[Health hazards resulting from occupational exposure to enfluran - overview of tests and analysis of admissible concentration values]. / Zagrozenia zdrowotne wynikajace z narazenia zawodowego na enfluran ­ przeglad badan i próba analizy wartosci dopuszczalnych stezen.

The aim of this work is to analyze the health hazards of enflurane exposure and to analyze the occupational exposure limits (OEL). The method of obtaining evidence based on a review of online databases of scientific journals was used. Enflurane is an inhalation anesthetic. Malignant hyperthermia, seizures, arrhythmias, respiratory depression and hypotension have been observed in patients. Occupational exposure to enflurane may occur in healthcare professionals. The target organ for enflurane is the central nervous system with a critical consequence of deterioration in psychomotor performance. In studies on volunteers recruited from the medical staff of operating rooms exposed to enflurane, a significant deterioration in the results of the Simple Reaction Time Test was shown. World experts' groups assume that the LOAEC (lowest observed adverse effect concentration) value for the deterioration of psychomotor test results is 5-10% of the MAC value (minimal anesthetic concentration), i.e., 6342-12 684 mg/m3. Assessment of the nephrotoxic potential of enflurane has shown that it is unlikely to occur because biotransformation of enflurane in humans results in a low peak serum fluoride concentration of 15 µmol/l. Early reports about liver damage in patients were not be supported. Occupational exposure epidemiological studies have raised concerns about the effects of anesthetic gas mixtures on the abortion rate or on fetal development and birth defects in children, but none of these studies specifically determined the type and concentration of anesthetic gases used. The carcinogenicity and mutagenicity studies were negative. Occupational exposure to enflurane is not monitored in Poland, as no standard value has been established for it in the air of the working environment. It is necessary to quickly introduce this anesthetic along with the applicable limit value to the OEL list. Med Pr. 2022;73(1):51-69.

Sequential V(A)/Q distributions in the normal rabbit by micropore membrane inlet mass spectrometry.

We developed micropore membrane inlet mass spectrometer (MMIMS) probes to rapidly measure inert-gas partial pressures in small blood samples. The mass spectrometer output was linearly related to inert-gas partial pressure (r(2) of 0.996-1.000) and was nearly independent of large variations in inert-gas solubility in liquid samples. We infused six inert gases into five pentobarbital-anesthetized New Zealand rabbits and used the MMIMS system to measure inert-gas partial pressures in systemic and pulmonary arterial blood and in mixed expired gas samples. The retention and excretion data were transformed into distributions of ventilation-to-perfusion ratios (V(A)/Q) with the use of linear regression techniques. Distributions of V(A)/Q were unimodal and broad, consistent with prior reports in the normal rabbit. Total blood sample volume for each VA/Q distribution was 4 ml, and analysis time was 8 min. MMIMS provides a convenient method to perform the multiple inert-gas elimination technique rapidly and with small blood sample volumes.

Determination of volatile anesthetics isoflurane and enflurane in mouse brain tissues using gas chromatography-mass spectrometry.

INTRODUCTION: A method for determination of the volatile anesthetics, isoflurane, and enflurane in mouse brain tissues using headspace gas chromatography-mass spectrometry (GC-MS) is described. METHODS: Halothane was used as internal standard (I.S.). Brain samples were completely homogenized in ice-cold water and isoflurane, enflurane, and I.S. were extracted with headspace. One milliliter of headspace gas was injected onto the GC-MS and separation was achieved by using porous layer open tubular (PLOT) capillary column with a solid stationary phase (GSC). As a result, isoflurane, enflurane, and halothane were cleanly separated. RESULTS: The method demonstrated satisfactory recovery (72% and 76% for isoflurane and enflurane, respectively) and linear calibration ranges of 0.015-2.20 and 0.0152-3.94 microg/sample for isoflurane and enflurane, respectively. Reproducibility calculated as CV% was 3.3-3.9% for all intraday and interday determinations. The procedure was applied for quantitation of isoflurane and enflurane in about 300 mouse brain samples for genetic behavioral study. DISCUSSION: The method was achieved and shown to be effective.

Enflurane as an internal standard in monitoring halogenated volatile anaesthetics by headspace gas chromatography-mass spectrometry.

Recently. we proposed the use of a run-only headspace-GC-MS method for the biological monitoring of ppb concentrations of unmodified volatile anaesthetics (isoflurane, sevoflurane and halothane, plus nitrous oxide) in post-shift urine of operating theatre personnel. The adoption of enflurane (a volatile anaesthetic no longer used in clinical practice) as a poper and viable internal standard improves intra-day and inter-day accuracy in halide quantitation, providing a GC-MS reference method useful in the practice of biomonitoring of exposure of operating theatre personnel to modern volatile anaesthetics (isoflurane. sevoflurane, halothane).

An unusual case of driving under the influence of enflurane.

An unusual case of driving under the influence of the volatile anaesthetic enflurane is reported. A markedly affected anaesthetist was sniffing at an enflurane-moistened handkerchief before he crashed into a lorry at a red traffic light. In the blood sample enflurane (2.92 mg/l) as well as diclofenac (0.28 mg/l) and 4-aminophenazone (24.4 mg/l) were found. The way of driving and the accident and the deficiency symptoms could be explained by the central suppressing effects of enflurane. The physician was considered as impaired and not suitable to drive at the time of the incidence.

Fatal recreational inhalation of enflurane.

We report here a case of fatal enflurane poisoning by recreational inhalation, apparently the first published report of such a case.

Fatal accidental enflurane intoxication.

Among reported cases of abuse of volatile anesthetics there is only one of enflurane intoxication. We report another fatal enflurane intoxication. A 21-year-old man found dead seemed to have experimented with enflurane. Three and one-half days after death high amounts of enflurane were detected in blood, brain, and subcutaneous fat. Gas chromatographic quantification revealed the following high enflurane concentrations: blood: 130 mg/l-1, brain: 350 mg/l-1, and subcutaneous fat: 100 mg/l-1. Histologic signs of drug-induced damage were lacking. No suicide intentions became known. It was concluded that the young man died of an accidental intoxication while abusing enflurane.

Minimal alveolar concentrations for halothane, enflurane, and isoflurane in the cat.

The minimal alveolar concentrations for halothane, enflurane, and isoflurane in the domestic cat were found to be 1.19 +/- 0.05 (SEM)%, 2.37 +/- 0.06%, and 1.61 +/- 0.04%, respectively. During the potency studies, it was observed that enflurane and isoflurane resulted in shorter wake-up times, compared with halothane. However, enflurane and isoflurane produced electroencephalographic (EEG) and clinical signs of CNS irritability (EEG spiking, myoclonus) in normocapnic or mildly hypocapnic cats. In addition, enflurane and isoflurane caused greater airway irritability (coughing, salivation) than did halothane.

A lower solubility recommends the use of desflurane more than isoflurane, halothane, and enflurane under low-flow conditions.

STUDY OBJECTIVE: To determine whether the lower solubility of desflurane, over that of isoflurane, enflurane, and halothane, favors its use in low-flow anesthesia. DESIGN: Prospective clinical study. SETTING: Technical University of Munich. PATIENTS: 40 elderly (> or = 65 yrs), ASA physical status II and III surgical patients. INTERVENTIONS: All patients were anesthetized and received delivered concentrations (FD) of 4% desflurane, 1.5% isoflurane, 1.8% enflurane, or 0.9% halothane (n = 10 patients for each anesthetic) in a fresh gas inflow of 3 L/min (high-flow), until end-tidal target concentrations (FA) of 2% desflurane, 0.5% isoflurane, 0.6% enflurane, and 0.3% halothane were obtained. After 30 minutes, the inflow was decreased to 1 L/min (low-flow), and the FD and the inspired concentration (FI) were adjusted to maintain the target concentration. MEASUREMENTS AND MAIN RESULTS: The concentrations of the halogenated anesthetics, as well as nitrous oxide, oxygen (O2), and carbon dioxide, were measured in delivered gas at the common gas outlet and at the endotracheal tube connector. Transcutaneous O2 saturation, noninvasive blood pressure, and heart rate were also measured. During the first 30 minutes of high-flow administration, the target concentration was attained sooner with desflurane than with isoflurane, enflurane, or halothane (median levels: 4 min vs. 6 min, 8 min, or 10 min; p < 0.01). After the reduction of inflow to 1 L/min, FD had to be materially increased to maintain F1 and FA for the more soluble anesthetics, but not for desflurane. CONCLUSIONS: At low flows, FD provides a reasonable surrogate of F1 and FA for desflurane, but not for isoflurane, enflurane, or halothane. The rapid and predictable titrability of desflurane favors its safe use in low-flow technique.

Biological monitoring of occupational exposure to enflurane (ethrane) in operating room personnel.

Biological monitoring of occupational exposure to enflurane (ethrane) can be achieved by measuring concentrations of inorganic fluorides in the blood and urine and of enflurane in alveolar air and venous blood. Measurement of these concentrations, however, has limitations. Another method for monitoring exposure to enflurane is to measure its concentration in urine throughout the period of exposure. In this study, we measured the environmental and urinary concentrations of enflurane. Enflurane in the ambient atmosphere was determined in 18 operating theaters of eight hospitals in Italy. Ambient air concentrations exceeded the National Institute for Occupational Safety and Health-recommended time-weighted average exposure level of 1 ppm (median: 1.31 ppm). Enflurane was detected in urine of 159 exposed subjects (anesthetists, surgeons, and nurses). A significant correlation was found between enflurane concentration in urine produced during the shift and environmental concentration (r = 0.77, p = .0001). The results showed that urinary enflurane concentration can be used as an appropriate biological exposure index. The biological values proposed are 153 micrograms/l, corresponding to 75 ppm of environmental exposure; 22 micrograms/l, corresponding to 10 ppm of environmental exposure; and 3.5 micrograms/l, corresponding to 1 ppm of environmental exposure. The proposed values can be regarded as time-weighted average samples, reflecting exposure for a 4-h period.

Neurobehavioral functions in operating theatre personnel exposed to anesthetic gases.

Neurobehavioral functions in paramedical operating theatre personnel were assessed in a cross-sectional survey. Sixty-two subjects (40 males and 22 females) occupationally exposed to anesthetic gases were examined and compared to 46 unexposed hospital workers (18 males and 28 females). The Simple Reaction Time (SRT) test was selected from the MANS battery (Milan Automated Neurobehavioural System). In order to evaluate acute and subacute types of effects on performance, the test was administered before and after the work shift, at the beginning and at the end of the working week. In addition, the complete battery was administered during one working day without exposure to anesthetic gases. On the last day of the working week, atmospheric nitrous oxide (N2Oa) ranged from 7 to 553 ppm (geometric mean 62.6), atmospheric ethrane (ETHa) ranged from 0.1 to 18.8 ppm (geometric mean 1.3), and urinary N2O (N2Ou) ranged from 4 to 297 micrograms/l (geometric mean 26.8). An impairment of performance on the SRT test was observed at the end of the working week in subjects exposed to anesthetic gases compared to controls. This alteration was observed also considering only the subjects exposed to less than 55 micrograms/l (which is the Italian exposure limit for N2Ou, equivalent to 100 ppm for N2Oa). No significant differences were observed for the other psychometric tests. No dose-effect relationships where found between SRT test score and the indicators of exposure (N2Oa, ETHa, N2Ou).(ABSTRACT TRUNCATED AT 250 WORDS)

[Anesthesia programmed by enflurane]. / Anesthésie programmée à l'enflurane.

A microcomputer type 6502 is the central unity of a volatile anaesthetic injector for use in a closed circuit breathing system. Estimated calculations for quantity of anaesthetic liquid are done in agreement with the formula of J.W. Severinghaus and H. Lowe. Clinical assay is realised with enflurane. The syringe efficacy is controlled by permanent recorder of halogenate concentration in upper airways Fi-FA: infrared analysor cosma Rubis 3000).

Effects of maternal enflurane exposure on NR2B expression in the hippocampus of their offspring

This work aims to study the pathogenesis of learning and memory impairment in offspring rats resulting from maternal enflurane anesthesia by focusing on the expression of the N-methyl-d-aspartic acid receptor subunit 2B (NR2B) in the hippocampus of the offspring. Thirty female Sprague-Dawley rats were randomly divided into three groups: control (C group), 4 h enflurane exposure (E1 group), and 8 h enflurane exposure (E2 group) groups. Eight to ten days after the initiation of pregnancy, rats from the E1 and E2 groups were allowed to inhale 1.7% enflurane in 2 L/min oxygen for 4 h and 8 h, respectively. Rats from the C group were allowed to inhale 2 L/min of oxygen only. The Morris water maze was used to assay the learning and memory function of the offspring on postnatal days 20 and 30. RT-PCR and immunohistochemistry assays were then used to measure the mRNA levels and protein expression of NR2B, respectively. Relative to offspring rats from the C group, those from the E1 and E2 groups exhibited longer escape latencies, lesser number of crossings over the platform, and less time spent in the target quadrant in the spatial exploration test (P < 0.05). In addition, the mRNA and protein expression levels of NR2B in the hippocampus of offspring rats in the E1 and E2 groups were down-regulated (P < 0.05). No significant differences between the E1 and E2 groups were observed (P > 0.05) in terms of mRNA levels and protein expression of NR2B. The cognitive function of the offspring is impaired when maternal rats are exposed to enflurane during early pregnancy. A possible mechanism of this effect is related to the down-regulation of NR2B expression.

Este trabalho objetiva o estudo da patogênese de deficiência no aprendizado e memória de prole de ratos resultante da anestesia maternal por enflurano, por meio da expressão da subunidade 2B do receptor do ácidoN-metil-D-aspártico (NR2B) no hipocampo dos filhotes. Dividiram-se, aleatoriamente, 30 fêmeas de ratos Sprague-Dawley em três grupos: controle (grupo C), exposição ao enflurano por 4 h (grupo E1) e por 8 h (grupo E2). De oito a 10 dias após o início da gravidez, os ratos dos grupos E1 e E2 inalaram enflurano 1,7% em 2 L/min de oxigênio, por 4 h e 8 h, respectivamente. Ratos do grupo C inalaram apenas 2 L/min de oxigênio. O labirinto de água de Morris foi empregado para analisar as funções de aprendizado e memória da cria em 20 e 30 dias após o nascimento. Utilizaram-se ensaios de RT-PCR e de imuno-histoquímica para medir os níveis de mRNA e expressão da proteína do NR2B, respectivamente. Em comparação com os ratos controle do grupo C, aqueles dos grupos E1 e E2 exibiram latências de escape mais longas, menor número de travessias na plataforma e menos tempo gasto no quadrante alvo no teste de exploração espacial (P < 0,05). Adicionalmente, os níveis de expressão de mRNA e de proteína do NR2B no hipocampo dos filhotes nos grupos E1 e E2 estavam reduzidos (P < 0,05). Não se observaram diferenças significativas entre os grupos E1 e E2 (P < 0,05) quanto aos níveis de mRNA e à expressão de proteína de NR2B. A função cognitiva dos filhotes é prejudicada quando as mães são expostas ao enflurano durante o início da gravidez. O mecanismo possível para esse efeito está relacionado à diminuição na expressão de NR2B.