Background: Etomidate is frequently used to intubate traumatic brain injury (TBI) victims, even though it has been linked to adrenal insufficiency (AI) in some populations. Few studies have explored the risk of prolonged etomidateinduced AI among TBI victims. Objective: To determine the risk and the length of AI induced by etomidate in patients intubated for moderate and severe TBI. Methods: Participants in this observational study were moderate to severe intubated TBI victims aged $ 16 years. The anesthetic used (etomidate versus others) was determined solely by the treating emergency physician. Adrenocorticotropic hormone (ACTH) stimulation tests (250 mg) were performed 24, 48, and 168 hours after intubation. AI was defined as an increase in serum cortisol 1 hour post-ACTH test (delta cortisol) of less than 248.4 nmol/L. Results: Forty subjects (participation 42.6%) underwent ACTH testing. Fifteen received etomidate, and 25 received another anesthetic. There were no statistically significant differences between groups as to the cumulative incidence of AI at any measurement time. However, at 24 hours, exploratory post hoc analyses showed a significant decrease in delta cortisol (adjusted means: etomidate group: 305.1 nmol/L, 95% CI 214.7-384.8 versus other anesthetics: 500.5 nmol/L, 95% CI 441.8-565.7). This decrease was not present at 48 and 168 hours. Conclusion: In TBI victims, although a single dose of etomidate does not increase the cumulative incidence of AI as defined, it seems to decrease the adrenal response to an

Hydrogen sulfide is produced endogenously by a variety of enzymes involved in cysteine metabolism. Clinical data indicate that endogenous levels of hydrogen sulfide are diminished in various forms of cardiovascular diseases. The aim of the current study was to investigate the effects of hydrogen sulfide supplementation on cardiac function during reperfusion in a clinically relevant experimental model of cardiopulmonary bypass. Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 minutes of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or the sodium sulfide infusion (1 mg/kg/hour, n = 6). Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and pulmonary blood flow, vasodilator responses to acetylcholine and sodiumnitroprusside and pulmonary function were also determined. Administration of sodium sulfide led to a significantly better recovery of left and right ventricular systolic function (P < 0.05) after 60 minutes of reperfusion. Coronary blood flow was also significantly higher in the sodium sulfide-treated group (P < 0.05). Sodium sulfide treatment improved coronary blood flow, and preserved the acetylcholine-induced increases in coronary and pulmonary blood (P < 0.05). Myocardial ATP levels were markedly improved in the sulfide-treated group. Thus, supplementation of sulfide improves the recovery of myocardial and endothelial function and energetic status after hypothermic cardiac arrest during cardiopulmonary bypass. These beneficial effects occurred without any detectable adverse hemodynamic or cardiovascular effects of sulfide at the dose used in the current study. The aim of the current study was to test potential cytoprotective and anti-inflammatory effects of the novel biological mediator hydrogen sulfide in murine models. Murine J774 macrophages were grown in culture and exposed to cytotoxic concentrations of nitrosoglutathione, or peroxynitrite (a reactive species formed from the reaction of nitric oxide and superoxide). Pretreatment of the cells with sodium sulfide (60-300 µM) reduced the loss of cell viability elicited by the nitric oxide donor compound (3 mM) or by peroxynitrite (3 mM), as measured by the MTT method. Sodium sulfide did not affect cell viability in the concentration range tested. In mice subjected to bacterial lipopolysaccharide (LPS, 5 mg/kg i.p.), treatment of the animals with sodium sulfide (0.2 mg/kg/hour for 4 hours, administered in Alzet minipumps) reduced the LPSinduced increase in plasma IL-1β and TNFα levels. These responses were attenuated when animals were pretreated with the heme oxygenase inhibitor tin-protoporphyrin IX (6 mg/kg). The current results point to the cytoprotective and anti-inflammatory effects of hydrogen sulfide, in cells exposed to nitrosative stress, and in animals subjected to endotoxemia. Introduction It has been previously shown that the two forms of acute cholecystitis, acute acalculous cholecystiti...

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Rationale: Despite the efficacy and safety of low molecular weight heparin (LWMH) compared to unfractionated (UFH) in many patients, LMWH may bioaccumulate in patients with renal insufficiency which could cause an increased risk of bleeding. If LMWH thromboprophylaxis is safe in ICU patients with renal insufficiency, this could reduce the risk of DVT and HIT. Since the extent to which LMWH bioaccumulates in critically ill patients in prophylactic rather than therapeutic doses is unclear, our objective was to measure peak and trough anti-Xa levels during a multicenter randomized pilot trial of LMWH vs UFH for thromboprophylaxis in the medical-surgical ICU setting. Methods: We included 128 patients ≥18 years with an expected ICU stay ≥72h. We excluded patients with trauma, orthopedic, cardiac, or neurosurgery, severe hypertension, DVT, PE or hemorrhage within 3 mos, INR &gt;2ULN, PTT &gt;2ULN, platelets &lt;100 x109/L, and if creatinine clearance was &lt;30 ml/min on ICU admission. Trough anti-Xa levels were drawn when patients developed creatinine clearance &lt;30ml/min, trough and peak anti-Xa levels were drawn on Tuesdays and Thursdays regardless of serum creatinine, and random anti-Xa levels were drawn if patients had a bleeding event. Results: No differences were found in the 2 groups (median anti-Xa levels) as shown below. Conclusions: We did not observe LWMH or UFH bioaccumulation when administered in prophylactic doses in these critically ill patients with a range of renal dysfunction. Anti-Xa Levels Allocation Cr Cl &lt;30 (trough) Tues & Thurs (trough) Tues & Thurs (peak) Bleeding (random) Group A 8 tests in 2 pts 17 tests in 9 pts 17 tests in 9 pts 7 tests in 4 pts Group A 0.1 IU/mL 0.09 IU/mL 0.11 IU/mL 0.1 IU/mL Group B 23 tests in 5 pts 46 tests in 12 pts 46 tests in 12 pts 10 tests in 8 pts Group B 0.1 IU/mL 0.09 IU/mL 0.11 IU/mL 0.1 IU/mL