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BACKGROUND: Norepinephrine is effective in preventing spinal hypotension during cesarean birth; however, an optimal regimen has not been determined. We hypothesized that an initial bolus of norepinephrine improves efficacy of spinal hypotension prophylaxis beyond continuous norepinephrine alone. METHODS: In this double-blind, controlled study, 120 patients scheduled for cesarean birth under spinal anesthesia were randomly allocated to receive a norepinephrine bolus at 0.05 or 0.10 μg/kg, followed by norepinephrine infusion at a rate of 0.05 μg•kg -1 •min -1 . The primary outcome was the frequency of spinal hypotension during cesarean birth. The doses of the rescue drug (phenylephrine), frequency of nausea or vomiting, duration of hypotension, frequency of intraoperative hypertension, frequency of bradycardia, and fetal outcomes were also compared. RESULTS: One-hundred-fifteen patients were included in the analysis. Compared with the 0.05 μg/kg group, the frequency of spinal hypotension was lower in the 0.10 μg/kg group (20.7% vs 45.6%; odds ratio [OR], 0.31; 95% confidence interval (CI), 0.14-0.71; P = .004). Fewer rescue doses of phenylephrine (0 [0,0] vs 0 [0,80]; 95% CI for the difference, 0 (0-0); P = .006) were required, and the frequency of nausea or vomiting was lower (5.2% vs 17.5%; OR, 0.26; 95% CI, 0.07-0.99; P = .04) in the 0.10 μg/kg group. The duration of hypotension was shorter in the 0.10 μg/kg group than that in the 0.05 μg/kg group (0 [0,0] vs 0 [0,2]; 95% CI for the difference, 0 [0-0]; P = .006). The incidence of intraoperative hypertension, frequency of bradycardia, and fetal outcomes were comparable between the 2 groups. CONCLUSIONS: With a fixed-rate norepinephrine infusion of 0.05 μg•kg -1 •min -1 , the 0.10 μg/kg initial bolus was more effective in reducing the incidence of spinal hypotension compared with the 0.05 μg/kg initial bolus. (Anesth Analg 2023;136:94-100) KEY POINTS• Question: Does administration of an initial norepinephrine bolus during elective cesarean birth influence the prevention of spinal hypotension when providing continuous norepinephrine infusion? • Findings: With a fixed-rate norepinephrine infusion of 0.05 μg•kg -1 •min -1 , the frequency of spinal hypotension was lower with the administration of 0.10 μg/kg initial bolus than with 0.05 μg/kg initial bolus. • Meaning: With a fixed-rate norepinephrine infusion of 0.05 μg•kg -1 •min -1 , the 0.10 μg/kg initial bolus was more effective in reducing the incidence of spinal hypotension compared with the 0.05 μg/kg initial bolus.

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Background: The α7 nicotinic acetylcholine receptor (α7nAChR) is a promising therapeutic target in neurodegenerative diseases. This study examined the effects of surgery and anesthesia on α7nAChR expression in the central nervous system and determined the mechanisms by which α7nAChR mediates neuroprotection in perioperative neurocognitive disorders (PNDs) in aged mice.Methods: Eighteen-month-old male C57BL/6J mice underwent aseptic laparotomy under isoflurane anesthesia, maintaining spontaneous ventilation to establish the PNDs model. Agonists and antagonists of the α7nAChR and tropomyosin receptor kinase B (TrkB) receptors were administered before anesthesia. The α7nAChR expression, peripheral as well as hippocampal interleukin-1β (IL-1β), and the brain-derived neurotrophic factor (BDNF) levels were assessed. Separate cohorts of aged mice were tested for cognitive decline using the Morris water maze (MWM).Results: Surgery and anesthesia significantly suppressed α7nAChR expression in the hippocampus and cortex. Surgery-induced IL-1β upregulation in the serum as well as hippocampus and hippocampal microglial activation were reversed by the α7nAChR agonist. A significant reduction in the hippocampal BDNF levels were also observed. The α7nAChR stimulation reversed, and α7nAChR suppression promoted BDNF reduction in the hippocampus. Blocking the BDNF/TrkB signaling pathway abolished α7nAChR-induced neuroprotection in PNDs, as evidenced by poor cognitive performance in the MWM test.Conclusions: These data reveal that α7nAChR plays a key role in PNDs. The mechanisms of the anti-inflammatory pathway and BDNF/TrkB signaling pathways are involved in α7nAChR-meidiated neuroprotection in PNDs.

Background Postoperative delirium (POD) is a common complication after hip fracture surgery that is associated with various short- and long-term outcomes. The mechanism of POD may be associated with the oxidative stress process. Uric acid has been shown to provide a neuroprotective effect in various neurodegenerative diseases through its antioxidant properties. However, it is unclear whether lower preoperative serum uric acid levels are associated with the development of POD after hip fracture surgery. Therefore, this study assessed the association of lower preoperative uric acid levels in patients with POD during hospitalization. Methods This is a matched retrospective case-control study that included 96 older patients (≥65 y) who underwent hip fracture surgery. POD was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Patients diagnosed with POD (cases) were matched 1:1 with patients without POD (controls) on the basis of age, sex, and anesthesia type. The relationship between preoperative uric acid and POD was analyzed by multivariable analysis. Results The POD and non-POD groups each had 48 patients. In the univariate analysis, lower log preoperative serum uric acid value, higher neutrophil-to-lymphocyte ratio, and cerebrovascular disease were more likely in patients with POD than in those with no POD. Multivariable conditional logistic regression analysis showed that lower log preoperative serum uric acid (adjusted odds ratio [aOR], 0.028; confidence interval [CI], 0.001–0.844; p = 0.040), higher neutrophil-to-lymphocyte ratio (aOR, 1.314; 95% CI, 1.053–1.638; p = 0.015), and increased surgery duration (aOR, 1.034; 95% CI, 1.004–1.065; p = 0.024) were associated with increased risk of POD. Conclusions Lower preoperative serum uric acid levels may be an independent risk factor for POD after adjustment for possible confounding factors. However, large prospective studies are needed to confirm this finding.

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Background: Postoperative delirium (POD) is a common complication after hip fracture surgery that is associated with various short- and long-term outcomes. The mechanism of POD may be associated with the oxidative stress process. Uric acid has been shown to provide a neuroprotective effect in various neurodegenerative diseases through its antioxidant properties. Therefore, this study assessed the association of lower uric acid levels in patients with POD during hospitalization.Methods: This is a matched retrospective case-control study that included 96 older patients (≥65 y) who underwent hip fracture surgery. POD was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Patients diagnosed with POD (cases) were matched 1:1 with patients without POD (controls) on the basis of age, sex, and anesthesia type. The relationship between uric acid and POD was analyzed by multivariable analysis.Results: The POD and non-POD groups each had 48 patients. In the univariate analysis, lower serum uric acid level, higher neutrophil‑to‑lymphocyte ratio, and cerebrovascular disease were more likely in patients with POD compared with no POD. Multivariable conditional logistic regression analysis showed that lower serum uric acid (adjusted odds ratio [aOR], 0.994; confidence interval [CI], 0.988–1.000; p = 0.046), higher neutrophil‑to‑lymphocyte ratio (aOR, 1.323; 95% CI, 1.062–1.648; p = 0.013), and increased surgery duration (aOR, 1.034; 95% CI, 1.004–1.065; p = 0.024) were associated with increased risk of POD.Conclusions: Lower serum uric acid level may be an independent risk factor for POD after adjustment for possible confounding factors. However, large prospective studies are needed to confirm this finding.