A quantitative evaluation of aerosol generation during tracheal intubation and extubation

Summary The potential aerosolised transmission of severe acute respiratory syndrome coronavirus‐2 is of global concern. Airborne precaution personal protective equipment and preventative measures are universally mandated for medical procedures deemed to be aerosol generating. The implementation of these measures is having a huge impact on healthcare provision. There is currently a lack of quantitative evidence on the number and size of airborne particles produced during aerosol‐generating procedures to inform risk assessments. To address this evidence gap, we conducted real‐time, high‐resolution environmental monitoring in ultraclean ventilation operating theatres during tracheal intubation and extubation sequences. Continuous sampling with an optical particle sizer allowed characterisation of aerosol generation within the zone between the patient and anaesthetist. Aerosol monitoring showed a very low background particle count (0.4 particles.l−1) allowing resolution of transient increases in airborne particles associated with airway management. As a positive reference control, we quantitated the aerosol produced in the same setting by a volitional cough (average concentration, 732 (418) particles.l−1, n = 38). Tracheal intubation including facemask ventilation produced very low quantities of aerosolised particles (average concentration, 1.4 (1.4) particles.l−1, n = 14, p < 0.0001 vs. cough). Tracheal extubation, particularly when the patient coughed, produced a detectable aerosol (21 (18) l−1, 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 does not support the designation of elective tracheal intubation as an aerosol‐generating procedure. Extubation generates more detectable aerosol than intubation but falls below the current criterion for designation as a high‐risk aerosol‐generating procedure. These novel findings from real‐time aerosol detection in a routine healthcare setting provide a quantitative methodology for risk assessment that can be extended to other airway management techniques and clinical settings. They also indicate the need for reappraisal of what constitutes an aerosol‐generating procedure and the associated precautions for routine anaesthetic airway management.


Summary
The potential aerosolised transmission of severe acute respiratory syndrome coronavirus-2 is of global concern. Airborne precaution personal protective equipment and preventative measures are universally mandated for medical procedures deemed to be aerosol generating. The implementation of these measures is having a huge impact on healthcare provision. There is currently a lack of quantitative evidence on the number and size of airborne particles produced during aerosol-generating procedures to inform risk assessments. To address this evidence gap, we conducted real-time, high-resolution environmental monitoring in ultraclean ventilation operating theatres during tracheal intubation and extubation sequences. Continuous sampling with an optical particle sizer allowed characterisation of aerosol generation within the zone between the patient and anaesthetist. Aerosol monitoring showed a very low background particle count (0.4 particles.l À1 ) allowing resolution of transient increases in airborne particles associated with airway management. As a positive reference control, we quantitated the aerosol produced in the same setting by a volitional cough (average concentration, 732 (418) particles.l À1 , n = 38). Tracheal intubation including facemask ventilation produced very low quantities of aerosolised particles (average concentration, 1.4 (1.4) particles.l À1 , n = 14, p < 0.0001 vs. cough). Tracheal extubation, particularly when the patient coughed, produced a detectable aerosol (21 (18) l À1 , 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 does not support the designation of elective tracheal intubation as an aerosolgenerating procedure. Extubation generates more detectable aerosol than intubation but falls below the current criterion for designation as a high-risk aerosol-generating procedure. These novel findings from realtime aerosol detection in a routine healthcare setting provide a quantitative methodology for risk assessment that can be extended to other airway management techniques and clinical settings. They also indicate the need for reappraisal of what constitutes an aerosol-generating procedure and the associated precautions for routine anaesthetic airway management.

Introduction
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and associated coronavirus disease 2019    [2,3]. This direct droplet and indirect contact transmission are considered the predominant modes of spread of SARS-CoV-2, providing the rationale for physical distancing and hand hygiene as primary measures to reduce the incidence of COVID-19.
The extent to which SARS-CoV-2 is transmitted by the airborne route is a controversial topic [3][4][5][6]. Aerosolised particles (typically considered to be < 20 µm in diameter and particularly those of < 5 µm) may transmit infection by deposition on respiratory epithelium and can potentially transit the full extent of the respiratory tract. It is also feared that these small particles may remain airborne for long periods and may be carried far from the site of origin by air currents. The risks from aerosols and optimum methods of preventing transmission are under active debate [7][8][9][10]. To minimise airborne transmission of SARS-CoV-2 to healthcare workers, specific patient care activities have been designated as aerosol-generating procedures.
Tracheal intubation and extubation, manual ventilation via facemask and respiratory tract suctioning are all designated as aerosol-generating procedures [11][12][13]. Many organisations, including the World Health Organization and the public health bodies of the UK, have recommended that those undertaking these aerosol-generating procedures wear airborne precaution PPE consisting of a fitted facepiece (FFP3 or NR95), a long sleeved, fluid-resistant gown, gloves and eye protection [1,13].
The quantitative evidence base for these guidelines is weak and the relative magnitude of risk for each aerosolgenerating procedure is unknown [3,11]. The evidence for this designation is largely based on retrospective cohort and case-controlled studies of transmission during the severe acute respiratory syndrome (SARS) pandemic in 2003 [12,14]. A systematic review of these studies concluded that tracheal intubation was associated with a significant increase in risk of disease transmission but categorised the quality of available evidence as "very low quality based on GRADE" and identified that "a significant research gap exists in the epidemiology of the risk of transmission of acute respiratory infections from patients undergoing aerosol generating procedures to healthcare workers, and clinical studies should be carefully planned to address specific questions around the risks of transmission in these settings" [12]. An attempt to provide such evidence employed aerosol sampling traps placed in the vicinity of patients with H1N1 influenza during periods of hospital care, including some with aerosol-generating procedures, but this large study did not clearly demonstrate an increased risk above background of detecting virus RNA in the air [15]. There is still no quantitative evidence of increased aerosol generation from the designated aerosolgenerating procedures, which likely relates to the challenge of obtaining such measurements in routine healthcare settings.
When considering the risk of transmission of SARS-CoV-2, it is helpful to reflect on the definition of an aerosolgenerating procedure that has been expressly stated as "aerosol generating procedures are considered to have a greater likelihood of producing aerosols compared to coughing." [16]. There is a comparatively large quantitative evidence base around aerosolised particle generation by coughing from laboratory-based investigations with sizes ranging from visible droplets to submicron particles [17][18][19][20]. Given the uncertain balance of potential risks and benefits associated with the protective strategies put in place to limit viral transmission, it is important to quantitatively assess the degree to which individual aerosolgenerating procedures generate aerosolised particles. In this study, we have quantitated airborne particle emission in real-time during tracheal intubation and extubation, using particle analysis instruments in a working operating theatre environment and compared this with volitional coughs as a reference.

Methods
A prospective environmental monitoring study was conducted to quantitate the airborne particle size For recordings during tracheal extubation, the level of anaesthesia was lightened, spontaneous breathing allowed  . When plotted on the same scale as the cough (b) then this looks essentially flat and when shown on a ten-fold expanded scale below it can be seen that it is not significantly different to baseline as the confidence intervals always span zero (mean AE 95%CI). (c) Extubation recordings from each patient (n = 10) plotted as the average and individually as rows on heat map of number concentration of particles (lower, on same scale as b). This showed sporadic aerosol events (red, ringed) after cuff deflation set on a low baseline level of particles. The average concentration of aerosol shown above was low overall (mean AE 95%CI). (d) The extubation cough events (n = 5) had a similar aerosol particle size distribution to volitional coughs with a predominance of diameters < 1 µm (mean AE SD). (e) The extubation coughs were of a smaller magnitude than the volitional coughs (particle number concentration profile shown overlaid, mean AE 95%CI). A more nuanced picture is seen during the tracheal extubation sequence where aerosol concentration was greater than that seen with intubation but substantially less than a single cough. The total number of expectorated airborne particles (over a 5-min period) was similar to a single volitional cough. Indeed, a cough event was noted clinically in 50% of extubations and this was frequently detected as an aerosol spike. These extubation coughs produced a similar particle size distribution but there were fewer airborne particles than with volitional coughs (approximately 25%). Extubation cough aerosol was also transient and only detectable for approximately 5 s. Therefore, it would appear that aerosol generation during extubation with a cough is quantitatively different from extubation without a cough. Although a cough at extubation may be interpreted as a positive sign signalling the return of protective airway reflexes, it is likely to increase the risk of aerosolised particle generation. Therefore, mitigation strategies should be considered to reduce the risk of coughing and exposure to aerosols. As sampling showed much reduced particle numbers behind the patient's head compared with above their airway, clinician exposure could be reduced by the simple expedient of standing behind the patient's head (as is conventional) and, thus, out of the direct stream of any potential cough plume. Coughing on extubation could also be minimised by modifying the anaesthetic technique in higher risk patients [21].
The combination of monitoring within an ultraclean ventilation theatre and the use of a highly sensitive optical particle sampler has afforded sufficient resolution to quantitate aerosol generation in real time during anaesthetic delivery. To put this in context, it is worth noting that we are unaware of any previous recording of aerosol generated even by coughing in a routine healthcare environment as this normally requires highly specialised and controlled laboratory conditions [17][18][19][20]. The ultraclean laminar flow ventilation system theatre had a very low level of airborne particles (0.4 l À1 ); in comparison the baseline aerosolised particle concentration in a nearby nonlaminar theatre was more than 3 orders of magnitude higher Importantly, it should be acknowledged that we are unable to make any conclusion about the risk of actual SARS-CoV-2 transmission as aerosol generation is still only a presumed risk-factor and particle number concentration is a plausible but unproven surrogate measure of that infection risk. We have presented our data as mean particle concentration during the event, maximum concentration recorded during the epoch and total numbers of detected airborne particles and note that there is no available evidence to indicate which measure will prove to be the best surrogate measure of infection risk [3]. Other dimensions that are likely to be important are the size distribution of the aerosolised particles (which influences their airborne transport and ability to be carried into the respiratory tract), the total volume of expectorate (which can be derived if assumptions about sphericity and composition are made) and the concentration of live virions within the particles (not measured here). Each measure has limitations, but we consider that the average concentration over time gives the best estimate of the relative exposure smoothed over the at-risk period during which particles may be inhaled or deposited on mucous membranes. We note that the peak concentration is likely to overestimate the risk; for example, a single particle detected in a 1-s time bin during an intubation sequence (5-min period of recording) would correspond to a maximum of 60 particles.l À1 (with 1 l.min À1 air flow through the particle detector). However, this is probably better represented as the average concentration of 0.2 particles.l À1 when assessing the relative risk over time, reflecting the fact that no particles are detected for 299 of the 300 s recording period. Notwithstanding these considerations, we believe that our aerosol measurements constitute a valuable quantitative dataset and we note that the methodology could be applied to other anaesthetic airway management techniques and designated aerosolgenerating procedures to extend the relative risk ranking.
Our results for the risk of aerosol generation associated with tracheal intubation are at odds with previous retrospective evidence that was used to designate intubation in an aerosol-generating procedure [12,14].
These studies found an association between acquiring SARS and being in the room during intubation but without any measure of aerosol generation. It is difficult to directly compare these two sources of evidence: in our study, all patients received a controlled anaesthetic induction that included a neuromuscular blocking drug. Conversely, during the SARS epidemic patients were unwell, may have been coughing during the intubation sequence and it is likely that viral secretion was at peak levels at the point of By the definition noted earlier, aerosol-generating procedures are considered to have a greater likelihood of producing aerosols compared with coughing [16]. Our study indicates that the process of elective tracheal intubation produces a barely recordable increase in aerosol and, consequently, should not be designated as an aerosolgenerating procedure. When a patient coughs during tracheal extubation, a measurable particle plume is produced but the aerosol is still smaller than a single volitional cough. These relative risks aee4 of aerosol generation need to be balanced against the knowledge that the use of airborne precaution PPE has substantial impact on clinical practice. Additionally, methods introduced to mitigate the risks posed by bio-aerosols have reduced operating theatre turnover, decreased hospital productivity and increased waiting times for elective and cancer surgery.
A further important consideration relates to the cost and limited supply of PPE which has to be targeted to appropriate healthcare settings on the basis of risk. These results, therefore, should help inform future airborne prevention PPE guidelines by providing evidence on the relative risk of aerosol generation associated with tracheal intubation and extubation.