Pharmacology & Pharmacy, 2011, 2, 73-81
doi:10.4236/pp.2011.22009 Published Online April 2011 (
Copyright © 2011 SciRes. PP
Corticosteroids and ICU Course of Community
Acquired Pneumonia in Egyptian Settings
Nirmeen A. Sabry1, Emad El-Din Omar2
1Clinical Pharmacy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Critical Care Medicine, Fac-
ulty of Medicine, Cairo University, Cairo, Egypt.
Received February 2nd, 2011; revised February 12th, 2011; accepted February 21st, 2011.
Background: Pneumonia is the most common cause of community-acquired infection requiring ICU admission. 60% -
87% of pa ti en ts with sever e community ac qu ir ed pneumoni a (CAP) admitted to the ICU develops res piratory failure and
require mechanical ventilation (MV). Objectives: To assess the efficacy and safety of adjunctive low dose hydrocortisone
infusion treatment in Egyptian ICU patients with CAP. Methods: Hospitalized patients, clinically and radiologically
diagnosed with CAP, were rand omized t o re ceive hydr ocor tisone 12.5 mg/h IV infusion for 7 days or placeb o, along with
antibiotics. The end-points of the study were improvement in PaO2:FIO2 (PaO2:FIO2 > 300 or 100 increase from st udy
entry) and SOFA score by study day 8 and the development of delayed septic shock. Results: 80 patients were recruited,
40 of them received hydrocortisone and the remaining 40 received placebo. By study day 8, hydrocortisone treated pa-
tients showed a significant improvement in PaO2:FIO2 and chest radiograph score, and a significant reduction in
C-reactive protein (CRP) levels, Sepsis-related Organ Failure Assessment (SOFA) score, and delayed septic shock
compared to the control group. Hydro cortisone treatment wa s associated with a sign ificant reduc tion in the duration of
MV. However, hydrocortisone infusion did not show significant difference in the ICU mortality. Conclusions: adjunctive
7-day course of low dose hydrocortisone IV in patients with CAP hastens recovery of pneumonia and prevents the de-
velopment of sepsis related comp lications with a significant reduction in duration of the mechanical ventilation.
Keywords: Community-Acquired Pneumonia, Corticosteroids, Hydrocort isone, Pneumonia
1. Introduction
Community acquired pneumonia (CAP), which is a very
common reason for hospital admission, represents a po-
tentially life-threatening condition [1]. CAP is the first
infectious cause of death in developed countries [2], with
an estimate of 10% - 25% of CAP patients do not cure in
a timely manner [3]. The main reasons behind this delay
are: 1) development of complications e.g., post-obstructive
pneumonia, empyema, or lung abscess; 2) false percep-
tion of treatment failure. This perception may be attrib-
uted to the slow recovery in patients have superimposed
problems, e.g., malignancy, inflammations, heart failure,
or hospital-acquired infection [4].
Patients diagnosed with severe CAP normally require
admission to intensive care unit (ICU). More than 50%
of the patients admitted to the ICU develop respiratory
failure and require mechanical ventilation (MV) with a
high mortality rate [5].
Several studies have shown increased pulmonary and
circulating inammatory cytokine levels in patients with
severe CAP [6-9]. The levels of these mediators were
strongly associated with the presence of pneumonia [6],
bacteremia, and need for MV [7], Acute Physiology and
Chronic Health Evaluation (APACHE) II and multiple
organ dysfunction syndrome (MODS) scores [6,8,9]. It
was shown that there is a direct correlation between
CAP’s severity and the levels of circulating inflammatory
cytokines in CAP patients [6-8,10].
One of the main factors controlling the progression of
pneumonia is the host inflammatory response, which in-
creases excessively in non-responding pneumonia [11,12].
Many researchers were highly motivated to study the
relationship between host response and the level of stress.
These studies had a great focus on the role of intact hy-
pothalamic-pituitary-adrenal response to prevent the dis-
semination of pro-inflammatory storm from one organ to
another following local infection [13].
Corticosteroids, the most important natural inhibitors
of inammation, are not always effective in suppressing
Corticosteroids and ICU Course of Community Acquired Pneumonia in Egyptian Settings
life-threatening systemic inammation. The presence of
systemic inammation-induced tissue resistance to glu-
cocorticoids and/or inadequate adrenal output might ex-
plain why older clinical trials found no efcacy with a
time-limited course of massive doses of glucocorticoids
[14,15]. On the other hand, other studies have shown that
prolonged treatment with moderate doses of corticoster-
oids might improve intracellular down-regulation of in-
flammatory cytokine transcription and hasten the resolu-
tion of the illness [16,17].
In a multicentre study conducted on CAP patients ad-
mitted to the ICU and received antibiotic treatment. The
patients were randomly assigned to receive either hydro-
cortisone or placebo for 7 days. Treated patients showed
a significant improvement in PaO2:FIO2 and chest radio-
graph score. Also, a significant reduction in C-reactive
protein (CRP) levels, MODS score, and delayed septic
shock were observed, with a significant decline in the
periods the patients spent in hospital and mortality [18].
Salluh and co-authors investigated four studies fo-
cused on the use of corticosteroid in the management of
CAP [5]. They showed that, the administration of corti-
costeroids demonstrated an improvement in both the
physiological and clinical status without evidence for any
increased harm.
This issue is not new, as the use of steroids as an ad-
junct therapy in the management of pneumonia has been
recommended for more than 60 years [19]. The encour-
aging results of the recent low-dose hydrocortisone trials
together with the fact that, till the time of writing this
manuscript, glucocorticoids are not regularly used as a
treatment of pneumonia in the ICUs in the Egyptian hos-
pitals, generated the aim of the present study and evoked a
reassessment of the role of glucocorticoids in CAP in the
Egyptian ICUs.
2. Aim
The aim of the study was to assess the efficacy and safety
of adjunctive low dose hydrocortisone infusion treatment
in Egyptian ICU patients with CAP.
3. Methodology
3.1. Patients and Settings
This study was conducted between July 2010 and Janu-
ary 2011 where eighty adult subjects were enrolled in a
randomized, double blind, interventional study. The study
was conducted at critical care department, 3rd unit, Cairo
University, and the National Institute of Chest Diseases,
and Intensive Care Unit of Ain-Shams Hospital, Ain-
Shams University.
Each institutional review board approved the study
protocol, and the protocol of the study was registered in (ref. number: NCT01228110).
Patients to be eligible for this study should be meeting
the following criteria (1) presence of CAP, including two
minor or one major 1998 American Thoracic Society
(ATS) criterion for severe pneumonia which is modified
in 2007 [20].
Minor criteria included [18]
Respiratory rate > 30 bpm on admission;
Ratio of PaO2 to fraction of inspired oxygen
(PaO2:FIO2) < 250;
Chest radiograph showing bilateral involvement or
multilobar involvement;
Systolic blood pressure < 90 mm Hg; or diastolic
blood pressure < 60 mm Hg.
Major criteria included [18]
Requirement of MV;
Increase in the size of opacities on chest radiograph
of 50% at 48 hours;
Requirement of vasopressors > 4 hours; or
Serum creatinine 2 mg/dl or more.
Exclusion criteria:
Aspiration or hospital acquired pneumonia;
Discharge from hospital within the previous 14
Transferred from another hospital;
Immunosuppressed patients;
Chronic chest disease; TB, obstructive pneumonia;
cystic fibrosis, bronchiectasis;
Concomitant infections (e.g., sinusitis, urinary tract
Congestive heart failure (CHF);
Chronic renal or hepatic disease;
Acute burn injury;
Pregnancy; and
Major gastrointestinal bleed within 3 months of the
current hospitalization.
3.2. Study Design
Intervention group patients received maximal conven-
tional therapy plus intravenous hydrocortisone (loading
dose of 200 mg over 30 minutes, followed by 300 mg in
500 ml 0.9% saline at a rate of 12.5 mg/hr) for 7 days.
The Control group subjects were entitled to receive the
maximal conventional therapy plus equal volume of in-
travenous normal saline solution as placebo.
Patients continued to receive standard treatment after
Day 7, and in the incidences of hemodynamic instabili-
ties, hydrocortisone was administered according to the
physicians’ clinical judges.
The following variables were recorded:
1) demographic data (age, sex, DOB);
Copyright © 2011 SciRes. PP
Corticosteroids and ICU Course of Community Acquired Pneumonia in Egyptian Settings
Copyright © 2011 SciRes. PP
2) comorbidities;
3) routine laboratory screen and arterial blood gas
(ABG) at least once daily;
4) cause of pneumonia;
5) administered antibiotic regimen;
6) chest X-ray at least on admission and at day 8; and
7) Sepsis-related Organ Failure Assessment (SOFA)
score daily
8) days from diagnosis to death.
The primary outcomes were improvement in PaO2:FIO2
(PaO2:FIO2 > 300 or 100 increase from study entry),
SOFA score by day 8 and the development of delayed
septic shock. The adopted SOFA score was proposed by
Vincent et al. [21].
The number of MV-free days was defined as “the
number of days after ventilation wa s discontinued ” up to
study day 8. Shock was defined as “requirement of vaso-
pressors”. ARDS was defined by consensus criteria [22].
3.3. Statistical Analysis
Patients who were placed on systemic steroid therapy
concomitant were compared with those not receiving
steroids. Descriptive statistics were generated, specifically
means, standard deviations and ranges. To minimize type
I error, a p value equal to or less than 0.05 was taken as
cut-off level for the level of significance. The main tests
being used to analyze data extracted from this study are
the Mann-Whitney for nominal continuous data.
Wilcoxon signed rank test was also used to compare
the observed mean difference of the data arising when
the same individuals are studied more than once. The
chi-squared (X2) test for categorical data used to identify
by how much the two observations differ and also
whether this difference is more than might reasonably be
expected to occur in sampling. Statistical Package for
Social Science (SPSS) was used for data analysis.
4. Results
In total, 80 patients hospitalized with severe CAP were
recruited to be allocated to one of the two previously
described groups. Of these 80 subjects, 72.25% were
male with a mean (range) age of 62.23 (50 - 72) years.
At baseline, the 2 groups were comparable regarding
the general characteristics including age, sex, initial body
temperature, blood pressure, the diagnosis of underlying
diseases, severity of illness, MV and vasopressors re-
quirements, and microbiological results. The two groups
were also comparable regarding the respiratory rate > 30
bpm, PaO2:FIO2 < 200, chest X-ray assessment, and
other parameters at the beginning of the study (Table 1).
S. pneumoniae was the most common offending mi-
croorganism, followed by L. pneumophila, but the causa-
tive pathogen could not be identified in many of the pa-
tients as the culture specimen was sampled post antibiot-
ics initiation. Almost all patients were initially treated
empirically with intravenous antibiotic agents.
When the two study groups were compared, a signifi-
cant elevation in PaO2:FIO2 was recorded within the hy-
drocortisone group by the first day, and within the placebo
group by the 4th day (p = 0.027 and 0.01 respectively). By
day 8, a PaO2:FIO2 300 was observed in 10 (25%) pla-
cebo group patients versus 28 (70%) patients in the steroid
group with a level of significance of p = 0.003. PaO2:FIO2
improved by 100 from study entry was observed in 36
(90%) of the study group compared to 12 (30%) patients
in the placebo group (p < 0.001) (Table 2).
Table 1. Subject baseline characte ristic s in the tw o main groups.
Parameter Placebo (N = 40) Hydrocortisone (N = 40) p*
Male Distribution (%) 28 (70) 30 (75) 0.723**
Average Age in years (SD) 62.5 (4.26) 61.95 (6.97) 0.850
Age range in years 55-70 50 - 72
Average SOFA score (SD) 8.2 (1.46) 8.5 (1.52) 0.75
Average Body Temperature, °C (SD) 38.210 (0.43) 37.910 (0.61) 0.114
Average WBC count x 109/L (SD) 16.5 (4.11) 17.1 (3.97) 0.232
Number of patients on MV (%) 34 (85%) 26 (65%) 0.144**
Average PaO2:FIO2 (SD) 182 (52) 178 (48) 0.061
Number of patients with PaO2:FIO2 < 200 (%) 28 (70) 32 (80) 0.465**
Number of patients with catecholamine-dependent
septic shock (%) 4 (10) 8 (20) 0.376**
Average CRP (mg/dl) 58.7 (10.44) 55 (15.38) 0.438
Average Chest radiograph score (SD) 2.5 (0.58) 2.8 (0.71) 0.0.712
*p is the level of significance. ** Chi-square test was used to compare the groups at level of significance of < 0.05. SD: Standard Deviation. Mann Whitney
test was used to compare the groups at level of significance of < 0.05.
Corticosteroids and ICU Course of Community Acquired Pneumonia in Egyptian Settings
Table 2. Clinical and physiological characteristics by study day 8.
Parameter Placebo (N = 40) Hydrocortisone (N = 40) p*
Mean SOFA score (SD) 3.0 (0.90) 1.1 (0.53) 0.003
Number of patients on mechanical ventilation (%) 26 (65%) 10 (25%) 0.011**
Mean time from weaning of ventilated patients up to day 8 (SD) 1.2 (0.42) 3.4 (0.58) 0.01
Mean PaO2:FIO2 (SD) 243 (45) 338 (39) 0.0008
Number of patients with PaO2:FIO2 300 (%) 10 (25) 28 (70) 0.004**
Number of patients with PaO2:FIO2 improvement 100 from study
entry (%) 12 (30) 36 (90) 0.000**
Mean Chest radiograph score (SD) 2.7 (1.34) 1.3 (0.63) 0.0001
Number of patients with improvement in chest radiograph score
from Day 1 to 8 (%) 10 (25) 36 (90) 0.000**
Number of patients with MODS (%) 26 (65) 12 (30) 0.027**
Number of patients with Delayed septic shock (%) 14 (35) 2 (5) 0.018**
Number of patients with New ARDS (%) 6 (15%) 2 (5%) 0.292**
Mean CRP (mg/dl) (range) 36 (3 - 231) 17 (2 - 49) 0.0001
Number of Survival by day 8 (%) 34 (85%) 38 (95%) 0.633**
* p is the level of significance. Mann Whitney test was used to compare the groups at level of significance of < 0.05. ** Chi-square test was used to compare
e groups at level of significance of < 0.05. th
At study day 1, 34 versus 26 patients in placebo and
hydrocortisone groups respectively were placed on MV
(p = 0.18), while at day 8, 26 versus 10 patients in pla-
cebo and hydrocortisone groups respectively were still
ventilated (p = 0.01). Also, the hydrocortisone group
showed a significant reduction (p = 0.002) in the duration
of MV by day 8 (Figure 1).
group and 95% in the hydrocortisone group with no sig-
nificant difference between the two groups (p = 0.66). All
non-survivors required MV and had progression of ra-
diographic densities on chest radiograph. All (95%) but 2
patients developed pressor-dependent shock. The 2 pa-
tients without shock had L. pneumonia that progressed to
ARDS. Other complications included two (5%) liver
failure cases, and two (5%) lung abscess cases in the
placebo group, and two (5%) drug-induced hepatitis con-
ditions in the hydrocortisone-treated group (Figure 3).
A progressive reduction in CRP values was observed in
the hydrocortisone group. A significant difference (p =
0.0001) from the control group was reported by day 8
(Figure 2). Adverse events were few and the two groups were
When the two groups were compared with respect to
the major complications experienced by the recruited pa-
tients, it was found that 6 (15%) placebo patients developed
ARDS, 2 (5%) died by day 5; the other 4 (10%) died by
day 7. Survival to ICU discharge was 85% in the placebo
Day 0Day 2Day 4Day 6Day 8
Time (Day)
Placebo Group
Steroid Group
Day 0Day 1Day 2Day 3Day 4Day 5Day 6Day 7Day 8
Time (Day)
Steroid Group
Placebo Group
Figure 1. PaO2/FIO2 ratio curve during the study. Figure 2. CRP values during the study.
Copyright © 2011 SciRes. PP
Corticosteroids and ICU Course of Community Acquired Pneumonia in Egyptian Settings77
Patients with
delayed septic shock,
Patients with shock
not related to sepsis,
Patients with ARDS,
Patients with acute
renal failure, 15%
Patients with upper
bleeding, 5%
Patients with
Arrhythmia, 4%
Others, 10%
Patients with
delayed septic
shock, 5%
Patients with shock
not related to sepsis,
Patients with ARDS,
Patients with
Arrhythmia, 0%
Patients with acute
renal failure, 0%
Patients with upper
bleeding, 5%
Others, 5%
Figure 3. Complication during the Study, where (A) represents the complications in the placebo group, while (B) represents
the complications in the hydrocortisone group.
5. Discussion
Corticosteroids have been used successfully in the man-
agement of several infective and non-infective respira-
tory conditions, including miliary TB, [23] Pneumocystis
carinii pneumonia, [24] AIDS and other immunocom-
promised states, vasculitides [25] gastric acid aspiration,
[26] and ARDS [27]. Other studies have demonstrated
the efficacy of steroid in managing septic shock, [28]
meningitis, [29] and pneumonia caused by Pneumocystis
jiroveci [30].
Although this is not the first study evaluating the effi-
cacy and safety of hydrocortisone in patients with pneu-
monia, it is the first one to focus on management of CAP
in the Egyptian ICUs.
In the present study, hydrocortisone treated patients
showed a significant improvement in PaO2:FIO2, chest
radiograph score, and a significant decline in SOFA
score, CRP levels, and delayed septic shock when com-
pared to the control group. Hydrocortisone treatment was
associated with a significant decline in the duration of
MV. However, hydrocortisone infusion did not show
significant difference in the ICU mortality.
It is expected that systemic inflammation can occur in
Copyright © 2011 SciRes. PP
Corticosteroids and ICU Course of Community Acquired Pneumonia in Egyptian Settings
patients with severe CAP. Several studies have reported
increased local and systemic inflammatory cytokine lev-
els in CAP patients as the first step of the immune re-
sponse. These studies recommended the presence of a
fine balance between cytokine pro-inflammatory and
anti-inflammatory activities, which is very critical in the
host response [6,7,31]. Sibila et al. explained in a study
conducted on severe pneumonia patients, that despite the
inflammatory response initially being compartmentalised,
elevation in plasma cytokine levels is detected and was
strongly connected to poor prognosis [32].
Yende et al. in 2005, has demonstrated that patients
with increased levels of inflammatory cytokines prior to
infection were at higher risk of suffering from CAP. This
could be attributed to the up-regulated adherence of bac-
teria to human alveolar epithelial cells. This happens by
increasing expression of receptors that bind to these or-
ganisms suggesting an essential role of the inflammatory
response in the pathogenicity of the infection [33].
Evidence recommends that early administration of
corticosteroids may modify the inflammatory response
[34]. It is believed that corticoids inhibit the action of
many cytokines associated with pneumonia. At the mo-
lecular level, corticosteroids inhibits the transcription of
genes coding for cytokines, results in a decrease in the
release of macrophage-derived pro-inflammatory cyto-
kines [35], which in turn inhibits the T-cells and eosino-
phil functions. Production of leukotrienes and pros-
taglandins is also inhibited [36]. It is also possible that
corticosteroids may favorably alter pulmonary heamo-
dynamics [37].
The response to hydrocortisone treatment observed in
the present study and in other randomized trials of pa-
tients with septic shock [28,38-41] and severe pneumo-
cystis pneumonia [42] contrasts with the negative
ndings of older trials. These negative finding may be
related to the short duration of treatment [14,15]. Among
a number of studies in support of this hypothesis [14], a
randomized trial of patients with severe CAP found that a
single dose of hydrocortisone (10 mg/kg) before antibi-
otic administration showed no effect on plasma TNF-
levels [43].
On the other hand, Monton and coworkers [44] dem-
onstrated that the co-administration of steroids with anti-
biotic treatment reduces the lung inflammatory responses
in severe pneumonia and on MV, which supports the
results of the present study.
In 2006, Mikami et al. studied the effect of low dose
steroids on Japanese adult CAP patients, who received 40
mg intravenous prednisolone for 7 days. The steroids
group demonstrated faster stabilization, which lead to the
conclusion that, the administration of corticosteroids in
moderate-severe CAP, resolve the clinical symptoms and
shorten the duration of intravenous antibiotic therapy [45].
The same dose of prednisolone was used for the same
duration in a study conducted by Snijders et al., in 2010
and opposing to what was expected, the results were dif-
ferent. Although patients on prednisolone had faster de-
fervescence and faster decline in serum CRP levels com-
pared with placebo, data analysis did not show differences
in clinical outcome. Late failure was significantly more
common in the patients who had prednisolone than those
on placebo. So, it was concluded that 40 mg prednisolone
daily for one week does not improve the outcomes in
hospitalized patients diagnosed with CAP [46].
Keh et al. [28] confirmed the beneficial effects of
low-dose glucocorticoids, where rapid haemodynamic
stabilization was achieved in patients with septic shock
who received low doses of hydrocortisone. They con-
firmed that hydrocortisone attenuates the inflammatory
response, but does not have any effect on macrophages
and monocytes.
The correlation between organ failure, assessed by
MODS, and systemic inflammation, assessed by CRP,
suggests that a good clinical course is associated with
resolution of the inflammatory process whereas a clinical
deterioration is associated with ongoing inflammation.
The justification of the clinical improvement shown in
the present study can be based on what was explained by
Confalonieri et al., which was based on possible immu-
nomodulatory effects of the steroid infusion, thus accel-
erating the development of acute lung injury and multi-
organ failure [18].
It was also observed in the present study that, no evi-
dence for any increased risk of superinfection, bleeding,
or neuromuscular weakness, whereas hypernatremia and
hyperglycaemia occurred more frequently in the studied
subjects. Sprung et al., showed an increased incidence of
superinfection, including new episodes of sepsis or septic
shock, in the hydrocortisone group [47]. This variation in
the results may be attributed to the variation in the doses
used and the duration of the treatment, where in Sprung
et al. study, hydrocortisone was used for the longer treat-
ment period. Previous studies with high-dose corticoster-
oids have shown similar findings to the present study,
whereas the study conducted by the Acute Respiratory
Distress Syndrome (ARDS) Network [48] using higher
doses of corticosteroids and meta-analyses of studies that
used low doses [15,49] did not report higher rates of in-
fectious complications.
Despite these results, it is still important for physicians
to adopt prophylactic measures and to screen the patients
daily for possible complications.
Studies involving critically ill patients have reported
an association between corticosteroid therapy and the
incidence of neuromuscular weakness [48,50]. We did
Copyright © 2011 SciRes. PP
Corticosteroids and ICU Course of Community Acquired Pneumonia in Egyptian Settings79
not see this in the present study, although electrophysio-
logical testing was not performed.
Regarding the mortality, in contrast to what was found
in the present study, two studies found a significant re-
duction in mortality for patients with severe CAP treated
with corticosteroids [9,18]. Garcia-Vidal and colleagues
[9] evaluated 308 patients in a large retrospective sin-
gle-center cohort study and demonstrated that the use of
corticosteroids was strongly associated with a lower mor-
tality. The discrepancies between the two studies may be
attributed to the difference in the type of the study and
the adopted type of corticosteroid and the treatment dura-
tion period, were these patients were treated with a me-
dian dose of 45 mg/day of methylprednisolone for a
mean period of 11.4 days.
The study of Confalonieri and colleagues [18], showed
an impressive reduction in hospital mortality with a
7-day continuous infusion of hydrocortisone (240 mg/day).
This difference may be attributed to the difference in the
sample size used in the present study (80 patients) and in
Confalonieri study (46 patients).
Based upon the clinical observations, it is believed that
low dose of corticosteroid should be considered in addi-
tion to the antibacterial therapy together with an appro-
priate supportive care in the management of pneumonia.
This study should form the nucleus for other randomized
studies in Egypt as no other relevant studies are available
6. Study Limitation
The small sample size was the main weak point in pre-
sent study. This can be attributed to the self-funding na-
ture of the study. This limited sample size may have bi-
ased the estimate of the treatment effect on mortality, a
larger randomized trial is recommended to support the
mortality findings of this trial.
Secondly, old weaning guidelines were used and NIV
was not adopted in the two studied centers. However,
because of the parallel control nature of the study, the
two designed groups were treated in the same way,
where any difference in the outcomes between the two
studied groups could be attributed to the corticosteroid
Finally, in developing countries, due to limited access
to expensive diagnostic procedures, it was difficult to
assess the adrenal gland functions and the endogenous
7. Conclusion
Among the hospitalized patients with CAP, hydrocorti-
sone was associated with significant clinical improvement,
fastens recovery of pneumonia and prevented the devel-
opment of sepsis related complications with a significant
reduction in MV duration, but it does not affect the mor-
tality. At least for now, corticosteroids should routinely be
used as adjunctive therapy for CAP in the ICU.
8. Acknowledgements
This was a self-funded study. The authors would like to
acknowledge the great efforts made by the staff of the
ICUs in the study hospitals. Special thanks for Dr. Manal
El-Attar for her great help.
[1] M. Woodhead, “Community-Acquired Pneumonia,” In: J.
Franklin, Ed., Horizons in Medicine, Royal College of
Physicians, London, 2004, pp. 165-173.
[2] “Statistical Abstract of the United States,” 104th Edition,
Washington DC, US Government Printing Office, 1984.
[3] S. H. Feinsilver, A. M. Fein, M. S. Niederman, D. E.
Schultz and D. H. Faegenburg “Utility of Fiberoptic
Bronchoscopy in Nonresolving Pneumonia,” Chest, Vol.
98, No. 6, 1990, pp. 1322-1326.
[4] M. S. Niederman, L. A. Mandell, A. Anzueto, J. B. Bass,
W. A. Broughton, G. D. Campbell, N. Dean, T. File, M. J.
Fine, P. A. Gross, F. Martinez, T. J. Marrie, J. F. Plouffe,
J. Ramirez, G. A. Sarosi, A. Torres, R. Wilson and V. L.
Yu, “Guide Lines for the Management of Adults with
Community-Acquired Pneumonia. Diagnosis, Assessment
of Severity, Antimicrobial Therapy, and Prevention,”
American Journal of Respiratory and Critical Care
Medicine, Vol. 163, No. 7, 2001, pp. 1730-1754.
[5] J. Salluh, P. Póvoa, M. Soares, H. Castro-Faria-Neto, F.
Bozza and P. Bozza, “The Role of Corticosteroids in Se-
vere Community-Acquired Pneumonia: A Systematic
Review,” Critical Care, Vol. 12, No. 3, 2008, pp. 76-82.
[6] C. Monton, A. Torres, M. El-Ebiary, X. Filella, A.
Xaubet and J. P. De la Bellacasa, “Cytokine Expression in
Severe Pneumonia: A Bronchoalveolar Lavage Study,”
Critical Care Medicine, Vol. 27, No. 9, 1999, pp. 1745-
1753. doi:10.1097/00003246-199909000-00008
[7] S. Fernandez-Serrano, J. Dorca, M. Coromines, J. Car-
ratala, F. Gudiol and F. Manresa, “Molecular Inflamma-
tory Responses Measured in Blood of Patients with Se-
vere Community-Acquired Pneumonia,” Clinical and
Diagnostic Laboratory Immunology, Vol. 10, No. 5, 2003,
pp. 813-820.
[8] G. Antunes, S. A. Evans, J. L. Lordan and A. J. Frew,
“Systemic Cytokine Levels in Community-Acquired
Pneumonia and Their Association with Disease Severity,”
European Respiratory Journal, Vol. 20, No. 4, 2002, pp.
990-995. doi:10.1183/09031936.02.00295102
[9] C. Garcia-Vidal, E. Calbo, V. Pascual, C. Ferrer, S.
Quintana and J. Garau, “Effects of Systemic Steroids in
Patients with Severe Community-Acquired Pneumonia,”
European Respiratory Journal, Vol. 30, No. 5, 2007, pp.
Copyright © 2011 SciRes. PP
Corticosteroids and ICU Course of Community Acquired Pneumonia in Egyptian Settings
951-956. doi:10.1183/09031936.00027607
[10] H. Schutte, J. Lohmeyer, S. Rosseau, S. Ziegler, C.
Siebert, H. Kielisch, H. Pralle, F. Grimminger, H. Morr,
and W. Seeger, “Bronchoalveolar and Systemic Cytokine
Profiles in Patients with ARDS, Severe Pneumonia and
Cardiogenic Pulmonary Oedema,” European Respiratory
Journal, Vol. 9, No. 9, 1996, pp. 1858-1867.
[11] R. Mene´ndez, A. Torres, R. Zalacain, J. Aspa, J. J. Mar-
tin Villasclaras, L. Borderias, J. M. Benitez Moya, J.
Ruiz-Manzano, F. Rodriguez de Castro, J. Blanquer, D.
Perez, C. Puzo, F. Sanchez Gascon, J. Gallardo, C Alva-
rez and L. Molino, “Predictive Factors of Clinical Stabil-
ity in Community-Acquired Pneumonia,” Thorax, Vol. 59,
2004, pp. 960-965.
[12] M. Ioanas, M. Ferrer, M. Cavalcanti, .R Ferrer, S. Ewig,
X. Filella, J. P. dela Bellacasa and A. Torres, “Causes and
Predictors of Nonresponse to Treatment of ICU-Acquired
Pneumonia,” Critical Care Medicine, Vol. 32, No. 4,
2004, pp. 938-945.
[13] G. P. Chrouso, “Stressors, Stress, and Neuroendocrine
Integration of the Adaptive Response,” The 1997 Hans
Selye Memorial Lecture, Annals New York Academy of
Sciences, Vol. 851, 1998, pp. 311-335.
[14] G. U. Meduri, “An Historical Review of Glucocorticoid
Treatment in Sepsis. Disease Pathophysiology and the
Design of Treatment Investigation,” Sepsis, Vol. 3, 1999,
pp. 21-38. doi:10.1023/A:1009870524359
[15] P. C. Minneci, K. J. Deans, S. M. Banks, P. Q. Eichacker,
and C. Natanson, “Meta-Analysis: The Effect of Steroids
on Survival and Shock during Sepsis Depends on the
Dose,” Annals of International Medicine, Vol. 141, No. 1,
2004, pp. 47-56.
[16] P. E. Marik, S. M. Pastores, D. Annane, G. U. Meduri, W.
Arlt, C. L. Sprung, D. Keh, J. Briegel, A. Beishuizen, I.
Dimopoulou, S. Tsagarakis, M. Singer, G. P. Chrousos, G.
Zaloga, F. Bokhari and M. Vogeser, “Clinical Practice
Guidelines for the Diagnosis and Management of Corti-
costeroid Insufficiency in Critical Illness: Recommenda-
tions of an International Task Force,” Critical Care
Medicine, Vol. 36, No. 6, 2008, pp. 1937-1949.
[17] M. Mer, and G. A. Richards, “Pneumonia Corticosteroids
in Life-Threatening Varicella,” Chest, Vol. 114, No. 2,
1998, pp. 426-431. doi:10.1378/chest.114.2.426
[18] M. Confalonieri, R. Urbino, A. Potena, M. Piattella, P.
Parigi, G. Puccio, R. Della Porta, C. Giorgio, F. Blasi, R.
Umberger and G. U. Meduri, “Hydrocortisone Infusion
for Severe Community-Acquired Pneumonia: A Prelimi-
nary Randomized Study,” American Journal of Respira-
tory and Critical Care Medicine, Vol. 171, No. 3, 2005,
pp. 242-248.
[19] D. Perla and J. Marmorston, “Suprarenal Cortical Hor-
mone and Salt in the Treatment of Pneumonia and Other
Severe Infections,” Endocrinology, Vol. 27, No. 3, 1940,
pp. 367-374. doi:10.1210/endo-27-3-367
[20] S. Ewig, M. Ruiz, J. Mensa, M. A. Marcos, J. A. Marti-
nez, F. Arancibia, M. S. Niederman and A. Torres, “Se-
vere Community-Acquired Pneumonia: Assessment of
Severity Criteria,” American Journal of Respiratory and
Critical Care Medicine, Vol. 158, No. 4, 1998, pp. 1102
[21] J. L. Vincent, R. Moreno, J. Takala, S. Willatts, A. De
Mendonça, H. Bruining, C. K. Reinhart, P. M. Suter, and
L. G. Thijs. “The SOFA (Sepsis-Related Organ Failure
Assessment) Score to Describe Organ Dysfunction/Fai-
lure,” Intensive Care Medicine, Vol. 22, No. 7, 1996, pp.
707-710. doi:10.1007/BF01709751
[22] G. R. Bernard, A. Artigas, K. L. Brigham, J. Carlet, K.
Falke, L. Hudson, M. Lamy, J. R. LeGall, A. Morris and
R. Spragg, “The American-European Consensus Confer-
ence on ARDS: Definitions, Mechanisms, Relevant Out-
comes, and Clinical Trial Coordination,” American Jour-
nal of Respiratory and Critical Care Medicine, Vol. 149,
No. 3, 1994, pp. 818-24.
[23] T. Senderovitz and K. Viskun, “Corticosteroids in Tu-
berculosis,” Respiratory Medicine, Vol. 88, 1994, pp.
561-565. doi:10.1016/S0954-6111(05)80002-2
[24] S. A. Bozette, F. R. Sattler and J. Chiu, “A Controlled
Trial of Early Adjunctive Treatment with Corticosteroids
for Pneumocystis Carinii Pneumonia in the Acquired
Immunodeficiency Syndrome,” New England Journal of
Medicine, Vol. 323, No. 21, 1990, pp. 1451-1457.
[25] R. H. Leavitt and A. S. Fauci, “Pulmonary Vasculitis,”
American Review of Respiratory Diseases, Vol. 134, No.
1, 1986, pp. 149-166
[26] W. K. Bannister, A. J. Sattilano and R. D. Otis, “Thera-
peutic Aspects of Aspiration Pneumonitis in Experimen-
tal Animals,” Anesthiology, Vol. 23, 1961, pp. 440-445.
[27] C. U. Meduri, S. Headley, S. Carson, et al. “Methylpred-
nisolone Treatment of Late ARDS,” American Journal of
Respiratory and Critical Care Medicine, Vol. 155, 1997,
p. A391.
[28] D. Keh, T. Boehnke, S. Weber-Cartens, C. Schulz, O.
Ahlers, S. Bercker, H. Volk, W. Doecke, K. J. Falke and
H. Gerlach, “Immunologic and Hemodynamic Effects of
‘Low-Dose’ Hydrocortisone in Septic Shock. A Double
Blind, Randomized, Placebo-Controlled, Crossover
Study,” American Journal of Respiratory and Critical
Care Medicine, Vol. 167, No. 4, 2003, pp. 512-520.
[29] L. A. Mandell, R. G. Wunderink, A Anzueto, J. G. Bart-
lett, G. D. Campbell, A. Torres and C. G. Whitney,
“Guidelines for the Initial Management of Adults with
Community-Acquired Pneumonia: Diagnosis, Assess-
ment of Severity, and Initial Antimicrobial Therapy.
American Thoracic Society. Medical Section of the
American Lung Association,” American Review of Res-
piratory Diseases, Vol. 148, No. 5, 2007, pp. 1418-1426.
[30] M. Briel, R. Boscacci, H. Furrer and H. C. Bucher, “Ad-
junctive Corticosteroids for Pneumocystis Jiroveci Pneu-
monia in Patients with HIV infection: A Meta-Analysis of
Copyright © 2011 SciRes. PP
Corticosteroids and ICU Course of Community Acquired Pneumonia in Egyptian Settings
Copyright © 2011 SciRes. PP
Randomized Controlled Trials,” BMC Infectious Diseases,
Vol. 5, 2005, p. 101. doi:10.1186/1471-2334-5-101
[31] J. Puren, C. Feldman, N. Savage, P. J. Becker and C.
Smith, “Patterns of Cytokine Expression in Community-
Acquired Pneumonia,” Chest, Vol. 107, No. 5, 1995, pp.
1342-1349. doi:10.1378/chest.107.5.1342
[32] Sibila, C. Agusti and A. Torres, “Corticosteroids in Se-
vere Pneumonia,” European Respiratory Journal, Vol. 32,
No. 2, 2008, pp. 259-264.
[33] S. Yende, E. I. Tuomanen, R. Wunderink, A. Kanaya, A.
B. Newman, T. Harris, N. De Rekeneire and S. B.
Kritchevsky, “Preinfection Systemic Inflammatory Mark-
ers and Risk of Hospitalization Due to Pneumonia,”
American Journal of Respiratory and Critical Care
Medicine, Vol. 172, No. 11, 2005, pp. 1440-1446.
[34] C. U. Meduri, “The Role of the Host Defense Response in
the Progression and Outcome of ARDS: Pathophysi-
ological Correlations and Response to Gluococorticoid
Treatment,” European Respiratory Journal, Vol. 9, No.
12, 1996, pp. 2650-2670.
[35] P. J. Barnes and I. Adcock, “Anti-Inflammatory Actions
of Steroids: Molecular Mechanisms,” Trends in Pharma-
cological Sciences, Vol. 14, No. 12, 1993, pp. 436-441.
[36] S. Hong and L. Levine, “Inhibition of Arachidonic Acid
Release from Cells as the Biochemical Actions of
Anti-Inflammatory Steroids,” Proceedings of the Na-
tional Academy of Sciences USA, Vol. 73, No. 5, 1976, pp.
1730-1733. doi:10.1073/pnas.73.5.1730
[37] T. J. K. Toung, D. Bordos, D. W. Benson, D. Carter, G. D.
Zuidema, S. Permutt and L. Cameron, “Aspiration Pneu-
monia: Experimental Evaluation of Albumin and Steroid
Therapy,” Annals of Surgery, Vol. 183, No. 2, 1976, pp.
179-184. doi:10.1097/00000658-197602000-00016
[38] P. E. Bollaert, C. Charpentier, B. Levy, M. Debouverie, G.
Audibert and A. Larcan, “Reversal of Late Septic Shock
with Supraphysiologic Doses of Hydrocortisone,” Criti-
cal Care Medicine, Vol. 26, No. 4, 1998, pp. 645-650.
[39] K. Chawla, Y. Kupfer, I. Goldman and S. Tessler, “Hy-
drocortisone Reverses Refractory Septic Shock,” Critical
Care Medicine, Vol. 27, No. 1, 1999, p. A33.
[40] Yildiz, M. Doganay, B. Aygen, M. Guven, F. Keleutimur
and A. Tutuu, “Physiological-Dose Steroid Therapy in
Sepsis,” Critical Care, Vol. 6, No. 3, 2002, pp. 251-259.
[41] D. Annane, V. Sebille, C. Charpentier, P. E. Bollaert, B.
Francois, J. M. Korach, G. Capellier, Y. Cohen, E. Azou-
lay, G. Troche, et al., “Effect of Treatment with Low
Doses of Hydrocortisone and udrocortisone on Mortality
in Patients with Septic Shock,” Journal of the American
Medical Association, Vol. 288, No. 7, 2002, pp. 862-871.
[42] M. A. Jantz and S. A. Sahn, “Corticosteroids in Acute
Respiratory Failure,” American Journal of Respiratory
and Critical Care Medicine, Vol. 160, No. 4, 1999, pp.
[43] P. Marik, P. Kraus, J. Sribante, I. Havlik, J. Lipman and
D. W. Johnson, “Hydrocorisone and Tumor Necrosis Fac-
tor in Severe Community-Acquired Pneumonia: A Ran-
domized Controlled Study,” Chest, Vol. 104, No. 2, 1993,
pp. 389-392. doi:10.1378/chest.104.2.389
[44] C. Monton, S. Ewig, A. Torres, M. El-Ebiary, X. Filella,
A. Rano and A. Xaubet, “Role of Glucocorticoids on In-
flammatory Response in Nonimmunosuppressed Patients
with Pneumonia: A Pilot Study,” European Respiratory
Journal, Vol. 14, No. 1, 1999, pp. 218-220.
[45] K. Mikami, M. Suzuki, H. Kitagawa, M. Kawakami, N.
Hirota, H. Yamaguchi, O. Narumoto, Y. Kichikawa, M.
Kawai, H. Tashimo, H. Arai, T. Horiuchi and Y. Saka-
moto, “Efficacy of Corticosteroids in the Treatment of
Community-Acquired Pneumonia Requiring Hospitaliza-
tion,” Annals of International Medicine, Vol. 141, 2006,
pp. 47-56.
[46] D. Snijders, M. Johannes, A. Daniels, S. Casper, S. De
Graaff, S. Tjip, F. Van der Wer, G. Wim and A. Boersma,
“Efficacy of Corticosteroids in Community-acquired
Pneumonia,” American Journal of Respiratory and Criti-
cal Care Medicine, Vol. 181, No. 9, 2010, pp. 975-982.
[47] C. L. Sprung, D. Annane, D. Keh, R. Moreno, M. Singer,
K. Freivogel, Y. G. Weiss, J. Benbenishty, A. Kalenka, H.
Forst, P. F. Laterre, K. Reinhart, B. H. Cuthbertson, D.
Payen and J. Briegel, “Hydrocortisone Therapy for Pa-
tients with Septic Shock,” New England Journal of Medi-
cine, Vol. 358, No. 2, 2008, pp. 111-124.
[48] D. Annane, E. Bellissant, P. E. Bollaert, J. Briegel, D.
Keh and Y. Kupfer, “Corticosteroids for Severe Sepsis
and Septic Shock: A Systematic Review and Meta-
Analysis,” British Medical Association Journal, Vol. 329,
No. 7464, 2004, pp. 480-488.
[49] K. P. Steinberg, L. D. Hudson, R. B. Goodman, et al.,
“Efficacy and Safety of Corticosteroids for Persistent
Acute Respiratory Distress Syndrome,” New England
Journal of Medicine, Vol. 354, No. 16, 2006, pp. 1671-
[50] B. De Jonghe, T. Sharshar, J. P. Lefaucheur, et al., “Pare-
sis Acquired in the Intensive Care Unit: A Prospective
Multicenter Study,” Journal of the American Medical
Association, Vol. 288, No. 22, 2002, pp. 2859-2867.