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.

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%.

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.

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.

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.

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.

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.

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.

Amisulpride for the Rescue Treatment of Postoperative Nausea or Vomiting in Patients Failing Prophylaxis: A Randomized, Placebo-controlled Phase III Trial.

BACKGROUND: Although antiemetics are commonly used to prevent postoperative nausea or vomiting, the failure rate is appreciable and there is currently no generally accepted standard for rescue treatment of postoperative nausea or vomiting after failed prophylaxis. This prospective, randomized, double-blind, parallel-group, placebo-controlled, multicenter study was designed to test the hypothesis that intravenous amisulpride, a dopamine D2/D3-antagonist, is superior to placebo at treating established postoperative nausea or vomiting after failed prophylaxis. METHODS: A total of 2,285 adult patients undergoing surgery under general inhalational anesthesia and receiving standard antiemetic prophylaxis were enrolled at 23 sites in Canada, France, Germany, and the United States. Of these, 702 patients experienced postoperative nausea or vomiting in the 24-h period after surgery and were randomized to receive a single dose of 5 or 10 mg intravenous amisulpride or matching placebo. The primary endpoint was complete response, defined as no emesis or rescue antiemetic use for 24 h after study drug administration, excluding emesis in the first 30 min. Secondary endpoints included incidence of emesis and rescue medication use, nausea burden, time to treatment failure, and length of stay in postanesthesia care unit and hospital. RESULTS: Complete response occurred in significantly more patients receiving 10 mg amisulpride (96 of 230, 41.7%) than placebo (67 of 235, 28.5%), a 13.2% difference (95% CI, 4.6 to 21.8; odds ratio, 1.80; P = 0.006). A 5-mg dose of amisulpride did not show a significant benefit (80 of 237, 33.8%); the difference from placebo was 5.2% (95% CI, 3.1 to 13.6; odds ratio, 1.24; P = 0.109). The total number of adverse events recorded and proportion of patients with at least one adverse event were comparable between the placebo and amisulpride groups. No clinically relevant toxicities were observed. CONCLUSIONS: A single 10-mg dose of intravenous amisulpride was safe and more effective than placebo at treating established postoperative nausea or vomiting in patients failing postoperative nausea or vomiting prophylaxis.

Trainability of Cricoid Pressure Force Application: A Simulation-Based Study.

BACKGROUND: Aspiration of gastric contents is a leading cause of airway management-related mortality during anesthesia practice. Cricoid pressure (CP) is widely used during rapid sequence induction to prevent aspiration. National guidelines for CP suggest a target force of 10 N before and 30 N after loss of consciousness. However, few studies have rigorously assessed whether clinicians can be trained to consistently achieve these levels of force. We hypothesized that clinicians can be trained effectively to deliver 10-30 N during application of CP. METHODS: Clinicians (attending anesthesiologist, anesthesiology residents, certified registered nurse anesthetists, or operating room nurses) applied CP on a Vernier force plate simulator with measurements taken at 4 time points over 60 seconds, 2 measurements before and 2 measurements after loss of consciousness. A successful cycle required all 4 time points to be within the target range (10 ± 5 and 30 ± 5 N, respectively). After baseline assessment (n = 100 clinicians), a subset of 40 participants volunteered for education on recommended force targets, underwent self-regulated practice, and then performed 30 1-minute cycles of high-frequency simulation analyzed by cumulative sum analysis to assess their change in performance. RESULTS: At baseline, 5 cycles (1.3% [confidence interval {CI}, 0.3%-2.50%]) out of 400 were successful. Performance improved after education and self-regulated practice (16% successful cycles [CI, 7.8%-25%]), and performance during the last 4 of 30 cycles was 45% (CI, 33%-58%). The odds of success increased over time (odds ratio, 1.1; P < .001). By cumulative sum analysis, however, no subject crossed the h0 line, indicating that no one achieved proficiency of the predefined target forces. CONCLUSIONS: At baseline, performance was poor at achieving target forces specified by national guidelines. Simulation-based training improved the success rate, but no participant achieved the predefined threshold for proficiency.

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.

Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery.

Background: Uncertainty remains about the effects of aspirin in patients with prior percutaneous coronary intervention (PCI) having noncardiac surgery. Objective: To evaluate benefits and harms of perioperative aspirin in patients with prior PCI. Design: Nonprespecified subgroup analysis of a multicenter factorial trial. Computerized Internet randomization was done between 2010 and 2013. Patients, clinicians, data collectors, and outcome adjudicators were blinded to treatment assignment. (ClinicalTrials.gov: NCT01082874). Setting: 135 centers in 23 countries. Patients: Adults aged 45 years or older who had or were at risk for atherosclerotic disease and were having noncardiac surgery. Exclusions were placement of a bare-metal stent within 6 weeks, placement of a drug-eluting stent within 1 year, or receipt of nonstudy aspirin within 72 hours before surgery. Intervention: Aspirin therapy (overall trial, n = 4998; subgroup, n = 234) or placebo (overall trial, n = 5012; subgroup, n = 236) initiated within 4 hours before surgery and continued throughout the perioperative period. Of the 470 subgroup patients, 99.9% completed follow-up. Measurements: The 30-day primary outcome was death or nonfatal myocardial infarction; bleeding was a secondary outcome. Results: In patients with prior PCI, aspirin reduced the risk for the primary outcome (absolute risk reduction, 5.5% [95% CI, 0.4% to 10.5%]; hazard ratio [HR], 0.50 [CI, 0.26 to 0.95]; P for interaction = 0.036) and for myocardial infarction (absolute risk reduction, 5.9% [CI, 1.0% to 10.8%]; HR, 0.44 [CI, 0.22 to 0.87]; P for interaction = 0.021). The effect on the composite of major and life-threatening bleeding in patients with prior PCI was uncertain (absolute risk increase, 1.3% [CI, -2.6% to 5.2%]). In the overall population, aspirin increased the risk for major bleeding (absolute risk increase, 0.8% [CI, 0.1% to 1.6%]; HR, 1.22 [CI, 1.01 to 1.48]; P for interaction = 0.50). Limitation: Nonprespecified subgroup analysis with small sample. Conclusion: Perioperative aspirin may be more likely to benefit rather than harm patients with prior PCI. Primary Funding Source: Canadian Institutes of Health Research.

Amisulpride Prevents Postoperative Nausea and Vomiting in Patients at High Risk: A Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Postoperative nausea and vomiting causes distress for patients and can prolong care requirements. Consensus guidelines recommend use of multiple antiemetics from different mechanistic classes as prophylaxis in patients at high risk of postoperative nausea and vomiting. The prophylactic efficacy of the dopamine D2/D3 antagonist amisulpride in combination with other antiemetics was investigated. METHODS: This double-blind, randomized, placebo-controlled, international, multicenter trial was conducted in 1,147 adult surgical patients having three or four postoperative nausea and vomiting risk factors. Patients were randomized to receive either intravenous amisulpride (5 mg) or matching placebo at induction of general anesthesia, in addition to one standard, nondopaminergic antiemetic, most commonly ondansetron or dexamethasone. Vomiting/retching, nausea, and use of rescue medication were recorded for 24 h after wound closure. The primary endpoint was complete response, defined as no emesis or rescue medication use in the 24-h postoperative period. RESULTS: Complete response occurred in 330 of 572 (57.7%) of the amisulpride group and 268 of 575 (46.6%) of the control group (difference 11.1 percentage points; 95% CI, 5.3 to 16.8; P < 0.001). The incidences of emesis (13.8% vs. 20.0%, P = 0.003), any nausea (50.0% vs. 58.3%, P = 0.002), significant nausea (37.1% vs. 47.7%, P < 0.001), and rescue medication use (40.9% vs. 49.4%, P = 0.002) were significantly lower in the amisulpride group. Adverse events and laboratory and electrocardiogram abnormalities occurred no more frequently with amisulpride than with placebo. CONCLUSIONS: Intravenous amisulpride was safe and effective as prophylaxis of postoperative nausea and vomiting when given in combination with an antiemetic from another class to adult patients at high risk for suffering postoperative nausea and vomiting undergoing elective surgery under inhalational general anesthesia. VISUAL ABSTRACT: An online visual overview is available for this article at http://links.lww.com/ALN/B727.

Impact of valve-less vs. standard insufflation on pneumoperitoneum volume, inflammation, and peritoneal physiology in a laparoscopic sigmoid resection experimental model.

BACKGROUND: Standard insufflators compensate for intra-abdominal pressure variations with pressure spikes. Our aim was to evaluate the impact of a stable, low-pressure pneumoperitoneum induced by a valve-less insufflator, on working space, hemodynamics, inflammation, and peritoneal physiology, in a model of laparoscopic sigmoid resection. MATERIALS AND METHODS: Twelve pigs (47 ± 3.3 kg) were equipped for invasive hemodynamic monitoring and randomly assigned to Standard (n = 6) vs. valve-less (n = 6) insufflation. Animals were positioned in a 30° Trendelenburg on a CT scan bed. A low-pressure pneumoperitoneum (8 mmHg) was started and duration was set for 180 min. Abdominal CT scans were performed, under neuromuscular blockade, before, immediately after, and 1 and 3 h after insufflation. Pneumoperitoneum volumes were calculated on 3D reconstructed CT scans. After creation of a mesenteric window, capillary blood was obtained by puncturing the sigmoid serosa and local lactatemia (mmol/L) was measured using a handheld analyzer. Surgical resection was performed according to the level of lactates, in order to standardize bowel stump perfusion. IL-1 and IL-6 (ng/mL) were measured repeatedly. The peritoneum was sampled close to the surgical site and distantly for the oxygraphic assessment of mitochondrial respiration. A pathologist applied a semi-quantitative score to evaluate the anastomosis. RESULTS: Mean arterial pressure, pulse, body temperature, oximetry, systemic lactatemia, and local lactates were similar. IL-6 was lower in the valve-less group, reaching a statistically significant difference after 3 h of insufflation (64.85 ± 32.5 vs. 133.95 ± 59.73; p = 0.038) and 48 h (77.53 ± 68.4 vs. 190.74 ± 140.79; p = 0.029). Peritoneal mitochondrial respiration was significantly increased after the survival period, with no difference among the groups. The anastomoses in the valve-less group demonstrated a lower acute (p = 0.04) inflammatory infiltration. The mean anterior posterior thickness was slightly, yet significantly higher in the valve-less group, on all post-insufflation CT scans. CONCLUSIONS: Valve-less insufflation achieved a slightly higher working space and a lower systemic and localized inflammatory response in this experimental setting.

Incidence of akathisia after postoperative nausea and vomiting prophylaxis with droperidol and ondansetron in outpatient surgery: A multicentre controlled randomised trial.

BACKGROUND: Akathisia, a distressing movement disorder induced by butyrophenones, has been described with low doses of droperidol used for postoperative nausea and vomiting (PONV) prophylaxis, but the incidence remains unclear. OBJECTIVES: To determine the incidence of akathisia after PONV prophylaxis with two doses of droperidol in comparison with ondansetron, in patients undergoing ambulatory surgery. We hypothesised that the incidence of akathisia is higher with droperidol than that with ondansetron. DESIGN: Randomised controlled double blind trial. SETTING: Two University Hospital Centres and two private Clinics from January to September 2014. PATIENTS: Patients (n=297) undergoing general anaesthesia for ambulatory surgery were randomly allocated to receive PONV prophylaxis with droperidol (0.625 or 1.25 mg) or ondansetron 4 mg; patients of the three groups also received 4 mg of dexamethasone. Exclusion criteria were contraindication to droperidol and ondansetron, use of psychotropic medications or benzodiazepines or history of psychotic illness. INTERVENTIONS: Participants received droperidol (0.625 or 1.25 mg) or ondansetron 4 mg during general anaesthesia. After discharge from the postanaesthesia care unit presence and severity of akathisia were assessed using the Barnes Akathisia Rating Scale at 4 h postoperatively. MAIN OUTCOME MEASURES: Score of the Global Clinical Assessment of Akathisia of Barnes Akathisia Rating Scale. RESULTS: The number of akathisia observed was 1/118 (0.8%) in the ondansetron group, 1/84 (1.2%) in droperidol 0.625 mg group, and 3/87 (3.4%) in droperidol 1.25 mg group. The akathisia rate difference among the three groups was not significant (P = 0.52). We could not demonstrate significant differences in the incidence of akathisia between the two doses of droperidol. The only case of marked akathisia treated with benzodiazepines was observed after droperidol 1.25 mg. CONCLUSION: The use of droperidol or ondansetron for PONV prophylaxis is associated to a low incidence of akathisia (0.8 to 3.4%) after general anaesthesia for ambulatory surgery. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01942343.

Intravenous Amisulpride for the Prevention of Postoperative Nausea and Vomiting: Two Concurrent, Randomized, Double-blind, Placebo-controlled Trials.

BACKGROUND: Two essentially identical, randomized, double-blind, placebo-controlled, parallel-group phase III studies evaluated the efficacy of intravenous amisulpride, a dopamine D2/D3 antagonist, in the prevention of postoperative nausea and vomiting in adult surgical patients. METHODS: Adult inpatients undergoing elective surgery during general anesthesia and having at least two of the four Apfel risk factors for postoperative nausea and vomiting were enrolled at 9 U.S. and 10 European sites. A single 5-mg dose of amisulpride or matching placebo was given at induction of anesthesia. The primary endpoint was complete response, defined as no vomiting/retching and no use of antiemetic rescue medication in the 24-h postoperative period. Nausea incidence was a secondary endpoint. RESULTS: Across the two studies, 689 patients were randomized and dosed with study medication, of whom 626 were evaluable per protocol. In the U.S. study, 46.9% (95% CI, 39.0 to 54.9) of patients achieved complete response in the amisulpride group compared to 33.8% (95% CI, 26.2 to 42.0) in the placebo group (P = 0.026). In the European study, complete response rates were 57.4% (95% CI, 49.2 to 65.3) for amisulpride and 46.6% (95% CI, 38.8 to 54.6) for placebo (P = 0.070). Nausea occurred less often in patients who received amisulpride than those who received placebo. There was no clinically significant difference in the safety profile of amisulpride and placebo; in particular, there were no differences in terms of QT prolongation, extrapyramidal side effects, or sedation. CONCLUSIONS: One of the two trials demonstrated superiority, while pooling both in a post hoc change to the plan of analysis supported the hypothesis that amisulpride was safe and superior to placebo in reducing the incidence of postoperative nausea and vomiting in a population of adult inpatients at moderate to high risk of postoperative nausea and vomiting.

Precision real-time evaluation of bowel perfusion: accuracy of confocal endomicroscopy assessment of stoma in a controlled hemorrhagic shock model.

BACKGROUND AND AIMS: Confocal laser endomicroscopy (CLE) can provide real-time evaluation of bowel perfusion. We aimed to evaluate CLE perfusion imaging in a hemorrhagic shock model. MATERIALS AND METHODS: Five pigs were equipped to ensure hemodynamic monitoring. Three ileostomies per animal (total n = 15) were randomly created (T0). Blood was withdrawn targeting a mean arterial pressure of 40 mmHg (shock phase, T1), for 90 min. Infusion of Ringer's lactate was started and continued for 90 min (T2). At the different time points: (a) stomas' mucosa was scanned with CLE; (b) capillary lactates were measured on blood obtained by puncturing stomas' mucosa; and (c) full-thickness stomas' biopsies were sampled for histology, mitochondrial respiratory rate (V 0 = basal and V ADP = respiratory rate in excess of adenosine diphosphate), and levels of superoxide anion evaluation. Functional capillary density (FCD) was measured using ad hoc software. RESULTS: Confocal scanning provided consistent and specific imaging of bowel hypoperfusion at T1: vascular hyperpermeability (blurred and enlarged capillaries) and edema (enhanced visualization of the brush border due to increased intercellular spaces and fluorescein leakage). At the end of T2, there was an improved capillary flow. FCD-A index expressed statistically significant correlation with (1) stoma capillary lactates (p = 0.023); (2) systemic capillary lactates (p = 0.031); (3) inflammation pathology score (p = 0.048); (4) central venous pressure (p = 0.0043); and (5) pulmonary artery pressure (p = 0.01). Stoma capillary lactates (mmol/L) were significantly increased at T1 (8.81 ± 4.23; p < 0.0001) and at T2 (4.77 ± 3.13; p < 0.01) when compared to T0 inclusion values (1.86 ± 0.56). V 0 and V ADP (pmol O2/min/mg tissue) were both significantly decreased at T1 versus T0 (p < 0.007 and p < 0.01, respectively) and recovered by the end of reanimation (T2 vs. T0, p = n.s.). Mean O 2·- production (µmol/min/mg/dry tissue) increased at T1 and significantly decreased at T2. CONCLUSIONS: Confocal laser endomicroscopy (CLE) imaging could identify morphological signs congruent with biochemical markers of bowel perfusion and could be useful for assessment of stomas.

Comparative analysis of resuscitation using human serum albumin and crystalloids or 130/0.4 hydroxyethyl starch and crystalloids on skeletal muscle metabolic profile during experimental haemorrhagic shock in swine: A randomised experimental study.

BACKGROUND: Protection against acute skeletal muscle metabolic dysfunction and oxidative stress could be a therapeutic target in volume expansion for severely bleeding patients. OBJECTIVES: This experimental pilot study in swine aims at comparing 130/0.4 hydroxyethyl starch (HES) with 4% albumin along with crystalloid perfusion for first-line volume expansion in haemorrhagic shock with a particular emphasis on oxidative stress and muscular mitochondrial function. DESIGN: Randomised experimental study. SETTING: Digestive Cancer Research Institute Preclinical Laboratory, Strasbourg University Hospital, France, from February 2012 to June 2013. ANIMALS: Twenty large white pigs. INTERVENTION: Pressure-controlled haemorrhagic shock and volume resuscitation using either 4% human serum albumin or 130/0.4 HES along with crystalloid perfusion were performed in 20 large white pigs. MAIN OUTCOME MEASURES: Muscular biopsy of gastrocnemius muscle was performed for metabolomics screening, mitochondrial respiratory chain assessment and electron spin resonance reactive oxygen species production along with arterial and venous reactive oxygen species production at baseline, at the completion of shock, at 90 min and at 180 min after volume expansion. RESULTS: There was no difference between the two groups in measurements of skeletal muscle superoxide production. In a pooled analysis, there was a statistically significant decrease in gastrocnemius muscle creatine content from baseline to 90 min (P < 0.05) and 180 min (P < 0.05). Muscular lactate content and mitochondrial respiratory chain oxidative capacity remained constant at the respective time points. CONCLUSION: In this pilot experimental study in swine, during pressure-controlled haemorrhagic shock treated with either albumin or 130/0.4 HES in conjunction with crystalloid perfusion, skeletal muscle metabolic profile was unaltered. ETHICAL APPROVAL NUMBER: 38.2012.01.031.

Impact of nitrous oxide on the haemodynamic consequences of venous carbon dioxide embolism: An experimental study.

BACKGROUND: Nitrous oxide (N2O) is still considered an important component of general anaesthesia. However, should gas embolisation occur as result of carbon dioxide (CO2) pneumoperitoneum, N2O may compromise safety, as the consequences of a gas embolus consisting of a combination of CO2 and N2O may be more severe than CO2 alone. OBJECTIVE: This experimental study was designed to compare the cardiopulmonary consequences of gas embolisation with a N2O/CO2 mixture, or CO2 alone. DESIGN: Experimental study. SETTING: Research Institute Against Digestive Cancer laboratory, Strasbourg, France. ANIMALS: Seven Large-White pigs receiving standardised inhalation anaesthesia. INTERVENTIONS: Each animal, acting as its own control, was studied in two successive experimental conditions - intravenous gas injections of 2 ml kg of 100% CO2 and 2 ml kg of a gas mixture consisting of 10% N2O and 90% CO2. MAIN OUTCOMES MEASURES: Haemodynamic and ventilatory consequences of embolisation with the gases. RESULTS: We found that the haemodynamic (heart rate, mean arterial blood pressure, central venous pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure and transoesophageal echocardiography parameters) and ventilatory (arterial oxygen saturation, end-tidal CO2 concentration and mixed venous oxygen saturation) consequences of embolisation with either 100% CO2 or 10% N2O with 90% CO2 were similar. CONCLUSION: The findings of this study may alleviate concerns that the use of N2O, as a part of a balanced general anaesthesia technique, may have greater adverse consequences should embolisation of pneumoperitoneal gas containing N2O occur.