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Shanghai 2019 Expert Coronary Disease Comprehensive Treatment Consensus
【Editor's note】 On March 1, the "Chinese Journal of Infectious Diseases" network hosted by the Shanghai Medical Association pre-published the "Shanghai Expert Consensus for Comprehensive Treatment of Coronavirus 2019" .htm), which has aroused widespread concern in the industry, and Shanghai TV also carried a news report last night. This consensus was composed of 30 experts representing the strongest medical force in the treatment of Shanghai's new coronavirus pneumonia, through a summary of more than 300 patients in clinical research, and fully drawing on the experience of the treatment of domestic and foreign counterparts, and finally formed the "Shanghai Plan". At the end of the article, a list of these 30 experts (18 authors and 12 consultants) from various medical institutions in Shanghai is attached.
Corona virus disease 2019 (COVID-19) was first reported in Wuhan, Hubei Province on December 31, 2019. As a respiratory infectious disease, COVID-19 has been included in the category B infectious diseases as stipulated in the Law of the People ’s Republic of China on the Prevention and Control of Infectious Diseases, and is managed as a category A infectious disease.
With the deepening of the understanding of the disease, all parts of the country have accumulated certain experience in the prevention and control of COVID-19. The Shanghai New Coronary Virus Disease Clinical Treatment Expert Group follows the national new coronavirus pneumonia diagnosis and treatment plan, and fully draws on the treatment experience of domestic and foreign counterparts to improve the success rate of clinical treatment and reduce the mortality rate of patients. The goal is to prevent the progress of the disease and gradually reduce the disease. The proportion of heavy patients improves its clinical prognosis. On the basis of continuous optimization and refinement of the treatment plan, an expert consensus has been formed on the relevant clinical diagnosis and treatment.
1. Etiology and epidemiology
2019 novel coronavirus (2019 novel coronavirus, 2019-nCoV) is a novel coronavirus belonging to the genus β. On February 11, 2020, the International Committee on Taxonomy of Viruses (ICTV) named the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Both COVID-19 patients and those with asymptomatic infections can transmit 2019-nCoV. Transmission through the respiratory tract droplets is the main route of transmission, and can also be transmitted through contact. In confined enclosed spaces, there is also the risk of aerosol transmission. 2019-nCoV can be detected in the stool, urine and blood of COVID-19 patients; some patients may still have a positive stool pathogenic nucleic acid test after the pathogenic nucleic acid test of respiratory specimens is negative. The crowd is generally susceptible. Children and infants also have the disease, but the condition is mild.
2. Clinical features and diagnosis
(1) Clinical features The incubation period is 1-14 days, mostly 3-7 days, with an average of 6.4 days. The main manifestations are fever, fatigue, and dry cough. May be accompanied by symptoms such as runny nose, sore throat, chest tightness, vomiting, and diarrhea. Some patients have mild symptoms, and a few have no symptoms or pneumonia.
The elderly and those with basic diseases such as diabetes, hypertension, coronary atherosclerotic heart disease, and extreme obesity are prone to develop severe illness after infection. Some patients have symptoms such as dyspnea 1 week after the onset of symptoms. In severe cases, they may progress to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction. The time to progress to severe disease is about 8.5 days. It is worth noting that in the course of severe and critically ill patients, the disease can be moderate to low fever, or even no obvious fever. Most patients have a good prognosis, and deaths are more common in the elderly and those with chronic underlying diseases. Early CT examination showed multiple small patches or ground glass shadows, the internal texture of which could be thickened with grid-like strips, with obvious extrapulmonary bands. After a few days, the lesions increased and the scope expanded, showing extensive lungs, multiple ground glass shadows or infiltrating lesions, some lung consolidation, bronchial inflation often occurred, and pleural effusions were rare. A few patients progressed rapidly, and the imaging changes peaked on days 7 to 10 of the course of the disease. Typical "white lung" performance is rare. After entering the recovery period, the lesions were reduced, the scope was reduced, the exudative lesions were absorbed, some of the fibrous cords appeared, and some patients could be completely absorbed.
In the early stage of the disease, the total number of white blood cells in the peripheral blood was normal or decreased, and the lymphocyte count decreased. In some patients, abnormal liver function may occur, and the levels of lactate dehydrogenase, myozyme, and myoglobin increased; troponin levels increased. Most patients have elevated CRP and ESR levels, and normal procalcitonin levels. In severe cases, the level of D-dimer is increased, other blood coagulation indicators are abnormal, the level of lactic acid is increased, the peripheral blood lymphocytes and CD4 + T lymphocytes are progressively reduced, as well as electrolyte disturbance, acid-base imbalance, etc., to metabolic alkalosis See more. In the progressive stage of the disease, there may be increased levels of inflammatory cytokines (such as IL-6, IL-8, etc.).
(2) Diagnostic criteria
1. Suspected cases:
Combined with the following comprehensive analysis of epidemiological history and clinical manifestations. Any one of the epidemiological history and any two of the clinical manifestations, or no clear epidemiological history but three of the clinical manifestations, are diagnosed as suspected cases.
① Epidemiological history: travel history or residence history of Wuhan City and surrounding areas, or other communities with case reports within 14 days before the onset of illness; history of contact with 2019-nCoV infection (positive nucleic acid test) within 14 days of onset ; Contacted patients with fever or respiratory symptoms from Wuhan City and surrounding areas, or from communities with case reports within 14 days before the onset of disease; clustered onset.
② Clinical manifestations: fever and (or) respiratory symptoms; with the above-mentioned imaging features of the new coronavirus pneumonia; the number of white blood cells in the early stage of the disease is normal or decreases, and the lymphocyte count decreases.
2. Confirmed cases:
A person who has one of the following etiological evidences is diagnosed as a confirmed case.
① Real-time fluorescent reverse transcription PCR test positive for 2019-nCoV nucleic acid.
② Viral gene sequencing found to be highly homologous to the known 2019-nCoV.
③ In addition to nasopharyngeal swabs, sputum is collected as much as possible, and patients with tracheal intubation can collect lower respiratory tract secretions and send viral nucleic acid test positive.
(3) Differential diagnosis
It is mainly distinguished from influenza virus, parainfluenza virus, adenovirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, severe acute respiratory syndrome (SARS) coronavirus and other known viral pneumonia , With Mycoplasma pneumoniae, Chlamydia pneumonia and bacterial pneumonia. In addition, it must be distinguished from non-infectious diseases such as pulmonary interstitial lesions and organizing pneumonia caused by connective tissue diseases such as vasculitis and dermatomyositis.
(4) Clinical classification
1. Mild: Mild clinical symptoms, no pneumonia manifestations on imaging examination.
2. Common type: It has fever, respiratory tract and other symptoms. Pneumonia can be seen on imaging examination. The early warning of the seriousness of ordinary patients should be strengthened. Based on current clinical research, the elderly (age> 65 years) with underlying disease, CD4 + T lymphocyte count <250 / µL, blood IL-6 levels increased significantly, 2 to 3 days of lung imaging revealed lesions Significant progress> 50%, lactate dehydrogenase (LDH)> 2 times the upper limit of normal, blood lactate ≥3 mmol / L, metabolic alkalosis, etc. are early warning indicators of severe disease.
3. Heavy: meets any of the following.
① Shortness of breath, ≥30 breaths / min;
② Arterial oxygen saturation (SaO2) ≤93% in resting state;
③ Arterial partial pressure of oxygen, PaO2) / fraction of inspired oxygen (FiO2) ≤300 mmHg (1 mmHg = 0.133 kPa). At high altitudes (altitude above 1 000 m), PaO2 / FiO2 should be corrected according to the following formula: PaO2 / FiO2 × [atmospheric pressure (mmHg) / 760]. Pulmonary imaging examination showed that the lesions significantly progressed within 24 to 48 hours> 50% were managed according to the severity.
4. Critical severity: Those who meet any of the following can be judged as critical.
① Respiratory failure occurs and mechanical ventilation is required;
② Shock occurs;
③ Other organ failures require ICU monitoring and treatment.
(5) Clinical monitoring
Monitor patients' clinical manifestations, vital signs, fluid volume in and out, gastrointestinal function and mental status every day. Dynamic monitoring of end-of-finger oxygen saturation of all patients. For severe and critically ill patients, blood gas analysis should be carried out in time according to the change of the condition; blood routine, electrolyte, CRP, procalcitonin, LDH, blood coagulation function indexes, blood lactic acid, etc. should be tested at least once every 2 days; , ESR, IL-6, IL-8, lymphocyte subsets, at least once every 3 days; chest imaging examination, usually every 2 days. For patients with ARDS, it is recommended to perform routine ultrasound examination of the heart and lungs beside the bed to observe the extravascular lung water and heart parameters. For extracorporeal membrane oxygenation (ECMO) patient monitoring, refer to the ECMO implementation chapter.
3. Treatment plan
(1) Antiviral treatment You can try hydroxychloroquine sulfate or chloroquine phosphate, Abidor oral, interferon nebulized inhalation, interferon κ is preferred, or interferon α recommended by the national program can also be used. It is not recommended to use 3 or more antiviral drugs at the same time. It should be stopped in time after the viral nucleic acid turns negative. The efficacy of all antiviral drugs still needs to be evaluated by further clinical studies. For severe and critical viral nucleic acid positive patients, the recovery period plasma can be tried. For detailed operation and management of adverse reactions, please refer to the "Clinical Treatment Program for the Recovery Period of New Coronary Pneumonia Patients Recovered" promulgated by the National Health Commission (first trial version). Infusion within 14 days of onset may have a better effect. If viral nucleic acid is continuously detected later in the course of the disease, plasma therapy can also be used in the recovery phase of the recovered person.
(2) Treatment of light and ordinary patients
Supportive treatment needs to be strengthened to ensure adequate calories; pay attention to the balance of water and electrolytes and maintain the stability of the internal environment; closely monitor patient vital signs and finger oxygen saturation. Give effective oxygen therapy measures in time. In principle, antibacterial drugs and glucocorticoids are not used. It is necessary to closely observe the changes in the patient's condition. If there is significant progress in the condition and there is a risk of becoming severe, it is recommended to take comprehensive measures to prevent the disease from progressing to severe. You can use low-dose short-term glucocorticoids as appropriate ). It is recommended to use heparin anticoagulation and high-dose vitamin C treatment. Low molecular weight heparin 1 to 2 sticks / d continues until the patient's D-dimer level returns to normal. Once the fibrinogen degradation product (FDP) ≥10 µg / mL and / or D-dimer ≥5 μg / mL, normal heparin is used for anticoagulation. Vitamin C is 50 to 100 mg / kg per day, intravenously, and the continuous use time aims at significantly improving the oxygenation index. If the lung lesion progresses, it is recommended to use a large dose of broad-spectrum protease inhibitor ulinastatin 600 to 1 million units / d, until the lung imaging examination is improved. Once a "cytokine storm" occurs, it is recommended to use intermittent short veno-venuous hemofiltration (ISVVH).
(3) Supporting treatment of organ function in severe and critically ill patients
1. Protection and maintenance of circulatory function: implement the principle of early active controlled fluid replacement. It is recommended to evaluate the effective volume and start fluid therapy as soon as possible after admission. Severe patients can choose intravenous route or transcolonal route for fluid resuscitation according to conditions. The supplemented liquid is preferably lactated Ringer's solution. Regarding vasoactive drugs, norepinephrine combined with dopamine is recommended to maintain vascular tone and increase cardiac output. For patients with shock, norepinephrine is the first choice. It is recommended that small doses of vasoactive drugs be started at the same time as fluid resuscitation to maintain stable circulation and avoid excessive fluid infusion. Recommend the use of drugs that protect the heart of severe and critically ill patients, and try to avoid the use of sedative drugs that have an inhibitory effect on the heart. For patients with sinus bradycardia, isoproterenol can be used. It is recommended that for patients with sinus rhythm, heart rate <50 beats / min and hemodynamic instability, intravenous pumping of low dose isoproterenol or dopamine to maintain heart rate is about 80 beats / min.
2. Reducing pulmonary interstitial inflammation: 2019-nCoV causes severe pulmonary interstitial lesions that will cause deterioration of lung function. It is recommended to use large dose of broad-spectrum protease inhibitor ulinastatin.
3. Protection of kidney function: It is recommended to use reasonable anticoagulation therapy and appropriate liquid therapy as soon as possible. Please refer to the chapter of "Prevention of Cytokine Storm" and the Protection and Maintenance of Circulatory Function.
4. Protection of intestinal function: Prebiotics can be used to improve the intestinal microecology of patients. Use raw rhubarb (15 ~ 20 g plus 150 ml of warm boiling water) or Dachengqi decoction orally or enema.
5. Nutritional support: Gastrointestinal nutrition is preferred, via nasal feeding or via jejunal route. The first choice is whole protein nutritional preparation, with an energy of 25 ～ 35 kcal / kg per day (1 kcal = 4.184 kJ).
6. Prevention of "cytokine storm": It is recommended to use high-dose vitamin C and unfractionated heparin for anticoagulation. Large-dose vitamin C is intravenously injected at 100-200 mg / kg per day. The continuous use time aims at significantly improving the oxygenation index. Dose broad-spectrum protease inhibitor ulinastatin, given 1.6 million units, once every 8 h, under mechanical ventilation, when the oxygenation index> 300 mmHg can be reduced to 1 million units / d. Anticoagulation can be taken Treatment protects endothelial cells and reduces cytokine release. When FDP ≥10 µg / mL and / or D-dimer ≥5 μg / mL, heparin (3 ～ 15 IU / kg per hour) is used for anticoagulation. Heparin is used for the first time. The patient's coagulation function and platelets must be rechecked after 4 h. ISVVH is used, 6 to 10 h per day.
7. Sedative muscle relaxation and artificial hibernation therapy: patients with mechanical ventilation or receiving ECMO should be sedated on the basis of analgesia. For patients with severe man-machine confrontation when establishing artificial airways, it is recommended to use small doses of muscle relaxants in a short course. It is recommended that hibernation therapy be used in critically ill patients with oxygenation index <200 mmHg. Artificial hibernation therapy can reduce the body's metabolism and oxygen consumption, and at the same time dilate the blood vessels in the lungs to significantly improve oxygenation. It is recommended to use continuous intravenous bolus injection, and the patient's blood pressure needs to be closely monitored. Use opioids and dexmedetomidine cautiously. Because severe IL-6 levels often cause bloating, opioids should be avoided; 2019-nCoV can still suppress the function of the sinoatrial node and sinus bradycardia occurs, so you should be careful about the heart Inhibiting sedative drugs. In order to prevent the occurrence and aggravation of lung infection, try to avoid prolonged excessive sedation. When conditions permit, the muscle relaxant drug should be withdrawn 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, SaO2≤93% under resting air inhalation, or SaO2 <90% after activity, or oxygenation index (PaO2 / FiO2) is 200-300 mmHg; With or without respiratory distress; continuous oxygen therapy is recommended.
② High-flow nasal cannula oxygen therapy (HFNC), receiving nasal cannula or mask oxygen therapy for 1 to 2 hours of oxygenation fails to meet the treatment requirements, and respiratory distress does not improve; or hypoxemia during treatment And (or) increased respiratory distress; or an oxygenation index of 150-200 mmHg; HFNC is recommended.
③ Noninvasive positive pressure ventilation (NPPV), HFNC receiving 1 to 2 hours of oxygenation does not achieve the therapeutic effect, and respiratory distress does not improve; or hypoxemia and / or respiratory distress increase during treatment; or When the oxygenation index is 150-200 mmHg; NPPV can be used.
④ Invasive mechanical ventilation, receiving HFNC or NPPV treatment for 1 to 2 hours, oxygenation fails to meet the treatment requirements, and respiratory distress does not improve; or hypoxemia and / or respiratory distress worsens during treatment; or oxygenation index <150 mmHg; invasive ventilation should be considered. The preferred protective ventilation strategy with a small tidal volume (4-8 mL / kg ideal body mass) as the core.
9. Implementation of ECMO: Those who meet one of the following conditions may consider implementing ECMO.
① PaO2 / FiO2 <50 mmHg over 1 h;
② PaO2 / FiO2 <80 mmHg over 2 h;
③ Arterial blood pH <7.25 with PaCO2> 60 mmHg over 6 h ECMO mode is the preferred venous-venous ECMO.
(4) Special problems in treatment and treatment
1. Application of glucocorticoids: Glucocorticoids need to be used with caution. Imaging examination showed obvious progress of pneumonia. In the state of resting non-oxygenated patients, SaO2≤93% or shortness of breath (breath rate ≥30 breaths / min) or oxygenation index ≤300 mmHg, especially the progress of the disease is obviously accelerated Glucocorticoids can be added at the time of intubation risk. When patients can maintain effective blood oxygen concentration through intubation or ECMO support, it is recommended to quickly withdraw the use of glucocorticoids. For non-critically ill patients using methylprednisolone, the recommended dose is controlled at 20-40 mg / d, critically ill patients are controlled at 40-80 mg / d, and the course of treatment is generally 3-6 days. Can be increased or decreased according to body weight.
2. Use of immunomodulating drugs: Subcutaneous injection of thymus fascin 2 to 3 times a week has a certain effect on improving the patient's immune function, preventing the seriousness of the disease, and shortening the detoxification time. Due to the lack of specific antibodies, high-dose intravenous human immunoglobulin therapy is not supported. However, in some patients, the level of lymphocytes is low, and there is a risk of co-infection with other viruses. Intravenous infusion of human immunoglobulin 10 g / d can be used for 3 to 5 days.
3. Accurate diagnosis and treatment of bacterial and fungal infections: clinical microbial monitoring of all severe and critically ill patients. The sputum and urine of the patients are collected every day for culture, and the patients with high fever are cultured in time. All suspected sepsis patients with indwelling vascular catheters should be sent for peripheral venous blood culture and catheter blood culture. All patients with suspected sepsis may consider collecting peripheral blood for etiological molecular diagnostic tests, including PCR-based molecular biological testing and next-generation sequencing. Elevated procalcitonin levels have a suggestive value in the diagnosis of sepsis / septic shock. When patients with new coronavirus pneumonia worsen, there is an increase in CRP levels, which is not specific for the diagnosis of sepsis caused by bacterial and fungal infections. The critically ill patients with open airways are often susceptible to bacterial infections and fungal infections later. If sepsis occurs, empirical anti-infective treatment should be given as soon as possible. For patients with septic shock, empirical antimicrobial drugs can be used in combination before obtaining an etiological diagnosis, while covering the most common Enterobacteriaceae, Staphylococcus and Enterococcus infections. Patients with infection after hospitalization can choose β-lactamase inhibitor complex. If the treatment effect is not good, or the patient is severe septic shock, carbapenem drugs can be used. If considering the combination of enterococcal and staphylococcal infections, glycopeptide drugs (vancomycin) can be added for empirical treatment, daptomycin can be used for bloodstream infections, and linezolid can be used for lung infections. Catheter-related infections in critically ill patients should be highly valued, and treatment should be empirically covered with methicillin-resistant staphylococci. Can choose glycopeptide drugs (vancomycin) for empirical treatment. Candida infections are also more common in critically ill patients. If necessary, treatment with Candida should be covered empirically. Echinocandins can be added. With the prolonged hospitalization of critically ill patients, drug-resistant infections also gradually increase, and the use of antibacterial drugs must be adjusted according to drug sensitivity tests.
4. In-hospital infection prevention and control:
① According to the 2019 National Health and Health Commission "Basic System of Infection Prevention and Control in Medical Institutions (Trial)", actively implement evidence-based infection prevention and control clustered intervention strategies to effectively prevent ventilator-related pneumonia Catheter-related bloodstream infection, catheter-related urinary tract infection, carbapenem-resistant Gram-negative bacilli and other multi-resistant bacteria and fungal infection.
② Strictly abide by the National Health Commission's "Guidelines for the Prevention and Control of New Coronavirus Infections in Medical Institutions (First Edition)", "Guidelines on the Scope of Use of Common Medical Protective Equipment in the Prevention and Control of New Coronavirus Infection Pneumonia (Trial)", and "New Coronary Pneumonia During the epidemic, the technical guidelines for the protection of medical personnel (Trial) strengthened process management, correctly selected and used personal protective equipment such as masks, isolation clothing, protective clothing, eye masks, protective masks, gloves, etc., and strictly implemented the implementation of various disinfection and isolation measures. Minimize the risk of nosocomial infections and put an end to 2019-nCoV infections in hospitals for medical staff.
5. Treatment of infants and young children: mild children only need symptomatic oral administration. In addition to symptomatic oral administration, ordinary children can be treated with syndrome differentiation. If combined with bacterial infections, antibacterial drugs can be added. In critically ill children, symptomatic supportive therapy is the mainstay, and ribavirin injection antiviral therapy is given empirically, 15 mg / kg (2 times / d), and the course of treatment does not exceed 5 days.
(5) Treatment plan of integrated Chinese and Western medicine The combination of traditional Chinese and western medicine in the treatment of new coronavirus pneumonia can improve the synergistic effect. For adult patients, treatment by differentiation of syndromes with traditional Chinese medicine can improve the condition. For mild patients, the syndrome of wind-heat syndrome will be treated with the addition and subtraction of Yinqiaosan; the gastrointestinal symptoms are the main symptoms, and the syndrome of dampness and dampness will be treated with Huopiaoxialing decoction and Sanren decoction. For ordinary patients, those with syndrome of heat and stagnation of lungs are given the addition and subtraction of the Chinese medicine Maxingshigan Decoction; those with syndrome of dampness and depression of the lungs are given with the addition and subtraction treatment of Chinese medicine Dayuanyin and Ganlu Disinfectant, which can be controlled to a certain extent The progression of the disease reduces the occurrence of normal-to-heavy type; for anorexia, vomiting, bloating, fatigue, anxiety and insomnia, the addition and subtraction of the Chinese medicine Xiaochaihu Tang can significantly improve the symptoms. For severe patients, if the fever does not retreat, even high fever, abdominal distension, dry fecal closure, and those who are heat-toxic and closed lungs, give the Chinese medicine Dachengqi decoction enema to relieve the heat and relieve the fever or reduce the fever. Baihu Decoction, Shengjiangsan and Xuanbai Chengqi Decoction were added or removed to cut off the disease and reduce the occurrence of severe to critical illness. Children with light-weight patients, who are classified as epidemics, can use Yinqiaosan or Xiangsusan to add or subtract. Ordinary children with dampness and heat and closed lungs are given the addition and subtraction of Maxing Shigan Decoction and Sanren Decoction; those with moderate scorch and damp heat accompanied by abdominal distension, moss, greasy vomiting, etc., may not be added or subtracted. Severe patients with closed lung disease (currently rare in the country) can refer to adult Xuanbai Chengqi Decoction and Ganlu Disinfectant Dan addition and subtraction; if the toxic heat is vigorous, the intestinal qi is not clear, and the food and medicine are not enough, short-term emergency rhubarb decoction enema.
(6) Discharge standard At the same time, those who meet the following conditions may be considered to be discharged:
① body temperature returned to normal> 3 days;
② respiratory symptoms improved significantly;
③ lung imaging examination showed significant improvement of acute exudative lesions;
④ negative nucleic acid test for two consecutive respiratory samples At least 1 d apart);
⑤ After the nucleic acid test of the respiratory tract specimen is negative, the nucleic acid test of the fecal pathogen is also negative;
⑥ The total course of disease exceeds 2 weeks.
(VII) Health management of discharged patients
1. For discharged patients, close follow-up should still be performed. It is recommended to follow up at the designated follow-up clinic in the second and fourth weeks after the patient is discharged from the hospital.
2. When the patient is discharged from the hospital, his place of residence and address in this city should be specified.
3. After leaving the hospital, the patient rests at home for 2 weeks to avoid activities in public places, and must wear a mask when going out.
4. According to the patient's address (including the hotel or hotel), the relevant district health committee shall organize the corresponding medical institution to do good health management. Within 2 weeks, a professional visits the patient twice a day to measure the patient's body temperature, inquire about his health status, and conduct relevant health education.
5. If fever and / or respiratory symptoms reappear, the corresponding medical institution should report to the District Health and Health Commission and the District Center for Disease Control and Prevention in a timely manner, and assist in sending them to a designated medical institution within the jurisdiction.
6. After receiving the report, the district health committee and the district disease prevention and control center shall report to the superior department in time.
Conflict of interest All authors declare that there is no conflict of interest References slightly