Functional Status and Quality of Life 6 Months After Extracorporeal Membrane Oxygenation Therapy for COVID-19-Related Pulmonary Failure.

Extracorporeal membrane oxygenation (ECMO) is increasingly used in COVID-19-related pulmonary failure and the number of patients recovering from COVID-19 is growing. Here, we assess survival and recovery 6 months after ECMO for COVID-19. From April 2020 to September 2021, n = 60 (60.5 [51.0-65.0] years, 23.3% female) were treated with venovenous/venoarterial ECMO for COVID-19. 41.7% were weaned off ECMO, survival-to-discharge was 40.0% (n = 24). Age (63.0 [60.0-66.8] vs. 55.0 [43.8-60.0] years, p < 0.001), vasoactive support (97.2% vs . 75.0%, p = 0.013), and pre-ECMO SOFA scores (13.0 [12.0-14.8] vs. 12.0 [10.0-13.8] p = 0.036) correlated with nonsurvival. All patients aged >65 years, with histories of neoplasia, immunocompromise, chronic renal failure, or frailty died. After 6 months, 20 were alive (6-month survival 33.3%, survival conditioned on survival-to-discharge 83.3%), with follow-up in 19. 57.9% showed no relevant, 26.3% moderate, 15.8% severe deficits. Cardiopulmonary status was satisfactory (mMRC level: 84.2% ≤2). 73.7% were independent in daily life. Cognitive impairments were frequent (52.6%). 26.3% showed moderate depression, 15.8% posttraumatic stress disorder. Social and work life were considerably affected. Extracorporeal membrane oxygenation thus can serve as salvage therapy in COVID-19, but advanced age, immunocompromise, histories of neoplasia, and frailty must be considered as relative contraindications. Age, vasoactive support, and SOFA scores assist discriminating in daily practice. Deficits after 6 months are substantial, and efforts need to focus on long-term recovery.

Treatment of Refractory Cardiac Arrest by Controlled Reperfusion of the Whole Body: A Multicenter, Prospective Observational Study.

Background: Survival following cardiac arrest (CA) remains poor after conventional cardiopulmonary resuscitation (CCPR) (6-26%), and the outcomes after extracorporeal cardiopulmonary resuscitation (ECPR) are often inconsistent. Poor survival is a consequence of CA, low-flow states during CCPR, multi-organ injury, insufficient monitoring, and delayed treatment of the causative condition. We developed a new strategy to address these issues. Methods: This all-comers, multicenter, prospective observational study (69 patients with in- and out-of-hospital CA (IHCA and OHCA) after prolonged refractory CCPR) focused on extracorporeal cardiopulmonary support, comprehensive monitoring, multi-organ repair, and the potential for out-of-hospital cannulation and treatment. Result: The overall survival rate at hospital discharge was 42.0%, and a favorable neurological outcome (CPC 1+2) at 90 days was achieved for 79.3% of survivors (CPC 1+2 survival 33%). IHCA survival was very favorable (51.7%), as was CPC 1+2 survival at 90 days (41%). Survival of OHCA patients was 35% and CPC 1+2 survival at 90 days was 28%. The subgroup of OHCA patients with pre-hospital cannulation showed a superior survival rate of 57.1%. Conclusions: This new strategy focusing on repairing damage to multiple organs appears to improve outcomes after CA, and these findings should provide a sound basis for further research in this area.

Ground truth labels challenge the validity of sepsis consensus definitions in critical illness.

BACKGROUND: Sepsis is the leading cause of death in the intensive care unit (ICU). Expediting its diagnosis, largely determined by clinical assessment, improves survival. Predictive and explanatory modelling of sepsis in the critically ill commonly bases both outcome definition and predictions on clinical criteria for consensus definitions of sepsis, leading to circularity. As a remedy, we collected ground truth labels for sepsis. METHODS: In the Ground Truth for Sepsis Questionnaire (GTSQ), senior attending physicians in the ICU documented daily their opinion on each patient's condition regarding sepsis as a five-category working diagnosis and nine related items. Working diagnosis groups were described and compared and their SOFA-scores analyzed with a generalized linear mixed model. Agreement and discriminatory performance measures for clinical criteria of sepsis and GTSQ labels as reference class were derived. RESULTS: We analyzed 7291 questionnaires and 761 complete encounters from the first survey year. Editing rates for all items were > 90%, and responses were consistent with current understanding of critical illness pathophysiology, including sepsis pathogenesis. Interrater agreement for presence and absence of sepsis was almost perfect but only slight for suspected infection. ICU mortality was 19.5% in encounters with SIRS as the "worst" working diagnosis compared to 5.9% with sepsis and 5.9% with severe sepsis without differences in admission and maximum SOFA. Compared to sepsis, proportions of GTSQs with SIRS plus acute organ dysfunction were equal and macrocirculatory abnormalities higher (p < 0.0001). SIRS proportionally ranked above sepsis in daily assessment of illness severity (p < 0.0001). Separate analyses of neurosurgical referrals revealed similar differences. Discriminatory performance of Sepsis-1/2 and Sepsis-3 compared to GTSQ labels was similar with sensitivities around 70% and specificities 92%. Essentially no difference between the prevalence of SIRS and SOFA ≥ 2 yielded sensitivities and specificities for detecting sepsis onset close to 55% and 83%, respectively. CONCLUSIONS: GTSQ labels are a valid measure of sepsis in the ICU. They reveal suspicion of infection as an unclear clinical concept and refute an illness severity hierarchy in the SIRS-sepsis-severe sepsis spectrum. Ground truth challenges the accuracy of Sepsis-1/2 and Sepsis-3 in detecting sepsis onset. It is an indispensable intermediate step towards advancing diagnosis and therapy in the ICU and, potentially, other health care settings.

Results of the CAPSID randomized trial for high-dose convalescent plasma in patients with severe COVID-19.

BACKGROUNDCOVID-19 convalescent plasma (CCP) has been considered a treatment option for COVID-19. This trial assessed the efficacy of a neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment.METHODSPatients (n = 105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. The primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21.ResultsThe primary outcome occurred in 43.4% of patients in the CCP group and 32.7% in the control group (P = 0.32). The median time to clinical improvement was 26 days in the CCP group and 66 days in the control group (P = 0.27). The median time to discharge from the hospital was 31 days in the CCP group and 51 days in the control group (P = 0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies, the primary outcome occurred in 56.0% of the patients (vs. 32.1%), with significantly shorter intervals to clinical improvement (20 vs. 66 days, P < 0.05) and to hospital discharge (21 vs. 51 days, P = 0.03) and better survival (day-60 probability of survival 91.6% vs. 68.1%, P = 0.02) in comparison with the control group.ConclusionCCP added to standard treatment was not associated with a significant improvement in the primary and secondary outcomes. A predefined subgroup analysis showed a significant benefit of CCP among patients who received a larger amount of neutralizing antibodies.Trial registrationClinicalTrials.gov NCT04433910.FundingBundesministerium für Gesundheit (German Federal Ministry of Health): ZMVI1-2520COR802.

Maintaining oxygen delivery is crucial to prevent intestinal ischemia in critical ill patients.

BACKGROUND: Intestinal ischemia is a common complication with obscure pathophysiology in critically ill patients. Since insufficient delivery of oxygen is discussed, we investigated the influence of oxygen delivery, hemoglobin, arterial oxygen saturation, cardiac index and the systemic vascular resistance index on the development of intestinal ischemia. Furthermore, we evaluated the predictive power of elevated lactate levels for the diagnosis of intestinal ischemia. METHODS: In a retrospective case-control study data (mean oxygen delivery, minimum oxygen delivery, systemic vascular resistance index) of critical ill patients from 02/2009-07/2017 were analyzed using a proportional hazard model. General model fit and linearity were tested by likelihood ratio tests. The components of oxygen delivery (hemoglobin, arterial oxygen saturation and cardiac index) were individually tested in models. RESULTS: 59 out of 874 patients developed intestinal ischemia. A mean oxygen delivery less than 250ml/min/m2 (LRT vs. null model: p = 0.018; LRT for non-linearity: p = 0.012) as well as a minimum oxygen delivery less than 400ml/min/m2 (LRT vs null model: p = 0.016; LRT for linearity: p = 0.019) were associated with increased risk of the development of intestinal ischemia. We found no significant influence of hemoglobin, arterial oxygen saturation, cardiac index or systemic vascular resistance index. Receiver operating characteristics analysis for elevated lactate levels, pH, CO2 and central venous saturation was poor with an area under the receiver operating characteristic of 0.5324, 0.52, 0.6017 and 0.6786. CONCLUSION: There was a significant correlation for mean and minimum oxygen delivery with the incidence of intestinal ischemia for values below 250ml/min/m2 respectively 400ml/min/m2. Neither hemoglobin, arterial oxygen saturation, cardiac index, systemic vascular resistance index nor elevated lactate levels could be identified as individual risk factors.

Lung Protection vs. Infection Resolution: Interleukin 10 Suspected of Double-Dealing in COVID-19.

The pathological processes by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that make the virus a major threat to global health are insufficiently understood. Inefficient viral clearance at any stage is a hallmark of coronavirus disease 2019 (COVID-19). Disease severity is associated with increases in peripheral blood cytokines among which interleukin 10 (IL-10) increases particularly early and independent of patient age, which is not seen in active SARS-CoV infection. Here, we consider the known multi-faceted immune regulatory role of IL-10, both in protecting the lung from injury and in defense against infections, as well as its potential cellular source. While the absence of an IL-10 response in SARS is thought to contribute to early deterioration, we suspect IL-10 to protect the lung from early immune-mediated damage and to interfere with viral clearance in COVID-19. This may further both viral spread and poor outcome in many high-risk patients. Identifying the features of the viral genotype, which specifically underlie the different IL-10 dynamics as an etiological endotype and the different viral load kinetics and outcomes as clinical phenotype, may unveil a new immune evasive strategy of SARS-CoV-2.

Differential Network Testing Reveals Diverging Dynamics of Organ System Interactions for Survivors and Non-survivors in Intensive Care Medicine.

Statistical network analyses have become popular in many scientific disciplines, where an important task is to test for differences between two networks. We describe an overall framework for differential network testing procedures that vary regarding (1) the network estimation method, typically based on specific concepts of association, and (2) the network characteristic employed to measure the difference. Using permutation-based tests, our approach is general and applicable to various overall, node-specific or edge-specific network difference characteristics. The methods are implemented in our freely available R software package DNT, along with an R Shiny application. In a study in intensive care medicine, we compare networks based on parameters representing main organ systems to evaluate the prognosis of critically ill patients in the intensive care unit (ICU), using data from the surgical ICU of the University Medical Centre Mannheim, Germany. We specifically consider both cross-sectional comparisons between a non-survivor and a survivor group and longitudinal comparisons at two clinically relevant time points during the ICU stay: first, at admission, and second, at an event stage prior to death in non-survivors or a matching time point in survivors. The non-survivor and the survivor networks do not significantly differ at the admission stage. However, the organ system interactions of the survivors then stabilize at the event stage, revealing significantly more network edges, whereas those of the non-survivors do not. In particular, the liver appears to play a central role for the observed increased connectivity in the survivor network at the event stage.

A quantitative CT parameter for the assessment of pulmonary oedema in patients with acute respiratory distress syndrome.

OBJECTIVES: The aim of this study was to establish quantitative CT (qCT) parameters for pathophysiological understanding and clinical use in patients with acute respiratory distress syndrome (ARDS). The most promising parameter is introduced. MATERIALS AND METHODS: 28 intubated patients with ARDS obtained a conventional CT scan in end-expiratory breathhold within the first 48 hours after admission to intensive care unit (ICU). Following manual segmentation, 137 volume- and lung weight-associated qCT parameters were correlated with 71 clinical parameters such as blood gases, applied ventilation pressures, pulse contour cardiac output measurements and established status and prognosis scores (SOFA, SAPS II). RESULTS: Of all examined qCT parameters, excess lung weight (ELW), i.e. the difference between a patient's current lung weight and the virtual lung weight of a healthy person at the same height, displayed the most significant results. ELW correlated significantly with the amount of inflated lung tissue [%] (p<0.0001; r = -0.66) and was closely associated with the amount of extravascular lung water (EVLW) (p<0.0001; r = 0.72). More substantially than the oxygenation index (PaO2/FiO2) or any other clinical parameter it correlated with the patients' mean SOFA- (p<0.0001, r = 0.69) and SAPS II-Score (p = 0.0005, r = 0.62). Patients who did not survive intensive care treatment displayed higher values of ELW in the initial CT scans. CONCLUSIONS: ELW could serve as a non-invasive method to quantify the amount of pulmonary oedema. It might serve as an early radiological marker of severity in patients with ARDS.

Influence of quality of intensive care on quality of life/return to work in survivors of the acute respiratory distress syndrome: prospective observational patient cohort study (DACAPO).

BACKGROUND: Significant long-term reduction in health-related quality of life (HRQoL) is often observed in survivors of the acute respiratory distress syndrome (ARDS), and return to work (RtW) is limited. There is a paucity of data regarding the relationship between the quality of care (QoC) in the intensive care unit (ICU) and both HRQoL and RtW in ARDS survivors. Therefore, the aim of our study was to investigate associations between indicators of QoC and HRQoL and RtW in a cohort of survivors of ARDS. METHODS: To determine the influence of QoC on HRQoL and RtW 1 year after ICU-discharge, ARDS patients were recruited into a prospective multi-centre patient cohort study and followed up regularly after discharge. Patients were asked to complete self-report questionnaires on HRQoL (Short Form 12 physical component scale (PCS) and mental component scale (MCS)) and RtW. Indicators of QoC pertaining to volume, structural and process quality, and general characteristics were recorded on ICU level. Associations between QoC indicators and HrQoL and RtW were investigated by multivariable linear and Cox regression modelling, respectively. B values and hazard ratios (HRs) are reported with corresponding 95% confidence intervals (CIs). RESULTS: 877 (of initially 1225 enrolled) people with ARDS formed the DACAPO survivor cohort, 396 were finally followed up to 1 year after discharge. The twelve-month survivors were characterized by a reduced HRQoL with a greater impairment in the physical component (Md 41.2 IQR [34-52]) compared to the mental component (Md 47.3 IQR [33-57]). Overall, 50% of the patients returned to work. The proportion of ventilated ICU patients showed significant negative associations with both 12 months PCS (B = - 11.22, CI -20.71; - 1,74) and RtW (HR = 0,18, CI 0,04;0,80). All other QoC indicators were not significantly related to outcome. CONCLUSIONS: Associations between ICU QoC and long-term HrQoL and RtW were weak and largely non-significant. Residual confounding by case mix, treatment variables before or during ICU stay and variables pertaining to the post intensive care period (e.g. rehabilitation) cannot be ruled out. TRIAL REGISTRATION: Clinicaltrials.govNCT02637011. (December 22, 2015, retrospectively registered).

The quality of acute intensive care and the incidence of critical events have an impact on health-related quality of life in survivors of the acute respiratory distress syndrome - a nationwide prospective multicenter observational study.

Background: Initial treatment (ventilator settings, rescue therapy, supportive measures), and prevention of critical events improve survival in ARDS patients, but little data exists on its effect on health-related quality of life (HRQOL) and return to work (RtW) in survivors. We analyzed the association of the intensity of treatment at ARDS onset and the incidence of critical events on HRQOL and RtW a year after ICU discharge. Methods: In a prospective multi-centre cohort study, the intensity of treatment and the incidence of critical events were determined at 61 ICUs in Germany. At 3, 6, and 12 months, 396 survivors reported their HRQOL (Short-Form 12) and RtW. The parameters of the intensity of acute management (lung protective ventilation, prone position, hemodynamic stabilization, neuromuscular blocking agents), and critical events (hypoxemia, hypoglycemia, hypotension) were associated with HRQOL and RtW. Results: Patients ventilated at ARDS onset with a low tidal volume (VT≤7 ml/kg) had higher arterial carbon dioxide levels (PaCO2=57.5±17 mmHg) compared to patients ventilated with VT>7ml/kg (45.7±12, p=0.001). In a multivariate adjusted dichotomized analysis, a better mental 3-month SF-12 was observed in the higher VT-group (mean 43.1±12) compared to the lower VT-group (39.5±9, p=0.042), while a dichotomized analysis for driving pressures (≤14 mbar vs >14 mbar) did not show any difference neither in PaCO2 levels nor in HRQOL parameters. A decrease in the mental (6-month: 40.0±11 vs 44.8±13, p=0.038) and physical SF-12 (12-month: 38.3±11 vs 43.0±13, p=0.015) was reported from patients with hypoglycemia (blood glucose <70 mg/dl) compared to those without hypoglycemic episodes. More frequent vasopressor use with mean arterial pressure ≥65 mmHg was associated with an impaired physical SF-12 (6-month: 38.8±10) compared to less vasopressor use (43.0±11, p=0.019). Conclusions: In acute management of ARDS, a lower VT strategy associated with hypercapnia, as well as the frequent usage of catecholamines and the management of blood glucose may influence short-term HRQOL of survivors. The awareness of these findings is of clinical importance for the acute and post-ICU care.

Outcome of Oral and Intra-arterial Nimodipine Administration After Aneurysmal Subarachnoid Haemorrhage - A Single-centre Study.

BACKGROUND: Oral nimodipine is administered to improve clinical outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). In this study, clinical outcome in patients with and without oral nimodipine administration was assessed. MATERIALS AND METHODS: A total of 105 patients did not receive oral nimodipine but did receive intra-arterial nimodipine in the occurrence of hemodynamically relevant vasospasm after aSAH, whereas 74 patients received applications of both. Demographic/radiological details and clinical presentation were abstracted from the case records. RESULTS: Patient baseline characteristics were comparable, a predominance of endovascular coiling was shown in cohort 2 (p=0.0135). Severity of initial aSAH and clinical status at admission (Hunt and Hess) was significantly higher in those receiving oral nimodipine. Incidence of angiographic vasospasm was significantly higher in patients not treated with oral nimodipine (p=0.0305); a significantly better outcome measured by the National Institute of Health Stroke Scale (p=0.0213), was noted in those receiving oral nimodipine. CONCLUSION: Oral nimodipine administration improved clinical outcome of patients after aSAH and should be administered routinely for such patients.

German-wide prospective DACAPO cohort of survivors of the acute respiratory distress syndrome (ARDS): a cohort profile.

PURPOSE: While most research focuses on the association between medical characteristics and residual morbidity of survivors of the acute respiratory distress syndrome (ARDS), little is known about the relation between potentially modifiable intensive care unit (ICU) features and the course of health-related quality of life (HRQoL). Accordingly, the DACAPO study was set up to elucidate the influence of quality of intensive care on HRQoL and return to work (RtW) in survivors of ARDS. The continued follow-up of these former ICU patients leads to the establishment of the DACAPO (survivor) cohort. PARTICIPANTS: Sixty-one ICUs all over Germany recruited patients with ARDS between September 2014 and April 2016. Inclusion criteria were: (1) age older than 18 years and (2) ARDS diagnosis according to the 'Berlin definition'. No further inclusion or exclusion criteria were applied. 1225 patients with ARDS could be included in the DACAPO ICU sample. Subsequently, the 876 survivors at ICU discharge form the actual DACAPO cohort. FINDINGS TO DATE: The recruitment of the participants of the DACAPO cohort and the baseline data collection has been completed. The care-related data of the DACAPO cohort reveal a high proportion of adverse events (in particular, hypoglycaemia and reintubation). However, evidence-based supportive measures were applied frequently. FUTURE PLANS: Three months, 6 months and 1 year after ICU admission a follow-up assessment is conducted. The instruments of the follow-up questionnaires comprise the domains: (A) HRQoL, (B) RtW, (C) general disability, (D) psychiatric symptoms and (E) social support. Additionally, an annual follow-up of the DACAPO cohort focusing on HRQoL, psychiatric symptoms and healthcare utilisation will be conducted. Furthermore, several add-on projects affecting medical issues are envisaged. TRIAL REGISTRATION NUMBER: NCT02637011.

Association of Microcirculation, Macrocirculation, and Severity of Illness in Septic Shock: A Prospective Observational Study to Identify Microcirculatory Targets Potentially Suitable for Guidance of Hemodynamic Therapy.

PURPOSE: Clinically unapparent microcirculatory impairment is common and has a negative impact on septic shock, but specific therapy is not established so far. This prospective observational study aimed at identifying candidate parameters for microcirculatory-guided hemodynamic therapy. ClinicalTrials.gov : NCT01530932. MATERIALS AND METHODS: Microcirculatory flow and postcapillary venous oxygen saturation were detected during vaso-occlusive testing (VOT) on days 1 (T0), 2 (T24), and 4 (T72) in 20 patients with septic shock at a surgical intensive care unit using a laser Doppler spectrophotometry system (O2C). RESULTS: Reperfusional maximal venous capillary oxygen saturation (SvcO2max) showed negative correlations with Simplified Acute Physiology Score II (SAPSII)/Sequential Organ Failure Assessment (SOFA) score, norepinephrine dosage, and lactate concentration and showed positive correlations with cardiac index (CI). At T24 and T72, SvcO2max was also inversely linked to fluid balance. With respect to any predictive value, SvcO2max and CI determined on day 1 (T0) were negatively correlated with SAPS II/SOFA on day 4 (T72). Moreover, SvcO2max measured on day 1 or day 2 was negatively correlated with cumulated fluid balance on day 4 ( r= -.472, P < .05 and r = -.829, P < .001). By contrast, CI neither on day 1 nor on day 2 was correlated with cumulated fluid balance on day 4 ( r = -.343, P = .17 and r = -.365, P = .15). CONCLUSION: In patients with septic shock, microcirculatory reserve as assessed by SvcO2max following VOT was impaired and negatively correlated with severity of illness and fluid balance. In contrast to CI, SvcO2max determined on day 1 or day 2 was significantly negatively correlated with cumulative fluid balance on day 4. Therefore, early microcirculatory measurement of SvcO2max might be superior to CI in guidance of sepsis therapy to avoid fluid overload. This has to be addressed in future clinical studies.

Bedside implantation of a new temporary vena cava inferior filter - Safety and efficacy results of the European ANGEL-Registry.

PURPOSE: Pulmonary embolism (PE) is a frequently occurring complication in critically ill patients. Simultaneous occurrence of PE and life-threatening bleeding, may render medical anticoagulation impossible. For these patients, inferior vena cava filters (IVCF) present a valuable therapeutic alternative. The Angel® catheter is a novel IVCF that provides temporary protection from PE and is implanted at bedside. The primary objective of the European Angel® catheter registry is to evaluate the safety and efficacy of this IVCF. MATERIAL AND METHODS: The European Angel® catheter registry is an observational, multi-centre registry. Patients from four countries and eight sites that have undergone Angel® catheter implantation between March 2013 and February 2017 were enrolled. RESULTS: A total of 114 critically ill patients were included. The main indication for implantation was a high-risk for PE in combination with contraindications for anticoagulation (69.3%). One clinically non-significant PE (0.9%) occurred in a patient with an indwelling Angel® catheter. No cases of catheter associated serious complications were observed. CONCLUSION: Data shows that the Angel® catheter is a safe and effective approach to overcome the acute phase of critically ill patients with a high risk for the development of PE or an established PE, when an anticoagulation therapy is contraindicated.

Is There an Influence of Routine Daily Transcranial Doppler Examination on Clinical Outcome in Patients After Aneurysmal Subarachnoid Hemorrhage?

BACKGROUND: Transcranial Doppler (TCD) is widely used as a daily routine method to detect vasospasm in patients after aneurysmal subarachnoid hemorrhage (aSAH); however, there are only limited data about the real benefit of this examination. Therefore, the clinical outcome of 2 cohorts with and without daily TCD after aSAH was assessed. METHODS: All patients included in this study received a standardized diagnostic and treatment protocol. Fifty patients admitted with aSAH from January 2013 to December 2013 received daily TCD measurements; 39 patients admitted from January 2014 to September 2014 received no TCD measurements. Data on clinical grade (Hunt and Hess grade), severity of bleeding (Barrow Neurological Institute grade), localization of aneurysm, and angiographic or clinically relevant vasospasm were collected prospectively. The Glasgow Outcome Scale, modified Rankin Scale, and the National Institute of Health Stroke Scale were used as clinical outcome parameters. RESULTS: Patient baseline characteristics and clinical data were comparable; treatment modality of the aneurysm was not different between the groups (P = 0.7756). No significant difference between the Hunt and Hess grade (P = 0.818) and the Barrow Neurological Institute grade (P = 0.1551) was observed. There was also no significance concerning the incidence of angiographic or clinically relevant vasospasm between both groups (P = 0.5842 and P = 0.7933). Glasgow Outcome Scale, mRS, and National Institute of Health Stroke Scale as the primary outcome parameters showed no significant difference in morbidity and mortality between both groups (mortality P = 0.8544). CONCLUSIONS: With the limitation of an explorative cohort study, the results indicate that routine TCD studies do not improve the overall outcome of patients after aSAH.

Inhalation of the BK(Ca)-opener NS1619 attenuates right ventricular pressure and improves oxygenation in the rat monocrotaline model of pulmonary hypertension.

BACKGROUND: Right heart failure is a fatal consequence of chronic pulmonary hypertension (PH). The development of PH is characterized by increased proliferation of vascular cells, in particular pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells. In the course of PH, an escalated right ventricular (RV) afterload occurs, which leads to increased perioperative morbidity and mortality. BK(Ca) channels are ubiquitously expressed in vascular smooth muscle cells and their opening induces cell membrane hyperpolarization followed by vasodilation. Moreover, BK activation induces anti-proliferative effects in a multitude of cell types. On this basis, we hypothesized that treatment with the nebulized BK channel opener NS1619 might be a therapy option for pulmonary hypertension and tested this in rats. METHODS: (1) Rats received monocrotaline injection for PH induction. Twenty-four days later, rats were anesthetized and NS1619 or the solvent was administered by inhalation. Systemic hemodynamic parameters, RV hemodynamic parameters, and blood gas analyses were measured before as well as 30 and 120 minutes after inhalation. (2) Rat PASMCs were stimulated with PDGF-BB in the presence and absence of NS1619. AKT, ERK1 and ERK2 activation were investigated by western blot analyses, and relative cell number was determined 48 hours after stimulation. RESULTS: Inhalation of a 12 µM and 100 µM NS1619 solution significantly reduced RV pressure without affecting systemic arterial pressure. Blood gas analyses demonstrated significantly reduced carbon dioxide and improved oxygenation in NS1619-treated animals pointing towards a considerable pulmonary shunt-reducing effect. In PASMC's, NS1619 (100 µM) significantly attenuated PASMC proliferation by a pathway independent of AKT and ERK1/2 activation. CONCLUSION: NS1619 inhalation reduces RV pressure and improves oxygen supply and its application inhibits PASMC proliferation in vitro. Hence, BK opening might be a novel option for the treatment of pulmonary hypertension.

Accuracy of prehospital focused abdominal sonography for trauma after a 1-day hands-on training course.

OBJECTIVES: To establish a training course for Prehospital Focused Abdominal Sonography for Trauma (P-FAST) and to evaluate the accuracy of the participants after the course and at the trauma scene. METHODS: A training programme was developed to provide medical staff with the skills needed to perform P-FAST. In order to evaluate the accuracy of P-FAST performed by the students, nine participants (five emergency doctors and four paramedics) were followed during their course and in practice after the course. An assessment was made of 200 ultrasound procedures performed during the course in healthy volunteers and in patients with peritoneal dialysis or ascites. Regular P-FAST performed on-scene by the participants commenced immediately following the course. The results for the nine participants (C-group, course group) were compared with those members of medical staff with more than 3 years of experience in FAST (P-group, professional group). A group of physicians untrained in P-FAST served as a control (I-group, indifferent group). P-FAST findings were further verified by subsequent FAST and CT scans in the emergency department. RESULTS: After the training programme the C-group performed 39 P-FAST procedures without any false negative or false positive findings (100% accuracy). In the P-group, 112 procedures were performed with one false positive case. In the I-group there were 2 false negative cases among the 46 procedures performed. CONCLUSION: Following completion of a 1-day P-FAST course, participants were able to perform ultrasound procedures at the scene of an accident with a high level of accuracy.

Prehospital and Emergency Department Ultrasound in Blunt Abdominal Trauma.

Blunt abdominal trauma is a challenging aspect of trauma management. Early detection has a major impact on patient outcome. In contrast to physical examination, computed tomography is known to be a sensitive and specific test for blunt abdominal injuries. However, it is time-consuming and thus contraindicated in hemodynamically unstable patients. Therefore, focused assessment with sonography for trauma (FAST) offers a fast and easily applicable screening method to identify patients for urgent laparotomy without any further diagnostics. FAST detects, with high sensitivity, intraperitoneal fluid that accumulates in dependent areas indicating blunt abdominal trauma. FAST has been established as a gold standard early screening method for blunt abdominal trauma when performing trauma management in the emergency department (ED) based on the Advanced Trauma Life Support(®) algorithm. The development of hand-held ultrasound devices facilitated the introduction of FAST into prehospital trauma management. It was demonstrated that prehospital FAST (p-FAST) can be performed with high sensitivity and specificity, and can lead to significant changes in prehospital trauma therapy and management. Standardized training with both theoretical and hands-on modules is mandatory in order to gain the skills required to perform FAST or p-FAST well.