Local anesthetics are used in various purposes from topical and infiltration anesthesia to peripheral nerve or central neural blockade. Even though local anesthetics are relatively safe, they can have some toxic and adverse effects. Prolonged sensory and motor block is another example of an unwanted complication. The primary objective of this study was to determine whether insulin has a reversal effect on the peripheral (sciatic) nerve block with lidocaine or bupivacaine.

The present study using brain death model of rats was designed to examine whether prophylactic administration of volatile anesthetics and propofol prevent the epinephrine-induced arrhythmias. A Fogarty catheter was placed intracranially for induction of brain death. After brain death, the rats were randomly assigned to five groups: the control group (no anesthetics), the sevoflurane group (0.8%), the isoflurane group (0.5%), the halothane group (0.3%), and the propofol group (195 μg·kg(-1) ·min(-1)). These anesthetics were about 30% of ED50 of each anesthetic. The arrhythmogenic dose of epinephrine was determined in each anesthetic group. In addition, we examined left ventricular levels of connexin 43 phosphorylation 30 min after administration of each anesthetic with Western blot analysis. The arrhythmogenic dose of epinephrine in the sevoflurane group was significantly higher than that in the control group, while the arrhythmogenic dose of epinephrine in any other anesthetic group was not different. On the other hand, the ratio of phosphorylated-connexin 43/total connexin 43 was also similar among the study groups. Thus, prophylactic administration of subanesthetic dose of sevoflurane is effective in preventing epinephrine-induced arrhythmias after brain death, but phosphorylation of connexin is not involved in the antiarrhythmic property of sevoflurane.

How to effectively control the postoperative pain of patients is extremely important to clinicians. Transversus abdominis plane (TAP) block is a novel analgesic method reported to greatly decrease postoperative pain. However, in many areas, there still exists a phenomenon of surgeons using wound infiltration (WI) with conventional local anesthetics (not liposome anesthetics) as the main means to decrease postoperative pain because of traditional wisdom or convenience. Here, we compared the analgesic effectiveness of the two different methods to determine which method is more suitable for adult patients. Materials and methods. A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TAP block and WI without liposome anesthetics in adult patients were performed. Frequently used databases were extensively searched. The main outcomes were postoperative pain scores in different situations (at rest or during movement) and the time until the first use of rescue analgesics. The secondary outcomes were postoperative nausea and vomiting (PONV) incidence and patient satisfaction scores.

Taking into account that there are controversial antioxidative effects of inhalational anesthetics isoflurane and sevoflurane and absence of comparison of genotoxicity of both anesthetics in animal model, the aim of this study was to compare DNA damage and antioxidant status in Wistar rats exposed to a single time to isoflurane or sevoflurane. The alkaline single-cell gel electrophoresis assay (comet assay) was performed in order to evaluate DNA damage in whole blood cells of control animals (unexposed; n = 6) and those exposed to 2% isoflurane (n = 6) or 4% sevoflurane (n = 6) for 120 min. Plasma antioxidant status was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. There was no statistically significant difference between isoflurane and sevoflurane groups regarding hemodynamic and temperature variables (P > 0.05). Sevoflurane significantly increased DNA damage compared to unexposed animals (P = 0.02). In addition, Wistar rats anesthetized with isoflurane showed higher antioxidative status (MTT) than control group (P = 0.019). There were no significant differences in DNA damage or antioxidant status between isoflurane and sevoflurane groups (P > 0.05). In conclusion, our findings suggest that, in contrast to sevoflurane exposure, isoflurane increases systemic antioxidative status, protecting cells from DNA damage in rats.

Hypertriglyceridemia is an uncommon but a well-established etiology of acute pancreatitis leading to significant morbidity and mortality. The risk and severity of acute pancreatitis increase with increasing levels of serum triglycerides. It is crucial to identify hypertriglyceridemia as the cause of pancreatitis and initiate appropriate treatment plan. Initial supportive treatment is similar to management of other causes of acute pancreatitis with additional specific therapies tailored to lower serum triglycerides levels. This includes plasmapheresis, insulin, heparin infusion, and hemofiltration. After the acute episode, diet and lifestyle modifications along with hypolipidemic drugs should be initiated to prevent further episodes. Currently, there is paucity of studies directly comparing different modalities. This article provides a comprehensive review of management of hypertriglyceridemia induced acute pancreatitis. We conclude by summarizing our treatment approach to manage hypertriglyceridemia induced acute pancreatitis.

Propofol, an intravenous anesthetic agent, is widely used for inducing and maintaining anesthesia during surgical procedures and for sedating intensive care unit patients. In the clinic, rapid elimination is one of the major advantages of propofol. Meanwhile, the biotransformation and drug interactions of propofol in rat livers are still little known. In this study, we evaluated the ring-oxidative metabolism of propofol in phenobarbital-treated rat livers and possible drug interactions. Administration of phenobarbital to male Wistar rats significantly increased levels of hepatic cytochrome P450 (CYP) 2B1/2 and microsomal pentoxyresorufin O-dealkylase (PROD) activity. Analyses by high-performance liquid chromatography and liquid chromatography mass spectroscopy revealed that propofol was metabolized by phenobarbital-treated rat liver microsomes into 4-hydroxypropofol. In comparison, PROD activity and 4-hydroxy-propofol production from propofol metabolism were suppressed by orphenodrine, an inhibitor of CYP2B1/2, and a polyclonal antibody against rat CYP2B1/2 protein. Furthermore, exposure of rats to propofol did not affect the basal or phenobarbital-enhanced levels of hepatic CYP2B1/2 protein. Meanwhile, propofol decreased the dealkylation of pentoxyresorufin by phenobarbital-treated rat liver microsomes in a concentration-dependent manner. Taken together, this study shows that rat hepatic CYP2B1/2 plays a critical role in the ring-oxidative metabolism of propofol into 4-hydroxypropofol, and this anesthetic agent can inhibit CYP2B1/2 activity without affecting protein synthesis.

Since an ethical issue has been raised regarding the use of the well-known anesthetic agent chloral hydrate, owing to its mutagenic and carcinogenic effects in animals, attention of neuroscientists has turned to finding out an alternative agent able to meet not only potency, safety, and analgesic efficacy, but also reduced neuroprotective effect for stroke research. The aim of this study was to compare the potential of chloral hydrate and isoflurane for both modulating the action of the experimental neuroprotectant MK801 and exerting analgesia. After middle cerebral artery occlusion in rats, no difference was observed in 24 h survival rate, success of ischemia, or infarct volume reduction between both anesthetics. However, isoflurane exerted a more pronounced analgesic effect than chloral hydrate as evidenced by formalin test 3 hours after anesthesia onset, thus encouraging the use of isoflurane in experimental stroke models.

Bupivacaine, a common local anesthetic, causes serious nerve injury, especially in diabetic patients, as high glucose has been reported to enhance bupivacaine-induced neurotoxicity. However, the key regulator for synergism remains unknown. To our surprise, the expression of repair protein Ku70 is suppressed, while the high-glucose environment induces DNA oxidative damage in neurons. Here, we aim to investigate whether the inhibition of Ku70 by high-glucose conditions aggrandized bupivacaine-induced DNA damage. Consistent with previous results, bupivacaine induced reactive oxygen species production and upregulated Ku70 and cleaved caspase-3 expressions at both transcript and protein levels and ultimately caused nucleic acid damage and apoptosis in human neuroblastoma (SH-SY5Y) cells. High-glucose treatment inhibited the expression of Ku70 and enhanced bupivacaine-induced neurotoxicity. In contrast, the overexpression of Ku70 mitigated DNA damage and apoptosis triggered by bupivacaine and high glucose. In conclusion, our data indicated that local anesthetics may aggravate nerve toxicity in a high-glucose environment.

Demand is increasing for safer inhalational anesthetics for use in pediatric anesthesia. In this regard, researchers have debated whether isoflurane is more toxic to the developing brain than desflurane. In the present study, we compared the effects of postnatal exposure to isoflurane with those of desflurane on long-term cognitive performance and investigated the role of the Akt/GSK3β signaling pathway. Postnatal day 6 (P6) mice were exposed to either isoflurane or desflurane, after which the phosphorylation levels of Akt/GSK3β and learning and memory were assessed at P8 or P31. The phosphorylation levels of Akt/GSK3β and learning and memory were examined after intervention with lithium. We found that isoflurane, but not desflurane, impaired spatial learning and memory at P31. Accompanied by behavioral change, only isoflurane decreased p-Akt (ser473) and p-GSK3β (ser9) expressions, which led to GSK3β overactivation. Lithium prevented GSK3β overactivation and alleviated isoflurane-induced cognitive deficits. These results suggest that isoflurane is more likely to induce developmental neurotoxicity than desflurane in context of multiple exposures and that the Akt/GSK3β signaling pathway partly participates in this process. GSK3β inhibition might be an effective way to protect against developmental neurotoxicity.

Topical delivery of local anesthetics (LAs) is commonly used to decrease painful sensations, block pain throughout procedures, and alleviate pain after surgery. Dermal and/or transdermal delivery of LAs has other advantages, such as sustained drug delivery and decreased systemic adverse effects. This study reports the development of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles coated with chitosan for the sustained release and topicality of benzocaine (BZC) and topical delivery. BZC PLGA nanoparticles or nonencapsulated drugs were further incorporated into Poloxamer hydrogels (Pluronic™ F-127). The nanoparticles showed a mean diameter of 380 ± 4 nm, positive zeta potential after coating with chitosan (23.3 ± 1.7 mV), and high encapsulation efficiency (96.7 ± 0.02%). Cellular viability greater than 70% for both fibroblasts and keratinocytes was observed after treatment with nanoparticles, which is in accordance with the preconized guidelines for biomedical devices and delivery systems. Both the nanoparticles and hydrogels were able to modulate BZC delivery and increase drug permeation when compared to the nonencapsulated drug. Furthermore, the incorporation of limonene into hydrogels containing BZC-loaded nanoparticles increased the BZC permeation rates. Non-Newtonian and pseudoplastic behaviors were observed for all hydrogel nanoformulations with or without nanoparticles. These results demonstrate that the hydrogel-nanoparticle hybrids could be a promising delivery system for prolonged local anesthetic therapy.

Electroencephalogram (EEG) signal analysis is commonly employed to extract information on the brain dynamics. It mainly targets brain status and communication, thus providing potential to trace differences in the brain's activity under different anesthetics. In this article, two kinds of gamma-amino butyric acid (type A -GABAA) dependent anesthetic agents, propofol and desflurane (28 and 23 patients), were studied and compared with respect to EEG spectrogram dynamics. Hilbert-Huang Transform (HHT) was employed to compute the time varying spectrum for different anesthetic levels in comparison with Fourier based method. Results show that the HHT method generates consistent band power (slow and alpha) dominance pattern as Fourier method does, but exhibits higher concentrated power distribution within each frequency band than the Fourier method during both drugs induced unconsciousness. HHT also finds slow and theta bands peak frequency with better convergence by standard deviation (propofol-slow: 0.46 to 0.24; theta: 1.42 to 0.79; desflurane-slow: 0.30 to 0.25; theta: 1.42 to 0.98) and a shift to relatively lower values for alpha band (propofol: 9.94 Hz to 10.33 Hz, desflurane 8.44 Hz to 8.84 Hz) than Fourier one. For different stage comparisons, although HHT shows significant alpha power increases during unconsciousness stage as the Fourier did previously, it finds no significant high frequency (low gamma) band power difference in propofol whereas it does in desflurane. In addition, when comparing the HHT results within two groups during unconsciousness, high beta band power in propofol is significantly larger than that of desflurane while delta band power behaves oppositely. In conclusion, this study convincingly shows that EEG analyzed here considerably differs between the HHT and Fourier method.