EVMS Critical Care COVID-19 Management Protocol

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Salient Points

This article’s focus is the recommended approach to COVID-19 based on the best (and most recent) available literature including the Shanghai Management Guideline for COVID and recent information from Italy. It focuses on not reinventing the treatment plan but to learn from the experience of others around the world. It is important to recognise that COVID-19 does not cause typical ARDS this disease must be treated differently and it is likely that mechanical ventilation may be exacerbating this situation by causing ventilator induced lung injury.   Patients suffer from oxygenation failure and not lung failure. Furthermore, this is predominantly an immune and clotting disorder and not a lung disease.

Heparin anticoagulation and high dose Vit C treatment are recommended

  • LMWH – 1 – 2mg/kg/day
  • Continue till patient’s D-dimer levels returns to normal
  • Once FDP >= 10ug / mL and / or D-dimer level return to normal, switch to Unfractionated Heparin.
  • Vitamin C – dose – 50 – 100mg/kg/day – administered until improvement in oxygenation index.

Subtypes of Infection

  • Asymptomatic – Elevated IFN-1
  • Mildly/symptomatic – Elevated IFN-1 and IL-6
  • Early Pulmonary – Elevated IFN-1 and D-dimer, Severely elevated IL-6
  • Pulmonary:Coagulopathic – Elevated IFN-1 and IL-6, Severely elevated D-dimer
  • Later Pulmonary:Inflammopathic – Elevated IFN-1, Severely elevated IL-6 and D-dimer
  • Late Pulmonary/HLH – Elevated IFN-1, Severely elevated IL-6 and D-dimer

Detailed Summary

Prophylaxis

  • Vitamin C 500 mg BID and Quercetin 250-500 mg BID
  • Zinc 75-100 mg/day (acetate, gluconate or picolinate). Zinc lozenges are preferred. After 1-2 months, reduce the dose to 30-50 mg/day.
  • Melatonin (slow release): Begin with 0.3mg and increase as tolerated to 1-2 mg at night
  • Vitamin D3 1000-4000 u/day (optimal dose unknown).

For Mildly Symptomatic patients (at home):

  • Vitamin C 500mg BID and Quercetin 250-500 mg BID (if available)
  • Zinc 75-100 mg/day • Melatonin 6-12 mg at night (the optimal dose is unknown)
  • Vitamin D3 1000-4000 u/day
  • Optional: Hydroxychloroquine 400mg BID day 1 followed by 200mg BID for 4 days

For Mildly Symptomatic patients (on floor):

  • Vitamin C 500mg BID and Quercetin 250-500 mg BID (if available)
  • Zinc 75-100 mg/day
  • Melatonin 6-12 mg at night (the optimal dose is unknown)
  • Vitamin D3 1000-4000 u/day
  • Methylprednisolone 40 mg daily
  • Enoxaparin 40-60 mg daily
  • Optional: Hydroxychloroquine 400mg BID day 1 followed by 200mg BID for 4 days
  • N/C 2L /min if required (max 4 L/min; consider early t/f to ICU for escalation of care).
  • Avoid Nebulization and Respiratory treatments. Use “Spinhaler” or MDI and spacer if required. • Avoid non-invasive ventilation
  • T/f EARLY to the ICU for increasing respiratory signs/symptoms.

For Respiratory symptoms (SOB; hypoxia- requiring N/C ≥ 4 L min: admit to ICU):

Essential Treatment (dampening the STORM)

  1. Methylprednisolone 80 mg loading dose then 40mg q 12 hourly for at least 7 days and until transferred out of ICU.
    Alternative approach: Hydrocortisone 50 mg q 6 hourly.
  2. Ascorbic acid (Vitamin C) 3g IV q 6 hourly for at least 7 days and/or until transferred out of ICU. Note caution with POC glucose testing.
  3. Full anticoagulation: Unless contraindicated it is suggested full anticoagulation (on admission to the ICU) with enoxaparin, i.e 1 mg kg s/c q 12 hourly. Heparin is suggested with CrCl < 15 ml/min.
    Alternative approach: Half-dose rTPA: 25mg of tPA over 2 hours followed by a 25mg tPA infusion administered over the subsequent 22 hours, with a dose not to exceed 0.9 mg/kg followed by full anticoagulation.

    On transfer to the floor, consider reducing enoxaparin to 40-60 mg /day.

Note: Early termination of ascorbic acid and corticosteroids will likely result in a rebound effect.

Additional Treatment Components

  1. Melatonin 6-12 mg at night (the optimal dose is unknown).
  2. Magnesium: 2 g stat IV. Keep Mg between 2.0 and 2.4 mmol/l.
    Prevent hypomagnesemia (which increases the cytokine storm and prolongs Qtc).
  3. Optional: Azithromycin 500 mg day 1 then 250 mg for 4 days
  4. Optional: Atorvastatin 40-80 mg/day. Of theoretical but unproven benefit. Statins have been demonstrated to reduce mortality in the hyper-inflammatory ARDS phenotype. Statins have pleiotropic anti-inflammatory, immunomodulatory, antibacterial and antiviral effects. In addition, statins decrease expression of PAI-1 8.
    Broad-spectrum antibiotics are superadded if bacterial pneumonia is suspected based on procalcitonin levels and resp. culture. Co-infection with other viruses appears to be uncommon, however a full respiratory viral panel is still recommended. Superadded bacterial infection is reported to be uncommon.
  5. Maintain euvolemia – Due to the prolonged symptomatic phase with flu-like symptoms (6-8 days) patients may be volume depleted. Cautious rehydration with 500ml boluses of ringers lactate may be warranted, ideally guided by noninvasive hemodynamic monitoring.

Diuretics should be avoided unless the patient has obvious intravascular volume overload.

  1. Early norepinephrine for hypotension. While angiotenin II agonists has a limited role in septic shock, this drug may uniquely be beneficial in patients with COVID-19 as they downregulate ACE-2 Receptor.

Escalation of respiratory support (steps);

  • Try to avoid intubation
  • Accept permissive hypoxemia (keep O2 Saturation > 84%)
  • N/C 1-6 L/min
  • High Flow Nasal cannula (HFNC) up to 60-80 L/min
  • Trial of inhaled Flolan
  • Attempt proning
  • Intubation only by an expert intubator – No Bagging;
  • Full PPE.
  • Crash/emergency intubations should be avoided.
  • Volume protective ventilation; Lowest driving pressure and lowest PEEP as possible.
  • Keep driving pressures < 15 cmH2O.
  • Moderate sedation to prevent self-extubation

Note – There is widespread concern that using HFNC could increase the risk of viral transmission. There is however, no evidence to support this fear.

HFNC is a better option for the patient and the health care system than intubation and mechanical ventilation. CPAP/BiPAP may be used in select patients, notably those with COPD exacerbation or heart failure.

  1.  Treatment of secondary HLH
    1. High dose corticosteroids – Methylprednisolone 120 mg q 8 hourly for at least 3 days, then wean accruing to CRP, IL-6, Ferritin etc.
    2. Tocilizumab (IL-6 inhibitor) as per dosing guideline.
    3. Consider plasma exchange
  2.  Monitoring
    1. Daily: PCT, CRP, IL-6, BNP, Troponins, Ferritin, Neutrophil-Lymphocyte ratio, D-dimer, Mg, CRP and Ferritin
    2. Thromboelastogram (TEG) on admission and repeated as indicated.
    3. In patients receiving IV vitamin C, a laboratory glucose check is recommended to confirm the blood glucose levels.
    4. Monitor QTc interval if using chloroquine/hydroxychloroquine and azithromycin and monitor Mg++
    5. No routine CT scans, follow CXR and chest ultrasound.
    6. Follow ECHO closely; Patients may develop a severe cardiomyopathy
    7. Post ICU management
      1. Enoxaparin 40-60 mg s/c daily
      2. Methylprednisone 40 mg day, the wean slowly
      3. Vitamin C 500 mg PO BID
      4. Melatonin 3-6 mg at night

Reference Link : https://www.nature.com/articles/s41591-020-0843-2

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