The Development Of Clinical Practice Guidelines Based On Traditional Chinese Medicine In The Treatment Of Sepsis And Its Re-evaluation Research

Background and objective:Every year 5.3 million patients died of sepsis in the world.Since its high incidence,mortality and medical cost,sepsis has always been the research hotspot in medical field of severe conditions.At present,large dose of antibiotics are given to sepsis patients,which induces drug resistance and heave financial burden to patients.Recent research shows good results in sepsis treated by integrated medicine,which can inhibit excessive inflammatory response,overcome immune dysfunction,alleviate multiple organ failure and decrease mortality.Its curative effect is better than that treated by exclusive Western medicine.However,in the treatment of sepsis by traditional Chinese medicine(TCM)it has been found that there lacks strict standardized guidance in selection of herbal intervention,timing of using TCM given and methods,which affects TCM's advantages in the treatment of sepsis.Our research,based on the senior experts clinical experience in the treatment of sepsis has carried out systematic searching of the existing evidences in evidence-based medicine,and conducted reevaluation so as to know the level and strength of the recommended evidences.Then,we have worked out the Clinical Guidance for Treatment of Commonly-seen Infectious Diseases with Exclusive Medicinals/Antibiotics.Sepsis.After the Guidance was released,re-evaluation was carried out with questionnaire to ascertain its clinical applicability.Our aim is to work out the above mentioned Guidance,used as a reference for doctors in their treatment of sepsis with TCM and increase the cure rate,decrease mortality,and lay a foundation for future research of prevention and treatment of sepsis.Methods:(1)Clearing the problems in the treatment of sepsis by TCM:Three steps:First,we mapped out the preliminary interview outlines according to the suggestions made by Doctor Liu Qingquan,who had rich clinical experience in the treatment of sepsis and other specialists,and related clinical literature reports.Second,according to this outline,in-depth interviews were conducted respectively with senior experts in different regions who are experienced in TCM treatment for sepsis,including Chief Physician Xi Zhaoqing of Jiangsu Province Hospital of Chinese Medicine,Chief Physician Cao Bin of China-Japan Friendship Hospital and Chief Physician Li Jun of Guangdong Province Hospital of Chinese Medicine.Third,on the basis of expert opinions,all members of our team,including 3 clinical experts,1 methodological expert,2 project secretaries and 10 students,demonstrated the results of in-depth interviews,and then formed the clinical issues of TCM in treating sepsis.(2)Determining the levels of evidence and strength of recommendations of clinical practice guideline on TCM therapy for sepsis:Based on the above work,we systematically searched three English databases(Medline,Embase and Cochrane Library)and four Chinese databases(CNKI,VIP,CBM and Wanfang),and retrieved 3 guideline databases(NGC,G-I-N and NICE).The inclusion/exclusion criteria were defined according to the different types of literature.After rigorous screening,we obtained clinical guidelines/expert consensus,systematic reviews and clinical research literatures related to sepsis treatment.AGREE II,AMSTAR and RoB were used respectively to evaluate the quality of clinical guidelines/expert consensus,systematic reviews and clinical research literatures.Delphi method was used to form consensus recommendations;GRADE tool was used to form evidence level and recommendation intensity for recommendations.(3)Re-evaluation of the applicability and availability of clinical practice guideline on TCM therapy for sepsis:After the publication of Clinical Practice Guideline on TCM Therapy Alone or Combined with Antibiotics for Sepsis,211 valid questionnaires were collected.The contents of the questionnaire survey include the quality level of the guideline,the applicability,the reduction of antibiotic via application of TCM,the update recommendations,the evaluation of application conformity,the evaluation of application effect,the overall evaluation,etc.The applicability and clinical availability of the guideline were analyzed descriptively by counting statistics.Results:(1)Based on the long-term experience of Prof.Liu Qingquan to treat sepsis and the collating of the previous clinical literatures on sepsis,an outline of in-depth interviews with experts was formulated.According to the contents of in-depth interviews with 3 experts and the demonstration of experts in our team,the clinical issues of Clinical Practice Guideline on TCM Therapy Alone or Combined with Antibiotics for Sepsis were determined as follows:?How to reduce the emergence of drug-resistant bacteria with TCM??How to combat the appeared drug-resistant bacteria with TCM??How to change the resistance of drug-resistant bacteria or pan-resistant bacteria with TCM??How to prevent multiple infections caused by fungi and viruses with TCM??How to treat inflammatory response syndrome with TCM??How to fight against immune disorders with TCM??How to treat gastrointestinal dysfunction with TCM??How to treat coagulation disorders with TCM?(2)Through the systematic search of Chinese and English electronic databases and clinical practice guideline databases,we obtained the following targeted sources based on inclusion and exclusion criteria:13 guidelines/expert consensus on sepsis,129 English literatures and 1109 Chinese literatures on the treatment of sepsis by TCM(13 systematic reviews were included).Thus,the evidence set to develop the guideline on TCM for sepsis was formed.After evaluating the quality of clinical guidelines/expert consensus,systematic reviews and clinical research literatures using AGREE II,AMSTAR and RoB respectively,a total of 8 interventions were included in this guideline to form recommendations,including Xuebijing Injection,Shenfu Injection,Qingwen Baidu Decoction,Shengmai Powder,Qingying Decoction,Sini Decoction,Wenpi Decoction and Xijiao Dihuang Decoction.Recommendations for 5 commonly used but poorly evidenced TCM interventions were added using Delphi method,including Houpo Sanwu Decoction,acupoint sticking therapy,acupuncture therapy,Xuanbai Chengqi Decoction and enemas of Chinese medicine.Using GRADE tools and approaches,it was found that the strong recommendations included Qingwen Baidu Decoction,Xuebijing Injection,Shengmai Powder and Shengfu Injection,while weak recommendations included Qingying Decoction,Sini Decoction,Houpo Sanwu Decoction,acupoint sticking therapy,acupuncture therapy,Xuanbai Chengqi Decoction,Wenpi Decoction,enemas of Chinese medicine and Xijiao Dihuang Decoction.(3)According to the previous evaluation methods for the applicability and availability of guidelines,the questionnaire of this study was formulated.A total of 500 questionnaires were sent out and 211 valid questionnaires were retrieved.84.36%of the doctors surveyed worked in the third-class hospitals,and 72.51%were with the title of the attending physician or below.In the applicability evaluation,the results showed that the reasonable proportion of the quality level indicators(area of application,use of terms,main points of diagnosis,classification of TCM syndrome,therapeutic principles and methods,applicability and clinical efficacy)exceeded 90%.For the applicability,coordination and compatibility of the content,reasonableness and integrity of the structure,comparison with their own institution's management,comparison with other institution's management,and rational proportion of safety all exceed 90%.Rational proportion of affordability and convenience was between 85%and 90%.81.04%of the respondents believed that TCM could reduce the use of antibiotics,of which 56.87%believed that it could reduce the using time of antibiotics,and 18.01%believed that it could reduce dosage of antibiotics.Among the update recommendations,"combination with clinical practice" occurred most frequently,which is 30 times.Other recommendations were clinical evidence,promotional efforts,TCM characteristics and regular updates,in that order.In the availability evaluation,the results showed that the reasonable proportion of all indicators of application conformity(therapeutic principles and methods,classification of TCM syndrome,prevention of complications and rehabilitation adjustment)exceeded 95%.In the evaluation of application effect,the results showed that for 13 interventions,namely Qingwen Baidu Decoction,Xuebijing Injection,Shengmai Powder,Shenfu Injection,Qingying Decoction,Sini Decoction,Houpo Sanwu Decoction,acupoint sticking therapy,acupuncture therapy,Xuanbai Chengqi Decoction,Wenpi Decoction,enemas of Chinese medicine and Xijiao Dihuang Decoction,the percentages of being considered effective were 88.16%,84.36%,88.63%,90.04%,86.26%,84.36%,85.31%,72.99%,75.83%,81.04%,70.61%,87.68%and 79.15%,respectively.In the overall evaluation,most respondents(124,116 and 114 people respectively)believed that the overall efficacy,overall safety and overall affordability of the guideline were satisfying.74,79 and 78 people think that the overall efficacy,overall safety and overall affordability were very satisfying,respectively.Conclusions:(1)When drug-resistant bacteria infection,inflammatory response syndrome and immune disorders develops with sepsis,and sepsis-related complications occurs,the choice of TCM interventions,specific timing and dosage of TCM are the main clinical issues faced by clinicians in China when applying TCM to treat sepsis.(2)The clinical interventions of TCM for sepsis have strong and weak recommendations.Strong recommendations include Qingwen Baidu Decoctio,Xuebijing Injection,Shengmai Powder and Shengfu Injection.Weak recommendations include Qingying Decoction,Sini Decoction,Houpo Sanwu Decoction,acupoint sticking therapy,acupuncture therapy,Xuanbai Chengqi Decoction,Wenpi Decoction,enemas of Chinese medicine and Xijiao Dihuang Decoction.Based on these,Clinical Practice Guideline on TCM Therapy Alone or Combined with Antibiotics for Sepsis is formulated.(3)By designing of questionnaires for clinical application of Clinical Practice Guideline on TCM Therapy Alone or Combined with Antibiotics for Sepsis,investigating and gathering statistics,we find that,to a certain extent,this guideline has applicability and availability.It can provide valuable guidance for treatment of sepsis with TCM,and make TCM to work better in sepsis treatment.