Comparison of S-ketamine and midazolam for intravenous preoperative sedative and anxiolytic effects in preschool children: study protocol for a randomized controlled clinical trial.

BACKGROUND: Preoperative anxiety management is gaining particular attention in paediatric anaesthesia. Pharmacological and non-pharmacological resorts can be implemented to address this special issue. Despite the various approaches currently used for preoperative sedation in children, the different sedative and anti-anxiety effects between the newly marketed anaesthetic, S-ketamine, and the traditional sedative, midazolam, are still unclear. METHODS: This is a patient- and assessor-blinded randomized controlled clinical trial. Participants (n = 110) will receive S-ketamine (0.5 mg/kg) or midazolam (0.08 mg/kg) intravenously administrated at a ratio of 1:1 in the anaesthesia holding area. The primary outcome of this study is the sedative effect evaluated via the change in the modified Yale preoperative anxiety scale. It will be performed at two timepoints: in the pre-anaesthetic holding area before premedication (baseline, marked as T0) and about 5 min after premedication in the operating room without the existence of their guardians (marked as T1). Our secondary objectives include the parent separation anxiety score, postoperative agitation, caregivers' and anaesthesia care providers' satisfaction, and mask compliance. DISCUSSION: This randomized controlled trial is the first study to compare the anti-anxiety effect of intravenous S-ketamine and midazolam. We will provide a new approach for the clinical management of preoperative anxiety in preschool children posted for elective surgery. TRIAL REGISTRATION: ChiCTR2300069998. Registered on 30 March 2023.

Incidence and Risk Factors of Postoperative Severe Discomfort After Elective Surgery Under General Anesthesia: A Prospective Observational Study.

PURPOSE: Patient comfort is an important concern in patients receiving surgery, but the seriousness of discomfort during recovery is unknown. We investigated the incidence of postoperative discomfort based on the Standardized Endpoints in Perioperative Medicine initiative for patient comfort, and identified the risk factors. DESIGN: This was a single-center prospective observational study. METHODS: We enrolled adult patients who underwent elective surgery under general anesthesia between July and December 2018 at West China Hospital of Sichuan University (ChiCTR1800017324). The primary outcome was the incidence of postoperative severe discomfort (PoSD), defined as occurring when a patient experienced a severe rating in two or more domains in the six domains in the Standardized Endpoints in Perioperative Medicine initiative on the same day, including rest pain, postoperative nausea, and vomiting, dissatisfaction of gastrointestinal recovery, dissatisfaction of mobilization, sleep disturbance, and recovery. A generalized estimated equation was constructed to find risk factors of PoSD. FINDINGS: In total, 440 patients completed the study. The incidence of PoSD was 28% on postoperative day (POD) 1, 13% on POD 2, 9% on POD 3, and 3.6% on both POD 5 and 7. The most common discomfort was serious sleep disturbance, ranging from 43% to 10% in the first week after surgery. Longer operative time (odds ratio [95% confidence interval]: 1.56 [1.19 to 2.05], P = .001), gastrointestinal surgery (5.03[2.08,12.17], P < .001), orthopaedic surgery (3.03 [1.35,6.79], P = .007), ear, nose, and throat (ENT) surgery (3.50 [1.22,10.02], P = .020) and postoperative complications (1.77 [1.03-3.04], P = .038) were significant risk factors of PoSD. CONCLUSIONS: The incidence of PoSD after elective surgery under general anesthesia is high. Sleep disturbance was the most common problem identified. Anesthesia providers and perianesthesia nurses may need to optimize anesthetic application, combine different anesthesia methods, improve perioperative management, and provide interventions to reduce and to treat discomfort after surgeries.

Dexmedetomidine and Netrin-1 Combination Therapy Inhibits Endoplasmic Reticulum Stress by Regulating the ERK5/MEF2A Pathway to Attenuate Cerebral Ischemia Injury.

The complexity of hard-to-treat diseases such as ischemic stroke strongly undermines the therapeutic potential of available treatment options. Therefore, current developments have gently shifted from a focus on monotherapy to combined or multiple therapies. Both dexmedetomidine and Netrin-1 have anti-neuronal apoptosis effects, but the mechanism is still unclear. The study aimed to estimate the efficacy of dexmedetomidine and Netrin-1 combination therapy against ERS-induced apoptosis after cerebral ischemia injury in vivo and in vitro, and whether the mechanism is related to the ERK5/MEF2A pathway. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) in vivo, 90 min ischemia and 24 h reperfusion. The hippocampus slices used to establish oxygen-glucose deprivation (OGD) injury model in vitro. Neterin-1 and Dexmedetomidine were pretreated and post-treated, respectively, before and after the model establishment. MEF2A knockdown was performed by microinjection of AAV9-MEF2A RNAi vector. Orthodromic population spike (OPS) at the end of reoxygenation were recorded. Neurobehavioral tests, TTC staining, Nissl staining, TUNEL staining were performed to assess the effect of the drugs. The expression of CHOP, GRP78, MEF2A, ERK5, and p-ERK5 were investigated by Western blot and immunofluorescence staining. Neurological deficit score, infarct volume, the expression of GRP78, CHOP, and neural apoptotic rate of MCAO group increased markedly. Combination of dexmedetomidine and Netrin-1 resulted in lower infarct volumes and fewer neurological impairments, higher OPS recovery rate, and less damaged and apoptotic cells after cerebral ischemia injury. Furthermore, expression levels of GRP78 and CHOP decreased in the combination therapy group, and it was more effective than the single drug group. Meanwhile, Combination of dexmedetomidine and Netrin-1 increased MEF2A expression and promoted ERK5 phosphorylation. However, the protective effect of dexmedetomidine combined with Netrin-1 in improving neurological function was significantly eliminated by pre-knockdown MEF2A. The neuroprotective effects of dexmedetomidine combined with Netrin on cerebral ischemia-reperfusion injury and hippocampal hypoxia injury in terms of ERS. The synergistic effect of combination therapy is related to the activation of ERK5/MEF2A signaling pathway.

Pharmacokinetic and pharmacodynamic properties of ciprofol emulsion in Chinese subjects: a single center, open-label, single-arm dose-escalation phase 1 study.

We conducted a single-center, single-arm, open-label, dose-escalation phase 1 clinical trial to evaluate the tolerability of a single intravenous injection of ciprofol emulsion for the induction of short-term general anesthesia. Four doses of ciprofol (0.15 mg/kg, n = 2; 0.4 mg/kg, n = 10; 0.6 mg/kg, n = 6; 0.9 mg/kg, n = 6) were administered. Twenty-four subjects were enrolled, with 18 subjects in the 0.4 to 0.9 mg/kg dosage groups included in the data analysis. In total, 37 mild and 4 moderate adverse events (AEs), including 9 abnormal limb movements (3 moderate cases), 8 cases of sinus bradycardia, 11 cases of prolonged QTcF interval (including 1 moderate case), and 1 case of hypotension, were found, but no serious AEs were reported. The Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores rapidly decreased after ciprofol administration. The duration of recovery of the verbal response, loss of verbal response duration, the duration of MOAA/S ≤1 and the duration until the return of responsiveness were all increased in a dose-dependent manner. The durations of bispectral index values <60 (6, 8 and 12 min) were similar to the durations of loss of verbal response (6, 8 and 14 min) and MOAA/S ≤1 (5, 5.5 and 13.5 min) in the 0.4, 0.6 and 0.9 mg/kg dose groups, respectively. The plasma concentration reached a peak value approximately 2 min after injection in the 0.4-0.9 mg/kg groups and all subjects fully recovered after ciprofol administration, with the shortest time being 9.2 min in the 0.4 mg/kg group. A ciprofol dosing regimen of 0.4-0.9 mg/kg was well-tolerated and exhibited rapid onset and recovery properties.

Impacts of Preoperative Smoking and Smoking Cessation Time on Preoperative Peripheral Blood Inflammatory Indexes and Postoperative Hospitalization Outcome in Male Patients with Lung Cancer and Surgery Treatment.

Objective s To investigate the effects of preoperative smoking and smoking cessation time on preoperative peripheral blood inflammatory indexes and postoperative hospitalization outcomes in male patients with lung cancer and surgery therapy.Methods We retrospectively enrolled 637 male patients who underwent curative-intent lung cancer resection between January 2014 and December 2016. Patients were classified as the current smokers, the never smokers, and the ex-smokers based on their smoking history, and the ex-smokers were allocated into five subgroups according to their smoking cessation times (CeT): CeT≤6 weeks, 6weeks10years. The preoperative peripheral blood white blood cells (WBCs), albumin, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), intraoperative blood loss, 30-day mortality, in-hospital days, hospitalization costs, intensive care unit (ICU), admission days and placement time of closed thoracic drainage tube were compared among different groups.Results There were significant differences in WBC (F=5.275, P<0.001) and albumin (F=2.470, P<0.05) among patients of current smokers, ex-smokers with different smoking cessation time, and never-smokers. The blood WBC count in current smokers (7.7×10 9/L) was significantly higher than that in ex-smokers (7.0×10 9/L)and never-smokers (5.9×10 9/L) (t=-2.145, P<0.05; t=-6.073, P<0.01, respectively). The level of peripheral blood albumin in current smokers (41.1 g/L) was lower than that in ex-smokers (42.1 g/L) and never-smokers (43.2 g/L) (t=2.323, P<0.05; t=3.995, P<0.01, respectively). The level of peripheral blood NLR in current smokers (3.7) was higher than that in ex-smokers (3.1) and never smokers (2.8) (t=-1.836, P<0.05; t=-2.889, P<0.01, respectively). There was no significant difference in WBC, albumin and NLR among five subgroups of different smoking cessation time. No significant difference was observed in intraoperative blood loss, 30-day mortality, hospitalization costs, hospital stay, ICU stay and placement time of closed thoracic drainage tube among groups either. Conclusion Smoking increases the preoperative inflammatory indexes in peripheral blood of lung cancer patients. Smoking cessation has beneficial effect on reducing levels of these inflammatory indexes, which may be not impacted by the time length of smoking cessation. Therefore, lung cancer patients should be encouraged to quit smoking at any time.

Clinical Efficacy of Ultrasound-Mediated Transdermal Lidocaine and Capsaicin Delivery for the Treatment of Allodynia Caused by Herpes Zoster.

OBJECTIVE: To investigate the efficacy of ultrasound-mediated drug delivery for allodynia caused by herpes zoster. DESIGN: Unblinded randomized controlled study with two treatment groups and an additional control group. SUBJECTS: Patients hospitalized with allodynia caused by herpes zoster were enrolled. METHODS: Patients were randomly assigned to three groups: ultrasound-mediated transdermal drug delivery (group U), lidocaine intradermal injection (group I), or control group (group C). The primary outcome was pain intensity associated with allodynia, assessed with the visual analog scale (VAS) while brushing the skin with clothing after treatment stimulated allodynia. The secondary outcomes included an emotional functioning score (ES), average gabapentin consumption, and incidence of adverse events of each group. RESULTS: Sixty patients were enrolled in the study, but two of them failed to complete the treatment process. Therefore, 58 patients were included in the final analysis. All groups had lower VAS and ES scores after treatment compared with baseline. The VAS scores in groups U and I decreased significantly more than in group C (P < 0.05). Mean VAS scores in group U on days 1, 2, and 3 were lower than in group C (P < 0.01). ES was significantly lower in group U compared with groups I and C after treatment (P < 0.001). Average gabapentin consumption and incidence of adverse events in group C were higher than in the other two groups. CONCLUSIONS: In this study of treatment of allodynia caused by herpetic zoster, ultrasound-mediated lidocaine and capsaicin delivery provided better pain relief and improved emotional functioning compared with intradermal blockade with local anesthetics.

The Critical Role of Cannabinoid Receptor 2 in URB602-Induced Protective Effects Against Renal Ischemia-Reperfusion Injury in the Rat.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and even induces remote organ damage. Accumulating proofs demonstrates that the endocannabinoid system may provide a promising access for treatment strategy of renal IRI associated AKI. In the current study, using the established renal IRI model of rat, we tested the hypothesis that pretreatment of URB602, 30 min before renal IRI, alleviates kidney injury and relevant distant organ damage via limiting oxidative stress and inflammation. Using Western blot analysis and LC-MS/MS, renal IRI showed to increase the levels of 2-arachidonoylglycerol (2-AG) in kidneys as well as COX-2, PGE2, TXA2, and decrease N-arachidonoylethanolamine (anandamide, AEA); the expressions of renal cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) were unchanged. The URB602 pretreatment in renal IRI, further enhanced renal 2-AG which is high affinity to both CB1 and CB2, and reduced renal COX-2 which is involved in the regulation of renal perfusion and inflammation. AM630 (CB2 antagonist) almost blocked all the antioxidant, anti-inflammatory and nephroprotective effects of URB602, whereas AM251 (CB1 antagonist) showed limited influence, and parecoxib (COX-2 inhibitor) slightly ameliorated renal function at the dose of 10 mg/kg. Taken together, our data indicate that URB602 acts as a reactive oxygen species scavenger and anti-inflammatory media in renal IRI mainly depending on the activation of CB2.

Astrocyte morphology: Diversity, plasticity, and role in neurological diseases.

Astrocytes are the most abundant glial cells in the central nervous system (CNS) and participate in synaptic, circuit, and behavioral functions. The well-developed protoplasmic astrocytes contain numerous processes forming well-delineated bushy territories that overlap by as little as 5% at their boundaries. This highly complex morphology, with up to approximately 80% of the cell's membrane constituted by fine processes with dimensions on the tens of nanometer scale and high surface area to volume ratios, comes in contact with synapses, blood vessels, and other glial cells. Recent progress is challenging the conventional view that astrocytes are morphologically homogeneous throughout the brain; instead, they display circuit- and region-specific morphological diversity that may contribute to the heterogeneous astrocyte-neuron spatiotemporal interplay in different brain areas. Further, the fine structure of astrocytes is found to be highly plastic and activity-dependent. We are beginning to understand how astrocyte structural plasticity contributes to brain functions. The change/loss of astrocyte morphology, traditionally known as a hallmark for reactive astrogliosis, is a common pathological feature in many neurological disorders. However, recent data suggest the fine structural deficits preceding reactive astrogliosis may drive disease progression. This review summarizes recent advances in astrocyte morphological diversity, plasticity, and disease-related deficits.

The Effects of Safflower Yellow on Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Randomized, Controlled Clinical Trial.

OBJECTIVES: To evaluate the efficacy of safflower yellow in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: In a prospective, randomized, controlled trial, 127 patients who met the inclusion criteria were enrolled and were randomly divided into two groups. The control group included 64 patients treated according to the global strategy for diagnosis, management, and prevention of COPD (www.goldcopd.org, updated 2011). The intervention group included 63 patients who received intravenous infusions of safflower yellow (100 mg of safflower yellow dissolved in 250 ml 0.9% saline) once daily for 14 consecutive days in addition to standard diagnosis and treatment. The difference in the average length of the hospital stay between the two groups of patients was determined. The follow-up period was 28 days; the differences in symptoms, clinical indicators, and 28-day mortality in the two groups were compared. Statistical analysis was conducted using SPSS 22.0 software to determine whether there were statistically significant differences (P <0.05) between groups. RESULTS: There were no statistically significant differences between the intervention group and the control group in changes in secondary indicators. There were no statistically significant differences in the 28-day mortality or in the survival curves of the two groups (P=0.496 and P=0.075, respectively). Safflower yellow treatment of AECOPD may relieve the patient's clinical symptoms, such as dyspnoea, shorten the average length of hospital stay (P=0.006, respectively), and decrease the duration of mechanical ventilation. CONCLUSION: Safflower yellow in the treatment of AECOPD has a degree of clinical value. This trial is registered under the identifier ChiCTR-IPR-17014176.

A comparison of exposure of Glottis using the Airtraq or the Macintosh Laryngoscope in Potentially difficult airway management: A self-controlled clinical trial.

OBJECTIVE: To compare glottis exposure of the same patients with potentially difficult tracheal intubation (PDTI) subjected to Airtraq laryngoscopy and Macintosh laryngoscopy under consciousness and topical anesthesia. METHODS: A total of 147 PDTI patients with American Society of Anesthesiologists (ASA) I-III were subjected to Airtraq and Macintosh laryngoscopy performed by experienced anesthesiologists under consciousness and topical anesthesia. RESULTS: All patients were successfully intubated. Among them, three patients were intubated with fiberoptic bronchoscopy, 13 with Macintosh laryngoscopy and 131 with Airtraq laryngoscopy. Of the patients with Cormack and Lehance (C&L) Grade-I glottic view, 88 were subjected to Airtraq laryngoscopy and five to Macintosh laryngoscopy; Of the patients with C&L Grade-II glottic view, 56 were subjected to Airtraq laryngoscopy and 21 to Macintosh bronchoscopy; Of the patients with C&L Grade-III glottic view, three were subjected to Airtraq laryngoscopy and 112 to Macintosh bronchoscopy; Of the patients with C&L Grade-IV glottic view, none was subjected to Airtraq laryngoscopy and 9 to Macintosh laryngoscopy. CONCLUSIONS: Airtraq laryngoscopy could significantly improve the glottis exposure and reduce the difficulty of intubation for patients with potentially tracheal intubation compared to the traditional Macintosh laryngoscopy.

Effectiveness and Safety of a Novel Approach for Management of Patients with Potential Difficult Mask Ventilation and Tracheal Intubation: A Multi-center Randomized Trial.

BACKGROUND:: Patients with potential difficult mask ventilation (DV) and difficult intubation (DI) are often managed with awake intubation, which can be stressful for patients and anesthesiologists. This prospective randomized study evaluated a new approach, fast difficult airway evaluation (FDAE). We hypothesized that the FDAE approach would reduce the need for awake intubation. METHODS:: After obtaining informed consent, 302 patients with potential DV/DI undergoing elective surgeries were randomly assigned to the FDAE group (Group E) and the control group (Group C). In Group E, patients were gradually sedated, and adequacy of manual mask ventilation during spontaneous breathing was assessed at various sedation levels. Awake intubation was applied in those with inadequate mask ventilation. In Group C, DI was evaluated under local anesthesia. However, the care team could intubate under general anesthesia if the vocal cords were visible. The primary outcome was the rate of awake intubations in both groups and the induction efficiency assessed by the induction time. The secondary outcome was the incidence of serious complications. RESULTS: The rate of awake intubation was significantly lower in Group E than that in Group C (5.81% vs. 36.05%, χ2 = 42.3, P < 0.001). The induction time was much shorter in Group E than in Group C (11.85 ± 4.82 min vs. 18.71 ± 7.85 min, t = 5.39, P < 0.001). There was no significant difference in the incidence of intubation related complications between the two groups. Patients in Group E had a much lower incidence of recall (9.68% vs. 44.90%, χ2 = 47.68, P < 0.001) of the induction process and higher satisfaction levels than patients in Group C (t = 15.36, P < 0.001). CONCLUSIONS: The FDAE significantly reduces the need for awake intubation and improves the efficiency of the intubation process without comprising safety in patients with potential difficult mask ventilation and DI. TRIAL REGISTRATION:: No. ChiCTR-TRC-11001418; http://www.gctr.org/cn/proj/show.aspx?proj=1562.

Characterization of PD-L1 expression in Chinese non-small cell lung cancer patients with PTEN expression as a means for tissue quality screening.

The goal of this study is to evaluate PD-L1 prevalence and its association with major clinical characteristics in Chinese non-small cell lung cancer (NSCLC) patients to inform the clinical development of anti-PD1/PD-L1 agents in this population. We used phosphatase and tensin homolog (PTEN) expression through IHC as a surrogate tissue quality marker to screen surgical NSCLC samples in tissue microarray (TMA; 172 cases) or whole-section (268 cases) format. The samples were then analyzed with a clinically validated PD-L1 IHC assay. The results were correlated with baseline characteristics and clinical outcomes. PTEN IHC showed that 108 TMA samples and 105 whole-section samples qualified for PD-L1 IHC. With a clinically relevant cutoff, 41.7% of the TMA samples were PD-L1 positive. PD-L1 level was much lower in EGFR-mutant patients and seemed to be a favorable prognostic factor for both overall survival (OS) and recurrence-free survival (RFS). These findings were confirmed in the whole-section samples except that their survival data were not mature enough for correlation analysis. In summary, PD-L1 expression was detected in approximately 40% of PTEN-qualified Chinese NSCLC samples, negatively correlated with EGFR mutation and seemed to be a favorable prognostic factor for both OS and RFS. Notably, the different results from PTEN-qualified and PTEN-disqualified samples underscore the importance of tissue quality control prior to biomarker testing.

The pre-amputation pain and the postoperative deafferentation are the risk factors of phantom limb pain: a clinical survey in a sample of Chinese population.

BACKGROUND: To provide an overview of phantom limb pain (PLP) in China. This includes the prevalence of PLP and possible risk factors. METHODS: In a retrospective study, telephone interviews were conducted with 391 amputation patients who underwent extremity amputations at a tertiary hospital in China. RESULTS: PLP was found in 29% of the amputees. Pre-amputation pain (OR = 10.4, P = 0.002) and postoperative analgesia (OR = 4.9, P = 0.008) were identified as high-risk factors for PLP. 82.1% of PLP patients experienced pre-amputation pain. The average pain intensity of PLP was 5.1 ± 2.2, with 31.9% having severe intensity. The effects of PLP on the quality of the PLP patients were as follows: 7.8% of the patients had to limit their daily life and 29.0% of the patients had to limit their social activities. 17.3 and 25.7% of patients experienced depression and sleeping disorder respectively, while 18.9% had loss of interest and even 16.1% of PLP patients had attempted suicide. No effective treatments were found in 78.9% of these patients. CONCLUSIONS: PLP has markedly affected the lives of patients. Pre-amputation pain and postoperative epidural analgesia might be risk factors for the phantom limb pain after amputation. Prevention of pre-amputation pain and sudden post-amputation deafferentation should be recommended to the amputees.

Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord.

Patients with tumors that metastasize to bone frequently suffer from debilitating pain, and effective therapies for treating bone cancer are lacking. This study employed a novel strategy in which herpes simplex virus (HSV) carrying a small interfering RNA (siRNA) targeting platelet-derived growth factor (PDGF) was used to alleviate bone cancer pain. HSV carrying PDGF siRNA was established and intrathecally injected into the cavum subarachnoidale of animals suffering from bone cancer pain and animals in the negative group. Sensory function was assessed by measuring thermal and mechanical hyperalgesia. The mechanism by which PDGF regulates pain was also investigated by comparing the differential expression of pPDGFRα/ß and phosphorylated ERK and AKT. Thermal and mechanical hyperalgesia developed in the rats with bone cancer pain, and these effects were accompanied by bone destruction in the tibia. Intrathecal injection of PDGF siRNA and morphine reversed thermal and mechanical hyperalgesia in rats with bone cancer pain. In addition, we observed attenuated astrocyte hypertrophy, down-regulated pPDGFRα/ß levels, reduced levels of the neurochemical SP, a reduction in CGRP fibers and changes in pERK/ERK and pAKT/AKT ratios. These results demonstrate that PDGF siRNA can effectively treat pain induced by bone cancer by blocking the AKT-ERK signaling pathway.

Propofol administration improves neurological function associated with inhibition of pro-inflammatory cytokines in adult rats after traumatic brain injury.

BACKGROUND: Neurological deficits following traumatic brain injury (TBI) result in dramatic impacts on the survivors, but the effect of propofol and associated mechanism are waiting to be determined. METHODS: Adult male Sprague-Dawley rats were randomly assigned into Sham, TBI, TBI+Intralipid and TBI+Propofol group. Modified Feeney method was adopted to generate TBI model from free hammer fall injury, and animals in TBI+Propofol group were immediately treated with propofol administration for 2hours after TBI, rats after TBI without propofol treatment was used as injury control, intralipid as vehicle in propofol was injected in TBI+intralipid group. Then, neurological severity scores (NSS) were evaluated at 1, 3, 7 and 14days. Moreover, the expressions of IL-1ß, IL-6 and TNF-α mRNA and protein were examined using quantitative real time-polymerase chain reaction and Western blot, immunohistochemical staining was used to localize cytokines. RESULTS: The NSS increased greatly in the rats induced by TBI, while propofol could effectively decreased NSS, confirming the neuroprotective effect of propofol. Moreover, the mRNA expressions of IL-1ß, IL-6 and TNF-α, at 1, 3, 7days after operation (dpo), were significantly augmented in the injured cortex, compared with sham one. But there was no difference between TBI and TBI+Intralipid group, but markedly decreased after propofol treatment. Additionally, the protein level of IL-1ß, IL-6 and TNF-α in four groups determined by Western blot and immunohistochemistry showed the similar change with mRNA expression. CONCLUSION: Propofol treatment could elicit a robust neuroprotective response, resulting in significant neurological function improvement for TBI rats, which was independent with intralipid. The underlying molecular mechanism may be partially associated with an inhibition of pro-inflammatory cytokines.

Effects of Safflower Yellow on the Treatment of Severe Sepsis and Septic Shock: A Randomized Controlled Clinical Trial.

Objective. To evaluate the clinical effect of safflower yellow on the treatment of severe sepsis and septic shock. Methods. 85 patients with severe sepsis and septic shock were randomly selected to receive either therapy according to the international guidelines for management of severe sepsis and septic shock (Surviving Sepsis Campaign 2012) (control group, n = 45) or conventional therapy plus safflower yellow (study group, n = 40). The 28-day mortality and 28-day Kaplan-Meier survival curves were compared as primary outcomes. Results. The 28-day mortality from all causes and in-hospital mortality were significantly lower in the study group (50%, 17.5%) as compared to the control group (78.58%, 54.76%) (P = 0.007, all causes, P < 0.001, in-hospital), and the 28-day Kaplan-Meier survival curve was higher in the study group than in the control group (P = 0.008, all causes, P < 0.001, in-hospital, Log Rank). 72 hours after treatment, secondary outcomes including heart rate, leukocyte counts, lactate levels, and platelet counts of patients in the study group were ameliorated significantly as compared with the control group. Conclusion. This study offers a potential new strategy employing safflower yellow to more effectively treat patients with severe sepsis and septic shock. This trial is registered with identifier ChiCTR-TRC-14005196.

Validation of the Chinese Version of the Quality of Recovery-15 Score and Its Comparison with the Post-Operative Quality Recovery Scale.

BACKGROUND: The Quality of Recovery-15 scale (QoR-15) is an easy-to-use score for assessing the quality of post-operative recovery. OBJECTIVES: The primary aim of the present study was to translate the QoR-15 into the Chinese language and validate it. The secondary aim was to compare it with the Post-operative Quality Recovery Scale (PQRS). METHODS: The Chinese version of the QoR-15 (QoR-15C) was developed according to the methods adopted by the International Quality of Life Assessment project. A total of 470 patients undergoing surgery and general anesthesia completed the QoR-15C and the PQRS before or on the day of surgery, and on post-operative days (POD)-1, -3, and -30. To validate the QoR-15C, we assessed validity, reliability, responsiveness, and clinical feasibility and compared them with those of the PQRS. RESULTS: Convergent validity showed the Pearson's r coefficient of the QoR-15C with visual analog scale and the PQRS to be 0.63 and 0.10, respectively. Predictive validity showed it had significant correlations with duration of anesthesia, duration of operation, time in post-anesthesia care unit, time in intensive care unit, and length of hospital stay. Discriminant validity showed it differed between patients who had a good or poor recovery, and decreased with increasing grades (indicating difficulty and complexity) of surgery. The intraclass correlation coefficient, split-half coefficient, and Cronbach's α were 0.99, 0.70, and 0.76, respectively. The standardized effect size ranged from 0.85 to 1.20, and the standardized response mean ranged from 0.93 to 1.27. Compared with the QoR-15C, the PQRS may have inferior convergent validity (0.36 vs. 0.63), and split-half reliability (0.63 vs. 0.70). Furthermore, the PQRS took longer to complete: 4.20 (standard deviation 0.79) versus 1.57 (standard deviation 0.65) min. CONCLUSIONS: Similar to the original English version, the QoR-15C reveals satisfactory psychometric properties. Furthermore, it may be a more valid, reliable, and easy-to-use scale than the PQRS.

Comparison of Incidence of hypoxia during modified rapid sequence induction and an alternative technique: a prospective randomized controlled trial.

BACKGROUND: We evaluated the effects and safety of an alternative technique for rapid sequence intubation in children predicting to have high risk of pulmonary aspiration in this prospective, randomized, placebo-controlled study. METHODS: One hundred sixty-five children predicting to have high risk of pulmonary aspiration were randomly allocated to spontaneous breathing maintained induction and intubation group (Group S) and the modified rapid sequence group (Group C). The primary outcome was the incidence of hypoxemia around the intubation period, which was defined as SpO2<90% at any time during the induction and 10 min after the endotracheal intubation. Secondary outcomes included the incidence of pulmonary aspiration, gastroesophageal reflux and other major adverse events associated with the induction and intubation. RESULTS: There were no differences in the incidence of hypoxemia around the intubation period between Group C and Group S; 25.9% vs. 14.8% (P=0.079). The incidence of severe hypoxemia appeared higher in Group C than Group S but not statistical significance, 6.2% vs. 2.5% (P=0.246). Simultaneously, gastroesophageal reflux (upper esophageal pH≤4) was detected in 4.93% children in Group C and 2.47% in group S, which was not significantly different between the two groups (P=0.552). There were no witnessed aspirations in all subjects. CONCLUSION: Sevoflurane based deep sedation with spontaneous respiration maintained technique is not superior to modified rapid sequence induction but can be an alternative technique for anesthesia induction for those predicting to have high risk of aspiration in children.

Nerve Blockage Attenuates Postoperative Inflammation in Hippocampus of Young Rat Model with Surgical Trauma.

It is hypothesized that central nervous system inflammation induced by systematic inflammation due to surgical trauma plays a critical role in postoperative cognitive dysfunction. The potential inhibitory effect of nerve blockage with local anesthetics on peripheral inflammatory response has been reported. We hypothesize that nerve blockage may be effective in reducing postoperative inflammation and cognitive decline. The rats at the age of 4 weeks were subjected to general anesthesia and humeral fracture fixation, in combination with brachial plexus block, saline versus ropivacaine, respectively. The rats from control group underwent general anesthesia only. The expression of proinflammatory cytokines in plasma and in hippocampus was measured. Open field test and new object recognition task were performed before surgery and on postoperative days (POD) 1, 3, and 7. Compared with control group, the level of cytokines in plasma and hippocampus revealed an obvious increase in surgery groups. The effect of brachial plexus block on decreasing cytokines was observed. The rats exposed to surgery without brachial plexus block showed behavior impairment. Our results indicated that nerve blockage could downregulate proinflammatory cytokines in hippocampus after humeral fixation surgery, which may ameliorate the postoperative cognitive dysfunction in young rats.