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Catheter-directed thrombolysis for submassive pulmonary embolism: meta-analysis supports improved outcomes compared with anticoagulation alone
The literature shows conflicting results on the use of catheter-directed thrombolysis (CDT) and systemic anticoagulation (SA) alone in patients suffering submassive pulmonary emboli (sPE). Ismayl et al (Am J Cardiol 2022;178:154) conducted a meta-analysis, which included the results from 11 observational and 1 randomised clinical trials. The analysis compared the outcomes of 1871 patients who received both CDT and SA, to the outcomes of a second group composed of 7918 patients, who received (SA) alone. The use of CDT was associated with significantly lower in-hospital mortality (relative risk (RR) 0.41, 95% CI 0.30 to 0.56, p<0.001, I2=0%), 30-day mortality (RR 0.37, 95% CI 0.18 to 0.73, p=0.004, I2=0%), 90-day mortality (RR 0.36, 95% CI 0.17 to 0.72, p=0.004, I2=0%) and a tendency toward lower 1-year mortality (RR 0.56, 95% CI 0.29 to 1.05, p=0.07, I2=36%) compared with SA. There were no statistically significant differences between the two strategies in major and minor bleeding, blood transfusion and hospital length of stay. The study strengths include that the patient population are representative of clinical practice with large patient numbers providing good statistical power. The limitations of the observational and retrospective nature of the majority of the data are mitigated by propensity matching analysis. Overall, this study expands the evidence supporting CDT as first-line therapy for sPE, however, further randomised clinical trials are needed to lead to CDT being adopted into major guidelines and widespread clinical practice.
High-flow nasal cannula in acute COPD exacerbations with mild hypercapnia and without acidosis: no demonstrable benefit over conventional oxygen therapy
Patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) and hypercapnia without acidosis are managed with conventional oxygen therapy (COT), with non-invasive ventilation not recommended due to the lack of evidence. However, there is an increasing evidence of the physiological and clinical benefits of high-flow nasal cannula (HFNC) in patients with respiratory failure. Xia et al (Critical Care 2022;26:109), conducted a multicentred randomised controlled trial, to assess if HFNC could reduce intubation rate compared with COT in patients with compensated mild hypercapnia (pH ≥7.35 and arterial partial pressure of carbon dioxide >45 mm Hg) admitted to 16 tertiary hospitals in China with acute exacerbations of COPD. The study found that HFNC did not reduce the need for intubation (HFNC 4/58, COT 1/172; p=0.198). Interestingly, HFNC was associated with a longer hospital stay (HFNC 9 days, IQR 7–13; COT 8 days, IQR 7–11) and higher costs (HFNC US$2298, IQR US$1613–US$3782; COT US$2005, IQR US$1439–US$2968). However, the primary outcome rate was well below expected (<3% in the study, against an estimated control rate of 11% with treatment effect reducing to 3%) meaning that the study was significantly underpowered. Further research with larger sample size would be needed to demonstrate a clinical benefit but given the very low event rate it is questionable whether this would be clinically meaningful.
Temporary transvenous phrenic nerve stimulation in patients difficult to wean from invasive ventilation: proof of concept but not ready for clinical practice
A small proportion of patients are difficult to wean from invasive mechanical ventilation (IMV) in the Intensive Care Unit (ICU) but contribute significantly to healthcare costs. Ventilator-induced diaphragm dysfunction is a suggested cause of weaning delay and may be modulated by diaphragm pacing. In this multicentre, open-labelled, randomised, controlled study Dres et al (Am J Respir Crit Care 2022;205:1169) aimed to evaluate the effects of temporary transvenous diaphragm neurostimulation (TTDN) on successful weaning compared with a protocolised weaning. A total of 112 patients were randomised with 57 having the temporary diaphragm pacing wire inserted. The reported complications were low with the majority (79%) of patients receiving >50% of planned stimulation sessions. There was no difference in the proportion of patients weaned by day 30 (TTDN 82%, usual care 74%; difference 7%, 95% CI −10% to 25%, p=0.59). There was evidence that the pacing had a physiological impact with a dose response relationship between stimulation sessions and improvement in voluntary respiratory muscle strength, as measured by maximal inspiratory pressures and in US measures of diaphragm contractility. The study demonstrates the feasibility of TTPN in difficult to wean patients and suggests a potential for clinical improvement but the low recruitment rate indicates some of the challenges that need to be overcome for this to enter clinical practice. It is possible, however, that given the multifactorial nature of weaning-failure, an intervention targeting the diaphragm alone may not be sufficient to achieve an improved weaning outcome.
Barotrauma in patients with COVID-19 infection on IMV: higher rates but no clear impact on outcome
Many clinicians noted an apparent high incidence of barotrauma during IMV in patients with COVID-19 induced acute respiratory distress syndrome (ARDS). McGuinness et al (Radiology 2022;297:E252) used a retrospective single centre study to compare the incidence of barotrauma (eg, pneumothorax, pneumomediastinum) in patients on IMV with COVID-19 to a group of non-COVID patients from the same time period (cohort A), as well as a historical cohort (cohort B). A non-blinded review of images retrieved by keyword search from electronic health record was performed by two trained radiologists to help ascertain legitimacy and type of barotrauma; cases of procedure-associated barotrauma were excluded, overall survival, general demographics and dates of admission and discharge were recorded. A total of 601 COVID-19 and 196 non-COVID-19 patients were identified with a further 285 patients included in the historical cohort. COVID-19 positive patients receiving IMV identified over a time period of 1 month, had a high barotrauma rate of 15% (95% Cl 12% to 18%), compared with a 0.5% in cohort A, and 10% (95% CI 7% to 14%) in cohort B of the non-COVID-19 patients. Interestingly, there was impact of barotrauma on survival in group with COVID-19. These findings, align with elevated barotrauma rates during severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus outbreaks, suggesting that coronavirus infections specifically increase barotrauma risk. The authors examined the relationship between demographic factors and barotrauma, which indicated higher rates in younger patients. However, there were no data presented on ventilator settings which is important to differentiate whether the higher rates are related to treatment effects or COVID-19 infection itself. These findings suggest that rates of barotrauma, an adverse event associated with longer hospital stay and mortality, were higher in COVID-19 patients requiring IMV compared with non-COVID-19 ARDS patients. Better understanding of how ventilator pressure differentials may affect barotrauma rates in COVID-19 patients is needed.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.