Nociceptive Flexion Reflex Threshold is No Suitable Marker for Diagnosing Opioid-Induced Hyperalgesia.

Background: Opioid induced hyperalgesia (OIH) describes a state of altered pain sensation due to opioid exposure. It often occurs among persons with opioid use disorder receiving substitution therapy. Methods: The purpose of this study was to find out, whether OIH diagnosis could be facilitated by an objective pain indicating marker: the Nociceptive Flexion Reflex (NFR). Forty persons with opioid use disorder, 20 of them maintained on methadone and 20 treated with buprenorphine, as well as a control group of 20 opioid-free subjects, were examined. It was aimed to find out whether and in which way these opioid agonists alter reflex threshold (NFR-T). A cold-pressor test was performed to investigate the prevalence of OIH. Furthermore, electrical stimulation and electromyography analyzation were used for NFR-T measurement. Subjective pain ratings were evaluated with a numeric rating scale. Results: Significantly increased sensitivity to cold pressor pain was found in both maintenance groups when compared to their opioid-free counterparts (p < 0.001). Neither methadone nor buprenorphine showed any effect on NFR-T. This might be explained by the reflex approaching at the wrong location in the central nervous system. Consequently, NFR-T is not a suitable marker for diagnosing OIH. Conclusion: Although methadone and buprenorphine have been proven to cause OIH, no effect on NFR-T was observed. A statistically significant effect could have been observed with a larger number of participants. Further research, with special focus on patients' adjuvant medication, should be conducted in the future, to facilitate diagnosis of OIH and provide appropriate pain management for maintenance patients.

Determination of glomerular filtration rate "en passant" after high doses of iohexol for computed tomography in intensive care medicine-a proof of concept.

Accurate assessment of renal function is of great clinical and scientific importance, as it is an important pharmacokinetic covariate of pivotal drugs. The iohexol clearance is nearly identical to the glomerular filtration rate, but its determination usually requires an intravenous injection and therefore bears intrinsic risks. This motivates to showcase an "en passant" approach to quantification of renal function without additional risk or blood sampling beyond routine care using real-world data. We enrolled 37 intensive care patients who received high doses of iohexol for computed tomography imaging, and quantified series of iohexol plasma concentrations by high-performance liquid chromatography (HPLC-UV). Iohexol clearance was derived by both log-linear regression and nonlinear least squares fitting and compared to glomerular filtration rate estimated by the CKD-EPI-2021 formulas. Nonlinear fitting not only turned out to be more accurate but also more robust in handling the irregularly timed data points. Concordance of iohexol clearance against estimations based on both creatinine and cystatin C showed a slightly higher bias (-3.44 mL/min/1.73 m2) compared to estimations based on creatinine alone (-0.76 mL/min/1.73 m2), but considerably narrower limits of agreement (±42.8 vs. 56 mL/min/1.73 m2) and higher Lin's correlation (0.84 vs. 0.72). In summary, we have demonstrated the feasibility and performance of the "en passant" variant of the iohexol method in intensive care medicine and described a working protocol for its application in clinical practice and pharmacologic studies.

Over-expression of cFos by the Transcription Factors NFATc2 and Sp1 in Pancreatic Cancer Cells.

BACKGROUND/AIM: The transcription factors NFATc2 and Sp1 play a key role in the progression of pancreatic cancer because they interact inside the cells and exert their carcinogenic effect through transcriptional modification. Drugs can also induce a variety of oncogenic signalling cascades. The risk of tumour progression and metastasis seems to be significantly increased in the perioperative period. Our research group has previously demonstrated the function of the interaction between NFATc2 and Sp1 in pancreatic cancer and has identified the proto-oncogene cFos as a target gene. We also found that the anaesthetic drug propofol has anti-tumour properties. The aim of the present study was to investigate the effect of propofol on the expression of the transcription factors NFATc2, Sp1 and cFos in the pancreatic cancer cell lines PaTu 8988t and PANC-1 and to analyse the relevance of this effect for the cells. MATERIALS AND METHODS: Stimulation with propofol and its effects on the expression of NFATc2, Sp1 and cFos were assessed by immunoblot. Cell cycle distribution was analysed by flow cytometry, and cell proliferation was measured with the ELISA BrdU assay. Propofol and siRNA against cFos were used for stimulation. RESULTS: Propofol regulated the expression of NFATc2, Sp1 and cFos. Stimulation with 250 µM or 500 µM propofol decreased NFATc2, Sp1 and cFos signalling in the Western blot analysis. At the same time, propofol significantly inhibited proliferation and activated cell cycle. The same proliferation behaviour was observed after transient cFos inhibition. These effects were potentiated by simultaneous stimulation with propofol and transient inhibition of cFos, further inhibiting cell proliferation. Interestingly, the cell cycle activation observed after stimulation with propofol alone was reversed in both cell lines. CONCLUSION: Anaesthetists only see oncological patients in a short time window. However, the perioperative period is increasingly recognised as a very vulnerable time with a major impact on tumour progression. Further studies are needed to identify the underlying mechanisms and to verify their clinical relevance, especially in anaesthesia.

Effect of NFATc2- and Sp1-mediated TNFalpha Regulation on the Proliferation and Migration Behavior of Pancreatic Cancer Cells.

BACKGROUND/AIM: One in two people will develop a tumor during their lifetime. Adenocarcinoma of the pancreas is one of the most aggressive types of cancer in humans with very poor long-term survival. A central role in the carcinogenesis of pancreatic cancer has been attributed to NFAT transcription factors. Previous studies have identified the transcription factor Sp1 as a binding partner of NFATc2 in pancreatic cancer. Using expression profile analysis, our group was able to identify the tumor necrosis factor TNFalpha as a target gene of the interaction between NFATc2 and Sp1. The present study investigated the effect of TNFalpha over-expression via the transcription factors NFATc2 and Sp1 on the pancreatic cancer cell lines PaTu 8988t and PANC-1. MATERIALS AND METHODS: Transient transfection of NFATc2, Sp1, and TNFalpha siRNAs and their effects on the expression were investigated with immunoblot. Cell proliferation was measured with the ELISA BrdU assay. Cell migration was assayed with a Cell Migration Assay Kit using a Boyden chamber. RESULTS: Inhibition of the transfection factors NFATc2, Sp1, or TNFalpha by siRNA significantly inhibited proliferation, which was exacerbated when using the combination of NFATc2 and Sp1. TNFalpha was able to counterbalance this effect. In contrast to proliferation, migration of pancreatic cancer cells was increased by inhibiting these transfection factors. CONCLUSION: Tumor progression is strongly influenced by transcriptional changes in signaling cascades and oncogene mutations as well as by changes in tumor suppressor genes. Further studies are needed to understand the underlying mechanisms of these processes.

Intraoperative suggestions to prevent postoperative delirium in patients undergoing transaortic valvular replacement: a randomized placebo-controlled trial.

BACKGROUND: Postoperative delirium (POD) is a serious complication following anaesthesia and surgery and significantly influences postoperative outcome especially in the elderly population. Intraoperative music and positive suggestions influence postoperative outcomes by attenuating analgesic demand and increasing patient satisfaction. AIMS: Here, we examined the effect of intraoperative music and positive suggestions on the development of POD in aged patients undergoing transcatheter aortic valve replacement (TAVR) procedure under general anaesthesia. METHODS: For this randomized placebo-controlled study, eligible patients without cognitive deficit, indicated by a MMSE < 10 points, were anesthetized using remifentanil and sevoflurane. Anaesthetic depth was guide with bispectral index. An audiotape with positive suggestions was applied from a MP3 player via headphones. POD, pain and PONV was assessed. CAM-ICU and Nu-DESC were done twice daily for the first 5 days. RESULTS: Of 140 patients 118 patients could be analysed (57 male, 80.6 ± 5.1 years). POD was diagnosed in 16 patients (12.7%). POD was significantly more often observed in male (12, 21.1%) than in female (4, 6.6%, p = 0.02) and in patients with a low MMSE (23.6 ± 4.5 vs. 26.8 ± 2.8, p = 0.001). Anaesthetic depth did not influence the incidence of POD. Intraoperative music and suggestions did not affect the rate of POD, pain, analgesic requirement or PONV. DISCUSSION: In patients undergoing TAVR male sex and low MMSE scoring are associated with an increase in POD. CONCLUSIONS: Intraoperative music and positive suggestions do not influence the incidence of POD in this patient group. STUDY REGISTRATION: DRKS: 00024444, start of registration: 4.02.202, final registration: 17.09.2021.

Prognostic factors for favorable outcomes after veno-venous extracorporeal membrane oxygenation in critical care patients with COVID-19.

BACKGROUND: Patients with COVID-19 and severe acute respiratory failure may require veno-venous extracorporeal membrane oxygenation (VV ECMO). Yet, this procedure is resource-intensive and high mortality rates have been reported. Thus, predictors for identifying patients who will benefit from VV ECMO would be helpful. METHODS: This retrospective study included 129 patients with COVID-19 and severe acute respiratory failure, who had received VV ECMO at the University Medical Center Regensburg, Germany, between 1 March 2020 and 31 December 2021. Patient-specific factors and relevant intensive-care parameters at the time of the decision to start VV ECMO were investigated regarding their value as predictors of patient survival. In addition, the intensive-care course of the first 10 days of VV ECMO was compared between survivors and patients who had died in the intensive care unit. RESULTS: The most important parameters for predicting outcome were patient age and platelet count, which differed significantly between survivors and non-survivors (age: 52.6±8.1 vs. 57.4±10.1 years, p<0.001; platelet count before VV ECMO: 321.3±132.2 vs. 262.0±121.0 /nL, p = 0.006; average on day 10: 199.2±88.0 vs. 147.1±57.9 /nL, p = 0.002). A linear regression model derived from parameters collected before the start of VV ECMO only included age and platelet count. Patients were divided into two groups by using receiver operating characteristics (ROC) analysis: group 1: 78% of patients, mortality 26%; group 2: 22% of patients, mortality 75%. A second linear regression model included average blood pH, minimum paO2, and average pump flow on day 10 of VV ECMO in addition to age and platelet count. The ROC curve resulted in two cut-off values and thus in three groups: group 1: 25% of patients, mortality 93%; group 2: 45% of patients, mortality 31%; group 3: 30% of patients, mortality 0%.

Effect of Propofol and Etomidate on the Proliferation, Cell-cycle Distribution, Apoptosis and Necrosis of Pancreatic Tumour Cells.

BACKGROUND/AIM: The influence of surgical interventions and anaesthesiological procedures on tumour progression was investigated as early as the 1920s. In current cancer management, the perioperative phase is increasingly being considered a vulnerable period with an increased risk of tumour cell dissemination due to medication, surgical manipulation, and immunosuppression. The extent to which narcotics administered in the perioperative setting influence the oncological outcomes of patients with pancreatic cancer is still unclear. MATERIALS AND METHODS: To investigate the effect of propofol and etomidate on the proliferation, cell-cycle distribution, apoptosis, and necrosis of pancreatic tumour cells in vitro, PaTu 8988t and Panc-1 pancreatic cancer cells were treated with 0-1,000 µM propofol or etomidate for 24 h each. Cell proliferation was measured with enzyme-linked immunosorbent-bromodeoxyuridine assay. The apoptosis rate was analysed with annexin V staining and the cell-cycle distribution with flow cytometry. RESULTS: Propofol at 1,000 µM induced apoptosis and inhibited cell proliferation. The cell cycle showed an increased S-phase and reduced cells in the G1-phase. At 100 µM, propofol significantly inhibited proliferation of the pancreatic cancer cell line PaTu 8988t and reduced cells in the G2-phase in the cell cycle. Etomidate had no effects on cell-cycle distribution, proliferation, apoptosis, and necrosis at the concentrations used. CONCLUSION: In this study, propofol was shown to have anticancer effects by induction of apoptosis and inhibition of cell proliferation, while etomidate did not affect pancreatic cancer cells. However, it is too early to make any recommendation for changes in clinical practice and further clinical studies are warranted to investigate the effect of anaesthetics on cancer progression.

Evaluation of models for prognosing mortality in critical care patients with COVID-19: First- and second-wave data from a German university hospital.

BACKGROUND: In a previous study, we had investigated the intensive care course of patients with coronavirus disease 2019 (COVID-19) in the first wave in Germany by calculating models for prognosticating in-hospital death with univariable and multivariable regression analysis. This study analyzed if these models were also applicable to patients with COVID-19 in the second wave. METHODS: This retrospective cohort study included 98 critical care patients with COVID-19, who had been treated at the University Medical Center Regensburg, Germany, between October 2020 and February 2021. Data collected for each patient included vital signs, dosage of catecholamines, analgosedation, anticoagulation, and antithrombotic medication, diagnostic blood tests, treatment with extracorporeal membrane oxygenation (ECMO), intensive care scores, ventilator therapy, and pulmonary gas exchange. Using these data, expected mortality was calculated by means of the originally developed mathematical models, thereby testing the models for their applicability to patients in the second wave. RESULTS: Mortality in the second-wave cohort did not significantly differ from that in the first-wave cohort (41.8% vs. 32.2%, p = 0.151). As in our previous study, individual parameters such as pH of blood or mean arterial pressure (MAP) differed significantly between survivors and non-survivors. In contrast to our previous study, however, survivors and non-survivors in this study showed significant or even highly significant differences in pulmonary gas exchange and ventilator therapy (e.g. mean and minimum values for oxygen saturation and partial pressure of oxygen, mean values for the fraction of inspired oxygen, positive expiratory pressure, tidal volume, and oxygenation ratio). ECMO therapy was more frequently administered than in the first-wave cohort. Calculations of expected mortality by means of the originally developed univariable and multivariable models showed that the use of simple cut-off values for pH, MAP, troponin, or combinations of these parameters resulted in correctly estimated outcome in approximately 75% of patients without ECMO therapy.

The Effects of Analgesics on the Migration of Pancreatic Cancer Cells.

BACKGROUND/AIM: Adenocarcinoma of the pancreas is one of the most aggressive malignant diseases in humans. Characteristics of this tumour type are poor response to radiotherapy and chemotherapeutic agents as well as metastasis in the absence of an organ capsule. The best therapeutic option is surgical removal of the tumour followed by chemotherapy or radiotherapy. Yet, even after surgical R0-resection, the 5-year survival probability is only about 20% because of the high recurrence rate of this tumour and complications due to metastases. Furthermore, recent studies have shown that the perioperative period is a particularly vulnerable phase, during which tumour progression and metastasis may be facilitated. The effects of analgesics administered during the perioperative period are still unknown. The present work investigated the effects of analgesics on pancreatic cancer cell migration in vitro. MATERIALS AND METHODS: The migratory potential of pancreatic cancer cells was analysed using a Cell Migration Assay Kit with a Boyden chamber, in which cells migrate through a semi-permeable membrane under different stimuli. Cell concentration was measured by reading fluorescence (Ex/Em=530/590 nm) in a plate reader. RESULTS: Migration in PANC-1 pancreatic cancer cells was significantly decreased after 24 h stimulation with 100 µM of ropivacaine, 100 nM of sufentanil, 1,000 µM of ropivacaine and 1,000 nM of sufentanil. In the PaTu 8988t cell line, incubation with 10 µM of ropivacaine caused a slight but statistically significant increase in migration, whereas lidocaine, metamizole and paracetamol did not significantly affect migration. CONCLUSION: The risk of tumour progression and metastasis seems to be increased during major oncological surgical interventions. The recent advances in the molecular and biological understanding of pathogenesis of pancreatic cancer have not yet significantly improved patient outcome. Therefore, further studies are needed to identify the underlying mechanisms of this aggressive tumour and establish new therapeutic options for the future.

[Management of COVID-19 mass casualty incidents in nursing and retirement homes]. / Managementstrategie für den Massenanfall von Erkrankten/Infizierten in Alten- und Pflegeheimen im Kontext der COVID-19-Pandemie.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, outbreaks in inpatient care facilities, which grow into a large-scale emergency scenario, are frequently observed. A standardized procedure analogous to algorithms for mass casualty incidents (MCI) is lacking. METHODS: Based on a case report and the literature, the authors present a management strategy for infectious MCI during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and distinguish it from traumatic MCI deployment tactics. RESULTS: This management strategy can be divided into three phases, beginning with the acute emergency response including triage, stabilization of critical patients, and transport of patients requiring hospitalization. Phase 2 involves securing the facility's operational readiness, or housing residents elsewhere in case staff are infected or quarantined to a relevant degree. Phase 3 marks the return to regular operations. DISCUSSION: Phase 1 is based on usual MCI principles, phase 2 on hospital crisis management. Avoiding evacuation of residents to relieve hospitals is an important operational objective. The lack of mission and training experience with such situations, the limited applicability of established triage algorithms, and the need to coordinate a large number of participants pose challenges. CONCLUSION: This strategic model offers a practical, holistic approach to the management of infectious mass casualty scenarios in nursing facilities.

Contribution of High Viral Loads, Detection of Viral Antigen and Seroconversion to Severe Acute Respiratory Syndrome Coronavirus 2 Infectivity.

BACKGROUND: From a public health perspective, effective containment strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be balanced with individual liberties. METHODS: We collected 79 respiratory samples from 59 patients monitored in an outpatient center or in the intensive care unit of the University Hospital Regensburg. We analyzed viral load by quantitative real-time polymerase chain reaction, viral antigen by point-of-care assay, time since onset of symptoms, and the presence of SARS-CoV-2 immunoglobulin G (IgG) antibodies in the context of virus isolation from respiratory specimens. RESULTS: The odds ratio for virus isolation increased 1.9-fold for each log10 level of SARS-CoV-2 RNA and 7.4-fold with detection of viral antigen, while it decreased 6.3-fold beyond 10 days of symptoms and 20.0-fold with the presence of SARS-CoV-2 antibodies. The latter was confirmed for B.1.1.7 strains. The positive predictive value for virus isolation was 60.0% for viral loads >107 RNA copies/mL and 50.0% for the presence of viral antigen. Symptom onset before 10 days and seroconversion predicted lack of infectivity with negative predictive values of 93.8% and 96.0%. CONCLUSIONS: Our data support quarantining patients with high viral load and detection of viral antigen and lifting restrictive measures with increasing time to symptom onset and seroconversion. Delay of antibody formation may prolong infectivity.

Effects of Ketamine, S-Ketamine and MK 801 on Integrin Beta-3-mediated Cell Migration in Pancreatic Carcinoma.

Introduction: Pancreatic ductal adenocarcinoma is one of the most aggressive malignancies in humans. The main reason for its unfavourable prognosis is the combination of rapid tumour growth, early-onset metastasis and currently still inadequate diagnostic and therapeutic options. Thus, only very few patients are eligible for radical resection of the primary tumour as the only curative treatment option available so far. In the perioperative period, tumour progression and metastasis are facilitated by the activation of key signalling pathways and the altered regulation of transcription factors. Various tumour entities have shown increased expression of the integrin-3 receptor subunit, which correlates with more rapid tumour progression and metastasis through advanced migration, invasion and proliferation. The influence of perioperative medication and postoperative pain management remains unclear. To investigate the effects of ketamine, s-ketamine and MK 801 on integrin beta-3-mediated cell migration in pancreatic cancer cells in vitro. Methods: The effects of ketamine, s-ketamine and MK 801 on integrin beta-3 expression were investigated with immunoblot. Cell migratory potentials were analysed using a Cell Migration Assay Kit with a Boyden chamber, in which cells migrate through a semipermeable membrane under different stimuli. Results: Stimulation with ketamine and MK 801 significantly promoted migration in pancreatic cancer cells, increasing the expression of integrin beta-3. Conclusion: Novel therapeutic approaches target the effective modulation of specific signalling and transcription pathways. The prerequisite for such 'target therapies' is comprehensive knowledge about the respective carcinogenesis. Further studies are required to identify the underlying disease mechanisms of pancreatic carcinoma.

Renal Recovery after the Implementation of an Electronic Alert and Biomarker-Guided Kidney-Protection Strategy following Major Surgery.

Background: The facilitation of early recovery of acute kidney injury (AKI) is an important step to improve outcome, particularly because of the limited therapeutic interventions currently available for AKI. The combination of an electronic alert and biomarker-guided kidney-protection strategy implemented in the routine care may have an impact on the incidence of early complete reversal of AKI after major non-cardiac surgery. Methods: We studied 294 patients in two cohorts before (n = 151) and after protocol implementation (n = 143). Data collection required 6 months for each cohort. The kidney-protection protocol included an electronic alert to detect patients who were eligible for urinary biomarker [TIMP2 × IGFBP7]-guided kidney-protection intervention. Intervention was stratified according to three levels of immediate AKI risk: low, moderate, and high. After intervention, postoperative changes in the glomerular filtration rate (eGFR) were identified with a tracking software that included an alert for nephrology consultation if the eGFR had declined by >25% from the preoperative reference value. Primary outcome was early AKI recovery, i.e., the complete reversal of any AKI stage to absence of AKI within the first 7 postoperative days. Results: Protocol implementation significantly increased the recovery of AKI (36/46, 78% compared to control 27/48, 56%, (p = 0.025)) and reduced the length of the ICU stay (p < 0.001). There was no significant difference in the overall incidence of all AKI and moderate and severe AKI in the first 7 postoperative days: 46/143 (32%) and 12/151 (8%) in the protocol implementation group compared to 48/151 (32%) and 18/151 (12%) in the historical control group. Patients with AKI reversal within the first 7 postoperative days had lower in-hospital mortality than patients without AKI reversal. Conclusions: Implementing a combined electronic alert and biomarker-guided kidney-protection strategy in routine care improved early recovery of AKI after major surgery.

Metabolic imbalance of T cells in COVID-19 is hallmarked by basigin and mitigated by dexamethasone.

Metabolic pathways regulate immune responses and disrupted metabolism leads to immune dysfunction and disease. Coronavirus disease 2019 (COVID-19) is driven by imbalanced immune responses, yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 87 patients with confirmed SARS-CoV-2 infection, 6 critically ill non-COVID-19 patients, and 47 uninfected controls, we found an immunometabolic dysregulation in patients with progressed COVID-19. Specifically, T cells, monocytes, and granulocytes exhibited increased mitochondrial mass, yet only T cells accumulated intracellular reactive oxygen species (ROS), were metabolically quiescent, and showed a disrupted mitochondrial architecture. During recovery, T cell ROS decreased to match the uninfected controls. Transcriptionally, T cells from severe/critical COVID-19 patients showed an induction of ROS-responsive genes as well as genes related to mitochondrial function and the basigin network. Basigin (CD147) ligands cyclophilin A and the SARS-CoV-2 spike protein triggered ROS production in T cells in vitro. In line with this, only PCR-positive patients showed increased ROS levels. Dexamethasone treatment resulted in a downregulation of ROS in vitro and T cells from dexamethasone-treated patients exhibited low ROS and basigin levels. This was reflected by changes in the transcriptional landscape. Our findings provide evidence of an immunometabolic dysregulation in COVID-19 that can be mitigated by dexamethasone treatment.

Brain multimodality monitoring in patients suffering from acute aneurysmal subarachnoid hemorrhage: clinical value and complications.

Brain multimodality monitoring measuring brain tissue oxygen pressure, cerebral blood flow, and cerebral near-infrared spectroscopy may help optimize the neurocritical care of patients with aneurysmal subarachnoid hemorrhage and delayed cerebral ischemia. We retrospectively looked for complications associated with the placement of the probes and checked the reliability of the different tools used for multimodality monitoring. In addition, we screened for therapeutic measures derived in cases of pathological values in multimodality monitoring in 26 patients with acute aneurysmal subarachnoid hemorrhage. Computed tomography scans showed minor hemorrhage along with the probes in 12 patients (46.2%). Missing transmission of values was observed in 34.1% of the intended time of measurement for cerebral blood flow probes and 15.5% and 16.2%, respectively, for the two kinds of probes measuring brain tissue oxygen pressure. We identified 744 cumulative alarming values transmitted from multimodality monitoring. The most frequent intervention was modifying minute ventilation (29%). Less frequent interventions were escalating the norepinephrine dosage (19.9%), elevating cerebral perfusion pressure (14.9%) or inspiratory fraction of inspired oxygen (7.5%), transfusing red blood cell concentrates (1.2%), initiating further diagnostics (2.3%) and neurosurgical interventions (1.9%). As well, 355 cases of pathological values had no therapeutic consequence. The reliability of the measuring tools for multimodality monitoring regarding a continuous transmission of values must be improved, particularly for cerebral blood flow monitoring. The overall high rate of missing therapeutic responses to pathological values derived from multimodality monitoring in patients with aneurysmal subarachnoid hemorrhage underlines the need for structured tiered algorithms. In addition, such algorithms are the basic requirement for prospective multicenter studies, which are urgently needed to evaluate the role of multimodality monitoring in treating these patients.

Reliability of prognostic biomarkers after prehospital extracorporeal cardiopulmonary resuscitation with target temperature management.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) performed at the emergency scene in out-of-hospital cardiac arrest (OHCA) can minimize low-flow time. Target temperature management (TTM) after cardiac arrest can improve neurological outcome. A combination of ECPR and TTM, both implemented as soon as possible on scene, appears to have promising results in OHCA. To date, it is still unknown whether the implementation of TTM and ECPR on scene affects the time course and value of neurological biomarkers. METHODS: 69 ECPR patients were examined in this study. Blood samples were collected between 1 and 72 h after ECPR and analyzed for S100, neuron-specific enolase (NSE), lactate, D-dimers and interleukin 6 (IL6). Cerebral performance category (CPC) scores were used to assess neurological outcome after ECPR upon hospital discharge. Resuscitation data were extracted from the Regensburg extracorporeal membrane oxygenation database and all data were analyzed by a statistician. The data were analyzed using non-parametric methods. Diagnostic accuracy of biomarkers was determined by area under the curve (AUC) analysis. Results were compared to the relevant literature. RESULTS: Non-hypoxic origin of cardiac arrest, manual chest compression until ECPR, a short low-flow time until ECPR initiation, low body mass index (BMI) and only a minimal need of extra-corporeal membrane oxygenation support were associated with a good neurological outcome after ECPR. Survivors with good neurological outcome had significantly lower lactate, IL6, D-dimer, and NSE values and demonstrated a rapid decrease in the initial S100 value compared to non-survivors. CONCLUSIONS: A short low-flow time until ECPR initiation is important for a good neurological outcome. Hypoxia-induced cardiac arrest has a high mortality rate even when ECPR and TTM are performed at the emergency scene. ECPR patients with a higher BMI had a worse neurological outcome than patients with a normal BMI. The prognostic biomarkers S100, NSE, lactate, D-dimers and IL6 were reliable indicators of neurological outcome when ECPR and TTM were performed at the emergency scene.

Lower blood pH as a strong prognostic factor for fatal outcomes in critically ill COVID-19 patients at an intensive care unit: A multivariable analysis.

BACKGROUND: Data of critically ill COVID-19 patients are being evaluated worldwide, not only to understand the various aspects of the disease and to refine treatment strategies but also to improve clinical decision-making. For clinical decision-making in particular, prognostic factors of a lethal course of the disease would be highly relevant. METHODS: In this retrospective cohort study, we analyzed the first 59 adult critically ill Covid-19 patients treated in one of the intensive care units of the University Medical Center Regensburg, Germany. Using uni- and multivariable regression models, we extracted a set of parameters that allowed for prognosing in-hospital mortality. RESULTS: Within the cohort, 19 patients died (mortality 32.2%). Blood pH value, mean arterial pressure, base excess, troponin, and procalcitonin were identified as highly significant prognostic factors of in-hospital mortality. However, no significant differences were found for other parameters expected to be relevant prognostic factors, like low arterial partial pressure of oxygen or high lactate levels. In the multivariable logistic regression analysis, the pH value and the mean arterial pressure turned out to be the most influential prognostic factors for a lethal course.