A randomized controlled trial of the intraoperative use of noninvasive ventilation versus supplemental oxygen by face mask for procedural sedation in an electrophysiology laboratory.

PURPOSE: The efficacy of noninvasive ventilation (NIV) during procedures that require sedation and analgesia has not been established. We evaluated whether NIV reduces the incidence of respiratory events. METHODS: In this randomized controlled trial, we included 195 patients with an American Society of Anesthesiologists Physical Status of III or IV during electrophysiology laboratory procedures. We compared NIV with face mask oxygen therapy for patients under sedation. The primary outcome was the incidence of respiratory events determined by a computer-driven blinded analysis and defined by hypoxemia (peripheral oxygen saturation < 90%) or apnea/hypopnea (absence of breathing for 20 sec on capnography). Secondary outcomes included hemodynamic variables, sedation, patient safety (composite scores of major or minor adverse events), and adverse outcomes at day 7. RESULTS: A respiratory event occurred in 89/98 (95%) patients in the NIV group and in 69/97 (73%) patients with face masks (risk ratio [RR], 1.29; 95% confidence interval [CI], 1.13 to 1.47; P < 0.001). Hypoxemia occurred in 40 (42%) patients in the NIV group and in 33 (34%) patients with face masks (RR, 1.21; 95% CI, 0.84 to 1.74; P = 0.30). Apnea/hypopnea occurred in 83 patients (92%) in the NIV group vs 65 patients (70%) with face masks (RR, 1.32; 95% CI, 1.14 to 1.53; P < 0.001). Hemodynamic variables, sedation, major or minor safety events, and patient outcomes were not different between the groups. CONCLUSIONS: Respiratory events were more frequent among patients receiving NIV without any safety or outcome impairment. These results do not support the routine use of NIV intraoperatively. STUDY REGISTRATION: ClinicalTrials.gov (NCT02779998); registered 4 November 2015.

RéSUMé: OBJECTIF: L'efficacité de la ventilation non invasive (VNI) pendant les interventions nécessitant une sédation et une analgésie n'a pas été établie. Nous avons évalué si la VNI réduisait l'incidence des complications respiratoires. MéTHODE: Dans cette étude randomisée contrôlée, nous avons inclus 195 patient·es de statut physique III ou IV selon l'American Society of Anesthesiologists pendant des interventions en laboratoire d'électrophysiologie. Nous avons comparé la VNI à l'oxygénothérapie par masque facial pour les patient·es sous sédation. Le critère d'évaluation principal était l'incidence des complications respiratoires déterminée par une analyse en aveugle assistée par ordinateur et définie par une hypoxémie (saturation périphérique en oxygène < 90 %) ou une apnée/hypopnée (absence de respiration pendant 20 secondes à la capnographie). Les critères d'évaluation secondaires comprenaient les variables hémodynamiques, la sédation, la sécurité des patient·es (scores composites des événements indésirables majeurs ou mineurs) et les issues indésirables au jour 7. RéSULTATS: Un événement respiratoire est survenu chez 89/98 (95 %) patient·es du groupe VNI et chez 69/97 (73 %) patient·es ayant un masque facial (risque relatif [RR], 1,29; intervalle de confiance [IC] à 95 %, 1,13 à 1,47; P < 0,001). Une hypoxémie est survenue chez 40 (42 %) patient·es du groupe VNI et chez 33 (34 %) patient·es ayant un masque facial (RR, 1,21 ; IC à 95 %, 0,84 à 1,74; P = 0,30). Une hypoxémie est survenue chez 40 (42 %) patient·es du groupe VNI et chez 33 (34 %) patient·es ayant un masque facial (RR, 1,21; IC 95 %, 0,84 à 1,74; P = 0,30). Les variables hémodynamiques, la sédation, les événements de sécurité majeurs ou mineurs et les issues pour les patient·es n'étaient pas différents entre les groupes. CONCLUSION: Les complications respiratoires étaient plus fréquentes chez les patient·es recevant une VNI sans aucun impact sur la sécurité ou les issues. Ces résultats n'appuient pas l'utilisation systématique de la VNI en peropératoire. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT02779998); enregistrée le 4 novembre 2015.

Impact of Head-of-Bed Posture on Brain Oxygenation in Patients with Acute Brain Injury: A Prospective Cohort Study.

BACKGROUND: Therapeutic head positioning plays a role in the management of patients with acute brain injury. Although intracranial pressure (ICP) is typically lower in an upright posture than in a flat position, limited data exist concerning the effect of upright positioning on brain oxygenation and circulation. We sought to determine the impact of supine (0°) and semirecumbent (15° and 30°) postures on ICP, brain oxygenation, and brain circulation. METHODS: An observational cohort study was conducted between February 2012 and September 2015. Twenty-three patients with severe acute brain injury were successively observed at head elevations of 30°, 15°, and 0°. Postural-induced changes in ICP, cerebral perfusion pressure, brain tissue oxygenation pressure, and transcranial Doppler findings were simultaneously measured during three repeated experiments: 24 h after admission to the intensive care unit (exp1), 24 h later (exp2), and 96 h later (exp3). Cerebral perfusion pressure, arterial blood gases, hemoglobin content, and body temperature remained unchanged during the three experiments. RESULTS: Using linear random-slope mixed models, we found that during the early phase of acute brain injury (exp1), lowering the head posture from 30° to 15°, and then to 0°, was associated with a gradual mean ICP increase of 2.6 mm Hg (1.4-3.7 mm Hg; P < 0.001); and from 30° to 0°, an increase of 7.4 mm Hg (6.3-8.6 mm Hg; P < 0.001). Furthermore, brain tissue oxygenation pressure and mean blood flow velocity improved when the head posture was lowered from 30° to 0° by 1.2 mm Hg (0.2-2.3 mm Hg) and 4.1 cm/s (0.0-8.2 cm/s), respectively (both P < 0.05). CONCLUSIONS: Changing the positioning of stable patients with acute brain injury resulted in opposite changes of ICP versus brain oxygenation and circulation. This information supports the concept of an individualized approach to head positioning that is based on the multimodal monitoring of brain parameters.

EASL-ALEH 2015 algorithm for the use of transient elastography in treatment-naive patients with hepatitis B: An independent validation.

Various non-invasive methods have been evaluated in chronic hepatitis B, but none of them have been fully validated for the assessment of liver fibrosis. The issued EASL-ALEH 2015 guidelines provide detailed algorithms based on LSM and ALT serum levels. The aim of our study was to validate the diagnostic accuracy of this algorithm and to better understand discrepancies. Four hundred and thirteen patients from 3 centres were retrospectively included. All included patients were classified for fibrosis stage according to results of a liver biopsy. The overall diagnostic value was expressed with AUROCs given with 95% confidence intervals for the diagnostic targets. For each diagnostic target, optimal cut-offs were determined according to the Youden method. For the population of patients with ALT9 kPa, respectively. For patients with ALT>N but ≤5N (n = 306), AUROCs of transient elastography were 0.79 (0.73-0.84) and 0.84 (0.75-0.92) for F ≥ 2 and F ≥ 3 diagnostic targets. The prevalence of significant fibrosis was, respectively, 15%, 52% and 85% when LSM was <6kPa, between 6 and 12 kPa or >12 kPa. Our study independently validates the EASL-ALEH algorithm based on ALT levels and LSM assessed by transient elastography.

Ten-year outcomes of islet transplantation in patients with type 1 diabetes: Data from the Swiss-French GRAGIL network.

To describe the 10-year outcomes of islet transplantation within the Swiss-French GRAGIL Network, in patients with type 1 diabetes experiencing high glucose variability associated with severe hypoglycemia and/or with functional kidney graft. We conducted a retrospective analysis of all subjects transplanted in the GRAGIL-1c and GARGIL-2 islet transplantation trials and analyzed components of metabolic control, graft function and safety outcomes over the 10-year period of follow-up. Forty-four patients were included between September 2003 and April 2010. Thirty-one patients completed a 10-year follow-up. Ten years after islet transplantation, median HbA1c was 7.2% (6.2-8.0) (55 mmol/mol [44-64]) versus 8.0% (7.1-9.1) (64 mmol/mol [54-76]) before transplantation (p < .001). Seventeen of 23 (73.9%) recipients were free of severe hypoglycemia, 1/21 patients (4.8%) was insulin-independent and median C-peptide was 0.6 ng/ml (0.2-1.2). Insulin requirements (UI/kg/day) were 0.3 (0.1-0.5) versus 0.5 (0.4-0.6) before transplantation (p < .001). Median (IQR) ß-score was 1 (0-4) (p < .05 when comparing with pre-transplantation values) and 51.9% recipients had a functional islet graft at 10 years. With a 10-year follow-up in a multicentric network, islet transplantation provided sustained improvement of glycemic control and was efficient to prevent severe hypoglycemia in almost 75% of the recipients.

Comparison of strategies for monitoring and treating patients at the early phase of severe traumatic brain injury: the multicentre randomised controlled OXY-TC trial study protocol.

INTRODUCTION: Intracranial hypertension is considered as an independent risk factor of mortality and neurological disabilities after severe traumatic brain injury (TBI). However, clinical studies have demonstrated that episodes of brain ischaemia/hypoxia are common despite normalisation of intracranial pressure (ICP). This study assesses the impact on neurological outcome of guiding therapeutic strategies based on the monitoring of both brain tissue oxygenation pressure (PbtO2) and ICP during the first 5 days following severe TBI. METHODS AND ANALYSIS: Multicentre, open-labelled, randomised controlled superiority trial with two parallel groups in 300 patients with severe TBI. Intracerebral monitoring must be in place within the first 16 hours post-trauma. Patients are randomly assigned to the ICP group or to the ICP + PbtO2 group. The ICP group is managed according to the international guidelines to maintain ICP≤20 mm Hg. The ICP + PbtO2 group is managed to maintain PbtO2 ≥20 mm Hg in addition to the conventional optimisation of ICP. The primary outcome measure is the neurological status at 6 months as assessed using the extended Glasgow Outcome Scale. Secondary outcome measures include quality-of-life assessment, mortality rate, therapeutic intensity and incidence of critical events during the first 5 days. Analysis will be performed according to the intention-to-treat principle and full statistical analysis plan developed prior to database freeze. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of Sud-Est V (14-CHUG-48) and from the National Agency for Medicines and Health Products Safety (Agence Nationale de Sécurité du Médicament et des produits de santé) (141 435B-31). Results will be presented at scientific meetings and published in peer-reviewed publications.The study was registered with ClinTrials NCT02754063 on 28 April 2016 (pre-results).

Glycemic variability indices can be used to diagnose islet transplantation success in type 1 diabetic patients.

AIMS: High glycemic variability (GV) is the major indication for islet transplantation (IT) in patients with type 1 diabetes (T1D). The actual criteria used to assess graft function do not consider GV improvement. Our study aimed to describe GV indices' evolution in T1D patients who benefited from IT during the TRIMECO trial and to evaluate if thresholds might be defined to diagnose IT success. METHODS: We collected data from 29 patients of the TRIMECO trial, a clinical trial (NCT01148680) comparing the metabolic efficacy of IT with intensive insulin therapy. Based on CGM data, we analyzed mean glucose level and four GV indices (standard deviation, coefficient of variation, MAGE and GVP) before (M0) and 6 months (M6) after IT. RESULTS: Each GV index decreased significantly between M0 and M6: SD 53.9 mg/dL [44.6-61.5] versus 20.1 mg/dL [13.5-24.3]; CV 35.2% [30.6-37.7] versus 17.3% [12.0-20.5]; MAGE 134.9 mg/dl [111.2-155.8] versus 51.9 mg/dL [32.4-62.4]; GVP 35.3% [24.9-47.2] versus 12.2% [6.2-18.8] (p ≤ 0.0001). Thresholds diagnosing IT success at 6 months post-transplant were an SD at 22.76 mg/dL (sensibility 88.89%, specificity 80.00%), a CV at 17.47% (sensibility 88.89%, specificity 70.00%), a MAGE at 54.81 mg/dL (sensibility 88.89%, specificity 80.00%) and a GVP at 12.27% (sensibility 88.89%, specificity 70.00%). CONCLUSIONS: This study confirms a positive impact of IT on GV. The proposed thresholds allow an easy evaluation of IT success using only CGM data and may be a clinical tool for the follow-up of transplanted patients.

Perioperative pain and post-operative nausea and vomiting (PONV) management after day-case surgery: The SFAR-OPERA national study.

OBJECTIVES: Since pain and post-operative nausea and vomiting (PONV) are the main reasons for failed discharge after day-case surgery, assessing pain and PONV is important. The aim was to describe the perioperative pain and PONV management within selected day-case surgical procedures in France. METHODS: The OPERA trial was carried out on given days between December 2013 and December 2014. Each participating centre was required to fill out 3 separate questionnaires aiming at describing (1) protocols about pain and PONV, (2) patients' characteristics and procedures, (3) analgesic and PONV practice patterns for selected procedures. RESULTS: Over the two days of investigation in each of the 221 randomly selected healthcare institutions, 7382 patients were included, of whom 2144 patients above 12 years underwent one of 10 selected procedures. Among responding institutions, 40% [33;47] had a dedicated pain management written protocol. Combination of tramadol and paracetamol was the most commonly prescribed (78% [71;83] of centres). Oral morphine was prescribed in 59/199 (30% [23; 37]) centres, for home treatment in 25/59 (42% [30; 56]) centres. However, there was no standardised take-home analgesic and PONV strategies for selected surgical procedures at risk of moderate to severe pain. PONV management guidance after discharge was included in only 12 % of centres. CONCLUSION: This survey demonstrates that practice patterns for pain treatment and PONV prophylaxis after ambulatory surgery vary among French centres and are not always in line with national guidelines. Strategies to improve practices and make them more homogeneous are necessary.

Islet transplantation versus insulin therapy in patients with type 1 diabetes with severe hypoglycaemia or poorly controlled glycaemia after kidney transplantation (TRIMECO): a multicentre, randomised controlled trial.

BACKGROUND: Islet transplantation is indicated for patients with type 1 diabetes with severe hypoglycaemia or after kidney transplantation. We did a randomised trial to assess the efficacy and safety of islet transplantation compared with insulin therapy in these patients. METHODS: In this multicentre, open-label, randomised controlled trial, we randomly assigned (1:1) patients with type 1 diabetes at 15 university hospitals to receive immediate islet transplantation or intensive insulin therapy (followed by delayed islet transplantation). Eligible patients were aged 18-65 years and had severe hypoglycaemia or hypoglycaemia unawareness, or kidney grafts with poor glycaemic control. We used computer-generated randomisation, stratified by centre and type of patient. Islet recipients were scheduled to receive 11 000 islet equivalents per kg bodyweight in one to three infusions. The primary outcome was proportion of patients with a modified ß-score (in which an overall score of 0 was not allocated when stimulated C-peptide was negative) of 6 or higher at 6 months after first islet infusion in the immediate transplantation group or 6 months after randomisation in the insulin group. The primary analysis included all patients who received the allocated intervention; safety was assessed in all patients who received islet infusions. This trial is registered with ClinicalTrials.gov, number NCT01148680, and is completed. FINDINGS: Between July 8, 2010, and July 29, 2013, 50 patients were randomly assigned to immediate islet transplantation (n=26) or insulin treatment (n=24), of whom three (one in the immediate islet transplantation group and two in the insulin therapy group) did not receive the allocated intervention. Median follow-up was 184 days (IQR 181-186) in the immediate transplantation group and 185 days (172-201) in the insulin therapy group. At 6 months, 16 (64% [95% CI 43-82]) of 25 patients in the immediate islet transplantation group had a modified ß-score of 6 or higher versus none (0% [0-15]) of the 22 patients in the insulin group (p<0·0001). At 12 months after first infusion, bleeding complications had occurred in four (7% [2-18]) of 55 infusions, and a decrease in median glomerular filtration rate from 90·5 mL/min (IQR 76·6-94·0) to 71·8 mL/min (59·0-89·0) was observed in islet recipients who had not previously received a kidney graft and from 63·0 mL/min (55·0-71·0) to 57·0 mL/min (45·5-65·1) in islet recipients who had previously received a kidney graft. INTERPRETATION: For the indications assessed in this study, islet transplantation effectively improves metabolic outcomes. Although studies with longer-term follow-up are needed, islet transplantation seems to be a valid option for patients with severe, unstable type 1 diabetes who are not responding to intensive medical treatments. However, immunosuppression can affect kidney function, necessitating careful selection of patients. FUNDING: Programme Hospitalier de Recherche Clinique grant from the French Government.

How Long Should Routine EEG Be Recorded to Get Relevant Information?

OBJECTIVE: The optimal duration of routine EEG (rEEG) has not been determined on a clinical basis. This study aims to determine the time required to obtain relevant information during rEEG with respect to the clinical request. METHOD: All rEEGs performed over 3 months in unselected patients older than 14 years in an academic hospital were analyzed retrospectively. The latency required to obtain relevant information was determined for each rEEG by 2 independent readers blinded to the clinical data. EEG final diagnoses and latencies were analyzed with respect to the main clinical requests: subacute cognitive impairment, spells, transient focal neurologic manifestation or patients referred by epileptologists. RESULTS: From 430 rEEGs performed in the targeted period, 364 were analyzed: 92% of the pathological rEEGs were provided within the first 10 minutes of recording. Slowing background activity was diagnosed from the beginning, whereas interictal epileptiform discharges were recorded over time. Moreover, the time elapsed to demonstrate a pattern differed significantly in the clinical groups: in patients with subacute cognitive impairment, EEG abnormalities appeared within the first 10 minutes, whereas in the other groups, data could be provided over time. CONCLUSION: Patients with subacute cognitive impairment differed from those in the other groups significantly in the elapsed time required to obtain relevant information during rEEG, suggesting that 10-minute EEG recordings could be sufficient, arguing in favor of individualized rEEG. However, this conclusion does not apply to intensive care unit patients.

The structure, organisation and perioperative management of ambulatory surgery and anaesthesia in France: Methodology of the SFAR-OPERA study.

The organization of health care establishments and perioperative care are essential for ensuring the quality of care and safety of patients undergoing outpatient surgery. In order to correctly inventory these organizations and practices, in 2013-2014, the French society of anaesthesia and intensive care organized an extensive practical survey in French ambulatory surgery units entitled the "OPERA" study (Organisation periopératoire de l'anesthésie en chirurgie ambulatoire). From among all of the ambulatory surgery centres listed by the Agences régionales de santé (Regional health agencies, France), 206 public and private centres were randomly selected. A structural (typology, organization) survey and a medical-practice survey (focusing on the management of postoperative pain, nausea and vomiting as well as the prevention of venous thromboembolism) were collected and managed by a prospective audit of practices occurring on two randomly selected days. The latter was further accompanied by an additional audit specifically focussing on ten representative procedures: (1) stomatology surgery (third molar removal); (2) knee arthroscopy; (3) surgery of the abdominal wall (including inguinal hernia); (4) perianal surgery; (5) varicose vein surgery; (6) digestive laparoscopy-cholecystectomy; (7) breast surgery (tumourectomy); (8) uterine surgery; (9) hallux valgus and (10) hand surgery (excluding carpal tunnel). Over the 2 days of observation, 7382 patients were included comprising 2174 patients who underwent one of the procedures from the above list. The analysis of these data will provide an overview of the organization of health establishments, the modalities thus supported and compliance with standards.