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Despite the recent Sepsis-3 consensus, the Systemic Inflammatory Response Syndrome (SIRS) criteria continue to be assessed and recommended. Such use implies equivalence and interchangeability of criteria. Thus, we aimed to test whether such criteria are indeed equivalent and interchangeable.

Urine output (UO) criterion may increase the sensitivity of the definition of acute kidney injury (AKI). We determined whether the empirically derived definition for oliguria (<0.5 ml/kg/h) is independently associated with adverse outcome. Data analysis included hourly recorded UO from the prospective, multicenter FINNAKI study conducted in 16 Finnish intensive care units. Confounder-adjusted association of oliguria of different severity and duration primarily with the development of AKI defined by creatinine criterion (Cr-AKI) or renal replacement therapy (RRT) was assessed. Secondarily, we determined the association of oliguria with 90-day mortality. Of the 1966 patients analyzed for the development of AKI, 454 (23.1%) reached this endpoint. Within this AKI cohort, 312 (68.7%) developed Cr-AKI, 21 (4.6%) commenced RRT without Cr-AKI, and 121 (26.7%) commenced RRT with Cr-AKI. Episodes of severe oliguria (<0.1 ml/kg/h) for more than 3 h were independently associated with the development of Cr-AKI or RRT. The shortest periods of consecutive oliguria independently associated with an increased risk for 90-day mortality were 6–12 h of oliguria from 0.3 to <0.5 ml/kg/h, over 6 h of oliguria from 0.1 to <0.3 ml/kg/h, and severe oliguria lasting over 3 h. Thus, our findings underlie the importance of hourly UO measurements.

Objective:To determine if using freshest available rather than standard-issue red blood cells (RBCs) can reduce mortality in critically ill intensive care unit patients. Our study is the largest ongoing randomised controlled trial (RCT) of RBC age in critically ill patients and will help determine if the use of the freshest available RBCs should become standard policy for the critically ill.

Resuscitation of patients presenting with hemorrhagic shock after major trauma has evolved to incorporate multiple strategies to maintain tissue perfusion and oxygenation while managing coagulation disorders. We aimed to study changes across time in long-term outcomes in patients with major trauma. A retrospective observational study in a single major trauma center in Australia was conducted. We included all patients with major trauma and massive blood transfusion within the first 24 h during a 6-year period (from 2006 to 2011). The main outcome measures were Glasgow Outcome Score–Extended (GOSE) and work capacity at 6 and 12 months. There were 5,915 patients with major trauma of which 365 (6.2; 95 confidence interval 95 CI, 5.6 – 6.8) received a massive transfusion. The proportion of major trauma patients receiving a massive transfusion decreased across time from 8.2 to 4.4 (P< 0.01). There were statistically significant trends toward lower volumes of red blood cell transfusion and higher ratios of fresh-frozen plasma to red blood cells (P< 0.01). Among massively transfused patients, there was no significant change in measured outcomes during the study period, with a persistent 23 mortality in hospital, 52 unfavorable GOSE at 6 months, and 44 unfavorable GOSE at 12 months. Massive transfusion was independently associated with unfavorable outcomes at 6 months after injury (adjusted odds ratio, 1.56; 95 CI, 1.05 – 2.31) but not at 12 months (adjusted odds ratio, 0.85; 95 CI, 0.72 – 1.01). A significant reduction in massive transfusion rates was observed. Unfavorable long-term outcomes among patients receiving a massive transfusion after trauma were frequent with a substantial proportion of survivors experiencing poor functional status 1 year after injury.

Hypothermia improves outcome in resuscitated patients and newborns with hypoxic brain injury. We studied the safety and feasibility of mild hypothermia in awake patients with stroke after intravenous thrombolysis.

The aim of this study was to assess the association of hemodynamic factors with 90-day mortality in critically ill patients with severe acute pancreatitis (SAP).

Methylprednisolone is a widely used glucocorticoid. In this study, a possible interaction of itraconazole, a potent inhibitor of CYP3A4, with orally administered methylprednisolone was examined. In this double‐blind, randomized, 2‐phase crossover study, 10 healthy volunteers received either 200 mg itraconazole or placebo orally once a day for 4 days. On day 4, each subject ingested a dose of 16 mg methylprednisolone. Plasma concentrations of methylprednisolone, cortisol, itraconazole, and hydroxyitraconazole were determined by HPLC up to 24 hours. Itraconazole increased the total area under the plasma methylprednisolone concentration‐time curve 3.9‐fold compared with placebo (1968 ± 470 ng · hr/mL versus 520 ± 125 ng · hr/mL [mean ± SD]; P< .001). The peak plasma concentration of methylprednisolone was increased 1.9‐fold (221 ± 49 ng/mL versus 118 ± 25 ng/mL; P< .001), and its elimination half‐life was increased 2.4‐fold (4.4 ± 0.7 hours versus 1.9 ± 0.3 hours; P< .001) by itraconazole. The mean plasma cortisol concentration during the itraconazole phase, measured 24 hours after ingestion of methylprednisolone, was only about 13% of that during the placebo phase (18 ± 23 ng/mL versus 139 ± 60 ng/mL; P< .001). Itraconazole considerably increases plasma concentrations and effects of oral methylprednisolone, probably by inhibiting its CYP3A4‐mediated metabolism. Care should be taken if itraconazole or other potent inhibitors of CYP3A4 are used concomitantly with oral methylprednisolone, particularly during long‐term use. Clinical Pharmacology & Therapeutics(1998) 64, 363–368; doi:

Background: Quinidine is eliminated mainly by CYP3A4-mediated metabolism. Itraconazole interacts with some but not all of the substrates of CYP3A4; it is therefore important to study the possible interaction of itraconazole with quinidine.Methods: A double-blind, randomized, two-phase crossover study design was used with nine healthy volunteers. Itraconazole (200 mg) or placebo was ingested once a day for 4 days. A single 100 mg oral dose of quinidine sulfate was ingested on day 4. Plasma concentrations of quinidine, itraconazole, and hydroxyitraconazole, as well as cumulative excretion of quinidine into urine, were determined up to 24 hours. The ECG, heart rate, and blood pressure were also recorded up to 24 hours.Results: On average the peak plasma concentration of quinidine increased to 1.6-fold (p < 0.05), and the area under the concentration-time curve of quinidine increased to 2.4-fold (p < 0.01) by itraconazole. The elimination half-life of quinidine was prolonged 1.6-fold (p < 0.001), and the area under the 3-hydroxyquinidine/quinidine ratio-time curve decreased to one-fifth (p < 0.001) by itraconazole. The renal clearance of quinidine decreased 50% (p < 0.001) by itraconazole, whereas the creatinine clearance was unaffected. The QTcinterval correlated with the concentrations of quinidine during both itraconazole and placebo phases (r2= 0.71 and r2= 0.79, respectively; p < 0.01), although only minor changes between the phases were observed in other pharmacodynamic variables.Conclusions: Itraconazole increases plasma concentrations of oral quinidine, probably by inhibiting the CYP3A4 isozyme during the first-pass and elimination phases of quinidine. The decreased renal clearance of quinidine might be the result of the inhibition of P-glycoprotein-mediated tubular secretion of quinidine by itraconazole. The concentrations of quinidine should be closely monitored if itraconazole or some other potent CYP3A inhibitors are used with quinidine.