The Hallway Consult — Issue #25: Cooling Duration After Cardiac Arrest, Post-Arrest Oxygen Targets, and Catheter-Directed Thrombolysis for PE

Cooling Duration After Cardiac Arrest: ICECAP

Therapeutic hypothermia after out-of-hospital cardiac arrest (OHCA) is standard practice, but how long to keep a patient cold has never had a real answer — current protocols running 24 hours are based more on convention than evidence. ICECAP was built to find the right duration using a response-adaptive design that could steer enrollment toward whichever durations were actually performing best.

Researchers at 71 U.S. hospitals enrolled 1,158 comatose adults after OHCA between 2020 and 2025. Every patient was cooled to 33°C — the trial did not test cooling versus no cooling — and was randomized to one of ten possible durations, from 6 hours up to 72 hours. All patients reached target temperature within 4 hours of arrest. The cohort included 883 patients with nonshockable initial rhythms and 275 with shockable rhythms; median age was 61.

The primary outcome was 90-day neurologic function. In the nonshockable group, the adaptive model calculated only a 51% probability that 6 hours was the shortest duration still achieving the best possible outcome — in plain terms, the trial could not meaningfully distinguish between durations. The shockable group showed the same pattern. Notably, the adaptive algorithm never steered patients into the longest planned arms (60 or 72 hours) — the longest duration actually populated with patients was 48 hours, itself a signal that longer cooling wasn't pulling ahead. There was no difference in mortality and no difference on any secondary outcome across durations. The trial stopped early after a planned interim analysis showed longer cooling simply wasn't going to win.

One finding outside the primary endpoint is worth carrying into every family conversation: some patients, particularly in the nonshockable group, regained consciousness more than two weeks after their arrest, and overall survival in that group outpaced prior cooling cohorts. Early prognostication — withdrawing care on day 3 or 5 based on an assumption that the patient has had every chance to wake up — may be acting on incomplete information.

Bottom line: In this 1,158-patient adaptive RCT, no cooling duration from 6 up to 48 hours (the longest durations actually used — the model never allocated patients to the planned 60- or 72-hour arms) improved 90-day neurologic outcome, mortality, or any secondary outcome over 6 hours. This doesn't tell us whether cooling itself helps (every patient here was cooled), but it supports using the shortest effective duration rather than defaulting to prolonged cooling, and it argues for patience before early withdrawal-of-care decisions.

Meurer WJ, Yeatts SD, Geocadin RG, et al; SIREN Investigators. Duration of Therapeutic Hypothermia After Out-of-Hospital Cardiac Arrest: The ICECAP Randomized Clinical Trial. JAMA. 2026.

Oxygen Targets After Cardiac Arrest: LOGICAL

Hyperoxia after ROSC has long been suspected of worsening reperfusion injury in an already-vulnerable brain, and conservative oxygen strategies have shown promise in general critically ill populations. LOGICAL tested whether that logic holds specifically for the post-cardiac-arrest brain, where the stakes of getting oxygenation wrong are highest.

This open-label, assessor-blinded trial ran across 39 sites in Australia, 13 in New Zealand, and 1 in Ireland, enrolling adults who were mechanically ventilated in the ICU after cardiac arrest with suspected ischemic encephalopathy. Of 1,840 patients enrolled, 1,821 were analyzed: 873 randomized to a conservative oxygen strategy (SpO2 alarm limits 90–95%, FiO2 weaned toward 0.21) and 948 to a liberal strategy (minimum FiO2 0.3, no upper SpO2 limit). Real separation between the groups was confirmed — conservative patients spent far less time with SpO2 ≥97% than liberal patients (21.2% of hours vs 53.0%).

The primary outcome was favorable functional outcome (extended Glasgow Outcome Scale 5–8) at 180 days. It occurred in 38.2% of the conservative group versus 39.7% of the liberal group — an adjusted absolute difference of −0.9% (95% CI −5.5 to 3.7), no significant difference. There was no benefit in any prespecified subgroup. Secondary outcomes told the same story: survival at 180 days (48.0% vs 49.7%), quality of life, cognitive scores, ventilator duration, and discharge-home rates were all essentially identical between groups.

This is a clean negative trial, not an equivocal one — the separation in actual oxygen exposure between arms was real and confirmed, so the lack of benefit isn't explained by a failure to actually implement conservative targets. The trial was conducted in well-resourced health systems (Australia, New Zealand, Ireland), which is worth noting for generalizability, but there's no signal here suggesting tight oxygen titration changes outcomes after cardiac arrest.

Bottom line: In this 1,821-patient RCT with confirmed separation in oxygen exposure between arms, targeting conservative oxygen (SpO2 90–95%) after cardiac arrest did not improve 180-day favorable functional outcome compared with liberal oxygen (38.2% vs 39.7%), nor any secondary outcome. Avoiding hyperoxia remains reasonable general ICU practice, but meticulous SpO2 titration specifically for neuroprotection after cardiac arrest is not supported by this trial.

The LOGICAL Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Conservative Oxygen for Unresponsive Patients after Cardiac Arrest. N Engl J Med. 2026.

Catheter-Directed Thrombolysis for Intermediate-High-Risk PE: PRAGUE-26

Intermediate-high-risk PE — hemodynamically stable but with RV dysfunction and positive biomarkers — sits in an uncomfortable middle ground: too sick for anticoagulation alone to feel fully reassuring, not sick enough to justify full-dose systemic thrombolysis and its bleeding risk. Catheter-directed approaches have been used as a lower-bleeding-risk compromise for years, but without a trial powered to show whether they actually change outcomes in this specific population. PRAGUE-26 was built to answer that.

This open-label trial across 11 Czech centers randomized 558 patients with intermediate-high-risk PE to conventional catheter-directed thrombolysis (standard infusion catheters, no ultrasound assistance) plus anticoagulation, or anticoagulation alone. CDT patients received a total alteplase dose of 20 mg through the catheter (10 mg for unilateral PE) — a fraction of a systemic thrombolytic dose.

The primary endpoint — a composite of death, recurrent PE, or cardiorespiratory decompensation/collapse within 7 days — occurred in 0.7% of the CDT group versus 6.8% of the anticoagulation-alone group (RR 0.10, 95% CI 0.02–0.44, P < .001), an absolute risk reduction of 6.1% and a number needed to treat of 17. The benefit was driven almost entirely by fewer episodes of cardiorespiratory decompensation or collapse (0.7% vs 5.4%), not by death or recurrent PE individually — meaning CDT appears to be preventing the acute deterioration event itself, which fits the mechanism of directly reducing clot burden and RV strain.

Bleeding didn't track with the benefit: BARC ≥2 bleeding at 7 days was essentially identical between groups (4.6% vs 5.0%, P = .846). The one caveat worth naming plainly rather than glossing over: two intracranial hemorrhages occurred in the CDT group and zero in the anticoagulation-alone group. That numeric imbalance didn't reach statistical significance in a trial of this size, but ICH in PE patients who would otherwise be walking around on anticoagulation alone is the exact outcome that would make any clinician pause, and it deserves to be watched in future, larger trials rather than dismissed because the p-value didn't cross threshold.

Bottom line: In this 558-patient RCT of intermediate-high-risk PE, catheter-directed thrombolysis plus anticoagulation reduced the 7-day composite of death, recurrent PE, or cardiorespiratory decompensation (0.7% vs 6.8%, NNT 17) compared with anticoagulation alone, without a statistically significant increase in major bleeding — though 2 intracranial hemorrhages occurred in the CDT group versus 0 in the control group, a numeric imbalance worth tracking rather than ignoring. This is the first trial to directly support CDT as more than a bleeding-sparing alternative to systemic lysis in this population.

Kočka V, et al. Catheter-Directed Thrombolysis in Intermediate-High-Risk Pulmonary Embolism. N Engl J Med. 2026.

The Hallway Consult is built for EM clinicians who want the useful version of the literature. Forward it to a colleague if it helped.

www.hallwaymedicine.com

— The Hallway Consult team