Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Objectives:We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies.Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries.Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT(> MIC) (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving beta-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of >= 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025].Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections

Fluid challenges in intensive care: the FENICE study A global inception cohort study

Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC.This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC.2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500-1000). The median time was 24 min (40-60 min), and the median rate of FC was 1000 [500-1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57-61 %). In 43 % (CI 41-45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34-37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20-24 %). No safety variable for the FC was used in 72 % (CI 70-74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response.The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts

Background: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. Methods: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1–15, 2002 (SOAP study, n = 3147), and May 8–18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days. Results: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1–7) days after admission in SOAP and 2 (1–6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH2O) and driving pressure (> 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. Conclusion: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH2O and driving pressure > 14 cmH2O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies

Faut-il contrôler la fièvre dans les infections sévères ? [Is control fever mandatory in severe infections?]

National audienceTemperature control during severe sepsis is currently used in intensive care and involves 66% and 70% of severe sepsis and septic shock, respectively. Nevertheless, the conclusive evidence of the benefit of such a strategy is still lacking.We might wonder, with regards to experimental works and recent noninterventional studies, about the risk of a control strategy on an ongoing infectious process, the patient’s outcome, and the safety of the means implemented to obtain temperature control. On the other hand, it is also demonstrated that fever increases oxygen consumption, which may lead in some clinical situations to tissular ischemia and that fever may be associated with a deleterious focal inflammatory process. Methods to control the temperature include external and/or internal cooling and/or antipyretic medications such as paracetamol and nonsteroidal antiinflammatory drugs. In septic patients, external cooling and paracetamol are the mains means used to control temperature. Despite the uncertainties about the benefit to control or not the temperature, it could be stated that extreme temperature (hypo- or hyperthermia) should be avoided and that the benefit/risk of temperature control must be individually weighted. © 2015, Société de réanimation de langue française (SRLF) and Springer-Verlag France

ARDS of Early or Late Onset Does It Make a Difference?

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Mort encéphalique : vers de nouveaux critères de confirmation angioscannographique ?

National audienceObjectifs.– Étudier l’opacification en angioscanner de l’artère basilaire et des veines de fosse postérieure en situation de mort encéphalique clinique afin d’identifier de nouveaux critères scannographiques mieux corrélés avec les critères cliniques. Patients et méthodes.– Trente-trois patients consécutifs explorés en angioscanner pour confirmer le diagnostic clinique de mort encéphalique ont été rétrospectivement inclus de juillet 2011 à juillet 2012. L’analyse des images relevait.–l’opacification des artères cérébrales moyennes en M4 et des veines cérébrales internes (critères de référence pour le diagnostic d’arrêt circulatoire) ainsi que de l’artère basilaire et des veines de fosse postérieure (réseau pétreux et vermien). Résultats.– Trente-six angioscanners ont été réalisés : pour 3 patients, deux angioscanners successifs ont été effectués en raison de la négativité du premier. Les 4 critères de référence étaient remplis sur 32 angioscanners (89 %) : les artères M4 restaient opacifiés sur 4 scanners dont 1 pour lequel les veines cérébrales internes, les veines pétreuses et les veines vermiennes étaient aussi opacifiées. Ce dernier scanner était le seul examen parmi les 36 réalisés pour lequel les veines pétreuses et des veines cérébrales internes étaient opacifiées. Les veines vermiennes restaient opacifiées sur 2 scanners (avec artères M4 toujours opacifiées) et l’artère basilaire sur 7 scanners (dont 6 avec critères de référence remplis). Parmi 5 scanners réalisés chez des patients avec craniectomie, les artères M4 restaient opacifiées sur 1 examen alors que les veines pétreuses et les veines cérébrales internes n’étaient jamais opacifiées. La non opacification conjointe des veines cérébrales internes et des veines pétreuses obtenait une sensibilité de 97 % pour le diagnostic angioscannographique d’arrêt circulatoire encéphalique (versus 89 % pour les critères de référence). Conclusion.– La non opacification conjointe des veines pétreuses et des veines cérébrales internes permet d’augmenter la sensibilité du diagnostic angioscannographique d’arrêt circulatoire encéphalique, y compris chez les patients avec craniectomie