Anesthesiology Research Analysis

Time-resolved cryo-EM under non-equilibrium captured μ-opioid receptor–Gαiβγ activation intermediates across partial, full, and super-agonists, linking ligand-specific efficacy to distinct activation trajectories. The work provides a structural framework to rationalize efficacy and signaling bias. These insights can inform design of safer opioid therapeutics with improved analgesia-to-toxicity profiles.

Impact: Mechanistic advance mapping ligand efficacy to MOR activation states, creating a blueprint for biased agonist development and safer analgesics.

Clinical Implications: While not practice-changing today, the structural atlas can guide discovery of opioids with reduced respiratory depression and adverse effects.

Using in vivo calcium imaging, opto/chemogenetics, and EEG across volatile and IV anesthetics, dmPAG glutamatergic neurons were shown to be suppressed under anesthesia and active during wakefulness. Activation delayed induction, accelerated emergence, and reduced burst-suppression, while inhibition potentiated anesthetic effects. Findings identify a convergent arousal substrate across agents with translational potential for emergence control.

Impact: Identifies a causal arousal node that generalizes across anesthetic classes, enabling future neuromodulation or pharmacologic strategies to optimize emergence and EEG dynamics.

Clinical Implications: Motivates translational work to test dmPAG-targeted neuromodulation and to interpret intraoperative EEG more mechanistically for emergence management.

A multicenter randomized trial (n=2,365) found no reduction in 28-day in-hospital mortality when ketamine was used instead of etomidate for RSI in critically ill adults. Ketamine was associated with a higher incidence of peri-intubation cardiovascular collapse, while other prespecified safety outcomes were similar. Results provide definitive comparative effectiveness data for induction agent choice.

Impact: Settles a long-standing controversy on RSI induction agents in the critically ill; will influence airway guidelines and hemodynamic management.

Clinical Implications: Do not prefer ketamine over etomidate expecting survival benefit; anticipate higher risk of peri-intubation collapse with ketamine and prepare for aggressive hemodynamic support.

In a large multicenter RCT (~1,435 open abdominal cases), a driving pressure–guided high PEEP strategy with recruitment maneuvers did not reduce postoperative pulmonary complications versus standard low PEEP. High PEEP increased intraoperative hypotension and vasoactive use; low PEEP saw more transient desaturations. Findings argue against routine use of individualized high-PEEP recruitment bundles.

Impact: Definitive evidence refining intraoperative ventilation protocols toward safer, less hemodynamically harmful strategies.

Clinical Implications: Avoid routine high-PEEP recruitment strategies; prioritize low tidal volume ventilation and individualized PEEP based on hemodynamic tolerance.

PRISMA-style synthesis of 20 RCTs (n=3,459) showed that adjunct low-dose, short-course systemic corticosteroids probably reduce short-term mortality in severe non-COVID pneumonia (RR 0.73) and show benefit across ARDS trials, with little to no increase in hospital-acquired infections. Corticosteroids may also reduce secondary shock in severe pneumonia.

Impact: High-level evidence addressing a long-standing question in severe pneumonia/ARDS management with immediate practice and guideline implications.

Clinical Implications: Consider adjunct low-dose, short-course systemic corticosteroids in severe pneumonia/ARDS while maintaining infection surveillance and tailoring to contraindications.