Aerosol-Generating Procedures (AGPs)

OVERVIEW

Aerosol-generating procedures (AGPs) are medical procedures that produce minute particles that become suspended in the air (known as aerosols). They are of concern as they potentially increase the transmission risk for pathogens that can spread via aerosols.

  • UK NHS guidance identifies AGPs as procedures as those with a greater likelihood of producing aerosols than coughing (Nestor et al, 2021), however this requirement is not used in most definitions
  • AGPs are also known as aerosol-generating medical procedures (AGMPs).

The concept and classification of AGPs is controversial, however. Some argue that the real issue is one of “aerosol-generating patients” rather than “aerosol-generating procedures” and that the concept of AGPs should be discarded (Hamilton et al, 2021).

HISTORY

As described by Hamilton et al (2021), interest in AGPs arose following the 2003 SARS epidemic.

  • Certain procedures appeared to be (1) associated with higher rates of SARS transmission and (2) theoretically capable of producing aerosols
    • Epidemiological evidence supporting this was “very low quality” (Tran et al, 2015)
    • Evidence supporting the aerolising nature of many of the procedures was also lacking, and often based on the precautionary principle and low quality mechanistic studies (Jackson et al, 2020)
  • Procedures were subsequently dichotomised into AGP (“high risk”) and non-aerosol generating where the risk of infectious aerosols was thought to be minimal. This classification was adopted by the WHO and numerous national and professional bodies around the world.

RATIONALE

In medicine, aerosols (also termed droplet nuclei or respiratory particles) are (Judson and Munster, 2019):

  • minute particles that remain suspended in the air for long periods of time
  • Can be solid or liquid
  • travel beyond 6 ft from the source patient (the distance traditionally used for “droplet” rather than “airborne” transmission)
  • Pass through standard surgical masks

The size cut-off used for aerosol particles varies in the literature and is relevant to aerosol dispersal and particle deposition (Judson and Munster, 2019):

  • <5 um diameter particles are “respirable” in that they can remain suspended in air and pass into small airways and alveoli
  • <20um is sometimes used as a cut-off, as particles of this size may dessicate to form smaller droplet nuclei prior to deposition on surfaces, whereas particles >20um tend not to enter the lower respiratory tract but deposit on surfaces in the upper respiratory tract.
  • This relates to the dichotomy of “large” and “small” respiratory particles that forms the basis of the dominant paradigm of infection control precautions (i.e. “droplet precautions” versus “airborne precautions”).
    • Traditionally, it was thought that large droplets settle rapidly and travel short distances (e.g. <6 feet or <1-2m) whereas small droplets evaporate faster than they settle forming droplet nuclei that may remain suspended and travel longer distances.
    • However, in reality this dichotomy is arbitrary and inaccurate as sneezes and coughs produce multiphase turbulent gas clouds containing clusters of droplets with a continuum of droplet sizes (<1 μm to >100 μm)  (Bourouiba et al, 2020; Tang et al, 2021). 
    •  Droplets of varied sizes can travel up to 8m and may remain suspended in the air for minutes to hours.
    • Numerous factors other than droplet size affect travel distance and rate of deposition (Tang et al, 2021), including:
      • the momentum with which they are expelled, 
      • characteristics of the surrounding air flow (speed, turbulence, direction, temperature and relative humidity)
  • From an aerosol sicence perspective, there is no definite size cut-off for particles to be considered an aerosol, only the requirement that they be suspended in a gas – and particles up to 100 μm diameter may form aerosols in the right conditions (Tang et al, 2021)

Mechanisms for the generation of virus-transmitting aerosols (Morawska, 2006) include:

  • high shear stresses (e.g. from high velocity gas flow) or mechanical disruption (e.g. lung surgery) disrupting the surface tension of virus-laden fluid
  • low temperature (e.g <60°C) evaporation processes where viral material could survive
  • aerodynamic interactions between streams of materials that could intensify or spread new or pre-existing aerosols

Transmission of infection via aerosol has 3 requirements (Jones and Brosseau, 2015):

  • aerosol generation (containing pathogens)
  • environmental viability (of the pathogen in the aerosol)
  • access to target tissue (resulting in infection)

Aerosols can provide the mechanism of transfer for a number of important pathogens (Liu et al, 2020). Hence, AGPs are an infectious risk when performed on patients infected with these pathogens.

PATHOGENS THAT MAY BE SPREAD BY AGPs

Pathogens that may be spread via AGPs are generally those considered to spread by the “airborne route”. They include (Tellier et al, 2019):

  • Coronaviruses (SARS, MERS, COVID19)
  • Ebola
  • Influenza (however, the potential for “airborne” versus “droplet” tranmission remains controversial)
  • Measles
  • Smallpox
  • Varicella zoster (chickenpox)

LIST OF AGPs

The WHO lists the following clinical procedures as AGPs (WHO, 2021):

  • Autopsy procedures
  • Bronchoscopy
  • Cardiopulmonary resuscitation (including chest compressions)
  • Dentistry procedures
  • Manual ventilation (before intubation)
  • Non-invasive ventilation
  • Sputum induction using nebulised hypertonic saline
  • Tracheal intubation
  • Tracheotomy

However, there is no universal consensus as to what constitutes an aerosol-generating procedure. Jackson et al (2020) additionally identified the following procedures as AGPs, based on high level consensus agreement of guidance documents and academic publications in their systematic review:

  • Airway suctioning
  • Breaking closed ventilation systems (intentionally or unintentionally)
  • Chest physiotherapy
  • Coughing
  • Extubation
  • High-flow oxygen therapy
  • High-frequency oscillatory ventilation
  • Nasopharyngeal aspirate
  • Nasopharyngoscopy or laryngoscopy
  • Nebulised or aerosol therapy
  • Tracheostomy procedures

Numerous other procedures have variously been listed as “potential” AGPs, such as thoracic surgery and gastrointestinal endoscopy. Different professional bodies tend to have different procedure lists emphasising procedures relevant to their areas of interest.

Note that some procedures listed as an AGP, such as tracheal intubation, do not produce high velocity gas flow or generate aerosols, rather they put the proceduralist at risk of an exposure to a concomitant “aerosol generating event” (the term used by the Safe Airway Society (Brewster et al, 2020)) such as patient coughing. 

Note that apart from medical procedures, numerous common activities produce aerosols from the respiratory tract (Morawska, 2006). These include:

  • Breathing – especially physical activities that involve vigorous exhalation (e.g. running)
  • Coughing
  • Laughing
  • Singing
  • Sneezing

There is also potential for aerosolising particles from non-respiratory body fluids, for instance from toilet use or wet cleaning indoor surfaces (Morawska, 2006).

PROS AND CONS OF THE AGP CLASSIFICATION

Advantages

  • Identifies potentially high risk procedures and situations for aerosol-mediated transmission of pathogens
  • Allows consideration of mitigation strategies for these procedures/ situations
  • Epidemiological studies of the SARS outbreak suggest that certain AGPs are associated with increased risk of infection transmission (Tran et al, 2015). Similarly, the intubateCOVID study found 1 in 10 HCWs involved in intubation of a patient with COVID19contracted COVID19 in the subsequent weeks (El-Boghdadly et al, 2021)

Disadvantages

  • Lack of a consensus definition or list of AGPs
  • Unclear levels of risk with different AGPs
  • Aerosol generation alone is not sufficient for infection transmission (varies with host susceptibility and nature of the pathogen: threshold pathogen content of aerosols, environmental stability, exposure of target site, and pathogenicity) – furthermore, even if a procedure is not in itself aerosol generating it may still be “high risk” for infection transmission (e.g. due to proximity to a coughing patient)
  • Mechanisms and quantities of aerosols generated by different AGPs are generally poorly understood – some do not actually produce aerosols (e.g. tracheal intubation)
  • The dichotomy between “large” (“droplet spread”) and “small” (“airborne spread”) respiratory particles is arbitrary and inaccurate
  • The concept of AGPs potentially shifts the focus of infection control away from the “aerosol-generating patient”, examples where this is problematic include:
    • when only “droplet precautions” are used by HCWs caring for coughing patients with SARS-CoV-2 when AGPs are not being performed.
    • when unproven mitigation strategies are used for specific AGPs, e.g. “aerosol boxes” for intubation are not effective, make the procedure more slower and difficult, and carry additional safety risks (Begley et al, 2020; Simpson et al, 2020)
  • Stigma associated with a procedure being labelled an AGP may lead to anxiety about performing the procedure or it may be withheld inappropriately (Chui et al, 2022)
  • The AERATOR studies of airway management procedures have found that little or no additional aerosol was generated compared with patient breathing and/or coughing (see below)

EVIDENCE 

General caveats

Morgernstern (2020) has identified numerous important caveats when considering the evidence for AGPs, which are adapted below:

  • Available data is from small studies, with generally low quality study designs and are at risk of bias
  • Mode of transmission or the component of a procedure responsible for transmission is typically unclear
  • Studies may be confounded by severity of illness, in that more severe patients may be more likely to require AGPs and also be more likely to transmit infection (e.g. due to coughing and proximity)
  • Differences in how aerosols are measured (e.g. devices used, variations in baseline measurements, particle number versus distance an exhaled plume travels), and even how they are defined (e.g. particle size) make comparisons difficult
  • Production of aerosols and risk of transmission do not necessarily correlate
  • Transmission risk can be modified by use of PPE and environmental modifiers
  • Most studies focused on SARS, and more recently on SARS-CoV-2

Morgernstern (2020) is further recommended for its evidence-based review of a wide range of AGPs.

Do AGPs increase risk of infection transmission?

Tran et al (2015)

  • a systematic review that identified 5 case-control and 5 retrospective cohort studies that evaluated transmission of SARS to HCWs. 
  • Procedures reported to present an increased risk of transmission included [n; pooled OR(95%CI)]
    • tracheal intubation [n = 4 cohort; 6.6 (2.3, 18.9), and n = 4 case-control; 6.6 (4.1, 10.6)]
    • non-invasive ventilation [n = 2 cohort; OR 3.1(1.4, 6.8)]
    • tracheotomy [n = 1 case-control; 4.2 (1.5, 11.5)] 
    • manual ventilation before intubation [n = 1 cohort; OR 2.8 (1.3, 6.4)]
  • Other intubation associated procedures, endotracheal aspiration, suction of body fluids, bronchoscopy, nebulizer treatment, administration of O2, high flow O2, manipulation of O2 mask or BiPAP mask, defibrillation, chest compressions, insertion of nasogastric tube, and collection of sputum were not significant. 
  • Criticisms of the findings are that the studies included were small, had “vey low quality” (GRADE)  study designs, did not assess use of personal protective equipment (PPE) compliance, did not assess route of transmission, and may not be generalisable beyond SARS transmission.
  • This study informed many subsequent lists of AGPs, though many of the procedures not found to have an association were still included (e.g. considered “potential” AGPs).

IntubateCOVID study (El-Boghdadly et al, 2021)

  • prospective international multicentre cohort study recruiting healthcare workers (n=1718 from 503 hospitals in 17 countries) participating in tracheal intubation of patients with suspected or confirmed COVID19 (5148 intubation episodes)
  • primary endpoint was the incidence of laboratory-confirmed COVID19 diagnosis or new symptoms requiring self-isolation or hospitalisation after a tracheal intubation episode. This was reported by 10.7% HCWs over a median follow-up of 32 days.
  • This study showed a high rate of COVID19 transmission to HCWs following involvement in intubation. The rate was likely 10-100-fold greater than community transmission. However, what component of intubation (if any) was responsible for infection or whether aerosols were involved is uncertain.

Do airway management and oxygen delivery devices produce aerosols?

AERATOR studies of airway management and oxygen delivery device

  • The AERATOR group have performed a series of studies aimed at measuring aerosol emissions for a number of procedures, with key findings listed below
  • Tracheal intubation (Brown et al, 2021)
    • Real-time, high-resolution environmental monitoring of aerosol particle emissions  was performed in ultraclean ventilation operating theatres during tracheal intubation and extubation sequences
      • Background particle count was very low (0.4 particles/L) 
      • a volitional cough was used as a positive reference control (mean concentration, 732 particles/L, n = 38). 
    • Tracheal intubation including facemask ventilation produced very low quantities of aerosolised particles (mean concentration, 1.4 particles/L, n = 14, p < 0.0001 vs. cough). 
    • Tracheal extubation, particularly when the patient coughed, produced a detectable aerosol (21 particles/L, n = 10) which was 15-fold greater than intubation (p = 0.0004) but 35-fold less than a volitional cough (p < 0.0001). 
    • The study did not support the classification of tracheal intubation as an AGP, nor extubation as a “high risk” AGP.
  • Suraglotic airway (SGA) use (Shrimpton et al, 2021)
    • Aerosol emissions were recorded for insertion and removal of 12 SGAs in patients in an operating theatre
    • SGA insertion and removal had aerosol emission measurements that were no different to baseline and <4% of those recorded from patient coughing
  • Face-mask ventilation (FMV) (Shrimpton et al, 2021)
    • Aerosol emissions were recorded for 11 patients in an operating theatre during tidal breathing and were found to be markedly above baseline
    • Recordings during FMV were similar to baseline, and even with an intentional leak were markedly less than for tidal breathing.
    • Aerosol emissions for FMV, even with an intentional leak, for 10 times lower than for a patient cough
  • Continuous Positive Airway Pressure (CPAP) and High Flow Nasal Oxygen (HFNO) (Hamilton et al, 2021)
    • Aerosol emissions were measured in healthy volunteers (n=25 subjects; 531 measures)
    • CPAP (with exhalation port filter) produced less aerosol than breathing, speaking and coughing (even with large >50 L/min face mask leaks).
    • HFNO was associated with aerosol emission, but it was from the machine and unlikely to carry virus particles.
  • Criticisms of AERATOR study group studies include:
    • Uncertainty regarding type of aerosol participle detector that should be used or the size of particles that should be targetted
    • Measurements performed in small number of cases
    • Some results may have been affected by the high number of air exchanges in te operating theatre (Dhillon et al, 2021)
    • Aerosols may have been underestimated due to sampling strategy used including inlet location relative to the patient and the sampling rate of air for measurement  (Dhillon et al, 2021)
    • Do not measure the risk of infection transmission

Airway management during elective surgery (Dhillon et al, 2021)

  • Aerosols were measured (482,960 data points) using 3 different techniques in a standard positive pressure operating theatre for 3 patients undergoing elective endonasal pituitary surgery
    • FMV (200-300 times), tracheal tube insertion (30-50 times) and cuff inflation (30-50 times) generated small particles above background noise that remained suspended in airflows and spread from the patient’s facial region throughout the confines of the operating theatre. 
    • Patient coughing, noted during extubation, generated 15-125 times as many small particles as background noise.
    • Unlike the AERATOR study group, an Ultraclean Ventilator System was not in use in the operating theatre raising the possibility that aerosols from alternate sources may have been measured (Shrimpton et al, 2022)
  • The authors concluded that these airway management procedures were AGPs, due to the marked increase above baseline. This contradicts the findings of the AERATOR group study on tracheal intubation (for unclear reasons, see criticisms above). However, compared with coughing, only FMV was associated with more particles generated (not other aspects of intubation or extubation). Later the authors collaborated with the AERATOR group on their subsequent FMV study (Shripton et al, 2022), described above, which found minimal aerosol emissions even with an intentional leak.

Other studies of oxygen delivery devices

  • Wilson et al (2021)
    • measured aerosol emissions from ten healthy subjects during six respiratory activities (quiet breathing; talking; shouting; forced expiratory manoeuvres; exercise; and coughing) and compared them with three respiratory therapies (HFNO and single or dual circuit non-invasive positive pressure ventilation (NIPPV)). Activities were repeated while wearing facemasks. 
    • Findings:
      • When compared with quiet breathing, exertional respiratory activities increased particle counts 34.6-fold during talking and 370.8-fold during coughing (p < 0.001). 
      • High-flow nasal oxygen at 60 L/.min increased particle counts 2.3-fold (p = 0.031) during quiet breathing. 
      • Single and dual circuit non-invasive respiratory therapy at 25/10 cm H2O with quiet breathing increased counts by 2.6-fold and 7.8-fold, respectively (both p < 0.001). 
      • During exertional activities, respiratory therapies and facemasks reduced emissions compared with activities alone.
  • Gaeckle et al (2020)
    • The size and number concentration of respiratory particles (0.37um to 20um) generated from healthy participants were measured when different oxygen therapy modalities were used: nonhumidified nasal cannula, face mask, heated and humidified HFNC, and NIPPV.
    • Findings:
      • Median particle concentration ranged from 0.041 to 0.168 particles/cm3. 
      • Median diameter ranged from 1.01 to 1.53 μm. 
      • Cough significantly increased the number of particles measured. 
      • Measured aerosol concentration did not significantly increase with the use of either humidified HFNC or NIPPV or other oxygen delivery modality. This was the case during normal breathing, talking, deep breathing, and coughing.
  • As with the AERATOR study group findings, these studies found that respiratory therapies produced substantially less aerosols than respiratory activities such as coughing and exertional breathing

A rapid review of aerosol generating procedures (AGPs) (NHS, 2022)

  • The available evidence to support the removal of any procedures currently included on the UK AGP list was assessed.
  • The authors advised consideration of the removal of the following procedures from the UK AGP list:
    • tracheal intubation and extubation (in anaesthetised patients)
    • FMV
    • NIV including CPAP
    • HFNO

Does cardiopulmonary resuscitation (CPR) produce aerosols?

Different guidelines suggest CPR is aerosol generating, others suggest not. Some include airway management procedures as part of CPR (discussed above, though studies were not in the context of cardiac arrest patients). This section focusses on defibrillation and chest compressions.

Couper et al (2020)

  • A systematic review of 11 studies: two cohort studies, 1 case control study, 5 case reports, and 3 manikin randomised controlled trials. 
  • Findings:
    • no direct evidence that chest compressions or defibrillation either are or are not associated with aerosol generation or transmission of infection. 
    • manikin studies found that donning of PPE delays treatment delivery. 
  • Evidence certainty was low for all outcomes.

PRECAUTIONS FOR AGPs

Precautions against aerosol-borne pathogens should be taken when caring for (potentially) infected patients regardless of whether an AGP is being performed. 

  • the risk of transmission from patient activities such as coughing is likely as high or higher as from an AGP. 
  • additional AGP-specific precautions for HCWs are often warranted as they require time in proximity to an infectious patient or may interfere with other risk mitigation strategies (e.g. PPE breach during CPR)

Mitigation strategies

Pope et al (2022) identify 4 categories of mitigation strategies for AGPs:

  • Risk stratification
    • Risk assess each patient
  • Environment
    • Single room
    • Negative pressure
    • Minimal number of personnel
    • Doors closed for set period of time after the procedure
    • High rate of air exchanges in the room (this is the only environmental measure that protects HCWs in the room, rather than just limiting spread to those outside the room)
    • CDC recommendations:
      • ICU room: 6 total air exchanges per hour
      • Operating theatre: 15 total air exchanges per hour
  • Airborne PPE (in addition to Contact PPE)
    • Face mask (FFP3 or N95)
    • Water-resistant gown 
    • Eye protection (face shield/ visor/ goggles)
    • Gloves
  • Procedure
    • Performed by the most qualified operator available
    • Consider alternatives to performing the procedure
    • Consider procedure modifications to decrease risk (e.g. video laryngoscopy instead of direct laryngoscopy)

Risk matrix approach

Hamilton et al (2021) have argued convincingly that the concept of AGPs should be discarded, given the flaws in the classification and that activities like coughing produce aerosols many magnitudes higher. Instead, they suggest the use of risk matrix for patient care, such as this for SARS-CoV-2 transmission:

  • Patient risk (the most important risk factor)
    • Risk based on symptoms (e.g. coughing, high respiratory exertion), diagnostic test  positivity, vaccination status, and immunocompetence. 
  • Duration of exposure
    • length of time required to be in close proximity increases risk of transmission.
  • Health-care practitioner risk from COVID-19
    • Age, sex, body mass index, comorbidities, vaccination status.
  • Proximity risk
    • Activities that require close contact are higher risk – e.g. mouth care, throat examination, intubation
  • Environmental risk
    • Ventilation, air exchanges, humidity, temperature

CONCLUSION

AGPs are controversial, as the concept and classification lacks universal agreement and has many flaws.

  • For pathogens that can be spread by aerosols – such as SARS-CoV-2 – mitigation strategies should be used to decrease the risk of transmission for any close contact, regardless of whether an AGP is performed.
  • Mitigation strategies should include risk stratification, use of appropriate PPE, modification of the environment, and modification of the procedure where appropriate. 

REFERENCES

FOAM and web resources

Journal articles and guidelines

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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