Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization. Hydrocortisone and tumor necrosis factor in severe community-acquired pneumonia. A randomized controlled study. Dexamethasone for treatment of patients mechanically ventilated for lower respiratory tract infection caused by respiratory syncytial virus. Ampicillin dosage and use of prednisolone in treatment of pneumonia: co-operative controlled trial.
We hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications. In a multicenter trial, patients admitted to the Intensive Care Unit (ICU) with severe community-acquired pneumonia received protocol-guided antibiotic treatment and were randomly assigned to hydrocortisone infusion or placebo. Hydrocortisone was given as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7 days. Primary end-points of the study were improvement in Pa(O(2)):FI(O(2)) (Pa(O(2)):FI(O(2)) > 300 or >/= 100 increase from study entry) and multiple organ dysfunction syndrome (MODS) score by Study Day 8 and reduction in delayed septic shock. Forty-six patients entered the study. At study entry, the hydrocortisone group had lower Pa(O(2)):FI(O(2)), and higher chest radiograph score and C-reactive protein level. By Study Day 8, treated patients had, compared with control subjects, a significant improvement in Pa(O(2)):FI(O(2)) (p = 0.002) and chest radiograph score (p < 0.0001), and a significant reduction in C-reactive protein levels (p = 0.01), MODS score (p = 0.003), and delayed septic shock (p = 0.001). Hydrocortisone treatment was associated with a significant reduction in length of hospital stay (p = 0.03) and mortality (p = 0.009). Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia.
                The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization.
                An open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan.
                Thirty-one adult CAP patients who required hospitalization were enrolled.
                Fifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate-severe subgroup but not as significant in the mild-moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses.
                In moderate-severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy. Community-acquired pneumonia is a major cause of death in third world countries. Antimicrobial therapy may have little impact on the natural history of patients with severe pneumonia. We hypothesized that the intrapulmonary production of tumor necrosis factor-alpha (TNF-alpha) may be responsible for the progressive lung injury and shock commonly seen in patients with severe pneumonia after commencing antibiotic therapy.
                To investigate the effects of a single bolus of hydrocortisone on the clinical course and serum TNF-alpha levels of patients with severe community-acquired pneumonia.
                Randomized placebo-controlled study.
                Multidisciplinary ICU of a tertiary care teaching hospital.
                Patients with three or more British Thoracic Society criteria of severe pneumonia were studied. Patients were randomized to receive either a single dose of hydrocortisone (10 mg/kg) or placebo 30 min prior to commencing antibiotic therapy. Patients were treated with cefotaxime and other antibiotics as clinically indicated. Blood for TNF-alpha was taken at the time of hospital admission and repeated 2, 6, and 12 h after starting antibiotic therapy.
                Thirty patients were studied: 16 received placebo and 14 received hydrocortisone. The patients who received placebo tended to be sicker than the patients who received hydrocortisone. The baseline TNF-alpha value was 989 +/- 374 pg/ml in the placebo group and 827 +/- 394 pg/ml in the hydrocortisone group. In both groups of patients, the TNF-alpha levels did not change significantly with time. There was no correlation between the TNF-alpha levels and the APACHE II score, lung injury score, or outcome. The only variable that predicted outcome was the APACHE II score.
                Bactericidal antibiotics do not increase serum TNF-alpha levels in patients with severe pneumonia. Hydrocortisone given prior to antibiotic treatment had no effect on the serum TNF-alpha levels or the clinical course of patients with severe community-acquired pneumonia. A study was undertaken to evaluate the efficacy of dexamethasone in patients mechanically ventilated for lower respiratory infection caused by respiratory syncytial virus (RSV-LRTI).
                In a multicentre randomised controlled trial patients were randomised to receive either intravenous dexamethasone (0.15 mg/kg 6 hourly for 48 hours) or placebo. End points were the duration of mechanical ventilation, length of stay (LOS) in the pediatric intensive care unit (PICU) and in hospital, and the duration of supplemental oxygen administration.
                Thirty seven patients received dexamethasone and 45 received placebo. There was no significant difference in any of the end points between the two groups. In a post hoc analysis patients were stratified into those with mild gas exchange anomalies (PaO(2)/FiO(2) >200 mm Hg and/or mean airway pressure </= 10 cm H(2)O, bronchiolitis group) and those with severe gas exchange anomalies (PaO(2)/FiO(2) </=200 mm Hg and mean airway pressure >10 cm H(2)O, pneumonia group). In the 39 patients with bronchiolitis the duration of mechanical ventilation was 4.3 days shorter in the dexamethasone group than in the placebo group (4.9 v 9.2 days, 95% CI -7.8 to -0.8, p=0.02) and the duration of supplemental oxygen was 3.6 days shorter (7.7 v 11.3 days, 95% CI -8.0 to -0.1, p=0.048). No differences in end points were found in the pneumonia group.
                Dexamethasone had no beneficial effect in patients mechanically ventilated for RSV-LRTI but was found to have a beneficial effect in patients with bronchiolitis. A controlled trial was carried out to investigate whether the rate of recovery from pneumonia treated with ampicillin is dose related. Sixty-three patients received 1 g ampicillin daily and 63 received 2 g ampicillin daily for seven or 14 days depending on the rate of response. Twenty patients in each of these groups received, in addition, 20 mg prednisolone daily for seven days. The treatment groups were comparable and the results of treatment were similar in the four groups. The only difference which was of statistical significance was that a larger proportion of patients receiving 1 g ampicillin daily became afebrile within one week. All the ampicillin rashes occurred in the patients receiving 2 g ampicillin daily with and without prednisolone. Ampicillin 1 g daily appears to be adequate dosage in the treatment of pneumonia, and the rate of recovery has not been shown to be accelerated by using 2 g. No deleterious effects were noted with additional prednisolone therapy and this appeared to increase the rate at which the patients became afebrile, although the figures were not statistically significant.
In most patients with pneumonia, corticosteroids are generally beneficial for accelerating the time to resolution of symptoms. However, evidence from the included studies was not strong enough to make any recommendations.