Christian Putensen

Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial

IMPORTANCEnHigh-dose intravenous administration of sodium selenite has been proposed to improve outcome in sepsis by attenuating oxidative stress. Procalcitonin-guided antimicrobial therapy may hasten the diagnosis of sepsis, but effect on outcome is unclear.nnnOBJECTIVEnTo determine whether high-dose intravenous sodium selenite treatment and procalcitonin-guided anti-infectious therapy in patients with severe sepsis affect mortality.nnnDESIGN, SETTING, AND PARTICIPANTSnThe Placebo-Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT), a multicenter, randomized, clinical, 2u2009×u20092 factorial trial performed in 33 intensive care units in Germany, was conducted from November 6, 2009, to June 6, 2013, including a 90-day follow-up period.nnnINTERVENTIONSnPatients were randomly assigned to receive an initial intravenous loading dose of sodium selenite, 1000 µg, followed by a continuous intravenous infusion of sodium selenite, 1000 µg, daily until discharge from the intensive care unit, but not longer than 21 days, or placebo. Patients also were randomized to receive anti-infectious therapy guided by a procalcitonin algorithm or without procalcitonin guidance.nnnMAIN OUTCOMES AND MEASURESnThe primary end point was 28-day mortality. Secondary outcomes included 90-day all-cause mortality, intervention-free days, antimicrobial costs, antimicrobial-free days, and secondary infections.nnnRESULTSnOf 8174 eligible patients, 1089 patients (13.3%) with severe sepsis or septic shock were included in an intention-to-treat analysis comparing sodium selenite (543 patients [49.9%]) with placebo (546 [50.1%]) and procalcitonin guidance (552 [50.7%]) vs no procalcitonin guidance (537 [49.3%]). The 28-day mortality rate was 28.3% (95% CI, 24.5%-32.3%) in the sodium selenite group and 25.5% (95% CI, 21.8%-29.4%) (Pu2009=u2009.30) in the placebo group. There was no significant difference in 28-day mortality between patients assigned to procalcitonin guidance (25.6% [95% CI, 22.0%-29.5%]) vs no procalcitonin guidance (28.2% [95% CI, 24.4%-32.2%]) (Pu2009=u2009.34). Procalcitonin guidance did not affect frequency of diagnostic or therapeutic procedures but did result in a 4.5% reduction of antimicrobial exposure.nnnCONCLUSIONS AND RELEVANCEnNeither high-dose intravenous administration of sodium selenite nor anti-infectious therapy guided by a procalcitonin algorithm was associated with an improved outcome in patients with severe sepsis. These findings do not support administration of high-dose sodium selenite in these patients; the application of a procalcitonin-guided algorithm needs further evaluation.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT00832039.

Determinants of prescription and choice of empirical therapy for hospital-acquired and ventilator-associated pneumonia

The objectives of this study were to assess the determinants of empirical antibiotic choice, prescription patterns and outcomes in patients with hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in Europe. We performed a prospective, observational cohort study in 27 intensive care units (ICUs) from nine European countries. 100 consecutive patients on mechanical ventilation for HAP, on mechanical ventilation >48 h or with VAP were enrolled per ICU. Admission category, sickness severity and Acinetobacter spp. prevalence >10% in pneumonia episodes determined antibiotic empirical choice. Trauma patients were more often prescribed non-anti-Pseudomonas cephalosporins (OR 2.68, 95% CI 1.50–4.78). Surgical patients received less aminoglycosides (OR 0.26, 95% CI 0.14–0.49). A significant correlation (p<0.01) was found between Simplified Acute Physiology Score II score and carbapenem prescription. Basal Acinetobacter spp. prevalence >10% dramatically increased the prescription of carbapenems (OR 3.5, 95% CI 2.0–6.1) and colistin (OR 115.7, 95% CI 6.9–1,930.9). Appropriate empirical antibiotics decreased ICU length of stay by 6 days (26.3±19.8 days versus 32.8±29.4 days; p = 0.04). The antibiotics that were prescribed most were carbapenems, piperacillin/tazobactam and quinolones. Median (interquartile range) duration of antibiotic therapy was 9 (6–12) days. Anti-methicillin-resistant Staphylococcus aureus agents were prescribed in 38.4% of VAP episodes. Admission category, sickness severity and basal Acinetobacter prevalence >10% in pneumonia episodes were the major determinants of antibiotic choice at the bedside. Across Europe, carbapenems were the antibiotic most prescribed for HAP/VAP.

Prognostic value of platelet-derived growth factor in patients with severe sepsis.

Primary objective: Platelet-derived growth factor-BB (PDGF-BB) has been shown to promote the structural integrity of the vessel wall and to increase wound healing capacity. Aim of the present study was to determine the role of PDGF-BB in the context of outcome of septic patients. Furthermore, the effect of treatment with recombinant human activated protein C (rhAPC) on plasma levels of PDGF-BB in severe sepsis was evaluated as well as the in vitro effect of rhAPC on PDGF-BB-release from human endothelial cells (HUVEC). Research design, methods and procedures: PDGF-BB levels were measured in 46 patients on day 3 of severe sepsis. Twenty-one of these patients received treatment with rhAPC. The in vitro effect of rhAPC on PDGF-BB-messenger RNA synthesis and release of PDGF-BB into supernatants was measured by reverse transcriptase-polymerase chain reaction and ELISA-methods. Main outcomes and results: Survivors of severe sepsis presented with higher PDGF-BB levels than non-survivors (p < 0.05). Septic patients with PDGF-BB levels below 200 pg/ml were 7.3 times more likely (RR = 7.3, 95% CI: 1.4–44.5; p < 0.05) to die from sepsis than patients with higher PDGF-BB values. RhAPC (1–10 μg/ml) stimulated endothelial PDGF-BB-messenger RNA transcription and PDGF-BB-release in vitro. Plasma levels of PDGF-BB in patients receiving rhAPC were significantly (p < 0.01) higher (median 277.7; 25–75th percentiles: 150.5–414.4 pg/ml) than in patients not treated with rhAPC (median: 125.6; 25–75th percentiles: 55.3–344.7 pg/ml). Conclusions: The ability of rhAPC to upregulate endothelial PDGF-BB production may represent a new molecular mechanism by which rhAPC controls vessel wall homeostasis and increases tissue healing capacity in severe sepsis. PDGF-BB may serve as useful laboratory marker to predict survival in patients presenting with severe sepsis.

Predictors of hippocampal atrophy in critically ill patients.

Hippocampal atrophy is presumably one morphological sign of critical illness encephalopathy; however, predictors have not yet been determined.

Outcome of acute respiratory distress syndrome in university and non-university hospitals in Germany

BackgroundThis study investigates differences in treatment and outcome of ventilated patients with acute respiratory distress syndrome (ARDS) between university and non-university hospitals in Germany.MethodsThis subanalysis of a prospective, observational cohort study was performed to identify independent risk factors for mortality by examining: baseline factors, ventilator settings (e.g., driving pressure), complications, and care settings—for example, case volume of ventilated patients, size/type of intensive care unit (ICU), and type of hospital (university/non-university hospital). To control for potentially confounding factors at ARDS onset and to verify differences in mortality, ARDS patients in university vs non-university hospitals were compared using additional multivariable analysis.ResultsOf the 7540 patients admitted to 95 ICUs from 18 university and 62 non-university hospitals in May 2004, 1028 received mechanical ventilation and 198 developed ARDS. Although the characteristics of ARDS patients were very similar, hospital mortality was considerably lower in university compared with non-university hospitals (39.3% vs 57.5%; pu2009=u20090.012). Treatment in non-university hospitals was independently associated with increased mortality (OR (95% CI): 2.89 (1.31–6.38); pu2009=u20090.008). This was confirmed by additional independent comparisons between the two patient groups when controlling for confounding factors at ARDS onset. Higher driving pressures (OR 1.10; 1 cmH2O increments) were also independently associated with higher mortality. Compared with non-university hospitals, higher positive end-expiratory pressure (PEEP) (meanu2009±u2009SD: 11.7u2009±u20094.7 vs 9.7u2009±u20093.7 cmH2O; pu2009=u20090.005) and lower driving pressures (15.1u2009±u20094.4 vs 17.0u2009±u20095.0 cmH2O; pu2009=u20090.02) were applied during therapeutic ventilation in university hospitals, and ventilation lasted twice as long (median (IQR): 16 (9–29) vs 8 (3–16) days; pu2009<u20090.001).ConclusionsMortality risk of ARDS patients was considerably higher in non-university compared with university hospitals. Differences in ventilatory care between hospitals might explain this finding and may at least partially imply regionalization of care and the export of ventilatory strategies to non-university hospitals.

Is internal jugular vein extensibility associated with indices of fluid responsiveness in ventilated patients

Ultrasound of the inferior vena cava provides rapid and non‐invasive assessment of fluid responsiveness. We hypothesized that the extensibility of the internal jugular vein (IJV) as well reflects intravascular volume state. We assessed IJV dimensions together with pulse pressure variation (PPV) as dynamic index for fluid responsiveness in mechanically ventilated patients.

Intraoperative ventilation settings and their associations with postoperative pulmonary complications in obese patients

Background: There is limited information concerning the current practice of intraoperative mechanical ventilation in obese patients, and the optimal ventilator settings for these patients are debated. We investigated intraoperative ventilation parameters and their associations with the development of postoperative pulmonary complications (PPCs) in obese patients. Methods: We performed a secondary analysis of the international multicentre Local ASsessment of VEntilatory management during General Anesthesia for Surgery’ (LAS VEGAS) study, restricted to obese patients, with a predefined composite outcome of PPCs as primary end‐point. Results: We analysed 2012 obese patients from 135 hospitals across 29 countries in Europe, North America, North Africa, and the Middle East. Tidal volume was 8.8 [25th–75th percentiles: 7.8–9.9] ml kg−1 predicted body weight, PEEP was 4 [1–5] cm H2O, and recruitment manoeuvres were performed in 7.7% of patients. PPCs occurred in 11.7% of patients and were independently associated with age (P<0.001), body mass index ≥40 kg m−2 (P=0.033), obstructive sleep apnoea (P=0.002), duration of anaesthesia (P<0.001), peak airway pressure (P<0.001), use of rescue recruitment manoeuvres (P<0.05) and routine recruitment manoeuvres performed by bag squeezing (P=0.021). PPCs were associated with an increased length of hospital stay (P<0.001). Conclusions: Obese patients are frequently ventilated with high tidal volume and low PEEP, and seldom receive recruitment manoeuvres. PPCs increase hospital stay, and are associated with preoperative conditions, duration of anaesthesia and intraoperative ventilation settings. Randomised trials are warranted to clarify the role of different ventilatory parameters in obese patients. Clinical trial registration: NCT01601223.

End-of-life perceptions among physicians in intensive care units managed by anesthesiologists in Germany: a survey about structure, current implementation and deficits

BackgroundStructural aspects and current practice about end-of-life (EOL) decisions in German intensive care units (ICUs) managed by anesthesiologists are unknown. A survey among intensive care anesthesiologists has been conducted to explore current practice, barriers and opinions on EOL decisions in ICU.MethodsIn November 2015, all members of the German Society of Anesthesiology and Intensive Care Medicine (DGAI) and the Association of German Anesthesiologists (BDA) were asked to participate in an online survey to rate the presence or absence and the importance of 50 items. Answers were grouped into three categories considering implementation and relevance: Category 1 reflects high implementation and high relevance, Category 2 low and low, and Category 3 low and high.ResultsFive-hundred and forty-one anesthesiologists responded. Only four items reached ≥90% agreement as being performed “yes, always” or “mostly”, and 29 items were rated “very” or “more important”. A profound discrepancy between current practice and attributed importance was revealed. Twenty-eight items attributed to Category 1, six to Category 2 and sixteen to Category 3. Items characterizing the most urgent need for improvement (Category 3) referred to patient outcome data, preparation of health care directives and interdisciplinary discussion, standard operating procedures, implementation of practical instructions and inclusion of nursing staff and families in the process.ConclusionThe present survey affirms an urgent need for improvement in EOL practice in German ICUs focusing on advanced care planning, distinct aspects of changing goals of care, implementation of standard operating procedures, continuing education and reporting of outcome data.

Potentially modifiable respiratory variables contributing to outcome in ICU patients without ARDS: a secondary analysis of PRoVENT

AbstractBackgroundThe majority of critically ill patients do not suffer from acute respiratory distress syndrome (ARDS). To improve the treatment of these patients, we aimed to identify potentially modifiable factors associated with outcome of these patients.nMethodsThe PRoVENT was an international, multicenter, prospective cohort study of consecutive patients under invasive mechanical ventilatory support. A predefined secondary analysis was to examine factors associated with mortality. The primary endpoint was all-cause in-hospital mortality.nResults935 Patients were included. In-hospital mortality was 21%. Compared to patients who died, patients who survived had a lower risk of ARDS according to the ‘Lung Injury Prediction Score’ and received lower maximum airway pressure (Pmax), driving pressure (ΔP), positive end-expiratory pressure, and FiO2 levels. Tidal volume size was similar between the groups. Higher Pmax was a potentially modifiable ventilatory variable associated with in-hospital mortality in multivariable analyses. ΔP was not independently associated with in-hospital mortality, but reliable values for ΔP were available for 343 patients only. Non-modifiable factors associated with in-hospital mortality were older age, presence of immunosuppression, higher non-pulmonary sequential organ failure assessment scores, lower pulse oximetry readings, higher heart rates, and functional dependence.ConclusionsHigher Pmax was independently associated with higher in-hospital mortality in mechanically ventilated critically ill patients under mechanical ventilatory support for reasons other than ARDS.Trial Registration ClinicalTrials.gov (NCT01868321).

Common carotid artery diameter responds to intravenous volume expansion: an ultrasound observation.

BackgroundIn case of intravascular fluid depletion, large veins react to volume expansion with dilation. Little is known about the reaction of arterial vessels. We herein report on the effect of a standardized fluid bolus on the diameter of the common carotid artery (CCA) and its association with hemodynamic parameters, assessed in 20 mechanically ventilated patients after cardiac surgery. CCA was visualized using ultrasound, and the percentage increase in diastolic diameter was calculated by measuring before and after administration of crystalloid infusion solution. Invasive arterial blood pressure and pulse pressure variation (PPV) were assessed in parallel.ResultsMedian diastolic CCA diameter was 6.2 (Q1–Q3: 5.4–7.1)xa0mm, and it significantly increased to 6.7 (5.8–7.3) mm upon fluid administration [5.0 (1.9–10.5)xa0% increase]. Mean arterial blood (MAP) pressure likewise increased from 68 (70–73) to 85 (71–100)xa0mmHg, whereas PPV was significantly reduced from 17.6 (16.8–23.9) to 13.2 (6.7–18.1)xa0%. There was a significant association between the change in CCA diameter and the hemodynamic response (delta-MAP: rxa0=xa00.53, delta-PPV: rxa0=xa00.56; pxa0<xa00.05). Furthermore, carotid diameter measured before volume expansion significantly correlated with the delta-PPV upon fluid administration (rxa0=xa0−0.5; pxa0=xa00.02).ConclusionsDiameter of the CCA increases in response to intravascular volume expansion. Additional studies on the interplay between carotid geometry and intravascular fluid status are necessary.