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Background: Recent studies point to a fundamental distinction between population-based and individual-based anaesthetic pharmacology. At the population level, anaesthetic potency is defined as the relationship between drug concentration and the likelihood of response to a stimulus. At the individual level, even when the anaesthetic concentration is held constant, fluctuations between the responsive and unresponsive states are observed. Notably, these spontaneous fluctuations exhibit resistance to state transitions Rst. Therefore, the response probability in each individual depends not just upon the drug concentration, but also upon responses to previous stimuli. Here, we hypothesise that Rst is distinct from drug potency and is differentially modulated by different anaesthetics.Methods: Adult (14-24 weeks old) C57BL/6J male mice (n=60) were subjected to repeated righting reflex (RR) assays at equipotent steady-state concentrations of isoflurane (0.6 vol%), sevoflurane (1.0 vol%), and halothane (0.4 vol%).Results: Fluctuations in RR were observed for all tested anaesthetics. Analysis of these fluctuations revealed that Rst was differentially modulated by different anaesthetics (F[2, 56.01]=49.59; P<0.0001). Fluctuations in RR were modelled using a stochastic dynamical system. This analysis confirmed that the amount of noise that drives behavioural state transitions depends on the anaesthetic agent (F[2, 42.86]=16.72; P<0.0001).Conclusions: Whilst equipotent doses of distinct anaesthetics produce comparable population response probabilities, they engage dramatically different dynamics in each individual animal. This manifests as a differential aggregate propensity to exhibit state transitions. Thus, resistance to state transitions is a fundamentally distinct, novel measure of individualised anaesthetic pharmacology. [ABSTRACT FROM AUTHOR]

Background: Halothane is one of commonly inhalation anesthetic use in Iraq and the rest of the countries. Anesthetic is substance which reduce sensitivity to pain or is drug used to induce anesthesia that lead to temporary loss sensa-tion or awareness consciousness and which block only sensation of pain stimuli Aim of study : This study was requested by Iraqi ministry of health to focus on the side effects of halothane on the patients and health, a study was perform-ed to evaluate the effects of the halothane anesthetic waste to induced sister chromatid exchange (SCE) and micronuclei (MN) in peripheral lymphocytes and buccal cells respectively in operation room workers (ORWs). Material and Methods : SCE and MN,a sensitive measure of genotoxicity were counted SCE in peripheral blood lymphocytes and MN in buccal mucosa cells for 40 ORWs exposure to halothane gases waste and 20 healthy person as con-trol who had never works in operation room. Results : All of the ORWs exposure to halothane gases waste, have cells with SCE and MN frequencies, in analysis, ORWs was significantly increased SCE in ≥ 10 year and ≤ 5 year compared with control group with mean±SD (11.31± 0.9 and 7.67±0.33)respectively vs mean±SD (5.55±1.6), P< 0.001).fothermore, a significantly increased higher MN frequency with mean± SD (7.53±0.78 and 5.02±0.53) in ORWs with ≥ 10 year and ≤ 5 year respectively comparison with their control group with mean±SD (2.40±0.40),(p<0.001).Also non-significant differences in SCE and MN frequencies according to the gender. Conclusion : The chromosome damage and genotoxicity are related to the ORWs daily exposure to halothane waste and may be increased by accumula-tive with duration of exposure to free radical and reactive oxygen species lead to damage in their cells of peripheral lymphocytes and buccal cells over time of work. [ABSTRACT FROM AUTHOR]

The new inhalation anesthetic agent sevoflurane introduced recently in the clinical practice, having lower blood gas solubility allow for rapid induction, has less myocardial depressant effects may make it a suitable agent for induction as well as maintenance of anaesthesia. Hence, the current research was conducted to compare intubation, induction, haemodynamic and emergence characteristics of halothane and sevoflurane. This comparative clinical study was carried out at Krishna Institute of Medical Sciences and Hospital, Karad. From the present study it is seen that, Halothane in the concentration of 0.5-5% produces induction in 137.8 secs (SD 33.3secs) and sevoflurane in the concentration of 1-7% produces induction in 70.95 secs (SD 14.6secs). Thus sevoflurane produces significantly rapid induction compared to halothane (p<0.05). [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the pharmacokinetics of morphine in combination with dexmedetomidine and maropitant injected intramuscularly in dogs under general anaesthesia. Eight healthy dogs weighing 25.76 ± 3.16 kg and 3.87 ± 1.64 years of age were used in a crossover study. Dogs were randomly allocated to four groups: (1) morphine 0.6 mg/kg; (2) morphine 0.3 mg/kg + dexmedetomidine 5 μg/kg; (3) morphine 0.3 mg/kg + maropitant 1 mg/kg; (4) morphine 0.2 mg/kg + dexmedetomidine 3 μg/kg + maropitant 0.7 mg/kg. Blood samples were collected before, 15 and 30 min, and 1, 2, 3 4, 6 and 8 hr after injection of the test drugs. Plasma concentration of the drugs was determined by liquid chromatography‐mass spectrometry. The elimination half‐life (T1/2) of morphine was higher and the clearance rate (CL) was lower when combined with dexmedetomidine (T1/2 = 77.72 ± 20.27 min, CL = 119.41 ± 23.34 ml kg−1 min−1) compared to maropitant (T1/2 = 52.73 min ± 13.823 ml kg−1 min−1, CL = 178.57 ± 70.55) or morphine alone at higher doses (T1/2 = 50.53 ± 12.55 min, CL = 187.24 ± 34.45 ml kg−1 min−1). Combining morphine with dexmedetomidine may increase the dosing interval of morphine and may have a clinical advantage. [ABSTRACT FROM AUTHOR]

Malignant hyperthermia is rare inherited disorder in our part of the world; there are only few cases reported in literature in India who were suspected of having this condition. The overall incidence of malignant hyperthermia during general anesthesia is estimated to range from 1: 5000 to 1: 50,000–100,000 and mortality rate is estimated to be

Previous results show that halothane gas anaesthesia has a suppressive effect on the visually evoked single-cell activities in the feline caudate nucleus (CN). In this study, we asked whether the low-frequency neuronal signals, the local field potentials (LFP) are also suppressed in the CN of anaesthetized animals.To answer this question, we compared the LFPs recorded from the CN of two halothane-anaesthetized (1.0%), paralyzed, and two awake, behaving cats during static and dynamic visual stimulation. The behaving animals were trained to perform a visual fixation task.Our results denoted a lower proportion of significant power changes to visual stimulation in the CN of the anesthetized cats in each frequency range (from delta to beta) of the LFPs, except gamma. These differences in power changes were more obvious in static visual stimulation, but still, remarkable differences were found in dynamic stimulation, too. The largest differences were found in the alpha and beta frequency bands for static stimulation. Concerning dynamic stimulation, the differences were the biggest in the theta, alpha and beta bands.Similar to the single-cell activities, remarkable differences were found between the visually evoked LFP changes in the CN of the anaesthetized, paralyzed and awake, behaving cats. The halothane gas anaesthesia and the immobilization suppressed the significant LFP power alterations in the CN to both static and dynamic stimulation. These results suggest the priority of the application of behaving animals even in the analysis of the visually evoked low-frequency electric signals, the LFPs recorded from the CN.

Although morphine has been used for treatment-resistant dyspnea in end-stage heart failure patients, information on its cardiovascular safety profile remains limited. Morphine was intravenously administered to halothane-anesthetized dogs (n=4) in doses of 0.1, 1 and 10 mg/kg/10 min with 20 min of observation period. The low and middle doses attained therapeutic (0.13 µg/mL) and supratherapeutic (0.97 µg/mL) plasma concentrations, respectively. The low dose hardly altered any of the cardiovascular variables except that the QT interval was prolonged for 10-15 min after its start of infusion. The middle dose reduced the preload and afterload to the left ventricle for 5-15 min, then decreased the left ventricular contractility and mean blood pressure for 10-30 min, and finally suppressed the heart rate for 15-30 min. Moreover, the middle dose gradually but progressively prolonged the atrioventricular conduction time, QT interval/QTcV, ventricular late repolarization period and ventricular effective refractory period without altering the intraventricular conduction time, ventricular early repolarization period or terminal repolarization period. A reverse-frequency-dependent delay of ventricular repolarization was confirmed. The high dose induced cardiohemodynamic collapse mainly due to vasodilation in the initial 2 animals by 1.9 and 3.3 min after its start of infusion, respectively, which needed circulatory support to treat. The high dose was not tested further in the remaining 2 animals. Thus, intravenously administered morphine exerts a rapidly appearing vasodilator action followed by slowly developing cardiosuppressive effects. Morphine can delay the ventricular repolarization possibly through I Kr inhibition in vivo, but its potential to develop torsade de pointes will be small.

Objectives: Prolongation of cardiac repolarization, especially the heart rate-corrected QT (QTc) interval, is associated with life-threatening dysrhythmias. This study aimed to identify the anesthetic with the lowest risk of prolonging cardiac repolarization and provide guidance for anesthesia management in patients with cardiac diseases or long QT syndrome., Methods: Randomized controlled trials (RCTs) comparing the effects of anesthetics on cardiac repolarization indices were searched for in multiple databases. The primary outcome was QTc; and the secondary outcomes were other repolarization indices. A network meta-analysis was conducted using a frequentist approach and registered with the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022304970)., Results: Thirteen RCTs investigating 953 adults with normal QTc interval and without cardiovascular diseases were included. Direct meta-analyses found that propofol had less influence than sevoflurane (95% confidence interval (CI): 16.10, 33.54) and desflurane (95% CI: 4.85, 35.36), and sevoflurane had less influence than desflurane (95% CI: 6.96, 19.39) on QTc prolongation. Network analysis found that propofol had less influence than sevoflurane (95% CI: 17.78, 29.63), halothane (95% CI: 11.29, 41.24), desflurane (95% CI: 23.79, 39.88), and isoflurane (95% CI: 20.11, 46.10), and sevoflurane had less influence than desflurane (95% CI: 0.43, 15.82) on QTc prolongation. The rank order of cumulative ranking curve analysis was propofol (100%), sevoflurane (63.8%), halothane (49.5%), desflurane (21.1%), and isoflurane (15.6%). The direct meta-analysis found that propofol had less influence than sevoflurane on QT prolongation (95% CI: 23.12, 57.86). Other secondary outcomes showed no conclusive findings., Conclusions: This meta-analysis found that propofol had a minimal effect on QTc prolongation, followed by sevoflurane and desflurane in adults with normal QTc interval and without cardiovascular diseases. Propofol is the best anesthetic for adult patients with long QT syndrome or cardiac diseases, but still needs more robust evidence.

Although instrumental for optimizing their pharmacological activity, a molecular understanding of the preferential interactions given by volatile anesthetics is quite poor. This paper confirms the ability of halothane to work as a hydrogen‐bond (HB) donor and gives the first experimental proof that halothane also works as a halogen‐bond (HaB) donor in the solid state and in solution. A halothane/hexamethylphosphortriamide co‐crystal is described and its single‐crystal X‐ray structure shows short HaBs between bromine, or chlorine, and the phosphoryl oxygen. New UV/Vis absorption bands appear upon addition of diazabicyclooctane and tetra(n‐butyl)ammonium iodide to halothane solutions, indicating that nitrogen atoms and anions may mediate the HaB‐driven binding processes involving halothane as well. The ability of halothane to work as a bidentate/tridentate tecton by acting as a HaB and HB donor gives an atomic rationale for the eudismic ratio shown by this agent. [ABSTRACT FROM AUTHOR]

Malignant hyperthermia (MH) is an inherited, pharmacogenetic disorder of the skeletal muscle, characterized by dangerous hypermetabolic state after anaesthesia with succinylcholine and/ or volatile halogenated anesthetic agents, clinically manifested as hyperpyrexia and related complications like tachycardia, tachypnoea, 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 anaesthesia (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 anaesthetic agent. [ABSTRACT FROM AUTHOR]

Background: The variable clinical presentation of malignant hyperthermia (MH), a disorder of calcium signalling, hinders its diagnosis and management. Diagnosis relies on the caffeine-halothane contracture test, measuring contraction forces upon exposure of muscle to caffeine or halothane (FC and FH, respectively). Patients with above-threshold FC or FH are diagnosed as MH susceptible. Many patients test positive to halothane only (termed 'HH'). Our objective was to determine the characteristics of these HH patients, including their clinical symptoms and features of cytosolic Ca2+ signalling related to excitation-contraction coupling in myotubes.Methods: After institutional ethics committee approval, recruited patients undergoing contracture testing at Toronto's MH centre were assigned to three groups: HH, doubly positive (HS), and negative patients (HN). A clinical index was assembled from musculoskeletal symptoms and signs. An analogous calcium index summarised four measures in cultured myotubes: resting [Ca2+]cytosol, frequency of spontaneous cytosolic Ca2+ events, Ca2+ waves, and cell-wide Ca2+ spikes after electrical stimulation.Results: The highest values of both indexes were found in the HH group; the differences in calcium index between HH and the other groups were statistically significant. The principal component analysis confirmed the unique cell-level features of the HH group, and identified elevated resting [Ca2+]cytosol and spontaneous event frequency as the defining HH characteristics.Conclusions: These findings suggest that HH pathogenesis stems from excess Ca2+ leak through sarcoplasmic reticulum channels. This identifies HH as a separate diagnostic group and opens their condition to treatment based on understanding of pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

We analyzed electropharmacological characteristics of microminipigs under halothane-anesthesia using anti-influenza virus drug oseltamivir, which has been known to possess multi-channel blocking properties, including Na+, Ca2+ and K+ channels (n = 4). Oseltamivir in doses of 0.3, 3 and 30 mg/kg was intravenously infused over 10 min with an interval of 20 min, which provided peak plasma concentrations 1.4, 7.4 and 125.5 µg/mL, respectively. The low dose did not alter any of the cardiovascular variables. The middle dose decreased the heart rate at 30 min after the start of the infusion. The high dose transiently returned the heart rate toward the baseline for 10-15 min, but decreased it for 20-60 min; decreased the mean blood pressure for 5-60 min; prolonged the PR interval for 10-60 min, and the QRS width for 10-20 min; but shortened the QT interval for 10-30 min, and the QTc for 5-60 min. Thus, oseltamivir can suppress the sinus automaticity, and atrioventricular nodal and intraventricular conduction; and decrease the mean blood pressure, extents of which were greater in microminipigs than in beagle dogs in our previous observation in spite of similar plasma concentrations, reflecting higher sensitivity of microminipigs for Na+ and Ca2+ channel inhibition than that of beagle dogs. In contrast to beagle dogs, oseltamivir shortened the repolarization period in microminipigs, indicating that oseltamivir can more potently inhibit the inward currents than the outward ones in the hearts of microminipigs. This information may help improve utilizatione of microminipigs as a laboratory animal. [ABSTRACT FROM AUTHOR]

Lithium is one of the classical drugs that have been widely used for treating bipolar disorder. However, several cardiac side effects including sick sinus syndrome, bundle branch block, ventricular tachycardia/fibrillation, non-specific T-wave abnormalities in addition to Brugada-type electrocardiographic changes have been noticed in patients who were given antidepressant, anticonvulsant, and/or antipsychotic drugs besides lithium. In this study, we assessed cardiohemodynamic and electrophysiological effects of lithium carbonate by itself to begin to analyze onset mechanisms of its cardiovascular side effects. Lithium carbonate in intravenous doses of 0.1, 1, and 10 mg/kg over 10 min was cumulatively administered with an interval of 20 min to the halothane-anesthetized beagle dogs (n = 4), which provided peak plasma Li+ concentrations of 0.02, 0.18, and 1.79 mEq/L, respectively, reflecting sub-therapeutic to toxic concentrations. The low and middle doses prolonged the ventricular effective refractory period at 30 min and for 5-30 min, respectively. The high dose decreased the heart rate for 45-60 min, delayed the intraventricular conduction for 15-20 min and the ventricular repolarization at 45 min, and prolonged the effective refractory period for 5-60 min. No significant change was detected in the other cardiovascular variables. Thus, lithium alone may have a wide safety margin against hemodynamic adverse events; however, it would directly and/or indirectly inhibit Na+ and K+ channels, which may synergistically increase the ventricular refractoriness from the sub-therapeutic concentration and decrease the heart rate at the supra-therapeutic one. These findings may partly explain its clinically observed various types of arrhythmias as well as electrocardiographic changes. [ABSTRACT FROM AUTHOR]

Presents an application of regularization method to joint treatment of ab initio and experimental vibrational data for mono-, di- and tri-substituted haloethanes. Details on the regularization application method; Effects of fluoro- and chloro-substitution on the force field parameters; Improvement in calculated geometrical parameters.

Keywords: Freons; halothane; fluoroalkyl/vinyl source; nucleophilic/electrophilic reaction; fluorine-containing compounds EN Freons halothane fluoroalkyl/vinyl source nucleophilic/electrophilic reaction fluorine-containing compounds 1 1 1 09/12/23 20230901 NES 230901 The cover picture shows the use of freons and halothane as building blocks for constructing fluorinated materials as well as pharmaceuticals. Freons, halothane, fluoroalkyl/vinyl source, nucleophilic/electrophilic reaction, fluorine-containing compounds. [Extracted from the article]

In the development stage, brain has a higher level of vulnerability than the adult brain to anesthetic agents. The aim of this study was to investigate the effects of red amaranth extract to brain derived neurotrophic factor (BDNF) and AMPA glutamate receptor subunit 1 (Glur1) expressions as biomarkers of cognitive and neuroplasticity in rat hippocampus areas exposed to inhaled anesthetics halothane and sevoflurane. The design of this study was a randomized posttest only control group. This study was conducted at the Department of Biochemistry Faculty of Medicine, Universitas Airlangga, and the anesthetic procedures were performed at the Veterinary Hospital, Faculty of Veterinary Medicine Universitas Airlangga during the period of May–October 2014. The subjects of this study were 23 white male rats (Rattus norvegicus) wistar strain, aged 1–1.5 months, weighted approximately 60–100 grams in a healthy physical condition. The subjects were divided into 5 groups, K (control); K1 (1 MAC halothane); K2 (red amaranth 800 mg/kgBW + 1 MAC halothane); K3 (1 MAC sevoflurane); and K4 (red amaranth 800mg/kgBW+1 MAC sevoflurane). The results of this study showed a decrease in the expression of BDNF when halothane and sevoflurane were administered. Red amaranth treatment prior to anesthetic gases exposure preserved and increased BDNF expression (p=0.000) while GLUR1 expression increased in the group that received halothane and sevoflurane administration and decreased back to normal in the group that received red amaranth treatment prior to exposure to anesthetic gases (p=0.000). In conclusion, red amaranth extract has the potential effect to prevent cognitive neurotoxicity on the cognitive function in rats exposed to anesthetic gases.

Foreign body aspiration is a leading cause of mortality in children of age group 1-3 years and presents significant challenges to the anaesthesiologist in maintaining oxygenation and ventilation while there is instrumentation of the airway by the endoscopist. Here, we report a two-year-old child who came to the emergency room with sudden onset breathlessness, coughing and bluish discolouration. The foreign body lodged in the right mainstem bronchus was removed with the help of a rigid bronchoscope and oxygenation was maintained with jet ventilation. The cooperation between the anaesthesiologist and the endoscopist, proper timing of the procedure, choice of anaesthetic technique and familiarity with equipments saved the child.