Translation: Diagnosis and Treatment Protocol for COVID-19 (Trial Version 10)

In order to further strengthen the diagnosis and treatment of novel coronavirus infection (COVID-19), we revised the Diagnosis and Treatment Protocol for COVID-19 (Revised Trial Version 9) to Diagnosis and Treatment Protocol for COVID-19 (Trial Version 10). 1. Etiological characteristics Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the β-genus coronaviruses. It has an envelope, and the virus particle is round or oval, with a diameter ranging 60–140 nm. It contains four structural proteins, namely, the spike (S) protein, the envelope (E) protein, the matrix protein (M) and the nucleoprotein (N) protein. The genome of SARS-CoV-2 is a single-stranded positive-sense RNA molecule with a total length of approximately 29.9 kb. The open reading frames contained within the genome are arranged in sequence as 5′-replicase (ORF1a/ORF1b)-S-ORF3a-ORF3b-E-M-ORF6-ORF7a-ORF7b-ORF8-N-ORF9a-ORF9b-ORF10–3′. The RNA genome is wrapped by the N protein, forming a nucleocapsid, a core structure of the virus particle, surrounded by lipid bilayer membrane, in which the S protein, the M protein and the N protein of SARS-CoV-2 are embedded. After invading the human respiratory tract, SARS-CoV-2 mainly relies on the receptor binding domain of the S protein on the virus cell surface to recognize the host cell receptor angiotensin-converting enzyme 2, and then interacts with the receptor, allowing the virus to enter host cells. During the epidemic and transmission of SARS-CoV-2 in the population, its genes have frequently shown mutations. When different subvariants or lineages of SARS-CoV-2 infect the human body simultaneously, these viruses might recombine, resulting in the emergence of recombinant virus strains. Certain mutations or recombinations will affect the biological characteristics of the virus. For instance, mutations of specific amino acids on the S protein enhance the affinity between SARS-CoV-2 and angiotensin-converting enzyme 2, and concomitantly the ability of the virus to replicate and spread between cells. Some amino acid mutations on the S protein will also increase viral immune escape from vaccines and reduce the cross-protection between different subvariants, resulting in breakthrough infections and a certain proportion of reinfections. As of the end of 2022, five variants of concern, namely, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529), have been designated by the World Health Organization. Compared with other variants of concern such as Delta, the transmissibility and immune escape ability of the Omicron variant, which emerged in the population in November 2021, have been significantly enhanced and the Omicron variant has promptly replaced the Delta variant as the dominant global epidemic variant since early 2022. Up to now, the five subvariants of Omicron (BA.1, BA.2, BA.3, BA.4 and BA.5) have successively evolved into 709 serial lineages, including 72 recombinant lineages. As SARS-CoV-2 continues to spread around the world, new subvariants of Omicron will continuously emerge. The dominant Omicron variant strain that has been prevalent globally for several months is BA.5.2, but since October 2022, subvariants such as BF.7, BQ.1 and BQ.1.1 and recombinant variant strains such as XBB, which all have stronger immune escape ability and transmissibility, have spread rapidly and replaced BA.5.2 as the dominant epidemic strains in some countries and regions. Evidence at home and abroad has shown that the pulmonary pathogenicity of Omicron variant strains is significantly weakened, and the clinical manifestations have changed from pneumonia to upper respiratory tract infections. The diagnostic accuracy of polymerase chain reaction tests commonly used in China have not been affected, but the neutralizing efficacy of some marketed monoclonal antibody-based drugs has been noticeably reduced. SARS-CoV-2 is sensitive to ultraviolet light, organic solvents, such as ether, 75% ethanol, peracetic acid and chloroform, and chlorine-containing disinfectants. Chlorine-containing disinfectants and 75% ethanol, which are more commonly used in clinical practices and laboratories, can effectively inactivate the virus, but chlorhexidine fails to inactivate the virus. 2. Epidemiological characteristics 2.1. Source of infection SARS-CoV-2-infected patients are the main source of infection. The infection can be contagious at the incubation stage and is strongly infectious within 3 days after symptom onset. 2.2. Route of transmission (i) Transmission of the virus happens mainly via respiratory droplets and close contact. (ii) The virus can be spread by aerosols in a relatively enclosed environment. (iii) Contact with objects contaminated with the virus can also cause infections. 2.3. Susceptible groups People are generally susceptible. Immunity can be acquired after infection or vaccination. The elderly population and patients with serious underlying diseases have a higher incidence of severe disease and death after infection than the general population, and the risk of severe disease development and death can be reduced by vaccination. 3. Prevention 3.1. SARS-CoV-2 vaccination SARS-CoV-2 vaccination can reduce the incidence of SARS-CoV-2 infection and morbidity, which is an effective means to reduce the incidence of severe disease and death. Anyone who meets the requirements should be vaccinated. Anyone who is eligible for booster immunization should be vaccinated timely for boosting immunity. 3.2. General precautions Maintain a good personal and environmental hygiene, keep a balanced diet, get proper exercise and adequate rest and avoid over fatigue. Improve health literacy and develop good hygienic habits and lifestyles, such as keeping “1-meter distance,” washing hands frequently, wearing masks, using communal chopsticks and covering mouth and nose when coughing or sneezing. Keep indoor well-ventilated and use personal protection. 4. Clinical characteristics 4.1. Clinical manifestations The incubation period is most commonly 2–4 days. The main manifestations include dry throat, sore throat, cough and commonly moderate to low fever. Some patients can also experience high fever, and the duration of the fever usually does not exceed 3 days. Some patients present symptoms such as muscular soreness, decrease or loss of smell and taste, nasal congestion, runny nose, diarrhea and conjunctivitis. A few patients have progressive conditions, with persistent fever and pneumonia-related manifestations. Severe patients develop dyspnea and/or hypoxemia after 5–7 days and may progress rapidly to acute respiratory distress syndrome, septic shock, refractory metabolic acidosis, coagulopathy and multiple organ failure. Rare cases may manifest central nervous system involvement. The clinical manifestations of children after infection are similar to those of adults, especially high fever is relatively common. Some children may have atypical symptoms, presenting with gastrointestinal symptoms such as vomiting and diarrhea, or only manifesting as low response and tachypnea. Acute laryngitis or laryngotracheitis such as hoarseness, or asthma or lung wheezing may occur in a few children, but severe respiratory distress rarely occurs. Febrile convulsions occur in a few children, and life-threatening neurological complications such as encephalitis, meningitis and encephalopathy or even acute necrotizing encephalopathy, acute disseminated encephalomyelitis and Guillain-Barré syndrome may occur in rare cases. Infected children may also develop multisystem inflammatory syndrome (MIS-C) with main manifestations such as fever with rash, non-suppurative conjunctivitis, mucosal inflammation, hypotension or shock, coagulation disorder, acute gastrointestinal symptoms and encephalopathy like convulsions and encephaledema. Once it happens, the disease can deteriorate rapidly within a short time. Most patients have a good prognosis. The prognosis is poorer for the elderly, patients with chronic underlying diseases, women in the third trimester of pregnancy and in the perinatal period and obese people. 4.2. Laboratory tests 4.2.1. General findings In the early stages of the disease, the peripheral white blood cell count is normal or decreased and the lymphocyte count is decreased. Some patients have elevated levels of liver enzymes, lactate dehydrogenase, muscle enzymes, myoglobin, troponin and ferritin. Some patients have elevated levels of C-reactive protein (CRP) and erythrocyte sedimentation rate and normal levels of procalcitonin. Among severe and critical cases, D-dimer increases, peripheral blood lymphocytes progressively decrease and inflammatory factors increase. 4.2.2. Pathogenic and serological findings (i) Nucleic acid detection: SARS-CoV-2 nucleic acids can be detected in respiratory tract specimens (nasopharyngeal swabs, throat swabs, sputum and other trachea extracts) and other specimens using nucleic acid amplification detecting methods. Fluorescence quantitative polymerase chain reaction is currently the most commonly used detection method for SARS-CoV-2. (ii) Antigen detection: SARS-CoV-2 antigens can be detected in respiratory specimens using colloidal gold methods and immunofluorescence methods. The detection speed is fast, and its sensitivity is positively correlated with the viral load of infected patients. Positive antigen detection supports SARS-CoV-2 diagnosis, but a negative result cannot rule it out. (iii) Virus isolation and culture: SARS-CoV-2 can be isolated from and cultured through respiratory tract specimens and feces. (iv) Serological detection: SARS-CoV-2-specific immunoglobulin IgM and IgG antibodies are positive. The positive rate is low within 1 week after onset. The IgG antibody levels at the convalescence stage is four times or more higher than that at the acute stage, which indicates retrospective diagnostic significance. 4.3. Chest imaging In the early stage, chest imaging of patients complicated with pneumonia shows multiple small patchy shadows and interstitial changes, more apparent in the lung periphery. As the disease progresses, imaging shows multiple ground glass opacities and infiltrates in both lungs. In severe cases, pulmonary consolidation may occur. However, pleural effusion is rare. 5. Diagnosis 5.1. Diagnosis principle Diagnosis should be made based on comprehensive analysis of epidemiological history, clinical manifestations and laboratory tests. A positive nucleic acid test for SARS-CoV-2 is the primary diagnostic criterion. 5.2. Diagnosis criteria (i) Presence of aforementioned COVID-19-related clinical manifestations; (ii) Presence of one or more of the following etiological or serological evidences: Positive for SARS-CoV-2 nucleic acids; Positive for SARS-CoV-2 antigen; Positive isolation and culture of SARS-CoV-2; The SARS-CoV-2-specific IgG antibody level at the convalescence stage is four times or more higher than that at the acute stage. 6. Clinical classifications 6.1. Mild cases The main manifestations are upper respiratory tract infections with symptoms such as dry throat, sore throat, cough and fever. 6.2. Moderate cases There are symptoms of persistent high fever >3 days and/or cough and tachypnea, with a respiratory rate (RR) < 30 breaths/min and oxygen saturation > 93% on fingertip pulse oximeter taken at resting state. Radiological imaging shows characteristic manifestations of COVID-19 pneumonia. 6.3. Severe cases Adult cases meeting any of the following criteria and not being explained by other reasons except COVID-19: (i) Tachypnea, with RR ≥ 30 breaths/min; (ii) Oxygen saturation ≤ 93% on fingertip pulse oximeter taken at resting state; (iii) Arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤ 300 mmHg (1 mmHg = 0.133 kPa). In high-altitude areas (at an altitude of over 1000 m above the sea level), PaO2/FiO2 shall be corrected according to the following formula: PaO2/FiO2 × [760/atmospheric pressure (mmHg)]; (iv) Cases with chest imaging that shows obvious lesion progression >50% within 24–48 hours shall be managed as severe cases. Child cases meeting any of the following criteria: (i) Ultra-hyperpyrexia or high fever lasting more than 3 days; (ii) Tachypnea (RR ≥ 60 breaths/min for infants aged below 2 months; RR ≥ 50 breaths/min for infants aged 2–12 months; RR ≥ 40 breaths/min for children aged 1–5 years and RR ≥ 30 breaths/min for children above 5 years old) independent of fever and crying; (iii) Oxygen saturation ≤ 93% on fingertip pulse oximeter taken at resting state; (iv) Presence of nasal fluttering, three concave signs and wheezing; (v) Disturbance of consciousness or convulsion; (vi) Difficulty feeding and signs of dehydration. 6.4. Critical cases Cases meeting any of the following criteria: (i) Respiratory failure and requiring mechanical ventilation; (ii) Shock; (iii) With other organ failure that requires intensive care unit management. 7. Populations at high risk of severe and critical conditions (i) The elderly over 65 years old, especially those who have not been fully vaccinated against SARS-CoV-2; (ii) Patients with underlying conditions such as cardiovascular and cerebrovascular diseases (including hypertension), chronic lung diseases, diabetes, chronic liver and kidney diseases and tumors, as well as patients with maintenance dialysis; (iii) Individuals with immune deficiency (such as AIDS patients, or in a state of immune dysfunction due to long-term use of corticosteroids or other immunosuppressive drugs); (iv) Obese people (body mass index ≥30); (v) Women in the third trimester of pregnancy and in the perinatal period; (vi) Heavy smokers. 8. Clinical early warning indicators of severe and critical cases 8.1. Adults Adults with the following indications are at risk of deterioration. (i) Progressive exacerbation of hypoxemia or respiratory distress; (ii) Deterioration of tissue oxygenation index (such as oxygen saturation on fingertip pulse oximeter and oxygenation index) or progressive elevation of lactic acid; (iii) The peripheral blood lymphocytes decrease progressively, or peripheral blood inflammatory factors, such as interleukin-6, CRP and ferritin, increase progressively; (iv) Coagulation function-related indicators such as D-dimer significantly increase; (v) Chest imaging shows rapid development of lung lesions in a short period of time. 8.2. Children (i) RR increases; (ii) Poor mental reaction, drowsiness and convulsion; (iii) Peripheral blood lymphocytes decrease and/or blood platelets decrease; (iv) Low (high) blood glucose level and/or increasing lactate level; (v) Inflammation factors, such as CRP, procalcitonin and ferritin, increase significantly; (vi) Aspartate aminotransferase, alanine aminotransferase and/or creatine kinase increase significantly; (vii) Coagulation function-related indicators such as D-dimer significantly increase; (viii) Cranial imaging shows encephaledema or other changes, or chest imaging shows rapid development of lung lesions in a short period of time; (ix) Children who have underlying diseases. 9. Differential diagnosis (i) Manifestations of COVID-19 need to be distinguished from those of upper respiratory tract infections caused by other viruses. (ii) COVID-19 is mainly distinguished from Mycoplasma pneumoniae infection and known viral pneumonias, such as influenza virus infection, adenovirus infection and respiratory syncytial virus infection. (iii) COVID-19 should also be distinguished from non-infectious diseases such as vasculitis, dermatomyositis and organizing pneumonia. (iv) In children with rash and mucous membrane damage, COVID-19 should be distinguished from Kawasaki disease. 10. Case finding and reporting Medical institutions of all types and at all levels, upon discovering COVID-19 cases, should directly report them through the National Notifiable Infectious Diseases Reporting Information System according to regulations. 11. Treatment 11.1. General treatment (i) Isolation management and treatment shall be implemented in accordance with the respiratory infectious disease requirements. Ensure sufficient caloric intake for patients; monitor their water and electrolyte balance to maintain internal environment stability. Physical cooling or antipyretic medications can be used for those with high fever. Anti-cough medications and expectorants can be used for those with severe cough and sputum. (ii) Closely monitor vital signs of high-risk population with severe conditions, especially oxygen saturation under resting, and simultaneously monitor related indicators for underlying diseases. (iii) Necessary examinations should be performed according to patients’ conditions, such as routine blood and urine examination, CRP, biochemical indicators (liver enzyme, myocardial enzyme, renal function etc), coagulation function, arterial blood gas analysis and chest imaging. (iv) According to patients’ conditions, provide normative and effective oxygen therapy, including nasal catheter and mask oxygenation and nasal high-flow oxygen therapy. (v) Antibiotic drug treatment: blind or inappropriate use of antibiotic drugs should be avoided, especially combined use of broad-spectrum antibiotics. (vi) Patients with underlying diseases should be treated accordingly. 11.2. Antiviral therapy 11.2.1. Nirmatrelvir/ritonavir tablets combipack Applicable for adults with mild and moderate conditions within 5 days of onset and with risk factors for progression to severe conditions. Usage: 300 mg nirmatrelvir combined with 100 mg ritonavir, once every 12 hours, for 5 consecutive days. The instructions should be read carefully before use, and it cannot be used in combination with drugs, such as pethidine and ranolazine, which are highly dependent on CYP3A for clearance and can cause serious and/or life-threatening adverse reactions at an elevated plasma concentration. It should not be used during pregnancy until the potential benefits to the mother outweigh the potential risks to the fetus. Use during lactation is not recommended. Patients with moderate renal impairment should take half of nirmatrelvir, and patients with severe hepatic and renal impairment should not be administered. 11.2.2. Azvudine tablets Applicable for adults with moderate COVID-19. Usage: take one whole tablet into an empty stomach, 5 mg each time, once a day (qd), for no more than 14 days. The instructions should be read carefully. Pay attention to the interaction with other drugs, adverse reactions and other problems. Use during pregnancy and lactation is not recommended. Use with caution in patients with moderate and severe hepatic and renal impairment. 11.2.3. Molnupiravir capsules Applicable for adults with mild and moderate conditions within 5 days of onset and with high-risk factors for progression to severe conditions. Usage: 800 mg, take orally once every 12 hours, for 5 consecutive days. Use during pregnancy and lactation is not recommended. 11.2.4. Monoclonal antibody: Ambavirumab/romisvirumab injection The combination therapy is applicable for adult and adolescent cases (12–17 years of age, weight ≥ 40 kg) with mild and moderate conditions and with risk factors for progression to severe conditions. Usage: the dosage of the two drugs is 1000 mg, respectively. Before administration, the two drugs are diluted with 100 mL 0.9% sodium chloride, respectively, and given by sequential intravenous infusion at a rate of no more than 4 mL/min, with 100 mL 0.9% sodium chloride flushing the tubing during the interval between the administration of the two drugs. Patients should be clinically monitored during the infusion and observed for at least 1 hour after the infusion is completed. 11.2.5. Intravenous injection of COVID-19 human immunoglobulin Applicable in the early stage of the disease for patients with high risk factors, high viral loads and rapid disease progression. The dosages of intravenous infusion are 100 mg/kg for mild cases, 200 mg/kg for moderate cases and 400 mg/kg for severe cases, respectively. The patients can be re-infused daily according to the improvement of the patient’s condition, no more than five times in total. 11.2.6. Convalescent plasma treatment Applicable in the early stage of the disease for patients with high risk factors, high viral loads and rapid disease progression. The infusion dose is 200–500 mL (4–5 mL/kg). It can be decided to re-infuse or not in accordance with individual conditions of patients and their viral loads. 11.2.7. Other antiviral drugs approved by the National Medical Products Administration 11.3. Immunotherapy 11.3.1. Glucocorticoid therapy For patients with progressive deterioration of oxygenation indicators, rapid progress in imaging and excessive activation of the body’s inflammatory responses, glucocorticoids can be used for a short period of time (no longer than 10 days). Dexamethasone 5 mg/day or methylprednisolone 40 mg/day is recommended; avoid long-term and high-dose glucocorticoids administration to reduce side effects. 11.3.2. Interleukin 6 (IL-6) inhibitors: Tocilizumab For severe and critical cases with an increased level of IL-6 in laboratory testing, tocilizumab can be used for treatment. The initial dose is 4–8 mg/kg with the recommended dose of 400 mg, diluted with 0.9% sodium chloride to 100 mL. The infusion time should be more than 1 hour. If the initial medication is not effective, one extra administration can be given after 12 hours (same dose as before). No more than two administrations should be given with the maximum single dose no more than 800 mg. Watch out for allergic reactions. Administration of tocilizumab is prohibited for people with active infections such as tuberculosis. 11.4. Anticoagulation treatment Applicable for moderate, severe and critical cases with high risk factors and rapid disease progression. Low molecular weight heparin and unfractionated heparin are recommended in a manner of therapeutic dose for those without contraindications. When a thromboembolic event occurs, treatment should be performed according to corresponding guidelines. 11.5. Prone position treatment Prone position treatment is recommended for moderate, severe and critical cases with high risk factors and rapid disease progression, no less than 12 hours a day. 11.6. Psychological intervention Patients often suffer from anxiety and fear, and they should be supported by psychological counseling, supplemented by medication when necessary. 11.7. Support treatment of severe and critical cases 11.7.1. Treatment principle On the basis of the aforementioned treatment, complications should be proactively prevented, underlying diseases should be treated, secondary infections should also be prevented and organ function support should be provided timely. 11.7.2 Respiratory support (i) Nasal cannulas or masks for oxygen inhalation Severe cases with PaO2/FiO2 lower than 300 mmHg should receive oxygen therapy immediately. The patients should be closely observed for a short time (1–2 hours) after receiving nasal cannulas or masks for oxygen inhalation. If respiratory distress and/or hypoxemia of the patient cannot be alleviated, high-flow nasal-catheter oxygenation (HFNC) or noninvasive ventilation (NIV) should be used. (ii) HFNC or NIV Patients with PaO2/FiO2 lower than 200 mmHg should receive HFNC or NIV. For patients who are receiving HFNC or NIV without contraindications, prone position ventilation, namely awake prone position ventilation, is recommended at the same time, and the treatment time in prone position should be more than 12 hours. Some patients are at high risk of failure when treated with HFNC or NIV, and their symptoms and signs need to be closely monitored. If the condition does not improve after a short period of treatment (1–2 hours), especially if hypoxemia still does not improve or respiratory frequency or tidal volume is too large or respiratory effort is too strong after prone position treatment, it is likely that HFNC or NIV treatment is not effective. Invasive mechanical ventilation should be applied in time. (iii) Invasive mechanical ventilation In general, when PaO2/FiO2 is lower than 150 mmHg, especially for those who have strong respiratory efforts, endotracheal intubation should be considered for invasive mechanical ventilation. However, in view of the atypical clinical manifestations of hypoxemia in partial patients with severe and critical COVID-19, PaO2/FiO2 should not be used as the only indication of endotracheal intubation and invasive mechanical ventilation. Real-time evaluation should be conducted based on the clinical manifestations and organ functions of patients. It is worth noting that delayed endotracheal intubation may be more harmful. Early and appropriate invasive mechanical ventilation is an important treatment for critical cases. Pulmonary protective ventilation strategy should be used. Pulmonary re-tensioning is recommended for patients with moderate to severe acute respiratory distress syndrome, or when FiO2 of invasive mechanical ventilation is higher than 50%. Whether to repeatedly perform pulmonary re-tensioning techniques can be determined according to its reactiveness. It should be noted that some COVID-19 patients have poor reactiveness to pulmonary re-tensioning, and barotrauma caused by excessive positive end expiratory pressure (PEEP) should be avoided. (iv) Airway management It is recommended to use an active heating humidifier for airway humidification and use a loop heating guide wire if possible to ensure the humidification effect. It is recommended to use closed sputum suction and bronchoscope suction if necessary and actively carry out airway clearance treatment, such as vibration expectoration, high-frequency thoracic oscillation, postural drainage, etc; in the case of stable oxygenation and hemodynamics, passive and active activities should be carried out as soon as possible to promote sputum drainage and pulmonary rehabilitation. (v) Extracorporeal membrane oxygenation (ECMO) Timing of ECMO: if the outcome of protective ventilation and prone position ventilation is poor under optimal mechanical ventilation conditions (FiO2 ≥ 80%, tidal volume of 6 mL/kg of ideal body weight, PEEP ≥5 cmH2O and no contraindications) and one of the following indications is met, ECMO should be considered as soon as possible: PaO2/FiO2 < 50 mmHg for more than 3 hours; PaO2/FiO2 < 80 mmHg for more than 6 hours; Arterial blood pH < 7.25, PaCO2 > 60 mmHg for more than 6 hours and RR > 35 breaths/min; RR > 35 breaths/min, arterial blood pH < 7.2 and platform pressure >30 cmH2O. Critical cases that meet the ECMO indications and have no contraindications should start ECMO treatment as soon as possible to avoid delay in treatment and a poor prognosis. Mode selection of ECMO: veno-venous ECMO mode, which is the most frequently used mode, can be selected when only respiratory support is required; veno-arterial ECMO mode can be selected when both respiratory and circulatory support are required simultaneously; in case of brachiocephalic hypoxia during veno-arterial ECMO, veno-arterial-venous ECMO can be applied. After the implementation of ECMO, lung protective ventilation strategy can be strictly administered. Recommended initial setup parameters are as follows: tidal volume <4–6 mL/kg ideal body weight, platform pressure ≤25 cmH2O, generated pressure <15 cmH2O, PEEP 5–15 cmH2O, RR 4–10 breaths/min and FiO2 < 50%. ECMO can be used in combination with prone ventilation for patients with difficulty in maintaining oxygenation or with strong respiratory effort, with significant consolidation of gravity-dependent region in both lungs or requiring active secretion drainage from airways. The cardiopulmonary compensation ability of children is weaker than for adults, and they are more sensitive to hypoxia. Therefore, more active oxygen therapy and ventilator support strategies and more relaxed indications should be applied for children than for adults. Routine application of pulmonary re-tensioning is not recommended. 11.7.3. Circulatory support For critical cases complicated with shock, on the basis of adequate fluid resuscitation, vasoactive drugs should be used, and changes in blood pressure, heart rate and urine volume as well as lactate and base excess should be closely monitored. Hemodynamic monitoring should be performed when necessary. 11.7.4. Acute kidney injury and renal replacement therapy Active efforts should be made to look for causes of acute kidney injury in critical cases, such as low perfusion and drugs. While actively eliminating the causes, the balance of fluid, acid-base and electrolyte should be maintained. The indications of continuous renal replacement therapy (CRRT) include: (a) hyperkalemia; (b) severe acidosis; (c) pulmonary edema or water overload that does not respond to diuretics. 11.7.5. Treatment of special conditions in children (i) Acute laryngitis or laryngotracheitis Upper airway obstruction and hypoxia intensity should be assessed first. Oxygen therapy should be administered to cases with hypoxia. Moist ambient air should be kept to avoid irritability and crying of children. Glucocorticoid is the first choice for drug treatment. Dexamethasone (0.15–0.6 mg/kg, maximum dose of 16 mg) or prednisolone (1 mg/kg) can be taken orally for mild cases; dexamethasone (0.6 mg/kg, maximum dose of 16 mg) is the first choice for moderate and severe cases; intravenous or intramuscular injection of dexamethasone should be considered for cases who are unable to take orally. Budesonide aerosol inhalation (2 mg) can also be administered. Patients with severe airway obstruction should be intubated or perform tracheotomy and mechanical ventilation to ensure airway maintenance. In case of emergency, L-epinephrine aerosol inhalation (0.5 mL/kg each time, maximum dose of 5 mL) for