An Overview of Analytical Methods for the Estimation of Propofol in Pharmaceutical Formulations, Biological Matrices, and Hair Marker.

Propofol (PFL) owing to its excellent inhibitory property of neurotransmitters in CNS by positive modulation of ligand gated ion channels to an integrated chloride channeled GABAA thereby acts as a general anesthetic. It differs from other general anesthetics chemically and pharmacologically as it has lesser side effects compared to other general anesthetics and is most commonly used. The present review focuses on two aspects (a) various analytical methods used in quantification of Propofol in pharmaceutical formulations and (b) various analytical methods used to determine Propofol in biological matrices and some biological markers like hair and end tidal nasal air for forensic purpose to estimate drug concentration in suspected cases. Here the various analytical methods are developed using different parameters and validation of employed methods are discussed. Estimated parameters like the linearity, LOQ (Limit of quantification), % recovery, slope, intercept, validation are discussed for the individual method. The critical quality attributes like the wavelength of detection, columns, flow rate, gas flow, and the sample preparation methods for the determination of PFL by bioanalytical methods are also discussed. Type of electrode, mechanism involved and the potential voltage applied for a particular electrochemical method are also discussed.

Was Mafeisan an Anesthetic in Ancient China?

According to the Chinese historical books, Records of the Three Kingdoms () and Book of the Later Han (), Hua Tuo (, 140 - 208), a Traditional Chinese medicine (TCM) physician invented Mafeisan, an oral herbal general anesthetic, more than 1800 years ago during Eastern Han Dynasty. However, no written record of ingredients of the original Mafeisan has been found anywhere so far although there have been several similar anesthetic prescriptions published in TCM books later. There has been controversy over the existence of Mafeisan and even Hua Tuo in Chinese literature. We did extensive literature search and analysis, and believe that there indeed was Mafeisan in Hua Tuo's time.

Volatile general anesthetic sensing with organic field-effect transistors integrating phospholipid membranes.

The detailed action mechanism of volatile general anesthetics is still unknown despite their effect has been clinically exploited for more than a century. Long ago it was also assessed that the potency of an anesthetic molecule well correlates with its lipophilicity and phospholipids were eventually identified as mediators. As yet, the direct effect of volatile anesthetics at physiological relevant concentrations on membranes is still under scrutiny. Organic field-effect transistors (OFETs) integrating a phospholipid (PL) functional bio inter-layer (FBI) are here proposed for the electronic detection of archetypal volatile anesthetic molecules such as diethyl ether and halothane. This technology allows to directly interface a PL layer to an electronic transistor channel, and directly probe subtle changes occurring in the bio-layer. Repeatable responses of PL FBI-OFET to anesthetics are produced in a concentration range that reaches few percent, namely the clinically relevant regime. The PL FBI-OFET is also shown to deliver a comparably weaker response to a non-anesthetic volatile molecule such as acetone.

Comparison of relative distribution of ketamine and norketamine in decomposed skeletal tissues following single and repeated exposures.

Bone was analyzed for ketamine and norketamine to examine whether different patterns of drug exposure could be discriminated. Rats received (intraperitoneally) one 75 mg/kg dose (Acute-1 and Acute-2 groups), three 25-mg/kg doses 1 hour apart (Repeated group), or nine single daily ketamine doses of 75 mg/kg followed by a 24-h washout period (Chronic group). Following euthanasia, all animals decomposed to skeleton outdoors. Ground samples of recovered bone underwent methanolic extraction and analysis by gas chromatography-mass spectrometry after solid-phase extraction. Drug levels (mass normalized response ratios) were compared across bone types and exposure pattern. Bone type significantly influenced drug level for the Acute-1 and Repeated dose groups, and the drug/metabolite level ratio (DMLR) for the Acute-1 group. Mean ketamine and norketamine level and DMLR varied by up to 8-fold, 7-fold and 3-fold, respectively, in the Acute-1 group, and by up to 24-fold, 5-fold and 10-fold, respectively, in the Repeated group. Drug level and DMLR differed significantly between the Acute-1 and Repeated groups for most bone types. In the Chronic group, only 1/16 and 4/16 samples were positive for ketamine and norketamine, respectively. All Acute-2 samples were positive for ketamine and norketamine. The Acute-2 and Chronic groups differed significantly in ketamine and norketamine levels, and DMLR.

Neurotoxicidad de los anestésicos generales / No disponible

La anestesia general es uno de los grandes avances de la medicina y permite realizar cirugías cada vez más complejas de forma segura. Pero no está exenta de riesgos. La neurotoxicidades uno de estos riesgos. Este trabajo es una revisión de los últimos avances en este tema, centrándonos en las edades extremas de la vida donde la vulnerabilidad sobre el sistema nervioso centrales mayor (AU)

General anesthesia is one of the greatest achievements in medicine that permits to make complex surgeries on a secure and safe way, although it has its own risks. Neurotoxicity is one of them. This article is a revision of the last achievements on this matter, focusing on the extreme ages of life where vulnerability on the central nervous system is higher (AU)

A novel electronic algorithm for detecting potentially insufficient anesthesia: implications for the prevention of intraoperative awareness.

OBJECTIVE: A recent clinical trial compared a minimum alveolar concentration (MAC)-based protocol to an electroencephalography (EEG)-based protocol for the prevention of intraoperative awareness. One limitation of this study design is that MAC-based protocols are not sensitive to the use of intravenous agents, while EEG-based protocols are. Our objective was to develop a MAC alert that incorporates intravenous agents. METHODS: We developed an electronic algorithm and alerting system that calculates a total age-adjusted MAC value based on inhalational agents, but also incorporates intravenous agents. We retrospectively applied the algorithm to adult general anesthesia cases over a 1 year period to assess the frequency of alert triggers, using thresholds of <0.8, <0.7, <0.6, <0.5 and <0.4 age-adjusted MAC. We also electronically analyzed 12 cases of intraoperative awareness that occurred over a 4-year period for the frequency of alert triggers using the same thresholds. Finally, we calculated positive and negative likelihood ratios based on these analyses. RESULTS: Over a 1-year period we identified 15,091 cases without self-reported awareness that were valid for analysis. At all age-adjusted MAC thresholds, the incidence of triggered alerts was higher in the awareness cases. The threshold of<0.8 age-adjusted MAC was associated with the highest negative likelihood ratio; the<0.5 age-adjusted MAC was associated with the highest positive likelihood ratio. CONCLUSIONS: Our novel electronic alerting system incorporates both age-adjusted MAC and intravenous anesthesia, and triggers with a higher frequency in cases of awareness. These data suggest the potential for our system to alert clinicians to insufficient anesthesia.

Low minimum alveolar concentration alarm: a standard for prevention of awareness during general anaesthesia maintained by inhalational anaesthetics.

Awareness during general anaesthesia is a rare but significant problem that can be frightening to the patients. We suggest that newer generation monitors should include this facility to provide a low alarm limit to MAC settings so as to improve the quality of patient care. Also we suggest that a "near empty" alarm be incorporated into vaporizers which can warn the anaesthesiologist prior to development of possible light plane of anaesthesia. We hope that adopting these two features can help enhance patient safety and can further aid in quality assurance.

Anesthesia awareness and the bispectral index.

BACKGROUND: Awareness during anesthesia is a serious complication with potential long-term psychological consequences. Use of the bispectral index (BIS), developed from a processed electroencephalogram, has been reported to decrease the incidence of anesthesia awareness when the BIS value is maintained below 60. In this trial, we sought to determine whether a BIS-based protocol is better than a protocol based on a measurement of end-tidal anesthetic gas (ETAG) for decreasing anesthesia awareness in patients at high risk for this complication. METHODS: We randomly assigned 2000 patients to BIS-guided anesthesia (target BIS range, 40 to 60) or ETAG-guided anesthesia (target ETAG range, 0.7 to 1.3 minimum alveolar concentration [MAC]). Postoperatively, patients were assessed for anesthesia awareness at three intervals (0 to 24 hours, 24 to 72 hours, and 30 days after extubation). RESULTS: We assessed 967 and 974 patients from the BIS and ETAG groups, respectively. Two cases of definite anesthesia awareness occurred in each group (absolute difference, 0%; 95% confidence interval [CI], -0.56 to 0.57%). The BIS value was greater than 60 in one case of definite anesthesia awareness, and the ETAG concentrations were less than 0.7 MAC in three cases. For all patients, the mean (+/-SD) time-averaged ETAG concentration was 0.81+/-0.25 MAC in the BIS group and 0.82+/-0.23 MAC in the ETAG group (P=0.10; 95% CI for the difference between the BIS and ETAG groups, -0.04 to 0.01 MAC). CONCLUSIONS: We did not reproduce the results of previous studies that reported a lower incidence of anesthesia awareness with BIS monitoring, and the use of the BIS protocol was not associated with reduced administration of volatile anesthetic gases. Anesthesia awareness occurred even when BIS values and ETAG concentrations were within the target ranges. Our findings do not support routine BIS monitoring as part of standard practice. (ClinicalTrials.gov number, NCT00281489 [ClinicalTrials.gov].).

NMR study of general anesthetic interaction with nAChR beta2 subunit.

The molecular basis of anesthetic interaction with membrane proteins has been explored via determination of anesthetic effects on the structure and dynamics of the extended second transmembrane domain (TM2e) of the human neuronal nicotinic acetylcholine receptor (nAChR) beta(2) subunit in dodecylphosphocholine (DPC) micelles by (1)H and (15)N solution-state NMR. Both 1-chloro-1,2,2-trifluorocyclobutane (F3) and isoflurane, two volatile general anesthetics, induced nonuniform changes in chemical shifts among residues in TM2e. Saturation transfer difference NMR experiments further confirmed the direct anesthetic interaction with TM2e. A significant and more specific anesthetic interaction was observed on three leucine residues at the helix C-terminus. Although the TM2e helical structure remained after addition of anesthetics, plausible shortening and lengthening of helix hydrogen bonds were evidenced by periodic changes in backbone amide chemical shifts. The TM2e backbone dynamics were determined on the basis of the (15)N relaxation rate constants, R(1) and R(2), and the (15)N-[(1)H] NOE using the model-free approach. The global tumbling time (11.7 ns) of TM2e in micelles slightly increased ( approximately 12.3-12.5 ns) in the presence of anesthetics. The order parameter, S(2), exceeded 0.9 for all (15)N-labeled residues, showing a restricted internal motion. Anesthetics appear to have minor effect on the TM2e's internal motion. This study provided the basis for subsequent more comprehensive studies of anesthetic effects on the transmembrane domain complex of neuronal nAChR.

[Identification and evaluation of liver damage in subjects exposed to occupational risk from general anesthetics]. / Identificazione e valutazione del danno epatico in soggetti esposti a rischio occupazionale da anestetici generali.

BACKGROUND: The program Hepascore was produced by an interdisciplinary group working in the Laboratory of Clinical Informatics of the San Giovanni Battista Hospital in Turin with the aim of supporting physicians in the early diagnosis of hepatic damage and in its qualitative and quantitative characterization. The methodology used by this program can be useful especially for investigations concerning Industrial Medicine, which intend to control the occupational risk due to environmental exposure, not only to perform an early diagnosis (secondary prevention), but also to control the temporal evolution of the disease, by comparing significant data in a reproducible way. OBJECTIVE: This study was conducted with the aim of monitoring, by using the screening protocol of Hepascore, a group of workers exposed to an occupational risk by general anaesthetics, assessing the reliability of the proposed model and comparing it to the conventional approach in a cost/effectiveness analysis. METHODS: We evaluated 280 subjects (nurses and physicians) professionally exposed to anaesthetic gas; the environmental presence of anaesthetic agents was tested in all operating room of the hospital by the measurement of halogenated anaesthetics and nitrogen protoxide in the air. All the 280 subjects were submitted to a complete clinical evaluation and laboratory analyses, as recommended by monitoring protocols; in parallel, but independently from the clinical evaluation, also the sequential way used in the program Hepascore (a first screening phase evaluating only a few laboratory parameters, followed by a confirmation phase based on a larger number of blood tests with more restricted limits) was performed. The protocol applied in this study foresaw that subjects in which clinical evaluation and/or Hepascore brought to suspect a 'likely' liver alteration, had to be investigated thoroughly and to be reevaluated after 6 months by clinical examination and by Hepascore. RESULTS: The environmental determinations did never demonstrate the presence of anaesthetics over the threshold value (50 ppm for the N2O and 2 ppm for halogenated anaesthetics). The conventional clinical evaluation recognized as pathological 22 subjects with one or more liver parameters altered, which were explained as mild cytolytic or cholestatic alterations. The screening protocol carried out by Hepascore in the preliminary phase evidenced as pathological 38 subjects on 280 and 22 of them (corresponding to the 22 subjects identified by the clinical evaluation) were confirmed in the following phase (disease likely). CONCLUSIONS: This fact confirms that the sequential approach used by Hepascore provides the same outcomes obtained by performing all tests in the entire population under study, allowing a saving of 57% of the total cost spent for the traditional evaluation. The sequential approach proposed by Hepascore could be employed in all the clinical settings in which an evaluation of liver functional state is required, both in presence of environmental risk factors and in the case of a programme for the optimization of the population's food habits.