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.

• Klíčová slova
• chirality, enantioseparation, general anesthetics, inhalational anesthetics, pharmacodynamics, pharmacokinetics, stereochemistry,
• MeSH
• anestetika inhalační * MeSH
• enfluran MeSH
• halothan MeSH
• isofluran * MeSH
• stereoizomerie MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• anestetika inhalační * MeSH
• enfluran MeSH
• halothan MeSH
• isofluran * MeSH

Liposomes were used as biomimetic models in capillary electrokinetic chromatography (EKC) for the determination of distribution constants (KD) of certain local anesthetics and a commonly used preservative. Synthetic liposomes comprised phosphatidylcholine and phosphatidylglycerol phospholipids with and without cholesterol. In addition, ghost liposomes made from red blood cell (RBC) lipid extracts were used as pseudostationary phase to acquire information on how the liposome composition affects the interactions between anesthetics and liposomes. These results were compared with theoretical distribution coefficients at pH 7.4. In addition to 25°C, the distribution constants were determined at 37 and 42°C to simulate physiological conditions. Moreover, the usability of five electroosmotic flow markers in liposome (LEKC) and micellar EKC (MEKC) was studied. LEKC was proven to be a convenient and fast technique for obtaining data about the distribution constants of local anesthetics between liposome and aqueous phase. RBC liposomes can be utilized for more representative model of cellular membranes, and the results indicate that the distribution constants of the anesthetics are greatly dependent on the used liposome composition and the amount of cholesterol, while the effect of temperature on the distribution constants is less significant.

• Klíčová slova
• Cholesterol, Distribution constants, EOF markers, Liposome electrokinetic chromatography, Local anesthetics, Red blood cell lipids,
• MeSH
• anestetika lokální chemie   MeSH
• chromatografie micelární elektrokinetická kapilární * MeSH
• erytrocyty metabolismus   MeSH
• fosfatidylcholiny chemie   MeSH
• fosfolipidy chemie   izolace a purifikace   MeSH
• lidé MeSH
• lidokain chemie   MeSH
• lipidové dvojvrstvy chemie   MeSH
• liposomy chemie   MeSH
• teplota MeSH
• voda chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anestetika lokální MeSH
• fosfatidylcholiny MeSH
• fosfolipidy MeSH
• lidokain MeSH
• lipidové dvojvrstvy MeSH
• liposomy MeSH
• voda MeSH

• Klíčová slova
• ANESTHETICS, LOCAL *, LIVER *,
• MeSH
• anestetika lokální * MeSH
• anestetika * MeSH
• hydrolýza MeSH
• játra * MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anestetika lokální * MeSH
• anestetika * MeSH

In continuation of our published review on general inhalational anesthetics, the current article presents a survey of intravenous agents for general anaesthesia. From chemical point of view these compounds belong to structurally diverse categories, such as barbiturates - thiopental (Sodium pentothal®, Trapanal®, Pentothal®), methohexital (Brevital®), and hexobarbital (Evipan®, Hexenal®, Citopan®, Tobinal®); non-barbiturate derivatives - ketamine (Ketalar® Ketaset®), esketamine (Ketanest®), and etomidate (Amidate®, Hypnomidate®), phenolic derivatives - propofol (Diprivan®); steroid derivatives - mixture of alfadolone and alfaxalone (Althesin® in human and Saffan® in veterinary anesthesia); and derivatives of phenylacetic acid - propanidid (Epontol®, Sombrevin®). Most of these compounds are chiral, with the exception of propofol and propanidid. Apart from etomidate and esketamine, they are used in the form of their racemates. Besides their characteristics and mechanism of action, attention is centred also on their chiral properties.

• Klíčová slova
• chirality, general anesthetics, intravenous anesthetics, pharmacodynamics, pharmacokinetics, stereochemistry,
• MeSH
• alfaxalon-alfadolon - směs * MeSH
• anestetika intravenózní farmakologie   MeSH
• etomidát * farmakologie   MeSH
• lidé MeSH
• methohexital MeSH
• propanidid MeSH
• propofol * farmakologie   MeSH
• thiopental MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alfaxalon-alfadolon - směs * MeSH
• anestetika intravenózní MeSH
• Esketamine MeSH Prohlížeč
• etomidát * MeSH
• methohexital MeSH
• propanidid MeSH
• propofol * MeSH
• thiopental MeSH

General anesthesia can be caused by various, chemically very different molecules, while several other molecules, many of which are structurally rather similar to them, do not exhibit anesthetic effects at all. To understand the origin of this difference and shed some light on the molecular mechanism of general anesthesia, we report here molecular dynamics simulations of the neat dipalmitoylphosphatidylcholine (DPPC) membrane as well as DPPC membranes containing the anesthetics diethyl ether and chloroform and the structurally similar non-anesthetics n-pentane and carbon tetrachloride, respectively. To also account for the pressure reversal of anesthesia, these simulations are performed both at 1 bar and at 600 bar. Our results indicate that all solutes considered prefer to stay both in the middle of the membrane and close to the boundary of the hydrocarbon domain, at the vicinity of the crowded region of the polar headgroups. However, this latter preference is considerably stronger for the (weakly polar) anesthetics than for the (apolar) non-anesthetics. Anesthetics staying in this outer preferred position increase the lateral separation between the lipid molecules, giving rise to a decrease of the lateral density. The lower lateral density leads to an increased mobility of the DPPC molecules, a decreased order of their tails, an increase of the free volume around this outer preferred position, and a decrease of the lateral pressure at the hydrocarbon side of the apolar/polar interface, a change that might well be in a causal relation with the occurrence of the anesthetic effect. All these changes are clearly reverted by the increase of pressure. Furthermore, non-anesthetics occur in this outer preferred position in a considerably smaller concentration and hence either induce such changes in a much weaker form or do not induce them at all.

• MeSH
• 1,2-dipalmitoylfosfatidylcholin chemie   MeSH
• anestetika celková * farmakologie   MeSH
• anestezie * MeSH
• chloroform chemie   MeSH
• lipidové dvojvrstvy chemie   MeSH
• membrány MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1,2-dipalmitoylfosfatidylcholin MeSH
• anestetika celková * MeSH
• chloroform MeSH
• lipidové dvojvrstvy MeSH

OBJECTIVE: To investigate the effect of volatile anesthetics on the rates of postoperative myocardial infarction (MI) and cardiac death after coronary artery bypass graft (CABG). DESIGN: A post hoc analysis of a randomized trial. SETTING: Cardiac surgical operating rooms. PARTICIPANTS: Patients undergoing elective, isolated CABG. INTERVENTIONS: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes. MEASUREMENTS AND MAIN RESULTS: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03). CONCLUSIONS: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality.

• Klíčová slova
• cancer, cardiac surgery, cardioprotection, mortality, myocardial infarction, volatile anesthetics,
• MeSH
• anestetika inhalační * MeSH
• anestetika intravenózní MeSH
• infarkt myokardu * farmakoterapie   epidemiologie   MeSH
• koronární bypass metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pooperační komplikace diagnóza   epidemiologie   prevence a kontrola   MeSH
• propofol * MeSH
• senioři MeSH
• sevofluran MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• anestetika inhalační * MeSH
• anestetika intravenózní MeSH
• propofol * MeSH
• sevofluran MeSH

The effect of equitoxic doses of three carbamate local anesthetics (pentacaine, carbisocaine and heptacaine), and a derivative of lidocaine (trimecaine) on the acid-base balance of blood was studied in conscious rabbits. In addition, changes in arterial blood pH induced by local anesthetics in relation to lipophilicity of the respective drugs were evaluated. All the drugs administered at the dose of half of LD50 induced a significant decrease in the arterial blood pH as well as in the plasma bicarbonate level and in the blood base excess. The observed acidosis was compensated within a 60 minute period by hyperventilation. The local anesthetic-induced decrease in the blood pH, expressed as AUC, correlated to some extent with the partition coefficient of these agents. These findings suggest that the acidifying effect of local anesthetics may be dependent on their lipophilicity.

• MeSH
• acidóza krev   MeSH
• anestetika lokální toxicita   MeSH
• chemické jevy MeSH
• činčila MeSH
• fyzikální chemie MeSH
• hydrogenuhličitany krev   MeSH
• koncentrace vodíkových iontů MeSH
• králíci MeSH
• LD50 MeSH
• oxid uhličitý krev   MeSH
• poruchy acidobazické rovnováhy krev   chemicky indukované   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anestetika lokální MeSH
• hydrogenuhličitany MeSH
• oxid uhličitý MeSH

OBJECTIVE: There is initial evidence that the use of volatile anesthetics can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalization following coronary artery bypass graft (CABG) surgery. Nevertheless, small randomized controlled trials have failed to demonstrate a survival advantage. Thus, whether volatile anesthetics improve the postoperative outcome of cardiac surgical patients remains uncertain. An adequately powered randomized controlled trial appears desirable. DESIGN: Single blinded, international, multicenter randomized controlled trial with 1:1 allocation ratio. SETTING: Tertiary and University hospitals. INTERVENTIONS: Patients (n=10,600) undergoing coronary artery bypass graft will be randomized to receive either volatile anesthetic as part of the anesthetic plan, or total intravenous anesthesia. MEASUREMENTS AND MAIN RESULTS: The primary end point of the study will be one-year mortality (any cause). Secondary endpoints will be 30-day mortality; 30-day death or non-fatal myocardial infarction (composite endpoint); cardiac mortality at 30day and at one year; incidence of hospital re-admission during the one year follow-up period and duration of intensive care unit, and hospital stay. The sample size is based on the hypothesis that volatile anesthetics will reduce 1-year unadjusted mortality from 3% to 2%, using a two-sided alpha error of 0.05, and a power of 0.9. CONCLUSIONS: The trial will determine whether the simple intervention of adding a volatile anesthetic, an intervention that can be implemented by all anesthesiologists, can improve one-year survival in patients undergoing coronary artery bypass graft surgery.

• Klíčová slova
• Cardiac anesthesia, Cardiac surgery, Intensive care, Randomized trial, Total intravenous anesthesia, Volatile anesthetics,
• MeSH
• analýza přežití MeSH
• anestetika inhalační * aplikace a dávkování   chemie   MeSH
• anestezie v kardiochirurgii * škodlivé účinky   metody   MeSH
• dospělí MeSH
• koronární bypass * škodlivé účinky   metody   mortalita   MeSH
• lidé MeSH
• nemoci koronárních tepen mortalita   chirurgie   MeSH
• pooperační komplikace * etiologie   prevence a kontrola   MeSH
• volatilizace MeSH
• výsledky a postupy - zhodnocení (zdravotní péče) MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• anestetika inhalační * MeSH

BACKGROUND: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). METHODS: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. RESULTS: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. CONCLUSIONS: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia. (Funded by the Italian Ministry of Health; MYRIAD ClinicalTrials.gov number, NCT02105610.).

• MeSH
• anestetika celková farmakologie   MeSH
• anestetika intravenózní MeSH
• aplikace inhalační MeSH
• celková anestezie MeSH
• elektivní chirurgické výkony MeSH
• intravenózní anestezie * MeSH
• jednoduchá slepá metoda MeSH
• Kaplanův-Meierův odhad MeSH
• koronární bypass * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mortalita MeSH
• nemoci koronárních tepen mortalita   patofyziologie   chirurgie   MeSH
• senioři MeSH
• tepový objem MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• pragmatická klinická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• anestetika celková MeSH
• anestetika intravenózní MeSH

The aim of the paper was to study the effect of carbisocaine, a new local anesthetic with high liposolubility on incorporation of 32P into individual and total phospholipids and to compare its effect with that of other local anesthetics (procaine, lidocaine, cinchocaine, heptacaine). Carbisocaine decreased 32P incorporation into neutral phospholipids and increased the incorporation into acid phospholipids, presumably by inhibiting phosphatidate phosphohydrolase, similarly as reported for other anesthetics (Brindley and Bowley 1975). The increased incorporation of 32P into phosphatidylserine induced by carbisocaine suggests that this phospholipid is also synthetised from phosphatidic acid. At low concentrations, the local anesthetics studies were found to increase 32P incorporation into total phospholipids, whereas at high concentrations they reduced 32P incorporation. This biphasic effect is in agreement with the incorporation of 14C from glucose into lipids (Lassánová et al. 1984) and with the effect of cinchocaine on glycerol incorporation into phospholipids (Allan and Michell 1975), suggesting that local anesthetics affect de novo synthesis of phosphatidic acid. Carbisocaine increased 32P incorporation into phospholipids, in concentrations lower by several orders of magnitude as compared to the other local anesthetics studied. A rough correlation was observed between the concentrations at which the local anesthetics showed stimulatory effect on 32P incorporation, and the average effective concentrations of the respective anesthetics. No such correlation could be found for carbisocaine.

• MeSH
• anestetika lokální farmakologie   MeSH
• fosfáty metabolismus   MeSH
• fosfolipidy biosyntéza   MeSH
• karbamáty farmakologie   MeSH
• kinetika MeSH
• krysa rodu Rattus MeSH
• mozek metabolismus   MeSH
• radioizotopy fosforu MeSH
• synaptozomy účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anestetika lokální MeSH
• carbizocaine MeSH Prohlížeč
• fosfáty MeSH
• fosfolipidy MeSH
• karbamáty MeSH
• radioizotopy fosforu MeSH