Admission S100B fails as neuro-marker but is a good predictor for intrahospital mortality in major trauma patients.

BACKGROUND: S100 B is an extensively studied neuro-trauma marker, but its specificity and subsequently interpretation in major trauma patients might be limited, since extracerebral injuries are known to increase serum levels. Thus, we evaluated the potential role of S100B in the assessment of severe traumatic brain injury (TBI) in multiple injured patients upon emergency room (ER) admission and the first days of intensive care unit (ICU) stay. METHODS: Retrospective study employing trauma registry data derived from a level 1 trauma center. Four cohorts of patients were grouped: isolated TBI (iTBI), polytrauma patients with TBI (PT + TBI), polytrauma patients without TBI (PT-TBI) and patients without polytrauma or TBI (control). S100B-serum levels were assessed immediately after admission in the emergency room and during the subsequent ICU stay. Values were correlated with injury severity score (ISS), Glasgow Coma Score (GCS) and in-hospital mortality. RESULTS: 780 predominantly male patients (76 %) with a median age of 48 (30-63) and a median ISS of 24 (17-30) were enrolled in the study. Admission S100B correlated with ISS and TBI severity defined by the GCS (both p < 0.0001) but not with head abbreviated injury score (AIS) (p = 0.38). Compared with survivors, non-survivors had significantly higher median S100B levels in the ER (6.14 µg/L vs. 2.06 µg/L; p < 0.0001) and at ICU-day 1 (0.69 µg/L vs. 0.17 µg/L; p < 0.0001). S100B in the ER predicted mortality with an area under curve (AUC) of 0.77 (95 % CI 0,70-0,83, p < 0.0001), vs. 0.86 at ICU-day 1 (95 % CI 0,80-0,91, p < 0.0001). CONCLUSION: In conclusion, S100B is a valid biomarker for prediction of mortality in major trauma patients with a higher accuracy when assessed at the first day of ICU stay vs. immediately after ER admission. Since S100B did not correlate with pathologic TBI findings in multiple injured patients, it failed as predictive neuro-marker because extracerebral injuries demonstrated a higher influence on admission levels than neurotrauma. Although S100B levels are indicative for injury severity they should be interpreted with caution in polytrauma patients.

DOAC plasma concentration upon hospital admission in a cohort of trauma patients. An observational real-life study.

PURPOSE: Due to a better safety profile, direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic events. However, little is known about DOAC plasma concentrations in trauma patients upon hospital admission. Thus, we investigated the frequency and extent of DOAC possible over- and underdosing in trauma patients upon hospital admission. METHODS: In this single-center retrospective study, DOAC plasma concentrations of adult trauma patients were analyzed with specific calibrated anti-IIa (dabigatran) and anti-Xa (apixaban, edoxaban and rivaroxaban) tests within 4 h after hospital admission. RESULTS: A total of 210 trauma patients, admitted between 2019 and 2022, were included in the analyses. Low DOAC levels < 30 ng/mL were detected in 13.3% of the patients. In 7.1% of the patients, DOAC plasma levels ranged between 300-399 ng/mL and further 7.1% exhibited plasma concentrations > 400 ng/mL. The highest incidence of high to very high DOAC plasma concentration was observed for patients on rivaroxaban and dabigatran. A moderate correlation was observed between dabigatran plasma concentration and estimated glomerular filtration rate (rho = - 0.5338, p = 0.0003). For rivaroxaban no clear association between plasma concentration and liver or renal function could be detected. Patients on statins had significantly higher DOAC concentration in comparison with those not taking statins (153 (76-274) vs 108 (51-217) ng/mL, p = 0.046). CONCLUSION: The current study revealed that patients on dabigatran and rivaroxaban were prone to higher DOAC plasma levels upon hospital admission in comparison with apixaban and edoxaban. DOAC plasma level measurement in trauma patients might be warranted due to unpredictively low or high plasma concentrations. However, the clinical impact of altered plasma levels on both, bleeding and thromboembolic events, remains to be determined by future studies.

Role of DOAC plasma concentration on perioperative blood loss and transfusion requirements in patients with hip fractures.

BACKGROUND: There is an ever-increasing number of hip fracture (HF) patients on direct oral anticoagulants (DOAC). The impact of DOAC plasma level prior to HF surgery on perioperative blood loss and transfusion requirements has not been investigated so far. MATERIALS AND METHODS: In this retrospective study of HF patients on DOACs admitted to the AUVA Trauma Center Salzburg between February 2015 and December 2021. DOAC plasma levels were analysed prior to surgery. Patients were categorized into four DOAC groups: Group A < 30 ng/mL, Group B 30-49 ng/mL, Group C 50-79 ng/mL, and Group D ≥ 80 ng/mL. Haemoglobin concentration was measured upon admission, prior to surgery, after ICU/IMC admission, and on day 1 and 2 post-surgery. Difference in the blood loss via drains, transfusion requirements and time to surgery were compared. RESULTS: A total of 155 subjects fulfilled the predefined inclusion criteria. The median age of the predominantly female patients was 86 (80-90) years. Haemoglobin concentration in Group D was lower upon admissions but did not reach statistical significance. The decrease in haemoglobin concentration over the entire observation time was comparable between groups. Blood transfusion requirements were significantly higher in Group D compared to Group A and B (p = 0.0043). Time to surgery, intra- and postoperative blood loss via drains were not different among groups. CONCLUSION: No strong association between the DOAC plasma levels and perioperative blood loss was detected. Higher transfusion rates in patients with DOAC levels ≥ 80 ng/mL were primarily related to lower admission haemoglobin levels. DOAC concentration measurement is feasible and expedites time to surgery.

[Emergency missions in Tyrol in spring 2020 : Influence of COVID-19-A retrospective observational study focusing on air rescue]. / Notärztliche Einsätze in Tirol im Frühjahr 2020 : Der Einfluss von COVID-19 ­ eine retrospektive Beobachtungsstudie mit Fokus Luftrettung.

BACKGROUND: Tyrol, a province of Austria with about 760,000 inhabitants, was one of the first regions in Europe, along with northern Italy, to be affected by the pandemic spread of the coronavirus in spring 2020. A lockdown with far-reaching restrictions in all areas of life occurred from 16 March 2020. Restrictions were imposed in the areas of gastronomy, trade and free mobility as well as in recreational sports. The ski resorts were closed and due to the strong winter tourism in Tyrol, this meant that about 340,000 people left the region. In the province of Tyrol comprehensive emergency medical care is provided by 13 ground-based emergency medical systems (NEF) in combination with air rescue (16 emergency medical helicopters, some of which are seasonal). Normally, this system provides emergency medical care for approx. 1 million people; however, in spring 2020 during the first lockdown, the number of people to be cared for was approx. 30% less. In order to protect the emergency medical teams as best as possible from infections and thus the system from failures, the Integrated Control Center Tyrol (Landesleitstelle Tirol GmbH) adapted the release order for emergency medical resources. The aim of the study is to describe the influence of the pandemic in spring 2020 on the emergency medical services in Tyrol in comparison to the three preceding years. METHODS: A retrospective survey of all emergency helicopter missions and ground-based emergency physician missions in Tyrol in the period 15 March 2020-15 May 2020, as well as in the same period of the previous years 2017-2019, was conducted. Detailed figures on medical procedures and patient-related data were collected from 6 ÖAMTC helicopter bases. In addition, all ground-based emergency physician missions from all 13 physician systems including appeal mission diagnoses were collected in the same period. RESULTS: The total number of emergency helicopter missions and ground-based emergency physician missions showed a significant decrease during the observational period (67.3% and 39.8%, respectively). In the area of ground-based emergency medical resources, there was a significant increase in respiratory and CNS diseases during the observational period. The range of emergency helicopter missions showed a significant shift from sports and leisure missions to internal medicine and neurological emergencies and the duration of missions was significantly longer. The NACA score was higher with a significant decrease in NACA 3 scores in favor of NACA 4 and 5. The circulatory status of patients during the observational period was significantly more often documented as unstable. Hypertension, impending shock and circulatory arrest occurred more frequently in the trend. Cardiac massage, oxygen administration, circulatory drugs and specific monitoring were used more frequently in 2020. Analgesics were administered less frequently. In air rescue, there was no infection of rescue workers in the field. CONCLUSION: The first pandemic wave in Tyrol and the consecutive lockdown from 16 March 2020 had a massive impact on emergency medical care in Tyrol, both quantitatively and in terms of the spectrum of operations and emergency medical interventions. The decline in patient numbers was highly relevant, especially in air rescue and can be explained in part by the discontinuation of tourism, the general exit restrictions and the restrictive disengagement order. This decline primarily affected patients in the NACA 3 category and the analgesic administration measure. The patients treated had a higher NACA score and the emergency procedures were more extensive during the observational period. The measures to protect the emergency helicopter team from infections were presumably successful as no infections occurred.

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.

Conventional and Pro-Inflammatory Pathways of Fibrinolytic Activation in Non-Traumatic Hyperfibrinolysis.

Hyperfibrinolysis (HF) frequently occurs after severe systemic hypoperfusion during major trauma and out-of-hospital cardiac arrest (OHCA). In trauma-induced HF, hypoperfusion, the activation of protein C (APC), and the release of tissue plasminogen activator (t-PA) have been identified as the driving elements of premature clot breakdown. The APC pathway also plays a role in inflammatory responses such as neutrophil extracellular trap formation (NETosis), which might contribute to lysis through cleavage of fibrin by neutrophil elastases. We investigated whether the APC and the plasminogen pathway were general drivers of HF, even in the absence of a traumatic incident. Additionally, we were interested in inflammatory activation such as the presence of NETs as potential contributing factors to HF. A total of 41 patients with OHCA were assigned to a HF and a non-HF group based on maximum lysis (ML) in thromboelastometry. Thrombin-antithrombin (TAT)-complex, soluble thrombomodulin (sTM), APC-PC inhibitor complex, t-PA, PAI-1, t-PA-PAI-1 complex, plasmin-antiplasmin (PAP), d-dimers, neutrophil elastase, histonylated DNA (hDNA) fragments, and interleukin-6 were assessed via immunoassays in the HF group vs. non-HF. APC-PC inhibitor complex is significantly higher in HF patients. Antigen levels of t-PA and PAI-1 do not differ between groups. However, t-PA activity is significantly higher and t-PA-PAI-1 complex significantly lower in the HF group. Consistent with these results, PAP and d-dimers are significantly elevated in HF. HDNA fragments and neutrophil elastase are not elevated in HF patients, but show a high level of correlation, suggesting NETosis occurs in OHCA as part of inflammatory activation and cellular decay. Just as in trauma, hypoperfusion, the activation of protein C, and the initiation of the plasminogen pathway of fibrinolysis manifest themselves in the HF of cardiac arrest. Despite features of NETosis being detectable in OHCA patients, early pro-inflammatory responses do not appear be associated with HF in cardiac arrest.

Operability of a Resonance-Based Viscoelastic Haemostatic Analyzer in the High-Vibration Environment of Air Medical Transport.

Trauma and bleeding are associated with a high mortality, and most of these deaths occur early after injury. Viscoelastic haemostatic tests have gained increasing importance in goal-directed transfusion and bleeding management. A new generation of small-sized and thus portable ultrasound-based viscoelastic analysers have been introduced in clinical practice. We questioned whether a promising candidate can be used in emergency helicopters, with a focus on the susceptibility to vibration stress. We investigated whether the high vibration environment of an emergency helicopter would affect the operability of an ultrasound-based viscoelastic analyser and would yield reproducible results in flight and on the ground. We drew blood from 27 healthy volunteers and performed simultaneous analyses on two TEG 6s. Each measurement was performed in-flight on board an Airbus H135 emergency helicopter and was repeated on the ground, close to the flight area. Results from both measurements were compared, and the recorded tracings and numeric results were analysed for artifacts. Vibratometric measurements were performed throughout the flight in order to quantify changes in the magnitude and character of vibrations in different phases of helicopter operation. The high vibration environment was associated with the presence of artifacts in all recorded tracings. There were significant differences in citrated Kaolin + Heparinase measurements in-flight and on the ground. All other assays increased in variability but did not show significant differences between the two time points. We observed numerous artifacts in viscoelastic measurements that were performed in flight. Some parameters that were obtained from the same sample showed significant differences between in-flight and on-ground measurements. Performing resonance-based viscoelastic tests in helicopter medical service is prone to artifacts. However, a 10 min delay between initiation of measurement and take-off might produce more reliable results.

Multiplate Platelet Function Testing upon Emergency Room Admission Fails to Provide Useful Information in Major Trauma Patients Not on Platelet Inhibitors.

Platelet dysfunction is a suggested driver of trauma-induced coagulopathy. However, there is still a paucity of data regarding the impact of injury pattern on platelet function and the association of platelet dysfunction on transfusion requirements and mortality. In this retrospective cohort study, patients were grouped into those with isolated severe traumatic brain injury (TBI group), those with major trauma without TBI (MT group), and a combination of both major trauma and traumatic brain injury (MT + TBI group). Platelet function was assessed by whole blood impedance aggregometry (Multiplate®, MP). Three different platelet activators were used: adenosine-diphosphate (ADP test), arachidonic acid (ASPI test), and thrombin activated peptide-6 (TRAP test). Blood transfusion requirements within 6 h and 24 h and the association of platelet dysfunction on mortality was investigated. A total of 328 predominantly male patients (75.3%) with a median age of 53 (37-68) years and a median ISS of 29 (22-38) were included. No significant difference between the TBI group, the MT group, and the MT + TBI group was detected for any of the investigated platelet function tests. Unadjusted and adjusted for platelet count, the investigated MP assays revealed no significant group differences upon ER admission and were not able to sufficiently predict massive transfusion, neither within the first 6 h nor for the first 24 h after hospital admission. No association between platelet dysfunction measured by MP upon ER admission and mortality was observed. Conclusion: Injury pattern did not specifically impact platelet function measurable by MP. Platelet dysfunction upon ER admission measurable by MP was not associated with transfusion requirements and mortality. The clinical relevance of platelet function testing by MP in trauma patients not on platelet inhibitors is questionable.

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.

Thromboelastometry fails to detect autoheparinization after major trauma and hemorrhagic shock.

BACKGROUND: Heparan sulfate is an integral component of the glycocalyx that provides an anticoagulant layer close to the endothelium. Hypoperfusion, inflammation, and sympathoadrenal activation following major trauma result in glycocalyx shedding and subsequent release of heparan sulfate into the bloodstream. The possible anticoagulant effect of this "autoheparinization" has been suggested as a potential driver of trauma-induced coagulopathy. We investigated whether thromboelastometry can be used to detect trauma-induced autoheparinization. METHODS: This study comprised three parts. First, in a retrospective clinical study of 264 major trauma patients, the clotting time (CT) in the intrinsic activation (INTEM) and intrinsic activation plus heparinase (HEPTEM) assays were evaluated upon emergency room admission. Second, in an in vivo experimental rat model of hemorrhagic-traumatic shock, the release of heparan sulfate was investigated with INTEM and HEPTEM analyses of whole blood. Third, in vitro spiking of whole blood from healthy volunteers was undertaken to assess the effects of clinically relevant quantities of heparan sulfate and heparin on CT in the INTEM and HEPTEM assays. RESULTS: In the first part, severe injury and hemorrhagic shock was not associated with any increases in INTEM CT versus HEPTEM CT. Part 2 showed that an approximate threefold increase in heparan sulfate resulting from hemorrhagic traumatic shock in rats did not prolong INTEM CT, and no significant differences between INTEM CT and HEPTEM CT were observed. Third, spiking of whole blood with heparan sulfate had no impact on INTEM CT, whereas heparin elicited significant prolongation of INTEM CT. CONCLUSION: Despite structural similarity between heparan sulfate and heparin, the amounts of heparan sulfate shed in response to trauma did not exert an anticoagulant effect that was measurable by the intrinsically activated CT in thromboelastometry. The extent to which heparan sulfate contributes to trauma-induced coagulopathy has yet to be elucidated. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

[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.

Analgesia in pediatric trauma patients in physician-staffed Austrian helicopter rescue: a 12-year registry analysis.

BACKGROUND: As pediatric patients are typically rare among helicopter emergency medical systems (HEMS), children might be at risk for oligo-analgesia due to the rescuer's lack of experience and the fear of side effects. METHODS: In this retrospective analysis, data was obtained from the ÖAMTC HEMS digital database including 14 physician staffed helicopter bases in Austria over a 12-year timeframe. Primary missions involving pediatric trauma patients (< 15 years) not mechanically ventilated on-site were included. Analgesia was assessed and compared between the age groups 0-5, 6-10 and 11-14 years. RESULTS: Of all flight missions, 8.2% were dedicated to children < 15 years. Analgetic drugs were administered in 31.4% of all primary missions (3874 of 12,324), wherefrom 2885 were injured and non-ventilated (0-5 yrs.: n = 443; 6-10 yrs.: n = 902; 11-14 yrs.: n = 1540). The majority of these patients (> 75%) suffered moderate to severe pain, justifying immediate analgesia. HEMS physicians typically chose a monotherapy with an opioid (n = 1277; 44.3%) or Esketamine (n = 1187; 41.1%) followed by the combination of both (n = 324; 11.2%). Opioid use increased (37.2% to 63.4%) and Esketamine use decreased (66.1% to 48.3%) in children < 6 vs. > 10 years. Esketamine was more often administered in extremity (57.3%) than in head (41.5%) or spine injuries (32.3%). An intravenous access was less often established in children < 6 years (74.3% vs. 90.8%; p < 0.001). Despite the use of potent analgesics, 396 missions (13.7%) were performed without technical monitoring. Particularly regarding patient data at handover in hospital, merely < 10% of all missions featured complete documentation. Therefore, sufficient evaluation of the efficacy of pain relief was not possible. Yet, by means of respiratory measures required during transport, severe side effects such as respiratory insufficiency, were barely noted. CONCLUSIONS: In the physician-staffed HEMS setting, pediatric trauma patients liberally receive opioids and Esketamine for analgesia. With regard to severe respiratory insufficiency during transport, the application of these potent analgesics seems safe.

Impact of Idarucizumab and Andexanet Alfa on DOAC Plasma Concentration and ClotPro® Clotting Time: An Ex Vivo Spiking Study in A Cohort of Trauma Patients.

Specific antagonists have been developed for the reversal of direct oral anticoagulants (DOAC). We investigated the impact of these reversal agents on the plasma concentration and visco-elastic test results of dabigatran and factor Xa inhibitors. After baseline measurements of dabigatran, the plasma concentration, and the visco-elastic ClotPro® ecarin clotting time (ECA-CT), we added the reversal agent Idarucizumab in vitro and these two analyses were repeated. Likewise, the baseline plasma concentration of apixaban, edoxaban, and rivaroxaban as well as ClotPro® Russell's viper venom test clotting time (RVV-CT) were measured and reanalyzed following Andexanet alfa spiking. We analyzed fifty blood samples from 37 patients and 10 healthy volunteers. Idarucizumab decreased the measured dabigatran plasma concentration from 323.9 ± 185.4 ng/mL to 5.9 ± 2.3 ng/mL and ECA-CT from 706.2 ± 344.6 s to 70.6 ± 20.2 s, (all, p < 0.001). Andexanet alfa decreased the apixaban concentration from 165.1 ± 65.5 ng/mL to 9.8 ± 8.1 ng/mL, edoxaban from 152.4 ± 79.0 ng/mL to 36.4 ± 19.2 ng/mL, and rivaroxaban from 153.2 ± 111.8 ng/mL to 18.1 ± 9.1 ng/mL (all p < 0.001). Andexanet alfa shortened the RVV-CT of patients with apixaban from 239.2 ± 71.7 s to 151.1 ± 30.2 s, edoxaban from 288.2 ± 65.0 s to 122.7 ± 37.1 s, and rivaroxaban from 225.9 ± 49.3 s to 103.7 ± 12.1 s (all p < 0.001). In vitro spiking of dabigatran-containing blood with Idarucizumab substantially reduced the plasma concentration and ecarin-test clotting time. Andexanet alfa lowered the concentration of the investigated factor Xa-inhibitors but did not normalize the RVV-CT. In healthy volunteers' blood, Idarucizumab spiking had no impact on ECA-CT. Andexanet alfa spiking of non-anticoagulated blood prolonged RVV-CT (p = 0.001), potentially as a consequence of a competitive antagonism with human factor Xa.

High Interleukin-6 Plasma Concentration upon Admission Is Predictive of Massive Transfusion in Severely Injured Patients.

Severe bleeding remains a prominent cause of early in-hospital mortality in major trauma patients. Thus, prompt prediction of patients at risk of massive transfusion (MT) is crucial. We investigated the ability of the inflammatory marker interleukin (IL)-6 to forecast MT in severely injured trauma patients. IL-6 plasma levels were measured upon admission. Receiver operating characteristic curves (ROCs) were calculated, and sensitivity and specificity were determined. In this retrospective study, a total of 468 predominantly male (77.8%) patients, with a median injury severity score (ISS) of 25 (17-34), were included. The Youden index for the prediction of MT within 6 and 24 h was 351 pg/mL. Patients were dichotomized into two groups: (i) low-IL-6 < 350 pg/mL and (ii) high-IL-6 ≥ 350 pg/mL. IL-6 ≥ 350 pg/mL was associated with a lower prothrombin time index, a higher activated partial thromboplastin time, and a lower fibrinogen concentration compared with IL-6 < 350 pg/mL (p <0.0001 for all). Thromboelastometric parameters were significantly different between groups (p <0.03 in all). More patients in the high-IL-6 group received MT (p <0.0001). The ROCs revealed an area under the curve of 0.76 vs. 0.82 for the high-IL-6 group for receiving MT in the first 6 and 24 h. IL-6 ≥ 350 pg/mL predicted MT within 6 and 24 h with a sensitivity of 45% and 58%, respectively, and a specificity of 89%. IL-6 ≥ 350 pg/mL appears to be a reasonable early predictor for coagulopathy and MT within the first 6 and 24 h intervals. Large-scale prospective studies are warranted to confirm these findings.

Analgesia in adult trauma patients in physician-staffed Austrian helicopter rescue: a 12-year registry analysis.

BACKGROUND: Sufficient analgesia is an obligation, but oligoanalgesia (NRS> 3) is frequently observed prehospitally. Potent analgesics may cause severe adverse events. Thus, analgesia in the helicopter emergency medical service (HEMS) setting is challenging. Adequacy, efficacy and administration safety of potent analgesics pertaining to injured patients in HEMS were analysed. METHODS: Observational study evaluating data from 14 year-round physician-staffed helicopter bases in Austria in a 12-year timeframe. RESULTS: Overall, 47,985 (34.3%) patients received analgesics, 26,059 of whom were adult patients, injured and not mechanically ventilated on site. Main drugs administered were opioids (n=20,051; 76.9%), esketamine (n=9082; 34.9%), metamizole (n=798; 3.1%) and NSAIDs (n=483; 1.9%). Monotherapy with opioids or esketamine was the most common regimen (n=21,743; 83.4%), while opioids together with esketamine (n= 3591; 13.8%) or metamizole (n=369; 1.4%) were the most common combinations. Females received opioids less frequently than did males (n=6038; 74.5% vs. n=14,013; 78.1%; p< 0.001). Pain relief was often sufficient (> 95%), but females more often had moderate to severe pain on arrival in hospital (n=34; 5.0% vs. n=59; 3.2%; p=0.043). Administration of potent analgesics was safe, as indicated by MEES, SpO2 and respiratory rates. On 10% of all missions, clinical patient assessment was deemed sufficient by HEMS physicians and monitoring was spared. CONCLUSIONS: Opioids and esketamine alone or in combination were the analgesics of choice in physician-staffed HEMS in Austria. Analgesia was often sufficient, but females more than males suffered from oligoanalgesia on hospital arrival. Administration safety was high, justifying liberal use of potent analgesics in physician-staffed HEMS.

Idarucizumab in major trauma patients: a single centre real life experience.

INTRODUCTION: Trauma care providers are facing an increasing number of elderly patients on direct oral anticoagulants prior to injury. For dabigatran etexilate (DAB), the specific antagonist idarucizumab (IDA) has been approved since 2015 as a reversal agent. However, only limited data regarding the use of IDA in trauma patients are available. METHODS: We performed a retrospective analysis of trauma patients under DAB for whom IDA administration was deemed necessary to reverse DAB's antithrombotic effect. RESULTS: A total of 15 (9 male) patients were treated with IDA during the study period. The mean age was 81 ± 10 years. Intracranial haemorrhage (n = 7) and long bone fractures (n = 5) were the most common types of injury. Three patients were diagnosed as polytrauma. In all but one patient, atrial fibrillation was the indication for DAB intake. The median dose of IDA was 2.5 g (IQR 2.5-5). IDA administration decreased DAB plasma levels from 112.4 (IQR 73.4-123.4) to 5 (IQR 4-12) ng/mL (p = 0.031), thrombin time from 114.8 ± 48.3 to 16.2 ± 0.5 s (p < 0.0001) and activated partial thromboplastin time form 45.4 ± 11.3 to 34.2 ± 7.0 s (p = 0.0025). No thromboembolic events or side effects attributed to IDA were observed. All patients survived until hospital discharge. CONCLUSIONS: In trauma patients under DAB prior to injury, IDA decreased DAB plasma levels and normalized coagulation parameters. IDA appears to be safe, and no serious side effects were observed in this small cohort of patients.

Efficacy of prehospital administration of fibrinogen concentrate in trauma patients bleeding or presumed to bleed (FIinTIC): A multicentre, double-blind, placebo-controlled, randomised pilot study.

BACKGROUND: Trauma-induced coagulopathy (TIC) substantially contributes to mortality in bleeding trauma patients. OBJECTIVE: The aim of the study was to administer fibrinogen concentrate in the prehospital setting to improve blood clot stability in trauma patients bleeding or presumed to bleed. DESIGN: A prospective, randomised, placebo-controlled, double-blinded, international clinical trial. SETTING: This emergency care trial was conducted in 12 Helicopter Emergency Medical Services (HEMS) and Emergency Doctors' vehicles (NEF or NAW) and four trauma centres in Austria, Germany and Czech Republic between 2011 and 2015. PATIENTS: A total of 53 evaluable trauma patients aged at least 18 years with major bleeding and in need of volume therapy were included, of whom 28 received fibrinogen concentrate and 25 received placebo. INTERVENTIONS: Patients were allocated to receive either fibrinogen concentrate or placebo prehospital at the scene or during transportation to the study centre. MAIN OUTCOME MEASURES: Primary outcome was the assessment of clot stability as reflected by maximum clot firmness in the FIBTEM assay (FIBTEM MCF) before and after administration of the study drug. RESULTS: Median FIBTEM MCF decreased in the placebo group between baseline (before administration of study treatment) and admission to the Emergency Department, from a median of 12.5 [IQR 10.5 to 14] mm to 11 [9.5 to 13] mm (P = 0.0226), but increased in the FC Group from 13 [11 to 15] mm to 15 [13.5 to 17] mm (P = 0.0062). The median between-group difference in the change in FIBTEM MCF was 5 [3 to 7] mm (P < 0.0001). Median fibrinogen plasma concentrations in the fibrinogen concentrate Group were kept above the recommended critical threshold of 2.0 g l-1 throughout the observation period. CONCLUSION: Early fibrinogen concentrate administration is feasible in the complex and time-sensitive environment of prehospital trauma care. It protects against early fibrinogen depletion, and promotes rapid blood clot initiation and clot stability. TRIAL REGISTRY NUMBERS: EudraCT: 2010-022923-31 and ClinicalTrials.gov: NCT01475344.

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.