Brigham and Women's Hospitals


Updated: October 12, 2020

Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS)


  1. Histology of COVID-19 associated lung disease shows bilateral diffuse alveolar damage with cellular fibromyxoid exudates, desquamation of pneumocytes, pulmonary edema, and hyaline membrane formation. There is also some evidence of direct viral injury to lung tissue, not just inflammatory sequelae. (Xu et al, Lancet Respir Med, 2020).
  2. Anecdotally, patients with COVID-related lung disease have significantly higher compliance than is typical for their shunt fraction, indicating this may be a very different phenotype than typical ARDS. The explanation remains unclear, with pulmonary perfusion dysregulation posited as one possible explanation. (Gattinoni, AJRCCM, 2020)
  3. The SARS-CoV-2 virus binds to the ACE2 receptor as its target receptor for cell entry which may be an explanation for many of the pathophysiological manifestations of infection. The ACE2 receptor is expressed by select populations of cells including the pulmonary endothelium, Alveolar Type 2 cells, proximal renal tubule cells, gastrointestinal epithelial cells, and many other others. The cells that express ACE2 may be the cell populations injured by infection or targeted by the immune response. Hypothesized manifestations include the following:
  1. In the pulmonary endothelium, ACE2 acts to downregulate angiotensin II (a potent vasoconstrictor) while increasing levels of angiotensin (1,7) (a vasodilator). Infection with SARS-CoV-2 may impair this pathway or may lead to imbalances in the ACE/ACE2 pathways with uncertain effects on hypoxic vasoconstriction mechanisms. Impairment of this pathway may induce increased shunt and resultant hypoxia.
  2. Alveolar Type 2 cells secrete surfactant. Their selective injury caused by SARS-CoV-2 infection may lead to selective loss of surfactant in a subgroup of patients resulting in increased derecruitment at low opening pressures and a highly PEEP sensitivity to maintaining lung function. These patients may experience prolonged recovery periods dependent on repopulation of Alveolar Type 2 cells and reconstitution of surfactant.

Definition of Acute Respiratory Distress Syndrome (ARDS)

  1. Most patients with COVID-19 who require ICU level of care will develop ARDS.
  2. The Berlin definition of ARDS requires the following four criteria:
  1. Acute (onset over 1 week or less)
  2. Bilateral opacities detected on CT or chest radiograph
  3. PF ratio <300mmHg with a minimum of 5 cmH20 PEEP (or CPAP)
  4. Must not be fully explained by cardiac failure or fluid overload


PaO2/FiO2 (on PEEP/CPAP >5)

Mortality (all cause, cohort)










Time course

  1. Anecdotally, many report that progression of hypoxemic respiratory failure occurs rapidly (within ~12-24 hours).
  2. From onset of symptoms, the median time to:
  1. Development of ARDS: 8-12 days (Wang et al, JAMA, 2020; Zhou et al, Lancet, 2020; Huang et al, Lancet, 2020)
  2. Mechanical ventilation: 10.5-14.5 days (Huang et al, Lancet, 2020; Zhou et al, Lancet, 2020)

Hypoxemia Management

Supplemental Oxygen Support

  1. Goals of therapy:
  1. Maintain target SpO2 92-96%
  1. Target SpO2 88-94% in patients with oxygen-dependent COPD
  1. Maintain stable work of breathing
  1. Goal respiratory rate < 24
  2. Target normal respiratory effort (no signs of accessory muscle use or obvious increased respiratory work)
  1. Supplemental oxygen support:
  1. Initial oxygen delivery should be humidified nasal cannula (NC) titrated from 1 to 6 LPM to meet goals of therapy.
  2. If goals of therapy are not met at 6 LPM NC then advance to either:
  1. Oxymizer mustache:
  1. Initiate at 6 LPM
  2. Titrate to maximum of 12 LPM to meet goals of therapy
  1. Venturi mask
  1. Initiate at FiO2 40% (check device’s instructions to determine minimum flow rate needed to achieve 40%)
  2. Titrate to maximum of FiO2 60% to meet goals of therapy (some devices are not able to achieve Fi02 of 60%, please discuss with RT)
  1. Considerations during oxygen support escalation:
  1. Clarify goals of care and appropriateness of ICU hospitalization prior to escalating to ICU transfer and pursuing intubation
  2. Consider awake self-proning in selected patients
  3. Consider the rate of change of oxygen escalation as well as pre-existing cardiopulmonary disease in determining threshold for ICU transfer (such as COPD patient with pre-existing supplement oxygen use at baseline)
  4. Consider Pulmonary Consult if there are concerns for other etiologies of hypoxia
  1. If appropriate, consult ICU for triage and evaluation:
  1. If SpO2 < 92% (<88% in COPD) or unstable work of breathing at
  1. Oxymizer at 10 LPM or Venturi mask at FiO2 50%
  1. ICU triage (pager #39999)


  1. If appropriate, call airway team for intubation:
  1. If SpO2 < 92% or unstable work of breathing at:
  1. Oxymizer at 12 LPM or Venturi mask at FiO2 60%
  1. Page Anesthesia for intubation
  1. STAT line if code/ emergent (pager #26555)
  2. Regular line for routine/ non-urgent Anesthesia needs (pager #11668)
  1. Notify team if you anticipate needing arterial line or central access, as they may be able to place the line while in full intubating PPE
  2. Notify team of any known prior difficult intubations, prior head or neck surgery or radiation therapy, or know airway abnormalities
  1. Pre-oxygenation for patients on advanced supplemental oxygen support:
  1. Increase Venturi mask to FiO2 100% (consult RT if not possible with your device) or Oxymizer to 15 LPM prior to planned intubated
  1. Avoid NIPPV or HFNC to stave off intubation (see discussion above)
  1. For patients already on NIPPV/HFNC, transition to Venturi mask or non-rebreather mask if possible, ideally 45 minutes prior to intubation
  1. Rapid Sequence Induction(RSI) should be performed by the most experienced airway provider without bag-valve masking and using a video laryngoscope (SCCM COVID19 Guidelines)(APSF Considerations for Airway Manipulation, 3/20/2020).
  1. For more detailed instructions, see Intubation
  1. Intubations outside the ICU should be attended by the Resource RT, who can facilitate early and appropriate ventilator settings
  2. After intubation, see “Initial Mechanical Ventilation for next steps

Non-invasive Positive Pressure Ventilation (NIPPV)

  1. COVID-19 Confirmed or PUI patients
  1. NIPPV should be utilized for the same indications as used in COVID-19 negative patients:
  1. Obstructive Sleep Apnea or Tracheobronchomalacia: Patients on home nocturnal CPAP or BiPAP should continue nocturnal NIPPV.
  2. Pulmonary edema
  3. COPD exacerbation and other reversible hypercapnia
  4. NIPPV should be generally avoided in the same situations that NIPPV is generally avoided in COVID-19 negative patients (e.g., severe ARDS without short-term reversibility; contra-indications such as altered mental status, aspiration risk, secretions).
  1. If NIPPV is used:
  1. NIPPV is an aerosol generating procedure that requires proper infection control precautions.
  2. Use BWH NIPPV machine with dual limb with a HEPA filter and BWH mask without anti-asphyxia valve.
  1. If the patient is unable to tolerate the BWH mask or machine, there should be a multi-disciplinary discussion about the benefits and risks of the patient using their home NIPPV mask/machine or other single-limb NIPPV machine and mask with anti-asphyxiation valve.
  1. Use with strict airborne precautions, including N95s and a negative pressure room.
  2. Ensure masks/devices fit well and there is minimal air leak (which can cause significant lateral air travel (Hui et al, Eur Respir J, 2019)).

High-Flow Nasal Cannula (HFNC)

  1. Concerns about aerosolization
  1. Early in the COVID-19 pandemic, our institution avoided HFNC in COVID-19 confirmed and PUI patients given the indeterminate data on aerosol and HCW transmission risk. Since then, we have demonstrated that our PPE and isolation protocols have effectively prevented HCW transmission of COVID-19 in several types of aerosol generating procedures, both short-term (e.g., intubation, nebulizer in non-intubated patient) and prolonged (e.g., coughing, 12L oxymizer).
  1. Many partner organizations and other major medical centers that use HFNC with similar PPE have so far not reported increased viral transmission when using HFNC
  1. Data remain incomplete on the relative aerosol generation of HFNC (compared with NIPPV, coughing, nebulization, etc), and the impact of flow rate on aerosol generation
  1. One non-peer reviewed preprint tested aerosol levels in healthy volunteers and concluded that there was no variation in aerosol level among room air, 6L/min NC, 15 L/min NRB, 30L/min HFNC and 60 L/min HFNC regardless of coughing.(Iwashyna et al. MedRxivPreprint, 2020) Similarly, a randomized, controlled crossover trial of HFNC versus conventional oxygen mask found no increase in air or contact surface contamination by bacteria, though the particulate size for bacteria is very different than for viruses (Leung et al, J Hosp Infect, 2020)
  1. COVID-19 Confirmed or PUI patients
  1. HFNC can be used if it would clinically benefit patients as determined by the primary team. Early data shows COVID-19 patients might avoid intubation using HFNC, though no mortality benefit has been found in this population (Demoule et al. AJRCCM, 2020)
  1. The primary hypoxemia management pathway is as described above. HFNC can be added to the pathway for select patients at the discretion of the primary team
  2. Indications are the same as for COVID-19 negative patients
  3. Contraindications are the same as for COVID-19 negative patients
  1. Coughing is not a contraindication
  2. Special approval is not required
  1. It can be used in both DNR/DNI and Full Code patients
  2. Self-proning is allowed on HFNC if the patient meets all other self-proning criteria (see below)
  1. If HFNC is used:
  1. Discuss risks and benefits with MD, RN, and RT
  2. Follow infection control guidance, with strict airborne precautions including N95s and a negative pressure room.
  3. Setup is the same as for COVID-19 negative patients
  1. Heated and humidified oxygen should be used
  2. Flow rate up to 60L/min is allowed. Consider starting with 30L/min and increasing flow if it will benefit the patient (there is a theoretical risk for increased aerosolization at higher flow rates, though data is very limited)
  1. Encourage the patient to wear a surgical mask, though it is not required (often poorly tolerated)
  2. We recommend against travel on HFNC if possible. Convert to a nonrebreather option if possible. If travel is needed and conversion is not possible, discuss with infection control (patient should wear a mask during transport).
  3. Reassess daily to assure HFNC is medically indicated, or if the patient might benefit from intubation:
  1. Is there concern for the work of breathing? (accessory muscle use, difficulty speaking, tachypnea)
  2. Is there concern for volumtrauma or barotrauma that could worsen ARDS?
  3. Is HFNC meeting the patient’s oxygenation goals?


  1. Potential benefits of self-proning:
  1. Proning is thought to provide physiologic benefits for patients with COVID infection: it improves recruitment of alveoli in dependent areas of the lungs and it may improve perfusion to ventilated areas, improving V/Q mismatching. Typically proning is used in ventilated ICU patients, however the same benefits may accrue to non-ventilated patients.
  2. Intubated proning: Proning is one of the mainstays of ARDS therapy for intubated patients, showing both 28 day and 90 day mortality benefit in the PROSEVA 2013 trial. In intubated ARDS patients with P/F <150
  3. Self-proning (non-intubated) in non-Covid-19 patient cohorts: ARDS, after lung transplant, and post-surgery. These small studies showed that self-proning was associated with lab, radiographic, or clinical improvement
  1. In one observational study, (Scaravilli et al, J of Critical Care, 2015) 15 patients with pneumonia underwent a total of 43 self-proning procedures Of the 43 procedures, 24 were performed with O2 mask, 1 with HFNC, 11 with helmet CPAP, 7 with NIV., with an average of 3 hours, range 2-8 hours. They found improvement in P/F ratio Pre P/F 127 +/- 49 --> Prone 186 +/- 72 --> Post 141 +/- 64 (p < 0.05). and PaO2 without complications. (“displacement of indwelling catheters, facial edema, pressure sores, pressure neuropathies, compression of nerves, and retinal vessels or vomiting”)
  2. In another limited study of 20 patients (Ding et al, Critical Care, 2020) with ARDS with P/F < 200 requiring NIV or HFNC of at least PEEP of 5 and FiO2 of 0.5 who underwent self-proning for at least 30 minutes, many fewer (45%) required intubation than would have been expected based on previous data (75%)
  1. Use in COVID-19:
  1. In one study (N=24), Covid-19 patients tolerated self-proning for 1 hr (17%, all required intubation within 72 hours), 1 to 3 hrs (21%) or more than 3 hrs (63%). Only 1 of the patients who tolerated proning for more than 1 hr was intubated in 10d follow-up. The only patients with a significant increase in PaO2 were the patients who self-proned for at least 3 hours (74 mmHg to 95 mmHg). This increase in PaO2 was not sustained after re-supination. Back pain was a limiting factor to self-proning (Elharrar et al, JAMA, 2020)
  1. Patient Selection:
  1. Eligibility:
  1. Self-proning can be used on stable patients (on room air or on supplemental oxygen) and as a “rescue” for those who have escalating supplemental O2 requirements.
  2. Multidisciplinary discussion is required with provider, RT, and RN.
  3. Patient must be able to move independently and have the cognitive and physical status to supinate themselves if they become uncomfortable. This includes the ability to prone/supinate while safely managing their supplemental oxygen, IV tubing, SpO2 monitor and other leads and attachments (within reason).
  1. Contraindications:
  1. Absolute:
  1. Inability to independently supinate or pronate safely (see above)
  2. Imminent risk of intubation (see “when to stop self-proning”)
  3. Spinal instability
  4. Facial or pelvic fractures
  5. Open chest or unstable chest wall
  6. Open abdomen
  1. Relative contraindications:
  1. Altered mental status
  2. Nausea or vomiting
  3. NIPPV
  1. Protocol:
  1. RN documentation
  1. RN should document prone/supine in the EPIC flowsheet under “Daily Cares” with every vitals sign check
  2. In addition, RN documents just prior to proning, 1 hr after proning, and then at termination of proning:
  1. Supine/Prone position, patients subjective assessment of their breathing, Sp02 (ABG not required), oxygen device and flow rates, respiratory rate.
  2. The goal is to identify which patients respond to this treatment using objective and subjective criteria
  1. Monitoring
  1. Continuous O2 monitoring is required. If telemetry indicated, EKG leads can remain on anterior chest wall for continuous monitoring; attempt to avoid pressure
  1. Prior to proning
  1. Make plans in advance for toileting, call bell, entertainment, and cellular phone
  2. If possible, place the bed in reverse Trendelenburg (head above feet, 10 degrees) to help reduce intraocular pressure.
  3. Have patient empty bladder
  4. Educate the patient. Explain the procedure and rationale of the intervention to the patient. “Lying on your stomach is what we call prone position. This position can improve your breathing, helping your lungs to expand to get oxygen to the rest of your body. It may help you feel better.”
  5. Arrange tubing to travel towards the top of the bed, not across the patient, to minimize risk of dislodging. Ensure support devices are well-secured to the patient. (Ex. Sleeve over IV access site, position urinary catheter)
  6. Assess pressure areas to avoid skin breakdown and use skin protective devices as needed
  1. Prone position
  1. The patient should lay on their abdomen (arms at sides or in “swimmer” position).
  2. If a patient is unable to tolerate, they may rotate to lateral decubitus or partially prop to the side (in between proning and lateral decubitus) using pillows or waffle cushioning as needed. Ideally the patient should be fully proned rather than on the side as there is currently no data about whether side positioning is beneficial.
  1. Time spent proning
  1. Patient should try proning every 4 hrs, and stay proned as long as tolerated. Proning is often limited by patient discomfort, but they should be encourage to reach achievable goals, like 1-2 hours (or as long as possible).
  2. Patient should attempt to prone at night as tolerated
  3. Our ideal goal is 16 hrs per 24 hours (e.g., 4 times for 4 hours each session) based on common interpretations of the PROSEVA trial (proning of intubated patients, Guerin et al, NEJM, 2013). However, we realize that few (if any) patients will tolerate 16 hrs of proning per 24 hrs.
  1. When to stop awake proning
  1. Patient may choose to stop self-proning at any time
  2. If intubation is within a patient’s goals of care, consider ceasing proning if the patient has an escalating oxygen requirement leading to concern for intubation (e.g. an escalating Venturi mask requirement in 40% - 60% range).
  3. Self-proning can be done while on Venturi mask or Non-Rebreathing Mask (NRB) with multi-disciplinary discussion for safety
  4. For patients who are DNI, it would be reasonable to continue Self-proning up to maximal levels of supplemental O2.

Initial Mechanical Ventilation

Checklist following intubation

  1. Set the initial ventilator settings:
  1. Initiate ARDS ventilation as described below
  2. Determine PEEP and mechanics as described below
  3. Assure adequate sedation as described below
  1. Obtain STAT portable CXR to confirm endotracheal tube location
  1. Prioritize CXR and vent settings over procedures (such as central venous catheter placement) if possible.
  1. Complete the “Mechanical Ventilation with Sedation” orderset in EPIC
  2. Obtain an ABG (preferred) or a VBG within 30 minutes
  1. Calculate P/F ratio from initial post-intubation ABG. Adjust oxygenation as described below
  2. Goal pH 7.20 to 7.45 adjust ventilation as described below

Initial ARDS Ventilation Settings

  1. Set mode to volume control (AC/VC)
  2. Set Initial tidal volume (Vt):
  1. Vt = 6 ml/kg (based on ideal body weight [IBW] from ARDSnet table, see table below)
  1. IBW men (kg) = 50 + 2.3 (height in inches – 60)
  2. IBW women (kg) = 45.5 + 2.3 (height in inches – 60)

  1. Set Initial respiratory rate
  1. Typical starting rates will be 16-24 titrated to goal minute ventilation of 5-8 L/min
  2. Consider starting rates of 24-28 titrated to goal minute ventilation of 8-12 L/min in setting of acidosis (pH < 7.25) pre-intubation
  1. Set an Initial PEEP based on BMI (empirically chosen targets):
  1. BMI < 40: PEEP 5
  2. BMI ≥ 40: PEEP 10
  1. Initial FiO2: 100% on intubation then rapidly wean to SpO2 92-96% (Barrot et al, N Engl J Med, 2020)

Determining PEEP and mechanics

  1. Titrate FiO2 and PEEP for oxygenation
  1. Initiate PEEP based on BMI, per above, and then titrate PEEP and FiO2 to target oxygenation SpO2 92-96% as per the following guidelines:
  1. BMI < 40: titrate PEEP and FiO2 as per the ARDSnet LOW PEEP table

  1. BMI ≥ 40: titrate PEEP and FiO2 as per the ARDSnet HIGH PEEP table

  1. If SpO2 < 92% or > 96% then titrate PEEP and FiO2 according to the ARDSnet table as per BMI
  2. Special consideration: anecdotal reports of COVID-19 patients describe a compliant, highly PEEP dependent phenotype in which PEEP management may not strictly adhere to specified ARDSnet tables (e.g., FiO2 0.4 - 0.5 but does not tolerate PEEP <10)
  3. Avoid elevated plateau pressures (with goal ≤ 30), particularly if using the higher PEEP table. Special cases (e.g., morbid obesity, burns) may need extra diagnostics, such as esophageal balloons, which we do not recommend for routine use given limited resources and infection risk.
  1. Obtain respiratory mechanics:
  1. Plateau pressure (with goal ≤ 30, management below)
  2. Static compliance

Sedation and Ventilator Synchrony

Pain, Agitation, Delirium model

  1. Pharmacologic therapy is chosen to target pain, agitation, and delirium in that order (both assessment and treatment).
  1. Please see the chart below for details, and the BWH Guidelines for Pain Agitation and Delirium in Mechanically Ventilated Patients for full detail (Partners login required)
  1. Strategies to minimize shortages and improve patient care: