An elderly woman with multiple comorbidities suffered from COVID 19 moderate disease - was managed conservatively
Case presentation with current treatment modalities
1. A case of respiratory Distress –
managed with Non Invasive
Ventilation and HFNO
DR. SANGHAMITRA SINHA
MBBS, FCCCM
SR CRITICAL CARE
SHRI MOOLCHAND KHAIRATIRAM HOSPITAL
DR. ASHISH ARORA
MD PULMONOLOGY, IDCCM
ICU CONSULTANT
SHRI MOOLCHAND KHAIRATIRAM HOSPITAL
2. History
66y, F
Comorbidities: HTN, BA, post B/L TKR,
Hysterectomy, Umbilical Hernia Repair
Allergic to Aspirin, Sulpha Drugs
CC:
Fever (T max 1020F) with Chills + Rigor x 5days
SOB x 5days
COVID 19 RT PCR + on Day 4 of illness
Started on: Tab Doxycycline, Tab Ivermectin, Tab
Prednisolone at home
3. Day 6 Presented to ED → admitted to Covid ward
Generalised weakness
Vitals:
BP 160/90mmHg
HR 88/min
Afebrile
RR 24/min
SpO2 94% on RA
Chest: B/L Coarse creps with wheeze
Other systems - WNL
Relevant investigations sent
Initial Treatment :
Oxygen therapy
Inj Ceftriaxone 1gm IV q12h
Inj Methylprednisolone 40 mg IV q24h
Inj Enoxaparin 40 mg SC q24h
Other supportive medications including nebulisation,
PPI, Bronchodilators, MVI, Vitamin C
Insulin for glycemic control
5. Day 7
Clinical deterioration:
SOB
Cold clammy extremities
Chest : b/l crepitations + wheeze
Transfer to COVID ICU
NIV support
Started on Inj. Remdesivir for 5 days
Day 8 1 unit convalescent plasma transfused
6. Day 9
Remained critically ill :
On continuous NIV support: FiO2 0.8
Hyperglycemic on Insulin infusion
ABG : persistent ↓ PaO2 with ↑ lactate
CXR: ↑ opacities (GGOs)
Interventions:
Central venous catheterization: CVP monitoring
+ Central venous access
Repeat cultures sent and antibiotics escalated
to Piperacilin – Tazobactam
Started on HFNO @40L/min
7. Day 21 Started on Oral Hypoglycemics
Day 20 Transferred to ward on Portable BiPAP (Intermittent)
Day 18
Clinically stable:
Oxygen tapered, 6L/min on portable BiPAP
After 9 days of ICU Care
8. Day 22
Decompensated post ambulation:
Sudden onset breathlessness
Desaturation to SpO2 78%
Cold clammy extremities
Progressive drowsiness with gasping respiration
Interventions:
Connected to portable BiPAP with high flow Oxygen
Managed with bronchodilators, IV Mg++, Steroids, LMWH
Urgent CT Chest: s/o worsening b/l COVID pneumonitis
Repeat cultures – sterile
Patient improved clinically
Conscious, alert
Maintained with portable BiPAP – intermittent during the day and continuous overnight
9. Day 26
CVC removed
All medications deescalated to oral
Day 28
Started on Tab Nintedanib 100mg q12h (to prevent further fibrosis)
10. Day 30: PATIENT WAS DISCHARGED
OXYGEN INHALATION (TITRATE TO SPO2 94%)
NIV SUPPORT (18/6) DAYTIME WHILE SLEEPING, OVERNIGHT CONTINUOUS
DRUGS:
ANTIBIOTICS/ANTIFUNGAL – 3DAYS MORE
TAB NINTEDANIB 100MG Q12H X 7DAYS (ANTIFIBROTIC)
TAB RIVAROXABAN 10MG Q24H X 7DAYS
TAB METHYLPREDNISOLONE (MEDROL) 8MG Q12H X 7DAYS → TO TAPER THEREAFTER
FORMOTEROL NEBULIZATION 0.5MG Q12H
OHA + INSULIN AS PER SLIDING SCALE
ANTIHYPERTENSIVES
OTHER SUPPORTIVE MEDICATIONS
11. Home Care
Oxygen Support:
Needed BiPAP support as
mentioned upto 2-3 weeks
Oxygen concentrator for
occasional desaturations on
mobilisation
Now tapered to only 1hour
during daytime and 2hrs during
night
Mobilization:
Anxiety to mobilise due to event
on Day 22
Presently ambulatory without
support
Physiotherapy:
Steam inhalation q12h
Incentive spirometry q24h
(evening)
Chest physiotherapy q24h at
bedtime
19. Corticosteroids
RECOVERY: Randomized Evaluation of COVID-19 therapy trial among
hospitalized patients
> 11,500 patients enrolled from > 175 NHS hospital organizations in
the UK
RECOVERY Collaborative Group. NEJM. 2020 Jul 17.
20. Corticosteroids
RECOVERY Collaborative Group. NEJM. 2020 Jul 17.
Recovery trial : evidence that treatment with Dexamethasone at a dose of 6mg once daily for upto 10days reduces
28day mortality in COVID 19 patients on respiratory support
21. Corticosteroids
Recommendation for use
• Any oxygen requirement (with or without elevated inflammatory markers)
• Inflammatory markers raised
Dose
• IV Methylprednisolone 0.5 to 1 mg/kg
• Dexamethasone 0.1 to 0.2 mg/kg
Duration: 3 to 5 days (may be prolonged on a case-to-case basis)
Ministry of Health and Family Welfare. DGHS. Government of India. Version 5
22. Treatment of Moderate COVID-19
Antivirals
Anti-
inflammatory
Anticoagulati
on
Corticosteroids
Anti-IL6 Therapy
23. Anti IL-6 Therapy
Use has been extrapolated from
other cytokine release syndromes
Shown to be beneficial in
observational studies
Fu. J Translational Medicine. 2020;18:164.
24. Tocilizumab
RCTs showed that tocilizumab did not reduce short-term mortality
Reduced risk of mechanical ventilation in hospitalized COVID-19 patients (RR = 0.71, 95%
CI 0.52-0.96, I2 = 0%)
No higher risk of infections or adverse events seen
Tleyjeh IM, et al. CMI. 2020 Nov 5.
25. Tocilizumab
Indication
Off-label use
May be in Moderate to severe
disease
Not improving despite steroids
Considered in severely raised
inflammatory markers (IL-6 > 5x
ULN)
Active bacterial infections to be
ruled out before starting therapy
Ministry of Health and Family Welfare. DGHS. Government of India. Version 5
Other parameters used are at least 3 of the
following in patients with p/f ratio < 300
CRP > 10 x ULN
Ferritin > 1000 ng/mL
D-dimer > 10 x ULN
LDH > 2 x ULN
Sciascia S, et al. Clin Exp Rheumatol. 2020;38(3):529-532.
Dose
4 to 8 mg/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, if
needed)
27. Anticoagulation
LMWH is preferred in once daily S/C dosing of 0.5 mg/kg
UFH is preferred in patients with renal insufficiency
D-dimer levels may help guide anticoagulation
Estimate bleeding risk with well validated risk scores (eg. HAS-
BLED score of ≥ 3 signifies a high bleeding risk)
Ministry of Health and Family Welfare. DGHS. Government of India. Version 5
28. Treatment of Moderate COVID-19
Antivirals
Anti-
inflammatory
Anticoagulati
on
Remdesivir
Convalescent
Plasma
29.
30. WHO Solidarity Trial
Consortium. NEJM.
2021, Feb 11.
Remdesivir did not show any
statistical significance
Hydoxychloroquine showed to
have increased Mortality
31.
32. Remdesivir
Adenosine nucleotide
analogue prodrug
Mechanism: Competes
for incorporation with
adenosine triphosphate
(ATP)
WHO Solidarity Trial Consortium. NEJM. 2021, Feb 11.
33. Remdesivir
Effects are seen best in patients with early presentation and those requiring only low
flow oxygen
All patients must have eGFR determined and hepatic laboratory testing before
initiation
Recent report on 46 patients with renal dysfunction (30 with AKI and 16 with ESRD)
found no drug related worsening of renal function
IV Dosage Over 30-120 Mins
Patients Not Requiring
Invasive Mechanical
Ventilation
Patients Requiring
Invasive Mechanical
Ventilation
Adults and pediatric
patients ≥ 40 kg
Loading 200 mg on Day 1 200 mg on Day 1
Maintena
nce
100 mg on Days 2-5* 100 mg on Days 2-10
*Treatment may be increased to 10 days in patients not demonstrating clinical improvement at Day 5 of treatment.
Thakare S. et al. Kirereports. 2020. Oct 10.
34. Remdesivir
Contraindications
AST/ALT > 5 x Upper limit of normal
Renal insufficiency
eGFR < 30 mL/min/1.73m2
Need for hemodialysis
Pregnancy and lactating women
Children < 12 years
Ministry of Health and Family Welfare. DGHS. Government of India. Version 5
37. Convalescent Plasma
PLACID Trial
Open label, multicenter, parallel group RCT
235 Convalescent plasma vs 229 SoC
Primary outcome mesure: Composite of progression to severe disease (p/f <
100) or all cause mortality at 28 days
Number of events: 44 (19%) vs 41 (18%) with SoC
Adjusted risk ratio = 1.04 (95% CI 0.71-1.54)
Limitations exist: Limited data in mild disease, unknown
efficacy with early administration, lack of
standardization of antibody titres
Agarwal A, et al. BMJ. 2020 Oct 22;371.
38. Convalescent Plasma
228 Plasma vs 105 Placebo
Median time of institution = 8 (5, 10) days
Patients with oxygen saturation < 93%
This trial and a Cochrane living meta-analysis suggest no
benefit in terms of mortality or clinical improvement with
plasma
If considered for therapy, best given in early disease (within 1
week of illness onset)
Simonovich VA et al. NEJM. 2020. Nov 24.
39. Convalescent Plasma
Considerations
ABO compatibility and cross-matching required
Plasma IgG (against S-protein) > 1:640
Monitoring required for reactions
Avoided in patients with IgA deficiency or immunoglobulin allergy
Dose
Variable, ranging from 4 to 13 mL/kg
Usually used as a single dose of 200 mL given over at least 2 hours
Ministry of Health and Family Welfare. DGHS. Government of India. Version 5
40. Convalescent Plasma
Potential Adverse Events
Transfusion-transmitted infections (i.e., HIV,
HBV, HCV)
Allergic or anaphylactic reactions
Hemolytic reactions
Febrile nonhemolytic reactions
TRALI
TACO
Hypothermia
Metabolic complications
Posttransfusion purpura
Theoretical Risks
Antibody-dependent enhancement of
infection
Attenuation of immune response and
susceptibility to re-infection
Convalescent Plasma EUA Fact Sheet for Healthcare Providers.
The median time from the onset of Covid-19 symptoms to enrollment was 8 days (interquartile range, 5 to 10). An oxygen saturation below 93% while the patient was breathing ambient air was the most common severity criterion for enrollment, and more than 90% of the patients were receiving oxygen and glucocorticoids at the time of entry into the trial (Table 1).
The median volume of infused convalescent plasma was 500 ml (interquartile range, 415 to 600). Of the 215 patients from whom a baseline total anti–SARS-CoV-2 IgG antibody level could be obtained, the median titer was 1:50 (interquartile range, 0 to 1:800); 46.0% of patients had no detectable antibody level