NIHR Signal New evidence available on corticosteroids added to antibiotics in severe pneumonia

Published on 9 November 2015

For adults admitted to hospital with severe pneumonia, this review found that adding corticosteroids to the usual antibiotic treatment may be beneficial. The evidence was less supportive of using corticosteroids in people with less severe pneumonia. Results showed modest benefits in allowing patients to reach a clinically stable recovery and leave hospital an average of one day earlier. Reduced need for artificial breathing support was the main benefit for people with non-severe pneumonia. The review showed that using corticosteroids increased levels of blood sugar. This and other potential adverse events were not well investigated, as people at risk of them were excluded from most studies.

The current 2014 NICE guideline on pneumonia does not recommend routinely offering a corticosteroid to patients with community‑acquired pneumonia unless they have other conditions for which this treatment is indicated. The guideline is due to be reviewed in late 2016.

Before changing practice further trials would be helpful, to see if it is possible to replicate the findings and to clarify which corticosteroid to use, at what dose, and for whom. A more thorough assessment of potential adverse events, in people at higher risk of diabetes for example, would also help to quantify the potential downsides of a change in practice.

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Why was this study needed?

Pneumonia is common, particularly in winter, with between 5 and 11 in every 1,000 adults catching pneumonia each year. The illness is much more dangerous for those who smoke, are elderly, have existing lung conditions or an impaired immune system. The impact of pneumonia is large in terms of treatment costs and loss of life: between 22 and 42% of adults with community acquired pneumonia are admitted to hospital and 5 to 14% of people with more severe illness die from the condition.

Antibiotics are the main treatment for pneumonia. A 2011 systematic review of six small trials found that adding corticosteroid treatment increased speed of recovery slightly, but the evidence was not strong. The current review aimed to update the evidence on benefits and potential side effects of add-on corticosteroid treatment for people who had been admitted to hospital with pneumonia.

What did this study do?

This systematic review included 13 randomised controlled trials, with 2,005 participants. It updated and added to a 2011 review with a further nine trials. The majority of trial participants were men in their sixties. All the studies compared add-on treatment with corticosteroid (such as dexamethasone, prednisolone or hydrocortisone) with inactive placebo treatment. All the patients were receiving antibiotics as the main treatment for their pneumonia. The main outcomes were mortality from all causes, time to clinical stability and days to discharge from hospital.

This systematic review was rigorously carried out using the same approach as the Cochrane review it aimed to update. The underlying trials were at moderate or low risk of bias. However, there were few trials for each outcome, and most trials excluded participants who were at risk of adverse events. This limits our confidence in the findings and the relevance of the research to severe pneumonia.

What did it find?

The effects of corticosteroids in the trials were:

  • Length of hospital stay was reduced by average of one day in the three studies which had low risk of bias for this outcome (1,288 participants, mean difference 1.00 days, 95%CI, -1.79 to -0.21 days).
  • Time to clinical stability – meaning regaining normal values for basic functions such as body temperature and breathing rate – was shorter by just over a day in the five studies which measured this (1,180 participants, mean difference -1.22 days, CI -2.08 to -0.35 days).
  • Mortality from all causes was only significantly reduced when the data was pooled from six trials (388 participants) on severe pneumonia (risk ratio [RR] 0.39, 95% confidence interval [CI] 0.20 - 0.77). However, the authors thought that this effect might be spurious.
  • The need for mechanical ventilation was reduced in the five studies that measured this outcome (1,060 participants, a range of severity of pneumonia, RR, 0.45 [CI, 0.26 to 0.79]). There was most benefit for people with less severe pneumonia.
  • A severe complication of pneumonia called acute respiratory distress syndrome was uncommon overall, but risk was reduced when trial participants received corticosteroids (4 trials, 945 participants, RR 0.24, CI 0.10 – 0.56).
  • The main side effect of corticosteroid treatment – risk of raised blood glucose - was increased (6 trials, 1,534 participants, RR 1.49, CI 1.01 to 2.19). However, patients at risk of side effects of corticosteroid treatment were excluded from most trials.

What does current guidance say on this issue?

The current 2014 NICE guideline on pneumonia does not recommend routinely offering a corticosteroid to patients with community‑acquired pneumonia unless they have other conditions which are usually treated with corticosteroid treatment. The guidance is due to be reviewed in late 2016.

What are the implications?

Pneumonia is a common and potentially costly condition to treat, so at first sight implementing the findings of this review could offer significant savings. Reducing hospital stays for pneumonia by one day saves £192 on average. For the 175,000 people admitted to hospital with community-acquired pneumonia in 2013/14 this could have saved over £33 million. The benefits of corticosteroid treatment applied mainly to those with severe pneumonia who are more likely to need more costly intensive care and mechanical breathing support. Approaches to corticosteroid treatment and underlying antibiotic therapy varied widely between studies, therefore the researchers call for more research into the potential impact of any change in practice.

Citation

Siemieniuk RA, Meade MO, Alonso-Coello P, et al. Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia: A Systematic Review and Meta-analysis. Ann Intern Med. 2015;163(7):519-28.

Bibliography

British Lung Foundation. Pneumonia [internet]. London: British Lung Foundation; 2013.

Chen Y, Li K, Pu H, Wu T. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2011;(3):CD007720.

Lim WS, Baudouin S, George R, et al. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009;64(Suppl 3):iii1-iii55.

NHS Choices. Pnemonia [internet]. NHS Choices; 2014.

NICE. Pneumonia: Diagnosis and management of community- and hospital-acquired pneumonia in adults. CG191. London: National Institute for Health and Care Excellence; 2014.

NICE. Costing statement: Pneumonia – diagnosis and management of community- and hospital acquired pneumonia in adults. Implementing the NICE guideline on pneumonia (CG191). London: National Institute for Health and Care Excellence; 2014.

Why was this study needed?

Pneumonia is common, particularly in winter, with between 5 and 11 in every 1,000 adults catching pneumonia each year. The illness is much more dangerous for those who smoke, are elderly, have existing lung conditions or an impaired immune system. The impact of pneumonia is large in terms of treatment costs and loss of life: between 22 and 42% of adults with community acquired pneumonia are admitted to hospital and 5 to 14% of people with more severe illness die from the condition.

Antibiotics are the main treatment for pneumonia. A 2011 systematic review of six small trials found that adding corticosteroid treatment increased speed of recovery slightly, but the evidence was not strong. The current review aimed to update the evidence on benefits and potential side effects of add-on corticosteroid treatment for people who had been admitted to hospital with pneumonia.

What did this study do?

This systematic review included 13 randomised controlled trials, with 2,005 participants. It updated and added to a 2011 review with a further nine trials. The majority of trial participants were men in their sixties. All the studies compared add-on treatment with corticosteroid (such as dexamethasone, prednisolone or hydrocortisone) with inactive placebo treatment. All the patients were receiving antibiotics as the main treatment for their pneumonia. The main outcomes were mortality from all causes, time to clinical stability and days to discharge from hospital.

This systematic review was rigorously carried out using the same approach as the Cochrane review it aimed to update. The underlying trials were at moderate or low risk of bias. However, there were few trials for each outcome, and most trials excluded participants who were at risk of adverse events. This limits our confidence in the findings and the relevance of the research to severe pneumonia.

What did it find?

The effects of corticosteroids in the trials were:

  • Length of hospital stay was reduced by average of one day in the three studies which had low risk of bias for this outcome (1,288 participants, mean difference 1.00 days, 95%CI, -1.79 to -0.21 days).
  • Time to clinical stability – meaning regaining normal values for basic functions such as body temperature and breathing rate – was shorter by just over a day in the five studies which measured this (1,180 participants, mean difference -1.22 days, CI -2.08 to -0.35 days).
  • Mortality from all causes was only significantly reduced when the data was pooled from six trials (388 participants) on severe pneumonia (risk ratio [RR] 0.39, 95% confidence interval [CI] 0.20 - 0.77). However, the authors thought that this effect might be spurious.
  • The need for mechanical ventilation was reduced in the five studies that measured this outcome (1,060 participants, a range of severity of pneumonia, RR, 0.45 [CI, 0.26 to 0.79]). There was most benefit for people with less severe pneumonia.
  • A severe complication of pneumonia called acute respiratory distress syndrome was uncommon overall, but risk was reduced when trial participants received corticosteroids (4 trials, 945 participants, RR 0.24, CI 0.10 – 0.56).
  • The main side effect of corticosteroid treatment – risk of raised blood glucose - was increased (6 trials, 1,534 participants, RR 1.49, CI 1.01 to 2.19). However, patients at risk of side effects of corticosteroid treatment were excluded from most trials.

What does current guidance say on this issue?

The current 2014 NICE guideline on pneumonia does not recommend routinely offering a corticosteroid to patients with community‑acquired pneumonia unless they have other conditions which are usually treated with corticosteroid treatment. The guidance is due to be reviewed in late 2016.

What are the implications?

Pneumonia is a common and potentially costly condition to treat, so at first sight implementing the findings of this review could offer significant savings. Reducing hospital stays for pneumonia by one day saves £192 on average. For the 175,000 people admitted to hospital with community-acquired pneumonia in 2013/14 this could have saved over £33 million. The benefits of corticosteroid treatment applied mainly to those with severe pneumonia who are more likely to need more costly intensive care and mechanical breathing support. Approaches to corticosteroid treatment and underlying antibiotic therapy varied widely between studies, therefore the researchers call for more research into the potential impact of any change in practice.

Citation

Siemieniuk RA, Meade MO, Alonso-Coello P, et al. Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia: A Systematic Review and Meta-analysis. Ann Intern Med. 2015;163(7):519-28.

Bibliography

British Lung Foundation. Pneumonia [internet]. London: British Lung Foundation; 2013.

Chen Y, Li K, Pu H, Wu T. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2011;(3):CD007720.

Lim WS, Baudouin S, George R, et al. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009;64(Suppl 3):iii1-iii55.

NHS Choices. Pnemonia [internet]. NHS Choices; 2014.

NICE. Pneumonia: Diagnosis and management of community- and hospital-acquired pneumonia in adults. CG191. London: National Institute for Health and Care Excellence; 2014.

NICE. Costing statement: Pneumonia – diagnosis and management of community- and hospital acquired pneumonia in adults. Implementing the NICE guideline on pneumonia (CG191). London: National Institute for Health and Care Excellence; 2014.

Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia: A Systematic Review and Meta-analysis

Published on 11 August 2015

Siemieniuk, R. A.,Meade, M. O.,Alonso-Coello, P.,Briel, M.,Evaniew, N.,Prasad, M.,Alexander, P. E.,Fei, Y.,Vandvik, P. O.,Loeb, M.,Guyatt, G. H.

Ann Intern Med , 2015

Background: Community-acquired pneumonia (CAP) is common and often severe. Purpose: To examine the effect of adjunctive corticosteroid therapy on mortality, morbidity, and duration of hospitalization in patients with CAP. Data Sources: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through 24 May 2015. Study Selection: Randomized trials of systemic corticosteroids in hospitalized adults with CAP. Data Extraction: Two reviewers independently extracted study data and assessed risk of bias. Quality of evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation system by consensus among the authors. Data Synthesis: The median age was typically in the 60s, and approximately 60% of patients were male. Adjunctive corticosteroids were associated with possible reductions in all-cause mortality (12 trials; 1974 patients; risk ratio [RR], 0.67 [95% CI, 0.45 to 1.01]; risk difference [RD], 2.8%; moderate certainty), need for mechanical ventilation (5 trials; 1060 patients; RR, 0.45 [CI, 0.26 to 0.79]; RD, 5.0%; moderate certainty), and the acute respiratory distress syndrome (4 trials; 945 patients; RR, 0.24 [CI, 0.10 to 0.56]; RD, 6.2%; moderate certainty). They also decreased time to clinical stability (5 trials; 1180 patients; mean difference, -1.22 days [CI, -2.08 to -0.35 days]; high certainty) and duration of hospitalization (6 trials; 1499 patients; mean difference, -1.00 day [CI, -1.79 to -0.21 days]; high certainty). Adjunctive corticosteroids increased frequency of hyperglycemia requiring treatment (6 trials; 1534 patients; RR, 1.49 [CI, 1.01 to 2.19]; RD, 3.5%; high certainty) but did not increase frequency of gastrointestinal hemorrhage. Limitations: There were few events and trials for many outcomes. Trials often excluded patients at high risk for adverse events. Conclusion: For hospitalized adults with CAP, systemic corticosteroid therapy may reduce mortality by approximately 3%, need for mechanical ventilation by approximately 5%, and hospital stay by approximately 1 day. Primary Funding Source: None.

Pneumonia is inflammation of the lungs that can be a complication of respiratory infection. As a result of inflammation, the lungs fill with fluid, which can make breathing difficult and painful. The symptoms are a feverish, flu-like illness, which is most common in the winter and may follow on from having flu. Those at greatest risk of getting pneumonia include people with impaired immune systems, while those at higher risk of severe illness after catching pneumonia include those with pre-existing lung or heart conditions.

Pneumonia is usually treated with antibiotics and supplemental oxygen if the illness is severe. Vaccines are available against the most common infectious cause, Streptococcus pneumoniae, also flu vaccine helps by protecting against one of the predisposing conditions.

Expert commentary

This meta-analysis included studies which used different doses of steroids and antibiotics and different definitions of pneumonia severity. There was no trend towards mortality benefit amongst 1586 patients with less severe pneumonia. Significant mortality benefit was reported for 388 patients with severe pneumonia but the authors suggested that this finding “is probably spurious”. The other reported benefits (reduced need for mechanical ventilation, reduced length of hospital stay and reduced risk of ARDS) appear more robust. Clinicians who wish to consider corticosteroid therapy for pneumonia need to know which patients to treat, which steroid to use, what dose to administer and the optimal duration of treatment. More trials will be required to answer these vital questions.

Dr Ronan O'Driscoll, Consultant Physician, Respiratory Medicine, Salford Royal Foundation NHS Trust