COVID-19 Treatment Protocol
·
Risk stratification
|
Mild to Moderate (輕至中度)
|
Severe 重度
|
Critical 極重度
|
|
Asymptomatic
Mild: No dyspnea or CXR infiltrate
Moderate: lower respiratory disease with SpO2>-94 on
Room air
|
SpO2<94 on Room air
Respiratory distress
RR>30
Lung infiltrates>50%
|
ICU care
ARDS
Sepsis/septic shock
Multi-organ failure
|
·
不建議 Lopinavir/Ritonavir; interferon;
colchicine; hydroxychloroquine; ivermectin,
convalescent plasma]
Antiviral: Remdesivir 需向疾管署申請
|
·
Recommendation
for Usage
o
Severe
or Critical
·
Dosing
o
200 mg
IVF on day 1, followed by 100 mg once daily from day 2-5.
o
治療時已使用呼吸器可延長至10天.
·
Renal/hepatic
dose adjustment
o
eGFR<30
not on HD: NOT recommended unless benefit > risk
o
HD: no
dose adjustment (dialysis reducing concentrations by ~50%)
o
Hepatic
impairment: no adjustment recommended
·
Administration
o
凍晶乾燥注射液調製: 加入19ml注射用水，搖30秒，靜置2-3分鐘，澄清稀釋溶液濃度為5mg/ml，再打入250ml N/S(輕輕翻轉輸注袋，使混合均勻，但不要搖)。
o
輸注時間為30-120分鐘，若發生輸注反應則降低一半輸注速率
o
不建議用其他溶液稀釋也不建議與其他藥物同時給藥
·
Warning
and Precaution
o
輸注反應,
AST/ALT升高 (肝臟發炎症狀需停藥或ALT>10x ULN但無症狀),
prothrombin time (PT) 延長, 心律過緩。
*Remdesivir的助溶劑Sulfobutyl ether beta-cyclodextrin (SBECD)可能會累積在腎功能較差的病人，並惡化腎功能
·
Monitoring
o
eGFR, AST/ALT , Infusion reaction
·
Drug
interaction : hydroxychloroquine (Risk
X)
·
實證:無法降低死亡率。可加速恢復與減少住院時間
|
Corticosteroid: Dexamethasone
|
·
Recommendation
for Usage
o
Severe
or critical
o
不建議於不需要用氧氣的病人, 無資料支持使用超過 10 天
·
Dosing
o
6mg
daily (IV or PO) for up to 10 days or until discharge. NO TAPER.
o
對懷孕女性For pregnant women
(1) 無早產風險者：prednisolone 40mg
daily or hydrocortisone 80mg
IV BID up to 10 days (2) 有早產風險須促進胎兒肺部成熟者：dexamethasone 6mg q12h IM x 4 doses (D1-2)、prednisolone
40mg daily或
hydrocortisone 80mg IV BID
(D3 起至多至 D10)。
·
Monitoring
parameters (臨床監控項目)
o
blood
sugar, mental status, fluid status
·
實證: 唯一藥物在隨機分配試驗下證實可降低死亡率
|
Interleukin-6 antagonist tocilizumab 需填臨採單
|
·
Recommendation
for Usage
o
台灣疾管署: 病患住院 3 天內，且入住 ICU 24 小時內或未入住 ICU 但發炎指數上升(CRP ≥ 7.5 mg/dL)
o
避免用在在免疫顯著不全、ALT>5 x ULN、胃腸道穿孔、失控的細菌真菌或非 SARS-CoV-2 感染、ANC<500、PLT<50
·
Dosing
o
8 mg/kg
as a single dose (maximum
dose: 800 mg)聯合glucocorticoids使用
o
勿與baricitinib合用
·
Administration
o
使用100ml infusion bag，輸注時間60分鐘，不用特別避光
·
Warning
and Precaution (警告與注意事項 )
o
Neutropenia
and thrombocytopenia, increase LFT
·
Monitor
(監控項目)
o
Hematological
profile
o
Infusion
reaction, may stop and reinitiate with slower infusion rate
· 實證 : 降低使用呼吸器的時間
|
JAK inhibitor: Baricitinib 需填臨採單
|
·
Recommendation
for Usage
o
台灣疾管署: 與 dexamethasone，或
dexamethasone + remdesivir 合併用於住院、需使用高流量氧氣或非侵襲性呼吸器但未插管病患； 病患住院 3 天內，且入住 ICU 24 小時內或未入住 ICU 但發炎指數上升 (CRP ≥ 7.5 mg/dL)
·
Dosing
o
4mg QD
per oral for 14 days or
until discharge
·
Renal/
Hepatic dose adjustment
o
30 ≤
eGFR < 60: 2mg QD
o
15 ≤
eGFR < 30: 1mg QD
o
eGFR
< 15: not recommended
o
Severe
impairment: Use is not recommended (has not been studied)
·
Administration
o
無法吞嚥者，可以嚼碎或用約10ml水溶解後服用
o
管灌者，可以用30水(室溫)溶解後服用
·
Warning
and Precaution
o
Risk of
infection, increase LFT, thrombosis, lymphopenia and anemia
·
Monitoring
parameters:
o
Hematological
profile, AST/ALT
·
實證: 縮短恢復時間
|
Anticoagulation (抗凝血劑)
- Thromboembolic events rate among Asian
population (Japan, China)6-7
- All hospitalized patients: 2.9; ICU patients:
46%
- DVT prophylaxis:
- Recommend for all critical patients.
- Recommend for severe patients with Padua
Score>4.
- Pauda score: Prior episode of VTE [3];
Thrombophilia [3]; Decreased mobility [3]; Active malignancy [3];
Previous trauma/surgery in a month [2]; Age >70 [1];
Hear/respiratory failure [1]; Ischemic stroke or MI [1]; Acute
rheumatologic disorder/acute infection [1]; Obesity [1]; Hormonal
therapy [1]
- Contraindication: PLT<30, active or recently
bleed, hematoma, HIT
- Dose: Enoxaparin 40mg SC daily, 30mg
if CrCl<30; heparin 5000u sc q12h if HD
- Discontinue upon discharge
- DVT treatment:
- Consider escalation to therapeutic dose: O2>2L, elevated CRP,
ferritin, procal, D-dimer>3
- Dose: Enoxaparin 1mg/kg q12h (CrC<30:
1mg/kg q24h; HD: 0.8mg/kg q24h or heparin infusion APTT goal 60)
- Discharge with DOAC (apixaban preferred in CKD)
for at least 3 months
|
Neutralizing Antibodies: bamlanivib/etesevimab; casirivimab/imdevimabmab
(即將引進台灣)
|
·
Indication:
For outpatient/ED use only. Mild to moderate patient at risk of progression to severe. Or admitted to the hospital for non-COVID-19 related reasons.
·
Risk
factors:
o
BMI≥35;
CKD; DM, immunosuppressive disease/treatment, ≥65 y/o; ≥55 y/o with CV
disease or lung disease
·
Dose:
o
casirivimab
600mg + imdevimab 600mg IV single dose
o
bamlanivimab
700mg +estesevimab 1400mg IV
(preferred) or SC single dose
·
Adverse
reaction: infusion reaction chills fever, urticarijp4a, pruritus, flushing
·
Bamlanivib
700mg monotherapy is not recommended; did not show a significant ↓in
viral load
·
Evidence:
o
Decrease
viral load, decrease hospitalization/ED visits
|
Supportive care (支持照顧)
o
Oxygen therapy
o
Fluid and
Nutrition
o
Antipyretic
§
Acetaminophen is
preferred over NSAIDs
§
Need not to
discontinue NSAIDs for chronic use
o
Anti-cough
medications
o
Avoid
nebulization
§
To prevent
aerosolization of SARS-CoV-2, prefer MDI or DPI
o
Stress ulcer
prophylaxis in the following patients
·
Mechanical
ventilation > 48hr
·
High bleeding
risk (Plt< 50,000 ; INR>1.5 or APTT>2X of Normal value)
·
History of GI
ulceration or GI bleeding within the past year
·
On NSAIDs or
antiplatelet agents
May consider in patients using dexamethasone
n
Empiric treatment for bacterial pneumonia
Not recommended to routinely administer empiric therapy for bacterial
pneumonia.
Data suggest low rates (4-8%) of bacterial +
viral co-infection with SARS-CoV-2
If empiric antibiotic therapy is initiated,
make a microbial diagnosis and reevaluate the need to continue antibiotic therapy
daily. Discontinue if procalcitonin< 0.25 with no leukocytosis
Empiric regimen
·
Ceftriaxone
2g IV q24h (5-7 days)+ azithromycin 500mg po daily x 3 days
·
Piperacillin/tazobactam
indicated for recent hospitalization neutropenia or when pseudomonas coverage
is desired
·
Reference
1.
Taiwan CDC新型冠狀病毒（SARS-CoV-2）感染臨床處置暫行指引第十一版
2.
台灣重症COVID-19照顧簡要指引
3.
NIH
4.
IDSA Guidelines
on the Treatment and Management of Patients with COVID-19
5.
COVID-19
Real-time Learning Network
6.
Iba et al.
International Journal of Hematology. 2021. 113: 330-336
7.
Fujiwara. J
Infect Chemother. 2021. 27: 869-875
和信醫院藥劑科林蘭熙/洪維宏藥師
