Treatment

There are a number of standard hygiene practices that have been recommended to protect against infection and further spread of the virus. These include:

• social distancing

  • ​6 feet apart 

• covering mouth and nose during sneezing with medical mask or flexed elbow

• prophylactically wearing mask in public

• washing hands regularly with soap and water or alcohol-base hand rub

• having the appropriate personal protection equipment (PPE) for healthcare workers

• stay at home if sick but seek medical attention if symptoms worsen (eg. difficulty breathing, chest pain)

 

Sweden did NOT enforce this

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Supportive

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Right Ventricular Dysfunction

Right ventricular management plays a vital role in reducing the high mortality rate. Conventional hemodynamic measurements using volume responsiveness methods can not provide accurate guidance in the face of right ventricular dysfunction. These indirect methods are dependent on both normal heart-lung interaction and normal RV function. Such noninvasive monitors indicate the need for more fluid when in fact that may be the opposite if the right ventricle is overloaded (1).

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• transthoracic ECHOcardiogram

• transesophageal ECHOcardiogram

• ClariTEE (72 hour) probe

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Non-Invasive Mechanical Ventilation

• high-flow nasal cannula

• use CPAP for 1 hour and re-evaluate - if not effective, consider intubation (Martin notes)

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Intubation

• rapid sequence intubation

• no bagging

• avoid nebulizers

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Invasive Mechanical Ventilation

High oxygen requirements were seen soon after initiation of mechanical ventilation. Plateau pressure 25 cm of water and driving pressure 12-13 cm of water. 

• apparently early on, high PEEP is probably NOT the right strategy and may be harmful; this is not ARDS in the early phase of the illness (Martin notes)

• avoid spontaneous ventilation early on because may be harmful (Martin notes)

• ARDS 7P's:

  • protective lung ventilation

  • PEEP​

  • paralytics

  • proning 

  • prostacyclins (inhaled)

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Extubation

• the earliest occurred in 8 days which suggests that mechanical ventilation is prolonged (days to weeks) and the readiness for extubation is unlikely to occur early 

• age range of extubated patients was 23-88 years which suggests that age may not be a sole indicator for successful extubation

• wait longer than usual when extubating because of the high re-intubation rate; don't intubate if markers of inflammation are still high (Martin notes)

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Re-intubation (Martin notes)

• common

• airway swelling, stridor 

  • important to do leak test because of the airway swelling​

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splitting ventilators

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Pulmonary microvascular thrombosis

• anticoagulate? is this too risky?

• LMWH being used because running out of pumps

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Anticoagulation (Yajnik)

• consider ASA 81 mg if there is significantly rising thrombocytosis

• lovenox 40 mg daily, follow anti-Xa levels to ensure adequacy of ppx

• systemic anticoagulation if D-dimer greater 1000 usually day 7-11

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ECHOcardiography

• increased right ventricular dysfunction without increased pulmonary pressures (Martin notes)

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Bronchoscopy

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Renal Failure / Fluid Balance

• these patients are showing up severely dehydrated (eg. fevers, hyperventilation)

• hypovolemia impedes gas exchange 

• high rates of AKI / CVVHD from overzealous diuresis (Martin notes)

• hypovolemia leads to poor pulmonary perfusion and increased dead space 

• oliguria has improved by dropping the PEEP likely from the hypovolemia (Martin notes)

• inferior vena cava ultrasonography might assist with this (Debesa)

• CVVHD increases mortality 

  • circuits clot frequently ​- use aggressive systemic anticoagulation (Martin notes)

• avoid HYPERvolemia

• microthrombi in the kidney also probably contributing to AKI (Martin notes)

• peritoneal dialysis being done because running out of CVVHD machines or use it like intermittent dialysis and sharing machines (Martin notes)

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Acetazolamide (Diamox) 

• for patients with L-phenotype (HAPE-like)

• 250 mg q12h

• reduces hypoxic pulmonary vasoconstriction

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Ascorbic Acid (Vitamin C)

• interferes with glucose oxidase assays in POCT and continuous glucose monitoring giving you a falsely elevated blood glucose 

• also interferes with HbgA1c testing giving falsely elevated results 

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Prone Position

• essential and should be done early 

• if P/F ratio remains < 150 on PEEP > 10 and FiO2 > 60%

• proning patients on CPAP very effective (in most cases they can prone themselves)

• many centres use a P/F ratio threshold of ???

• early on in the disease, the benefits of proning lasts less than 4 hours when turned back to supine; as the disease progresses more into an ARDS picture, the effect is more long lasting 

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Steroids

• Asthmatic that had received systemic glucocorticoids within 1 week before ICU admission, as outpatients for presumed asthma exacerbation, had severe respiratory failure requiring mechanical ventilation. Previous studies of patients that received glucocorticoids for phylogenetically similar viruses (SARS-CoV 2003 and MERS-CoV) were associated with higher plasma viral load, longer duration of viremia and worse clinical outcomes (17-20). This is in contrast to recent studies that suggest glucocorticoids may be associated with improved outcomes in patients with COVID-19 and ARDS (21). 

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inhaled Nitric Oxide

• good results

• tachyphylaxis after 4-5 days 

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inhaled Prostacyclin

• good results

• seems to work early in the disease

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Remdesivir

• 200mg IV x 1, followed by 100mg q24h (max: 10 days)

• insufficient information to report associated outcomes

• prodrug metabolized by CYP3A4 (concomitant inhibitors of CYP3A4 should be avoided)

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Hydroxychloroquine (Plaquenil)​

• LD: 400mg PO bid x 1 day; MD: 200mg PO b id x 4 days

• no adjustments with renal failure

• zinc 50mg bid as a cofactor ???

• G6PD, methemoglobinemia, especially with vitamin C and iNO 

• obtain baseline ECG; avoid if QTC>500 msec

 

Chloroquine

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Tocilizumab (Actemra)

• 4mg/kg IV (upto 400mg); dose may be repeated once in 12-24 hours for suboptimal response)

• IL-6 antagonist

• don't give if IL-6 level is less than 6 picograms/mL

• anecdotal accounts have good results with 2 doses (reduced second dose) 

• cytokine release syndrome: 4-8mg/kg IV x 1; max: 400mg per dose (may repeat second dose)

• check IL-6 level for response 

• indications:

  • COVID-19 (+)​

  • moderate ARDS on mechanical ventilation

  • P/F < 200

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Siltuximab

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Lopinavir / Ritonavir

• 400/100mg PO q12 x 14 days

• no adjustments with renal failure

• check HIV antibodies; if HIV+ would not use as monotherapy

• consider adding Interferon-beta (0.25mg SC every other day for 14 days)

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Sarilumab

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Azithromycin

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Herd Immunity

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Convalescent plasma

• antibody rich plasma from patients that have recovered from COVID-19

• potential to lessen the severity or shorten the length of illness

• Donate Covid-19 plasma website

• every unit different because from different donors

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Vaccine

• in development 

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ECMO

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References: (1) Miller A, Mandeville J. Predicting and Measuring Fluid Responsiveness with Echocardiography. Echo Res Pract. 2016, https://doi.org/10.1530/erp-16-0008, (17) Peiris et al, Lancet, 2003, (18) Lee et al, J Clin. Virol, 2004, (19) Arabi et al, Am J Respir Crit Care med, 2018 (20) Lansbury et al, Crit Care Med, 2019 (21) Wu et al, JAMA Intern Med, 2020