Bupivacaine-fentanyl isobaric spinal anesthesia reduces the risk of ICU admission in elderly patients undergoing lower limb orthopedic surgery.

BACKGROUND: To evaluate if bupivacaine-fentanyl isobaric spinal anesthesia could reduce the risk of ICU admission compared with general anesthesia in elderly patients undergoing lower limb orthopedic surgery. METHODS: This study comprised a retrospective review of all lower limb orthopedic surgeries performed at our hospital between January 2013 and December 2019. According to anesthesia methods, patients were divided into the spinal anesthesia group (n = 1,728) and the general anesthesia group (n = 188). The primary outcome evaluated was the occurrence of ICU admission. Secondary outcomes included hemodynamic changes, postoperative complications, and mortality. RESULTS: Repeated measure analysis of variance indicated that the difference between the two groups in the systolic blood pressure (SBP) was not significant before anesthesia (T0), immediately after anesthesia (T1), and before leaving the operation room (T8) (P > 0.05), but significant (P < 0.01) from 5 min after anesthesia (T2) to after operation (T7). The proportions of ICU admission (6.4% vs. 23.8%, P < 0.01) and unplanned intubation (0.1% vs. 3.8%, P < 0.01) were significantly lower in the spinal anesthesia group compared with those in the general anesthesia group. Multivariate logistic regression revealed that after controlling for potential confounding factors, the odds of ICU admission for patients in the spinal anesthesia group was 0.240 times (95% CI 0.115-0.498; P < 0.01) than those in the general anesthesia group. CONCLUSIONS: Bupivacaine-fentanyl isobaric spinal anesthesia significantly reduced the risk of ICU admission and unplanned intubation, and provided better intraoperative hemodynamics in elderly patients undergoing lower limb orthopedic surgery. TRIAL REGISTRATION: This study has been registered in the Chinese Clinical Trial Registry (ChiCTR2000033411).

Efficacy of dexmedetomidine combined with ropivacaine on postoperative analgesia and delirium in elderly patients with total knee arthroplasty.

This study aimed to investigate the impact of dexmedetomidine combined with ropivacaine on continuous femoral nerve block (CFNB) in postoperative analgesia and delirium in elderly patients with total knee arthroplasty (TKA). A total of 120 patients who undergone TKA were randomly assigned into group D + R (dexmedetomidine combined with ropivacaine) and group R (only ropivacaine), with 60 cases in each group. The pain scores at rest and exercise at 6 h, 12 h, 24 h, and 48 h postoperatively. The occurrence of delirium on Day 1, Day 2, and Day 3 postoperatively were measured, and the sleep quality was evaluated before surgery, the night of surgery, and 24 h postoperatively to observe the occurrence of postoperative complications. The Visual analogu scale (VAS) of group D + R at 12 h, 24 h, and 48 h postoperatively were lower than those of group R in both rest and exercise states. The incidence of postoperative delirium in group D + R was lower than that in group R on Day 1 and Day 2. Pittsburgh sleep quality index (PSQI) scores in group D + R were lower than those in group R. There was no significant difference in postoperative adverse reactions between the two groups. Dexmedetomidine combined with ropivacaine improves postoperative analgesia and sleep quality, and alleviates the occurrence of postoperative delirium in elderly patients with TKA.

[Analysis of relevant factors influencing the 30-day survival rate of patients with cardiac arrest and cardiopulmonary resuscitation: research based on 8-year data of a class III hospital].

OBJECTIVE: To investigate the survival of patients with cardiac arrest and cardiopulmonary resuscitation (CA-CPR), and to analyze the factors influencing survival at 30 days after restoration of spontaneous circulation (ROSC). METHODS: A retrospective cohort study was conducted. Clinical data of 538 patients with CA-CPR admitted to the People's Hospital of Ningxia Hui Autonomous Region from January 2013 to September 2020 were enrolled. The gender, age, underlying disease, cause of CA, type of CA, initial rhythm, presence or absence of endotracheal intubation, defibrillation, use of epinephrine, and 30-day survival rate of patients were collected. The etiology of CA and 30-day survival rate among patients with different ages were compared, as well as the clinical data between patients who survived and died at 30 days after ROSC were also compared. Multivariate Logistic regression was used to analyze the relevant factors affecting the 30-day survival rate of patients. RESULTS: Among 538 patients with CA-CPR, 67 patients with incomplete information were excluded, and 471 patients were enrolled. Among 471 patients, 299 were males and 172 were females. Aged from 0 to 96 years old, 23 patients (4.9%) were < 18 years old, 205 patients (43.5%) were 18 to 64 years old, and 243 patients (51.6%) were ≥ 65 years old. 302 cases (64.1%) achieved ROSC, and 46 patients (9.8%) survived for more than 30 days. The 30-day survival rate of patients aged < 18 years old, 18-64 years old and ≥ 65 years old was 8.7% (2/23), 12.7% (26/205) and 7.4% (18/243), respectively. The main causes of CA in patients younger than 18 years were severe pneumonia (13.1%, 3/23), respiratory failure (13.1%, 3/23), and trauma (13.1%, 3/23). The main causes were acute myocardial infarction (AMI; 24.9%, 51/205), respiratory failure (9.8%, 20/205), and hypoxic brain injury (9.8%, 20/205) in patients aged 18-64 years old, and AMI (24.3%, 59/243) and respiratory failure (13.6%, 33/243) in patients aged ≥ 65 years old. Univariate analysis results revealed that the 30-day survival rate of patients with CA-CPR may be related to the the cause of CA was AMI, initial rhythm was ventricular tachycardia/ventricular fibrillation, endotracheal intubation and epinephrine. Multivariate Logistic regression analysis results showed that CA was caused by AMI [odds ratio (OR) = 0.395, 95% confidence interval (95%CI) was 0.194-0.808, P = 0.011] and endotracheal intubation (OR = 0.423, 95%CI was 0.204-0.877, P = 0.021) was a protective factor for 30 days of survival after ROSC in patients with CA-CPR. CONCLUSIONS: The 30-day survival rate of CA-CPR patients was 9.8%. The 30-day survival rate of CA-CPR patients with AMI after ROSC is higher than that of patients with other CA causes, and early endotracheal intubation can improve the prognosis of patients.

Heparin alleviates LPS-induced endothelial injury by regulating the TLR4/MyD88 signaling pathway.

Heparin is a commonly used in the clinic, however, Heparin's effect on endothelial injury remains unclear. The aim of the present study was to evaluate the effects and possible mechanisms of action underlying heparin treatment in lipopolysaccharide (LPS)-induced endothelial injury in vitro. TNF-α, IL-1ß, IL-6 and IFN-γ levels were measured using ELISA. Cell proliferation was measured using a 5-ethynyl-2'-deoxyuridine (EdU) assay. The number of apoptotic cells and apoptotic rate were evaluated using TUNEL assays and flow cytometry, respectively. Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88) and NF-κB (p65) gene expression was evaluated using reverse transcription-quantitative PCR, whilst TLR4, MyD88 and p-NF-κB (p65) protein expression was evaluated using western blot analysis. The levels of phosphorylated NF-κB in the nucleus were evaluated using cellular immunofluorescence. Compared with those in the normal control group, TNF-α, IL-1ß, IL-6 and IFN-γ levels were significantly increased in the LPS group (P<0.001). In addition, 5-ethynyl-2'-deoxyuridine (EdU)-positive cells were significantly increased and apoptosis was significantly decreased (P<0.001). TLR4, MyD88 and NF-κB (p65) expression was also significantly increased (P<0.001). Compared with those in the LPS group, following heparin treatment, TNF-α, IL-1ß, IL-6 and IFN-γ levels were significantly decreased (P<0.05), whilst the number of EdU-positive cells was significantly increased and the level of apoptosis was significantly decreased (P<0.05). TLR4, MyD88 and NF-κB (p65) expression was also significantly decreased by heparin in a dose-dependent manner (P<0.001). Small interfering RNA-TLR4 transfection exerted similar effects to those mediated by heparin in alleviating endothelial injury. In conclusion, heparin suppressed LPS-induced endothelial injury through the regulation of TLR4/MyD88/NF-κB (p65) signaling in vitro.

MicroRNA-216a-5p in lipopolysaccharide-induced endothelial injury.

MicroRNAs (miRNAs/miRs) are a type of non-coding RNA that are closely associated with disease development and treatment. The present study aimed to investigate the role of miR-216a-5p in lipopolysaccharide (LPS)-induced endothelial injury in vitro. The EdU assay was performed to detect EdU-positive cells, while flow cytometric analysis was performed to detect apoptotic cells. Reverse transcription-quantitative PCR and western blot analyses were performed to detect the expression levels of miR-216a-5p, Toll-like receptor 4 (TLR4), MyD88 and nuclear factor (NF)-κB(p65) and phosphorylated (p)-NF-κB(p65). Furthermore, p-NF-κB(p65) nuclear expression level was detected via cellular immunofluorescence. The dual-luciferase reporter assay was performed to verify the association between miR-216a-5p and TLR4. The results demonstrated that the number of EdU-positive cells significantly decreased, the apoptotic rate significantly increased, and TLR4, MyD88 and NF-κB(p65) mRNA expression levels were significantly upregulated.TLR4, MyD88 and p-NF-κB(p65) protein expression levels were significantly upregulated and p-NF-κB(p65) nuclear concentration was significantly enhanced in the small interfering RNA-miR-216a-5p and LPS groups (P<0.001, respectively) compared with the negative control group. However, the addition of miR-216a-5p significantly increased the number of EdU-positive cells, significantly decreased the apoptotic rate and significantly downregulated the mRNA expression levels of TLR4, MyD88 and NF-κB(p65), as well as the protein expression levels of TLR4, MyD88 and p-NF-κB(p65). In addition, the p-NF-κB(p65) nuclear concentration was significantly decreased in the miR-216a-5p group (P<0.001, respectively) compared with the LPS group. Taken together, the results suggest that overexpression of miR-216a-5p suppresses the effects of LPS induced endothelial injury.

Effects on newborns of applying bupivacaine combined with different doses of fentanyl for cesarean section.

BACKGROUND: The choice of anesthesia for cesarean section is very important. AIM: To compare the effects of applying bupivacaine combined with different doses of fentanyl on newborns after cesarean section. METHODS: We randomly divided one hundred and twenty patients undergoing cesarean section into the following 4 groups: group B (bupivacaine group), group BF10 (bupivacaine combined with 10 µg fentanyl), group BF30 (bupivacaine combined with 30 µg fentanyl) and group BF50 (bupivacaine combined with 50 µg fentanyl). The heart rate, mean arterial pressure, block plane fixation time and sensory block time were recorded. Umbilical artery blood was then collected immediately after fetal delivery for blood gas analysis and qualitative detection of fentanyl. Additionally, data on the neonatal 1-min and 5-min Apgar scores, results of umbilical artery blood gas analysis and qualitative detection of fentanyl in umbilical artery blood were recorded. RESULTS: Although the mean arterial pressure decreased in all four groups at 3 min after anesthesia, the percentage of the decrease was less than 20% of the baseline. In addition, there were no significant differences in the 1-min or 5-min Apgar scores or the umbilical artery blood gas analysis among the four groups (P > 0.05). Moreover, the concentration of fentanyl in umbilical artery blood was qualitatively detected using an ELISA kit, and the results in the four groups were negative. CONCLUSION: Bupivacaine combined with fentanyl spinal anesthesia is effective in cesarean section.

The ERK/CREB/PTN/syndecan-3 pathway involves in heparin-mediated neuro-protection and neuro-regeneration against cerebral ischemia-reperfusion injury following cardiac arrest.

BACKGROUND: Heparin, a commonly used anticoagulant, has been found to improve cerebral ischemia-reperfusion injury (CIR-CA) following cardiopulmonary resuscitation (CPR). Here, we aimed to explore the role of pleiotrophin (PTN)/syndecan-3 pathway in heparin therapy for CIR-CA. MATERIALS AND METHODS: The CA-CPR model was constructed in Sprague-Dawley (SD) rats, which were treated with low molecular weight heparin, and the neurological changes and brain histopathological changes were evaluated. For in-vitro experiments, the ischemic injury model of primary neurons was established by oxygen and glucose deprivation (OGD), and the neuron regeneration was detected via the Cell counting Kit-8 (CCK8) method, flow cytometry and microscopy. CREB antagonist (KG-501), ERK antagonist (PD98059) and si-PTN were used respectively to inhibit the expression of CREB, ERK and PTN in cells, so as to explore the role of heparin in regulating neuronal regeneration. RESULTS: Compared with the sham rats, the neurological deficits and cerebral edema of CA-CPR rats were significantly improved after heparin treatment. Heparin also attenuated OGD-mediated neuronal apoptosis and promoted neurite outgrowth in vitro. Moreover, heparin attenuated CA-CPR-mediated neuronal apoptosis and microglial neuroinflammation. In terms of the mechanism, heparin upregulated the expression of ERK, CREB, NF200, BDNF, NGF, PTN and syndecan-3 in the rat brains. Inhibition of ERK, CREB and interference with PTN expression notably weakened the heparin-mediated neuroprotective effects and restrained the expression of ERK/CREB and PTN/syndecan-3 pathway. CONCLUSION: Heparin attenuates the secondary brain injury induced by CA-CPR through regulating the ERK/CREB-mediated PTN/syndecan-3 pathway.

The Effect of Prophylactic Anticoagulation with Heparin on the Brain Cells of Sprague-Dawley Rats in a Cardiopulmonary-Cerebral Resuscitation Model.

After a cardiac arrest (CA) of 5 to 10 min, a marked activation of blood coagulation occurs and microthrombi are found in the cerebral vessels. These microcirculatory disturbances directly affect the outcome on cardiopulmonary resuscitation (CPR). The purpose of this study was to investigate the effects and potential mechanisms of prophylactic anticoagulation on rat brain cells after cerebral CPR. After setting up an asphyxial CA model, we monitored the basic parameters such as the vitals and survival rate of the rats and assessed the respective neurological deficit (ND) and histological damage (HD) scores of their brain tissues. We, furthermore, investigated the influence of heparin on the expressions of TNF-α, IL-1ß, CD40, NF-κB, and HIF-1α after asphyxial CA. The results showed that anticoagulation with heparin could obviously improve the outcome and prognosis of brain ischemia, including improvement of neurological function recovery and prevention of morphological and immunohistochemical injury on the brain, while significantly increasing the success rate of CPR. Treatment with heparin significantly inhibited the upregulation of CD40, NF-κB, and HIF-1α induced by asphyxial CA. Thrombolysis treatment may improve the outcome and prognosis of CPR, and future clinical studies need to evaluate the efficacy of early heparin therapy after CA.

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.

Investigation of the protective effect of heparin pre-treatment on cerebral ischaemia in gerbils.

Context: The interruption of cerebral blood circulation may cause stroke characterized by high neurological deficits (NDs) as a result of neuronal dysfunction or destruction. Heparin may exert a neuroprotective effect against cerebral ischaemia/reperfusion injury. Objective: The objective of this study was to investigate the mechanism underlying the effects of heparin pre-treatment on cerebral injury in the gerbil. Materials and methods: A total of 80 healthy Mongolian gerbils were randomly divided into four groups to establish cerebral ischaemia model by bilateral carotid artery occlusion: control (no anaesthesia and surgery), sham (no occlusion), non-anticoagulation (occlusion), and anti-coagulation treatment groups (50 IU/100 g heparin pre-treated, occlusion). Gerbils were anesthetized with 40 mg/kg pentobarbital sodium through intraperitoneal injection before operation except for the control group. Then, the ND and histopathological damage (HD) scores were determined. The percentage of tumour necrosis factor (TNF)-α- and interleukin (IL)-1ß-positive cells were calculated based on immunohistochemical results. The mRNA and protein levels of caspase-9, caspase-8, FasL, and calpain were evaluated with real-time polymerase chain reaction (RT-PCR) and western blotting, respectively. Results: Compared with non-anticoagulation group, heparin pre-treatment (50 IU/100 g) delayed the onset of dyspnoea (p < 0.05), and showed a significant decrease in ND (p < 0.01), mortality rate (p < 0.05), HD (p < 0.01) and percentage of positive cells for TNF-α, IL-1ß (p < 0.01) in cerebral ischaemia gerbils. Besides, the expression levels of caspase-9, caspase-8, FasL, and calpain were reduced after pre-treatment with 50 IU/100 g heparin. Discussion and conclusions: The damage caused to gerbil brain was reduced upon pre-treatment with heparin, possibly through the amelioration of neuronal cell apoptosis and expression of TNF-α and IL-1ß. These findings are expected to provide a new breakthrough in the study and treatment of cerebral ischaemia.

Monoacylglycerol Lipase Inactivation by Using URB602 Mitigates Myocardial Damage in a Rat Model of Cardiac Arrest.

OBJECTIVES: Monoacylglycerol lipase participates in organ protection by regulating the hydrolysis of the endocannabinoid 2-arachidonoylglycerol. This study investigated whether blocking monoacylglycerol lipase protects against postresuscitation myocardial injury and improves survival in a rat model of cardiac arrest and cardiopulmonary resuscitation. DESIGN: Prospective randomized laboratory study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rat (n = 96). INTERVENTIONS: Rats underwent 8-minute asphyxia-based cardiac arrest and resuscitation. Surviving rats were randomly divided into cardiopulmonary resuscitation + URB602 group, cardiopulmonary resuscitation group, and sham group. One minute after successful resuscitation, rats in the cardiopulmonary resuscitation + URB602 group received a single dose of URB602 (5 mg/kg), a small-molecule monoacylglycerol lipase inhibitor, whereas rats in the cardiopulmonary resuscitation group received an equivalent volume of vehicle solution. The sham rats underwent all of the procedures performed on rats in the cardiopulmonary resuscitation and cardiopulmonary resuscitation + URB602 groups minus cardiac arrest and asphyxia. MEASUREMENTS AND MAIN RESULTS: Survival was recorded 168 hours after the return of spontaneous circulation (n = 22 in each group). Compared with vehicle treatment (31.8%), URB602 treatment markedly improved survival (63.6%) 168 hours after cardiopulmonary resuscitation. Next, we used additional surviving rats to evaluate myocardial and mitochondrial injury 6 hours after return of spontaneous circulation, and we found that URB602 significantly reduced myocardial injury and prevented myocardial mitochondrial damage. In addition, URB602 attenuated the dysregulation of endocannabinoid and eicosanoid metabolism 6 hours after return of spontaneous circulation and prevented the acceleration of mitochondrial permeability transition 15 minutes after return of spontaneous circulation. CONCLUSIONS: Monoacylglycerol lipase blockade may reduce myocardial and mitochondrial injury and significantly improve the resuscitation effect after cardiac arrest and cardiopulmonary resuscitation.

Inhibition of Fatty Acid Amide Hydrolase Improves Depressive-Like Behaviors Independent of Its Peripheral Antinociceptive Effects in a Rat Model of Neuropathic Pain.

BACKGROUND: Neuropathic pain is often associated with depression. Enhancing endocannabinoids by fatty acid amide hydrolase (FAAH) inhibitors relieves neuropathic pain and stress-induced depressive-like behaviors in animal models. However, it is unclear whether FAAH inhibitor can relieve neuropathic pain-induced depression by or not by its antinociceptive effects. METHODS: Adult male Wistar rats with chronic constriction injury (CCI) to the sciatic nerve were treated with the systemic FAAH inhibitor URB597 (5.8 mg·kg·day, intraperitoneally) or peripherally acting FAAH inhibitor URB937 (1.6 mg·kg·d, intraperitoneally; n = 11-12). The treatment was applied from the 15th day after surgery and continued for 15 days. Mechanical withdrawal threshold was examined by Von Frey test before surgery and on the 28th day after CCI. Depressive-like behaviors were evaluated by forced swimming test (FST) and novelty-suppressed feeding (NSF) after 15-day treatment. The levels of anandamide and 2-arachidonoylglycerol in hippocampus were examined by liquid chromatography and mass spectrometry. Hippocampal neurogenesis including proliferation, differentiation, and survival of newborn cells was assessed by immunohistochemistry. RESULTS: After CCI injury, the rats developed significantly nociceptive and depressive-like behaviors, indicated by persistent mechanical hypersensitivity in Von Frey test, significantly prolonged immobility time in FST (sham: 84.2 ± 13.4 seconds versus CCI: 137.9 ± 18.8 seconds; P < .001), and protracted latency to feed in NSF (sham: 133.4 ± 19.4 seconds versus CCI: 234.9 ± 33.5 seconds; P < .001). For the CCI rats receiving treatment, compared to vehicle placebo group, pain threshold was increased by both URB597 (3.1 ± 1.0 vs 11.2 ± 1.2 g; P < .001) and URB937 (3.1 ± 1.0 vs 12.1 ± 1.3 g; P < .001). Immobility time of FST was reduced by URB597 (135.8 ± 16.6 vs 85.3 ± 17.2 seconds; P < .001) but not by URB937 (135.8 ± 16.6 vs 129.6 ± 17.8 seconds; P = .78). Latency to feed in NSF was also reduced by URB597 (235.9 ± 30.5 vs 131.8 ± 19.8 seconds; P < .001) but not by URB937 (235.9 ± 30.5 vs 232.2 ± 33.2 seconds; P = .72). Meanwhile, CCI decreased the number of proliferating cells and reduced survival of new mature neurons in hippocampus. URB597 but not URB937 treatment improved these cellular deficits. CONCLUSIONS: Inhibition of FAAH can improve depressive-like behaviors induced by neuropathic pain independent of its peripheral antinociceptive action. Enhanced neurogenesis in hippocampus might contribute to the antidepressive effects of URB597.

Melatonin improves neurological outcomes and preserves hippocampal mitochondrial function in a rat model of cardiac arrest.

Cerebral injury after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR) has been implicated in the poor prognosis of CA survivors. This study was designed to evaluate the impact of melatonin on postresuscitation neurological outcomes and to explore the underlying mechanism. Sprague-Dawley rats were randomly assigned to four groups: sham group, CPR group, melatonin pretreatment group (Pre-M) and posttreatment group (Post-M). For the last 2 groups, daily melatonin gavage was performed for 12 consecutive days before or 24 hours after rat survival from CA/CPR. No statistical differences were observed in heart rate (HR), mean arterial blood pressure (MAP), and end-tidal carbon dioxide (ETCO2) at baseline and after restoration of spontaneous circulation (ROSC) among groups. However, melatonin pretreatment or posttreatment significantly improved neurological deficit score and memory and spatial learning ability after CA/CPR. Further studies demonstrated that the complex I- and complex-II supported mitochondrial respiration were greatly increased under melatonin treatment. In addition, melatonin treatment preserved the mitochondrial-binding hexokinase II (HKII) and ATP levels and suppressed the upregulated protein lysine acetylation in hippocampus after CA/CPR. In conclusion, using a rat asphyxial CA model we have demonstrated that treatment with melatonin either before or after CA/CPR provides a promising neuroprotective effect, and this protection was mediated by increasing mitochondrial HKII expression, suppressing protein acetylation and improving mitochondrial function in hippocampus.