21 Aug 12

Do low-dose corticosteroids improve mortality or shock reversal in patients with septic shock?

Posted in Sepsis, Steroid at 20:48 by Laci

By R Sherwin, A Garcia, R Bilkovski

J Emerg Med. 2012;43:7-12.

The management of septic shock has undergone a significant evolution in the past decade. A number of trials have been published to evaluate the efficacy of low-dose corticosteroid administration in patients with septic shock.

Methods
The Sepsis Sub-committee of the American Academy of Emergency Medicine Clinical Practice Committee performed an extensive search of the contemporary literature and identified seven relevant trials.

Results
Six of the seven trials reported a mortality outcome of patients in septic shock. Analysis of the data revealed that the relative risk (RR) of 28-day all-cause mortality in septic shock patients who received low-dose corticosteroids was 0.92 (95% confidence interval [CI] 0.79–1.07). All seven trials reported data concerning shock reversal or the withdrawal of vasopressors. Pooled results revealed that the RR of shock reversal is 1.17 (95% CI 1.07–1.28), which suggests that there may be significant improvement in shock reversal after corticosteroid administration. It is important to understand that two of the seven studies reviewed were disproportionately represented and accounted for 799 of 1005 patients (80%) considered for this recommendation.

Conclusions
The evidence suggests that low-dose corticosteroids may reverse shock faster; however, mortality is not improved for the overall population.

02 May 09

Use of corticosteroids in acute lung injury and acute respiratory distress syndrome

Posted in ALI/ARDS, Steroid at 1:08 by Laci

By B Tang, JC Craig, GD Eslick, I Seppelt, AS McLean

Crit Care Med  2009;37:1594-1603

Controversy remains as to whether low-dose corticosteroids can reduce the mortality and morbidity of acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS) without increasing the risk of adverse reactions. We aimed to evaluate all studies investigating prolonged corticosteroids in low-to-moderate dose in ALI or ARDS.

Datasources
MEDLINE, EMBASE, Current Content, and Cochrane Central Register of Controlled Trials, and bibliographies of retrieved articles.

Study selection
Randomized controlled trials (RCTs) and observational studies reported in any language that used 0.5-2.5 mg.kg-1.d-1 of methylprednisolone or equivalent to treat ALI/ARDS.

Data extraction
Data were extracted independently by two reviewers and included study design, patient characteristics, interventions, and mortality and morbidity outcomes.

Data synthesis
Both cohort studies (five studies, n = 307) and RCTs (four trials, n = 341) showed a similar trend toward mortality reduction (RCTs relative risk 0.51, 95% CI 0.24-1.09; p = 0.08; cohort studies relative risk 0.66, 95% CI 0.43-1.02; p = 0.06). The overall relative risk was 0.62 (95% CI 0.43-0.91; p = 0.01). There was also improvement in length of ventilation-free days, length of intensive care unit stay, Multiple Organ Dysfunction Syndrome Score, Lung Injury Scores, and improvement in PaO2/FiO2. There was no increase in infection, neuromyopathy, or any major complications. There was significant heterogeneity in the pooled studies. Subgroup and meta-regression analyses showed that heterogeneity had minimal effect on treatment efficacy; however, these findings were limited by the small number of studies used in the analyses.

Conclusion
The use of low-dose corticosteroids was associated with improved mortality and morbidity outcomes without increased adverse reactions. The consistency of results in both study designs and all outcomes suggests that they are an effective treatment for ALI or ARDS. The mortality benefits in early ARDS should be confirmed by an adequately powered randomized trial.

12 Mar 09

Interaction of vasopressin infusion, corticosteroid treatment, and mortality of septic shock

Posted in Inotropic support, Sepsis, Steroid at 23:11 by Laci

J A Russell, K R Walley, A C Gordon, D J Cooper, P C Hébert, J Singer for the Vasopressin and Septic Shock Trial (VASST) Investigators

Crit Care Med 2009;37:811-818

Vasopressin and corticosteroids are often added to support cardiovascular dysfunction in patients who have septic shock that is nonresponsive to fluid resuscitation and norepinephrine infusion. However, it is unknown whether vasopressin treatment interacts with corticosteroid treatment.

Design
Post hoc substudy of a multicenter randomized blinded controlled trial of vasopressin vs. norepinephrine in septic shock.

Setting
Twenty-seven Intensive Care Units in Canada, Australia, and the United States.

Patients
Seven hundred and seventy-nine patients who had septic shock and were ongoing hypotension requiring at least 5 μg/min of norepinephrine infusion for 6 hours.

Interventions
Patients were randomized to blinded vasopressin (0.01-0.03 units/min) or norepinephrine (5-15 μg/min) infusion added to open-label vasopressors. Corticosteroids were given according to clinical judgment at any time in the 28-day postrandomization period.

Measurements
The primary end point was 28-day mortality. We tested for interaction between vasopressin treatment and corticosteroid treatment using logistic regression. Secondary end points were organ dysfunction, use of open-label vasopressors and vasopressin levels.

Main results
There was a statistically significant interaction between vasopressin infusion and corticosteroid treatment (p = 0.008). In patients who had septic shock and were also treated with corticosteroids, vasopressin, compared to norepinephrine, was associated with significantly decreased mortality (35.9% vs. 44.7%, respectively, p = 0.03). In contrast, in patients who did not receive corticosteroids, vasopressin was associated with increased mortality compared with norepinephrine (33.7% vs. 21.3%, respectively, p = 0.06). In patients who received vasopressin infusion, use of corticosteroids significantly increased plasma vasopressin levels by 33% at 6 hours (p = 0.006) to 67% at 24 hours (p = 0.025) compared with patients who did not receive corticosteroids.

Conclusions
There is a statistically significant interaction between vasopressin and corticosteroids. The combination of low-dose vasopressin and corticosteroids was associated with decreased mortality and organ dysfunction compared with norepinephrine and corticosteroids.

01 Apr 08

Dexamethasone in adults with bacterial meningitis

Posted in Infection, Steroid at 19:29 by Laci

By J de Gans, D van de Beek for the European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators

NEJM 2002;347:1549-1556

Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis. In studies of bacterial meningitis in animals, adjuvant treatment with corticosteroids has beneficial effects.

Methods
We conducted a prospective, randomized, double-blind, multicenter trial of adjuvant treatment with dexamethasone, as compared with placebo, in adults with acute bacterial meningitis. Dexamethasone (10 mg) or placebo was administered 15 to 20 minutes before or with the first dose of antibiotic and was given every 6 hours for four days. The primary outcome measure was the score on the Glasgow Outcome Scale at eight weeks (a score of 5, indicating a favorable outcome, vs. a score of 1 to 4, indicating an unfavorable outcome). A subgroup analysis according to the causative organism was performed. Analyses were performed on an intention-to-treat basis.

Results
A total of 301 patients were randomly assigned to a treatment group: 157 to the dexamethasone group and 144 to the placebo group. The base-line characteristics of the two groups were similar. Treatment with dexamethasone was associated with a reduction in the risk of an unfavorable outcome (relative risk, 0.59; 95 percent confidence interval, 0.37 to 0.94; P=0.03). Treatment with dexamethasone was also associated with a reduction in mortality (relative risk of death, 0.48; 95 percent confidence interval, 0.24 to 0.96; P=0.04). Among the patients with pneumococcal meningitis, there were unfavorable outcomes in 26 percent of the dexamethasone group, as compared with 52 percent of the placebo group (relative risk, 0.50; 95 percent confidence interval, 0.30 to 0.83; P=0.006). Gastrointestinal bleeding occurred in two patients in the dexamethasone group and in five patients in the placebo group.

Conclusions
Early treatment with dexamethasone improves the outcome in adults with acute bacterial meningitis and does not increase the risk of gastrointestinal bleeding.

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