Daily Anesthesiology Research Analysis
Three impactful anesthesiology papers span perioperative renal protection, mechanistic neurotoxicity of early-life anesthesia, and analgesic effects on sleep-circadian biology. A randomized trial shows urine output–guided intraoperative hydration reduces postoperative acute kidney injury after CRS-HIPEC, while two mechanistic studies illuminate Igfbp2-dependent thalamic-amygdala circuitry in neonatal anesthesia-induced fear memory deficits and demonstrate pregabalin, unlike morphine, restores sl
Summary
Three impactful anesthesiology papers span perioperative renal protection, mechanistic neurotoxicity of early-life anesthesia, and analgesic effects on sleep-circadian biology. A randomized trial shows urine output–guided intraoperative hydration reduces postoperative acute kidney injury after CRS-HIPEC, while two mechanistic studies illuminate Igfbp2-dependent thalamic-amygdala circuitry in neonatal anesthesia-induced fear memory deficits and demonstrate pregabalin, unlike morphine, restores sleep architecture and circadian rhythms in neuropathic pain.
Research Themes
- Perioperative renal protection via urine output–guided hydration
- Circuit-level mechanism of neonatal anesthesia-induced cognitive deficits (Igfbp2 in PVT→CeA)
- Analgesic-specific modulation of sleep architecture and circadian rhythms in neuropathic pain
Selected Articles
1. Effect of Urine-guided Intraoperative Hydration on Incidence of Acute Kidney Injury after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei: A Randomized Trial.
In adults undergoing CRS with cisplatin-based HIPEC for pseudomyxoma peritonei, targeting a higher intraoperative urine output (≥3 mL/kg/h or ≥200 mL/h) reduced 7-day AKI (21.4% vs 39.3%; RR 0.55) and lowered 30-day major complications compared with routine hydration, without safety trade-offs. Findings support urine output–guided hydration as a renal-protective strategy in this high-risk setting.
Impact: This randomized trial demonstrates a pragmatic, actionable strategy that significantly reduces postoperative AKI and complications in a high-risk oncologic surgery. It provides immediate guidance for intraoperative fluid management goals.
Clinical Implications: Adopt intraoperative urine output–guided hydration targets (≥3 mL/kg/h or ≥200 mL/h) during CRS-HIPEC to reduce AKI and early complications. Protocols should balance diuresis with hemodynamics and consider cisplatin nephrotoxicity.
Key Findings
- Urine-guided hydration reduced 7-day AKI (21.4% vs 39.3%; RR 0.55; 95% CI 0.33–0.89; P=0.012).
- AKI by urine output criteria was lower with urine-guided hydration (21.4% vs 35.7%; RR 0.60; 95% CI 0.36–0.99; P=0.040).
- Major complications within 30 days were fewer (36.9% vs 56.0%; RR 0.66; 95% CI 0.47–0.92; P=0.013).
- No difference in adverse events between groups.
Methodological Strengths
- Randomized, intention-to-treat design with clear KDIGO-based AKI endpoint
- Pragmatic intraoperative protocol with objective urine output targets
Limitations
- Single-center trial and moderate sample size
- Not powered for mortality or renal replacement therapy endpoints; blinding not specified
Future Directions: Confirm efficacy and safety in multicenter trials, optimize fluid/diuretic algorithms, and evaluate long-term renal outcomes and cost-effectiveness.
2. Igfbp2 Downregulation in PVT-CeA Glutamatergic Circuits Drives Neonatal Anesthesia-Induced Fear Memory Deficits.
Repeated neonatal anesthesia impaired fear memory in adolescent mice via downregulation of Igfbp2 and reduced spine density in PVT glutamatergic neurons. Causal manipulations showed that activating PVT neurons or restoring Igfbp2 in PVT→CeA projections rescues deficits, whereas inhibition or Igfbp2 knockdown induces them, identifying Igfbp2 as a circuit-specific therapeutic target.
Impact: This study provides a causal, circuit-level mechanism linking early-life anesthesia to later cognitive deficits and pinpoints Igfbp2 as a modifiable node, advancing translational targets for neuroprotection.
Clinical Implications: While preclinical, the identification of Igfbp2 in PVT→CeA circuitry suggests avenues for biomarker development and neuroprotective strategies to mitigate anesthesia-related neurodevelopmental risk.
Key Findings
- Repeated neonatal anesthesia impaired fear memory and reduced excitability and spine density in PVT glutamatergic neurons in both sexes.
- Igfbp2 expression in PVT glutamatergic neurons was decreased; restoring Igfbp2 or activating PVT neurons rescued memory deficits.
- Targeted manipulation of PVT→CeA projections (optogenetic activation or Igfbp2 restoration) blocked deficits, while inhibition or Igfbp2 knockdown induced similar impairments.
Methodological Strengths
- Multimodal causal approach (optogenetics, viral manipulation) with projection-specific interventions
- Sex-inclusive design and cellular-morphological readouts (spine density) supporting mechanism
Limitations
- Preclinical mouse model; external validity to human infants is uncertain
- Specific anesthesia paradigms and behavioral domain (fear memory) may not capture broader cognition
Future Directions: Define upstream regulators of Igfbp2, assess biomarkers in humans, and test neuroprotective strategies targeting PVT→CeA circuitry in translational models.
3. Differential Effects of Pregabalin and Morphine on the Sleep-Wake Cycle and Circadian Rhythms in Mice with Neuropathic Pain.
In SNI-induced neuropathic pain, REM sleep during the light phase and circadian rhythms of locomotion and temperature were disrupted. Continuous pregabalin, but not morphine, restored REM sleep, circadian rhythmicity, spinal circadian gene expression, and increased sleep spindles and 3.5–5.5 Hz REM power, indicating drug-specific effects on sleep-circadian regulation.
Impact: This study bridges analgesic pharmacology with sleep and circadian biology, revealing pregabalin’s unique capacity to restore sleep architecture and circadian rhythms in neuropathic pain, with translational implications for analgesic selection.
Clinical Implications: In neuropathic pain patients with sleep-circadian disturbances, pregabalin may be preferred over opioids to improve sleep quality and circadian alignment alongside analgesia.
Key Findings
- SNI reduced REM sleep duration during the light phase in both sexes and increased wakefulness in females.
- SNI impaired circadian rhythmicity of locomotion and body temperature; pregabalin, not morphine, restored these rhythms.
- Pregabalin reversed SNI-induced changes in spinal circadian gene expression and increased sleep spindles and 3.5–5.5 Hz REM power.
Methodological Strengths
- Continuous wireless EEG/EMG, locomotion, and temperature monitoring
- Assessment in both sexes for SNI effects plus molecular profiling of spinal circadian genes
Limitations
- Drug administration tested only in male mice; generalizability across sexes for drug effects unknown
- Preclinical model and continuous dosing may not reflect clinical regimens
Future Directions: Translate to clinical sleep studies in neuropathic pain, examine sex-specific responses to pregabalin, and dissect upstream regulators of spinal circadian gene normalization.