The Latest in Critical Care: October 6, 2025
Corticosteroids for critical illness; Tirofiban for stroke (ASSET IT); late tPA (HOPE trial); Does BIS monitoring help?; Adamgammadex for NMB reversal
Corticosteroids for critical illness: “lumping” meta-analysis says yes
In a meta-analysis of 43 randomized trials enrolling 10,853 critically ill patients, steroids reduced short-term mortality by ~15%, ICU stays by ~2 days, ventilation duration by ~4 days, and shock duration, with improved oxygenation, without increasing infection rates or bleeding—all at the low, low price of an increase in hyperglycemia.
The meta-analysis combined multiple well-known studies dating back decades with broad enrollment criteria, from severe pneumonia (CAPE COD) to sepsis with shock (APROCCHSS).
Corticosteroids are now recommended for most patients with ARDS (of any severity) and sepsis with shock, by various major critical care societies.
Tirofiban to improve outcomes after mechanical thrombectomy for ischemic stroke (ASSET-IT trial et al)
After mechanical thrombectomy, patients with ischemic stroke sometimes experience reocclusion of the culprit large vessel, worsening outcomes.
Tirofiban is an antiplatelet glycoprotein IIb/IIIa inhibitor marketed in the U.S. for decades as Aggrastat® for the management of ACS with PCI. Although it has largely been supplanted by more potent antiplatelet agents like clopidogrel and prasugrel, IV tirofiban is still used adjunctively during or after PCI for high-risk or complex STEMI cases.
Four recent randomized trials have explored potential roles for tirofiban in the management of ischemic stroke. All four trials were conducted in China.
RESCUE BT (JAMA 2022): No benefit from tirofiban in large vessel occlusion patients when given before thrombectomy
RESCUE BT2 (NEJM 2023): Improved neurologic outcomes in mixed group of ischemic stroke patients randomized to tirofiban
TREND (JAMA Neurol 2024): Improved neurologic outcomes in non-cardioembolic ischemic stroke with tirofiban treatment.
In the latest ASSET-IT trial (NEJM 2025), tirofiban also led to improved outcomes after mechanical thrombectomy in non-cardioembolic ischemic stroke.
Patients treated with tirofiban in these trials tended to have more intracranial hemorrhages (e.g., 1.7% vs. 0 in ASSET-IT).
Outside China, tirofiban is only being tested among a planned 240 patients at 13 centers in Spain, in the ATILA trial.
—Tao et al, Early Tirofiban Infusion after Intravenous Thrombolysis for Stroke , NEJM 2025
tPA after 4.5 hours for ischemic stroke (HOPE trial)
How long after an ischemic stroke could thrombolytics bring more benefit than harm?
The EXTEND trial (NEJM 2019) showed that thrombolysis with alteplase improved outcomes in patients presenting as long as 9 hours after ischemic stroke symptom onset. These patients did not undergo thrombectomy (being enrolled largely in the pre-thrombectomy era) and were carefully selected, with automated perfusion imaging showing they had hypoperfused but salvageable regions of brain. However, symptomatic intracerebral hemorrhages occurred in 6% of those receiving alteplase vs 1% with placebo.
EXTEND persuaded European and Australasian guidelinists in 2020-2021 to recommend alteplase up to 9 hours after ischemic stroke onset if advanced imaging showed salvageable brain tissue. EXTEND was conducted mostly in Australasia.
U.S. guidelinists (AHA/ASA) did not modify their guidance significantly, continuing to recommend alteplase within 4.5 hours of stroke onset followed by thrombectomy, or thrombectomy alone after 4.5 hours. (Flexibility was advised for unknown onset, so-called “wake-up” strokes.)
Other trials followed, with varying enrollment criteria, limiting their generalizability:
In the latest, the HOPE trial (JAMA 2025) randomized 372 patients presenting with ischemic stroke up to 24 hours after symptom onset to either alteplase or placebo. Although most had large vessel occlusions, thrombectomy was not performed (it was available but deferred in these patients for varying reasons; this was in China).
Those receiving alteplase had significantly higher rates of functional independence (40% vs 26%), at the expense of more symptomatic intracranial hemorrhages (3.8% vs 0.5%); mortality was equivalent in both arms (11%).
Most U.S. hospitals do not offer rapid CT perfusion or thrombectomy. Transport to the nearest stroke center can provide major potential advantages to optimize care for ischemic stroke.
Due to national differences between health care systems, the HOPE results should be considered hypothesis-generating only.
Processed EEG (BIS) monitoring’s effect on outcomes: meta-analysis
A meta-analysis concluded that processed EEG monitoring (aka bispectral index or BIS) led to lower total sedative doses, opioid doses, and length of stay, without reducing duration of mechanical ventilation. The study combined observational data with randomized trials of high statistical heterogeneity and risk for publication bias, and should be considered hypothesis generating only.
—Jaworska et al. Evaluation of Objective Sedation Monitoring Practices in Critically Ill Adult Patients: A Systematic Review and Meta-Analysis. Critical Care Explorations 2025.
A Cochrane review in 2018, limited to only RCTs, remains the reference meta-analysis. There were only four studies available, of low quality, and no conclusions could be drawn as to any effects of processed EEG monitoring on clinical outcomes including length of stay, sedation doses, or mortality.
—Shetty et al. BIS monitoring versus clinical assessment for sedation in mechanically ventilated adults in the intensive care unit and its impact on clinical outcomes and resource utilization. Cochrane Database Systematic Reviews 2018.
Adamgammadex for neuromuscular blockade reversal
Adamgammadex is a neuromuscular blockade reversal agent with a similar structure to sugammadex. Adamgammadex reversed rocuronium-induced neuromuscular block equivalently well to sugammadex in a head-to-head comparison trial. Developed and produced in China as a potentially less-allergenic alternative to sugammadex, adamgammadex continues to await FDA approval.
—Zhao et al. Efficacy and safety of adamgammadex for reversing rocuronium-induced deep neuromuscular block: a multicentre, randomised, double-blind, positive-controlled phase III trial. BJA 2025
Physiology Flashback!
ICU Physiology in 1000 Words: Airway Pressure Release Ventilation – Part 1
Jon-Emile S. Kenny MD [@heart_lung]