Can stimulating the orexin receptor improve both sleepiness and cataplexy in narcolepsy type 1? In this episode of PRISM Rounds, we examine the First Light and Radiant Light phase 3 trials of oveporexton.

Across two 12-week trials, oveporexton produced substantial improvements in objective wakefulness, patient-reported sleepiness, and cataplexy compared with placebo. We discuss what those changes could mean for patients, why urinary frequency and insomnia matter, and what remains uncertain about long-term safety and comparisons with existing treatments.

Read the trial: https://www.nejm.org/doi/full/10.1056/NEJMoa2601598

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Tags

narcolepsy type 1, oveporexton, orexin, hypocretin, cataplexy, excessive daytime sleepiness, sleep medicine, clinical trials, First Light trial, Radiant Light trial, NEJM, PRISM Rounds

Choosing between high-flow nasal cannula, noninvasive ventilation (NIV), CPAP, and conventional oxygen is one of the most common decisions in critical care. The new 2026 American Thoracic Society (ATS) Clinical Practice Guideline provides updated, evidence-based recommendations across the spectrum of acute respiratory failure.

In Season 1, Episode 62 of PRISM Rounds, we examine the guideline published in the American Journal of Respiratory and Critical Care Medicine and explore what its recommendations mean for bedside practice.

We discuss four critical clinical questions:

1. Acute hypoxemic respiratory failure: Why is high-flow nasal cannula strongly recommended over conventional oxygen, and when should clinicians consider NIV or CPAP?

2. Acute hypercapnic respiratory failure: Why does NIV remain first-line therapy, and when might high-flow oxygen be a reasonable alternative?

3. Preoxygenation before intubation: How can HFNC and NIV reduce peri-intubation hypoxemia?

4. Postextubation respiratory support: Which patients benefit from preventive NIV or HFNC, and how can we reduce reintubation?

We also examine the strength and certainty of the evidence, important limitations of network meta-analyses, and the distinction between reducing intubation and improving survival.

The central clinical question: Are we choosing the right respiratory support strategy for the right patient, and recognizing early enough when that strategy is failing?

This episode is designed for intensivists, pulmonologists, emergency physicians, respiratory therapists, critical care fellows, and other clinicians managing acute respiratory failure.

Primary Reference:
Goel NN, Ferreyro BL, et al. Noninvasive respiratory support for adult patients with acute respiratory failure: An official American Thoracic Society Clinical Practice Guideline. American Journal of Respiratory and Critical Care Medicine. 2026;212(9):2135–2158.

https://doi.org/10.1093/ajrccm/aamag302

Listen and subscribe to PRISM Rounds on Apple Podcasts, Spotify, Youtube or visit https://www.prismrounds.com.

Evidence reviewed. Clinical decisions informed.

Tags

ritical Care

Pulmonary Medicine

ATS Guidelines

Noninvasive Ventilation

NIV

High-Flow Nasal Cannula

HFNC

CPAP

Acute Respiratory Failure

Hypoxemic Respiratory Failure

Hypercapnic Respiratory Failure

COPD Exacerbation

Mechanical Ventilation

Preoxygenation

Extubation

Intensive Care Medicine

Evidence-Based Medicine

Clinical Practice Guidelines

Respiratory Therapy

PRISM Rounds

Can therapeutic plasma exchange save lives in acute-on-chronic liver failure, or does it simply delay the inevitable?

In Season 1, Episode 61 of PRISM Rounds, we examine a 2026 randomized controlled trial published in Hepatology evaluating therapeutic plasma exchange in 194 patients with acute-on-chronic liver failure (ACLF).

The findings are striking. Plasma exchange reduced 28-day mortality from 63.9% to 44.3%, an absolute difference of nearly 20 percentage points. However, by 90 days, mortality was similar between groups, and more than 40% of patients could not complete the planned treatment.

We examine the trial's methodology, treatment complications, and clinical implications alongside the 2023 EASL guidelines and a 2025 meta-analysis of plasma exchange in ACLF.

The central question: Does plasma exchange meaningfully alter the course of liver failure, or does it provide a temporary bridge to hepatic recovery or transplantation?

Join us as we explore what this trial should, and should not, change in ICU practice.

Read the primary study:
https://doi.org/10.1097/HEP.0000000000001755

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Visit https://www.prismrounds.com for more episodes.

Tags

Critical Care, Intensive Care, Hepatology, Acute-on-Chronic Liver Failure, ACLF, Therapeutic Plasma Exchange, Plasmapheresis, Liver Failure, Liver Transplantation, Randomized Controlled Trial, Evidence-Based Medicine, ICU Research, PRISM Rounds

In this episode of PRISM Rounds, we examine a new randomized clinical trial comparing olanzapine with low-dose dexmedetomidine for established delirium in critically ill adults.

The primary outcome was neutral: patients in both groups had a median of 3 days alive without delirium or coma. But the study also found more adverse events with dexmedetomidine and a provocative difference in 90-day mortality that demands careful interpretation.

We place these findings in the context of MIND-USA, AID-ICU, SPICE III, nocturnal dexmedetomidine studies, and the 2025 PADIS guideline update. The key issue is not simply which drug performed better, but whether ICU clinicians are asking medications to do different jobs: prevent delirium, control agitation, or actually treat established delirium.

We discuss what this trial adds, its major limitations, why the mortality signal should remain hypothesis-generating, and what the results should—and should not—change at the bedside.

Primary article:
https://doi.org/10.1093/ajrccm/aamag235

Listen and subscribe on Apple Podcasts, Spotify, YouTube, or at https://www.prismrounds.com

PRISM Rounds, critical care, ICU, delirium, ICU delirium, dexmedetomidine, olanzapine, antipsychotics, sedation, agitation, PADIS, MIND-USA, AID-ICU, SPICE III, mechanical ventilation, intensive care medicine, pulmonary critical care, evidence based medicine, journal club, randomized controlled trial, FOAMcc, FOAMed

Tags

How long should comatose patients remain at 33°C after out-of-hospital cardiac arrest?

In this episode of PRISM Rounds, we examine the icecap randomized clinical trial, which studied 1,158 comatose OHCA survivors who had already been rapidly cooled to 33°C. Patients were assigned to different cooling durations ranging from 6 to 72 hours.

Longer cooling did not improve neurological recovery, mortality, or secondary neurological outcomes. We discuss the adaptive trial design, the separate shockable and nonshockable rhythm cohorts, the meaning of the approximately 50% probability that 6 hours was the shortest optimal duration, and why this does not establish a universal six-hour protocol.

The episode places icecap in context with TTM, TTM2, and HYPERION while keeping clear that these trials addressed different temperature-management questions.

Read the study:
https://jamanetwork.com/journals/jama/fullarticle/2852508

Subscribe to PRISM Rounds on Apple Podcasts, Spotify, or YouTube, and visit:
https://www.prismrounds.com

Tags:
icecap, cardiac arrest, out-of-hospital cardiac arrest, OHCA, targeted temperature management, therapeutic hypothermia, post-cardiac arrest care, neuroprotection, neurological recovery, TTM, TTM2, HYPERION, critical care, intensive care, emergency medicine, resuscitation, ICU, fever prevention, modified Rankin Scale, PRISM Rounds

In Season 1, Episode 58 of PRISM Rounds, we review the 2025 Society of Critical Care Medicine guideline for the treatment of heat stroke and translate its recommendations into practical bedside decisions for emergency and critical care clinicians.

We discuss why active cooling should begin immediately, why cold- or ice-water immersion is preferred when feasible, and why the guideline emphasizes both the speed of cooling and the goal of reaching a core temperature below about 39°C within 30 minutes. We also review what to do when immersion is not practical and how the guideline approaches classic versus exertional heat stroke.

The episode also covers therapies that should generally be avoided. Routine acetaminophen, NSAIDs, salicylates, and dantrolene are not recommended for temperature reduction, and prophylactic antibiotics or antiseizure medications should be limited to research settings.

An important theme is the strength of the recommendations versus the strength of the evidence. Several recommendations are strong despite very low-certainty evidence, reflecting the practical and ethical difficulty of conducting randomized trials that delay effective cooling in patients with true heat stroke.

The bedside message is simple: recognize heat stroke early, start the fastest feasible active cooling strategy, continue simultaneous resuscitation and organ support, and avoid medications that do not address the underlying problem.

Read the guideline:
https://doi.org/10.1097/CCM.0000000000006551

More PRISM Rounds:
https://www.prismrounds.com

Available on Apple Podcasts, Spotify, YouTube, and other major podcast platforms.

Tags:
PRISM Rounds, S01E58, critical care, ICU, heat stroke, heatstroke, hyperthermia, SCCM, Society of Critical Care Medicine, emergency medicine, cooling, cold water immersion, ice water immersion, exertional heat stroke, classic heat stroke, temperature management, dantrolene, antipyretics, heat illness, resuscitation, evidence based medicine, clinical guidelines, guideline review, medical education, FOAMed, pulmonary critical care

Should we wait for a patient with intermediate-high-risk pulmonary embolism to deteriorate before pursuing reperfusion—or intervene before the right ventricle fails?

In this episode of PRISM Rounds, we examine PRAGUE-26, a multicenter randomized trial published in the New England Journal of Medicine comparing conventional catheter-directed thrombolysis with low-dose alteplase plus anticoagulation against anticoagulation alone in patients with intermediate-high-risk acute pulmonary embolism.

The headline result is striking: the 7-day composite of death, recurrent pulmonary embolism, or cardiorespiratory decompensation or collapse occurred in 0.7% with catheter-directed thrombolysis versus 6.8% with standard care. But the interpretation requires nuance. The benefit was driven primarily by fewer episodes of cardiorespiratory deterioration, not a demonstrated mortality reduction. Overall major bleeding was not clearly increased, yet two intracranial hemorrhages occurred in the thrombolysis group and none with anticoagulation alone.

We break down patient selection, the low-dose alteplase strategy, the composite endpoint, rescue reperfusion, early RV recovery, bleeding risk, and the limitations of an open-label trial conducted in experienced tertiary cardiovascular centers. Most importantly, we ask what prague-26 should change at the bedside: Does this trial support routine early catheter-directed thrombolysis, or does it help us identify the selected patient who should undergo reperfusion before overt hemodynamic collapse?

The article was published online in the New England Journal of Medicine on August 31, 2026, DOI 10.1056/NEJMoa2608012.

PRISM Trials / PRISM Rounds:
Visit PRISM Trials

Journal article:
Read “Catheter-Directed Thrombolysis in Intermediate-High-Risk Pulmonary Embolism” in NEJM

Tags:
#PRISMRounds #PRISMTrials #CriticalCare #CriticalCareMedicine #ICU #PulmonaryCriticalCare #PulmonaryMedicine #Pulmonology #PulmonaryEmbolism #PE #IntermediateHighRiskPE #SubmassivePE #CatheterDirectedThrombolysis #CDT #Thrombolysis #Alteplase #Anticoagulation #Reperfusion #PERT #PulmonaryEmbolismResponseTeam #RightVentricle #RVFailure #RightHeartStrain #HemodynamicCollapse #CardiorespiratoryDecompensation #Shock #VTE #VenousThromboembolism #EmergencyMedicine #Cardiology #InterventionalCardiology #IntensiveCare #ClinicalTrials #RandomizedTrial #RCT #EvidenceBasedMedicine #MedicalEducation #JournalClub #NEJM #FOAMed #FOAMcc #MedEd #EvidenceBasedCriticalCare

In this episode of PRISM Rounds, we discuss the SAVE-O2 AI randomized clinical trial, which tested autonomous closed-loop oxygen titration versus usual manual oxygen adjustment in 300 hospitalized adults receiving supplemental oxygen.

The autonomous system kept patients in the target SpO2 range much more often, 85% vs 63%, while also reducing time spent in hypoxemia and, even more strikingly, hyperoxemia. We break down what the trial shows, what it does not show, the importance of pulse oximetry accuracy and skin pigmentation, and whether improved oxygen control is enough to justify broader implementation.

We also discuss the accompanying editorial by Weingart and Matthay, which explores the potential impact on clinician workload, oxygen stewardship, resource-limited settings, and the next generation of implementation and outcomes studies.

SAVE-O2 AI trial, JAMA Internal Medicine
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2026.4023
DOI: https://doi.org/10.1001/jamainternmed.2026.4023

Invited Commentary: Potential Transformative Impact of Autonomous Oxygen Delivery in Hospitalized Patients
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2026.4038
DOI: https://doi.org/10.1001/jamainternmed.2026.4038

Find more episodes at www.prismrounds.com and subscribe on Apple Podcasts or Spotify.

Tags
#PRISMRounds #SAVE02AI #CriticalCare #ICU #PulmonaryCriticalCare #OxygenTherapy #Hypoxemia #Hyperoxemia #PulseOximetry #ClosedLoopControl #ArtificialIntelligence #DigitalHealth #ClinicalTrials #RandomizedTrial #JAMAInternalMedicine #RespiratoryCare #FOAMcc #MedEd