Protocol for the diagnosis and treatment of severe and critical COVID-19 case...

医智宝

The  plan for the diagnosis and treatment of severe and critical COVID-19 cases (second edition on trial)

      Ⅰ Applicable groups
      Patients diagnosed as severe or critically ill in accordance with" diagnosis and treatment program of COVID-19  (trial version 5 revision) "  by the Chinese Health Commission.
    (Ⅰ) Heavy duty
     Meet any of the following:
     1. Respiratory distress, respiratory rate (RR) ≥30 / min;
     2. Resting state, oxygen saturation ≤93% in the absence of oxygen;
     3. Partial pressure (PaO2)/ oxygen uptake (FiO2)≤300mmHg;
     4. Comply with any of the above, according to the heavy management; Or, even though the above severe diagnostic criteria have not been met, the cases should also be managed as severe cases: 50% of the lesions showed significant progression of > within 24-48 hours according to pulmonary imaging; > 60 years old, with severe chronic diseases including hypertension, diabetes, coronary heart disease, malignant tumor, structural pulmonary disease, pulmonary heart disease and immunosuppression.

     (Ⅱ) Critical type
     Meet any of the following:
     1. Respiratory failure and need mechanical ventilation;
     2. Shock;
     3. Patients with other organ failure should be admitted to ICU for treatment.

医智宝

  Ⅱ Diagnosis and treatment of severe patients
      (Ⅰ) Clinical early warning indicators
      In severe cases, vital signs, SpO2, state of consciousness, and clinical routine organ function assessment are required. Monitoring contents according to the needs of the disease: blood routine, urine routine, biochemical indicators (liver and kidney function, lactic acid, blood glucose, electrolyte, lactate dehydrogenase, etc.), markers of myocardial injury, C-reactive protein, procalcitonin, coagulation function, arterial blood gas analysis, electrocardiogram and chest imaging examination.
     In addition, changes in the following indicators should alert the disease to deterioration:
     1. Peripheral blood lymphocyte count decreased progressively; B lymphocytes were significantly decreased and CD4 and CD8 T cells were continuously decreased.
     2. Inflammatory factors such as IL-6 and reactive protein in peripheral blood increased progressively;
     3. The lactic acid index of tissue oxygenation increased progressively;
     4. High resolution CT showed rapid expansion of lesions.


    (Ⅱ) Treatment
     1. Principles of treatment
     Bed rest, support treatment, ensure adequate heat; Maintain water, electrolyte and acid-base balance; Timely oxygen therapy, mechanical ventilation and other life support measures to prevent and treat complications; Treatment of underlying diseases; Prevent secondary infections. In a word, the patients can survive the course of severe disease in the most effective life support state.

医智宝

  2. Oxygen therapy and respiratory support
      (1) In patients with hypoxemia, PaO2/FiO2 is 200-300mmhg.
      1) Nasal catheter or mask should be used for oxygen inhalation, and respiratory distress and/or hypoxemia should be evaluated in a timely manner. It is recommended that the nasal catheter oxygen flow should not exceed 5L/ min. Mask oxygen therapy oxygen flow is generally 5-10L/ min.
      2) Transnasal hyperflow oxygen therapy (HFNC) : When the patient has no improvement in respiratory distress and/or hypoxemia 2 hours after receiving nasal catheter or mask, transnasal hyperflow oxygen therapy should be used.
Noninvasive mechanical ventilation (NIV) or invasive mechanical ventilation should be used if the oxygenation index is not improved or further worsened after 2 hours of the above high-flow oxygen therapy.

      (2) In patients with hypoxemia, PaO2/FiO2 is 150-200 mmHg.
NIV for treatment is the first choice. The failure rate of treatment with noninvasive mechanical ventilation in such patients is high and should be closely monitored. If the condition does not improve or even worsen within a short time (1-2 h), endotracheal intubation and invasive mechanical ventilation should be performed in time.

      (3) In patients with hypoxemia, PaO2/FiO2 is less than 150 mmHg.
      1) Invasive mechanical ventilation.
      The lung protective mechanical ventilation strategy, namely neap tidal volume (4-6ml/kg ideal body weight) and low inspiratory pressure (platform pressure < 30cmH2O), was implemented to reduce ventilate related lung injury. Lung retensibility should be evaluated based on optimal oxygenation
PEEP is set by the method or fiO2-PEEP corresponding table (the low PEEP setting method for ARDSnet).
      2) Pulmonary retraction.
      If invasive mechanical ventilation with FiO2 above 0.5 is required to achieve the goal of oxygenation (or meet the criteria for moderate to severe ARDS), lung retention therapy can be adopted. Before lung retensioning, retensibility evaluation should be performed, including ultrasound, P-V curve, electrical impedance imaging (EIT), etc.
      3) Prone position.
      If PaO2/FiO2 is consistently below 150mmHg, prone ventilation should be considered for more than 12 hours a day.
      4) Invasive mechanical ventilation for evacuation.
      After treatment, if the oxygenation index of the patient improves (PaO2/FiO2 is continuously greater than 200mmHg) and the patient is conscious and circulatory is stable, the evaluation and withdrawal procedure can be started.

      (4) Extracorporeal membrane oxygenation (ECMO).
      1) Start time of ECMO. Evaluation and implementation of ECMO should be considered as early as possible when protective ventilation and prone ventilation are not effective and the following conditions are met:
      Under the optimal ventilation conditions (FiO2≥0.8, tidal volume 6 ml/kg ideal body weight, PEEP≥10 cmH2O without contraindications), it conforms to one of the following conditions:
      A)PaO2/FiO2 < 50 mmHg over 3h;
      B)PaO2/FiO2 < 80 mmHg over 6h;
      C)FiO2 1.0, PaO2/FiO2 < 100 mmHg;
      D) arterial blood pH < 7.25, PaCO2 > 60 mmHg over 6h, and respiration rate > 35 times/min;
      E) respiratory rate > 35 times/time, arterial blood pH < 7.2 and platform pressure >30cmH2O;
      F) Combined with cardiogenic shock or cardiac arrest.
      2) Contraindication of ECMO.
      Combined with an unrecoverable primary disease; Anticoagulant contraindications exist; Under the condition of high mechanical ventilation setting (FiO2 > 0.9, platform pressure > 30 cmH2O), mechanical ventilation was over 7 days. Over 70 years of age; Immunosuppression; There are anatomic malformations or vascular lesions in the surrounding large vessels.
      3) Selection of ECMO treatment mode.
      The VV-ECMO mode is recommended. When circulatory failure occurs, the cause and presence of cardiogenic shock should be determined to determine whether the VA-ECMO pattern is required.

医智宝

      3. Circular monitoring and support
      1) Follow the principle of tissue perfusition-oriented hemodynamic therapy, closely monitor the patient's circulation status, and hemodynamic instability occurs (shock, systolic blood pressure <90mmHg or 40mmHg lower than the basic blood pressure, or vascularization is required
Drugs, severe arrhythmia, etc.), should carefully identify the causes, correctly deal with different types of shock, improve tissue perfusion, and actively deal with severe arrhythmia.
      2) The hemodynamic monitoring technology that is simple and easy to maintain and manage should be selected. Intra - technical invasive hemodynamic monitoring near the bed is not recommended. When conditions permit, ultrasonic Doppler monitoring is a non-invasive and convenient means of monitoring, which should be actively applied
Adopted.
      3) When hemodynamic instability occurs, in terms of volume management, efforts should be made to maintain the minimum blood volume that meets tissue perfusion, so as to avoid volume overload and aggravate lung injury. Appropriate volume resuscitation is given, if necessary, with common vasoactive drugs such as noradrenaline. Patients with acute cor pulmonale (ACP) are prone to severe pulmonary lesions and high respiratory support conditions. Right heart function should be closely monitored and strategies to improve oxygenated pulmonary protective ventilation should be used to reduce pulmonary circulation resistance. When cardiac enzymes (especially troponin) or/or BMP are significantly elevated, cardiac function needs to be closely monitored for cardiogenic shock.

      4. Nutritional support therapy
      1) Patients with severe COVID-19 should be screened for nutritional risk according to the NRS2002 score.
      2) Early initiation of enteral nutrition. Early use of PN alone or complementary PN combined EN is not recommended.
      3) For patients with unstable hemodynamics, nutritional support should be started as soon as possible after fluid resuscitation and basically stable hemodynamics. Delayed initiation of nutritional support is not recommended for non-life-threatening, controlled hypoxemia or compensatory/permissive hypercapnia, even during prone ventilation or ECMO.
      4) It is recommended to indwelling nasogastric tube for gastric nutrition in severe patients. Postpyloric feeding, such as nasointestinal tube, is recommended for patients who are not suitable for gastric nutrition.
      5) For severe patients, target feeding amount is 25-30kcal//kg/d, starting with low dose. Nourishing feeding (infusion rate 10-20kcal/h or 10-30ml/h) may be considered if feeding intolerance occurs.
      6) To enhance protein supply, the target protein requirement is 1.5-2.0g/kg/d. When protein intake is insufficient, it is recommended to add protein powder in addition to standard whole protein preparation.
      7) heavy COVID - 19 patients can use enteral nutrition preparations that are rich in Ω - 3 fatty acids. Fat milk rich in EPA and DHA can be added to parenteral nutrition.
      8) Take appropriate measures to prevent vomiting and reflux in patients receiving EN.
      9) In case of feeding-related diarrhea, it is suggested to change the infusion way or formula composition of nutrient solution.

医智宝

      5. Antiviral therapy
      Lopinavir/Ritonavir may be tried within 10 days of onset for a course of no more than 2 weeks. Adverse drug reactions and interactions with other drugs should be closely monitored during medication.

      6. Human immunoglobulin (IVIG)
      At present, there is no sufficient evidence-based medical evidence to support the clinical efficacy of IVIG on coronavirus, and it can be applied to critically ill patients as appropriate.

      7. Convalescent plasma
      Convalescent plasma from novel Coronavirus antibody can be used as an option for specific therapy in patients with early COVID-19. If convalescent plasma is used, protective antibody titer levels in the plasma should be measured.

      8. Glucocorticoid
      There is currently no evidence-based medical evidence to support the use of glucocorticoids to improve the prognosis of severe COVID-19, and the routine use of glucocorticoids is not recommended. For patients with progressive deterioration of oxygenation indexes, rapid imaging progress, and excessive activation of inflammatory response in the body, medrone 40mg Q12h for 5 days for short-term treatment can be considered, and whether patients have contraindications of hormone use should be analyzed before use.

       9. Antibacterial therapy
      Routine use of antimicrobial agents is not recommended unless there is clear evidence of bacterial infection. It should be noted that the course of disease in severe patients is usually longer than 5-7 days, and there are manifestations of cellular immunosuppression, especially in patients admitted to ICU requiring invasive mechanical ventilation and secondary bacterial or fungal infection.
      If conditions permit, should actively carry out respiratory pathogen monitoring, targeted anti-infection treatment. Antimicrobial selection should consider covering drug-resistant bacteria if there is a history of antimicrobial use within 90 days, a hospital stay of more than 72 hours, or a history of structural lung disease.

      10. Other medications
      Thymosin 1 is recommended for severe patients with low lymphocyte count and low cellular immune function. Intestinal microecological regulator can be used to maintain intestinal microecological balance. As for the use of proprietary Chinese medicines, xuebijing may be considered, although it is currently in clinical trials.

      11. Venous thromboembolism (VTE)
In severe patients, due to long bed time and often associated with abnormal coagulation function, attention should be paid to the risk of VTE and appropriate anticoagulation therapy.

      12. Analgesia and sedation
Patients with heavy mechanical ventilation should be given appropriate analgesia and sedation treatment, according to the patient's condition and treatment measures to set targets for analgesia and sedation; Human care for patients with severe COVID-19 must be emphasized.

      13.AKI and multiorgan function
Severe patients may be associated with multiple organ function damage, including brain, kidney, liver, digestive tract, coagulation function, etc., so attention should be paid to evaluating organ function and strengthening organ function support during treatment.
The proportion of patients with AKI is not high, so the timing of renal replacement therapy should be carefully evaluated. In general, renal replacement therapy should be used at KDIGO standard stage 2, which is 2-2.9 times the baseline creatinine increment, with urine output lasting less than 0.5ml/kg/h for more than 12 hours.

医智宝

      14.Chinese medicine treatment
      (1) Refer to the" diagnosis and treatment program of COVID-19  (trial version 5 revision) " for prescriptions applicable to severe and critical cases.(The Attached)
      (2) The prescription recommended in the Notice of" "On the recommendation ： “lung-Cleansing detoxification soup" for combined therapy of Chinese and Western treatment to COVID-19 ”(The Attached)

      (3) Intravenous medication
       1) Severe cases:
      Xuebijing injection 100ml plus normal saline 250ml once a day, and Shengmai injection 100ml plus normal saline 250ml once a day.
      If the body temperature is higher than 38.5℃, Xiyanping injection of 100mg plus 250ml normal saline, once a day. (Note: increasing the number of stools after medication is a reaction to medication and has the effect of catharsis and elimination of heat.)
      2) Critical illness:
      Xuebijing injection 100ml plus normal saline 250ml once a day, and Shengmai injection 100ml plus normal saline 250ml once a day. At the same time reduce the amount of fluid, ensure the patient fluid support treatment, do not increase the volume, reduce the burden of pulmonary edema and the heart.
      3) For those with high fever, take 1 pill of Angong niuhuang, once a day.
      4) Shock: add 100ml of Shenfu injection and 250ml of normal saline, once a day.

Ⅲ Criteria for transfer out of icu
Patients with severe COVID-19 should be transferred out of the INTENSIVE care unit as early as possible when their condition is stable and their oxygenation is improved and they do not require life support. Roll-out criteria (all to be met) :
1.Be aware. As requested, analgesics, sedatives and/or muscle relaxants have been discontinued;
2. Mechanical ventilation has been evacuated. Breathing air or low flow oxygen (nasal airway)
(tube or ordinary mask), respiratory rate <30 times/min, SpO2>93%;
3. Stable circulation. No booster and fluid resuscitation required;
4. No other acute progressive visceral dysfunction. No supportive care is required
Measures such as blood purification.

医智宝

     the" diagnosis and treatment program of COVID-19  (trial version 5 revision) " for prescriptions applicable to severe and critical cases:
     (Ⅳ) Traditional Chinese medicine treatment. This disease belongs to the category of epidemic disease in Traditional Chinese medicine. Because of feeling the rage caused by epidemic disease, each place can treat the disease according to the disease, local climate characteristics and different physical conditions, and refer to the following plan for treatment based on syndrome differentiation.


      1. Medical observation period
      (1) Clinical manifestations: fatigue with gastrointestinal discomfort   
      Recommended Chinese patent medicine: Huoxiang Zhengqi Capsule (pills, water, oral liquid)
      (2) Clinical manifestations : fatigue with fever

      Recommended Chinese patent medicine: Jinhua Qinggan Granule, Lianhua Qingwen Capsule (granule), Shufeng Jitotoxic capsule (granule), Fangfeng Tongsheng Pill (granule)

      2. Clinical treatment period
      (1) Early stage: cold, dampness and depression of the lungs
      Clinical manifestations: aversion to cold, fever or absence of heat, dry cough, dry pharynx, fatigue, chest tightness, wan Pii, or emesis, loose stool. Tongue light or light red, moss white greasy, pulse moisten.
      Recommended prescription: Atractylodes atractylodes (15g), dried tangerine peel (10g), magnolia officinalis (10g), huoxiang (10g), grass fruit (6g), raw ephedra herb (6g), qiang fruit (10g), ginger (10g), betel nut (10g)

      (2) Middle stage: Coronavirus closes the lungs
      Clinical manifestations: body heat does not retreat or alternating cold and hot, cough phlegm, or yellow phlegm, abdominal distension and constipation. Chest stuffy, cough wheeze, movement wheezes. Tongue red, moss yellow greasy or dry, pulse number.
      Recommended prescription: 10g apricot, 30g raw plaster, 30g trichosanthes kirilowii, 6g rheaba (lower), 6g epaba semen draba, 10g semen draba, 10g peach kernel, 6g caocarpa, 10g penang, 10g atractylodes rhizoma
      Recommended proprietary Chinese medicines: Xiyanping injection, Xuebijing injection

      (3) Severe stage: internal closure and external detachment
      Clinical manifestations: dyspnea, frequent wheezing or need for assisted ventilation, accompanied by dizziness, irritability, sweating cold limbs, purple tongue, thick greasy or dry coating, large and rootless pulse.
      Recommended prescription: ginseng 15g, black Aconite tablet 10g (decocted first), cornus officinalis 15g, suhexiang pill or Angong Niuhuang pill  

      Recommended Proprietary Chinese medicine: Xuebijing injection, Shenfu injection, Shengmai injection


      (4) Recovery period: deficiency of lung and spleen
      Clinical manifestations: shortness of breath, fatigue, tolerance and vomiting, piquancy, weakness of stool, loose stool, fat tongue, moss white greasy.
      Recommended prescription: Pinellia ternata 9g, tangerine peel 10g, Codonopsis pilosula 15g, Processed radix Astragali 30g, Poria cocos 15g, Huoxiang 10g, and Amomum kern 6g (posterior lower)


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附中文内容：

（四）中医治疗。 本病属于中医疫病范畴，病因为感受疫戾之气，各地可根据病情、当地气候特点以及不同体质等情况，参照下列方案进行辨证论治。
1.医学观察期
（1）临床表现：乏力伴胃肠不适推荐中成药：藿香正气胶囊（丸、水、口服液）
（2）临床表现2：乏力伴发热推荐中成药：金花清感颗粒、连花清瘟胶囊（颗粒）、疏风解毒胶囊（颗粒）、防风通圣丸（颗粒）

2.临床治疗期
（1）初期：寒湿郁肺
临床表现：恶寒发热或无热，干咳，咽干，倦怠乏力，胸闷，脘痞，或呕恶，便溏。舌质淡或淡红，苔白腻，脉濡。 推荐处方：苍术15g、陈皮10g、厚朴10g、藿香10g、草果6g、生麻黄6g、羌活10g、生姜10g、槟郎10g

（2）中期：疫毒闭肺
临床表现：身热不退或往来寒热，咳嗽痰少，或有黄痰，腹胀便秘。胸闷气促，咳嗽喘憋，动则气喘。舌质红，苔黄腻或黄燥，脉滑数。
推荐处方：杏仁10g、生石膏30g、瓜蒌30g、生大黄6g（后下）、生炙麻黄各6g、葶苈子10g、桃仁10g、草果6g、槟郎10g、苍术10g
推荐中成药：喜炎平注射剂，血必净注射剂

（3）重症期：内闭外脱
临床表现：呼吸困难、动辄气喘或需要辅助通气，伴神昏，烦躁，汗出肢冷，舌质紫暗，苔厚腻或燥，脉浮大无根。
推荐处方：人参15g、黑色附子片10g（先煎）、山茱萸15g，送服苏合香丸或安宫牛黄丸 推荐中成药：血必净注射液、参附注射液、生脉注射液 、
（4）恢复期：肺脾气虚
临床表现：气短、倦怠乏力、纳差呕恶、痞满，大便无力，便溏不爽，舌淡胖，苔白腻。
推荐处方：法半夏9g、陈皮10g、党参15g、炙黄芪30g、茯苓15g、藿香10g、砂仁6g（后下）

医智宝

     In COVID-19, it is suggested to use "lung-clearing and detoxification Soup" to treat patients with mild, common or severe syndrome in TCM by combining Chinese and western medicine.
     "Lungclearing and detoxifying Soup" comes from the combination of traditional Chinese medicine's classic prescriptions, including Maxing Shigan Soup, Zhugan Ephedra soup, Xiaochaihu soup, Wuling Powder, with a mild taste.
      Prescription composition:
       Ephedra 9g,  prepared licorice 6g, almond 9g, plaster stone 15-30g (Fried first ) , cassia twig 9g ,  alisma 9g, umbellate pore fungus 9 g ，Largehead Atractylodes Rhizome 9g, poria cocos 15g,  Chinese thorowax 16g, radix scutellariae 6g, ginger pinellia 9g, the ginger 9g, Butterbur flower 9g, blackberry lily 9g,  asarum 9g, yam 12g, dried immature fruit of citron orange 6g, dried tangerine or orange peel 6g, ageratum 9g.
      Take as follows:
      The Traditional Chinese medicine decoction pieces, decocted in water for daily dose, morning and evening twice (40 minutes after meal), warm dose, three doses of a course of treatment;
      If possible, you can take half bowl of rice soup after taking the medicine, and up to 1 bowl more if your tongue is dry and body fluid is deficient.
      If the patient does not have fever then the dosage of gypsum should be small, fever or strong heat can increase the dosage of gypsum;
      If the symptoms improve but do not heal, then take the second course of treatment. If the patient has special conditions or other basic diseases, the second course of treatment can be modified according to the actual situation, and the drug will be stopped when the symptoms disappear.
      Combined with the clinical observation of doctors in many places, this prescription is suitable for mild, ordinary and severe patients. In the treatment of critically ill patients, it can be reasonably used in combination with the actual situation of patients.
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附中文内容：《关于推荐在中西医结合救治新型冠状病毒感染的肺炎中使用“清肺排毒汤”的通知》


      在中西医结合救治新型冠状病毒感染的肺炎中，对轻型、普通型和重症型患者的中医治疗，建议按国家推荐使用“清肺排毒汤”进行治疗。
    “清肺排毒汤”来源于中医经典方剂组合，包括麻杏石甘汤、射干麻黄汤、小柴胡汤、五苓散，性味平和。
       处方组成为：
       麻黄9克、炙甘草6克、杏仁9克、生石膏15—30克（先煎）、桂枝9克、泽泻9克、猪苓9克、白术9克、茯苓15克、柴胡16克、黄芩6克、姜半夏9克、生姜9克、紫菀9克、冬花9克、射干9克、细辛6克、山药12克、枳实6克、陈皮6克、藿香9克。
      服用方法为：
      传统中药饮片，水煎服每天一服，早晚两次（饭后40分钟），温服，三服一个疗程；
      如有条件，每次服完药可加服大米汤半碗，舌干津液亏虚者可多服至1碗；
      如患者不发热则生石膏的用量要小，发热或壮热可加大生石膏用量；
      若症状好转而未痊愈则服用第二个疗程，若患者有特殊情况或其他基础病，第二疗程可以根据实际情况修改处方，症状消失则停药。
      结合多地医生临床观察，此方适用于轻型、普通型、重型患者，在危重型患者救治中可结合患者实际情况合理使用。