Marc Pass

A 27-year-old elite-level professional cyclist presented to the emergency department with a 6-hour history of chest pain and vomiting after prematurely aborting a competitive event. ECG demonstrated anterior ST segment elevation myocardial infarction, and blood tests revealed a grossly elevated high-sensitivity troponin T. Emergent coronary angiography confirmed the presence of a thrombus in the mid-left anterior descending artery with possible spontaneous coronary artery dissection. The patient recovered well following balloon angioplasty and thrombus aspiration, despite delayed recognition, invasive investigation and intervention.

Importance: Propofol and the α2 agonists dexmedetomidine and clonidine are used for sedation in patients with critical illness receiving mechanical ventilation. Evidence about the cost-effectiveness of intravenous (IV) sedation with these medications is lacking. Objective: To investigate the cost-effectiveness of dexmedetomidine-, clonidine-, and propofol-based IV sedation in patients with critical illness receiving mechanical ventilation. Design, Setting, and Participants: This economic evaluation used within-trial cost-utility analysis with a 6-month time horizon comparing dexmedetomidine-, clonidine-, and propofol-based IV sedation from a UK National Health Service and Personal Social Services perspective, with individual-level data collected from the Alpha 2 Agonists for Sedation to Produce Better Outcomes From Critical Illness (A2B) trial. Adults with critical illness receiving mechanical ventilation, with an anticipated total requirement for mechanical ventilation of at least 2 days, from 41 intensive care units in the UK were included. Recruitment ran from December 2018 through October 2023; the last date of follow-up was December 10, 2023. Interventions: Dexmedetomidine, clonidine, or propofol IV sedation. Patients receiving α2 agonists were permitted to receive supplemental propofol to achieve the target sedation score if required. Main Outcomes and Measures: Incremental costs and quality-adjusted life years (QALYs) gained between dexmedetomidine-based vs propofol-based and clonidine-based vs propofol-based IV sedation were assessed. Mean net monetary benefits with each medication were assessed. Results: Among 1404 adults with critical illness receiving mechanical ventilation (mean [SD] age, 59.2 [14.9] years; 901 male [64.2%]), the mean (SD) Acute Physiology and Chronic Health Evaluation (APACHE) II score was 20.3 (8.2). The incremental cost for dexmedetomidine vs propofol was $1273 (95% CI, -$5000 to $7545), and for clonidine vs propofol, it was -$1328 (-$7114 to $4459). For dexmedetomidine vs propofol, there were 0.0008 QALYs (95% CI, -0.0198 to 0.0214 QALYs) gained, and for clonidine vs propofol, there were -0.0019 QALYs (95% CI, -0.0221 to 0.0181 QALYs) gained. Mean net monetary benefits for dexmedetomidine, clonidine, and propofol were -$53 278 (95% CI, -$58 063 to -$48 493), -$50 882 (95% CI, -$55 003 to -$46 762), and -$52 036 (95% CI, -$56 230 to -$47 834), respectively, at a maximum willingness to pay for a QALY of $16 250. Conclusions and Relevance: In this study, dexmedetomidine-, clonidine-, and propofol-based IV sedation in patients with critical illness receiving mechanical ventilation had similar costs and QALYs. These findings suggest that economic considerations should not affect which sedative these patients receive.

<bold>Introduction:</bold> The pro-thrombotic nature of critically unwell patients with severe COVID-19 has been well established (Helms J et al. Intensive Care Medicine 2020; 46:1089-1098); however less well documented is the association with non-severe cases of COVID-19. We hypothesised that the increased incidence in pulmonary embolism (PE) we observed during the early phase of the pandemic could be due to thrombogenicity related to non-severe COVID-19 disease. <bold>Methods:</bold> All CT Pulmonary Angiograms (CTPAs) performed during a 7-week period in May-June 2020 and a historical cohort from the same time period in 2019, in one university teaching hospital, were screened for PE. Characteristics including presenting symptomatology, COVID-19 status and PE risk-stratification were gathered via electronic medical records. <bold>Results:</bold> 240 CTPAs were performed during the 2020 study period, and 263 during the 2019 equivalent. In 2019, 18% of CTPAs were positive for PE, compared to 25% in 2020 - 35% of CTPAs in patients categorised as highly-suspicious or confirmed COVID-19 and 20% of CTPAs in patients not suspected to have COVID-19. Radiological evidence of right heart strain was present in 42% of patients in 2020 and 15% in 2019. Syncope and ‘sub-acute breathlessness’ were more common presenting symptoms in 2020 compared to 2019. <bold>Conclusions:</bold> Our data is suggestive of a COVID-induced pro-thrombotic state which appears to be present even in those with mild-moderate disease. Our findings support a higher risk profile in those presenting with PE during the COVID pandemic and the presenting symptomatology suggests a need to recognise persistent, sub-acute breathlessness as a potential symptom of PE, rather than attributing it to uncomplicated COVID-19 recovery.