A quantitative evaluation of aerosol generation during cardiopulmonary resuscitation.

It is unclear if cardiopulmonary resuscitation is an aerosol-generating procedure and whether this poses a risk of airborne disease transmission to healthcare workers and bystanders. Use of airborne transmission precautions during cardiopulmonary resuscitation may confer rescuer protection but risks patient harm due to delays in commencing treatment. To quantify the risk of respiratory aerosol generation during cardiopulmonary resuscitation in humans, we conducted an aerosol monitoring study during out-of-hospital cardiac arrests. Exhaled aerosol was recorded using an optical particle sizer spectrometer connected to the breathing system. Aerosol produced during resuscitation was compared with that produced by control participants under general anaesthesia ventilated with an equivalent respiratory pattern to cardiopulmonary resuscitation. A porcine cardiac arrest model was used to determine the independent contributions of ventilatory breaths, chest compressions and external cardiac defibrillation to aerosol generation. Time-series analysis of participants with cardiac arrest (n = 18) demonstrated a repeating waveform of respiratory aerosol that mapped to specific components of resuscitation. Very high peak aerosol concentrations were generated during ventilation of participants with cardiac arrest with median (IQR [range]) 17,926 (5546-59,209 [1523-242,648]) particles.l-1 , which were 24-fold greater than in control participants under general anaesthesia (744 (309-2106 [23-9099]) particles.l-1 , p < 0.001, n = 16). A substantial rise in aerosol also occurred with cardiac defibrillation and chest compressions. In a complimentary porcine model of cardiac arrest, aerosol recordings showed a strikingly similar profile to the human data. Time-averaged aerosol concentrations during ventilation were approximately 270-fold higher than before cardiac arrest (19,410 (2307-41,017 [104-136,025]) vs. 72 (41-136 [23-268]) particles.l-1 , p = 0.008). The porcine model also confirmed that both defibrillation and chest compressions generate high concentrations of aerosol independent of, but synergistic with, ventilation. In conclusion, multiple components of cardiopulmonary resuscitation generate high concentrations of respiratory aerosol. We recommend that airborne transmission precautions are warranted in the setting of high-risk pathogens, until the airway is secured with an airway device and breathing system with a filter.

A quantitative evaluation of aerosol generation during awake tracheal intubation.

Aerosol-generating procedures are medical interventions considered high risk for transmission of airborne pathogens. Tracheal intubation of anaesthetised patients is not high risk for aerosol generation; however, patients often perform respiratory manoeuvres during awake tracheal intubation which may generate aerosol. To assess the risk, we undertook aerosol monitoring during a series of awake tracheal intubations and nasendoscopies in healthy participants. Sampling was undertaken within an ultraclean operating theatre. Procedures were performed and received by 12 anaesthetic trainees. The upper airway was topically anaesthetised with lidocaine and participants were not sedated. An optical particle sizer continuously sampled aerosol. Passage of the bronchoscope through the vocal cords generated similar peak median (IQR [range]) aerosol concentrations to coughing, 1020 (645-1245 [120-48,948]) vs. 1460 (390-2506 [40-12,280]) particles.l-1 respectively, p = 0.266. Coughs evoked when lidocaine was sprayed on the vocal cords generated 91,700 (41,907-166,774 [390-557,817]) particles.l-1 which was significantly greater than volitional coughs (p < 0.001). For 38 nasendoscopies in 12 participants, the aerosol concentrations were relatively low, 180 (120-525 [0-9552]) particles.l-1 , however, five nasendoscopies generated peak aerosol concentrations greater than a volitional cough. Awake tracheal intubation and nasendoscopy can generate high concentrations of respiratory aerosol. Specific risks are associated with lidocaine spray of the larynx, instrumentation of the vocal cords, procedural coughing and deep breaths. Given the proximity of practitioners to patient-generated aerosol, airborne infection control precautions are appropriate when undertaking awake upper airway endoscopy (including awake tracheal intubation, nasendoscopy and bronchoscopy) if respirable pathogens cannot be confidently excluded.

Anaesthetists' current practice and perceptions of aerosol-generating procedures: a mixed-methods study.

The evidence base surrounding the transmission risk of 'aerosol-generating procedures' has evolved primarily through quantification of aerosol concentrations during clinical practice. Consequently, infection prevention and control guidelines are undergoing continual reassessment. This mixed-methods study aimed to explore the perceptions of practicing anaesthetists regarding aerosol-generating procedures. An online survey was distributed to the Membership Engagement Group of the Royal College of Anaesthetists during November 2021. The survey included five clinical scenarios to identify the personal approach of respondents to precautions, their hospital's policies and the associated impact on healthcare provision. A purposive sample was selected for interviews to explore the reasoning behind their perceptions and behaviours in greater depth. A total of 333 survey responses were analysed quantitatively. Transcripts from 18 interviews were coded and analysed thematically. The sample was broadly representative of the UK anaesthetic workforce. Most respondents and their hospitals were aware of, supported and adhered to UK guidance. However, there were examples of substantial divergence from these guidelines at both individual and hospital level. For example, 40 (12%) requested respiratory protective equipment and 63 (20%) worked in hospitals that required it to be worn whilst performing tracheal intubation in SARS-CoV-2 negative patients. Additionally, 173 (52%) wore respiratory protective equipment whilst inserting supraglottic airway devices. Regarding the use of respiratory protective equipment and fallow times in the operating theatre: 305 (92%) perceived reduced efficiency; 376 (83%) perceived a negative impact on teamworking; 201 (64%) were worried about environmental impact; and 255 (77%) reported significant problems with communication. However, 269 (63%) felt the negative impacts of respiratory protection equipment were appropriately balanced against the risks of SARS-CoV-2 transmission. Attitudes were polarised about the prospect of moving away from using respiratory protective equipment. Participants' perceived risk from COVID-19 correlated with concern regarding stepdown (Spearman's test, R = 0.36, p < 0.001). Attitudes towards aerosol-generating procedures and the need for respiratory protective equipment are evolving and this information can be used to inform strategies to facilitate successful adoption of revised guidelines.

Quantitative evaluation of aerosol generation from upper airway suctioning assessed during tracheal intubation and extubation sequences in anaesthetized patients.

BACKGROUND: Open respiratory suctioning is defined as an aerosol generating procedure (AGP). Laryngopharyngeal suctioning, used to clear secretions during anaesthesia, is widely managed as an AGP. However, it is uncertain whether upper airway suctioning should be designated as an AGP due to the lack of both aerosol and epidemiological evidence. AIM: To assess the relative risk of aerosol generation by upper airway suctioning during tracheal intubation and extubation in anaesthetized patients. METHODS: This prospective environmental monitoring study was undertaken in an ultraclean operating theatre setting to assay aerosol concentrations during intubation and extubation sequences, including upper airway suctioning, for patients undergoing surgery (N=19). An optical particle sizer (particle size 0.3-10 µm) sampled aerosol 20 cm above the patient's mouth. Baseline recordings (background, tidal breathing and volitional coughs) were followed by intravenous induction of anaesthesia with neuromuscular blockade. Four periods of laryngopharyngeal suctioning were performed with a Yankauer sucker: pre-laryngoscopy, post-intubation, pre-extubation and post-extubation. FINDINGS: Aerosol was reliably detected {median 65 [interquartile range (IQR) 39-259] particles/L} above background [median 4.8 (IQR 1-7) particles/L, P<0.0001] when sampling in close proximity to the patient's mouth during tidal breathing. Upper airway suctioning was associated with a much lower average aerosol concentration than breathing [median 6.0 (IQR 0-12) particles/L, P=0.0007], and was indistinguishable from background (P>0.99). Peak aerosol concentrations recorded during suctioning [median 45 (IQR 30-75) particles/L] were much lower than during volitional coughs [median 1520 (IQR 600-4363) particles/L, P<0.0001] and tidal breathing [median 540 (IQR 300-1826) particles/L, P<0.0001]. CONCLUSION: Upper airway suctioning during airway management was not associated with a higher aerosol concentration compared with background, and was associated with a much lower aerosol concentration compared with breathing and coughing. Upper airway suctioning should not be designated as a high-risk AGP.

Quantitative evaluation of aerosol generation during manual facemask ventilation.

Manual facemask ventilation, a core component of elective and emergency airway management, is classified as an aerosol-generating procedure. This designation is based on one epidemiological study suggesting an association between facemask ventilation and transmission during the SARS-CoV-1 outbreak in 2003. There is no direct evidence to indicate whether facemask ventilation is a high-risk procedure for aerosol generation. We conducted aerosol monitoring during routine facemask ventilation and facemask ventilation with an intentionally generated leak in anaesthetised patients. Recordings were made in ultraclean operating theatres and compared against the aerosol generated by tidal breathing and cough manoeuvres. Respiratory aerosol from tidal breathing in 11 patients was reliably detected above the very low background particle concentrations with median [IQR (range)] particle counts of 191 (77-486 [4-1313]) and 2 (1-5 [0-13]) particles.l-1 , respectively, p = 0.002. The median (IQR [range]) aerosol concentration detected during facemask ventilation without a leak (3 (0-9 [0-43]) particles.l-1 ) and with an intentional leak (11 (7-26 [1-62]) particles.l-1 ) was 64-fold (p = 0.001) and 17-fold (p = 0.002) lower than that of tidal breathing, respectively. Median (IQR [range]) peak particle concentration during facemask ventilation both without a leak (60 (0-60 [0-120]) particles.l-1 ) and with a leak (120 (60-180 [60-480]) particles.l-1 ) were 20-fold (p = 0.002) and 10-fold (0.001) lower than a cough (1260 (800-3242 [100-3682]) particles.l-1 ), respectively. This study demonstrates that facemask ventilation, even when performed with an intentional leak, does not generate high levels of bioaerosol. On the basis of this evidence, we argue facemask ventilation should not be considered an aerosol-generating procedure.

A quantitative evaluation of aerosol generation during supraglottic airway insertion and removal.

Many guidelines consider supraglottic airway use to be an aerosol-generating procedure. This status requires increased levels of personal protective equipment, fallow time between cases and results in reduced operating theatre efficiency. Aerosol generation has never been quantitated during supraglottic airway use. To address this evidence gap, we conducted real-time aerosol monitoring (0.3-10-µm diameter) in ultraclean operating theatres during supraglottic airway insertion and removal. This showed very low background particle concentrations (median (IQR [range]) 1.6 (0-3.1 [0-4.0]) particles.l-1 ) against which the patient's tidal breathing produced a higher concentration of aerosol (4.0 (1.3-11.0 [0-44]) particles.l-1 , p = 0.048). The average aerosol concentration detected during supraglottic airway insertion (1.3 (1.0-4.2 [0-6.2]) particles.l-1 , n = 11), and removal (2.1 (0-17.5 [0-26.2]) particles.l-1 , n = 12) was no different to tidal breathing (p = 0.31 and p = 0.84, respectively). Comparison of supraglottic airway insertion and removal with a volitional cough (104 (66-169 [33-326]), n = 27), demonstrated that supraglottic airway insertion/removal sequences produced <4% of the aerosol compared with a single cough (p < 0.001). A transient aerosol increase was recorded during one complicated supraglottic airway insertion (which initially failed to provide a patent airway). Detailed analysis of this event showed an atypical particle size distribution and we subsequently identified multiple sources of non-respiratory aerosols that may be produced during airway management and can be considered as artefacts. These findings demonstrate supraglottic airway insertion/removal generates no more bio-aerosol than breathing and far less than a cough. This should inform the design of infection prevention strategies for anaesthetists and operating theatre staff caring for patients managed with supraglottic airways.

Erratum to 'Angiotensin converting enzyme inhibitors and angiotensin receptor blockers' [BJA Education 20 (2020) 362-367].

[This corrects the article DOI: 10.1016/j.bjae.2020.07.004.].

A quantitative evaluation of aerosol generation during tracheal intubation and extubation.

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.

A 17-year experience in perioperative anaphylaxis 1998-2015: harmonizing optimal detection of mast cell mediator release.

BACKGROUND: Sheffield NARCOS (National Adverse Reactions Advisory Service) investigates suspected perioperative anaesthetic reactions using serial tryptase, urinary methylhistamine (UMH) and clinical information. Further recommendations for additional allergy clinic assessment are provided. OBJECTIVE: To establish a robustly measurable protocol for identifying mast cell mediator (MMR) release in this cohort. To compare these thresholds with previously suggested thresholds and algorithms. METHOD: A review of 3455 NARCOS cases referred with a suspected perioperative allergic reaction. Tryptase, UMH and clinical details were analysed. A total of 1746 cases were graded using the Ring and Messmer scale. Reaction grade, tryptase and UMH changes were compared with statistical and graphical presentations appropriate to non-normally distributed measurements using Analyse-IT software. RESULTS: Sensitive strategies such as 3 µg/L or 20% are measurable and translatable and would substantially increase detection of potentially relevant changes in tryptases. Adequate quality assurance for low-level measurement is needed. An incremental threshold of 20% would identify potential MMR in an additional 14% of cases with peak tryptase (Tp) between 5 and 14 µg/L and a further 15% with Tp below 5 µg/L. Further work is required to establish the diagnostic performance characteristics of this more sensitive approach. UMH also identified up to 120 further cases of potential MMR in the absence of tryptase increments. CONCLUSIONS AND CLINICAL RELEVANCE: Future studies should establish and compare the predictive performance characteristics of each strategy against clinical phenotypes. A single agreed definition of positive serial tryptases is needed to enable robust evaluation of diagnostic strategies. This could serve as a harmonized standard for comparative studies of case series from different centres.

The United Kingdom Primary Immune Deficiency (UKPID) Registry: report of the first 4 years' activity 2008-2012.

This report summarizes the establishment of the first national online registry of primary immune deficency in the United Kingdom, the United Kingdom Primary Immunodeficiency (UKPID Registry). This UKPID Registry is based on the European Society for Immune Deficiency (ESID) registry platform, hosted on servers at the Royal Free site of University College, London. It is accessible to users through the website of the United Kingdom Primary Immunodeficiency Network (www.ukpin.org.uk). Twenty-seven centres in the United Kingdom are actively contributing data, with an additional nine centres completing their ethical and governance approvals to participate. This indicates that 36 of 38 (95%) of recognized centres in the United Kingdom have engaged with this project. To date, 2229 patients have been enrolled, with a notable increasing rate of recruitment in the past 12 months. Data are presented on the range of diagnoses recorded, estimated minimum disease prevalence, geographical distribution of patients across the United Kingdom, age at presentation, diagnostic delay, treatment modalities used and evidence of their monitoring and effectiveness.

Raised tryptase without anaphylaxis or mastocytosis: heterophilic antibody interference in the serum tryptase assay.

Mast cell tryptase (MCT) is a key diagnostic test for mastocytosis and anaphylaxis. High serum tryptase levels are also one of the risk factors for adverse reaction in venom immunotherapy, yet occasional patients are seen with raised levels in the absence of either diagnosis. False positive results can be due to assay interference by heterophilic antibodies such as rheumatoid factor (RF) and human anti-mouse antibodies (HAMA). We therefore investigated heterophilic antibody interference by rheumatoid factor activity and HAMA as a cause of raised MCT results in the Phadia tryptase assay. Serum samples from 83 patients were assayed for MCT and rheumatoid factor before and after the use of heterophilic antibody blocking tubes (HBT). Samples with more than 17% reduction in MCT with detectable RF were then assayed for HAMA. Fourteen (17%) of the 83 samples with positive RF showed a >17% decrease in mast cell tryptase after HBT blocking. Post-HBT, eight of 14 (57%) reverted from elevated to normal range values with falls of up to 98%. RF levels were also decreased significantly (up to 75%). Only one of the 83 tested was apparently affected by HAMA in the absence of detectable IgM RF. In conclusion, any suspicious MCT result should be checked for heterophilic antibodies to evaluate possible interference. False positive MCT levels can be caused by rheumatoid factor. We suggest a strategy for identifying assay interference, and show that it is essential to incorporate this caveat into guidance for interpretation of MCT results.

Molecular delineation of deletions on 2q37.3 in three cases with an Albright hereditary osteodystrophy-like phenotype.

A minority of the reported cases of terminal 2q37 deletion clinically resemble Albright hereditary osteodystrophy (AHO)/pseudopseudohypoparathyroidism and have only mild-to-moderate mental retardation. Our molecular and cytogenetic fluorescence in situ hybridization (FISH) findings on an additional three patients further reduce the size of the minimal critical region deleted in this syndrome to about 3 Mb. This region includes the G-protein-coupled receptor 35 (GPR35), glypican 1 (GPC1), and serine/threonine protein kinase 25 (STK25) genes on 2q37.3. We have further defined several polymorphic variants within the coding region and flanking regions of GPR35 gene, which could potentially be useful for rapid detection of GPR35 gene deletion. We postulate that the absence of GPR35 may, at least partly, account for the phenotypic resemblance to the AHO. We also believe that the deletion of GPR35 could be responsible for the entity brachydactyly mental retardation syndrome (OMIM #600430), which was coined based on the above minority of patients with terminal 2q37 deletion. We recommend that every patient with AHO phenotype should undergo 2q subtelomeric FISH screen and subsequently a molecular study on the GPR35 gene. GPC1 and/or STK25 haploinsufficiency may also contribute to the AHO-like phenotype.

Inheritance of osteosarcoma and Paget's disease of bone: a familial loss of heterozygosity study.

Pagetoid osteosarcoma is a complication of Paget's disease of bone. Sarcomatous transformation is most often seen in severe, long-standing Paget's disease. Familial clustering of Paget's disease has been described with apparent autosomal dominant inheritance with high penetrance by the sixth decade. Although definitive proof of the specific gene involved remains elusive, some researchers have shown loss of heterozygosity in a region of chromosome 18q in a relatively high percentage of studied patients affected with either Paget's disease alone, in Pagetoid osteosarcoma, and in uncomplicated osteosarcoma. Our patient was diagnosed with Pagetoid osteosarcoma and had a first-degree relative with history of the same. We hypothesized that our patient's tumor samples might contain a similar genetic abnormality. Our analysis of several polymorphic markers from the chromosome 18q21-22 region showed loss of maternally inherited alleles throughout the region. This finding is similar to those described previously and provides further evidence of a susceptibility region relating to this disease. This report describes a father and son, their young ages at diagnosis of Pagetoid sarcoma, the identical sites of disease involvement, and a loss of heterozygosity study illustrating the inheritance of the presumed defective gene.

Cognitive deficits associated with a recently reported familial neurodegenerative disease: familial encephalopathy with neuroserpin inclusion bodies.

BACKGROUND: We recently discovered an autosomal dominant disease causing a progressive dementia. The disease is caused by a point mutation in the gene coding for the serine protease inhibitor (ie, serpin) neuroserpin. The mutation results in an unstable neuroserpin protein that readily aggregates into intraneuronal inclusions that we identify as Collins bodies. The bodies are distributed throughout the cerebral hemispheres but are significantly more numerous in the cortex and the substantia nigra. We have named the disease familial encephalopathy with neuroserpin inclusion bodies (FENIB). OBJECTIVES: To describe the cognitive and neurophysiological changes exhibited by individuals with FENIB and to correlate the phenotypic expression of the disease with the neuropathological findings. DESIGN: Multiple case studies using neuropsychological assessment, electroencephalography (EEG), magnetic resonance imaging (MRI), and single-photon emission computed tomographic (SPECT) studies of family members were performed. Using these measures, we also compared family members in whom the mutation is present with family members in whom the mutation was absent to control for nonspecific familial factors. SUBJECTS: Nine individuals (5 women, aged 31-64 years; 4 men, aged 43-67 years) from 2 generations of family members related to the first reliably identified individual with symptoms of this disease. Symptoms, by self-report and reports of other family members, ranged from asymptomatic to severe dementia. Six of the 9 individuals carried the disease mutation. RESULTS: All subjects with the mutation demonstrated some cognitive changes, with the greatest demonstrated by subjects older than 40 years. The changes included restricted attention, concentration, and response regulation functions, reduced controlled oral fluency (word-list generation), and restricted visuospatial organization. In general, recall memory was not as affected as other cognitive domains. The most severely affected subject demonstrated global dementia with prominent frontal lobe features. Findings on SPECT showed anomalies limited to frontal areas in the less affected subjects and more global, patchy areas of hypoperfusion in the more severely affected subjects. The 3 oldest and most affected subjects demonstrated slowing on EEG findings. The MRI findings were noncontributory except in the 2 most severe cases, which showed global cortical atrophy. CONCLUSIONS: Cognitive changes in mildly to moderately affected subjects were characterized by deficits in frontal and frontal-subcortical area-dependent processes. Continued progressive deterioration of cerebral functions with relative sparing of recall memory suggests a unique dementia associated with this disease.