β1-blocker in sepsis. Hasegawa Daisuke,Sato Ryota,Nishida Osamu Journal of intensive care BACKGROUND:The use of ultrashort-acting β1-blockers recently has attracted attention in septic patients with non-compensatory tachycardia. We summarized the metabolic and hemodynamic effects and the clinical evidence of ultrashort-acting β1-blockers. MAIN BODY:A recent meta-analysis showed that ultrashort-acting β1-blockers reduced the mortality in septic patients with persistent tachycardia. However, its mechanism to improve mortality is not fully understood yet. We often use lactate as a marker of oxygen delivery, but an impaired oxygen use rather than reduced oxygen delivery has been recently proposed as a more reasonable explanation of hyperlactatemia in patients with sepsis, leading to a question of whether β1-blockers affect metabolic systems. While the stimulation of the β2-receptor accelerates glycolysis and lactate production, the role of β1-blocker in lactate production remains unclear and studies investigating the role of β1-blockers in lactate kinetics are warranted. A meta-analysis also reported that ultrashort-acting β1-blockers increased stroke volume index, while it reduced heart rate, resulting in unchanged cardiac index, mean arterial pressure, and norepinephrine requirement at 24 h, leading to an improvement of cardiovascular efficiency. On the other hand, a recent study reported that heart rate reduction using fast esmolol titration in the very early phase of septic shock caused hemodynamic instability, suggesting that ultrashort-acting β1-blockers should be started only after completing initial resuscitation. While many clinicians still do not feel comfortable controlling sinus tachycardia, one randomized controlled trial in which the majority had sinus tachycardia suggested the mortality benefit of ultrashort-acting β1-blockers. Therefore, it still deems to be reasonable to control sinus tachycardia with ultrashort-acting β1-blockers after completing initial resuscitation. CONCLUSION:Accumulating evidence is supporting the use of ultrashort-acting β1-blockers while larger randomized controlled trials to clarify the effect of ultrashort-acting β1-blockers are still warranted. 10.1186/s40560-021-00552-w
    The current evidence for the treatment of sepsis with Xuebijing injection: Bioactive constituents, findings of clinical studies and potential mechanisms. Li Chengyu,Wang Ping,Li Min,Zheng Rui,Chen Shiqi,Liu Si,Feng Zhiqiao,Yao Yongming,Shang Hongcai Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Xuebijing (XBJ) injection is a Chinese medicine containing extracts from Carthamus tinctorius L. (Carthami Flos, hong hua, Asteraceae), Paeonia lactiflora Pall. (Paeoniae radix rubra, chi shao, Ranunculaceae), Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma, chuan xiong, Umbelliferae), Salvia miltiorrhiza Bge. (Salviae miltiorrhizae Radix Et Rhizoma, dan shen, Labiatae) and Angelica sinensis (Oliv.) Diels (Angelicae sinensis Radix, dang gui, Umbelliferae). It has been approved for the treatment of sepsis in China since 2004 and has been widely used as an add-on treatment for sepsis or septic shock with few side effects. AIM OF THE STUDY:The aim of the present review was to analyse up-to-date information related to the treatment of sepsis with XBJ, including the bioactive constituents, clinical studies and potential mechanisms, and to discuss possible scientific gaps, to provide a reliable reference for future studies. MATERIALS AND METHODS:Scientific resources concentrating on treating sepsis with XBJ were searched through PubMed, the Chinese National Knowledge Infrastructure (CNKI) and WanFang databases from inception to November 2018. Dissertations were also searched, and eligible dissertations were selected. Studies related to the identification of constituents, bioactive components and their targets of action or pathways, clinical trials, and animal or cellular experiments that explored pharmacological mechanisms were manually selected. The quality of reporting and methodology of the included pharmacological experiments were assessed using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines and the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)'s risk of bias tool. RESULTS:A total of 108 relative studies were eventually included, containing 12 bioactivity research studies, 10 systematic reviews on clinical trials and 86 animal or cellular experiments. We noted that as identification methods progressed, further constituents could be detected in XBJ. XBJ was also found to have "multi-ingredient, multi-target and multi-pathway" effects. The systematic review revealed that XBJ could improve the 28-day mortality and other indexes, such as the APACHE II score, body temperature, and white blood cell (WBC) count, to some extent. A major organ protection effect was demonstrated in septic rats. Pharmacological investigations suggested that XBJ acts in both the early and late stages of sepsis by anti-inflammatory, anti-coagulation, immune regulation, vascular endothelial protection, anti-oxidative stress and other mechanisms. However, most of the included studies were poorly reported, and the risk of bias was unclear. CONCLUSIONS:With respect to the multiple therapeutic mechanisms contributing to both the early and late stages of sepsis, the multiple effective constituents detected and randomized controlled trials (RCTs) performed to prove its efficacy, XBJ is a promising therapy for the treatment of sepsis. However, although XBJ has shown some efficacy for the treatment of sepsis, there are currently some scientific gaps. More studies concerning the pharmacokinetics, interactions with antibiotics, real-world efficacy and safety, pharmacological mechanisms of the bioactive components and large-scale clinical trials should be conducted in the future. 10.1016/j.jep.2020.113301
    Effect of nurse-led, goal-directed lung physiotherapy on prognosis of patients with sepsis caused by Acinetobacter baumannii pulmonary infection. Chen Jianwei,Zhou Runshi,Li Zunzhu,Li Qi,Long Yun,Wang Hao,Cui Na International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases OBJECTIVES:To investigate the role of nurse-led, goal-directed lung physiotherapy on the prognosis of patients with sepsis caused by Acinetobacter baumannii pulmonary infection. METHODS:Patients with sepsis caused by A. baumannii pulmonary infection were recruited and divided into a control group (phase 1) and a treatment group (phase 2). Both groups received standard therapy for sepsis, and patients in phase 2 also received nurse-led, goal-directed lung physiotherapy. The primary outcome measure was 28-day mortality. RESULTS:Among 742 patients with sepsis, 201 were diagnosed with A. baumannii pulmonary infection. Compared with patients in phase 1, patients in phase 2 had a significantly shorter duration of mechanical ventilation {median 4 (interquartile range (IQR) 3-5] vs 5 (IQR 3-12) days; P = 0.004}, lower intensive care unit (ICU) mortality [13.6% (18/132) vs 27.5% (19/69); P = 0.016] and lower 28-day mortality [21.2% (28/132) vs 37.7% (26/69); P = 0.012]. As a protective factor, nurse-led, goal-directed lung physiotherapy (odds ratio 0.341, 95% confidence interval 0.155-0.751; P = 0.008) was an independent risk factor for 28-day mortality. CONCLUSIONS:Nurse-led, goal-directed lung physiotherapy shortened the duration of mechanical ventilation and ICU stay, and decreased ICU mortality and 28-day mortality in patients with sepsis caused by A. baumannii pulmonary infection. 10.1016/j.ijid.2020.11.196
    The cellular basis of organ failure in sepsis-signaling during damage and repair processes. Bauer M,Wetzker R Medizinische Klinik, Intensivmedizin und Notfallmedizin Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. This definition, updated in 2016, shifted the conceptual focus from exclusive attention to the systemic inflammatory response toward the multifactorial tissue damage that occurs during the progression of infection to sepsis and shock. Whereas targeting the inflammatory host response to infection did not translate into improved clinical management of sepsis, recent findings might shed new light on the maladaptive host-pathogen interaction in sepsis and pave the way for "theranostic" interventions. In addition to the well-known resistance responses of the immune system that result in pathogen clearance, "disease tolerance" has recently been acknowledged as a coping mechanism of presumably equal importance. We propose that both defense mechanisms, "resistance" and "disease tolerance", can get out of control in sepsis. Whereas excessive activation of resistance pathways propagates tissue damage via immunopathology, an inappropriate "tolerance" might entail immunoparalysis accompanied by fulminant, recurrent or persisting infection. The review introduces key signaling processes involved in infection-induced "resistance" and "tolerance". We propose that elaboration of these signaling pathways allows novel insights into sepsis-associated tissue damage and repair processes. Moreover theranostic opportunities for the specific treatment of sepsis-related hyperinflammation or immunoparalysis will be introduced. Agents specifically affecting either hyperinflammation or immunoparalysis in the course of sepsis might add to the therapeutic toolbox of personalized care in the field of organ dysfunction caused by infection. (This article is freely available.). 10.1007/s00063-020-00673-4
    The role of the quick sequential organ failure assessment score (qSOFA) and modified early warning score (MEWS) in the pre-hospitalization prediction of sepsis prognosis. Usul Eren,Korkut Semih,Kayipmaz Afsin Emre,Halici Ali,Kavalci Cemil The American journal of emergency medicine OBJECTIVE:Many biomarkers and scoring systems to make clinical predictions about the prognosis of sepsis have been investigated. In this study, we aimed to assess the use of the quick sequential organ failure assessment score (qSOFA) and modified early warning score (MEWS) scoring systems in emergency health care services for sepsis to predict intensive care hospitalization and 28-day mortality. METHOD:Patients who arrived by ambulance at the Emergency Department (ED) of Dışkapı YıldırımBeyazıt Training and Research Hospital between January 2017 and December 2019, and who were diagnosed with sepsis and admitted to the hospital were included in the study. Demographic data and physiological parameters from 112 ambulance case delivery forms were recorded.QSOFA and MEWS scores were calculated from vital parameters. RESULTS:Of the 266 patients diagnosed with sepsis, 50% (n = 133) were female, and the mean age was 74.8 ± 13. The difference between the rate of intensive care (ICU) hospitalization and mortality for patients with a high MEWS and qSOFA score and patients whose MEWS and qSOFA score were lower was found to be statistically significant (p < 0.05). Thus, the criteria for MEWS and qSOFA could determine ICU hospitalization and early mortality. Those with a high MEWS value had a mortality rate approximately 1.24 times higher than those with a low MEWS value (p < 0.001, 95% CI: 1.110-1.385), while those with a high qSOFA score had a mortality rate approximately 2.0 times higher than those with a low qSOFA score (p < 0.001, 95% CI: 1.446-2.693). Those with a high MEWS were 1.34 times more likely than hose with a lower MEWS to require ICU hospitalization (p < 0.001, 95% CI: 1.1773-1.5131), while patients with a high qSOFA score were 3.21 times more likely than those with a lower qSOFA score to require ICU care (p < 0.001, 95% CI: 2.2289-4.6093). CONCLUSION:Although qSOFA and MEWS are clinical scores used to identify septic patients outside the critical care unit, we believe that patients already diagnosed with sepsis can be assessed with qSOFA and MEWS prior to hospitalization to predict intensive care hospitalization and mortality. qSOFA was found be more valuable than MEWS in determining the prognosis of pre-hospitalization sepsis. 10.1016/j.ajem.2020.09.049
    The role of eosinophils in sepsis and acute respiratory distress syndrome: a scoping review. Al Duhailib Zainab,Farooqi Malik,Piticaru Joshua,Alhazzani Waleed,Nair Parameswaran Canadian journal of anaesthesia = Journal canadien d'anesthesie PURPOSE:Septic shock and acute respiratory distress syndrome (ARDS) are characterized by a dysregulated immune host response that may respond to steroid therapy. Eosinophils contribute to type 2 inflammation that often responds to steroid therapy; their role in immune dysregulation and outcomes in sepsis and ARDS is unclear. SOURCE:A systematic search of Cochrane Library, MEDLINE, and EMBASE was performed from inception to 9 September 2020. The search comprised the following terms: eosinophils, sepsis, septic shock, and ARDS. Two reviewers independently screened abstracts and texts and extracted data on disease severity and clinical outcomes. PRINCIPAL FINDINGS:Thirty-nine studies were identified: 30 evaluated serum eosinophil count in sepsis, one evaluated eosinophil activity in sepsis, three assessed bronchoalveolar lavage (BAL) eosinophil count in ARDS, four assessed eosinophil activity in ARDS, and one assessed peripheral eosinophil count in ARDS. Eleven studies showed an association between eosinopenia and sepsis, and eight studies found persistent eosinopenia at > 48 hr of intensive care unit admission to predict mortality and readmission in septic patients. Three studies found BAL eosinophil count to be low in ARDS, although one found that levels rose in late-phase ARDS. Three studies found eosinophil activity markers in BAL to be high in ARDS and correlate with ARDS severity. CONCLUSION:Persistent peripheral eosinopenia is a marker of bacterial sepsis and is independently associated with poor outcomes. Bronchoalveolar lavage eosinophil counts are low in early-phase ARDS, but increase in late-phase ARDS, while elevated markers of eosinophil activity correlate with ARDS severity. Further studies understanding the mechanisms leading to eosinopenia in sepsis and increased eosinophil activity in ARDS are needed. 10.1007/s12630-021-01920-8