Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: further evidence for survival and safety and implications for early treatment

OBJECTIVE: To provide further evidence for the efficacy and safety of drotrecogin alfa (activated) treatment in severe sepsis. DESIGN: Single-arm, open-label, trial of drotrecogin alfa (activated) treatment in severe sepsis patients. Enrollment began in March 2001 and day-28 follow-up completed in January 2003. SETTING: ENHANCE took place in 25 countries at 361 sites. PATIENTS: Patients with known or suspected infection, three or four systemic inflammatory response syndrome criteria, and one or more sepsis-induced organ dysfunctions. Of 2,434 adults entered, 2,378 received drotrecogin alfa (activated), and of these, 2,375 completed the protocol. INTERVENTIONS: Drotrecogin alfa (activated) was infused at a dose of 24 mug/kg/hr for 96 hrs. MEASUREMENTS AND MAIN RESULTS: The 28-day all-cause mortality approximated that observed in PROWESS (25.3% vs. 24.7%). Although patients in ENHANCE had increased serious bleeding rates compared with patients in the drotrecogin alfa (activated) arm of PROWESS (during infusion, 3.6% vs. 2.4%; postinfusion, 3.2% vs. 1.2%; 28-day, 6.5% vs. 3.5%), increased postinfusion bleeding suggested a higher background bleeding rate. Intracranial hemorrhage was more common in ENHANCE than PROWESS (during infusion, 0.6% vs. 0.2%; 28-day, 1.5% vs. 0.2%). The incidence of fatal intracranial hemorrhage was the same during infusion (0.2%) and higher at 28 days (0.5% vs. 0.2%). ENHANCE patients treated within 0-24 hrs from their first sepsis-induced organ dysfunction had lower observed mortality rate than those treated after 24 hrs (22.9% vs. 27.4%, p = .01). CONCLUSIONS: ENHANCE provides supportive evidence for the favorable benefit/risk ratio observed in PROWESS and suggests that more effective use of drotrecogin alfa (activated) might be obtained by initiating therapy earlier.     

Long-term outcomes in patients requiring stay of more than 48 hours in the intensive care unit following coronary bypass surgery

BACKGROUND: The primary objective of this study was to determine the long-term outcomes of all patients requiring prolonged intensive care unit (ICU) stay following coronary bypass surgery (CABG) surgery. METHODS: All patients undergoing CABG surgery between 1998 and 2002 were reviewed. Prolonged ICU stay was defined as more than 48 hours. Short-term (in-hospital) and long-term (postdischarge) outcomes were evaluated using available databases. RESULTS: Of 3139 patients who underwent CABG surgery, 598 required an ICU stay of more than 48 hours (19%). The in-hospital mortality for patients requiring prolonged ICU stay was 10.0% as compared with 1.2% for the remainder of patients (P < .0001). The median length of hospitalization for patients requiring prolonged stay was 11 days (IQR 7-18) as compared to 6 days (IQR 5-7). The median follow-up of patients who survived to discharge was 31 months with a 100% follow-up. Using Cox proportional hazard ratio, patients who required a prolonged ICU stay were found to have a significant lower survival and freedom from cardiac readmission to the hospital. Prolonged ICU stay was an independent predictor of composite outcome (death + readmission) with a hazard ratio of 1.8 (1.5-2.1). CONCLUSIONS: Prolonged ICU stay following CABG resulted in increased early and late mortality and lower freedom from readmission to hospital for cardiac reasons.     

Identification of risk factors for 30-day postoperative complications in patients undergoing primary ventral hernia repair: a prospective cohort study of 2,374 patients

Background

Primary ventral hernia is a common condition. Surgical repair is associated with complications, but no clear predictive risk factors have been identified. The European Hernia Society classification offers a structured framework to describe hernias and to analyze postoperative complications. Given this structured nature, the European Hernia Society classification might prove useful for preoperative patient or treatment classification. The objective of this study was to investigate the European Hernia Society classification as a predictor for complications within 30 days after primary ventral hernia surgery.

Tobacco withdrawal symptoms and urges to smoke in pregnant versus non-pregnant smokers

We compared tobacco withdrawal in pregnant and non-pregnant smokers abstaining from smoking for 24h. Female smokers completed an internet-based questionnaire, including the Minnesota Nicotine Withdrawal Scale-Revised (MNWS). They also rated additional withdrawal items and strength of urge to smoke. Consenting women were randomized to either: (i) abstain from smoking for 24h or (ii) smoke as usual. After 24h they rated their withdrawal again. We included a 'smoking as usual' group as we wished to establish that smoking abstinence increased withdrawal symptoms. Two-hundred and seventy-five women completed both the initial and the 24h questionnaire and reported abstaining (n=115, 17% pregnant) or smoking (n=160, 21% pregnant) as requested. Exclusively among abstinent smokers, we compared symptoms for the pregnant and non-pregnant groups. After 24h pregnant women had significantly lower scores than non-pregnant women for the mean MNWS (p=0.004) and for three individual MNWS symptoms (angry, p=0.010; anxious, p=0.048; impatient, p=0.011), with adjustments for baseline cigarette consumption and baseline withdrawal scores. Overall, on the first day of smoking abstinence, pregnant women are likely to report less severe tobacco withdrawal than non-pregnant women.     

A new self-expanding aortic stent valve with annular fixation: in vitro haemodynamic assessment

Objective: Balloon-expandable stent valves require flow reduction during implantation (rapid pacing). The present study was designed to compare a self-expanding stent valve with annular fixation versus a balloon-expandable stent valve. Methods: Implantation of a new self-expanding stent valve with annular fixation (Symetis^®, Lausanne, Switzerland) was assessed versus balloon-expandable stent valve, in a modified Dynatek Dalta^® pulse duplicator (sealed port access to the ventricle for transapical route simulation), interfaced with a computer for digital readout, carrying a 25 mm porcine aortic valve. The cardiovascular simulator was programmed to mimic an elderly woman with aortic stenosis: 120/85 mmHg aortic pressure, 60 strokes/min (66.5 ml), 35% systole (2.8 l/min). Results: A total of 450 cardiac cycles was analysed. Stepwise expansion of the self-expanding stent valve with annular fixation (balloon-expandable stent valve) resulted in systolic ventricular increase from 120 to 121 mmHg (126 to 830 ± 76 mmHg)*, and left ventricular outflow obstruction with mean transvalvular gradient of 11 ± 1.5 mmHg (366 ± 202 mmHg)*, systolic aortic pressure dropped distal to the valve from 121 to 64.5 ± 2 mmHg (123 to 55 ± 30 mmHg) N.S., and output collapsed to 1.9 ± 0.06 l/min (0.71 ± 0.37 l/min* (before complete obstruction)). No valve migration occurred in either group. (* = p < 0.05). Conclusions: Implantation of this new self-expanding stent valve with annular fixation has little impact on haemodynamics and has the potential for working heart implantation in vivo. Flow reduction (rapid pacing) is not necessary.     

The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is not appropriate for withholding surgery in high-risk patients with aortic stenosis: a retrospective cohort study

Background  

The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is a widely used risk assessment tool in patients with severe aortic stenosis to determine operability and to select patients for alternative therapies such as transcatheter aortic valve implantation. The objective of this study was to determine the accuracy of the EuroSCORE in predicting mortality following aortic valve replacement (AVR).