Exhaled breath is found to be better than blood samples for determining propofol concentrations in the brain tissues of rats.

The correlation between propofol concentration in exhaled breath (CE) and plasma (CP) has been well-established, but its applicability for estimating the concentration in brain tissues (CB) remains unknown. Given the impracticality of directly sampling human brain tissues, rats are commonly used as a pharmacokinetic model due to their similar drug-metabolizing processes to humans. In this study, we measuredCE,CP, andCBin mechanically ventilated rats injected with propofol. Exhaled breath samples from the rats were collected every 20 s and analyzed using our team's developed vacuum ultraviolet time-of-flight mass spectrometry. Additionally, femoral artery blood samples and brain tissue samples at different time points were collected and measured using high-performance liquid chromatography mass spectrometry. The results demonstrated that propofol concentration in exhaled breath exhibited stronger correlations with that in brain tissues compared to plasma levels, suggesting its potential suitability for reflecting anesthetic action sites' concentrations and anesthesia titration. Our study provides valuable animal data supporting future clinical applications.

Calibration and validation of ultraviolet time-of-flight mass spectrometry for online measurement of exhaled ciprofol.

Ciprofol (HSK 3486, C14H20O), a novel 2,6-disubstituted phenol derivative similar to propofol, is a new type of intravenous general anaesthetic. We found that the exhaled ciprofol concentration could be measured online by ultraviolet time-of-flight mass spectrometry (UV-TOFMS), which could be used to predict the plasma concentration and anaesthetic effects of ciprofol. In this study, we present the calibration method and validation results of UV-TOFMS for the quantification of ciprofol gas. Using a self-developed gas generator to prepare different concentrations of ciprofol calibration gas, we found a linear correlation between the concentration and intensity of ciprofol from 0 parts per trillion by level (pptv) to 485.85 pptv (R2 = 0.9987). The limit of quantification was 48.59 pptv and the limit of detection was 7.83 pptv. The imprecision was 12.44% at 97.17 pptv and was 8.96% at 485.85 pptv. The carry-over duration was 120 seconds. In addition, we performed a continuous infusion of ciprofol in beagles, measured the exhaled concentration of ciprofol by UV-TOFMS, determined the plasma concentration by high-performance liquid chromatography, and monitored the anaesthetic effects as reflected by the bispectral index value. The results showed that the exhaled and plasma concentrations of ciprofol were linearly correlated. The exhaled ciprofol concentration correlated well with the anaesthetic effect. The study showed that we could use UV-TOFMS to provide a continuous measurement of gaseous ciprofol concentration at 20 second intervals.

[Propofol: use, toxicology and assay features]. / Propofol: primenenie, toksikologicheskaya kharakteristika i osobennosti opredeleniya.

The study objective is to review the literature on the use, pharmacological properties, toxicology, and assay methods for intravenous anesthetic propofol. The scope and forms of propofol use, its pharmacokinetics, biotransformation features, which occurs more than 90% in the liver, and side effects associated with propofol use for anesthesia, are addressed. Propofol infusion syndrome (also known as PrIS) and deaths from propofol overdose due to medical errors, abuse, suicide attempts, and homicide are reported. Propofol identification and assay methods based on high-performance liquid chromatography (HPLC), gas chromatography with mass spectrometry (GC-MS), and liquid chromatography (LC) are described. The features of the methods performance are outlined; biological materials (the study objects) are listed: mainly blood and plasma, as well as urine, bile, hair, etc. The relevance of a comprehensive forensic chemical study of propofol is indicated, though there are few forensic studies of propofol.

Determination of etomidate and etomidate acid in hair using liquid chromatography-tandem mass spectrometry.

Etomidate, with efficacy similar to that of propofol, has been used as a propofol substitute because propofol is a designated narcotic drug, and an increase in the frequency of illegal distribution and misuse has been reported in Korea. Previous analytical studies on etomidate used blood and urine. For long-term use and timing estimation, a method for etomidate analysis using hair should be developed. Therefore, in this study, an analytical method using LC-MS/MS was developed to determine etomidate and its major metabolite in hair. Human hair samples were segmented after washing to eliminate possible contaminants on the hair and stirred with methanol. The LC-MS/MS conditions were optimized, and the chromatographic separation time was 10 min. Selectivity, linearity, limit of detection, limit of quantification, precision, accuracy, recovery, process efficiency, matrix effect, and stability were evaluated to validate the analytical method. The calibration curves ranged from 0.25 to 50 pg/mg for etomidate and 2-250 pg/mg for etomidate acid; the coefficients of determination were higher than 0.997. The intra- and inter-assay precision results for all the compounds were <15% and satisfied at recovery, process efficiency, matrix effect, and stability. In addition, this method was applied to the hair of 4 rats which are administered with etomidate to evaluate. The etomidate concentrations in the rat hair ranged from 2.60 to 8.50 pg/mg, and the etomidate acid concentrations were 2.06-7.13 pg/mg. Thus, this method can be used as basic data for monitoring etomidate in hair.

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.

Fluoride-assisted liquid chromatography-tandem mass spectrometry method for simultaneous analysis of propofol and its metabolites without derivatization in urine.

The misuse of propofol for recreational purposes has become a serious social issue. Accordingly, practical and sensitive analytical methods to investigate the chronic abuse and toxicity of propofol are required. However, current propofol determination methods using liquid chromatography-mass spectrometry (LC-MS/MS) suffer from problems associated with loss in sample preparation due to its volatility and its poor ionization efficiency and collision-induced dissociation in mass spectrometry. Herein, we have developed a sensitive and accurate fluoride-assisted LC-MS/MS method combined with direct-injection for propofol determination. Ionization via fluoride-ion attachment/induced deprotonation, effected by ammonium fluoride in the mobile phase, was found to dramatically improve the sensitivity of propofol without derivatization. Furthermore, direct injection without derivatization enables the simultaneous analysis of propofol and its phase II metabolites without analyte loss. The optimal concentration of ammonium fluoride in the mobile phase was found to be 1 mM under methanol conditions. The linearity is good (R2 ≥ 0.999) and the intra- and inter-day precisions for propofol determination are between 1.9 and 8.7%. The accuracies range from 87.5% to 105.4% and the limits of detection and quantitation for propofol in urine are 0.15 and 0.44 ng mL-1, respectively. The present method was successfully applied to human urine and showed a sufficient sensitivity to determine propofol and five phase II metabolites over 48 h in human urine after administration. Consequently, the fluoride-assisted LC-MS/MS method was demonstrated to be sensitive, accurate, and practical for the determination of propofol and its metabolites.

Drug detection in decomposed cadavers confirms testimonial evidence in a case of serial homicides.

Toxicology investigation on human's buried dead bodies is a rare and challenging task in the forensic field. As requested by the Judicial Authority, this work aimed to verify testimonial evidence that emerged during a criminal investigation involving multiple murder cases. The statements indicated an improper medical administration of one or more alleged drugs (propofol, morphine, diazepam, and midazolam) which presumably caused the deaths. Since the supposed crimes took place several years before, the task of the present work was to obtain results to support the charges. The analyses involved 18 biological samples taken from four exhumed bodies, three of which were female and one male, each buried in a different date and mode. Each sample was treated with specific purification and extraction techniques (LLE - SPE) after the addition of the deuterated analogs of the searched analytes (propofol-d17, morphine-d3, diazepam-d5, midazolam-d4) as internal standards. Afterwards, the extracts were subjected to qualitative analysis by gas chromatography-mass spectrometry-Electron Impact (GC/MS - EI), both in full scan and SIM mode. Propofol, morphine, and diazepam were identified in the corpses. It supports testimonials that were administered just before the deaths occurred.

Breath-by-breath measurement of intraoperative propofol by unidirectional anisole-assisted photoionization ion mobility spectrometry via real-time correction of humidity.

Humidity as a major issue affects the quantitative performance of ion mobility spectrometry (IMS) in field applications. According to the kinetic equations of ion-molecular reaction, the intensity ratio of the product ion peak (PIP) over the reactant ion peak (RIP) is proposed as a quantitative factor to correct real-time humidity variation. By coupling this method with a unidirectional anisole-assisted photoionization IMS, direct breath-by-breath measurement of intraoperative propofol was achieved for the first time, which provided more clinical information for studying the anesthetics pharmacokinetics. Although the signal intensities of the RIP and the propofol PIP both declined along with the increase of humidity, the intensity ratio of Propofol/(RIP + Propofol) kept almost constant in a wide relative humidity range of 0%-98%, enabling direct quantitation of exhaled propofol with varying humidity. Furthermore, interfering ion peaks resulted from the high concentration humidity and anesthetics in single exhalation were eliminated during the balanced anesthesia as the exhaled sample was diluted by the unidirectional gas flow scheme. As a demonstration, breath-by-breath variation profiles of propofol were obtained via monitoring end-tidal propofol concentration of intraoperative anesthetized patients (n = 7). The analyses were quantitative, corrected for humidity in real-time, without measuring the humidity content of each breath sample during operation, which show potential for the quantitative analysis of other high humidity samples.

Influência do tramadol associado à levobupicavaína epidural sobre a taxa de propofol e variáveis fisiológicas, em cadelas submetidas à mastectomia e à ovário-histerectomia / [Influence of tramadol combined with epidural levobupicavaine, on the propofol infusion rate and physiological variables, in female dogs undergoing mastectomy and ovariohysterectomy]

Objetivou-se avaliar os efeitos fisiológicos e sobre o consumo do propofol, relativos à anestesia epidural com levobupivacaína isolada ou associada a diferentes doses de tramadol. Para tal, 18 cadelas foram pré-tratadas com acepromazina, utilizando-se propofol para indução e manutenção anestésicas. Conforme o protocolo epidural instituído, formaram-se três grupos (n=6) tratados com levobupivacaína isolada (1,5mg/kg) (GL) ou acrescida de 2mg/kg (GLT2) ou 4mg/kg (GLT4) de tramadol, respectivamente. As fêmeas foram submetidas à mastectomia e à ovário-histerectomia (OH), registrando-se as variáveis fisiológicas nos períodos pré (TB e T0) e transanestésicos (T10 a T70), bem como a taxa mínima de propofol necessária. Houve redução da FC para o GL e o GLT4 em relação ao GLT2 (T30 a T70), detectando-se, no GL, redução da PAS e da PAD em relação ao TB. Maiores taxas de infusão do propofol foram necessárias para o GL (0,70±0,12mg/kg/min) em relação ao GLT2 (0,50±0,19mg/kg/min) e ao GLT4 (0,50±0,19mg/kg/min). Conclui-se que o tramadol potencializou o propofol, ao ofertar analgesia, independentemente da dose administrada. Todos os protocolos testados foram seguros e eficazes em cadelas submetidas à mastectomia e à OH.(AU)

The aim of this study was to evaluate the physiological and on propofol-sparing effects related to epidural anesthesia with levobupivacaine alone or combined with different doses of tramadol. For this purpose, 18 female dogs were pretreated with acepromazine, using propofol for induction and maintenance of anesthesia. Based on a previously established epidural (L7-S1) protocol, three groups (n=6) were treated with either levobupivacaine alone (1.5mg.k-1) (GL) or in association with to 2mg.kg-1 (GLT2) or 4mg.kg-1 (GLT4) of tramadol, respectively. These dogs were all undergoing mastectomy and ovariohysterectomy (OH). The physiological data were registered in the pre (TB and T0) and trans-anesthetic periods (T10 - T70), as well as the consumption of propofol. There was a reduction in the HR for GL and GLT4 in relation to GLT2 (T30 - T70) and reductions in SAP and DAP in relation to TB in the GL group. Higher continuous infusion rate of propofol were required for GL (0.70±0.12mg.kg-1.min-1) relative to GLT2 (0.50±0.19mg.kg-1.min-1) and GLT4 (0.50±0.19mg.kg-1.min-1). It was concluded that tramadol potentiated propofol, offering analgesia independently of its administered dose. All protocols tested were safe and effective in female dogs undergoing mastectomy and OH.(AU)

Online monitoring of end-tidal propofol in balanced anesthesia by anisole assisted positive photoionization ion mobility spectrometer.

Online measuring end-tidal propofol concentration during balanced anesthesia is important for anesthetists to learn the patient's anesthesia depth as exhaled propofol concentration is well related to blood propofol concentration. In previous work, exhaled propofol was detected using acetone assisted negative photoionization ion mobility spectrometer, however, the existence of high concentration sevoflurane interfered the response of propofol. In this work, an anisole assisted photoionization ion mobility spectrometer operated in positive mode was developed to sensitively and selectively measure the end-tidal propofol by eliminating the interferences of exhaled humidity and sevoflurane during balanced anesthesia. Anisole molecular ion is stable enough not to go under proton transfer reaction with water presents in the exhaled breath. Hence, the exhaled humidity related peaks were eliminated and only one propofol product ion peak (K0 = 1.50 cm2 V-1 s-1) was observed. The relative standard deviation (RSD) ranging from 0.64%-0.91% showed good repeatability and the quantitative range was 0.2-40 ppbv with a response time of 4 s. Finally, the performance of the proposed method was demonstrated by monitoring end-tidal propofol of balanced anesthetized patients during gastric cancer surgery.

Coexistence of oil droplets and lipid vesicles in propofol drug products.

Propofol is intravenously administered oil-in-water emulsion stabilized by egg lecithin phospholipids indicated for the induction and maintenance of general anesthesia or sedation. It is generally assumed to be structurally homogenous as characterized by commonly used dynamic light scattering technique and laser diffraction. However, the excessive amount of egg lecithin phospholipids added to the propofol formulation may, presumably, give rise to additional formation of lipid vesicles (i.e., vesicular structures consisting of a phospholipid bilayer). In this study, we investigate the use of high-resolution cryogenic transmission electron microscopy (cryo-TEM) in morphological characterization of four commercially available propofol drug products. The TEM result, for the first time, reveals that all propofol drug products contain lipid vesicles and oil droplet-lipid vesicle aggregated structures, in addition to oil droplets. Statistical analysis shows the size and ratio of the lipid vesicles varies across four different products. To evaluate the impact of such morphological differences on active pharmaceutical ingredient (API)'s distribution, we separate the lipid vesicle phase from other constituents via ultracentrifuge fractionation and determine the amount of propofol (2,6-diisopropylphenol) using high performance liquid chromatography (HPLC). The results indicate that a nearly negligible amount of API (i.e., NMT 0.25% of labeled content) is present in the lipid vesicles and is thus primarily distributed in the oil phase. As oil droplets are the primary drug carriers and their globule size are similar, the findings of various lipid vesicle composition and sizes among different propofol products do not affect their clinical outcomes.

Evaluating Propofol Concentration in Blood From Exhaled Gas Using a Breathing-Related Partition Coefficient.

BACKGROUND: The anesthetic side effects of propofol still occur in clinical practice because no reliable monitoring techniques are available. In this regard, continuous monitoring of propofol in breath is a promising method, yet it remains infeasible because there is large variation in the blood/exhaled gas partial pressure ratio (RBE) in humans. Further evaluations of the influences of breathing-related factors on RBE would mitigate this variation. METHODS: Correlations were analyzed between breathing-related factors (tidal volume [TV], breath frequency [BF], and minute ventilation [VM]) and RBE in 46 patients. Furthermore, a subset of 10 patients underwent pulmonary function tests (PFTs), and the parameters of the PFTs were then compared with the RBE. We employed a 1-phase exponential decay model to characterize the influence of VM on RBE. We also proposed a modified RBE (RBEM) that was not affected by the different breathing patterns of the patients. The blood concentration of propofol was predicted from breath monitoring using RBEM and RBE. RESULTS: We found a significant negative correlation (R = -0.572; P < .001) between VM and RBE (N = 46). No significant correlation was shown between PFTs and RBE in the subset (N = 10). RBEM demonstrated a standard Gaussian distribution (mean, 1.000; standard deviation [SD], 0.308). Moreover, the predicted propofol concentrations based on breath monitoring matched well with the measured blood concentrations. The 90% prediction band was limited to within ±1 µg·mL. CONCLUSIONS: The prediction of propofol concentration in blood was more accurate using RBEM than when using RBE and could provide reference information for anesthesiologists. Moreover, the present study provided a general approach for assessing the influence of relevant physiological factors and will inform noninvasive and accurate breath assessment of volatile drugs or metabolites in blood.

Development of a LC-MS/MS method for determination of propofol-glucuronide in hair and preliminary study on relationships between dose and hair concentration.

Propofol abuse has been reported worldwide, suggesting the need to establish analytical methods for human biological samples to investigate the abuse of propofol. This study aimed to investigate the relationship between dose and hair concentration using a simple and rapid analytical method developed and validated in this study. In the sample preparation, hair samples were washed with distilled water and methanol and extracted in methanol during 16h at room temperature. After centrifugation and evaporation, the residue was reconstituted and filtered through a 0.22µm membrane filter before LC-MS/MS analysis. The precursor-to-product ion transitions were 353 → 175, 113 for propofol glucuronide and m/z 370 → 175, 113 for internal standard(propofol glucuronide-d17). The calibration curves were satisfactory (R2=0.9997) and the limits of detection and quantification were 2 and 5pg/mg, respectively. In addition, this study collected the history of propofol use from subjects using a questionnaire and analyzed subjects' hair samples using a validated analytical method. As a result, the concentrations of propofol glucuronide ranged from 7 to 122pg/mg (mean : 51pg/mg). There were cases of positive relationships, but generally there was no correlation between dose and hair concentration.

[Climate footprint of halogenated inhalation anesthetics]. / Klimateffekterna från anestesin kan minska.

This study estimated the climate footprint of halogenated inhalation anesthetics in Sweden and estimated effects of a decreased use of these compounds. We collected data on sales of desflurane, sevoflurane and isoflurane in Sweden during 2017 and calculated the mass of CO2 equivalents (CO2e) using Global Warming Potential data over 100 years for the compounds. Inhalation anesthetics contributed by 5000 tons of CO2e which corresponds to 0.005 percent of the Swedish climate footprint. By replacing desflurane with sevoflurane the footprint can be reduced by 73 percent. By replacing sevoflurane with intravenous propofol the climate effect can be reduced further by at least 2 orders of magnitude.

Development of a highly sensitive gas chromatography-mass spectrometry method preceded by solid-phase microextraction for the analysis of propofol in low-volume cerebral microdialysate samples.

To date, the commonly used intravenous anesthetic propofol has been widely studied, and fundamental pharmacodynamic and pharmacokinetic characteristics of the drug are known. However, propofol has not yet been quantified in vivo in the target organ, the human brain. Here, cerebral microdialysis offers the unique opportunity to sample propofol in the living human organism. Therefore, a highly sensitive analytical method for propofol quantitation in small sample volumes of 30 µL, based on direct immersion solid-phase microextraction was developed. Preconcentration was followed by gas chromatographic separation and mass spectrometric detection of the compound. This optimized method provided a linear range between the lower limit of detection (50 ng/L) and 200 µg/L. Matrix-matched calibration was used to compensate recovery issues. A precision of 2.7% relative standard deviation between five consecutive measurements and an interday precision of 6.4% relative standard deviation could be achieved. Furthermore, the permeability of propofol through a cerebral microdialysate system was tested. In summary, the developed method to analyze cerebral microdialysate samples, allows the in vivo quantitation of propofol in the living human brain. Additionally the calculation of extracellular fluid levels is enabled since the recovery of the cerebral microdialysis regarding propofol was determined.

Survival of Staphylococcus epidermidis in Propofol and Intralipid in the Dead Space of Intravenous Injection Ports.

We tested whether propofol or Intralipid inoculated with Staphylococcus epidermidis would promote bacterial growth within an intravenous (IV) injection hub, a site prone to bacterial contamination. In tubes incubated under optimal conditions, S epidermidis exhibited growth in Intralipid, but not in propofol. In contrast, within the IV hub incubated with either propofol or intralipid at room temperature, S epidermidis bacterial numbers declined with time, and virtually no contamination remained after 12 hours. These data suggest that certain IV lines are inhospitable for S epidermidis.

Dopant-assisted photoionization positive ion mobility spectrometry coupled with time-resolved purge introduction for online quantitative monitoring of intraoperative end-tidal propofol.

Online monitoring of end-tidal propofol provides important information of anesthesia deepness for anesthetists as propofol concentrations in plasma and breath are well correlated. In this work, a dopant-assisted photoionization positive ion mobility spectrometry (DAPI-PIMS) coupled with time-resolved purge introduction was developed for online quantitative monitoring end-tidal propofol. With optimized dopant, toluene, the selectivity and sensitivity of propofol was improved as interference from sevoflurane was eliminated. Using the time-resolved purge introduction, the response of propofol and moisture was separated due to their absorption differences on the inwall of the fluorinated ethylene propylene (FEP) sample loop, ensuring sensitive measurement of end-tidal propofol with a short response time of 4 s. The quantitative equation derived from the second order reaction kinetics model extended the quantitative range of propofol from 0.2 ppbv to 45 ppbv. Finally, the method was used to monitor the intraoperative end-tidal propofol of six patients, and the results nicely demonstrated its feasibility in practical clinical environment.

Determination of Cyanide by Microdiffusion Technique Coupled to Spectrophotometry and GC/NPD and Propofol by Fast GC/MS-TOF in a Case of Poisoning.

A man was found dead in a hotel located near Rome (Italy). The man was still holding a syringe attached to a butterfly needle inserted in his left forearm vein. The syringe contained a cloudy pinkish fluid. In the hotel room the Police found a broken propofol glass vial plus four sealed ones, an opened NaCl plastic vial and six more still sealed, and a number of packed smaller disposable syringes and needles. An opened plastic bottle containing a white crystalline powder labeled as potassium cyanide was also found. Systematic toxicological analysis (STA), carried out on blood, urine and bile, evidenced only the presence of propofol in blood and bile. So the validated L-L extraction protocol and the GC/MS-TOF method for the confirmation of propofol in the biological fluids optimized in our laboratory was applied to blood, urine and bile. The concentration of propofol resulted to be 0.432 µg/mL in blood and 0.786 µg/mL in bile. The quantitative determination of cyanide in blood was carried out by microdiffusion technique coupled to spectrophotometric detection obtaining a cyanide concentration of 5.3 µg/mL. The quantitative determination was then confirmed by GC/NPD and the concentration of cyanide resulted to be 5.5 µg/mL in blood and 1.7 µg/mL in bile. Data emerging from autopsy findings, histopathological exams and the concentrations of cyanide suggested that death might be due to poisoning caused by cyanide, however, respiratory depression caused by propofol could not be excluded.

Online Monitoring of Intraoperative Exhaled Propofol by Acetone-Assisted Negative Photoionization Ion Mobility Spectrometry Coupled with Time-Resolved Purge Introduction.

Online monitoring of exhaled propofol concentration is important for anesthetists to provide adequate anesthesia as propofol concentrations in plasma and breath are correlated reasonably well. Exhaled propofol could be detected by 63Ni ion mobility spectrometry in negative ion mode; however, the radioactivity of 63Ni source restricts its clinical application due to safety, environmental, and regulatory concerns. An acetone-assisted negative photoionization ion mobility spectrometer (AANP-IMS) using a side-mounted vacuum ultraviolet (VUV) lamp in the unidirectional (UD) flow mode was developed for sensitive measurement of exhaled propofol by producing a high percentage of O2-(H2O) n. An adsorption sampling and time-resolved purge introduction system was developed to eliminate the interference of residual inhaled anesthetic sevoflurane based on their different adsorptions between propofol and sevoflurane on the inwall of the fluorinated ethylene propylene (FEP) sample loop. The effects of the inner diameter and the length of the sample loop on the signal intensity of propofol and the time-resolution between propofol and sevoflurane were theoretically and experimentally investigated. A sample loop with 3 mm i.d. and 150 cm length allowed sensitive measurement of exhaled propofol with a response time of 4 s, a linear response range for propofol was achieved to be 0.2 to 14 ppbv with a limit of detection (LOD) of 60 pptv, and the quantification of propofol was not influenced by the change of the sevoflurane concentration. Finally, the performance of monitoring exhaled propofol during surgery was demonstrated on a patient undergoing laparoscopic distal pancreatectomy combined with cholecystectomy.

Evaluation of the stability and stratification of propofol and ketamine mixtures for pediatric anesthesia.

BACKGROUND: The combination of propofol and ketamine is commonly used for total intravenous anesthesia. These drugs can be delivered in different syringes or in the same syringe. We hypothesized that the drugs might separate and different concentrations of each drug could be found in different parts of the syringe during the procedure period when they were mixed in 1 syringe. METHODS: Twelve 60-mL polypropylene syringes were prepared by mixing propofol and ketamine as 4 groups on the basis of propofol/ketamine mixture ratios (5:1 and 6.7:1) and propofol solution concentrations. Syringes were placed upright in the vertical position into a rack and kept at room temperature (21.5-22.5°C), in daylight conditions and were not moved for 360 minutes. Samples of the mixture were taken from both the top and the bottom of the syringe. The first 1 mL of the samples was discarded, the following second 1 mL of the samples was filtered using 0.2-µm polytetrafluoroethylene filters and measured twice (n = 6). Samples were taken at the following time intervals: T0, T10, T30, T60, T90, T120, T180, T240, T300, and T360 min. Syringes were checked visually for any color change and separation lines between the drugs. RESULTS: There were no significant differences between the propofol and ketamine concentrations of the top and bottom samples in all 4 groups. In addition, there were no statistically significant changes of propofol and ketamine concentrations of samples over 360 minutes in any of the 4 groups. No visual changes were observed during 6 hours' observation. CONCLUSION: The results of our measurements demonstrated that mixtures of propofol (1% and 2%) and ketamine at 5:1 and 6.7:1 ratios could be used in terms of mixture homogeneity and stability in a polypropylene syringe during a 6-hour period at room temperature.