Sleeping with Elevated Upper Body Does Not Attenuate Acute Mountain Sickness: Pragmatic Randomized Clinical Trial

PURPOSE: Acute mountain sickness commonly occurs following ascent to high altitude and is aggravated following sleep. Cephalad fluid shifts have been implicated. We hypothesized that sleeping with the upper body elevated by 30 degrees reduces the risk of acute mountain sickness. METHODS: In a pragmatic, randomized, observer-blinded field study at 4554 meters altitude, we investigated 134 adults aged 18-70 years with a Lake Louise score between 3 and 12 points on the evening of their arrival at the altitude. The individuals were exposed to sleeping on an inflatable cushion elevating the upper body by 30 degrees or on a sham pillow in a horizontal position. The primary endpoint was the change in the Acute Mountain Sickness-Cerebral (AMS-C) score in the morning after sleeping at an altitude of 4554 meters compared with the evening before. Sleep efficiency was the secondary endpoint. RESULTS: Among 219 eligible mountaineers, 134 fulfilled the inclusion criteria and were randomized. The AMS-C score increased by 0.250 +/- 0.575 in the control group and by 0.121 +/- 0.679 in the intervention group (difference 0.105; 95% confidence interval, -0.098-0.308; P = .308). Oxygen saturation in the morning was 79% +/- 6% in the intervention group and 78% +/- 6% in the control group (P = .863). Sleep efficiency did not differ between groups (P = .115). CONCLUSIONS: Sleeping with the upper body elevated by 30 degrees does not lead to relevant reductions in acute mountain sickness symptoms or hypoxemia at high altitude. (C) 2020 Elsevier Inc. All rights reserved

Macrophage Migration Inhibitory Factor Predicts Outcome in Complex Aortic Surgery

The perioperative inflammatory response is associated with outcome after complex aortic repair. Macrophage migration inhibitory factor (MIF) shows protective effects in ischemia-reperfusion (IR), but also adverse pro-inflammatory effects in acute inflammation, potentially leading to adverse outcome, which should be investigated in this trial. This prospective study enrolled 52 patients, of whom 29 (55.7%) underwent open repair (OR) and 23 (44.3%) underwent endovascular repair (ER) between 2014 and 2015. MIF serum levels were measured until 72 h post-operatively. We used linear mixed models and ROC analysis to analyze the MIF time-course and its diagnostic ability. Compared to ER, OR induced higher MIF release perioperatively; at 12 h after ICU admission, MIF levels were similar between groups. MIF course was significantly influenced by baseline MIF level (P = 0.0016) and acute physiology and chronic health evaluation (APACHE) II score (P = 0.0005). MIF level at 24 h after ICU admission showed good diagnostic value regarding patient survival [sensitivity, 80.0% (28.4–99.5%); specificity, 51.2% (35.1–67.1%); AUC, 0.688 (0.534–0.816)] and discharge modality [sensitivity, 87.5% (47.3–99.7%); specificity, 73.7% (56.9–86.6%), AUC, 0.789 (0.644–0.896)]. Increased perioperative MIF-levels are related to an increased risk of adverse outcome in complex aortic surgery and may represent a biomarker for risk stratification in complex aortic surgery

Key summary of German national treatment guidance for hospitalized COVID-19 patients Key pharmacologic recommendations from a national German living guideline using an Evidence to Decision Framework (last updated 17.05.2021)

Purpose This executive summary of a national living guideline aims to provide rapid evidence based recommendations on the role of drug interventions in the treatment of hospitalized patients with COVID-19. Methods The guideline makes use of a systematic assessment and decision process using an evidence to decision framework (GRADE) as recommended standard WHO (2021). Recommendations are consented by an interdisciplinary panel. Evidence analysis and interpretation is supported by the CEOsys project providing extensive literature searches and living (meta-) analyses. For this executive summary, selected key recommendations on drug therapy are presented including the quality of the evidence and rationale for the level of recommendation. Results The guideline contains 11 key recommendations for COVID-19 drug therapy, eight of which are based on systematic review and/or meta-analysis, while three recommendations represent consensus expert opinion. Based on current evidence, the panel makes strong recommendations for corticosteroids (WHO scale 5-9) and prophylactic anticoagulation (all hospitalized patients with COVID-19) as standard of care. Intensified anticoagulation may be considered for patients with additional risk factors for venous thromboembolisms (VTE) and a low bleeding risk. The IL-6 antagonist tocilizumab may be added in case of high supplemental oxygen requirement and progressive disease (WHO scale 5-6). Treatment with nMABs may be considered for selected inpatients with an early SARS-CoV-2 infection that are not hospitalized for COVID-19. Convalescent plasma, azithromycin, ivermectin or vitamin D-3 should not be used in COVID-19 routine care. Conclusion For COVID-19 drug therapy, there are several options that are sufficiently supported by evidence. The living guidance will be updated as new evidence emerges

Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery – a sub-analysis of the RIPHeart-Study

Abstract Background The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. Methods We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. Results A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10− 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10− 5 from the GWAS. Conclusions We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery. Trial registration The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010

In Reply

We appreciate the interest of Lagier et al. in our article.1 The authors highlighted in their letter the work of Montaigne et al.,2 who have recently published on the circadian rhythm in relation to ischemia reperfusion injury in a single-center retrospective propensity-matched cohort study addressing this subject on 596 (matched-pairs) patients undergoing aor-tic valve replacement with or without coronary artery bypass grafting, together with a single-center randomized study in 88 patients undergoing isolated aortic valve replacement, in which the perioperative myocardial injury has been assessed with the geometric mean of perioperative cardiac troponin T release

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

Abstract 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