Andreas Duma

Summary: Background: Knowledge about longitudinal changes in epidemiological data at mass gathering events is sparse. The goal of this study was to determine and compare the type, severity and frequency of illnesses at a large music festival over 7 consecutive years (2011–2017). Methods: Prospectively collected data from the rescue operation protocols of an Austrian music festival were retrieved and analyzed. Patient presentation rates (PPR) and transport to hospital rates (TTHR) were calculated and compared between years. Linear regression was used to investigate the association between (a) total number of visitors and number of patient presentations, and (b) environmental factors and temperature related medical emergencies. A descriptive analysis of pertinent medical logistics management was performed. Results: The median (minimum to maximum) PPR and TTHR were 12.01 (9.33 in 2016 to 20.86 in 2011) and 0.57 (0.40 in 2017 to 1.06 in 2013) per 1000 visitors, respectively. In linear regression models, no significant associations were found between the number of visitors and either the total number of patient presentations, NACA 1–2 or NACA 3–5 classified emergencies. Environmental temperature had a significant impact on heat related patient presentations (p < 0.001). Conclusion: There were significant differences and a high variance in both PPR and TTHR over the years. Contrary to our expectations, the number of visitors did not predict the number of patient presentations. Ambient temperature was associated with the number of heat related emergencies but not with the number of cold related emergencies. Prevention strategies, such as the removal of insect nests, resulted in significantly fewer insect related emergencies.

Early diagnosis of acute compartment syndrome (ACS) of the leg is essential to improve the outcome. Direct invasive measurement is currently recommended to measure intracompartmental pressure. A non-invasive and reproducible means of making the diagnosis would be a step forward. The purpose of this exploratory study was to investigate the feasibility of non-invasive ultrasound-guided angle measurement as a surrogate of increased pressure in a model of ACS. A model of ACS was generated by infusion of saline into the anterior compartment of the leg of human cadavers to incrementally increase the intracompartmental pressure from 10 to 100 mmHg. In 40 legs (20 cadavers), the angle (TFA, tibia-fascia angle) between the anterolateral cortex of the tibia and the fascia of the anterior compartment was measured at each 10 mmHg pressure increase using ultrasound in a standardized transversal plane. A multilevel linear regression model was used to estimate intracompartmental pressure from delta TFA (ΔTFA). TFA (mean [± SD]) increased from 61.0° (± 12.0°) at 10 mmHg up to 81.1° (± 11.1°) at 100 mmHg compartment pressure. Each increase ΔTFA by one degree was associated with an increase in pressure by 3.9 mmHg (95% CI, 3.8–4.0, p < 0.001). We found that intracompartmental pressure of the anterior compartment of the calf can be well estimated by ultrasound-based ΔTFA in this post mortem experiment. Our findings indicate that non-invasive TFA measurement is feasible and it is reasonable that this will hold true in real life, but the findings are too preliminary to be used in clinical practice now.

EDITOR’S PERSPECTIVE: What We Already Know about This Topic: The incidence of major adverse cardiac events after electroconvulsive therapy is not known What This Article Tells Us That Is New: Major adverse cardiac events and death after electroconvulsive therapy are infrequent and occur in about 1 of 50 patients and after about 1 of 200 to 500 electroconvulsive therapy treatments Background: Cardiac events after electroconvulsive therapy have been reported sporadically, but a systematic assessment of the risk is missing. The goal of this study was to obtain a robust estimate of the incidence of major adverse cardiac events in adult patients undergoing electroconvulsive therapy. Methods: Systematic review and meta-analysis of studies that investigated electroconvulsive therapy and reported major adverse cardiac events and/or mortality. Endpoints were incidence rates of major adverse cardiac events, including myocardial infarction, arrhythmia, pulmonary edema, pulmonary embolism, acute heart failure, and cardiac arrest. Additional endpoints were all-cause and cardiac mortality. The pooled estimated incidence rates and 95% CIs of individual major adverse cardiac events and mortality per 1,000 patients and per 1,000 electroconvulsive therapy treatments were calculated. Results: After screening of 2,641 publications and full-text assessment of 284 studies, the data of 82 studies were extracted (total n = 106,569 patients; n = 786,995 electroconvulsive therapy treatments). The most commonly reported major adverse cardiac events were acute heart failure, arrhythmia, and acute pulmonary edema with an incidence (95% CI) of 24 (12.48 to 46.13), 25.83 (14.83 to 45.00), and 4.92 (0.85 to 28.60) per 1,000 patients or 2.44 (1.27 to 4.69), 4.66 (2.15 to 10.09), and 1.50 (0.71 to 3.14) per 1,000 electroconvulsive therapy treatments. All-cause mortality was 0.42 (0.11 to 1.52) deaths per 1,000 patients and 0.06 (0.02 to 0.23) deaths per 1,000 electroconvulsive therapy treatments. Cardiac death accounted for 29% (23 of 79) of deaths. Conclusions: Major adverse cardiac events and death after electroconvulsive therapy are infrequent and occur in about 1 of 50 patients and after about 1 of 200 to 500 electroconvulsive therapy treatments.

BACKGROUND: The diagnosis of myocardial infarction (MI) after noncardiac surgery has traditionally relied on using relatively insensitive contemporary cardiac troponin (cTn) assays. We hypothesized that using a recently introduced novel high-sensitivity cTnT (hscTnT) assay would increase the detection rate of perioperative MI. METHODS: In this ancillary study of the Vitamins in Nitrous Oxide trial, readjudicated incidence rates of myocardial injury (new isolated cTn elevation) and MI were compared when diagnosed by contemporary cTnI versus hscTnT. We probed various relative (eg, >50%) or absolute (eg, +5 ng/L) hscTnT change metrics. Inclusion criteria for this ancillary study were the presence of a baseline and at least 1 postoperative hscTnT value. RESULTS: Among 605 patients, 70 patients (12%) had electrocardiogram changes consistent with myocardial ischemia; 82 patients (14%) had myocardial injury diagnosed by contemporary cTnI, 31 (5.1%) of which had an adjudicated MI. After readjudication, 67 patients (11%) were diagnosed with MI when using hscTnT, a 2-fold increase. Incidence rates of postoperative myocardial injury ranged from 12% (n = 73) to 65% (n = 393) depending on the hscTnT metric used. Incidence rates of MI using various hscTnT change metrics and the presence of ischemic electrocardiogram changes, but without event adjudication, ranged from 3.6% (n = 22) to 12% (n = 74), a >3-fold difference. New postoperative hscTnT elevation, either by absolute or relative hscTnT change metric, was associated with an up to 5-fold increase in 6-month mortality. CONCLUSIONS: The use of hscTnT compared to contemporary cTnI increases the detection rate of perioperative MI by a factor of 2. Using different absolute or relative hscTnT change metrics may lead to under- or overdiagnosis of perioperative MI.

Background: Esketamine is traditionally administered via intravenous or intramuscular routes. In this study we developed a pharmacokinetic model of inhalation of nebulized esketamine with special emphasis on pulmonary absorption and bioavailability. Methods: Three increasing doses of inhaled esketamine (dose escalation from 25 to 100 mg) were applied followed by a single intravenous dose (20 mg) in 19 healthy volunteers using a nebulizer system and arterial concentrations of esketamine and esnorketamine were obtained. A multicompartmental pharmacokinetic model was developed using population nonlinear mixed-effects analyses. Results: The pharmacokinetic model consisted of three esketamine, two esnorketamine disposition and three metabolism compartments. The inhalation data were best described by adding two absorption pathways, an immediate and a slower pathway, with rate constant 0.05 ± 0.01 min^–1 (median ± SE of the estimate). The amount of esketamine inhaled was reduced due to dose-independent and dose-dependent reduced bioavailability. The former was 70% ± 5%, and the latter was described by a sigmoid E_MAX model characterized by the plasma concentration at which absorption was impaired by 50% (406 ± 46 ng/ml). Over the concentration range tested, up to 50% of inhaled esketamine is lost due to the reduced dose-independent and dose-dependent bioavailability. Conclusions: We successfully modeled the inhalation of nebulized esketamine in healthy volunteers. Nebulized esketamine is inhaled with a substantial reduction in bioavailability. Although the reduction in dose-independent bioavailability is best explained by retention of drug and particle exhalation, the reduction in dose-dependent bioavailability is probably due to sedation-related loss of drug into the air.

Background: While electroconvulsive therapy is widely regarded as a lifesaving and safe procedure, evidence regarding its effects on myocardial cell injury is sparse. The objective of this investigation was to determine the incidence and magnitude of new cardiac troponin elevation after electroconvulsive therapy using a novel high-sensitivity cardiac troponin I assay. Methods: This was a prospective cohort study in adult patients undergoing electroconvulsive therapy in a single academic center (up to three electroconvulsive therapy treatments per patient). The primary outcome was new high-sensitivity cardiac troponin I elevation after electroconvulsive therapy, defined as an increase of high-sensitivity cardiac troponin I greater than 100% after electroconvulsive therapy compared to baseline with at least one value above the limit of quantification (10 ng/l). Twelve-lead electrocardiogram and high-sensitivity cardiac troponin I values were obtained before and 15 to 30 min after electroconvulsive therapy; in a subset of patients, an additional 2-h high-sensitivity cardiac troponin I value was obtained. Results: The final study population was 100 patients and a total of 245 electroconvulsive therapy treatment sessions. Eight patients (8 of 100; 8%) experienced new high-sensitivity cardiac troponin I elevation after electroconvulsive therapy with a cumulative incidence of 3.7% (9 of 245 treatments; one patient had two high-sensitivity cardiac troponin I elevations), two of whom had a non–ST-elevation myocardial infarction (incidence 2 of 245; 0.8%). Median high-sensitivity cardiac troponin I concentrations did not increase significantly after electroconvulsive therapy. Tachycardia and/or elevated systolic blood pressure developed after approximately two thirds of electroconvulsive therapy treatments. Conclusions: Electroconvulsive therapy appears safe from a cardiac standpoint in a large majority of patients. A small subset of patients with preexisting cardiovascular risk factors, however, may develop new cardiac troponin elevation after electroconvulsive therapy, the clinical relevance of which is unclear in the absence of signs of myocardial ischemia.

BACKGROUND: This study sought to determine whether preoperatively measured high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) improve cardiac risk prediction in patients undergoing major noncardiac surgery compared with the standard risk indices. METHODS: In this ancillary study to the Vitamins in Nitrous Oxide trial, patients were included who had preoperative hs-cTnT and NT-proBNP measured (n = 572). Study outcome was the incidence of postoperative myocardial infarction (MI) within the first 3 postoperative days. hs-cTnT was considered elevated if >14 ng/L and NT-proBNP if >300 ng/L. Additional cutoff values were investigated on the basis of receiver operating characteristic statistics. Biomarker risk prediction was compared with Lee’s Revised Cardiac Risk Index (RCRI) with the use of standard methods and net reclassification index. RESULTS: The addition of hs-cTnT (>14 ng/L) and NT-proBNP (>300 ng/L) to RCRI significantly improved the prediction of postoperative MI (event rate 30/572 [5.2%], Area under the receiver operating characteristic curve increased from 0.590 to 0.716 with a 0.66 net reclassification index [95% confidence interval 0.32–0.99], P < .001). The use of 108 ng/L as a cutoff for NT-proBNP improved sensitivity compared with 300 ng/L (0.87 vs 0.53). Sensitivity, specificity, positive, and negative predictive value for hs-cTnT were 0.70, 0.60, 0.09, and 0.97 and for NT-proBNP were 0.53, 0.68, 0.08, and 0.96. CONCLUSIONS: The addition of cardiac biomarkers hs-cTnT and NT-proBNP to RCRI improves the prediction of adverse cardiac events in the immediate postoperative period after major noncardiac surgery. The high negative predictive value of preoperative hs-cTnT and NT-proBNP suggest usefulness as a “rule-out” test to confirm low risk of postoperative MI.