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Treatment of 2019 novel coronavirus pneumonia based on the theory of 'three syndromes and three methods'

Chinese Critical Care Medicine.2020;32(1):5-7. doi:10.3760/cma.j.issn.2095-4352.2020.01.003

The latest diagnosis and treatment plan (4th edition) of 2019 novel coronavirus pneumonia has been issued. The diagnosis and treatment plan highlights the concept of integrated traditional Chinese and Western medicine, and Xuebijing injection was referred for three times. Xuebijing injection was successfully developed based on the theory of 'three syndromes and three methods'. The theory of 'three syndromes and three methods' is a theoretical system of integrated traditional Chinese and Western medicine on critical diseases proposed by Professor Wang Jinda and his team in the 1970s, and it is one of the main contents of Wang Jinda's academic thought. The theory of 'three syndromes and three methods' has a deep foundation of traditional Chinese medicine theory, and it is still being continuously enriched and improved. It is also supported by multiple evidence-based data. Therefore, 'three syndromes and three methods' has rich theoretical connotation and tenacious vitality.

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"Five-minute emergency life chain" centering on department of emergency and intensive care unit patients: experience in the integration of department of emergency and intensive care unit of Yichang Central People's Hospital in Hubei Province

Jun YANG ; Zhaohui ZHANG

Chinese Critical Care Medicine.2019;31(10):1179-1184. doi:10.3760/cma.j.issn.2095-4352.2019.10.001

Yichang Central People's Hospital is a large prefecture-level tertiary hospital in Hubei Province. Since the late foundation and interdisciplinary characteritics, the department of emergency and critical care medicine faced many difficulties during development. Based on the actual situation of the hospital, leaders of the hospital and two disciplines advocated their core values of "putting patients' interests first and building team spirit". In consideration of the timeliness, multidisciplinary collaboration and importance of critical care, the department of emergency and critical care medicine in Yichang Central People's Hospital of Hubei Province was set up, and an integrated first-aid platform was established. The concept of "5-minute emergency life chain" was proposed, which highlighted the status and role of the department of emergency and critical care medicine in modern medical rescue and modern general hospitals. In the past 5 years, the emergency department and intensive care unit have made rapid development, including successful establishment of national demonstration centers for chest pain and stroke. Quality of the discipline has also been greatly improved, and a new construction path of department of the emergency and critical care medicine has been created.

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Minimum quality threshold in preclinical sepsis studies (MQTiPSS): quality threshold for types of infections and organ dysfunction endpoints

Lixue WANG ; Chao REN ; Renqi YAO ; Xianzhong XIAO ; Yongming YAO

Chinese Critical Care Medicine.2019;31(10):1185-1193. doi:10.3760/cma.j.issn.2095-4352.2019.10.002

Although the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review has not been done for preclinical models. To address this deficit, a Wiggers-Bernard Conference on preclinical sepsis modeling reviewed the 260 most highly cited papers between 2003 and 2012 using sepsis models to create a series of recommendations. This PartⅡreport provides recommendations for the types of infections and documentation of organ injury in preclinical sepsis models. Concerning the types of infections, the review showed that the cecal ligation and puncture model was used for 44% of the studies while 40% injected endotoxin. Recommendation #8 (numbered sequentially from PartⅠ): endotoxin injection should not be considered as a model of sepsis; live bacteria or fungal strains derived from clinical isolates are more appropriate. Recommendation #9: microorganisms should replicate those typically found in human sepsis. Sepsis-3 states that sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, but the review of the papers showed limited attempts to document organ dysfunction. Recommendation #10: organ dysfunction definitions should be used in preclinical models. Recommendation #11: not all activities in an organ/system need to be abnormal to verify organ dysfunction. Recommendation #12: organ dysfunction should be measured in an objective manner using reproducible scoring systems. Recommendation #13: not all experiments must measure all parameters of organ dysfunction, but investigators should attempt to fully capture as much information as possible. These recommendations are proposed as "best practices" for animal models of sepsis.

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Chinese expert consensus on polymyxins in the clinical practice

Chinese Critical Care Medicine.2019;31(10):1194-1198. doi:10.3760/cma.j.issn.2095-4352.2019.10.003

Polymyxin, a polypeptide antibiotic, derived from the culture of bacillus polymucilis, was introduced in the 1950s and used in clinical practice, but was replaced by safer antimicrobials due to its renal toxicity. In the recent years, with the increasing incidence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacilli infections, polymyxin is reintroduced into the clinic because it is assumed an important role in the treatment of MDR infections and XDR infections. In order to regulate the clinical applications of polymyxin, we organized experts in relevant fields to develop expert consensus on polymyxin for reference, including parameters like pharmacokinetics and pharmacodynamics, dosage and usage, contraindications and relative contraindications, clinical applications and adverse reactions.

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Xuebijing injection versus placebo for critically ill patients with severe community-acquired pneumonia: a randomized controlled trial: research results and clinical value

Chinese Critical Care Medicine.2019;31(10):1199-1203. doi:10.3760/cma.j.issn.2095-4352.2019.10.004

This article is based on the research paper named Xuebijing injection versus placebo for critically ill patients with severe community-acquired pneumonia: a randomized controlled trial which was published in Critical Care Medicine (CCM), introducing its study results and relevant clinical value. Moreover, we attached two peer experts' comments on this study for the readers' reference.

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Sepsis: advancements in controversy

Xiangyou YU ; Xinxin DU

Chinese Critical Care Medicine.2019;31(10):1204-1207. doi:10.3760/cma.j.issn.2095-4352.2019.10.005

Sepsis is one of the leading causes of inpatient deaths worldwide and is a major challenge in clinical work. The diagnosis and treatment of sepsis has been a research hotspot in critical care medicine. Through the efforts during the past decades, deeper understanding of the pathophysiology of sepsis and progress in the treatment have been made. But the latest sepsis guidelines and bundle strategies remain controversial, and clinical researches on sepsis are mixed. So far, there is no specific therapy for sepsis, and the mortality is still very high. Important researches and viewpoints in the field of sepsis in recent years are summarized and analyzed, so as to provide reference for the treatment of sepsis patients.

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Mechanism of delayed apoptosis of peripheral blood neutrophils in severely burned patients

Xinxin QI ; Yunxi YANG ; Jiamin HUANG ; Ran SUN ; Lu LIU ; Bingwei SUN

Chinese Critical Care Medicine.2019;31(10):1208-1211. doi:10.3760/cma.j.issn.2095-4352.2019.10.006

Objective: To observe the changes of peripheral blood neutrophil apoptosis rate and the effect of p38 mitogen-activated protein kinase (p38MAPK) inhibitor on peripheral blood neutrophil apoptosis in severely burned patients. Methods: Severe burn patients [burn area ≥ 30% total body surface area (TBSA), deep Ⅱ to Ⅲ degrees, burn index ≥ 20%, age > 20 years old] admitted to the department of burn and plastic surgery of Affiliated Suzhou Hospital of Nanjing Medical University from January to May in 2019 and health examination volunteers during the same period were enrolled. The peripheral blood neutrophils were isolated by Ficoll gradient centrifugation. The neutrophils of severely burned patients were divided into burn group and p38MAPK inhibitor SB203580 group (after 30 minutes incubation at room temperature and 24 hours incubation in incubator); the neutrophils of healthy volunteers were used as control group. The apoptosis of neutrophils was detected by flow cytometry; the level of reactive oxygen species (ROS) in neutrophils was detected by fluorescence probe; the expression of p38MAPK protein and its phosphorylation (p-p38MAPK) level were detected by Western Blot. Results: Compared with the control group, the apoptosis rate of neutrophils in burn group was significantly decreased [(37.42±3.14)% vs. (50.20±9.87)%, P < 0.05], and the ROS production level in neutrophils was significantly increased (fluorescence intensity: 83.28±0.29 vs. 75.23±0.34, P < 0.05). The apoptosis rate of neutrophils in SB203580 group was further lower than that in burn group [(25.51±1.56)% vs. (37.42±3.14)%, P < 0.05], and the level of ROS production was further higher than that in burn group (fluorescence intensity: 95.56±3.67 vs. 83.28±0.29, P < 0.05). There was no significant difference in the protein expression of p38MAPK among the three groups. The p-p38MAPK protein level in burn group was significantly lower than that in control group (p-p38MAPK/p38MAPK: 0.45±0.06 vs. 0.91±0.09, P < 0.05), while the expression level of p-p38MAPK in SB203580 group was further lower than that in burn group (p-p38MAPK/p38MAPK: 0.22±0.04 vs. 0.45±0.06, P < 0.05). Conclusion Peripheral blood neutrophil apoptosis delayed and ROS production were increased in severely burned patients. The mechanism may be related to p38MAPK pathway inhibitor.

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In vitro activity of ceftazidime-avibactam combined with colistin against extensively drug-resistant Pseudomonas aeruginosa

Qing MEI ; Shike GENG ; Xiaowei FANG ; Yuxi HE ; Lu LIU ; Mingyan XU ; Chunyan ZHU ; Aijun PAN

Chinese Critical Care Medicine.2019;31(10):1212-1218. doi:10.3760/cma.j.issn.2095-4352.2019.10.007

Objective: To evaluate the in vitro activity of ceftazidime-avibactam (CAZ-AVI) alone or in combination with colistin (COL) against clinically isolated extensively drug-resistant Pseudomonas aeruginosa (XDR-PA). Methods: Minimum inhibitory concentration (MIC) of 16 clinical XDR-PA isolates was determined by broth dilution method and chessboard design when CAZ-AVI and COL were used alone or in combination, then the combined inhibitory concentration index (FICI) was calculated. Class A [Klebsiella pneumoniae carbapenemase β-lactamase (bla_KPC), Guiana extended-spectrum β-lactamase (bla_GES)], Class B [imipenemase β-lactamase (bla_IMP), Verona-Integronmetallo β-lactamase (bla_VIM), New Delhi metallo β-lactamase (bla_NDM), German imipenemase β-lactamase (bla_GIM), Sao Paulo metallo -β- lactamase (bla_SPM)], Class C [AmpC β-lactamase (bla_AmpC)], Class D [oxacillinase β-lactamase (bla_OXA)] β- lactamase-related resistance genes were detected by polymerase chain reaction. Drug-resistant mutation frequencies of each strain were determined on a drug-containing plate. The time kill curves of three XDR-PA were plotted by colony counting method. A biofilm model was established in vitro, and the synergistic effect of CAZ-AVI and COL on biofilm inhibition was detected by methythiazolyl tetrazolium assay (MTT). Results: The MICs of 16 XDR-PA for CAZ-AVI ranged from 1 mg/L to 128 mg/L, and three of the isolates showed resistance (MIC > 8 mg/L). The FICI range of CAZ-AVI combined with COL was 0.312-1.000. Four isolates were synergistic, while the other 12 isolates were additive. Three isolates resistant to CAZ-AVI contained Class B resistance genes such as bla_IMP and bla_VIM, while 13 susceptible isolates carried resistance genes belonging to Class A, C or D. The logarithm values of mutation frequencies of drug resistance in CAZ-AVI group, COL group and combination group were -4.81±0.88, -7.06±0.69 and -9.70 (-9.78, -9.53), respectively. There were significant differences among the three groups (H = 33.601, P < 0.001), and between every two groups (adjusted P < 0.05). In time kill curves, the phytoplankton load of three XDR-PA decreased more than 6 log CFU/L when these two drugs were used together, and number of PA1819 planktonic bacteria decreased more than 5.1 log CFU/L compared with monotherapy group. Viable quantity in biofilm (A₄₉₀) of normal saline group, CAZ-AVI group, COL group and CAZ-AVI-COL group were 0.665±0.068, 0.540±0.072, 0.494±0.642 and 0.317±0.080, respectively. There was significant difference between the other two groups (all P < 0.001), except for that between CAZ-AVI group and COL group (P = 0.109). Conclusions CAZ-AVI combined with COL can effectively improve the bactericidal effect of each drug alone on XDR-PA. The regimen can also reduce the production of drug-resistant bacteria and inhibit the formation of biofilm. Therefore, it is a potential treatment for XDR-PA infection.

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Effects of body temperature on the prognosis of patients with septic shock

Dingye WU ; Liang DONG ; Song GAO ; Junfeng HENG ; Jie YAN ; Zheng YAN ; Shiqi LU

Chinese Critical Care Medicine.2019;31(10):1219-1223. doi:10.3760/cma.j.issn.2095-4352.2019.10.008

Objective: To observe the effects of abnormal body temperature and the area under temperature curve on the prognosis of patients with septic shock. Methods: A retrospective cohort study was conducted. Patients with septic shock admitted to intensive care unit (ICU) of Wuxi People's Hospital Affiliated to Nanjing Medical University from September 2013 to June 2019 were enrolled. Data were obtained from the hospital case database, including the gender, age, infection source, the length of ICU stay, sequential organ failure assessment (SOFA) score, 21-day prognosis; within the first 24 hours and throughout the period in ICU, the maximum temperature (24 h Tmax, Tmax), lowest temperature (24 h Tmin, Tmin), and the temperature range (24 h Tmax-min, Tmax-min) were aggregated. The area under temperature curve when body temperature was higher than T (A _> _T), or lower than T (A_< T), and area section between T1 and T2 (A_T1-T2) was calculated respectively. Patients were divided into survival group and death group according to 21-day prognosis. Binary Logistic regression was used to analyze the effect of the above temperature indices on the prognosis. Results: 635 septic shock patients were enrolled in the study. 476 patients were survived and 159 died within 21 days. Compared with the survival group, the age, SOFA score were higher in the death group, while the length of ICU stay was shorter. There was no significant difference in gender or infection source between two groups. After adjusting for gender, age, the length of ICU stay and SOFA score, binary Logistic regression analysis showed that the increase of Tmax, decrease of Tmin, and increase of Tmax-min were risk factors for 21-day mortality [Tmax: odds ratio (OR) = 2.959, 95% confidence interval (95%CI) was 1.620-5.398, P < 0.001; Tmin: OR = 0.329, 95%CI was 0.140-0.790, P = 0.012; Tmax-min: OR = 3.258, 95%CI was 1.840-5.471, P < 0.001], while 24 h Tmax, 24 h Tmin and 24 h Tmax-min were not related to prognosis. A_{< 36.0 ℃} (OR = 1.335, 95%CI was 1.102-1.745, P = 0.014), and A_{> 38.0 ℃} (OR = 1.041, 95%CI was 1.019-1.077, P = 0.001) showed positive correlation with 21-day mortality. When the T level was set at 38.0-40.0 ℃, for every 1 ℃×hour increase in A _> _T, the 21-day relative risk of death increased by 4.1%-83.2%. Conclusion When the body temperature of patients with septic shock is lower than 36.0 ℃, or higher than 38.0 ℃, the 21-day relative risk of death rose with the increase of the magnitude and duration of abnormal body temperature.

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Value of heparin-binding protein in diagnosis of sepsis in adult patients: a Meta-analysis

Min CHEN ; Jiahui YUAN ; Zhouxin YANG ; Guolong CAI

Chinese Critical Care Medicine.2019;31(10):1224-1230. doi:10.3760/cma.j.issn.2095-4352.2019.10.009

Objective: To evaluate the application of heparin-binding protein (HBP) in diagnosis of sepsis in adult patients. Methods: An extensive search for the Chinese and English literatures from the PubMed, Embase, the Cochrane Library, Wanfang data, CNKI and VIP up to July 2019 was performed. The articles regarding HBP for the diagnosing of sepsis in adult patients were enrolled. Two researchers independently extracted related literature. The quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-Disc 1.4 and STATA 12.0 were used for Meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. Summary receiver operating characteristic (SROC) curves and area under the curve (AUC) were used to evaluate the diagnostic performance of HBP for sepsis. Deek funnel plot was used to detect publication bias. Results: A total of 10 studies with 1 884 patients were included in this Meta-analysis. The quality of the literature was relatively moderate. HBP in plasma were detected by enzyme linked immunosorbent assay (ELISA) in all studies. The studies showed substantial heterogeneity, and random effect model was used for Meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.80 [95% confidence interval (95%CI) was 0.77-0.83], 0.80 (95%CI was 0.78-0.82), 3.96 (95%CI was 2.45-6.41), 0.28 (95%CI was 0.20-0.39) and 14.63 (95%CI was 6.83-31.30) respectively. The pooled AUC was 0.86 and the Cochran-Q was 0.79. To explore the potential sources of heterogeneity, subgroup analyses were performed based on the severity of the disease, diagnostic criteria and region. However, the results indicated that no methodological covariates affected the diagnostic accuracy of HBP, indicating that there was still unexplained heterogeneity. In addition, the sensitivity analysis by removing individual studies were performed. No outlier study was identified and the results were relatively stable and reliable. Deek funnel plot showed little publication bias. Conclusions There is preferable value of HBP for diagnosis of sepsis in adult patients. However, it needs to be further confirmed by large multicenter studies.

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