Daily Anesthesiology Research Analysis
Three studies stand out today in anesthesiology: a global analysis shows a 27% reduction in greenhouse gas impact from volatile anesthetics driven by desflurane declines; high-precision LC/MS pharmacokinetics reveal intranasal oxytocin has extremely low bioavailability (~0.7%), with a public dosing simulator provided; and a prospective cardiac surgery cohort identifies actionable renal NIRS rSO2 thresholds predicting acute kidney injury.
Summary
Three studies stand out today in anesthesiology: a global analysis shows a 27% reduction in greenhouse gas impact from volatile anesthetics driven by desflurane declines; high-precision LC/MS pharmacokinetics reveal intranasal oxytocin has extremely low bioavailability (~0.7%), with a public dosing simulator provided; and a prospective cardiac surgery cohort identifies actionable renal NIRS rSO2 thresholds predicting acute kidney injury.
Research Themes
- Sustainable anesthesia and climate action
- Translational perioperative pharmacology and dosing
- Perioperative organ protection and monitoring
Selected Articles
1. Plasma pharmacokinetics of intravenous and intranasal oxytocin in nonpregnant adults.
Using LC/MS, the authors showed that intravenous oxytocin follows a robust two-compartment model, whereas intranasal oxytocin has very low bioavailability (~0.7%) and high intersubject variability. LC/MS concentrations exceeded ELISA, and a public simulator was released to inform dosing in future studies.
Impact: This work resolves long-standing uncertainty around intranasal oxytocin by providing specific, LC/MS-based PK and an open simulator, likely redirecting clinical and translational research. It challenges assumptions about intranasal efficacy and supports more reliable dosing strategies.
Clinical Implications: Intranasal oxytocin is unlikely to achieve therapeutic systemic levels; trials and clinical use should reconsider this route or adjust expectations. Intravenous dosing can be modeled more reliably, and the simulator can guide future dosing strategies.
Key Findings
- Intravenous oxytocin PK is well described by a two-compartment model (0% bias; 18% median inaccuracy).
- Intranasal oxytocin shows very low bioavailability (~0.7%) with substantial intersubject variability (47% median inaccuracy).
- LC/MS yields systematically higher oxytocin concentrations than ELISA in simultaneous samples.
- A publicly available dosing simulator was created to inform future oxytocin studies.
Methodological Strengths
- Sensitive and specific LC/MS assay with NONMEM population PK modeling
- Registered prospective studies with dual-assay comparison (LC/MS vs ELISA)
Limitations
- Small sample size of healthy, nonpregnant adults limits generalizability
- Intranasal PK characterized by high variability; mechanism of low absorption not fully elucidated
Future Directions: Define mechanistic barriers to nasal absorption, evaluate alternative delivery systems or dosing strategies, and test PK–PD links in target populations with the simulator.
BACKGROUND: The development of oxytocin as a therapeutic agent outside of obstetrics has been hampered by antibody-based assays that lack specificity, leading to inconsistent and incompletely reported pharmacokinetic models to guide drug dosing. This study describes the population plasma pharmacokinetics of intravenous and intranasal oxytocin using a sensitive and specific liquid chromatography-tandem mass spectroscopy (LC/MS) assay. METHODS: Two studies in healthy adult men and nonpregnant women were performed, the first with intravenous oxytocin 16.7 μg over 1 or 10 min and the second with intravenous oxytocin 13.7 μg over 30 min and, on a separate day, intranasal oxytocin 100 μg (n=24). Venous plasma oxytocin concentration was measured using LC/MS and enzyme-linked immunosorbent assay. Pharmacokinetic parameters were estimated using NONMEM. RESULTS: The pharmacokinetics of intravenous oxytocin were well described by a two-compartment model (0% bias, 18% median inaccuracy). The two-compartment model for intranasal oxytocin was characterised by substantial subject-to-subject variability (9% median bias, 47% median inaccuracy). Nasal oxytocin bioavailability was 0.7%. Oxytocin samples assayed with LC/MS were systematically higher than simultaneous samples assayed with enzyme-linked immunosorbent assay. CONCLUSIONS: The pharmacokinetics of intravenous oxytocin are well described by a two-compartment model. The low bioavailability (<1%) and large intersubject variability in plasma oxytocin after intranasal dosing could partially explain the inconsistent reports of oxytocin efficacy in the clinical literature with this delivery method. A publicly available simulator was created to guide oxytocin dosing in future studies. CLINICAL TRIAL REGISTRATION: NCT03929367 (Study 1) and NCT05672667 (Study 2).
2. Greenhouse gas impact from medical emissions of halogenated anaesthetic agents: a sales-based estimate.
Using global sales data (2014–2023) from 91 countries, the authors estimate a 27% reduction in carbon dioxide–equivalent impact from halogenated anesthetics, driven largely by decreased desflurane use in high-income countries. The work highlights rising desflurane use in some middle-income settings and identifies replacement with sevoflurane as a major mitigation lever.
Impact: Provides the first comprehensive, global, longitudinal estimate of climate impact from anesthetic volatiles, directly informing policy, procurement, and clinical practice changes toward low-impact agents.
Clinical Implications: Supports eliminating desflurane formularies, favoring sevoflurane or TIVA where feasible, adopting low-flow anesthesia, and targeting education and policy in middle-income regions to curb rising desflurane use.
Key Findings
- Global greenhouse gas impact from halogenated anesthetics fell by 27% over 2014–2023.
- Decreased desflurane use in high-income countries largely drove the decline.
- Some middle-income countries showed increased desflurane use, suggesting targeted mitigation needs.
- Replacing desflurane/isoflurane with sevoflurane could markedly reduce climate impact.
Methodological Strengths
- Large, multinational dataset covering 80% of the global population
- Consistent 10-year time series with standardized conversion to CO2-equivalents
Limitations
- Sales data are proxies for use and may not perfectly reflect actual emissions
- Coverage excludes some countries; assumptions in conversion factors may introduce uncertainty
Future Directions: Link sales/use to measured waste gas emissions, expand coverage to 100% of countries, and evaluate impacts of low-flow protocols and alternative techniques (e.g., TIVA) on real-world emissions.
BACKGROUND: Halogenated anaesthetic agents are potent greenhouse gases, but little is known about the trajectory of their use and their greenhouse gas impact on a global level. The primary aim of this study was to estimate the global greenhouse gas impact of halogenated anaesthetic agents over the preceding 10 years. METHODS: We obtained global medical sales data for sevoflurane, desflurane, isoflurane, halothane, and methoxyflurane from the IQVIA MIDAS database between 2014 and 2023. We calculated their annual greenhouse gas impact, expressed as carbon dioxide equivalents (CO FINDINGS: The 91 countries in the dataset represented 97·8%, 90·5%, and 66·2% of the population in high-income, upper-middle-income, and low-income or lower-middle-income countries, respectively, and covered 80·0% of the global population in 2023. The greenhouse gas impact of halogenated anaesthetic agents decreased by 27% from 2754 kilotons of CO INTERPRETATION: The global greenhouse gas impact from halogenated anaesthetic agents is falling due to lower use of desflurane in high-income countries. Efforts to reverse the increased use of desflurane in middle-income countries are needed. Replacing desflurane and isoflurane with sevoflurane constitutes an opportunity to markedly reduce the greenhouse gas impact from halogenated anaesthetic agents. FUNDING: The Thelma Zoega Foundation, The Anna and Edwin Berger Foundation, Region Skåne, and a Swedish Government grant for clinical research within the Swedish National Health Service (ALF).
3. Intraoperative Renal Near-Infrared Spectroscopy Monitoring as a Predictor of Renal Outcomes in Cardiac Surgery.
In a prospective cohort of 357 CPB patients, intraoperative renal rSO2 time below 80%, 70%, and 60% thresholds strongly predicted postoperative AKI. Notably, >30 minutes with rSO2 <60% yielded 96.5% specificity and 86.4% sensitivity, suggesting actionable thresholds for intraoperative management.
Impact: Provides practical intraoperative thresholds for renal rSO2 that stratify AKI risk with high diagnostic performance, enabling targeted hemodynamic and renal-protective interventions.
Clinical Implications: Consider continuous renal NIRS in high-risk cardiac surgery; avoid >30 min with rSO2 <60% through fluid optimization, vasopressor support, and perfusion management; prioritize postoperative surveillance in patients breaching thresholds.
Key Findings
- Postoperative AKI occurred in 12.3% (44/357) of CPB patients and was associated with older age, longer surgery/CPB/cross-clamp times, and greater transfusion/IABP use.
- Time with renal rSO2 below 80%, 70%, and 60% robustly predicted AKI; >30 minutes below 60% predicted AKI with 96.5% specificity and 86.4% sensitivity.
- AKI patients had significantly longer ICU stays, underscoring clinical impact.
Methodological Strengths
- Prospective design with continuous intraoperative rSO2 monitoring and KDIGO-defined AKI
- ROC analysis with clear, actionable thresholds demonstrating high specificity and sensitivity
Limitations
- Single-center, observational design limits causal inference and generalizability
- No randomized intervention testing whether threshold-guided management reduces AKI
Future Directions: Multicenter validation and randomized trials testing threshold-guided hemodynamic/renal-protective strategies to reduce AKI incidence.
BACKGROUND Acute renal failure (ARF) is a critical complication following open-heart surgery, significantly impacting morbidity and mortality. This study aimed to evaluate the association between intraoperative renal near-infrared spectroscopy (NIRS) findings and postoperative ARF in 357 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). MATERIAL AND METHODS This prospective study included 357 patients undergoing open-heart surgery with CPB. ARF diagnosis was based on KDIGO criteria. NIRS sensors were placed bilaterally at the T12/L2 level under ultrasound guidance, and renal oxygenation (rSO2) values were continuously monitored intraoperatively. Patients were categorized into ARF and non-ARF groups for comparative analysis. RESULTS ARF developed in 12.3% (n=44) of patients. ARF patients were older (p=0.024) and had longer surgery (p<0.001), CPB (p=0.004), and aortic cross-clamping durations (p=0.013). They required more blood products (p<0.001) and intra-aortic balloon pump support (p=0.027). Intensive care unit stays were significantly longer in ARF patients (p=0.036). NIRS analysis showed significant rSO2 reductions in ARF patients. Time spent with rSO2 below 80%, 70%, and 60% was a strong predictor of ARF. Receiver operating characteristic (ROC) analyses demonstrated that time exceeding 30 minutes below the 60% threshold predicted ARF with 96.5% specificity and 86.4% sensitivity. CONCLUSIONS Intraoperative NIRS monitoring is crucial for detecting renal perfusion abnormalities during high-risk surgeries. Declines below 80%, 70%, and 60% thresholds strongly predict ARF. Timely interventions, such as fluid resuscitation and hemodynamic support, can mitigate risks. ARF patients require intensive postoperative monitoring due to prolonged ICU stays and complications.