Weekly Anesthesiology Research Analysis
This week’s anesthesiology literature highlighted three high-impact directions: mechanistic neuroprotection by ketamine against anesthetic-induced GABAA overactivity with translational memory-sparing potential; device-enabled diaphragm neurostimulation showing improved weaning probability but with increased serious adverse events; and a large RCT demonstrating that acute normovolemic hemodilution does not reduce allogeneic transfusion in cardiac surgery. Together these papers refine perioperativ
Summary
This week’s anesthesiology literature highlighted three high-impact directions: mechanistic neuroprotection by ketamine against anesthetic-induced GABAA overactivity with translational memory-sparing potential; device-enabled diaphragm neurostimulation showing improved weaning probability but with increased serious adverse events; and a large RCT demonstrating that acute normovolemic hemodilution does not reduce allogeneic transfusion in cardiac surgery. Together these papers refine perioperative pharmacologic strategies, ventilator-weaning devices, and blood-conservation policies while underscoring the need for careful safety and implementation studies.
Selected Articles
1. Ketamine-induced Sustained Modulation of γ-Aminobutyric Acid Type A Receptor Function in Mouse Hippocampal Neurons after Anesthesia.
Preclinical work shows ketamine prevents anesthetic-triggered sustained increases in tonic GABAA currents via facilitation of BDNF–TrkB/GSK-3β signaling, reduces α5-GABAA surface expression, and mitigates recognition and spatial memory deficits after sevoflurane in mice, suggesting a non–NMDA-dependent cognitive-sparing mechanism.
Impact: Reveals a novel, translatable mechanism (BDNF–TrkB facilitation and α5-GABAA modulation) by which ketamine may protect cognitive function after general anesthesia, providing strong rationale for clinical trials targeting postoperative cognitive decline.
Clinical Implications: Supports designing randomized trials of perioperative ketamine as an adjunct to reduce postoperative cognitive impairment, and prompts consideration of therapies targeting TrkB or α5-GABAA receptors.
Key Findings
- Ketamine prevented sustained increases in tonic GABAA currents induced by etomidate and sevoflurane.
- Protection mediated via BDNF–TrkB signaling through a GSK-3β-dependent pathway, independent of NMDA antagonism.
- Ketamine reduced cell-surface α5-GABAA receptor expression and prevented recognition/spatial memory deficits in mice.
2. Temporary Transvenous Diaphragm Neurostimulation for Weaning from Mechanical Ventilation (RESCUE-3).
In a multicenter randomized trial (mITT n=216, early stop), twice-daily temporary transvenous diaphragm neurostimulation increased 30-day weaning success (70% vs 61%; adjusted HR 1.34) and likely reduced ventilation duration by ~2.5 days but was associated with higher rates of serious adverse events, while 30-day mortality was similar.
Impact: First multicenter randomized evidence that a device-based diaphragm stimulation strategy can probabilistically improve weaning in difficult-to-wean patients, marking an important step toward mechanistic device therapies in critical care despite safety concerns.
Clinical Implications: May be considered for selected difficult-to-wean patients under structured protocols and monitoring; however, increased serious adverse events mandate patient selection, robust safety surveillance, and larger confirmatory trials before wide adoption.
Key Findings
- 30-day weaning success: 70% (treatment) vs 61% (control); adjusted HR 1.34 (95% CrI 1.01–1.78); posterior probability 97.9%.
- Likely reduction in ventilation duration by ~2.5 days (posterior probability 97.1%),
- Higher serious adverse event rate in treatment arm (36% vs 24%); similar 30-day mortality.
3. A Randomized Trial of Acute Normovolemic Hemodilution in Cardiac Surgery.
In a large multinational RCT (n=2010), acute normovolemic hemodilution did not reduce the proportion of patients receiving allogeneic red-cell transfusion during hospitalization (27.3% vs 29.2%; RR 0.93; P=0.34). Safety outcomes were similar, though reoperation for bleeding was numerically higher in the ANH arm.
Impact: Definitive, high-quality negative evidence against routine ANH for transfusion reduction in contemporary cardiac surgery, redirecting practice toward proven multimodal blood-conservation strategies.
Clinical Implications: Routine use of ANH for transfusion reduction in cardiac surgery is not supported; centers should reassess ANH programs and prioritize other evidence-based blood-conservation measures.
Key Findings
- Allogeneic red-cell transfusion: 27.3% (ANH) vs 29.2% (usual care); RR 0.93 (95% CI 0.81–1.07); P=0.34.
- No benefit of ANH on myocardial infarction, stroke, acute kidney injury, ICU need, length of stay, or 30-day mortality.
- Slight numerical increase in reoperation for bleeding in ANH group (3.8% vs 2.6%).