Inpatients

In inpatients suspected of having COVID-19, a nasopharyngeal or salivary specimen should be obtained rst. Universally, organizations recommend against the use of bronchoscopy as the rst line testing modality in those with suspected COVID-19. The AABIP/CHEST guidelines recommend that in the setting of severe or progressive disease requiring intubation with additional testing is needed, it is appropriate to obtain a lower respiratory specimen to establish a diagnosis of COVID-19 or other diagnosis which would change management [6]. Notably, this is an ungraded statement based on expert consensus from September 2020, prior to vaccine availability as well as prior to availability of several COVID-19 speci c treatments. Initial data at that time suggested that bronchoalveolar lavage does have an increased sensitivity of 93%, compared to 72% in sputum and 63% in nasal swabs [24].

Universal Screening of Asymptomatic

Patients

In both inpatients and outpatients requiring bronchoscopy without a clinical concern for concomitant COVID-19 infection, multiple society recommendations are for a COVID-19 test within 72 h of the procedure when community transmission of COVID-19 is present [6, 7]. Additionally, consideration of repeating screening questions within 24 h of the procedure such as asking about symptoms, contacts, and travel history could be useful [7]. Again, as positivity rates, variant strains, and vaccination rates changed, there have been changes in data regarding the utility of testing. After initial uncertainty about transmission rates among asymptomatic persons, by late 2020 and early 2021, it was apparent that more than 50% of transmissions were among this population, con rming the need for public health measures to control the pandemic [25]. This veri ed the practice of many healthcare systems of screening all patients in an effort to prevent patient harm of operative complications related to COVID-19 and decrease exposure

and transmission to healthcare personnel [26]. Vaccination decreases asymptomatic infections found on pre-­procedure screening, from 3.2% to 1.4% in a large study in the United States [27]. Indeed, the very idea of community transmission and the need for universal testing is dif cult to assess as changes in viral strain and differences in population vaccination status vary throughout the pandemic.

COVID-19 Clearance

Current RT-PCR tests have been demonstrated to detect RNA for prolonged periods of times, but do not automatically correlate with infectivity. Current recommendations from the American Society of Anesthesiologists (ASA) and Anesthesia Patient Safety Foundation (APSF), based on the NIH/CDC guidelines, for clearance recommend [28]:

•\ Classi cation by symptoms:

––Asymptomatic.

––Mild to moderately symptomatic (no pneumonia or hypoxemia).

––Severe or critical illness (pneumonia, hypoxemic respiratory failure, or shock).

•\ Classifying severely immunocompromised patient separately, despite presence or absence of symptoms.

•\ In asymptomatic patients who are not severely immunocompromised, isolation and transmission-­based precautions may be discontinued after a minimum of 10 days from their rst positive viral test.

•\ Discontinuing isolation and other transmis- sion-based precautions in mild to moderate patients who are not severely immunocompromised when:

––10 days have passed since symptom onset.

––At least 24 h have passed since last fevers without antipyretics.

––Symptoms are improved.

•\ In those with severe or critical illness or anyone who is severely immunocompromised, the CDC recommends discontinuing isolation and other symptom-based precautions when

––At least 10, and up to 20, days have passed since rst symptoms.

––At least 24 h have passed since last fevers, without use of antipyretics.

––Symptoms are improved.

These recommendations should be integrated with information of other risks, especially pulmonary complications post-operatively, in decision making. A large, multi-country collaborative suggests that when possible, surgery should be delayed up to 7 weeks following COVID-19 and even longer in patients with persistent symptoms at 7 weeks [17]. There is now evidence that those requiring hospitalization for COVID-19 have residual changes in pulmonary function and radiographs for up to 6 months [29]. Using these data, the ASA/APSF guidelines suggest the following wait times for surgery:

•\ Four weeks for asymptomatic patients or recovery from only mild, non-respiratory symptoms.

•\ Six weeks for a symptomatic patient who did not require hospitalization.

•\ Eight to ten weeks for a symptomatic patient who is diabetic, immunocompromised, or hospitalized.

•\ Twelve weeks for a patient admitted to the ICU due to COVID-19.

The ASA/APSF acknowledges that these guidelines cannot be de nitive and, again, each patient’s perioperative risk assessment should be individualized [28]. Indeed, a side-by-side comparison of these recommendations with the triage levels and procedural timing recommended by the SAB reveals contrasting recommendations. The de nition of severe immunocompromised is also variable, but usually includes those undergoing chemotherapy, those within 1 year of a stem cell or solid organ transplant, those with HIV and a CD4 count <200, those with combined primary immunode ciency disorder, and those treated with prednisone >20 mg/day for more than 14 days. Though these are the most recent guidelines from the ASA/APSF, at the time of this writing the CDC has again updated their guidelines,

with those who are asymptomatic and not moderately or severely immunocompromised isolation could be discontinued at 5 days from rst positive test. This certainly highlights the continued lack of data around safety of procedures in those with recent COVID-19 and the need for a thoughtful approach by a multi-­disciplinary team that individualizing a plan for patient needs and urgency of a procedure.

Bronchoscopy Procedure

in COVID-­19 Respiratory Failure

The role of bronchoscopy in any mechanically ventilated patient is variable by disease pathology, clinical parameters, and acuity. Data suggest bronchoscopy in COVID-19 patients requiring mechanical ventilation is performed more often than mechanically ventilated patients with ARDS due to other causes, but is highly institution speci c, with many institutions avoiding all aerosol generating procedures, including bronchoscopy and many airway clearance treatments, in this population. For example, early in the pandemic in NYC, approximately 33% of intubated patients at one institution underwent bronchoscopy [13]. This is in contrast with the majority of other hospitals globally, where bronchoscopy in COVID-­19 patients was not performed due to a combination of the overall overwhelming clinical burden on the healthcare systems and the fear of provider exposure [14, 15].

The potential bene ts of bronchoscopy in COVID 19 for those requiring mechanical ventilation appear to fall into two categories: airway clearance of mucus and identi cation of secondary pathogens [16, 29–31]. Early bacterial co-­infection is thought to affect up to 30% of patients with COVID-19 respiratory failure within the rst 24 h of ventilation and bacterial pneumonia at any point during mechanical ventilation is associated with worse outcomes, with different pathogens identi ed more commonly at different time courses in COVID-19 patients [32, 33]. Fungal pneumonia, usually aspergillus species, has also be recognized as a pathogen in critically ill COVID patients and is associ-

ated with higher mortality [34]. It should be noted that the SAB guidelines recommend as 1C (strong recommendation/low quality evidence) bronchoscopy on inpatients with suspected or known COVID-19 be avoided, including routine toileting bronchoscopy. They use a 2C (weak recommendation/low quality evidence) that bronchoscopy be considered in selected situations including evaluation for alternative or co-infections, complication evaluation, and therapeutic aspiration [7].

When performing bronchoscopy in COVID 19 positive patients on the ventilator, the logistics and preparation is also institution dependent; variations include use of neuro-muscular blockade pre-procedure to minimize coughing, positioning including if patients who are in prone position are considered candidates for bronchoscopy, ventilator manipulations including circuit clamping, apnea for parts or all of the procedure, experience level of the bronchoscopist, and amount of fuid instilled for bronchoalveolar lavage. Identifying a strategy concordant with institution speci c policies is a must for all proceduralists, and all team members should be comfortable with the preparation and plan.

Our approach to bronchoscopy in ICU patients with active COVID-19 includes the following: use of PPE according to the societal guidelines discussed above and illustrated in Fig. 9.2. Pre-­ procedure discussion with the proceduralist, bedside nurse, respiratory therapist and other team members should take place outside the patient room prior to the procedure, with goals of identifying any potential needs, including accounting for all equipment that might be needed, and any anticipated barriers. All equipment should be accounted for prior to entering the room. If available, a negative pressure room should be used. The team should be thoughtful to minimize post-­ procedure bedside care, which includes making sure continuous infusion medications supply is adequate and any lab draws are done prior to the procedure. Procedural timeout should be performed outside the room and only necessary staff should be in the room. At our institutions we’ve found a single attending physician provider, as the most experienced provider, is usually suf-cient with additional staff available outside the room if needed. A disposable bronchoscope should be used if available. The patient should be preoxygenated with 100% FIO2. If the team

Pre-procedure

•Minimize staff exposure: most experienced bronchoscopist; RN and RT only if necessary

•Anticipate needs including:

•PPE

•Medications

•Procedure & sampling equipment (disposable if possible)

•Emergency equipment

•Proper donning of PPE

•Assure negative pressure room with adequate air exchanges and pressure differential

•Consent/procedural timeout outside of room

•Review responses to adverse events

Intra-procedure

•Set up all equipment before disrupting ventilator circuit

•Preoxygenate patient with 100% FIO2

•If neuromuscular blockade is planned, give two minutes prior to initiation of bronchoscopy

•Place sampling container inline with scope and suction

•Minimize ventilator circuit breaks:

•Apneic bronchoscopy OR

•Disconnect ventilator inspiratory limb and clamp endotracheal tube prior to inserting bronchoscope, reconnect after bronchoscope inserted

Post-procedure

•Minimize circuit breaks

•Restart ventilation if performed apneic OR

•Clamp endotracheal tube and disconnect inspiratory limb prior to removing bronchoscope

•Minimize staff exposure: adjust medication drips, refresh empty IV bags, and collect other labs prior to leaving room

•Wipe non-disposable equipment being removed from room with antiviral wipe

•Proper doffing of PPE

•Appropriate handling of specimens per laboratory protocol

has decided the use neuromuscular blockade, it should be given approximately 2 min prior to initiation of bronchoscopy and the team should wait for complete ventilator synchrony to begin the procedure. The bronchoscope should be lubricated, connected to suction, and inserted into the bronchoscopy endotracheal tube adaptor prior to procedure start. If there is a plan to collect specimens, the collection container, such as a Lukens’s trap, should be put in-line pre-procedure. To minimize aerosolization, the existing endotracheal tube should be clamped and the ventilator paused or the inspiratory limb disconnected. The bronchoscope and adaptor should be inserted and connected, the endotracheal tube unclamped, and ventilation resumed unless the procedure is being performed apneic. If the bronchoscopy is for specimen collection for secondary infectious workup, a brief inspection may be warranted but otherwise the lobe or segment of interest should be lavaged and specimen collected in quick succession to minimize overall scope time. Aerosol minimizing precautions should then be performed in reverse: the bronchoscope should be withdrawn into the proximal endotracheal tube which is then clamped below; with the ventilator paused or disconnected, the bronchoscope and adaptor can be removed from the circuit. If there is a concern for de-recruitment or high potential for post-procedure hypoxemia, a higher FIO2 should be considered to be kept in place after the proceduralist leaves the room to minimize staff having to enter to adjust ventilator settings. Remote management of the ventilator can also be considered if available.

Special considerations in this population include when there is a need for bronchoscopy for airway clearance. Minimal data exist for success rates of use of mucolytics such as DNAse and N-acetyl cysteine, though we have used each of these with some success in those with thick and/or copious secretions. Clot removal with cryotherapy for pulmonary hemorrhage has been successful for multiple patients with COVID-19 with restoration of ventilation or oxygenation as well as radiographic improvement [13, 15]. Using extensive cryotherapy without exposing the room to aerosols from the ventilator is more

challenging than simple bronchoscopy with lavage. Similarly, bronchoscopy in those with tracheostomy tubes instead of oral or nasal endotracheal tubes are unable to have a fully closed circuit throughout due to the inability to clamp the tube. Complete neuromuscular blockade and disconnection at end expiration can be considered as a substitute.

Teams should be prepared with a plan for when there is a breach of PPE during a bronchoscopy or other aerosol generating procedure. The procedure should be immediately terminated if possible; if not possible another proceduralist should be prepared to immediately take over. Prior statements recommend isolation of the exposed providers, but have not been updated since vaccinations became available [7]. Post-exposure symptom monitoring is a must and testing should be deferred to institutional policies and the infection control team at the institution.

There is limited data around bronchoscopy outside of the ICU in patients on mechanical ventilation for COVID-19, but similar precautions should be taken. If using an operating room or procedure suite, ideally negative airfow should be maintained and everyone in contact with the patient should wear appropriate PPE. Appropriate post-procedure time should be allowed to diminish any residual droplets to remain before another case. The use of open ventilation circuits, such as those used with rigid bronchoscopy or jet ventilation, should not be used unless no alternative procedural or ventilation strategy exists.

Bronchoscopy intheNon-intubated COVID-19 Patient

The same precautions should be taken in regard to PPE around bronchoscopy in the non-­ intubated patient with COVID-19. Triage strategies as noted above should be utilized, notably the SAB recommends bronchoscopy be performed within 2 weeks for those with lung nodules suspicious for early-stage cancer, a nodule or mass with adenopathy needing staging, or known lung cancer with possible progression of disease when bronchoscopy would alter the treatment

course [7]. Optimization of the ventilation and oxygenation strategy have to be more carefully weighed in non-intubated patients positive for COVID-19: avoiding exposure of additional staff such as an anesthesiologist and anesthesia team can be bene cial overall but the bronchoscopist also has to balance the risk of respiratory failure and the need for emergency staff entrance, putting those staff at risk of inadequate time to don PPE. Given the increase in aerosol generation in the non-­intubated patient with COVID-19 and the decreased life-threatening nature of speci cally identi ed co-infections, we in general defer bronchoscopy for suspected usual typical or atypical organisms, especially in the immuno-intact host. The role of bronchoscopy in those non-intubated patients with COVID-19 who are immunosuppressed, such as those status post solid organ or stem cell transplant or those with severe neutropenia, the bene t of targeted therapy has to be weighed again the risk of patient decompensation and staff exposure. Depending on currently circulating strains and population vaccination status, this risk: bene t ratio is situationally dependent for both inpatients and outpatients.

Bronchoscopy inPatients with Persistent Radiographic Abnormalities After COVID-19

CT abnormalities in survivors of COVID-19 are common. Seventy percent of CT scans were abnormal in COVID-19 ARDS survivors at 3 months post-hospitalization, with reticularndings in 49% and brotic patterns in 21% [35]. This appears to still be within a convalescence period, with only approximately a third of similar patients demonstrating changes at 6 months withndings including consolidation, opaci cation, reticulation, and brotic-like changes including traction bronchiectasis and honeycombing. Age and illness severity metrics during acute illness appear to correlate with presence and severity of radiographic ndings [36]. Those with broticndings have been shown to be persistent and correlate with pulmonary function test abnormalities at 12 months post-recovery [37]. There are cur-

rently no guidelines for the utility of bronchoscopy in these patients, especially given the lack of available treatment for brotic post-­COVID ARDS. Other radiographic ndings include that of organizing pneumonia (OP), with one study showing approximately 5% of hospitalized survivors with this nding on CT done 6 weeks after hospitalization with higher variability than thebrotic patients in the initial level of illness. It has also been demonstrated that OP treated with corticosteroids can result in a robust symptom and radiographic response [38]. Given the potential for treatment and the overlap of OP with infectious pneumonia such as post-viral bacterial pneumonia, there may be a role for bronchoscopy in select patients. Indeed, if co-­existing infection, such as post-viral bacterial or fungal infection, is suspected, it may be reasonable to pursue bronchoscopy after suf cient time has passed per the guidelines noted above, or sooner if clinical ben- e ts warrant [6–12].

Specimen Handling, Equipment

Processing, and Room Turnover

Specimens sent for SARS-CoV-2 testing should include at least 2–3 mL of fuid and placed in a labeled sterile, dry container. They must be processed in an appropriate laboratory: routine viral testing/staining/examination for SARS-CoV-2 can be assessed in a biosafety level 2 facility [39]. Disposable equipment, including bronchoscopes, should be used whenever possible [6, 7]. Reusable bronchoscopy equipment can be processed with standard cleaning followed by high-level disinfection. There are no current recommendations supporting the use of additional cleaning maneuvers, though staff should wear full PPE and be appropriately trained and experienced [6, 40]. According to one study SARS-CoV-2 can remain aerosolized for up to 3 h and is viable on plastic and stainless-steel surfaces for up to 72 h [41]. Therefore, prior to bronchoscopy, the turnover of the procedure room and patient recovery process should follow pre-establish protocol. Institutional infection control teams should dictate this process, which is dependent on the ventilation capa-