Tabel 1.

Rencana pengobatan dan eskalasi yang dikeluarkan oleh NHS Inggris untuk
pasien COVID-19 yang dewasa [ 53 ].

3.3.4. Ventilasi mekanik yang Invasif

Bukti terkahir dari tinjauan baru-baru ini oleh King's College Hospital NHS
serta pedoman yang dikeluarkan oleh WHO menyimpulkan bahwa kasus parah yang
memerlukan ventilasi mekanis dapat memperoleh manfaat dengan prinsip-prinsip
berikut:

1) Penggunaan volume tidal rendah (4–8 ml/kg prediksi berat badan (PBW))
dan target tekanan plateau <30 cmH20 (<28 cmH20 pada anak-anak):
 Dewasa: Volume tidal awal 6 ml/kgPBW (dapat dinaikkan menjadi 8
ml/kg PBW jika volume tidal awal tidak dapat ditoleransi).
 Anak-anak: Target volume tidal 3-6 ml/kg PBW (dapat ditingkatkan
menjadi 5–8 ml/kg PBW dalam kasus dengan kepatuhan pernapasan
yang terjaga baik) [25].
 2) Pada aturan umum, titrasi positive end-expiratory pressure (PEEP) harus
dipandu oleh Fraksi Oksigen Terinspirasi (Fi02) yang diperlukan untuk
mencapai saturasi oksigen arteri yang diinginkan (Sp02). Pengaturan yang
disajikan pada Tabel 2 telah diturunkan dari uji coba ARDSnet dan dapat
digunakan untuk mencapai Sp02> 90% [25,54].
3) Tekanan jalan napas awal yang membebaskan ventilasi harus
dipertimbangkan pada pasien tertentu. [55].
4) Pertimbangkan prone ventilation secepatnya pada pasien di mana tidak ada
perbaikan yang diamati setelah 12 jam pengoptimalan ventilator (yaitu
PaO2 / FiO2 <150). Prone Ventilation harus berlangsung 12-16 jam sehari
[25,55].
5) Hiperkapnia permisif dapat dipertimbangkan jika parameter hemodinamik
yang baik dapat dipertahankan sebagai lawan dari bentuk ventilasi yang
dapat menyebabkan kerusakan paru lebih lanjut [25,55].

3.3.5. Extracorporeal membrane oxygenation (ECMO)

Kasus COVID-19 dengan hipoksemia refrakter meskipun dengan ventilasi

pelindung paru harus menerima ECMO jika layanan extracorporeal life support
(ECLS) tersedia [25].
3.3.6. Resusitasi cairan dan vasopresor

Pada orang dewasa, resusitasi cairan harus diberikan sebagai bolus cairan
kristaloid 250-500 ml selama 15-30 menit diikuti dengan penilaian kelebihan cairan
setelah setiap bolusnya. Vasopresor dapat digunakan jika syok septik (Tabel 3) tetap
ada meskipun dilakukan resusitasi cairan untuk mempertahankan mean arterial
pressure (MAP) ≥65 mmHg. sebuah penelitian terbaru menunjukkan, pasien berusia
di atas 65 tahun, MAP 60-65 mmHg masih dapat diterima [25,57]. Pada orang
dewasa norepinefrin adalah obat pilihan yang dapat ditambah dengan epinefrin atau
vasopresin untuk mempertahankan target MAP. Pada anak-anak, resusitasi cairan
harus diberikan dalam bentuk bolus cairan kristaloid 10-20 mL/kg selama 30-60
menit diikuti dengan penilaian kelebihan cairan setelah setiap bolus. Vasopresor
dapat digunakan jika tanda-tanda syok septik (Tabel 3) dan / atau kelebihan cairan
diamati atau jika ada tanda ketidakmampuan untuk mempertahankan parameter
tekanan darah yang sesuai dengan usia. Pada anak-anak, epinefrin adalah obat
pilihan, dengan suplementasi norepinefrin jika syok septik berlanjut [25].
3.4. Manajemen medis

CDC menjelaskan komentar WHO tentang penggunaan kortikosteroid dan

selanjutnya menjelaskan bahwa penggunaannya dapat memperpanjang replikasi virus
bila digunakan pada virus yang mirip dengan COVID-19 seperti MERS-CoV [59].
Ketika pasien datang dengan SARI, WHO menyarankan untuk memberikan
antimikroba empiris yang kemungkinan dapat mengobati agen penyebab dalam 1 jam
penilaian dengan sepsis yang dikonfirmasi. Perawatan ini harus didasarkan pada
diagnosis klinis - apakah pneumonia yang didapat di komunitas atau rumah sakit -
dan dirawat sesuai dengan pedoman lokal [25]. Sebaliknya, Wang et al. telah
menyarankan bahwa penggunaan antibiotik spektrum luas yang tidak tepat harus
dihindari kecuali ada bukti infeksi bakteri sekunder [42].

Baru-baru ini, pelopor tes laboratorium menyarankan bahwa mungkin ada

obat yang sudah digunakan untuk virus lain yang dapat diterapkan pada COVID-19.
Remdesivir-agen antivirus spektrum luas-adalah analog adenosin yang mampu
mengganggu rantai RNA virus yang baru lahir sehingga menyebabkan penghentian
rantai yang prematur, dan sebelumnya telah diuji untuk pengobatan virus Ebola.
Ketika remdesivir disuntikkan ke dalam sel Vero E6 yang terinfeksi COVID-19,
antivirus tersebut secara efektif menghambat virus. Ketika diuji dalam garis sel
manusia (sel Huh-7) virus secara efektif menghambat [60]. Ini mendukung
pernyataan CDC bahwa remdesivir memiliki aktivitas in vitro melawan COVID-19
[61]. Penelitian lebih lanjut diperlukan untuk mengonfirmasi penggunaan Remdesivir
terhadap COVID-19, namun National Institute of Allergy and Infectious Diseases
saat ini sedang melakukan uji coba double-blind randomised controlled penggunaan
remdesivir pada pasien dengan infeksi COVID-19, dengan hasil tertunda [62 ].

Obat familiar lain yang mungkin dapat dipakai untuk COVID-19 adalah
chloroquine; itu secara tradisional digunakan sebagai antimalaria serta melawan
penyakit autoimun. Mekanisme kerja chloroquine meningkatkan pH endosom
melebihi yang diperlukan untuk fusi virus dan sel sementara juga mengganggu
glikosilasi reseptor seluler pada virus serupa seperti SARS-CoV. Ketika chloroquine
dimasukkan ke dalam sel Vero E6 yang terinfeksi COVID-19, chloroquine
tampaknya mengobati infeksi pada tahap awal dan tahap masuk infeksi. chloroquine
juga dapat meningkatkan modulasi kekebalan sel, berpotensi meningkatkan
kemanjuran obat in vivo. Secara umum, chloroquine murah dan aman digunakan, dan
didistribusikan secara luas ke semua sistem organ termasuk paru-paru saat
dikonsumsi secara oral. (Gambar 6) [63].

Obat onkologi adalah kelas lain dengan minat yang terus meningkat. Beberapa
obat onkologi – meskipun hasil laboratorium menjanjikan - tidak dapat ditoleransi
oleh manusia karena dosis yang dibutuhkan jauh lebih tinggi daripada dosis
terapeutik yang ditetapkan untuk penyakit lain. Sebaliknya, obat anti-inflamasi telah
disarankan karena efek respon inflamasi yang signifikan pada kerusakan paru-paru
dan menyebabkan kematian. Tabel 4 merinci tiga agen antiinflamasi yang
diujicobakan pada COVID19. Mekanisme kerja yang mendasari mereka melibatkan
penghambatan pensinyalan JAK STAT sehingga mengurangi peningkatan sitokin
yang terlihat pada pasien dengan COVID-19 [64].
3.5. Tatalaksana Operasi

Transplantasi paru ganda pertama berhasil dilakukan pada seorang pasien di

China dengan kerusakan paru bilateral yang ireversibel sekunder akibat COVID-19
pada 29 Februari 2020. Pria berusia 59 tahun itu terinfeksi SARS-CoV-2 pada 26
Januari 2020, dan meskipun tes berulang mengkonfirmasi resolusi dan tidak adanya
infeksi yang sedang berlangsung, intubasi endotrakeal yang berkepanjangan,
ventilasi, dan terapi ECMO tetap diperlukan. Tim di Rumah Sakit Rakyat Wuxi,
dipimpin oleh ahli bedah kardiotoraks Dr.Chen Jinguy, melakukan operasi 5 jam
tersebut. Operasi berhasil dilakukan dengan pasien yang membutuhkan observasi
pasca operasi dan terapi medis untuk menghindari infeksi atau reaksi penolakan [65].

3.6. Mengukur respons

Karena pilihan pengobatan yang tersedia terbatas, kemampuan untuk

mengukur tanggapan terhadap pengobatan menjadi tantangan. Ketika pasien diuji
untuk infeksi awal, hasil positif didasarkan pada deteksi asam nukleat untuk infeksi
SARS-CoV-2. Ketika menilai pasien dengan kondisi yang memburuk, telah tercatat
bahwa CRP meningkat secara signifikan dan albumin rendah [31]. Meskipun tidak
ada pedoman yang jelas tentang evaluasi tanggapan terhadap pengobatan suportif,
sebuah studi oleh Cascella et al. telah menyarankan bahwa evaluasi laboratorium
sampel dari pasien harus menunjukkan bebas virus sebelum keluar dari pengamatan
dalam bentuk dua spesimen saluran pernapasan yang negatif dan diambil setidaknya
24 jam [66,67].

4. Hasil

Data saat ini menunjukkan bahwa ada sekitar 1.664.384 kasus aktif di seluruh
dunia, di mana 97% (n = 1.623.355) menunjukkan gejala ringan COVID-19 dan 3%
(n = 41.029) pasien yang terinfeksi serius (membutuhkan terapi oksigen) atau kondisi
kritis (membutuhkan ventilasi mekanis). Dari kasus tertutup (n = 834.069), 79% (n =
663.477) individu yang terinfeksi telah pulih dari penyakit atau telah berhasil
dipulangkan dari rumah sakit. 21% (n = 171.017) dari kasus ini meninggal karena
penyakit atau komplikasi terkait [7]. Saat ini, laporan situasi WHO ke-46
memperkirakan rasio kematian kasar COVID-19 berada di antara 3 dan 4%
berdasarkan data saat ini [68]. Waktu rata-rata untuk pemulihan dari timbulnya gejala
adalah sekitar 2 minggu pada kasus ringan dan 3-6 minggu pada individu yang sakit
berat atau kritis [34].

5. Kesimpulan

Dengan puncak 101.736 kasus baru yang dikonfirmasi pada 3 April 2020
[69], ada kekhawatiran bahwa temuan ini dapat mengindikasikan penyebaran
penyakit secara eksponensial. Penerapan dan kepatuhan terhadap social distancing
yang lebih ketat untuk menekan dan mengurangi penyebaran COVID-19 akan
terbukti sangat penting di bulan-bulan mendatang. Pedoman terbaru yang berbasis
bukti untuk manajemen akut COVID-19 sangat penting untuk memandu dokter
melewati pandemi yang berkembang pesat. Ketika bukti baru muncul, sangat penting
mengenai pilihan pengobatan saat ini dan yang potensial sering dievaluasi ulang
untuk memberikan perawatan terbaik dalam keadaan yang belum pernah terjadi
sebelumnya.

Ethical approval

None required.

Sources of funding

None.

Author contribution

Maria Nicola: significant role in concept production and writing of manuscript,

editing and approval of final draft.
Niamh O'Neill: significant role in writing of initial manuscript, editing and approval
of final draft.
Catrin Sohrabi: contribution to writing of manuscript, editing and approval of final
draft.
Mehdi Khan: contribution to writing of manuscript, editing and approval of final
draft.
Riaz Agha: senior author, role in supervising concept production, collection of papers
and approval of final draft.
Guarantor
Niamh O'Neill: Corresponding Author, niamh@ijspg.com.
Riaz Agha: Senior author, mail@riazagha.com.
Data statement
Data dalam ulasan ini tidak bersifat sensitif dan dapat diakses di domain publik. Oleh
karena itu, data tersedia dan tidak bersifat rahasia.
Declaration of competing interest
None.
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