Calcium/calmodulin-dependent protein kinaseⅡ (CaMKⅡ) has multiple functions, which made it play a central role in cardiovascular disease. Especially it activates numerous downstream targets in various signaling pathways that promotes vascular disease, heart failure, myocardial hypertrophy and arrhythmias. CaMKⅡcan impact calcium balance and increase calcium leak in myocardial cell via phosphorylating L type calcium channel, Ryanodine receptor (RyR 2) and phos?pholamban (PLN), and regulate ATP sensitive potassium current (IKATP) and late sodium current by affecting sodium channels and potassium channels. In addition, It can directly regulate transcription via activating the silk crack the original activated protein kinases (MAPKs) and acetylation enzyme (HDAC). These mechanisms have important roles in myocardial hypertro?phy, heart failure and arrhythmia. So we focus to demonstrating the structure and action mechanism of CaMKⅡto improve a new therapy of cardiovascular disease.

Cardiac contractile dysfunction and arrhythmic genesis are resulted from disturbed intracellular Na+and Ca2+ handling under condition of oxidation stress. Stress-induced intracellular signaling regulated mechanisms in which many activated stress kinases, such as cAMP-dependent protein kinase A, protein kinase C , Ca/calmodulin-dependent pro-tein kinaseⅡand classical pathways, are known to be involved. However, it is becoming increasingly evident that reactive oxygen species may directly oxidize these kinases, Na+and Ca2+channel protein and transporters, which lead to changing of intracellular Na+and Ca2+accumulation, and to trigger of arrhythmias.

Objective To observe and explore the effects of different tidal volume (VT) ventilation on right ventricular (RV) function in patients with critical respiratory failure.Methods Consecutive respiratory failure patients who were treated with invasive ventilator over 24 h in the Department of Critical Care Medicine at the Fourth Hospital of Hebei Medical University from June to December in 2015 were enrolled in this study.Clinical data including patients′ vital signs, ventilator parameters and RV echocardiography were collected within 6 h (D0), day1(D1), day2 (D2) and day3 (D3) after ventilation started.According to the VT, patients with acute respiratory distress syndrome (ARDS) were assigned to low VT group [S6, ≤6 ml/kg predicted body weight (PBW)] and high VT group (L6, >6 ml/kg PBW), while non-ARDS patients were also assigned to low VT group (S8, ≤8 ml/kg PBW) and high VT group (L8, >8 ml/kg PBW).Results A total of 84 patients were enrolled in this study.44.2% ARDS patients and 58.5% non-ARDS patients were in low VT groups.After ventilation, tricuspid annulus plane systolic excursion(TAPSE)decreased progressively in S6 [from 18.30(16.70,20.70) mm to 17.55(15.70,19.50) mm, P=0.001], L6 [from 19.50(17.00,21.00) mm to 16.30(15.00,18.00) mm P=0.001], S8[from 18.00(16.00,21.00) mm to 16.50(15.50,18.00) mm, P=0.001] and L8 [from 19.00(17.50,21.50) mm to 16.35(15.15,17.00) mm, P=0.001] groups.However, TAPSE decreased less in small VT groups (S6 and S8) than those of in large VT groups (S8 and L8) without significant differences.There were not statistical differences between different VT groups in terms of ventilation days, including right ventricle area/left ventricle area (RVarea/LVarea),TAPSE,peak mitral flow velocity of the early rapid filling wave (E),peak mitral flow velocity of the late rapid filling wave (A),early diastolic velocity of the tricuspid annulus (e′),pulmonary artery systolic pressure,inferior vena cava diameter (all P>0.05).Compared to L6 group, low VT (S6 group) resulted in decreased mortality at 28 days [1/19 vs 37.5%(9/24), P=0.014].There were not statistical differences between different VT groups in terms of ventilation days, length of intensive care unit stay, length of hospital stay (all P>0.05).Logistic regression analysis showed that VT could be the independent factor of TAPSE (OR=1.104,95%CI 0.100-1.003,P=0.049).Conclusions Positive pressure mechanical ventilation resulted in RV systolic dysfunction.Lower VT may have the protective effect on RV function.Trial registration Chinese Clinical Trial Registry,ChiCTR-POC-15007563.

ObjectiveTo evaluate the value of lung ultrasound score (LUS) on assessing the severity and prognosis in patients with acute respiratory distress syndrome (ARDS), and to investigate its correlation with oxygenation index, acute physiology and chronic health evaluationⅡ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score, and clinical pulmonary infection score (CPIS), and other traditional parameters.Methods A prospective double-blind cohort study was conducted. Sixty-two ARDS patients conformed to the Berlin diagnostic criteria admitted to intensive care unit (ICU) of Beijing Huaxin Hospital from October 2013 to December 2014 were enrolled, including 14 cases with mild, 18 moderate, and 30 severe ARDS; among them 37 cases were of ARDS with pulmonary origin, and 25 non-pulmonary ARDS; 35 patients survived, and 27 died. The clinical data and scores of all patients were recorded by one specialized observer, including baseline data, hemodynamic parameters, lactate, respiratory parameters, and APACHEⅡ, SOFA and CPIS scores. Another observer of recording was responsible for the results of lung ultrasound, LUS, and echocardiogram. The correlation between LUS and oxygenation index as well as APACHEⅡ, SOFA and CPIS scores was analyzed by bivariate correlation analysis. Receiver operator characteristic curve (ROC) was plotted, and the predictive value, sensitivity and specificity of mild ARDS, moderate ARDS, severe ARDS and mortality by LUS were calculated. Results LUS had a negative correlation with oxygenation index (r = -0.755,P< 0.001), a good positive correlation with APACHEⅡ (r = 0.504,P< 0.001), SOFA (r = 0.461,P< 0.001) and CPIS (r = 0.571,P< 0.001) was found. LUS in the pulmonary ARDS group had a positive correlation with CPIS (r = 0.399,P< 0.05), and a positive correlation was found in non-pulmonary ARDS group (r = 0.350,P< 0.05), which indicated that the correlation in pulmonary ARDS was more satisfactory than that in non-pulmonary ARDS. LUS in the pulmonary ARDS group was significantly higher than that in non-pulmonary ARDS group (22.1±4.9 vs. 11.3±2.1,t = 11.667,P< 0.001); LUS in mild, moderate, severe ARDS groups was 9.9±1.7, 14.0±1.4, 23.6±4.1. The predictive value for mild ARDS by LUS was 7.0, sensitivity of 87.0%, specificity of 89.0%; that for moderate ARDS was 11.0, sensitivity of 89.0%, specificity of 87.0%; that for severe ARDS was 8.0, sensitivity of 90.0%, specificity of 88.5%. LUS was 24.3±3.8 in the death group, and 12.7±2.9 in the survival group. Area under ROC curve (AUC) was calculated, and the patients with LUS> 19.0 had a high mortality, sensitivity for predicting death was 84.0%, and specificity of 89.0%.Conclusion Bedside LUS, which is simple and easily available, could evaluate the changes in pulmonary ventilation area of ARDS, and its degree of severity, and prognosis including prediction of mortality of the patients.

Critical ultrasonography is widely used in ICU and has become an indispensable tool for clinicians. However, besides operator-dependency of critical ultrasonography, lack of standardized training mainly result in the physicians′ heterogenous ultrasonic skill. Therefore, standardized training as well as strict quality control plays the key role in the development of critical ultrasonography. We present this quality control standards to promote better development of critical ultrasonography.

Objective:To describe the features of point-of-care cardiopulmonary ultrasound (POCUS) in the critically ill patients and analyze the independent factors associated with treatment changes after POCUS assessment.Methods:This was a prospective multicentric observational study from January to December 2018 in 13 intensive care units (ICU) in China. Consecutive patients admitted to the ICU were enrolled, POCUS were performed within the first 24 h of admission. The POCUS parameters included acute or chronic cardiac abnormality, diameter of inferior vena cava (IVC) at end-expiration, right ventricular systolic function, systolic and diastolic function of left ventricle (LV) and lung ultrasound score. The general features of patients and performers were recorded. Based on the treatment proposed by the performer before and after POCUS assessment, the patients were divided into treatment changed and unchanged groups. Factors associated with treatment changes were identified by multiple logistic regression analysis.Results:Totally 1 913 patients were enrolled including 322 (16.8%) patients with shock, 638 (33.3%) patients with respiratory failure, 139 (7.3%) patients with both shock and respiratory failure and 814 (42.6%) perioperative patients. POCUS had contributed to treatment changes in 1 204 (62.9%) patients, including 867 (72.0%) cases involved fluid management. Univariate analysis showed that there were significant differences in general characteristics of patients, performers and POCUS parameters between groups(all P<0.05). Logistic regression analysis showed that independent factors of treatment changes included ministry of education or university affiliated teaching hospitals (vs.general hospitals, OR=1.891, 95% CI=1.314-2.722, P<0.001 and OR=1.644, 95% CI=1.152-2.347, P=0.006 separately), middle and senior title performers (vs.primary title, OR=2.112, 95% CI=1.358-3.284, P=0.001, OR=3.271, 95% CI=2.129-5.025, P<0.001 separately), mechanical ventilation (vs.without, OR=0.488, 95% CI 0.381-0.626, P<0.001), IVC diameter ≤1 cm (vs.1-2 cm, OR=0.317, 95% CI 0.231-0.434, P<0.001), LV ejecting fraction <50% (vs.≥50%, OR=0.328, 95% CI=0.210-0.512, P<0.001), lung ultrasound score of 6-12 and >12 points(vs.score ≤ 6 points, OR=0.237, 95% CI=0.178-0.315, P<0.001 and OR=0.619, 95% CI=0.457-0.837, P=0.002 separately). Conclusions:POCUS assessment contributes to treatment changes, most of which involves fluid management strategy, in 62.9% critical patients. The independent influencing factors associated with POCUS parameters includes IVC diameter at end-expiratory, LV systolic function and lung ultrasound score. The performers′ title and hospital grade also have a noticeable effect.

Severe patients with coronaviras disease 2019 (COVID-19) are characterized by persistent lung damage, causing respiratory failure, secondary circulatory changes and multiple organ dysfunction after virus invasion. Because of its dynamic, real-time, non-invasive, repeatable and other advantages, critical ultrasonography can be widely used in the diagnosis, assessment and guidance of treatment for severe patients. Based on the recommendations of critical care experts from all over the country who fight against the epidemic in Wuhan, this article summarizes the guidelines for the treatment of COVID-19 based on critical ultrasonography, hoping to provide help for the treatment of severe patients. The recommendations mainly cover the following aspects: (1) lung ultrasound in patients with COVID-19 is mainly manifested by thickened and irregular pleural lines, different types of B-lines, shred signs, and other consolidation like dynamic air bronchogram; (2) Echocardiography may show right heart dysfunction, diffuse cardiac function enhancement, stress cardiomyopathy, diffuse cardiac depression and other multiple abnormalities; (3) Critical ultrasonography helps with initiating early treatment in the suspect patient, screening confirmed patients after intensive care unit admission, early assessment of sudden critical events, rapid grading assessment and treatment based on it; (4) Critical ultrasonography helps to quickly screen for the etiology of respiratory failure in patients with COVID-19, make oxygen therapeutic strategy, guide the implementation of lung protective ventilation, graded management and precise off-ventilator; (5) Critical ultrasonography is helpful for assessing the circulatory status of patients with COVID-19, finding chronic cardiopulmonary diseases and guiding extracorporeal membrane oxygenation management; (6) Critical ultrasonography contributes to the management of organs besides based on cardiopulmonary oxygen transport; (7) Critical ultrasonography can help to improve the success of operation; (8) Critical ultrasonography can help to improve the safety and quality of nursing; (9) When performing critical ultrasonography for patients with COVID-19, it needs to implement three-level protection standard, pay attention to disinfect the machine and strictly obey the rules from nosocomial infection. (10) Telemedicine and artificial intelligence centered on critical ultrasonography may help to improve the efficiency of treatment for the patients with COVID-19. In the face of the global spread of the epidemic, all we can do is to share experience, build a defense line, We hope this recommendations can help COVID-19 patients therapy.

To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.