Remote ischemic conditioning (RIC) protects against sustained myocardial ischemia. Because of overlapping mechanisms, this protection may be altered by glyceryl trinitrate (GTN), which is commonly used in the treatment of patients with chronic ischemic heart disease. We investigated whether long-term GTN treatment modifies the protection by RIC in the rat myocardium and human endothelium. We studied infarct size (IS) in rat hearts subjected to global ischemia-reperfusion (I/R) in vitro and endothelial function in healthy volunteers subjected to I/R of the upper arm. In addition to allocated treatment, rats were coadministered with reactive oxygen species (ROS) or nitric oxide (NO) scavengers. Rats and humans were randomized to 1) control, 2) RIC, 3) GTN, and 4) GTN + RIC. In protocols 3 and 4, rats and humans underwent long-term GTN treatment for 7 consecutive days, applied subcutaneously or 2 h daily transdermally. In rats, RIC and long-term GTN treatment reduced mean IS (18 ± 12%, P = 0.007 and 15 ± 5%, P = 0.002) compared with control (35 ± 13%). RIC and long-term GTN treatment in combination did not reduce IS (29 ± 12%, P = 0.55 vs. control). ROS and NO scavengers both attenuated IS reduction by RIC and long-term GTN treatment. In humans, I/R reduced endothelial function ( P = 0.01 vs. baseline). Separately, RIC and long-term GTN prevented the reduction in endothelial function caused by I/R; given in combination, prevention was lost. RIC and long-term GTN treatment both protect against rat myocardial and human endothelial I/R injury through ROS and NO-dependent mechanisms. However, when given in combination, RIC and long-term GTN treatment fail to confer protection. NEW & NOTEWORTHY Remote ischemic conditioning (RIC) and long-term glyceryl trinitrate (GTN) treatment protect against ischemia-reperfusion injury in both human endothelium and rat myocardium. However, combined application of RIC and long-term GTN treatment abolishes the individual protective effects of RIC and GTN treatment on ischemia-reperfusion injury, suggesting an interaction of clinical importance.

Background Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome. Methods This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan–Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality. Results A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow–Pittsburgh Cerebral Performance Categories 1–2) was observed in 94% of these patients. Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow < 100 min, pH > 6.8 and lactate < 15 mmol/L increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort. Logistic regression identified asystole (RR 1.36, 95% CI 1.18–1.57), pulseless electrical activity (RR 1.20, 95% CI 1.03–1.41), initial pH < 6.8 (RR 1.28, 95% CI 1.12–1.46) and lactate levels > 15 mmol/L (RR 1.16, 95% CI 1.16–1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52–0.76). Conclusions A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.

Background: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is commonly used to provide haemodynamic support for patients with severe cardiac failure. However, timing ECMO weaning remains challenging. We aimed to examine if an integrative weaning approach based on predefined haemodynamic, respiratory and echocardiographic criteria is associated with successful weaning.Methods: All patients weaned from ECMO between April 2017 and April 2019 at Aarhus University Hospital, Denmark, were consecutively enrolled. Predefined haemodynamic, respiratory and echocardiographic criteria were assessed before and during ECMO flow reduction. A weaning attempt was commenced in haemodynamic stable patients and patients remaining stable at minimal flow were weaned from ECMO. Comparisons were made between patients who met the criteria for weaning at first attempt and patients who did not meet these criteria. Patients completing a full weaning attempt with no further need for mechanical support within 24 h were defined as successfully weaned.Results: A total of 38 patients were included in the study, of whom 26 (68%) patients met the criteria for weaning. Among these patients, 25 (96%) could be successfully weaned. Successfully weaned patients were younger and had less need for inotropic support and ECMO duration was shorter. Fulfilling the weaning criteria was associated with successful weaning and both favourable 30-d survival and survival to discharge. Conclusion:An integrative weaning approach based on haemodynamic, respiratory and echocardiographic criteria may strengthen the clinical decision process in predicting successful weaning in patients receiving ECMO for refractory cardiac failure. Editorial CommentThis report concerns testing of a standardized protocol to wean patients of venoarterial ECMO, based on haemodynamic, respiratory and echocardiographic assessment. Among those who fulfilled the entry criteria for weaning, 96% were successfully separated from ECMO. Notable limitations are small sample size and a lack of comparison group receiving nonprotocolized weaning. The results support meticulous systematic assessment of patients on VA-ECMO to facilitate timely and successful weaning. How to cite this article: Mørk SR, Frederiksen CA, Nielsen RR, et al. A systematic approach to weaning from extracorporeal membrane oxygenation in patients with refractory cardiac failure. Acta Anaesthesiol Scand.

No abstract

Background Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly that can be congenital or acquired. Unruptured aneurysms may be asymptomatic but can present as malignant arrhythmias, acute chest pain, and even sudden cardiac death. Both ruptured and unruptured SVAs may have fatal complications, thus prompt diagnosis and surgery is critical. Case summary We report a successful surgical repair of an unruptured aneurysm of the left sinus of Valsalva presenting as acute coronary syndrome. Coronary angiography (CAG) and cardiac multislice computed tomography (CT) revealed a large unruptured aneurysm of the left sinus of Valsalva. Surgical repair was performed by resection of the aneurysm, aortic valve replacement with composite graft, and coronary artery bypass. Discussion Aneurysm of the left sinus of Valsalva is an extremely rare condition. Correct diagnosis can be done by echocardiography, CAG, or CT. Non-ruptured aneurysms should be surgically repaired if they are associated with significant symptoms or if their size enlarge rapidly.

Background In refractory out-of-hospital cardiac arrest (OHCA) with prolonged whole-body ischemia, global tissue injury proceeds even after establishment of circulation with extracorporeal cardiopulmonary resuscitation (ECPR). We aimed to investigate the role of biomarkers reflecting hypoperfusion, inflammation, and organ injury in prognostication of patients with refractory OHCA managed with ECPR. Methods This nationwide retrospective study included 226 adults with refractory OHCA managed with ECPR in Denmark (2011-2020). Biomarkers the first days after ECPR-initiation were assessed. Odds ratio of favorable neurological status (Cerebral Performance Category 1-2) at hospital discharge were estimated by logistic regression analyses. Cut-off values were calculated using the Youden’s index. Results Fifty-six patients (25%) survived to hospital discharge, 51 (91%) with a favorable neurological status. Factors independently associated with favorable neurological status were low flow time &lt;81 minutes, admission leukocytes ≥12.8 × 109/L, admission lactate &lt;13.2 mmol/L, alkaline phosphatase (ALP) &lt; 56 (day1) or &lt;55 U/L (day2), and day 1 creatine kinase MB (CK-MB) &lt; 500 ng/mL. Selected biomarkers (leukocytes, C-reactive protein, and lactate) were significantly better predictors of favorable neurological status than classic OHCA-variables (sex, age, low-flow time, witnessed arrest, shockable rhythm) alone (p = 0.001) after hospital admission. Conclusion Biomarkers of hypoperfusion (lactate), inflammation (leukocytes), and organ injury (ALP and CK-MB) were independently associated with neurological status at hospital discharge. Biomarkers of hypoperfusion and inflammation (at hospital admission) and organ injury (days 1 and 2 after ECPR) may aid in the clinical decision of when to prolong or terminate ECPR in cases of refractory OHCA.

No abstract

No abstract