Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

Cigarette smoking is linked to an increased risk of delirium following arthroplasty in patients suffering from osteoarthritic pain.

AIMS: Postoperative delirium (POD) is a common postoperative complication, and the potential relationship between cigarette smoking and POD is still unclear. The current study evaluated the relationship between preoperative smoking status in patients suffering from osteoarthritic pain and POD after total knee arthroplasty (TKA). METHODS: A total of 254 patients who had undergone unilateral TKA were enrolled between November 2021 and December 2022, with no gender limitation. Preoperatively, patients' visual analog scale (VAS) scores at rest and during movement, hospital anxiety and depression (HAD) scores, pain catastrophizing scale (PCS) scores and smoking status were collected. The primary outcome was the incidence of POD, which was evaluated by the confusion assessment method (CAM). RESULTS: A total of 188 patients had complete datasets for final analysis. POD was diagnosed in 41 of 188 patients (21.8%) who had complete data for analysis. The incidence of smoking was significantly higher in Group POD than in Group Non-POD (22 of 41 patients [54%] vs. 47 of 147 patients [32%], p < 0.05). The postoperative hospital stays were also longer than those of Group Non-POD (p < 0.001). Multiple logistic regression analysis showed that preoperative smoking (OR: 4.018, 95% CI: 1.158-13.947, p = 0.028) was a risk factor for the occurrence of POD in patients with TKA. The length of hospital stay was correlated with the occurrence of POD. CONCLUSIONS: Our findings suggest that patients who smoked preoperatively were at increased risk of developing POD following TKA.

Corrigendum: Flurbiprofen used in one-lung ventilation improves intraoperative regional cerebral oxygen saturation and reduces the incidence of postoperative delirium.

[This corrects the article DOI: 10.3389/fpsyt.2022.889637.].

Microglia sustain anterior cingulate cortex neuronal hyperactivity in nicotine-induced pain.

BACKGROUND: Long-term smoking is a risk factor for chronic pain, and chronic nicotine exposure induces pain-like effects in rodents. The anterior cingulate cortex (ACC) has been demonstrated to be associated with pain and substance abuse. This study aims to investigate whether ACC microglia are altered in response to chronic nicotine exposure and their interaction with ACC neurons and subsequent nicotine-induced allodynia in mice. METHODS: We utilized a mouse model that was fed nicotine water for 28 days. Brain slices of the ACC were collected for morphological analysis to evaluate the impacts of chronic nicotine on microglia. In vivo calcium imaging and whole-cell patch clamp were used to record the excitability of ACC glutamatergic neurons. RESULTS: Compared to the vehicle control, the branch endpoints and the length of ACC microglial processes decreased in nicotine-treated mice, coinciding with the hyperactivity of glutamatergic neurons in the ACC. Inhibition of ACC glutamatergic neurons alleviated nicotine-induced allodynia and reduced microglial activation. On the other hand, reactive microglia sustain ACC neuronal excitability in response to chronic nicotine, and pharmacological inhibition of microglia by minocycline or liposome-clodronate reduces nicotine-induced allodynia. The neuron-microglia interaction in chronic nicotine-induced allodynia is mediated by increased expression of neuronal CX3CL1, which activates microglia by acting on CX3CR1 receptors on microglial cells. CONCLUSION: Together, these findings underlie a critical role of ACC microglia in the maintenance of ACC neuronal hyperactivity and resulting nociceptive hypersensitivity in chronic nicotine-treated mice.

Dexmedetomidine alleviates anxiety-like behavior in mice following peripheral nerve injury by reducing thehyperactivity of glutamatergic neurons in the anterior cingulate cortex.

BACKGROUND: Treatment of chronic pain is challenged by concurrent anxiety symptoms. Dexmedetomidine is known to produce sedation, analgesia, and anxiolysis. However, the neural mechanism of dexmedetomidine-elicited anxiolysis remains elusive. Here, we aimed to test the hypothesis that the anterior cingulate cortex might be involved in dexmedetomidine-induced anxiolysis in pain. METHODS: A common peroneal nerve ligation mouse model was used to test the dexmedetomidine-induced analgesia and anxiolysis by assessing mechanical allodynia, open-field, light-dark transition, and acoustic startle reflex tests. In vivo calcium signal fiber photometry and ex vivo whole-cell patch-clamp recordings were used to measure the excitability of glutamatergic neurons in anterior cingulate cortex. Modulation of glutamatergic neurons was performed by chemogenetic inhibition or activation via viral injection. RESULTS: Compared with vehicle, dexmedetomidine (4 µg/kg) alleviated mechanical allodynia (P < 0.001) and anxiety-like behaviors (P < 0.001). The glutamatergic neurons' excitability after dexmedetomidine administration was lower than that of the vehicle group (P = 0.001). Anxiety-like behaviors were rescued by inhibiting glutamatergic neurons in the model mice. Nociception-related anxiety-like behavior was induced by activation of glutamatergic neurons, which was rescued by dexmedetomidine. CONCLUSIONS: The reduction in glutamatergic neuronal activity in anterior cingulate cortex may be involved in dexmedetomidine-elicited anxiolysis in chronic pain.

Efficacy and safety of remimazolam besylate in bronchoscopy for adults: A multicenter, randomized, double-blind, positive-controlled clinical study.

Background: With the development of fiberoptic bronchoscopy in the diagnosis and treatment of various pulmonary diseases, the anesthesia/sedation requirements are becoming more demanding, posing great challenges for patient safety while ensuring a smooth examination/surgery process. Remimazolam, a brand-new ultra-short-acting anesthetic, may compensate for the shortcomings of current anesthetic/sedation strategies in bronchoscopy. Methods: This study was a prospective, multicenter, randomized, double-blind, parallel positive controlled phase 3 clinical trial. Subjects were randomized to receive 0.2 mg/kg remimazolam besylate or 2 mg/kg propofol during bronchoscopy to evaluate the efficacy and safety of remimazolam. Results: A total of 154 subjects were successfully sedated in both the remimazolam group and the propofol group, with a success rate of 99.4% (95%CI of the adjusted difference -6.7 × 10%-6% to -5.1 × 10%-6%). The sedative effect of remimazolam was noninferior to that of propofol based on the prespecified noninferiority margin of -5%. Compared with the propofol group, the time of loss of consciousness in the remimazolam group (median 61 vs. 48s, p < 0.001), the time from the end of study drug administration to complete awakening (median 17.60 vs. 12.80 min, p < 0.001), the time from the end of bronchoscopy to complete awakening (median 11.00 vs. 7.00 min, p < 0.001), the time from the end of study drug administration to removal of monitoring (median 19.50 vs. 14.50 min, p < 0.001), and the time from the end of bronchoscopy to removal of monitoring (median 12.70 vs. 8.60 min, p < 0.001) were slightly longer. The incidence of Adverse Events in the remimazolam group and the propofol group (74.8% vs. 77.4%, p = 0.59) was not statistically significant, and none of them had Serious Adverse Events. The incidence of hypotension (13.5% vs. 29.7%, p < 0.001), hypotension requiring treatment (1.9% vs. 7.7%, p = 0.017), and injection pain (0.6% vs. 16.8%, p < 0.001) were significantly lower in the remimazolam group than in the propofol group. Conclusion: Moderate sedation with 0.2 mg/kg remimazolam besylate is effective and safe during bronchoscopy. The incidence of hypotension and injection pain was less than with propofol, but the time to loss of consciousness and recovery were slightly longer. Clinical Trial Registration: clinicaltrials.gov, ChiCTR2000039753.

Flurbiprofen used in one-lung ventilation improves intraoperative regional cerebral oxygen saturation and reduces the incidence of postoperative delirium.

Background: We previously demonstrated that flurbiprofen increased arterial oxygen partial pressure and reduced intrapulmonary shunts. The present study aims to investigate whether flurbiprofen improves intraoperative regional cerebral oxygen saturation (rScO2) and reduces the incidence of postoperative delirium (POD) in elderly patients undergoing one-lung ventilation (OLV). Methods: One hundred and twenty patients undergoing thoracoscopic lobectomy were randomly assigned to the flurbiprofen-treated group (n = 60) and the control-treated group (n = 60). Flurbiprofen was intravenously administered 20 minutes before skin incision. The rScO2 and partial pressure of arterial oxygen (PaO2) were recorded during the surgery, and POD was measured by the Confusion Assessment Method (CAM) within 5 days after surgery. The study was registered in the Chinese Clinical Trial Registry with the number ChiCTR1800020032. Results: Compared with the control group, treatment with flurbiprofen significantly improved the mean value of intraoperative rScO2 as well as the PaO2 value (P < 0.05, both) and significantly reduced the baseline values of the rScO2 area under threshold (AUT) (P < 0.01) at 15, 30, and 60 min after OLV in the flurbiprofen-treated group. After surgery, the POD incidence in the flurbiprofen-treated group was significantly decreased compared with that in the control group (P < 0.05). Conclusion: Treatment with flurbiprofen may improve rScO2 and reduce the incidence of POD in elderly patients undergoing thoracoscopic one-lung ventilation surgery for lung cancer. Clinical trial registration: http://www.chictr.org/cn/, identifier ChiCTR1800020032.

Effect of Perineural Dexamethasone with Ropivacaine in Continuous Serratus Anterior Plane Block for Postoperative Analgesia in Patients Undergoing Video-Assisted Thoracoscopic Surgery.

Purpose: The goal of this study was to evaluate the analgesic efficiency of dexamethasone with ropivacaine in continuous serratus anterior plane block (cSAPB) after video-assisted thoracoscopic surgery (VATS). Patients and Methods: Sixty-six patients who underwent VATS were randomized into two groups. All patients received cSAPB postoperatively, and patients in Group RD received 20 mL of 0.375% ropivacaine plus 0.1 mg/kg dexamethasone followed by an infusion of 0.2% ropivacaine plus 0.02 mg/kg/hour dexamethasone at a rate of 5 mL/h in patient-controlled analgesia (PCA) pump. Patients in Group R received 20 mL of 0.375% ropivacaine with normal saline followed by an infusion of 5 mL/h of 0.2% ropivacaine in PCA pump. Fifty milligrams of tramadol was given as rescue medication when the visual analog scale (VAS) score was ≥4 at rest. The primary outcomes were the sum of pressing number within 48 hours postoperatively and the time to the first patient-controlled bolus. The secondary outcomes were VAS scores, the incidence of rescue analgesia, wound infection and nausea/vomiting. Results: Within 48 hours postoperatively, the sum of pressing number was more in Group R (18.33 ± 3.149 vs 16.09 ± 3.292, P = 0.006), and the Log Rank Test showed a significant difference in time to the first patient-controlled bolus (P = 0.006). After the PCA infusion finished, there were significantly lower VAS scores in Group RD at 60 and 72 hours postoperatively (P < 0.001). Additionally, the incidence of rescue analgesia in Group R was significantly more than that in Group RD (P < 0.001). No incision infection was observed in any patient. Conclusion: The cSAPB with ropivacaine plus dexamethasone prolonged the duration of analgesia and motor blockade, reduced pain intensity and rescued analgesia requirements after the end of PCA infusion for patients undergoing VATS, which provide further improvement to continuous perineural block.

Angiotensin II type 2 receptor pharmacological agonist, C21, reduces the inflammation and pain hypersensitivity in mice with joint inflammatory pain.

Primary and secondary hyperalgesia develop in response to chronic joint inflammation due to peripheral and central mechanisms. Synovial macrophage and spinal microglia are involved in pain sensitization in arthritis. The level of angiotensin II type 2 receptor (AT2R) is related to the severity of arthritis. This study aimed to determine the role of AT2R in primary and secondary hyperalgesia in joint inflammatory pain in mice. After intra-articular CFA injection, primary hyperalgesia in the ipsilateral knee joint was measured by pressure application meter and gait analysis, secondary hypersensitivity in ipsilateral hind-paw was measured by von-Frey and Hargreaves tests following a combination of global AT2R-deficient (Agtr2-/-) mice and AT2R pharmacological agonist C21. Synovial macrophage and spinal microglia were collected for flow cytometry. Morphological reconstruction of microglia was detected by immunostaining. AT2R expression was investigated by quantitative polymerase chain reaction and western blot. Neuronal hyperactivity was evaluated by c-Fos and CGRP immunostaining. We found that pain hypersensitivity and synovial inflammation in Agtr2-/- mice were significantly exacerbated compared with wild-type mice; conversely, systemically administrated C21 attenuated both of the symptoms. Additionally, spinal microglia were activated, and an abundant increase of spinal AT2R was expressed on activated microglia in response to peripheral joint inflammation. Intrathecally-administrated C21 reversed the secondary hypersensitivity, accompanied by alleviation of spinal microglial activation, spinal neuronal hyperactivity, and calcitonin gene-related peptide content. These findings revealed a beneficial role of AT2R activating stimulation against pain hypersensitivity in joint inflammatory pain via direct modulation of synovial macrophage and spinal microglial activity.

What is the impact of perioperative cerebral oxygen desaturation on postoperative delirium in old population: a systemic review and meta-analysis.

BACKGROUND: Perioperative cerebral oxygen saturation (ScO2) has been reported to associate with postoperative delirium (POD) which is a common postoperative complication, however, the results were inconclusive. Therefore, we aimed to conduct an up-to-date review and meta-analyze the relationship between perioperative ScO2 and POD. METHODS: We systematically searched PubMed, Embase and Web of science through January 13, 2022. The pooled results were estimated through a random-effects model meta-analysis and expressed as odds ratios (ORs) and standard mean differences (SMDs), accompanied with 95% confident intervals (CIs). RESULTS: Finally, of 467 searched articles, ten articles were included. A total of six studies reported the baseline ScO2 value and the pooled result showed that preoperative baseline ScO2 was lower in POD groups (SMD = - 0.41, 95% CI - 0.64 to - 0.18). And beyond that, the pooled OR across four literatures about preoperative low ScO2 on POD was 3.44 (95% CI 1.69, 7.02). In contrast, insignificant differences were detected in baseline/lowest ScO2 value during intraoperative and postoperative period. Additionally, there were no statistically significant associations for intraoperative and postoperative low ScO2 effect on POD risk. Meta-regress analysis has found no significant impact factors. CONCLUSIONS: Based on current evidence, POD patients have a lower ScO2, and ScO2 desaturation may increase POD incidence, indicating the role of ScO2 underlying pathological mechanisms. For generalizability of evidence, we should rely on high-quality, considering more comprehensively longitudinal, interdisciplinary studies.

Continuous Serratus Anterior Plane Block Improved Early Pulmonary Function After Lung Cancer Surgical Procedure.

BACKGROUND: Serratus anterior plane block (SAPB) has been proven to be an efficient way to control postoperative pain. This study explored whether the use of continuous SAPB in combination with flurbiprofen could improve early pulmonary function in lung cancer patients undergoing video-assisted thoracoscopic surgery (VATS). METHODS: From July 2019 to April 2020, patients who scheduled for elective lung resection undergoing VATS were randomly allocated to receive patient-controlled SAPB in combination with intravenous flurbiprofen or patient-controlled intravenous analgesia. Postoperative pulmonary function variables, including forced expiratory volume in 1 second, and forced vital capacity were collected before and 24, 48, and 72 hours after Surgical Procedure. Pain intensity was measured at rest and on coughing. Comfort scores during breathing exercises, postoperative pulmonary complications, and adverse events were recorded. RESULTS: A substantial reduction in lung function was exhibited in both groups after Surgical Procedure (P < .001), but lung function variables in the continuous SAPB group were significantly higher (P < .001) throughout the postoperative period up to 72 hours, regardless of the surgical procedure type. Meanwhile, there were significant differences of pain intensity at rest and on coughing between the groups (P < .001). The incidence of pneumonia, pulmonary atelectasis, hypoxemia, vomiting, and the comfort score in the continuous SAPB group was significantly lower (P < .05). CONCLUSIONS: Postoperative acute pain treatment with continuous SAPB in combination with flurbiprofen enhanced pulmonary function and reduced postoperative pulmonary complications in lung cancer patients undergoing VATS.

The Role of Serratus Anterior Plane Block During in Video-Assisted Thoracoscopic Surgery.

Although thoracoscopy has characteristics such as a small surgical incision and low stress response, post-surgical pain after a thoracoscopic operation is no less than that after a thoracotomy. Moreover, poor post-surgical pain management is likely to cause an increased incidence of postoperative pulmonary complications (PPCs) and chronic post-surgical pain. The serratus anterior plane block (SAPB) is a regional anesthesia method whereby local anesthetics (LAs) are injected into the serratus anterior space to block the lateral cutaneous branch of the intercostal nerve, long thoracic nerve, and dorsal thoracic nerve. The block range of the SAPB covers the incisions of video-assisted thoracoscopic surgery (VATS) and the site of the chest tube, which are often located in the antero-lateral chest wall. Therefore, the SAPB can achieve effective analgesia in VATS. For example, 0.125% to 0.25% levobupivacaine (20-25 ml) is widely used for thoracic surgery, which can achieve effective analgesia and avoid adverse reactions. Moreover, it has advantages compared with thoracic segmental epidural block (TEA) and thoracic paravertebral block (TPVB), such as simple operation, increased safety, fewer complications, and hemodynamic stability. In addition, adequate analgesia is helpful for pulmonary function recovery and reduces the incidence of PPCs. This article introduces the anatomical mechanism of the SAPB, diverse operation approaches, how to choose drugs and adjuvants, and the resulting impacted area range. It summarizes the advantages and disadvantages of the SAPB compared with other analgesic methods and posits that the SAPB is beneficial to the recovery of postoperative lung function, which provides more options for postoperative analgesia after VATS.

Operation, Effectiveness, and Limitations of Continuous Serratus Anterior Plane Blocks for Thoracoscopic Surgery in Adults.

PURPOSE: This randomized, double-blind study evaluated the effectiveness and limitations of continuous serratus anterior plane block (cSAPB) by comparing the effect of cSAPB to patient-controlled intravenous analgesia (PCIA) on postoperative acute pain after thoracoscopic surgery in adults. PATIENTS AND METHODS: Sixty-six patients who underwent elective video-assisted thoracoscopic surgery (VATS) were randomly allocated to cSAPB or PCIA groups (n=33 per group) after surgery. For the cSAPB group, patients were treated by an initial does of 20 mL ropivacaine (0.375%), followed by continuous infusion at a rate of 5 mL/h of ropivacaine (0.2%) and a patient-controlled bolus of 5 mL ropivacaine (0.2%). PCIA started with an initial does of 0.03 µg/kg sufentanil, followed by a basal infusion of 0.03 µg/kg/h sufentanil and a patient-controlled bolus of 0.03 µg/kg sufentanil. Visual analog scale (VAS) and other items were examined postoperatively. The area under the curve of VAS-time (AUCVAS-time) at rest and on coughing in the first 24 hours postoperatively were primary outcomes. RESULTS: At the first 24 hours postoperatively, patients in the cSAPB group exhibited a smaller AUCVAS-time at rest (44.0±17.1 vs 68.9±11.8 cm·h, P<0.001) and AUCVAS-time on coughing (67.1±8.8 vs 78.0±12.5 cm·h, P<0.001) compared with those in the PCIA group. The differences in means of VAS score at rest were more than 1.0 cm between the two groups, however, on coughing they were less than 1.0 cm at each observation point. Additionally, patients in the cSAPB group had a longer time to first patient-controlled bolus (15.8±7.6 vs 10.6±8.6 hours, P=0.011). Furthermore, a higher rank of satisfaction was recorded with patients in the cSAPB group. CONCLUSION: cSAPB using PCA devices might be superior to traditional intravenous continuous analgesia, particularly with an advantage of pain relief at rest following VATS operation. Meanwhile, cSAPB lacks a satisfactory analgesic effect on cough.

Role of activin receptor-like kinase 1 in vascular development and cerebrovascular diseases.

Activin receptor-like kinase 1 (ALK1) is a transmembrane serine/threonine receptor kinase of the transforming growth factor beta (TGFß) receptor superfamily. ALK1 is specifically expressed in vascular endothelial cells, and its dynamic changes are closely related to the proliferation of endothelial cells, the recruitment of pericytes to blood vessels, and functional differentiation during embryonic vascular development. The pathophysiology of many cerebrovascular diseases is today understood as a disorder of endothelial cell function and an imbalance in the proportion of vascular cells. Indeed, mutations in ALK1 and its co-receptor endoglin are major genetic risk factors for vascular arteriovenous malformation. Many studies have shown that ALK1 is closely related to the development of cerebral aneurysms, arteriovenous malformations, and cerebral atherosclerosis. In this review, we describe the various roles of ALK1 in the regulation of angiogenesis and in the maintenance of cerebral vascular homeostasis, and we discuss its relationship to functional dysregulation in cerebrovascular diseases. This review should provide new perspectives for basic research on cerebrovascular diseases and offer more effective targets and strategies for clinical diagnosis, treatment, and prevention.

Intraoperative Flurbiprofen Treatment Alters Immune Checkpoint Expression in Patients Undergoing Elective Thoracoscopic Resection of Lung Cancer.

OBJECTIVES: This study aimed to determine the effect of intraoperative administration of flurbiprofen on postoperative levels of programmed death 1 (PD-1) in patients undergoing thoracoscopic surgery. MATERIALS AND METHODS: In this prospective double-blind trial, patients were randomized to receive intralipid (control group, n = 34, 0.1 mL/kg, i.v.) or flurbiprofen axetil (flurbiprofen group, n = 34, 50 mg, i.v.) before induction of anesthesia. PD-1 levels on T cell subsets, inflammation, and immune markers in peripheral blood were examined before the induction of anesthesia (T0) and 24 h (T1), 72 h (T2), and 1 week (T3) after surgery. A linear mixed model was used to determine whether the changes from baseline values (T0) between groups were significantly different. RESULTS: The increases in the percentage of PD-1(+)CD8(+) T cells observed at T1 and T2 in the control group were higher than those in the flurbiprofen group (T1: 12.91 ± 1.65 vs. 7.86 ± 5.71%, p = 0.031; T2: 11.54 ± 1.54 vs. 8.75 ± 1.73%, p = 0.004), whereas no differences were observed in the changes in the percentage of PD-1(+)CD4(+) T cells at T1 and T2 between the groups. Moreover, extensive changes in the percentage of lymphocyte subsets and inflammatory marker concentrations were observed at T1 and T2 after surgery and flurbiprofen attenuated most of these changes. CONCLUSIONS: Perioperative administration of flurbiprofen attenuated the postoperative increase in PD-1 levels on CD8(+) T cells up to 72 h after surgery, but not after this duration. The clinical relevance of changes in PD-1 levels to long-term surgical outcome remains unknown.

Renin-angiotensin-system, a potential pharmacological candidate, in acute respiratory distress syndrome during mechanical ventilation.

While effective treatments for acute respiratory distress syndrome (ARDS) are lacking, mechanical lung ventilation can sustain adequate gas exchange in critically ill patients with respiratory failure due to ARDS. However, as a result of the phenomenon of ventilator-induced lung injury (VILI), there is an increasing need to seek beneficial pharmacological therapies for ARDS. Recent studies have suggested the renin-angiotensin system (RAS), which consists of the ACE/Ang-II/AT1R axis and ACE2/Ang-(1-7)/MasR axis, plays a dual role in the pathogenesis of ARDS and VILI. This review highlights the deleterious action of ACE/Ang-II/AT1R axis and the beneficial role of ACE2/Ang-(1-7)/MasR axis, as well as AT2R, in VILI and ARDS, and also discusses the possibility of targeting RAS components with pharmacological interventions to improve outcomes in ARDS.

Effect of Transversus Abdominis Plane Block on Postoperative Pain after Colorectal Surgery: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To assess the analgesic efficacy of transversus abdominis plane (TAP) block in patients undergoing colorectal surgery (CRS). MATERIALS AND METHODS: The databases of PubMed, ISI Web of Science, and Embase were searched, and randomized controlled studies (RCTs) that compared TAP block to control for relief of postoperative pain in patients who underwent CRS were included. Outcomes, including postoperative pain at rest and with movement, morphine use, postoperative nausea and vomiting, and the length of hospital stay, were analyzed using STATA software. The weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) or relative risk with 95% CI were used to present the strength of associations. RESULTS: A total of 7 RCTs with 511 patients were included. The results of this study suggested that TAP block significantly relieved postoperative pain during postanesthetic recovery after CRS at rest and during movement (WMDs were -0.98 [95% CI -1.57 to -0.38] and -0.68 [-1.07 to -0.30], respectively), and also decreased pain intensity during movement 24 h after CRS (WMD: -0.57 [95% CI -1.06 to -0.08]). TAP block significantly reduced opioid consumption within 24 h when compared to controls, with a WMD of 15.66 (95% CI -23.93 to -7.39). However, TAP block did not shorten the length of hospital stay. CONCLUSIONS: TAP block was an effective approach for relief of postoperative pain and reduced postoperative consumption of morphine. More RCTs with large sample sizes are required to confirm these findings.

Astragaloside IV prevents kidney injury caused by iatrogenic hyperinsulinemia in a streptozotocin­induced diabetic rat model.

Diabetic patients are able to manage their blood glucose with exogenous insulin but, ultimately, remain at risk of diabetic nephropathy (DN). Long­term use of insulin may lead to iatrogenic hyperinsulinemia, which has been suggested to cause kidney injury. However, there are no effective interventions for iatrogenic hyperinsulinemia leading to kidney damage. In the present paper, the hypothesis that astragaloside IV (AS­IV), a novel saponin purified from Astragalus membranaceus (Fisch) Bunge, may prevent DN in iatrogenic hyperinsulinemic diabetic rats through antioxidative and anti­inflammatory mechanisms was investigated. Diabetes was induced with streptozotocin (STZ) (55 mg/kg) by intraperitoneal injection in rats. At 1 week following STZ injection, the diabetic rats were treated with Levemir subcutaneously for 4 weeks. Diabetic rat insulin levels >30 µU/ml were considered as iatrogenic hyperinsulinemia. Rats were divided into six groups (n=8 per group): Iatrogenic hyperinsulinemic rats, and iatrogenic hyperinsulinemic rats treated with Tempol and AS­IV at 2.5, 5 and 10 mg/kg/day, intragastric infusion, for 12 weeks. The normal rats were used as a non­diabetic control group. AS­IV ameliorated albuminuria, mesangial cell proliferation, basement membrane thickening and podocyte foot process effacement in iatrogenic hyperinsulinemic rats. In iatrogenic hyperinsulinemic rat renal tissues, malondialdehyde, interleukin­1ß (IL­1ß), tumor necrosis factor­α (TNF­α), type IV collagen and laminin levels were increased, whereas glutathione peroxidase and superoxide dismutase activity levels were decreased. Nicotinamide adenine dinucleotide phosphate oxidase 4 expression and extracellular signal­regulated kinase 1/2 (ERK1/2) activation were upregulated, and canonical transient receptor potential cation channel 6 (TRPC6) protein expression was downregulated. However, all these abnormalities were attenuated by AS­IV. These findings suggested that AS­IV prevented rat kidney injury caused by iatrogenic hyperinsulinemia by inhibiting oxidative stress, IL­1ß and TNF­α overproduction, downregulating ERK1/2 activation, and upregulating TRPC6 expression.

Goal-directed fluid restriction using stroke volume variation and cardiac index during one-lung ventilation: a randomized controlled trial.

BACKGROUND: Goal-directed therapy confers a strong prognosis in patients undergoing major cardiac or noncardiac surgery. The present study investigated whether intraoperative goal-directed fluid restriction (GDFR) using stroke volume variation (SVV) and cardiac index could improve oxygenation and postoperative outcome in patients undergoing one-lung ventilation (OLV). METHODS: A Total of 168 patients scheduled for elective thoracoscopic lobectomy under OLV were randomized into the GDFR protocol (group G) or conventional fluid therapy groups (group C). Patients in group C underwent conventional fluid therapy based on mean arterial pressure (MAP), central venous pressure (CVP), and urine volume, whereas those in group G received GDFR protocol associated with the SVV from 10-13% and the cardiac index was controlled at a minimum of 2.5 L/min/m2. The primary outcome variable was PaO2/FiO2. The secondary outcomes were other pulmonary variables and lung mechanics, inflammatory response, the incidence of postoperative pulmonary complications, and the length of hospital stay. RESULTS: During surgery, the PaO2/FiO2 ratio in group G was more than that of group C at 30 and 60 min after OLV, 10 min after re-expansion, and the end of the operation (259±29 vs. 314±34; 253±30 vs. 308±35; 341±34 vs. 394±39; 349±35 vs. 401±39, respectively, all P<0.001). Compared to conventional fluid therapy, GDFR protocol also significantly improved the hemodynamic and lung mechanics with the initiation of OLV. The incidence of postoperative pulmonary complications such as acute lung injury and pneumonia, and the length of hospital stay were decreased by GDFR protocol as compared to conventional fluid therapy (all P<0.05). However, there were no significant differences between groups with respect to the concentration of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10). CONCLUSIONS: The GDFR protocol based on SVV and cardiac index applied in patients undergoing OLV improves intraoperative pulmonary oxygenation. It can also reduce the postoperative complications and length of hospital stay. However, the GDFR strategy cannot reduce the local or systemic inflammation. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR-INR-16008288, Registered 20 April, 2016.