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 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

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

ICU-Acquired Hypernatremia Is Associated with Persistent Inflammation, Immunosuppression and Catabolism Syndrome

Developing hypernatremia while on intensive care unit (ICU) is a common problem with various undesirable effects. A link to persistent inflammation, immunosuppression and catabolism syndrome (PICS) can be established in two ways. On the one hand, hypernatremia can lead to inflammation and catabolism via hyperosmolar cell stress, and on the other, profound catabolism can lead to hypernatremia via urea-induced osmotic diuresis. In this retrospective single-center study, we examined 115 patients with prolonged ICU stays (&ge;14 days) and sufficient renal function. Depending on their serum sodium concentrations between ICU day 7 and 21, allocation to a hypernatremic (high) and a nonhypernatremic group (low) took place. Distinct signs of PICS were detectable within the complete cohort. Thirty-three of them (28.7%) suffered from ICU-acquired hypernatremia, which was associated with explicitly higher signs of inflammation and ongoing catabolism as well as a prolonged ICU length of stay. Catabolism was discriminated better by the urea generation rate and the urea-to-creatinine ratio than by serum albumin concentration. An assignable cause for hypernatremia was the urea-induced osmotic diuresis. When dealing with ICU patients requiring prolonged treatment, hypernatremia should at least trigger thoughts on PICS as a contributing factor. In this regard, the urea-to-creatinine ratio is an easily accessible biomarker for catabolism

Invasive Fungal Infections: The Early Killer after Liver Transplantation

Background: Liver transplantation is a standard of care and a life-saving procedure for end-stage liver diseases and certain malignancies. The evidence on predictors and risk factors for poor outcomes is lacking. Therefore, we aimed to identify potential risk factors for mortality and to report on overall 90-day mortality after orthotopic liver transplantation (OLT), especially focusing on the role of fungal infections. Methods: We retrospectively reviewed medical charts of all patients undergoing OLT at a tertiary university center in Europe. Results: From 299 patients, 214 adult patients who received a first-time OLT were included. The OLT indication was mainly due to tumors (42%, 89/214) and cirrhosis (32%, 68/214), including acute liver failure in 4.7% (10/214) of patients. In total, 8% (17/214) of patients died within the first three months, with a median time to death of 15 (1–80) days. Despite a targeted antimycotic prophylaxis using echinocandins, invasive fungal infections occurred in 12% (26/214) of the patients. In the multivariate analysis, patients with invasive fungal infections had an almost five times higher chance of death (HR 4.6, 95% CI 1.1–18.8; p = 0.032). Conclusions: Short-term mortality after OLT is mainly determined by infectious and procedural complications. Fungal breakthrough infections are becoming a growing concern. Procedural, host, and fungal factors can contribute to a failure of prophylaxis. Finally, invasive fungal infections may be a potentially modifiable risk factor, but the ideal perioperative antimycotic prophylaxis has yet to be determined