Effect of perioperative benzodiazepine use on intraoperative awareness and postoperative delirium: a systematic review and meta-analysis of randomised controlled trials and observational studies.

BACKGROUND: Benzodiazepine use is associated with delirium, and guidelines recommend avoiding them in older and critically ill patients. Their perioperative use remains common because of perceived benefits. METHODS: We searched CENTRAL, MEDLINE, CINAHL, PsycInfo, and Web of Science from inception to June 2021. Pairs of reviewers identified randomised controlled trials and prospective observational studies comparing perioperative use of benzodiazepines with other agents or placebo in patients undergoing surgery. Two reviewers independently abstracted data, which we combined using a random-effects model. Our primary outcomes were delirium, intraoperative awareness, and mortality. RESULTS: We included 34 randomised controlled trials (n=4354) and nine observational studies (n=3309). Observational studies were considered separately. Perioperative benzodiazepines did not increase the risk of delirium (n=1352; risk ratio [RR] 1.43; 95% confidence interval [CI]: 0.9-2.27; I2=72%; P=0.13; very low-quality evidence). Use of benzodiazepines instead of dexmedetomidine did, however, increase the risk of delirium (five studies; n=429; RR 1.83; 95% CI: 1.24-2.72; I2=13%; P=0.002). Perioperative benzodiazepine use decreased the risk of intraoperative awareness (n=2245; RR 0.26; 95% CI: 0.12-0.58; I2=35%; P=0.001; very low-quality evidence). When considering non-events, perioperative benzodiazepine use increased the probability of not having intraoperative awareness (RR 1.07; 95% CI: 1.01-1.13; I2=98%; P=0.03; very low-quality evidence). Mortality was reported by one randomised controlled trial (n=800; RR 0.90; 95% CI: 0.20-3.1; P=0.80; very low quality). CONCLUSIONS: In this systematic review and meta-analysis, perioperative benzodiazepine use did not increase postoperative delirium and decreased intraoperative awareness. Previously observed relationships of benzodiazepine use with delirium could be explained by comparisons with dexmedetomidine. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42019128144.

Focal and pseudo/rotational activations in human atrial fibrillation defined with automated periodicity mapping.

INTRODUCTION: Defining atrial fibrillation (AF) wave propagation is challenging unless local signal features are discrete or periodic. Periodic focal or rotational activity may identify AF drivers. Our objective was to characterize AF propagation at sites with periodic activation to evaluate the prevalence and relationship between focal and rotational activation. METHODS: We included 80 patients (61 ± 10 years, persistent AF 49%) from the FaST randomized trial that compared the efficacy of adjunctive focal site ablation versus pulmonary vein isolation. Patients underwent left atrial (LA) activation mapping with a 20-pole circular catheter during spontaneous or induced AF. Five-second bipolar and unipolar electrograms in AF were analyzed. Periodic sites were identified by spectral analysis of the bipolar electrogram. Activation maps of periodic sites were constructed using an automated, validated tracking algorithm, and classified into three patterns: focal sites (FS), rotation (RO), or pseudo-rotation (pRO). RESULTS: The most common propagation pattern at periodic sites was FS for 5-s in all patients (4.9 ± 1.9 per patient). RO and pRO were observed in two and seven patients, respectively, but were all transient (3-5 cycles). Activation from a FS evolved into transient RO/pRO in five patients. No patient had autonomous RO/pRO activations. Patients with RO/pRO had greater LA surface area with periodicity (78 ± 7 vs. 63 ± 16%, p = .0002) and shorter LA periodicity CL (166 ± 10 vs. 190±28 ms, p = .0001) than the rest. CONCLUSION: Using automated, regional AF periodicity mapping, FS is more prevalent and temporally stable than RO/pRO. Most RO/pRO evolve from neighboring FS. These findings and their implications for AF maintenance require verification with global, panoramic mapping.

Focal source and trigger mapping in atrial fibrillation: Randomized controlled trial evaluating a novel adjunctive ablation strategy.

BACKGROUND: Intraoperative mapping has demonstrated focal activations during human atrial fibrillation (AF). These putative AF sources can manifest sustained periodic bipolar and unipolar QS electrograms (EGMs). We have automated the detection of these EGM features using our validated Focal Source and Trigger (FaST) computational algorithm. OBJECTIVE: The purpose of this study was to conduct a randomized controlled pilot evaluating the feasibility and efficacy of FaST mapping/ablation as an adjunct to pulmonary vein isolation (PVI) in reducing AF recurrence. METHODS: We randomized 80 patients with high-burden paroxysmal or persistent AF (age 61 ± 10 years; 75% male) to PVI alone (n = 41) or PVI+FaST mapping/ablation (n = 39). The primary endpoint was time to AF recurrence >30 seconds between 3 and 12 months after 1 procedure. RESULTS: FaST sites were identified in all but 1 patient and were localized to pulmonary vein (PV) (2.1 ± 1.1 per patient) and extra-PV regions (2.8 ± 1.4 per patient). FaST mapping and ablation times were 27 ± 9 minutes and 8.5 ± 5 minutes, respectively. Patients with AF termination during ablation had greater AF cycle length prolongation with PVI+FaST than PVI (Δ20 ± 14 ms vs Δ5 ± 17 ms; P = .046). Freedom from AF recurrence at 12 months was higher in PVI+FaST vs PVI for patients off antiarrhythmic drugs (74% vs 51%; hazard ratio 0.48; 95% confidence interval 0.21-1.08; P = .064) but did not quite reach statistical significance. Major adverse events were similar between the 2 groups. CONCLUSION: In this randomized controlled pilot, real-time FaST mapping provided an intuitive, automated approach for localizing focal AF sources. FaST ablation as an adjunct to PVI may reduce AF recurrence, which requires verification with a larger multicenter trial.

Differential association of diabetes mellitus and female sex with impaired myocardial flow reserve across the spectrum of epicardial coronary disease.

AIMS: Diabetes mellitus (DM) affects the macro- and microvasculature, leading to impairment in coronary vascular reactivity. Microvascular dysfunction is more prevalent in females compared to males, leading to increased cardiovascular risk in women. The purpose of this study was to quantify the association between diabetes and female sex on myocardial flow reserve (MFR) across the spectrum of epicardial coronary artery disease (CAD). METHODS AND RESULTS: In 222 patients with known or suspected CAD (63.7 ± 10.7 years, 66 females, 85 with diabetes) who had rubidium-82 positron emission tomography (PET) and invasive coronary angiography within 6 months, a multiple linear regression model was developed to predict MFR based on clinical risk factors and imaging results across a spectrum of regional epicardial disease. A significant interaction effect suggested that impairment of MFR is accelerated in diabetics with increasing severity of epicardial disease. Furthermore, female sex (-13%), decade of age (-6%), ischaemia on electrocardiogram (-10%), resting rate-pressure product (-3%), and rest end-diastolic volume (-0.2%) were associated with reductions in MFR independent of the combined extent and severity of epicardial disease. CONCLUSION: In the presence of significant obstructive epicardial disease, MFR decreases more rapidly in patients with DM compared to those without. Additional patient demographics and risk factors such as female sex and older age, and stress PET functional parameters should also be considered in the clinical interpretation of MFR. This has implications for the diagnosis and management of CAD patients with these and other risk factors for microvascular disease.

Acute urinary retention after Black Widow envenomation: a case report.

Latrodectism following Black Widow envenomation is rare in Canada. We present the case of a previously healthy 50 year old male who presented with an acute abdomen, hypertension, and urinary retention. After a thorough work up it was determined to be as a result of a Black Widow spider bite. Due to climate change we may see more cases of Latrodectism in the future and it should be considered as a differential diagnosis in anyone presenting with an acute abdomen after an insect bite.