Low intraoperative end-tidal carbon dioxide levels are associated with improved recurrence-free survival after elective colorectal cancer surgery.

STUDY OBJECTIVE: Higher levels of carbon dioxide (CO2) increase the invasive abilities of colon cancer cells in vitro. Studies assessing target values for end-tidal CO2 concentrations (EtCO2) to improve surgical outcome after colorectal cancer surgery are lacking. Therefore, we evaluated whether intraoperative EtCO2 was associated with differences in recurrence-free survival after elective colorectal cancer (CRC) surgery. DESIGN: Single center, retrospective analysis. SETTING: Anesthesia records, surgical databases and hospital information system of a tertiary university hospital. PATIENTS: We analyzed 528 patients undergoing elective resection of colorectal cancer at Heidelberg University Hospital between 2009 and 2018. INTERVENTIONS: None. MEASUREMENTS: Intraoperative mean EtCO2 values were calculated. The study cohort was equally stratified into low-and high-EtCO2 groups. The primary endpoint measure was recurrence-free survival until last known follow-up. Groups were compared using Kaplan-Meier analysis. Cox-regression analysis was used to control for covariates. Sepsis, reoperations, surgical site infections and cardiovascular events during hospital stay, and overall survival were secondary outcomes. MAIN RESULTS: Mean EtCO2 was 33.8 mmHg ±1.2 in the low- EtCO2 group vs. 37.3 mmHg ±1.6 in the high-EtCO2 group. Median follow-up was 3.8 (Q1-Q3, 2.5-5.1) years. Recurrence-free survival was higher in the low-EtCO2 group (log-rank-test: p = .024). After correction for confounding factors, lower EtCO2 was associated with increased recurrence-free survival (HR = 1.138, 95%-CI:1.015-1.276, p = .027); the hazard for the primary outcome decreased by 12.1% per 1 mmHg decrease in mean EtCO2. 1-year and 5-year survival was also higher in the low-EtCO2 group. We did not find differences in the other secondary endpoints. CONCLUSIONS: Lower intraoperative EtCO2 target values in CRC surgery might benefit oncological outcome and should be evaluated in confirmative studies.

Clinical accuracy of instrument-based SARS-CoV-2 antigen diagnostic tests: a systematic review and meta-analysis.

BACKGROUND: During the COVID-19 pandemic, antigen diagnostic tests were frequently used for screening, triage, and diagnosis. Novel instrument-based antigen tests (iAg tests) hold the promise of outperforming their instrument-free, visually-read counterparts. Here, we provide a systematic review and meta-analysis of the SARS-CoV-2 iAg tests' clinical accuracy. METHODS: We systematically searched MEDLINE (via PubMed), Web of Science, medRxiv, and bioRxiv for articles published before November 7th, 2022, evaluating the accuracy of iAg tests for SARS-CoV-2 detection. We performed a random effects meta-analysis to estimate sensitivity and specificity and used the QUADAS-2 tool to assess study quality and risk of bias. Sub-group analysis was conducted based on Ct value range, IFU-conformity, age, symptom presence and duration, and the variant of concern. RESULTS: We screened the titles and abstracts of 20,431 articles and included 114 publications that fulfilled the inclusion criteria. Additionally, we incorporated three articles sourced from the FIND website, totaling 117 studies encompassing 95,181 individuals, which evaluated the clinical accuracy of 24 commercial COVID-19 iAg tests. The studies varied in risk of bias but showed high applicability. Of 24 iAg tests from 99 studies assessed in the meta-analysis, the pooled sensitivity and specificity compared to molecular testing of a paired NP swab sample were 76.7% (95% CI 73.5 to 79.7) and 98.4% (95% CI 98.0 to 98.7), respectively. Higher sensitivity was noted in individuals with high viral load (99.6% [95% CI 96.8 to 100] at Ct-level ≤ 20) and within the first week of symptom onset (84.6% [95% CI 78.2 to 89.3]), but did not differ between tests conducted as per manufacturer's instructions and those conducted differently, or between point-of-care and lab-based testing. CONCLUSION: Overall, iAg tests have a high pooled specificity but a moderate pooled sensitivity, according to our analysis. The pooled sensitivity increases with lower Ct-values (a proxy for viral load), or within the first week of symptom onset, enabling reliable identification of most COVID-19 cases and highlighting the importance of context in test selection. The study underscores the need for careful evaluation considering performance variations and operational features of iAg tests.

Effect of acyclovir therapy on the outcome of mechanically ventilated patients with lower respiratory tract infection and detection of herpes simplex virus in bronchoalveolar lavage: protocol for a multicentre, randomised controlled trial (HerpMV).

INTRODUCTION: Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients and is associated with a worse outcome. The aim of this study is to determine whether antiviral therapy in HSV-positive patients improves outcome. METHODS AND ANALYSIS: Prospective, multicentre, open-label, randomised, controlled trial in parallel-group design. Adult, mechanically ventilated patients with pneumonia and HSV type 1 detected in bronchoalveolar lavage (≥105 copies/mL) are eligible for participation and will be randomly allocated (1:1) to receive acyclovir (10 mg/kg body weight every 8 hours) for 10 days (or until discharge from the intensive care unit if earlier) or no intervention (control group). The primary outcome is mortality measured at day 30 after randomisation (primary endpoint) and will be analysed with Cox mixed-effects model. Secondary endpoints include ventilator-free and vasopressor-free days up to day 30. A total of 710 patients will be included in the trial. ETHICS AND DISSEMINATION: The trial was approved by the responsible ethics committee and by Germany's Federal Institute for Drugs and Medical Devices. The clinical trial application was submitted under the new Clinical Trials Regulation through CTIS (The Clinical Trials Information System). In this process, only one ethics committee, whose name is unknown to the applicant, and Germany's Federal Institute for Drugs and Medical Devices are involved throughout the entire approval process. Results will be published in a journal indexed in MEDLINE and CTIS. With publication, de-identified, individual participant data will be made available to researchers. TRIAL REGISTRATION NUMBER: NCT06134492.

Feasibility of Fluid Responsiveness Assessment in Patients at Risk for Increased Intracranial Pressure.

Background: Effective fluid management is important for patients at risk of increased intracranial pressure (ICP). Maintaining constant cerebral perfusion represents a challenge, as both hypovolemia and fluid overload can severely impact patient outcomes. Fluid responsiveness tests, commonly used in critical care settings, are often deemed potentially hazardous for these patients due to the risk of disrupting cerebral perfusion. Methods: This single-center, prospective, clinical observational study enrolled 40 patients at risk for increased ICP, including those with acute brain injury. Informed consent was obtained from each participant or their legal guardians before inclusion. The study focused on the dynamics of ICP and cerebral perfusion pressure (CPP) changes during the Passive Leg Raise Test (PLRT) and the End-Expiratory Occlusion Test (EEOT). Results: The results demonstrated that PLRT and EEOT caused minor and transient increases in ICP, while consistently maintaining stable CPP. EEOT induced significantly lower ICP elevations, making it particularly suitable for use in high-risk situations. Conclusions: PLRT and EEOT can be considered feasible and safe for assessing fluid responsiveness in patients at risk for increased ICP. Notably, EEOT stands out as a preferred method for high-risk patients, offering a dependable strategy for fluid management without compromising cerebral hemodynamics.

Thoracic Epidural Analgesia Is Not Associated With Improved Survival After Pancreatic Surgery: Long-Term Follow-Up of the Randomized Controlled PAKMAN Trial.

BACKGROUND: Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are common forms of analgesia after pancreatic surgery. Current guidelines recommend EDA over PCIA, and evidence suggests that EDA may improve long-term survival after surgery, especially in cancer patients. The aim of this study was to determine whether perioperative EDA is associated with an improved patient prognosis compared to PCIA in pancreatic surgery. METHODS: The PAKMAN trial was an adaptive, pragmatic, international, multicenter, randomized controlled superiority trial conducted from June 2015 to October 2017. Three to five years after index surgery a long-term follow-up was performed from October 2020 to April 2021. RESULTS: For long-term follow-up of survival, 109 patients with EDA were compared to 111 patients with PCIA after partial pancreatoduodenectomy (PD). Long-term follow-up of quality of life (QoL) and pain assessment was available for 40 patients with EDA and 45 patients with PCIA (questionnaire response rate: 94%). Survival analysis revealed that EDA, when compared to PCIA, was not associated with improved overall survival (OS, HR, 1.176, 95% HR-CI, 0.809-1.710, P = .397, n = 220). Likewise, recurrence-free survival did not differ between groups (HR, 1.116, 95% HR-CI, 0.817-1.664, P = .397, n = 220). OS subgroup analysis including only patients with malignancies showed no significant difference between EDA and PCIA (HR, 1.369, 95% HR-CI, 0.932-2.011, P = .109, n = 179). Similar long-term effects on QoL and pain severity were observed in both groups (EDA: n = 40, PCIA: n = 45). CONCLUSIONS: Results from this long-term follow-up of the PAKMAN randomized controlled trial do not support favoring EDA over PCIA in pancreatic surgery. Until further evidence is available, EDA and PCIA should be considered similar regarding long-term survival.

Evaluating time until ligation in a novel tourniquet - A crossover randomized-controlled trial.

INTRODUCTION AND AIM: Severe external hemorrhage is a significant reason for morbidity and mortality in adults; thus, the swift and correct application of a tourniquet by laypersons can be lifesaving. We conducted this randomized-controlled cross-over study to investigate the use of a novel tourniquet. METHODS: Participants were recruited at the Heidelberg University Hospital. Eligible participants were ≥ 18 years old with a medical background but without prior experience in applying a tourniquet. Participants were 1:1 randomized to the intervention group (PAX tourniquet) or the control group (SAM or CAT tourniquet). In the control group, participants underwent another randomization to either the SAM or CAT tourniquet without a predefined allocation ratio. Hyperspectral measurements were undertaken (i) before ligation, (ii) 30 s after ligation, and (iii) 30 s after the reopening of the tourniquet. The primary outcome was time until ligation before crossover between the respective groups. The analysis of secondary endpoints included all attempts to assess a possible learning effect, intraoperator variability, and hyperspectral measurements. Participants were crossed to the other study group after a brief wash-out phase. RESULTS: In total, 50 participants were recruited, resulting in 100 attempts. A success rate of 98% was observed across the study population. Time until ligation was 49 s and 56 s (p = 0.572) in the intervention and control group, respectively. However, there was a significant difference between the PAX and SAM (54 vs 75 s; p = 0.037) and the SAM and CAT tourniquet (75 vs. 47 s; p = 0.015). Further, we observed a significant learning effect in participants allocated to the control group first, with a median reduction of 9 s in the time until ligation. Hyperspectral measurements showed a significant decrease in perfusion and tissue oxygenation after ligation. Further, a significant increase in perfusion and tissue oxygenation was found after reopening the tourniquet compared to the baseline measurement. CONCLUSION: The novel PAX tourniquet can be applied quickly and effectively by medical personnel without prior experience in applying a tourniquet.

Comparison of Two Viscoelastic Testing Devices in a Parturient Population.

Background: Viscoelastic hemostatic assays (VHAs) have become an integral diagnostic tool in guiding hemostatic therapy, offering new opportunities in personalized hemostatic resuscitation. This study aims to assess the interchangeability of ClotPro® and ROTEM® delta in the unique context of parturient women. Methods: Blood samples from 217 parturient women were collected at three timepoints. A total of 631 data sets were eligible for our final analysis. The clotting times were analyzed via extrinsic and intrinsic assays, and the clot firmness parameters A5, A10, and MCF were analyzed via extrinsic, intrinsic, and fibrin polymerization assays. In parallel, the standard laboratory coagulation statuses were obtained. Device comparison was assessed using regression and Bland-Altman plots. The best cutoff calculations were used to determine the VHA values corresponding to the established standard laboratory cutoffs. Results: The clotting times in the extrinsic and intrinsic assays showed notable differences between the devices, while the extrinsic and intrinsic clot firmness results demonstrated interchangeability. The fibrinogen assays revealed higher values in ClotPro® compared to ROTEM®. An ROC analysis identified VHA parameters with high predictive values for coagulopathy exclusion and yet low specificity. Conclusions: In the obstetric setting, the ROTEM® and ClotPro® parameters demonstrate a significant variability. Device- and indication-specific transfusion algorithms are essential for the accurate interpretation of measurements and adequate hemostatic therapy.

Efficacy of therapies for post dural puncture headache.

PURPOSE OF REVIEW: Clinical management of postdural puncture headache (PDPH) remains an interdisciplinary challenge with significant impact on both morbidity and quality of life. This review aims to give an overview of the most recent literature on prophylactic and therapeutic measures and to discuss novel findings with regard to currently published consensus practice guideline recommendations. RECENT FINDINGS: Although current evidence does not support a recommendation of any specific prophylactic measure, new data is available on the use of intrathecal catheters to prevent PDPH and/or to avoid invasive procedures. In case of disabling or refractory symptoms despite conservative treatments, the epidural blood patch (EBP) remains the therapeutic gold standard and its use should not be delayed in the absence of contraindications. However, recent clinical studies and meta-analyses provide additional findings on the therapeutic use of local anesthetics as potential noninvasive alternatives for early symptom control. SUMMARY: There is continuing research focusing on both prophylactic and therapeutic measures offering promising data on potential alternatives to invasive procedures, although there is currently no treatment option that comes close to the effectiveness of an EBP. A better understanding of PDPH pathophysiology is not only necessary to identify new therapeutic targets, but also to recognize patients who benefit most from current treatments, as this might enhance their therapeutic efficacy.

miR-Blood - a small RNA atlas of human blood components.

miR-Blood is a high-quality, small RNA expression atlas for the major components of human peripheral blood (plasma, erythrocytes, thrombocytes, monocytes, neutrophils, eosinophils, basophils, natural killer cells, CD4+ T cells, CD8+ T cells, and B cells). Based on the purified blood components from 52 individuals, the dataset provides a comprehensive repository for the expression of 4971 small RNAs from eight non-coding RNA classes.

Severe trauma associated cardiac failure.

Although significant efforts have been made to enhance trauma care, the mortality rate for traumatic cardiac arrest (TCA) remains exceedingly high. Therefore, our institution has implemented special measures to optimize the treatment of major trauma patients. These measures include a prehospital Medical Intervention Car (MIC) and a 'code red' protocol in the trauma resuscitation room for patients with TCA or shock. These measures enable the early treatment of reversible causes of TCA and have resulted in a significant number of patients achieving adequate ROSC. However, a significant proportion of these patients still die due to circulatory failure shortly after. Our observations from patients who underwent clamshell thoracotomy or received echocardiographic evaluation in conjunction with current scientific findings led us to conclude that dysfunction of the heart itself may be the cause. Therefore, we propose discussing severe trauma-associated cardiac failure (STAC) as a new entity to facilitate scientific research and the development of specific treatment strategies, with the aim of improving the outcome of severe trauma.

Tranexamic Acid Administration During Liver Transplantation Is Not Associated With Lower Blood Loss or With Reduced Utilization of Red Blood Cell Transfusion.

BACKGROUND: Current clinical guidelines recommend antifibrinolytic treatment for liver transplantation to reduce blood loss and transfusion utilization. However, the clinical relevance of fibrinolysis during liver transplantation is questionable, a benefit of tranexamic acid (TXA) in this context is not supported by sufficient evidence, and adverse effects are also conceivable. Therefore, we tested the hypothesis that use of TXA is associated with reduced blood loss. METHODS: We performed a retrospective cohort study on patients who underwent liver transplantation between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariable and multivariable linear regression analyses were used to determine the association between TXA administration and the primary end point intraoperative blood loss and the secondary end point intra- and postoperative red blood cell (RBC) transfusions. For further secondary outcome analyses, the time to the first occurrence of a composite end point of hepatic artery thrombosis, portal vein thrombosis, and thrombosis of the inferior vena cava were analyzed using a univariable and multivariable Cox proportional hazards model. RESULTS: Data from 779 transplantations were included in the final analysis. The median intraoperative blood loss was 3000 mL (1600-5500 mL). Intraoperative TXA administration occurred in 262 patients (33.6%) with an average dose of 1.4 ± 0.7 g and was not associated with intraoperative blood loss (regression coefficient B, -0.020 [-0.051 to 0.012], P = .226) or any of the secondary end points (intraoperative RBC transfusion; regression coefficient B, 0.023 [-0.006 to 0.053], P = .116), postoperative RBC transfusion (regression coefficient B, 0.007 [-0.032 to 0.046], P = .717), and occurrence of thrombosis (hazard ratio [HR], 1.110 [0.903-1.365], P = .321). CONCLUSIONS: Our data do not support the use of TXA during liver transplantation. Physicians should exercise caution and consider individual factors when deciding whether or not to administer TXA.

[Guideline-conform treatment of sepsis]. / Leitliniengerechte Therapie der Sepsis.

The time to administration of broad-spectrum antibiotics and (secondarily) to the initiation of hemodynamic stabilization are the most important factors influencing survival of patients with sepsis and septic shock; however, the basic prerequisite for the initiation of an adequate treatment is that a suspected diagnosis of sepsis is made first. Therefore, the treatment of sepsis, even before it has begun, is an interdisciplinary and interprofessional task. This article provides an overview of the current state of the art in sepsis treatment and points towards new evidence that has the potential to change guideline recommendations in the coming years. In summary, the following points are critical: (1) sepsis must be diagnosed as soon as possible and the implementation of a source control intervention (in case of a controllable source) has to be implemented as soon as (logistically) possible. (2) In general, intravenous broad-spectrum antibiotics should be given within the first hour after diagnosis if sepsis or septic shock is suspected. In organ dysfunction without shock, where sepsis is a possible but unlikely cause, the results of focused advanced diagnostics should be awaited before a decision to give broad-spectrum antibiotics is made. If it is not clear within 3 h whether sepsis is the cause, broad-spectrum antibiotics should be given when in doubt. Administer beta-lactam antibiotics as a prolonged (or if therapeutic drug monitoring is available, continuous) infusion after an initial loading dose. (3) Combination treatment with two agents for one pathogen group should remain the exception (e.g. multidrug-resistant gram-negative pathogens). (4) In the case of doubt, the duration of anti-infective treatment should rather be shorter than longer. Procalcitonin can support the clinical decision to stop (not to start!) antibiotic treatment! (5) For fluid treatment, if hypoperfusion is present, the first (approximately) 2L (30 ml/kg BW) of crystalloid solution is usually safe and indicated. After that, the rule is: less is more! Any further fluid administration should be carefully weighed up with the help of dynamic parameters, the patient's clinical condition and echo(cardio)graphy.

Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine.

Sepsis is characterised by a dysregulated host immune response to infection. Despite recognition of its significance, immune status monitoring is not implemented in clinical practice due in part to the current absence of direct therapeutic implications. Technological advances in immunological profiling could enhance our understanding of immune dysregulation and facilitate integration into clinical practice. In this Review, we provide an overview of the current state of immune profiling in sepsis, including its use, current challenges, and opportunities for progress. We highlight the important role of immunological biomarkers in facilitating predictive enrichment in current and future treatment scenarios. We propose that multiple immune and non-immune-related parameters, including clinical and microbiological data, be integrated into diagnostic and predictive combitypes, with the aid of machine learning and artificial intelligence techniques. These combitypes could form the basis of workable algorithms to guide clinical decisions that make precision medicine in sepsis a reality and improve patient outcomes.

Extracellular Vesicles as Possible Plasma Markers and Mediators in Patients with Sepsis-Associated Delirium-A Pilot Study.

Patients with sepsis-associated delirium (SAD) show severe neurological impairment, often require an intensive care unit (ICU) stay and have a high risk of mortality. Hence, useful biomarkers for early detection of SAD are urgently needed. Extracellular vesicles (EVs) and their cargo are known to maintain normal physiology but also have been linked to numerous disease states. Here, we sought to identify differentially expressed proteins in plasma EVs from SAD patients as potential biomarkers for SAD. Plasma EVs from 11 SAD patients and 11 age-matched septic patients without delirium (non-SAD) were isolated by differential centrifugation, characterized by nanoparticle tracking analysis, transmission electron microscopy and Western blot analysis. Differential EV protein expression was determined by mass spectrometry and the resulting proteomes were characterized by Gene Ontology term and between-group statistics. As preliminary results because of the small group size, five distinct proteins showed significantly different expression pattern between SAD and non-SAD patients (p ≤ 0.05). In SAD patients, upregulated proteins included paraoxonase-1 (PON1), thrombospondin 1 (THBS1), and full fibrinogen gamma chain (FGG), whereas downregulated proteins comprised immunoglobulin (IgHV3) and complement subcomponent (C1QC). Thus, plasma EVs of SAD patients show significant changes in the expression of distinct proteins involved in immune system regulation and blood coagulation as well as in lipid metabolism in this pilot study. They might be a potential indicator for to the pathogenesis of SAD and thus warrant further examination as potential biomarkers, but further research is needed to expand on these findings in longitudinal study designs with larger samples and comprehensive polymodal data collection.

Comparison of Fluid Replacement with Sterofundin ISO® vs. Deltajonin® in Infants Undergoing Craniofacial Surgery-A Retrospective Study.

In recent decades, infusion solutions such as NaCl 0.9% and lactate Ringer's solution have been replaced in clinical practice. Since 2017, the national guidelines for perioperative infusion therapy in children recommend balanced isotonic solutions to maintain fluid balance. The composition of balanced infusion solutions varies with respect to their electrolyte content. Hyperchloremia may be mistaken for hypovolemia and may interfere with volume therapy in pediatric patients. Sterofundin ISO® balanced solution contains 127 mmol/L chloride and may cause hyperchloremic acidosis if administered in large volumes. OBJECTIVES: The purpose of this study was to compare the effects of Sterofundin ISO® (SF) therapy with the balanced isochloremic solution Deltajonin® (DJ) (106 mmol/L chloride) on the acid-base status in infants undergoing craniofacial surgery. METHODS: This retrospective, non-blinded study included 100 infants undergoing craniectomy due to isolated nonsyndromic sagittal craniosynostosis. The first 50 infants received Sterofundin ISO®. Due to changes in national guidelines, the infusion was changed to the isoionic Deltajonin® in an additional 50 infants in 2017. Pre- and postoperative values of chloride, pH, base excess, bicarbonate, and albumin and phosphate were determined, and the strong-ion difference, strong-ion gap, anion gap, and weak acids were calculated. RESULTS: Both groups were comparable in terms of their age, sex, underlying disease, preoperative electrolytes (except K at 3.9 ± 0.3 mmol/L (SF) vs. 4.1 ± 0.3 mmol/L (DJ) and lactate 8.7 ± 2.1 (SF) vs. 9.6 ± 2.6 mmol/L (DJ)). In the Sterofundin ISO® group, hyperchloremic metabolic acidosis was observed in 19 patients, whereas only 2 infants in the Deltajonin® group had hyperchloremic metabolic acidosis. The postoperative chloride level was 111 ± 2.7 mmol/L (SF) vs. 108 ± 2.4 mmol/L (DJ). The difference in anion gap was 12.5 ± 3.0 mmol/L (SF) vs. 14.6 ± 2.8 mmol/L (DJ), and the difference in SIDa (apparent strong-ion difference) was 30.9 mmol/L (SF) vs. 33.8 mmol/L (DJ). CONCLUSIONS: Hyperchloremic acidosis can be induced by the volume replacement with high-chloride-concentration crystalloids such as Sterofundin ISO®. This can be detected using the Stewart model.

Out-of-hospital cardiac arrest treated with prehospital double sequential external defibrillation during eCPR in refractory VF - a case report.

BACKGROUND: Double sequential external defibrillation (DSED) has demonstrated increased survival with good neurological outcome in a recent randomized controlled trial. DSED has not been studied in patients with extracorporeal cardiopulmonary resuscitation (eCPR). CASE: We present the first case of prehospital eCPR with ongoing refractory ventricular fibrillation (VF), terminated by DSED. After six shocks, return of spontaneous circulation was initially achieved; however, the patient went into recurrent VF. ECPR was performed prehospital, with VF still refractory after three more shocks. DSED successfully terminated VF and showed a further increase in etCO2 and near-infrared spectroscopy cerebral oximetry values. CONCLUSION: DSED can be a sufficient strategy for patients in refractory VF while on eCPR and should be evaluated in further studies.

Fibrinolytic potential as a risk factor for postpartum hemorrhage.

Background: Postpartum hemorrhage (PPH) is still the leading cause of maternal morbidity and mortality worldwide. While impaired fibrin polymerization plays a crucial role in the development and progress of PPH, recent approaches using viscoelastic measurements have failed to sensitively detect early changes in fibrinolysis in PPH. This study aimed to evaluate whether women experiencing PPH show alterations in POC-VET fibrinolytic potential during childbirth and whether fibrinolytic potential offers benefits in the prediction and treatment of PPH. Methods: Blood samples were collected at three different timepoints: T0 = hospital admission (19 h ± 18 h prepartum), T1 = 30-60 min after placental separation, and T2 = first day postpartum (19 h ± 6 h postpartum). In addition to standard laboratory tests, whole-blood impedance aggregometry (Multiplate) and viscoelastic testing (VET) were performed using the ClotPro system, which included the TPA-test lysis time, to assess the POC-VET fibrinolytic potential, and selected coagulation factors were measured. The results were correlated with blood loss and clinical outcome markers. Severe PPH was defined as a hemoglobin drop > 4g/dl and/or the occurrence of shock or the need for red blood cell transfusion. Results: Blood samples of 217 parturient women were analyzed between June 2020 and December 2020 at Heidelberg University Women's Hospital, and 206 measurements were eligible for the final analysis. Women experiencing severe PPH showed increased fibrinolytic potential already at the time of hospital admission. When compared to non-PPH, the difference persisted 30-60 min after placental separation. A higher fibrinolytic potential was accompanied by a greater drop in fibrinogen and higher d-dimer values after placental separation. While 70% of women experiencing severe PPH showed fibrinolytic potential, 54% of those without PPH showed increased fibrinolytic potential as well. Conclusion: We were able to show that antepartal and peripartal fibrinolytic potential was elevated in women experiencing severe PPH. However, several women showed high fibrinolytic potential but lacked clinical signs of PPH. The findings indicate that high fibrinolytic potential is a risk factor for the development of coagulopathy, but further conditions are required to cause PPH.

[Hemoperfusion in anesthesia and intensive care medicine: benefits, risks, and evidence for different systems]. / Hämoperfusion in Anästhesie und Intensivmedizin: Chancen, Risiken und Evidenz verschiedener Systeme.

BACKGROUND: Hemoperfusion is a technique for the extracorporeal elimination of endogenous and exogenous toxins and harmful mediators by adsorption. It can be used as a stand-alone device, as part of a heart-lung machine or extracorporeal membrane oxygenation (ECMO) or, as is currently the case, integrated into a kidney replacement procedure. In the meantime, various suppliers offer devices with different technologies. OBJECTIVE: The aim of this work was to evaluate the benefits, risks and evidence of the different systems, how they work and for which indications they are approved in Germany. METHOD: To achieve this goal, a narrative assessment of the existing literature and guidelines for different indications was performed. The focus was on in vivo studies. RESULTS: In principle, a distinction must be made in adsorption techniques between pure adsorption and the combination as adsorption and kidney replacement therapy. The adsorbers available in Germany include Cytosorb®, HA-330, Seraph®-100 and Toraymyxin. Combined procedures (adsorption and kidney replacement) are offered with coupled plasma filtration and adsorption (CPFA) and oXiris®. Most adsorbers have been developed for cytokine and endotoxin removal in patients with sepsis; however, to date, no randomized controlled trial (RCT) has demonstrated a survival benefit when using hemoperfusion. Therefore, the S3 guidelines for treatment of sepsis and the surviving sepsis campaign guidelines advise against its routine use. When the corona pandemic began, hemoperfusion was considered as a promising therapeutic approach. Cytosorb®, Seraph®-100, and oXiris® received emergency approval by the FDA to be used in critically ill patients with COVID-19, so questions arose about the appropriateness and importance of its use; however, the data generated did not show positive results, so its use cannot be recommended routinely either. In addition, they are not mentioned as a treatment option in the current guidelines. The use of adsorption procedures in patients with liver failure and rhabdomyolysis has only been rudimentarily studied, so any evidence is currently lacking. The only adsorber that has CE approval in Germany for both applications is Cytosorb®. In the next few years, studies will have to follow that investigate the efficacy and thus either justify or refute the use in clinical routine. Hemoperfusion procedures are used in the heart-lung machine as part of cardiac surgery for either cytokine or anticoagulant adsorption. No congruent data are available to support the use for the elimination of cytokines. If emergency cardiac surgery is required in a patient with pre-existing anticoagulation, hemoperfusion procedures can be used to prevent bleeding complications. Cytosorb® has CE approval for this indication. All available techniques are nonselective adsorption processes, so that adsorption of known and unknown substances can occur. Unintentional adsorption of drugs, such as various anti-infective agents is a relevant risk, especially when used in patients with sepsis. DISCUSSION: Various adsorption systems can eliminate different known and unknown substances. Currently, there is a lack of evidence for all indications and systems to justify their routine use except in clinical trials. Future clinical trials should evaluate the potential benefits but also dangers, so that in the meantime the routine use can be justified or a recommendation against the use can be given.

Out-of-hospital cardiac arrest in children: an epidemiological study based on the German Resuscitation Registry identifying modifiable factors for return of spontaneous circulation.

AIM: This work provides an epidemiological overview of out-of-hospital cardiac arrest (OHCA) in children in Germany between 2007 and 2021. We wanted to identify modifiable factors associated with survival. METHODS: Data from the German Resuscitation Registry (GRR) were used, and we included patients registered between 1st January 2007 and 31st December 2021. We included children aged between > 7 days and 17 years, where cardiopulmonary resuscitation (CPR) was started, and treatment was continued by emergency medical services (EMS). Incidences and descriptive analyses are presented for the overall cohort and each age group. Multivariate binary logistic regression was performed on the whole cohort to determine the influence of (1) CPR with/without ventilation started by bystander, (2) OHCA witnessed status and (3) night-time on the outcome hospital admission with return of spontaneous circulation (ROSC). RESULTS: OHCA in children aged < 1 year had the highest incidence of the same age group, with 23.42 per 100 000. Overall, hypoxia was the leading presumed cause of OHCA, whereas trauma and drowning accounted for a high proportion in children aged > 1 year. Bystander-witnessed OHCA and bystander CPR rate were highest in children aged 1-4 years, with 43.9% and 62.3%, respectively. In reference to EMS-started CPR, bystander CPR with ventilation were associated with an increased odds ratio for ROSC at hospital admission after adjusting for age, sex, year of OHCA and location of OHCA. CONCLUSION: This study provides an epidemiological overview of OHCA in children in Germany and identifies bystander CPR with ventilation as one primary factor for survival. Trial registrations German Clinical Trial Register: DRKS00030989, December 28th 2022.