 2009. Hoare 2006 Hoare Z, Lim WS. Pneumonia: update on diagnosis and management. BMJ 2006;332:3. ICHEWG 1997 International Conference on Harmonisation Expert Working Group. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonised tripartite guideline. Guideline for good clinical practice. 1997 CFR & ICH Guidelines. 1st Edition. Vol. 1, PA, USA: Barnett International/PAREXEL, 1997. Lefebvre 2009 Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 [updated February 2009], The Cochrane Collaboration Available from www.cochranehandbook.org. Leroy 2004 Leroy O, Soubrier S. Hospital-acquired pneumonia: risk factors, clinical features, management, and antibiotic resistance. Infectious Diseases 2004;10(3):1715. Ostapchuk 2004 Ostapchuk M, Roberts DM, Haddy R. Community-acquired pneumonia in infants and children. American Family Physician 2004;70(5):899908. Plouffe 1996 Plouffe JF, Herbert MT, File TM Jr, Baird I, Parsons JN, Kahn JB, et al.Ooxacin versus standard therapy in treatment of communityacquired pneumonia requiring hospitalization. Antimicrobial Agents and Chemotherapy 1996;40(5):11759.
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Additional references
Adcock 2000 Adcock IM, Ito K. Molecular mechanisms of corticosteroid actions. Monaldi Archives for Chest Disease 2000;256(3):66. Annane 2009 Annane D, Bellissant E, Bollaert PE, Briegel J, Confalonieri M, Gaudio RD, et al.Corticosteroids in the treatment of severe sepsis and septic shock in adults. JAMA 2009;301(22):236275.
RevMan 2008 The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008. Seale 1986 Seale JP, Compton MR. Side-effects of corticosteroid agents. Medical Journal of Australia 1986;144(3):13942. Wipf 1999 Wipf JE, Lipsky BA, Hirschmann JV, Boyko EJ, Takasugi J, Peugeot RL, et al.Diagnosing pneumonia by physical examination: relevant or relic?. Archives of Internal Medicine 1999;159(10):10827. Wu 2007 Wu T, Liu G. The concepts, design, practice and report of allocation concealment and blinding. Chinese Journal of EvidenceBased Medicine 2007;7(3):2037. Indicates the major publication for the study
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CHARACTERISTICS OF STUDIES Characteristics of included studies [ordered by study ID]

Cao 2007 Methods Design: randomized controlled trial Method of randomisation: adequate. Randomisation numbers were generated by computer Concealment of allocation: adequate. The randomisation numbers were sealed in envelopes Outcome assessor blinding: unclear Withdrawals/drop-outs: all participants accounted for Country: China Eligible: not clearly stated in the article Randomised: 120 (30 in control group, 30 in budesonide (Pulmicort) group, 30 in clarityne (loratadine tablets) group, 30 in thymosin or Transfer Factor injection) Completed: 120 Age: from 3 months to 14 years old. The detail of the age proportion in each group was not stated in the article Sex: 76 males and 44 females in the study, but the detail of the sex proportion in each group was not stated in the article Diagnosis: not clearly stated in the article Control group: azithromycin or erythromycin Budesonide (Pulmicort): azithromycin or erythromycin as control group plus budesonide (Pulmicort) inhalation 250 to 500 g/d for 7 days Clarityne group: azithromycin or erythromycin as control group plus oral clarityne (loratadine tablets) for 1 month Thymosin or Transfer Factor injection: thymosin 5 mg or Transfer Factor 1 U per time, twice a week for 1 month The period until clinical symptoms resolved The frequency of recurrent respiratory tract infections The level of serum eosinophil cationic protein (ECP), eosinophils (EOS), interleukin-4 (IL- 4) and total immunoglobulin E (T- IgE) In the article there was no description about the randomisation method. We telephoned the author and were told that the allocation sequence was generated by computer and the randomized numbers were sealed in envelopes. The assignment of the treatment for each participant was done by opening the envelopes
Participants
Interventions
Outcomes
Notes
Risk of bias Item Adequate sequence generation? Authors judgement Unclear Description Randomisation method was not mentioned in the article Not mentioned in the article
22
Allocation concealment?
No
Cao 2007
(Continued)
Blinding? All outcomes
No
Not stated clearly in the text. We contacted the author who told us it was single-blinded because the doctor knew the assignment of the treatment No missing data in the study
Incomplete outcome data addressed? All outcomes Free of selective reporting? Free of other bias?
Yes
Unclear No
Not described Not clearly stated in the article
Confalonieri 2005 Methods Design: randomized, double-blind, placebo-controlled trial Method of randomisation: adequate. Randomisation schemes were generated in blocks of 10 for each participating site by a central randomisation centre Concealment of allocation: adequate. The randomisation assignment was given to the recruiting centre in sealed envelopes Outcome assessor blinding: yes Withdrawals/drop-outs: all participants accounted for, apart from 2 participants who met the exclusion criteria after randomisation Eligible: assessed 121 for eligibility, 52 met eligibility criteria and 48 participants consented to the study Randomised: 48 (24 in hydrocortisone infusion group, 24 in placebo group) Completed: 46 (23 in hydrocortisone infusion group, 23 in placebo group) Age: hydrocortisone infusion group: 60.4 ( 17.3), placebo group: 66.6 ( 14.7) Sex (male): hydrocortisone infusion group: 15, placebo group: 17 Diagnosis: clinical and radiographic evidence of pneumonia Hydrocortisone infusion group: hydrocortisone was given as an intravenous 200 mg loading bolus followed by an infusion (hydrocortisone 240 mg in 500 cc 0.9% saline) at a rate of 10 mg/hour for 7 days and protocol-guided antibiotic treatment Placebo group: protocol-guided antibiotic treatment plus placebo Improvement in PaO2 :FiO2 (PaO2 :FiO2 300 or 100 increase from study entry) Multiple organ dysfunction syndrome (MODS) score by study day 8 Development of delayed septic shock Duration of mechanical ventilation Length of ICU and hospital stay Survival until hospital discharge and to 60 days after discharge Randomisation schemes were generated in blocks of 10 for each participating site by a central randomisation centre. The randomisation assignment was given to the recruiting centre in sealed envelopes
Participants
Interventions
Outcomes
Notes
Risk of bias
Confalonieri 2005
(Continued)
Item Adequate sequence generation?
Authors judgement Yes
Description Randomisation schemes were generated in blocks of 10 for each participating site by a central randomisation centre The randomisation assignment was provided to the recruiting centre in sealed envelopes The participants did not know whether they were given hydrocortisone or placebo All participants accounted for, except 2 participants who met the exclusion criteria after randomisation Not described Not clearly stated in article
Yes
Blinding? All outcomes Incomplete outcome data addressed? All outcomes
Yes
Yes
Free of selective reporting? Free of other bias?
Unclear Unclear
Marik 1993 Methods Design: prospective, randomized, placebo-controlled trial Method of randomisation: adequate; participants were randomized by a random number generator to receive either hydrocortisone or placebo Concealment of allocation: unclear Outcome assessor blinding: yes Withdrawals/drop-outs: all participants accounted for Eligible: not stated Randomised: 30 (14 in hydrocortisone group, 16 in placebo group) Completed: 30 (14 in hydrocortisone group, 16 in placebo group) Age: hydrocortisone group: 40.6 14.7, placebo group: 31.7 12.8 Sex: not stated in the article Diagnosis: the diagnosis of pneumonia was based on clinical signs and symptoms of lower respiratory tract infection The participants received 10 mg/kg of hydrocortisone or placebo intravenously 30 minutes prior to starting antibiotic therapy All participants were treated with cefotaxime 1 g intravenously every 6 hours The level of Tumour Necrosis Factor- in both groups The length of stay in the ICU APACHE score Mortality
Participants
Interventions
Outcomes
24
Marik 1993
(Continued)
Notes
Participants were randomized by a random number generator to receive either hydrocortisone or placebo
Risk of bias Item Adequate sequence generation? Authors judgement Yes Description Participants were randomized by a random number generator to receive either hydrocortisone or placebo It was not clearly stated in the text The participants did not know the drug they were given No missing data in the trial
Allocation concealment? Blinding? All outcomes Incomplete outcome data addressed? All outcomes Free of selective reporting? Free of other bias? McHardy 1972 Methods
No Yes
Yes
Unclear Unclear
Not reported Not described
The study was carried out in the respiratory wards of the City Hospital, Edinburgh, New South Wales, Australia. Parallel design 126 participants were included and no children under 12 years of age. The criteria for inclusion were radiological evidence of pneumonia or clinical evidence of pneumonia if no pre-treatment chest radiograph was available. Participants with pneumonia were excluded if they were either classed as desperately ill and judged to be at risk of dying within 24 hours, if they were known to be hypersensitive to penicillin or ampicillin. Patients with diabetes mellitus or symptoms of recent peptic ulceration were included in the ampicillin dosage trial but excluded from the random allocation of prednisolone The participants were divided into four groups, 43 in group 1, 20 in group 2, 43 in group 3 and 20 in group 4 Pariticipants in group 1 were administered ampicillin 1 g daily; ampicillin 1 g plus prednisolone 20 mg daily in group 2; ampicillin 2 g daily in group 3 and ampicillin 2 g plus prednisolone 20 mg daily in group 4 1. Death 2. Duration of treatment 3. Change of treatment 4. Resolution of temperature 5. Clearance of pathogens from sputum or laryngeal swabs
25
Participants
Interventions
Outcomes
McHardy 1972
(Continued)
6. Maximum radiological clearance Notes Risk of bias Item Adequate sequence generation? Authors judgement Unclear Description The method of generating the allocation sequence was not described in detail Allocation concealment was not mentioned Not mentioned
No
Blinding? All outcomes Incomplete outcome data addressed? All outcomes Mikami 2007 Methods
No
Yes
Design: prospective, randomized, open-label, controlled trial Method of randomisation: unclear Concealment of allocation: adequate Outcome assessor blinding: yes Withdrawals/drop-outs: all participants were accounted for Eligible: 110 hospitalized participants with adult CAP; 60 met eligibility criteria and 31 patients consented to the study Randomised: 31 Completed: 31 (15 in steroid group, 16 in control group) Age: steroid group: 75.9 ( 16.0), control group: 68.4 ( 22.8) Sex (male): steroid group: 73.3%, control group: 75.0% Diagnosis: the diagnosis of CAP was based on clinical signs and symptoms of lower respiratory tract infections. Radiographic abnormalities consistent with infection were neither pre-existing nor caused by any other previous conditions Steroid group: 40 mg of prednisolone intravenously for 3 days plus intravenous antibiotics within 8 hours of hospital arrival and modied based on culture results Control group: intravenous antibiotics within 8 hours of hospital arrival and modied based on culture results Length of hospital stay Duration of IV antibiotic treatment and time required to stabilise vital signs The investigators were not actively involved in the treatment of the participants and the physicians who took care of the participants were not informed of the outcome parameters. Decisions on the time to discharge or the time to nish intravenous antibiotic
26
Participants
Interventions
Outcomes
Notes
Mikami 2007
(Continued)
therapy were made with objective data and were dependent on the condition of the participant Sources of the drugs not stated Risk of bias Item Adequate sequence generation? Authors judgement Unclear Description Mentioned randomisation in the article, but did not describe the method Did not mention this in the article An open-label study
Allocation concealment? Blinding? All outcomes Incomplete outcome data addressed? All outcomes Free of selective reporting? Free of other bias? van Woensel 2003 Methods
No No
Unclear
No missing data
Unclear Unclear
Not reported Not described
Design: prospective, multicentre, randomized, double-blind, placebo-controlled trial Method of randomisation: adequate Concealment of allocation: adequate Outcome assessor blinding: yes Withdrawals/drop-outs: 3 participants dropout Eligible: 155 eligible patients. Not randomized (n = 70) including not approached for participation (n = 29), more than 24 hours mechanical ventilation (n = 12), corticosteroids before randomisation (n = 11), and no permission from parents (n = 18) Randomised: 85 (39 in steroid group, 46 in control group) Completed: 82 (37 in steroid group including 18 bronchiolitis and 17 pneumonia, 45 in control group including 21 bronchiolitis and 22 pneumonia) Age: steroid group: 5.9 (0.9), control group: 9.8 (1.6) Sex: steroid group male: 30, control group: 27 Diagnosis: the diagnosis was based on clinical signs and symptoms of lower respiratory tract infection. The presence of RSV infection was conrmed by direct immunouorescence assay (Imagen, Dako, Denmark) of a nasopharyngeal aspirate during the rst 24 hours after hospital admission The trial medication was intravenous dexamethasone (0.15 mg/kg 6-hourly for 48 hours) or placebo and had to be started within 24 hours after the start of mechanical ventilation
Participants
Interventions
27
van Woensel 2003
(Continued)
Outcomes
Duration of mechanical ventilation Length of stay in the PICU and in the hospital Duration of supplemental oxygen Participants were allocated to dexamethasone or placebo by computerized block randomisation in groups of 10, centrally performed by an independent pharmacist. Each participating centre received a randomisation list and the trial medication preparation protocol. The trial medication was prepared in advance in the pharmacy centre where the concealed randomisation list was kept until the study was completed. Each enrolled participant received the trial medication with the next number in sequence
Notes
Risk of bias Item Adequate sequence generation? Authors judgement Yes Description Participants were allocated to dexamethasone or placebo by computerized block randomisation in groups of 10, centrally performed by an independent pharmacist. Each participating centre received a randomisation list and the trial medication preparation protocol The trial medication was prepared in advance in the pharmacy centre where the concealed randomisation list was kept until the study was completed Each enrolled participant received the trial medication with the next number in sequence After enrolment 3 participants were withdrawn: 1 (dexamethasone group) because she died 4 days after admission due to severe cerebral oedema in combination with refractory seizures already existing before inclusion, and 2 because their medication vials (1 containing dexamethasone and the other placebo) were accidentally interchanged No report Not described
Yes
Blinding? All outcomes
Yes
Incomplete outcome data addressed? All outcomes
Yes
Free of selective reporting? Free of other bias?
Unclear Unclear
APACHE score = Acute Physiology and Chronic Health Evaluation Score

CAP = community-acquired pneumonia FIO2 = inspired oxygen concentration ICU = intensive care unit IV = intravenous PaO2 = partial pressure of oxygen in arterial blood PICU = Paediatric Intensive Care Unit RSV = respiratory syncytial virus SpO2 = saturation of blood oxygen
Characteristics of excluded studies [ordered by study ID]
Study Bai 2003 Cai 2007 Chen 2006 Chen 2006b Chen 2007
Reason for exclusion The author refused to explain the details of the study We contacted the trial author who told us it was a retrospective study We contacted the trial author who told us it was a retrospective study We contacted the trial author who told us it was a retrospective study The study mainly worked on the effect of ambroxol. We contacted the trial author who told us it was a retrospective study We contacted the trial author who told us that there was no blinding in the study and the participants were allocated by the date of administration We contacted the trial author who told us it was a retrospective study We contacted the trial author who told us it was a retrospective study We contacted the trial author who told us it was a retrospective study The treatment drug did not include corticosteroids We contacted the author but she refused to give details of the study We contacted the trial author who told us it was a retrospective study We contacted the trial author who told us it was a retrospective study A prospective study. The participants were allocated casually by the doctor and there was no blinding in the study We contacted the trial author who told us it was a retrospective study We contacted the author who told us the study was retrospective and prospective. In the prospective part, the participants were allocated by the doctor according to the date of administration
29
Chu 2009
Dai 2009 Fang 2003 Feng 2001 Finch 2002 Guan 2004 Han 2003 Han 2007 He 2008 Hong 2005 Huang 2008
(Continued)
Li 2006 Marks 1972
We contacted the trial author who told us it was a retrospective study Hydrocarbon pneumonia is one of the most signicant complications after ingestion of hydrocarbon distillates. Study did not meet our inclusion criteria An uncontrolled, retrospective, prospective study We contacted the trial author who told us it was a retrospective study Mainly compared the effect of Mucosolvan in the study We contacted the trial author who told us it was a retrospective study We contacted the trial author who told us it was a retrospective study We contacted the trial author who told us it was a retrospective study In the study the investigator compared the effect of corticosteroids plus Mucosolvan; this did not meet our intervention inclusion criteria We contacted the trial author who told us it was a retrospective study We could not contact the author as he had changed workplace, so we could not determine whether the study was a randomized controlled trial We contacted the trial author who told us it was a retrospective study We contacted the trial author who told us it was a retrospective study We contacted the author who told us it was a retrospective study. In addition, there were some other interventions in the corticosteroid group We contacted the trial author who told us it was a retrospective study
Mer 1998 Song 2005 Song 2008 Sun 2006 Tao 2008 Wang 2007 Wong 2006
Wu 2007 Wu 2009
Xie 2005 Zhang 2004 Zhao 2008
Zheng 2008
Characteristics of studies awaiting assessment [ordered by study ID]

Braun 1986 Methods Participants Interventions Outcomes We are trying to retrieve the article
30
Braun 1986
(Continued)
Notes Chen 2003 Methods Participants Interventions Outcomes Notes Confalnonier 2006 Methods Participants Interventions Outcomes Notes Dambrava 2006 Methods Participants Interventions Outcomes Notes Hatakeyama 1995 Methods Participants Interventions Outcomes
We could not nd the author as she had changed workplace
We are trying to retrieve the article
Hatakeyama 1995
(Continued)
Notes Lee 1980 Methods Participants Interventions Outcomes Notes Li 2005 Methods Participants Interventions Outcomes Notes Li 2007 Methods Participants Interventions Outcomes Notes Liu 2008 Methods Participants Interventions Outcomes
We are trying to contact the author to identify the randomisation method used
The author was abroad, so we could not contact her
Liu 2008
(Continued)
Notes Lv 1991 Methods Participants Interventions Outcomes Notes Ma 2006 Methods Participants Interventions Outcomes Notes Soboleva 2000 Methods Participants Interventions Outcomes Notes Wang 2008 Methods Participants Interventions Outcomes
The author was abroad, so we could not contact her
Wang 2008
(Continued)
Notes
34
DATA AND ANALYSES
Comparison 1. Hydrocortisone versus placebo
Outcome or subgroup title 1 Mortality 2 PaO2 :FIO2 improvement 100 from study entry 3 PaO2 :FIO2 4 Chest radiograph score 5 Improvement in chest radiograph score from day 1 to day 8 6 On mechanical ventilation 7 Length of stay in the ICU
No. of studies 2 1 1 1 1 2 1
No. of participants 76 46 46 46 46 76 30
Statistical method Peto Odds Ratio (Peto, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
Effect size 0.26 [0.05, 1.37] 2.5 [1.40, 4.47] 95.00 [45.17, 144.83] -1.5 [-2.10, -0.90] 4.2 [1.91, 9.21] 0.43 [0.22, 0.85] -0.30 [-3.81, 3.21]
Comparison 2. Prednisolone plus antibiotics versus antibiotics alone
Outcome or subgroup title 1 Death 1.1 Ampicillin (1g daily) vs ampicillin (1g daily) with prednisolone (20mg daily) 1.2 Ampicillin (2g daily) vs ampicillin (2g daily) with prednisolone (20mg daily) 2 Participants require to change the treatment 2.1 Ampicillin (1g daily) vs ampicillin (1g daily) plus prednisolone 2.2 Ampicillin (2g daily) vs ampicillin (2g daily) plus prednisolone 3 Duration of treatment (number of participants to be treated more than two weeks) 3.1 Ampicillin (1g) vs ampicillin (1g) plus prednisolone (20mg) 3.2 Ampicillin (2g) vs ampicillin (2g) plus prednisolone (20mg)
No. of studies 1 1
No. of participants 126 63
Statistical method Peto Odds Ratio (Peto, Fixed, 95% CI) Peto Odds Ratio (Peto, Fixed, 95% CI)
Effect size 1.41 [0.39, 5.04] 2.72 [0.56, 13.22]
63
Peto Odds Ratio (Peto, Fixed, 95% CI)
0.41 [0.05, 3.57]
1 1
126 63
Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)
0.84 [0.33, 2.14] 1.46 [0.27, 7.96]
63
Odds Ratio (M-H, Fixed, 95% CI)
0.64 [0.20, 2.01]
126
2.0 [0.53, 7.53]
63
3.08 [0.35, 27.48]
63
1.46 [0.27, 7.96]
35
4 Time to normalisation of spO2 (days) 5 Length of hospital stay (days) 6 Duration of IV antibiotics (days) 7 Time to normalisation of body temperature (days) 8 Time to normalisation of respiratory rate (days) 9 Time to normalisation of C reactive protein (days) 10 Time to normalisation of WBC (days)
1 1 1 1 1 1 1
31 31 31 31 31 31 31
Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
-2.10 [-4.43, 0.23] -4.20 [-10.14, 1.74] -3.80 [-6.94, -0.66] -3.6 [-6.28, -0.92] -3.40 [-5.52, -1.28] -4.1 [-7.15, -1.05] 2.00 [-0.61, 4.61]
Comparison 3. Budesonide (Pulmicort) plus antibiotics versus antibiotics only
Outcome or subgroup title 1 Time to clinical symptoms disappearing 2 Rate of relapse
No. of studies 1 1
No. of participants 60 60
Statistical method Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
Effect size -8.0 [-9.25, -6.75] -2.43 [-2.79, -2.07]
Comparison 4. Intravenous dexamethasone versus placebo
Outcome or subgroup title 1 Duration of mechanical ventilation 2 Duration of supplemental oxygen 3 Length of stay in the paediatric intensive care unit 4 Length of stay in the hospital
No. of studies 1 1 1 1
No. of participants 41 41 41 41
Statistical method Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
Effect size 0.80 [0.15, 1.45] 1.70 [0.75, 2.65] 0.20 [-0.50, 0.90] 2.60 [1.43, 3.77]
36
Analysis 1.1. Comparison 1 Hydrocortisone versus placebo, Outcome 1 Mortality.

Review: Corticosteroids for pneumonia
Comparison: 1 Hydrocortisone versus placebo Outcome: 1 Mortality
Study or subgroup
Experimental n/N
Control n/N 2/23 3/16
Peto Odds Ratio Peto,Fixed,95% CI
Weight
Confalonieri 2005 Marik 1993
0/23 1/14
35.4 % 64.6 %
0.13 [ 0.01, 2.13 ] 0.38 [ 0.05, 3.01 ]
Total (95% CI)
37
39
100.0 %
0.26 [ 0.05, 1.37 ]
Total events: 1 (Experimental), 5 (Control) Heterogeneity: Chi2 = 0.36, df = 1 (P = 0.55); I2 =0.0% Test for overall effect: Z = 1.59 (P = 0.11)
0.001 0.01 0.1 Favours experimental
10 100 1000 Favours control
Analysis 1.2. Comparison 1 Hydrocortisone versus placebo, Outcome 2 PaO2 :FIO2 improvement 100 from study entry.
Comparison: 1 Hydrocortisone versus placebo Outcome: 2 PaO2 :FIO2 improvement 100 from study entry
Study or subgroup
Experimental n/N
Control n/N 8/23
Risk Ratio M-H,Fixed,95% CI
Weight
Confalonieri 2005
20/23
100.0 %
2.50 [ 1.40, 4.47 ]
Total (95% CI)

Heterogeneity: not applicable
23
23
100.0 %
2.50 [ 1.40, 4.47 ]
Total events: 20 (Experimental), 8 (Control) Test for overall effect: Z = 3.09 (P = 0.0020)
0.01
0.1
10
100
Favours experimental
Favours control
37
Analysis 1.3. Comparison 1 Hydrocortisone versus placebo, Outcome 3 PaO2 :FIO2 .

Comparison: 1 Hydrocortisone versus placebo Outcome: 3 PaO2 :FIO2
Study or subgroup
Experimental N Mean(SD) 332 (80)
Control N 23 Mean(SD) 237 (92)
Mean Difference IV,Fixed,95% CI
Weight
Confalonieri 2005
23
100.0 %
95.00 [ 45.17, 144.83 ]
Total (95% CI)

23
23
100.0 %
95.00 [ 45.17, 144.83 ]
Test for overall effect: Z = 3.74 (P = 0.00019)
-100
-50
50
100
Favours control
Analysis 1.4. Comparison 1 Hydrocortisone versus placebo, Outcome 4 Chest radiograph score.
Comparison: 1 Hydrocortisone versus placebo Outcome: 4 Chest radiograph score
Study or subgroup
Experimental N Mean(SD) 1.1 (0.7)
Control N 23 Mean(SD) 2.6 (1.3)
Weight
Confalonieri 2005
23
100.0 %
-1.50 [ -2.10, -0.90 ]
Total (95% CI)

23
23
100.0 %
-1.50 [ -2.10, -0.90 ]
Test for overall effect: Z = 4.87 (P < 0.00001)
-2
-1
Favours control
38
Analysis 1.5. Comparison 1 Hydrocortisone versus placebo, Outcome 5 Improvement in chest radiograph score from day 1 to day 8.
Comparison: 1 Hydrocortisone versus placebo Outcome: 5 Improvement in chest radiograph score from day 1 to day 8
Study or subgroup
Experimental n/N
Control n/N 5/23
Weight
Confalonieri 2005
21/23
100.0 %
4.20 [ 1.91, 9.21 ]
Total (95% CI)

23
23
100.0 %
4.20 [ 1.91, 9.21 ]
Total events: 21 (Experimental), 5 (Control) Test for overall effect: Z = 3.58 (P = 0.00034)
0.001 0.01 0.1 Favours experimental
10 100 1000 Favours control
Analysis 1.6. Comparison 1 Hydrocortisone versus placebo, Outcome 6 On mechanical ventilation.

Comparison: 1 Hydrocortisone versus placebo Outcome: 6 On mechanical ventilation
Study or subgroup
Experimental n/N
Control n/N 15/23 4/16
Weight
Confalonieri 2005 Marik 1993
6/23 2/14
80.1 % 19.9 %
0.40 [ 0.19, 0.85 ] 0.57 [ 0.12, 2.66 ]
Total (95% CI)
37
39
100.0 %
0.43 [ 0.22, 0.85 ]
Total events: 8 (Experimental), 19 (Control) Heterogeneity: Chi2 = 0.17, df = 1 (P = 0.68); I2 =0.0% Test for overall effect: Z = 2.42 (P = 0.015)
0.01
0.1
10
100
Favours control
39
Analysis 1.7. Comparison 1 Hydrocortisone versus placebo, Outcome 7 Length of stay in the ICU.
Comparison: 1 Hydrocortisone versus placebo Outcome: 7 Length of stay in the ICU
Study or subgroup
Weight
Marik 1993
14
100.0 %
-0.30 [ -3.81, 3.21 ]
Total (95% CI)

14
16
100.0 %
-0.30 [ -3.81, 3.21 ]
-4
-2
Favours control
Analysis 2.1. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 1 Death.
Comparison: 2 Prednisolone plus antibiotics versus antibiotics alone Outcome: 1 Death
Study or subgroup
Experimental n/N
Control n/N
Weight
1 Ampicillin (1g daily) vs ampicillin (1g daily) with prednisolone (20mg daily) McHardy 1972 7/43 1/20 65.1 % 2.72 [ 0.56, 13.22 ]
Subtotal (95% CI)

Total events: 7 (Experimental), 1 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.24 (P = 0.21)
43
20
65.1 %
2.72 [ 0.56, 13.22 ]
2 Ampicillin (2g daily) vs ampicillin (2g daily) with prednisolone (20mg daily) McHardy 1972 2/43 2/20 34.9 % 0.41 [ 0.05, 3.57 ]
Subtotal (95% CI)

43
20
34.9 %
0.41 [ 0.05, 3.57 ]
Total (95% CI)

Total events: 9 (Experimental), 3 (Control)
86
40
100.0 %
1.41 [ 0.39, 5.04 ]
0.01
0.1
10
100
Favours control
(Continued . . . )
40
Study or subgroup
Experimental n/N
Control n/N
Weight
(. . . Continued) Peto Odds Ratio

Peto,Fixed,95% CI
Heterogeneity: Chi2 = 1.91, df = 1 (P = 0.17); I2 =48% Test for overall effect: Z = 0.53 (P = 0.60) Test for subgroup differences: Chi2 = 1.91, df = 1 (P = 0.17), I2 =48%
0.01
0.1
10
100
Favours control
Analysis 2.2. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 2 Participants require to change the treatment.
Comparison: 2 Prednisolone plus antibiotics versus antibiotics alone Outcome: 2 Participants require to change the treatment
Study or subgroup
Experimental n/N
Control n/N
Odds Ratio M-H,Fixed,95% CI
Weight
1 Ampicillin (1g daily) vs ampicillin (1g daily) plus prednisolone McHardy 1972 6/43 2/20 24.8 % 1.46 [ 0.27, 7.96 ]
Subtotal (95% CI)

43
20
24.8 %
1.46 [ 0.27, 7.96 ]
2 Ampicillin (2g daily) vs ampicillin (2g daily) plus prednisolone McHardy 1972 11/43 7/20 75.2 % 0.64 [ 0.20, 2.01 ]
Subtotal (95% CI)

43
20
75.2 %
0.64 [ 0.20, 2.01 ]
Total (95% CI)

86
40
100.0 %
0.84 [ 0.33, 2.14 ]
Heterogeneity: Chi2 = 0.63, df = 1 (P = 0.43); I2 =0.0% Test for overall effect: Z = 0.36 (P = 0.72)
0.01
0.1
10
100
Favours control
41
Analysis 2.3. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 3 Duration of treatment (number of participants to be treated more than two weeks).
Comparison: 2 Prednisolone plus antibiotics versus antibiotics alone Outcome: 3 Duration of treatment (number of participants to be treated more than two weeks)
Study or subgroup
Experimental n/N
Control n/N
Weight
1 Ampicillin (1g) vs ampicillin (1g) plus prednisolone (20mg) McHardy 1972 6/43 1/20 33.3 % 3.08 [ 0.35, 27.48 ]
Subtotal (95% CI)

43
20
33.3 %
3.08 [ 0.35, 27.48 ]
2 Ampicillin (2g) vs ampicillin (2g) plus prednisolone (20mg) McHardy 1972 6/43 2/20 66.7 % 1.46 [ 0.27, 7.96 ]
Subtotal (95% CI)

43
20
66.7 %
1.46 [ 0.27, 7.96 ]
Total (95% CI)

86
40
100.0 %
2.00 [ 0.53, 7.53 ]
Heterogeneity: Chi2 = 0.28, df = 1 (P = 0.60); I2 =0.0% Test for overall effect: Z = 1.02 (P = 0.31)
0.01
0.1
10
100
Favours control
42
Analysis 2.4. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 4 Time to normalisation of spO2 (days).
Comparison: 2 Prednisolone plus antibiotics versus antibiotics alone Outcome: 4 Time to normalisation of spO2 (days)
Study or subgroup
Control N 16 Mean(SD) 6.3 (4)
Weight
Mikami 2007
15
100.0 %
-2.10 [ -4.43, 0.23 ]
Total (95% CI)

15
16
100.0 %
-2.10 [ -4.43, 0.23 ]
-4
-2
Favours control
Analysis 2.5. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 5 Length of hospital stay (days).
Comparison: 2 Prednisolone plus antibiotics versus antibiotics alone Outcome: 5 Length of hospital stay (days)
Study or subgroup
Weight
Mikami 2007
15
100.0 %
-4.20 [ -10.14, 1.74 ]
Total (95% CI)

15
16
100.0 %
-4.20 [ -10.14, 1.74 ]
-10
-5
10
Favours control
43
Analysis 2.6. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 6 Duration of IV antibiotics (days).
Comparison: 2 Prednisolone plus antibiotics versus antibiotics alone Outcome: 6 Duration of IV antibiotics (days)
Study or subgroup
Weight
Mikami 2007
15
100.0 %
-3.80 [ -6.94, -0.66 ]
Total (95% CI)

15
16
100.0 %
-3.80 [ -6.94, -0.66 ]
-10
-5
10
Favours control
Analysis 2.7. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 7 Time to normalisation of body temperature (days).
Comparison: 2 Prednisolone plus antibiotics versus antibiotics alone Outcome: 7 Time to normalisation of body temperature (days)
Study or subgroup
Control N 16 Mean(SD) 7 (5.1)
Weight
Mikami 2007
15
100.0 %
-3.60 [ -6.28, -0.92 ]
Total (95% CI)

15
16
100.0 %
-3.60 [ -6.28, -0.92 ]
-100
-50
50
100
Favours control
44
Analysis 2.8. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 8 Time to normalisation of respiratory rate (days).
Comparison: 2 Prednisolone plus antibiotics versus antibiotics alone Outcome: 8 Time to normalisation of respiratory rate (days)
Study or subgroup
Weight
Mikami 2007
15
100.0 %
-3.40 [ -5.52, -1.28 ]
Total (95% CI)

15
16
100.0 %
-3.40 [ -5.52, -1.28 ]
-10
-5
10
Favours control
Analysis 2.9. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 9 Time to normalisation of C reactive protein (days).
Comparison: 2 Prednisolone plus antibiotics versus antibiotics alone Outcome: 9 Time to normalisation of C reactive protein (days)
Study or subgroup
Experimental N Mean(SD) 7.6 (3)
Weight
Mikami 2007
15
100.0 %
-4.10 [ -7.15, -1.05 ]
Total (95% CI)

15
16
100.0 %
-4.10 [ -7.15, -1.05 ]
-10
-5
10
Favours control
45
Analysis 2.10. Comparison 2 Prednisolone plus antibiotics versus antibiotics alone, Outcome 10 Time to normalisation of WBC (days).
Comparison: 2 Prednisolone plus antibiotics versus antibiotics alone Outcome: 10 Time to normalisation of WBC (days)
Study or subgroup
Weight
Mikami 2007
15
100.0 %
2.00 [ -0.61, 4.61 ]
Total (95% CI)

15
16
100.0 %
2.00 [ -0.61, 4.61 ]
-20
-10
10
20
Favours control
Analysis 3.1. Comparison 3 Budesonide (Pulmicort) plus antibiotics versus antibiotics only, Outcome 1 Time to clinical symptoms disappearing.
Comparison: 3 Budesonide (Pulmicort) plus antibiotics versus antibiotics only Outcome: 1 Time to clinical symptoms disappearing
Study or subgroup
Weight
Cao 2007
30
100.0 %
-8.00 [ -9.25, -6.75 ]
Total (95% CI)

30
30
100.0 %
-8.00 [ -9.25, -6.75 ]
-10
-5
10
Favours control
46
Analysis 3.2. Comparison 3 Budesonide (Pulmicort) plus antibiotics versus antibiotics only, Outcome 2 Rate of relapse.
Comparison: 3 Budesonide (Pulmicort) plus antibiotics versus antibiotics only Outcome: 2 Rate of relapse
Study or subgroup
Experimental N Mean(SD) 1 (0.53)
Weight
Cao 2007
30
100.0 %
-2.43 [ -2.79, -2.07 ]
Total (95% CI)

30
30
100.0 %
-2.43 [ -2.79, -2.07 ]
-4
-2
Favours control
Analysis 4.1. Comparison 4 Intravenous dexamethasone versus placebo, Outcome 1 Duration of mechanical ventilation.
Comparison: 4 Intravenous dexamethasone versus placebo Outcome: 1 Duration of mechanical ventilation
Study or subgroup
Weight
van Woensel 2003
19
100.0 %
0.80 [ 0.15, 1.45 ]
Total (95% CI)

19
22
100.0 %
0.80 [ 0.15, 1.45 ]
-4
-2
Favours control
47
Analysis 4.2. Comparison 4 Intravenous dexamethasone versus placebo, Outcome 2 Duration of supplemental oxygen.
Comparison: 4 Intravenous dexamethasone versus placebo Outcome: 2 Duration of supplemental oxygen
Study or subgroup
Weight
van Woensel 2003
19
100.0 %
1.70 [ 0.75, 2.65 ]
Total (95% CI)

19
22
100.0 %
1.70 [ 0.75, 2.65 ]
-4
-2
Favours control
Analysis 4.3. Comparison 4 Intravenous dexamethasone versus placebo, Outcome 3 Length of stay in the paediatric intensive care unit.
Comparison: 4 Intravenous dexamethasone versus placebo Outcome: 3 Length of stay in the paediatric intensive care unit
Study or subgroup
Weight
van Woensel 2003
19
100.0 %
0.20 [ -0.50, 0.90 ]
Total (95% CI)

19
22
100.0 %
0.20 [ -0.50, 0.90 ]
-1
-0.5
0.5
Favours control
48
Analysis 4.4. Comparison 4 Intravenous dexamethasone versus placebo, Outcome 4 Length of stay in the hospital.
Comparison: 4 Intravenous dexamethasone versus placebo Outcome: 4 Length of stay in the hospital
Study or subgroup
Weight
van Woensel 2003
19
100.0 %
2.60 [ 1.43, 3.77 ]
Total (95% CI)

19
22
100.0 %
2.60 [ 1.43, 3.77 ]
-4
-2
Favours control
APPENDICES Appendix 1. Embase.com search strategy

#16. #12 AND #15 #15. #13 OR #14 #14. random*:ab,ti OR placebo*:ab,ti OR factorial*:ab,ti OR crossover*:ab,ti OR cross-over:ab,ti OR cross over:ab,ti OR assign*: ab,ti OR allocat*:ab,ti OR volunteer*:ab,ti OR ((singl* OR doubl*) NEAR/2 (blind* OR mask*)):ab,ti #13. randomized controlled trial/exp OR single blind procedure/exp OR double blind procedure/exp OR crossover procedure/exp #12. #6 AND #11 #11. #7 OR #8 OR #9 OR #10 #10. prednisone*:ab,ti OR prednisolone*:ab,ti OR methylprednisolone*:ab,ti OR betamethasone*:ab,ti OR dexamethasone*:ab,ti OR triamcinolone:ab,ti OR hydrocortisone*:ab,ti #9. steroid*:ab,ti OR corticosteroid*:ab,ti #8. corticosteroid/exp #7. steroid/exp #6. #1 OR #2 OR #3 OR #4 OR #5 #5. adult respiratory distress syndrome:ab,ti OR acute respiratory distress syndrome:ab,ti OR ards:ab,ti #4. adult respiratory distress syndrome/de #3. cap:ab,ti OR hap:ab,ti #2. pneumon*:ab,ti #1. pneumonia/exp
49
HISTORY
Protocol rst published: Issue 2, 2009 Review rst published: Issue 3, 2011
CONTRIBUTIONS OF AUTHORS
All four review authors, Yuanjing Chen (YC), Ka Li (KL), Hongshan Pu (HP) and Taixiang Wu (TW) were responsible for developing and writing the protocol and review.
DECLARATIONS OF INTEREST
None known.
SOURCES OF SUPPORT Internal sources

West China Hospital, Sichuan University, China.
External sources
Cochrane Acute Respiratory Infections Group, Australia.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW

We were unable to conduct sensitivity analyses and funnel plots for analysing publication bias due to the small number of included studies.
50

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Corticosteroids for pneumonia (Review)

Corticosteroids for pneumonia

Description of the condition

Description of the intervention

How the intervention might work

Criteria for considering studies for this review

Why it is important to do this review

Search methods for identication of studies

Figure 1. Search strategy used in the Chinese databases

Data collection and analysis

Incomplete outcome data

Selective reporting bias

Other potential sources of bias

Risk of bias in included studies

Time to pneumonia resolution There were no reports of time to pneumonia resolution.

Summary of main results

Overall completeness and applicability of

Quality of the evidence

Potential biases in the review process

AUTHORS CONCLUSIONS Implications for practice

Agreements and disagreements with other studies or reviews

studies and the review process, the quality of evidence is low.

prolonged low-dose corticosteroid therapy can benet mortality or not.

Implications for research

References to studies included in this review

References to studies excluded from this review

References to studies awaiting assessment

CHARACTERISTICS OF STUDIES Characteristics of included studies [ordered by study ID]

Blinding? All outcomes

Not described Not clearly stated in the article

Item Adequate sequence generation?

Authors judgement Yes

Blinding? All outcomes Incomplete outcome data addressed? All outcomes

Free of selective reporting? Free of other bias?

Not reported Not described

Not reported Not described

van Woensel 2003

Blinding? All outcomes

Incomplete outcome data addressed? All outcomes

Free of selective reporting? Free of other bias?

APACHE score = Acute Physiology and Chronic Health Evaluation Score

Characteristics of excluded studies [ordered by study ID]

Li 2006 Marks 1972

Xie 2005 Zhang 2004 Zhao 2008

Characteristics of studies awaiting assessment [ordered by study ID]

We could not nd the author as she had changed workplace

We are trying to retrieve the article

We are trying to retrieve the article

We are trying to retrieve the article

We are trying to retrieve the article

The author was abroad, so we could not contact her

The author was abroad, so we could not contact her

We are trying to retrieve the article

DATA AND ANALYSES

Comparison 1. Hydrocortisone versus placebo

Comparison 2. Prednisolone plus antibiotics versus antibiotics alone

No. of participants 126 63

Effect size 1.41 [0.39, 5.04] 2.72 [0.56, 13.22]

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.41 [0.05, 3.57]

0.84 [0.33, 2.14] 1.46 [0.27, 7.96]

Odds Ratio (M-H, Fixed, 95% CI)

0.64 [0.20, 2.01]

Odds Ratio (M-H, Fixed, 95% CI)