A primer on available evidence and management of Covid -19 infection, with system wise pathophysiology and therapeutic strategies. Perspective of intensive care, with specific information and tips on intubation and ventilatory management of these patients. Focus on severe infections, and various manifestations. Serious symptoms: difficulty breathing or shortness of breath chest pain or pressure loss of speech or movement Seek immediate medical attention if you have serious symptoms. Always call before visiting your doctor or health facility.

1. Severe Covid-19
– management
Karthik Ponnappan T MD DM EDAIC
Assistant Professor
Anaesthesiology and Critical Care

2. Thanks to our
heroes

3. Covid-19 or SARS- Cov-2
Strain 229E in WI-38 cells. J Virol. 1967
Alissa Eckert, MS; Dan Higgins, CDC 2020

4. PRESENT
ABSENT

5. Severe SARS-CoV-2 infections: practical considerations and management strategy for intensivists. Intensive care medicine, 2020

6. Clinical Course
Zhou et al, Lancet, 2020

7. Clinical Course
Zhou et al, Lancet, 2020
From onset of symptoms, the median time to:
Development of ARDS: 8-12 days (Wang et al, JAMA, 2020; Zhou et
al, Lancet, 2020; Huang et al, Lancet, 2020)
Mechanical ventilation: 10.5-14.5 days (Huang et al, Lancet,
2020; Zhou et al, Lancet, 2020)

8. Clinical Course
12/23 patients needing critical care died

10. Labs
Lymphopenia, 35-83%
Mild hepatocellular injury pattern (AST / ALT
~200s), 28-38%
Anemia, 51%
Elevated inflammatory markers (IL-6, ESR, CRP,
or ferritin), 38-86%
Elevated CK, 13%
Elevated LDH, 76%
Low/normal procalcitonin, 94%
ncreased D-dimer, 36%

11. Diagnosis
RT-PCR testing
Turnaround time- 6 hours for
confirmation
False negatives possible

12. Imaging

13. Imaging

14. Imaging
CTs may be a luxury when ICUs are
overwhelmed!!

15. Imaging
Case courtesy of Dr Fabio Macori, Radiopaedia.org, rID: 74867

16. Imaging
Lung ultrasound
Smith et al, Anaesthesia 2020

17. Respiratory

18. Respiratory ARDS
Berlin

19. Respiratory

20. Respiratory

21. Respiratory

22. Respiratory
L-phenotype
Hypoxaemia with preserved CO2
clearance (Type 1 respiratory failure)
Low Elastance (i.e. high compliance)
V/Q matching
Recruitability (poor response to PEEP
and proning)
May be able to avoid mechanical
ventilation with appropriate oxygen
therapy
H phenotype
classic ARDS
Hypoxaemia +/- impaired CO2 clearance
(Type 1 and/or 2 respiratory failure)
High Elastance (i.e. low compliance)
V/Q matching
Recruitability ( response to PEEP and
proning)
Benefit from open lung approach

23. Respiratory
Matthay et al. Lancet 2020

24. Intubation

25. Intubation
AGP- Full PPE
Minimize personnel, senior
person at airway
Video laryngoscopy if
feasible
Follow preset protocol
Negative pressure room
30 minutes time for
aerosols to settle

26. Weaning and
Extubation
Zhou et al, Lancet,2020
● Icu Weaning protocol
● median-time to VAP onset of 8
days in retrospective study of
191 COVID patients in Wuhan
● A daily spontaneous awakening
trial
● Extubation protocol

27. Shock- arrest

28. Septic Shock
and Secondary
Infections
• Secondary bacterial infections a-
20% of non-survivors
Antibiotics within 1 hour
Map > 65mmHg, NE/VP
Conservative fluid strategy
WHO, COVID-19 Interim guidance,
March 2020

29. Septic Shock
and cytokine
storm
• severe COVID-19 may have
cytokine activation syndrome and
secondary HLH
fibrinogen, d-dimer, ferritin, c-reactive
protein (CRP is prognostic)
Neutrophil activation in shock
Corticosteroids, anti il6,ivig
maybe considered
Mehta et al, Lancet, 2020

30. Cardiogenic
shock Shock
• In 39% (n=29) of deaths in a series
of 68 patients in Wuhan
Elevated NT-proBNP, CvO2 < 60%
echo --depressed LV and/or RV
function
Cardiology- consider PAC
Dobutamine,
avoid beta blockers,calcium
blockers, anti htn
Ruan et al, Intensive Care Med, 2020

31. Cardiac
Cardiac injury- troponin >99th
percentile (7-22% of hospital pts)
Increases after 14 days of onset
Greater in non-survivors/ICU patients
Direct injury-
myocarditis
Demand ischemia
Stress
cardiomyopathy
Cytokine storm

32. Cardiac
Daily TnI, NTproBNP, 12
lead ECG
TTE only if indicated
Arhythmias/shock/failure
AF/flutter – Amio/Bblockers
Vent- Amio/Lido
ACS- cardiology

33. Renal
AKI – 2-29%
RRT- 5-23% of ICU patients
AKI  poor prognosis
Shock
Cytokine
storm
ATN
ACE2 in proximal
tubules
Direct injury
Proteinuria/hematuria
noted

34. Hematology

35. Hematology

36. Hematology
Zhou et al, Lancet, 2020

37. Hematology
Risk of VTE
• Systemic inflammatory response
• Stasis/critical illness
• Possibly direct endothelial damage
from viral injury/ACE2 binding

38. Hematology
Risk of VTE
Lin et al. Emerging Microbes & Infections. 2020
Luo et al Pathology & Pathobiology. 2020

39. Hematology
Risk of VTE
• Prophylactic LMWH or UFH may be of
benefit in those patients with severe
COVID-19 and D-dimer levels > 6
times the upper limit of normal
• If CrCl > 30: LMWH 40 mg SC daily
• If CrCl < 30 or AKI: UFH 5000 units
SC TID
• Hold if Platelets <30,000 or bleeding,
start compression devices

40. Hematology
Risk of DIC
Tang et al J Thromb Hemost. 2020
Out of 183 COVID-19 patients in Wuhan,
71% of non-survivors had DIC
Median onset 4 days after ICU admission
Measure ISTH DIC scores
Transfuse as per local protocol

41. Therapy
Early
Chloroquine
Hydroxychloroquine
Mid
Remdesvir
Convalescent
Plasma
Late
IL-6, IL-2, JAK
inhibitors, steroids

42. Therapy
Chloroquine/HCQ

43. Therapy
Chloroquine/HCQ
Require oxygen/ high risk for progression
Hcq- 5 day therapy-400 bd day 1, 200 mg bd for 5 days
Half life 7 days- therapeutic effect till day 10
CI- Epilepsy, porphyria, prolonged qtc
Daily ecg, avoid drugs prolonging QTc
Safe considering short duration of therapy
Yao et al, Clin Infect Dis, 2020

44. Therapy
Remdesivir
inhibits viral RNA-dependent RNA polymerase,
causing premature termination of RNA
transcription
200 mg IV loading dose, followed by 100
mg IV daily for a total of 5 or 10 days
A/E- LFT, phlebitis, nausea vomiting
Only for use in trials/compassionate use
from gilead

45. Therapy
Azithromycin
Conflicting results from 2 French studies, in
combination with HCQ
Can be used if concomitant CAP is
suspected- 500 mg for 5 days
Combination increases QTc bt 40 ms,
monitor ECG
Not for COVID 19 at present
Gautret et al, Int J Antimicrob Agents, 2020
Molina et al, Med Mal Infect, 2020

46. Therapy
Lopinavir/Ritonavir
Protease inhibitors/CYP3A4 inhibitors
No therapeutic benefit
Should not be used outside
trial setting
Cao et al, N Engl J Med, 2020

47. Therapy
Ivermectin- Anthelminthic
Nitazoxanide-antiprotozoal
Only in vitro action
Future trials may give better
idea
Not recommended outside trial
setting
Caly et al Antiviral Research. 2020

48. Therapy
Tocilizumab in china
Siltuximab in italy
In cytokine storm phase
Improvement noted in 2 small case series
Larger trials awaited
May use in severe cases after careful
consideration, rule out TB
Tocilizumab- serious opportunistic
infections/transaminits
Xu et al and Gritti et al, unpublished preprints. 2020

49. Therapy
Oseltamivir
Doesn’t work for COVID -19
Can be given to prevent co-infection
with influenza in flu season
Other neuraminidase inhibitors can also
be used
Watch LFTs

50. Corticosteroids
Not recommended for COVID-19
except as part of a clinical trial
Other indications;
● For asthma or COPD
exacerbation, - -40mg
prednisone PO or 30mg
methylprednisolone IV, once
daily x 3-5 days.
● For any shock with a history of
chronic steroid - 50mg
hydrocortisone IV Q6H
● For multipressor (>2 pressors) -
with 50mg hydrocortisone IV
Q6H
WHO, COVID-19 Interim guidance, March 2020

51. Plasma
therapy

52. Plasma
therapy

53. Therapy
Renin Angiotensin -
Aldosterone System
and SARS CoV-2

54. Therapy
Don’t stop ACEIs and ARBs!!

55. ICU
admission

56. ICU admission

57. ≤
ILBS COVID
19 protocol
CBC,LFT,
KFT,ECG, TropI,
proBNP,
PT INR,
Fibrinogen,D
dimer,CRP

58. Cover page, TIME
magazine April 20,2020