Antithrombin deficiency is associated with mortality and impaired organ function in septic pediatric patients: a retrospective study

Background Sepsis remains a major problem in intensive care medicine. It is often accompanied by coagulopathies, leading to thrombotic occlusion of small vessels with subsequent organ damage and even fatal multi-organ failure. Prediction of the clinical course and outcome—especially in the heterogeneous group of pediatric patients—is difficult. Antithrombin, as an endogenous anticoagulant enzyme with anti-inflammatory properties, plays a central role in controling coagulation and infections. We investigated the relationship between antithrombin levels and organ failure as well as mortality in pediatric patients with sepsis. Methods Data from 164 patients under the age of 18, diagnosed with sepsis, were retrospectively reviewed. Antithrombin levels were recorded three days before to three days after peak C-reactive protein to correlate antithrombin levels with inflammatory activity. Using the concept of developmental haemostasis, patients were divided into groups <1 yr and ≥1 yr of age. Results In both age groups, survivors had significantly higher levels of antithrombin than did deceased patients. An optimal threshold level for antithrombin was calculated by ROC analysis for survival: 41.5% (<1 yr) and 67.5% (≥1 yr). The mortality rate above this level was 3.3% (<1 yr) and 9.5% (≥1 yr), and below this level 41.7% (<1 yr) and 32.2% (≥1 yr); OR 18.8 (1.74 to 1005.02), p = 0.0047, and OR 4.46 (1.54 to 14.89), p = 0.003. In children <1 yr with antithrombin levels <41.5% the rate of respiratory failure (66.7%) was significantly higher than in patients with antithrombin levels above this threshold level (23.3%), OR 6.23 (1.23 to 37.81), p = 0.0132. In children ≥1 yr, both liver failure (20.3% vs 1.6%, OR 15.55 (2.16 to 685.01), p = 0.0008) and a dysfunctional intestinal tract (16.9% vs 4.8%, OR 4.04 (0.97 to 24.08), p = 0.0395) occurred more frequently above the antithrombin threshold level of 67.5%. Conclusion In pediatric septic patients, significantly increased mortality and levels of organ failure were found below an age-dependent antithrombin threshold level. Antithrombin could be useful as a prognostic marker for survival and occurrence of organ failure in pediatric sepsis

Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model

<p>Abstract</p> <p>Background</p> <p>Inhalation of N-chlorotaurine (NCT), an endogenous new broad spectrum non-antibiotic anti-infective, has been shown to be very well tolerated in the pig model recently. In the present study, inhaled NCT was tested for tolerability and efficacy in the infected bronchopulmonary system using the same model.</p> <p>Methods</p> <p>Anesthetized pigs were inoculated with 20 ml of a solution containing approximately 10⁸CFU/ml <it>Streptococcus pyogenes </it>strain d68 via a duodenal tube placed through the tracheal tube down to the carina. Two hours later, 5 ml of 1% NCT aqueous solution (test group, n = 15) or 5 ml of 0.9% NaCl (control group, n = 16) was inhaled via the tracheal tube connected to a nebulizer. Inhalation was repeated every hour, four times in total. Lung function and haemodynamics were monitored. Bronchoalveolar lavage samples were removed for determination of colony forming units (CFU), and lung samples for histology.</p> <p>Results</p> <p>Arterial pressure of oxygen (PaO₂) decreased rapidly after instillation of the bacteria in all animals and showed only a slight further decrease at the end of the experiment without a difference between both groups. Pulmonary artery pressure increased to a peak 1-1.5 h after application of the bacteria, decreased in the following hour and remained constant during treatment, again similarly in both groups. Histology demonstrated granulocytic infiltration in the central parts of the lung, while this was absent in the periphery. Expression of TNF-alpha, IL-8, and haemoxygenase-1 in lung biopsies was similar in both groups. CFU counts in bronchoalveolar lavage came to 170 (10; 1388) CFU/ml (median and 25 and 75 percentiles) for the NCT treated pigs, and to 250 (10; 5.5 × 10⁵) CFU/ml for NaCl treated pigs (p = 0.4159).</p> <p>Conclusions</p> <p>Inhaled NCT at a concentration of 1% proved to be very well tolerated also in the infected bronchopulmonary system. This study confirms the tolerability in this delicate body region, which has been proven in healthy pigs previously. Regarding efficacy, no conclusions can be drawn, mainly because of the limited test period of the model.</p

Tolerability of inhaled N-chlorotaurine in the pig model

<p>Abstract</p> <p>Background</p> <p>N-chlorotaurine, a long-lived oxidant produced by human leukocytes, can be applied in human medicine as an endogenous antiseptic. Its antimicrobial activity can be enhanced by ammonium chloride. This study was designed to evaluate the tolerability of inhaled N-chlorotaurine (NCT) in the pig model.</p> <p>Methods</p> <p>Anesthetized pigs inhaled test solutions of 1% (55 mM) NCT (n = 7), 5% NCT (n = 6), or 1% NCT plus 1% ammonium chloride (NH₄Cl) (n = 6), and 0.9% saline solution as a control (n = 7), respectively. Applications with 5 ml each were performed hourly within four hours. Lung function, haemodynamics, and pharmacokinetics were monitored. Bronchial lavage samples for captive bubble surfactometry and lung samples for histology and electron microscopy were removed.</p> <p>Results</p> <p>Arterial pressure of oxygen (PaO₂) decreased significantly over the observation period of 4 hours in all animals. Compared to saline, 1% NCT + 1% NH₄Cl led to significantly lower PaO₂values at the endpoint after 4 hours (62 ± 9.6 mmHg vs. 76 ± 9.2 mmHg, p = 0.014) with a corresponding increase in alveolo-arterial difference of oxygen partial pressure (AaDO₂) (p = 0.004). Interestingly, AaDO₂was lowest with 1% NCT, even lower than with saline (p = 0.016). The increase of pulmonary artery pressure (PAP) over the observation period was smallest with 1% NCT without difference to controls (p = 0.91), and higher with 5% NCT (p = 0.02), and NCT + NH₄Cl (p = 0.05).</p> <p>Histological and ultrastructural investigations revealed no differences between the test and control groups. The surfactant function remained intact. There was no systemic resorption of NCT detectable, and its local inactivation took place within 30 min. The concentration of NCT tolerated by A549 lung epithelial cells <it>in vitro </it>was similar to that known from other body cells (0.25–0.5 mM).</p> <p>Conclusion</p> <p>The endogenous antiseptic NCT was well tolerated at a concentration of 1% upon inhalation in the pig model. Addition of ammonium chloride in high concentration provokes a statistically significant impact on blood oxygenation.</p

Lung Sonography in Critical Care Medicine

During the last five decades, lung sonography has developed into a core competency of intensive care medicine. It is a highly accurate bedside tool, with clear diagnostic criteria for most causes of respiratory failure (pneumothorax, pulmonary edema, pneumonia, pulmonary embolism, chronic obstructive pulmonary disease, asthma, and pleural effusion). It helps in distinguishing a hypovolemic from a cardiogenic, obstructive, or distributive shock. In addition to diagnostics, it can also be used to guide ventilator settings, fluid administration, and even antimicrobial therapy, as well as to assess diaphragmatic function. Moreover, it provides risk-reducing guidance during invasive procedures, e.g., intubation, thoracocentesis, or percutaneous dilatational tracheostomy. The recent pandemic has further increased its scope of clinical applications in the management of COVID-19 patients, from their initial presentation at the emergency department, during their hospitalization, and after their discharge into the community. Despite its increasing use, a consensus on education, assessment of competencies, and certification is still missing. Deep learning and artificial intelligence are constantly developing in medical imaging, and contrast-enhanced ultrasound enables new diagnostic perspectives. This review summarizes the clinical aspects of lung sonography in intensive care medicine and provides an overview about current training modalities, diagnostic limitations, and future developments

ECMO Support in Refractory Cardiogenic Shock: Risk Factors for Mortality

Background: Veno-arterial extracorporeal membrane oxygenation (va-ECMO) is a specialized temporary support for patients with refractory cardiogenic shock. The true value of this potentially lifesaving modality is still a subject of debate. Therefore, we aimed to investigate the overall in-hospital mortality and identify potential risk factors for mortality. Methods: We retrospectively analyzed the data of 453 patients supported with va-ECMO over a period of 14 years who were admitted to intensive care units of a tertiary university center in Austria. Results: We observed in-hospital mortality of 40% for patients with refractory cardiogenic shock. Hemorrhage, ECMO initiation on weekends, higher SAPS III score, and sepsis were identified as significant risk factors for mortality. Hemorrhage was the most common adverse event (46%), with major bleeding events dominating in deceased patients. Thromboembolic events occurred in 25% of patients, followed by sepsis (18%). Conclusions: Although the rates of complications are substantial, a well-selected proportion of patients with refractory cardiogenic shock can be rescued from probable death. The reported risk factors could be used to increase the awareness of clinicians towards the development of new therapeutic concepts that may reduce their incidence

Diagnostic Modalities in Critical Care: Point-of-Care Approach

The concept of intensive care units (ICU) has existed for almost 70 years, with outstanding development progress in the last decades. Multidisciplinary care of critically ill patients has become an integral part of every modern health care system, ensuing improved care and reduced mortality. Early recognition of severe medical and surgical illnesses, advanced prehospital care and organized immediate care in trauma centres led to a rise of ICU patients. Due to the underlying disease and its need for complex mechanical support for monitoring and treatment, it is often necessary to facilitate bed-side diagnostics. Immediate diagnostics are essential for a successful treatment of life threatening conditions, early recognition of complications and good quality of care. Management of ICU patients is incomprehensible without continuous and sophisticated monitoring, bedside ultrasonography, diverse radiologic diagnostics, blood gas analysis, coagulation and blood management, laboratory and other point-of-care (POC) diagnostic modalities. Moreover, in the time of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, particular attention is given to the POC diagnostic techniques due to additional concerns related to the risk of infection transmission, patient and healthcare workers safety and potential adverse events due to patient relocation. This review summarizes the most actual information on possible diagnostic modalities in critical care, with a special focus on the importance of point-of-care approach in the laboratory monitoring and imaging procedures

ECMO in Cardiogenic Shock: Time Course of Blood Biomarkers and Associated Mortality

Background: Veno-arterial extracorporeal membrane oxygenation (va-ECMO) is a temporary life support for severe cardiogenic shock, gaining time for organ recovery, permanent assistance, or transplantation. In this work, we aimed to investigate the trends of blood biomarkers over the period of ECMO support and their role in patient outcome. Methods: This retrospective study comprised patients receiving va-ECMO support over the period of 14 years at a tertiary university center. Results: Of 435 patients, 62% (268/435) survived to discharge, and the most frequent adverse event was hemorrhage (46%), followed by thrombosis (25%). Deceased patients had increased blood levels of C-reactive protein, procalcitonin, and white blood cells during the whole observation period, with higher peaks compared with survivors. The multivariable model identified hemorrhage (HR 1.73, p = 0.005) and higher levels of procalcitonin (HR 1.01, p = 0.001) as independent risk factors for death. Conclusions: In our population of critically ill patients receiving va-ECMO support, deceased patients had increased inflammatory biomarkers during the whole observation period. Patients having higher values of procalcitonin and experiencing bleeding events showed an increased risk for mortality. Further studies focusing on inflammation in ECMO patients, clarifying its role in patient outcome and potential therapeutic interventions, are warranted

Oxygen availability in a HAPE-positive and a HAPE-negative woman before and during a visit to 3480 meters

Background: Testing the hypoxic ventilatory response (HVR) at low-altitude helps to detect those who do not hyperventilate appropriately in hypoxia but might not necessarily predict the HVR and the risk to develop acute mountain sickness (AMS) at high altitude. However, a low HVR seems to be particularly prevalent in individuals susceptible to high-altitude pulmonary edema (HAPE+). In this short communication, we assessed differences in physiological parameters in two comparable women before and 3 hours after exposure to 3,480 meters. One woman had a (clinically diagnosed) history of high-altitude pulmonary edema (HAPE+) while the other did well at previous exposures to high altitude (HAPE-).Methods: Heart rate, blood pressure, ventilation, arterial blood gas variables, arterial haemoglobin saturation, haemoglobin concentration, arterial oxygen content and delta plasma volume were measured or calculated before and after arrival at high altitude.Results: At high altitude, plasma volume decreased in the HAPE- woman which in turn increased haemoglobin concentration. Ventilation was elevated in the HAPE- but not in the HAPE + woman. Arterial oxygen content fell in the HAPE + while it was preserved in the HAPE- woman. This resulted from lower peripheral oxygen saturation (-35%), lower haemoglobin concentration (-12%) and lower arterial partial pressure of oxygen (-59%) in the HAPE+.Conclusion: Considerable haemoglobin desaturation and lack of haemoconcentration were characteristics of the HAPE + woman when exposed to high altitude, while the higher arterial oxygen content in the HAPE- woman was related to both haemoconcentration and hyperventilation (and associated haemoglobin saturation)

A Focused Review on the Maximal Exercise Responses in Hypo- and Normobaric Hypoxia: Divergent Oxygen Uptake and Ventilation Responses

The literature suggests that acute hypobaric (HH) and normobaric (NH) hypoxia exposure elicits different physiological responses. Only limited information is available on whether maximal cardiorespiratory exercise test outcomes, performed on either the treadmill or the cycle ergometer, are affected differently by NH and HH. A focused literature review was performed to identify relevant studies reporting cardiorespiratory responses in well-trained male athletes (individuals with a maximal oxygen uptake, VO2max &gt; 50 mL/min/kg at sea level) to cycling or treadmill running in simulated acute HH or NH. Twenty-one studies were selected. The exercise tests in these studies were performed in HH (n = 90) or NH (n = 151) conditions, on a bicycle ergometer (n = 178) or on a treadmill (n = 63). Altitudes (simulated and terrestrial) varied between 2182 and 5400 m. Analyses (based on weighted group means) revealed that the decline in VO2max per 1000 m gain in altitude was more pronounced in acute NH vs. HH (&minus;7.0 &plusmn; 1.4% vs. &minus;5.6 &plusmn; 0.9%). Maximal minute ventilation (VEmax) increased in acute HH but decreased in NH with increasing simulated altitude (+1.9 &plusmn; 0.9% vs. &minus;1.4 &plusmn; 1.8% per 1000 m gain in altitude). Treadmill running in HH caused larger decreases in arterial oxygen saturation and heart rate than ergometer cycling in acute HH, which was not the case in NH. These results indicate distinct differences between maximal cardiorespiratory responses to cycling and treadmill running in acute NH or HH. Such differences should be considered when interpreting exercise test results and/or monitoring athletic training

Small Drainage Volumes of Pleural Effusions Are Associated with Complications in Critically Ill Patients: A Retrospective Analysis

Pleural effusions are a common finding in critically ill patients and small bore chest drains (SBCD) are proven to be efficient for pleural drainage. The data on the potential benefits and risks of drainage remains controversial. We aimed to determine the cut-off volume for complications, to investigate the impact of pleural drainage and drained volume on clinically relevant outcomes. Medical records of all critically ill patients undergoing insertion of SBCD were retrospectively examined. We screened 13,003 chest radiographs and included 396 SBCD cases in the final analysis. SBCD drained on average 900 mL, with less amount in patients with complications (p = 0.003). A drainage volume of 975 mL in 24 h represented the optimal threshold for complications. Pneumothorax was the most frequent complication (4.5%), followed by bleeding (0.8%). Female and lighter-weighted patients experienced a higher risk for any complication. We observed an improvement in the arterial partial pressure of oxygen and respiratory quotient (p &lt; 0.001). We conclude that the small drainage volumes are associated with complications in critically ill patients—the more you drain, the safer the procedure gets. The use of SBCD is a safe and efficient procedure, further investigations regarding the higher rate of complications in female and lighter-weighted patients are desirable