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Covid 19 Management

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.

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Covid 19 Management

  1. 1. Severe Covid-19 – management Karthik Ponnappan T MD DM EDAIC Assistant Professor Anaesthesiology and Critical Care
  2. 2. Thanks to our heroes
  3. 3. Covid-19 or SARS- Cov-2 Strain 229E in WI-38 cells. J Virol. 1967 Alissa Eckert, MS; Dan Higgins, CDC 2020
  4. 4. PRESENT ABSENT
  5. 5. Severe SARS-CoV-2 infections: practical considerations and management strategy for intensivists. Intensive care medicine, 2020
  6. 6. Clinical Course Zhou et al, Lancet, 2020
  7. 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. 8. Clinical Course 12/23 patients needing critical care died
  9. 9. 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%
  10. 10. Diagnosis RT-PCR testing Turnaround time- 6 hours for confirmation False negatives possible
  11. 11. Imaging
  12. 12. Imaging
  13. 13. Imaging CTs may be a luxury when ICUs are overwhelmed!!
  14. 14. Imaging Case courtesy of Dr Fabio Macori, Radiopaedia.org, rID: 74867
  15. 15. Imaging Lung ultrasound Smith et al, Anaesthesia 2020
  16. 16. Respiratory
  17. 17. Respiratory ARDS Berlin
  18. 18. Respiratory
  19. 19. Respiratory
  20. 20. Respiratory
  21. 21. 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
  22. 22. Respiratory Matthay et al. Lancet 2020
  23. 23. Intubation
  24. 24. 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
  25. 25. 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
  26. 26. Shock- arrest
  27. 27. 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
  28. 28. 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
  29. 29. 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
  30. 30. 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
  31. 31. Cardiac Daily TnI, NTproBNP, 12 lead ECG TTE only if indicated Arhythmias/shock/failure AF/flutter – Amio/Bblockers Vent- Amio/Lido ACS- cardiology
  32. 32. 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
  33. 33. Hematology
  34. 34. Hematology
  35. 35. Hematology Zhou et al, Lancet, 2020
  36. 36. Hematology Risk of VTE • Systemic inflammatory response • Stasis/critical illness • Possibly direct endothelial damage from viral injury/ACE2 binding
  37. 37. Hematology Risk of VTE Lin et al. Emerging Microbes & Infections. 2020 Luo et al Pathology & Pathobiology. 2020
  38. 38. 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
  39. 39. 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
  40. 40. Therapy Early Chloroquine Hydroxychloroquine Mid Remdesvir Convalescent Plasma Late IL-6, IL-2, JAK inhibitors, steroids
  41. 41. Therapy Chloroquine/HCQ
  42. 42. 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
  43. 43. 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
  44. 44. 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
  45. 45. 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
  46. 46. 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
  47. 47. 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
  48. 48. 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
  49. 49. 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
  50. 50. Plasma therapy
  51. 51. Plasma therapy
  52. 52. Therapy Renin Angiotensin - Aldosterone System and SARS CoV-2
  53. 53. Therapy Don’t stop ACEIs and ARBs!!
  54. 54. ICU admission
  55. 55. ICU admission
  56. 56. ≤ ILBS COVID 19 protocol CBC,LFT, KFT,ECG, TropI, proBNP, PT INR, Fibrinogen,D dimer,CRP
  57. 57. Cover page, TIME magazine April 20,2020
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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.

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