key: cord-0734093-30tq5e86
authors: Sharma, Siddhartha; John, Rakesh; Patel, Sandeep; Neradi, Deepak; Kishore, Kamal; Dhillon, Mandeep S.
title: Bioaerosols in orthopedic surgical procedures and implications for clinical practice in the times of COVID-19: A systematic review and meta-analysis
date: 2021-03-28
journal: J Clin Orthop Trauma
DOI: 10.1016/j.jcot.2021.03.016
sha: 093e2a7961802d88225ed1c991e81e02c478a854
doc_id: 734093
cord_uid: 30tq5e86

INTRODUCTION: Orthopedic surgical procedures (OSPs) are known to generate bioaerosols, which could result in transmission of infectious diseases. Hence, this review was undertaken to analyse the available evidence on bioaerosols in OSPs, and their significance in COVID-19 transmission. METHODS: A systematic review was conducted by searching the PubMed, EMBASE, Scopus, Cochrane Library, medRxiv, bioRxiv and Lancet preprint databases for studies on bioaerosols in OSPs. Random-effects metanalysis was conducted to determine pooled estimates of key bioaerosol characteristics. Risk of bias was assessed by the RoB-SPEO tool; overall strength of evidence was assessed by the GRADE approach. RESULTS: 17 studies were included in the systematic review, and 6 in different sets of meta-analyses. The pooled estimate of particle density was 390.74 μg/m(3), Total Particle Count, 6.08 × 10(6)/m(3), and Microbial Air Contamination, 8.08 CFU/m(3). Small sized particles (</ = 0.5 μm) were found to be 37 and 1604 times more frequent in the aerosol cloud in comparison to medium and large sized particles respectively. 4 studies reported that haemoglobin could be detected in aerosols, and one study showed that HIV could be transmitted by blood aerosolized by electric saw and burr. The risk of bias for all studies in the review was determined to be high, and the quality of evidence, low. CONCLUSION: Whereas there is evidence to suggest that OSPs generate large amounts of bioaerosols, their potential to transmit infectious diseases like COVID-19 is questionable. High-quality research, as well as consensus minimum reporting guidelines for bioaerosol research in OSPs is the need of the hour.

The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has caused an unprecedented, catastrophic pandemic, which has adversely affected health care systems worldwide [1] [2] [3] [4] [5] [6] . This is the third known epidemic caused by a coronavirus, less than two decades after the SARS outbreak in 2002 and the Middle east respiratory disease (MERS) outbreak in 2012; it is very unlikely to be the last one 7 . The morbidity, mortality and the sheer global impact that this pandemic has had on all aspects of life surpasses that of the earlier two outbreaks by a massive margin 8 . Arguably, this is the worst healthcare crisis faced by humanity in the last century since the Spanish flu outbreak in 1918 9 . The pandemic has had a massive effect on the delivery of orthopaedic and trauma care services across the globe [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] . Non-urgent, elective surgeries have been deferred, and there has been an increased emphasis on non-operative management of fractures.

The two major routes of spread of the SARS-CoV-2 are via droplet transmission, which is defined as transmission by droplets or large aerosols directly from an infected person to a susceptible person over shorter distances, and via fomites. However, this virus can also be transmitted via airborne transmission. This refers to small inspirable aerosols, measuring less than 5 microns, which can be dispersed over longer distances by air currents 20 . Any medical or surgical procedure which potentially generates aerosols (Aerosol Generating Procedure -AGP), places the health care workers (HCWs) at risk of contracting the virus by all three modes.

However, the risk of airborne transmission is higher with AGPs, therefore operating room (OR) personnel are more vulnerable to this disease as compared to other HCWs.

Orthopaedic surgical procedures (OSP) are known to generate bioaerosols, owing to the use of high-speed, power drilling and cutting tools, electrocautery and pulse lavage 11, [20] [21] [22] [23] [24] .

Guidelines on the use of personal protective equipment (PPE), which have been in a constant state of evolution, have been recommended for surgical procedures by various international health organisations and medical bodies 21,25-30 . Although there is a general agreement that respirator masks and full PPE are necessary during orthopaedic surgical procedures on COVID-19 patients 21,31 , there is a dire urgency to soundly establish the evidence surrounding aerosol generation in OSPs. This is needed not only to aid in formulation of best practice guidelines as they pertain to orthopaedics ORs, but also to rationalize the use of PPE by OR personnel, the shortage of which continues to be a looming crisis worldwide. Literature on bioaerosols in OSPs in the wake of the COVID-19 pandemic is sparse, and limited to a few narrative and scoping reviews 15, 21, 32 . Hence, we conducted this systematic review and meta-analysis to identify and assimilate the available evidence on bioaerosols in OSPs and their potential for transmission of infectious diseases like COVID-19.

The present study had two key objectives: a. To determine the characteristics (amount and/or density, size, spread and infective potential etc.) of bioaerosols found in a typical orthopaedic OR environment b. To determine the characteristics of aerosols generated by different orthopaedics power tools.

This systematic review was conducted in accordance with the established guidelines from Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 33 . A protocol of the systematic review was formulated and published a priori 34 .

The search terms and search strategies were developed by two authors (SS and RJ) with input from all the authors. The primary search was conducted on the PubMed, Embase, Scopus and Cochrane Library, using a well-defined search strategy. Preprint server databases, viz. medRxiv, bioRxiv and Lancet preprints were also searched to identify unpublished studies (Table 1) 

Any original research study (including cohort, case-control, case series, cadaveric studies and studies, animal models, laboratory based experimental studies) looking at aerosol generation in OSP or aerosol generation by orthopaedic power tools was included. Both English and non-English articles were included. Studies looking at AGPs in specialties other than orthopaedic surgery, conference papers, review articles, expert or personal opinions, and editorials were excluded. Studies using the 'sham surgery' design were also excluded.

Two authors (SS and RJ) independently screened the titles and abstracts of all the articles identified in the initial search. In the event of disagreement, a consensus was reached by discussion, if needed with the intervention of the senior author (MSD). Articles retrieved during the searches were screened for relevance, and those identified as being potentially J o u r n a l P r e -p r o o f eligible were fully assessed against the inclusion and exclusion criteria, and accepted or rejected, as appropriate. The full-texts of all articles selected by either reviewer were obtained and made available to all authors of the review.

One investigator (SS) extracted the following data from each included study independently, using a pre-piloted data extraction form: study name, author name, research publication time, study design, study area/country and institute name, number of patients, research information resource, demographic characteristics, subspecialty/surgical procedure investigated, surgical instruments investigated and results/outcomes (including mean number and standard deviation of total and viable particles generated, mean size and standard deviation of particles, particle scatter characteristics, mean particle concentration, microbiological air contamination, contamination of OR personnel, presence of blood in aerosols). This extracted data was entered into a spreadsheet. Two authors (RJ and SP) independently cross checked the article list and data extraction spreadsheet to ensure that there were no duplicate articles, or duplicate information from the same population and also verified the accuracy of the data.

The quality of the studies included was appraised using the Risk of Bias in Studies estimating Prevalence of Exposure to Occupational risk factors (RoB-SPEO) tool 35 . The studies were individually rated as: low, probably low, probably high, high or no information based on bias assessment in eight separate domains. Although this tool is relatively new and has limited peer validation, the tool was well-suited for the purposes J o u r n a l P r e -p r o o f of this systematic review, has good inter-observer agreement and hence was selected for bias assessment for this systematic review.

The strength of evidence for key findings of the review was assessed by the GRADE approach 36 .

Both qualitative and quantitative analyses were performed. For qualitative analysis, appropriate tables and data visualization diagrams were constructed. The baseline data of included studies as well as all the pre-specified outcome measures were reported. 

The results of the search strategy have been summarized as per the PRSIMA flowchart ( Table 2 ). The combined searches yielded 4745 records. Full text was obtained for 59 studies, of which 17 were included in the systematic review and 6 studies were included in 5 different sets of meta-analyses.

Characteristics of the 19 studies included in this review have been summarized in Table 3 .

Majority of the studies (n=9, 47.4%) were prospective human studies; there were 4 cadaveric, J o u r n a l P r e -p r o o f 4 animal and 2 experimental studies. Arthroplasty, followed by spine surgery, was most commonly evaluated surgical procedure. Evaluation of aerosol generating devices included electrocautery, cutters, burrs, drills, saws and irrigators. Information on characteristics of individual studies and their salient findings has been presented in Table 4 .

Aerosol particle density in human surgeries was reported by two studies 37,38

(Supplementary Table 1 ). The pooled particle density was estimated to be 390.74 μg/m 3 (95% CI 162.70 -618.77 μg/m 3 ); heterogeneity was high for this analysis (I 2 = 60.3%, Chi Square P Value = 0.001) ( Figure 1 ).

Total particle counts (TPC) in human surgeries was reported by two studies 39,40 . The pooled TPC was estimated to be 6.08 x 10 6 per cubic meter (95% CI, 3.05 -9.11 x 10 6 per cubic meter); heterogeneity was high for this analysis (I 2 = 94.9%, Chi Square P Value = 0.000) ( Figure 2 ).

Counts of individual particle sizes were reported by five studies 40-44 . Whereas Birgand et al 41 reported the counts of 3 different particle sizes, the other 4 studies reported the counts of more than 3 different particle sizes. To simplify these results, we categorized particles as small (0.3 -0.5 μm), medium (0.5 -5 μm) and large (> 5 μm) size.

Furthermore, in order to determine which particle sizes were most commonly encountered in orthopedics ORs, we determined the ratio of small to medium size particles and small to large size particles (see Supplementary Table 2 for details on how J o u r n a l P r e -p r o o f study data was pooled into categories).

The pooled ratio of small to medium sized particles was estimated to be 37.4

(95% CI 25.89 -48.87); the heterogeneity for this estimate was high (I 2 = 99.6%, Chi

Square P Value = 0.000) ( Figure 3 ).

The pooled ratio of small to large sized particles was estimated to be 1604.4 (95% CI 1046.68-2162.07); the heterogeneity for this estimate was high (I 2 = 99.9%, Chi

Square P Value = 0.000) ( Figure 4 ).

Microbial air contamination (MAC) was evaluated by four human studies 39-41,43 . The pooled MAC was estimated to be 8.08 CFUs per cubic meters (95% CI, 3.36 -12.79);

the heterogeneity for the estimate was high (I 2 = 96.7%, Chi Square P Value = 0.001) ( Figure 5 ).

The presence of blood in aerosols was evaluated by four studies 22,45-47 ( Figure 6 ).

Aerosol spread was evaluated by 5 studies 48-52 , all of which used similar methodology ( Figure   7 ).

To determine whether the Human Immunodeficiency Virus (HIV) could spread via aerosols generated by surgical tools, Johnson et al 53 performed a laboratory study.

Human blood inoculated with the HIV virus was aerosolized by electrocautery, bone saw and a router (instrument similar to burr). The aerosols were then cultured for HIV virus.

The authors noted that HIV virus could be cultured from the aerosols of bone saw and router, but not electrocautery.

Hamer et al 54 studied the levels of albumin in aerosol, and determined whether this could be used as a surrogate to quantify aerosol concentration. The authors found that the J o u r n a l P r e -p r o o f albumin levels in aerosol are extremely low and did not change with the use of power tools. Hence, such estimation should not be considered as a reliable method to quantify aerosol levels.

Two studies 45,46 described the characteristics of aerosols generated by different power tools ( Table 7 , Figure 8 ). For the sake of simplicity, we categorized particles as small (0.3 -0.5 μm), medium (0.5 -5 μm) and large (> 5 μm ) size.

The oscillating saw was noted to produce 56 -68% 'medium' sized particles and 28 -40% 'small' sized particles ( Figure 8a ).

Jewett et al 46 investigated aerosol characteristics of two types of drills, i.e. the 'Hall drill', which is a high-speed, air-powered drill (Zimmer, Warsaw, Ind.) and the 'Shea drill', which is a high-speed drill with continuous irrigation (Xomed-Treace, Jacksonville, Fl.) Both drills were noted to produced particles of all sizes. Whereas the Hall drill produced 47% 'medium', 38% 'large' and 17% 'small' sized aerosols, the Shea drill produced 59% 'large', 31% 'medium' and 9% 'small' sized aerosols ( Figure 8b ).

Electrocautery was noted to produce aerosols with a predominance of 'small' sized particles. Whereas electrocautery in the 'cutting' mode produced 90 -95% 'small' sized particles, the 'coagulation mode' produced 60 -78% 'small' sized particles and 20 -37% 'medium' sized particles (Figure 8c and 8d). 

The overall risk of bias was judged to be 'high' for all studies. The domains pertaining to participant selection, non-blinding of study personnel and selective reporting of exposures were noted to have 'high' or 'probably high' risk of bias. On the other hand, the domains pertaining to misclassification, incomplete exposure data, conflicts of interest and differences in denominator and numerator were noted to have a 'low' or 'probably low' risk of bias (Figures 9 and 10 ).

The strength of evidence for parameters pertaining to aerosol density, total particle counts, microbial air contamination, ratio of small to medium and small to large size particles was rated as 'low' as per the GRADE working group grading of evidence 36 (Table 8) .

There is a lot of uncertainty in the literature surrounding aerosol generation during surgical procedures and the associated risk of viral transmission 21,32 . In 2014, the World Health Organization (WHO) defined an aerosol generating procedure (AGP) as 'any medical and patient care procedure that results in the production of airborne particles (aerosols)' 55 .

However, whether such aerosols can potentially transmit disease to healthcare workers is We also noted that the aerosol cloud generated in orthopedic surgical procedures tends to J o u r n a l P r e -p r o o f spread out over the entire operating room area and contaminates all personnel within it, with the head and body being the most highly contaminated regions.

Whereas these observations leave little uncertainty on generation of large amounts of bioaerosols in orthopedic procedures, the potential for these aerosols to spread viral infections, including COVID-19 remains debatable. The most important finding of our review in this regard is perhaps the lack of high-quality direct evidence on the infectivity of orthopedic bioaerosols.

We could find only one study 53 which showed that the HIV virus can be potentially transmitted through cool aerosols generated by bone saw and burrs. This study was conducted in 1991, and there have be no other studies to validate these observations. Given the fact that the SARS Coronavirus RNA can be found in blood in up to 79% of patients with COVID-19 60 , the potential for its spread via aerosols should be given due consideration.

The emergence of this pandemic has exposed many lacunae in the research on The key findings of this review, their implications and the recommendations for orthopedics surgical procedures in COVID-19 patients have been summarized in Table 9 .

However, these recommendations come with the caveat that the evidence from our review on infective potential of orthopedic bioaerosols can be considered indirect at best. Another key finding of our review is that aerosols generated during OSPs constitute of predominantly small-sized which tend to stay suspended in the air for longer periods. 61 Although they carry smaller number of microorganisms as compared to large-sized particles, their infective potential can be considered as equivalent 62, 63 . There is evidence that small particles as less in size as 1 microns can be retained in the respiratory tract; hence the need for respiratory masks. 61 Respiratory masks are classified based on their ability to filter small particles (0.3 microns being the cutoff size The study has several strengths. To the best of our knowledge, this is the first systematic review and meta-analysis so far, to focus on aerosol generation in OSPs. The protocol for the review was formulated and published a-priori 34 . We adhered strictly to PRISMA guidelines 33 (Supplementary Table 4 ). We performed extensive literature search across multiple databases, and also searched the grey literature to avoid missing unpublished studies. We also assessed the risk of bias and summarized the available evidence by the GRADE approach.

However, there are a number of limitations of this study. We noted a high risk of bias for all the studies included in the review, which can be primarily attributed to weak study design.

Furthermore, we noted that the outcome parameters reported were highly variable, we could

include only a few studies in the pooled analysis of key variables such as total particle counts and microbial air contamination. A high degree of statistical heterogeneity was also noted in all pooled analyses; this can be attributed to the differences in study populations, variability of measurements of aerosol characteristics. Heterogeneity in ratios of particle sizes may also be attributed to the fact that data from the authors' individual measurements 40,42-44 was pooled into three broad categories. Finally, most of the evidence available is indirect, and high-quality J o u r n a l P r e -p r o o f studies on infective potential of orthopedic bioaerosols are missing. These limitations are reflected well in our GRADE assessment of the available evidence.

The J o u r n a l P r e -p r o o f 

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A Novel Coronavirus from Patients with Pneumonia in China

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COVID-19: protecting health-care workers. The Lancet

CoViD-19 and ortho and trauma surgery: The Italian experience. Injury

COVID-19 and orthopaedic surgeons: the Indian scenario

Emerging coronaviruses: Genome structure, replication, and pathogenesis

Has COVID-19 subverted global health? The Lancet

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J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f • High Quality: Further research is unlikely to change our confidence in the effect of the estimate • Moderate Quality: Further research is likely to have an important impact on our confidence in the effect of the estimate and may change the estimate • Low Quality: Further research is likely to have an important impact on our confidence in the effect of the estimate is likely to change the estimate • Very Low Quality: We are very uncertain about the estimate J o u r n a l P r e -p r o o f Table 9 : Salient findings of this study and their implications for orthopedic surgical procedures in COVID-19 patients SNo.Finding Implication(s) What remedial measure(s) can be taken 1.The pooled total particle count in an orthopaedics OR is 6 x 10 6 per cubic meters, which corresponds to a ISO Class 9 cleanroom.Orthopedic ORs have high concentrations of bioaerosols.Minimize aerosol generation at source. Consider particle filters.

Aerosols in orthopaedics OR consist predominantly of small sized (0.3-0.5 microns or smaller) particles.Small-sized particles remain suspended in air for longer periods and may be inhaled.OR personnel should use N-95 respirators when operating on COVID-19 patients. Ensure adequate air-changes in between cases.

Aerosols in the orthopaedics OR tend to spread widely and contaminate a wide areaThe entire OR should be considered contaminated after each surgical procedureMinimize non-essential items in the OR. Thorough disinfection of all OR surfaces should be done after each case.

All OR personnel get contaminated by orthopedic aerosols. The surgeon and the assistant are contaminated the most during surgery; body is the most contaminated part.All OR personnel should be considered contaminated after each surgical procedure.PPE should be worn by all OR personnel. Well-established donning and doffing practices should be followed.

Orthopedic aerosols contain variable amounts of blood.There is a possibility of spread of blood-borne infections via the inhalational route.Minimize bleeding. Consider use of tourniquet. 6.Electrocautery produces high volumes of aerosols