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INFECTIOUS DISEASE/SYSTEMATIC REVIEW SNAPSHOT

TAKE-HOME MESSAGE
For adult patients with severe community-acquired pneumonia, corticosteroids
reduce morbidity and mortality. For pediatric patients and adults with nonsevere
community-acquired pneumonia, corticosteroids appear to reduce morbidity, but
not mortality.

Are Corticosteroids Beneficial in the Treatment of


METHODS Community-Acquired Pneumonia?
EBEM Commentators
Thomas Seagraves, MD
DATA SOURCES Michael Gottlieb, MD
The authors searched the Department of Emergency Medicine
Cochrane Acute Infections Group’s Rush University Medical Center
Specialized Register, the Cochrane Chicago, IL
Central Register of Controlled
Trials, MEDLINE, EMBASE, and Results
Latin American and Caribbean
Comparison of corticosteroids with control for community-acquired pneumonia.
Health Sciences Literature from
inception through March 2017 for No. of Studies Relative Risk
Outcome (No. of Participants) (95% CI) I2, %
eligible studies, without language or
publication restrictions. The Mortality (adults with severe CAP) 9 (995) 0.58 (0.40–0.84) 12
reference lists of all included Mortality (adults with nonsevere CAP) 4 (868) 0.95 (0.45–2.00) 0
Early clinical failure (adults with severe CAP) 5 (419) 0.32 (0.15–0.70) 74
studies and previous systematic Early clinical failure (adults with nonsevere CAP) 2 (905) 0.68 (0.56–0.83) 0
reviews were searched manually. In Early clinical failure (children) 2 (88) 0.41 (0.24–0.70) 25
addition, the authors searched Hyperglycemia 7 (1,578) 1.72 (1.38–2.14) 21
conference proceedings of major
infectious disease and intensive CI, Confidence interval; CAP, community-acquired pneumonia.
care meetings, as well as multiple
ongoing trial registries.
The search strategy initially yielded intravenous dexamethasone, hy-
STUDY SELECTION 4,273 potential studies. After drocortisone, or methylpredniso-
Eligible studies included adults or review, 17 randomized controlled lone, whereas 3 trials used oral
children with radiographically- trials containing 2,264 patients prednisone, and 1 trial did not put
confirmed community-acquired were included in the meta-analysis. limits on oral versus intravenous
pneumonia, health care–associated Thirteen randomized controlled routes. The average duration of
pneumonia, hospital-acquired trials (1,954 participants) studied treatment was 7 days. Seven trials
pneumonia, and ventilator- adult participants and 4 (310 par- used a duration of 7 days, 2 used 7
associated pneumonia who were ticipants) investigated pediatric to 10 days, 3 used 5 days, and 4
randomly assigned to populations. Of the 4 pediatric used 2 to 4 days. Most adult studies
corticosteroids versus either
studies, 2 trials investigated chil- used a corticosteroid dose equiva-
placebo or no treatment. Studies of
dren with solely Mycoplasma lent to 40 to 50 mg of prednisone
neonates, Pneumocystis jiroveci
pneumonia, and patients with HIV pneumoniae, 1 trial included any per day.
were excluded. There were no cause of pneumonia, and 1
limitations on the dose, route, or trial included children with respi- Corticosteroids were found to
duration of corticosteroid use. ratory syncytial virus. The 17 decrease mortality in adults with
Eligible studies reported on at least included studies had variable severe community-acquired pneu-
one of the following outcomes: all- routes of administration, classes of monia (defined as a Pneumonia
cause mortality, early clinical failure corticosteroid, and durations of Severity Index score 4), but not
treatment. Thirteen trials used in patients with nonsevere

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Systematic Review Snapshot

corticosteroids were shown to harmful, leading to increased lung


(defined as death from any cause, reduce clinical failure and time to inflammation, sepsis, and acute
radiographic progression, or clinical
clinical cure in bacterial respiratory distress syndrome.5
instability within 5 to 7 days), time
to clinical cure, development of
pneumonia, with no difference in One proposed mechanism for
respiratory failure (defined as the mortality rates. However, this was the beneficial role of cortico-
need for invasive or noninvasive based on limited data from 2 small steroids is reduction in cytokine
mechanical ventilation), studies. Corticosteroids were not release, thereby decreasing local
development of shock, transfer to associated with an overall inflammation at the site of
the ICU, duration of hospital stay, difference in adverse events or infection.6 Another possible role
duration of ICU stay, pneumonia secondary infection. However, of corticosteroids is in mitigating
complications (defined by the hyperglycemia was more common a Jarisch-Herxheimer–like reac-
individual study), secondary in adults given corticosteroids. tion (described as a heightened
infections greater than or equal to Overall, selection bias and attrition immune response to high
72 hours postrandomization, and bias were assessed to be low or cytokine burden shortly after
adverse events. Two authors
unclear, whereas performance initiation of antibiotics), which is
independently reviewed studies for
inclusion, with disagreements
bias was judged to be low for 9 thought to be similar to its role in
resolved by consensus with the trials, high for 7 trials, and unclear meningococcal meningitis.7
addition of a third reviewer if for 1 trial. Reporting bias was
needed. assessed as high for 14 trials and This is an update to a previous
low for 3 trials. review from 2016 that found a
DATA EXTRACTION AND decrease in the need for mechan-
ical ventilation, progression to
SYNTHESIS Commentary
acute respiratory distress syn-
Two authors independently
abstracted data from the individual Lower respiratory tract infections drome, and total length of hospital
studies, with disagreements remain the third most common stay for patients treated with
resolved by discussion and, as cause of death worldwide.1 In corticosteroids.8 The previous
necessary, in consultation with a 2013, pneumonia was the sixth review, however, did not
third reviewer. Risk ratios were leading cause of death among demonstrate a significant differ-
calculated for dichotomous data persons aged 65 years or older in ence in mortality rates or
and mean differences for the United States, and the most admission to the ICU, which was
continuous data. Bias was assessed common cause of death from an likely a result of a low adverse
with the Cochrane Risk of Bias tool infectious disease.2 Additionally, event rate. The current meta-
and overall quality of evidence was the treatment of pneumonia in the analysis included 12 new random-
assessed with the Grading of
United States costs in excess of ized controlled trials (4 of which
Recommendations Assessment,
$10 billion per year.3 Therefore, were studies examining cortico-
Development and Evaluation tool.
All differences were resolved there is great interest in providing steroid use in children) and
through discussion between the 2 improved treatments for the excluded 1 previously included
reviewers. Heterogeneity was reduction of morbidity, mortality, study (excluded because of use of
assessed with the I2 statistic. and costs in the management inhaled corticosteroids). This
of pneumonia. Corticosteroids meta-analysis showed reductions
have been suggested as one in mortality, clinical failure,
community-acquired pneumonia adjunct based on previous complication rates, length of hos-
(Table). The use of corticosteroids beneficial outcomes in other pitalization, total ICU stay, and
was also found to cause a infectious processes, including time to clinical cure, which was
reduction in early clinical failures, meningitis, pneumocystis pneu- most pronounced in patients with
time to clinical cure, length of monia, and tuberculosis.4 severe community-acquired pneu-
overall hospital stay, total Cytokine release and the resulting monia. It also showed reduced
ICU days, development of immune response are needed in a rates of early clinical failure
respiratory failure or shock, and host’s defense against an among patients with nonsevere
rates of pneumonia complications infection. However, an excess community-acquired pneumonia;
in adults. Among children, release of cytokines can be however, it did not demonstrate a

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Systematic Review Snapshot

difference in mortality in this limiting the conclusions that can 3. Niederman MS, McCombs JS, Unger AN,
et al. The cost of treating community-
subgroup. be drawn from those data. acquired pneumonia. Clin Ther.
1998;20:820-837.
The current systemic review has In summary, the current data sug- 4. Rhen T, Cidlowski JA. Antiinflammatory
several limitations that must be gest that corticosteroids reduce action of glucocorticoids—new mechanism
considered in light of the above for old drugs. N Engl J Med.
morbidity and mortality in severe 2005;353:1711-1723.
findings. First, the studies included community-acquired pneumonia. 5. Kellum JA, Kong L, Fink MP, et al.
in the meta-analysis varied in the Corticosteroids were also shown Understanding the inflammatory
doses, days of total treatment, and cytokine response in pneumonia and
to be beneficial in patients with sepsis: results of the Genetic and
type of corticosteroid adminis- nonsevere community-acquired Inflammatory Markers of Sepsis (GenIMS)
tered. Future studies should pneumonia who were admitted Study. Arch Intern Med.
compare the effect between to the hospital. The administration 2007;167:1655-1663.
6. Ellison RT 3rd, Donowitz GR. Acute
different types, doses, and treat- of corticosteroids was associated pneumonia. In: Mandell GL, Bennett JE, eds.
ment durations of corticosteroids. with an increased rate of hyper- Mandell, Douglas and Bennett’s Principles
Although statistical heterogeneity glycemia, without a difference in and Practice of Infectious Diseases. 8th ed.
was relatively low, there was a London, England: Churchill Livingstone;
other adverse events. 2015.
moderate amount of clinical het- 7. Brouwer MC, McIntyre P, Prasad K, et al.
erogeneity between the pop- Editor’s Note: This is a clinical Corticosteroids for acute bacterial meningitis.
ulations. Additionally, this review synopsis, a regular feature of the Cochrane Database Syst Rev.
Annals’ Systematic Review Snapshot 2015;(9):CD004405.
included patients with a variety of (SRS) series. The source for this 8. Gottlieb M, Bailitz J. Do corticosteroids
medical conditions (eg, chronic systematic review snapshot is: Stern provide benefit to patients with community-
obstructive pulmonary disease, A, Skalsky K, Avni T, et al. acquired pneumonia? Ann Emerg Med.
Corticosteroids for pneumonia. 2016;67:640-642.
diabetes), who may respond 9. Blum CA, Nigro N, Briel M, et al.
differently than patients without Cochrane Database Syst Rev.
Adjunct prednisone therapy
2017;12:CD007720.
these comorbidities. Moreover, for patients with community-
many of the outcomes were acquired pneumonia: a multicentre,
1. World Health Organization. The top 10 double-blind, randomised, placebo-
limited by small sample sizes, with causes of death. Available at: http://www. controlled trial. Lancet.
one study comprising nearly half who.int/mediacentre/factsheets/fs310/en/. 2015;385:1511-1518.
of all of the included patients.9 Accessed March 28, 2018.
Michael Brown, MD, MSc, Jestin N.
2. Xu J, Murphy SL, Kochanek KD, et al. Deaths:
Finally, the sample sizes in the final data for 2013. Natl Vital Stat Rep. Carlson, MD, MS, and Alan Jones, MD,
pediatric studies were very small, 2016;64:1-119. serve as editors of the SRS series.

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