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Transthoracic echocardiography is widely used in intensive care unit (ICU) to manage patients with acute circulatory failure. Recently, automated ultrasound (US) measurement applications have been developed but their clinical performance has not been evaluated yet. The aim of this study was to assess the agreement between automated and manual measurements of the velocity-time integral in the left ventricular outflow tract (VTI-LVOT) using the auto-VTI® tool. This prospective, single-center, interventional study included ICU patients with acute circulatory failure. The examination involved two successive manual measurements of VTI-LVOT (mean of 3 consecutive heartbeats in regular sinus rhythm, and 5 heartbeats in irregular rhythm), followed by a measurement using auto-VTI® software. In patients receiving a fluid challenge, trending ability in detecting fluid responsiveness was also evaluated. Seventy patients were included between January 19, 2020, and September 24, 2020, at the Nîmes University Hospital. The feasibility of the auto-VTI® was 94%. The mean difference between the two methods was 11% with limits of agreement from - 19% to 42%. The proportion of agreement at the 15% difference threshold was 68% [58%; 80%]. The precision and least significant change measured for the manual measurement of VTI were 7.4 and 10.5%, respectively, and by inference for the automated method 28% and 40%. The new auto-VTI® tool, despite interesting feasibility, demonstrated an insufficient agreement with a systematic bias and an insufficient precision limiting its implementation in critically ill patients.Clinical trial registration: ClinicalTrials.gov identifier: NCT04360304., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background & Aims: Ascites is a frequent complication of cirrhosis. In intensive care units, initial hemodynamic assessment is frequently performed by echocardiography. This study evaluated the feasibility and usefulness of early hemodynamic assessment in the gastroenterology ward., Methods: This observational cohort study prospectively included all patients admitted to a teaching hospital's gastroenterology unit for decompensated cirrhosis. A gastroenterologist with minimal training and an intensivist both performed an echocardiography exam. The primary outcome was inter-rater agreement and reliability for three echocardiography parameters: visual LVEF (Left Ventricular Ejection Fraction), subaortic VTI (velocity time integral) and E wave velocity. Secondary outcomes were agreement for presence of pleural effusion, description of 3 hemodynamics profiles (hypovolemic, hyperkinetic and intermediate), and 28-day mortality., Results: From March 2018 to March 2020, 53 patients were included. The median age was 62 years and 81% were men. Patients presented mostly advanced liver disease, with 43% Child-Pugh C and median MELD score of 15.2. The limits of agreement between intensivists and gastroenterologists for subaortic VTI were - 6.6 to 7.2 cm, and ranged from - 0.6 to 0.37 m.s -1 for E wave velocity. Clinically significant differences between intensivists and gastroenterologists were found in 22% for subaortic VTI and 24.5% for E wave velocity. Reliability was good for subaortic VTI (ICC: 0.79, 95% CI [0.58; 0.9;]) and moderate for E wave velocity (0.53, 95% CI [0.19; 0.74]). The three hemodynamics profiles had different prognosis, with a 28-day mortality for Hypovolemic, Intermediate and Hyperkinetic group of 31, 18, and 4%, respectively., Conclusion: Reliability of hemodynamic assessment by gastroenterologists was good, while agreement was unsatisfactory, advocating for further training. Transthoracic echocardiography can differentiate hypovolemia from hyperkinetic states. The role of transthoracic echocardiography in managing decompensated cirrhosis requires further study., Clinical Trial Number: NCT03650660., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Real-time ultrasound (US) guidance facilitates central venous catheterization in intensive care unit (ICU). New magnetic needle-pilot devices could improve efficiency and safety of central venous catheterization. This simulation trial was aimed at comparing venipuncture with a new needle-pilot device to conventional US technique., Methods: In a prospective, randomized, simulation trial, 51 ICU physicians and residents cannulated the right axillary vein of a human torso mannequin with standard US guidance and with a needle-pilot system, in a randomized order. The primary outcome was the time from skin puncture to successful venous cannulation. The secondary outcomes were the number of skin punctures, the number of posterior wall puncture of the axillary vein, the number of arterial punctures, the number of needle redirections, the failure rate, and the operator comfort., Results: Time to successful cannulation was shorter with needle-pilot US-guided technique (22 s (interquartile range (IQR) = 16-42) vs 25 s (IQR = 19-128); median of difference (MOD) = -9 s (95%-confidence interval (CI) -5, -22), p  < 0.001). The rates of skin punctures, posterior wall puncture of axillary vein, and needle redirections were also lower ( p  < 0.01). Comfort was higher in needle-pilot US-guided group on a 11-points numeric scale (8 (IQR = 8-9) vs 6 (IQR = 6-8), p  < 0.001)., Conclusions: In a simulation model, US-guided axillary vein catheterization with a needle-pilot device was associated with a shorter time of successful cannulation and a decrease in numbers of skin punctures and complications. The results plea for investigating clinical performance of this new device., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Ultrasound (US)-guided axillary vein (AV) catheterization has been considered as the preferred site of insertion to minimize catheter-related infections. Given its difficulty of realization, internal jugular vein (IJV) access remains, thus, the first choice of catheter insertion site. This descriptive study was aimed to assess the success and complication rates of in-plane short axis approach of IJV in the lower neck and the AV approach under US-guidance., Methods: In a prospective randomized controlled open-label pilot trial, all patients requiring central venous catheterization (CVC) in intensive care unit or operating room were randomly assigned to low IJV or AV groups. The primary objective was to estimate the overall success rate of both approaches. The secondary objectives were immediate complication rates, procedure durations, success rate after the first puncture, late complication rates (i.e., thrombosis, catheter colonization, and catheter-related infections), and nurse satisfaction regarding insertion site dressings., Results: One hundred and seventy-three out of two hundred and ten included patients were fully analyzed (90 and 83 in the IJV and AV approach groups, respectively). Overall success rates for IJV and AV sites were 96% (95% confidence interval (CI) [90-99]) and 89% (95% CI [81-94]) respectively. First puncture success rates were 90% and 80% respectively. The median overall procedure duration from US pre-procedural screening to guidewire insertion was 8 and 10 min in IJV and AV groups. Overall immediate complications rates for IJV and AV sites were 11.6% and 14.6%, respectively. Incidence of catheter colonization were 7.9% and 6.8% and catheter-related infection rate were 2.6% and 0%, respectively., Conclusion: In this pilot study, US-guided low IJV and AV approaches are safe and efficient techniques for CVC insertion associated with high success and low complications rates. Duration for guidewire insertion seemed to be shorter in the short axis in-plane IJV approach. It provides the basis for a future randomized trial comparing these two approaches., (© 2022 Wiley Periodicals LLC.)

Background: This prospective multicentre pilot study of patients scheduled for elective major abdominal surgery aimed to validate the fluid challenge (FC) proposed by the closed-loop (CL) system via anaesthesiologist assessment. Methods: This was a phase II trial consisting of two inclusion stages (SIMON method). Each FC (250 mL saline solution for 10 min) proposed by the CL was systematically validated by the anaesthesiologist who could either confirm or refuse the FC or give FC without the CL system. A ≥ 95% agreement between the CL and the anaesthesiologist was considered acceptable. Results: The study was interrupted after interim analysis of the first 19 patients (10 men, median age = 61 years, median body mass index = 26 kg/m2). The anaesthesiologists accepted 165/205 (80%) of fluid boluses proposed by the CL. Median cardiac index (CI) was 2.9 (interquartile: IQ (2.7; 3.4) L/min/m2) and the median coefficient of variation (CV) for CI was 13% (10; 17). Fifteen out of nineteen patients (79%) had a mean CI > 2.5 L/min/m2 or spent > 85% surgery time with pulse pressure variation < 13%. No adverse events related to the CL were reported. Conclusion: In this study of patients scheduled for elective major abdominal surgery, the agreement between CL and anaesthesiologist for giving fluid challenge was 80%, suggesting that CL cannot replace the physician but could help in decision making.

Background: Optimal management of community-acquired intra-abdominal infections (IAI) requires timely surgical source control and adequate anti-infective treatment., Objective: To describe the initial management of community-acquired IAI admitted to the emergency department and assess the association between the length of time to either diagnosis or therapeutic procedures and patient outcomes., Design: A prospective, multicentre, observational study., Setting: Thirteen teaching hospitals in France between April 2018 and February 2019., Patients: Two hundred and five patients aged at least 18 years diagnosed with community-acquired IAI., Main Outcome Measures: The primary outcome was hospital length of stay. The secondary outcome was hospital mortality., Results: Patients had a mean age of 56 (± 21) years and a median [interquartile] SAPS II of 26 [17 to 34]. Among the study cohort, 18% were postoperatively transferred to intensive care unit and 7% had died by day 28. Median [IQR] time to imaging, antibiotic therapy and surgery were 4 [2 to 6], 7.5 [4 to 12.5] and 9 [5.5 to 17] hours, respectively. The length of time to surgical source control [0.99, 95% confidence interval (CI), 0.98 to 0.99], SOFA greater than 2 [0.36 (95% CI, 0.26 to 0.651)], age greater than 60 years [0.65 (95% CI, 0.45 to 0.94)], generalized peritonitis [0.7 (95% CI, 0.56 to 0.89)] and laparotomy surgery [0.657 (95% CI, 0.42 to 0.78)] were associated with longer hospital length of stay. The duration of time to surgical source control [1.02 (95% CI, 1.01 to 1.04)], generalized peritonitis [2.41 (95% CI, 1.27 to 4.61)], and SOFA score greater than 2 [6.14 (95% CI, 1.40 to 26.88)] were identified as independent risk factors for 28-day mortality., Conclusion: This multicentre observational study revealed that the time to surgical source control, patient severity and generalized peritonitis were identified as independent risk factors for increased hospital LOS and mortality in community-acquired IAI. Organisational strategies to reduce the time to surgical management of intra-abdominal infections should be further evaluated., Study Registration: ClinicalTrials.gov on 1 April 2018, NCT03544203., (Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Microcirculatory alterations have been observed at the early phase of sepsis, although macrocirculation seems preserved. The aim of this study was to analyze the effect of crystalloid fluid therapy on mesenteric microcirculation, assessed by using the confocal laser endomicroscope Cellvizio®, in an endotoxic porcine model., Methods: It is a prospective endotoxic shock (lipopolysaccharide infusion) experimental trial. Piglets were divided into 3 groups: 6 in the sham group (no LPS injection, no fluid), 9 in the control group (LPS infusion, no fluid), and 6 in the crystalloids group (LPS infusion and fluid resuscitation with crystalloids). Fluid resuscitation consisted in a fluid bolus of 20 mL/kg 0.9% saline over 30 min followed by a 10 mL/kg/h fluid rate over 4 h. Mesenteric microcirculation was assessed using a confocal laser endomicroscope (Cellvizio®). Blood flow within capillaries was visually assessed according to the point of care microcirculation (POEM) score., Results: At baseline, the 3 groups were similar regarding hemodynamic, biological, and microcirculatory parameters. At T360, the POEM score significantly decreased in the control and crystalloids groups, whereas it remained unchanged in the sham group (respectively, 1.62 ± 1.06, 1.2 ± 0.45, and 5.0 ± 0, p = 0.011). There was no significant difference in cardiac output at T360 between the sham and crystalloids groups (3.1 ± 0.8 vs. 2.3 ± 0.6, p = 0.132) or between the control and crystalloids groups (2.0 ± 0.6 vs. 2.3 ± 0.6, p = 0.90)., Conclusion: There was no significant improvement of microcirculatory alterations after crystalloids resuscitation despite improvement in macrocirculatory parameters in early experimental sepsis., (© 2021 S. Karger AG, Basel.)

Our main objective was to describe the course of GLS during the first days of septic shock and to assess the agreement between GLS values and longitudinal strain measured in apical four chambers. A prospective observational single centre study was conducted at the Nimes University Hospital's ICU. All patients admitted for a diagnosis of septic shock without pre-existing heart disease were eligible. Echocardiography (LVEF and GLS) was performed on the first day, and repeated once between day 3 and day 5 then once between day 6 and day 8. We enrolled 40 consecutive patients. Four patients were excluded. In overall population, GLS at T1 was impaired (- 11.0%, IQR(interquartile range) [- 15; - 10]). On T2 exams, a significant improvement of the GLS (- 11% vs - 16% p = 0.02) was observed whereas LVEF remained stable over time. A good agreement between GLS and longitudinal strain measured on a four chambers view was found. Based on the Bland and Altman method, the mean of differences for T1 exams was 0.1 (95% CI [- 0.6; 0.8]) with limits of agreement ranging from - 4 to 4. Myocardial strain is depressed at the early phase of septic shock and improves over time. A single measurement of LS4C view appears sufficient at bedside., (© 2020. Springer Nature B.V.)

Beta-lactams are the most commonly prescribed antimicrobials in intensive care unit (ICU) settings and remain one of the safest antimicrobials prescribed. However, the misdiagnosis of beta-lactam-related adverse events may alter ICU patient management and impact clinical outcomes. To describe the clinical manifestations, risk factors and beta-lactam-induced neurological and renal adverse effects in the ICU setting, we performed a comprehensive literature review via an electronic search on PubMed up to April 2021 to provide updated clinical data. Beta-lactam neurotoxicity occurs in 10-15% of ICU patients and may be responsible for a large panel of clinical manifestations, ranging from confusion, encephalopathy and hallucinations to myoclonus, convulsions and non-convulsive status epilepticus. Renal impairment, underlying brain abnormalities and advanced age have been recognized as the main risk factors for neurotoxicity. In ICU patients, trough concentrations above 22 mg/L for cefepime, 64 mg/L for meropenem, 125 mg/L for flucloxacillin and 360 mg/L for piperacillin (used without tazobactam) are associated with neurotoxicity in 50% of patients. Even though renal complications (especially severe complications, such as acute interstitial nephritis, renal damage associated with drug induced hemolytic anemia and renal obstruction by crystallization) remain rare, there is compelling evidence of increased nephrotoxicity using well-known nephrotoxic drugs such as vancomycin combined with beta-lactams. Treatment mainly relies on the discontinuation of the offending drug but in the near future, antimicrobial optimal dosing regimens should be defined, not only based on pharmacokinetics/pharmacodynamic (PK/PD) targets associated with clinical and microbiological efficacy, but also on PK/toxicodynamic targets. The use of dosing software may help to achieve these goals.

Background: While aminoglycosides (AG) have been used for decades, debate remains on their optimal dosing strategy. We investigated the international practices of AG usage specifically regarding dosing and therapeutic drug monitoring (TDM) in critically ill patients. We conducted a prospective, multicentre, observational, cohort study in 59 intensive-care units (ICUs) in 5 countries enrolling all ICU patients receiving AG therapy for septic shock., Results: We enrolled 931 septic ICU patients [mean ± standard deviation, age 63 ± 15 years, female 364 (39%), median (IQR) SAPS II 51 (38-65)] receiving AG as part of empirical (761, 84%) or directed (147, 16%) therapy. The AG used was amikacin in 614 (66%), gentamicin in 303 (33%), and tobramycin in 14 (1%) patients. The median (IQR) duration of therapy was 2 (1-3) days, the number of doses was 2 (1-2), the median dose was 25 ± 6, 6 ± 2, and 6 ± 2 mg/kg for amikacin, gentamicin, and tobramycin respectively, and the median dosing interval was 26 (23.5-43.5) h. TDM of C max and C min was performed in 437 (47%) and 501 (57%) patients, respectively, after the first dose with 295 (68%) patients achieving a C max /MIC > 8 and 353 (71%) having concentrations above C min recommended thresholds. The ICU mortality rate was 27% with multivariable analysis showing no correlation between AG dosing or pharmacokinetic/pharmacodynamic target attainment and clinical outcomes., Conclusion: Short courses of high AG doses are mainly used in ICU patients with septic shock, although wide variability in AG usage is reported. We could show no correlation between PK/PD target attainment and clinical outcome. Efforts to optimize the first AG dose remain necessary. Trial registration Clinical Trials, NCT02850029, registered on 29th July 2016, retrospectively registered, https://www.clinicaltrials.gov.

Introduction: Blood lactate is a strong predictor of mortality in critically ill patients. Its monitoring implies repeated measurements. The EIRUS™ system (Maquet Critical Care AB, 17154, Solna, Sweden) is a new device allowing continuous lactate monitoring by intravascular micro dialysis. The present study aimed at assessing the accuracy of the EIRUS™ system in critically ill patients with circulatory failure., Methods: An observational cohort study was conducted in Nîmes University Hospital. Eligible patients were those with circulatory failure in which a specific central venous access was put in place by the physician in charge, allowing continuous lactate measurement by the EIRUS™ system. Lactate measurements obtained by the system were compared to lactate from arterial blood samples at H4 and H8 from the calibration, during the first 48hours of shock., Results: In all, 28 patients were included providing 244 pairs of measures. The Bland-Altman analysis showed a bootstrapped mean bias at H4 of 0.05 and 95% limits of agreement of -0.9 to 1.0mmol/L. At H8 the mean bias was 0.06 and 95% limits of agreement -1.1 to 1.2mmol/L. The global trend agreement [95% CI] for a pre-specified arbitrary threshold of 1mmol/L, defining clinically significant variations, between H0 and H4 and H4 and H8 was 91.6% [85.1; 95.9] and 89.5% [82.3; 94.4], respectively., Conclusion: The EIRUS™ device provided an overall accurate measurement of lactate in critically ill patients with circulatory failure. Detection of lactate variations over time is less precise and technical issues may limit its clinical use., (Copyright © 2020 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: Fluid challenge (FC) is one of the most common practices in Intensive Care Unit (ICU). The present study aimed to evaluate whether echocardiographic assessment of the response to FC at the end of the infusion or 20 min later could affect the results of the FC., Methods: This is a prospective, observational, multicenter study including all ICU patients in septic shock requiring a FC of 500 mL crystalloids over 10 min. Fluid responsiveness was defined as a > 15% increase in stroke volume (SV) assessed by velocity-time integral (VTI) measurements at baseline (T 0 ), at the end of FC (T 10 ), then 10 (T 20 ) and 20 min (T 30 ) after the end of FC., Results: From May 20, 2014, to January 7, 2016, a total of 143 patients were enrolled in 11 French ICUs (mean age 64 ± 14 years, median IGS II 53 [43-63], median SOFA score 10 [8-12]). Among the 76/143 (53%) patient responders to FC at T 10 , 37 patients were transient responders (TR), i.e., became non-responders (NR) at T 30 (49%, 95%CI = [37-60]), and 39 (51%, 95%CI = [38-62]) patients were persistent responders (PR), i.e., remained responders at T 30 . Among the 67 NR at T 10 , 4 became responders at T30, (6%, 95%CI = [1.9-15.3]). In the subgroup analysis, no statistical difference in hemodynamic and echocardiographic parameters was found between groups., Conclusions: This study shows that 51.3% of initial responders have a persistent response to fluid 30 min after the beginning of fluid infusion and only 41.3% have a transient response highlighting that fluid responsiveness is time dependent., Trial Registration: ClinicalTrials.gov , NCT02116413 . Registered on April 16, 2014.

Background: Standard operating rooms (SOR) are assumed to be the best place to prevent microbial contamination when performing tissue procurement. However, mobilizing an operating room is time and cost consuming if no organ retrieval is performed. In such case, non-operating dedicated rooms (NODR) are usually recommended by European guidelines for tissue harvesting. Performing the tissue retrieval in the Intensive care unit (ICU) when possible might be considered as it allows a faster and simpler procedure., Objective: Our primary objective was to study the relationship between the risk of microbial contamination and the location (ICU, SOR or NODR) of the tissue retrieval in heart-beating and non-heart-beating deceased donors., Materials and Method: We retrospectively reviewed all deceased donors' files of the local tissue banks of Montpellier and Marseille from January 2007 to December 2014. The primary endpoint was the microbial contamination of the grafts. We built a multivariate regression model and used a GEE (generalized estimating equations) allowing us to take into account the clustered structure of our data., Results: 2535 cases were analyzed involving 1027 donors. The retrieval took place for 1189 in a SOR, for 996 in a hospital mortuary (NODR) and for 350 in an ICU. 285 (11%) microbial contaminations were revealed. The multivariate analysis found that the location in a hospital mortuary was associated with a lower risk of contamination (OR 0.43, 95% CI [0.2-0.91], p = 0.03). A procurement performed in the ICU was not associated with a significant increased risk (OR 0.62, 95% CI [0.26-1.48], p = 0.4)., Conclusion: According to our results, performing tissue procurement in dedicated non-sterile rooms could decrease the rate of allograft tissue contamination. This study also suggests that in daily clinical practice, transferring patients from ICU to SOR for tissue procurement could be avoided as it does not lead to less microbial contamination., Competing Interests: The authors have declared that no competing interests exist.

Background: Acute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy is the standard of care for severe acute kidney injury, the ideal time for initiation remains controversial., Methods: In a multicenter, randomized, controlled trial, we assigned patients with early-stage septic shock who had severe acute kidney injury at the failure stage of the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification system but without life-threatening complications related to acute kidney injury to receive renal-replacement therapy either within 12 hours after documentation of failure-stage acute kidney injury (early strategy) or after a delay of 48 hours if renal recovery had not occurred (delayed strategy). The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level (or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter), urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer, or anuria for at least 12 hours. The primary outcome was death at 90 days., Results: The trial was stopped early for futility after the second planned interim analysis. A total of 488 patients underwent randomization; there were no significant between-group differences in the characteristics at baseline. Among the 477 patients for whom follow-up data at 90 days were available, 58% of the patients in the early-strategy group (138 of 239 patients) and 54% in the delayed-strategy group (128 of 238 patients) had died (P=0.38). In the delayed-strategy group, 38% (93 patients) did not receive renal-replacement therapy. Criteria for emergency renal-replacement therapy were met in 17% of the patients in the delayed-strategy group (41 patients)., Conclusions: Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy. (Funded by the French Ministry of Health; IDEAL-ICU ClinicalTrials.gov number, NCT01682590 .).

Lung ultrasound (LUS) increases clinical diagnosis performance in intensive care unit (ICU). Real-time three-dimensional (3-D) imaging was compared with two-dimensional (2-D) LUS by assessing the global diagnosis concordance. In this single center, prospective, observational, pilot study, one trained operator performed a 3-D LUS immediately after a 2-D LUS in eight areas of interest on the same areas in 16 ventilated critically ill patients. All cine loops were recorded on a computer without visible link between 2-D and 3-D exams. Two experts blindly reviewed cine loops. Four main diagnoses were proposed: normal lung, consolidation, pleural effusion and interstitial syndrome. Fleiss κ and Cohen's κ values were calculated. In 252 LUS cine loops, the concordance between 2-D and 3-D exams was 83.3% (105/126), 77.6% (99/126) and 80.2% (101/126) for the trained operator and the experts respectively. The Cohen's κ coefficient value was 0.69 [95% Confidence Interval (CI) 0.58-0.80] for expert 1 meaning a substantial agreement. The inter-rater reliability was very good (Fleiss' κ value = 0.94 [95% CI 0.87-1.0]) for 3-D exams. The Cohen's κ was excellent for pleural effusion (κ= 0.93 [95% CI 0.76-1.0]), substantial for normal lung diagnosis (κ = 0.68 [95% CI 0.51-0.86]) and interstitial syndrome (κ = 0.62 [95% CI 0.45-0.80]) and fair for consolidation diagnoses (κ = 0.47 [95% CI 0.30-0.64]). In ICU ventilated patients, there was a substantial concordance between 2-D and 3-D LUS with a good inter-rater reliability. However, the diagnosis concordance for lung consolidation is poor.

Objectives: Surgical and medical ICU patients are at high risk of mortality and provide a significant cost to the healthcare system. The aim of this study is to describe the effect of pharmacist-led interventions on drug therapy and clinical strategies on ICU patient outcome and hospital costs., Design: Before and after study in two French ICUs (16 and 10 beds)., Patients: ICU patients., Intervention: From January 1, 2013, to June 30, 2015, a pharmacist observation period was compared with an intervention period in which a critical care pharmacist provided recommendations to clinicians regarding sedative drugs and doses, choice of mechanical ventilation mode and related settings, antimicrobial de-escalation, and central venous and urinary catheters removal. Differences in ICU and hospital length of stay, duration of mechanical ventilation, mortality rate, and hospital costs per patient were quantified between groups with patients matched for severity of illness (Simplified Acute Physiology Score II) at admission., Measurements and Main Results: From the 1,519 and 1,268 admitted patients during the observation and intervention periods, respectively, 1,164 patients were evaluable in both groups after matching for Simplified Acute Physiology Score II score. The intervention period was associated with mean (95% CI) reductions in patient hospital length of stay (3.7 d [5.2-2.3 d]; p < 0.001), ICU length of stay (1.4 d [2.3-0.5 d]; p < 0.005), duration of mechanical ventilation (1.2 d [2.1-0.3 d]; p < 0.01), and hospital costs per stay (2,560 euros [3,728-1,392 euros]; p < 0.001). The overall cost savings were 10,840 euros (10,727-10,952 euros) per month, mostly due to reduced consumption of sedatives and antimicrobials. No impact on mortality rate was identified., Conclusions: Critical care pharmacist-led interventions were associated with decreases in ICU and hospital length of stays and ICU drug costs.

Background: This study assessed the ability of 3-hour postoperative urinary tissue inhibitor of metalloproteinases-2 × insulin-like growth factor binding protein-7 ([TIMP-2] × [IGFBP-7]) to predict postoperative acute kidney injury (AKI) in patients undergoing cardiopulmonary bypass during cardiac surgery., Methods: Patients undergoing cardiac surgery with cardiopulmonary bypass were eligible for this study. Patients with initial chronic renal insufficiency requiring renal replacement therapy, patients <18 years of age, and parturients were not included. Anesthesia and hemodynamic management followed current practices. Urinary [TIMP2] × [IGFBP-7] was measured in 3-hour postoperative period. The primary objective was the occurrence of AKI (Kidney Disease: Improving Global Outcome [KDIGO] stage >0) within the first 48 hours postoperatively. The ability of urinary [TIMP-2] × [IGFBP-7] to predict postoperative AKI was assessed by building a receiver operating characteristic curve (with 95% confidence interval [CI] and by a gray zone approach that allowed either the prediction or the exclusion of postoperative AKI with a sensitivity >0.90 and a specificity >0.90)., Results: AKI occurred in 34 of 93 patients included (37%). The area under the receiver operating characteristic curve of urinary [TIMP-2] × [IGFBP-7] was 0.73 (95% CI, 0.62-0.83). The best cutoff value for urinary [TIMP-2] × [IGFBP-7] in predicting AKI was 0.3 ng/mL/1000 [0.09-1.40] (sensitivity = 76%; 95% CI, 73-97, specificity = 64%; 95% CI, 42-69). Urinary [TIMP-2] × [IGFBP-7] of <0.09 ng/mL/1000 and >1.40 ng/mL/1000 had a sensitivity and specificity >90% in predicting postoperative AKI. Fifty-nine patients (63%) were within the gray zone., Conclusions: In patients undergoing cardiopulmonary bypass during cardiac surgery, urinary [TIMP-2] × [IGFBP-7] could not accurately predict the occurrence of postoperative AKI.

Background: Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus., Methods: In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis. The primary outcome was a good functional outcome at 90 days, defined as a Glasgow Outcome Scale (GOS) score of 5 (range, 1 to 5, with 1 representing death and 5 representing no or minimal neurologic deficit). The main secondary outcomes were mortality at 90 days, progression to electroencephalographically (EEG) confirmed status epilepticus, refractory status epilepticus on day 1, "super-refractory" status epilepticus (resistant to general anesthesia), and functional sequelae on day 90., Results: A GOS score of 5 occurred in 67 of 138 patients (49%) in the hypothermia group and in 56 of 130 (43%) in the control group (adjusted common odds ratio, 1.22; 95% confidence interval [CI], 0.75 to 1.99; P=0.43). The rate of progression to EEG-confirmed status epilepticus on the first day was lower in the hypothermia group than in the control group (11% vs. 22%; odds ratio, 0.40; 95% CI, 0.20 to 0.79; P=0.009), but there were no significant differences between groups in the other secondary outcomes. Adverse events were more frequent in the hypothermia group than in the control group., Conclusions: In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).

Objective: This study aimed to compare 2 fluid infusion rates of lactated Ringer (LR) and hydroxyethyl starch (HES) 130/0.4 on hemodynamic restoration at the early phase of controlled hemorrhagic shock., Methods: Fifty-six anesthetized and ventilated piglets were bled until mean arterial pressure (MAP) reached 40 mm Hg. Controlled hemorrhage was maintained for 30 minutes. After this period, 4 resuscitation groups were studied (n=14 for each group): HES infused at 1 or 4mL/kg per minute or LR1 infused at 1 or 4mL/kg per minute until baseline MAP was restored. Hemodynamic assessment using PiCCO monitoring and biological data were collected., Results: Time to restore baseline MAP ±10% was significantly lower in LR4 group (11±11 minutes) compared to LR1 group (41±25 minutes) (P=.0004). Time to restore baseline MAP ±10% was significantly lower in HES4 group (4±3 minutes) compared to HES1 (11±4 minutes) (P=.0003). Time to restore baseline MAP ±10% was significantly lower with HES vs LR whatever the infusion rate. No statistically significant difference was observed in cardiac output, central venous saturation, extravascular lung water, and arterial lactate between 4 and 1 mL/kg per minute groups., Conclusions: In this controlled hemorrhagic shock model, a faster infusion rate (4 vs 1mL/kg per minute) significantly decreased the time for restoring baseline MAP, regardless of the type of infused fluid. The time for MAP restoration was significantly shorter for HES as compared to LR whatever the fluid infusion rate., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Whilst commonly performed in ICUs, renal replacement therapies (RRTs) differ in their solute clearances. There is a paucity of data on ciprofloxacin clearances in different RRT techniques. The aim of this study was to compare the population pharmacokinetics of ciprofloxacin during equal doses of continuous venovenous haemofiltration (CVVHF) and continuous venovenous haemodiafiltration (CVVHDF) in septic patients., Methods: Patients receiving 400 mg of ciprofloxacin intravenously 8 or 12 hourly and undergoing either CVVHF or CVVHDF were eligible. Up to 10 blood samples were collected over one dosing interval and analysed by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo simulation was undertaken using Pmetrics., Results: Eighteen sampling intervals were included (8 CVVHDF and 10 CVVHF) from 11 patients (6 patients having sampling during both RRT modes). A two-compartment linear model best described the data. Increasing patient weight was the only covariate associated with increasing drug clearance. The mean (SD) parameter estimates were: clearance, 10.7 (5.3) L/h; volume of distribution of the central compartment, 21.3 (11.3) L; rate constant for drug distribution from the central compartment to the peripheral compartment, 10.9 (4.3) L/h; and rate constant for drug distribution from the peripheral compartment to the central compartment, 2.3 (1.8) L/h. After accounting for patient weight, the mean ciprofloxacin clearance was not statistically different between CVVHF and CVVHDF [11.8 (9.9) and 10.3 (7.4) L/h, respectively, P = 0.43]., Conclusions: The present study indicates a high pharmacokinetic variability of ciprofloxacin during CVVHF and CVVHDF with no significant differences in clearance apparent. Based on patient weight, higher ciprofloxacin dosing regimens should be used in critically ill patients when difficult-to-treat pathogens are suspected., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Low first-dose peak serum concentrations of amikacin and gentamicin are commonly reported in ICU patients. The present study aimed to assess whether 30 mg/kg amikacin or 8 mg/kg gentamicin achieved target concentrations in ICU patients with severe sepsis., Patients and Methods: Sixty-three ICU patients (Simplified Acute Physiology Score II = 43 ± 16) with severe sepsis and an indication for intravenous amikacin (n = 47) or gentamicin (n = 16) were included. The first (30 mg/kg amikacin; 8 mg/kg gentamicin) and subsequent doses and corresponding peak concentrations (30 min after the completion of an infusion) were recorded. French guideline target concentrations were ≥60 and ≥30 mg/L for amikacin and gentamicin, respectively. A target pharmacokinetic/pharmacodynamic ratio of 10 × MIC was also measured., Results: Pulmonary, abdominal and urinary tract infections were diagnosed in 56 patients. Infection was confirmed in 37 patients (59%). The targeted first-dose peak concentration was achieved in 37/63 patients (59%) [amikacin 36/47 (77%) and gentamicin 1/16 (6%)], and 59/63 patients (94%) achieved the pharmacokinetic/pharmacodynamic ratio using the MIC data that were available from 21 patients. However, the second dose of aminoglycoside was withheld because of high trough concentrations in nearly half of patients who did not have renal dysfunction., Conclusions: In this study, 30 mg/kg amikacin and 8 mg/kg gentamicin led to target peak serum concentrations in 59% of patients., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Aim of the Study: Identifying clinical, electrophysiological and biological predictors for 6-month neurological outcome in survivors at day 3 after cardiac arrest (CA) treated with therapeutic hypothermia (TH)., Methods: We conducted a retrospective cohort study of adults comatose after out-of hospital CA treated with TH. All data were collected from medical charts and laboratory files., Results: Between January 2010 and March 2013, among the 130 analysed CA survivors, 27 (21%) had a good neurological outcome at 6 months and 103 (79%) had a poor neurological outcome, including 98 deaths. The Glasgow coma score motor response (GCS-M), pupillary reflexes and Neuron Specific Enolase (NSE) were the three best predictors of neurological outcome (P<0.0001). The area under the Receiver Operating Characteristic curve for NSE was 0.92 [0.84-0.99]., Conclusion: NSE values, GCS-M scores and pupillary reflexes are the best predictors of poor 6-month outcome after out-of-hospital CA treated with TH. Of these, NSE values have the best-isolated prognostic performance when above 28.8μg/L., (Copyright © 2015 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

The maintenance of homeostasis after severe injury requires the restoration of the physiological regulation of food intake. A wide array of functional alterations can hinder the intake of adequate amounts of nutrients to support the recovery from critical illness. These alterations encompass changes in the preprandial phase, reflected by a loss of appetite; changes in the prandial phase, yielding swallowing disorders; and changes in the postprandial phase, including impairments of gastric emptying, gut motility, and satiety. This tutorial aims to review these often overlooked features and to suggest recommendations for the nutrition rehabilitation of the critically ill., (© 2015 American Society for Parenteral and Enteral Nutrition.)