; for the SepNet-Critical Care Trials Group IMPORTANCE Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial. OBJECTIVE To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock.

Purpose: Insufficient antimicrobial exposure is associated with worse outcomes in sepsis. We evaluated whether therapeutic drug monitoring (TDM)-guided antibiotic therapy improves outcomes.Methods: Randomized, multicenter, controlled trial from January 2017 to December 2019. Adult patients (n = 254) with sepsis or septic shock were randomly assigned 1:1 to receive continuous infusion of piperacillin/tazobactam with dosing guided by daily TDM of piperacillin or continuous infusion with a fixed dose (13.5 g/24 h if eGFR ≥ 20 mL/min). Target plasma concentration was four times the minimal inhibitory concentration (range ± 20%) of the underlying pathogen, respectively, of Pseudomonas aeruginosa in empiric situation. Primary outcome was the mean of daily total Sequential Organ Failure Assessment (SOFA) score up to day 10.Results: Among 249 evaluable patients (66.3 ± 13.7 years; female, 30.9%), there was no significant difference in mean SOFA score between patients with TDM (7.9 points; 95% CI 7.1-8.7) and without TDM (8.2 points; 95% CI 7.5-9.0) (p = 0.39). Patients with TDM-guided therapy showed a lower 28-day mortality (21.6% vs. 25.8%, RR 0.8, 95% CI 0.5-1.3, p = 0.44) and a higher rate of clinical (OR 1.9; 95% CI 0.5-6.2, p = 0.30) and microbiological cure (OR 2.4; 95% CI 0.7-7.4, p = 0.12), but these differences did not reach statistical significance. Attainment of target concentration was more common in patients with TDM (37.3% vs. 14.6%, OR 4.5, CI 95%, 2.9-6.9, p < 0.001).

Introduction The aim of the study was to evaluate some of the underlying pathomechanisms of hydroxyethylstarch (HES) induced adverse effects on renal function using 24 porcine kidneys in an isolated perfusion model over six hours.

PurposeSecond-generation FloTrac software has been shown to reliably measure cardiac output (CO) in cardiac surgical patients. However, concerns have been raised regarding its accuracy in vasoplegic states. The aim of the present multicenter study was to investigate the accuracy of the third-generation software in patients with sepsis, particularly when total systemic vascular resistance (TSVR) is low.MethodsFifty-eight septic patients were included in this prospective observational study in four university-affiliated ICUs. Reference CO was measured by bolus pulmonary thermodilution (iCO) using 3–5 cold saline boluses. Simultaneously, CO was computed from the arterial pressure curve recorded on a computer using the second-generation (COG2) and third-generation (COG3) FloTrac software. CO was also measured by semi-continuous pulmonary thermodilution (CCO).ResultsA total of 401 simultaneous measurements of iCO, COG2, COG3, and CCO were recorded. The mean (95%CI) biases between COG2 and iCO, COG3 and iCO, and CCO and iCO were −10 (−15 to −5)% [−0.8 (−1.1 to −0.4) L/min], 0 (−4 to 4)% [0 (−0.3 to 0.3) L/min], and 9 (6–13)% [0.7 (0.5–1.0) L/min], respectively. The percentage errors were 29 (20–37)% for COG2, 30 (24–37)% for COG3, and 28 (22–34)% for CCO. The difference between iCO and COG2 was significantly correlated with TSVR (r2 = 0.37, p < 0.0001). A very weak (r2 = 0.05) relationship was also observed for the difference between iCO and COG3.ConclusionsIn patients with sepsis, the third-generation FloTrac software is more accurate, as precise, and less influenced by TSVR than the second-generation software.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-010-2098-8) contains supplementary material, which is available to authorized users.

IV midazolam 0.015 mg/kg administered 90 s before induction of anesthesia with etomidate is effective in reducing myoclonic movements and does not prolong recovery in unpremedicated patients after short procedures.

No abstract

These data show that the transpulmonary double indicator method may underestimate extravascular lung water and right ventricular preload when the perfusion to parts of the lung is obstructed.

IntroductionOne of the therapeutic essentials in severe sepsis and septic shock is an adequate fluid replacement to restore and maintain circulating plasma volume, improve organ perfusion and nutritive microcirculatory flow. The type of solution to be used as a fluid replacement remains under discussion. The aim of the study was to evaluate the effects of clinically used fluid replacement solutions on renal function and inflammatory response.MethodsA total of 23 anesthetized and ventilated female German Landrace pigs were investigated over 19 hours using a two-hit model that combined hemorrhagic and septic shock. The septic shock was induced using an Escherichia coli laden clot placed into the abdominal cavity. Infusions of 6% hydroxyethylstarch 130/0.42 in acetate (6% HES 130), 4% gelatin in acetate (4% gelatin) and 10% hydroxyethylstarch 200/0.5 in saline (10% HES200) compared to Ringer's acetate (RAc) were used for fluid replacement to maintain a central venous pressure of 12 mmHg. Ringer's acetate was also used in the sham-treated group (SHAM).ResultsAt study end the cardiac output (10% HES200 143 ± 48 ml/kgBW; 6% HES130 171 ± 47 ml/kgBW; RAc 137 ± 32 ml/kgBW; 4% gelatin 160 ± 42 ml/kgBW), as well as mean arterial pressure did not differ between groups. N-acetyl-beta-D-glucosamidase was significantly higher in the hydroxyethylstarch 200 (157 ± 115 U/g creatinine; P < 0.05) group compared to hydroxyethylstarch 130 (24 ± 9 U/g creatinine), Ringer's acetate (2 ± 3 U/g creatinine) and SHAM (21 ± 15 U/g creatinine) at the study's end. Creatinine significantly increased by 87 ± 84 percent of baseline in the 10% HES200 group compared to RAc and 6% HES130. We demonstrated in the histology of the kidneys a significant increase in osmotic-nephrosis like lesions for 4% gelatin compared to RAc, 6% HES130 and SHAM. Urine output was lowest in the 10% HES200 and 4% gelatin group, however not significantly.Interleukin(IL)-6 levels were significantly elevated in the 10% HES200 group (3,845 ± 1,472 pg/ml) two hours after sepsis induction compared to all other groups (6% HES130 1,492 ± 604 pg/ml; RAc 874 ± 363 pg/ml; 4% gelatin 1,623 ± 1,242 pg/ml).ConclusionsDespite similar maintenance of macrocirculation 6% hydroxyethylstarch 130/0.42 and Ringer's acetate significantly preserve renal function and attenuate tubular damage better than 10% hydroxyethylstarch 200/0.5 in saline.