OCOSO2: study protocol for a single-blinded, multicentre, randomised controlled trial assessing a central venous oxygen saturation-based goal-directed therapy to reduce postoperative complications in high-risk patients after elective major surgery.

BACKGROUND: Fluid loading-based goal-directed therapy is a cornerstone of anaesthesia management in major surgery. Its widespread application has contributed to a significant improvement in perioperative morbidity and mortality. In theory, only hypovolemic patients should receive fluid therapy. However, to achieve such a diagnosis, a surrogate marker of cardiac output adequacy must be used. Current methods of fluid loading-based goal-directed therapy do not assess cardiac output adequacy. Nowadays, new devices make it possible to continuously monitor central venous oxygen saturation (ScvO2) and therefore, to assess the adequacy of perioperative cardiac output during surgery. In major surgery, ScvO2-based goal-directed therapy can be used to enhance fluid therapy and improve patient outcomes. METHODS: We designed a prospective, randomised, single-blinded, multicentre controlled superiority study with a 1:1 allocation ratio. Patients to be included will be high-risk major surgery patients (> 50 years old, ASA score > 2, major intra-abdominal or intra-thoracic surgery > 90 min). Patients in the control group will undergo standard fluid loading-based goal-directed therapy, as recommended by the guidelines. Patients in the intervention group will have ScvO2-based goal-directed therapy and receive fluid loading only if fluid responsiveness and cardiac output inadequacy are present. The primary outcome will be the Comprehensive Complication Index on day five postoperatively. DISCUSSION: This study is the first to address the issue of cardiac output adequacy in goal-directed therapy. Our hypothesis is that cardiac output optimisation during major surgery achieved by continuous monitoring of the ScvO2 to guide fluid therapy will result in a reduction of postoperative complications as compared with current goal-directed fluid therapy practices. TRIAL REGISTRATION: ClinicalTrials.gov. NCT03828565. Registered on February 4, 2019.

Pre-operative distraction using electric ride-on cars for children undergoing elective ambulatory surgery: A randomised controlled trial.

BACKGROUND: Pre-operative anxiety occurs in 18 to 60% of children undergoing surgery and results in poor outcomes. Nonpharmacological methods of distraction are effective in alleviating peri-operative anxiety. In our institution, ride-on electric cars (ride-on e-cars) are routinely used by children undergoing ambulatory surgery as a mean of nonpharmacological distraction. OBJECTIVES: The aim of this study is to assess the effect of pre-operative distraction with ride-on e-cars on children's pre-operative anxiety when undergoing elective ambulatory surgery. DESIGN: This was a prospective, randomised, controlled, open-label study. SETTING: The study was carried out from September 2019 to September 2021 in the ambulatory paediatric surgery unit of our teaching hospital, in Marseille, France. PATIENTS: Children aged 2 to 10 years and weighing less than 35 kg undergoing elective ambulatory surgery were eligible. One hundred and fifteen children were included, 56 in the control group and 59 in the intervention group. INTERVENTION: Children in the control group were transported from the operating room (OR) waiting area to the OR using a trolley, while children in the intervention group used the ride-on e-cars, without pharmacological premedication or parental presence. MAIN OUTCOME MEASURES: The primary outcome was pre-operative anxiety at the end of the transport (prior going into the OR assessed by the modified Yale Preoperative Anxiety Score Short Form (mYPAS-SF). Secondary outcomes were the anxiety levels in children over time, as well as postoperative pain and agitation assessed with the Face Legs Activity Cry Consolability (FLACC) and Paediatric Anaesthesia Emergence Delirium (PAED) scales, respectively. RESULTS: The mYPAS-SF anxiety scores did not differ between the control group and the intervention group (39 ±â€Š19 vs. 37 ±â€Š21, P  = 0.574). The secondary outcomes were similar between the two groups. CONCLUSIONS: Our randomised controlled trial showed that the use of ride-on e-cars did not alter pre-operative anxiety as compared with standard transport in children undergoing elective ambulatory surgery. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03961581.

Antimicrobial Stewardship during COVID-19 Outbreak: A Retrospective Analysis of Antibiotic Prescriptions in the ICU across COVID-19 Waves.

The demographics and outcomes of ICU patients admitted for a COVID-19 infection have been characterized in extensive reports, but little is known about antimicrobial stewardship for these patients. We designed this retrospective, observational study to investigate our hypothesis that the COVID-19 pandemic has disrupted antimicrobial stewardship practices and likely affected the rate of antibiotic de-escalation (ADE), patient outcomes, infection recurrence, and multidrug-resistant bacteria acquisition. We reviewed the prescription of antibiotics in three ICUs during the pandemic from March 2020 to December 2021. All COVID-19 patients with suspected or proven bacterial superinfections who received antibiotic treatment were included. The primary outcome was the rate of ADE, and secondary outcomes included the rate of appropriate empirical treatment, mortality rates and a comparison with a control group of infected patients before the COVID-19 pandemic. We included 170 COVID-19 patients who received antibiotic treatment for a suspected or proven superinfection, of whom 141 received an empirical treatment. For the latter, antibiotic treatment was de-escalated in 47 (33.3%) patients, escalated in 5 (3.5%) patients, and continued in 89 (63.1%) patients. The empirical antibiotic treatment was appropriate for 87.2% of cases. ICU, hospital, and day 28 and day 90 mortality rates were not associated with the antibiotic treatment strategy. The ADE rate was 52.2% in the control group and 27.6% in the COVID-19 group (p < 0.001). Our data suggest that empirical antibiotic treatment was appropriate in most cases. The ADE rates were lower in the COVID-19 group than in the control group, suggesting that the stress associated with COVID-19 affected our practices.

Effects of a Chair Positioning Session on Awake Non-Intubated COVID-19 Pneumonia Patients: A Multicenter, Observational, and Pilot Study Using Lung Ultrasound.

BACKGROUND: LUS is a validated tool for the management of COVID-19 pneumonia. Chair positioning (CP) may have beneficial effects on oxygenation and lung aeration, and may be an easier alternative to PP. This study assessed the effects of a CP session on oxygenation and lung aeration (LA) changes in non-intubated COVID-19 patients. METHODS: A retrospective multicenter study was conducted in an ICU. We analyzed data from LUS exams and SpO2:FiO2 performed before/after a CP session in non-intubated COVID-19 patients. Patients were divided into groups of responders or non-responders in terms of oxygenation or LA. RESULTS: Thirty-three patients were included in the study; fourteen (44%) were oxygenation non-responders and eighteen (56%) were oxygenation responders, while thirteen (40.6%) and nineteen (59.4%) patients were classified as LA non-responders and responders, respectively. Changes in oxygenation and LA before/after a CP session were not correlated (r = -0.19, p = 0.3, 95% CI: -0.5-0.17). The reaeration scores did not differ between oxygenation responders and non-responders (1 (-0.75-3.75) vs. 4 (-1-6), p = 0.41). The LUS score was significantly correlated with SpO2:FiO2 before a CP session (r = 0.37, p = 0.04, 95% CI: 0.03-0.64) but not after (r = 0.17, p = 0.35, 95% CI: -0.19-0.50). CONCLUSION: A CP session was associated with improved oxygenation and LA in more than half of the non-intubated COVID-19 patients.

Effects of Hydroxychloroquine on Covid-19 in Intensive Care Unit Patients: Preliminary Results.

During the Covid-19 pandemic, many intensive care unit (ICU) patients received hydroxychloroquine. The primary objective of this study was to assess the effects of hydroxychloroquine according to its plasma concentration in ICU patients. A single-center retrospective study was performed from March to April 2020 in an ICU of a university hospital. All patients admitted to the ICU with confirmed Covid-19 pneumonia and treated with hydroxychloroquine were included. The study compared 17 patients in whom the hydroxychloroquine plasma concentration was in the therapeutic target (on-target) and 12 patients in whom the plasma concentration was below the target (off-target). The follow-up of patients was 15 days. No association was found between hydroxychloroquine plasma concentration and viral load evolution (P = 0.77). There was no significant difference between the two groups for duration of mechanical ventilation, length of ICU stay, in-hospital mortality, and 15-days mortality. These findings indicate that hydroxychloroquine administration for Covid-19 patients hospitalized in ICU is not associated with improved outcomes. Larger multicenter studies are needed to confirm these results.

De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial.

BACKGROUND: In patients with severe sepsis, no randomized clinical trial has tested the concept of de-escalation of empirical antimicrobial therapy. This study aimed to compare the de-escalation strategy with the continuation of an appropriate empirical treatment in those patients. METHODS: This was a multicenter non-blinded randomized noninferiority trial of patients with severe sepsis who were randomly assigned to de-escalation or continuation of empirical antimicrobial treatment. Recruitment began in February 2012 and ended in April 2013 in nine intensive care units (ICUs) in France. Patients with severe sepsis were assigned to de-escalation (n = 59) or continuation of empirical antimicrobial treatment (n = 57). The primary outcome was to measure the duration of ICU stay. We defined a noninferiority margin of 2 days. If the lower boundary of the 95 % confidence interval (CI) for the difference in patients assigned to the de-escalation group was less than 2 days, as compared with that of patients assigned to the continuation group, de-escalation was considered to be noninferior to the continuation strategy. Secondary outcomes included mortality at 90 days, occurrence of organ failure, number of superinfections, and number of days with antibiotics during the ICU stay. RESULTS: The median duration of ICU stay was 9 [interquartile range (IQR) 5-22] days in the de-escalation group and 8 [IQR 4-15] days in the continuation group, respectively (P = 0.71). The mean difference was 3.4 (95 % CI -1.7 to 8.5). A superinfection occurred in 16 (27 %) patients in the de-escalation group and six (11 %) patients in the continuation group (P = 0.03). The numbers of antibiotic days were 9 [7-15] and 7.5 [6-13] in the de-escalation group and continuation group, respectively (P = 0.03). Mortality was similar in both groups. CONCLUSION: As compared to the continuation of the empirical antimicrobial treatment, a strategy based on de-escalation of antibiotics resulted in prolonged duration of ICU stay. However, it did not affect the mortality rate.

Transmission of apoptosis in human colorectal tumor cells exposed to capecitabine, Xeloda, is mediated via Fas.

We developed an original in vitro model dedicated to the exploration of molecular pharmacology of the new oral fluoropyrimidine capecitabine (Xeloda). More specifically, in this report, we investigated whether apoptosis induced by capecitabine was mediated by the Fas/FasL system. To achieve this goal, a specific in vitro coculture model mixing hepatoma and human colorectal cell line was used. A bystander effect was observed between HepG2 and LS174T cells treated with capecitabine. Besides this, Xeloda showed a 7-fold higher cytotoxicity and markedly stronger apoptotic potential in thymidine phosphorylase (TP)-transfected LS174T-c2 cells. The striking enhancement of thymidylate synthase inhibition that we observed in cells with high TP activity was most probably at the origin of the potentiation of capecitabine antiproliferative efficacy. In addition, this increase of sensitivity was accompanied by a strong overexpression of the CD95-Fas receptor on the cell surface. Both Fas and FasL mRNA expression were triggered after exposing TP+ cells to the drug. This implication of Fas in Xeloda-induced apoptosis was next confirmed by using antagonistic anti-Fas and anti-FasL antibodies that proved to reverse capecitabine antiproliferative activity, thus highlighting the key role that Fas could play in the optimization of an antitumor response to fluoropyrimidine drugs. Our data, therefore, show that TP plays a key role in the capecitabine activity and that the Fas/FasL system could be considered as a new determinant for Xeloda efficacy.