Effect of Xenon Anesthesia Compared to Sevoflurane and Total Intravenous Anesthesia for Coronary Artery Bypass Graft Surgery on Postoperative Cardiac Troponin Release: An International, Multicenter, Phase 3, Single-blinded, Randomized Noninferiority Trial.

BACKGROUND: Ischemic myocardial damage accompanying coronary artery bypass graft surgery remains a clinical challenge. We investigated whether xenon anesthesia could limit myocardial damage in coronary artery bypass graft surgery patients, as has been reported for animal ischemia models. METHODS: In 17 university hospitals in France, Germany, Italy, and The Netherlands, low-risk elective, on-pump coronary artery bypass graft surgery patients were randomized to receive xenon, sevoflurane, or propofol-based total intravenous anesthesia for anesthesia maintenance. The primary outcome was the cardiac troponin I concentration in the blood 24 h postsurgery. The noninferiority margin for the mean difference in cardiac troponin I release between the xenon and sevoflurane groups was less than 0.15 ng/ml. Secondary outcomes were the safety and feasibility of xenon anesthesia. RESULTS: The first patient included at each center received xenon anesthesia for practical reasons. For all other patients, anesthesia maintenance was randomized (intention-to-treat: n = 492; per-protocol/without major protocol deviation: n = 446). Median 24-h postoperative cardiac troponin I concentrations (ng/ml [interquartile range]) were 1.14 [0.76 to 2.10] with xenon, 1.30 [0.78 to 2.67] with sevoflurane, and 1.48 [0.94 to 2.78] with total intravenous anesthesia [per-protocol]). The mean difference in cardiac troponin I release between xenon and sevoflurane was -0.09 ng/ml (95% CI, -0.30 to 0.11; per-protocol: P = 0.02). Postoperative cardiac troponin I release was significantly less with xenon than with total intravenous anesthesia (intention-to-treat: P = 0.05; per-protocol: P = 0.02). Perioperative variables and postoperative outcomes were comparable across all groups, with no safety concerns. CONCLUSIONS: In postoperative cardiac troponin I release, xenon was noninferior to sevoflurane in low-risk, on-pump coronary artery bypass graft surgery patients. Only with xenon was cardiac troponin I release less than with total intravenous anesthesia. Xenon anesthesia appeared safe and feasible.

Clinical and Economic Assessment of MyDiaCare, Digital Tools Combined With Diabetes Nurse Educator Support, for Managing Diabetes in South Africa: Observational Multicenter, Retrospective Study Associated With a Budget Impact Model.

BACKGROUND: In South Africa, diabetes prevalence is expected to reach 5.4 million by 2030. In South Africa, diabetes-related complications severely impact not only patient health and quality of life but also the economy. OBJECTIVE: The Diabetes Nurse Educator (DNE) study assessed the benefit of adding the MyDiaCare program to standard of care for managing patients with type 1 and type 2 diabetes in South Africa. An economic study was also performed to estimate the budget impact of adding MyDiaCare to standard of care for patients with type 2 diabetes older than 19 years treated in the South African private health care sector. METHODS: The real-world DNE study was designed as an observational, retrospective, multicenter, single-group study. Eligible patients were older than 18 years and had at least 6 months of participation in the MyDiaCare program. The MyDiaCare program combines a patient mobile app and a health care professional platform with face-to-face visits with a DNE. The benefit of MyDiaCare was assessed by the changes in glycated hemoglobin (HbA1c) levels, the proportion of patients achieving clinical and biological targets, adherence to care plans, and satisfaction after 6 months of participating in the MyDiaCare program. A budget impact model was performed using data from the DNE study and another South African cohort of the DISCOVERY study to estimate the economic impact of MyDiaCare. RESULTS: Between November 25, 2019, and June 30, 2020, a total of 117 patients (8 with type 1 diabetes and 109 with type 2 diabetes) were enrolled in 2 centers. After 6 months of MyDiaCare, a clinically relevant decrease in mean HbA1c levels of 0.6% from 7.8% to 7.2% was observed. Furthermore, 54% (43/79) of patients reached or maintained their HbA1c targets at 6 months. Most patients achieved their targets for blood pressure (53/79, 67% for systolic and 70/79, 89% for diastolic blood pressure) and lipid parameters (49/71, 69% for low-density-lipoprotein [LDL] cholesterol, 41/71, 58% for high-density-lipoprotein [HDL] cholesterol, and 59/71, 83% for total cholesterol), but fewer patients achieved their targets for triglycerides (32/70, 46%), waist circumference (12/68, 18%), and body weight (13/76, 17%). The mean overall adherence to the MyDiaCare care plan was 93%. Most patients (87/117, 74%) were satisfied with the MyDiaCare program. The net budget impact per patient with type 2 diabetes, older than 19 years, treated in the private sector using MyDiaCare was estimated to be approximately South African Rands (ZAR) 71,023 (US $4089) during the first year of introducing MyDiaCare. CONCLUSIONS: The results of using MyDiaCare program, which combines digital tools for patients and health care professionals with DNE support, suggest that it may be a clinically effective and cost-saving solution for diabetes management in the South African private health care sector.

Inhaled nitric oxide in patients with acute respiratory distress syndrome caused by COVID-19: treatment modalities, clinical response, and outcomes.

BACKGROUND: Inhaled nitric oxide (iNO) has been widely used in patients with COVID-19-related acute respiratory distress syndrome (C-ARDS), though its physiological effects and outcome are debated in this setting. The objective of this cohort study was to describe the modalities of iNO use, clinical response, and outcomes in a large cohort of C-ARDS patients. METHODS: Multicentre, retrospective cohort study conducted in France. RESULTS: From end February to December 2020, 300 patients (22.3% female) were included, 84.5% were overweight and 69.0% had at least one comorbidity. At ICU admission, their median (IQR) age, SAPS II, and SOFA score were 66 (57-72) years, 37 (29-48), and 5 (3-8), respectively. Patients were all ventilated according to a protective ventilation strategy, and 68% were prone positioned before iNO initiation. At iNO initiation, 2%, 37%, and 61% of patients had mild, moderate, and severe ARDS, respectively. The median duration of iNO treatment was 2.8 (1.1-5.5) days with a median dosage of 10 (7-13) ppm at initiation. Responders (PaO2/FiO2 ratio improving by 20% or more) represented 45.7% of patients at 6 h from iNO initiation. The severity of ARDS was the only predictive factor associated with iNO response. Among all evaluable patients, the crude mortality was not significantly different between responders at 6 h and their counterparts. Of the 62 patients with refractory ARDS (who fulfilled extracorporeal membrane oxygenation criteria before iNO initiation), 32 (51.6%) no longer fulfilled these criteria after 6 h of iNO. The latter showed significantly lower mortality than the other half (who remained ECMO eligible), including after confounder adjustment (adjusted OR: 0.23, 95% CI 0.06, 0.89, p = 0.03). CONCLUSIONS: Our study reports the benefits of iNO in improving arterial oxygenation in C-ARDS patients. This improvement seems more relevant in the most severe cases. In patients with ECMO criteria, an iNO-driven improvement in gas exchange was associated with better survival. These results must be confirmed in well-designed prospective studies.

Combination of inhaled nitrous oxide and oral opioids induces long-lasting analgesic effects in patients with neuropathic pain: ProtoTOP study post hoc exploratory analyses.

ABSTRACT: Experimental studies have suggested that nitrous oxide-induced analgesia depends on interactions with opioids. On the basis of these results, we hypothesized that the effects of inhaled nitrous oxide/oxygen (N 2 O/O 2 ) 50%-50% equimolar mixture (EMONO) on patients with neuropathic pain would be higher in those receiving concomitant opioids. To test this hypothesis, we did exploratory post hoc analyses of our recently published ProtoTOP study to compare the effects of EMONO and placebo in patients with or without concomitant opioid treatment. A total of 92 patients of the 221 (ie, 41.6%) included in the ProtoTOP study were concomitantly treated with opioids. In contrast with our previous analyses, average pain intensity was significantly decreased in comparison with placebo one week after the last treatment administration in patients treated with opioids, but not in those treated without opioid, and this effect was maintained over the 4-week follow-up period. Neuropathic pain symptom inventory (NPSI total and subscores) was also significantly more decreased after inhalation of EMONO in comparison with placebo only in patients receiving opioids. The proportion of patients with at least 30% pain reduction and of those reporting an overall improvement with the Patient Global Impression of Change were significantly higher only in this population of patients. In conclusion, these results complement our previous analyses with the identification of a specific population of responders to EMONO inhalation in patients with neuropathic pain. As suggested by experimental studies, we hypothesized that these long-lasting analgesic effects could depend on the anti-N-methyl-D-aspartate properties of N 2 O.

Safety and efficacy of an equimolar mixture of oxygen and nitrous oxide: a randomized controlled trial in patients with peripheral neuropathic pain.

ABSTRACT: Nitrous oxide (N2O) is an odorless and colorless gas routinely used as an adjuvant of anesthesia and for short-duration analgesia in various clinical settings mostly in the form of an N2O/O2 50%-50% equimolar mixture (EMONO). Experimental studies have suggested that EMONO could also induce long-lasting analgesic effects related to the blockade of N-methyl-D-aspartate receptors. We designed the first international multicenter proof of concept randomized, placebo-controlled study to assess the efficacy and safety of a 1-hour administration of EMONO or placebo (medical air) on 3 consecutive days up to 1 month after the last administration in patients with chronic peripheral neuropathic pain. A total of 240 patients were recruited in 22 centers in France and Germany and randomly assigned to 1 study group (120 per group). Average pain intensity (primary outcome), neuropathic pain characteristics (Neuropathic Pain Symptom Inventory), Patient Global Impression of Change, anxiety, depression, and quality of life were systematically assessed before and after treatment. The changes in average pain intensity between baseline and 7 days after the last administration were not significantly different between the 2 groups. However, evoked pain intensity (predefined secondary endpoint) and Patient Global Impression of Change (exploratory endpoint) were significantly improved in the EMONO group, and these effects were maintained up to 4 weeks after the last treatment administration. Mostly transient side effects were reported during the treatment administration. These encouraging results provide a basis for further investigation of the long-term analgesic effects of EMONO in patients with neuropathic pain.