management of severe covid pneumonia

1. SEVERE COVID
PNEUMONIA
DR. MAYANK PANDEY

2. INTRODUCTION
The ongoing outbreak of the coronavirus disease
2019 (covid-19) has posed immense challenges for the
research and medical communities.

4. SEVERE
COVID
PNEUMONIA
Severe covid-19 pneumonia as defined by the National Institutes
of Health, referring to individuals with SARS-CoV-2 infection
confirmed by polymerase chain reaction (PCR) testing who have
SpO2 < 90% on room air at sea level
A ratio of arterial partial pressure of oxygen to fraction of
inspired oxygen (PaO2/FiO2) <300 mm Hg,
Respiratory frequency >30 breaths/min, or
Lung infiltrates >50%.

5. NOVEL CORONA
VIRUS:
STRUCTURE
• SARS-CoV-2 is a positive
sense, single stranded
RNA enveloped virus in
the Betacoronavirus genus

6. PATHOGENESIS

7. Pathogenesis
Clinical and serologic evidence points to high
levels of serum IL-6, IL-1β, and TNF-α
which are associated with clinical instability
Compared with classic ARDS, autopsy studies
also indicate higher thrombus burden in
pulmonary capillaries
A greater pathogenic role of thrombotic and
microangiopathic vasculopathy in covid-19
related ARDS
Clinical observation of lymphopenia may be
associated with worsening disease

8. Pathogenesis
contd
Several unique pathophysiological
processes are postulated to be at play for
CARDS, such as
Intravascular thrombosis caused by loss
of endothelial barrier,
Prominent loss of hypoxic pulmonary
vasoconstriction resulting from
endothelial dysfunction, and
Excessive blood flow to collapsed lung
tissue

9. LAB MARKERS FOR DISEASE SEVERITY

12. RESPIRATORY
MANAGEMENT
Titration of oxygen therapy to
avoid hyperoxemia and hypoxemia
is strongly recommended for acute
hypoxemic respiratory failure.
A range of 90-96% oxygen
saturation is a reasonable target

13. The second goal of mechanical
ventilation in ARDS is to prevent
the constant opening and closing
of alveoli which may be injurious
to the lung(atelectrauma).
Positive end expiratory
pressure(PEEP) is titrated to keep
alveolar units open throughout the
respiratory cycle

14. PHENOTYPES OF COVID PNEUMONIA
Patients who had low elastance, low ventilation perfusion matching, low
recruitability and lung weight were named the “L type.”
May not require low tidal volume ventilation and attempts at recruitment
could bring harm
Should be placed on mechanical ventilation earlier to prevent spontaneous
high tidal volumes generated by the patients

15. • More consistent with classic ARDS (high
elastance, high ventilation/perfusion ratio, high
recruitability and lung weight) was referred to as
the “H type.”
• Treated like classic ARDS.

16. RESPIRATORY EQUIPMENTS FOR
SEVERE COVID PNEUMONIA

17. HIGH FLOW
NASAL
CANULA
HFNC oxygen therapy refers to the delivery of humidified
and heated oxygen at high flows,
Typically 20-60 L/min, which is titrated to a precise fraction
of inspired oxygen (FiO2).
Improved comfort by satisfying patient flow demand
Creates an oxygen reservoir in the upper airway thereby
reducing physiological dead space (reduced CO2
rebreathing), and
Provides a modest PEEP that could help recruit collapsed
alveoli with consequent reduction in work of breathing

18. ROX index (ratio of oxygen saturation by
pulse oximetry/FiO2 to respiratory rate) is
a bedside tool for predicting HFNC failure.
Patients with a ROX index ≥4.88 after 2, 6,
and 12 hours of treatment had low risk of
intubation,
Whereas a ROX index <3.85 at the same
time points was associated with a high risk
of failure.

19. NON INVASIVE
VENTILATION
Non-invasive ventilation (NIV) is delivered
through a face mask or a helmet that is
placed over the patient’s head
Application of NIV in the setting of acute
hypoxemic respiratory failure excluding
COPD and cardiogenic pulmonary edema
has been controversial
NIV was associated with higher intensive
care unit mortality among ARDS patients
with PaO2/FiO2 <150 mm Hg on
presentation

20. After 1 hour of initiation of NIV, expired tidal volumes >9 mL/kg of predicted
body weight and PaO2/FiO2 ≤200 mmHg independently predicted NIV failure
In the absence of concomitant COPD or pulmonary edema, the benefits of NIV
are uncertain in the management of CARDS
HFNC is the initial non-invasive support in severely hypoxemic patients with
CARDS.

21. Invasive
mechanical
ventilation
( IMV)
Endotracheal intubation should be done in
patients
Requiring vasopressor support or clinical
signs of shock
With altered mentation
Failure of HFNC or NIV
Neuromuscular blockade should be done early
to prevent patient ventilator dyssynchrony

22. Once intubated and deeply sedated, the Type L patients, if hypercapnic, can be ventilated
with volumes greater than 6 ml/kg (up to 8-9 ml/kg).
Prone positioning should be used only as a rescue maneuver
The PEEP should be reduced to 8-10 cmH2O, given that the recruitability is low and the
risk of hemodynamic failure increases at higher levels.
An early intubation may avert the transition to Type H phenotype.

23. The type H phenotype should be managed as classical ARDS with
Low tidal volume and High PEEP as per ARDSnet protocol.
OXYGENATION GOAL: PaO2 55-80 mmHg or SpO2 88-95%
PLATEAU PRESSURE GOAL: ≤ 30 cm H2O
pH GOAL: 7.30-7.45

26. • Time spent proning
should be ideally 16
hrs/day

27. V-V ECMO may be considered in patients with
refractory hypoxemia on invasive mechanical
ventilation, who do not respond to other
adjuvant therapies.

28. DRUG
TREAMENT OF
SEVERE COVID
PNEUMONIA
CORTICOSTEROIDS
ANTICOAGULATION
ANTIVIRAL : REMDESIVIR
IMMUNOMODULATORS:
TOCILIZUMAB, ITOLIZUMAB
EXPERIMENTAL/EMERGING
DRUGS

29. CORTICOSTEROIDS
Corticosteroids are the only therapeutic agents that have demonstrated a clear
mortality benefit in the treatment of severe covid-19.
While the evidence is most robust for dexamethasone , no evidence exists at
present to believe one steroid is superior to the other
However, recent evidence suggests that methyl prednisolone has better lung
penetration , making it a better choice

30. Inj Dexamethasone 6mg iv od, the dose can be escalated to 12 to 24 mg/day if
there is clinical worsening and patient is non diabetic.
Inj methyl prednisolone 1 – 2 mg/kg body weight
Should be initiated early in the pulmonary phase to counter immune dysregulation
Ideal time day 8 of symptoms when virus has a low tendency to replicate and
inflammatory response is persistent
However it must be emphasized that steroids should not be used in mild
asymptomatic patients or early on in the course of covid 19 if not indicated.

31. Anticoagulation
All moderate and severe symptomatic patients with
Age >18 yrs with no bleeding manifestations or thrombocytopenia
Spo2 <94%
RR>24/min
Pulse rate> 110/min
Evidence of pneumonia on CXR or CT
Should receive anticoagulation

32. Dosage
Unless contraindicated, FULL anticoagulation (on
admission to the ICU) with enoxaparin, i.e., 1 mg kg s/c
q 12 hourly (dose adjust with Cr Cl < 30mls/min) in
those patients with a D-dimer > 3-5 X ULN and those
with a rising D-dimer.
Heparin is suggested with CrCl < 15 ml/min.
In all other ICU patients medium dose anticoagulation;
enoxaparin 0.5 mg/kg q 12 hourly

33. REMDESIVIR
Remdesivir is an antiviral drug that acts by inhibiting viral RNA transcription
Consider Remdesivir in Patients who are within 10 days of symptom onset and are
RT-PCR positive for SARS-CoV-2, >18 yrs. Old,
Pneumonia confirmed by chest imaging,
Oxygen saturation of 94% or lower on room air, or
A ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF Ratio) of 300 mm Hg or less

34. Avoid Remdesivir if
known severe renal impairment (estimated
glomerular filtration rate estimated GFR
<30ml/min per 1.73 m2)
alanine aminotransferase or aspartate
aminotransferase more than five times the
upper limit of normal;
hepatic cirrhosis;

35. Dose: Inj Remdesivir 200 mg IV on day 1.
Then, 100 mg IV daily for next 4 days (can be extended up to 10 days in case of
progressive disease)
Only reduces days of hospitalization without significant improvement in mortality
rates

36. TOCILIZUMAB
Tocilizumab is a monoclonal antibody that blocks IL-6 receptors
May be considered within 24 to 48 hours of progression to severe disease when all of the below criteria are met
Severe disease
Significantly raised inflammatory markers (CRP &/or IL-6)
Not improving despite use of steroids
No active bacterial/ fungal infections

37. • The recommended dose is 4 to 8mg/kg (with a
maximum dose of 800 mg at one time) in 100
ml NS over 1 hour (dose can be repeated once
after 12 to 24 hours depending on clinical
response

38. • Itolizumab -Very small study -30 patient study.
• Dose-1.6 mg/kg in 250 ML NS over 6 hours.
(- 25 mg in the first hour and the remaining
dose over 5 hours)
• If well tolerated and improvement in patient
observed, clinician has the discretion to repeat
a dose (after 1 week for itolizumab or after 12
hours for tocilizumab only after expert
opinion)
• Informed consent is mandatory.
• Bevacizumab and Sarlijumab are other options

39. CYTOKINE STORM
Unremitting fever
Cytopenia, Hyper ferritinemia
If the patient in the second week having SOB (even with previous normal CT),
rising CRP above 50, CT worsening, fever onset in the second week, etc. points
towards impending cytokine storm.

40. • Daily CRP monitoring and steroid dose adjustments are crucial here
• Methylprednisolone pulse 250 mg to 1000 mg per day for 3 days
• Tocilizumab

41. Experimental
/Emerging
drugs

42. Tofacitinib/baricitinib
Start after 48 hours of initiation of steroid therapy,
where CRP fails to decrease by 50% from baseline, or
signs of clinical deterioration like persistence of fever or hypoxemia are noted on close follow
up.

43. Dosage
• Tab Baricitinib 4 mg once daily for 10 days
(*Renal modification - 2mg once daily if GFR
is between 30 to 60ml/min, avoid if GFR <
30 ml/min)
• Tablet Tofacitinib 10 mg twice daily for 10
days (* avoid if GFR < 30 ml/min)

44. Bevacizumab - (Avastin 400mg
single dose vial) –
It is an anti VEGF recombinant
humanized monoclonal antibody
It is being tried with severe Covid-
19,
Bevacizumab 7.5mg/kg body weight
+ 0.9% NaCl 100ml, intravenous drip

45. 2 Deoxy Glucose
The 2 DG drug, like glucose, spreads through the body, reaches the virus-infected cells and prevents virus
growth by stopping viral synthesis and destroys the virus energy production.
The drug also works on virus infection spread into lungs which help us to decrease patient’s dependability
on oxygen."
Has been developed in powder form and is ingested orally by dissolving it in water.
Phase III trial on (40 patients) report led to DCGI approval - 8th May 2021

46. Dose and Regimen: 2-DG: 45 mg/kg body weight AM + 45 mg/kg body
weight PM, twice daily for not more than 10 days.
DO NOT USE the reconstituted dose solution for further dosing of the
patient. Each dose of 2-DG should be prepared using a fresh sachet.
Monitoring of QTc interval on ECG, Blood glucose levels are essential.

47. Colchicine
Colchicine use: Except few studies, most of studies did
not find any significant improvement.
It is now being used in mild, moderate and severe cases
despite any recommendations by standard guidelines.
It is considered if fever persists despite paracetamol
Loading dose: 1.5 mg followed by 0.5 mg of colchicine 60
minutes later if no adverse gastrointestinal effects
Maintenance dosage: 0.5 mg BD until discharge or a
maximum of 21 days (reduce to OD if body weight <60 kg)
Contraindicated if eGFR<30mL/min/1.73m2

48. Discharge criteria
Severe covid pneumonia patients should be
discharged only after
• Clinical resolution of symptoms
• Patient tested negative by RTPCR once ( after resolution
of symptoms)

49. Conclusion
For people hospitalized with covid-19, 15-30% will go on to develop covid-19 associated
acute respiratory distress syndrome (CARDS).
Patients who died of severe SARS CoV-2 infection reveal presence of diffuse alveolar
damage consistent with ARDS but with a higher thrombus burden in pulmonary capillaries.
When used appropriately, high flow nasal cannula (HFNC) may allow CARDS patients to
avoid intubation
During invasive mechanical ventilation, low tidal volume ventilation and positive end
expiratory pressure (PEEP) titration to optimize oxygenation are recommended.

50. Corticosteroid treatment improves mortality for the
treatment of severe and critical covid-19
Remdesivir may have modest benefit in time to recovery in
patients with severe disease but no significant benefit in
mortality or other clinical outcomes

52. THANK YOU!!