Sandrine Wiramus

Long-term outcome in medical patients aged 80 or over following admission to an intensive care unit

IntroductionThe aim of this study was to evaluate factors influencing short- and long-term survival in medical patients aged 80 and over following admission to an intensive care unit.MethodsAll patients aged 80 years or over and admitted between 2001 and 2006 were included in this study. Survival was evaluated between the time of admission and June 2009; factors associated with mortality were determined. Health-related quality of life was evaluated using Short Form (SF)-36 in long-term survivors.ResultsFor the 299 patients included (mean age, 84 ± 4 y), hospital mortality was 55%. Factors independently associated with hospital mortality were a higher SAPS II score at ICU admission; the existence of a fatal disease as reflected by the McCabe score and a cardiac diagnosis at admission. In the 133 hospital survivors, median survival time was 710 days (95% CI, 499-921). Two-year mortality rates were 79% of the initial cohort and 53% of hospital survivors. The standardized ratio of mortality at 2 years after hospital discharge was 2.56 (95% CI, 2.08-3.12) when compared with age- and gender-adjusted mortality of the general population. Factors independently associated with mortality at 2 years after hospital discharge were SAPS II score at ICU admission and the McCabe score. Conversely, functional status prior to admission as assessed by Knaus or Karnofsky scores was not associated with long-term mortality. In long-term survivors, SF-36 physical function scores were poor but scores for pain, emotional well-being and social function were not much affected.ConclusionsThe severity of acute disease at admission influences mortality at the hospital and following discharge in patients aged 80 or over. Although up to 50% of patients discharged from the hospital were still alive at 2 years, mortality was increased when compared with the general population. Physical function of long-term hospital survivors was greatly altered.

Effect of Statin Therapy on Mortality in Patients With Ventilator-AssociatedPneumonia: A Randomized Clinical Trial

IMPORTANCE Observational studies have reported that statin use may be associated with improved outcomes of various infections. Ventilator-associated pneumonia (VAP) is the most common infection in the intensive care unit (ICU) and is associated with substantial mortality. OBJECTIVE To determine whether statin therapy can decrease day-28 mortality in patients with VAP. DESIGN, SETTING, AND PARTICIPANTS Randomized, placebo-controlled, double-blind, parallel-group, multicenter trial performed in 26 intensive care units in France from January 2010 to March 2013. For power to detect an 8% absolute reduction in the day-28 mortality rate, we planned to enroll 1002 patients requiring invasive mechanical ventilation for more than 2 days and having suspected VAP, defined as a modified Clinical Pulmonary Infection Score of 5 or greater. The futility stopping rules were an absolute increase in day-28 mortality of at least 2.7% with simvastatin compared with placebo after enrollment of the first 251 patients. INTERVENTIONS Participants were randomized to receive simvastatin (60 mg) or placebo, started on the same day as antibiotic therapy and given until ICU discharge, death, or day 28, whichever occurred first. MAIN OUTCOMES AND MEASURES Primary outcome was day-28 mortality. Day-14, ICU, and hospital mortality rates were determined, as well as duration of mechanical ventilation and Sequential Organ Failure Assessment (SOFA) scores on days 3, 7, and 14. RESULTS The study was stopped for futility at the first scheduled interim analysis after enrollment of 300 patients, of whom all but 7% in the simvastatin group and 11% in the placebo group were naive to statin therapy at ICU admission. Day-28 mortality was not lower in the simvastatin group (21.2% [95% CI, 15.4% to 28.6%) than in the placebo group (15.2% [95% CI, 10.2% to 22.1%]; P = .10; hazard ratio, 1.45 [95% CI, 0.83 to 2.51]); the between-group difference was 6.0% (95% CI, -3.0% to 14.9%). In statin-naive patients, day-28 mortality was 21.5% (95% CI, 15.4% to 29.1%) with simvastatin and 13.8% (95% CI, 8.8% to 21.0%) with placebo (P = .054) (between-group difference, 7.7% [95%CI, -1.8% to 16.8%). There were no significant differences regarding day-14, ICU, or hospital mortality rates; duration of mechanical ventilation; or changes in SOFA score. CONCLUSIONS AND RELEVANCE In adults with suspected VAP, adjunctive simvastatin therapy compared with placebo did not improve day-28 survival. These findings do not support the use of statins with the goal of improving VAP outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01057758.

High central venous oxygen saturation in the latter stages of septic shock is associated with increased mortality

IntroductionCurrent guidelines recommend maintaining central venous oxygen saturation (ScvO2) higher than 70% in patients with severe sepsis and septic shock. As high levels of ScvO2 may reflect an inadequate use of oxygen, our aim was to evaluate the relation between maximal ScvO2 levels (ScvO2max) and survival among intensive care unit (ICU) patients with septic shock.MethodsWe retrospectively analyzed data from all admissions to our ICU between January 2008 and December 2009. All septic shock patients in whom the ScvO2 was measured were included. The measures of ScvO2maxwithin the first 72 hours after the onset of shock were collected.ResultsA total of 1,976 patients were screened and 152 (7.7%) patients met the inclusion criteria. The level of ScvO2maxwas 85% (78 to 89) in the non-survivors, compared with 79% (72 to 87) in the survivors (P = 0.009).ConclusionsOur findings raise concerns about high levels of ScvO2 in patients with septic shock. This may reflect the severity of the shock with an impaired oxygen use. Future strategies may target an optimization of tissue perfusion in this specific subgroup of patients.

Overview of antimicrobial therapy in intensive care units

In the management of a patient with severe sepsis, it is important to suspect the infection early, to collect samples immediately after diagnosis and to promptly initiate a broad-spectrum antibiotic treatment. The choice of this empirical antimicrobial therapy should be based on host characteristics, site of infection, local ecology and pharmacokinetics/pharmacodynamics of antibiotics. In severe infection, guidelines recommend the use of a combination of antibiotics. After results of cultures are obtained, treatment should be re-evaluated to either de-escalate or escalate the antibiotic prescription. This is associated with optimal costs, decreased incidence of superinfection and minimal development of antimicrobial resistance. All these steps should rely on written protocols, and the compliance to these protocols should be continuously monitored in order to detect violations and implement corrective procedures.

Emerging drugs in sepsis.

Importance of the field: Sepsis remains a major cause of death in intensive care units. Despite an intense research, a new drug that is effective in reducing mortality in sepsis is still awaited. Areas covered in this review: The literature was analyzed with Pubmed™ during the 2008 – 2009 period. If required, seminal articles published before 2008 were cited. Clinical trials focusing on ‘sepsis’ were first assessed. Next, relevant experimental data in this field were reported. What the reader will gain: The goal of the review is to determine the role for new licensed antibiotics, to give an insight into the conflict on adjuvant therapies and to disclose new experimental concepts. Take home message: New licensed antibiotics will offer the opportunity to refine the treatment choices. Direct hemoperfusion using polymyxin B-immobilized fiber column may be an option in sepsis due to Gram-negative bacilli. Among non-antibiotic drugs, new ongoing studies will clarify the role of drotrecogin alfa (activated) and low dose hydrocortisone. The modulation of monocytic human leukocyte antigen-DR seems the most prominent treatment. The use of cardiovascular drugs requires well-conducted clinical trials. The regulation of high mobility group box 1, adenosine blockade or correction of the impaired energy production is still at the experimental level.

Hypoxia-inducible factor (HIF1α) gene expression in human shock states

IntroductionHypoxia-inducible factor-1 (HIF1) controls the expression of genes involved in the cellular response to hypoxia. No information is available on its expression in critically ill patients. Thus, we designed the first clinical study in order to evaluate the role of HIF1α as a prognosis marker in patients suffering from shock.MethodsFifty consecutive adult patients with shock and 11 healthy volunteers were prospectively enrolled in the study. RNA was extracted from whole blood samples and expression of HIF1α was assessed over the first four hours of shock. The primary objective was to assess HIF1α as a prognostic marker in shock. Secondary objectives were to evaluate the role of HIF1α as a diagnostic and follow-up marker. Patient survival was evaluated at day 28.ResultsThe causes of shock were sepsis (78%), hemorrhage (18%), and cardiac dysfunction (4%). HIF1α expression was significantly higher in the shock patients than in the healthy volunteers (121 (range: 72-168) versus 48 (range: 38-54) normalized copies, P <0.01), whatever the measured isoforms. It was similar in non-survivors and survivors (108 (range 84-183) versus 121(range 72-185) normalized copies, P = 0.92), and did not significantly change within the study period.ConclusionsThe present study is the first to demonstrate an increased expression of HIF1α in patients with shock. Further studies are needed to clarify the potential association with outcome. Our findings reinforce the value of monitoring plasma lactate levels to guide the treatment of shock.

Antibiotic therapy in patients with septic shock.

The management of a patient with severe sepsis is first to diagnose the infection, to collect samples immediately after diagnosis and to initiate promptly broad-spectrum antibiotic treatment. The choice of empirical antimicrobial therapy should be based on host characteristics, site of infection, local ecology and the pharmacokinetics and pharmacodynamics of the antibiotics. In severe infection, guidelines recommend the use of a combination of antibiotics. After results of cultures are obtained, treatment should be re-evaluated to either de-escalate or escalate the antibiotics. This is associated with optimal costs, decreased incidence of superinfection and reduced development of antimicrobial resistance. All these steps should be based on written protocols, and compliance to these protocols should be monitored continuously in order to detect violations and implement corrective procedures.

Monitoring of plasma creatinine and urinary γ-glutamyl transpeptidase improves detection of acute kidney injury by more than 20%*

Objectives:We sought to determine how early we can detect acute kidney injury inpatients at intensive care unit admission by combining the use of plasma creatinine and urinary &ggr;-glutamyl transpeptidase. Design:Prospective study including development (n = 100) and validation (n = 56) cohorts. Settings:Intensive care unit of a university hospital. Interventions:None. Measurements and Main Results:To determine acute kidney injury, we subtracted measured creatinine clearance from theoretical creatinine clearance with a 25% reduction signifying acute kidney injury. Its incidence in 100 consecutive patients was 36%. An indexed urinary &ggr;-glutamyl transpeptidase–to–urinary creatinine ratio was significantly increased in the patients with acute kidney injury and did not correlate with plasma creatinine (p = .3). Using a predefined threshold of indexed urinary &ggr;-glutamyl transpeptidase–to–urinary creatinine ratio (>12.4 units/mmol) and plasma creatinine (>89 &mgr;mol/L), acute kidney injury detection was significantly improved, making it possible to detect 22 (22%) additional patients with acute kidney injury. This finding was confirmed in the validation group. The rates of false-positive results were 30% and 19% in the data development and internal validation cohorts, respectively. Conclusions:The use of low-cost, widely available markers (creatinine and urinary &ggr;-glutamyl transpeptidase) increases the detection of acute kidney injury. Further studies are needed to determine the impact on outcome with the use of these biomarkers.

Two-dimensional-strain echocardiography in intensive care unit patients: A prospective, observational study

Two‐dimensional‐strain echocardiography (2D‐strain) is a promising technique for the early detection of myocardial dysfunction. Our study was aimed to assess its feasibility in the intensive care unit (ICU). Our secondary goal was to determine if 2D‐strain could predict the patients outcome.

Occult pulmonary embolism in intensive care unit patients undergoing chest computed tomography scan: incidence and effect on outcomes.

OBJECTIVE To determine the incidence of occult pulmonary embolism (PE) and the associated morbidity in an intensive care unit (ICU). DESIGN Retrospective study. SETTING Fifteen-bed ICU of a university hospital. PARTICIPANTS Two hundred patients who underwent chest computed tomography (CT) scans with administration of contrast. INTERVENTIONS The patients were classified into 3 groups: (1) Occult PE if the chest CT scan was not taken, specifically for elucidating the diagnosis of PE, but it confirmed this diagnosis; (2) non-occult PE if the chest CT scan was taken to elucidate a suspected diagnosis of PE and confirmed this diagnosis; and (3) the chest CT scan did not confirm this diagnosis. The analysis was conducted to identify the effect of a diagnosis of occult PE on the outcomes of patients. MEASUREMENTS AND MAIN RESULTS Among the 200 patients who underwent chest CT scan, 27 (13%) patients had PE, in whom 18 (9%) were classified as occult PE and 9 (4.5%) as non-occult PE. The duration of ICU stay was increased in patients with PE, as compared with the controls (23 [18-48] days v 17 [10-20] days v 14 [7-29] days; p = 0.02 for occult PE, non-occult PE, and controls, respectively). No difference was observed in mortality rate among the 3 groups. CONCLUSION Occult PE was found in 9% of the cohort. This emphasized the need for developing diagnostic strategies in high-risk patients. Future studies should aim at assessing interventions for preventing this event.