Preoperative ketamine administration for prevention of postoperative neurocognitive disorders after major orthopedic surgery in elderly patients: A multicenter randomized blinded placebo-controlled trial.

BACKGROUND: Preventive anesthetic impact on the high rates of postoperative neurocognitive disorders in elderly patients is debated. The Prevention of postOperative Cognitive dysfunction by Ketamine (POCK) study aimed to assess the effect of ketamine on this condition. METHODS: This is a multicenter, randomized, double-blind, interventional study. Patients ≥60 years undergoing major orthopedic surgery were randomly assigned in a 1:1 ratio to receive preoperative ketamine 0.5 mg/kg as an intravenous bolus (n = 152) or placebo (n = 149) in random blocks stratified according to the study site, preoperative cognitive status and age. The primary outcome was the proportion of objective delayed neurocognitive recovery (dNR) defined as a decline of one or more neuropsychological assessment standard deviations on postoperative day 7. Secondary outcomes included a three-month incidence of objective postoperative neurocognitive disorder (POND), as well as delirium, anxiety, and symptoms of depression seven days and three months after surgery. RESULTS: Among 301 patients included, 292 (97%) completed the trial. Objective dNR occurred in 50 (38.8%) patients in the ketamine group and 54 (40.9%) patients in the placebo group (OR [95% CI] 0.92 [0.56; 1.51], p = 0.73) on postoperative day 7. Incidence of objective POND three months after surgery did not differ significantly between the two groups nor did incidence of delirium, anxiety, apathy, and fatigue. Symptoms of depression were less frequent in the ketamine group three months after surgery (OR [95% CI] 0.34 [0.13-0.86]). CONCLUSIONS: A single preoperative bolus of intravenous ketamine does not prevent the occurrence of dNR or POND in elderly patients scheduled for major orthopedic surgery. (Clinicaltrials.gov NCT02892916).

Guidelines on perioperative optimization protocol for the adult patient 2023.

OBJECTIVE: The French Society of Anesthesiology and Intensive Care Medicine [Société Française d'Anesthésie et de Réanimation (SFAR)] aimed at providing guidelines for the implementation of perioperative optimization programs. DESIGN: A consensus committee of 29 experts from the SFAR was convened. A formal conflict-of-interest policy was developed at the outset of the process and enforced throughout. The entire guidelines process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence. METHODS: Four fields were defined: 1) Generalities on perioperative optimization programs; 2) Preoperative measures; 3) Intraoperative measures and; 4) Postoperative measures. For each field, the objective of the recommendations was to answer a number of questions formulated according to the PICO model (population, intervention, comparison, and outcomes). Based on these questions, an extensive bibliographic search was carried out using predefined keywords according to PRISMA guidelines and analyzed using the GRADE® methodology. The recommendations were formulated according to the GRADE® methodology and then voted on by all the experts according to the GRADE grid method. As the GRADE® methodology could have been fully applied for the vast majority of questions, the recommendations were formulated using a "formalized expert recommendations" format. RESULTS: The experts' work on synthesis and application of the GRADE® method resulted in 30 recommendations. Among the formalized recommendations, 19 were found to have a high level of evidence (GRADE 1±) and ten a low level of evidence (GRADE 2±). For one recommendation, the GRADE methodology could not be fully applied, resulting in an expert opinion. Two questions did not find any response in the literature. After two rounds of rating and several amendments, strong agreement was reached for all the recommendations. CONCLUSIONS: Strong agreement among the experts was obtained to provide 30 recommendations for the elaboration and/or implementation of perioperative optimization programs in the highest number of surgical fields.

Metabolomic Impact of Lidocaine on a Triple Negative Breast Cancer Cell Line.

Background: Metabolomics and onco-anesthesia are two emerging research fields in oncology. Metabolomics (metabolites analysis) is a new diagnostic and prognostic tool that can also be used for predicting the therapeutic or toxic responses to anticancer treatments. Onco-anesthesia studies assess the impact of anesthesia on disease-free and overall survival after cancer surgery. It has been shown that local anesthetics (LA), particularly lidocaine (LIDO), exert antitumor properties both in vitro and in vivo and may alter the biologic fingerprints of cancer cells. As LA are known to impair mitochondrial bioenergetics and byproducts, the aim of the present study was to assess the impact of LIDO on metabolomic profile of a breast cancer cell line. Methods: Breast cancer MDA-MB-231 cells were exposed for 4 h to 0.5 mM LIDO or vehicle (n = 4). The metabolomic fingerprint was characterized by high resolution magic angle spinning NMR spectroscopy (HRMAS). The multivariate technique using the Algorithm to Determine Expected Metabolite Level Alteration (ADEMA) (Cicek et al., PLoS Comput. Biol., 2013, 9, e1002859), based on mutual information to identify expected metabolite level changes with respect to a specific condition, was used to determine the metabolites variations caused by LIDO. Results: LIDO modulates cell metabolites levels. Several pathways, including glutaminolysis, choline, phosphocholine and total choline syntheses were significantly downregulated in the LIDO group. Discussion: This is the first study assessing the impact of LIDO on metabolomic fingerprint of breast cancer cells. Among pathways downregulated by LIDO, many metabolites are reported to be associated with adverse prognosis when present at a high titer in breast cancer patients. These results fit with the antitumor properties of LIDO and suggest its impact on metabolomics profile of cancer cells. These effects of LIDO are of clinical significance because it is widely used for local anesthesia with cutaneous infiltration during percutaneous tumor biopsy. Future in vitro and preclinical studies are necessary to assess whether metabolomics analysis requires modification of local anesthetic techniques during tumor biopsy.

Deleterious Effects of Remote Ischaemic Per-conditioning During Lower Limb Ischaemia-Reperfusion in Mice.

OBJECTIVE: The aim of this study was to investigate whether remote ischaemic per-conditioning might protect skeletal muscle during lower limb ischaemia-reperfusion (IR). METHODS: Twenty-three male C57BL/6 mice were randomised into three groups: sham group (n = 7), IR group (unilateral tourniquet induced three hours of ischaemia followed by 24 hours of reperfusion, n = 8), and remote ischaemic per-conditioning group (RIPerC) (three cycles of 10 minute IR episodes on the non-ischaemic contralateral hindlimb, n = 8). Oxygraphy, spectrofluorometry, and electron paramagnetic resonance spectroscopy were performed in order to determine mitochondrial respiratory chain complexes activities, mitochondrial calcium retention capacity (CRC) and reactive oxygen species (ROS) production in skeletal muscle. RESULTS: IR impaired mitochondrial respiration (3.66 ± 0.98 vs. 7.31 ± 0. 54 µmol/min/g in ischaemic and sham muscles, p = .009 and p = .003 respectively) and tended to impair CRC (2.53 ± 0.32 vs. 3.64 ± 0.66 µmol/mg in ischaemic and sham muscles respectively, p = .066). IR did not modify ROS production (0.082 ± 0.004 vs. 0.070 ± 0.004 µmol/min/mg in ischaemic and sham muscles respectively, p = .74). RIPerC failed to restore mitochondrial respiration (3.82 ± 0.40 vs. 3.66 ± 0.98 µmol/min/g in ischaemic muscles from the RIPerC group and the IR group respectively, p = .45) and CRC (2.76 ± 0.3 vs. 2.53 ± 0.32 µmol/mg in ischaemic muscles from the RIPerC group and the IR group respectively, p = .25). RIPerC even impaired contralateral limb mitochondrial respiration (3.85 ± 0.34 vs. 7.31 ± 0. 54 µmol/min/g in contralateral muscles and sham muscles respectively, -47.3%, p = .009). CONCLUSION: RIPerC failed to protect ischaemic muscles and induced deleterious effects on the contralateral non-ischaemic muscles. These data do not support the concept of RIPerC.

Effects of Warmed and Humidified CO2 Surgical Site Insufflation in a Novel Experimental Model of Magnetic Compression Colonic Anastomosis.

Background. Pneumoperitoneum insufflation with warmed and humidified carbon dioxide (WH-CO2) can prevent heat loss and increase tissue oxygenation. We evaluated the impact of localized WH-CO2 insufflation on the anastomotic healing process. Methods. Sixty male Wistar rats were randomized: Group 1 (control, n = 12), Group 2 (cold and dry CO2, CD-CO2, n = 24), and Group 3 (WH-CO2, n = 24). A magnetic compression side-to-side colonic anastomosis was performed under 60-minute local abdominal CO2 flow insufflation. Animal temperature was recorded. IL-1, IL-6, and CRP levels were assessed before and after insufflation and on postoperative day (POD) 7 and POD 10. Endoscopic follow-up was performed on POD 7 and POD 10. A burst pressure (BP) test of the specimen was performed on POD 10, and histopathological analysis was then performed. Metabolomics of the anastomotic site was determined. Results. Seven rats (5 CD-CO2 group, 1 WH-CO2 group, and 1 control group) died during the survival period. Necropsies revealed intestinal occlusions (n = 2). One additional rat from the CD-CO2 group was sacrificed on POD 7 due to intestinal perforation. The postoperative course was uneventful in the remaining cases. There was no difference in BP among the groups. Thermal monitoring confirmed that WH-CO2 insufflation was effective to reduce heat loss. IL-1 levels were statistically and significantly lower on POD 10 in the WH-CO2 group than the CD-CO2 group but not lower than the control group. CRP levels, histopathology, and metabolomics did not show any difference between the 3 groups. Conclusions. WH-CO2 was effective to preserve core temperature. However, it did not improve anastomotic healing.

A novel, automated, quantification of abnormal lung parenchyma in patients with COVID-19 infection: Initial description of feasibility and association with clinical outcome.

OBJECTIVE: Ground-glass opacities are the most frequent radiologic features of COVID-19 patients. We aimed to determine the feasibility of automated lung volume measurements, including ground-glass volumes, on the CT of suspected COVID-19 patients. Our goal was to create an automated and quantitative measure of ground-glass opacities from lung CT images that could be used clinically for diagnosis, triage and research. DESIGN: Single centre, retrospective, observational study. MEASUREMENTS: Demographic data, respiratory support treatment (synthetised in the maximal respiratory severity score) and CT-images were collected. Volume of abnormal lung parenchyma was measured with conventional semi-automatic software and with a novel automated algorithm based on voxels X-Ray attenuation. We looked for the relationship between the automated and semi-automated evaluations. The association between the ground-glass opacities volume and the maximal respiratory severity score was assessed. MAIN RESULTS: Thirty-seven patients were included in the main outcome analysis. The mean duration of automated and semi-automated volume measurement process were 15 (2) and 93 (41) min, respectively (p=8.05*10-8). The intraclass correlation coefficient between the semi-automated and automated measurement of ground-glass opacities and restricted normally aerated lung were both superior to 0.99. The association between the automated measured lung volume and the maximal clinical severity score was statistically significant for the restricted normally aerated (p=0.0097, effect-size: -385mL) volumes and for the ratio of ground-glass opacities/restricted normally aerated volumes (p=0.027, effect-size: 3.3). CONCLUSION: The feasibility and preliminary validity of automated impaired lung volume measurements in a high-density COVID-19 cluster was confirmed by our results.

Bayesian predictive probabilities: a good way to monitor clinical trials.

BACKGROUND: Bayesian methods, with the predictive probability (PredP), allow multiple interim analyses with interim posterior probability (PostP) computation, without the need to correct for multiple looks at the data. The objective of this paper was to illustrate the use of PredP by simulating a sequential analysis of a clinical trial. METHODS: We used data from the Laryngobloc trial that planned to include 480 patients to demonstrate the equivalence of success between a laryngoscopy performed with the Laryngobloc® device and a control device. A crossover Bayesian design was used. The success rates of the two laryngoscopy devices were compared. Interim analyses, computed from random numbers of subjects, were simulated. RESULTS: The PostP of equivalence rapidly reached the predefined bound of 0.95. The PredP computed with an equivalence margin of 10% reached the efficacy bound between 352 and 409 of the 480 included patients. If a frequentist analysis had been made on the basis of 217 out of 480 subjects, the study would have been prematurely stopped for equivalence. The PredP indicated that this result was nonetheless unstable and that the equivalence was, thus far, not guaranteed. CONCLUSIONS: Based on these interim analyses, we can conclude with a sufficiently high probability that the equivalence would have been met on the primary outcome before the predetermined end of this particular trial. If a Bayesian approach using PredP had been used, it would have allowed an early termination of the trial by reducing the calculated sample size by 15-20%.

Risk-adapted strategy or universal multimodal approach for PONV prophylaxis?

The issue of postoperative nausea and vomiting (PONV) remains important in surgical practice, contributing to patient distress, slower recovery, and increased use of healthcare resources. Many surgical patients report it to be a worse problem than pain. Numerous findings of research indicate that PONV significantly affects patients' well-being and is among the important determinants of patient satisfaction with perioperative care. Numerous investigations have confirmed the efficacy of combining pharmacological interventions indicating that PONV is a clinical complication that is in principle avoidable. Nonetheless, PONV continues to be bothersome for too many patients. Thus, perhaps the biggest challenge across the field is to achieve a uniformly high standard of PONV management using the currently available resources. Although a risk-adapted approach has been advocated in the past, the current trend incorporated in clinical guidelines support a more liberal approach of multimodal antiemetic prevention. The current article emphasizes pros and cons of the various approaches to PONV prophylaxis and depicts most promising strategies to achieve a "PONV-free hospital."

Surgical Support for Severe COVID-19 Patients: A Retrospective Cohort Study in a French High-Density COVID-19 Cluster.

Background. The COVID-19 epidemic has resulted in a massive surge in the need for intensive care unit (ICU) care. To avoid being overwhelmed, hospitals had to adapt and support the ICU teams in structured ICU care including involving surgical teams. This work aims at describing the collaborative efforts between the ICU care team and the Surgical Task Force (STF) during a surge of ICU activity in a University Hospital in a French high-density COVID-19 cluster. Study Design. This retrospective single center study analyzed the STF workflow and the ICU population. The study included 55 patients hospitalized in our ICU, ICU-converted step-down units, and post-anesthesia care units. The primary measure was the global daily STF activity. The secondary measure was the daily activity for each of the 5 tasks accomplished by the STF. Results. The STF attempted 415 phone calls for 55 patients' families, 237 mobilizations of patients requiring prone positions, follow-up of 20 patients requiring medevac, and contribution to ethical discussion for 2 patients. The mean (SD) daily number of successful phones calls, ethical discussions, mobilizations of patients requiring prone positions and medevac follow-up were 18 (7), .1 (.4), 10 (7), and 2 (3), respectively. No actions for discharge summaries writing were required. The maximum number of daily mobilizations for patients requiring prone positions was 25. The maximum number of daily attempted phone calls and successful phone calls were 37 and 26, respectively. Conclusion. Surgeons' technical and nontechnical skills represented an effective support for ICU teams during the COVID-19 pandemic.

Theory and practical use of Bayesian methods in interpreting clinical trial data: a narrative review.

The critical reading of scientific articles is necessary for the daily practice of evidence-based medicine. Rigorous comprehension of statistical methods is essential, as reflected by the extensive use of statistics in the biomedical literature. In contrast to the customary frequentist approach, which never uses or gives the probability of a hypothesis, Bayesian theory uses probabilities for both hypotheses and data. This statistical approach is increasingly used for analyses of clinical trial data and for applied machine learning. The aim of this review is to compare general Bayesian concepts with frequentist methods to facilitate a better understanding of Bayesian theory for readers who are not familiar with this approach. The review is intended to be used in combination with a checklist we have devised for reading reports analysed by Bayesian methods. We compare and contrast the different approaches of Bayesian vs frequentist statistical methods by considering data from a clinical trial that lends itself to this comparative approach.

A consensus checklist to help clinicians interpret clinical trial results analysed by Bayesian methods.

INTRODUCTION: In the context of an increasing number of publications of trial data analysed by Bayesian methods, clinicians need support to better understand Bayesian statistical methods. The existing checklists are intended for people who already know these methods. We aimed to establish and validate a checklist that contains a group of items considered crucial in interpreting the results of a phase III RCT analysed with Bayesian methods. METHODS: A team of biostatisticians created a checklist of previously reported items and additional items identified from a literature review. Using three different articles in three rounds, the items were then validated by residents in anaesthesiology with no skills in statistics. RESULTS: Based on an initial item list, three rounds led to a consensus checklist. Eleven items were considered important information to be specified for understanding the validity of the results. Of these, three were considered essential: specification of the prior, source of the prior (when prior is informative), and the effect size point estimate with its credible interval. CONCLUSION: The checklist can help clinicians interpret the results of a phase III randomised clinical trial analysed by Bayesian methods, even clinicians with no particular knowledge of statistics, to ensure that the major elements of the statistical section are present and valid. Care should be taken in interpreting the results of a trial analysed by Bayesian methods that are not reported with these three essential items because the validity of the results cannot be established.

Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting.

This consensus statement presents a comprehensive and evidence-based set of guidelines for the care of postoperative nausea and vomiting (PONV) in both adult and pediatric populations. The guidelines are established by an international panel of experts under the auspices of the American Society of Enhanced Recovery and Society for Ambulatory Anesthesia based on a comprehensive search and review of literature up to September 2019. The guidelines provide recommendation on identifying high-risk patients, managing baseline PONV risks, choices for prophylaxis, and rescue treatment of PONV as well as recommendations for the institutional implementation of a PONV protocol. In addition, the current guidelines focus on the evidence for newer drugs (eg, second-generation 5-hydroxytryptamine 3 [5-HT3] receptor antagonists, neurokinin 1 (NK1) receptor antagonists, and dopamine antagonists), discussion regarding the use of general multimodal PONV prophylaxis, and PONV management as part of enhanced recovery pathways. This set of guidelines have been endorsed by 23 professional societies and organizations from different disciplines (Appendix 1).Guidelines currently available include the 3 iterations of the consensus guideline we previously published, which was last updated 6 years ago; a guideline published by American Society of Health System Pharmacists in 1999; a brief discussion on PONV management as part of a comprehensive postoperative care guidelines; focused guidelines published by the Society of Obstetricians and Gynecologists of Canada, the Association of Paediatric Anaesthetists of Great Britain & Ireland and the Association of Perianesthesia Nursing; and several guidelines published in other languages.The current guideline was developed to provide perioperative practitioners with a comprehensive and up-to-date, evidence-based guidance on the risk stratification, prevention, and treatment of PONV in both adults and children. The guideline also provides guidance on the management of PONV within enhanced recovery pathways.The previous consensus guideline was published 6 years ago with a literature search updated to October 2011. Several guidelines, which have been published since, are either limited to a specific populations or do not address all aspects of PONV management. The current guideline was developed based on a systematic review of the literature published up through September 2019. This includes recent studies of newer pharmacological agents such as the second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, a dopamine antagonist, neurokinin 1 (NK1) receptor antagonists as well as several novel combination therapies. In addition, it also contains an evidence-based discussion on the management of PONV in enhanced recovery pathways. We have also discussed the implementation of a general multimodal PONV prophylaxis in all at-risk surgical patients based on the consensus of the expert panel.

Validation of the translated Quality of Recovery-15 questionnaire in a French-speaking population.

BACKGROUND: Quality of recovery is an important component of perioperative health status. The 15-item Quality of Recovery (QoR-15) scale is a validated multidimensional questionnaire that measures postoperative quality of recovery. The aim of this study was to translate and assess the psychometric properties of a French version of the QoR-15 scale (QoR-15F) to measure postoperative recovery in French-speaking patients. METHODS: After translation into French of the original English version of the QoR-15 scale, psychometric validation of the QoR-15F scale to measure postoperative quality of recovery was performed. This psychometric validation included validity, reliability, responsiveness, and feasibility. The QoR-15F scale was administered before operation and on Postoperative day 1 in French-speaking patients. Patient-perceived global recovery assessment was measured at Postoperative day 1 using a VAS. RESULTS: We enrolled 150 patients, and 144 completed the study protocol. The completion rate of administered questionnaires was 100%. Pearson (r) correlation between postoperative QoR-15F and the global recovery assessment by the patient was 0.60 (P<0.0001). As expected, there was a significant negative correlation between QoR-15F score and duration of surgery (r=-0.29; P<0.01), duration of PACU stay (r=-0.21; P=0.01), and duration of hospital stay (r=-0.34; P<0.01). Cronbach's alpha was 0.81, split-half alpha was 0.83, and the global test-retest intra-class coefficient was 0.98 (0.95-0.99). CONCLUSIONS: The QoR-15F is a valid and reliable tool to measure postoperative quality of recovery in French-speaking patients. The psychometric properties to measure postoperative quality of recovery were similar to the seminal English version. CLINICAL TRIAL REGISTRATION: NCT03578068.

Bayesian analysis from phase III trials was underused and poorly reported: a systematic review.

OBJECTIVES: We assessed the reporting of replicability items with the BayesWatch guidelines and crucial items of Bayesian analyses with the Reporting Of Bayes Used in clinical STudies (ROBUST) guidelines in reports of phase III trials. STUDY DESIGN AND SETTING: A literature search of Cochrane CENTRAL, Ovid MEDLINE, and EMBASE database was conducted to identify phase III trials using Bayesian methods for their primary outcome. Two reviewers performed the study selection process independently. RESULTS: From 5,404 articles retrieved, 49 reports of trials were included. The median [interquartile range] number of correctly reported items was four of seven [3-5] for ROBUST guidelines and seven of 10 [6-8] for BayesWatch guidelines. The proportion of correct reporting widely varied among items. The most frequently reported items from BayesWatch were the least specific (objectives, designs, and reporting of results). Specific Bayesian items (analytic technique and prior specifications) were poorly reported. Priors were given for two-thirds of studies and were justified for 22%. Sensitivity analyses were reported for 57% of trials. CONCLUSION: Bayesian methods are underused in phase III trials. Reports frequently lack descriptions of essential methodological components of the Bayesian analysis, such as the description of priors, which remains a critical key to interpreting Bayesian analyses. PROSPERO: CRD42017054929.

Protocol for TRAUMADORNASE: a prospective, randomized, multicentre, double-blinded, placebo-controlled clinical trial of aerosolized dornase alfa to reduce the incidence of moderate-to-severe hypoxaemia in ventilated trauma patients.

BACKGROUND: Acute respiratory distress syndrome continues to drive significant morbidity and mortality after severe trauma. The incidence of trauma-induced, moderate-to-severe hypoxaemia, according to the Berlin definition, could be as high as 45%. Its pathophysiology includes the release of damage-associated molecular patterns (DAMPs), which propagate tissue injuries by triggering neutrophil extracellular traps (NETs). NETs include a DNA backbone coated with cytoplasmic proteins, which drive pulmonary cytotoxic effects. The structure of NETs and many DAMPs includes double-stranded DNA, which prevents their neutralization by plasma. Dornase alfa is a US Food and Drug Administration-approved recombinant DNase, which cleaves extracellular DNA and may therefore break up the backbone of NETs and DAMPs. Aerosolized dornase alfa was shown to reduce trauma-induced lung injury in experimental models and to improve arterial oxygenation in ventilated patients. METHODS: TRAUMADORNASE will be an institution-led, multicentre, double-blinded, placebo-controlled randomized trial in ventilated trauma patients. The primary trial objective is to demonstrate a reduction in the incidence of moderate-to-severe hypoxaemia in severe trauma patients during the first 7 days from 45% to 30% by providing aerosolized dornase alfa as compared to placebo. The secondary objectives are to demonstrate an improvement in lung function and a reduction in morbidity and mortality. Randomization of 250 patients per treatment arm will be carried out through a secure, web-based system. Statistical analyses will include a descriptive step and an inferential step using fully Bayesian techniques. The study was approved by both the Agence Nationale de la Sécurité du Médicament et des Produits de Santé (ANSM, on 5 October 2018) and a National Institutional Review Board (CPP, on 6 November 2018). Participant recruitment began in March 2019. Results will be published in international peer-reviewed medical journals. DISCUSSION: If early administration of inhaled dornase alfa actually reduces the incidence of moderate-to-severe hypoxaemia in patients with severe trauma, this new therapeutic strategy may be easily implemented in many clinical trauma care settings. This treatment may facilitate ventilator weaning, reduce the burden of trauma-induced lung inflammation and facilitate recovery and rehabilitation in severe trauma patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03368092. Registered on 11 December 2017.

Validation of MRI for Volumetric Quantification of Atelectasis in the Perioperative Period: An Experimental Study in Swine.

Background: Impairment of pulmonary aeration is a frequent postoperative complication that is associated with adverse outcome. Diagnosis and quantification of impaired pulmonary aeration by CT scan is limited due to concern for exposure to ionizing radiation. Magnetic resonance imaging (MRI) represents a potential radiation-free alternative for this use. We undertook an experimental study to validate the use of MRI to quantify pulmonary aeration impairment. Methods: Ten large white pigs were studied before intubation, after intubation, 2 h after non-protective mechanical ventilation and after intra-tracheal negative pressure suction to induce atelectasis. A lung CT scan immediately followed by a lung MRI were performed at all four time points. On the 40 CT images lung volumes corresponding to non-aerated, poorly aerated, normally aerated, and overinflated voxels were measured based on their radiodensity. Similarly, on the 40 MRI images lung volumes corresponding to non-aerated and aerated voxels were measured based on their signal intensity. The correlation between non-aerated lung by MRI vs., CT scans, and with PaO2/FiO2 measured at each of the four time points was assessed with the Pearson' correlation coefficient, bias and limits of agreement. Results: Pearson correlation coefficient, bias and limits of agreements between the CT non-aerated lung volumes and MRI abnormal lung volumes were 0.88, -16 ml, and (-108, 77), respectively. Pearson correlation coefficient between PaO2/FiO2 and abnormal lung volumes measured with MRI was -0.60. Conclusion: In a preclinical swine model, quantitative measurements of pulmonary atelectasis by MRI-imaging are well correlated with the gold standard, i.e., densitometric scan CT measurements.

Randomized, Double-Blind, Placebo-Controlled Study of Intravenous Amisulpride as Treatment of Established Postoperative Nausea and Vomiting in Patients Who Have Had No Prior Prophylaxis.

BACKGROUND: Postoperative nausea and vomiting (PONV) occurs commonly in surgical patients despite widespread prophylactic antiemetic use. Rescue options are currently limited. 5HT3 antagonists are most frequently used for prophylaxis, but if they fail, additional doses are not effective as rescue medication. Intravenous (IV) amisulpride, a well-studied D2/D3 antagonist, has been shown in trials to prevent PONV. This study was designed to determine if amisulpride could be used to treat established PONV in patients at low-to-moderate risk of PONV who had not received any prior prophylaxis. METHODS: Men and women aged over 18 years were permitted to enroll if they were to undergo general inhalational anesthesia, expected to last at least 1 hour, for an outpatient or inpatient surgical procedure. Patients who then suffered PONV were randomized equally to 1 of 3 single-dose IV regimens: placebo or 5 or 10 mg amisulpride. The primary end point was complete response, defined as no emesis in the period 30 minutes to 24 hours after study drug treatment and no use of rescue medication in the entire 24-hour period. RESULTS: One thousand nine hundred eighty-eight patients were enrolled preoperatively, of whom 560 were randomized to a treatment arm. Complete response occurred in 39 of 181 patients (21.5%) in the placebo group compared to 60 of 191 patients (31.4%; P = .016) and 59 of 188 patients (31.4%; P = .016) in the amisulpride 5 and 10 mg groups, respectively. The adverse event profile of amisulpride at either dose was similar to placebo. CONCLUSIONS: IV amisulpride at 5 and 10 mg was safe and efficacious in the treatment of established PONV in surgical patients undergoing general anesthesia with no prior PONV prophylaxis.

The impact of warmed and humidified CO2 insufflation during robotic radical prostatectomy: Results of a randomized controlled trial.

BACKGROUND: Cool and dry gas insufflation during laparoscopy induces hypothermia and cytokine increase, with significant perioperative morbidity. Our aim was to assess if warmed and humidified CO2 insufflation with HumiGard™ device can achieve significant benefits over standard insufflation in terms of risk of hypothermia, cytokine response, blood gases, and intra- and postoperative parameters, in the setting of robot-assisted radical prostatectomy (RARP). METHODS: This was a prospective, randomized controlled clinical trial. Sixty-four patients with prostate cancer undergoing RARP were randomized to receive warmed and humidified CO2 insufflation with HumiGard device, plus hot air warming blanket (treatment group, H + WB), or standard CO2 insufflation, plus hot air warming blanket (control group, WB). Body core temperature (BCT), plasma levels of IL-6 and TNF-α, pain scores, and intraoperative parameters were recorded. The data were analyzed according to the Bayesian paradigm. RESULTS: Intraoperative BCT increased in both groups during surgery, with a statistically significant difference favoring group H + WB, ending at 0.2°C higher on average than group WB. No difference across groups was shown for cytokine levels. Blood gas parameters were not affected by warmed CO2 insufflation. No statistical differences were noted for pain scores and the other intra- and postoperative parameters. CONCLUSIONS: During RARP, warm and humidified CO2 insufflation with the HumiGard device was more effective than the standard CO2 insufflation in maintaining the patient's heat homeostasis, even if the difference was minimal. No imbalances were detected on blood gas analyses. No benefit could be shown in terms of cytokine levels and pain scores.