Here is edition 7 of the hottest critical care trials and papers generating buzz across Critical Care Reviews, EMCrit/PulmCrit, REBEL EM, LITFL, The Bottom Line, and many others. A huge thank you as always to all the incredible curators in the FOAMed community — you know who you are!
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ORIENTAL-MEVO — Endovascular Treatment for Medium Vessel Occlusion Stroke
NEJM
Medium vessel occlusions (MeVO) — branches beyond the main M1/M2 — have historically been left to thrombolytics alone while thrombectomy was reserved for large vessel occlusions. This large RCT from China directly challenges that. The ORIENTAL-MEVO trial found that endovascular treatment for medium vessel occlusion strokes significantly improved 90-day functional outcomes compared to medical therapy alone. A genuine practice-changer for stroke and neurocritical care teams globally, and generating significant debate about how far down the vascular tree we should be intervening.
TNK-PLUS — Tenecteplase Before Thrombectomy for Late-Window Stroke
JAMA
Should we be giving tenecteplase to patients in the 4.5–24 hour window before proceeding to endovascular treatment for ischaemic stroke? This Chinese multicentre RCT says yes. TNK-PLUS found that intravenous tenecteplase prior to endovascular treatment in this extended time window improved outcomes compared to thrombectomy alone. Published alongside INSTANT and CHOICE-2 in a landmark JAMA stroke triple-bill that dominated neurocritical care discussions on #FOAMed throughout May and June.
INSTANT — Tirofiban After Tenecteplase in Acute Ischaemic Stroke
JAMA
The second of the JAMA stroke triple-bill. The INSTANT trial evaluated whether adding intravenous tirofiban (a GP IIb/IIIa inhibitor) after an inadequate response to tenecteplase improved outcomes in acute ischaemic stroke patients. The investigators found that tirofiban after tenecteplase increased the likelihood of improved outcomes at 90 days. A genuinely exciting result that adds nuance to the expanding acute stroke pharmacotherapy toolkit. Paired with TNK-PLUS and CHOICE-2 for the full picture.
CHOICE-2 — Intra-Arterial Alteplase After Successful Thrombectomy
JAMA
The third stroke blockbuster in JAMA’s May triple-bill. After successful mechanical thrombectomy, should we be giving adjunctive intra-arterial alteplase to improve microvascular reperfusion? The CHOICE-2 trial from Spain addresses this head on. Published back-to-back with TNK-PLUS and INSTANT, this trio represents the most significant update to acute stroke management since the original thrombectomy trials. Essential reading for neurointensivists, stroke physicians, and ED teams everywhere.
FASTEST — Recombinant Factor VIIa for Spontaneous Intracerebral Haemorrhage
LANCET
This phase 3 multicentre RCT tested recombinant activated factor VIIa versus placebo in patients with spontaneous intracerebral haemorrhage treated within 2 hours of symptom onset — an ultra-early haemostatic strategy. With haematoma expansion being the key driver of deterioration in ICH, the logic is compelling. The full trial results and subsequent commentaries are now generating sustained critical care and neurology discussion on #FOAMcc. An important read for any unit managing spontaneous ICH.
FLORALI-3 — High-Flow vs Standard Oxygen in Acute Hypoxaemic Respiratory Failure
NEJM
Frat and colleagues are back with another FLORALI instalment — this multicentre RCT compares high-flow nasal oxygen against standard oxygen therapy in patients with acute hypoxaemic respiratory failure. With FLORALI (2015) being one of the foundational HFNO trials, this update in a broader patient population is eagerly anticipated and carries significant weight. Directly relevant to every ED, acute medicine, and ICU team managing hypoxaemic patients — and generating predictable debate on #FOAMed about who gets HFNO and when.
EITVent — Electrical Impedance Tomography-Guided PEEP in ARDS
American Journal of Respiratory and Critical Care Medicine
Can bedside electrical impedance tomography (EIT) improve outcomes in ARDS by personalising PEEP titration? This Chinese multicentre RCT (Yuan et al.) evaluated whether EIT-guided PEEP — balancing lung overdistension against collapse — reduced mortality in ARDS patients compared to the standard lower PEEP/FiO₂ table strategy. Precision ventilation is the direction of travel in ARDS management, and this is the most rigorous RCT yet to test it. Highly relevant for respiratory and critical care teams and generating excited discussion across #CritCare and #FOAMcc.
SHOSREB — Remimazolam vs Propofol for Short-Term ICU Sedation
Intensive Care Medicine
Remimazolam — a newer ultra-short-acting benzodiazepine with organ-independent metabolism — going head to head with propofol for short-term light sedation in the ICU. This Chinese multicentre, single-blind RCT (Yang et al.) provides the most rigorous comparative data yet on remimazolam as an ICU sedative agent. With propofol infusion syndrome a real concern and our sedative armamentarium limited, a viable alternative would be genuinely welcome. Results and safety data being closely scrutinised on #ICUMedicine and #FOAMcc.
IMMUNOSEP – precision immunotherapy in sepsis
JAMA
I missed this one earlier in the series!
The future of sepsis treatment may be personalised — and ImmunoSep is the trial that makes that case most compellingly yet. This double-blind, double-dummy, placebo-controlled phase 2 RCT enrolled 276 sepsis patients across 6 countries, stratified by immune phenotype: those with macrophage activation-like syndrome (MALS, defined by markedly elevated ferritin) received anakinra, while those with sepsis-induced immunoparalysis (low HLA-DR expression) received recombinant interferon-gamma. The result: 35.1% of the precision immunotherapy group achieved a clinically meaningful reduction in SOFA score by day 9, versus 17.9% with placebo. No significant mortality difference at 28 days — but as Derek Angus wrote in the accompanying JAMA editorial, this is “the end of the beginning.” Covered extensively by The Bottom Line, PulmCCM, and EMCrit — generating major #FOAMcc discussion about whether precision sepsis immunotherapy has finally arrived.
HFNO After Cardiac Surgery — Randomised Clinical Trial
JAMA Network Open
High-flow nasal oxygen after cardiac surgery versus standard care: does it reduce post-operative pulmonary complications and reintubation rates? This Australian RCT (Litton et al.) tackles a practically important question for every cardiac surgery unit. Post-operative respiratory failure is a major driver of ICU readmission and prolonged stay after cardiac surgery, and simple, scalable respiratory support interventions are urgently needed. Discussed across anaesthesia, cardiac surgery, and critical care #FOAMed communities.
FAST — Rapid Antimicrobial Susceptibility Testing for Gram-Negative Bacteraemia
JAMA
This open-label RCT (Banerjee et al.) tested whether rapid phenotypic antimicrobial susceptibility testing directly from positive blood culture bottles — alongside standard susceptibility testing — improved clinical outcomes in patients with gram-negative bloodstream infections. The primary outcome was a desirability of outcome ranking (DOOR) at day 30. Despite clinical intuition that faster results should help, the trial showed no clear benefit — an important cautionary finding for antimicrobial stewardship programmes investing in rapid diagnostic platforms. Widely discussed on #FOAMed and #InfectiousDiseases.
CLIP-II — Cryopreserved vs Liquid-Stored Platelets in Cardiac Surgery Bleeding
JAMA
Liquid-stored platelets have a shelf life of just 5–7 days, creating logistical headaches, wastage, and periodic shortages — particularly in smaller hospitals, remote centres, and military settings. Cryopreserved platelets, stored at -80°C with dimethyl sulfoxide, last up to 2 years. The promise is obvious. But do they actually work as well? The CLIP-II trial — a multicentre, double-blind, parallel-group randomised non-inferiority trial across 11 Australian tertiary hospitals — compared cryopreserved against conventional liquid-stored platelets in 202 cardiac surgery patients at high risk of bleeding. The primary outcome was chest drain blood loss in the first 24 hours after ICU admission. Non-inferiority was not established: 605mL vs 535mL (ratio of geometric means 1.13, 95% CI 0.96–1.34) — the confidence interval crossed the non-inferiority margin. Cryopreserved platelets were associated with higher intraoperative and total perioperative blood loss, with patients requiring more red cells, plasma, and cryoprecipitate. Ventilation duration and ICU stay were longer in the cryopreserved group. Presented at CCR Down Under 2025, covered by The Bottom Line, and generating debate about whether cryopreserved products can ever replace liquid-stored in routine cardiac surgery. An important cautionary result for services planning cryopreserved blood product programmes.
Therapeutic Plasma Exchange in Acute-on-Chronic Liver Failure — RCT
Hepatology
Therapeutic plasma exchange (TPE) as a bridge to recovery or transplantation in acute-on-chronic liver failure (ACLF): this RCT (Swaroop et al.) reports that TPE significantly improved short-term survival in ACLF patients. ACLF carries devastating mortality and has few effective interventions beyond liver transplantation — a positive TPE result is therefore genuinely exciting. Highly relevant for liver units, hepatologists, and critical care teams managing this increasingly prevalent and difficult condition.
Targeted Hyponatraemia Correction — Randomised Trial
NEJM Evidence
How fast should we be correcting hyponatraemia? This RCT (Refardt et al.) directly compares a targeted correction strategy versus usual care in hospitalised patients with hyponatraemia — a ubiquitous electrolyte disturbance in ICU and acute medicine. Both overcorrection (osmotic demyelination syndrome) and undercorrection carry real risks, yet practice varies enormously. This trial provides the most rigorous guidance yet for a problem every acute physician faces daily. Making waves on #ICUMedicine and #FOAMed.
OxyKids — Oxygen Saturation Thresholds in Children with Acute Respiratory Distress
Lancet Respiratory Medicine
What SpO₂ target should we be aiming for in children with acute respiratory distress? This multicentre, open, parallel-group RCT (Louman et al.) directly compares different oxygen saturation thresholds in paediatric patients — a deceptively simple question with major implications for how much supplemental oxygen children receive during acute illness. Getting oxygen targets right matters in both directions: hypoxaemia harms, but hyperoxaemia has its own toxicity. Critical reading for paediatric emergency and intensive care teams.
PROMPT BOLUS — Balanced Crystalloid vs 0.9% Saline in Paediatric Septic Shock
NEJM
The balanced vs saline fluid debate arrives in paediatric septic shock. This large RCT (Balamuth et al.) randomised children treated for septic shock to balanced crystalloid or 0.9% saline resuscitation. With SMART, PLUS, and BaSICS having shaped adult practice, the paediatric landscape has lagged behind. This is the definitive paediatric RCT on the question — and children are emphatically not small adults when it comes to electrolyte handling. An essential read for paediatric intensivists and emergency physicians.
BESS — Endotracheal Surfactant for Life-Threatening Bronchiolitis in Infants
Lancet Respiratory Medicine
A fascinating, novel intervention for one of the most common reasons infants end up in PICU. This phase 2, randomised, blinded, sham-controlled trial (Semple et al.) tested endotracheal surfactant in infants with life-threatening bronchiolitis requiring invasive ventilation. The rationale: bronchiolitis impairs surfactant function, and exogenous surfactant might improve respiratory mechanics. If positive in future phases, this could change the management of the most critically ill infants with bronchiolitis globally.
DESIGNATION — Intraoperative Driving Pressure-Guided High PEEP vs Standard Low PEEP
JAMA — 2025/2026
This large perioperative RCT compares intraoperative driving pressure-guided high PEEP against standard low PEEP for reducing postoperative pulmonary complications. Featured prominently on the CCR Hot Trials 2026 list and the companion to the PRIME-AIR negative result from Episode 6 — together they paint a nuanced picture of intraoperative lung protection. Read alongside PRIME-AIR to understand the full perioperative ventilation picture. Widely discussed at anaesthesia and critical care conferences in 2026.
Lifestyle Intervention in ICU Survivors — RCT
Critical Care Medicine — Published March 16th 2026
The companion trial to iRehab from Episode 6 — but this one tests a combined lifestyle intervention (physical activity, dietary optimisation, and psychological support) for recovery in ICU survivors. Christiaanse et al. deliver the most holistic post-ICU rehabilitation RCT to date. As post-intensive care syndrome becomes an increasing focus globally, understanding which components of rehabilitation packages actually drive recovery is crucial. Important context for anyone designing or commissioning post-ICU follow-up services.
Left Ventricular Unloading in High-Risk PCI — RCT
NEJM — 2026 (394:1779–1789)
Should we be unloading the left ventricle with a mechanical circulatory support device (Impella) during high-risk percutaneous coronary intervention — before the patient deteriorates into cardiogenic shock? This RCT (Perera et al.) tackles the prophylactic MCS-in-high-risk-PCI question with the rigour it deserves. With high-risk PCI volumes rising and MCS devices more widely available, the haemodynamic support decision is clinically common but evidence-poor. Critical reading for cardiologists, cardiac anaesthetists, and cardiac ICU teams.
Quick Hits from the Trenches
- The JAMA stroke triple-bill (TNK-PLUS, INSTANT, CHOICE-2) + ORIENTAL-MEVO dominating neurocritical care and stroke service planning discussions globally
- FLORALI-3 reigniting the HFNO vs standard oxygen debate for the general hypoxaemic patient — again
- EITVent generating genuine excitement about personalised PEEP titration finally arriving at the bedside in ARDS
- FASTEST trial — ultra-early haemostasis in ICH: compelling rationale, hotly debated results
- FAST trial — a cautionary tale for rapid diagnostics: faster results don’t automatically mean better outcomes
- Plasma exchange in ACLF: one of the few genuinely positive interventions in a condition with devastating mortality
- Paediatric critical care again well represented: OxyKids, PROMPT BOLUS, and BESS all demand attention
- iRehab (Episode 6) continues to dominate #ICUMedicine discussions — DESIGNATION and LIFESTYLE INTERVENTION extending the post-ICU survivorship theme into Episode 7
Stay tuned for Episode 8!
JW and Team x
