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Malignant hypothermia (MH) is a potentially fatal hypermetabolic reaction of skeletal muscle. It is an autosomal dominant disorder that generally occurs in people with RYR1, CACNA1S, or STAC3 mutations. And these genetic abnormalities often cause the imperfection of calcium release channels of skeletal muscle. The incidence of MH among different racial groups across the world ranges from approximately 1:5,000-1:250,000, but there is no national statistic MH incidence in China. It is not clear whether there are racial or regional differences in the incidence, but patients under 18 years old may be more affected. MH can be triggered by anesthetics, or other stimuli, such as strenuous exercise, heat-stroke, and emotional stress. While viral infection, statins, hyperglycemia, and muscle metabolic dysfunctions might accelerate the onset of MH. The onset of MH is insidious and rapid, with the preclinical stage characterized by rigidity of the masseter muscle, a high level of end-tidal carbon dioxide, and a sharp and persistent increase in body temperature. Medical history, family history, clinical presentation, in vitro caffeine-halothane contracture testing (IVCT/CHCT) and genetic testing are commonly diagnostic methods of MH. As soon as the onset of MH is suspected, immediate cessation of exposure to stimuli, call for professional support, and access to dantrolene are the highest priorities. For symptomatic treatment, "5C principles" were summarized as an algorithm to guide clinicians.

Introduction Malignant Hyperthermia (MH) is a pharmacogenetic, hereditary and autosomal dominant syndrome triggered by halogenates/succinylcholine. The In Vitro Contracture Test (IVCT) is the gold standard diagnostic test for MH, and it evaluates abnormal skeletal muscle reactions of susceptible individuals (earlier/greater contracture) when exposed to caffeine/halothane. MH susceptibility episodes and IVCT seem to be related to individual features. Objective To assess variables that correlate with IVCT in Brazilian patients referred for MH investigation due to a history of personal/family MH. Methods We examined IVCTs of 80 patients investigated for MH between 2004‒2019. We recorded clinical data (age, sex, presence of muscle weakness or myopathy with muscle biopsy showing cores, genetic evaluation, IVCT result) and IVCT features (initial and final maximum contraction, caffeine/halothane concentration triggering contracture of 0.2g, contracture at caffeine concentration of 2 and 32 mmoL and at 2% halothane, and contraction after 100 Hz stimulation). Results Mean age of the sample was 35±13.3 years, and most of the subjects were female (n=43 or 54%) and MH susceptible (60%). Of the 20 subjects undergoing genetic investigation, 65% showed variants in RYR1/CACNA1S genes. We found no difference between the positive and negative IVCT groups regarding age, sex, number of probands, presence of muscle weakness or myopathy with muscle biopsy showing cores. Regression analysis revealed that the best predictors of positive IVCT were male sex (+12%), absence of muscle weakness (+20%), and personal MH background (+17%). Conclusions Positive IVCT results have been correlated to male probands, in accordance with early publications. Furthermore, normal muscle strength has been confirmed as a significant predictor of positive IVCT while investigating suspected MH cases.

Silylated-acetylated cyclodextrin (CD) derivatives have recently been investigated, via nuclear magnetic resonance (NMR) spectroscopy, as chiral sensors for substrates that are endowed and devoid of fluorine atoms, and the importance of Si-F interaction in the discrimination phenomena has been assessed. Here, the contributions of both superficial interactions and inclusion processes were further evaluated by extending the records to other chiral fluorinated substrates of interest for pharmaceutical applications. Non-equivalences were measured for both the 1H and 19F resonances in equimolar mixtures with the CDs; the promising results also supported the use of chiral sensors in sub-stoichiometric amounts. Finally, the occurrence of inclusion processes was evaluated by analyzing the intermolecular dipolar interactions by means of ROESY (Rotating-frame Overhauser Enhancement Spectroscopy) experiments. The study confirmed that the γCD derivative is the best chiral solvating agent for the fluorinated substrates investigated, likely due to the higher number of silyl moieties that can be involved in Si-F interactions. The contribution of inclusion processes to the enantiodiscrimination was also confirmed by comparison with the α- and β-analogues. Overall, the CD derivatives proved to be able to discriminate fluorinated substrates even when used in sub-stoichiometric amounts.

Elevation of the head and expiratory negative airway pressure (ENAP) ventilation can both significantly alter cardiovascular hemodynamics. The impact of head-up tilt (HUT) position on mechanically regulated ENAP ventilation-induced hemodynamics was assessed in microminipigs under halothane anesthesia (n = 4) in the absence and presence of adrenergic blockade. Supine ENAP ventilation increased cardiac output, but decreased mean right atrial, systolic pulmonary arterial, and mean left atrial pressures without significantly altering heart rate or aortic pressure. With HUT, the magnitude of ENAP ventilation-induced reduction in right and left atrial pressures was attenuated. HUT minimally altered ENAP ventilation-induced increase in cardiac output and reduction in pulmonary arterial systolic pressure. In addition, with up to 10 cm of HUT there was a significant increase in mean right atrial pressure with and without the ENAP ventilation, whereas HUT did not alter the other hemodynamic variables irrespective of ENAP ventilation. These observations suggest that head elevation augments venous return from the brain irrespective of the ENAP ventilation. Additional studies with pharmacological adrenergic blockade revealed that ENAP ventilation-induced increases in cardiac output and decreases in pulmonary systolic pressure were minimally altered by sympathetic nerve activity, irrespective of the head position. However, the observed ENAP ventilation-induced decreases in right and left atrial pressures were largely dependent upon adrenergic activity. These experimental findings may provide insight into future clinical application of HUT and ENAP for patients with head injury and hypotension.

Although NMDA receptor antagonist memantine is considered to be better tolerated than cholinesterase inhibitors on treating Alzheimer's disease, several types of cardiovascular adverse events have been associated with memantine treatment, including hypertension, myocardial infarction, severe bradycardia and QT-interval prolongation. In order to clarify how memantine induces these cardiovascular adverse events, we assessed its electropharmacological effects using the halothane-anesthetized dogs (n = 4). Memantine hydrochloride was intravenously administered in doses of 0.01, 0.1 and 1 mg/kg over 10 min, providing subtherapeutic, clinically-relevant and supratherapeutic concentrations, respectively. The low to high doses increased the mean blood pressure and left ventricular contraction and enhanced the atrioventricular nodal conduction, suggesting an increase of sympathicotonic output from the central nervous system similarly to donepezil, which might induce myocardial ischemia in patients with coronary artery disease. Meanwhile, the high dose suppressed the intra-atrial conduction and the low to high doses inhibited the intra-ventricular conduction, indicating potential to induce severe bradycardic adverse event by advanced cardiac conduction block in susceptible patients. Memantine alone did not induce repolarization delay, indicating lack of risk for inducing torsade de pointes. Thus, these in vivo experimental findings may provide basic information to better understand the clinically observed adverse events of memantine.

The mitochondrial electron transport chain (mETC) contains molecular targets of volatile general anesthetics (VGAs), which places carriers of mutations at risk for anesthetic complications. TheND-2360114andmt:ND2del1lines of fruit flies (Drosophila melanogaster) that carry mutations in core subunits of Complex I of the mETC, replicate numerous characteristics of Leigh syndrome (LS) caused by orthologous mutations in mammals and serve as models of LS.ND-2360114flies are behaviorally hypersensitive to volatile anesthetic ethers and develop an age- and oxygen-dependent anesthetic-induced neurotoxicity (AiN) phenotype after exposure to isoflurane but not to the related anesthetic sevoflurane. The goal of this paper was to investigate whether the alkane volatile anesthetic halothane and other mutations in Complex I and in Complexes II-V of the mETC cause AiN. We found that (i)ND-2360114andmt:ND2del1were susceptible to toxicity from halothane; (ii) in wildtype flies halothane was toxic under anoxic conditions; (iii) alleles of accessory subunits of Complex I predisposed to AiN; and (iv) mutations in Complexes II-V did not result in an AiN phenotype. We conclude AiN is neither limited to ether anesthetics nor exclusive to mutations in core subunits of Complex I.Previous presentationsparts of the data were presented in abstract form at the 63rdAnnual Drosophila Research Conference in San Diego, March 2022.

As the number of radiotherapy and radiology diagnostic procedures increases from year to year, so does the use of general volatile anaesthesia (VA). Although considered safe, VA exposure can cause different adverse effects and, in combination with ionising radiation (IR), can also cause synergistic effects. However, little is known about DNA damage incurred by this combination at doses applied in a single radiotherapy treatment. To learn more about it, we assessed DNA damage and repair response in the liver tissue of Swiss albino male mice following exposure to isoflurane (I), sevoflurane (S), or halothane (H) alone or in combination with 1 or 2 Gy irradiation using the comet assay. Samples were taken immediately (0 h) and 2, 6, and 24 h after exposure. Compared to control, the highest DNA damage was found in mice receiving halothane alone or in combination with 1 or 2 Gy IR treatments. Sevoflurane and isoflurane displayed protective effects against 1 Gy IR, while with 2 Gy IR the first adverse effects appeared at 24 h post-exposure. Although VA effects depend on liver metabolism, the detection of unrepaired DNA damage 24 h after combined exposure with 2 Gy IR indicates that we need to look further into the combined effects of VA and IR on genome stability and include a longer time frame than 24 h for single exposure as well as repeated exposure as a more realistic scenario in radiotherapy treatment., Kako se broj radioterapijskih i radioloških dijagnostičkih postupaka iz godine u godinu povećava, tako raste i primjena hlapljivih anestetika za opću anesteziju. Iako se smatralo sigurnim, izlaganje hlapljivim anesteticima može izazvati različite štetne učinke, a u kombinaciji s ionizirajućim zračenjem može izazvati i sinergijske učinke. Međutim, malo se zna o oštećenju DNA koje uzrokuje ova kombinacija u dozama primijenjenima u jednom izlaganju u radioterapiji. Kako bismo saznali više o tome, alkalnim komet-testom analizirali smo oštećenje DNA i odgovor na popravak u jetrenom tkivu muških Swiss albino miševa nakon izlaganja samo izofluranu, sevofluranu ili halotanu, odnosno u kombinaciji sa zračenjem od 1 ili 2 Gy. Uzorci su uzeti odmah (0 h) te 2, 6 i 24 sata nakon izlaganja. U usporedbi s kontrolom, najveća oštećenja DNA utvrđena su u miševa koji su primili halotan, sam ili u kombinaciji sa zračenjem od 1 ili 2 Gy. Sevofluran i izofluran pokazali su zaštitne učinke nakon izlaganja zračenju od 1 Gy, a pri 2 Gy prve nuspojave pojavile su se 24 sata nakon izlaganja. Iako učinci hlapljivih anestetika ovise o metabolizmu jetre, otkrivanje nepopravljenog oštećenja DNA 24 sata nakon kombinirane izloženosti sa zračenjem od 2 Gy upućuje na to da trebamo nastaviti istraživati kombinirane učinke hlapljivih anestetika i ionizirajućega zračenja na stabilnost genoma i obuhvatiti šire razdoblje nakon jednokratne izloženosti (duže od 24 sata). Također treba obuhvatiti višekratna izlaganja kao realističniji scenarij u liječenju radioterapijom.

The Solubility of Halothane in Blood and Tissue Homogenates. By Larson CP, Eger EI, Severinghaus JW. Anesthesiology 1962; 23:349–55. Measured samples of human and bovine blood, human hemoglobin, and tissue homogenates from human fat and both human and bovine liver, kidney, muscle, whole brain, and separated gray and white cortex were added to stoppered 2,000-ml Erlenmeyer flasks. To each flask, 0.1 ml of liquid halothane was added under negative pressure using a calibrated micropipette. After the flask was agitated for 2 to 4 h to achieve equilibrium between the gas and blood or tissue contents, a calibrated infrared halothane analyzer was used to measure the concentration of halothane vapor. Calculated partition coefficients ranged from 0.7 for water to 2.3 for blood and from 3.5 for human or bovine kidney to 6 for human whole brain or liver and 8 for human muscle. Human peritoneal fat had a value of 138. The human blood–gas partition coefficient of 2.3 as determined by this equilibration method was well below the previously published value of 3.6.

Mutations in the type 1 ryanodine receptor (RyR1), a Ca2+ release channel in skeletal muscle, hyperactivate the channel to cause malignant hyperthermia (MH) and are implicated in severe heat stroke. Dantrolene, the only approved drug for MH, has the disadvantages of having very poor water solubility and long plasma half-life. We show here that an oxolinic acid-derivative RyR1-selective inhibitor, 6,7-(methylenedioxy)-1-octyl-4-quinolone-3-carboxylic acid (Compound 1, Cpd1), effectively prevents and treats MH and heat stroke in several mouse models relevant to MH. Cpd1 reduces resting intracellular Ca2+, inhibits halothane- and isoflurane-induced Ca2+ release, suppresses caffeine-induced contracture in skeletal muscle, reduces sarcolemmal cation influx, and prevents or reverses the fulminant MH crisis induced by isoflurane anesthesia and rescues animals from heat stroke caused by environmental heat stress. Notably, Cpd1 has great advantages of better water solubility and rapid clearance in vivo over dantrolene. Cpd1 has the potential to be a promising candidate for effective treatment of patients carrying RyR1 mutations., Mutations in ryanodine receptor 1 (RyR1), a Ca2+ release channel in skeletal muscle, cause malignant hyperthermia (MH) and are involved in heat stroke. Here, the authors show that an oxolinic acid-derivative RyR1 inhibitor effectively prevents and treats MH and heat stroke in various MH mouse models.

Anaesthetic agents and doses used can significantly impact cerebrocortical responsiveness as assessed by electroencephalography (EEG). The objective of this study was to evaluate the effect of three different halothane concentrations on the EEG of Rock Doves using measures of frequency distribution and burst suppression. Eight healthy Rock Doves (Columba livia) were anaesthetized with halothane in oxygen, their tracheas intubated and their lungs mechanically ventilated. Five minutes of EEG were recorded at three multiples of minimum anaesthetic concentration (MAC), 1× MAC (1.6%), 1.5× MAC (2.4%) and 2× MAC (3.2%), presented in ascending then descending order. Fast Fourier transformation of the raw EEG record gave the median frequency (F50), spectral edge frequency (F95) and the total power (Ptot). Burst suppression, expressed as inactive compared to active EEG (%), was calculated on a representative two-minute section of the raw EEG. Data were analysed using repeated-measures one-way ANOVA with Tukey post hoc correction for comparison of 1×, 1.5× and 2× MAC. Three of eight birds demonstrated negligible (&lt, 1%) burst suppression. No effect of halothane concentration on burst suppression incidence was seen. A significant decrease in all measured frequency variables (F50, p = 0.04, F95p = 0.02, Ptotp &lt, 0.0001) occurred between 1× and 2× MAC. Halothane anaesthesia at MAC multiples of 1×, 1.5× and 2× in the Rock Dove can be considered suitable where cortical responsiveness is desired.

Die maligne Hyperthermie (MH) ist eine lebensbedrohliche hypermetabolische Krise. Sie kann im Verlauf einer Allgemeinanästhesie durch die Verwendung bestimmter Narkosegase auftreten. Zu den Symptomen zählen unter anderem eine generalisierte Muskelrigidität und ein rapider Anstieg der Körpertemperatur. Dies kann zu schweren Folgeschäden oder zum Tod führen. Ursächlich für die MH ist eine Störung der Kalziumhomöostase in den quergestreiften Skelettmuskelzellen. Eine zentrale Rolle spielt hierbei der Ryanodin-Rezeptor 1 (RyR1). Dieser Kanal ist für die myoplasmatische Freisetzung von intrazellulär gespeichertem Kalzium verantwortlich. In der folgenden Arbeit wurde die Änderung der Kalziumfreisetzung aus intrazellulären Speichern durch den Einfluss des Inhalationsanästhetikums Halothan an einem Mausmodell der MH näher untersucht. Besondere Aufmerksamkeit wurde dabei auf die Rolle einer Modulation des myoplasmatischen Membranpotentials gelegt.

Cell-cell communication via gap junction channels is known to be inhibited by the anesthetics heptanol, halothane and isoflurane; however, despite numerous studies, the mechanism of gap junction channel gating by anesthetics is still poorly understood. In the early nineties, we reported that gating by anesthetics is strongly potentiated by caffeine and theophylline and inhibited by 4-Aminopyridine. Neither Ca

The immune system of 90-day old piglets of SM-1 Novosibirsk breed piglets depends on sex and stress-reactivity. Stress-reactivity was measured using halothane test. The immunologic testing was performed 30 days after weaning. Our results show that overall piglet immune system demonstrated high proliferative activity of T- and B- immunocompetent cells with active formation of mature active T-and B-lymphocytes and did not show signs of immunosuppression. Compared to guilts, barrows had higher concentration of leucocytes, T-and B-lymphocytes, killer-supressor T-cells, activated and poorly differentiated T-lymphocytes. Gilts had higher production of inductor-helper T-cells, IgM and IgG when compared to barrows. Stress-resistant piglets had higher concentration of B-lymphocytes, IgM and IgG whereas stress-sensitive piglets had higher concentration of T-lymphocytes, supressor-killer T-cells and thymus T-lymphocytes. Gilts had higher concentration of inductor-helper T-cells than killer-supressor T-cells. Gilts overall had intensive antibody synthesis, however, stress-resistant gilts had higher IgG synthesis compared to stress-sensitive gilts. In barrows immature T-lymphocytes differentiated mainly into killer-supressor T-cells. The adaptivity of barrow immune system was characterized by high circulatory B-lymphocytes and IgM. Stress-sensitive barrows had lower antibody synthesis levels and higher T-lymphophoesis compared to stress-resistant barrows.

Induction of anesthesia using an inhalation agent remains a fundamental technique due to its rapid induction and emergence. Sevoflurane is preferred over halothane for its faster induction of anesthesia and lesser complications. Studies on sevoflurane in pediatrics have established it as safe and effective. However, its effectiveness in adults is very limited. Hence, this study was conducted to compare the induction and intubating conditions, hemodynamic profiles, and emergence from anesthesia with sevoflurane and halothane in adults and pediatric patients. This randomized clinical study was carried out for a period of 2 years (November 2006-September 2008) in the Anesthesiology Department of a Krishna Institute of Medical Sciences (Deemed to be) University. Eighty patients of American Society of Anesthesiologists Class I and II were randomly assigned to halothane group and sevoflurane group with 40 patients in each group. Patients were induced and intubated with increasing concentrations of halothane from 0.5% to 5% and sevoflurane 1% to 7% in 50% nitrous oxide and 50% oxygen mixture. Recordings of vitals including induction and intubation time, recovery characteristics, and recovery and discharge time was also recorded. There was a statistically significant difference between sevoflurane and halothane in the induction and intubation time indicating that sevoflurane had faster induction and shorter intubation time compared to that of halothane. Patients in halothane group had more incidence of coughing, intolerance, salivation, breathe holding, rigidity, and movement as compared to sevoflurane group. The mean time to consciousness, response to verbal commands, orientation, and recovery room discharge time was significantly shorter in sevoflurane group as compared to halothane group. Sevoflurane can be a suitable alternative to halothane for induction of anesthesia in patients with a shorter induction and intubation time with better hemodynamic stability. This study was approved by the Institutional Ethics Committee (KIMSDU/IEC-307/028/14/11/2006).

We assessed concentration-dependent effects of halothane or isoflurane inhalation on the electrocardiographic and hemodynamic variables using a cross-over design in intact beagle dogs (n = 4). Elevation of inhaled halothane from 1.0% to 2.0% or isoflurane from 1.5% to 2.5% decreased the mean blood pressure and prolonged the QRS width without significantly altering the heart rate, PR interval or QT interval. However, the observed changes disappeared after regressions of both anesthetic conditions to their initial settings. These results indicate that hypotension-induced, reflex-mediated increase of sympathetic tone may have counterbalanced the direct negative chronotropic, dromotropic and repolarization slowing effects of the anesthetics.

We compared dl-sotalol-induced electrocardiographic responses in intact dogs using a repeated-measures design among 1% halothane anesthesia, 1.5% isoflurane anesthesia with nitrous oxide (N2O), and conscious state to clarify influences of the anesthetics (n = 4). Basal PR interval was longer in halothane than either in isoflurane with N2O or in conscious state, reflecting sympathetic nerve suppression for the atrioventricular node by halothane. Both anesthetics exhibited longer basal QRS width than conscious state, suggesting their ventricular INa inhibition. Also, both anesthetics showed longer basal QT interval, QTcF and Tpeak-Tend than conscious state, indicating their ventricular IKr inhibition. Meanwhile, dl-sotalol prolonged PR interval similarly in isoflurane with N2O and in conscious state, which was less great in halothane, suggesting further sympathetic nerve suppression for the atrioventricular node might be limited in halothane. dl-Sotalol prolonged QT interval and QTcF >3 times greater in either of the anesthetics than in conscious state; moreover, dl-sotalol prolonged Tpeak-Tend similarly in both anesthetics, but hardly altered it in conscious state; indicating isoflurane with N2O as well as halothane may have reduced the repolarization reserve to increase the sensitivity of ventricle toward IKr suppression. Thus, isoflurane with nitrous oxide could be useful for in vivo IKr assay like halothane.

Myocardial protection with volatile anesthetic agents have been suggested by multiple studies. These studies, however, are scattered and are often limited to a particular aspect of cardiac anesthesia. Older inhalational agents like halothane is known to cause significant hepatic damage in patients undergoing long duration surgeries while isoflurane is known to have marked vasodilating properties that also affects the coronary arteries leading to coronary “steal” phenomenon. Additionally, newer agents, like sevoflurane and desflurane, have shown more prominent cardioprotective effects than older agents. We searched ScholarOne, Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library. The medical subject headings (MeSH) terms “anaesthesia, inhalational,” “anaesthesia, intravenous, or TIVA,” and “Cardiac anaesthesia or Cardiac Surgery” were used. Additional studies were identified by review of the reference sections of all eligible studies. The aim of this review article is to bring together the evidences with newer inhalational agents and provide a holistic view of their benefits and shortcomings in cardiac anesthesia.

An efficient and convenient method for the synthesis of structurally unique and highly functionalized aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers has been developed. This approach exhibits a broad reaction scope, a simple operation and without the need of any expensive transition-metal catalyst, highly toxic or corrosive reagents. Notably, we demonstrate the potential utility of halothane for the synthesis of aryl gem-difluoroalkyl ethers containing the bromochloromethyl group.

Lamotrigine has been used for patients with epilepsy and/or bipolar disorder, overdose of which induced the hypotension, elevation of the atrial pacing threshold, cardiac conduction delay, wide complex tachycardia, cardiac arrest and Brugada-like electrocardiographic pattern. To clarify how lamotrigine induces those cardiovascular adverse events, we simultaneously assessed its cardiohemodynamic and electrophysiological effects using the halothane-anesthetized dogs (n = 4). Lamotrigine was intravenously administered in doses of 0.1, 1 and 10 mg/kg/10 min under the monitoring of cardiovascular variables, possibly providing subtherapeutic to supratherapeutic plasma concentrations. The low or middle dose of lamotrigine did not alter any of the variables. The high dose significantly delayed the intra-atrial and intra-ventricular conductions in addition to the prolongation of ventricular effective refractory period, whereas no significant change was detected in the other variables. Lamotrigine by itself has relatively wide safety margin for cardiohemodynamics, indicating that clinically reported hypotension may not be induced through its direct action on the resistance arterioles or capacitance venules. The electrophysiological effects suggested that lamotrigine can inhibit Na+ channel in the in situ hearts. This finding may partly explain the onset mechanism of lamotrigine-associated cardiac adverse events in the clinical cases. In addition, elevation of J wave was induced in half of the animals, suggesting that lamotrigine may have some potential to unmask Brugada electrocardiographic genotype in susceptible patients.

Dexmedetomidine is a most potent α-2 adrenergic selective agonist. It is one of the components of the racemic mixture of two enantiomers of medetomidine. It has a selectivity ratio of 1620/1(α 2/ α1), which is 5–10 times higher than that for detomidine (260/1) and xylazine (160/1. Dexmedetomidine produces consistent sedation, anxiolysis and muscle relaxation, which makes it a popular sedative agent in veterinary medicine. In veterinary practice, it is used for premedication and as an adjunct to general anaesthesia in several species. Similar to other alpha-2 agonists it exerts its effect through the action on alpha-2 adrenergic receptors. The sedative and anxiolytic effects of α-2 agonists are mediated by agonism of supraspinal autoreceptors situated in the pons, whereas analgesic effects are mediated by agonism of heteroreceptors located in the dorsal horn of the spinal cord. Dexmedetomidine causes a dose-dependent redistribution of blood flow and preserves blood flow to the most vital organs at the expense of organs like skin and pancreases and this distribution of blood flow is not affected by the type of anaesthesia. The pattern of cardiovascular changes may be affected by the dose used and the type of anaesthetic combined with dexmedetomidine. Most anaesthetic drugs, such as propofol, thiopental, isoflurane and halothane have cardiovascular and respiratory side effects that are dose-dependent. Dexmedetomidine is a good anaesthetic adjuvant for general anaesthesia which reduces intra-operative isoflurane consumption provides analgesic-sparing effect without affecting postoperative recovery profile and improved cardiovascular stability and contributes to the provision of balanced anaesthesia.

Studies on fluorinated inhalation anesthetics, including synthesis, physical chemistry and pharmacology, have been summarized in this review. Retrospecting the history of inhalation anesthetics revealed their increasing reliance on fluorine and ether structures. Halothane causes a rare but severe immune-based hepatotoxicity, which was replaced by enflurane in the 1970s. Isoflurane replaced enflurane in the 1980s, showing modest advantages (e.g. lower solubility, better metabolic stability, and without convulsive predisposition). Desflurane and sevoflurane came into use in the 1990s, which are better anesthetics than isoflurane (less hepatotoxicity, lower solubility, and/or markedly decreased pungency). However, they are still less than perfect. To gain more ideal inhalation anesthetics, a large number of fluorinated halocarbons, polyfluorocycloalkanes, polyfluorocycloalkenes, fluoroarenes, and polyfluorooxetanes, were prepared and their potency and toxicity were evaluated. Although the pharmacology studies suggested that some of these agents produced anesthesia, no further studies were continued on these compounds because they showed obvious lacking as anesthetics. Moreover, the anesthetic activity cannot be simply predicted from the molecular structures but has to be inferred from the experiments. Several regularities were found by experimental studies: 1) the potency and toxicity of the saturated linear chain halogenated ether are enhanced when its molecular weight is increased; 2) the margin of safety decreases and the recovery time is prolonged when the boiling point of the candidate increases; and 3) compounds with an asymmetric carbon terminal exhibit good anesthesia. Nevertheless, the development of new inhalation anesthetics, better than desflurane and sevoflurane, is still challenging not only because of the poor structure/activity relationship known so far but also due to synthetic issues.

Background Statin intake is associated with muscular side effects, among which the unmasking of latent myopathies and of malignant hyperthermia (MH) susceptibility have been reported. These findings, together with experimental data in small animals, prompt speculation that statin therapy may compromise the performance of skeletal muscle during diagnostic in vitro contracture tests (IVCT). In addition, statins might reduce triggering thresholds in susceptible individuals (MHS), or exacerbate MH progression. We sought to obtain empirical data to address these questions. Methods We compared the responses of 3 different muscles from untreated or simvastatin treated MHS and non-susceptible (MHN) pigs. MHS animals were also invasively monitored for signs of impending MH during sevoflurane anesthesia. Results Muscles from statin treated MHS pigs responded with enhanced in vitro contractures to halothane, while responses to caffeine were unaltered by the treatment. Neither agent elicited contractures in muscles from statin treated MHN pigs. In vivo, end- tide pCO2, hemodynamic evolution, plasma pH, potassium and lactate concentrations consistently pointed to mild acceleration of MH development in statin-treated pigs, whereas masseter spasm and rigor faded compared to untreated MHS animals. Conclusions The diagnostic sensitivity and specificity of the IVCT remains unchanged by a short-term simvastatin treatment in MHS swine. Evidence of modest enhancement in cardiovascular and metabolic signs of MH, as well as masked pathognomonic muscle rigor observed under simvastatin therapy suggest a potentially misleading influence on the clinical presentation of MH. The findings deserve further study to include other statins and therapeutic regimes.

Background According to the “three-compartment” model of ventilation-perfusion () inequality, increased scatter in the lung under general anesthesia is reflected in increased alveolar deadspace fraction (Vda/Va) customarily measured using end-tidal to arterial (a-a) partial pressure gradients for carbon dioxide. a-a gradients for anesthetic agents such as isoflurane are also significant but have been shown to be inconsistent with those for carbon dioxide under the three-compartment theory. The authors hypothesized that three-compartment Vda/Va calculated using partial pressures of four inhalational agents (Vda/Vag) is different from that calculated using carbon dioxide (Vda/Vaco2) measurements, but similar to predictions from multicompartment models of physiologically realistic “log-normal” distributions. Methods In an observational study, inspired, end-tidal, arterial, and mixed venous partial pressures of halothane, isoflurane, sevoflurane, or desflurane were measured simultaneously with carbon dioxide in 52 cardiac surgery patients at two centers. Vda/Va was calculated from three-compartment model theory and compared for all gases. Ideal alveolar (Pag) and end-capillary partial pressure (Pc’g) of each agent, theoretically identical, were also calculated from end-tidal and arterial partial pressures adjusted for deadspace and venous admixture. Results Calculated Vda/Vag was larger (mean ± SD) for halothane (0.47 ± 0.08), isoflurane (0.55 ± 0.09), sevoflurane (0.61 ± 0.10), and desflurane (0.65 ± 0.07) than Vda/Vaco2 (0.23 ± 0.07 overall), increasing with lower blood solubility (slope [Cis], –0.096 [–0.133 to –0.059], P < 0.001). There was a significant difference between calculated ideal Pag and Pc’g median [interquartile range], Pag 5.1 [3.7, 8.9] versus Pc’g 4.0[2.5, 6.2], P = 0.011, for all agents combined. The slope of the relationship to solubility was predicted by the log-normal lung model, but with a lower magnitude relative to calculated Vda/Vag. Conclusions Alveolar deadspace for anesthetic agents is much larger than for carbon dioxide and related to blood solubility. Unlike the three-compartment model, multicompartment scatter models explain this from physiologically realistic gas uptake distributions, but suggest a residual factor other than solubility, potentially diffusion limitation, contributes to deadspace. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Cannabis has increasingly been used for medical and recreational purposes. The main pharmacological compound in cannabis is tetrahydrocannabinol (THC), which has sedative, anxiolytic and analgesic effects. In some animal models, THC has also been shown to reduce the minimum alveolar concentration (MAC) of halothane and cyclopropane, but its effect on sevoflurane, currently the most commonly used inhalational anaesthetic agent, has not been investigated. Objective To investigate the effect of THC on the MAC of sevoflurane in rats. Methods Observer-blinded, randomised controlled trial. Setting Centre for Biomedical Research of the Medical University of Vienna, 2019. Individuals Thirty-eight adult Wistar rats. Interventions The rats were allocated randomly into one of two groups. Group A received THC 10 mg kg and group B received the corresponding volume of placebo via gastric gavage (administration through a tube placed in the distal oesophagus). The rats were then individually anaesthetised in an airtight sevoflurane-flooded chamber, and the MAC in both groups was determined using Dixon's up-and-down method. Blood samples were drawn to measure serum concentrations of THC. Main outcome measures The primary outcome was the MAC of sevoflurane in Groups A and B. Results The bootstrap estimate of the MAC of sevoflurane was 2.1 (95% confidence interval 1.8 to 2.4) vol% in the THC group and 2.8 (95% confidence interval 2.7 to 2.9) vol% in the placebo group, corresponding to a significant MAC reduction of 26% in response to THC. Conclusion Gastric administration of THC 10 mg kg significantly reduced the MAC of sevoflurane by 26%. Trial registration Not applicable.

Background The degree to which different volatile anesthetics depress carotid body hypoxic response relates to their ability to activate TASK potassium channels. Most commonly, volatile anesthetic pairs act additively at their molecular targets. We examined whether this applied to carotid body TASK channels. Methods We studied halothane and isoflurane effects on hypoxia-evoked rise in intracellular calcium (Ca2+i, using the indicator Indo-1) in isolated neonatal rat glomus cells, and TASK single-channel activity (patch clamping) in native glomus cells and HEK293 cell line cells transiently expressing TASK-1. Results Halothane (5%) depressed glomus cell Ca2+i hypoxic response (mean ± SD, 94 ± 4% depression; P < 0.001 vs. control). Isoflurane (5%) had a less pronounced effect (53 ± 10% depression; P < 0.001 vs. halothane). A mix of 3% isoflurane/1.5% halothane depressed cell Ca2+i response (51 ± 17% depression) to a lesser degree than 1.5% halothane alone (79 ± 15%; P = 0.001), but similar to 3% isoflurane alone (44 ± 22%; P = 0.224), indicating subadditivity. Halothane and isoflurane increased glomus cell TASK-1/TASK-3 activity, but mixes had a lesser effect than that seen with halothane alone: 4% halothane/4% isoflurane yielded channel open probabilities 127 ± 55% above control, versus 226 ± 12% for 4% halothane alone (P = 0.009). Finally, in HEK293 cell line cells, progressively adding isoflurane (1.5 to 5%) to halothane (2.5%) reduced TASK-1 channel activity from 120 ± 38% above control, to 88 ± 48% (P = 0.034). Conclusions In all three experimental models, the effects of isoflurane and halothane combinations were quantitatively consistent with the modeling of weak and strong agonists competing at a common receptor on the TASK channel. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Malignant hyperthermia (MH) is a potentially lethal reaction in those that are genetically predisposed, frequently triggered by inhaled anesthetics. MH is often difficult to diagnose because it is accompanied by signs and symptoms that are shared with other disorders. The diagnosis is further obscured in cardiac surgical patients, as the signs of MH can be masked by the cardiopulmonary bypass circuit (CPB) and the use of induced hypothermia. In this case-report, we describe the successful anesthetic management of a 65-year-old MH-susceptible female, confirmed via caffeine halothane contracture test, with aortic regurgitation and ascending aortic dilatation who underwent a Bentall procedure. We have also identified certain key measures for the safe anesthetic management of these patients.

No speci?c therapeutic drug has been found. In the absence of any specific therapy and non-availability of vaccine, anaesthetic ether (diethyl ether) is recommended to be used as a prophylactic and therapeutic intervention in the management of COVID-19 disease. Strong evidence based property of ether as lipid solvent has provided the impetus for this approach. The lipid content of the outer envelope of the virus is the weak-link to get dissolved ether and thus leading to disintegration of the single-stranded RNA. The viruses present inside the blood stream are bound to be killed by the presence of ether in the blood circulation. Keywords: Lipid bilayer, Lipid solvent, Oxygenation, Recreational, Halothane, Ether.

Introduction Emergence agitation is a common problem that can occur after administration of general anesthesia and during recovery time especially in pediatric patients, which can result in life-threatening events if not managed adequately and timely. Usage of modern inhalational anesthetic agents like sevoflurane, isoflurane, and also halothane is a common cause for emergence agitation. Currently, the use of propofol is gaining acceptance largely on decreasing emergence agitation in addition to prevention of postoperative nausea and vomiting. The objective of this study was to assess the effectiveness of prophylaxis administration of propofol on incidence & severity of emergence agitation on pediatric patients undergo ENT & ophthalmic surgery under general anesthesia. Methods and material An institutional-based prospective cohort study was conducted on 90 patients. Patients who take 1 mg/kg of propofol were grouped into exposed while if propofol were not given grouped to non-exposed. Data were collected through intraoperative observation & by using WATCH & PAED score the patients were observed at 5, 15 & 30 min in the recovery room. Incidence of emergence agitation was analyzed by chi-square test & Mann Whitney U test was applied for the severity of emergence agitation. A P-value less than 0.05 was declared as statistically significant. Result From a total of 90 study participants 64% of the non-exposed group & 31% of the exposed group were developed emergence agitation which was statistically significant with p = 0.002. The severity of agitation was also higher in the non-exposed group than the exposed group at 5, 15 & 30 min with p = 0.009, 0.013, and 0.011 respectively. Conclusion Administering 1 mg/kg propofol before the end of surgery in pediatrics ENT & ophthalmic procedure under general anesthesia is effective in reducing incidence & severity of emergence agitation. Based on our findings we recommend using 1 mg/kg propofol at the end of surgery to reduce the occurrence of emergency agitation., Highlights • Propofol is effective in reducing incidence and severity of emergence agitation in paediatric patient undergoes ENT and ophthalmic procedure. • 1 mg/kg propofol given at the end of surgery will reduce incidence of emergence agitation in paediatric patient undergo ENT and ophthalmic procedure. • 1 mg/kg propofol given at the end of surgery will reduce severity of emergence agitation in paediatric patient undergo ENT and ophthalmic procedure.

Since the advent of nitric oxide, diethyl ether, chloroform and cyclopropane, the greatest advancement in the area of general inhalational anesthetics has been achieved by the introduction of fluorinated anesthetics and the relevant chiral techniques. This progress led to marked decrease in mortality rates in anesthesia. In the group of chiral fluorinated compounds, halothane (Fluotan®), isoflurane (Foran®), desflurane (Supran®) and enflurane (Ehran®) are deployed as volatile anesthetics. Chiral anesthetics possess a stereogenic center in their molecules and thus exist as two enantiomers (S)-(+) and (R)-(-). Although these chiral anesthetics are used as racemates, it is crucial to study besides the bioactivities of the racemic compounds also the biological activity and other properties of the particular enantiomers. The present survey discusses the drug category known as inhalational anesthetics in regard to their chiral aspects. These compounds exhibit marked differences between the (R) and (S)-enantiomers in their pharmacodynamics, pharmacokinetics and toxicity. The main analytical technique employed in the enantioseparation of these compounds is gas chromatography (GC). This review lists the individual chiral phases (chiral selectors) used in the enantioseparation as well as in pharmacokinetic studies. The possibilities of preparation of these compounds in their enantiomerically pure form by means of stereoselective synthesis are also mentioned.

Aim To summarize the knowledge on the effect of anesthetics employed right before euthanasia on biological outcomes. Data source A systematic review of the literature to find studies with isoflurane, ketamine, halothane, pentobarbital, or thiopental just before euthanasia of laboratory rats or mice. Study selection Controlled studies with quantitative data available. Data extraction The search, data extraction, and risk of bias (RoB) were performed independently by two reviewers using a structured form. For each outcome, an effect size (ES) was calculated relative to the control group. Meta-analysis was performed using robust variance meta-regression for hierarchical data structures, with adjustment for small samples. Data synthesis We included 20 studies with 407 biological outcomes (110 unique). RoB analysis indicated that 87.5% of the domains evaluated showed unclear risk, 2% high risk, and 10.5% low risk. The effect size for all anesthetics considered together was 0.99 (CI95% = 0.75–1.23; p Conclusion We showed that anesthetics interfere differently with the majority of the outcomes assessed. However, our data did not support the use of one anesthetic over others or even the killing without anesthetics. We conclude that outcomes cannot be compared among studies without considering the killing method. This protocol was registered at Prospero (CRD42019119520). Funding: There was no direct funding for this research.

Preclinical and clinical studies have sought to better understand the effect of anesthetic agents, both volatile and intravenous, and perioperative adjuvant medications on immune function. The immune system has evolved to incorporate both innate and adaptive components, which are delicately interwoven and essential for host defense from pathogens and malignancy. This review summarizes the complex and nuanced relationship that exists between each anesthetic agent or perioperative adjuvant medication studied and innate and adaptive immune function with resultant clinical implications. The most commonly used anesthetic agents were chosen for review including volatile agents (sevoflurane, isoflurane, desflurane, and halothane), intravenous agents (propofol, ketamine, etomidate, and dexmedetomidine), and perioperative adjuvant medications (benzodiazepines, opioids, nonsteroidal anti-inflammatory drugs [NSAIDs], and local anesthetic agents). Patients who undergo surgery experience varying combinations of the aforementioned anesthetic agents and adjuncts, depending on the type of surgery and their comorbidities. Each has unique effects on immunity, which may be more or less ideal depending on the clinical situation. Further study is needed to better understand the clinical effects of these relationships so that patient-specific strategies can be developed to improve surgical outcomes.

IntroductionSystemic sclerosis is a potentially devastating disease in which the aetiology and pathogenesis has not yet been fully understood. It has been associated with occupational exposure to silica, vinyl chloride, solvents and other chemical agents.Case summaryIn this paper, we present the case of an anaesthetist who developed scleroderma after an occupational exposure to volatile anaesthetic gases (halothane, sevoflurane, isoflurane and enflurane) in operating theatres with poor scavenging systems and we discuss the possible causal link between occupational exposure and the disease.ConclusionsThe case reported is the second that we are aware of in recent years. Reporting scleroderma cases in workers may be the first step in assessing the causal link between occupational exposure to anaesthetic gases and the disease.

Chloroform has been used over decades in anesthesia before it was replaced by other volatile anesthetics like halothane or sevoflurane. Some of the reasons were inadmissible side effects of chloroform like bradycardia or neural illness. In the present study, we identified members of the G protein-activated inwardly rectifying potassium channel family (Kir3) expressed in Xenopus oocytes as potential common molecular targets for both the neural and cardiac effects of chloroform. Millimolar concentration currents representing a 1:10000 dilution of commercially available chloroform were used in laboratories that augment neuronal Kir3.1/3.2 currents as well as cardiac Kir3.1/3.4. This effect was selective and only observed in currents from Kir3 subunits but not in currents from Kir2 subunits. Augmentation of atrial Kir3.1/3.4 currents leads to an effective drop of the heart rate and a reduction in contraction force in isolated mouse atria.

Captive bolts or firearms are unsuitable for euthanasia of livestock when an intact brain is required for diagnostics. Injectable barbiturates can be used, but this method carries risk of poisoning animals eating the carcase. Intravenous saturated salt solutions have been used to euthanase heavily sedated ruminants and are cheap, readily available and not a risk to scavenging animals. However, there is concern that they may be painful or cause distress to animals that are not unconscious. This study aimed to determine the suitability of saturated salt solutions, in combination with xylazine, as a method of euthanasia of ruminants using a sheep model. Thirty-two sheep were sedated with xylazine (0.4 mg kg-1 IM) and euthanased with an intravenous overdose of pentobarbitone (PENT; n = 10), saturated potassium chloride (KCL; n = 11) or saturated magnesium sulphate (MGS; n = 10). Time until end of rhythmic breathing and cardiac arrest, and movement events were recorded. Conscious perception of pain was evaluated by measuring cortical brain activity by electroencephalography (EEG). There was no evidence of perceived pain or unpleasant sensory experience for any treatment as indicated by P50, P95 and Ptot and so all methods were deemed humane. Time until transient EEG was comparable for all treatments. Time until onset of isoelectric EEG was prolonged for KCL. Animals euthanased with KCL consistently exhibited severe reflex movements during infusion (eg kicking, convulsion). No severe movement events were observed in animals euthanased with MGS, hence, physiological and movement data support the preferential use of MGS over KCL.

The objective of this study was to investigate slaughtering performance, carcass grade, and quantitative traits of cuts according to seasonal influence by each month in pigs slaughtered in livestock processing complex (LPC) slaughterhouse in Korea, 2017. A total of 267,990 LYD (LandracexYorkshirexDuroc) pig data were used in this study. Results of slaughter heads, sex distribution, carcass weight, backfat thickness, grading class, total weight, and fat and lean meat percentages of each cut predicted by AutoFom. were obtained each month. The number of slaughtered pigs was the highest in early and late fall but the lowest in midsummer. Only in midsummer that the number of females was higher than that of castrates. During 2017, carcass weight was the lowest in late summer. Backfat thickness was in the range of 21-22 mm. In mid and late spring, pigs showed high 1+ grade ratio (37.05% and 36.15%, respectively). For traits of 11 cuts predicted by AutoFom III, porkbelly showed lower total weight, lean weight, and fat weight in midsummer to early fall but higher lean meat percentage compared to other seasons. Weights of deboned neck, loin, and lean meat were the highest in midfall compared to other seasons (p

We analyzed how the enhancement of net sarcoplasmic reticulum (SR) Ca2+ uptake may affect cardiac electrophysiological properties in vivo by using caldaret which can decrease SR diastolic Ca2+ leak, enhance SR Ca2+ reuptake and inhibit reverse-mode Na+/Ca2+ exchanger. Caldaret in doses of 0.5, 5 and 50 μg/kg was intravenously administered over 10 min to the halothane-anesthetized beagle dogs (n = 5), attaining pharmacologically active plasma concentration. The low and middle doses of caldaret increased the ventricular contraction, which could be explained by its on-target pharmacological activities. The high dose enhanced the sinus automaticity followed by its suppression in addition to the increase of the total peripheral resistance, which may be unfavorable for treating diastolic heart failure. The low and middle doses enhanced the atrioventricular conduction, which may have some potential for predisposing the atria to the onset of atrial fibrillation via an induction of mitral and/or tricuspid regurgitation. The middle and high doses of caldaret prolonged the ventricular effective refractory period without altering the intraventricular conduction or repolarization period, which may prevent the onset of ventricular arrhythmias. Thus, modulation of intracellular Ca2+ handling by caldaret can induce not only inotropic effect, but also various electrophysiological actions on the in situ heart. Keywords: Caldaret, Ryanodine receptor, Sarco/endoplasmic reticulum Ca2+-ATPase, Reverse-mode Na+/Ca2+ exchanger

Background Volatile anaesthetics are known to cause drug-induced liver injury, a hepatotoxic reaction characterised by antibodies to trifluoroacetylated lipid and protein adducts and cytochrome p450 2E1. The incidence of volatile anaesthetic drug-induced liver injury from older agents has been described, but modern agents have not been prospectively studied. Aim To determine prospectively the incidence of volatile anaesthetic drug-induced liver injury from sevoflurane and desflurane. Methods Adult surgical patients with a predicted post-operative stay of at least 4 days were recruited. If volatile anaesthetic was administered, liver biochemistry was performed regularly. Medications, observations and other investigations were documented. Patients with abnormal liver biochemistry were classified as likely volatile anaesthetic drug-induced liver injury or not based on clinical assessment, Roussel Uclaf Causality Assessment Method score, and the absence of other likely pathology. Some patients were also tested for antibodies to both trifluoroacetylated lipid and protein adducts, and cytochrome p450 2E1. Results A total of 209 patients were recruited, of which 121 were included for analysis. Post-operative liver biochemistry was abnormal in 62 patients (51.2%); further classified as not volatile anaesthetic drug-induced liver injury in 47 cases (38.8%), and likely volatile anaesthetic-drug induced liver injury in 15 cases (12.4%). Of the likely volatile anaesthetic drug-induced liver injury patients, only one had severe disease with alanine transaminase greater than five times the upper limit of normal, while four cases had moderate disease with alanine transaminase greater than three times the upper limit of normal. Thus, the incidence of clinically significant volatile anaesthetic drug-induced liver injury was 4.1%. No risk factors were identified. Conclusions Volatile anaesthetic drug-induced liver injury from modern agents seems to be as common (4.1%) as previously reported with older agents (3%), and may identify patients at risk of severe acute liver injury with subsequent re-exposure.

The continued development of anaesthetic agents since the late 18th century has paved the way for the progression of surgical techniques. Inhalational agents are used worldwide for the delivery of safe, effective anaesthesia. These include the volatile agents halothane, isoflurane, sevoflurane and desflurane, in addition to the anaesthetic gases nitrous oxide and xenon. Although the newer volatiles have an improved safety profile in comparison to older agents, the ideal anaesthetic agent remains elusive. It is vital for anaesthetists to understand the physical properties, pharmacodynamics and pharmacokinetics of the individual inhalational anaesthetic agents so that the most appropriate agent for a patient or procedure is selected and administered correctly.

Photoabsorption spectra of isoflurane and sevoflurane have been measured with synchrotron radiation over the photon range 5.0–10.8 eV. Low-lying excited singlet valence and Rydberg states are investigated and the assignments supported by quantum chemical calculations, the latter also helping to identify the triplet states. This provides the first comprehensive investigation of all excited electronic states up to the first ionisation energy. The Rydberg series converging to the ionisation energy limits are identified according to the magnitude of the quantum defects. The measured absolute cross-sections have been used to calculate the photolysis lifetimes of isoflurane and sevoflurane in the Earth’s atmosphere.

Inhalational anesthetics such as isoflurane, desflurane and halothane are the mainstay medications for surgical procedures; upon inhalation, they produce anesthesia described as reversible unconsciousness with the features of amnesia, sleep, immobility and analgesia. To date, how they produce anesthesia is unknown. This study proposes that carbonic anhydrase enzymes are likely targets mediating the actions of inhalational anesthetics. Carbonic anhydrase enzymes, commonly expressed in living organisms, utilize carbon dioxide (CO2) as a substrate and can generate H+ and HCO3- from CO2 with a great efficiency. There are remarkable lines of evidence for their likely roles in mediating anesthetic actions. Firstly, carbonic anhydrase enzymes are extensively expressed in the brain and spinal cord, and their importance in the brain activity, especially for the GABA and NMDA receptor signaling pathways, has been demonstrated in numerous studies. According to these studies, they provide HCO3- for GABA-A receptor activities and also buffer HCO3- excess resulting from NMDA receptor activation. Activation of GABA-A and inhibition of NMDA receptors are associated with the induction of anesthesia by the intravenous general anesthetics propofol and ketamine, respectively. Secondly, the carbonic anhydrase inhibitors topiramate and zonisamide are effectively used in the treatment of epilepsy for decades; their chronic use results in the requirement of increased levels of amobarbital in order to produce anesthesia in the epileptic patients during WADA test. In addition, given that CO2 is a substrate for these enzymes, their tertiary structure is likely has a hydrophobic pocket suitable for the anesthetic molecules to bind. Inhalational anesthetic molecules, which are lipophilic and inert in nature, have an ability to cross the membranes and inhibit carbonic anhydrases, which might not be accessible by topiramate and zonisamide. Unlike carbonic anhydrase inhibitors, they could bind to the hydrophobic pocket for CO2 molecules and produce a profound effect called anesthesia. Finally, there is a great deal of similarities between the physiological actions of inhalational anesthetics and carbonic anhydrase inhibitors; moreover well-known side effects of inhalational anesthetics could be associated with the inhibition of carbonic anhydrases. Therefore, this article presents a hypothesis that the anesthetic actions of inhalational anesthetics could be due to their inhibitory effects on the carbonic anhydrases. Investigating this hypothesis might lead to the development of new safer anesthetics, and more importantly it might reveal an endogenous anesthetic pathway, in which the carbonic anhydrase system is a component along with the GABA-A and NMDA receptor systems.

Malignant hyperthermia (MH) is an uncommon, autosomal dominant disorder of skeletal muscle, triggered by inhalational anaesthetics or depolarizing muscle relaxants. Masseter muscle rigidity (MMR) can be regarded as potentially a preceding sign for an MH reaction. Susceptibility to MH can be determined by the in vitro contracture test (IVCT) or DNA analysis where a familial variant is known. Our aims were to review patients with MMR, where IVCT and DNA analysis had been undertaken, to determine if DNA analysis could be used as an initial screening tool for MH susceptibility, and, by reviewing standard monitored variables (SMVs), to determine if any clinical characteristics could be used to differentiate between MMR patients who are MH susceptible (MHS) and those who are not. Patients with MMR were identified from the Palmerston North Hospital MH Reactions Database. IVCT and DNA analysis results were documented. DNA testing was performed retrospectively in the majority of patients as many patients had presented before DNA analysis was available. Forty-one patients were analysed. Fourteen were DNA positive/IVCT positive and six DNA positive only (48% in total), seven were IVCT positive/DNA negative and 14 were IVCT normal. Increased creatine kinase (>18,000 units/L) was consistent with MH susceptibility. Severity of MMR was not linked to MH susceptibility. This study confirmed that DNA analysis can be used as a first-line test for MH susceptibility in patients presenting with MMR (consistent with European MH Group recommendations). Creatine kinase was the only SMV that was significantly different between MHS and MH normal individuals.

Malignant hyperthermia (MH) is an inherited, pharmacogenetic disorder of the skeletal muscle, characterized by dangerous hypermetabolic state after anesthesia with succinylcholine and/ or volatile halogenated anesthetic agents, clinically manifested as hyperpyrexia and related complications like tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, rigid muscles, rhabdomyolysis and disseminated intravascular coagulation (DIC). Here we present a series of three cases of MH, admitted in our hospital in a span of 8 months for three different operative procedures to be done under general anesthesia (cleft lip repair, Duhamel's operation for Hirschsprung's disease and surgical repair of development dysplasia of hip), who developed probable hyperthermia owing to Halothane being used as an anesthetic agent. How to cite this article Laha S, Giri PP, Saha A, Gupta PP, De A. Life-threatening Episodes of Malignant Hyperthermia Following Halothane Anesthesia in Three Children: A Case Series and Review of Literature. Indian Journal of Critical Care Medicine, January 2019;23(1):47-50.

Malignant hyperthermia (MH) susceptibility caries broad implications for the care of pediatric surgical patients. While precautions must often be taken for only a vague family history, two options exist to assess MH-susceptibility. We evaluate the use of MH precautions and susceptibility testing at a freestanding children's hospital.This single institution retrospective cohort study identified patients of any age who received general anesthetics utilizing MH precautions over a five-year period. The electronic medical record was further queried for patients diagnosed with MH. The indication for MH precautions and uses of susceptibility testing are assessed. Secondary outcomes included a diagnosis of bona fide MH.A total of 125 patients received 174 anesthetics with MH precautions at a mean age of 114 months (0-363 months). Otolaryngology was the procedural service most frequently involved in the care of the cohort (n = 45; 26%). A reported personal or family history of MH (n = 102; 59%) was the most common indication for precautions, followed by muscular dystrophy (n = 29; 17%). No MH events occurred in the cohort and further review of ICD-9 and -10 diagnosis codes found no MH diagnoses. No study subjects received muscle biopsy and contracture testing and only 5 (4%) underwent genetic testing for genomic variants known to cause MH susceptibility. A case example is given to highlight the implications of a reported MH history.Otolaryngologists should maintain a familiarity with the precautions necessary to manage patients at risk for MH and MH-like reactions. Without an accessible test to rule out susceptibility, surgeons must rely on a careful history to appropriately utilize precautions. An inappropriate label of "MH-susceptible" may result in decreased access to care and treatment delays.

Charles Walter Suckling (1920–2013) is most remembered for being the discoverer of the inhalant anaesthetic halothane, which revolutionized anaesthesia and surgical practice. He was born in Teddington, Middlesex, but grew up largely in Wallasey, Merseyside, where his father was a cargo superintendent for imports from Australia produced by one of Charles’s maternal uncle's cooperatives. Charles was educated at Oldershaw Grammar School, Wallasey, and the University of Liverpool, where he obtained a first class honours degree in chemistry (1942). With this qualification he was directed to carry out national service in the chemical industry at ICI in Widnes and was subsequently able to obtain a scholarship to work towards a PhD at the University of Liverpool (1949), which he was awarded for the structural elucidation of the natural product santal, by classical organic chemical methods. The project leading to the discovery of halothane was begun in 1951 at ICI's Widnes Laboratory and was one of the first examples of rational drug design; halothane reached clinical practice in 1956. This and other industrial research innovations were recognized by his election to the Fellowship of the Royal Society in 1978. Charles’s career at ICI took him into both scientific and commercial management roles, including chairman of Paints Division and general manager of Research and Technology, a company-wide brief at head office, Millbank. After retiring from ICI (1982) he undertook many public service and charitable tasks, including membership of the Royal Commission on Environmental Pollution, for which he was awarded the CBE, and positions on the councils of the Royal College of Anaesthetists and Royal College of Art and Design. Charles retired from professional life fully in 2001. In 1946 he married Eleanor Margaret Watterson; their family comprised twin sons, both of whom became professional scientists, and a daughter, who became a medical doctor. Charles died at Knebworth, Hertfordshire, in 2013.