COVID-19 interventions

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Javaria Anwer M.D.[2]

Synonyms and keywords: SARS Cov2 interventions, Interventions in covid19, Novel coronavirus interventions

Overview

The feasibility of the strategy used for the management of a patient with COVID-19 depends on the patients' condition at the time of Continuous evaluation and titration of ongoing interventions ensures optimal results. The respiratory manifestations of COVID-19 may require some oxygen supplementation to ventilatory support. Autopsy findings of patients with COVID-19-associated acute respiratory distress syndrome (CARDS) demonstrated small airway occlusion due to necrosis and inflammation. The finding advocates the use of positive pressure ventilation to restore the collapsed airways. A balanced approach is required as a high end-inspiratory pressure increases the risk of lung alveolar injury.

Ventilatory support in COVID-19

• The COVID-19 respiratory complications that may require mechanical ventilation include: COVID-19-associated pneumonia, COVID-19-associated acute respiratory distress syndrome (CARDS) and COVID-19-associated respiratory failure. At the start, the recommendation to treat CARDS was similar to the ones used to treat ARDS due to other causes. During the initial course of the disease, in the absence of bacterial infection in COVID-19-associated pneumonia or CARDS, the patient has normal or even high pulmonary compliance. Thus, a patient can have severe hypoxemia in the absence of tachypnoea or dyspnea. Knowledge and experience of the unique features of the disease have led the guidelines to be modified/ specified.
• Acute hypoxemic respiratory failure and ARDS are more common respiratory complications in COVID-19 patients.

Supplemental Oxygen

• A patient with L (low lung elastance and V/Q ratio) type of COVID-19 associated pneumonia or CARDS will benefit from increased FiO2 the most. The therapy is particularly useful if the patient is non-dyspnic.
• Surviving Sepsis Campaign has the following recommendations regarding the use of supplemental oxygen in adults COVID-19 patients:
  • It is strongly recommended (with moderate-quality evidence) to start the supplemental oxygen if the Spo2 is < 90%. A weak recommendation states starting the supplemental oxygen at < 92% saturation.
  • In COVID-19 positive adult patients with acute hypoxemic respiratory failure on supplemental oxygen therapy, Spo2 should be maintained no higher than 96% (strong recommendation by Surviving Sepsis Campaign). This based upon the systematic review and meta-analysis of 25 RCTs that showed a linear association between the death risk and higher Spo2 targets.

Non-Invasive ventilation (NIV)

• According to Chinese experts based on there experience with COVID-19 patients, both HFNC and NIPPV methods should probably be utilized in patients with PaO2/FiO2 > 150 mmHg.
• NIV methods are easier and comfortable to use and work by inducing PEEP thus decreased the respiratory workload.
• Sufficient evidence to prove the superiority of one of the methods (HFNC or NIPPV) is unavailable as of now (July 2020). Limited studies have suggested that HFNC improves survival and lowers the intubation rate.
• Close monitoring for a deteriorating respiratory status and early intubation when indicated in a controlled setting, can help minimize the infection of health personnel and promise better patient health outcomes.

High Flow Nasal Cannula (HFNC)

• Also known as high flow nasal oxygen (HFNO) or Heated humidified high-flow (HHHF) therapy is a non-invasive technique. It is a technique of delivering heated and humidified high-flow oxygen via soft and flexible nasal prongs. Humidification prevents the drying of epithelium and facilitates the removal of mucosal secretions. Other advantages include pharyngeal dead space washout and PEEP effect.
• Surviving Sepsis Campaign (SSC) has the following recommendations regarding the use of HFNC in COVID-19 patients:
  • In COVID-19 positive adult patients with acute hypoxemic respiratory failure despite supplemental oxygen therapy, a weak recommendation suggests using HFNC over conventional oxygen therapy. A systematic review and meta-analysis of 9 RCTs showed that High Flow Nasal Cannula (HFNC) reduces the need for intubation.
  • A weak recommendation (low-quality evidence) also prefers using HFNC over Non-invasive positive pressure ventilation (NIPPV). It is possibly due to reduced mortality and decreased intubation risk, as proved by a RCT and a meta-analysis respectively. Patient comfort better oxygenation with HFNC than NIPPV is also one of the considering factors.

Non-Invasive Positive Pressure Ventilation (NIPPV)

• Non-invasive positive pressure ventilation (NIPPV) is a technique utilized for delivering mechanical ventilation without the use of endotracheal intubation or tracheostomy. It can be administered through a face mask, nasal mask, or a helmet and includes CPAP and BiPAP.
• Many patients who develop ARDS receive a trial of non-invasive positive pressure ventilation (NIPPV) before intubation for mechanical ventilation before they clinically deteriorate or become unable to maintain adequate oxygenation. Studies from China reported (4% to 13%) of COVID-19 patients to have received non-invasive positive pressure ventilation (NIPPV).
• Surviving Sepsis Campaign (SSC) has the following recommendations regarding the use of Non-invasive positive pressure ventilation (NIPPV) in adult COVID-19 patient with hypoxemic respiratory failure:
  • A weak recommendation (very low-quality evidence) suggests a trial of NIPPV, if HFNC is not available and endotracheal intubation not urgently indicated. with close monitoring and short-interval assessment for worsening of respiratory failure.
  • The SSC demonstrated its uncertainty regarding the safety and efficacy of helmet NIPPV in SARS Cov2 patients. Another study advocates and recommends the use of helmet NIPPV in COVID-19 care due to potential avoidance of air dispersion through the spring-valve. Having said that, the cost of a helmet may be an essential consideration for healthcare systems struggling financially.

Invasive Mechanical Ventilation (IMV)

• The vascular endothelial injury in COVID-19-associated acute respiratory distress syndrome (CARDS) and diverse mortality rates across the world in CARDS patients arbitrates the importance of different mechanical ventilation strategies.
• The Chinese CDC reports the case-fatality rate to be higher than 50% in patients who received invasive mechanical ventilation.
• According to the American Society of Anesthesiology based upon the experience of Chinese anesthesiologists, timely (neither premature nor late) intubation and ventilation most effectual breathing assistance.
• Mechanical ventilation can be used in patients who have labored breathing and are unable to maintain adequate gaseous exchange leading to hypoxemia and/or hypercapnia.
• Common clinical indications of mechanical ventilation include moderate to severe dyspnea, respiratory rate (RR) > 24-30/min, accessory muscle use for breathing, and abdominal paradox. It may also be used in patients who have an inadequate arterial partial pressure of oxygen or critically low PaO2 (PaO2 < 70 mm Hg), hypercapnia PaCO2 > 45 mm Hg, and PaO2/FiO2 ≤ 300 (corrected for altitude).

Ventilator settings

The following ventilator setting should be used:

• Mode: No mode of ventilation has been suggested to be superior to others.
• positive end-expiratory pressure (PEEP): The commonly used PEEP in the COVID-19 patients in Wuhan, China was less than 10 cm H2O. After lung recruitment maneuvers, PEEP is titrated down from a maximum of 20 cm H2O until the goals of oxygenation, plateau pressure, and compliance are all achieved. The CARDS Ventilator PEEP Titration Protocol can be viewed by clicking here.
  • Contraindications for the use of the PEEP may include untreated pneumothorax, very low blood pressure, elevated ICP, and pulmonary hypertension.
  • Complications of PEEP may include barotrauma, such as pneumothorax and/or decreased cardiac output.
• Tidal volume (Vt): Upto a maximum of 6 ml/kg of ideal body weight and lower inspiratory pressures.
• Plateau pressure (Pplat): < 28 to 30 cm H2O
• PEEP must be as high as possible to maintain the driving pressure (Pplat-PEEP) as low as possible (< 14 cmH2O). In Wuhan, COID-19 patients with acute hypoxemic respiratory failure showed a poor tolerance to high PEEP, possibly due to the severe lung damage by the SARS-CoV-2 virus and inflammatory reactions.

Extracorporeal membrane oxygenation (ECMO)

• The use of ECMO is recommended in COVID-19 patients with refractory hypoxemia or hypercapnia who have received invasive mechanical ventilation (IMV) and prone positioning. ECMO can help avoid ventilator-induced lung injury. It is recommended to use traditional indications in hospitals with sufficient medical resources. The WHO suggests referring patients with refractory hypoxemia despite lung-protective ventilation to the settings with expertise in ECMO. It is not known whether ECMO reduces mortality but 6.2% patients were treated with ECMO in Wuhan, China.

Stratagies to improve oxygenation

Prone position ventilation

• Prone positioning is thought to improve oxygenation by improving ventilation/perfusion (V/Q) mismatching via reduced shunting of blood through under-ventilated lung tissue.
• Research has shown that prone position ventilation in ARDS patients with acute hypoxemic respiratory failure and spontaneous or assisted breathing reduces the mortality by 28 and 90-days.
• The strategy was widely used in COVID-19 patients in Wuhan, China.
• Prone position is an early strategy rather than a desperate rescue therapy. A study by Lin Ding et al. suggests that the early application of prone ventilation with HFNC and NIV, especially in COVID-19 patients with moderate ARDS, can help avoid intubation. Prone position,with other adjunct therapies may probably be used for critically ill patients even during ECMO.
• Prone position for awake patients during spontaneous or assisted breathing during NIPPV or HFNC with mild-moderate ARDS was associated with an improved oxygenation. In addition, patients with an Spo2 of 95% or greater after an hour of the prone position had a lower rate of intubation. To answer the question about the effectiveness, two RCTs are in progress NCT04347941 and NCT04350723.
• The American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice and Surviving Sepsis Campaign guidelines strongly recommend (moderate evidence) Prone positioning for more than 12 hours/day in patients with severe ARDS.

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Special considerationss

• Lung recruitment maneuvers: Lung recruitment maneuver is the application of very high (up to 40 cm H2O) positive airway pressure during mechanical ventilation. It opens the collapsed alveoli, decreasing ventilation/perfusion (V/Q) mismatching thus improving the gas exchange. For ARDS patients, the maneuvers may help improve oxygenation and decrease the length of hospital stay with no positive effect on reducing mortality. The decision varies on a case by case basis depending upon lung condition and patient hemodynamics. On the trouble side, the maneuver may generate aerosols. High-quality evidence is lacking to support the use in ARDS patients.
• Paralytics: The paralytics may be used with sedatives and analgesics. In CARDS patients, Richmond Agitation Sedation Scale (RASS) score of (+2 to +4) even after optimal ventilatoy settings may indicate the use of deep sedation with paralytics. If used, short-term (24– 48 hours) and intermittent muscle relaxation is recommended. Prone position ventilation may also require muscle relaxation along with sedation. Paralytics are not recommended in an unless PaO2/FiO2 < 150 mmHg. The paralytics that are being used in CARDSpatients include: Succinylcholine chloride injection USP 200 mg/10 mL and cisatracurium besylate injection USP 20 mg/10 mL.

Aerosol Generation Risk Factors and Protective Measures

Source of aerosol generation	Protective Measures
Coughing	Utilize full Personal protective equipment (PPE) prior to entering intubation room Minimize period between removal of patient's PPE and application of face mask with viral filter Ensure sealing of face mask Adequate dosage and time for paralytic drugs
Face Mask Seal Leak	Optimum fitting of the face mask Vice (V-E) grip Use manual ventilation Ambu bag ETO2 monitoring
Intubation, NIV, manual ventilation, CPR, tracheostomy and bronchoscopy	WHO recommends the use of PPE that includes respirators, eye protection, gloves and gowns; aprons if gowns are not fluid resistant. Chest auscultation after intubation is not recommended due to aerosol transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Spo2, chest movements, capnography, fogging inside of the endotracheal tube, and the color of the patient’s skin and mucous membrane can be used to confirm a successful intubation.
Non-Invasive ventilation (HFNC and NIPPV)	Both HFNC and NIPPV methods used in COVID-19 patients generate aerosols. Concerns have been raised for a possible risk for transmission of COVID-19 to health care personnel. With the judicious use of the standard precautions and protective measures, the results for the aforementioned interventions have been promising. So, in addition to regular precautions such as the use of PPE followed during COVID-19 pandemic following precautions as advised by CDC to prevent airborne transmission should be taken: Airborne infection isolation room (AIIR) Restricting susceptible healthcare personnel Limiting transport and movement of the patient Use of fit-tested NIOSH-approved N95 or higher level respirator for healthcare personnel.