Annane steroids jama

We identified 17 randomized trials (n = 2138) and 3 quasi-randomized trials (n = 246) that had acceptable methodological quality to pool in a meta-analysis. Twenty-eight-day mortality for treated vs control patients was 388/1099 (%) vs 400/1039 (%) in randomized trials (risk ratio [RR], ; 95% confidence interval [CI], -; P = .05; I(2) = 53% by random-effects model) and 28/121 (%) vs 24/125 (%) in quasi-randomized trials (RR, , 95% CI, -; P = .83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (%) vs 264/599 (44%) (RR, ; 95% CI, -; P = .02). This treatment increased 28-day shock reversal (6 trials; 322/481 [%] vs 276/471 [%]; RR, ; 95% CI, -; P = .02; I(2) = 4%) and reduced intensive care unit length of stay by days (8 trials; 95% CI, - to -; P < .001; I(2) = 0%) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [%] vs 56/764 [%]; P = .50; I(2) = 0%), superinfection (14 trials; 184/998 [%] vs 170/950 [%]; P = .92; I(2) = 8%), or neuromuscular weakness (3 trials; 4/407 [1%] vs 7/404 [%]; P = .58; I(2) = 30%). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [%] vs 308/670 [46%]; P < .001; I(2) = 0%) and hypernatremia (3 trials; 127/404 [%] vs 77/401 [%]; P < .001; I(2) = 0%).

The best type of fluid replacement and optimal volume of resuscitation in the setting of severe sepsis have been heavily debated but studies have provided guidance to the clinician. One trial comparing 4% albumin with normal saline for fluid resuscitation found no difference in mortality at 28 days. 24 A 2004 meta-analysis similarly found no mortality advantage with the use of colloids compared with the use of crystalloids. 25 The trial of EGDT revealed that patients in the treatment arm received far greater volumes of fluid in the first 6 hours of resuscitation than those in the control arm. In a large study of European ICUs, patients with a positive fluid balance at 72 hours had a poor outcome. 26 In a clinical trial of patients with acute lung injury, the use of a conservative fluid strategy targeting a CVP lower than 4 mm Hg and a pulmonary artery occlusion pressure (PAOP) lower than 8 mm Hg was associated with a fewer number of ICU and ventilators days. 27 The preponderance of data would suggest that aggressive fluid management be done in the acute phase of sepsis, followed by a more conservative phase in the following few days.

Results  We identified 17 randomized trials (n = 2138) and 3 quasi-randomized trials (n = 246) that had acceptable methodological quality to pool in a meta-analysis. Twenty-eight-day mortality for treated vs control patients was 388/1099 (%) vs 400/1039 (%) in randomized trials (risk ratio [RR], ; 95% confidence interval [CI], -; P =.05; I 2 =53% by random-effects model) and 28/121 (%) vs 24/125 (%) in quasi-randomized trials (RR, , 95% CI, -; P  = .83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (%) vs 264/599 (44%) (RR, ; 95% CI, -; P  = .02). This treatment increased 28-day shock reversal (6 trials; 322/481 [%] vs 276/471 [%]; RR, ; 95% CI, -; P  = .02; I 2  = 4%) and reduced intensive care unit length of stay by days (8 trials; 95% CI, – to –; P  < .001; I 2  = 0%) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [%] vs 56/764 [%]; P  = .50; I 2  = 0%), superinfection (14 trials; 184/998 [%] vs 170/950 [%]; P  = .92; I 2  = 8%), or neuromuscular weakness (3 trials; 4/407 [1%] vs 7/404 [%]; P  = .58; I 2  = 30%). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [%] vs 308/670 [46%]; P  < .001; I 2  = 0%) and hypernatremia (3 trials; 127/404 [%] vs 77/401 [%]; P  < .001; I 2  = 0%).

The editorial that accompanied the Annane Trial [1] used the trial's results to argue against the blanket administration of corticosteroids in patients with septic shock, and instead to tailor their administration to those with relative adrenal insufficiency. Since then, several other trials have been published that bring even this recommendation into question. Among them, the largest and most well designed is the CORTICUS trial (2008), which also evaluated corticosteroids in septic shock. However, CORTICUS did not demonstrate the same mortality benefit at 28 days, even among patients with relative adrenal insufficiency. Some of the differences in outcomes may have resulted from the baseline characteristics of the populations studied. For example, patients in the Annane Trial were more critically ill both by SAPS II scores and by mortality in the placebo group (61% in the Annane Trial and 32% in CORTICUS), limiting the study's generalizability.

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Annane steroids jama

annane steroids jama

The editorial that accompanied the Annane Trial [1] used the trial's results to argue against the blanket administration of corticosteroids in patients with septic shock, and instead to tailor their administration to those with relative adrenal insufficiency. Since then, several other trials have been published that bring even this recommendation into question. Among them, the largest and most well designed is the CORTICUS trial (2008), which also evaluated corticosteroids in septic shock. However, CORTICUS did not demonstrate the same mortality benefit at 28 days, even among patients with relative adrenal insufficiency. Some of the differences in outcomes may have resulted from the baseline characteristics of the populations studied. For example, patients in the Annane Trial were more critically ill both by SAPS II scores and by mortality in the placebo group (61% in the Annane Trial and 32% in CORTICUS), limiting the study's generalizability.

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