Local anesthetics are widely used clinically for perioperative analgesia to achieve comfort in medical treatment. However, when the concentration of local anesthetics in the blood exceeds the tolerance of the body, local anesthetic systemic toxicity (LAST) will occur. With the development and popularization of positioning technology under direct ultrasound, the risks and cases of LAST associated with direct entry of the anesthetic into the blood vessel have been reduced. Clinical occurrence of LAST usually presents as a series of severe toxic reactions such as myocardial depression, which is life-threatening. In addition to basic life support (airway management, advanced cardiac life support, etc.), intravenous lipid emulsion (ILE) has been introduced as a treatment option in recent years and has gradually become the first-line treatment for LAST. This review introduces the mechanisms of LAST and identifies the clinical symptoms displayed by the central nervous system and cardiovascular system. The paper features the multimodal mechanism of LAST reversal by ILE, describes research progress in the field, and identifies other anesthetics involved in the resuscitation process of LAST. Finally, the review presents key issues in lipid therapy. Although ILE has achieved notable success in the treatment of LAST, adverse reactions and contraindications also exist; therefore, ILE requires a high degree of attention during use. More in-depth research on the treatment mechanism of ILE, the resuscitation dosage and method of ILE, and the combined use with other resuscitation measures is needed to improve the efficacy and safety of clinical resuscitation after LAST in the future.
Background: Perioperative acute kidney injury (AKI) is common in surgical patients and is associated with high morbidity and mortality. There are currently few options for AKI prevention and treatment. Due to its complex pathophysiology, there is no efficient medication therapy to stop the onset of the injury or repair the damage already done. Certain anesthetics, however, have been demonstrated to affect the risk of perioperative AKI in some studies. The impact of anesthetics on renal function is particularly important as it is closely related to the prognosis of patients. Some anesthetics can induce anti-inflammatory, anti-necrotic, and anti-apoptotic effects. Propofol, sevoflurane, and dexmedetomidine are a few examples of anesthetics that have protective association with AKI in the perioperative period. Summary: In this study, we reviewed the clinical characteristics, risk factors, and pathogenesis of AKI. Subsequently, the protective effects of various anesthetic agents against perioperative AKI and the latest research are introduced. Key Message: This work demonstrates that a thorough understanding of the reciprocal effects of anesthetic drugs and AKI is crucial for safe perioperative care and prognosis of patients. However, more complete mechanisms and pathophysiological processes still need to be further studied.
The Clavien-Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien-Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs).This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien-Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs.A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien-Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59).Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally.
The application of lidocaine can lead to nerve damage. Evidence suggests that patients with diabetic neuropathy are at a higher risk for neurotoxicity. In the present study, the successful induction of diabetic neuropathic pain (DNP) in rats via a high-sugar, high‑fat diet and intraperitoneal injection of 1% streptozotocin was verified and pronounced tactile allodynia was observed. It was found that intrathecal injections of hyperbaric lidocaine produced motor blocks of longer durations in the DNP model rats than in nondiabetic rats, or in DNP model rats injected with isobaric lidocaine. Histology of the lumbar 4‑5 spinal cord revealed a significant difference in neuropathology between the DNP and nondiabetic rats. Moreover, edematous neurons and TUNEL‑positive cells were observed in the hyperbaric lidocaine group. It was also found that the inhibition of p38 mitogen‑activated protein kinase (p38MAPK) played a neuroprotective role in response to hyperbaric lidocaine‑induced apoptosis in DNP rats, which indicates that p38MAPK plays a key role in the regulation of hyperbaric lidocaine‑induced apoptosis in DNP rats. These findings suggest that hyperbaric lidocaine can promote spinal cord neuronal apoptosis in rats with DNP. Furthermore, p38MAPK might play a key role in the regulation of hyperbaric lidocaine‑induced apoptosis in rats with DNP.
Objective
To investigate the JAK2 V617F gene mutations in myeloproliferative neoplasms (MPN) patients and its clinical significance.
Methods
120 patients were detected bone marrow pathological conditions with bone marrow cytology and biopsy analysis,and monitored the Ph chromosome and bcr-abl fusion gene. Genomic DNA from bone marrow cells was extracted from 120 patients, JAK2 V617F gene mutations were tested by fluorescence quantitative PCR.
Results
All patients of each MPN type presented their typical characteristics. Ph chromosome and bcr-abl fusion gene were negative. The positive rate of JAK2 V617F gene mutations was 66.7 % (80/120), among them the positive rate in polycythemia vera (PV) was 72.7 % (16/22), the positive rate in essential thrombocythemia (ET) was 66.0 % (62/94), and among 4 patients primary myelofibrosis (PMF) JAK2 V617F was positive in 2 cases. In JAK2 V617F positive PV patients, the white blood cell count (P = 0.001) and platelet count (P = 0.01) were significantly higher than those in negative patients. In JAK2 V617F positive ET patients, the white blood cell count was significantly higher than that in negative patients (P = 0.006). In PMF patients, there was no significant difference (P> 0.05).
Conclusion
JAK2 V617F gene mutations testing is helpful to the diagnosis and definite diagnosis of bcr-abl negative MPN, which promote the early detection and treatment.
Key words:
Myeloproliferative neoplasms; JAK2 V617F gene mutation; Polycythemia vera; Essential thrombocythemia; Primary myelofibrosis
Background: Surgery and anesthesia-induced perioperative neurocognitive disorder (PND) are closely related to NOD-like receptors (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome microglia inflammatory response. Inhibiting the occurrence of neuroinflammation is an important treatment method to improve postoperative delirium. Fewer NLRP3-targeting molecules are currently available in the clinic to reduce the incidence of postoperative delirium. Dexmedetomidine (DEX), an α2 adrenergic receptor agonist has been shown to have antioxidant and anti-inflammatory activities. The present study showed that DEX reduced the production of cleaved caspase1 (CASP1) and destroyed the NLRP3–PYD And CARD Domain Containing (PYCARD)–CASP1 complex assembly, thereby reducing the secretion of IL-1β interleukin beta (IL-1β). DEX promoted the autophagy process of microglia and reduced NLRP3 expression. More interestingly, it promoted the ubiquitination and degradation of NLRP3. Thus, this study demonstrated that DEX reduced NLRP3-mediated inflammation through the activation of the ubiquitin-autophagy pathway. This study provided a new mechanism for treating PND using DEX. Methods: C57BL/6 mice were pre-administered DEX 3 days in advance, and an abdominal exploration model was used to establish a perioperative neurocognitive disorder model. The anti-inflammatory effect of DEX was explored in vivo by detecting NLRP3-CASP1/IL-1β protein expression and behavioral testing. Primary microglia were stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP) in vitro , the expression of CASP1 and IL-1β was detected in the supernatant of cells, and the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) and sequestosome 1 (SQSTM1) was examined in the cytoplasm. Meanwhile, Co-immunoprecipitation (Co-IP) was used to detect NLRP3 protein ubiquitination so as to clarify the new mechanism underlying the anti-inflammatory effect of DEX. Results: Pre-administration of DEX reduced the protein expression of NLRP3, CASP1, and IL-1β in the hippocampus of mice induced by surgery and also improved the impairment of learning and memory ability. At the same time, DEX also effectively relieved the decrease in spine density of the hippocampal brain induced by surgery. DEX decreased the cleaved CASP1 expression, blocked the assembly of NLRP3–PYCARD–CASP1 complex, and also reduced the secretion of mature IL-1β in vitro . Mechanically, it accelerated the degradation of NLRP3 inflammasome via the autophagy–ubiquitin pathway and reduced the green fluorescent protein/red fluorescent protein MAP1LC3B ratio, which was comparable to the effect when using the autophagy activator rapamycin (Rapa). Furthermore, it increased the ubiquitination of NLRP3 after LPS plus ATP stimulated microglia. Conclusion: DEX attenuated the hippocampal brain inflammation by promoting NLRP3 inflammasome degradation via the autophagy–ubiquitin pathway, thus improving cognitive impairment in mice.
Objective: To evaluate whether brachial artery peak velocity variation(ΔVp) during a Valsalva maneuver(VM) could predict fluid responsiveness in spontaneously breathing patients. Methods: Ninety-six patients required radial artery catheter for elective surgery of Ningbo Yinzhou People's Hospital from December 2014 to June 2016 were enrolled. The brachial artery Doppler signal was recorded to measure the ΔVp while the VM was performed.Then doing the volume expansion (VE) , the cardiac output variation (ΔCO) before and after VE were measured.Pearson correlational analyses were conducted between ΔVp and ΔCO. Also the sensitivity and specificity of ΔVp were determined in predicting fluid responsiveness by the receiver operating characteristic (ROC) curve. Results: Patients were classified as group responders (n=24) and group non-responders (n=72). Responder was defined as cardiac output increased≥15% after VE.The ΔVp correlated well with ΔCO (r=0.792, P<0.01). The area under ROC curve was 0.903, with the ΔVp cut-off of 33%, the sensitivity of 87% and the specificity of 82%(P<0.01). Conclusion: Brachial artery peak velocity variation during a valsalva maneuver is a feasible method for predicting fluid responsiveness in spontaneously breathing patients.目的：评价瓦式(Valsalva)动作过程中的肱动脉峰流速变化(ΔVp)能否预测自主呼吸患者的容量反应性。 方法：选择2014年12月至2016年6月宁波市鄞州人民医院需行桡动脉穿刺的择期全麻手术患者96例，超声记录瓦式动作过程中的ΔVp，随后进行容量负荷试验(VE)，并记录心输出量变化(ΔCO)，以容量负荷试验后CO增加≥15%为有反应组，采用Pearson相关分析对ΔVp和ΔCO做相关性研究，绘制ΔVp的受试者工作特征曲线(ROC曲线)，确定ΔVp预测容量反应性的敏感度、特异度、诊断阈值及曲线下面积。 结果：本研究共有24例容量负荷试验有反应，72例容量负荷试验无反应。ΔVp与ΔCO具有相关性(r＝0.792，P<0.01)。ΔVp值诊断容量反应性ROC曲线下面积为0.903(P<0.01)，其中ΔVp诊断阈值为33%，诊断容量反应性的敏感度为87%，特异度为82%。 结论：肱动脉峰流速结合瓦式动作可以作为预测自主呼吸患者容量反应性的指标。.
This study examined the sedative effect of, and hemodynamic response to dexmedetomidine administration in propofol-sedated swine. Sixteen swine were subjects. After anesthetic induction and preparation, the propofol infusion rate was adjusted to maintain a bispectral index (BIS) value between 55 and 65 (i.e., baseline). With the propofol infusion rate fixed at the baseline rate, dexmedetomidine was infused continuously at a rate of 0.2, 0.4, and 0.7 μg·kg –1·h–1 for one hour at each rate. The BIS value and hemodynamic parameters were recorded at each step. Dexmedetomidine decreased the BIS value, mean arterial blood pressure, heart rate, cardiac output, and mixed venous oxygen saturation in a dose-dependent manner. The systemic vascular resistance (SVR) did not change, but the pulmonary vascular resistance (PVR) increased. Oxygen delivery (DO2) and oxygen consumption (VO2) decreased. A small dose of dexmedetomidine (0.2 μg·kg–1·h–1) greatly enhanced the sedative effects of propofol with only small changes in hemodynamics and systemic oxygen balance, suggesting it may be useful in reducing the propofol dose requirement. However, dexmedetomidine 0.4 μg·kg–1·h –1 suppressed cardiac contractility, and 0.7 μg·kg–1·h–1 induced hemodynamic instability and further systemic oxygen imbalance while the additional sedative effect was limited. A lower dose of dexmedetomidine may be recommended when using it in combination with propofol.
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