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 patient's condition at the time of presentation. Continuous evaluation and titration of ongoing interventions ensure 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. Interventions posing a risk of aerosol transmissions should be carried out after using all the required precautions such as the use of PPE and AIIR room with minimal healthcare personnel in the room.

Ventilatory support in COVID-19

• The feasibility of the strategy used for the management of a patient with COVID-19 depends on the patient's condition at the time of presentation. Continuous evaluation and titration of ongoing interventions ensure 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.
• 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 type (low lung elastance and V/Q ratio) of COVID-19-associated pneumonia or CARDS benefit from increased FiO2 the most. The therapy is particularly useful if the patient is non-dyspnic.
• In SARS Cov2 positive adult patients the Surviving Sepsis Campaign (SSC) strongly recommendeds (with moderate-quality evidence):
  • To start the supplemental oxygen if the Spo2 is < 90%. Starting the supplemental oxygen at < 92% saturation has weak recommendation.
  • Maintain Spo2 no higher than 96% in patients with with acute hypoxemic respiratory failure on supplemental oxygen therapy. The recommendation is 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)

• NIV methods are easier and comfortable to use and work by inducing PEEP thus decreased the respiratory workload. Based on the COVID-19 experience of the Chinese experts , both HFNC and NIPPV methods should probably be utilized in patients with PaO2/FiO2 > 150 mmHg.
• 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.
• Inspiratory pressures should be 10 cmH2O and expiratory pressures be 5 cmH2O with 1.0 FiO2.

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. A hypercapnic patient should not be administered HFNC.
• Sufficient evidence to prove the superiority of one of the methods (HFNC or NIPPV) is lacking. But HFNC is preferred 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.
• In acute hypoxemic respiratory failure despite supplemental oxygen therapy, SSC suggests using HFNC over conventional oxygen therapy (weak recommendation). A systematic review and meta-analysis of 9 RCTs showed that High Flow Nasal Cannula (HFNC) reduces the need for intubation.
• Target SpO2 should be 88% -94% with minimal flow rates under 30L/min. Low flow rates help minimize aerosolization. PEEP ranges from 5-15 and peak airway pressure ranges from 8-10 cmH2O.

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 NIPPV.
• In adults with COVID-19 and hypoxemic respiratory failure, if HFNC is not available and endotracheal intubation not urgently indicated, a trial of NIPPV can be given. Type L patients with dyspnea can benefit from NIV. Close monitoring and short-interval assessment for worsening of respiratory failure is required. (weak recommendation by SSC).
• The safety and efficacy of helmet NIPPV in SARS Cov2 patients is questionable. One study advocates 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. Early intubation may prevent the transition from type L (low elastance and V/Q ratio) to (high elastance and V/Q ratio) phenotype of CARDS.

Intubation

According to Americal Heart Association (AHA), intubation is indicated in:

• Gas exchange abnormality: Respiratory failure (usually hypoxic in COVID-19), PaO2/FiO2 <150 (corrected for altitude), NIV with FiO2 >0.6 and inability to maintain SpO2 >90%, unresponsiveness to HFNC therapy, hypercapnia (PaCO2 > 45 mm Hg) with acidosis (PH< 7.3), increased work of breathing with deteriorating respiratory function.
• Airway protection: Alterened mental status and neurological dysfuntions.
• Pulmonary toilet: To remove excessive pulmonary secretions.

Ventilator settings

The following ventilator setting should be used:

• Mode: No mode of ventilation has been suggested to be superior to others. AHA recommends assist control PRVC.
• Respiratory rate: 20-25 breaths/min.
• Tidal volume (Vt): 4–8 ml/kg predicted body weight and lower inspiratory pressures. Excess Vt causes alveolar overdistension and worse CARDS.
• Plateau pressure (Pplat): <30 cm H2O and peak inspiratory pressure:<35 cmH2O.
• FiO2: <0.6
• Positive end-expiratory pressure (PEEP): Based upon the data of 8 RCTs on ARDS, mean ± SD PEEP was 15.1 ± 3.6 cm H2O (higher) versus 9.1 ± 2.7 cm H2O (lower). Patients receiving higher PEEP had better oxygenation (PaO2/FiO2). It is recommended that moderate or severe CARDS patients receive higher levels of PEEP.
  • Titration for CARDS: After lung recruitment maneuvers, PEEP can be titrated down from a maximum of 20 cm H2O until the goals of oxygenation, plateau pressure, and compliance are all achieved. 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. The PEEP should be reduced to 8–10 cmH2O in prone positioning ventilation. The CARDS Ventilator PEEP Titration Protocol can be viewed by clicking here.
  • Types: Patients with “H type” (high elastance and V/Q ratio) CARDS, may benefit from higher PEEP and lower tidal volumes. Patients with “L type” (low lung elastance and V/Q ratio) CARDS may benefit from lower PEEP and higher tidal volumes. If Type L patient is hypercapnic, volumes greater than 6 ml/kg (up to 8–9 ml/kg) can be helpful.
  • 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. CARDS patients on high PEEP had no associated complications or increased mortality.
• Maintenance Goals: pH= 7.25-7.42, paO2 >60/ SpO2= 88-96%, paCO2= 40-65/ETCO= 35-60 mmHg (permissive hypercapnia).

Extracorporeal membrane oxygenation (ECMO)

• Venovenous type of ECMO (VV ECMO) drains blood from a large central vein, oxygenates it, and removes carbon dioxide via the gas-exchange device. The blood is then reinfused. ECMO can help avoid ventilator-induced lung injury.
• The use of ECMO is has been recommended in COVID-19 patients with refractory hypoxemia or high driving pressure, or hypercapnia/respiratory acidosis despite invasive mechanical ventilation (IMV) and lung-protective measures such as higher PEEP or prone positioning. The strategies can be combined such as in Type H patients, who should be treated as severe ARDS patients with higher PEEP, if compatible with hemodynamics, prone positioning and ECMO. The WHO suggested 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. A definitive recommendation requires additional evidence for or against the use of ECMO in patients with CARDS.

Summary of SSC recommendations regarding initial management of hypoxic COVID-19 patients.

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.
• 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 SSC guidelines strongly recommend (moderate evidence) Prone positioning for more than 12 hours/day in patients with severe ARDS. In mechanically ventilated patients with PaO2/FiO2 <150, prone positioning can be used.

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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 analgesics (fentanyl, hydromorphone) and sedatives (benzodiazepines, propofol). 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: Concerns have been raised for a possible risk for transmission of COVID-19 to health care personnel due to aerosol transmission. With the judicious use of the standard precautions and protective measures, the results for the mentioned interventions have been promising.

Source of aerosol generation	Protective Measures
Coughing	Utilize full Personal protective equipment (PPE) prior to entering the intubation room. Minimize period between removal of patient's PPE and application of face mask with viral filter. Ensure sealing of the face mask. Use of local lidocaine via ETT or during procedures such as bronchoscopy and opoids in minimum dose.
Face Mask Seal Leak	Optimum fitting of the face mask. Vice (V-E) grip Use manual ventilation Ambu bag ETO2 monitoring
Non-Invasive ventilation, bronchoscopy, CPR extubation, and manual ventilation	WHO recommends the use of PPE that includes respirators, eye protection, gloves and gowns; aprons if gowns are not fluid resistant. 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. The staff who are expected to help during the procedure should be informed and ready with PPEs. If possible, use disposable bronchoscope or cleaning the suction channels with the cleaning solutions used for highly infectious materials.
Intubation	Above mentioned precautions such as the use of PPE and AIIR with minimal personnel in the room should be followed. 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.
Tracheostomy	Above mentioned precautions such as the use of PPE and AIIR with minimal personnel in the room should be followed. During the procedure, minimal use of diathermy, and maintenance of bloodless fields should be ensured. Post-procedure, reduce the frequency of changing an inner cannula and cuff pressure checks to a possible minimum for the patient. Post tracheostomy, humidification can be provided via heat and moisture exchange filter or a water-based humidification such as hypertonic saline nebulizers. Patients should use facemasks and tracheostomy shields during trials of tracheostomy cuff deflation.

Bronchoscopy

• Very limited studies are available on the use of bronchoscopy in COVID-19 patients due to a very high risk of aerosol transmission. Bronchopy as a well-tolerated therapeutic intervention, performed in mechanically ventilated patients with COVID-19 have been reported in an observational study. FiO2 was increased to SpO2 of 95%–98% before the intervention. Precautions such as the use of a negative-pressure room, PPE, and duration of the procedure never more than 10 minutes were observed. The study showed that patients can benefit from therapeutic bronchoscopy for the removal of thick hypersecretions in the airway (most common complication observed). Guided mini-BAL can also help confirm the clinical suspicion of superinfection.

Tracheostomy

• Standard decision making for tracheostomy in a COVID patient is practiced. But owing to the potential of aerosol spread of the infection certain considerations should be kept in mind, such as the safety of other the patient's family, other patients, healthcare personnel, and the resources available.
• Tracheostomy should be delayed until at least the 10th day of mechanical ventilation. It should be considered only when the patient is clinically improving. The decision of extubation should be limited to the patients who have a high chance of success.

Cardiopulmonary resuscitation (CPR)

American Heart Association's (AHA) interim BLS Healthcare Provider Adult Cardiac Arrest Algorithm for Suspected or Confirmed COVID-19 Patients can be accessed by clicking here.