Search Results (16)

An understanding of snake venom pharmacokinetics is essential for determining clinical outcomes of envenoming and developing therapeutic approaches to the treatment of envenoming, especially regarding the timing and optimal dosage of antivenom administration. Daboia siamensis (Eastern Russell’s viper) envenoming causes systemic coagulopathy and severe hemorrhage including acute kidney injury. These toxic outcomes can be diminished by the administration of high quantities of Russell’s viper antivenom. This study aimed to determine the correlation between the clinical profiles of D. siamensis envenomed patients and experimental data by measuring plasma venom concentration and conducting histopathological analyses of heart, kidney, and liver tissues in rats 6 h after experimental D. siamensis envenomation. Intramuscular (i.m.) administration of D. siamensis venom to anesthetized rats (200 µg/kg) resulted in a rapid absorption of venom which reached a peak concentration at 60 min before declining and then plateauing. Urine samples detected 209.3 ± 21.6 ng/mL of D. siamensis venom following i.m. administration at 6 h. Histopathological studies showed morphological changes in heart, kidney, and liver tissues following 3 h experimental envenoming and exhibited a higher degree of severity at 6 h. A retrospective study of the clinical profile and laboratory examination of Russell’s viper envenomed patients in Central Thailand was also evaluated, showing that systemic coagulopathy and local effects were commonly observed in the early stage of D. siamensis envenoming. An abnormal increase in creatinine levels was found in 13.6% of the population. Early administration of specific antivenom within 1–2 h following envenoming is highly recommended to prevent life-threatening outcomes such as severe coagulation and acute kidney injury. Full article

Background: Using hydrogels for the controlled release of drugs is beneficial for patients, who then receive the proper dose of the medicinal substance. In addition, the formulation can provide more consistent drug absorption while reducing the frequency of dosing. Objectives: The aim of this investigation is to propose a novel HA (sodium hyaluronate)-based hydrogel for intra-articular injection doped with synthetic polymers and incorporated with bupivacaine hydrochloride (Bu) as a local anesthetic. The other aim of this study is to reveal the effects of the formulation’s ingredients on its viscosity and the relationship between the hydrogel’s viscosity and drug release. Methods: First, HA-based hydrogels doped with synthetic polymers and incorporated with Bu were prepared. A study of the hydrogels’ viscosities was performed using a rotational viscometer. Release tests were carried out by employing a paddle-over-disk apparatus following the USP/Ph.Eur guidelines. The drug concentrations in the acceptor fluid were analyzed spectrophotometrically. Results: It was found that the viscosity of the hydrogels doped with synthetic polymers was higher than the viscosity of the hydrogels made with only HA. The viscosity of the hydrogels doped with AX (ammonium acryloyldimethyltaurate/VP copolymer) was the highest, measuring 6750 ± 160 cP and 12623 ± 379 cP with and without Bu, respectively. The results of the kinetic experiment indicate that the Higuchi and Korsmeyer–Peppas models best described the drug release. Bu was released the most slowly from the formulation doped with AX. The release rate constants obtained from the Higuchi and Korsmeyer–Peppas models were k_H = 4.4 ± 0.2 mg × min^−1/2 and k_K-P = 3.4 ± 0.2 × 10⁻² min^–N, respectively. The half-release time, calculated using the Higuchi model, was the longest for the formulation doped with AX, at 199.5 ± 17.6 min. Conclusions: This indicates that the incorporation of AX into the hydrogel may prolong the drug dissolution. The hydrogel doped with AX was the optimal formulation for the controlled release of Bu. Full article

Background: Pediatric regional anesthesia has been driven by the gradual rise in the adoption of opioid-sparing strategies and the growing concern over the possible adverse effects of general anesthetics on neurodevelopment. Nonetheless, performing regional anesthesia studies in a pediatric population is challenging and accounts for the scarce evidence. This study aimed to review the scientific foundation of studies in cadavers to assess regional anesthesia techniques in children. Methods: We searched the following databases MEDLINE, EMBASE, and Web of Science. We included anatomical cadaver studies assessing peripheral nerve blocks in children. The core data collected from studies were included in tables and comprised block type, block evaluation, results, and conclusion. Results: The search identified 2409 studies, of which, 16 were anatomical studies on the pediatric population. The techniques evaluated were the erector spinae plane block, ilioinguinal/iliohypogastric nerve block, sciatic nerve block, maxillary nerve block, paravertebral block, femoral nerve block, radial nerve block, greater occipital nerve block, infraclavicular brachial plexus block, and infraorbital nerve block. Conclusion: Regional anesthesia techniques are commonly performed in children, but the lack of anatomical studies may result in reservations regarding the dispersion and absorption of local anesthetics. Further anatomical research on pediatric regional anesthesia may guide the practice. Full article

Background and Objectives: Redistribution hypothermia occurs during anesthesia despite active intraoperative warming. Prewarming increases the heat absorption by peripheral tissue, reducing the central to peripheral heat gradient. Therefore, the addition of prewarming may offer a greater preservation of intraoperative normothermia as compared to intraoperative warming only. Materials and Methods: A single-center clinical trial of adults scheduled for non-cardiac surgery. Patients were randomized to receive or not a prewarming period (at least 10 min) with convective air devices. Intraoperative temperature management was identical in both groups and performed according to a local protocol. The primary endpoint was the incidence, the magnitude and the duration of hypothermia (according to surgical time) between anesthetic induction and arrival at the recovery room. Secondary outcomes were core temperature on arrival in operating room, surgical site infections, blood losses, transfusions, patient discomfort (i.e., shivering), reintervention and hospital stay. Results: In total, 197 patients were analyzed: 104 in the control group and 93 in the prewarming group. Core temperature during the intra-operative period was similar between groups (p = 0.45). Median prewarming lasted 27 (17–38) min. Regarding hypothermia, we found no differences in incidence (controls: 33.7%, prewarming: 39.8%; p = 0.37), duration (controls: 41.6% (17.8–78.1), prewarming: 45.2% (20.6–71.1); p = 0.83) and magnitude (controls: 0.19 °C · h⁻¹ (0.09–0.54), prewarming: 0.20 °C · h⁻¹ (0.05–0.70); p = 0.91). Preoperative thermal discomfort was more frequent in the prewarming group (15.1% vs. 0%; p < 0.01). The interruption of intraoperative warming was more common in the prewarming group (16.1% vs. 6.7%; p = 0.03), but no differences were seen in other secondary endpoints. Conclusions: A preoperative prewarming period does not reduce the incidence, duration and magnitude of intraoperative hypothermia. These results should be interpreted considering a strict protocol for perioperative temperature management and the low incidence of hypothermia in controls. Full article

Teodorico Borgognoni was born in Lucca in 1205 and was appointed bishop of Bitonto and Cervia in 1262 and 1270. Following his father, he learned the art of surgery and collected relevant recipes in his most important work, entitled Cyrurgia seu filia principis. Among the disciplines reported in this work, the most interesting and innovative is anesthesia. The recipes in this field contribute to Borbognoni’s consideration as the forerunner of modern anesthesia. Such recipes have been reported in other manuscripts from the Middle Ages, like Manuscript No. 1939. In the present work, we investigate the traditional preparations handed down in this manuscript, focusing on type of preparation and botanical ingredients. The results highlight that exploited ingredients can be divided into three groups: the first comprises plants already known for their narcotic effects, the second includes ingredients acting as an adjuvant for absorption or reducing the metabolism, and the last group includes ingredients not associated with biological activity to explain their presence in anesthetic recipes. This third group is of particular interest for future biological investigations. Our goal is to rekindle attention to the work of Teodorico Borgognoni on traditional preparation for anesthetic purposes: a topic often underestimated by ethnobotanical surveys. Full article

Inhalational anesthesia is supplied through an assisted ventilation system. It is mostly composed of xenon or nitrous oxide, halogenated hydrocarbons (HHCs), and oxygen. In order to reduce costs of the anesthesia compounds, the remaining anesthetics present in exhalation are recycled and reused, in order to minimize the amount of fresh anesthesia. An alkali hydroxide mixture (called soda lime) is employed in order to remove CO₂ from the exhalation. However toxic compounds may be formed during the reaction of soda lime with halogenated hydrocarbons. Ionic liquids (ILs) have several advantages such as non-volatility, functionality, high carbon solubility, and low energy requirements for regeneration. In the framework of this research, carbon dioxide removal with ionic liquids has been numerically studied. COMSOL multi-physics finite element software has been applied. It solves the continuity, fluid flow, and diffusion equations. A new algorithm has been developed for calculating the infrared (IR) radiation absorption of CO₂. Its absorption coefficient has wavelength-dependent properties. The gaseous absorption coefficient has been calculated by using HITRAN spectral database. It has been found that the CO₂ is absorbed almost completely by the 1-ethyl-3-methylimidazolium dicyanamide ([emim][DCA]) ionic liquid after a period of 1000 s. It has been shown that the absorption coefficient of CO₂ can be neglected in the interval below 1.565 μm, and then at 1.6 μm, it increases to the same order as that for CO. Thus, it is possible to detect CO₂ by applying a laser diode which is capable to transmit IR radiation at a wavelength of 1.6 μm. This time period is a function of the diffusion coefficient of the CO₂ in the membrane and in the ionic liquid. Full article

Biodetoxification using intravenous lipid emulsion (ILE) in acute poisoning is of growing interest. As well as for local anesthetics, ILE is currently used to reverse toxicity caused by a broad-spectrum of lipophilic drugs. Both pharmacokinetic and pharmacodynamic mechanisms have been postulated to explain its possible benefits, mainly combining a scavenging effect called “lipid sink” and cardiotonic activity. Additional mechanisms based on ILE-attributed vasoactive and cytoprotective properties are still under investigation. Here, we present a narrative review on lipid resuscitation, focusing on the recent literature with advances in understanding ILE-attributed mechanisms of action and evaluating the evidence supporting ILE administration that enabled the international recommendations. Many practical aspects are still controversial, including the optimal dose, the optimal administration timing, and the optimal duration of infusion for clinical efficacy, as well as the threshold dose for adverse effects. Present evidence supports the use of ILE as first-line therapy to reverse local anesthetic-related systemic toxicity and as adjunct therapy in lipophilic non-local anesthetic drug overdoses refractory to well-established antidotes and supportive care. However, the level of evidence is low to very low, as for most other commonly used antidotes. Our review presents the internationally accepted recommendations according to the clinical poisoning scenario and provides the precautions of use to optimize the expected efficacy of ILE and limit the inconveniences of its futile administration. Based on their absorptive properties, the next generation of scavenging agents is additionally presented. Although emerging research shows great potential, several challenges need to be overcome before parenteral detoxifying agents could be considered as an established treatment for severe poisonings. Full article

Multidrug-resistant bacteria can lead to skin wound infections, pain and long-term treatment. The development of high-performance dressings for the treatment of infected skin wounds represents a necessary requirement. In this paper it was designed and synthesized adhesive hydrogel films containing active agents such as hyaluronic acid (HA) and lidocaine, as local anesthetic. HA is an extremely effective and long-lasting moisturizer, biocompatible, with a regenerating effect, promoting the regeneration of damaged skin. lidocaine has been incorporated to relieve acute pain and improve patient comfort and endurance. Films without HA and lidocaine were also produced as control sample. The successful synthesis of films obtained at room temperature, from aqueous solutions, was also confirmed by Fourier transform infrared analysis, X-ray diffraction and scanning electron analysis. Water absorption, adhesion and mechanical strength of the films-based hydrogel are improved with the introduction of HA and lidocaine, leading to the rapid skin wound healing process. The obtained materials will be used as promising materials able to restore the structural and functional properties of the skin. Wet adhesive backing films with good adhesion to skin, encapsulating HA with different molecular weights and lidocaine were developed to explore their potential to be used as a patch for painless treatment and healing of skin wounds. The cytocompatibility studies confirmed that the obtained films-based hydrogel have demonstrated no cytotoxic effect. Full article

Syzygium aromaticum (clove) has been used as a dental analgesic, an anesthetic, and a bioreducing and capping agent in the formation of metallic nanoparticles. The main objective of this study was to evaluate the antimicrobial effect in oral microorganisms of biogenic silver nanoparticles (AgNPs) formed with aqueous extract of clove through an ecofriendly method “green synthesis”. The obtained AgNPs were characterized by UV-Vis (ultraviolet-visible spectroscopy), SEM-EDS (scanning electron microscopy–energy dispersive X-ray spectroscopy), TEM (transmission electron microscopy), and ζ potential, while its antimicrobial effect was corroborated against oral Gram-positive and Gram-negative microorganisms, as well as yeast that is commonly present in the oral cavity. The AgNPs showed absorption at 400–500 nm in the UV-Vis spectrum, had an average size of 4–16 nm as observed by the high-resolution transmission electron microscopy (HR-TEM), and were of a crystalline nature and quasi-spherical form. The antimicrobial susceptibility test showed inhibition zones of 2–4 mm in diameter. Our results suggest that AgNPs synthesized with clove can be used as effective growth inhibitors in several oral microorganisms. Full article

Pain is a common symptom that impairs the quality of life for people around the world. Local anesthetics widely used for pain relief have a number of side effects, which makes the development of both new drugs and new ways to control their activity particularly important. Photopharmacology makes it possible to reduce the side effects of an anesthetic and control its biological activity in the body. The purpose of this work was to create a new light-controlled local anesthetic and study its biological activity in animals. A compound with a simple scheme of synthesis was chosen to shift the UV-Vis absorption band towards the visible range of the spectrum and was synthesized for the first time. Some computer calculations were performed to make sure that the aforementioned changes would not lead to loss of biological activity. The micellar form of the new compound was prepared, and in vivo biological studies were carried out in rabbits. The existence of a local anesthetic effect, which disappeared almost completely on irradiation with light (λ = 395 nm), was shown using the surface anesthesia model. Moreover, the possibility of multiple reversible changes in the biological activity of ethercaine under the action of light was demonstrated. The latter compound manifests no local irritating effect, either. The data obtained indicate the prospects for the development of new compounds based on azobenzene for light-controlled local anesthesia. Full article

This study investigated the cardiopulmonary effects and pharmacokinetics of dexmedetomidine (DEX) used as an adjunctive analgesic for regional anesthesia of the oral cavity with levobupivacaine in anesthetized dogs. Forty dogs were randomly assigned to four groups of 10 dogs. All dogs received levobupivacaine (4 blocks) with DEX IO (infraorbital block, n = 10) or IA (inferior alveolar block, n = 10) or placebo (PLC; n = 10) or DEX (n = 10) was injected intravenously (IV) after administration of levobupivacaine. The dose of DEX was always 0.5 µg/kg. Cardiopulmonary parameters were recorded, and blood was drawn for the quantification of DEX in plasma using LC-MS/MS. Heart rate was lower in all LB + DEX groups, while mean arterial pressure (MAP) was higher in the LB + DEX IV and LB + DEX IA groups compared to the LB + PLC IV group. Compared to DEX IV, IO and IA administration resulted in lower MAP up to 2 min after application. Absorption of DEX was faster at IO administration (C_max and T_max were 0.47 ± 0.08 ng/mL and 7.22 ± 1.28 min and 0.76 ± 0.09 ng/mL and 7.50 ± 1.63 min for the IO and IA block, respectively). The IA administration resulted in better bioavailability and faster elimination (t_1/2 was 63.44 ± 24.15 min and 23.78 ± 3.78 min for the IO and IA block, respectively). Perineural administration of DEX may be preferable because of the less pronounced cardiovascular response compared to IV administration. Full article

This case report describes a modified approach for a thoracic paravertebral block by performing a bilateral ultrasound-assisted injection of 12 mL of 0.5% levobupivacaine near the thoracic intervertebral foramen, combined with general anesthesia, in a patient who underwent emergent laparotomy for small intestinal volvulus. Two continuous catheter sets were used for a bilateral continuous block with levobupivacaine 0.25% at a rate of 5–8 mL/h. No complications during the execution of the block were recorded. No supplemental opioids were administered and the patient was hemodynamically stable, requiring no pharmacological cardiovascular support during surgery. At the end of the surgical procedure, the patient received a continuous flow of 0.2% levobupivacaine as postoperative analgesia, at a basal flow of 4 mL/h per each side, a bolus of 4 mL, and a lockout time of 60 min was used. The postoperative pain on the Numeric Rating Scale was 2 at rest and it was 4 in motion, without neurological or respiratory sequelae due to block in the first 72 h after surgery. Full article

The work reported here focuses on an evaluation of a novel heat stable formulation of a uterotonic peptide drug oxytocin involving stability testing under elevated temperatures and toxicokinetic response generated by sublingual (SL) administration in rabbits. The formulation was thermotolerant, maintaining the potency of oxytocin in the form of a fast-dissolving tablet at the end of 2-year storage at 30 °C/65% relative humidity with less than 5% loss in oxytocin content based on analytical high performance liquid chromatography (HPLC). The toxicokinetic results in rabbits showed that the fast-dissolving tablet was safe without any reactogenicity or toxicity associated with SL administration or the excipients present in the formulation. The SL route elicited rapid absorption of oxytocin in plasma within 5 min of administration although lower than intramuscular (IM) administration. IM resulted in area under the curve (AUC) values approximately 5 times higher than SL oxytocin. However, due to the limitations encountered during SL administration in an anesthetized rabbit model, the relevance of heat stable oxytocin formulation that has the flexibility to be adapted in different formats may warrant a human clinical study to determine whether therapeutically relevant plasma levels for treating postpartum hemorrhage can be generated via alternate non-injectable routes of administration. Full article

Reliable protocols for short-term anesthetics are essential to safeguard animal welfare during medical investigations. The aim of the study was to assess the adequacy and reliability of an anesthetic protocol and to evaluate physiological and clinical responses, in relation to the drug plasma concentrations, for pigs undergoing short-term anesthesia. A second aim was to see whether an intravenous dosage could prolong the anesthesia. The anesthesia was induced by an intramuscular injection of dexmedetomidine, tiletamine-zolazepam, and butorphanol in 12 pigs. In six of the pigs, a repeated injection intravenously of one-third of the initial dose was given after one hour. The physiological and clinical effects from induction to recovery were examined. Plasma concentrations of the drugs were analyzed and pharmacokinetic parameters were calculated. Each drug’s absorption and time to maximal concentration were rapid. All pigs were able to maintain spontaneous respiration. The route of administration did not alter the half-life of the drug. The results suggest that intramuscular administration of the four-drug combination provides up to two hours of anesthesia with stable physiological parameters and an acceptable level of analgesia while maintaining spontaneous respiration. A repeated intravenous injection may be used to extend the time of anesthesia by 30 min. Full article

In clinical practice, the catheter has to be placed at an accurate position during anesthesia administration. However, effectively guiding the catheter to the accurate position in deeper tissues can be difficult for an inexperienced practitioner. We aimed to address the current issues associated with catheter placement using a novel smart assistance system for blood vessel catheter placement. We used a hollow introducer needle embedded with dual wavelength (690 and 850 nm) optical fibers to advance the tip into the subclavian vessels in anesthetized piglets. The results showed average optical density changes, and the difference between the absorption spectra and hemoglobin concentrations of different tissue components effectively identified different tissues (p < 0.05). The radial basis function neural network (RBFNN) technique was applied to distinguish tissue components (the F-measure value and accuracy were 93.02% and 94%, respectively). Finally, animal experiments were designed to validate the performance of the proposed system. Using this system based on oximetry, we easily navigated the needle tip to the target vessel. Based on the experimental results, the proposed system could effectively distinguish different tissue layers of the animals. Full article