Tracheal intubation in critically ill adults with a physiologically difficult airway. An international Delphi study.

PURPOSE: Our study aimed to provide consensus and expert clinical practice statements related to airway management in critically ill adults with a physiologically difficult airway (PDA). METHODS: An international Steering Committee involving seven intensivists and one Delphi methodology expert was convened by the Society of Critical Care Anaesthesiologists (SOCCA) Physiologically Difficult Airway Task Force. The committee selected an international panel of 35 expert clinician-researchers with expertise in airway management in critically ill adults. A Delphi process based on an iterative approach was used to obtain the final consensus statements. RESULTS: The Delphi process included seven survey rounds. A stable consensus was achieved for 53 (87%) out of 61 statements. The experts agreed that in addition to pathophysiological conditions, physiological alterations associated with pregnancy and obesity also constitute a physiologically difficult airway. They suggested having an intubation team consisting of at least three healthcare providers including two airway operators, implementing an appropriately designed checklist, and optimizing hemodynamics prior to tracheal intubation. Similarly, the experts agreed on the head elevated laryngoscopic position, routine use of videolaryngoscopy during the first attempt, preoxygenation with non-invasive ventilation, careful mask ventilation during the apneic phase, and attention to cardiorespiratory status for post-intubation care. CONCLUSION: Using a Delphi method, agreement among a panel of international experts was reached for 53 statements providing guidance to clinicians worldwide on safe tracheal intubation practices in patients with a physiologically difficult airway to help improve patient outcomes. Well-designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties.

Efficacy and adverse events profile of videolaryngoscopy in critically ill patients: subanalysis of the INTUBE study.

BACKGROUND: Tracheal intubation is a high-risk procedure in the critically ill, with increased intubation failure rates and a high risk of other adverse events. Videolaryngoscopy might improve intubation outcomes in this population, but evidence remains conflicting, and its impact on adverse event rates is debated. METHODS: This is a subanalysis of a large international prospective cohort of critically ill patients (INTUBE Study) performed from 1 October 2018 to 31 July 2019 and involving 197 sites from 29 countries across five continents. Our primary aim was to determine the first-pass intubation success rates of videolaryngoscopy. Secondary aims were characterising (a) videolaryngoscopy use in the critically ill patient population and (b) the incidence of severe adverse effects compared with direct laryngoscopy. RESULTS: Of 2916 patients, videolaryngoscopy was used in 500 patients (17.2%) and direct laryngoscopy in 2416 (82.8%). First-pass intubation success was higher with videolaryngoscopy compared with direct laryngoscopy (84% vs 79%, P=0.02). Patients undergoing videolaryngoscopy had a higher frequency of difficult airway predictors (60% vs 40%, P<0.001). In adjusted analyses, videolaryngoscopy increased the probability of first-pass intubation success, with an OR of 1.40 (95% confidence interval [CI] 1.05-1.87). Videolaryngoscopy was not significantly associated with risk of major adverse events (odds ratio 1.24, 95% CI 0.95-1.62) or cardiovascular events (odds ratio 0.78, 95% CI 0.60-1.02). CONCLUSIONS: In critically ill patients, videolaryngoscopy was associated with higher first-pass intubation success rates, despite being used in a population at higher risk of difficult airway management. Videolaryngoscopy was not associated with overall risk of major adverse events. CLINICAL TRIAL REGISTRATION: NCT03616054.

Peri-intubation Cardiovascular Collapse in Patients Who Are Critically Ill: Insights from the INTUBE Study.

Rationale: Cardiovascular instability/collapse is a common peri-intubation event in patients who are critically ill. Objectives: To identify potentially modifiable variables associated with peri-intubation cardiovascular instability/collapse (i.e., systolic arterial pressure <65 mm Hg [once] or <90 mm Hg for >30 minutes; new/increased vasopressor requirement; fluid bolus >15 ml/kg, or cardiac arrest). Methods: INTUBE (International Observational Study to Understand the Impact and Best Practices of Airway Management In Critically Ill Patients) was a multicenter prospective cohort study of patients who were critically ill and undergoing tracheal intubation in a convenience sample of 197 sites from 29 countries across five continents from October 1, 2018, to July 31, 2019. Measurements and Main Results: A total of 2,760 patients were included in this analysis. Peri-intubation cardiovascular instability/collapse occurred in 1,199 out of 2,760 patients (43.4%). Variables associated with this event were older age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.02-1.03), higher heart rate (OR, 1.008; 95% CI, 1.004-1.012), lower systolic blood pressure (OR, 0.98; 95% CI, 0.98-0.99), lower oxygen saturation as measured by pulse oximetry/FiO2 before induction (OR, 0.998; 95% CI, 0.997-0.999), and the use of propofol as an induction agent (OR, 1.28; 95% CI, 1.05-1.57). Patients with peri-intubation cardiovascular instability/collapse were at a higher risk of ICU mortality with an adjusted OR of 2.47 (95% CI, 1.72-3.55), P < 0.001. The inverse probability of treatment weighting method identified the use of propofol as the only factor independently associated with cardiovascular instability/collapse (OR, 1.23; 95% CI, 1.02-1.49). When administered before induction, vasopressors (OR, 1.33; 95% CI, 0.84-2.11) or fluid boluses (OR, 1.17; 95% CI, 0.96-1.44) did not reduce the incidence of cardiovascular instability/collapse. Conclusions: Peri-intubation cardiovascular instability/collapse was associated with an increased risk of both ICU and 28-day mortality. The use of propofol for induction was identified as a modifiable intervention significantly associated with cardiovascular instability/collapse.Clinical trial registered with clinicaltrials.gov (NCT03616054).

Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients From 29 Countries.

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure <65 mm Hg at least once, <90 mm Hg for >30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation <80%) or cardiac arrest. The secondary outcomes included intensive care unit mortality. Results: Of 3659 patients screened, 2964 (median age, 63 years; interquartile range [IQR], 49-74 years; 62.6% men) from 197 sites across 5 continents were included. The main reason for intubation was respiratory failure in 52.3% of patients, followed by neurological impairment in 30.5%, and cardiovascular instability in 9.4%. Primary outcome data were available for all patients. Among the study patients, 45.2% experienced at least 1 major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 42.6% of all patients undergoing emergency intubation, followed by severe hypoxemia (9.3%) and cardiac arrest (3.1%). Overall ICU mortality was 32.8%. Conclusions and Relevance: In this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events-in particular cardiovascular instability-were observed frequently.

Lost in transition: the challenges of getting airway clinicians to move from the upper airway to the neck during an airway crisis.

Technical and psychological factors make performance of an emergency front-of-neck airway (eFONA) a challenging procedure for clinical teams involved in airway management. When 'cannot intubate, cannot oxygenate' (CICO) emergencies occur, eFONA is frequently performed too late or not at all. The concept of transition to eFONA comprises simultaneous efforts to prevent and prepare for eFONA before a declaration of CICO in an effort to facilitate its timely and effective implementation. Although such a transition represents an appealing idea, attention to many aspects of airway practice is required for it to become an effective intervention.

Consensus statement: Safe Airway Society principles of airway management and tracheal intubation specific to the COVID-19 adult patient group.

INTRODUCTION: This statement was planned on 11 March 2020 to provide clinical guidance and aid staff preparation for the coronavirus disease 2019 (COVID-19) pandemic in Australia and New Zealand. It has been widely endorsed by relevant specialty colleges and societies. MAIN RECOMMENDATIONS: Generic guidelines exist for the intubation of different patient groups, as do resources to facilitate airway rescue and transition to the "can't intubate, can't oxygenate" scenario. They should be followed where they do not contradict our specific recommendations for the COVID-19 patient group. Consideration should be given to using a checklist that has been specifically modified for the COVID-19 patient group. Early intubation should be considered to prevent the additional risk to staff of emergency intubation and to avoid prolonged use of high flow nasal oxygen or non-invasive ventilation. Significant institutional preparation is required to optimise staff and patient safety in preparing for the airway management of the COVID-19 patient group. The principles for airway management should be the same for all patients with COVID-19 (asymptomatic, mild or critically unwell). Safe, simple, familiar, reliable and robust practices should be adopted for all episodes of airway management for patients with COVID-19. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: Airway clinicians in Australia and New Zealand should now already be involved in regular intensive training for the airway management of the COVID-19 patient group. This training should focus on the principles of early intervention, meticulous planning, vigilant infection control, efficient processes, clear communication and standardised practice.

Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C.

Transcriptional control in large genomes often requires looping interactions between distal DNA elements, such as enhancers and target promoters. Current chromosome conformation capture techniques do not offer sufficiently high resolution to interrogate these regulatory interactions on a genomic scale. Here we use Capture Hi-C (CHi-C), an adapted genome conformation assay, to examine the long-range interactions of almost 22,000 promoters in 2 human blood cell types. We identify over 1.6 million shared and cell type-restricted interactions spanning hundreds of kilobases between promoters and distal loci. Transcriptionally active genes contact enhancer-like elements, whereas transcriptionally inactive genes interact with previously uncharacterized elements marked by repressive features that may act as long-range silencers. Finally, we show that interacting loci are enriched for disease-associated SNPs, suggesting how distal mutations may disrupt the regulation of relevant genes. This study provides new insights and accessible tools to dissect the regulatory interactions that underlie normal and aberrant gene regulation.

The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements.

The mammalian genome harbors up to one million regulatory elements often located at great distances from their target genes. Long-range elements control genes through physical contact with promoters and can be recognized by the presence of specific histone modifications and transcription factor binding. Linking regulatory elements to specific promoters genome-wide is currently impeded by the limited resolution of high-throughput chromatin interaction assays. Here we apply a sequence capture approach to enrich Hi-C libraries for >22,000 annotated mouse promoters to identify statistically significant, long-range interactions at restriction fragment resolution, assigning long-range interacting elements to their target genes genome-wide in embryonic stem cells and fetal liver cells. The distal sites contacting active genes are enriched in active histone modifications and transcription factor occupancy, whereas inactive genes contact distal sites with repressive histone marks, demonstrating the regulatory potential of the distal elements identified. Furthermore, we find that coregulated genes cluster nonrandomly in spatial interaction networks correlated with their biological function and expression level. Interestingly, we find the strongest gene clustering in ES cells between transcription factor genes that control key developmental processes in embryogenesis. The results provide the first genome-wide catalog linking gene promoters to their long-range interacting elements and highlight the complex spatial regulatory circuitry controlling mammalian gene expression.

A novel method for the genome-wide high resolution analysis of DNA damage.

DNA damage occurs via endogenous and exogenous genotoxic agents and compromises a genome's integrity. Knowing where damage occurs within a genome is crucial to understanding the repair mechanisms which protect this integrity. This paper describes a new development based on microarray technology which uses ultraviolet light induced DNA damage as a paradigm to determine the position and frequency of DNA damage and its subsequent repair throughout the entire yeast genome.