Mitochondrial dysfunction precedes hippocampal IL-1ß transcription and cognitive impairments after low-dose lipopolysaccharide injection in aged mice.

Acute cognitive impairments termed delirium often occur after inflammatory insults in elderly patients. While previous preclinical studies suggest mitochondria as a target for reducing neuroinflammation and cognitive impairments after LPS injection, fewer studies have evaluated the effects of a low-grade systemic inflammation in the aged brain. Thus, to identify the significance of mitochondrial dysfunction after a clinically relevant systemic inflammatory stimulus, we injected old-aged mice (18-20 months) with low-dose lipopolysaccharide (LPS, 0.04 mg/kg). LPS injection reduced mitochondrial respiration in the hippocampus 24 h after injection (respiratory control ratio [RCR], state3u/state4o; control = 2.82 ± 0.19, LPS = 2.57 ± 0.08). However, gene expression of the pro-inflammatory cytokine IL-1ß was increased (RT-PCR, control = 1.00 ± 0.30; LPS = 2.01 ± 0.67) at a more delayed time point, 48 h after LPS injection. Such changes were associated with cognitive impairments in the Barnes maze and fear chamber tests. Notably, young mice were unaffected by low-dose LPS, suggesting that mitochondrial dysfunction precedes neuroinflammation and cognitive decline in elderly patients following a low-grade systemic insult. Our findings highlight mitochondria as a potential therapeutic target for reducing delirium in elderly patients.

Effect of local anesthetic volume (20 vs. 40 ml) on the analgesic efficacy of costoclavicular block in arthroscopic shoulder surgery: a randomized controlled trial.

BACKGROUND: Among the various diaphragm-sparing alternatives to interscalene block, costoclavicular block (CCB) demonstrated a low hemidiaphragmatic paresis (HDP) occurrence but an inconsistent analgesic effect in arthroscopic shoulder surgery. We hypothesized that a larger volume of local anesthetic for CCB could provide sufficient analgesia by achieving sufficient supraclavicular spreading. METHODS: Sixty patients scheduled for arthroscopic rotator cuff repair were randomly assigned to receive CCB using one of two volumes of local anesthetic (CCB20, 0.75% ropivacaine 20 ml; CCB40, 0.375% ropivacaine 40 ml). The primary outcome was the rate of complete analgesia (0 on the numeric rating scale of pain) at 1 h postoperatively. The secondary outcomes included a sonographic assessment of local anesthetic spread, diaphragmatic function, pulmonary function, postoperative opioid use, and other pain-related experiences within 24 h postoperatively. RESULTS: The rates of complete analgesia were not significantly different (23.3% [7/30] and 33.3% [10/30] in the CCB20 and CCB40 groups, respectively; risk difference 10%, 95% CI [-13, 32], P = 0.567). There were no significant differences in other pain-related outcomes. Among the clinical factors considered, the only factor significantly associated with postoperative pain was the sonographic observation of supraclavicular spreading. There were no significant differences in the incidence of HDP and the change in pulmonary function between the two groups. CONCLUSIONS: Using 40 ml of local anesthetic does not guarantee supraclavicular spread during CCB. Moreover, it does not result in a higher rate of complete analgesia compared to using 20 ml of local anesthetic in arthroscopic shoulder surgery.

Continuous cardiac output estimation using a new modified Fick method during off-pump coronary artery bypass graft surgery: a retrospective observational study.

PURPOSE: Several technical aspects of the Fick method limit its use intraoperatively. A data-driven modification of the Fick method may enable its use in intraoperative settings. METHODS: This two-center retrospective observational study included 57 (28 and 29 in each center) patients who underwent off-pump coronary artery bypass graft (OPCAB) surgery. Intraoperative recordings of physiological data were obtained and divided into training and test datasets. The Fick equation was used to calculate cardiac output (CO-Fick) using ventilator-determined variables, intraoperative hemoglobin level, and SvO2, with continuous thermodilution cardiac output (CCO) used as a reference. A modification CO-Fick was derived and validated: CO-Fick-AD, which adjusts the denominator of the original equation. RESULTS: Increased deviation between CO-Fick and CCO was observed when oxygen extraction was low. The root mean square error of CO-Fick was decreased from 6.07 L/min to 0.70 L/min after the modification. CO-Fick-AD showed a mean bias of 0.17 (95% CI 0.00-0.34) L/min, with a 36.4% (95% CI 30.6-44.4%) error. The concordance rates of CO-Fick-AD ranged from 73.3 to 87.1% depending on the time interval and exclusion zone. CONCLUSIONS: The original Fick method is not reliable when oxygen extraction is low, but a modification using data-driven approach could enable continuous estimation of cardiac output during the dynamic intraoperative period with minimal bias. However, further improvements in precision and trending ability are needed.

Comparative effects of desflurane and sevoflurane on intraoperative peripheral perfusion index: a retrospective, propensity score matched, cohort study.

Desflurane is known to have a larger vasodilatory effect than that of sevoflurane. However, its generalizability and effect size in actual clinical practice are yet to be proven. Patients aged ≥ 18 years who underwent noncardiac surgery under general anesthesia using inhalation anesthetics (desflurane or sevoflurane) were matched 1:1 by propensity score. The mean intraoperative perfusion index (PI) of each patient were compared between the two groups. Propensity score matching of 1680 patients in the study cohort identified 230 pairs of patients. PI was significantly higher in the desflurane group (median of paired difference, 0.45; 95% CI 0.16 to 0.74, p = 0.002). PI durations below 1.0 and 1.5 were significantly longer in the sevoflurane group. Mean arterial pressure (MAP) and durations of low MAP did not differ significantly between the two groups. Generalized linear mixed models revealed that the use of sevoflurane, mean MAP, mean heart rate, age, and duration of anesthesia had significant negative effects (lower PI), whereas mean age-adjusted minimum alveolar concentration of inhalation agent had a positive effect on PI (higher value). Intraoperative PI was significantly higher in patients administered desflurane than sevoflurane. However, the impact of the choice between desflurane and sevoflurane on intraoperative PI in this clinical setting was minimal.

Comparison of Polynucleotide, Sodium Hyaluronate, and Crosslinked Sodium Hyaluronate for the Management of Painful Knee Osteoarthritis: A Multi-Center, Randomized, Double-Blind, Parallel-Group Study.

OBJECTIVE: To compare the clinical effectiveness of sodium polynucleotide, classic hyaluronic acid, and crosslinked hyaluronic acid for the management of painful knee osteoarthritis. DESIGN: Randomized, double-blind, parallel-group clinical trial. SETTING: Multicenter study. SUBJECTS: Patients with chronic painful knee osteoarthritis. METHODS: Ninety patients were selected and randomized into polynucleotide, classic hyaluronic acid, and crosslinked hyaluronic acid groups (30 per group). Intra-articular injections of the viscosupplement for each group were administered to the patients three times at one-week intervals. The primary outcome was differences in changes of weight-bearing pain scores at 16 weeks between the groups. The secondary outcomes were changes in the intensity of knee pain during weight-bearing, walking, and rest, and functional disability, quality of life, and adverse events during the 16-week follow-up period. RESULTS: At 16 weeks, the polynucleotide group showed a higher reduction in pain score using a Visual Analog Scale score (0-100) than the classic hyaluronic acid (-17.6 [95% CI = -35.1 to -0.1]; P = .048) and crosslinked hyaluronic acid (-22.4 [95% CI = -41.5 to -3.3]; P = .016) groups. The polynucleotide and crosslinked hyaluronic acid groups showed an early-onset reduction in knee pain during weight-bearing, walking, and rest. All three groups showed reductions in functional disability and improved quality of life at 16 weeks without inter-group differences. No severe adverse events were reported throughout the study period. CONCLUSION: Polynucleotide significantly relieves pain more and relieves pain faster in patients with knee osteoarthritis than classic and crosslinked hyaluronic acid, with improved health-related quality of life.

Comparison between Fourth-Generation FloTrac/Vigileo System and Continuous Thermodilution Technique for Cardiac Output Estimation after Time Adjustment during Off-Pump Coronary Artery Bypass Graft Surgery: A Retrospective Cohort Study.

(1) Background: Previous studies reported limited performance of arterial pressure waveform-based cardiac output (CO) estimation (FloTrac/Vigileo system; CO-FloTrac) compared with the intermittent thermodilution technique (COint). However, errors due to bolus maneuver and intermittent measurements of COint could limit its use as a reference. The continuous thermodilution technique (COcont) may relieve such limitations. (2) Methods: The performance of CO-FloTrac was retrospectively assessed using continuous recordings of intraoperative physiological data acquired from patients who underwent off-pump coronary artery bypass graft (OPCAB) surgery with CO monitoring using both CO-FloTrac and COcont. Optimal time adjustments between the two measurements were determined based on R-squared values. (3) Results: A total of 134.2 h of data from 30 patients was included in the final analysis. The mean bias was -0.94 (95% CI, -1.35 to -0.52) L/min and the limits of agreements were -3.64 (95% CI, -4.44 to -3.08) L/min and 1.77 (95% CI, 1.21 to 2.57) L/min. The percentage error was 66.1% (95% CI, 52.4 to 85.8%). Depending on the time scale and the size of the exclusion zone, concordance rates ranged from 61.0% to 75.0%. (4) Conclusion: Despite the time adjustments, CO-FloTrac showed non-negligible overestimation, clinically unacceptable precision, and poor trending ability during OPCAB surgery.

Randomised comparison between superior trunk and costoclavicular blocks for arthroscopic shoulder surgery: A noninferiority study.

BACKGROUND: Superior trunk block (STB) provides noninferior analgesia to the interscalene block and reduces the risk of hemidiaphragmatic paralysis (HDP). Recently, supraclavicular spreading has also been shown to occur during costoclavicular block (CCB), presenting as an alternative analgesic technique for shoulder surgery. OBJECTIVE: The aim of this study was to determine whether there is a difference in postoperative pain scores and HDP incidence between STB and CCB. DESIGN: Prospective randomised controlled trial. SETTING: Chungnam National University Hospital in Daejeon from January to July 2021. PATIENTS: Seventy patients, aged 20 to 70 years with ASA Physical Status classifications I to III and scheduled for elective arthroscopic rotator cuff repair were recruited. INTERVENTION: Ultrasound-guided STB or CCB was performed with 20 ml 0.5% ropivacaine. MAIN OUTCOME MEASURES: The primary outcome was the pain score (numeric rating scale, NRS) at 1 h postsurgery. A 1.4 (NRS) noninferiority margin was set a priori . The incidence of HDP, postoperative change of pulmonary function and postoperative opioid use were included as secondary outcomes. RESULTS: The pain score was higher in the CCB group compared with the STB group at 1 h postoperatively (median difference, 2; 95% confidence interval (CI), 1 to 3; noninferiority was not demonstrated). Two patients in the CCB group received a rescue interscalene block due to severe postoperative pain. The incidence of complete HDP was lower in the CCB group (risk difference, -26%; 95% CI, -6 to -45%; P  < 0.001). The median reduction in forced vital capacity and forced expiratory volume in 1 s were also significantly lower in the CCB group. CONCLUSION: Although the incidence of HDP was lower, CCB did not show noninferiority in immediate postoperative analgesia compared with STB in arthroscopic shoulder surgery. CLINICAL TRIAL REGISTRATION: Clinical Trial Registry of Korea (KCT0005822, principal investigator: Boohwi Hong) on 25 January 2021 ( https://cris.nih.go.kr ).

Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice.

Early exposures to anesthetics can cause long-lasting changes in excitatory/inhibitory synaptic transmission (E/I imbalance), an important mechanism for neurodevelopmental disorders. Since E/I imbalance is also involved with addiction, we further investigated possible changes in addiction-related behaviors after multiple ketamine anesthesia in late postnatal mice. Postnatal day (PND) 16 mice received multiple ketamine anesthesia (35 mg kg-1, 5 days), and behavioral changes were evaluated at PND28 and PND56. Although mice exposed to early anesthesia displayed normal behavioral sensitization, we found significant increases in conditioned place preference to both low-dose ketamine (20 mg kg-1) and nicotine (0.5 mg kg-1). By performing transcriptome analysis and whole-cell recordings in the hippocampus, a brain region involved with CPP, we also discovered enhanced neuronal excitability and E/I imbalance in CA1 pyramidal neurons. Interestingly, these changes were not found in female mice. Our results suggest that repeated ketamine anesthesia during neurodevelopment may influence drug reward behavior later in life.

Association between Sagittal Cervical Spinal Alignment and Degenerative Cervical Spondylosis: A Retrospective Study Using a New Scoring System.

(1) Background: Prolonged neck flexion is thought to cause harmful loading on the cervical spine. Along with the degenerative process, cervical alignment tends to change toward lordotic curvature. The association between cervical alignment and cervical spondylosis remains unclear. (2) Methods: Three raters retrospectively assessed cervical radiographies of outpatients at a tertiary center in 2019 using degenerative cervical spondylosis score (DCS score; a newly developed scoring system), C2-7 absolute rotational angle (ARA), and C2-7 sagittal vertical axis (SVA). (3) Results: A total of 561 patients were included in the analysis. Multiple regression analysis with adjustments for age and sex revealed that C2-7 ARA, rather than SVA, was a significant parameter for degenerative spondylosis. The interaction between age and C2-7 ARA was significant, indicating that the increase in DCS score with increasing age was more pronounced in patients with kyphotic cervical alignment. The direct effect of age on DCS score was 0.349 (95% CI 0.319 to 0.380, p < 0.001) and the proportion of the mediation effect of C2-7 ARA was −0.125 (p < 0.001). (4) Conclusions: C2-7 ARA was significantly associated with DCS after adjustment for both age and sex. Subjects with more kyphotic cervical alignment showed a greater correlation between increased DCS score and older age.

General Anesthesia During Neurodevelopment Reduces Autistic Behavior in Adult BTBR Mice, a Murine Model of Autism.

Preclinical studies suggest that repeated exposure to anesthetics during a critical period of neurodevelopment induces long-term changes in synaptic transmission, plasticity, and behavior. Such changes are of great concern, as similar changes have also been identified in animal models of neurodevelopmental disorders (NDDs) such as autism. Because of overlapping synaptic changes, it is also possible that anesthetic exposures have a more significant effect in individuals diagnosed with NDDs. Thus, we evaluated the effects of early, multiple anesthetic exposures in BTBR mice, an inbred strain that displays autistic behavior. We discovered that three cycles of sevoflurane anesthesia (2.5%, 1 h) with 2-h intervals between each exposure in late postnatal BTBR mice did not aggravate, but instead improved pathophysiological mechanisms involved with autistic behavior. Sevoflurane exposures restored E/I balance (by increasing inhibitory synaptic transmission), and increased mitochondrial respiration and BDNF signaling in BTBR mice. Most importantly, such changes were associated with reduced autistic behavior in BTBR mice, as sociability was increased in the three-chamber test and repetitive behavior was reduced in the self-grooming test. Our results suggest that anesthetic exposures during neurodevelopment may affect individuals diagnosed with NDDs differently.

Diagnostic Accuracy of Magnetic Resonance Imaging for Sagittal Cervical Spine Alignment: A Retrospective Cohort Study.

(1) Background: Although radiography performed on the subject in an upright position is considered the standard method for assessing sagittal cervical alignment, it is frequently determined, or reported, based on MRI performed on the subject in a supine position. (2) Methods: Cervical alignment observed in both imaging modalities was assessed using four methods: the C2-7 Cobb angle, the absolute rotation angle (ARA), Borden's method, and the sagittal vertical axis (SVA). Cervical alignment was determined (lordosis, kyphosis, and straight) based on radiography. Then, the diagnostic cut-off values for the MRI images and their corresponding diagnostic accuracies were assessed. (3) Results: The analysis included 142 outpatients. The determined diagnostic cut-off values for lordosis, using three measurements (Cobb angle, ARA, and Borden's method), were -8.5°, -12.5°, and 3.5 mm, respectively, and the cut-off values for kyphosis were -4.5°, 0.5°, and -1.5 mm, respectively. The cut-off value for SVA > 40 mm was 19.5 mm. The Cobb angle, ARA, and Borden's method, on MRI, showed high negative predictive values for determining kyphosis. The SVA on MRI measurements also showed high negative predictive values for determining >40 mm. (4) Conclusions: MRI measurements may be predictive of cervical alignment, especially for the exclusion of kyphosis and SVA > 40 mm. However, caution is needed in the other determinations using MRI, as their accuracies are limited.

A retrospective comparison for prediction of optimal length of right subclavian vein catheterization in infants: landmark-based estimation vs. linear regression model.

BACKGROUND: The optimal insertion length for right subclavian vein catheterization in infants has not been determined. This study retrospectively compared landmark-based and linear regression model-based estimation of optimal insertion length for right subclavian vein catheterization in pediatric patients of corrected age < 1 year. METHODS: Fifty catheterizations of the right subclavian vein were analyzed. The landmark related distances were: from the needle insertion point (I) to the tip of the sternal head of the right clavicle (A) and from A to the midpoint (B) of the perpendicular line drawn from the sternal head of the right clavicle to the line connecting the nipples. The optimal length of insertion was retrospectively determined by reviewing post-procedural chest radiographs. Estimates using a landmark-based equation (IA + AB - intercept) and a linear regression model were compared with the optimal length of insertion. RESULTS: A landmark-based equation was determined as IA + AB - 5. The mean difference between the landmark-based estimate and the optimal insertion length was 1.0 mm (95% limits of agreement -18.2 to 20.3 mm). The mean difference between the linear regression model (26.681 - 4.014 × weight + 0.576 × IA + 0.537 × AB - 0.482 × postmenstrual age) and the optimal insertion length was 0 mm (95% limits of agreement -16.7 to 16.7 mm). The difference between the estimates using these two methods was not significant. CONCLUSION: A simple landmark-based equation may be useful for estimating optimal insertion length in pediatric patients of corrected age < 1 year undergoing right subclavian vein catheterization.

Perineural Epinephrine for Brachial Plexus Block Increases the Incidence of Hypotension during Dexmedetomidine Infusion: A Single-Center, Randomized, Controlled Trial.

BACKGROUND: Sedation using dexmedetomidine is frequently associated with hypotension. In contrast, epinephrine, a commonly used adjunctive agent in regional anesthesia, is a potent vasopressor. We hypothesized that perineural epinephrine used in brachial plexus blockade may reduce hypotension during dexmedetomidine infusion. METHODS: Patients scheduled for upper extremity surgery were randomly allocated into a control and an epinephrine group. All patients received brachial plexus blockade, consisting of 25 mL of a 1:1 mixture of 1% lidocaine and 0.75% ropivacaine, with patients in the epinephrine group also receiving 125 µg epinephrine. Intraoperative sedation was induced using dexmedetomidine at a loading dose of 1 µg/kg and maintenance dose of 0.4 µg/kg/hr. The primary outcome was the incidence of intraoperative hypotension or hypotension in the post-anesthesia care unit (PACU). RESULTS: One hundred and thirty patients were included (65 per group). The incidence of hypotension was significantly higher in the epinephrine than in the control group (80.6% vs. 56.9%, p = 0.009). The duration of hypotension and the maximal change in blood pressure were also greater in the epinephrine group. CONCLUSIONS: Perineural epinephrine for brachial plexus blockade does not reduce hypotension due to dexmedetomidine infusion and may actually augment the occurrence of hypotensive events.

IKBKB siRNA-Encapsulated Poly (Lactic-co-Glycolic Acid) Nanoparticles Diminish Neuropathic Pain by Inhibiting Microglial Activation.

Activation of nuclear factor-kappa B (NF-κB) in microglia plays a decisive role in the progress of neuropathic pain, and the inhibitor of kappa B (IκB) is a protein that blocks the activation of NF-κB and is degraded by the inhibitor of NF-κB kinase subunit beta (IKBKB). The role of IKBKB is to break down IκB, which blocks the activity of NF-kB. Therefore, it prevents the activity of NK-kB. This study investigated whether neuropathic pain can be reduced in spinal nerve ligation (SNL) rats by reducing the activity of microglia by delivering IKBKB small interfering RNA (siRNA)-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles. PLGA nanoparticles, as a carrier for the delivery of IKBKB genes silencer, were used because they have shown potential to enhance microglial targeting. SNL rats were injected with IKBKB siRNA-encapsulated PLGA nanoparticles intrathecally for behavioral tests on pain response. IKBKB siRNA was delivered for suppressing the expression of IKBKB. In rats injected with IKBKB siRNA-encapsulated PLGA nanoparticles, allodynia caused by mechanical stimulation was reduced, and the secretion of pro-inflammatory mediators due to NF-κB was reduced. Delivering IKBKB siRNA through PLGA nanoparticles can effectively control the inflammatory response and is worth studying as a treatment for neuropathic pain.

The Analgesic Efficacy of Nefopam in Patient-Controlled Analgesia after Laparoscopic Gynecologic Surgery: A Randomized, Double-Blind, Non-Inferiority Study.

Opioid-sparing effects of nefopam during patient-controlled analgesia (PCA) are well demonstrated. We hypothesized that postoperative pain control with an opioid-equivalent dose of nefopam as a single analgesic agent for PCA would not be inferior to fentanyl in laparoscopic gynecologic surgery. In total, 135 patients were randomly assigned to the N (nefopam 200 mg), NF (fentanyl 500 mcg + nefopam 100 mg), and F (fentanyl 1000 mcg) groups (n = 45 patients per group). The primary outcome was the numerical rating scale (NRS) score at rest at 6 h postoperatively, and the non-inferiority limit was set to 1. Secondary outcomes were pain severity and incidence of nausea and vomiting for 48 h postoperatively. Mean differences (MD) in primary outcome between the N and F groups were 0.4 (95% confidence interval (CI) -0.5 to 1.3). The upper limit of 95% CI exceeded the non-inferiority limit. The N group showed higher pain scores than the NF group (MD, 1.1; 95% CI, 0.3-1.9) in pairwise comparisons. No significant intergroup differences were observed in the cumulative dose of PCA usage and incidence of postoperative nausea and vomiting (PONV). In laparoscopic gynecological surgery, nefopam alone showed limited efficacy for postoperative pain control.

Comparison of the ulnar nerve blockade between intertruncal and corner pocket approaches for supraclavicular block: a randomized controlled trial.

BACKGROUND: The corner pocket (CP) approach for supraclavicular block (SCB) prevents ulnar nerve (UN) sparing due to needle proximity to the lower trunk. Improved ultrasound resolution has suggested that the intertruncal (IT) approach is a suitable alternative method. We compared efficiency of these two approaches on the UN blockade. METHODS: Sixty patients were randomized to undergo SCB using the ultrasound-guided CP or IT approach. For lower trunk blockade, 10 ml of local anesthetic agents (1 : 1 mixture of 0.75% ropivacaine and 1% lidocaine) were injected in the CP (CP approach) or between the lower and middle trunks (IT approach). Additional 15 ml was injected identically to block the middle and upper trunks in both groups. Sensory and motor blockade was evaluated after intervention. RESULTS: Complete sensory blockade (75.9% [22/29] vs. 43.3% [13/30], P = 0.023) and complete motor blockade (82.8% [24/29] vs. 50.0% [15/30], P = 0.017) of the UN at 15 min after SCB were significantly more frequent in the IT than in the CP group. Sensory block onset time of the UN was significantly shorter in the IT compared to the CP group (15.0 [10.0, 15.0] min vs. 20.0 [15.0, 20.0] min, P = 0.012). CONCLUSIONS: The IT approach provided a more rapid onset of UN blockade than the CP approach. These results suggest that the IT approach is a suitable alternative to the CP approach and can provide faster surgical readiness.

Comparison of continuous and single interscalene block for quality of recovery score following arthroscopic rotator cuff repair.

BACKGROUND: Continuous interscalene brachial plexus block (CISB) is well known to reduce postoperative pain and to improve patient satisfaction. However, the effect of CISB on the quality of postoperative recovery is unknown. We Compared the quality of recovery from arthroscopic rotator cuff repair in patients who received CISB or single interscalene brachial plexus block (SISB). METHODS: This prospective non-randomized controlled trial with propensity score matching enrolled 134 patients undergoing arthroscopic surgery for rotator cuff repair. Each patient received an interscalene block before surgery. One group had a catheter insertion 30 min after the end of surgery and started patient-controlled regional analgesia (PCRA, n = 49). The other group received intravenous patient-controlled analgesia (IV-PCA, n = 85). The primary outcome was the quality of recovery (QoR-40) score. Also, postoperative analgesia, sleep quality, and postoperative complications were evaluated. RESULTS: The two groups had similar QoR-40 score on postoperative day-1 (POD1), but the PCRA group had a significantly greater QoR-40 score on POD2 (156.0, IQR: 143.0, 169.0 vs. 171.0, IQR: 159.0, 178.0; p < 0.001). The IV-PCA group received more analgesics during the 2 days after surgery, especially during night-time, and had a higher prevalence of sleep disturbances. The time to first additional analgesics request was significantly longer in PCRA group (14 hours, 95% CI: 13-16 vs. 44 hours, 95% CI: 28-not applicable). The incidence of postoperative nausea and vomiting significantly lower in the PCRA group (16.3% vs 46.9%, p = 0.002). CONCLUSION: CISB showed a higher quality of recovery score than SISB with IV-PCA in arthroscopic rotator cuff repair, probably related to the effective analgesia, improved sleep quality, and reduced opioid-related complications.

Effects of Sevoflurane on Lewis Lung Carcinoma Cell Proliferation In Vivo and In Vitro.

Background and objectives: There are several studies that sevoflurane could enhance proliferation of cancer cells, while others suggest no effect on clinical outcome. We conducted in vivo and in vitro experiments to investigate the effects of sevoflurane, a volatile anesthetic, on proliferation and outcomes of Lewis lung carcinoma (LLC) cells. Materials and Methods: A total of 37 mice were injected with LLC cells to compare the tumor size and survival of the sevoflurane exposed group (sevo group) and control group. The sevo group was exposed to 2% sevoflurane and 4 L/min of oxygen for 1 h per day 3 times per week, and the control group was exposed only to 4 L/min of oxygen. In vitro study, 12 plates incubated with LCC cells. 6 plates were exposed to 2% sevoflurane for 1 hr/day for 3 days and 6 plates were not exposed, and cell proliferation was compared after 3 days. Results: There were no significant differences in survival or tumor size between mice exposed to sevoflurane and control mice (survival: 29.06 ± 4.45 vs. 28.76 ± 3.75, p = 0.836; tumor size: 0.75 (0.41-1.02) vs. 0.49 (0.11-0.79), p = 0.153). However, in vitro study, the proliferation of LLC cells exposed to sevoflurane increased by 9.2% compared to the control group (p = 0.018). Conclusions: Sevoflurane (2 vol%) exposure could promote proliferation of LLC cells in vitro environment, but may not affect proliferation of LLC cells in vivo environment. These results suggest that in vitro studies on the effects of anesthetics on cancer may differ from those of in vivo or clinical studies.

Interval-dependent neurotoxicity after multiple ketamine injections in late postnatal mice.

PURPOSE: Measuring the neurotoxic effects of multiple anesthetic exposures during neurodevelopment is complex due to the numerous factors that can affect the outcome. While we recently discovered that the interval between multiple sevoflurane exposures can affect the level of neurotoxicity, the significance of interval for other anesthetic agents is unknown. Thus, we evaluated the significance of dosing interval in the neurotoxic effects of multiple ketamine injections in postnatal day (PND) 17 mice. METHODS: PND17 mice of both sexes were intraperitoneally injected with ketamine (35 mg/kg) three times at short (2 h) or long (24 h) intervals. Changes in synaptic transmission were measured in hippocampal pyramidal neurons 5 days after the last injection, and behavioral changes were assessed at the age of 8 weeks. Values are presented as mean ± SD. RESULTS: Whereas short-interval ketamine injections enhanced excitatory synaptic transmission, as evidenced by an increased frequency of miniature excitatory postsynaptic currents (mEPSCs; ketamine, 0.09 ± 0.07 Hz; control, 0.06 ± 0.03 Hz), long-interval ketamine injections did not; instead, they decreased the amplitude of miniature inhibitory postsynaptic currents (mIPSCs; ketamine, 47.72 ± 6.90 pA; control, 51.21 ± 7.65 pA,). However, only long-interval ketamine injections induced long-term changes in anxiety behavioral in the open-field test (decrease in center duration; ketamine, 400.1 ± 162.8 s; control, 613.3 ± 312.7 s). CONCLUSIONS: Multiple ketamine injections induce interval-dependent, long-lasting synaptic changes and behavioral impairments. Future studies should carefully consider the dosing interval as a significant factor when studying the neurotoxic effects of multiple anesthetic exposures.

General anesthesia activates the mitochondrial unfolded protein response and induces age-dependent, long-lasting changes in mitochondrial function in the developing brain.

General anesthesia induces changes in dendritic spine number and synaptic transmission in developing mice. These changes are rather disturbing, as similar changes are seen in animal models of neurodevelopmental disorders. We previously suggested that mTor-dependent upregulation of mitochondrial function may be involved in such changes. To further understand the significance of mitochondrial changes after general anesthesia during neurodevelopment, we exposed young mice to 2.5 % sevoflurane for 2 h followed by injection of rotenone, a mitochondrial complex I inhibitor. In postnatal day 17 (PND17) mice, intraperitoneal injection of rotenone not only blocked sevoflurane-induced increases in mitochondrial function, it also prevented sevoflurane-induced changes in excitatory synaptic transmission. Interestingly, similar changes were not observed in younger, neonatal mice (PND7). We next assessed whether the mitochondrial unfolded protein response (UPRmt) acted as a link between anesthetic exposure and mitochondrial function. Expression of UPRmt proteins, which help maintain protein-folding homeostasis and increase mitochondrial function, was increased 6 h after sevoflurane exposure. Our results show that a single, brief sevoflurane exposure induces age-dependent changes in mitochondrial function that constitute an important mechanism for the increase in excitatory synaptic transmission in late postnatal mice, and also suggest mitochondria and UPRmt as potential targets for preventing anesthesia toxicity.