UPDATE COVID19 - Shanghai 2019 comprehensive treatment of coronavirus disease expert consensus Shanghai Treatment Expert Group SIFIC Infection Evidence-Based Information 6 days ago Sunday, March 8, 2020
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Shanghai 2019 comprehensive treatment of coronavirus disease expert consensus Shanghai Treatment Expert Group SIFIC Infection Evidence-Based Information 6 days ago // Shanghai 2019 comprehensive treatment of coronavirus disease expert consensus //Expert Group on Clinical Treatment of New Coronary Virus Disease in ShanghaiCoronavirus disease 2019 (COVID-19) was first reported in Wuhan, Hubei Province, on 31 December 2019. COVID-19 as a respiratory infectious disease, has been included in the "People's Republic of China Infectious Disease Prevention and Control Law" provisions of class B infectious diseases, according to class A infectious diseases management.With the deepening of understanding of disease, all over the country in COVID-19 prevention and treatment have accumulated some experience. Shanghai new coronavirus disease clinical treatment expert group followthe national new coronavirus pneumonia diagnosis and treatment program, fully absorb the experience of domestic and foreign counterparts, in order to improve the success rate of clinical treatment and reduce the patient mortality rate of the goal, to prevent the progress of the disease, gradually reduce the proportion of seriously ill patients, improve its clinical prognosis. On the basis of continuous optimization and refinement of treatment plan, expert consensus opinions have been formed on the relevant clinical diagnosis and treatment work.01 Pathogens and epidemiological characteristics2019 New Coronavirus (2019 novel coronavirus, 2019-nCoV) is a new type of coronavirus belonging to beta. On 11 February 2020, the International Committee on Virus Classification (The International Committee on The On Taxonomy of Viruses, ICTV) named the virus Severe Acute Respiratory Syndrome Coronavirus 2 (acute acute respiratory corona syndrome 2, SARS-CoV-2).CoVID-19 patients and asymptomatic infections can spread 2019-nCoV. The transmission by respiratory droplets is the main route of transmission and can also be transmitted through contact. There is also a risk of aerosol propagation in confined spaces. 2019-nCoV can be detected in the feces, urine and blood of COVID-19 patients, and some patients can still be tested positive for fecal nucleic acid after negative testing for pathogen nucleic acid in respiratory samples. Crowds are generally susceptible. Children and infants also have the disease, but the disease is mild.02 Clinical Characteristics and Diagnostics(i) Clinical characteristicsThe incubation period is 1 to 14 d, mostly 3 to 7 d, with an average of 6.4 d. To fever, fatigue, dry cough as the main performance. Can be accompanied by runny nose, sore throat, chest tightness, vomiting and diarrhea and other symptoms. Some patients had mild symptoms, and a few had no symptoms or pneumonia.The elderly and those with diabetes, hypertension, coronary atherosclerosis heart disease, extreme obesity and other underlying diseases are prone to develop into severe illness after infection. Some patients develop symptoms such as breathing difficulties 1 week after onset of the disease, and severe cases can progress to acute respiratory distress syndrome (acute respiratory distress syndrome, ARDS) and multi-organ functional impairment. The time to progress to critical illness is approximately 8.5 d.It is worth noting that heavy, critical patients can have low to medium heat in the course of the disease, or even no obvious fever. Most patients have a good prognosis, with deaths mostly in the elderly and those with chronic underlying diseases.Early CT examination is characterized by multiple small patches or grinding glass shadows, the inner texture can be meshed strip-shaped thick shadow, with the lung band obvious. A few days later the lesions increased, the scope expanded, a wide range of double lung, multiple grinding glass shadow or immersion lesions, part of the lung real change, often bronchial inflatable signs, chest fluid is rare. A small number of patients progressed rapidly, with the change in imaging reaching a peak in the 7th to 10th day of the course. Typical "white lung" performance is rare. After entering the recovery period, the lesions are reduced, the scope is reduced, the oozing lesions are absorbed, some of the fibrous slats appear, and some patients can be completely absorbed.The total number of peripheral white blood cells in patients with early onset was normal or decreased, the lymphocyte count decreased, some patients could have abnormal liver function, lactic acid dehydrogenase, myosise and myoglobin levels increased; In most patients, CRP and ESR levels were elevated and calcium-lowering levels were normal. In severe cases, d-dipolymer levels increased, other blood clotting indicators abnormal, lactic acid levels increased, peripheral blood lymphocytes and CD4-T lymphocytes for sexual reduction, as well as electrolyte disorders, acid-base imbalance, etc., to metabolic alkali poisoning is more common. Elevated levels of inflammatory cytokines (e.g. IL-6, IL-8, etc.) can occur during the progression of the disease.(ii) Diagnostic criteria1. Suspected cases:Combined with the following comprehensive analysis of epidemiological history and clinical manifestations. Any one of the epidemiological history that meets any 2 of clinical manifestations, or 3 of which have no clear epidemiological history but are consistent with clinical manifestations, are diagnosed as suspected cases.(1) Epidemiological history: 14 d before the onset of the disease in Wuhan City and surrounding areas, or other case-reported community travel history or residence history;(2) Clinical manifestations: fever and/or respiratory symptoms; with the above-mentioned new coronavirus pneumonia imaging characteristics; the total number of white blood cells in the early stages of the disease is normal or decreased, and lymphocytes count decreased.2. Confirmed cases:A person with one of the following pathogenic evidence is diagnosed as a confirmed case.(1) Real-time fluorescent reverse transcription PCR test 2019-nCoV nucleic acid positive.(2) Viral gene sequencing found homologous with known 2019-nCoV height.(3) In addition to nasopharyngeal swabs, it is recommended to leave sputum as far as possible, the implementation of tracheal intubation patients can collect lower respiratory secretions sent to viral nucleic acid detection.(iii) Differential diagnosisMainly with influenza virus, para-flu virus, adenovirus, respiratory syncytial virus, rhinovirus, human lung virus, severe acute respiratory syndrome (severe acute respiratory syndrome, SARS) coronavirus and other known viral pneumonia identification, with pneumonia mycoplasma, chlamydia pneumonia and bacterial pneumonia identification.In addition, it is necessary to identify with non-infectious diseases, such as vasculitis, dermatitis and other connective tissue diseases caused by pulmonary lesions and metastivis.(4) Clinical type1. Light:Clinical symptoms were mild, and imaging examination did not show pneumonia.2. Normal:With fever, respiratory tract and other symptoms, imaging examination can be seen pneumonia performance.Early warning of severe illness in common patients should be strengthened. Based on the current clinical research, the elderly (age 65 years old), accompanied by basic diseases, CD4-T lymphocytes 250 / sl, blood IL-6 levels significantly increased, 2 to 3 d pulmonary imaging examination found significant progress of lesions , lactic dehydrogenase (lactic dehydrogenase, LDH) , 2 times the normal value limit, hetic acidity 3 mmol/3. Heavy:Conforms to any of the following.(1) The appearance of shortness of breath, breathing frequency of 30 times / min;(2) In the state of rest, the oxygen saturation of the arterial blood (arterial oxygen saturation, SaO2) is 93%;(3) Arterial blood oxygen fractionpressure (arterial partial pressure of oxygen, PaO2)/oxygen concentration (inspired oxygen, FiO2) s 300 mmHg (1 mmHg s.133 kPa). High altitude (over 1,000 m) areas should be corrected for PaO2/FiO2 in accordance with the following formula: PaO2/FiO2 x (mmHg)/760).Lung imaging examination showed that 24 to 48 h internal lesions significantly progress . . . 50% of the people were managed by heavy duty.4. Critical type:Those who meet any of the following can be judged to be critical.(1) respiratory failure, and the need for mechanical ventilation;(2) The appearance of shock;(3) Combining other organ failure, ICU monitoring treatment is required.(v) Clinical monitoringDynamic monitoring of patients' clinical performance, vital signs, fluid inandance, gastrointestinal function and mental state are monitored daily.Dynamic monitoring of oxygen saturation of the end of the blood in all patients is monitored.For patients with severe and critical conditions, blood gas analysis was carried out in a timely manner according to changes in the condition; blood routine, electrolyte, CRP, calcite, LDH, clotting function indicators, blood lactic acid, etc., at least 1 test per 2 d; liver function, renal function, ESR, IL-6, IL-8, lymphocyte subgroup, at least 1 test per 3 d; chest imaging examination, usually 1 test per 2 d.For ARDS patients, a routine ultrasound of the heart and lungs next to the bed is recommended to observe the parameters of the extravascular pulmonary water and heart. In vitro membrane pulmonary oxygenation (extracorporeal membrane oxygenation, ECMO) patient monitoring refers to the implementation section of ECMO.03 Treatment(i) Antiviral therapyCan be tried hydroxychloroquine or chlorpyrifos phosphate oral, abidore oral, interferon atomized inhalation, preferred interferon. It is not recommended to use 3 or more antiviral drugs at the same time. The virus nucleic acid should be deactivated in time after the virus nucleic acid has turned negative. The efficacy of all antiviral drugs has yet to be evaluated in further clinical studies.For patients with positive nucleic acid for heavy and critical viral nucleic acids, the recovery stage plasma may be trialled. Detailed operation and management of adverse reactions refer to the National Health And Health Commission issued by the National Health Commission of the "new coronary pneumonia rehabilitation plasma clinical treatment plan" (trial first edition) . Infusion within 14 d may be more effective, in the later stages of the course, if the continuous detection of viral nucleic acids, can also be trialled in the recovery period plasma treatment.(ii) Treatment of light and general patientsSupport treatment needs to be strengthened to ensure adequate heat, attention to water, electrolyte balance, maintain internal environmental stability, close monitoring of patients' vital signs and oxygen saturation. Timely and effective oxygen therapy measures. Antibacterial drugs and glucocorticoids are not used in principle.Patients need to be closely monitored, and if there is a significant progression and a risk of becoming serious, comprehensive measures are recommended to prevent the disease from progressing to a heavy level, with caution as appropriate (see the application section of glucocorticoids). Heparin anticoagulant and high-dose vitamin C treatment is recommended. Low-molecular heparin 1 to 2 /d, continued until the patient's D-diipolymer level returned to normal. Once the fibrin degradation product (fibrino degradation product, FDP) is 10 sg/mL and/or D-diipolymer s.5 sg/mL, use ordinary heparin anticoagulant. Vitamin C 50 to 100 mg/kg per day, intravenous drips, continuous use time to oxygenation index significantly improved as the goal.If there is progress in lung lesions, it is recommended to apply high-dose broad-spectrum protease inhibitors of 60 to 1 million units/d, continuing to improve the imaging examination of the lungs. Intermittent short-short-term blood filtration (intermittent short veno-venuous hemofiltration, ISVVH) is recommended in the event of a cytokine storm.(iii) The function of organs in critically ill patients supports treatment1. Protection and maintenance of the cycle function:The principle of early active control rehydration is implemented. It is recommended to assess effective capacity and initiate fluid therapy as soon as possible after admission. Heavy-duty patients can choose intravenous pathways or through colon pathways for fluid resuscitation. The supplementary liquid is preferred lactic acid ringer.For vascular active drugs, norepinephrine combined with dopamine is recommended to maintain vascular tension and increase heart displacement. For patients with shock, norepinephrine is preferred, and it is recommended to start using small doses of vascularly active drugs at the same time as fluid resuscitation to maintain circulatory stability and avoid excessive fluid infusion.Heavy, critically critical patients are recommended to use heart-protecting drugs and to avoid sedatives that inhibit the heart. Isopropyl epinephrine can be used in patients with sinustal tashimitosy. It is recommended that for patients with sinus heart rhythm, heart rate of 50 times/min and hemodynamic instability, intravenous pumping of small doses of isopropyl epinephrine or dopamine to maintain heart rate at about 80 times/min.2. Reduce inflammation of the pulmonary ito:2019-nCoV causes severe pulmonary interstitial lesions that can cause lung function deterioration, and high-dose broad-spectrum protease inhibitors are recommended.3. Protection of kidney function:Early and reasonable anticoagulant therapy and appropriate liquid therapy are recommended. See the section on the prevention and treatment of cytokine storms, the protection and maintenance of cycling functions.4. Protection of intestinal function:Bionics can be used to improve the intestinal microecology of patients. Use raw yellow (15 to 20 g plus 150 ml of warm boiling blisters) or large gas soup or enemas.5. Nutritional support:Preferred gastrointestinal nutrition, through nasal feeding or through the empty intestine. The preferred whole protein nutrition preparation is 25 to 35 kcal/kg per day (1 kcal x 4.184 kJ).6. Prevention and control of cytokine storms:High doses of vitamin C and ordinary heparin anticoagulant are recommended. High doses of vitamin C are intravenously injected 100 to 200 mg/kg per day. Continuous use time is aimed at a significant improvement in oxygenation index. It is recommended to apply high-dose broad-spectrum protease inhibitors, given 1.6 million units per 8 h 1 time, in a mechanical ventilation state, when the oxygenation index of 300 mmHg can be reduced to 1 million units/d. Anticoagulant therapy can be used to protect endothelial cells and reduce cytokine release, FDP s 10 sg/mL and/or D-diipolymers s5 sg/mL to ordinary heparin (3 to 15 IU/kg per hour) anticoagulant. The patient's clotting function and platelets must be reviewed at 4 h after first use of heparin. With ISVVH, 6 to 10 h per day.7. Sedative muscle looseness and artificial hibernation therapy:Patients with mechanical ventilation or receiving ECMO need to be sedated on an algemotheic basis. For patients with severe human-machine resistance when establishing artificial airways, it is recommended to apply small doses of muscle loose medicine for short-range use. Hibernation therapy is recommended for patients with oxygenation index of 200 mmHg.Artificial hibernating therapy can reduce the body's metabolism and oxygen consumption, while expanding blood vessels in the lungs and significantly improve oxygenation, it is recommended to use continuous intravenous injection of the method of medication, the patient's blood pressure needs to be closely monitored.Be careful with opioids and right metamida. Due to the presence of severe patients with abnormal LEVELs of IL-6 and easy to lead to bloating, should avoid the use of opioids, and 2019-nCoV can inhibit the function of sinus and the occurrence of sinus tachycardia, so should be careful lying with the heart inhibited sedatives. In order to prevent the occurrence and aggravation of lung infection, try to avoid excessive sedation for a long time, the condition should be allowed to withdraw the muscle loose medicine as soon as possible. It is recommended to closely monitor the depth of sedation.8. Oxygen therapy and breathing support:(1) nasal catheter or mask oxygen therapy, restand air conditions SaO2 , or after the activity SaO2 90%, or oxygenation index (PaO2/FiO2) for 200 to 300 mm Hg; accompanied or not accompanied by respiratory distress;(2) by nasal high-flow oxygen therapy (high-flow nasal cannula oxygen therapy, HFNC), receiving nasal catheteror or mask oxygenation 1 to 2 h oxygenation does not meet the treatment requirements, breathing distress does not improve;(3) Non-invasive positive pressure ventilation (non-invasive positive ventilation, NPPV), receiving HFNC 1 to 2 h oxygenation is not effective at treatment, no improvement in respiratory distress; or in the course of treatment hypoxemia and/or respiratory distress increased; or oxygenation index of 150 to 200 mmHg;(4) When there is invasive mechanical ventilation, receiving HFNC or NPPV treatment 1 to 2 h oxygenated does not meet the treatment requirements, breathing distress does not improve, or in the course of treatment hypoxemia and/or respiratory distress aggravated, or oxygenation index 150 mm Hg, should be considered for invasive ventilation. A protective ventilation strategy with low tide air volume (4 to 8 mL/kg ideal mass) as the core is preferred.9. Implementation of ECMO:An ECMO may be considered if one of the following conditions is met.(1) PaO2/FiO2 50 mmHg more than 1 h;(2) PaO2/FiO2 80 mmHg exceeds 2 h; (3) arterial blood pH of 7.25 and accompanied by PaCO2 60 mmHg more than 6 h. THE ECMO MODE PREFERRED INTRAVENOUS-VENVEAL ECMO.(4) Special problems in treatment and treatment1. Application of glucocorticoids:Caution should be used with glucocorticoids. Imaging examination suggests that there is significant progress in pneumonia, resting in the state of non-oxygen patients SaO2 , 93% or shortness of breath (breathing frequency of 30 times / min) or oxygenation index of 300 mmHg, especially the progressof the disease significantly accelerated, in the face of intubation risk can be added to the glucocorticoid.Patients are advised to withdraw their use of glucocorticoids quickly when intubation or ECMO support can maintain effective blood oxygen concentrations. For non-severe patients using metastasis nylon, the recommended dose is controlled at 20 to 40 mg/d, severe patients control at 40 to 80 mg/d, the course of treatment is generally 3 to 6 d. Depending on the body mass discretion, the amount of increase or decrease.2. Use of immunomodulating drugs:Injection of thymus peptides twice a week has some effect on improving the immune function of patients, preventing severe illness and shortening the detox time. Due to the lack of specific antibodies, the use of intravenous human immunoglobulin therapy in large doses is not currently supported. However, some patients have low lymphocyte levels and are at risk of combining other viral infections, and can infuse human immunoglobulin 10 g/d intravenously, with a course of 3 to 5 d.3. Precise diagnosis and treatment of combined bacterial and fungal infections:Clinical microbiological monitoring of all critically ill and critically ill patients. Every day to take the patient's sputum and urine for culture, high fever patients in a timely blood culture. All suspected sepsis patients with an vascular catheter should be sent to the peripheral peripheral venous blood culture and catheter blood culture at the same time. All suspected sepsis patients may consider collecting peripheral blood for germological molecular diagnostic examination, including PCR-based molecular biology testing and second-generation sequencing.Elevated levels of calcitonin were indicative for the diagnosis of sepsis/sepsis shock. When the condition of the new coronavirus pneumonia worsens, there is an increase in THE level of CRP, and the increase of CRP level is not specific to the diagnosis of sepsis caused by bacterial and fungal infections.Critically ill patients with open airways tend to be prone to bacterial and fungal infections later in life. If sepsis occurs, empirical anti-infection treatment should be given as soon as possible. For patients with septic shock, empirical antimicrobials can be combined before obtaining an pathogen diagnosis, while covering the most common e. coli, staphylococcal and enterococci infections. Infected persons who occur after hospitalization may be able to use beta-lactamase inhibitor complexes.If the treatment effect is not good, or the patient is severe infectious shock, can be replaced with carbon penicillin drug treatment. If you consider the combination of enterococci and staphylococcus infection, can be added to the glycopeptide drug (vancomycin) for empirical treatment, blood flow infection optional dattomycin, lung infection-based can be selected linazine.Attention should be paid to catheter-related infections in critically ill patients, and the treatment should be empirically covered with staphylococcus staphylococcus resistant to methicillin. Empirical treatment with glycopeptide drugs (vancomycin) is optional.Candida infection is also more common in critically ill patients, if necessary, experience coverage candidatreatment, can be added to the drug echiconobacteria.As the length of hospital stay for seriously ill patients increases, drug-resistant infections are gradually increasing, and the use of antimicrobialdrugs must be adjusted according to drug-sensitive tests.4. Hospital infection prevention and control:(1) According to the 2019 National Health and Health Commission "Basic System for Infection Prevention and Control of Medical Institutions (Trial)" ( 13), actively implement evidence-based infection prevention and control cluster intervention strategy, effective prevention of ventilator-related pneumonia, intravascular catheter-related blood flow infection, catheter-related urinary tract infection, carbon penicillin drug-resistant grameel-negative bacillus and other multi-drug-resistant bacteria and fungal infections.(2) Strictly comply with the requirements of the National Health and Health Commission's Technical Guide for the Prevention and Control of New Coronary Virus Infections in Medical Institutions (First Edition) "Guidelines on the Use of Common Medical Protection Supplies in The Prevention and Control of New Coronary Virus Infections (Trial)" "Technical Guidelines for the Protection of Medical Personnel during the Outbreak of New Coronary Pneumonia (Trial)" 5,16), strengthen the process management, the correct selection and use of masks, isolation clothing, protective clothing, eye masks, protective masks, gloves and other personal protective supplies, strict implementation of disinfection and isolation measures, to minimize the risk of hospital infection, to eliminate medical personnel in the hospital 2019-nCoV infection.5. Treatment of infants and young children:Light children only need oral administration. In addition to oral administration of the disease in ordinary children, dialectical Chinese medicine treatment may be considered. If a bacterial infection is combined, an antibacterial drug can be added. Critically ill children are mainly supported by the treatment of the disease, the experience of the libavirin injection antiviral treatment, 15 mg/kg (2 times/d), the course of treatment does not exceed 5 d.(5) The combination of Chinese and Western medicine treatment schemesThe combination of Chinese and Western medicine to treat the new coronavirus pneumonia can improve the synergistic effect.For adult patients, the condition can be improved by dialectical treatment of Chinese medicine. For light patients, the certificate is that the person who is a wind-hot witness gives the chinese medicine silver warp plus subtraction treatment, mainly gastrointestinal symptoms, the proof is wet to stop Weiyang to give the pupu xia soup, three ren Tonga minus.For ordinary patients, the certificate is hot evil lung, to give chinese medicine hemp apricot gantonga reduction; For heavy patients, if the fever does not retreat, even high fever, bloating, feces dry closed knot, the evidence is a hot poison closed lung, to give Chinese medicine large gas soup enema to pass through the diarrhea fever, so that the fever is reduced or heat back, can also be used Chinese medicine white tiger soup, lifting and dispersing and xuan white gas Tonga reduction treatment, so as to cut off the disease, reduce the occurrence of heavy to critical type.Children light patients, the evidence of the time-borne disease guard, can be used silver warp or incense sanois plus and minus. Ordinary type of children, wet hot closed lung, to give the apricot soup three ren Tonga reduction;Heavy patients if the epidemic poisonclosed lungs (currently rare in the country) can refer to adultXuanBai gas soup with ganlu disinfection Tanga minus;(6) Discharge criteriaAt the same time, those who meet the following conditions may consider being discharged from the hospital:(1) The body temperature is back to normal . . . 3 d;(2) The respiratory symptoms improved significantly;(3) Lung imaging examination showed a significant improvement in acute oozing lesions;(4) Two consecutive respiratory specimen nucleic acid test negative (sampling time at least 1 d interval);(5) After the respiratory sample nucleic acid test is negative, the fecal pathogen nucleic acid test is also negative;(6) The total course of the disease is more than 2 weeks.(7) Health management of discharged patients1. For discharged patients, close follow-up should still be made. Follow-up is recommended in the 2nd and 4th weeks after the patient is discharged from the hospital to the designated follow-up clinic.2. When a patient is discharged from the hospital, he or she should be clear about his/her place of residence and address in the city.3. Patients stay at home for 2 weeks after discharge from hospital, avoid activities in public places, must wear a mask when they go out.4. According to the patient's address (including hotels or hotels), the relevant district health and health committee organized by the corresponding medical institutions to do a good job of health management. For 2 weeks, professionals will be able to measure a patient's temperature twice a day, ask about their health status, and conduct health education.5. If fever and/or respiratory symptoms occur again, the corresponding medical institution shall promptly report to the District Health and Health Commission, District Centers for Disease Control and Prevention, and assist in sending the designated medical institutions within the jurisdiction for medical treatment.6. District Health Committee, District Centerfor for Disease Control and Prevention received the report, timely report to the higher authorities.Members of the Expert GroupWriting experts (in order of last name pinyin): Yu Yuan (Severe Medical Department of Renji Hospital affiliated with Shanghai Jiaotong University School of Medicine), Hu Bijie (Infection Department of Zhongshan Hospital affiliated with Fudan University), Li Feng (Respiratory Medicine, Shanghai Public Health Clinical Center), Li Xin (Cardiosurgery/ECMO Treatment of Sun Yat-sen Hospital affiliated with Fudan University) Center), Li Yingchuan (The Anesthesiology Department of the Sixth People's Hospital affiliated with Shanghai Jiaotong University), Lu Hongzhou (Infection and Immunology Department of Shanghai Public Health Clinical Center), Mao Enqiang (Emergency Department of Ruijin Hospital, Shanghai Jiaotong University Medical College), Yu Hongping (Severe Medical Department of Ruijin Hospital, Shanghai Jiaotong University Medical College), Shi Kehua (Respiratory Department of Chinese Medicine Hospital affiliated with Shanghai University of Traditional Chinese Medicine), Wang Wei (Lung Circulation Department of Shanghai Lung Hospital affiliated with Tongji University), Wang Qibing (Testing Department of Zhongshan Hospital affiliated with Fudan University), Wang Sheng (Emergency Critical Care Department of the Tenth People's Hospital affiliated with Tongji University), Yu Kanglong (Shanghai Jiaotong University Affiliated No. First People's Hospital Emergency and Critical Care Department, Zeng Mei (Hospital Infection Department affiliated with Fudan University), Zhang Wei (Respiratory Department of Shuguang Hospital affiliated with Shanghai University of Traditional Chinese Medicine), Zhang Wenhong (Hospital Infection Department of Huashan Hospital affiliated with Fudan University), Zhu Duming (Severe Medical Department of Sun Yat-sen Hospital affiliated with Fudan University), Zhu Lei (Respiratory Department of Sun Yat-sen Hospital affiliated with Fudan University)Consult an expert (sorted by last name pinyin):Li Qiang (Respiratory Department of Oriental Hospital affiliated with Tongji University), Li Xiangyang (Respiratory Department of East China Hospital affiliated with Fudan University), Yu Jieming (Respiratory Department of Ruijin Hospital affiliated with Shanghai Jiaotong University School of Medicine), Song Yuanlin (Respiratory Department of Zhongshan Hospital affiliated with Fudan University), Tian Rui (Critical Department of First People's Hospital affiliated with Shanghai Jiaotong University), Wang Xingpeng (Shanghai Shenkang Hospital Development Center), Wu Yinggen (Longhua Hospital affiliated with Shanghai University of Traditional Chinese Medicine), Xu Jinfu (Respiratory Department of Shanghai Lung Hospital affiliated with Tongji University), Xu Jie (Infection Department of the Ninth People's Hospital affiliated with Shanghai Jiaotong University Medical College), Zhang Huiyong (Lung Department of Longhua Hospital affiliated with Shanghai University of Traditional Chinese Medicine), Zhu Tongyu (Urology, Shanghai Public Health Clinical Center), Zhu Yuchen (Emergency Department, Huashan Hospital, Affiliated with Fudan University)Conflicts of interestAll authors declare that there is no conflict of interestReferences (slightly)上海市2019冠状病毒病综合救治专家共识 上海救治专家组 SIFIC感染循证资讯 6 days ago // 上海市2019冠状病毒病综合救治专家共识 //上海市新型冠状病毒病临床救治专家组2019冠状病毒病（corona virus disease 2019, COVID-19）于2019年12月31日首次在湖北省武汉市被报告[1,2]。COVID-19作为呼吸道传染病，已被纳入《中华人民共和国传染病防治法》规定的乙类传染病，按甲类传染病管理。随着对疾病认识的深入，全国各地在COVID-19防控与诊治方面均积累了一定的经验。上海市新型冠状病毒病临床救治专家组遵循国家新型冠状病毒肺炎诊疗方案[3]，充分吸取国内外同行的救治经验，以提高临床救治成功率和降低患者病死率为目标，阻止病情进展，逐步降低了病重患者的比例，提高其临床预后。在不断优化和细化救治方案的基础上，就相关临床诊治工作形成了专家共识意见。01 病原学及流行病学特征2019新型冠状病毒（2019 novel coronavirus，2019-nCoV）是属于β属的新型冠状病毒。2020年2月11日，国际病毒分类委员会（The International Committee on Taxonomy of Viruses，ICTV）将该病毒命名为严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2，SARS-CoV-2）[4]。COVID-19患者及无症状感染者均可传播2019-nCoV。经呼吸道飞沫传播是主要传播途径，亦可通过接触传播。在局限的封闭空间内，还有气溶胶传播的风险。COVID-19患者的粪便、尿液和血液中可检测到2019-nCoV；部分患者在呼吸道标本病原核酸检测阴性后，其粪便病原核酸检测仍可阳性。人群普遍易感。儿童及婴幼儿也有发病，但病情较轻。02 临床特征与诊断（一）临床特征潜伏期为1～14 d，多为3～7 d，平均为6.4 d。以发热、乏力、干咳为主要表现。可伴有流涕、咽痛、胸闷、呕吐和腹泻等症状。部分患者症状轻微，少数患者无症状或无肺炎表现。老年人及患有糖尿病、高血压、冠状动脉粥样硬化性心脏病、极度肥胖等基础疾病者感染后易发展为重症。部分患者在发病后1周出现呼吸困难等症状，严重者可进展为急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）及多器官功能损伤。进展至重症的时间约为8.5 d。值得注意的是，重型、危重型患者病程中可为中低热，甚至无明显发热。多数患者预后良好，死亡病例多见于老年人和有慢性基础疾病者。早期CT检查表现为多发小斑片或磨玻璃影，其内纹理可呈网格索条状增粗影，以肺外带明显。数天后病灶增多，范围扩大，呈双肺广泛、多发磨玻璃影或浸润病灶，部分出现肺实变，常有支气管充气征，胸腔积液少见。少数患者进展迅速，在病程第7至10天，影像学变化达高峰。典型的"白肺"表现少见。进入恢复期后，病灶减少，范围缩小，渗出性病变吸收，部分出现纤维索条影，部分患者病灶可完全吸收。发病早期患者外周血白细胞总数正常或减少，淋巴细胞计数减少，部分患者可出现肝功能异常，乳酸脱氢酶、肌酶和肌红蛋白水平增高；可见肌钙蛋白水平增高。多数患者CRP和ESR水平升高，降钙素原水平正常。严重者D-二聚体水平升高，其他出凝血指标异常，乳酸水平升高，外周血淋巴细胞和CD4+T淋巴细胞进行性减少，以及电解质紊乱、酸碱失衡等，以代谢性碱中毒多见。在病情进展阶段可出现炎症细胞因子（如IL-6、IL-8等）水平升高[5]。（二）诊断标准1．疑似病例：结合下述流行病学史和临床表现综合分析。有流行病学史中的任何一项且符合临床表现中任意2项，或无明确流行病学史但符合临床表现中的3项，均诊断为疑似病例。①流行病学史：发病前14 d内有武汉市及周边地区,或其他有病例报告社区的旅行史或居住史；发病前14 d内与2019-nCoV感染(核酸检测阳性)者有接触史；发病前14 d内曾接触过来自武汉市及周边地区,或来自有病例报告社区的发热或有呼吸道症状的患者；聚集性发病。②临床表现：发热和（或）呼吸道症状；具有上述新型冠状病毒肺炎影像学特征；发病早期白细胞总数正常或降低,淋巴细胞计数减少。2．确诊病例：具备下述病原学证据之一者即诊断为确诊病例。①实时荧光反转录PCR检测2019-nCoV核酸阳性。②病毒基因测序发现与已知的2019-nCoV高度同源。③除鼻咽拭子外，建议尽可能留取痰液，实施气管插管患者可采集下呼吸道分泌物送病毒核酸检测。（三）鉴别诊断主要与流行性感冒病毒、副流感病毒、腺病毒、呼吸道合胞病毒、鼻病毒、人偏肺病毒、严重急性呼吸综合征（severe acute respiratory syndrome，SARS）冠状病毒等其他已知病毒性肺炎鉴别，与肺炎支原体、衣原体肺炎和细菌性肺炎等鉴别。此外，还要与非感染性疾病，如血管炎、皮肌炎等结缔组织疾病引起的肺间质性病变和机化性肺炎等鉴别[6,7]。（四）临床分型1．轻型：临床症状轻微，影像学检查未见肺炎表现。2．普通型：具有发热、呼吸道等症状，影像学检查可见肺炎表现。应加强普通型患者重症化的早期预警。基于目前的临床研究表明，老年（年龄>65岁），伴有基础疾病，CD4+T淋巴细胞数<250/µL，血IL-6水平明显上升，2～3 d肺部影像学检查发现病灶明显进展>50%，乳酸脱氢酶（lactic dehydrogenase，LDH）>2倍正常值上限，血乳酸≥3 mmol/L，代谢性碱中毒等均是重症化的早期预警指标[8]。3．重型：符合以下任意一项者。①出现气促，呼吸频率≥30次/min；②在静息状态下，指动脉血氧饱和度（arterial oxygen saturation，SaO2）≤93%；③动脉血氧分压（arterial partial pressure of oxygen，PaO2）/吸氧浓度（fraction of inspired oxygen，FiO2）≤300 mmHg（1 mmHg=0.133 kPa）。高海拔（海拔超过1 000 m）地区应根据以下公式对PaO2/FiO2进行校正：PaO2/FiO2×[大气压(mmHg)/760]。肺部影像学检查显示24～48 h内病灶明显进展>50%者按重型管理。4．危重型：符合以下任意一项者可判断为危重型。①出现呼吸衰竭，且需要机械通气；②出现休克；③合并其他器官功能衰竭，需ICU监护治疗。（五）临床监测每天动态监测患者的临床表现、生命体征、出入液量、胃肠道功能和精神状态。对所有患者动态监测指末血氧饱和度。对于重症及危重症患者，根据病情变化及时进行血气分析；血常规、电解质、CRP、降钙素原、LDH、凝血功能指标、血乳酸等，每2 d至少检测1次；肝功能、肾功能、ESR、IL-6、IL-8、淋巴细胞亚群，每3 d至少检测1次；胸部影像学检查，通常情况下每2 d检查1次。对于ARDS患者，建议常规行床旁心脏和肺的超声检查，观察其血管外肺水和心脏的参数。体外膜肺氧合（extracorporeal membrane oxygenation，ECMO）患者监测参照ECMO的实施章节。03 救治方案（一）抗病毒治疗可试用硫酸羟氯喹或磷酸氯喹、阿比多尔口服，干扰素雾化吸入，首选干扰素κ。不建议同时使用3种或以上抗病毒药物。在病毒核酸转阴后应及时停用。所有抗病毒治疗药物的疗效还有待于进一步的临床研究来评估。对于重型和危重型病毒核酸阳性患者，可试用康复者恢复期血浆。详细操作及不良反应管理参照国家卫生健康委颁布的《新冠肺炎康复者恢复期血浆临床治疗方案》（试行第一版）[3]。起病14 d内予以输注可能疗效更好，在病程后期如持续检出病毒核酸，也可试用康复者恢复期血浆治疗。（二）轻型和普通型患者的治疗需加强支持治疗，保证充分热量；注意水、电解质平衡，维持内环境稳定；密切监测患者生命体征和指氧饱和度等。及时给予有效氧疗措施。原则上不使用抗菌药物和糖皮质激素。需密切观察患者病情变化，若病情出现显著进展并有转为重型风险时，建议采取综合措施阻止疾病进展为重型，可酌情谨慎使用低剂量短程糖皮质激素（具体方案见糖皮质激素的应用章节）。推荐使用肝素抗凝和大剂量维生素C治疗[9,10]。低分子肝素1～2支/d，持续至患者D-二聚体水平恢复正常。一旦纤维蛋白降解产物（fibrinogen degradation product,FDP）≥10 µg/mL和（或）D-二聚体≥5 μg/mL，则改用普通肝素抗凝。维生素C每天50～100 mg/kg，静脉滴注，持续使用时间以氧合指数显著改善为目标。如出现肺部病灶进展，推荐应用大剂量广谱蛋白酶抑制剂60～100万单位/d，持续至肺部影像学检查改善。一旦出现"细胞因子风暴"，建议采用间断短时血液滤过（intermittent short veno-venuous hemofiltration，ISVVH）[11]。（三）重症与危重症患者的脏器功能支持治疗1．循环功能的保护与维持：实施早期积极的控制性补液原则。推荐入院后尽快评估有效容量和启动液体治疗。重型患者可根据条件选用静脉途径或经结肠途径进行液体复苏。补充的液体首选乳酸林格液。关于血管活性药物，推荐去甲肾上腺素联合多巴胺维持血管张力和增加心排量。对于发生休克的患者，首选去甲肾上腺素，建议在液体复苏同时开始应用小剂量血管活性药物，维持循环稳定并避免液体输注过多。推荐重型、危重型患者使用保护心脏的药物，尽量避免使用对心脏有抑制作用的镇静药物。对于窦性心动过缓患者，可使用异丙肾上腺素。建议对窦性心律、心率<50次/min并伴有血流动力学不稳定的患者，静脉泵注小剂量异丙肾上腺素或多巴胺维持心率在80次/min左右。2．减轻肺间质炎症：2019-nCoV导致严重的肺间质病变会引起肺功能恶化，建议使用大剂量广谱蛋白酶抑制剂。3．肾脏功能的保护：推荐尽早合理抗凝治疗和恰当的液体治疗。参见"细胞因子风暴"的防治、循环功能的保护与维持章节。4．肠道功能的保护：可使用益生元改善患者肠道微生态。使用生大黄（15～20 g加150 ml温开水泡制）或大承气汤口服或灌肠。5．营养支持：首选胃肠内营养，经鼻饲或经空肠途径。首选整蛋白营养制剂，能量为每天25～35 kcal/kg（1 kcal=4.184 kJ）。6．"细胞因子风暴"的防治：推荐使用大剂量维生素C和普通肝素抗凝。大剂量维生素C每天100～200 mg/kg静脉注射。持续使用时间以氧合指数显著改善为目标。推荐应用大剂量广谱蛋白酶抑制剂，给予160万单位，每8 h 1次，在机械通气状态下，当氧合指数>300 mmHg时可减量至100万单位/d。可采取抗凝治疗保护内皮细胞与减少细胞因子释放，FDP≥10 µg/mL和（或）D-二聚体≥5 μg/mL时予普通肝素（每小时3～15 IU/kg）抗凝。初次使用肝素后4 h必须复查患者凝血功能和血小板。采用ISVVH，每天6～10 h。7．镇静肌松与人工冬眠疗法：机械通气或接受ECMO患者需在镇痛基础上镇静。对于建立人工气道时有严重人机对抗的患者，建议短程应用小剂量肌松药物。建议氧合指数<200 mmHg的重症患者可采用冬眠疗法。人工冬眠疗法可降低机体的代谢和氧耗，同时扩张肺部血管而显著改善氧合，建议采用持续静脉推注的方法用药，需密切监测患者血压。谨慎使用阿片类药物和右美托咪定。因重症患者常存在IL-6水平异常而易导致腹胀，应避免使用阿片类药物；而2019-nCoV尚可抑制窦房结的功能而发生窦性心动过缓，因此应慎用对心脏有抑制作用的镇静药物。为防止肺部感染的发生与加重，尽量避免长时间的过度镇静，条件许可时应尽快撤停肌松药物。建议密切监测镇静深度。8．氧疗和呼吸支持：①鼻导管或面罩氧疗，静息吸空气条件下SaO2≤93%，或活动后SaO2<90%，或氧合指数（PaO2/FiO2）为200～300 mmHg；伴或不伴呼吸窘迫；均推荐持续氧疗。②经鼻高流量氧疗（high-flow nasal cannula oxygen therapy，HFNC），接受鼻导管或面罩氧疗1～2 h氧合达不到治疗要求，呼吸窘迫无改善；或治疗过程中低氧血症和（或）呼吸窘迫加重；或氧合指数为150～200 mmHg；推荐HFNC。③无创正压通气（noninvasive positive pressure ventilation，NPPV），接受HFNC 1～2 h氧合达不到治疗效果，呼吸窘迫无改善；或治疗过程中低氧血症和（或）呼吸窘迫加重；或氧合指数为150～200 mmHg时；可以选用NPPV。④有创机械通气，接受HFNC或NPPV治疗1～2 h氧合达不到治疗要求，呼吸窘迫无改善；或治疗过程中低氧血症和（或）呼吸窘迫加重；或氧合指数<150 mmHg时；应考虑有创通气。首选以小潮气量（4～8 mL/kg理想体质量）为核心的保护性通气策略。9．ECMO的实施：满足以下条件之一者可考虑实施ECMO。① PaO2/FiO2< 50 mmHg超过1 h；② PaO2/FiO2<80 mmHg超过2 h；③动脉血pH值<7.25并伴有PaCO2>60 mmHg超过6 h。ECMO模式首选静脉-静脉ECMO。（四）救治中的特殊问题及处理1．糖皮质激素的应用：需谨慎使用糖皮质激素。影像学检查提示肺炎出现明显进展，静息未吸氧状态下患者SaO2≤93%或呼吸急促（呼吸频率≥30次/min）或氧合指数≤300 mmHg，特别是病情进展速度明显加快，面临插管风险时可加用糖皮质激素。患者在插管或ECMO支持可维持有效血氧浓度时，则建议迅速撤退糖皮质激素的使用。对于非重症患者使用甲泼尼龙，建议剂量控制在20～40 mg/d，重症患者控制在40～80 mg/d，疗程一般为3～6 d。可根据体质量酌量增减[12]。2．免疫调节药物的使用：每周2次皮下注射胸腺肽，对提高患者免疫功能、阻止病情重症化、缩短排毒时间有一定效果。由于缺乏特异性抗体，目前不支持大剂量使用静脉输注人免疫球蛋白治疗。但部分患者淋巴细胞水平低下，且有合并其他病毒感染的风险，可静脉输注人免疫球蛋白10 g/d，疗程为3～5 d。3．合并细菌、真菌感染的精准诊治：对所有重症和危重症患者进行临床微生物监测。每天留取患者痰液和尿液进行培养，高热患者及时行血培养。所有留置血管导管的疑似脓毒症患者，均应同时送检外周静脉血血培养和导管血培养。所有疑似脓毒症患者可考虑采集外周血进行病原学分子诊断检查，包括基于PCR的分子生物学检测及二代测序。降钙素原水平升高对诊断脓毒症/脓毒性休克具有提示意义。新型冠状病毒肺炎患者病情加重时，存在CRP水平升高，CRP水平升高对诊断细菌和真菌感染引起的脓毒症缺乏特异性。气道开放的危重型患者后期往往易合并细菌感染和真菌感染。若发生脓毒症，则应尽快给予经验性抗感染治疗。对于脓毒性休克患者，获得病原学诊断前可联合使用经验性抗菌药物，同时覆盖最为常见的肠杆菌科细菌、葡萄球菌和肠球菌感染。住院后发生感染者可选用β内酰胺酶抑制剂复合物。若治疗效果不佳，或患者为重症感染性休克，可换用碳青霉烯类药物治疗。如考虑合并肠球菌和葡萄球菌感染，可加用糖肽类药物（万古霉素）进行经验性治疗，血流感染可选用达托霉素，以肺部感染为主则可选用利奈唑胺。应高度重视危重症患者的导管相关感染，治疗应经验性覆盖甲氧西林耐药的葡萄球菌。可选用糖肽类药物（万古霉素）进行经验性治疗。念珠菌感染在危重症患者中也较为常见，必要时应经验性覆盖念珠菌治疗，可加用棘白菌素类药物。随着重症患者住院时间延长，耐药感染也逐渐增加，此时须根据药物敏感试验调整抗菌药物的使用。4．院内感染防控：①根据2019年国家卫生健康委《医疗机构感染预防与控制基本制度（试行）》[13]，积极推行循证感染防控集束化干预策略，有效预防呼吸机相关肺炎、血管内导管相关血流感染、导尿管相关尿路感染、碳青霉烯耐药革兰阴性杆菌等多重耐药菌和真菌感染。②严格遵照国家卫生健康委《医疗机构内新型冠状病毒感染预防与控制技术指南(第一版)》《新型冠状病毒感染的肺炎防控中常见医用防护用品使用范围指引(试行)》《新冠肺炎疫情期间医务人员防护技术指南(试行)》的要求[14,15,16]，加强流程管理，正确选择和使用口罩、隔离衣、防护服、眼罩、防护面罩、手套等个人防护用品，严格各项消毒隔离措施的落实，最大限度地降低医院感染风险，杜绝医务人员的医院内2019-nCoV感染。5．婴幼儿的治疗：轻型患儿仅需对症口服给药治疗。普通型患儿除对症口服给药治疗外，可考虑辨证中药治疗。若合并细菌感染，可加用抗菌药物。重危患儿以对症支持治疗为主，经验给予利巴韦林注射剂抗病毒治疗，15 mg/kg（2次/d），疗程不超过5 d。（五）中西医结合救治方案中西医结合救治新型冠状病毒肺炎能提高协同疗效。对于成人患者，通过中医药辨证施治可改善病情。对于轻型患者，证属风热表证者给予中药银翘散加减治疗；以胃肠道症状为主，证属湿遏卫阳者给予藿朴夏苓汤、三仁汤加减。对于普通型患者，证属热邪郁肺者，给予中药麻杏石甘汤加减；证属湿毒郁肺者，给予中药达原饮、甘露消毒丹等加减治疗，可在一定程度上控制病情进展，减少普通型转重型的发生；对于纳差、呕恶、腹胀、乏力、焦虑失眠等，给予中药小柴胡汤加减治疗，可明显改善症状。对于重型患者，如果发热不退，甚至高热、腹胀、粪便干燥闭结，证属热毒闭肺者，给予中药大承气汤灌肠以通腑泻热，使发热减轻或热退，也可用中药白虎汤、升降散和宣白承气汤加减治疗，从而截断病情，减少重型转为危重型的发生。儿童轻型患者，证属时疫犯卫，可用银翘散或香苏散加减。普通型患儿，湿热闭肺者，给予麻杏石甘汤合三仁汤加减；伴腹胀苔腻呕恶等中焦湿热者，可予不换金正气散加减。重型患者若疫毒闭肺（目前全国罕见）可参考成人宣白承气汤合甘露消毒丹加减；若毒热炽盛，腑气不通，食药不下，亦短期予生大黄煎汤灌肠救急。（六）出院标准同时符合以下条件者可考虑出院：①体温恢复正常>3 d；②呼吸道症状明显好转；③肺部影像学检查显示急性渗出性病变明显改善；④连续两次呼吸道标本核酸检测阴性（采样时间至少间隔1 d）；⑤呼吸道标本核酸检测阴性后，粪便病原核酸检测也阴性；⑥总病程超过2周。（七）出院患者的健康管理1．对于出院患者，目前仍应密切随访。建议在患者出院后的第2周和第4周至指定的随访门诊进行随访。2．患者出院时，应明确其在本市的居住场所和地址。3．患者出院后居家休息2周，避免在公共场所活动，必须外出时应佩戴口罩。4．根据患者住址(包括宾馆或酒店)，由相关区卫生健康委组织对应医疗机构做好健康管理。2周内专业人员每天2次上门测量患者体温，询问其健康状况，并开展相关健康宣教。5．如再次出现发热和（或）呼吸道症状等时，对应医疗机构应及时向区卫生健康委、区疾病预防控制中心报告，并协助送辖区内指定医疗机构就诊。6．区卫生健康委、区疾病预防控制中心接到报告后，及时报告上级部门。专家组成员执笔专家（按姓氏拼音排序）：皋源(上海交通大学医学院附属仁济医院重症医学科)、胡必杰（复旦大学附属中山医院感染科）、李锋（上海市公共卫生临床中心呼吸内科）、李欣（复旦大学附属中山医院心外科/ECMO治疗中心）、李颖川（上海交通大学附属第六人民医院麻醉科）、卢洪洲（上海市公共卫生临床中心感染与免疫科）、毛恩强（上海交通大学医学院附属瑞金医院急诊科）、瞿洪平（上海交通大学医学院附属瑞金医院重症医学科）、石克华（上海中医药大学附属市中医医院呼吸科）、王岚（同济大学附属上海市肺科医院肺循环科）、王齐兵（复旦大学附属中山医院检验科）、王胜（同济大学附属第十人民医院急诊危重病医学科）、俞康龙（上海交通大学附属第一人民医院急诊与危重病科）、曾玫（复旦大学附属儿科医院感染科）、张炜（上海中医药大学附属曙光医院呼吸科）、张文宏（复旦大学附属华山医院感染科）、诸杜明（复旦大学附属中山医院重症医学科）、朱蕾（复旦大学附属中山医院呼吸科）咨询专家（按姓氏拼音排序）：李强（同济大学附属东方医院呼吸科）、李向阳（复旦大学附属华东医院呼吸科）、瞿介明（上海交通大学医学院附属瑞金医院呼吸科）、宋元林（复旦大学附属中山医院呼吸科）、田锐（上海交通大学附属第一人民医院危重病科）、王兴鹏（上海申康医院发展中心）、吴银根（上海中医药大学附属龙华医院）、徐金富（同济大学附属上海市肺科医院呼吸科）、许洁（上海交通大学医学院附属第九人民医院感染科）、张惠勇（上海中医药大学附属龙华医院肺病科）、朱同玉（上海市公共卫生临床中心泌尿外科）、祝禾辰（复旦大学附属华山医院急诊科）利益冲突所有作者均声明不存在利益冲突参考文献（略）
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