The effect of inadvertent systemic hypothermia after mechanical thrombectomy in patients with large-vessel occlusion stroke.

Background and aims: Postinterventional hypothermia is a frequent complication in patients with large-vessel occlusion strokes (LVOS) after mechanical thrombectomy (MT). This inadvertent hypothermia might potentially have neuroprotective but also adverse effects on patients' outcomes. The aim of the study was to determine the rate of hypothermia in patients with LVOS receiving MT and its influence on functional outcome. Methods: We performed a monocentric, retrospective study using a prospectively derived databank, including all LVOS patients receiving MT between 2015 and 2021. Predictive values of postinterventional body temperature and body temperature categories (hyperthermia (≥38°C), normothermia (35°C-37.9°C), and hypothermia (<35°C)) on functional outcome were analyzed using multivariable Bayesian logistic regression models. Favorable outcome was defined as modified Rankin Scale (mRS) ≤3. Results: Of the 480 included LVOS patients with MT (46.0% men; mean ± SD age 73 ± 12.9 years), 5 (1.0%) were hyperthermic, 382 (79.6%) normothermic, and 93 (19.4%) hypothermic. Postinterventional hypothermia was significantly associated with unfavorable functional outcome (mRS > 3) after 90 days (OR 2.06, 95% CI 1.01-4.18, p = 0.045). For short-term functional outcome, patients with hypothermia had a higher discharge NIHSS (OR 1.38, 95% CI 1.06 to 1.79, p = 0.015) and a higher change of NIHSS from admission to discharge (OR 1.35, 95% CI 1.03 to 1.76, p = 0.029). Conclusion: Approximately a fifth of LVOS patients in this cohort were hypothermic after MT. Hypothermia was an independent predictor of unfavorable functional outcomes. Our findings warrant a prospective trial investigating active warming during MT.

What is the best way to keep the patient warm during technical rescue? Results from two prospective randomised controlled studies with healthy volunteers.

BACKGROUND: Accidental hypothermia is a manifest problem during the rescue of entrapped victims and results in different subsequent problems as coagulopathy and wound infection. Different warming methods are available for the preclinicial use. However, their effectiveness has hardly been evaluated. METHODS: In a first step a survey among German fire brigades was performed with questions about the most used warming methods. In a second step two crossover studies were conducted. In each study two different warming method were compared with forced air warming - which is the most frequently used and highly effective warming method in operation rooms (Study A: halogen floodlight vs. forced air warming; Study B: forced air warming vs. fleece blanket). In both studies healthy volunteers (Study A: 30 volunteers, Study B: 32 volunteers) were sitting 60 min in a cold store. In the first 21 min there was no subject warming. Afterwards the different warming methods were initiated. Every 3 min parameters like skin temperature, core body temperature and cold perception on a 10-point numeric rating scale were recorded. Linear mixed models were fitted for each parameter to check for differences in temperature trajectories and cold perception with regard to the different warming methods. RESULTS: One hundred fifty-one German fire brigades responded to the survey. The most frequently used warming methods were different rescue blankets (gold/silver, wool) and work light (halogen floodlights). Both studies (A and B) showed significantly (p < 0.05) higher values in mean skin temperature, mean body temperature and total body heat for the forced air warming methods compared to halogen floodlight respectively fleece blanket shortly after warming initiation. In contrast, values for the cold perception were significantly lower (less unpleasant cold perception) during the phase the forced air warming methods were used, compared to the fleece blanket or the halogen floodlight was used. CONCLUSION: Forced air warming methods used under the standardised experimental setting are an effective method to keep patients warm during technical rescue. Halogen floodlight has an insufficient effect on the patient's heat preservation. In healthy subjects, fleece blankets will stop heat loss but will not correct heat that has already been lost. TRIAL REGISTRATION: The studies were registered retrospectively on 14/02/2022 on the German Clinical Trials registry (DRKS) with the number DRKS00028079.

Effects of Anesthesia Changes During Maintenance ECT: A Longitudinal Comparison of Seizure Quality Under Anesthesia Using Propofol/Esketamine Versus Methohexital.

INTRODUCTION: The effectiveness of ECT relies on the induction of a generalized cerebral seizure. Among others, seizure quality (SQ) is potentially influenced by the anesthetic drug used. Commonly used anesthetics comprise barbiturates, etomidate, propofol, and esketamine, with different characteristics and impacts on seizure parameters. So far, no studies have compared the influence of methohexital vs. a combination of propofol/esketamine on established SQ parameters. METHODS: This retrospective longitudinal study compared eight established SQ parameters (PSI, ASEI, MSC, midictal amplitude, motor and electroencephalography (EEG) seizure duration, concordance, PHR) before and after the change from propofol/esketamine to methohexital in 34 patients under maintenance ECT. Each patient contributed four measurements, two before and two after the anesthesia change. Anesthesia dose, stimulus dose, electrode placement, and concomitant medication remained unchanged throughout the analyzed treatments. RESULTS: Under methohexital (M=88.97 mg), ASEI (p=0.039 to 0.013) and midictal amplitude (p=0.022 to<0.001) were significantly lower, whereas seizure duration (motor and EEG) was significantly longer when compared to propofol/esketamine (M=64.26 mg/51.18 mg; p=0.012 to<0.001). PSI, MSC, seizure concordance, and PHR were not affected by the anesthetic used. DISCUSSION: Although to what extent these parameters correlate with the therapeutic effectiveness remains ambiguous, a decision for or against a particular anesthetic could be considered if a specific SQ parameter needs optimization. However, no general superiority for one specific substance or combination was found in this study. In the next step, anesthetic effects on treatment response and tolerability should be focused on.

[Prehospital stroke treatment in German-speaking countries]. / Praxis der präklinischen Schlaganfallversorgung im deutschsprachigen Raum: Eine Umfrage unter den ärztlichen Leitungen Rettungsdienst in Deutschland, Österreich und der Schweiz.

Background: The prognosis of stroke patients can be improved by adherence to clinical guidelines. Objective: To analyse the current state of organisation of prehospital stroke treatment in Germany, Austria and Switzerland with a focus on guideline adherence. Materials and methods: All medical directors of emergency medical services (MDEMS) in Germany (n = 178), Austria (n = 9) and Switzerland (n = 32) were invited to complete an anonymous online survey (unipark.com, Tivian XI GmbH, Cologne, Germany) which was available for 10 weeks from April-June 2020. Participants were asked for information regarding structural organisation, clinical treatment and strategic/tactical aspects. Results: The survey was completed 69 times and 65 datasets were analysed (4 participants without MDEMS status): 73.8% (n = 48) were MDEMS from Germany, 15.4% (n = 10) from Switzerland and 10.8% from Austria (n = 7). The survey results show relevant differences in the infrastructure of and the approach to prehospital stroke treatment. Standard operating procedures for stroke treatment were in place in 93.3% (n = 61) of the EMS areas. Furthermore, 37% (n = 24) of the EMS areas differentiated between stroke with mild and severe symptoms and 15.4% (n = 10) used specific scores for the prehospital prediction of large vessel occlusion strokes (LVOS). Conclusions: Our data highlight the heterogeneity of prehospital stroke treatment in Germany, Austria and Switzerland. Consistent use of appropriate scores for LVOS prediction and a higher adherence to recent clinical guideline in general are measures that should be taken to optimise the prehospital treatment of stroke patients.

Guedel oropharyngeal airway: The validation of facial landmark-distances to estimate sizing in children - Visualisation by magnetic resonance imaging (GUEDEL-I): A prospective observational study.

OBJECTIVE: To validate the ERC-recommended facial landmark-distance for oropharyngeal airway sizing in children. METHODS: We conducted a prospective observational study in anaesthetised, spontaneously breathing children ≤12 years undergoing cranial MRI. Oropharyngeal airways were inserted following the distance from the maxillary incisors to the mandibular angle. Primary outcome was the rate of properly sized oropharyngeal airways on MRI, defined as the distal end positioned within 10 mm from the epiglottis without contacting it. Secondary outcomes were the occurrence of tongue protrusion, oropharyngeal airways clinical efficacy, and related adverse events. Furthermore, we calculated probabilities for the estimation of proper size when considering five facial landmark-distances and optimal rules based on biometric parameters. RESULTS: In 94 children with a mean (SD) age of 4.7 (±3) years, 47.9% [95%-CI 38%-57.9%] oropharyngeal airways were properly sized, while 23.4% [95%-CI 15.9%-33%] were undersized, and 28.7% [95%-CI 20.5%-38.7%] oversized. Tongue protrusion occurred in 59.1% [95%-CI 38.2%-77.2%] of undersized and 15.6% [95%-CI 7.6%-29.2%] of properly sized oropharyngeal airways. No oropharyngeal airway required replacement. Comparing probabilities for five landmark-distances, "maxillary incisors to the angle of the mandible" proved superior for proper sizing at 41.2% [95%-CI 32%-51.7%]. The best-fit formula was "22.43 + 17.54 × log(weight[kg])" with a probability of 61.7% [95%-CI 51.5%-70.9%]. CONCLUSION: Although the facial landmark-distance "maxillary incisors to the angle of the mandible" does not reliably predict oropharyngeal airway size, no clinical problems have been encountered. Since it can be considered the least inaccurate facial landmark-distance, it can serve as an approximation, but the efficacy of oropharyngeal airways should be evaluated clinically. REGISTERED CLINICAL TRIAL: German Clinical Trials Register; DRKS00025918.

Blood Culture Headspace Gas Analysis Enables Early Detection of Escherichia coli Bacteremia in an Animal Model of Sepsis.

(1) Background: Automated blood culture headspace analysis for the detection of volatile organic compounds of microbial origin (mVOC) could be a non-invasive method for bedside rapid pathogen identification. We investigated whether analyzing the gaseous headspace of blood culture (BC) bottles through gas chromatography-ion mobility spectrometry (GC-IMS) enables differentiation of infected and non-infected; (2) Methods: BC were gained out of a rabbit model, with sepsis induced by intravenous administration of E. coli (EC group; n = 6) and control group (n = 6) receiving sterile LB medium intravenously. After 10 h, a pair of blood cultures was obtained and incubated for 36 h. The headspace from aerobic and anaerobic BC was sampled every two hours using an autosampler and analyzed using a GC-IMS device. MALDI-TOF MS was performed to confirm or exclude microbial growth in BCs; (3) Results: Signal intensities (SI) of 113 mVOC peak regions were statistically analyzed. In 24 regions, the SI trends differed between the groups and were considered to be useful for differentiation. The principal component analysis showed differentiation between EC and control group after 6 h, with 62.2% of the data variance described by the principal components 1 and 2. Single peak regions, for example peak region P_15, show significant SI differences after 6 h in the anaerobic environment (p < 0.001) and after 8 h in the aerobic environment (p < 0.001); (4) Conclusions: The results are promising and warrant further evaluation in studies with an extended microbial panel and indications concerning its transferability to human samples.

Identification of volatile compounds from bacteria by spectrometric methods in medicine diagnostic and other areas: current state and perspectives.

Diagnosis of bacterial infections until today mostly relies on conventional microbiological methods. The resulting long turnaround times can lead to delayed initiation of adequate antibiotic therapy and prolonged periods of empiric antibiotic therapy (e.g., in intensive care medicine). Therewith, they contribute to the mortality of bacterial infections and the induction of multidrug resistances. The detection of species specific volatile organic compounds (VOCs) emitted by bacteria has been proposed as a possible diagnostic approach with the potential to serve as an innovative point-of-care diagnostic tool with very short turnaround times. A range of spectrometric methods are available which allow the detection and quantification of bacterial VOCs down to a range of part per trillion. This narrative review introduces the application of spectrometric analytical methods for the purpose of detecting VOCs of bacterial origin and their clinical use for diagnosing different infectious conditions over the last decade. KEY POINTS: • Detection of VOCs enables bacterial differentiation in various medical conditions. • Spectrometric methods may function as point-of-care diagnostics in near future.

Headspace analyses using multi-capillary column-ion mobility spectrometry allow rapid pathogen differentiation in hospital-acquired pneumonia relevant bacteria.

BACKGROUND: Hospital-acquired pneumonia (HAP) is a common problem in intensive care medicine and the patient outcome depends on the fast beginning of adequate antibiotic therapy. Until today pathogen identification is performed using conventional microbiological methods with turnaround times of at least 24 h for the first results. It was the aim of this study to investigate the potential of headspace analyses detecting bacterial species-specific patterns of volatile organic compounds (VOCs) for the rapid differentiation of HAP-relevant bacteria. METHODS: Eleven HAP-relevant bacteria (Acinetobacter baumanii, Acinetobacter pittii, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, Serratia marcescens) were each grown for 6 hours in Lysogeny Broth and the headspace over the grown cultures was investigated using multi-capillary column-ion mobility spectrometry (MCC-IMS) to detect differences in the VOC composition between the bacteria in the panel. Peak areas with changing signal intensities were statistically analysed, including significance testing using one-way ANOVA or Kruskal-Wallis test (p < 0.05). RESULTS: 30 VOC signals (23 in the positive ion mode and 7 in the negative ion mode of the MCC-IMS) showed statistically significant differences in at least one of the investigated bacteria. The VOC patterns of the bacteria within the HAP panel differed substantially and allowed species differentiation. CONCLUSIONS: MCC-IMS headspace analyses allow differentiation of bacteria within HAP-relevant panel after 6 h of incubation in a complex fluid growth medium. The method has the potential to be developed towards a feasible point-of-care diagnostic tool for pathogen differentiation on HAP.

GC-IMS headspace analyses allow early recognition of bacterial growth and rapid pathogen differentiation in standard blood cultures.

Outcome of patients with blood stream infections (BSI) depends on the rapid initiation of adequate antibiotic therapy, which relies on the fast and reliable identification of the underlying pathogen. Blood cultures (BC) using CO2-sensitive colorimetric indicators and subsequent microbiological culturing are the diagnostic gold standard but turnaround times range between 24 and 48 h. The detection of volatile organic compounds of microbial origin (mVOC) has been described as a feasible method for identifying microbial growth and to differentiate between several microbial species. In this study, we aimed to investigate the ability of mVOC analyses using a gas chromatograph coupled to an ion mobility spectrometer (GC-IMS) for the recognition of bacterial growth and bacterial differentiation in BCs. Therefore, samples of whole blood and diluted bacterial suspension were injected into aerobic and anaerobic BC bottles and incubated for 8 h. Headspace samples from cultures of Escherichia coli (DSM 25944), Staphylococcus aureus (DSM 13661), and Pseudomonas aeruginosa (DSM 1117) were investigated hourly and we determined at which point of time a differentiation between the bacteria was possible. We found specific mVOC signals in the headspace over growing BCs of all three bacterial species. GC-IMS headspace analyses allowed faster recognition of bacterial growth than the colorimetric indicator of the BCs. A differentiation between the three investigated species was possible after 6 h of incubation with a high reliability in the principal component analysis. We concluded that GC-IMS headspace analyses could be a helpful method for the rapid detection and identification of bacteria in BSI.

Detecting Early Markers of Ventilator-Associated Pneumonia by Analysis of Exhaled Gas.

OBJECTIVES: The detection of microbial volatile organic compounds or host response markers in the exhaled gas could give an earlier diagnosis of ventilator-associated pneumonia. Gas chromatography-ion mobility spectrometry enables noninvasive, rapid, and sensitive analysis of exhaled gas. Using a rabbit model of ventilator-associated pneumonia we determined if gas chromatography-ion mobility spectrometry is able to detect 1) ventilator-associated pneumonia specific changes and 2) bacterial species-specific changes in the exhaled gas. DESIGN: Experimental in vivo study. SETTING: University research laboratory. SUBJECTS: Female New Zealand White rabbits. INTERVENTIONS: Animals were anesthetized and mechanically ventilated. To induce changes in the composition of exhaled gas we induced ventilator-associated pneumonia via endobronchial instillation of either Escherichia coli group (n = 11) or Pseudomonas aeruginosa group (n = 11) after 2 hours of mechanical ventilation. In a control group (n = 11) we instilled sterile lysogeny broth endobronchially. MEASUREMENTS AND MAIN RESULTS: Gas chromatography-ion mobility spectrometry gas analysis, CT scans of the lungs, and blood samples were obtained at four measurement points during the 10 hours of mechanical ventilation. The volatile organic compound patterns in the exhaled gas were compared and correlated with ventilator-associated pneumonia severity. Sixty-seven peak areas showed changes in signal intensity in the serial gas analyses. The signal intensity changes in 10 peak regions differed between the groups. Five peak areas (P_648_36, indole, P_714_278, P_700_549, and P_727_557) showed statistically significant changes of signal intensity. CONCLUSIONS: This is the first in vivo study that shows the potential of gas chromatography-ion mobility spectrometry for early detection of ventilator-associated pneumonia specific volatile organic compounds and species differentiation by noninvasive analyses of exhaled gas.

The Prevalence and Clinical Relevance of ASA Nonresponse After Cardiac Surgery: A Prospective Bicentric Study.

We aimed to identify the prevalence of acetylsalicylic acid (ASA) nonresponse in patients after coronary artery bypass graft (CABG) surgery and the possible consequences for the rate of major cardiovascular events. This prospective, observational, bicentric cohort study was conducted in two German University hospitals. A total of 400 patients (200 in each study center) undergoing elective CABG surgery were enrolled after written informed consent. Platelet function was analyzed on day 3 (d3) and day 5 (d5) postoperatively following stimulation with arachidonic acid (ASPItest) and with thrombin receptor-activating peptide 6 (TRAPtest) using multiple electrode aggregometry (Multiplate). Individuals with an ASPItest ≥40 AU·min were categorized as ASA nonresponders. A 1-year follow-up recorded the combined end point of cardiovascular events, hospital admissions, or deaths related to cardiovascular disease. The prevalence of ASA nonresponse was 51.5% on d3, and it significantly increased to 71.3% on d5 ( P = .0049). The area under the aggregation curve in the TRAPtest ( P < .0001), the platelet count on d5 ( P = .009), and the cardiopulmonary bypass time ( P = .01) were identified as independent predictors of an ASA nonresponse. A 1-year follow-up recorded 54 events fulfilling criteria for the combined end point with no difference between ASA responders and nonresponders. This study indicates a high incidence of perioperative ASA nonresponse in patients following CABG. No effect on the incidence of cardiovascular events was recorded in the 1-year follow-up. Therefore, a randomized dosage adjustment trial should elucidate whether a tailored ASA treatment after CABG surgery represents a useful concept.

Effects of regional perfusion block in healthy and injured lungs.

BACKGROUND: Severe hypoperfusion can cause lung damage. We studied the effects of regional perfusion block in normal lungs and in the lungs that had been conditioned by lavage with 500 ml saline and high V T (20 ml kg-1) ventilation. METHODS: Nineteen pigs (61.2 ± 2.5 kg) were randomized to five groups: controls (n = 3), the right lower lobe block alone (n = 3), lavage and high V T (n = 4), lung lavage, and high V T plus perfusion block of the right (n = 5) or left (n = 4) lower lobe. Gas exchange, respiratory mechanics, and hemodynamics were measured hourly. After an 8-h observation period, CT scans were obtained at 0 and 15 cmH2O airway pressure. RESULTS: Perfusion block did not damage healthy lungs. In conditioned lungs, the left perfusion block caused more edema in the contralateral lung (777 ± 62 g right lung vs 484 ± 204 g left; p < 0.05) than the right perfusion block did (581 ± 103 g right lung vs 484 ± 204 g left; p n.s.). The gas/tissue ratio, however, was similar (0.5 ± 0.3 and 0.8 ± 0.5; p n.s.). The lobes with perfusion block were not affected (gas/tissue ratio right 1.6 ± 0.9; left 1.7 ± 0.5, respectively). Pulmonary artery pressure, PaO2/FiO2, dead space, and lung mechanics were more markedly affected in animals with left perfusion block, while the gas/tissue ratios were similar in the non-occluded lobes. CONCLUSIONS: The right and left perfusion blocks caused the same "intensity" of edema in conditioned lungs. The total amount of edema in the two lungs differed because of differences in lung size. If capillary permeability is altered, increased blood flow may induce or increase edema.

Total intravenous anaesthesia using propofol and sufentanil allows controlled long-term ventilation in rabbits without neuromuscular blocking agents.

The aim of this study was to evaluate a total intravenous anaesthesia (TIVA) protocol using propofol and sufentanil without neuromuscular blocking agents (NBAs) for a non-recovery lung pathology study in rabbits including 10 h of pressure-controlled ventilation. TIVA was started with 20 mg/kg/h propofol and 0.5 µg/kg/h sufentanil. The depth of anaesthesia was assessed by reflex testing and monitoring of spontaneous movements or respiratory efforts. Vital parameters were monitored to assess the effects of the TIVA protocol. The infusion rates were increased whenever reflex testing indicated inadequate depth of anaesthesia, and were reduced when vital parameters indicated unnecessarily deep levels. Median infusion rates of 35 mg/kg/h propofol and 2.0 µg/kg/h sufentanil were needed to ensure an adequate depth of anaesthesia. This protocol suppressed spontaneous movements, breathing and palpebral reflexes, but was unable to suppress corneal and pedal withdrawal reflexes. Since significant drops in arterial blood pressure (ABP) were observed and the animals were not exposed to painful procedures, positive corneal and pedal withdrawal reflexes were tolerated. In conclusion, propofol and sufentanil is a suitable combination for long-term anaesthesia in non-recovery lung pathology models in rabbits without painful procedures. ABP must be monitored carefully because of the circulatory side-effects, but it is an inappropriate surrogate marker for depth of anaesthesia. Due to the lack of neuromuscular blockade this TIVA protocol allows the adjustment of infusion rates based on reflex testing. The resulting decreased risk of unnoticed awareness is a decisive refinement in anaesthesia for similar studies including long-term mechanical ventilation in rabbits.

The pre-hospital administration of tranexamic acid to patients with multiple injuries and its effects on rotational thrombelastometry: a prospective observational study in pre-hospital emergency medicine.

BACKGROUND: Hyperfibrinolysis (HF) is a major contributor to coagulopathy and mortality in trauma patients. This study investigated (i) the rate of HF during the pre-hospital management of patients with multiple injuries and (ii) the effects of pre-hospital tranexamic acid (TxA) administration on the coagulation system. METHODS: From 27 trauma patients with pre-hospital an estimated injury severity score (ISS) ≥16 points blood was obtained at the scene and on admission to the emergency department (ED). All patients received 1 g of TxA after the first blood sample was taken. Rotational thrombelastometry (ROTEM) was performed for both blood samples, and the results were compared. HF was defined as a maximum lysis (ML) >15 % in EXTEM. RESULTS: The median (min-max) ISS was 17 points (4-50 points). Four patients (15 %) had HF diagnosed via ROTEM at the scene, and 2 patients (7.5 %) had HF diagnosed via ROTEM on admission to the ED. The median ML before TxA administration was 11 % (3-99 %) vs. 10 % after TxA administration (4-18 %; p > 0.05). TxA was administered 37 min (10-85 min) before ED arrival. The ROTEM results before and after TxA administration did not significantly differ. No adverse drug reactions were observed after TxA administration. DISCUSSION: HF can be present in severely injured patients during pre-hospital care. Antifibrinolytic therapy administered at the scene is a significant time saver. Even in milder trauma fibrinogen can be decreased to critically low levels. Early administration of TxA cannot reverse or entirely stop this decrease. CONCLUSIONS: The pre-hospital use of TxA should be considered for severely injured patients to prevent the worsening of trauma-induced coagulopathy and unnecessarily high fibrinogen consumption. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT01938768 (Registered 5 September 2013).