Neuroprotective and neuroregenerative drugs after severe traumatic brain injury : A narrative review from a clinical perspective.

Traumatic brain injuries cause enormous individual and socioeconomic burdens. Survivors frequently struggle with motor handicaps as well as impaired cognition and emotion. In addition to the primary mechanical brain damage, complex secondary mechanisms are the main drivers of functional impairment. Many of these pathophysiological mechanisms are now well known: excitotoxic amino acids, breakdown of the blood-brain barrier, neuroinflammation with subsequent damage to cell organelles and membranes, cerebral edema, and apoptotic processes triggering neuronal death; however, paracrine resilience factors may counteract these processes. Specific neuroprotective and neuroregenerative intensive care therapies are few. This review highlights medical approaches aimed at mitigating secondary damage and promoting neurotrophic processes in severe traumatic brain injury. Some pharmacologic attempts that appeared very promising in experimental settings have had disappointing clinical results (progesterone, cyclosporine A, ronopterin, erythropoietin, dexanabinol). Thus, the search for drugs that can effectively limit ongoing posttraumatic neurological damage is ongoing. Some medications appear to be beneficial: N­methyl-D-aspartate receptor (NMDA) antagonists (esketamine, amantadine, Mg++) reduce excitotoxicity and statins and cerebrolysin are known to counteract neuroinflammation. By supporting the impaired mitochondrial energy supply, oxidative processes are inhibited and neuroregenerative processes, such as neurogenesis, angiogenesis and synaptogenesis are promoted by citicoline and cerebrolysin. First clinical evidence shows an improvement in cognitive and thymopsychic outcomes, underlined by own clinical experience combining different therapeutic approaches. Accordingly, adjuvant treatment with neuroprotective substances appears to be a promising option, although more randomized prospective studies are still needed.

Citicoline for the Management of Patients with Traumatic Brain Injury in the Acute Phase: A Systematic Review and Meta-Analysis.

BACKGROUND: Citicoline or CDP-choline is a neuroprotective/neurorestorative drug used in several countries for the treatment of traumatic brain injury (TBI). Since the publication of the controversial COBRIT, the use of citicoline has been questioned in this indication, so it was considered necessary to undertake a systematic review and meta-analysis to evaluate whether citicoline is effective in the treatment of patients with TBI. METHODS: A systematic search was performed on OVID-Medline, EMBASE, Google Scholar, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Ferrer databases, from inception to January 2021, to identify all published, unconfounded, comparative clinical trials of citicoline in the acute phase of head-injured patients- that is, treatment started during the first 24 h. We selected studies on complicated mild, moderate, and severe head-injured patients according to the score of the Glasgow Coma Scale (GCS). The primary efficacy measure was independence at the end of the scheduled clinical trial follow-up. RESULTS: In total, 11 clinical studies enrolling 2771 patients were identified by the end. Under the random-effects model, treatment with citicoline was associated with a significantly higher rate of independence (RR, 1.18; 95% CI = 1.05-1.33; I2, 42.6%). The dose of citicoline or the administration route had no effect on outcomes. Additionally, no significant effects on mortality were found, and no safety concerns were noticed. CONCLUSIONS: This meta-analysis indicates some beneficial effects of citicoline's increasing the number of independent patients with TBI. The most important limitation of our meta-analysis was the presumed heterogeneity of the studies included. REGISTRATION: PROSPERO CRD42021238998.

Efficacy and Safety of Methoxyflurane for Treatment of Acute Traumatic Pain by EMTs during Alpine Rescue Operations: The "PainDrop" Trial.

Background: Treatment of acute traumatic pain is a core task for mountain rescue services. Intravenous access, however, is often difficult, and the vast majority of missions are carried out without a physician at the scene. The spectrum of analgesics available for use by non-physician personnel is limited. Inhaled analgesics, such as methoxyflurane, might prove useful, but currently no data exist on their application by non-physicians in the alpine setting.Methods: This prospective observational alpine field study was conducted over a period of 15 months. Patients suffering traumatic injuries with moderate to severe pain (pain score ≥ 5) after downhill bike accidents in the Tyrol mountains (1,362 m to 2,666 m above sea level) were enrolled. Teams of four mountain rescue service members, one of them a trained EMT, treated the patients with 3 ml of methoxyflurane by inhaler. We measured efficacy as reduction in pain from baseline to 15 minutes after treatment on a numerical rating scale. Safety was assessed by change in vital signs or occurrence of side-effects. Sample-size calculations were based on the efficacy outcome and yielded a need for 20 patients at a power of 0.8.Results: From June 29, 2020 to September 30, 2021, a total of 20 patients (two females; mean age 37 years) were included. The mean initial pain score was 7.2 (SD 1.0) points. After 15 minutes, pain was significantly reduced by a mean of 2.9 (SD 1.4) points. No major adverse events or relevant changes in vital signs were observed.Conclusion: The use of methoxyflurane by EMTs during alpine rescue operations in our study proved to be safe and efficient. We observed no reduction in the efficacy of the inhaler device at moderate altitude.

Influence of positive end-expiratory pressure on arterial blood pressure in mechanically ventilated trauma patients in the field: a retrospective cohort study.

Ventilation with positive end-expiratory pressure (PEEP) may result in decreased venous return to the heart and therefore decrease cardiac output. We evaluated the influence of PEEP ventilation on arterial blood pressure in the field in 296 posttraumatic intubated patients being treated by a helicopter emergency medical service in a retrospective cohort study. Initial systolic blood pressure on the scene, upon hospital admission and their mean difference were compared between patients being ventilated with no/low PEEP (0-0.3 kPa) and moderate PEEP (0.3-1 kPa). In a subgroup analysis of initially hemodynamic unstable patients (systolic blood pressure < 80 mmHg), systolic blood pressure was compared between patients being ventilated with no/low or moderate PEEP Further, the mean difference between initial systolic blood pressure and upon hospital admission was correlated with the chosen PEEP. Systolic arterial blood pressure of patients being ventilated with no/low PEEP improved from 105 ± 36 mmHg to 112 ± 38 mmHg, and that of patients being ventilated with moderate PEEP improved from 105 ± 38 mmHg to 119 ± 27 mmHg. In initially unstable patients being ventilated with no/low PEEP systolic blood pressure improved from initially 55 ± 36 mmHg to 78 ± 30 mmHg upon hospital admission, and in those being ventilated with moderate PEEP, the systolic blood pressure improved from 43 ± 38 mmHg to 91 ± 27 mmHg. There was no significant correlation between the chosen PEEP and the mean difference of systolic blood pressure (Pearson's correlation, r = 0.07, P = 0.17). Ventilation with moderate PEEP has no adverse effect on arterial systolic blood pressure in this cohort of trauma patients requiring mechanical ventilation. Initially unstable patients being ventilated with moderate PEEP tend to be hemodynamically more stable.

A novel pharmacological treatment concept for neuroprotection in severe traumatic brain injury-Two case reports.

Severe traumatic brain injury (sTBI) is a major cause of death and disability worldwide, resulting in a significant individual and socioeconomic burden. Current treatment guidelines do not include any recommendations for neuroprotective or neuoregenerative drugs. Here, we present a combined treatment with Cerebrolysin and Citicoline in two cases. Both drugs are experimentally better than clinically proven in their own effectiveness, but there is almost no clinical data on the combination of the two. Our case study hints at a promising approach that may improve neurological outcome after sTBI. The first patient was a 29 years male motorcyclist suffered polytrauma in a high-speed accident. He had severe bilateral chest trauma and fractures in both thighs and an sTBI. In addition to surgical and standard neurocritical care according to the evidence-based guidelines, he was given neuroprotective therapy with Cerebrolysin (50 ml/day) and Citicoline (3 g/day), by continuous intravenous infusion (IV), for 21 days. The second patient was a 30 years male ski mountaineer who had suffered a fall over 300 m in open terrain. In addition to the sTBI, he had fractures in the cervical spine, ribs, pelvis, and lower extremities, as well as lung contusions and massive soft tissue trauma. After initial treatment in a local hospital, he was transferred to our department and received the same neuroprotective drugs, like all of our patients with sTBI. Considering the severity of the injuries (Injury Severity Score [ISS]: 43/50, Revised Trauma Score [RTS: 5.0304, 2.7794]) and the unfavorable outcome probability (Hukkelhoven Score) of 93.1% and 82.6%, the outcomes of both patients are surprisingly encouraging 1 year after the accident. They achieved a Glasgow Outcome Score of 6 and 5 and grades 2 and 4 on the modified Rankin Scale, respectively. Currently, both are able to take care of themselves in activities of daily life to a large extent. Neuroprotective drugs may improve the regeneration of cell membranes, improve blood brain barrier integrity, and reduce neuroinflammation leading to secondary damage to the injured brain. Our clinical experience and data suggest that the combined administration of Citicoline and Cerebrolysin may contribute to better recovery, without relevant side effects. However, it would be important to validate these results by means of a controlled, prospective study.

Anaesthetic considerations for high-risk patient kyphoplasty.

Patients with vertebral compression fractures are often indicated for balloon kyphoplasty. Many of them are elderly with severe comorbidities, which puts them at high risk for general anaesthesia. Surgery under infiltration of local anaesthetic with or without mild sedation is therefore the preferred technique used by many surgeons. However, patients reported moderate­to­severe pain during the procedure. A combination of regional anaesthesia with analgo-sedation offers an interesting alternative to general anaesthesia as well as infiltration administered by the surgeon. In this article we present, apart from general anaesthesia, various regional anaesthetic techniques suitable for high-risk patients, including neuraxial anaesthesia, paravertebral block as well as a novel "erector spinae plane block" at the level of the fractured vertebra. We explore their effectiveness and safety profile, as well as advantage of supplementation of adequate analgo-sedation (Ref. 40). Keywords: erector spinae plane block, kyphoplasty, regional anaesthesia, paravertebral block, neuraxial anaesthesia.

Usability and effectiveness of inhaled methoxyflurane for prehospital analgesia - a prospective, observational study.

BACKGROUND: Pain relief in the prehospital setting is often insufficient, as the administration of potent intravenous analgesic drugs is mostly reserved to physicians. In Australia, inhaled methoxyflurane has been in routine use by paramedics for decades, but experience in Central European countries is lacking. Thus, we aimed to assess whether user friendliness and effectiveness of inhaled methoxyflurane as sole analgesic match the specific capabilities of local ground and air-based EMS systems in Austria. METHODS: Observational study in adult trauma patients (e.g. dislocations, fracture or low back pain following minor trauma) with moderate to severe pain (numeric rating scale [NRS] ≥4). Included patients received a Penthrop® inhaler containing 3 mL of methoxyflurane (maximum use 30 min). When pain relief was considered insufficient (NRS reduction < 3 after 10 min), intravenous analgesics were administered by an emergency physician. The primary endpoint was effectiveness of methoxyflurane as sole analgesic for transport of patients. Secondary endpoints were user friendliness (EMS personell), time to pain relief, vital parameters, side effects, and satisfaction of patients. RESULTS: Median numeric pain rating was 8.0 (7.0-8.0) in 109 patients. Sufficient analgesia (reduction of NRS ≥3) was achieved by inhaled methoxyflurane alone in 67 patients (61%). The analgesic effect was progressively better with increasing age. Side effects were frequent (n = 58, 53%) but mild. User satisfaction was scored as very good when pain relief was sufficient, but fair in patients without benefit. Technical problems were observed in 16 cases (14.7%), mainly related to filling of the inhaler. In every fifth use, the fruity smell of methoxyflurane was experienced as unpleasant. No negative effects on vital signs were observed. CONCLUSION: In prehospital use, inhaled methoxyflurane as sole analgesic is effective for transport of trauma patients (62%) with moderate to severe pain. Older patients benefit especially from inhaled methoxyflurane. Side effects are mild and vital parameters unaffected. Thus, inhaled methoxyflurane could be a valuable device for non-physician EMS personnel rescue services also in the central Europe region.

[Volatile anesthetics for prehospital analgesia by paramedics-An overview]. / Volatile Anästhetika zur präklinischen Analgesie durch Rettungssanitäter ­ Eine Übersicht.

Treatment of acute pain is a central task in emergency medicine. Yet, prehospital pain relief is often insufficient or delayed since the administration of potent intravenous analgesic drugs (such as opioids) is mostly limited to physicians due to legal restrictions or training deficiencies in Germany and Austria. Frequently, prehospitally operating emergency physicians have to be demanded later for anguished patients limiting disposability of physicians for patients who are in a potentially life-threatening condition. Thus, inhaled analgesics could represent an interesting alternative.A mixture of 50% nitrous oxide and 50% oxygen (N2O, Livopan®) has been available in Germany and Austria for several years; however, prehospital use of Livopan has been merely realized and only one trial has been published. In addition, methoxyflurane (Penthrop®), a volatile anesthetic from the group of the dialkyl esters (2-dichloro-1:1-difluoroethyl-methyl-ester) was approved for the treatment of moderate to severe pain following trauma in adults in many European countries in recent years and was brought onto the market in Austria in 2018. Several in-hospital trials demonstrated high effectiveness in this setting.This article discusses the effects and prehospital areas of application of both substances in the light of the existing literature. We provide a narrative overview of the current study situation and report on a recently performed prehospital application study of methoxyflurane (Penthrop®) from Austria.The need for pressurized gas cylinders for the use of N2O represents a certain limitation in prehospital use. Furthermore, in certain injuries such as of the inner ear or a pneumothorax N2O should not be used and the risk of diffusion hypoxemia has to be addressed. Users should be particularly careful and limit the use in alcohol addicts and vegans. The advances of N2O are that it is odorless, has a fast onset of action, the usability in patients over 1 month old and has stabilizing effects on the circulation. Plenty of literature regarding prehospital as well as in-hospital use of nitrous oxide in emergency, obstetric and pediatric settings show its effectiveness as a single drug as well as in combination with other analgesics, such as paracetamol or various opioids. Its long tradition in Anglo-American countries is also based on its safety and low rate of side effects.Methoxyflurane is easier to store and handle and may be slightly more effective in severe pain after trauma; however, its approval is restricted to adults, where it works significantly better with increasing age, based on the declining minimal alveolar concentration (MAC) of all inhaled anesthetics with increasing age. Furthermore, decades of use of inhaled methoxyflurane in Australia have shown the drug is effective, safe and low in side effects and has a broad spectrum of applications. The use of methoxyflurane is limited in patients with severe hepatic or renal insufficiency and the characteristic odor has been described as unpleasant by some patients. In Europe, three large in-hospital trials showed strong pain relief in trauma patients, even comparable to opioids.Overall, based on the current evidence, the use of nitrous oxide and even more of methoxyflurane may be recommended also for prehospital use by skilled paramedics.

Implementation of Crisis-Resource-Management-based Team Training in Lower Austria.

OBJECTIVE: Sequelae of medical errors are a significant problem in acute care. Human-factor-based events are frequent but avoidable causes. Thus, non-technical skills are crucial. In 2008, crisis-resource-management (CRM)-based simulation training was established for the medical staff of the Lower Austria Regional Hospitals, one of the largest hospital operators in Europe. METHODS: Implementation and development of simulation training from 2008 until today are described, costs and performance data retrospectively analysed over a 10-year period. The applied methodology and organisational aspects of CRM training are highlighted. To complete the picture, activities triggered through CRM training throughout the hospitals with potential to further improve patient safety are shown. RESULTS: With an initial funding of €100,000 by the Landeskliniken Holding and course rates of €350 to €500, a simulation programme was established for approximately 1,900 co-workers in the acute care setting. In the past 10 years, more than 2,300 doctors and nurses took part in one of the courses, held by 14 qualified trainers. Training was held in the simulation centre as well as in hospitals. Over the time, simulation facilities have been expanded to 8 different manikins, high-fidelity ventilation and monitoring simulation. In addition, a variety of patient safety activities like implementation of critical incident reporting, OR checklists and anaesthesia briefing was accompanied by the trainer team. The total cost of the project was just under €20, 00,000. CONCLUSION: Simulation-based CRM training was successfully introduced and sustainably institutionalised at the NOE LKH group of hospitals. The demand for and acceptance of the training were both excellent. The previous costs of training were relatively low; the organisational model of an independent, non-profit registered association allowed the training activities to be implemented without reducing the availability of the instructors in their clinical roles.

Computer tomographic assessment of gastric volume in major trauma patients: impact of pre-hospital airway management on gastric air.

BACKGROUND: Gastric dilation is frequently observed in trauma patients. However, little is known about average gastric volumes comprising food, fluids and air. Although literature suggests a relevant risk of gastric insufflation when endotracheal intubation (ETI) is required in the pre-hospital setting, this assumption is still unproven. METHODS: Primary whole body computed tomographic (CT) studies of 315 major trauma patients admitted to our Level 1 Trauma Centre Salzburg during a 7-year period were retrospectively assessed. Gastric volumes were calculated employing a CT volume rendering software. Patients intubated in the pre-hospital setting by emergency physicians (PHI, N = 245) were compared with spontaneously breathing patients requiring ETI immediately after arrival in the emergency room (ERI, N = 70). RESULTS: The median (range) total gastric content and air volume was 402 (26-2401) and 94 (0-1902) mL in PHI vs. 466 (59-1915) and 120 (1-997) mL in ERI patients (p = .59 and p = .35). PHI patients were more severely injured when compared with the ERI group (injury severity score (ISS) 33 (9-75) vs. 25 (9-75); p = .004). Mortality was higher in the PHI vs. ERI group (26.8% vs. 8.6%, p = .001). When PHI and ERI patients were matched for sex, age, body mass index and ISS (N = 50 per group), total gastric content and air volume was 496 (59-1915) and 119 (0-997) mL in the PHI vs. 429 (36-1726) and 121 (4-1191) mL in the ERI group (p = .85 and p = .98). Radiologic findings indicative for aspiration were observed in 8.1% of PHI vs. 4.3% of ERI patients (p = .31). Gastric air volume in patients who showed signs of aspiration was 194 (0-1355) mL vs. 98 (1-1902) mL in those without pulmonary CT findings (p = .08). CONCLUSION: In major trauma patients, overall stomach volume deriving from food, fluids and air must be expected to be around 400-500 mL. Gastric dilation caused by air is common but not typically associated with pre-hospital airway management. The amount of air in the stomach seems to be associated with the risk of aspiration. Further studies, specifically addressing patients after difficult airway management situations are warranted.

Comparing the McGrath Mac Video Laryngoscope and Direct Laryngoscopy for Prehospital Emergency Intubation in Air Rescue Patients: A Multicenter, Randomized, Controlled Trial.

OBJECTIVES: Tracheal intubation in prehospital emergency care is challenging. The McGrath Mac Video Laryngoscope (Medtronic, Minneapolis, MN) has been proven to be a reliable alternative for in-hospital airway management. This trial compared the McGrath Mac Video Laryngoscope and direct laryngoscopy for the prehospital setting. DESIGN: Multicenter, prospective, randomized, controlled equivalence trial. SETTING: Oesterreichischer Automobil- und Touring Club (OEAMTC) Helicopter Emergency Medical Service in Austria, 18-month study period. PATIENTS: Five-hundred fourteen adult emergency patients (≥ 18 yr old). INTERVENTIONS: Helicopter Emergency Medical Service physicians followed the institutional algorithm, comprising a maximum of two tracheal intubation attempts with each device, followed by supraglottic, then surgical airway access in case of tracheal intubation failure. No restrictions were given for tracheal intubation indication. MEASUREMENTS MAIN RESULTS: The Primary outcome was the rate of successful tracheal intubation; equivalence range was ± 6.5% of success rates. Secondary outcomes were the number of attempts to successful tracheal intubation, time to glottis passage and first end-tidal CO2 measurement, degree of glottis visualization, and number of problems. The success rate for the two devices was equivalent: direct laryngoscopy 98.5% (254/258), McGrath Mac Video Laryngoscope 98.1% (251/256) (difference, 0.4%; 99% CI, -2.58 to 3.39). There was no statistically significant difference with regard to tracheal intubation times, number of attempts or difficulty. The view to the glottis was significantly better, but the number of technical problems was increased with the McGrath Mac Video Laryngoscope. After a failed first tracheal intubation attempt, immediate switching of the device was significantly more successful than after the second attempt (90.5% vs 57.1%; p = 0.0003), regardless of the method. CONCLUSIONS: Both devices are equivalently well suited for use in prehospital emergency tracheal intubation of adult patients. Switching the device following a failed first tracheal intubation attempt was more successful than a second attempt with the same device.

Postponing intubation in spontaneously breathing major trauma patients upon emergency room admission does not impair outcome.

BACKGROUND: Pre-hospital emergency anaesthesia and tracheal intubation are life-saving interventions in trauma patients. However, there is evidence suggesting that the risks associated with both procedures outweigh the benefits. Thus, we assessed whether induction of anaesthesia and tracheal intubation of trauma patients can be postponed in spontaneously breathing patients until emergency room (ER) admission without increasing mortality. METHODS: Retrospective analysis of major trauma patients either intubated on-scene by an emergency medical service (EMS) physician (pre-hospital intubation, PHI) or within the first 10 min after admission at a level 1 trauma centre (emergency room intubation, ERI). Data was extracted from the German Trauma Registry, hospital patient data management and electronic clinical information system. RESULTS: From a total of 946 major trauma cases documented between 2010 and 2017, 294 patients matched the study inclusion criteria. Mortality rate of PHI (N = 258) vs. ERI (N = 36) patients was 26.4% vs. 16.7% (p = 0.3). After exclusion of patients with severe traumatic brain injury and/or pre-hospital cardiac arrest, mortality rate of PHI (N = 100) vs. ERI patients (N = 29) was 6% vs. 17.2%, (p = 0.07). Median on-scene time was significantly (p < 0.01) longer in PHI (30 min; IQR: 21-40) vs. ERI patients (20 min; IQR: 15-28). CONCLUSIONS: There was no statistical difference in mortality rates of spontaneously breathing trauma patients intubated on-scene when compared with patients intubated immediately after hospital admission. Due to the retrospective study design and small case number, further studies evaluating the impact of airway management timing in sufficiently breathing trauma patients are warranted.

Landiolol in patients with septic shock resident in an intensive care unit (LANDI-SEP): study protocol for a randomized controlled trial.

BACKGROUND: In patients with septic shock, the presence of an elevated heart rate (HR) after fluid resuscitation marks a subgroup of patients with a particularly poor prognosis. Several studies have shown that HR control in this population is safe and can potentially improve outcomes. However, all were conducted in a single-center setting. The aim of this multicenter study is to demonstrate that administration of the highly beta1-selective and ultrashort-acting beta blocker landiolol in patients with septic shock and persistent tachycardia (HR ≥ 95 beats per minute [bpm]) is effective in reducing and maintaining HR without increasing vasopressor requirements. METHODS: A phase IV, multicenter, prospective, randomized, open-label, controlled study is being conducted. The study will enroll a total of 200 patients with septic shock as defined by The Third International Consensus Definitions for Sepsis and Septic Shock criteria and tachycardia (HR ≥ 95 bpm) despite a hemodynamic optimization period of 24-36 h. Patients are randomized (1:1) to receive either standard treatment (according to the Surviving Sepsis Campaign Guidelines 2016) and continuous landiolol infusion to reach a target HR of 80-94 bpm or standard treatment alone. The primary endpoint is HR response (HR 80-94 bpm), the maintenance thereof, and the absence of increased vasopressor requirements during the first 24 h after initiating treatment. DISCUSSION: Despite recent studies, the role of beta blockers in the treatment of patients with septic shock remains unclear. This study will investigate whether HR control using landiolol is safe, feasible, and effective, and further enhance the understanding of beta blockade in patients with septic shock. TRIAL REGISTRATION: EU Clinical Trials Register; EudraCT, 2017-002138-22 . Registered on 8 August 2017.

Landiolol for managing post-operative atrial fibrillation.

Beta-blockers are a potential option to manage peri-operative atrial fibrillation. Landiolol is a new ultra-short beta-blocker with a half-life of only 4 minutes and very high beta-1 selectivity which has been used for treatment and prevention of atrial fibrillation in pulmonary surgery and gastro-intestinal surgery. Due to its limited negative inotropic effect and high beta-1 selectivity landiolol allows for control of heart rate with minimal impact on blood pressure. Landiolol is well tolerated by the respiratory system. Additional benefits are related to the regulation of the inflammatory response and blunting of the adrenergic pathway. There is a limited number of trials with total of 61 patients undergoing lung resection or oesophagectomy who developed post-operative atrial fibrillation and were treated with landiolol. The experience with landiolol for prevention is more documented than landiolol application for treatment of post-operative atrial fibrillation. There are 9 comparative studies with a total of 450 patients administered landiolol for prevention of post-operative atrial fibrillation. The use of low dosage (5-10mcg/kg/min) is usually sufficient to rapidly control heart rate which is associated with earlier and higher rate of conversion to sinus rhythm as compared to the controls. The excellent tolerance of landiolol at lower dosage (3-5mcg/kg/min) allows to initiate prophylactic use during surgery and postoperatively. Landiolol prophylaxis is associated with reduced incidence of post-operative atrial fibrillation without triggering adverse events related to a beta-blockade.

Emergency management of patients with ST-segment elevation myocardial infarction in Eastern Austria: a descriptive quality control study.

BACKGROUND: Myocardial infarction is a time-critical condition and its outcome is determined by appropriate emergency care. Thus we assessed the efficacy of a supra-regional ST-segment elevation myocardial infarction (STEMI) network in Easternern Austria. METHODS: The Eastern Austrian STEMI network serves a population of approx. 766.000 inhabitants within a region of 4186 km2. Established in 2007, it now comprises 20 pre-hospital emergency medical service (EMS) units (10 of these physician-staffed), 4 hospitals and 3 cardiac intervention centres. Treatment guidelines were updated in 2012 and documentation within a web-based STEMI registry became mandatory. For this retrospective qualitative control study, data from February 2012-April 2015 was assessed. RESULTS: A total of 416 STEMI cases were documented, and 99% were identified by EMS within 6 (4.0-8.0) minutes after arrival. Median time loss between onset of pain and EMS call was 54 (20-135) minutes; response, pre-hospital and door-to-balloon times were 14 (10-20), 46 (37-59) and 45 (32-66) minutes, respectively. When general practitioners were involved, time between onset of pain and balloon inflation significantly increased from 180 (135-254) to 218 (155-348) minutes (p < .001). A pre-hospital time < 30 min was achieved in 25.8% of all patients during the day vs. 11.6% during the night (p < .001). Three hundred forty-five patients (83%) were subjected to primary percutaneous coronary intervention (PPCI), and 6.5% were thrombolysed by EMS. Pre-hospital complication rate was 18% (witnessed cardiac arrest 7%, threatening arrhythmias 6%, cardiogenic shock 5%). Twenty-four hours and hospital mortality rate were 1.2 and 2.8%, respectively. DISCUSSION: Optimal patient care and subsequently outcome of STEMI is strongly determined by a short patient-decision time to call EMS and by the first medical contact to balloon time (FMCBT). Supra-regional networks are key in order to increase the efficacy and efficiency of health care. The goal of 120 min FMCBT was achieved in 78% of our patients immediately managed by EMS, thus indicating room for improvement. CONCLUSION: In conclusion, results from the Eastern Austrian STEMI network shed light on the necessity of increasing patient awareness in order to minimize any time loss derived by delayed EMS calls. Involvement of family physicians resulted in prolonged FMCBT. A stronger utilization of rescue helicopters could further improve the efficacy of this supra-regional network. Nevertheless PPCI rates, time intervals and outcome rates compare well with international benchmarks.

Success rates of pre-hospital difficult airway management: a quality control study evaluating an in-hospital training program.

BACKGROUND: Competence in emergency airway management is key in order to improve patient safety and outcome. The scope of compulsory training for emergency physicians or paramedics is quite limited, especially in Austria. The purpose of this study was to review the difficult airway management performance of an emergency medical service (EMS) in a region that has implemented a more thorough training program than current regulations require, comprising 3 months of initial training and supervised emergency practice and 3 days/month of on-going in-hospital training as previously reported. METHODS: This is a subgroup analysis of pre-hospital airway interventions performed by non-anesthesiologist EMS physicians between 2006 and 2016. The dataset is part of a retrospective quality control study performed in the ground EMS system of Wiener Neustadt, Austria. Difficult airway missions recorded in the electronic database were matched with the hospital information system and analyzed. RESULTS: Nine hundred thirty-three of 23060 ground EMS patients (4%) required an airway intervention. In 48 cases, transient bag-mask-valve ventilation was sufficient, and 5 patients needed repositioning of a pre-existing tracheostomy cannula. Eight hundred thirty-six of 877 patients (95.3%) were successfully intubated within two attempts; in 3 patients, a supraglottic airway device was employed first line. Management of 41 patients with failed tracheal intubation comprised laryngeal tubes (n = 21), intubating laryngeal mask (n = 11), ongoing bag-mask-valve ventilation (n = 8), and crico-thyrotomy (n = 1). There was no cannot intubate/cannot ventilate situation. Blood gas analysis at admission revealed hypoxemia in 2 and/or hypercapnia in 11 cases. CONCLUSION: During the 11-year study period, difficult airways were encountered in 5% but sufficiently managed in all patients. Thus, the training regime presented might be a feasible and beneficial model for training of non-anesthesiologist emergency physicians as well as paramedics.

S(+)-ketamine : Current trends in emergency and intensive care medicine.

S(+)-ketamine, the pure dextrorotatory enantiomer of ketamine has been available for clinical use in analgesia and anesthesia for more than 25 years. The main effects are mediated by non-competitive inhibition of the N-methyl-D-aspartate (NMDA) receptor but S(+)-ketamine also interacts with opioid receptors, monoamine receptors, adenosine receptors and other purinergic receptors. Effects on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, metabotropic glutamate receptors (mGluR) and L­type calcium chanels have also been described. S(+)-ketamine stimulates the sympathetic nerve system, making it an ideal drug for analgosedation or induction of anesthesia in instable patients. In addition, the neuroprotective properties, bronchodilatory, antihyperalgesic or antiepileptic effects provide interesting therapeutic options. In this article we discuss the numerous effects of S(+)-ketamine under pharmacological and clinical aspects especially for typical indications in emergency medicine as well as intensive care.

Citicoline in severe traumatic brain injury: indications for improved outcome : A retrospective matched pair analysis from 14 Austrian trauma centers.

Goal-oriented management of traumatic brain injury (TBI) can save the lives and/or improve the long-term outcome of millions of affected patients worldwide. Additionally, enhancing quality of life will save enormous socio-economic costs; however, promising TBI treatment strategies with neuroprotective agents, such as citicoline (CDP-choline), lacked evidence or produced contradictory results in clinical trials. During a prehospital TBI project to optimize early TBI care within 14 Austrian trauma centers, data on 778 TBI patients were prospectively collected. As preceding evaluations suggested a beneficial outcome in TBI patients treated at the Wiener Neustadt Hospital (WNH), we aimed to investigate the potential role of citicoline administration, solely applied in WNH, in those patients. In a retrospective subgroup analysis we compared 67 patients from WNH with citicoline administration and 67 matched patients from other Austrian centers without citicoline use. Patients with Glasgow Coma Scale score <13 on site and/or Abbreviated Injury Scale of the region "head" >2 were included. Our analysis revealed significantly reduced rates of intensive care unit (ICU) mortality (5% vs. 24%, p < 0.01), in-hospital mortality (9% vs. 24%, p = 0.035) and 6­month mortality (13% vs. 28%, p = 0.031), as well as of unfavorable outcome (34% vs. 57%, p = 0.015) and observed vs. expected ratio for mortality (0.42 vs. 0.84) in the WNH (citicoline receivers) group. Despite the limitations of a retrospective subgroup analysis our findings suggest a possible correlation between early and consequent citicoline administration and beneficial outcomes. Therefore, we aim to set up an initiative for a prospective, multicenter randomized controlled trial with citicoline in sTBI (severe TBI) patients.

Analgosedation of adult patients with elevated intracranial pressure : Survey of current clinical practice in Austria.

BACKGROUND: Analgesia and sedation are key items in intensive care. Recently published S3 guidelines specifically address treatment of patients with elevated intracranial pressure. METHODS: The Austrian Society of Anesthesiology, Resuscitation and Intensive Care Medicine carried out an online survey of neurointensive care units in Austria in order to evaluate the current state of practice in the areas of analgosedation and delirium management in this high-risk patient group. RESULTS: The response rate was 88%. Induction of anesthesia in patients with elevated intracranial pressure is carried out with propofol/fentanyl/rocuronium in >80% of the intensive care units (ICU), 60% use midazolam, 33.3% use esketamine, 13.3% use barbiturates and 6.7% use etomidate. For maintenance of analgosedation up to 72 h, propofol is used by 80% of the ICUs, followed by remifentanil (46.7%), sufentanil (40%) and fentanyl (6.7%). For long-term sedation, 86.7% of ICUs use midazolam, 73.3% sufentanil and 73.3% esketamine. For sedation periods longer than 7 days, 21.4% of ICUs use propofol. Reasons for discontinuing propofol are signs of rhabdomyolysis (92.9%), green urine, elevated liver enzymes (71.4% each) and elevated triglycerides (57.1%). Muscle relaxants are only used during invasive procedures. Inducing a barbiturate coma is rated as a last resort by 53.3% of respondents. The monitoring methods used are bispectral index (BIS™, 61.5% of ICUs), somatosensory-evoked potentials (SSEP, 53.8%), processed electroencephalography (EEG, 38.5%), intraparenchymal partial pressure of oxygen (pO2, 38.5%) and microdialysis (23.1%). Sedation and analgesia are scored using the Richmond agitation and sedation score (RASS, 86.7%), sedation agitation scale (SAS, 6.7%) or numeric rating scale (NRS, 50%) and behavioral pain scale (BPS, 42.9%), visual analogue scale (VAS), critical care pain observation tool (CCPOT, each 14.3%) and verbal rating scale (VRS, 7.1%). Delirium monitoring is done using the confusion assessment method for intensive care units (CAM-ICU, 46.2%) and intensive care delirium screening checklist (ICDSC, 7.7%). Of the ICUs 46.2% do not carry out delirium monitoring. CONCLUSION: We found good general compliance with the recommendations of the current S3 guidelines. Room for improvement exists in monitoring and the use of scores to detect delirium.