Sanjay Gandhi Postgraduate Institute of

Medical Sciences, Lucknow, India

COVID – 19: THE PROTOCOL BOOK

 Foreword

Emergence of novel Corona virus disease- 2019 or COVID-19 at the beginning of the year
2020 has posed an unprecedented and overwhelming challenge to the health care providers
all over the world. The COVID-19 pandemic has engulfed almost the whole world,
compelling medical institutions, hospitals and health care systems to re-invent themselves, to
provide appropriate care to COVID-19 patients and safeguard the medical personnel from
getting infected themselves. SGPGIMS Lucknow was entrusted the job of creating the apex
level-3 category Covid-care facility for the state of Uttar Pradesh by the government, a job
that we have undertaken and completed in a very short span of time, by creating the
“Rajdhani Covid Hospital” or RCH. Unlike most other medical conditions that we are so
used to managing based on pre-existing evidence based clinical practice guidelines, protocols
had to be drawn up afresh for the care of COVID-19 patients, and organizing various aspects
of functioning of the RCH. Besides, an institute like ours has to continue managing a whole
spectrum of patients with varied medical conditions who are not infected with COVID-19,
but need to be safe-guarded against the same while undergoing treatment, for which too
appropriate protocols were prepared and implemented. This mammoth job of creating
protocols and implementing various aspects of care and services at SGPGIMS was entrusted
to the SGPGI Covid task-force, and the 17 teams or committees as part of it.

This COVID-19 protocol book has been compiled by the members of the SGPGI Covid task-
force and other faculty members of the institute. This protocol book can work as a ready
recknoner of the clinical protocols, including the ICU protocols being used for management
of COVID-19 patients, their pre- hospital screening, transportation, admission and discharge,
and all other aspects of managing the services and care of these patients at SGPGIMS and
RCH. This protocol book also provides a concise account of protocols and SOP’s we are
using for organizing the work in non-COVID areas of our hospital. These protocols are
dynamic ones, having undergone number of changes and modifications, and will undergo
further changes in coming weeks and months, owing to new information and guidelines from
various regulatory bodies coming to light. Needless to say, a lot of work has gone into
organizing and delivering care to COVID-19 patients at SGPGI, as also in compiling this
protocol book, which has been done by a large number of committed faculty members and
other cadres of the institute. I thank all of them, for compiling this useful compendium which
can guide care of COVID-19 patients and organization of services in various hospitals and
settings elsewhere in the country.

Prof Radha Krishan Dhiman

Director SGPGIMS Lucknow, Chairman, SGPGI Covid Task-force
 COVID-19 Management Protocol
SGPGIMS, Lucknow Ver 1.4 Sep. 1 2020
COVID Positive Patient

Categorize based on Severity of Illness

Asymptomatic OR very mild disease Persistent fever, and cough, constitutional symptoms, Moderate Severe
Fever, Mild URTI, No dyspnoea uncontrolled comorbid conditions /risk factors for Pneumonia with no signs of severe disease Respiratory distress requiring assisted ventilation
severe disease RR ≥ 24/ min, SPO2 ≤ 94 % on Room Air RR ≥ 30/min, SPO2 ≤ 90% on Room Air

• Home Isolation • Admit in Isolation Ward • Admit in ICU/HDU, oxygen support through nasal • Cautious trial of CPAP/NIV, HFNC to avoid intubation
• Contact and Droplet precautions • Contact and Droplet precautions cannulae or high flow delivery systems if needed • Inj. Remdesivir 200 mg IV on Day 1 followed by
• Strict hand hygiene • Strict hand hygiene • Target SpO2: 92-96% (88-92% in COPD). 100mg OD for 4 days
• For patients with high risk of severe disese1. • Tab. Hydroxychloroquine (400mg) BD on 1st day • Awake proning should be given to all who tolerate it. • IV methylprednisolone 1.0 to 2 mg/kg or dexame-
followed by 200mg 1 BD for 4 days for patients with thasone 0.1- 0.2 mg/kg for 7 - 10 days if not already
high risk of severe disese1. (after ECG Assessment)
• All patients should have daily 12-lead ECG given (To be tapered over 2 - 4 weeks depending on
Tab. Hydroxychloroquine (400mg) BD on 1st radiological involvement and clinical recovery)
day followed by 200mg 1 BD for 4 days with Tab Azithromycin 500 mg OD x 5 days • Follow CRP, D-dimer & Ferritin, Fibrinogen, Procalci-
OR OR tonin every 48-72 hourly: CBC, KFT/LFT daily • Therapeutic dose of UFH or LMWH (after excluding
Tab Ivermectin 12mg OD x 3day s with Tab Doxicy Tab Ivermectin 12mg OD x 3day s with Tab Doxicy coagulopathy or thrombocytopenia or high risk of
cline 100 mg BD x 5 days cline 100 mg BD x 5 days • Inj. Remdesivir 200 mg IV on Day 1 followed by bleeding3
OR OR 100mg OD for 4 days. • Inj. Thiamine 100 mg IV OD, Inj. Vit C 1.5gm IV 6
Tab. Favipirivir 1800mg BD on Day 1, followed by Tab. Favipirivir 1800mg BD on Day 1, followed by • Convalescent plasma in early moderate disease hourly
800mg BD x 13 days 800mg BD x 13 days
• • Monitor inflammatory markers daily
• Tab Zinc 50 mg BD • Tab Zinc 50 mg BD Consider IV methylprednisolone 0.5 - 1 mg/kg or
dexamethasone 0.1- 0.2 mg/kg for 7 - 10 days • ** Inj. Tocilizumab or Methylprednisolone pulse for
• Tab Vit C 500mg BD • Tab Vit C 500mg BD (within 48 hours of admission or if oxygen require- Mx of Cytokine storm and ARDS (Off Label, Individu-
alise))
ment is increasing and if inflammatory markers are
• Symptomatic treatment for cough and fever
• Symptomatic treatment for cough and fever increased) • Mechanical ventilation if unable to maintain satura-
(bronchodilators, mucolytic, paracetamol) tion, increased work of breathing or development of
(bronchodilators, mucolytic, paracetamol) •
• Monitor closely for warning signs:
• Obtain baseline CBC, LFT/RFT, CRP, D-dimer & Prophylactic dose of UFH2 or LMWH2 (e.g., enoxapa- hemodynamic instability
Chest pain, dyspnoea, Tachypnoea, cyanosis,
Ferritin, Fibrinogen, Procalcitonin rin 40 mg per day SC) • Conventional ARDS Net strategy
altered mentation • Obtain HRCT Thorax • Inj. Thiamine 100 mg IV OD, Inj. Vit C 1.5gm IV 6 hrly • Proning, recruitment manoeuvres
• Monitor closely for warning signs • Antibiotics if suspecting infection according to local • Management of septic shock as per SSC guidelines
policy and control of co-morbid condition.
• Chest pain, dyspnoea, tachypnoea, cyanosis, and local antibiotic policy
altered mentation • Monitor for: Increased WOB, Hemodynamic insta- • Convalescent Plasma as rescue therapy or on com-
bility , Increase in oxygen requirement passionate grounds.

Ferritin > 500 mg/dl • Inj. Remdesivir 200 mg IV on Day 1 followed by 100mg OD
CRP > 50 mg/dl for 4 days
D-dimers > 2 times ULN OR CT SEVERITY SCORE 4 > 20
• Prophylactic dose of UFH2 or LMWH2 (e.g., enoxaparin 40
Fibrinogen > 500 mg/dl mg per day SC)

Testing Discharge
While attending suspect case as per above protocol based on clinical assessment, testing shall be resorted to and if negative—
After clinical improvement, discharge according to state discharge policy
manage in Non-Covid facility according to clinical diagnosis

1. Highrisk patients for Severe Disease 2. LMWH: Low Molecular Weight Heparin: if no contraindication or high risk of bleeding: UFH: Unfractionated Heparin
- Age > 60 years 3. Risk of Bleeding: Use validated score for assessing bleeding risk (e.g. HAS-BLED Score), Use D-Dimer and SIC for further risk stratification (SIC score ≥
- HTN, Diabetets Mellitus and other immunocompromising conditions. 24 portends high thrombotic risk)
- Chronic lung, kidney or liver disease 4. Yang et al. CT Severity Score: An Imaging Tool for Assessing Severe COVID-19. Radiology: Cardiothoracic Imaging. Published Online: Mar 30 2020
- Cerebrovascular disease ** Informed consent mandatory before use of off label drugs.
Source: MoHFW/ICMR
- Obesity BMI > 25 kg/m2

1
 Sanjay Gandhi Post Graduate Institute of

COVID -19: CLINICAL MANAGEMENT PROTCOL

Background
Coronaviruses are large group of viruses that cause illness in humans and animals. Rarely,
animal coronaviruses can evolve and infect people and then spread between people such as
has been seen with MERS and SARS. The outbreak of Novel coronavirus disease (COVID-
19) was initially noticed in a seafood market in Wuhan city in Hubei Province of China in
mid-December 2019, has now spread to 214 countries/territories/areas worldwide. WHO
(under International Health Regulations) has declared this outbreak as a “Public Health
Emergency of International Concern” (PHEIC) on 30thJanuary 2020 WHO subsequently
declared COVID-19 a pandemic on 11th March, 2020.

Disease Epidemiology
Current available evidence for COVID-19 suggests that the causative virus (SARS-CoV-2)
has a zoonotic source closely related to bat-origin SARS-like coronavirus. It is an enveloped
RNA beta coronavirus related to the Severe Acute Respiratory Syndrome (SARS) virus, and
the virus has been shown to use the angiotensin-converting enzyme 2 (ACE2) receptor for
cell entry.
The persons infected by the novel coronavirus are the main source of infection. Direct
person-to-person transmission occurs through close contact, mainly through respiratory
droplets that are released when the infected person coughs, sneezes, or talks. These droplets
may also land on surfaces, where the virus remains viable. Infection can also occur if a
person touches an infected surface and then touches his or her eyes, nose, or mouth.
The median incubation period is 5.1 days (range 2–14 days). The precise interval during
which an individual with COVID-19 is infectious is uncertain. As per the current evidence,
the period of infectivity starts 2 days prior to onset of symptoms and lasts up to 8 days. The
extent and role played by pre-clinical/ asymptomatic infections in transmission still remain
under investigation.

2
Pathophysiology
Most patients with COVID-19 predominantly have a respiratory tract infection associated
with SARS-CoV-2 infection. However, in a small proportion of cases, they can progress to a
more severe and systemic disease characterized by the Acute Respiratory Distress Syndrome
(ARDS), sepsis and septic shock, multiorgan failure, including acute kidney injury and
cardiac injury.
Autopsy findings in China and European countries showed endothelial damage of pulmonary
vasculature, microvascular thrombosis and hemorrhage linked to extensive alveolar and
interstitial inflammation that ultimately result in COVID-19 vasculopathy, pulmonary
intravascular coagulopathy, hypercoagulability, ventilation perfusion mismatch, and
refractory ARDS. Hypoxemia, secondary to ARDS may also activate the coagulation
cascade.

Case definitions
Suspect case
A patient with acute respiratory illness (fever and at least one sign/symptom of respiratory
disease, e.g., cough, shortness of breath), AND a history of travel to or residence in a location
reporting community transmission of COVID-19 disease during the 14 days prior to symptom
onset
OR
A patient with any acute respiratory illness AND having been in contact with a confirmed or
probable COVID-19 case in the last 14 days prior to symptom onset
OR
A patient with severe acute respiratory illness (fever and at least one sign/symptom of
respiratory disease, e.g., cough, shortness of breath; AND requiring hospitalization) AND in
the absence of an alternative diagnosis that fully explains the clinical presentation.

Probable Case
A suspect case for whom testing for the COVID-19 virus is inconclusive.
OR
A suspect case for whom testing could not be performed for any reason.
Confirmed Case
A person with laboratory confirmation of COVID-19 infection, irrespective of clinical signs
and symptoms.

3
Clinical Features
Most common clinical features are:
1. Fever
2. Cough
3. Fatigue
4. Shortness of breath
5. Expectoration
6. Myalgia
7. Rhinorrhea, sore throat, diarrhea
8. Loss of smell (anosmia) or loss of taste (ageusia) preceding the onset of respiratory
symptoms has also been reported
Older people and immune-suppressed patients in particular may present with atypical
symptoms such as fatigue, reduced alertness, reduced mobility, diarrhoea, loss of appetite,
delirium, and absence of fever. Children might not have reported fever or cough as frequently
as adults. As per data from Integrated Health Information Platform (IHIP)/ Integrated Disease
Surveillance Programme (IDSP) portal case investigation forms for COVID 19 (n=15,366),
the details on the signs and symptoms reported are (as on 11.06.2020), fever (27%), cough
(21%), sore throat (10%), breathlessness (8%), Weakness (7%), running nose (3%) and others
24%.

Risk factors for severe disease

1. Obesity
2. Age more than 60 years (increasing with age).
3. Underlying non-communicable diseases (NCDs): diabetes, hypertension, cardiac
disease, chronic lung disease, cerebro-vascular disease, chronic kidney disease,
immune-suppression and cancer.

Laboratory evaluation
In all patients following baseline investigations should be done:
1. CBC
2. Serum electrolytes, Liver function tests, Renal function tests
3. PT/INR, aPTT
4. Urine R/M
5. CXR

4
 6. Electrocardiogram
7. Serum, Ferritin, CRP, LDH, Procalcitonin
8. Plasma Fibrinogen
9. Arterial blood gases (In patients having saturation < 94% on room air)

Classification of Severity:
The classification of severity is done on the basis of clinical and lab parameters:
1. Category A – Mild disease

a. Patients with uncomplicated upper respiratory tract infection, may have mild
symptoms such as fever, cough, sore throat, nasal congestion, malaise,
headache.
b. Patients with RR < 20/ min, not requiring any oxygen supplementation (SpO2
> 96% on Room Air) and normal CXR.
c. Laboratory criteria:
(i) NLR < 3.2
(ii) CRP < 40
(iii) LDH < 300
(iv) Ferritin < 500 mg/dl
(v) D-dimers < 500ng/ml
(vi) IL-6 < 5 times ULN
d. CT criteria:
(i) Less than 25% involvement of the lung parenchyma

2. Category B – Moderate disease

a. Patients features in category A with dyspnoea with or without exertion

b. Patients with RR > 24/min, SpO2 < 94% on Room Air

c. CXR showing bilateral patchy homogenous/heterogenous opacities

d. Laboratory criteria:
(i) NLR > 3.2
(ii) CRP – 40 – 125
(iii) LDH – 300 - 400
(iv) Ferritin – 500 - 800 mg/dl
(v) D-dimers – 500 – 1000 ng/ml
(vi) IL-6 – 5 - 10 times ULN

5
 e. CT criteria:
(i) 25 - 75% involvement
3. Category C – Severe disease

a. Patients features in category A with dyspnoea at rest

b. Patients with RR > 30/min, SpO2 < 90% on Room Air

c. CXR showing bilateral diffuse homogenous/heterogenous opacities

d. Hemodynamic instability.

e. Presence of altered mentation.

f. Laboratory criteria:
(i) NLR > 5.5
(ii) CRP > 125
(iii) Ferritin > 800 mg/dl
(iv) D-dimers > 1000 ng/ml
(v) IL-6 > 10 times ULN
g. CT criteria:
(i) More than 75% involvement of lung parenchyma
Basic Principles
1. Categorize into A, B, C based on Symptoms, SpO2 & Respiratory Rate
2. Supportive Care
a. Finger Pulse Oximeter for continuous monitoring of Heart rate and Oxygen
saturation
b. Start oxygen with Mask at saturation of 94% or lower
c. HFNC to be used if there is failed oxygen therapy and Non-invasive
ventilation (NIV) to be used appropriately with two limb circuit expiratory
filters.
d. Counselling of COVID19 patients (By Counsellor/psychologist/psychiatrist)

e. Normal feeding, no dietary restrictions, good oral hydration

f. Maintenance IV fluids (If indicated)
g. Maintain blood glucose levels <180 mg/dl.
h. If Patient is on ACE inhibitors/ARBs, should be continued
i. Avoid using NSAIDs other than Paracetamol Unless Absolutely Necessary

6
 j. Antibiotic selection in case of superadded bacterial pneumonia should be
according to institution antibiogram.

Management
Category A
Mild cases should be managed preferably at L1 facilities but early identification of at-
risk population should be done with detailed history for comorbidities listed in risk
factors for severe disease.
1. Admit in Isolation Ward
2. Contact and Droplet precautions
3. Strict hand hygiene
4. Maintain adequate hydration
5. Pharmacological therapy
• Tab. Hydroxychloroquine (400mg) BD on 1st day followed by 200mg 1 BD
for 4 days for patients with high risk of severe disese1. (after ECG
Assessment) with Tab Azithromycin 500 mg OD x 5 days
OR
Tab Ivermectin 12mg OD x 3day s with Tab Doxycy-cline 100 mg BD x 5
days
OR
Tab. Favipirivir 1800mg BD on Day 1, followed by 800mg BD x 13 days
• Symptomatic treatment for cough and fever (bronchodilators, mucolytic,
paracetamol)
• Vitamin C 500mg BD PO
• Zinc 50 mg BD PO
• Prophylactic LMWH should be given to all patients if not contraindicated.
(Enoxaparin 1mg/kg or Dalteparin 100 IU/kg)
6. Patients should be monitored for signs and symptoms of complications that should
prompt urgent referral. Patients with risk factors for severe illness should be
monitored closely, given the possible risk of deterioration. If they develop any
worsening symptoms (such as mental confusion, difficulty breathing, persistent pain
or pressure in the chest, bluish coloration of face/lips, dehydration, decreased urine
output, etc.), they should be immediately admitted to HDU/ICU
7. Monitor inflammatory markers every 72 hours or if any sign of deterioration.
8. All patients with persistent fever, and cough, constitutional symptoms, uncontrolled

7
 comorbid conditions /risk factors for severe disease should be investigated with baseline
CBC, LFT/RFT, CRP, D-dimer & Ferritin, Fibrinogen, Procalcitonin and HRCT Thorax.
If serum Ferritin > 500 mg/dl, serum CRP > 50 mg/dl, plasma d-dimers > 2 times ULN
plasma Fibrinogen > 500 mg/dl OR CT Severity Index is > 20; Inj. Remdesivir should be
started and prophylactic LMWH should also be added if not already started.

9. Children with mild COVID-19 should be monitored for signs and symptoms of
clinical deterioration requiring urgent re-evaluation. These include difficulty in
breathing/fast or shallow breathing (for infants: grunting, inability to breastfeed), blue
lips or face, chest pain or pressure, new confusion, inability to awaken/not interacting
when awake, inability to drink or keep down any liquids. If any of the above features
are present child should be immediately transferred to ICU.
Category B
1. Admit to HDU/ICU
2. Contact and Droplet precautions
3. Strict hand hygiene
4. Maintain adequate hydration
5. Oxygen Support:
1. Target SpO2: 92-96% (88-92% in patients with COPD)
2. Oxygen supplementation should be started with nasal prongs. If unable to
maintain saturation with up to 6litre/min high flow oxygen delivery systems
should be used such as:
a. Venturi Mask
b. Non rebreathing reservoir bag masks
c. High Flow Nasal Cannula
If HFNC or simple nasal cannula is used, N95 mask should be applied over it.
3. Awake proning may be used as a rescue therapy.
1. All patients should have daily 12-lead ECG undergoing awake proning
2. Protocol for awake proning (Annexure 1)

Criteria to be fulfilled Avoid proning

Patients with oxygen requirement of > 6L on nasal Hemodynamic instability Close monitoring

prongs or 10 – 12 L/min on venturi mask Patients on not possible

HFNC and NIV can be suggested intermittent lateral
position
Normal mental status

Able to self-prone or change position with minimal

assistance

8
 Patients will undergo a rotational change in position from prone to lying on each side
to sitting up. Typical protocols include 30–120 minutes in prone position, followed by
30–120 minutes in left lateral decubitus, right lateral decubitus, and upright sitting
position.

6. Symptomatic treatment such as antipyretic (Paracetamol) for fever and pain, anti-
tussive for cough.
7. High dose Vitamin C 1.5gm IV 6 hourly
8. Parenteral Thiamine 100 mg IV OD
9. Anticoagulation
a. Prophylactic dose of UFH or LMWH (e.g., enoxaparin 60 mg per day SC)
Contraindications: End stage renal disease, active bleeding, emergency
surgery
Consider unfractionated heparin in ESRD
10. Corticosteroids
a. Consider IV methylprednisolone 0.5 to 1 mg/kg OR Dexamethasone 0.1 to 0.2
mg/kg for 5 – 7 days (preferably within 48 hours of admission or if oxygen
requirement is increasing and if inflammatory markers are increased). Review
the duration of administration as per clinical response.
11. Anti-virals
a. Inj. Remdesivir 200 mg on Day 1 followed by 100mg daily from Day
2 – 4 (under EUA).

12. Empirical therapy with Broad spectrum antibiotics according underlying

comorbidity.

a. If no comorbidity – Third generation cephalosporin with Doxycycline

b. Underlying DM or immune suppressing condition – Carbapenam plus

Tiecoplanin plus doxy/azithromycin should be started.
13. Control of co-morbid condition
14. Follow up CRP, D-dimer & Ferritin every 48-72 hourly (if available); CBC with
differential count, Absolute Lymphocyte count, KFT/LFT daily.
15. Consider anti-inflammatory therapy with anti-IL-6 if Ferritin or IL-6 doubles within
24 hours along with clinical and physiological signs of deterioration after ruling out
clinically significant secondary bacterial or fungal infection
16. Monitor for:
a. Increased work of breathing (use of accessary muscles)

9
 b. Hemodynamic instability
c. Increase in oxygen requirement
d. Rise in inflammatory doubling of IL-6 or Ferritin, CRP in 24 hours
17. If any of the above occurs, shift to ICU
18. Few patients with COVID-19 experience a secondary bacterial infection. Consider
empiric antibiotic therapy as per local antibiogram and guidelines in older people,
immune-compromised patients, and children < 5 years of age.
19. Convalescent Plasma should be given in early moderate disease if patients has persistent
hypoxia despite above measures. (Off label use)
Category C
1. Cautious trial of CPAP/NIV should be given as the therapeutic window in hypoxemic
respiratory failure is very small. Facility for mechanical ventilation should be ready
before attempting NIV
2. HFNC has shown to be of benefit in avoiding intubation in patients with very high
oxygen requirements.
3. Use conservative fluid management in patients with Severe Covid when there is no
evidence of shock.
4. Consider anti-inflammatory therapy with anti-IL-6 OR Methylprednisolone pulse
therapy (500 mg – 1000mg OD for 3days) if Ferritin or IL-6 doubles within 24
hours along with clinical and physiological signs of deterioration after ruling out
clinically significant secondary bacterial or fungal infection.
5. Corticosteroids
a. Consider IV methylprednisolone 1 to 2 mg/kg OR Dexamethasone 0.2 to 0.4
mg/kg for 7 – 10 days (preferably within 48 hours of admission or if oxygen
requirement is increasing and if inflammatory markers are increased). Review
the duration of administration as per clinical response. Dose may be tapered
according to radiological involvement and clinical recovery.
6. Anti-virals
b. Inj. Remdesivir 200 mg on Day 1 followed by 100mg daily from Day 2 – 4
(under EUA).

7. Empirical therapy with broad spectrum antibiotics according underlying comorbidity.

a. If no comorbidity – Third generation cephalosporin with Doxycycline
b. Underlying DM or immune suppressing condition – Carbapenam plus
Tiecoplanin plus doxy/azithromycin should be started.
7. Control of co-morbid condition

10
 8. Therapeutic dose of UFH or LMWH (e.g., enoxaparin 60 mg per day SC) after
excluding coagulopathy or thrombocytopenia or high risk of bleeding3

9. Inj. Thiamine 100 mg IV OD, Inj. Vit C 1.5gm IV 6 hourly

10. Mechanical ventilation if unable to maintain saturation, increased work of breathing
or development of hemodynamic instability
a. Conventional ARDS Net strategy
b. Proning, recruitment manoeuvres
11. Convalescent Plasma (Under Trial Setting) or rescue therapy on compassionate
grounds.
Management of hypoxemic respiratory failure and ARDS
Categorization of severity ARDS
• Mild ARDS: 200 mmHg < PaO2/FiO2 ≤ 300 mmHg (with PEEP or CPAP ≥5 cm
H2O)
• Moderate ARDS: 100 mmHg < PaO2/FiO2 ≤200 mmHg with PEEP ≥5 cm H2O)
• Severe ARDS: PaO2/FiO2 ≤ 100 mmHg with PEEP ≥5 cm H2O)
• When PaO2 is not available, SpO2/FiO2 ≤315 suggests ARDS (including in non-
ventilated patients)

Oxygenation targets — Ventilation strategy should be titrated to target a peripheral

oxygen saturation (SpO2) of ≥ 94 percent during initial resuscitation and ≥9 0 percent
for maintenance oxygenation. Hyperoxia should be avoided. Individualization of the
goal is important such that some patients may warrant a lower target (eg, patients with a
concomitant acute hypercapnic respiratory failure from chronic obstructive pulmonary
disease [COPD]) and others may warrant a higher target (eg, pregnancy).

Low flow oxygen — For patients with COVID-19, supplemental oxygenation with a
low flow system via nasal cannula or oxygen pendant (Annexure 1) is appropriate (ie,
up to 6 L/min). Although the degree of micro-organism aerosolization at low flow rates
is unknown, it is reasonable to surmise that it is minimal.

Higher flows of oxygen may be administered using a simple face mask, venturi face
mask, or nonrebreather mask (eg, up to 10 to 20 L/minute) for patients with higher
oxygen requirement. It is recommended that patients on nasal cannula to also wear a
droplet mask, especially during transport or when staff are in the room.

Patients with higher oxygen requirements — As patients progress, higher amounts of

oxygen are needed. Options at this point in non-COVID-19 patients are NRBM, Venturi
mask, high-flow oxygen via nasal cannulae (HFNC) or the initiation of noninvasive
11
ventilation (NIV). All these modalities have been used variably across the globe.

Noninvasive modalities or Invasive ventilation – Noninvasive modalities should be

preferred as initial modality rather than proceeding directly to intubation. We believe
that the decision to initiate noninvasive modalities, HFNC or NIV, should be made by
balancing the risks and benefits to the patient, the risk of exposure to healthcare
workers, and best use of resources. Clinical judgment should prevail always in these
circumstances.
HFNC versus NIV – Among the noninvasive modalities, HFNC is preferred over NIV
as an initial measure. The reasons cited in literature for this is better acceptability by the
patient, patient comfort and prevention Patient Self Inflicted Lung Injury (PSILI) due
to generation of very large tidal volumes with NIV. Overall, preference for HFNC is
based upon limited and inconsistent data. NIV may be appropriate in patients with
indications that have proven efficacy; these include patients with acute hypercapnic
respiratory failure from an acute exacerbation of chronic obstructive pulmonary disease
(AECOPD), patients with acute cardiogenic pulmonary edema, and patients with sleep
disordered breathing (eg, obstructive sleep apnea or obesity hypoventilation). Overall,
the data on the use of HFNC and NIV in patients with COVID-19 are limited. A
systematic review (Rochwerg et al; Ann Intern Med 2020) identified one trial evaluating
HFNC in patients with COVID-19, which suggested that it reduced the need for
mechanical ventilation. Another systematic review (Schünemann et al; Ann Intern Med
2020) that included evidence from patients with SARS and MERS as well as COVID-
19 reported that NIV might reduce the rate of intubation and mortality, based on low
quality evidence. However, NIV may also increase the risk for transmission of SARS-
CoV-2 to health care workers. Furthermore, the data on NIV are mixed, as some studies
suggest a high failure rate of NIV in patients with MERS and other causes of ARDS.

Monitoring – Patients on HFNC or NIV need close monitoring for progression with
frequent clinical and arterial blood gas evaluation to ensure effective ventilation
prevention of complications. A low threshold to intubate such patients, particularly if
they show any signs of rapid progression is recommended.

Precautions – HFNC and NIV are considered aerosol generating procedures. Thus,
when HFNC or NIV is used, airborne in addition to standard precautions should be
undertaken (ie, airborne infection isolation room [also known as a negative pressure
room], full personal protective equipment).

HFNC – Placing a surgical or N95 mask on the patient during HFNC when healthcare
workers are in the room decreases risk of transmission of infection to HCW.
12
Additionally, using low flow rates to start with may also be beneficial however
practicality of this has not been proved in clinical trials. Inhaled medications or gases
(eg, epoprostenol, nitric oxide bronchodilators) should be avoided during HFNC.

NIV – Full face NIV masks are preferred to minimize particle dispersion. The mask
should preferably have a good seal and should be non-vented. Use of a helmet has
beenproposed for delivering NIV to patients with COVID-19. If NIV is used, dual
limb circuitry with a filter on the expiratory limb on a critical care ventilator may
decrease dispersion compared with single limb circuitry on portable devices, although
data to support this are lacking. Starting with continuous positive airway pressure
(CPAP) using the lowest effective pressures (eg, 5 to 10 cm H2O) is suggested.

Nebulized medications (spontaneously breathing patients) — Nebulization with

bronchodilation may be required in patients with coexistent obstructive airway diseases
but concerns have been raised about aerosolization and potentially increase the risk of
transmission of COVID infection to HCWs. Generally, nebulized bronchodilator
therapy should be reserved for patients with diagnosed OADs otherwise, nebulized
therapy should be avoided. Metered dose inhalers (MDIs) with spacer devices are
preferred over nebulizers for management of chronic conditions (eg, asthma or COPD
controller therapy). Patients can use their own MDIs if the hospital does not have them
on formulary.

Potential for transmission of SARS-CoV-2 should inform the use of other interventions
in patients with documented or suspected COVID-19. It is prudent to minimize the
following:
a. Positive airway devices for chronic nocturnal ventilation support
b. Chest physical therapy or oscillatory devices
c. Oral or airway suctioning
d. Sputum induction should be avoided
e. Bronchoscopy should be avoided in spontaneously breathing patients and
limited to therapeutic indications (eg, life-threatening hemoptysis, central
airway stenosis).
f. If any of these therapies are performed, similar PPE to that described for
nebulizer therapy should be used.

Awake Self-Proning — Awake self proning is being increasingly advocated and is

being recommended that patients should spend as much time as possible in prone
position while on oxygen therapy or even on NIV. The rationale for this approach is
based upon limited direct evidence and anecdotal observations in the field as well as
13
indirect evidence of its efficacy in ventilated patients with acute respiratory distress
syndrome (ARDS). Emerging evidence suggests that proning is feasible and results in
improved oxygenation in some patients with COVID-19, regardless of whether they are
receiving supplemental oxygen only, HFNC, or NIV. It remains unclear whether
pronation averts intubation, accelerates recovery, or reduces mortality.

When to Intubate

Timing – Appropriate time of intubation in patient with COVID-ARDS is

controversial. Most patients with acute respiratory distress syndrome (ARDS) due to
COVID-19 will warrant intubation and mechanical ventilation. Delaying intubation
until the patient acutely decompensates is potentially harmful to the patient and
healthcare workers and is not advised. For patients with escalating oxygen
requirements, we monitor clinical and gas exchange parameters everyone to two hours
and have a low threshold to intubate patients with the following:
1. Rapid progression over hours
2. Lack of improvement on >50 L/minute of high flow oxygen and a fraction of
inspired oxygen (FiO2) >0.6
3. Evolving hypercapnia, increasing work of breathing, increasing tidal volume,
worsening mental status
4. Hemodynamic instability or multiorgan failure

Early intubation is often recommended but the definition of “early” is not clear. Use of
noninvasive means are traditionally used to avoid intubation. However, their use is
subject to controversy in patients with COVID-19. Clinicians should longitudinally
assess the patients and monitor the oxygen requirement and perform an objective
assessment of work of breathing make decision to intubate. The optimal timing of
intubation and mechanical ventilation is largely based on clinical judgment and
technical expertise in the field.

Precautions — Intubation is the highest risk procedure for droplet dispersion in patients
with COVID-19. While quantification of the risk has been poorly documented, one
prospective study of self-reported COVID-19 infection in healthcare workers reported a
cumulative incidence of 3.6, 6.1, and 8.5 percent at 7, 14, and 21 days post a tracheal
intubation procedure. Person intubating should be donning full PPE. Appropriate PPE
includes a fit-tested disposable N95 respirator mask, with eye protection or a powered
air-purifying respirator (PAPR), also known as an isolation suit. Intubation should be
performed in an airborne infection isolation room, if possible, by the most qualified
individual (eg, anesthesiologist) after proper preoxygenation since delayed and
14
unsuccessful attempts of intubation may prolong dispersion and place the patient at risk
of a respiratory arrest. Use of video laryngoscopy has been advocated by [Link]
preparations should be done before initiating the process of intubation such as preparing
the ventilator circuit, selecting appropriate settings and mode of ventilator, Closed
suction circuits should be utilized to minimize aerosolization. The expiratory limb on
the ventilator should have a HEPA filter to decrease contamination of the ventilator and
environment and protect staff when changing limb circuitry. To minimize exposure,
bundling intubation with other procedures is appropriate as is bundling the chest
radiograph for ETT and central venous catheter placement.

Use of transparent intubation box was associated with significant reduction in aerosol
deposition to the individual performing intubation, their PPE clothing, and the
surrounding environment as compared to doing it without box. Such devices are not yet
commercially available.

Ventilator Management of Acute Respiratory Distress Syndrome

It is unclear that whether different phases of COVID-19 pneumonitis require different

ventilatory strategies because Gattinoni and colleagues have highlighted the
nonuniformity of patients with COVID-19-associated ARDS and proposed the existence
of two primary phenotypes: type L (low values of elastance, pulmonary ventilation/

perfusion ratio, lung weight, and recruitability) and type H (high values of elastance,
right-to-left shunt, lung weight, and recruitability), with the latter being more consistent

15
with what they describe as typical severe ARDS. However, this hypothesis, remains
unproven and optimal ventilatory strategies based upon it are unclear. Until further data
are available, a lung protective “open lung strategy” is preferred that promotes lung
protection as outlined in the sections below.

Low tidal volume ventilation (LTVV) — As for all patients with ARDS, patients with
COVID-19 pneumonia who develop ARDS requiring mechanical ventilation should
receive LTVV targeting ≤6 mL/kg predicted body weight (PBW; range 4 to 8 mL/kg
PBW (table 3 and table 4)). A volume-limited assist control mode should be used,
beginning with a tidal volume of 6 mL/kg PBW, which targets a plateau pressure (Pplat)
≤30 cm H2O and applies positive end-expiratory pressure (PEEP). This approach is
based upon the standard ARDS Net strategy which have reported improved mortality
from LTVV in patients with ARDS. It is thought that low tidal volumes (VT) mitigate
alveolar overdistension induced by mechanical ventilation, which can cause additional
lung injury and mortality in patients with ARDS. An institutional protocol that promotes
LTVV to ventilated patients with ARDS is shown in the table below:

16
The use of a written protocol outlining how to provide LTVV is associated with
enhanced compliance in patients with ARDS.

In patients with ARDS, we prefer the use of standard variables (VT and Pplat, lung
compliance) rather than driving pressure to manage ventilator settings. However, the
driving pressure may have some value in patients with severe or refractory ARDS to
identify those with recruitable lung who may benefit from high levels of PEEP.

LTVV typically involve the following steps:

1. Choosing volume- or pressure-limited assist-control mode
2. Setting the initial VT and respiratory rate
3. Setting PEEP and fraction of inspired oxygen (FiO2)

Volume versus pressure-limited mode – While practice varies among clinicians, most
experts adhere to a strategy of LTVV, using a volume-limited assist-control mode.
However, a pressure-limited mode is an acceptable alternative if the resulting tidal
volumes are stable and consistent with the strategy of LTVV. In most patients with
ARDS, a volume-limited mode will produce a stable tidal volume while a pressure-
limited mode will deliver a stable airway pressure, assuming that breath-to-breath lung
mechanics and patient effort are stable. Regardless of whether volume-limited or
pressure-limited mode of ventilation is chosen, fully supported modes of mechanical
ventilation (eg, assist-control) are generally favored and partially supported modes (eg,
synchronized intermittent mandatory ventilation, should not be used)

Tidal volume and respiratory rate – LTVV using a protocol like that used in the
ARDS Network low tidal volume study trial as given in the picture above is
recommended. The initial VT is set at 6 mL/kg PBW and the initial respiratory rate is
set to meet the patient's minute ventilation requirements, provided it is ≤ 35 breaths per
minute (most often between 14 and 22 breaths/minute). The PBW is calculated using
the following equations (table 1 and table 2):
• For females: PBW (kg) = 45.5 + 0.91 * (height [cm] - 152.4)
• For males: PBW (kg) = 50 + 0.91 * (height [cm] - 152.4)

Over the next one to four hours, the patient’s clinical response, gas exchange, and Pplat
can be used to adjust the VT and respiratory rate, if necessary. Clinicians are
encouraged to make bedside adjustments to VT to ensure lung protective ventilation is
being appropriately administered and to assess response in real-time before obtaining
arterial blood gases. Typically, adjustments are made simultaneously to meet clinical

17
and gas exchange, as well as Pplat parameters.
• The goal Pplat is ≤30 cm H2O. The following is a general guideline for
adjustment of the VT based upon Pplat:
• When the Pplat is ≤30 cm H2O and VT is 6 mL/kg PBW, no further adjustments
are typically necessary.
• When the Pplat is >30 cm H2O and the VT is set at 6 mL/kg PBW or higher, the
VT should be decreased in 1 mL/kg PBW increments to a minimum of 4 mL/kg
PBW to reach the target plateau. Importantly, any decrease in VT may need to
be accompanied by an increase in respiratory rate to maintain an acceptable
minute ventilation.

If dyssynchrony is observed (typically, double triggering, the Pplat is <25 cm H2O, and
the VT is <6 mL/kg PBW, the VT can be increased in 1 mL/kg PBW increments to
Pplat >25 ≤30 cm H2O or VT reaches 6 mL/kg PBW (or 8 mL/kg PBW if
dyssynchrony is severe).

The goal Pplat of ≤30 cm H2O is based upon the ARDS Network LTVV study, which
showed benefit from this strategy. It is reasonable to keep the Pplat as low as possible,
using LTVV even if the Pplat is already below 30 cm H2O. Adjustments to the VT and
respiratory rate can also be made based upon gas exchange. There is no consensus
regarding an acceptable lower or upper limit for pH or partial arterial pressure of carbon
dioxide (PaCO2). However, most experts agree that while the ideal target is a pH 7.35
to 7.45, a pH below 7.25 and above 7.5 should be addressed while maintaining LTVV
(ie, a VT between 4 and 8 mL/kg PBW and a pPlat ≤30 cm H2O).

18
Positive end-expiratory pressure (PEEP) and fraction of inspired oxygen – The
goal of applied PEEP in patients with ARDS is to maximize and maintain alveolar
recruitment and subsequently improving oxygenation. A set PEEP at 5 cm H2O and
FiO2 at 1 at the onset of initiation of mechanical ventilation is recommended; the FiO2
is rapidly weaned over the next hour to target a peripheral saturation (SpO2) of 90 to 94
percent. Further adjustments of PEEP and FiO2 are then made using the strategy
outlined in the ARDS Network LTVV study. A reasonable oxygenation goal during
LTVV is a PaO2 between 55 and 80 mmHg (7.3 to 10.6 kPa) or an oxyhemoglobin
saturation between 88 and 95 percent.

Efficacy and harm – Collectively, evidence suggests that the early application of and
adherence to LTVV improves mortality, as well as other clinically important outcomes
in patients with ARDS.

LTVV is generally well-tolerated but potential adverse effects include:

Permissive hypercapnia – Hypercapnic respiratory acidosis eg, pH <7.35 and PaCO2

>45 mmHg) is aby product of LTVV which is generally well tolerated and helps in
maintaining a low alveolar pressure and minimize the complications of alveolar
overdistension (eg, ventilator-associated lung injury). Permissive hypercapnia has got
beneficial effects also such as better tissue oxygen delivery due to shift of oxygen
dissociation curve to right and anti-inflammatory properties by triggering gene
transcription against proinflammatory cytokines.

Auto-PEEP – Theoretically higher respiratory rates and decreases lung compliance

together may create auto-PEEP by decreasing the time available for complete
expiration. However, a subgroup analysis from the ARDS Network LTVV study
detected negligible quantities of auto-PEEP in both the LTVV and conventional
mechanical ventilation groups, indicating that auto-PEEP is rare during LTVV.
However, if auto-PEEP is suspected, clinicians should estimate the contribution of auto-
PEEP to the overall level of PEEP being delivered and manage it accordingly. Many
ventilators are equipped with automatic tool for auto PEEP estimation and if not present
an expiratory hold maneuver may be performed in completely paralyzed patient and
auto PEEP can calculated as the difference between total PEEP and set PEEP (PTot -
PExt) and managed accordingly by titrating PPE and respiratory rate.

Sedation – Logically speaking dyssynchrony should need higher sedation but a post-
hoc analysis of data from a single center involved in the ARDS Network LTVV study,

19
 there were no significant differences in the percentage of days patients received
sedatives, opioids, or neuromuscular blockade when the LTVV group was compared
with the conventional mechanical ventilation group

Failure of low tidal volume ventilation — For patients with COVID-19 that fail to
achieve adequate oxygenation with LTVV, we agree with other experts in the field who
have chosen prone ventilation as the preferred next step. For its application, we use
similar criteria to those in non-COVD-19 patients (ie, partial arterial pressure of
oxygen/fraction of inspired oxygen [PaO2:FiO2] ratio <150 mmHg, a FiO2 ≥0.6, and
PEEP ≥5 cm H2O; excessively high airway pressures; or recalcitrant hypoxemia),
although some experts use a higher PaO2:FiO2 ratio, given the good response seen in
this population.

Prone ventilation — The efficacy of prone position ventilation in ARDS is well

described in literature similar data for COVID related ARDS is lacking. But as of now it
is recommended that patients with COVID-19-related ARDS should also be subjected
prone ventilation for as long as is feasible without prematurely returning the patient to
the supine position (ie, 12 to 16 hours prone per day) and to perform the maneuver at
change of shift when sufficient staff are available.

The criteria for prong remain the same as for non COVID ARDS i.e. PaO2:FiO2 < 150
mmHg, FiO2 ≤0.6, PEEP > 10 cm H2O.

Additional measures — Additional options for patients in whom prone ventilation fails
include the following:

• Recruitment maneuvers – Recruitment maneuvers and high PEEP may be

attempted if the personnel have adequate experience for the same in patient
having refractory hypoxemia.

• Pulmonary vasodilators – These agents may be used as rescue therapy in patients with
refractory ARDS when other ventilatory strategies have failed. There is paucity of data
to promote or refute the use of these agents in COVID related ARDS. These agents can
improve ventilation-perfusion mismatch in patients with severe hypoxemia (eg,
PaO2:FiO2 <100) and may be especially helpful in those with decompensated or acute
pulmonary arterial hypertension [8].

Inhaled nitric oxide gas (iNO) and aerosolized epoprostenol, are the two commonly
employed agents in this regard.

20
Neuromuscular blockade – NMBA should be used in patients with refractory ARDS
have ventilator asynchrony. The use should be cautious and prolonged use should be
avoided because it is a risk factor for development of critical illness neuromyopathy
which is an impediment to successful weaning.

Extracorporeal membrane oxygenation (ECMO) – In selected patients with

refractory ARDS Veno-venous ECMO may be used as a rescue modality. The data
regarding its efficacy in COVID-ARDS is evolving and it has been increasingly used as
an adjunct support for patients presenting with acute viral pneumonia associated with
COVID-ARDS. The initial reports indicate that it is assisting in restoring patients' blood
oxygen saturation and reducing fatalities among the approximately 3% of severe cases
where it has been utilized. For critically ill patients, the mortality rate reduces from
around 59-71% with conventional therapy to approximately 46% with extracorporeal
membrane oxygenation.

General precautions
1. Avoidance of unnecessary disconnection with the endotracheal tube (ETT) in
ventilated patients with COVID-19 to avoid derecruitment and unnecessary
exposure of virus to the environment.
2. Appropriate humidification apparatus to minimize chances of VAP.
3. Appropriate cuff pressures (between 25 and 30 cm H2O)
4. All ventilators should have appropriate filters in place and agreed upon filter
change schedule (eg, every six hours). The ventilator should be wiped down
after every filter change.

Weaning – Standard weaning criteria should be used for extubation of patients

recovering from COVID-ARDS:
1. Patient should be afebrile, fully conscious orients and hemodynamically stable

21
 without any vasopressor support.
2. He should fulfil following criteria:
a. RR< 30/min
b. HR< 90/min
c. Rapid Shallow Breathing Index (RR/Tidal volume in liters) > 100
3. There should minimal mucoid ET secretions. Any evidence of incubating or
active lung infection should take as contraindication for weaning.
4. Patient should be able to maintain saturation above 94% on FIO2 of < 0.4 with a
PEEP support of > 6.

Extubation – Extubation should ideally be performed in an airborne isolation room.

Respiratory therapists and others in the room during extubation should adhere to strict
IPC and airborne precautions.

Extubation failures should be anticipated and facility for back up noninvasive

ventilation or HFNC should be available. Both low-flow and high-flow oxygen systems
should be set up and readily available.

Post-extubation care – A extubation failure rate of 6 – 11% is acceptable in a standard

ICU. Facilities for NIV support to avoid reintubation should be readily available and
threshold to reintubate should be low.

Management of septic shock

1. Recognize septic shock in adults when infection is suspected or confirmed AND
vasopressors are needed to maintain mean arterial pressure (MAP) ≥65 mmHg AND
lactate is >2 mmol/L, in absence of hypovolemia. Recognize septic shock in children
with any hypotension (systolic blood pressure [SBP] <5th centile or >2 SD below
normal for age) or two of the three of the following: altered mental state; tachycardia
or bradycardia (HR <90 bpm or >160 bpm in infants and HR<70 bpm or >150 bpm in
children); prolonged capillary refill (>2 sec) or warm vasodilation with bounding
pulses; tachypnea; mottled skin or petechial or purpuric rash; increased lactate;
oliguria; hyperthermia or hypothermia.
2. In the absence of a lactate measurement, use MAP and clinical signs of perfusion to
define shock. Standard care includes early recognition and the following treatments.
Within 1 hour of recognition: antimicrobial therapy and fluid loading and vasopressors for
hypotension. The use of central venous and arterial catheters should be based on resource
availability and individual patient needs.

22
3. In resuscitation from septic shock in adults, give at least 30 ml/kg of isotonic
crystalloid in adults in the first 3 hours. In resuscitation from septic shock in children
in well-resourced settings, give 20 ml/kg as a rapid bolus and up to 40-60 ml/kg in the
first 1 hr. Do not use hypotonic crystalloids, starches, or gelatins for resuscitation.
4. Fluid resuscitation may lead to volume overload, including respiratory failure. If there
is no response to fluid loading and signs of volume overload appear (for example,
jugular venous distension, crackles on lung auscultation, pulmonary oedema on
imaging, or hepatomegaly in children), then reduce or discontinue fluid
administration. This step is particularly important where mechanical ventilation is not
available. Alternate fluid regimens are suggested when caring for children in
resource- limited settings.
5. Crystalloids include normal saline and Ringer’s lactate. Determine need for additional
fluid boluses (250-1000 ml in adults or 10-20 ml/kg in children) based on clinical
response and improvement of perfusion targets. Perfusion targets include MAP (>65
mmHg or age- appropriate targets in children), urine output (>0.5 ml/kg/hr in adults, 1
ml/kg/hr. in children), and improvement of skin mottling, capillary refill, level of
consciousness, and lactate. Consider dynamic indices of volume responsiveness to
guide volume administration beyond initial resuscitation based on local resources and
experience. These indices include passive leg raising test, fluid challenges with serial
stroke volume measurements, or variations in systolic pressure, pulse pressure,
inferior vena cava size, or stroke volume in response to changes in intrathoracic
pressure during mechanical ventilation.
6. Administer vasopressors when shock persists during or after fluid resuscitation. The
initial blood pressure target is MAP ≥ 65 mmHg in adults and age-appropriate targets
in children.
7. If central venous catheters are not available, vasopressors can be given through a
peripheral IV, but use a large vein and closely monitor for signs of extravasation and
8. local tissue necrosis. If extravasation occurs, stop infusion. Vasopressors can also be
administered through intraosseous needles.
9. If signs of poor perfusion and cardiac dysfunction persist despite achieving MAP
target with fluids and vasopressors, consider an inotrope such as dobutamine.

23
 Annexure 1
Protocol for “awake proning” in patients with or suspected of having COVID-19

Proning intubated patients is a standard of care in the management of patients with ARDS in
intensive care. Its mechanism in improving oxygenation is by recruitment of dorsal lung units
and improving V/Q matching. This is similar in non-intubated patients (1) and may be
beneficial in the management of hypoxemia associated with COVID-19. However, prone
poisoning should not delay the referral to critical care if appropriate.
Criteria for proning:
1. Co-operative patient who is able to communicate clearly
2. The patient is able to change position themselves
3. Requiring approximately >40% oxygen and/or saturations <93%
4. Patients are haemodynamically stable with systolic blood pressure >90mmHg
Aim: To improve oxygen saturations in patients with or suspected of having COVID-19
Timed Position Changes:
If patient fulfils criteria for proning ask the patient to switch positions as follows. Monitor
oxygen saturations 15 minutes after each position change to ensure oxygen saturation has not
decreased
1. 30 minutes to 2 hours lying fully prone (bed flat)
2. 30 minutes to 2 hours lying on right side (bed flat)
3. 30 minutes to 2 hours sitting up (30-60 degrees) by adjusting head of the bed
4. 30 minutes to 2 hours lying on left side (bed flat)
5. 30 minutes to 2 hours lying prone again
6. Continue to repeat the cycle…….
The variable duration of prone positioning is to make the procedure as well tolerated as
possible. Sedation to allow proning should be avoided.
. If oxygen saturation decreases:
1. Check oxygen is connected to patient
2. Ask the patient to change to one of the other positions
3. Increase inspired oxygen if feasible
4. Refer to escalation plan if oxygen saturation not improving.
Discontinue prone positioning if
1. No improvement in oxygen saturations with change of position – ensure decision
regarding escalation of care made.
2. Consistent reduction in oxygen requirements to 28% or 4l/min oxygen via NC

24
 Annexure 2

Dosing & Preparation of Vasoactive Drugs

Drug Ampoule / STEP 1 STEP 2 STEP 3 STEP 4
vial Calculation of How to Infusion rate Actual drug
drug dose for prepare dose patient
preparation receiving
Noradrenaline/ 1 amp. Body weight × To be dissolved 1 ml/ hour 0.01
Adrenaline contains 2 0.03 =......mg in Distilled equals to mcg/kg/min
mg water or 5%
dextrose in a 50 3 ml/hour 0.03
ml syringe equals to mcg/kg/min

10 ml/hour 0.1 mcg/kg/min

equals to
Dobutamine 1 vial Body weight × 3 To be dissolved 3 ml / hr equals 3 mcg/kg / min
contains = ...... mg in Distilled to
250 mg water in a 50 ml
syringe 5 ml / hr equals 5 mcg/kg / min
to

Vasopressin 1 amp. To be dissolved 1.2ml/hour 0.02 units/min

Contains 20 in Distilled equals to
U water in a 20 ml
syringe 2.4ml/hour 0.04 units/min
equals to

3.6ml/hour 0.06 units/min

equals to
Hydrocortisone 1 vial To be dissolved 200 mg (2
(Septic shock) contains in distilled vials) infusion
100 mg water in a 50 ml over 24 hours
syringe

25
 Prevention of Complications

Anticipated Outcome Interventions

Reduce days of invasive mechanical • Use weaning protocols that include daily
ventilation assessment for readiness to breathe
spontaneously
• Minimize continuous or intermittent
sedation, targeting specific titration
endpoints (light sedation unless
contraindicated) or with daily interruption
of continuous sedative infusions
Reduce incidence of ventilator associated • Oral intubation is preferable to nasal
pneumonia intubation in adolescents and adults
• Keep patient in semi-recumbent position
(head of bed elevation 30- 45º)
• Use a closed suctioning system; periodically
drain and discard condensate in tubing
• Use a new ventilator circuit for each
patient; once patient is ventilated, change
circuit if it is soiled or damaged but not
routinely
• Change heat moisture exchanger when it
malfunctions, when soiled, or every 5–7
days

Reduce incidence of venous • Use pharmacological prophylaxis (low

thromboembolism molecular-weight heparin [preferred if
available] or heparin 5000 units
subcutaneously twice daily) in adolescents
and adults without contraindications. For
those with contraindications, use
mechanical prophylaxis (intermittent
pneumatic compression devices).
Reduce incidence of catheter related • Use a checklist with completion verified by
bloodstream infection a real-time observer as reminder of each
step needed for sterile insertion and as a

26
 daily reminder to remove catheter if no
longer needed
Reduce incidence of pressure Ulcers • Turn patient every two hours
Reduce Incidence of stress ulcers and • Give early enteral nutrition (within24-48
gastrointestinal bleeding hours of admission)
• Administer histamine-2 receptor blockers
or proton-pump inhibitors in patients with
risk factors for GI bleeding. Risk factors
for gastrointestinal bleeding include
mechanical ventilation ≥ 48 hours,
coagulopathy, renal replacement therapy,
liver disease, multiple co-morbidities, and
higher organ failure score
Reduce incidence of ICU-related weakness • Actively mobilize the patient early in the
course of illness when safe to do so

27
 Pharmacological Therapy – Dosage and Precautions

Hydroxychloroquine (HCQ)
Dose: Tab HCQ 400mg BD for 1 DAY followed by 200 mg BD x 4 Days
Contraindication for HCQ
a. QT Interval > 480ms
b. Pre-existing cardiomyopathy and cardiac rhythm disorders
c. History of Unexplained Syncope
d. Retinopathy,
e. Hypersensitivity to HCQ or 4-aminoquinoline compounds
f. G6PD deficiency
g. Epilepsy
h. Hypokalemia (K+ < 3 Meq)
Anticoagulant Agents
Pro Coagulant factors are increased in COVID-19 infection and associated with increased
risk of thrombosis. Pneumonia and sepsis are complicated by DIC, but although COVID-19
patients do have abnormalities of coagulation and are not atypical of DIC. The most marked
abnormality is an elevation of D-Dimer (if D-dimer is more than 1000ng/ml) but without a
parallel fall in platelet or prolongation of clotting time, this suggests that local rather
disseminated thrombin generation and fibrinolysis is taking place.
• Inj ENOXAPARIN 40MG S/C Once daily for mild and moderate. Twice daily in
severe cases OR
• Inj Fondaparinux 2.5mg OD SC OR
• Unfractioned Heparin 5000 Units BD SC

Risk of Bleeding:
Use validated score for assessing bleeding risk (e.g. HAS-BLED Score), Use D-Dimer
and SIC for further risk stratification (SIC score ≥ 24 portends high thrombotic risk).
Contraindications:
ESRD, active bleeding, emergency surgery, platelets < 20,000/mm3, BP >200/120 mmHg)

28
Remdesivir
Remdesivir (under Emergency Use Authorization) may be considered in patients with
moderate disease (those on oxygen) with none of the following contraindications:
 AST/ALT > 5 times Upper limit of normal (ULN)
 Severe renal impairment (i.e., eGFR < 30ml/min/m2 or need for haemodialysis)
 Pregnancy or lactating females
 Children (< 12 years of age)
 Can be given in cases of ESRD on maintenance haemodialysis under nephrologist
consultation
Dose: 200 mg IV on day 1 followed by 100 mg IV daily for 4 days (total 5 days)
No dose adjustment for Inj REMDESIVIR if eGFR >30ml/min

Convalescent plasma (Off Label) may be considered in patients with moderate disease who
are not improving (oxygen requirement is progressively increasing) despite use of steroids.
Special prerequisites while considering convalescent plasma include:
a. ABO compatibility and cross matching of the donor plasma
b. Neutralizing titer of donor plasma should be above the specific threshold (if the latter
is not available, plasma IgG titer (against S-protein RBD) above 1:640 should be
used)
c. Recipient should be closely monitored for several hours post transfusion for any
transfusion related adverse events
d. Use should be avoided in patients with IgA deficiency or immunoglobulin allergy
e. Dose: Dose is variable ranging from 4 to 13 ml/kg (usually 200 ml single dose given
slowly over not less than 2 hours

Tocilizumab (Off Label) may be considered in patients with severe disease with
progressively increasing oxygen requirements and in mechanically ventilated patients not
improving despite use of steroids. Long term safety data in COVID 19 remains largely
unknown. Special considerations before its use include:
a. IL-6 levels 50-100-fold higher than normal (Normal range 0 - 9.5pg/ml
b. Worsening trend of the inflammatory markers (Ferritin, LDH, CRP) (doubling within
24 hours)

29
 c. Deteriorating clinical condition with worsening of PaO2/Fio2 ratio (more than 25%
deterioration from the immediate previous value)
The drug is contraindicated in:
PLHIV, those with active infections (systemic bacterial/fungal), High Serum Procalcitonin,
Tuberculosis, active hepatitis, Absolute Neutrophil Count < 2000/mm3 and Platelet count <
50,000/mm3, hepatic and renal impairment; patients on chronic steroid therapy, Paediatric
patients <18 years old; Pregnancy and, Nursing mothers
Dose: 8mg/kg (maximum 800 mg at one time) given slowly in 100 ml NS over 1 hour;
dose can be repeated once after 12 to 24 hours if needed

Drugs Recently approved by DGCI

1. ITOLIZUMAB (An anti-CD6 IgG1 monoclonal antibody)
a. Indication:
1. IL-6 levels 50-100-fold higher than normal (Normal range 0 - 9.5pg/ml
2. Worsening trend of the inflammatory markers (Ferritin, LDH, CRP)
3. Deteriorating clinical condition with worsening of PaO2/Fio2 ratio (more than
25%
b. Deterioration from the immediate previous value).
c. Dose: 1st dose – 1.6mg/kg dose iv infusion
d. Subsequent dose: weekly 0.8mg/kg dose infusion over 4hours if required based on
lung function parameters
Contraindication:
PLHIV, those with active infections (systemic bacterial/fungal), High Serum. Procalcitonin,
Tuberculosis, active hepatitis, Absolute Neutrophil Count < 2000/mm3 and Platelet count <
1,00,000/mm3, hepatic and renal impairment; patients on chronic steroid therapy, Paediatric
patients <18 years old; Pregnancy and, Nursing mothers
Side effects:
a. In trial infusion reactions have been reported in 15% of the patients
b. In clinical practice also infusion reaction ranged from 12% to 15%
c. Other adverse events include Diahorea, Pruritus in 7 – 12 % of cases

30
Favipiravir
Mechanism of action: It is considered that favipiravir is metabolized in cells to a ribosyl
triphosphate form (favipiravir RTP) and that favipiravir RTP selectively inhibits RNA
polymerase involved in influenza viral replication
Indications: mild to moderate cases of COVID19 in adults >18yrs old
Dose: 1800mg bid followed by 800mg bid up to maximum of 14days
Contraindications: Hyperuricaemia, severe hepatic & renal impairment, Pregnant women
and lactating mothers
Side Effects: Increased Uric Acid levels, diarrhoea, decreased neutrophil counts, increase in
AST/ALT levels
Drug Interactions: Metabolised partly by Aldehyde Oxidase (AO) and partly by Xanthine
Oxidase (XO). Precautions for co-administration with Pyrazinamide, Repaglinide,
Theophyline, Famciclovir

31
 Oxygen delivery protocol
 Oxygen supplementation may be done done through simple face mask or nasal prongs @
3 - 6 liter/min if SpO2 < 94%

 Continuous close monitoring should be done with finger pulse oximetry or multiparametric
monitors if available.
 If patient is unable to maintain SpO2 > 94% on simple face mask or nasal prongs, Venturi
Masks OR Non rebreathing reservoir bag masks should be used @ a flow of 10-15L/min

 Oxygen delivered with various oxygen delivery devices (approximate FiO2%) is shown in
table below:

32
 HFNO (High Frequency Nasal Oxygen) and NIV (Non-invasive
Ventilation)
 When oxygen requirement increases to needing NRB, options of High Frequency Nasal Oxygen
(HFNO) or NIV should be considered.
 HFNC flow rates to be set from 30 -60 L/min titrating to maintain SpO2 ≥ 92%
 HFNC provides PEEP up to 5-6 cm H20 and can deliver FiO2 up to 100%

 If HFNC non-available or patient not maintaining SpO2 on flow rates up to 60L/min, initiate on
non-invasive ventilation (NIV) only with an ICU ventilator with two limbed circuit and expiratory
HME filter with a NIV mode available. Caution is to be exercised to not use potable home BiPAP
or CPAP machines with single circuit for these patients.

 Appropriate mask with good seal to be ensured when initiated on NIV. Helmet
masks/hoods if available, to be preferred to minimize aerosol contamination.
 Once initiated on NIV, close monitoring of respiratory variables hourly is important.
 Reassess clinical condition hourly, monitor and observe ABG’s 4-6hrly
 Look for signs of clinical improvement in the form of settling tachycardia, improving SpO2,
reduced tachypnea and reduced work of breathing.
 On NIV when there are signs of clinical deterioration in the form of worsening sensorium,
increased accessory muscles of breathing, raising Pco2, worsening pH on ABG ~ failure of NIV
has to be considered and patient has to be planned for intubation and mechanical ventilation after
consent from the family.

33
 Intubation and Mechanical Ventilation

Timing of intubation
 There is lack of high-quality evidence to provide guidance on optimal timing of
intubation in ARDS due to COVID-19.
 Intubation might be beneficial in patients with high respiratory drive and at high
risk of patient self-inflicted lung injury (PSILI)
 Non-invasive ventilation has been associated with worse outcomes when
PaO2/FiO2 ratio <150 in ARDS
 Consider timely intubation as indicated by refractory hypoxemia or hypercapnia,
and by objective evidence of high work of breathing on clinical examination
Indication for intubation:
 ARDS with PaO2/FiO2 < 200 (clinical judgement prevails)
 Worsening respiratory distress even on NIV
 Patient in Shock
Initial Settings:
Volume Control or Pressure control mode to me preferable used
Calculate predicted body weight (PBW)
• Males = 50 + 2.3 [height (inches) - 60]
• Females = 45.5 + 2.3 [height (inches) -60]
Tidal volume
 Low tidal volume ventilation (4-6ml/kg PBW) has been associated with improved
outcomes in patients with and without ARDS and should be used in COVID related
ARDS also.
 Tidal volume may be liberalized (up to 8 mL/kg PBW) in patients who are double
triggering, or if inspiratory airway pressure decreases below PEEP, keeping plateau
pressure <30 cm H2O36
 Ideally, driving pressure should be (Pplat - PEEP) ≤14 cm H2O
PEEP
 Higher PEEP might be beneficial in patients H Phenotype i.e. tose with with
high recruitability, with better gas exchange and reduced risk of ventilator-
induced lung injury
 Higher PEEP can be harmful in patients with L Phenotype i.e. those with low
recruitability, who have hypoxemia due largely to pulmonary vascular
pathology; high PEEP can lead to adverse haemodynamic effects or barotrauma

34
  Individualize PEEP; consider higher PEEP in patients with evidence of
higher potential for recruitment

Prone positioning
 Efficacy and safety of prone positioning in awake, non-intubated patients remain
unclear and are being evaluated in clinical trials in patients with COVID-19
(NCT04350723, NCT04347941, NCT04365959)
 In the absence of contraindications, use prone positioning in mechanically
ventilated patients with PaO2/FiO2 ratio <150 on FiO2 > 70%, PEEP > 8 and TV
6ml/kg.
 Early proning i.e. mechanical ventilation duration < 36 hours is associated with
better results
 Patient should be proned for 12 – 16 hours
 Multiple sessions are required till desirable results are achieved.
Venovenous ECMO
 Patients can develop refractory hypoxemia or have mechanics leading to
potentially injurious levels of mechanical ventilation, despite optimization of
conventional measures
 Venovenous ECMO may be considered in patients with refractory hypoxemia or
high driving pressures or respiratory acidosis despite conventional lung-protective
measures (eg, higher PEEP or prone positioning)

35
Adjunctive care in patients on ventilator

Prevention of VAP

Prevention of CRBSI

Prevention of UTI

36
 References

1. CLINICAL MANAGEMENT PROTOCOL: COVID-19 Government of India

Ministry of Health and Family Welfare Directorate General of Health Services
(EMR Division) Version 03.07.20
2. Development of Validation of Clinical risk score to predict the occurrence of
critical illness in hospitalized patient with COVID19. JAMA internal Medicine
– published online, May 12/05/2020
3. FACT SHEET FOR HEALTH CARE PROVIDERS EMERGENCY USE
AUTHORIZATION (EUA) OF REMDESIVIR (GS-5734™
4. TOCILIZUMAB Drug Monograph

5. ITOLIZUMAB Drug Monograph

6. FAVIPIRAVIR Drug Monograph

7. Matthew Wemple / Joshua O. Benditt. Fishman’s Pulmonary Diseases and

Disorders. Fifth Edition.
8. Pratik P. Pandharipande et al. Derivation and validation of SpO2/FiO2 ratio to
impute for PaO2/FiO2 ratio in the respiratory component of the Sequential
Organ Failure Assessment (SOFA) Score. Crit Care Med. 2009 April ; 37(4):
1317–1321.
9. George L Anesi Coronavirus disease 2019 (COVID-19): Critical care and
airway management issues. UpToDate. Inc.
10. Yang et al. CT Severity Score: An Imaging Tool for Assessing Severe COVID-19.
Radiology: Cardiothoracic Imaging. Published Online: Mar 30, 2020.
11. Prokop M et al. CO-RADS: A Categorical CT Assessment Scheme for Patients
Suspected of Having COVID-19—Definition and Evaluation. Radiology 2020
Aug;296(2): E97-E104.

37
 Standard Operating Procedure for Management of Patients Presenting
with Acute Respiratory Illness at RCH

This guideline provides recommendations for infection prevention and control in managing
patients with suspected or confirmed COVID-19 in the institute. These guidelines aim to
prevent transmission of COVID-19 infection in the institute. through the implementation of
appropriate infection prevention and control measures.

2. All patients presenting to the institute with acute respiratory illness will be primarily
admitted and evaluated at the emergency department (T3) of Rajdhani COVID-19
Hospital.
3. COVID-19 should be suspected as a possible etiology in all patients presenting to the
institute with acute respiratory illness.
4. Screening and Triage:
a. All patients with suspected COVID-19 should be screened at the first point of
contact i.e. the emergency department of Rajdhani COVID-19 Hospital.
b. COVID-19 should be considered as a possible etiology in all patients
presenting to the institute with SARI. Triaging of patients should be done
using standardized triage tools and standard first-line treatments should be
initiated.
5. Standard IPC measures should be implemented at all times in the management of
SARI.
6. All patients’ beds should be placed at least 1 metre apart regardless of whether they
are suspected to have COVID-19.
7. All health care personnel should be donning full PPE during management of these
patients
8. Immediate sample collection should be done and sent for COVID 19 testing by True
Nat and RT-PCR.
9. If RT-PCR is positive the patient should be transferred to ICU or Isolation ward of
COVID-19 hospital as applicable.

38
 10. Empirical therapy with Broad spectrum antibiotics according underlying comorbidity.
a. If no comorbidity – Third generation cephalosporin with Doxycycline
b. Underlying DM or immune suppressing condition – Carbapenam plus
Tiecoplanin plus doxy/azithromycin should be started
11. All patients with suggestive history and ILI and hypoxemic respiratory failure should
undergo an HRCT thorax and CORADS scoring should be done. In CORAD = 4 and
above: empirical Remdesivir 200 mg IV on Day 1 then 100 mg IV OD x 4days,
prophylactive dose anticoagulation with LMWH (Enoxaparin/Dalteparin) and
Dexamethasone 0.1 - 0.2 mg/kg OD may be started.
12. Contact and Droplet precautions
13. Strict hand hygiene
14. Maintain adequate hydration
15. Oxygen Support:
16. Target SpO2: 92-96% (88-92% in patients with COPD)
17. Oxygen supplementation should be started with nasal prongs. If unable to maintain
saturation with up to 6litre/min high flow oxygen delivery systems should be used
such as:
a. Venturi Mask
b. Non re-breathing reservoir bag masks
c. High Flow nasal cannula
d. If HFNC or simple nasal cannula is used, N95 mask should be applied over it.
18. Cautious trial of CPAP/NIV should be given as the therapeutic window in hypoxemic
respiratory failure is very small. Facility for mechanical ventilation should be ready
before attempting NIV
19. HFNC has shown to be of benefit in avoiding intubation in patients with very oxygen
requirements.
20. Use conservative fluid management in patients with Severe Covid when there is no
evidence of shock.
21. Mechanical ventilation if unable to maintain saturation, increased work of breathing
or development of hemodynamic instability (for details refer to chapter 1)
a. Conventional ARDS Net strategy should be implemented.
b. Proning, recruitment manoeuvres as rescue for refractory hypoxia

39
22. In case of high index of suspicion two sets of COVID testing (One TrueNat and One
RT PCR) should be obtained before labelling an individual as COVID-19 negative.
His hospital documents will be transferred online, and no documents will be taken out
of T3 including hospital file, treatment flow charts etc
23. Patient should be transferred out to the destination department according to
the Transfer- out SOP.

40