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).

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.

Dexmedetomidine prevents desflurane-induced motor neuron death through NF-KappaB pathway.

Desflurane is one of the commonly used general anaesthetics. Recently, it was reported that desflurane caused neurotoxicity, raising concerns in clinical use. In this study, we found desflurane could affect viability and maturation in motor neurons. Dexmedetomidine, a α2-adrenergic receptor agonist, could attenuate the effect of desflurane on motor neurons. This process was mediated by NF-KappaB signalling. Interestingly, we also found that dexmedetomidine could recover the lesion in motor function and memory impaired by desflurane. Collectively, our results showed the neurotoxic effect of desflurane in motor neurons. More importantly, this process was alleviated by dexmedetomidine, potentially showing its application in protecting motor neuron from neurotoxic agents. Significance of the study: This work provides the evidence to support the protective role of dexmedetomidine in desflurane-induced motor neuron death. Since desflurane is a widely used anaesthetic in surgery and leads to neuron death, the neuroprotective effect of dexmedetomidine holds promising clinical application.

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.