This is Dr. Marik's last protocol. for those in ICU. Please take note of the massive doses of Vitamin C he is giving them. It lines up with Dr. Shiva's recommendation. Your body at this point needs massive natural ammunition to win the battle, and C is their Solution. (Ascorbic Acid)
Respiratory symptoms (SOB; hypoxia- requiring N/C ≥ 4 L min: admit
to ICU):Additional Treatment Components (the Full Monty)
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. Alterative 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 (see below).
General schema for respiratory support in patients with COVID-19
TRY TO AVOID INTUBATION IF POSSIBLE
Low-Flow Nasal Cannula
■ Typically set at 1-6 Liters/Min
High Flow Nasal Cannula (Limitation on Flow Rate)
■ Accept permissive hypoxemia (O2 Saturation > 86%)
■ Titrate FiO2 based on patient’s saturation
■ Accept flow rates of 60 to 80 L/min
■ Trial of inhaled Flolan (epoprostenol)
■ Attempt proning (cooperative proning)
Invasive Mechanical Ventilation
■ Target tidal volumes of ~6 cc/kg
■ Lowest driving pressure and PEEP
■ Sedation to avoid self-extubation
■ Trial of inhaled Flolan
Prone Positioning
■ Exact indication for prone ventilation is unclear
■ Consider in patients with PaO2/FiO2 ration < 150
VV-ECMO
■ Indications remain unclear
■ Early discussion with ECMO center or team may be advisable
3. Full anticoagulation: Unless contraindicated we suggest 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). 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 floor, consider reducing enoxaparin to 40-60 mg /day. Note: Early termination of ascorbic acid and corticosteroids will likely result in a rebound effect.
4. Melatonin 6-12 mg at night (the optimal dose is unknown).
5. 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).
6. Optional: Azithromycin 500 mg day 1 then 250 mg for 4 days (has immunomodulating properties including downregulating IL-6; in addition Rx of concomitant bacterial pneumonia).
7. 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 pleotropic anti-inflammatory, immunomodulatory, antibacterial and antiviral effects. In addition, statins decrease expression of PAI-1
8. Broad-spectrum antibiotics if superadded bacterial pneumonia is suspected based on procalcitonin levels and resp. culture (no bronchoscopy).
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 (however, this may not be correct).
9. Maintain EUVOLEMIA (this is not non-cardiogenic pulmonary edema). Due to the prolonged “symptomatic phase” with flu-like symptoms (6-8 days) patients may be volume depleted. Cautious rehydration with 500 ml boluses of Lactate Ringers may be warranted, ideally guided by non-invasive hemodynamic monitoring. Diuretics should be avoided unless the patient has obvious intravascular volume overload.
10. Early norepinephrine for hypotension. While the angiotenin II agonist GiaprezaTM has a limited role in septic shock, this drug may uniquely be beneficial in patients with COVID-19 (downregulates ACE-2).
11. Escalation of respiratory support (steps); Try to avoid intubation if at all possible
■ Accept “permissive hypoxemia” (keep O2 Saturation > 84%)
■ N/C 1-6 L/min
■ High Flow Nasal canula (HFNC) up to 60-80 L/min
■ Trial of inhaled Flolan (epoprostenol)
■ Attempt proning (cooperative repositioning-proning; see Figure)
■ Intubation... by Expert intubator; Rapid sequence. 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.
Find the latest version at evms.edu/covidcare
■ Moderate sedation to prevent self-extubation
■ Trial of inhaled Flolan (epoprostenol)
■ Prone positioning
■ ?? ECMO < 60 yrs. and no severe commodities/organ failure.
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.
A group of patients with COVID-19 deteriorates very rapidly (see graphic below). Intubation and mechanical ventilation may be required in these patients.
12. Treatment of secondary HLH (increasing Ferritin, CRP and transaminases)
■ “High dose corticosteroids.” Methylprednisolone 120 mg q 8 hourly for at least 3 days, then wean accruing to CRP, IL-6, Ferritin etc.
■ Tocilizumab (IL-6 inhibitor) as per dosing guideline.
■ Consider plasma exchange 13. Monitoring
■ Daily: PCT, CRP, IL-6, BNP, Troponins, Ferritin, Neutrophil-Lymphocyte ratio, D-dimer, Mg, CRP and Ferritin are good biomarkers and track disease severity. Thromboelastogram (TEG) on admission and repeated as indicated.
■ In patients receiving IV vitamin C, the Accu-ChekTM POC glucose monitor will result in spuriously high blood glucose values. Therefore, a laboratory glucose is recommended to confirm the blood glucose levels.
■ Monitor QTc interval if using chloroquine/hydrochloroquine and azithromycin and monitor Mg++ (torsades is uncommon in monitored ICU patients)
■ No routine CT scans, follow CXR and chest ultrasound.
■ Follow ECHO closely; Pts develop a severe cardiomyopathy. 14. Post ICU management
a. Enoxaparin 40-60 mg s/c daily
b. Methylprednisone 40 mg day, the wean slowly c. Vitamin C 500 mg PO BID
d. Melatonin 3-6 mg at night
END This section, concludes Dr. Paul Marik's suggested Protocol. Show this link or protocol for your doctor when you consult your own doctor. Marik-Covid-Protocol-Summary.pdf
Go To Part 5
Respiratory symptoms (SOB; hypoxia- requiring N/C ≥ 4 L min: admit
to ICU):Additional Treatment Components (the Full Monty)
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. Alterative 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 (see below).
General schema for respiratory support in patients with COVID-19
TRY TO AVOID INTUBATION IF POSSIBLE
Low-Flow Nasal Cannula
■ Typically set at 1-6 Liters/Min
High Flow Nasal Cannula (Limitation on Flow Rate)
■ Accept permissive hypoxemia (O2 Saturation > 86%)
■ Titrate FiO2 based on patient’s saturation
■ Accept flow rates of 60 to 80 L/min
■ Trial of inhaled Flolan (epoprostenol)
■ Attempt proning (cooperative proning)
Invasive Mechanical Ventilation
■ Target tidal volumes of ~6 cc/kg
■ Lowest driving pressure and PEEP
■ Sedation to avoid self-extubation
■ Trial of inhaled Flolan
Prone Positioning
■ Exact indication for prone ventilation is unclear
■ Consider in patients with PaO2/FiO2 ration < 150
VV-ECMO
■ Indications remain unclear
■ Early discussion with ECMO center or team may be advisable
3. Full anticoagulation: Unless contraindicated we suggest 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). 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 floor, consider reducing enoxaparin to 40-60 mg /day. Note: Early termination of ascorbic acid and corticosteroids will likely result in a rebound effect.
4. Melatonin 6-12 mg at night (the optimal dose is unknown).
5. 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).
6. Optional: Azithromycin 500 mg day 1 then 250 mg for 4 days (has immunomodulating properties including downregulating IL-6; in addition Rx of concomitant bacterial pneumonia).
7. 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 pleotropic anti-inflammatory, immunomodulatory, antibacterial and antiviral effects. In addition, statins decrease expression of PAI-1
8. Broad-spectrum antibiotics if superadded bacterial pneumonia is suspected based on procalcitonin levels and resp. culture (no bronchoscopy).
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 (however, this may not be correct).
9. Maintain EUVOLEMIA (this is not non-cardiogenic pulmonary edema). Due to the prolonged “symptomatic phase” with flu-like symptoms (6-8 days) patients may be volume depleted. Cautious rehydration with 500 ml boluses of Lactate Ringers may be warranted, ideally guided by non-invasive hemodynamic monitoring. Diuretics should be avoided unless the patient has obvious intravascular volume overload.
10. Early norepinephrine for hypotension. While the angiotenin II agonist GiaprezaTM has a limited role in septic shock, this drug may uniquely be beneficial in patients with COVID-19 (downregulates ACE-2).
11. Escalation of respiratory support (steps); Try to avoid intubation if at all possible
■ Accept “permissive hypoxemia” (keep O2 Saturation > 84%)
■ N/C 1-6 L/min
■ High Flow Nasal canula (HFNC) up to 60-80 L/min
■ Trial of inhaled Flolan (epoprostenol)
■ Attempt proning (cooperative repositioning-proning; see Figure)
■ Intubation... by Expert intubator; Rapid sequence. 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.
Find the latest version at evms.edu/covidcare
■ Moderate sedation to prevent self-extubation
■ Trial of inhaled Flolan (epoprostenol)
■ Prone positioning
■ ?? ECMO < 60 yrs. and no severe commodities/organ failure.
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.
A group of patients with COVID-19 deteriorates very rapidly (see graphic below). Intubation and mechanical ventilation may be required in these patients.
12. Treatment of secondary HLH (increasing Ferritin, CRP and transaminases)
■ “High dose corticosteroids.” Methylprednisolone 120 mg q 8 hourly for at least 3 days, then wean accruing to CRP, IL-6, Ferritin etc.
■ Tocilizumab (IL-6 inhibitor) as per dosing guideline.
■ Consider plasma exchange 13. Monitoring
■ Daily: PCT, CRP, IL-6, BNP, Troponins, Ferritin, Neutrophil-Lymphocyte ratio, D-dimer, Mg, CRP and Ferritin are good biomarkers and track disease severity. Thromboelastogram (TEG) on admission and repeated as indicated.
■ In patients receiving IV vitamin C, the Accu-ChekTM POC glucose monitor will result in spuriously high blood glucose values. Therefore, a laboratory glucose is recommended to confirm the blood glucose levels.
■ Monitor QTc interval if using chloroquine/hydrochloroquine and azithromycin and monitor Mg++ (torsades is uncommon in monitored ICU patients)
■ No routine CT scans, follow CXR and chest ultrasound.
■ Follow ECHO closely; Pts develop a severe cardiomyopathy. 14. Post ICU management
a. Enoxaparin 40-60 mg s/c daily
b. Methylprednisone 40 mg day, the wean slowly c. Vitamin C 500 mg PO BID
d. Melatonin 3-6 mg at night
END This section, concludes Dr. Paul Marik's suggested Protocol. Show this link or protocol for your doctor when you consult your own doctor. Marik-Covid-Protocol-Summary.pdf
Go To Part 5