Curriculum Vitae

Critical Care Management of

COVID-19 Patients with

Mechanical Ventilation

Bambang Pujo Semedi

Dept. Anestesiologi dan Reanimasi FK UA – RSUD Dr Soetomo

Surabaya

Sejarah Pandemi Coronavirus

Berapa banyak pasien COVID-19 yang perlu perawatan kritis ?

• Seperempat (sekitar 25%) pasien yang dirawat di RS perlu perawatan di intensive care unit (ICU) (bervariasi prosentase nya)

• Sekitar 5 - 8 % dari total populasi yang terinfeksi

• China : kasus yang perlu ICU atau derajat beratberkisar 7-26 %

• Italy : Prosentase yang perlu ICU pada kasuspositif SARS-CoV-2 adalah 5-12 %, atau 16 % daripasien yang perlu dirawat di RS (preliminary reports)

Uptodate, April 2020

.. Berapa banyak pasien COVID-19 yang perluperawatan kritis ?

• USA :

• Negara bagian Washington

• 21 pasien kritis

• ICU admission rate : 81 %

• 71 % butuh ventilasi mekanik

• Makin tinggi kebutuhan bed ICU à makinbesar populasi geriatri di suatu tempat

• Analisis pada 2449 pasien :

• Perlu perawatan di RS : 20 s/d 31 %

• ICU admission rates : 4,9 – 11,5 %

Uptodate, April 2020

Clinical course and outcomes of critically ill patients with

SARS-CoV-2 pneumonia in Wuhan, China: a single-centered,

retrospective, observational study

Xiaobo Yang*, Yuan Yu*, Jiqian Xu*, Huaqing Shu*, Jia’an Xia*, Hong Liu*, Yongran Wu, Lu Zhang, Zhui Yu, Minghao Fang, Ting Yu, Yaxin Wang,

Shangwen Pan, Xiaojing Zou, Shiying Yuan, You Shang

Dari 710 pneumonia COVID-19 terkonfirmasi à 52 pasien kategori kritismenunjukkan gejala hypoxemia berat…

• perlu ventilasi mekanik : 37 (71%)

•mengalami ARDS : 35 (67%)

•meninggal s/d hari ke-28 : 32 (61,5%)

Usia tua merupakan faktor risiko

Case fatality rate (CFR) di ICU

• 1 provinsi di China

• 710 Kasus

• 52 ICU

• 22 perlu ventilator

• 19 meninggal (86%)

•UK (ICNRC)

• 165 ICU

• 98 perlu ventilator

• 79 meninggal (80,6%)

•New York

• 88,1 % pasien dengan ventilator meninggal

Lombardi, Italia

• 920 pasien (58% [95% CI,

56%-61%]) masih di ICU

• 256 (16% [95% CI, 14%-

18%]) telah keluar ICU

(pulang???)

• 405 meninggal ICU (26%

[95% CI, 23%-28%]).

Non-uniformity is characteristic of COVID-19

Hipoksemia berat, namun tidak disertaidengan penurunan

compliance paru

( 50% kasus yang diobservasi di Italia)

Tidak memenuhikriteria ARDS klasik

• Sering kali tidak terlihatdistress nafas, tetapimenunjukkan tanda klinishipoksemia berat (SILENT

atau HAPPY HYPOXEMIA)

• Tanda klinis : mild flu like syndrome to severe

pneumonia

• Hipokapnea – normokapnea –hiperkapnea

• Vary response to therapy

• PEEP, prone position, nitric oxide

Gattinoni. 2020

Non-uniformity in clinical presentation is determined by..

Non-uniformity

1. Severity of infection

2. Host response

3. Physiological reserve

4. Comorbidities

The ventilatory

responsiveness of the

patient to hypoxemia

the time elapsed between the onset of the disease and the observation in the

hospital

Gattinoni. 2020

Diseases Course of COVID-19

Luigi Camporata,2020

Perjalanan penyakitnya “UNPREDICTABLE”

Gejala ringan

• Demam

• Batuk

• Nyeri tenggorok

• Nasal congestion

•Malaise

• Headache

•Muscle pain

Pneumonia

ringan

• Pneumonia

• Tidak ada tandapneumonia berat

Sindroma klinis COVID-19

Pneumoniaberat

• Demam atau dugaaninfeksi saluran nafas

• Satu dari tanda ini :

• RR ≥ 30 x/min

• Severe respiratory distress

• SpO2 ≤ 90-93% on room air

ARDS

• Menurut Berlin Definition 2012

Sindroma klinis COVID-19

Butuh O2 therapy atau ventilasi mekanik

Prinsip Tatalaksana COVID-19

Antivirus

• Lopinavir/ritonavir +

interferon

• Favipiravir (Avigan)

• Remdesivir

• Kombinasi CQ atau

HCQ plus Azithromycin

• IVIg dosis tinggi

• Convalescent Plasma

Therapy

Anti inflamasi

• Steroids

• Anti-IL-6 :

Tocilizumab

Tindakan suportif

yang komprehensif

• Terapi oksigen dan

ventilasi mekanik

• Nutrisi

• Homeostasis internal

• Fluid control

• Antikoagulan

• HAIs setelah periode

awal perawatan ICU

14

Anti oksidan

• High dose Vit C

• High dose NAC

• Omega 3 plus

Glutition

Karakteristik pasien COVID-19 berat

Gagal

nafas

Gagal

Sirkulasi

Gagal Organ

Lain

Parenkim

paru

Sirkulasi

paruSeptik Hipovolemik Kardiogenik

↓ CO

Hipoperfusi

↓ volume

paru

Shunting

V/Q

mismatch

Dead space

Hipoksemia Hiperkarbia

HIPOKSIA BERAT

AKI

Hepatic

failure

Asidosis

Patofisiologi hipoksemia

pada COVID 19

Normal VasoplegiaAtelektasis

Shunt

Hipoksemia

V/Q =1 V/Q < 1 V/Q < 1

Venous Artery

O2

Hypoventilation,

normo perfusion

Normo ventilation,

high perfusionNormo ventilation,

normo perfusion

VasoplegiaAtelektasis

V/Q < 1 V/Q << 1

plus

edema

Vasoplegia

V/Q < 1Hypoventilation,

high perfusion

Right to Left shunt

• ↑ FiO2 tidak efektif bila“shunt unit” sangatbesar ( > 50% CO)

• Namun, jika “shunt unit” kecil : ↑FiO2

à ↑ CaO2

(arterial O2 content)

No shunt

Terapi O2 bermanfaat bila

”shunt unit” < 25%

Respons terhadap pemberian O2

menggambarkan derajat shunt

YaTidak

Ringan Sedang

Berat

Ringan

Berat

Luigi Camporata presentation

Syok,

hipertensi

pulmonal

Syok,

overventilasi,

ACP

Atelektasis,

syok,

trombosis

Dead spaceHipoksemia

Hiperkarbia

V/Q >1 V/Q >> 1

Trombosis

Silent lung

Normo ventilation,

low perfusion

Over ventilation,

low perfusion

• pH 7,41

• PaO2 59

• PaCO2 52

• HCO3 33

• BE 8,4

• FiO2 90

• SpO2 86

• RR : 20 x/menit

• Tidak merasa sesak

• Terlihat sedikit retraksi

• Nadi 90x/menit

• TD 120/80 mmHg

Laki, 67 tahun datang

dengan keluhan batuk dan

demam sejak 4 hari yll.

Riwayat kontak dengan

pasien COVID terkonfirmasi

Happy hypoxemia

Masker

12 lpm

Hypoxemia

Dysregulation of Pulmonary Perfusion

Pulmonary OedemaCollapse – “ARDS-like”

Pulmonary Micro-Thrombosis

• Low Elastance• Low V/Q• Low Recruitability• Limited “PEEP

response”

• High Elastance• Higher Recruitability• High R à L shunt• Higher “PEEP

response”

Phenotype L Phenotype H

COVID-19 Specific Pathophysiology

Luigi Camporata, UK

Tatalaksana pasien COVID 19 yang menggunakan ventilasi mekanik

sangat kompleks

Dukungan laboratorium yang cepat dan akurat sangat

menunjang keberhasilan terapi di ICU

Identifikasi pasien risiko tinggi…

• Umur > 65 tahun

• Komorbid:• Penyakit kardiovaskuler• Diabetes mellitus• Hipertensi• Penyakit paru kronik• Kanker• Gagal ginjal kronik

• Laboratorium :• Lymphopenia • ↑ Penanda inflamasi• ↑ D-dimer/PT• ↑ Enzim hepar• ↑ Troponin• ↑ Creatinine phosphokinase• ↑ Ferritin

• Scoring System• qSOFA/SOFA > 2• APACHE II >

26

Preventing clinical deterioration is better

Sun et al. Ann. Intensive Care (2020) 10:33

• RR > 30 x/m

• SpO2 < 95% dengan terapi O2

• HR > 120 x/m

• Faktor risiko tinggiCritical care management

Awake Prone Position

12-16 jam per hari

Terapi Suportif Dini dan Monitoring

Terapi suplemen oksigen

• Mulai 5 L/min dan titrasiflow rate nya sesuai target

• Gunakan alat disposable, single-use :

qNasal cannula

qSimple face mask

qMask with reservoir bag

Target SpO2

• Dewasa tidak hamil ≥ 90%

• Wanita hamil ≥ 92-95%

• Anak ≥ 90%

Anggap sebagai gagal nafas hipoksemik berat bila pasiendengan distress nafas tidak membaik dengan terapi O2

konvensional, HFNC, & NIV à VENTILASI MEKANIK

Eskalasi Terapi Oksigen

Awake Repositioning/Proning

Courtessy : EmDocs

Non-invasive vs Intubasi Dini

Pertimbangkan :

• Faktor risiko

• usia : geriatri

• komorbid : DM, cardiac diseases, kanker, etc

• smoker

• obese

• Fasilitas dan SDM (ketersediaan bed ICU dan perawat mahir)

• Perjalanan penyakit

• semakin memburuk dalam perjalanannya

• tidak membaik dengan terapi konvensional

• aritmia, asidosis berat, claustrophobia, dll

Hot issue….COVID-19 and haemostasis:

a position paper from Italian Society

on Thrombosis and Haemostasis

(SISET)

Marco Marietta1, Walter Ageno2, Andrea Artoni3, Erica De Candia4,5, Paolo Gresele6,

Marina Marchetti7, Rossella Marcucci8, Armando Tripodi3

Position paper

HAEMOSTASIS AND

THROMBOSIS

© S

IMTIP

RO

Srl

COVID-19 cytokine

storm: the interplay

between inflammation

and coagulation

Coronavirus disease 2019 (COVID-19)

has spread rapidly throughout the

globe. It is associated with significant

mortality, particularly in at-risk groups

with poor prognostic features at

hospital admission.1 The spectrum

of disease is broad but among

hospitalised patients with COVID-19,

pneumonia, sepsis, respiratory

failure, and acute respiratory distress

tightly controlled by negative

feedback loops and physiological

anticoagulants, such as antithrombin

III, tissue factor pathway inhibitor,

and the protein C system.5 During

inflammation, all three of these control

mechanisms can be impaired, with

reduced anti coagulant concentrations

due to reduced production and

increasing consumption. This defective

pro coagulant–anticoagulant balance

predisposes to the development

of microthrombosis, disseminated

intra vascular coagulation, and multi-

organ failure—evidenced in severe

COVID-19 pneumonia with raised

coagulation protease inhibitors. PAR-1

is the main thrombin receptor and

mediates thrombin-induced platelet

aggregation as well as the interplay

between coagulation, inflammatory,

and fibrotic responses, all of which

are important aspects of the patho-

physiology of fibroproliferative lung

disease,5 such as seen in COVID-19.

Although less likely to have an effect

on venous thromboembolism,

PAR-1 antagonists developed as

antiplatelet drugs for the treatment

of cardiovascular disease,8 might

potentially attenuate the deleterious

effects associated with activation of

Lancet Respir Med 2020

Published Online

April 27, 2020

https://doi.org/10.1016/

S2213-2600(20)30216-2

NA

SA W

orl

dvi

ew, E

arth

Ob

serv

ing

Sys

tem

Dat

a an

d

Info

rmat

ion

Sys

tem

(EO

SDIS

)/Sc

ien

ce P

ho

to L

ibra

ry

Fibrinous microthrombi in small sized pulmonary

arterioles, observed in 8 out of 10 patients (B-D)

Diffuse alveolar damage

in fatal COVID-19Dolhnikoff et.al, 2020

Mikrothrombi à ↑ dead space

• Refractory hypercarbia

• Difficult to treat using ventilator only

• Perlu ECMO, ECCO2 removal

What should we do?

• ↓ driving pressure

• ↓ PEEP

• ↑ FiO2

• Asses hipovolemik

pH

PaO2

PCO2

HCO3

BE

SaO2

P/F ratio

7,43

60

57

37,5

13,5

91

100

FiO2 60%

F

COVID-19 : hypoxemia,

hypotensive, with

severe respiratory

acidosis

Teuku Aswin Husain properties

Fluid, vasopressor,

or inotropic ?

Pulmonary

vasodilator & adjust

ventilator setting

Kasus 1

• Laki-laki, 56 tahun

• Keluhan flu like syndrome sejak 10 hari

sebelum MRS, keluhan sesak memberat 3

hari terakhir

• Dirawat di ward selama 6 hari dari RS à

ICU karena SpO2 80-88% dengan NRM 15

lpm à HFNC à membaik secara klinis

• Fluid restriction

• Prone position tidak nyaman

Foto thoraks

18Mei

41

26 Mei 2020

Foto thoraks

15Mei18Mei

42

31/05/2020

Terapi

WBC = 17.190 (31 Mei, 03.29) à

17.350 (12.41)

Neutrofil = 15,57 (31 Mei, 03.29) à

15,92 (12.41)

Limfosit = 0,71 (31 Mei, 03.29) à

0,67 (12.41)

NLR = 21,9 (31 Mei, 03.29) à 23,7

(12.41)

CRP = 25,6 (31 Mei)

PCT = 0,28 (31 Mei)

Suhu = 36,6

SOFA score = 4 (31 Mei)

• Cefosulbactam 1 g/8

jam (3)

• Avigan trial 600

mg/12 jam (loading

dose sebelumnya)

43

Renal Produksi Urine inisial = 2850 ml (1,7 ml/kg/jam)

Balans 24 jam = -1088 ml

Balance Kumulatif = -417 ml (H2)

BUN/SK = 13/1,0 (29 Mei) à 15/1 (31 Mei)

Na/K/Cl = 138/3,5 (31 Mei) à 139/3,5/101 (2 Juni)

Ca/Mg = 8,2/1,6 (31 Mei) à 7,6/1,5 (2 Juni)

GI Abdomen soepel, bising usus normal, NGT tidak

terpasang

Hepar SGOT/SGPT = 50/63 (29 Mei) à 26/69 (31 Mei)

Albumin = 2,8 (31 Mei) à 2,5 (2 Juni)

Bilirubin D/T = 0,39/0,84 (31 Mei)

44

Hiperinflamasi ?

Endokrin GDA = 356 (1 Jun)à223 (17.00)

HbA1c = 10,1 (31 Mei)

• Insulin 2 unit/jam

• Insulin 3x10 unit

Lain-lain • Vitamin C 400 mg /24 jam IV

drip

Nutrisi/Cairan Kebutuhan kalori

BB : 72 kg

TB : 168 cm

• Diet DM 1800 kkal

• Minum bebas tercatat (1000

ml/24 jam)

• Infus RL 500 ml/24 jam

Tn Na'am 45

Nadi 98-120x/menit, Tekanan darah 123-

185/71-108, MAP 90-111

Hb = 31 Mei 11,6 (10.35) à 11,3 (12.41)

PLT = 284.000 (31 Mei)

PPT/APTT = 11,3 / 24,5 (1 Jun) à

11,5/27,3 (2 Juni)INR = 1,1 (31 Mei) à 1,1 (2 Juni)

D-dimer = 103.700 (31 Mei) à Bolus 80

unit/kg BB UHF à 15.000-20.000 u/24 j

• TEG

• Echo awal tidak

menunjukkan

tanda right heart

failure atau

gambaran PE à

serial echo

46

• Tidak pernah mencapai target PTT à risk VTE tinggi

• Risiko emboli ↑ ↑ walaupun antikoagulan sudah adekwat

• Perlu evaluasi echocardiography serial untuk terapi lebih agresif

• Bila terjadi PE à ventilator tidak akan membantu

BGA

Resp. HFNC FiO2 70%, 50 lpm

à RR me↑ 35-

42x/menit, SpO2 93 -

94%, gelisah

Parameter 31 Mei 1 Jun 2 Juni

pH 7.47 7,39 7,42

pO2 79 65 89

pCO2 35.2 42 26

HCO3 26.2 25,4 16,9

BE 3 0,4 -7,6

SO2 96 92 97

P/F ratio 98.75 92,8 127

Asidosis metabolik

Intubasi,

ventilasi

mekanik

HFNC FiO2 70%

Membaik

pH 7,046

pO2 69

pCO2 125

HCO3 34,3

BE 4

SaO2 81

p/f 69

Kasus 2• Laki-laki 69 tahun dengan keluhan infeksi

pernafasan berat sejak 7 hari sebelum MRS.

• Rapid test negatif, tetapi hasil PCR swab positif àpneumonia covid 19.

• Masuk ICU isolasi karena SpO2 <93% dengan NRM, RR 26-28 x/menit, ada retraksi, HR 100x/menit, TD dalam batas normal

• Pasien tanpa komorbid menurut riwayatnya

Kasus 2

Terapi :

• Antiviral

• Antibiotik

• Awake prone position à memburuk à ventilasimekanik

• Enoxaparine 60 mg every 12 hrs à Heparin after patient has deteriorated then applied mechanical ventilation

Awake

prone position

SpO2 95-98%

Memburuk

Intubasi

1/5/2020 9/5/2020

X-ray Serial Mr R

12/05/2020

Mr. R

Days from onset of illness

Hospitalized

Positive RT PCR

Chest Xray peripherally bilateral

infiltrate

Oxygen supplementation

Enoxaparin

60 mg/12 j

Heparin à terapi agresif

Emergency

Department

Intensive Care Unit

Perburukan klinis,

disertai hipotensi à intubasi

• NRM 12-15 lpm

• Awake prone

• Restrictive fluid

D-dimer

221.000

Days of hospitalization

Mr. R

D d

ime

r AP

TT

> 80 mcg/ml

221 mcg/ml

Dosis UFH

Suspected

PE

Loading UFH

5000 U x 2

D-dimer 221 mcg/ml à aggressive UFH

TEG RESULT

pH darah dapat meramalkan prognosis..

Survivor

Bad prognosis

LMWH

UFH

LMWH

Incidence VTE in COVID-19

• In a French prospective multicenter cohort of 150 ICU

patients, 16.7% had pulmonary embolism despite

prophylactic anticoagulation.

• Patients with COVID-19 and ARDS had increased incidence

of pulmonary embolism compared to patients without

COVID-19-associated ARDS.1

• A Dutch study of 184 ICU patients reported a cumulative

incidence of venous thromboembolism (VTE) of 27% (95%

confidence interval, 17% to 32%), despite prophylaxis.2

1. Helms J, Tacquard C, Severac F, et al. High risk of thrombosis in patients in severe SARS-CoV-2

infection: a multicenter prospective cohort study. Intensive Care Med. 2020:[Preprint]. Available

at: https://www.esicm.org/wp-content/uploads/2020/04/863_author_proof.pdf.

2. Klok FA, Kruip M, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU

patients with COVID-19. Thromb Res. 2020. Available

at:https://www.ncbi.nlm.nih.gov/pubmed/32291094.

• A study that used routine ultrasounds reported VTE

incidence of 69%1 in those admitted to the ICU.

• An Italian study found a VTE rate of 22.2%.2

• Among 393 patients from New York, only 13 patients (3.3%)

experienced VTE; 10 of those patients (7.7%) were

mechanically ventilated, and three (1.1%) were not

mechanically ventilated.3

1. Llitjos JF, Leclerc M, Chochois C, et al. High incidence of venous thromboembolic events in anticoagulated

severe COVID-19 patients. J Thromb Haemost. 2020. Available

at:https://www.ncbi.nlm.nih.gov/pubmed/32320517.

2. Tavazzi G, Civardi L, Caneva L, Mongodi S, Mojoli F. Thrombotic events in SARS-CoV-2 patients: an urgent

call for ultrasound screening. Intensive Care Med. 2020. Available

at:https://www.ncbi.nlm.nih.gov/pubmed/32322918.

3. Goyal P, Choi JJ, Pinheiro LC, et al. Clinical characteristics of COVID-19 in New York City. N Engl J Med.

2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32302078.

TEG pada COVID 19mungkin akan memberi

informasi

Tidak

Ya

Primary

fibrinolysis

Secondary

fibrinolysis

RPL >15%

atau

LY30 >7,5%

No Ya

No

Yes

Yes

No

Yes

Yes

Yes

< 1 > 3

Fibrinolisis

primerFibrinolisis

sekunder

No

CI > 3

Zhou et al, 2019

Platelet

hyper

coagulability

Enzymatic

hypercoagulability

Platelet & Enzymatic

hypercoagulability

Interpretasi TEG

Tatalaksana TEV

aPTT (detik) Dosis Modifikasi

< 35 detik ( 1.2 x normal ) 80 unit/kg bolus, naikan drip 4 unit /kg/jam

35 - 45 ( 1.2 - 1.5 x normal ) 40 unit /kg bolus, naikan drip 2 unit /kg/jam

46 - 70 ( 1.5 - 2.3 x normal ) TIDAK ADA PERUBAHAN DOSIS

71 - 90 ( 2.3 x normal ) Dosis dikurangi : drip 4 unit /kg/jam

> 90 ( > 3 x normal ) Hentikan Heparin 1- jam d ip ni /kg/ jam

time ms and tricuspid regurgitation pressure gradient mmHg

Enoxaparin

o Dosis terapetik : 1 mg/kgBB SC, diberikan 2x sehari

UFH :

o Bolus 80 unit/kg atau 5.000 unit diikuti dengan infus 18

unit/kg/jam

o Sebelum pemberian heparin, diperiksa kadar trombosit

o Pemantauan aPTT : 6 – 24 jam (target mengikuti tabel 5)

Fondaparinux

o Berat badan < 50 kg : 5 mg SC sekali sehari

o Berat badan 50 – 100 kg : 7.5 mg SC sekali sehari

o Berat badan > 100 kg : 10 mg SC sekali sehari

Konsensus Penatalaksanaan

Tromboemboli Vena (TEV) pada Penyakit

Kritis

© S

IMTIP

RO

Srl

COVID-19 and haemostasis:

a position paper from Italian Society

on Thrombosis and Haemostasis

(SISET)

Marco Marietta1, Walter Ageno2, Andrea Artoni3, Erica De Candia4,5, Paolo Gresele6,

Marina Marchetti7, Rossella Marcucci8, Armando Tripodi3

Position paper

HAEMOSTASIS AND

THROMBOSIS

© S

IMTIP

RO

Srl

Mount Sinai COVID-19 Anticoagulation Algorithm

High Risk#

↑ O2 requirement

↑ D-dimers

↑ creatinine

↑ CRP

Yes

NoYes

Apixaban 5mg PO BID

(or heparin drip per

PE protocol)‡

No

CrCl >50

Apixaban 5mg BID‡

or Adjusted Dose

Enoxaparin*

Yes

Enoxaparin SC

1mg/kg BID

No

No

Hold anticoagulation if:

- Platelet count <50,000; INR>1.5

- Evidence of current or recent

bleeding

If patients take AC at home:

- May switch to therapeutic enoxaparin

or heparin (as per algorithm) for the

duration of hospitalization, unless

contraindicated

Rivaroxaban may be used in place

of Apixaban at any indication

†RRT – Renal Replacement Therapy

‡ If ≥80 years of age or weight ≤60 kg, reduce apixaban to 2.5 mg BID

* If CrCl <30: enoxaparin 0.5mg/kg BID with anti-Xa level after 3rd dose

Admitted patients with moderate or

severe COVID-19

Admitted to an ICU?

Heparin drip per PE

protocol (goal PTT 70 -

110) or Enoxaparin SC

1mg/kg BID.

Consider tPA protocol.

Apixaban 2.5-5mg PO

BID^ or

Enoxaparin SC 40mg QD

On RRT†

Yes

Obtain at baseline and daily:- CBC, PT/PTT, D-dimer

Discharged COVID-19 patient on

therapeutic anticoagulation while hospitalized

Consider Prophylactic AC for 2 weeks post

discharge (Apixaban 5mg PO BID for 2 wks)

Version 1.1 (April 9, 2020)Inclusion: All admitted patients with moderate or severe COVID-19Exclusion: High risk of bleeding as

judged by treating physician

#High Risk: No precise metrics exist. Consider exam (eg O2 sat<90%, RR >24), ↑O2

requirement (eg, ≥4L NC), labs (eg, ↑d-dimers, C-reactive protein)

^Efficacy and dose not established; prophylactic or treatment doses acceptable

Mount Sinai COVID-19 Anticoagulation Algorithm

Definition of high risk for progression to ICU- There is insufficient evidence to precisely define “high-risk” or provide specific cut-off values for

individual factors

- Clinicians should consider a combination of exam findings (e.g, labored breathing, RR >24, decreased

O2 sat<90%), increased O2 requirement (eg, ≥4L NC), and lab biomarkers (eg, elevated CRP, elevated

creatinine, rising d-dimer >1.0).

Rationale for early anticoagulation

- Pathophysiology of COVID-19 associated respiratory disease is consistent with pulmonary vascular

thromboemboli with increased dead space ventilation

- Autopsy studies have demonstrated venous thromboembolism in deceased coronavirus patients1

- Early anticoagulation is necessary to prevent propagation of microthrombi at disease presentation

- Anticoagulation may be associated with decreased mortality2

Rationale for choice of anticoagulant

- Heparins bind tightly to COVID-19 spike proteins3,4

- Heparins also downregulate IL-6 and directly dampen immune activation5

- DOACs do not appear to have these anti-inflammatory properties

- Rivaroxaban can be used in place of Apixaban in this algorithm

References

1. Xiang-Hua et al. Am J Respir Crit Care Med, 182 (3), 436-7. PMID: 20675682

2. Tang et al. J Thromb Haemost 2020 Mar 27. PMID: 32220112

3. Belouzard et al. Proc Natl Acad Sci, 2009 106 (14), 5871-6. PMID: 19321428

4. de Haan et al. J Virol. 2005 Nov; 79(22): 14451–14456. PMID: 16254381

5. Mummery et al. J Immunol, 2000. 165 (10), 5671-9. PMID: 1106792

Version 1.1 (April 9, 2020)

Take home message• Identifikasi perburukan klinis secara dini

• Prevention is always better

• Don’t be late to treat

• Hati-hati kemungkinan VTE/PE pada kasus D-

dimer yang tinggi dan terjadi perburukan

mendadak

• Ventilator BUKAN satu-satunya modalitas terapi

pada COVID 19 berat

• Dukungan laboratorium klinis yang cepat dan

akurat sangat penting à peran PatKlin sangat

krusial dalam perawatan di ICU