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Purpose: The benefits of low-dose steroids in septic shock remain controversial. We investigated if these low doses were able to induce their expected hormonal effects by analyzing the biological modifications observed during the study, which first demonstrated the survival benefit of low-dose steroids. Methods: This was a multicenter, placebo-controlled, randomized, double-blind study in which 299 septic shock patients received a 7-day treatment with a combination of hydrocortisone (50 mg intravenously four times daily) and fludrocortisone (50 μg orally once daily) or matching placebos. Gluco- and mineralocorticoid biological effects observed during the 7 days of treatment were compared between groups. Results: Steroids significantly decreased eosinophil counts from day 2 to day 7. Steroids significantly increased plasma glucose from day 2 (compared with placebos: +0.8 mmol/l) to day 7 (+1.8 mmol/l) and cholesterol from day 3 (+0.54 mmol/l) to day 7 (+0.39 mmol/l). Steroids significantly increased plasma sodium from day 3 (+2 mmol/l) to day 7 (+5 mmol/l) and significantly decreased plasma potassium on day 7 (−0.2 mmol/l). Steroids significantly decreased urinary sodium/potassium ratio from day 2 (−47 %) to day 7 (−57 %) and sodium fractional excretion from day 3 (−25 %) to day 7 (−66 %). Steroids significantly increased urine output on day 4 and 5 and osmolar clearance from day 4 to day 7, and decreased free-water clearance from day 4 to day 7, this effect being significant on day 4 and 6. Conclusions: In septic shock, low-dose steroids induced both gluco- and mineralocorticoid biological effects and seemed to improve renal function. Most of these effects appeared after 2-3 days of treatment and lasted at least until the end of treatment. [ABSTRACT FROM AUTHOR]

The article discusses the application of extracorporeal membrane oxygenation (ECMO) in cardiopulmonary disease. Topics discussed include alteration of drug's pharmacokinetics (PK) due to ECMO increasing risk of toxicity, maintaining the concentration of antibacterial drug above the minimum inhibitory concentration to ensure success of treatment, adsorption of drug being dependent on duration of use, and drugs used by ECMO patients such as cephalosporins and carbapenems having no effect on PK.

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The article discusses a study which investigated the risks and benefits of corticosteroid treatment in severe sepsis and septic shock. The study included 17 randomized and quasi-randomized trials of corticosteroids compared to placebo in adult patients. In 12 trials, study authors found that prolonged use of low-dose corticosteroids resulted to 28-day shock reversal and reduced intensive care unit length of stay. Other trials showed the link between corticosteroids, gastrointestinal bleeding, neuromuscular weakness and hyperglycemia. Study authors claimed that corticosteroids have beneficial effect on short-term mortality.

The article presents a randomized controlled trial that examined the use of the corticosteroid methylprednisolone to prevent laryngeal edema in patients after they had a tracheal intubation tube removed. Patients in the study were recruited from the intensive care units of hospitals and were ventilated for more than thirty-six hours. The authors found that intravenous administration of methylprednisolone before extubation reduced the occurrence of post-extubation laryngeal edema and suggest that the pretreatment with methylprednisolone be considered for patients prior to a planned extubation.

Phase III trials are aimed at assessing whether new treatments have superior efficacy than standards. Sequential methods, such as the single triangular test (STT) and the double triangular test (DTT), allow for early stopping of such trials. They use stopping boundaries which depend, for a binary endpoint, on π0 and π1 (response rates under standard and new treatment, respectively) and α and β (type I and II errors, respectively). Thus, a wrong estimation of π0 at planning phase might have an influence on their statistical properties. We assessed the extent of this influence by simulations regarding α, 1 − β, and average sample number (ASN) and compared the two methods with the one-sided and two-sided single-stage designs (SSD). There was no influence on α for any test and the power achieved by the one-sided or two-sided SSD was moderately affected by a wrong estimation of π0. However, important drifts (whose magnitude depended on chosen design) were observed for sequential methods concerning power and ASN in case of moderate under- or overestimation of π0 (±20% compared with its ‘true’ value). For example, when ‘true’ values of π0 and π1 are 0.30 and 0.40, respectively, using design values of 0.10 and 0.20, the power is 0.57 and 0.50 for the STT and DTT, respectively, instead of 0.95. When ‘true’ values of π0 and π1 are 0.10 and 0.20, respectively, using design values of 0.30 and 0.40, the ASN under H0 is 1309 and 2019 for the STT and DTT, respectively, instead of 392 and 601, respectively, using the right design. Using sequential methods in comparative clinical trials with binary responses requires a precise knowledge of the response rate under standard treatment to avoid losses in power or inappropriate increases in sample size. [ABSTRACT FROM AUTHOR]

Objective To assess the effects of corticosteroids on mortality in patients with severe sepsis and septic shock. Data sources Randomised and quasi-randomised trials of corticosteroids versus placebo (or supportive treatment alone) retrieved from the Cochrane infectious diseases group's trials register, the Cochrane central register of controlled trials, Medline, Embase, and LILACS. Review method Two pairs of reviewers agreed on eligibility of trials.One reviewer entered data on to the computer and four reviewers checked them. We obtained some missing data from authors of trials and assessed methodological quality of trials. Results 16/23 trials (n =2063) were selected. Corticosteroids did not change 28 day mortality (15 trials, n =2022; relative risk 0.92,95% confidence interval 0.75 to 1.14) or hospital mortality (13 trials, n =1418;0.89,0.71 to 1.11).There was significant heterogeneity. Subgroup analysis on long courses (≥5 days) with low dose (≤300 mg hydrocortisone or equivalent) corticosteroids showed no more heterogeneity.The relative risk for mortality was 0.80 at 28 days (five trials, n =465;0.67 to 0.95) and 0.83 at hospital discharge (five trials, n =465,0.71 to 0.97). Use of corticosteroids reduced mortality in intensive care units (four trials, n =425,0.83,0.70 to 0.97), increased shock reversal at 7 days (four trials, n =425; 1.60,1.27 to 2.03) and 28 days (four trials, n =425, 1.26,1.04 to 1.52) without inducing side effects. Conclusions For all trials, regardless of duration of treatment and dose, use of corticosteroids did not significantly affect mortality.With long courses of low doses of corticosteroids, however, mortality at 28 days and hospital morality was reduced. [ABSTRACT FROM AUTHOR]

Presents letters to the editor. Corticosteroids for patients with septic shock; Relationship between hormone replacement therapy, socioeconomic status, and coronary heart disease; Direct-to-consumer advertising of genetic testing; Mode of delivery and risk of postpartum rehospitalization.