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BACKGROUND: There is a concern that midazolam, when used as a component of sedation for colonoscopy, may impair cognition and prolong recovery. We aimed to identify whether midazolam produced short- and longer-term effects on multiple dimensions of recovery including cognition. METHODS: A 2-center double-blinded, placebo-controlled, parallel-group, randomized, phase IV study with a 1:1 allocation ratio was conducted in adults ≥18 years of age undergoing elective outpatient colonoscopy, with sufficient English language proficiency to complete the Postoperative Quality of Recovery Scale (PostopQRS). Participants were administered either midazolam (0.04 mg·kg−1) or an equivalent volume of 0.9% saline before sedation with propofol with or without an opiate. The primary outcome was incidence of recovery in the cognitive domain of the PostopQRS on day 3 after colonoscopy, which was analyzed using a χ2 test. Secondary outcomes included recovery in other domains of the PostopQRS over time, time to eye-opening, and hospital stay, and patient and endoscopist satisfaction. All hypotheses were defined before recruitment. RESULTS: During September 2015 to June 2018, 406 patients were allocated to either midazolam (n = 201) or placebo (n = 205), with one withdrawn before allocation. There was no significant difference in recovery in the cognitive domain of the PostopQRS on day 3 after colonoscopy (midazolam 86.8% vs placebo 88.7%, odds ratio, 0.838; 95% confidence interval [CI], 0.42–1.683; P= .625). Furthermore, there was no difference in recovery over time in the cognitive domain of the PostopQRS (P = .534). Overall recovery of the PostopQRS increased over time but was not different between groups. Furthermore, there were no differences between groups for nociceptive, emotive, activities-of-daily-living domains of the PostopQRS. Patient and endoscopist satisfaction were high and not different. There were no differences in time to eye-opening (midazolam 9.4 ± 12.8 minutes vs placebo 7.3 ± 0.7 minutes; P = .055), or time to hospital discharge (midazolam 103.4 ± 1.4 minutes vs placebo 98.4 ± 37.0 minutes; P = .516). CONCLUSIONS: The addition of midazolam 0.04 mg·kg−1 as adjunct to propofol and opiate sedation for elective colonoscopy did not show evidence of any significant differences in recovery in the cognitive domain of the PostopQRS, overall quality of recovery as measured by the PostopQRS, or emergence and hospital discharge times. The use of midazolam should be determined by the anesthesiologist.

Our automated deep learning-based approach identifies consolidation/collapse in LUS images to aid in the diagnosisof late stages of COVID-19 induced pneumonia, where consolidation/collapse is one of the possible associated pathologies. A common challenge in training such models is that annotating each frame of an ultrasound video requires high labelling effort. This effort in practice becomes prohibitive for large ultrasound datasets. To understand the impact of various degrees of labelling precision, we compare labelling strategies to train fully supervised models (frame-based method, higher labelling effort) and inaccurately supervised models (video-based methods, lower labelling effort), both of which yield binary predictions for LUS videos ona frame-by-frame level. We moreover introduce a novel sampled quaternary method which randomly samples only 10% of the LUS video frames and subsequently assigns (ordinal) categorical labels to all frames in the video based on the fraction of positively annotated samples. This method outperformed the inaccurately supervised video-based method of our previous work on pleural effusions. More surprisingly, this method outperformed the supervised frame-based approach with respect to metrics such as precision-recall area under curve (PR-AUC) and F1 score that are suitable for the class imbalance scenario of our dataset despite being a form of inaccurate learning. This may be due to the combination of a significantly smaller data set size compared to ourprevious work and the higher complexity of consolidation/collapse compared to pleural effusion, two factors which contribute to label noise and overfitting; specifically, we argue that our video-based method is more robust with respect to label noise and mitigates overfitting in a manner similar to label smoothing. Using clinical expert feedback, separate criteria were developed to exclude data from the training and test sets respectively for our ten-fold cross validation results, which resulted in a PR-AUC score of 73% and an accuracy of 89%. While the efficacy of our classifier using the sampled quaternary method must be verified on a larger consolidation/collapse dataset, when considering the complexity of the pathology, our proposed classifier using the sampled quaternary video-based method is clinically comparable with trained expertsand improves over the video-based method of our previous work on pleural effusions.

Levosimendan is emerging as a novel cardioprotective inotrope. Levosimendan augments myocardial contractility by sensitising contractile myofilaments to calcium without increasing myosin adenosine triphosphatase activity or oxygen consumption. Levosimendan activates cellular adenosine triphosphate-dependent potassium channels, a mechanism which is postulated to protect cells from ischaemia in a manner similar to ischaemic preconditioning. Levosimendan may therefore protect the ischaemic myocardium during ischaemia-reperfusion as well as improve the contractile function of the heart. Adenosine triphosphate-dependent potassium channel activation by levosimendan may also be protective in other tissues, such as coronary vascular endothelium, kidney and brain. Clinical trials in patients with decompensated heart failure and myocardial ischaemia show levosimendan to improve haemodynamic performance and potentially improve survival. This paper reviews the known pharmacology of levosimendan, the clinical experience with the drug to date and the potential use of levosimendan as a cardioprotective agent during surgery.

When used as an adjunct to local anaesthetic, opioid administered via the epidural route can improve the quality of analgesia. Reports of respiratory depression associated with epidural morphine use as a sole agent in the 1980s led to an increased use of lipophilic opioids, especially fentanyl. Although fentanyl is commonly used, controversy exists about its efficacy and site of action. It is possible that low-dose morphine may be more effective than fentanyl, without increasing the risk of respiratory depression.A retrospective audit was conducted of 200 consecutive patients undergoing coronary artery bypass surgery who received high thoracic epidural analgesia.One hundred patients who received fentanyl 2 µg/ml with 0.2% ropivacaine, prior to a change in our technique, were audited, followed by 100 patients who received 20 µg/ml morphine with 0.2% ropivacaine. Outcome measures included the incidence of Visual Analogue Score (VAS) ≥4/10; infusion rate adjustments; and side-effects. Patients receiving fentanyl were more likely to experience pain ≥4/10 (P8=0.002); the infusion rate was higher (P8=0.024); required more rate adjustments (P8=0.001); a greater need for noradrenaline (P8=0.001) and antiemetic drugs (P8=0.001). There were no significant differences between the groups for sedation scores or the incidence of respiratory depression.This audit suggests morphine 20 µg/ml may be superior to fentanyl 2 µg/ml, as an adjunct to 0.2% ropivacaine. We found a reduced number of infusion interventions and less inadequate patient analgesia.

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