Weekly Anesthesiology Research Analysis
This week’s anesthesiology literature delivered high-impact translational and clinical findings: LC/MS–based pharmacokinetics revealed that intranasal oxytocin has <1% bioavailability and an open dosing simulator to guide future studies; a multicenter phase‑3 RCT (SESAR) showed inhaled sevoflurane sedation in moderate–severe ARDS was inferior to propofol with fewer ventilator‑free days and worse 90‑day survival; and a global sales–based analysis estimated a 27% decline in CO2‑equivalent impact f
Summary
This week’s anesthesiology literature delivered high-impact translational and clinical findings: LC/MS–based pharmacokinetics revealed that intranasal oxytocin has <1% bioavailability and an open dosing simulator to guide future studies; a multicenter phase‑3 RCT (SESAR) showed inhaled sevoflurane sedation in moderate–severe ARDS was inferior to propofol with fewer ventilator‑free days and worse 90‑day survival; and a global sales–based analysis estimated a 27% decline in CO2‑equivalent impact from halogenated anaesthetics over the past decade driven by reduced desflurane use. Together these papers push practice changes (reconsider intranasal oxytocin use, prefer IV propofol for deep ARDS sedation) and policy/procurement decisions toward lower‑carbon agents.
Selected Articles
1. Plasma pharmacokinetics of intravenous and intranasal oxytocin in nonpregnant adults.
Using a sensitive LC/MS assay and population PK modeling, this prospective study reports robust two‑compartment kinetics for IV oxytocin and demonstrates that intranasal oxytocin has very low bioavailability (~0.7%) with high intersubject variability. LC/MS measurements exceeded ELISA values and a public dosing simulator was released to guide future studies.
Impact: Resolves longstanding uncertainty about intranasal oxytocin's systemic exposure using gold‑standard LC/MS and supplies an open simulator — likely to redirect translational studies and clinical trial design away from assumptions of effective nasal systemic dosing.
Clinical Implications: Clinicians and trialists should not assume therapeutic systemic levels from intranasal oxytocin; consider IV administration or alternative delivery systems for systemic effects and use the simulator for PK‑guided dosing in future studies.
Key Findings
- Intravenous oxytocin PK fits a two‑compartment model with low bias and acceptable inaccuracy.
- Intranasal oxytocin bioavailability ≈0.7% with large intersubject variability (median inaccuracy ~47%).
- LC/MS yields systematically higher oxytocin concentrations than ELISA in simultaneous samples.
- A publicly available dosing simulator was created to guide future oxytocin studies.
2. Inhaled Sedation in Acute Respiratory Distress Syndrome: The SESAR Randomized Clinical Trial.
A phase‑3, multicenter randomized trial in 687 adults with moderate–severe ARDS found inhaled sevoflurane sedation resulted in fewer ventilator‑free days at 28 days and lower 90‑day survival compared with intravenous propofol; early mortality and fewer ICU‑free days were also worse with sevoflurane.
Impact: A high‑quality, multicenter RCT demonstrating potential harm from a commonly discussed ICU sedation strategy directly informs clinical practice guidelines and mandates reassessment of volatile‑based ICU sedation in ARDS.
Clinical Implications: For moderate–severe ARDS requiring deep sedation, favor intravenous propofol over inhaled sevoflurane; institutions should review protocols that promote volatile sedation in ARDS and monitor outcomes if volatiles are used.
Key Findings
- Ventilator‑free days through day 28 were lower with sevoflurane vs propofol (median difference −2.1 days).
- Ninety‑day survival was lower with sevoflurane (47.1%) than propofol (55.7%); HR 1.31.
- Sevoflurane was associated with higher 7‑day mortality and fewer ICU‑free days through day 28.
3. Greenhouse gas impact from medical emissions of halogenated anaesthetic agents: a sales-based estimate.
Using IQVIA MIDAS global sales data (2014–2023) across 91 countries, authors estimated a 27% reduction in CO2‑equivalent impact from halogenated anesthetics over ten years, largely due to decreased desflurane use in high‑income countries, while some middle‑income countries showed rising desflurane use.
Impact: Provides the first comprehensive global, longitudinal estimate linking anesthetic agent market trends to greenhouse gas impact, directly informing procurement, formulary decisions, and climate‑oriented anesthesia policies.
Clinical Implications: Encourage formularies to remove or limit desflurane, favor lower‑impact agents such as sevoflurane or TIVA where clinically appropriate, adopt low‑flow anesthesia, and target education/policy interventions in middle‑income regions.
Key Findings
- Global greenhouse gas impact from halogenated anesthetics decreased by 27% between 2014 and 2023.
- Decrease was driven largely by reduced desflurane use in high‑income countries.
- Some middle‑income countries exhibited increased desflurane use, indicating targeted mitigation needs.