Good morning! Welcome to another edition of Pressure Support, a weekly newsletter simplifying pulmonary and critical care medicine—and the systems that shape it.

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September 10th, 2026

Among hemodynamically stable patients with intermediate-high–risk acute pulmonary embolism, does conventional catheter-directed thrombolysis with low-dose alteplase reduce early clinical deterioration compared with anticoagulation alone?

Intermediate-high–risk pulmonary embolism is one of the most uncomfortable categories in acute care. The patient is normotensive, so systemic thrombolysis is difficult to justify. But the RV is strained, biomarkers are positive, and we know a meaningful minority will deteriorate despite anticoagulation.

Our current strategy is usually close monitoring plus rescue reperfusion if the patient worsens. The problem is that rescue therapy often arrives after the physiology has already started to go downhill (the slippery slope).

PRAGUE-26 tested whether intervening earlier could prevent that slide.

The investigators enrolled 558 adults across 11 tertiary cardiovascular centers in the Czech Republic. Patients were 18 to 80 years old, had proximal acute PE, remained hemodynamically stable, had an sPESI score of at least 1, and had both RV dysfunction and an elevated troponin or natriuretic peptide level.

Patients were randomized to anticoagulation alone or anticoagulation plus catheter-directed alteplase. The intervention was deliberately simple: a standard 4-French valved infusion catheter with a 10-cm infusion segment, a 1-mg alteplase bolus through each catheter, and then 1 mg per hour per catheter. Most patients with bilateral PE received about 20 mg over nine hours.

This is one of the most interesting parts of the trial. The investigators did not use an ultrasound-facilitated proprietary catheter. They achieved a clinical result that looks broadly similar to HI-PEITHO using conventional infusion catheters at a similar alteplase dose.

That does not prove catheter delivery is superior to peripheral low-dose alteplase, and PRAGUE-26 did not directly compare conventional with ultrasound-assisted thrombolysis. But it makes the incremental value of expensive ultrasound augmentation even harder to defend without better head-to-head evidence.

The primary outcome was a 7-day composite of death from any cause, recurrent PE, or cardiorespiratory decompensation or collapse. Decompensation included cardiac arrest, shock with end-organ hypoperfusion, ECMO, intubation, new noninvasive ventilation, or a persistent National Early Warning Score of at least 9.

The primary outcome occurred in 2 of 280 patients receiving thrombolysis and 19 of 278 receiving standard care. Cardiorespiratory decompensation or collapse occurred in 2 versus 15 patients and drove most of the difference.

There were no deaths by day 7 in the thrombolysis group and four in the standard-care group. That signal is clinically important, but with only four early deaths, the trial cannot establish a mortality benefit.

Death, recurrent PE, or cardiorespiratory decompensation or collapse by day 7

The physiology moved in the expected direction. At 24 hours, the median RV-to-LV ratio was 0.94 with thrombolysis and 1.07 with standard care. ICU and hospital stays were also shorter, and more patients were in WHO functional class I at 30 days.

Those results support faster early recovery. They remain secondary outcomes without multiplicity adjustment, so they should not carry the same weight as the primary endpoint.

The overall bleeding numbers are reassuring. They do not prove that catheter-directed thrombolysis is equally safe, because the trial was not powered to exclude clinically meaningful differences in rare events.

Pay attention to the two intracranial hemorrhages.

For patients: Catheter-directed thrombolysis delivers a smaller dose of clot-dissolving medication through a catheter placed in the pulmonary arteries. In this trial, it substantially reduced the risk of early clinical worsening compared with anticoagulation alone.

The procedure has not been proven to improve survival, and it still carries a risk of serious bleeding in the brain. The decision should depend on the patient’s trajectory, bleeding risk, comorbidities, goals, and access to an experienced center rather than the presence of RV strain alone.

For pulmonary and critical care physicians: This trial should change the conversation more than it changes the protocol.

PRAGUE-26 and HI-PIETHO now point in the same direction: early low-dose catheter-directed fibrinolysis can reduce short-term deterioration in selected intermediate-high–risk PE. That makes it harder to dismiss catheter-directed thrombolysis as a therapy supported only by improvements in RV imaging.

Would you opt to treat every normotensive patient with RV strain and a positive troponin with CDT? Probably not. The absolute benefit depends on baseline risk, and the patients most likely to benefit are probably those showing meaningful clinical distress or a worsening trajectory despite anticoagulation (not those who happen to meet a biomarker definition while remaining comfortable and stable).

The practical change is a lower threshold for early PERT activation and transfer planning, which the updates PE guidelines already account for. If we wait for shock, we have already lost the preventive window the trial was designed to test. At the same time, we should explicitly weigh intracranial bleeding risk and avoid letting a favorable composite endpoint become a blanket procedural indication.

Let’s talk about the catheter choice, briefly. PRAGUE-26 used a conventional infusion catheter and produced results similar to an ultrasound-facilitated strategy. Ultrasound may still offer a technical advantage in some settings, but the burden is shifting toward proving that advantage rather than assuming it. Next up would be evaluating low dose alteplase administered peripherally!

This evidence also helps fill a gap left by the recent guidelines mentioned above, which recognized catheter-based therapies but could not draw firm lines between thrombolysis, mechanical thrombectomy, and other reperfusion strategies.

For the health system: The use of a standard infusion catheter (vs ultrasound) may matter economically. If conventional catheters can reproduce the outcomes of proprietary ultrasound-facilitated systems, hospitals should question whether the added device cost buys meaningful clinical benefit.

The larger financial question is whether preventing decompensation and shortening ICU or hospital stays offsets the cost and complexity of an invasive procedure. PRAGUE-26 suggests that it might, but the trial did not include a formal cost-effectiveness analysis and was not designed to compare device strategies (this should be next on the agenda!).

In summary, PRAGUE-26 provides strong randomized evidence that conventional catheter-directed low-dose alteplase can prevent early deterioration in carefully selected patients with intermediate-high–risk pulmonary embolism. The effect is clinically meaningful and consistent with HI-PEITHO, but it remains primarily a “decompensation story” not yet a “mortality story.” For now, the best application is earlier multidisciplinary evaluation, careful patient selection, and a healthy skepticism toward claims that more expensive catheter technology automatically produces better outcomes.

At ATS 2026, leaders like Laurah Turner and others argued that AI is already embedded in medical training, but we should use it to augment (not replace) judgment—because LLMs can hallucinate, overreliance can “de-skill” clinicians, and the biggest patient-safety risk may be errors of omission. I’m excited about AI for things like simulation training, summarizing charts, and reducing documentation burden, but we need clearer guardrails and benchmarks so it actually improves learning and clinical workflows instead of quietly making trainees less thoughtful and less safe.

A multicenter ICU cohort from China found obesity is a strong independent risk factor for developing sepsis-associated ARDS under both Berlin and expanded (HFNC-inclusive) criteria. Interestingly, obesity wasn’t linked to worse survival under the expanded definition, and under Berlin criteria it was associated with lower 90-day mortality in some subgroups.

This paper compares respiratory muscle strength, functional exercise capacity, and muscle oxygenation across people with COPD, PRISM, and healthy controls, to see how these groups differ. Basically it’s mapping out where PRISM and COPD sit on the spectrum vs healthy participants in terms of muscle performance and oxygenation.

This editorial breaks down evidence that rocuronium dose matters for rapid sequence intubation—using >1.2 mg/kg seems to improve first-pass intubation success (at least in ICU patients) compared with lower doses, based on secondary analyses of large airway trials.

This piece argues that COPD exacerbations aren’t just short-term flare-ups. Each one can shift a patient’s trajectory and raise the risk of future exacerbations, hospitalizations, and worse outcomes. The takeaway is to treat every exacerbation as a big warning sign and focus on prevention so the next one is less likely.

This MedPage Today piece covers a small prospective bronchoscopy study where microplastics showed up more often (and in higher counts) in BAL/airway tissue from people with newly diagnosed lung cancer than in controls, even after adjusting for smoking/age/sex—interesting finding, but still very much association, not causation. It’s a cool early human data point, but I’d love to see tighter exposure histories, contamination controls, and a clearer “so what” workflow for how we’d act on this in clinic or public health before it changes practice.

This cluster RCT in 91 care homes (1,158 residents) found that putting portable HEPA filters in communal rooms and residents’ bedrooms didn’t reduce winter respiratory infection episodes (and didn’t improve other infection outcomes or staff absenteeism) compared with usual infection-prevention practices. This is a good reminder that “engineering controls” can look great in lab settings, but in real-world care environments the achievable air changes, placement, and human factors may blunt any measurable clinical benefit—so the basics of IPC still matter most.

Let me know your feedback!

Keeping it simple,

Jared