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Background The purpose of this study was to compare the effects of scalp nerve block (SNB) and local anesthetic infiltration (LA) with 0.75% ropivacaine on postoperative inflammatory response, intraoperative hemodynamic response, and postoperative pain control in patients undergoing craniotomy. Methods Fifty-seven patients were admitted for elective craniotomy for surgical clipping of a cerebral aneurysm. They were randomly divided into three groups: Group S (SNB with 15 mL of 0.75% ropivacaine), group I (LA with 15 mL of 0.75% ropivacaine) and group C (that only received routine intravenous analgesia). Pro-inflammatory cytokine levels in plasma for 72 h postoperatively, hemodynamic response to skin incision, and postoperative pain intensity were measured. Results The SNB with 0.75% ropivacaine not only decreased IL-6 levels in plasma 6 h after craniotomy but also decreased plasma CRP levels and increased plasma IL-10 levels 12 and 24 h after surgery compared to LA and routine analgesia. There were significant increases in mean arterial pressure 2 and 5 mins after the incision and during dura opening in Groups I and C compared with Group S. Group S had lower postoperative pain intensity, longer duration before the first dose of oxycodone, less consumption of oxycodone and lower incidence of PONV through 48 h postoperatively than Groups I and C. Conclusion Preoperative SNB attenuated inflammatory response to craniotomy for cerebral aneurysms, blunted the hemodynamic response to scalp incision, and controlled postoperative pain better than LA or routine analgesia. Trial registration Clinicaltrials.gov NCT03073889 (PI:Xi Yang; date of registration:08/03/2017).

IntroductionPatients undergoing surgery frequently develop neuropsychological disturbances, including cognitive decline or memory impairment, and routine clinical procedures such as mechanical ventilation (MV) may affect acute-phase brain outcome. We aimed to investigate the effect of the prolonged MV on postoperative memory dysfunction in surgical mice.MethodsMale C57BL/6 mice were randomly divided into the following three groups: (1) The control group (group C) comprised anesthetized, unventilated animals; (2) the surgery group (subgroups S1h, S3h and S6h) was unventilated animals that underwent surgery under general anesthesia; and (3) the MV group (subgroups MV1h, MV3h and MV6h) was made up of animals under MV for 1 hour, 3 hours or 6 hours after surgery. Separate cohorts of animals were tested for memory function with fear conditioning tests or were killed at 6 hours, 1 day or 3 days postsurgery or post-MV to examine levels systemic and hippocampal interleukin (IL)-1β, IL-6 and tumor necrosis factor α (TNFα), and assessed synaptic structure and microglial activation. Nuclear factor κB (NF-κB) p65, cytochrome c, cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) activation were analyzed by Western blotting.ResultsThe MV6h group showed increased CD11b-immunopositive cells, synapse degeneration, cytochrome c release, cleaved caspase-3 and cleaved PARP-1 activation after surgery, as well as a decrease in freezing time after surgery. At 6 hours and 1 day post-MV, MV6h increased NF-κB activation and levels of systemic and hippocampal IL-1β, IL-6 and TNFα after surgery.ConclusionsProlonged MV after surgery further aggravates cognitive decline that may stem from upregulation of hippocampal IL-1β, IL-6 and TNFα, partially via activation of gliocytes in the surgical mouse hippocampus.

Postoperative delirium (POD) is a common complication following surgery and anesthesia (Surgery/Anesthesia). Mitochondrial dysfunction, which is demonstrated by energy deficits and excessively activated oxidative stress, has been reported to contribute to POD. The dynamic balance between mitochondrial fusion and fission processes is critical in regulating mitochondrial function. However, the impact of Surgery/Anesthesia on mitochondrial fusion/fission dynamics remains unclear. Here, we evaluate the effects of laparotomy under 1.4% isoflurane anesthesia for 2 hours on mitochondrial fission/fusion dynamics in the brain of aged mice. Mice in Surgery/Anesthesia group showed unbalanced fission/fusion dynamics, with decreased DISC1 expression and increased expression of Drp1 and Mfn2 in the mitochondrial fraction, leading to excessive mitochondrial fission and disturbed mitochondrial morphogenesis in the hippocampus and prefrontal cortex. In addition, surgical mice presented mitochondrial dysfunction, demonstrated by abnormally activated oxidative stress (increased ROS level, decreased SOD level) and energy deficits (decreased levels of ATP and MMP). Surgery/Anesthesia also decreased the expression of neuronal/synaptic plasticity-related proteins such as PSD-95 and BDNF. Furthermore, Surgery/Anesthesia induced delirium-like behavior in aged mice. In conclusion, Surgery/Anesthesia disturbed mitochondrial fission/fusion dynamics and then impaired mitochondrial function in the brain of aged mice; these effects may be involved in the underlying mechanism of POD.

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