Daily Anesthesiology Research Analysis

BACKGROUND: Acute kidney injury (AKI) is common after cytoreductive surgery (CRS) and hyperthermia intraperitoneal chemotherapy (HIPEC). Urine-guided hydration is found effective in preventing AKI in other high-risk patient populations. This study tested whether targeted intraoperative urine output maintenance and simultaneous hydration can reduce AKI in patients after CRS-HIPEC. METHODS: In this randomized trial, adult patients who were scheduled to undergo CRS and cisplatin-based HIPEC for pseudomyxoma peritonei were randomized to receive either urine-guided hydration (urine output greater than or equal to 3 ml ⋅ kg -1 ⋅ h -1 or greater than or equal to 200 ml ⋅ h -1 ) or routine hydration (urine output greater than or equal to 0.5 ml ⋅ kg -1 ⋅ h -1 ) during the procedure. The primary endpoint was the incidence of AKI within 7 days after surgery, diagnosed according to the Kidney Disease Improving Global Outcome criteria. RESULTS: From July 24, 2023, to July 18, 2024, 168 patients (mean age, 58 yr; 66.1% female sex) were enrolled and randomized; all were included in the intension-to-treat analysis. AKI incidence within 7 days was lower with urine-guided hydration than with routine hydration (21.4% [18 of 84] vs. 39.3% [33 of 84]; relative risk [RR], 0.55; 95% CI, 0.33 to 0.89; P = 0.012). Subgroup analysis showed that the proportion of AKI diagnosed according to urine criteria (urine output less than 0.5 ml ⋅ kg -1 ⋅ h -1 for 6 h or longer) was less with urine-guided hydration than with routine hydration (21.4% [18 of 84] vs. 35.7% [30 of 84]; RR, 0.60; 95% CI, 0.36 to 0.99; P = 0.040). Patients with urine-guided hydration developed fewer major complications within 30 days (36.9% [31 of 84] vs. 56.0% [47 of 84]; RR, 0.66; 95% CI, 0.47 to 0.92; P = 0.013). Adverse events did not differ between groups. CONCLUSIONS: In patients who underwent CRS and cisplatin-HIPEC for pseudomyxoma peritonei, intraoperative urine-guided hydration reduced postoperative AKI by more than 40% and was safe. A large trial is warranted to verify the results of this study.

Repeated neonatal general anesthesia results in long-term cognitive dysfunction; however, the underlying mechanisms remain unclear. This study finds that repeated neonatal anesthesia impaired fear memory in adolescent mice of both sexes, along with hypoactivated glutamatergic neurons in the paraventricular thalamus (PVT). Optogenetic activation of PVT glutamatergic neurons rescued fear memory deficits in anesthesia-treated mice, whereas optogenetic inhibition of these neurons recapitulated memory deficits in control mice. Specifically, repeated neonatal anesthesia reduced insulin-like growth factor-binding protein 2 (Igbp2) expression and dendritic spine density in PVT glutamatergic neurons in both males and females. Selectively manipulating PVT glutamatergic Igfbp2 mediated anesthesia-induced fear memory deficits through modulating neuron excitability and spine density. Notably, optogenetic activation or restoring Igfbp2 expression in glutamatergic projections from the PVT to the central amygdala (CeA) blocked anesthesia-induced memory impairment, whereas optogenetic inhibition or knocking down of Igfbp2 expression in these projections is sufficient to engender similar memory impairment in control mice. The findings demonstrate that Igfbp2 in glutamatergic neurons in the PVT afferents to the CeA mediates fear memory deficits caused by repeated neonatal anesthesia in mice of both sexes, highlighting Igfbp2 as a potential therapeutic target for repeated anesthesia-induced cognitive impairment.

BACKGROUND: Neuropathic pain is commonly associated with disturbances in sleep architecture and circadian rhythms, leading to fragmented sleep, body temperature fluctuations, and altered locomotion. While pregabalin and morphine are frequently prescribed for neuropathic pain management, their effects on sleep and circadian regulation are poorly understood. METHODS: To identify the effects of spared nerve injury (SNI) on sleep architecture and circadian rhythms, male and female C57BL/6JRJ mice were implanted with wireless transmitters for continuous monitoring of electroencephalogram, electromyogram, locomotion, and body temperature. After baseline recordings, SNI was performed, and mechanical and dynamic allodynia was assessed on days 3, 7, and 14 after the surgeries. Pregabalin (11 mg/kg each day) or morphine (6 mg/kg each day) was administered continuously to male mice via intraperitoneal osmotic minipumps. Recordings were repeated on postoperative days 7 and 14. RESULTS: SNI significantly disrupted the sleep-wake cycle by reducing rapid eye movement (REM) sleep duration during the light phase (the habitual sleeping phase for mice) in both sexes and increasing wakefulness in females, without significantly affecting non-REM sleep. Additionally, SNI significantly impaired the circadian rhythmicity of locomotion and body temperature. Pregabalin, but not morphine, significantly restored REM sleep to presurgical levels and restored locomotor activity and body temperature rhythmicity more effectively than morphine. At the molecular level, SNI altered spinal cord circadian gene expression, which pregabalin significantly reversed, whereas morphine showed mixed effects. Furthermore, pregabalin increased sleep spindle occurrence during sleep stage transitions and enhanced the power spectra within the 3.5- to 5.5-Hz range during REM sleep. Morphine did not significantly alter either sleep architecture or microstructure in SNI mice. CONCLUSIONS: Pregabalin, unlike morphine, restores SNI-disrupted sleep architecture, circadian rhythms, and spinal circadian gene expression.