The Impact of Morning Surgery or Afternoon Surgery on Postoperative Sleep Quality and Melatonin Levels of Elderly Patients: A Prospective, Randomized Study.

Objective: Postoperative sleep disturbance after surgery is not conducive to the recovery of patients. The purpose of this study was to determine the influence of the timing of surgery (morning vs afternoon) on the postoperative sleep quality of elderly patients and to analyze the relationship between the timing of surgery and the change in the melatonin level. Methods: Sixty patients who received hip surgery were randomly assigned to the Morning Group (Group M) or the Afternoon Group (Group A). The sleep quality was assessed by the Richards-Campbell Sleep Questionnaire. Before and after surgery, the nocturnal urine was collected over a 12-h period, and the 6-sulfatoxymelatonin concentration was measured. Also, the incidence of postoperative delirium (POD) was observed. Results: On the first and second nights after surgery, the sleep quality scores of the patients in Group A were greater than those in Group M, and there was no difference in the sleep quality scores between the two groups on the third night after surgery (P=0.000, P=0.002, P>0.05, respectively). In addition, the urine 6-sulphatoxymelatonin concentration was found to be greater in Group A than in Group M on the first night of surgery (P=0.00). Both the postoperative sleep quality scores and urine 6-sulphatoxymelatonin concentration were significantly less than those before surgery (P=0.00, P=0.00). Conclusion: The postoperative sleep quality scores and melatonin levels of elderly patients who received hip surgery under general anesthesia were significantly less than those of the patients before surgery. Furthermore, the short-term sleep quality of the patients who received surgery in the afternoon was better than that of the patients who received surgery in the morning. This difference may be related to the short-term change of the melatonin level after surgery.

Caloric Restriction Alleviates CFA-Induced Inflammatory Pain via Elevating ß-Hydroxybutyric Acid Expression and Restoring Autophagic Flux in the Spinal Cord.

Inflammatory pain is the most common type of pain encountered in clinical practice; however, the currently available treatments are limited by insufficient efficacy and side effects. Therefore, new methods to relieve inflammatory pain targeting new mechanisms are urgently needed. Preclinical investigations have shown that CR (calorie restriction) exerts analgesic effects in neuropathic and cancer pain; however, the effect of CR on chronic inflammatory pain remains unknown. During calorie restriction, autophagy, a lysosome-dependent degradation process, can be activated to support cell survival. In the present study, we investigated the analgesic effects of CR on complete Freund's adjuvant (CFA)-induced inflammatory pain. The accumulation of LC3-II and p62 showed impaired autophagic flux in the ipsilateral spinal cord of mice with CFA-induced inflammatory pain. CR alleviated mechanical allodynia and thermal hyperalgesia and reduced paw edema and pro-inflammatory factors following CFA administration. CR exerted an analgesic effect by restoring autophagic flux in the spinal cord. Regarding the mechanisms underlying the analgesic effects of CR, ß-hydroxybutyric acid (BHB) was studied. CR increased BHB levels in the ipsilateral spinal cord. Furthermore, exogenous BHB administration exerted an analgesic effect by restoring autophagic flux in the spinal cords of CFA-induced inflammatory pain mice. Taken together, these results illustrated that CR relieved inflammatory pain by restoring autophagic flux in the spinal cord, while BHB controlled the benefits of CR, suggesting that CR or BHB might be a promising treatment for inflammatory pain.

Anti-nociceptive Effects of Dexmedetomidine Infusion Plus Modified Intercostal Nerve Block During Single-port Thoracoscopic Lobectomy: A Double-blind, Randomized Controlled Trial.

BACKGROUND: Multimodal general anesthesia based on modified intercostal nerve block (MINB) has been found as a novel method to achieve an intraoperative opioid-sparing effect. However, there is little information about the effective method to inhibit visceral nociceptive stress during single-port thoracoscopic surgery. OBJECTIVE: To investigate whether a low-dose dexmedetomidine infusion followed by MINB might be an alternative method to blunt visceral stress effectively. STUDY DESIGN: Double-blind, randomized control trial. SETTING: Affiliated hospital from March 2020 through September 2020. METHODS: Fifty-four patients were randomized (1:1), 45 patients were included to receive dexmedetomidine with a 0.4 microgram/kg bolus followed by 0.4 microgram/kg/h infusion (group Dex) or saline placebo (group Con). During the operation, an additional dose of remifentanil 0.05-0.25 microgram/kg/min was used to keep mean arterial pressure (MAP) or heart rate (HR) values around 20% below baseline values. The primary outcome was to evaluate remifentanil consumption. Secondary outcomes included intraoperative hemodynamics, the first time to press an analgesia pump, and adverse effects. RESULTS: Remifentanil consumption during surgery was markedly decreased in the Dex group than in the Con group (0 [0-0] versus 560.0 [337.5-965.0] microgram; P = 0.00). MAP and HR in the Con group during the first 5 minutes after visceral exploration was significantly higher than in the Dex group (P < 0.05). Time to first opioid demand was significantly prolonged (P = 0.04) and postoperative length of stay was shortened slightly in the Dex group (P = 0.05). LIMITATIONS: This study was limited by the measurement of nociception. CONCLUSIONS: This study demonstrates that low-dose dexmedetomidine infusion combined with MINB might be an effective alternative method to blunt visceral stress in patients undergoing single-port thoracoscopic lobectomy. Furthermore, the analgesic effect of MINB was significantly prolonged after dexmedetomidine infusion.

Opioid-sparing effect of modified intercostal nerve block during single-port thoracoscopic lobectomy: Retraction: A randomised controlled trial.

BACKGROUND: Peripheral local anaesthetic blockade has an important role in multimodal postoperative analgesia after video-assisted thoracic surgery. Intercostal nerve block has an opioid-sparing effect after thoracoscopic surgery, but there is little information about an intra-operative opioid-sparing effect. OBJECTIVE: This prospective randomised trial was designed to evaluate the feasibility of a modified intercostal nerve block and its potential opioid-sparing effect during single-port thoracoscopic lobectomy. DESIGN: This was a randomised controlled study. SETTING: The First Affiliated Hospital of Anhui Medical University, Hefei, China, from January 2020 to April 2020. PATIENTS: Fifty patients scheduled for single-port thoracoscopic lobectomy were enrolled. INTERVENTION: Patients were randomised to receive the intercostal nerve block using 10 ml 0.35% ropivacaine (group MINB) or conventional general anaesthesia (group CGA). Following a bolus of 0.5 to 1.0 µg kg-1 remifentanil, it was then infused at 0.2 to 0.5 µg kg-1 min-1 during surgery to keep mean arterial pressure or heart rate values around 20% below baseline values. MAIN OUTCOME MEASURES: The primary outcome was intra-operative remifentanil consumption. RESULTS: Median [IQR] remifentanil consumption was reduced in the MINB group [0 µg (0 to 0 µg)] compared with the CGA group [1650.0 µg (870.0 to 1892.5 µg)]. The median difference was 1650.0 µg (95%CI 1200.0 to 1770.0 µg; P = 0.00). The total number of analgesic demands during the first 24 and 48 h in the MINB group was significantly less than in the CGA group (difference = 1; 95% CI 1 to 3; P = 0.00 and difference = 4; 95% CI 3 to 5; P = 0.00; respectively). The difference in time to first demand for analgesia was significant [difference = 728 min (95% CI 344 to 1381 min), P = 0.00] and also in the number of patients requiring additional tramadol (P = 0.03). CONCLUSION: We have shown intra-operative opioid-sparing with a modified intercostal nerve block during single-port thoracoscopic lobectomy, with opioid-sparing extending 48 h after surgery. However, the opioid-sparing effect was not associated with a reduction in opioid side effects. TRIAL REGISTRATION: http://www.chictr.org.cn, ChiCTR2000029337.

Outcomes of individualized goal-directed therapy based on cerebral oxygen balance in high-risk patients undergoing cardiac surgery: A randomized controlled trial.

STUDY OBJECTIVE: To investigate whether optimizing individualized goal-directed therapy (GDT) based on cerebral oxygen balance in high-risk surgical patients would reduce postoperative morbidity. DESIGN: This was a prospective, randomized, controlled study. SETTING: The study was performed in the First Affiliated Hospital of Anhui Medical University, Hefei, China, from April 2017 to July 2018. PATIENTS: 146 high-risk adult patients undergoing valve replacements or coronary artery bypass surgery with cardiopulmonary bypass (CPB) were enrolled. INTERVENTION: Patients were randomized to an individualized GDT group or usual care group. Individualized GDT was targeted to achieve the following goals: A less than 20% decline in the regional cerebral oxygen saturation (rScO2) level from baseline; a less than 20% decline in the mean arterial pressure (MAP) from baseline, as well as a bispectral index (BIS) of 45-60 before and after CPB and 40-45 during CPB. MEASUREMENTS: The primary outcome was a composite endpoint of 30-day mortality and major postoperative complications. MAIN RESULTS: 128 completed the trial and were included in the modified intention-to-treat analysis. Early morbidity was similar between the GDT (25 [39%] of 65 patients) and usual care groups (33 [53%] of 63 patients) (relative risk 0.73, 95% CI 0.50-1.08; P = 0.15). Secondary analysis showed that 75 (59%) of 128 patients achieved individual targets (irrespective of intervention) and sustained less morbidity (relative risk 3.41, 95% CI 2.19-5.31; P < 0.001). CONCLUSIONS: In high-risk patients undergoing cardiac surgery, individualized GDT therapy did not yield better outcomes, however, the achievement of preoperative individual targets may be associated with less morbidity. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03103633. Registered on 1 April 2017.

The Changes of Intrinsic Excitability of Pyramidal Neurons in Anterior Cingulate Cortex in Neuropathic Pain.

To find satisfactory treatment strategies for neuropathic pain syndromes, the cellular mechanisms should be illuminated. Central sensitization is a generator of pain hypersensitivity, and is mainly reflected in neuronal hyperexcitability in pain pathway. Neuronal excitability depends on two components, the synaptic inputs and the intrinsic excitability. Previous studies have focused on the synaptic plasticity in different forms of pain. But little is known about the changes of neuronal intrinsic excitability in neuropathic pain. To address this question, whole-cell patch clamp recordings were performed to study the synaptic transmission and neuronal intrinsic excitability 1 week after spared nerve injury (SNI) or sham operation in male C57BL/6J mice. We found increased spontaneous excitatory postsynaptic currents (sEPSC) frequency in layer II/III pyramidal neurons of anterior cingulate cortex (ACC) from mice with neuropathic pain. Elevated intrinsic excitability of these neurons after nerve injury was also picked up, which was reflected in gain of input-output curve, inter-spike interval (ISI), spike threshold and Refractory period (RP). Besides firing rate related to neuronal intrinsic excitability, spike timing also plays an important role in neural information processing. The precision of spike timing measured by standard deviation of spike timing (SDST) was decreased in neuropathic pain state. The electrophysiological studies revealed the elevated intrinsic excitation in layer II/III pyramidal neurons of ACC in mice with neuropathic pain, which might contribute to central excitation.

Perioperative risk factors and cumulative duration of "triple-low" state associated with worse 30-day mortality of cardiac valvular surgery.

ABSRACT: Hospital stay and mortality in high-risk patients after noncardiac surgery has been associated with a triple low anesthesia. However, the association between anesthesia-related factors and perioperative outcome after cardiac surgery remains unclear.We tested the effect of a novel triple low state: low mean arterial pressure (MAP) <65 mmHg and low bispectral index (BIS) <45 during a low target effect-site concentration (Ce) <1.5 µg ml-1 of propofol anesthesia on postoperative duration of hospitalization and 30-day mortality in cardiac valvular patients. In this prospective observational study, univariable and multivariable logistic regression analyses were used to determine whether perioperative factors, in particular, cumulative duration of triple low state were independently associated with duration of hospitalization and 30-day mortality among patients who underwent elective valvular replacement. 489 patients were included in the final analysis. After adjusting for related covariates, cumulative duration of the triple-low state was not associated with prolonged hospitalization (multivariable odds ratio: 1.007; 95 % confidence interval 0.997-1.017; P = 0.564), but was a significant predictor of 30-day mortality (multivariable odds ratio: 1.016; 95 % confidence interval 1.002-1.031; P = 0.030). Compared to a triple-low duration of <15 min, a duration >60 min increased the 30-day mortality rate by 8 times. After adjusting for patient- and procedure-related characteristics, the cumulative duration of a triple-low state (intraoperative low MAP, low BIS, and low Ce) was associated with poorer 30-day mortality, but not with prolonged duration of hospital stay.The mortality risk was even greater when a cumulative time >60 min.

Sufentanil attenuates impairment of the endothelium-dependent vasodilation induced by hypoxia-reoxygenation in the rat coronary artery.

Sufentanil has been used broadly in cardiac surgery, but the mechanisms by which it modulates coronary vascular tone after ischemia-reperfusion injury are largely unknown. Effects of sufentanil on coronary tone and on the relaxation of rat coronary arteries (CAs) in response to endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) relaxing agents in the presence of hypoxia-reoxygenation (H/R) was studied in an in vitro organ chamber setup. Sufentanil (10-7-10-4 mol/L) relaxed rat CA rings in endothelium-dependent and endothelium-independent manners. In endothelium-intact rings, preincubation of H/R-treated CAs with sufentanil (10-5 mol/L) significantly increased the acetylcholine response, but did not augment sodium nitroprusside-induced relaxation. Sufentanil-mediated potentiation of acetylcholine-induced relaxation was not affected by a nitric oxide synthase inhibitor or by intermediate- or small-conductance Ca2+-activated K+ channel blockers. However, potentiation was abolished by iberiotoxin (100 nmol/L), a selective inhibitor of large-conductance Ca2+-activated K+ channels, as well as Rp-cAMPS (30 µmol/L), a cyclic AMP-dependent protein kinase (PKA) inhibitor. Sufentanil induced endothelium-dependent and endothelium-independent relaxation and attenuated H/R-induced impairment of endothelium-dependent vasodilation in the rat CAs. The potentiating effect of sufentanil may involve activation of large-conductance Ca2+-activated K+ channels via cAMP-dependent mechanisms.

Comparison of the type and severity of early attentional network decline after total intravenous or epidural anesthesia in middle-aged women after gynecological surgery.

Compared with regional anesthesia, general anesthesia may increase the risk of postoperative cognitive decline. This study aimed to investigate the type and severity of attentional network decline and the recovery of attentional networks in middle-aged women after gynecological surgery. A total of 140 consenting women undergoing elective gynecological surgery were enrolled in the study. Patients were assigned randomly to receive either total intravenous anesthesia or epidural anesthesia. To determine the efficacy of the attentional networks, patients were examined for alerting, orienting, and executive networks on the preoperative day and on the first and fifth postoperative days using the attentional network test. Significant differences were observed in the effect scores of the three attentional networks at all time points. These effect scores differed significantly between groups and between 1 and 5 days postoperation (DPO). Participants showed significantly lower effect scores for the alerting and orienting network tasks and had more difficulties in resolving conflict at 1 DPO compared with the baseline. On comparing effect scores between baseline and 5 DPO, no significant differences on the alerting and orienting network tasks were observed in the epidural anesthesia group, a significant difference on the orienting network task was observed in the general anesthesia group, and significant differences on the executive control network were observed in both the groups. Compared with epidural anesthesia, total intravenous anesthesia is more likely to impair and delay the recovery of attentional networks in middle-aged women undergoing elective hysterectomy. The executive control function showed marked damage and there were difficulties in recovery from either type of anesthesia.

Dezocine prevents sufentanil-induced cough during general anesthesia induction: A randomized controlled trial.

BACKGROUND: Opioid-induced cough during induction of general anesthesia is a common phenomenon. Dezocine, a partial µ-receptors agonist and κ-receptors antagonist, has been documented effectively suppressing fentanyl-induced cough in general anesthesia induction. However, the effect of dezocine on sufentanil-induced cough is still unknown. METHODS: A total of 370 patients (American Society of Anesthesiologists physical status I-II), aged 18-70 years, undergoing elective surgery, were randomly divided into a control group (group C) and a dezocine group (group D) (n=185 in each group). Patients received dezocine 0.1mg/kg or an equal volume of 0.9% normal saline 2 min prior to intravenous sufentanil (0.5 µg/kg). The incidence and reflex degree of cough in patients were evaluated within 2 min after the injection of sufentanil in anesthesia induction period. RESULTS: No patient in group D had cough and 59 patients in group C had cough (severity of cough: mild, 7%; moderate, 11.4%; severe, 13.5%). The occurrence and reflex degree of cough in group D was significantly lower than that in group C (P=0.000). The highest heart rate (HR) and invasive blood pressure (IBP) values were higher in group C than those in group D (P<0.01) within 2 min after sufentanil administration, althought these values remained within safe limits. CONCLUSION: The results of current study suggest that administration of Dezocine 0.1mg/kg may effectively prevent the occurrence and reflex degree of sufentanil-induced irritating cough in general anesthesia induction in patients.

Opioid receptor A118G polymorphism does not affect the consumption of sufentanil and ropivacaine by patient-controlled epidural analgesia after cesarean section.

BACKGROUND: Previous reports have suggested that polymorphism of the opioid receptor A118G affects the efficacy of opioid analgesia. The aim of this study was to investigate whether such polymorphism contributed to variability in epidural mixture (sufentanil plus ropivacaine) requirements through patient-controlled epidural analgesia (PCEA) after cesarean section. METHODS: One hundred eighty consenting women undergoing elective cesarean delivery were enrolled in the study. Patients received sufentanil and ropivacaine for pain control after surgery. Sufentanil (50 mcg) diluted with 0.2% ropivacaine in a total volume of 100 mL was administered by PCEA with a background infusion rate of 2 mL/h and a pump program set to deliver 0.5-mL boluses with a lockout time of 15 minutes. The analgesic effect and adverse effects were measured with rating scales. The total consumption of the epidural mixture in the first 24 hours postoperatively was recorded. Blood samples were genotyped to classify patients into 3 groups according to A118G polymorphism. RESULTS: Of 161 patients included in the analysis, 63 were homozygous (AA), 81 were heterozygous (AG), and 17 were homozygous (GG) for the A118G polymorphism. No difference was observed among groups in the consumption of the epidural mixture within the first 24 hours postoperatively (P = 0.3). Satisfaction with analgesia, pain scores, and adverse effects were similar among the groups. CONCLUSIONS: The analgesic requirements of patients receiving sufentanil and ropivacaine through PCEA after caesarean section were not associated with A118G polymorphism.

Involvement of GSK3ß/ß-catenin signaling in the impairment effect of ketamine on spatial memory consolidation in rats.

The cellular mechanisms underlying amnesia produced by the analgesic ketamine are not clear. The current study examined the effects of ketamine on memory consolidation in rats trained in a Morris water maze task, and further tested whether the glycogen synthase kinase (GSK)3ß/ß-catenin signaling pathway was involved in mediating the effects of posttraining ketamine on retention. Adult male Sprague-Dawley rats were injected with ketamine (0, 25, 50, or 100mg/kg) immediately after an eight-trial water maze training session. A probe trial was carried out 24 h later to examine the effects of ketamine on memory. Rats hippocampi were subjected to western blot assays to measure levels of native versus phosphorylated (p) GSK3ß and ß-catenin protein. Memory performance was significantly impaired in rats injected with ketamine (100 mg/kg) after training. Western blots showed that p-GSK-3ß(Ser9) levels were reduced and p-ß-catenin(Ser33/37/Thr41) levels were elevated in ketamine treated rats during consolidation. These posttraining changes in hippocampal p-GSK-3ß and p-ß-catenin were blocked by injection of 100mg/kg ketamine immediately after training, indicating that the 100mg/kg dose of ketamine altered activation of GSK3ß/ß-catenin signaling pathway in the hippocampus. Acute injection of the GSK3ß specific inhibitor SB216763 (1 ng/0.5 µl/side) into area CA1 of the hippocampus after water maze training prevented ketamine-induced impairment of memory and blocked ketamine-induced effects on the GSK3ß/ß-catenin signaling pathway in the hippocampus. Our results suggest that an anesthetic dose of ketamine injected immediately after Morris water maze training impaired memory consolidation and support the hypothesis that GSK3ß/ß-catenin signaling may play a role in ketamine-induced retrograde amnesia.

Sufentanil limits the myocardial infarct size by preservation of the phosphorylated connexin 43.

Sufentanil, with a potent analgesia effect, has been wildly used in anesthesia and analgesia, especially for the cardiovascular surgeries. The aim of the study was to evaluate whether sufentanil provides cardioprotection and the effect of connexin 43 on the cardiac infarct size reduction. Sufentanil post-conditioning (bolus injection at 0.1, 0.3, 1, 3, 10 µg/kg) or ischemic post-conditioning (3 cycles of a 10s reperfusion alternating with a 10s ischemia) was induced in an intact rat heart model of ischemia-reperfusion injury. Both ischemic and sufentanil post-conditioning reduced the myocardial infarct size compared with control group. The infarct size limitation of sufentanil was dose-dependent, 1 µg/kg has the optimal effect and increasing dosage could not afford further cardioprotection. Connexin 43 underwent dephosphorylation in response to ischemia-reperfusion measured by Western blot at the anterior myocardium tissues of left ventricle while sufentanil preserved the phosphorylation of connexin 43. The results demonstrated that sufentanil limits myocardial infarct size which is similar with ischemic post-conditioning at the dosage of 1 µg/kg. Preservation of phosphorylation of connexin 43 plays an important role in the cardioprotection of ischemic and sufentanil post-conditioning.

Role of p38 mitogen-activated protein kinases in cardioprotection of morphine preconditioning.

BACKGROUND: p38 mitogen-activated protein kinases (MAPK) in ischemic preconditioning (IPC) may be essential to cardioprotection. We assessed whether protective effect of morphine-induced preconditioning (MPC) on myocardial ischemia and reperfusion injury in rat hearts involved p38 MAPK activation. METHODS: Male Spargue-Dawley rats (weighing 300-350 g) were randomly assigned to 1 of the following 8 groups: control (CON, saline vehicle, n=9), SB 203580 (SB, a p38 MAPK inhibitor, n=6), MPC (n=6), IPC (n=9), SB+MPC, SB+IPC, MPC+SB, and IPC+SB (n=6). Infarct sizes (IS), a percentage of the area at risk (AAR), were determined by triphenyltetrazolium (TTC) staining. Tissue samples were processed from the entire AAR of left ventricle for the determination of p38 MAPK protein expression (5 hearts/group). The bands representing the proteins were visualized using an enhanced chemiluminescence detection system. RESULTS: The IS/AAR was significantly reduced by IPC (12.9+/-1.6)% or MPC (25.3+/-2.9)% compared to the control (52.7+/-5.5)%. SB 203580 administered prior to preconditioning abolished the effect of IPC (SB+IPC: (43.8+/-2.6)%, P>0.05 vs CON, P<0.01 vs IPC), but not MPC (SB+MPC: (30.7+/-0.9)%, P<0.01 vs CON, P>0.05 vs MPC). Treatment with SB 203580 prior to sustained ischemia diminished the protective effect of both MPC (MPC+SB: (42.4+/-2.9)%, P>0.05 vs CON) and IPC (IPC+SB: (52.0+/-2.5)%, P>0.05 vs CON) on IS/AAR. In the IPC group, phospho-p38 MAPK protein increased significantly within 5 minutes into ischemia and remained elevated at 30 minutes into reperfusion, while phospho-p38 MAPK protein in the MPC group only increased significantly at 30 minutes into reperfusion. CONCLUSION: The activation of p38 MAPK just acts as a mediator of MPC, whereas it acts as both a trigger and a mediator in IPC.