Perioperative dexmedetomidine-induced delirium in a patient with schizophrenia: a case report.

BACKGROUND: Dexmedetomidine is a selective α2 receptor agonist with sedative, analgesic, anxiolytic, and anti-sympathetic effects. Dexmedetomidine is widely used for various surgical procedures performed under general anaesthesia and sedation in the intensive care unit. Dexmedetomidine was known to relieve or improve the symptoms of delirium. Schizophrenia is a common psychiatric disease, and the number of surgical patients with schizophrenia is increasing gradually. Dexmedetomidine-induced delirium in patients with schizophrenia is a particular case. CASE PRESENTATION: This patient was a 75-year-old woman (height: 156 cm; weight: 60 kg) with a 5-year history of schizophrenia. Her schizophrenia was well controlled with medications. She was scheduled for open reduction and internal fixation for a patellar fracture. Spinal anaesthesia was administered for surgery, and dexmedetomidine was administered intravenously to maintain sedation. The patient became delirious half an hour after the surgery began. The intravenous infusion of dexmedetomidine was discontinued immediately, intravenous propofol was subsequently administered, and the patient stopped experiencing dysphoria and fell asleep. After surgery, the patient stopped using propofol and recovered smoothly. She was transferred back to the general ward and was discharged from the hospital without any abnormal conditions on the 9th day after surgery. CONCLUSIONS: To the best of our knowledge, this is the first report of a patient with schizophrenia who developed delirium during the infusion of a normal dose of dexmedetomidine without an intravenous injection of any other sedative. The exact mechanism causing dexmedetomidine-induced delirium remains unclear, and this adverse reaction is rare and easy to ignore. Clinicians and pharmacists should be vigilant in identifying this condition.

Continuous Erector Spinae Plane Block for Postoperative Analgesia in Elderly Patients After Thoracoscopic Lobectomy.

PURPOSE: The purpose of this study was to compare the effect of ultrasound-guided continuous erector spinae plane block to continuous thoracic paravertebral block on postoperative analgesia in elderly patients who underwent thoracoscopic lobectomy. DESIGN: Randomized controlled trial. METHODS: Elderly patients (N = 50) who underwent nonemergent thoracoscopic lobectomy in the thoracic surgery department of our hospital from January 2019 to December 2020 were selected and randomly divided into continuous erector spinae block (ESPB; n = 25) group and continuous thoracic paravertebral block (TPVB; n = 25) group. The patients in the two groups were guided by ultrasound with ESPB or TPVB before anesthesia induction. The visual analog scale at rest and cough in 2 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours after surgery, the supplementary analgesic dosage of tramadol, time of tube placement, the stay time in postanesthesia care unit (PACU), the first ambulation time after surgery, the length of postoperative hospital stay and postoperative complications were recorded. FINDINGS: There were no significant differences between the two groups in visual analog scale score at rest and cough at each time point and supplementary analgesic dosage of tramadol within 48 hours after surgery (P > .05). The time of tube placement and the postoperative hospital stay in ESPB group was significantly shorter than that in TPVB group (P < .05). There were no differences in PACU residence time and first ambulation time between the two groups (P > .05). There were 4 patients in TPVB group and 2 patients in ESPB group who had nausea and vomiting (P > .05), 1 case of pneumothorax and 1 case of fever in the TPVB group. There were no incision infections or respiratory depression requiring clinical intervention in either group. CONCLUSIONS: Both ESPB and TPVB alleviated the patients postoperative pain effectively for elderly patients underwent thoracoscopic lobectomy. Compared with TPVB, patients with ESPB have a shorter tube placement time, fewer complications and faster postoperative recovery.

Bach1 modulates AKT3 transcription to participate in hyperglycaemia-mediated EndMT in vascular endothelial cells.

Hyperglycaemia-mediated endothelial-to-mesenchymal transition (EndMT) is involved in the occurrence and progression of cardiovascular complications in diabetic patients. Previous studies reported that AKT serine/threonine kinase 3 (AKT3) and Bric-a-brac/Tramtrack/Broad (BTB) and cap'n'collar (CNC) homology 1 (bach1) participates in endothelial injury and epithelial-to-mesenchymal transition. In the present study, we proposed that bach1 regulates AKT3 transcription, thus involved in hyperglycaemia-mediated EndMT in vascular endothelium. Our results indicated that hyperglycaemia/high glucose increased AKT3 expression and induced EndMT in aorta of diabetic rats and hyperglycaemic human umbilical vein endothelial cells (HUVECs). Moreover, inhibition of AKT3 expression reversed high glucose-mediated EndMT in HUVECs. Further, hyperglycaemia/high glucose augmented bach1 expression in aorta of diabetic rats and hyperglycaemic HUVECs. Furthermore, si-bach1 countered high glucose-induced AKT3 expression and EndMT in HUVECs. In addition, the effect of bach1 overexpression is similar to that of high glucose treatment, which was reversed by si-AKT3. ChIP assays found bach1 enriched in the promoter region of AKT3. Bach1 overexpression augmented AKT3 promoter activity, which lost after specific binding site mutation. Bach1 was involved in hyperglycaemia-induced EndMT via modulation of AKT3 transcription.

Comparison of the efficacy of ultrasound-guided erector spinae plane block and thoracic paravertebral block combined with intercostal nerve block for pain management in video-assisted thoracoscopic surgery: a prospective, randomized, controlled clinical trial.

BACKGROUND: The objective of this study was to compare analgesic efficacy of erector spinae plane block(ESPB) and thoracic paravertebral block(TPVB) combined with intercostal nerve block(ICNB) after video assisted thoracoscopic surgery(VATS). METHODS: Patients were enrolled into three groups according to analgesia technique as ICNB, TPVB + ICNB or ESPB + ICNB: respectively Group C(n = 58), Group T (n = 56) and Group E (n = 59). Patients were followed up by a trained data investigator at 2, 6, 8, 12, 24, 48 h after surgery, and the visual analog scale(VAS) at rest and coughing were recorded. The moderate and severe pain mean VAS ≥ 4 when coughing. The postoperative opioids consumption, incidence of postoperative nausea and vomiting (PONV), supplementary analgesic requirements within 48 h, length of stay in PACU, ambulation time, postoperative days in hospital and potential side effects, such as hematoma, hypotension, bradycardia, hypersomnia, uroschesis, pruritus and apnea were recorded. RESULTS: The incidence of moderate-to-severe pain was no significant difference between 3 groups in 24 h and 48 h (P = 0.720). There was no significant difference among the 3 groups in the resting pain intensity at 2, 6, 8, 12, 24 and 48 h after surgery(P > 0.05). In 2-way analysis of variance, the VAS when coughing in Group T were lower than that in Group C (mean difference = 0.15, 95%CI, 0.02 to 0.29; p = 0.028). While no difference was found when comparing Group E with Group C or Group T(P > 0.05). There was no difference between the three groups in the sufentanil consumption( within 24 h p = 0.472, within 48 h p = 0.158) and supplementary analgesic requirements(p = 0.910). The incidence of PONV and the length of stay in PACU, ambulation time and postoperative days in hospital were comparable in the 3 groups(P > 0.05). Two patients from Group T developed hematoma at the site of puncture. CONCLUSIONS: The present randomized trial showed that the analgesic effect of TPVB + ICNB was superior to that of INCB after VATS, the analgesic effect of ESPB was equivalent to that of TPVB and ICNB. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100049578. Registered 04 Aug 2020 Retrospectively registered.

The role and significance of angiotensin-converting enzyme 2 peptides in the treatment of coronavirus disease 2019.

Since the end of 2019, coronavirus disease 2019 (COVID-19) caused by the novel coronavirus (2019-nCoV) posed a serious threat to human health and life. Therefore, the discovery of drugs that can effectively prevent and treat COVID-19 is urgently warranted. In this article, the role and significance of angiotensin-converting enzyme 2 in drug development and the treatment of COVID-19 are discussed. It was found that the binding of ACE2 to SARS-CoV-2-RBD involved two core regions (31st and 353rd lysine) and 20 amino acids of the ACE2 protein. The mutation of these amino acids could lead to a great change of the binding ability of ACE2 and SARS-CoV-2-RBD. This information was important for us to find more efficient ACE2 peptides to block the 2019-nCoV infection. So during this study, we summarized the role of ACE2 in the regulation of 2019-nCoV infection and stress, and hypothesized that the development and optimization of ACE2 peptide can effectively block 2019-nCoV infection and reliably treat the COVID-19.

SET8 suppression mediates high glucose-induced vascular endothelial inflammation via the upregulation of PTEN.

Hyperglycemia-mediated endothelial inflammation participates in the pathogenesis of cardiovascular complications in subjects with diabetes. Previous studies reported that phosphatase and tensin homolog deleted on chromosome ten (PTEN) and SET8 participate in high glucose-mediated endothelial inflammation. In this study, we hypothesize that SET8 regulates PTEN expression, thus contributing to high glucose-mediated vascular endothelial inflammation. Our data indicated that plasma soluble intercellular adhesion molecule-1 (sICAM-1) and endothelial selectin (e-selectin) were increased in patients with diabetes and diabetic rats. PTEN expression was augmented in the peripheral blood mononuclear cells of patients with diabetes and in the aortic tissues of diabetic rats. Our in vitro study indicated that high glucose increased monocyte/endothelial adhesion, endothelial adhesion molecule expression and p65 phosphorylation in human umbilical vein endothelial cells (HUVECs). Moreover, high glucose led to endothelial inflammation via upregulation of PTEN. Furthermore, high glucose inhibited SET8 expression and histone H4 lysine 20 methylation (H4K20me1), a downstream target of SET8. SET8 overexpression reversed the effects of high-glucose treatment. shSET8-mediated endothelial inflammation was counteracted by siPTEN. Furthermore, SET8 was found to interact with FOXO1. siFOXO1 attenuated high glucose-mediated endothelial inflammation. FOXO1 overexpression-mediated endothelial inflammation was counteracted by siPTEN. H4K20me1 and FOXO1 were enriched in the PTEN promoter region. shSET8 increased PTEN promoter activity and augmented the positive effect of FOXO1 overexpression on PTEN promoter activity. Our in vivo study indicated that SET8 was downregulated and FOXO1 was upregulated in the peripheral blood mononuclear cells of patients with diabetes and the aortic tissues of diabetic rats. In conclusion, SET8 interacted with FOXO1 to modulate PTEN expression in vascular endothelial cells, thus contributing to hyperglycemia-mediated endothelial inflammation.

Individualized lung protective ventilation vs. conventional ventilation during general anesthesia in laparoscopic total hysterectomy.

Laparoscopic total hysterectomy is performed by carbon dioxide insufflation, Trendelenburg position and mechanical ventilation of patients under general anesthesia. However, this may induce pulmonary atelectasis and/or hyperdistention of the lungs. Multiple studies have indicated that mechanical ventilation with the use of low tidal volumes, moderate positive end-expiratory pressure (PEEP) and regular alveolar recruitment maneuvers may improve post-operative outcomes. However, the benefits of an individualized level of PEEP have not been clearly established. In the present study, it was hypothesized that a moderate fixed PEEP may not suit all patients and an individually-titrated PEEP during anesthesia may improve the peri-operative pulmonary oxygenation function. The aim of the present study was to compare the pulmonary oxygenation function and post-operative pulmonary complications (PPCs) in patients receiving individualized lung-protective mechanical ventilation (LPV) vs. conventional ventilation (CV) during laparoscopic total hysterectomy. The present study was a randomized double-blinded clinical trial on 87 patients who were randomly divided to receive CV or protective ventilation (PV). An optimal individualized PEEP value was determined using a static pulmonary compliance-directed PEEP titration procedure. Pulmonary oxygenation function, serum inflammatory factors, including interleukin-8 and Clara cell protein 16, the incidence of PPCs and the post-operative length of stay were also determined. Patients in the PV group exhibited improved pulmonary oxygenation function during and after the operation. The total percentage of PPCs during the first 7 days after surgery was significantly lower in the PV group compared with those in the CV group. In conclusion, as compared to CV, intra-operative individualized LPV significantly improved pulmonary oxygenation function and reduced the incidence of PPCs during the first 7 days after laparoscopic total hysterectomy (Clinical trial registration no. ChiCTR1900027738).

Dexmedetomidine attenuates lipopolysaccharide induced acute lung injury in rats by inhibition of caveolin-1 downstream signaling.

OBJECTIVE: Toll-like receptor 4(TLR-4)/nuclear factor-kappa B(NF-κB) pathway plays an important role in inducing acute lung injury (ALI). Studies have proved Dexmedetomidine (Dex) inhibits inflammatory response to mitigate lipopolysaccharide (LPS)-induced ALI and protect against multiorgan injury in various scenarios via restraining TLR-4/NF-κB signaling pathway. Many of the known downstream molecules have been orientated with a protein caveolin-1(Cav-1), which is supposed to take part in regulating TLR4-mediated inflammatory responses. However, its mechanisms have not been confirmed. The aim of this study is to evaluate the protective effects and potential mechanisms of Dex against LPS-induced ALI in male rats. METHODS: Male rats received tail-vein injection of LPS to form ALI model. Rats were administrated with intraperitoneal injection Dex0.5 h before ALI. At 6 h after LPS injection, bronchoalveolar lavage fluid (BALF) and lung tissue were harvested. We stained the lung tissue sections with hematoxylin eosin (HE) staining to observe the histopathological damage and measure the ALI pathology score. We also measured the wet-to-dry(W/D) weight ratio of lung tissue. Lung myeloperoxidase (MPO) and inflammatory cytokines in the BALF were detected by Enzyme-linked immunosorbent assay(ELISA). Protein levels of Cav-1, TLR-4 and NF-κB in lung tissue were tested by immunohistochemistry method. The mRNA expression of Cav-1, TLR4 and the NF-κB in lung tissue were measured to determine the related mechanisms by quantitative real-time polymerase chain reaction(RT-PCR). RESULTS: It was indicated that Dex pretreatment markedly mitigated pathomorphologic changes and pathological lung injury scores. Besides, Dex pretreatment obviously decreased the W/D weight ratio of lung tissue, attenuated MPO activity significantly, along with LPS-stimulated augment of lung inflammatory cells infiltration in BALF. Moreover, compared with LPS model group, Dex pretreatment apparently increased the protein levels of Cav-1 downregulated by sepsis and decreased the protein levels of TLR-4 and NF-κB in lung tissue. Furthermore, Dex pretreatment apparently upregulated the expression of Cav-1 mRNA, restrained TLR4 and NF-κB mRNA. CONCLUSION: Dex pretreatment protects against LPS-induced ALI via inhibiting the activation of the TLR-4/NF-kB signaling pathway by upregulating the expression of Cav-1 downregulated by sepsis.