Effects of esketamine on postoperative fatigue syndrome in patients after laparoscopic resection of gastric carcinoma: a randomized controlled trial.

BACKGROUND: Despite the implementation of various postoperative management strategies, the prevalence of postoperative fatigue syndrome (POFS) remains considerable among individuals undergoing laparoscopic radical gastrectomy. While the N-methyl-D-aspartic acid receptor antagonist esketamine has demonstrated efficacy in enhancing sleep quality and alleviating postoperative pain, its impact on POFS remains uncertain. Consequently, the objective of this study is to ascertain whether perioperative administration of esketamine can effectively mitigate the occurrence of POFS in patients undergoing laparoscopic radical gastrectomy. METHODS: A total of 133 patients diagnosed with gastric cancer were randomly assigned to two groups, namely the control group (Group C) (n = 66) and the esketamine group (Group E) (n = 67), using a double-blind method. The Group C received standardized anesthesia, while the Group E received esketamine in addition to the standardized anesthesia. The primary outcome measure assessed was the Christensen fatigue score at 3 days after the surgical procedure, while the secondary outcomes included the disparities in postoperative fatigue, postoperative pain, sleep quality, and adverse reactions between the two groups. RESULTS: In the group receiving esketamine, the fatigue scores of Christensen on the third day after surgery were significantly lower compared to the Group C (estimated difference, -0.70; 95% CI, -1.37 to -0.03; P = 0.040). Additionally, there was a significant decrease in the occurrence of fatigue in the Group E compared to the Group C on the first and third days following surgery (P < 0.05). Also, compared to individuals who had distal gastrectomy, those who had entire gastrectomy demonstrated a higher degree of postoperative tiredness reduction with esketamine. Furthermore, the Group E exhibited reduced postoperative pain and improved sleep in comparison to the Group C. Both groups experienced similar rates of adverse events. CONCLUSIONS: The use of esketamine during the perioperative period can improve POFS after laparoscopic radical gastrectomy, without adverse reactions. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2300072167) on 05/06 /2023.

Effectiveness of Chinese Herbal Medicine in Postoperative Fatigue Syndrome Following Total Joint Arthroplasty or Hip Fracture Surgery: Evidence from Randomized Controlled Trials.

BACKGROUND: There is no high-quality, evidence-based protocol for the treatment of postoperative fatigue syndrome (POFS) after total joint arthroplasty (TJA) or fracture surgery with Chinese herbal medicine (CHM). PURPOSE: The purpose of this study was to explore the efficacy of CHM in the treatment of POFS after TJA or hip fracture surgery (HFS). METHODS: We searched six databases to obtain randomized controlled trials (RCTs) of CHM for the treatment of POFS after TJA or HFS. The retrieval time limit was from the establishment of each database to August, 2022. According to the Cochrane Handbook for Systematic Reviews version 5.1, we used RevMan 5.3 to evaluate the quality of the studies. Stata 14.0 software was used to merge and analyze the data. The weighted mean difference (WMD) was the effect estimate for statistical analysis. We also performed subgroup analyses according to different types of surgeries. RESULTS: A total of 11 RCTs were included in this study, comprising 430 cases in the CHM group and 432 cases in the control group (CG). The meta-analysis results showed that there was no significant difference in the Brief Profile of Mood States (BPOMS) score (WMD=0.08, 95% confidence interval (CI): -0.29 to 0.45, P=0.688), Christensen Fatigue scale (CHFS) score (WMD = 0.15, 95% CI: -0.09 to 0.39, P=0.214) or Identity-Consequence Fatigue Scale (ICFS) score (WMD=-0.40, 95% CI: -1.84 to 1.05, P=0.589) between the CHM group and the CG on the first postoperative day. The use of CHM significantly reduced the BPOMS score (WMD=-0.85 and WMD=-3.01, respectively), CHFS score (WMD=-1.01 and WMD= -1.45, respectively), and ICFS score (WMD=-3.51 and WMD=-5.26) on postoperative days 3 and 7. Compared with the CG, the CHM group had significantly increased serum transferrin and IgG levels on postoperative days 3 and 7. The subgroup analysis results suggested that the application of CHM in HFS patients improved fatigue symptoms on postoperative days 3 and 7, while the application of CHM to treat POFS in TJA patients had great inconsistency in the evaluation of different indicators. CONCLUSION: The application of CHM improved the fatigue status of POFS patients after TJA or HFS and increased the levels of transferrin and IgG in serum, which is conducive to promoting the postoperative rehabilitation process of patients. The subgroup analysis results showed that the application of CHM to intervene in POFS in HFS patients had obvious benefits.

Effect of a single sub-dose of ketamine on postoperative fatigue syndrome in colorectal cancer patients undergoing radical laparoscopic surgery: A double-blind, pilot study.

BACKGROUND: This study aimed at examining the effect of a single sub-anesthetic dose of ketamine on postoperative fatigue syndrome (POFS) in patients undergoing radical laparoscopic surgery for colorectal cancer (CRC). METHODS: This prospective, double-blind, pilot study enrolled patients scheduled for radical laparoscopic surgery for CRC under general anesthesia. Eligible patients were randomized into the placebo and ketamine groups. The primary outcome was christensen score change at day 3. The secondary outcomes were the difference of Identity Consequence Fatigue Scale (ICFS) score between the placebo group and ketamine group at day 3 and level of serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, S100ß protein, and neuron-specific enolase (NSE). RESULTS: 32 participants were assigned to the ketamine group and 31 to the placebo group. Compared with placebo group, the Christensen score was lower in ketamine group at day 3 (absolute difference, -1.13; 95 % confidence interval [CI], -2.02 to -0.24; P = 0.012). Ketamine group was superior to the placebo group with regard to the ICFS scores at day 3 (absolute difference, -6.4; 95 % CI, -11.4 to -1.4; P = 0.013). The plasma TNF-α, IL-6, S100ß, and NSE levels were increased after operation compared with baseline in both groups and were significantly higher in placebo group than in ketamine group within 24 h after surgery (all P < 0.05). There was no significant difference of each safety evaluation indicator between the two groups (all P > 0.05). CONCLUSION: A single sub-anesthetic dose of ketamine may improve POFS in patients undergoing radical laparoscopic surgery for CRC, without postoperative adverse reactions.

Serum metabolite profiles of postoperative fatigue syndrome in rat following partial hepatectomy.

Postoperative fatigue syndrome is a general complication after surgery. However, there is no ''gold standard'' for fatigue assessment due to the lack of objective biomarkers. In this study, a rodent model of postoperative fatigue syndrome based on partial hepatectomy was firstly established and serum metabonomic method based on ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied. Partial least-squares discriminant analysis was used to identify the differential metabolites in 70% partial hepatectomy rats relative to sham rats and 30% partial hepatectomy rats, which showed 70% partial hepatectomy group was significantly distinguishable from 30% partial hepatectomy group and sham group. Eighteen serum metabolites responsible for the discrimination were identified. The levels of hypoxanthine, kynurenine, tryptophan, uric acid, phenylalanine, palmitic acid, arachidonic acid and oleic acid showed progressive elevation from sham group to 30% partial hepatectomy group to 70% partial hepatectomy group, and levels of valine, tyrosine, isoleucine, linoleyl carnitine, palmitoylcarnitine, lysophosphatidylcholine (16:0), lysophosphatidylcholine (20:3), citric acid, succinic acid and hippuric acid showed progressive declining trend from sham group to 30% partial hepatectomy group to 70% partial hepatectomy group. These potential biomarkers help to understand of etiology, pathophysiology and treatment of postoperative fatigue syndrome.

Improvement of ginsenoside Rb1 on inflammation of central nervous system in postoperative fatigue syndrome rats / 中草药

Objective: To explore the inflammatory factor and inflammation signal pathway in hippocampus of postoperative fatigue syndrome (POFS) rats, and to investigate the central mechanism of POFS and the anti-fatigue effect of ginsenoside Rb1. Methods: Ninety-six male SD rats were randomly divided into control, POFS, and ginsengoside Rb1 intervention groups (ginsengoside Rb1 groups), and each group was divided into subgroups by postoperative 1, 3, 5, and 7 d. The fatigue was assessed with open field test. The mRNA levels of inflammatory cytokines in hippocampus were measured by real-time quantitative PCR. The activation of p38MAPK enzyme was examined by Western blotting and immunohistochemisty. The translocation of NF-κB/p65 in nuclear was measured by Western blotting and immunohistofluorescence. Results: On postoperative day 1 and day 3, compared with the control group, the journey of rats in the POFS group declined (P < 0.01), while resting time increased (P < 0.01), the level of inflammation cytokines added, the expression of p-p38MAPK protein was enhanced and the ratio of NF-κB/p65 cytoplasm/NF-κB/p65/nuclear was also elevated (P < 0.05). Compared with the POFS group, the resting time of rats decreased (P < 0.05) on postoperative day 1 and day 5.On day 1 and day 3 after surgery, the journey of rats was enhanced (P < 0.01), the level of inflammation cytokines was declined and the ratio of NF-κB/p65 cytoplasm/NF-κB/p65/nuclear was decreased (P < 0.05). The levels of p-p38MAPK in postoperative day 3, day 5, and day 7 were also declined (P < 0.05). The results of immunohistochemisty and immunohistofluorescence were accordance with Western blotting. Conclusion: The inflammatory cytokine in hippocampus of POFS rats is increased and the inflammation signal pathway is activated. Ginsenoside Rb1 has some improvement effects on central fatigue in POFS rats. Key words:

Ginsenoside Rb1 improves postoperative fatigue syndrome by reducing skeletal muscle oxidative stress through activation of the PI3K/Akt/Nrf2 pathway in aged rats.

Ginsenoside Rb1 is reported to possess anti-fatigue activity, but the mechanisms remain unknown. The aim of this study was to investigate the molecular mechanisms responsible for the anti-fatigue effect of ginsenoside Rb1 on postoperative fatigue syndrome induced by major small intestinal resection (MSIR) in aged rat. Aged rats with MSIR were administrated with ginsenoside Rb1 (15 mg/kg) once a day from 3 days before surgery to the day of sacrifice, or with saline as corresponding controls. Rats without MSIR but going through the same surgery procedure were administrated with saline as blank controls. Anti-fatigue effect was assessed by an open field test; superoxide dismutase, reactive oxygen species and malondialdehyde in skeletal muscle were determined. The mRNA levels of Akt2 and Nrf2 in skeletal muscle were measured by real-time quantitative PCR. The activation of Akt and Nrf2 was examined by western blot and immunohistofluorescence. Our results revealed that ginsenoside Rb1 significantly increased the journey and the rearing frequency, decreased the time of rest in aged rats with MSIR. In addition, ginsenoside Rb1 significantly reduced reactive oxygen species and malondialdehyde release and increased the superoxide dismutase activity of skeletal muscle in aged rats with MSIR. Ginsenoside Rb1 also increased the expression of Akt2 and Nrf2 mRNA, up-regulated Akt phosphorylation and Nrf2 nuclear translocation. These findings indicate that ginsenoside Rb1 has an anti-fatigue effect on postoperative fatigue syndrome in aged rat, and the mechanism possibly involves activation of the PI3K/Akt pathway with subsequent Nrf2 nuclear translocation and induction of antioxidant enzymes.

Ginsenoside Rb1 improves energy metabolism in the skeletal muscle of an animal model of postoperative fatigue syndrome.

BACKGROUND: Postoperative fatigue syndrome (POFS) is a common clinical complication followed by almost every major abdominal surgery. Ginsenoside Rb1 (GRb1), a principle ginsenoside in ginseng, could exert a potent anti-fatigue effect on POFS. However, the mechanism is still unknown. Previous studies revealed that alterations in the energy metabolism in the skeletal muscle may play a vital role in the development and progression of fatigue. In the present study, we investigate the effect of GRb1 on energy metabolism in the skeletal muscle of a rat model of POFS induced by major small intestinal resection. METHODS: GRb1 (10 mg/kg) was intraperitoneally administrated once daily for 1, 3, 7, and 10 d from the operation day, respectively. The locomotor activity was recorded every day, and total food intake was calculated starting from 24 h after surgery. After GRb1 treatment was completed, blood and skeletal muscle were sampled. The level of blood glucose was determined by an automatic biochemical analyzer. The content of adenosine triphosphate (ATP) in skeletal muscle was determined by high-performance liquid chromatography. The activity of energy metabolic enzymes Na(+)-K(+)-ATPase, pyruvate kinase, and succinate dehydrogenase (SDH) was assessed by commercially available kits. RESULTS: The results revealed that GRb1 could increase locomotor activity of POFS rats and significantly increase their total food intake postoperatively (P < 0.05). Furthermore, GRb1 also significantly increased ATP content in the skeletal muscle of POFS rats (P < 0.05). Meanwhile, the activity of Na(+)-K(+)-ATPase and SDH in the skeletal muscle of POFS rats was enhanced by GRb1 (P < 0.05). However, no significant differences in blood glucose and pyruvate kinase were found between the POFS and GRb1 treatment rats (P > 0.05). CONCLUSIONS: These results suggest that GRb1 may improve skeletal muscle energy metabolism in POFS, and the underlying mechanism may be associated with an increase in the content of ATP and an enhancement in the activity of energy metabolic enzymes such as Na(+)-K(+)-ATPase ATPase and SDH in the skeletal muscle.

Effect of ginsenoside Rb1 on neurotrophic factors in elderly rats with postoperative fatigue syndrome / 中草药

Objective: To investigate the dynamical variation of the hippocampal neurotrophic factors (NTF) in elderly rats with postoperative fatigue syndrome (POFS) and the antifatigue mechanism of ginsengside Rb1. Methods: Ninety-six elderly male SD rats were randomly divided into Sham, POFS model, and ginsengoside Rb1 intervention groups, and each group was divided into subgroups by postoperative 6 h, 1, 3, and 7 d. The hippocampus was removed at each time point after open field test (OFT) to detect the mRNA expression levels of nerve growth factors (NGF) and brain-derived neurotrophic factors (BDNF) by Real-time PCR; The content of protein was detected by radioimmunoassay; The ultrastructural changes in hippocampus CA1 area were observed by electron microscopy. Results: Compared with the Sham group, the number through lattice in OFT of rats in the POFS model group declined (P < 0.01), while resting time increased (P < 0.01); The expression level of NGF and BDNF mRNA in the POFS model group declined (P < 0.05, 0.01), the expression level of corresponding protein declined (P < 0.05). Compared with the POFS model group, the number through lattice in OFT of rats in the Rb1 group increased (P < 0.05), the expression level of NGF and BDNF mRNA of rats in Rb1 group increased (P < 0.05, 0.01), and the expression level of corresponding protein also increased (P < 0.01). Electron microscopy results showed that compared with the Sham group, the ultrastructures of the hippocampal neurons of rats were significantly damaged in the POFS model group, which were relatively impromed in the Rb1 group. Conclusion: The expression level of NTF inelderly rats with POFS declines, the hippocampal neurons are damaged to a certain extent and the application of ginsenoside Rb1 may have the improvement to POFS in elderly rats.

Effect of ginsenoside Rb1 on central oxidative stress of rats with postoperative fatigue syndrome / 中草药

Objective: To investigate the central oxidative stress characteristics of rats with postoperative fatigue syndrome (POFS) and the antifatigue mechanism of ginsenosides Rb1. Methods: Rat models of POFS were established by using the 70% middle part of small bowel resection method. Ninety-six SD rats were randomly divided into control, model, and ginsenoside Rb1 (GRb1, 10 mg/kg) groups by weight. Rats in each group were administered 1 h before operation and were then divided into four subgroups at days 1, 3, 7, and 10. Morris water-maze test was done on postoperative days 2-7. Meanwhile, grasping test, malondialdehyde (MDA) content, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities were detected on postperative days 1, 3, 7, and 10 and the ultrastructure of hippocampal CA1 area was observed through electron microscope. Results: Compared with the control group, the maximum grip of model rats had an obvious decline on days 3, 7, and 10 (P < 0.05). The total average escape latency was significantly extended (P < 0.05) and the platform crossing times were significantly reduced (P < 0.05). Compared with the model group, the above indexes of rats in GRb1 group were effectively improved after the intervention (P < 0.05). Compared with the control group, on postoperative days 1 and 3, the MDA content was obviously increased (P < 0.05) and SOD activity was obviously raised (P < 0.05). On postoperative day 7, GSH-Px activity was obviously raised (P < 0.05). After the intervention of GRb1, the MDA content was effectively decreased (P < 0.05), SOD and GSH-Px activities were effectively improved (P < 0.05). Electron microscope showed that the ultrastructure of hippocampal CA1 area of rats in GRb1 group was significantly improved. Conclusion: Surgical stress leads to the state change of central oxidative stress; GRb1 could reduce the damage of oxidative stress by strengthening the activity of central anti-oxidant enzymes, so as to protecte central neurons, which may be one of the mechanisms against POFS.

Effects of enteral nutrition combined with panaxoside Rb1 on mouse models of postoperative fatigue syndrome / 中华临床营养杂志

Objective To explore the therapeutical effects of enteral nutrition (EN) combined with panaxoside Rb1 on mouse modles of postoperative fatigue syndrome. Methods Totally, 72 male Sprague-Dawley mice were randomly divided into control group, model group, EN group, EN associated with high/middle/low dose panaxoside Rb1 groups (EHP group, EMP group, and ELP group, n = 12 in each group). Changes in body weight were measured before and after interventions. Learning and memory playback abilities, physical strength,and vim state were evaluate by Morris Water Maze test and Improved Tail Suspension test. Serum transferrin, prealbumin, fibronectin, and interleukin-2 levels were measured with ELISA. Serum albumin level was assayed with Bromcresol Green colorimetric technique. CD4 + and CD8 + proportions were assayed by flow cytometry. Results The body weight grew alternately in each group without significant differences ( P ＞ 0.05 ) except for model group.The latency period was significantly shorter in EN combined with panaxoside Rbl group than that in model group ( P ＜ 0. 05 ) , and the frequencies of crossing platform in EHP group and EMP group were significantly higher than those in model group ( P ＜ 0. 01 ). The areas of struggling above domain in EHP group and EMP group were significantly larger than those in model group ( P ＜ 0. 05 ), and the accumulated static time of rest in EHP group, EMP group, and ELP group was significantly shorter than that in model group ( P ＜ 0.05 ). Serum transferrin, prealbumin, fibronectin levels in EN combined with panaxoside Rb1 group were significantly higher than those in model group ( all P ＜ 0.05 ). The CD4 + T proportion and interleukin-2 level in EHP group, EMP group, and ELP group were significantly higher than those in model group (both P ＜0.05 ); however, CD8 + T proportion was not significantly different between three panaxoside Rbl groups and model group (P ＞ 0. 05 ). Conclusion EN combined with panaxoside Rb1 can improve postoperative fatigue syndrome in a dose-dependent way, which may be explained by the fact that it can strengthen the postoperative nutrition, restrain hypermetabolism, and increase immunity.

Effect of rhGH on rat model of postoperative fatigue / 第三军医大学学报

Objective To investigate the effects of rhGH on rat model of postoperative fatigue syndrome (POFS) and to study its mechanism. Methods A total of 36 SD rats were randomly divided into 3 groups. The model group and rhGH group were estalished into the model of POFS by partial resection of the liver, and administrated with the same volume of physiological saline and rhGH, and control group was without any treatment. The behavioral changes and the disorder of nutrition intake after operation, stress reaction (pathological changes of mucous membrane in small intestine) and the liver albumin expression were observed. Results The rhGH could improve behavioral changes of rat model and increase the serum levels of the iron, total protein, albumin and globulin as the index of nutrition, and restore the injury of the mucous membrane resulted from the stress reaction and increase the expression of the liver albumin. Conclusion rhGH can shorten the time of POFS and mitigate POFS of rat model.

Effect of recombinant growth hormone on the aged patients after abdominal surgery / 肠外与肠内营养

Objectives: To research the effects of recombinant human growth hormone(rhGH) with total parenteral nutrition(TPN) on the old patients following abdominal surgery. Methods: 26 old patients receiving TPN after major abdominal surgery were selected and distributed to study group(rhGH+TPN, n =13) and control group(TPN only, n =13).For 7 days after operation, rhGH (8 U/d) or normal saline(in control group) were used. The patients' weight, serum albumin, right hand grip, sleep time and the time of incision cicatrized were determined. Results: The increase of weight, level of plasma albumin, grip power of right hand and sleep time were improved more in study group than those in control group. The incision cicatrized time was also shortened in study group. Conclusions: Growth hormone can promote protein synthesis, accelerate incision healing and reduce the postoperative fatigue syndrome.

Establishment and assessment of a model of abdominal postoperative fatigue syndrome in rats / 中国普通外科杂志

Objective To establish and assess a model of abdominal postoperative fatigue syndrome (POFS) in rats. Methods After 70% hepatectomy was performed, the following observations of the animals were made:general condition, rat tail suspension test,weight carrying swim fatigue test,serum levels of albumin,ferrition,and iron,pathologic assessment of injury of small intestinal mucosa and hepatic albumin gene expression .Results After 70% hepatectomy of the rats,their general candition was poor,the level of physical tolerance decreased,they showed a certain amount of depression,and marked changes were found in nutritional index,stress injury of small intestinal mucosa and hepatic albumin gene expression.Conclusions A 70% hepatectomy rat model has the basic characteristics of clinical abdominal POFS, and can be used as an experimental animal model for the study of abdominal POFS.