Daily Anesthesiology Research Analysis
Analyzed 81 papers and selected 3 impactful papers.
Summary
Three studies stand out today: a single-center RCT found that pre-emptive haptoglobin during cardiopulmonary bypass was associated with worse postoperative renal indices, cautioning against this practice. A mechanistic Cell paper identified molecular markers (OSMR, SST) for human ‘sleeping’ nociceptors and showed selective modulation in volunteers, opening avenues for neuropathic pain therapeutics. An offline reinforcement learning system (rECMOmender) produced clinically aligned, interpretable recommendations for venovenous ECMO management.
Research Themes
- AI-driven decision support for critical care (ECMO) management
- Negative randomized evidence altering perioperative kidney protection strategies
- Molecular definition and modulation of nociceptor subtypes informing pain therapeutics
Selected Articles
1. Molecular architecture of human dermal sleeping nociceptors.
Using Patch-seq and cross-species transcriptomics, the authors identify OSMR and SST as molecular markers of human mechano-insensitive C-fiber nociceptors and demonstrate selective modulation by oncostatin M in human volunteers. This defines a long-sought human targetable nociceptor subtype and provides translational evidence for neuromodulatory strategies in neuropathic pain.
Impact: First molecular characterization and selective human modulation of CMis nociceptors establishes actionable targets for neuropathic pain—a frequent perioperative and chronic pain challenge.
Clinical Implications: OSMR/SST may enable patient stratification and development of targeted analgesics or neuromodulation for neuropathic pain. Oncostatin M–OSMR signaling emerges as a candidate pathway for intervention.
Key Findings
- Identified OSMR and SST as marker genes for mechano-insensitive C-fiber nociceptors (CMis) using Patch-seq.
- Selective modulation of CMis demonstrated in healthy human volunteers by dermal oncostatin M (OSMR ligand).
- Cross-species integration (pig/human) and spatial transcriptomics established the molecular architecture of human dermal CMis.
Methodological Strengths
- Multimodal approach combining electrophysiology with single-cell, single-nucleus, and spatial transcriptomics.
- Translational validation including functional human volunteer modulation.
Limitations
- Sample sizes for human functional testing are not detailed and may be limited.
- Clinical efficacy and safety of targeting OSMR/SST pathways remain untested in patients with neuropathic pain.
Future Directions: Prospective interventional trials targeting OSMR signaling in neuropathic pain; development of selective agonists/antagonists; biomarker-driven stratification in analgesic trials.
Human dermal sleeping nociceptors display ongoing activity in neuropathic pain, affecting 10% of the population. Despite advances in rodents, a molecular marker for these mechano-insensitive C-fibers (CMis) in human skin remains elusive, preventing targeted therapy. Using a Patch-seq approach, we combined single-cell transcriptomics, following electrophysiological characterization, with single-nucleus and spatial transcriptomics from pigs and integrated our findings with cross-species and human transcriptomic data. We functionally identified CMis in pig sensory neurons with patch clamp, using adapted protocols from human microneurography. We identified oncostatin M receptor (OSMR) and somatostatin (SST) as marker genes for CMis. Following dermal injection in healthy human volunteers, oncostatin M, the ligand of OSMR, exclusively modulates CMis. Our findings characterize the molecular architecture of human dermal sleeping nociceptors, providing a framework for mechanistic insight into neuropathic pain and potential therapeutic strategies.
2. Influence of Pre-emptive Haptoglobin on Postoperative Acute Kidney Injury in Cardiac Surgical Patients: A Randomized Controlled Trial.
In a single-center open-label RCT halted for safety, pre-emptive haptoglobin guided by serum-free hemoglobin during CPB was associated with a greater rise in postoperative creatinine compared to standard care. Multivariable analysis identified pre-emptive haptoglobin as independently increasing ΔCr.
Impact: Provides randomized evidence against a biologically plausible but unproven renal-protective practice in cardiac surgery, potentially changing intraoperative management.
Clinical Implications: Avoid pre-emptive haptoglobin administration based solely on free hemoglobin thresholds during CPB; reserve use for clear clinical indications while awaiting confirmatory multicenter trials.
Key Findings
- Trial stopped early after interim analysis due to safety concerns.
- Pre-emptive haptoglobin group had higher median ΔCr vs standard care (0.20 vs 0.14 mg/dL; P = .05).
- Multiple linear regression identified pre-emptive haptoglobin as an independent predictor of increased ΔCr (P = .03).
Methodological Strengths
- Randomized controlled design with predefined primary endpoint (ΔCr within 48 hours).
- Objective biochemical trigger (serum free hemoglobin) for intervention.
Limitations
- Single-center, open-label design and small sample size (n=67 analyzed).
- Early termination and surrogate primary outcome limit generalizability and clinical endpoint inference.
Future Directions: Multicenter, blinded RCTs with clinical AKI endpoints (KDIGO stages), renal replacement therapy, and long-term renal outcomes to validate or refute harm signals.
BACKGROUND: Haptoglobin may reduce hemolysis-induced kidney injury in patients undergoing cardiovascular surgery with cardiopulmonary bypass (CPB). Haptoglobin may be given empirically when hemolytic urine is observed, or pre-emptively when detected by elevated free hemoglobin concentrations. In the present study, we investigated whether pre-emptive haptoglobin therapy guided by serum-free hemoglobin concentrations could prevent postoperative renal dysfunction in patients who underwent major cardiovascular surgery using CPB. METHODS: This study was a single-center, open-label, randomized controlled trial. Adult patients who underwent major cardiovascular surgery using CPB were included. Serum-free hemoglobin concentrations were measured in all patients who consented for this study. Patients with free hemoglobin concentrations that reached 0.05 g/dL were randomized to either (i) pre-emptive haptoglobin therapy group or (ii) standard of care group. Patients in the pre-emptive haptoglobin therapy group were administered 4000 U of haptoglobin when serum-free hemoglobin concentration reached 0.05 g/dL within 2 hours after the start of CPB. In the standard of care group, 4000 U of haptoglobin was administered when hemolytic urine was confirmed after the start of CPB. The primary outcome was the difference between the preoperative creatinine concentration and the maximum creatinine concentration within 48 hours after surgery (ΔCr). RESULTS: The study was terminated with the results of interim analysis due to patients' safety concerns. Finally, 34 patients in the pre-emptive haptoglobin therapy group and 33 in the standard of care group were included in the analysis. Median (interquartile range) ΔCr values were 0.20 (0.05-0.44) in the pre-emptive haptoglobin therapy group and 0.14 (0.04-0.19) in the standard of care group (P = .05). Multiple linear regression analysis with ΔCr as objective variable and preoperative estimated glomerular filtration rate (eGFR), age, and randomize group as explanatory variables revealed that pre-emptive administration of haptoglobin significantly increased ΔCr (P = .03). CONCLUSIONS: The interim study results demonstrated that in patients undergoing major cardiovascular surgery using CPB, pre-emptive haptoglobin administration worsened Cr values and independently associated with increased ΔCr.
3. rECMOmender: Reinforcement Learning for Decision Support in Venovenous Extracorporeal Membrane Oxygenation Management.
An offline reinforcement learning agent trained on 184 VV-ECMO cases produced stable, interpretable recommendations aligned with clinician practice, favoring moderate FiO2 and PEEP while avoiding high PEEP. The model suggested more decisive adjustments, indicating potential to support earlier and more efficient weaning strategies.
Impact: Introduces a clinically aligned, interpretable AI for ECMO-ventilator co-management using conservative Q-learning—an innovative step toward safe decision support in high-stakes critical care.
Clinical Implications: May assist intensivists with parameter tuning and weaning decisions, reduce excessive PEEP use, and standardize care patterns; requires prospective validation before clinical deployment.
Key Findings
- Recommendations aligned with clinician FiO2 distributions (40–50% most frequent) and favored PEEP 9–11 cm H2O while reducing high PEEP use by 73.43%.
- Generated stable, interpretable actions across five parameters (FiO2, PEEP, RR, sweep gas, blood flow) with fitted Q evaluation.
- Suggested more decisive adjustments than clinicians (overall 120% increase in major adjustments).
Methodological Strengths
- Conservative Q-learning with physiologically informed reward shaping.
- Multiple model variants and fitted Q evaluation with action distribution comparisons to clinician practice.
Limitations
- Retrospective single-center dataset without prospective clinical impact evaluation.
- Potential confounding and bias; action-effect causality not established.
Future Directions: Prospective, clinician-in-the-loop trials to test safety, efficacy, and workflow integration; external validation across centers; exploration of continuous action spaces and counterfactual policy evaluation.
CONTEXT: Management of ventilator and venovenous extracorporeal membrane oxygenation (ECMO) settings in critically ill adults requires individualized decisions to balance oxygenation, ventilation, and complication risks. Existing approaches rely heavily on clinician experience, with limited decision support tools available. HYPOTHESIS: An offline reinforcement learning agent trained on real-world venovenous ECMO clinical data can generate safe, interpretable, and clinically aligned recommendations for ECMO and ventilator management, including support for earlier and more efficient weaning. METHODS AND MODELS: We conducted a retrospective study using electronic health record data from 184 adult patients who underwent venovenous ECMO at a tertiary care center. rECMOmender was developed using conservative Q-learning with a physiologically informed reward structure. Multiple model variants were compared across discrete and continuous action spaces and two reward formulations. Performance was assessed using fitted Q evaluation, comparison of action distributions, and alignment with clinician practice. RESULTS: rECMOmender generated stable, interpretable recommendations across five key parameters: Fio2, positive end-expiratory pressure (PEEP), respiratory rate, sweep gas flow, and blood flow rate. It selected Fio2 values in the 40-50% range most frequently (46.75% vs. 45.65% for clinicians) and favored PEEP of 9-11 cm H2O (43.94% vs. 34.28%), while using high PEEP settings (13-20 cm H2O) 73.43% less often. Compared with clinicians, rECMOmender increased large parameter shifts (> 1 bin) by 72.53% for Fio2, 348.15% for PEEP, 299.21% for respiratory rate, 96.68% for sweep gas, and 34.16% for blood flow, resulting in an overall 120.37% increase in major adjustments (3105 vs. 1409). INTERPRETATIONS AND CONCLUSIONS: rECMOmender demonstrated dynamic but safety conscious adjustments that aligned with clinical patterns, indicating potential as a decision support tool that complements clinician judgment.