[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.

Comparison of effects of anaesthesia with desflurane and enflurane on liver function.

INTRODUCTION: Although most general anaesthesia procedures are performed without any complications, volatile agents may have adverse effects on various living systems. This study aimed to compare the effects of desflurane and enflurane on liver function. METHODS: 40 patients, who were in the ASA I-III risk groups and were planned to undergo head and neck surgery of at least three hours' duration, were randomly divided into two groups: the desflurane (Group D) and enflurane groups (Group E). Venous blood samples (5 ml) of the patients were obtained before anaesthesia induction, in the postoperative first hour and on the first and seventh days. The samples were centrifuged and then stored at -80 degrees Celsius until the determination of glutathione S-transferase (GST) levels. For maintenance of anaesthesia in Group D, desflurane (6 percent) was used, while in Group E, enflurane (1.2 percent) was used. RESULTS: GST levels were significantly higher in Group E in the postoperative first hour (p-value is 0.002), and on the first day (p-value is 0.025) and seventh day (p-value is 0.035), although there were no differences preoperatively (p-value is more than 0.05). When postoperative levels were compared with preoperative levels, the postoperative GST levels of Group E were significantly higher (first hour [p-value is 0.008], first day [p-value is 0.010], seventh day [p-value is 0.038]). CONCLUSION: Subclinical hepatic injury after anaesthesia continues to be an issue of interest, particularly with the development of new, more sensitive methods of measuring GST levels. The increase in GST concentration after anaesthesia is thought to be a result of reduced hepatic blood flow. This study has shown that desflurane has fewer effects than enflurane on liver function tests in lengthy operations of up to 330 minutes.

Pre-operative prediction of 'dry taps'.

OBJECTIVES: The treatment of children with 'glue ear' often presents surgeons with the question of whether or not to insert a grommet when myringotomy reveals no fluid in the middle ear. We present a study designed to assess which factors contribute to the presence of a 'dry tap'. DESIGN: We prospectively gathered data from a cohort of 280 children (504 myringotomies). The cohort included two subgroups, one received halothane and nitrous oxide anaesthesia, and the other received enflurane anaesthesia. SETTING: The ENT department of a district general hospital. PARTICIPANTS: Children (aged less than 17 years) requiring myringotomy. MAIN OUTCOME MEASURES: The presence of a 'glue' or dry tap at myringotomy was documented. We also recorded data on the following: pre- and post-induction tympanometry; age; season; anaesthetic type; and the delay from listing to actual operation. RESULTS: A non type B pre-induction tympanogram and delay to operation were strong indications of finding a dry tap at surgery. CONCLUSIONS: In our study population, the proportion of dry taps at myringotomy was 18 per cent. The presence of a dry tap was rarely due to the induction of anaesthesia. Multivariate analysis revealed that the combination of factors most likely to predict a dry tap were non type B tympanogram and delay to operation.

[Effect of volatile inhalational anesthetics on cerebral blood volume and oxygen status in children].

The investigation evaluated the effect of various volatile anesthetics on cerebral blood volume and oxygen status in sick children at the stage of anesthesia induction. Ninety-two children were distributed into 3 groups: Groups 1 (n = 36) and 2 (n = 24) underwent stepwise induction with halothane and enflurane, respectively. Group 3 (n = 32) had vital capacity rapid inhalation induction with sevoflurane. Cerebral oximetry (NIRS method) was used to measure the content of hydroxyhemoglobin, deoxyhemoglobin, the total level of hemoglobin and to assess regional cerebral tissue saturation (rSO2). Halothane was ascertained to increase cerebral blood volume by 20.5% whereas enflurane and sevoflurane increased it only by 8.8 and 9.0%, respectively. In all cases, the value of rSO2 remained comparatively high, by exceeding the baseline level by 3-5%.

[Induction of anesthesia with halogen-containing anesthetic agents in children].

The study has comparatively evaluated the effectiveness and safety of halothane, enflurane, and isoflurane in children during induction. Seventy hundred and eight patients aged 1-14 years who had ASA I-II anesthetic risks were examined. Gas induction was performed as monoanesthesia through the semi-open circuit with high gas flow (100% O2 6 l/min) in combination with halothane (n = 236), enflurane (n = 236), or isoflurane (n = 236) without N2O. The authors have compared the following criteria: the speed and comfort of induction, the parameters of hemodynamics and external respiration, and the rate of adverse reactions and complications during induction. The studies have established that in terms of comfort, safety, and the rate clinical effect achievement, the drugs of choice for gas induction in children are enflurane and, to a lesser extent, halothane. Gas induction with isoflurane should not be performed in children since the agent rather frequently exerts an irritant action on the upper airways, which reduces the speed of initial narcosis and increases the likelihood of one or another adverse reactions; however; it has advantages as a less hemodynamic effect.

Fluoride metabolism in smokers and non-smokers following enflurane anaesthesia.

BACKGROUND: Inorganic fluoride is released by the metabolism of enflurane and the increased serum fluoride concentrations may impair renal function. Tobacco smoke consists of numerous reactive compounds that can either induce or inhibit drug metabolism. Studies on the interaction of smoking with anaesthetic drug metabolism and possible toxicity are warranted. METHODS: Sixteen non-smoking and 17 smoking (>10 cigarettes day(-1)) generally healthy women undergoing elective gynaecological surgery were given 1 MAC (minimum alveolar concentration)-hour standardized anaesthesia with enflurane in oxygen-air mixture. The serum inorganic fluoride and renal function markers beta(2)-microglobulin, tumour-associated trypsin inhibitor (TATI) and serum creatinine were measured for 48 h. RESULTS: The greatest inorganic fluoride concentration was between 8.4 and 21.0 (mean 13.8 (SD 3.4)) micromol litre(-1) in the non-smokers and between 8.6 and 38.0 (18.7 (7.0)) micromol litre(-1) in the smokers; the mean difference was 4.9 micromol litre(-1) (95% confidence interval (CI) 1.0-8.8, P<0.05). Serum beta(2)-microglobulin, TATI and creatinine were not increased. Serum inorganic fluoride concentrations were significantly greater in the smokers compared with the non- smokers 1, 2, 3 and 6 h after 1 MAC-hour inhalation with enflurane (P<0.05). Inorganic fluoride concentrations were still increased 24 h after anaesthesia in both groups. Urine beta(2)-microglobulin and TATI creatinine ratio remained at low values during the whole 48-h period in both groups. CONCLUSIONS: Regular smoking is associated with an increase in serum inorganic fluoride concentration after anaesthesia with enflurane, but there are no signs of renal damage.

[Effects of enflurane on myocardial reperfusion injury during cardiac surgery with cardiopulmonary bypass].

OBJECTIVE: To study the effects of inhalation enflurane (Enf) before aortic clamping on myocardial reperfusion injury in cardiac surgery with cardiopulmonary bypass (CPB). METHODS: hirty patents undergoing selective cardiac valve replacement were randomly allocated to three groups. Group I and group II inhaled 1.0 MAC and 0.5 MAC Enf before clamping aorta, respectively. Group III was the control group interval administration with Fentanyl. RESULTS: Immediately upon aortic clamp release (T2), the value of CK-MB, MDA and SOD of all the groups was significantly increased, however,their concentration did not peak significantly until T3 and T4(10 and 30 min after clamp aorta release). The levels at 60 min (T5) and 24 hours (T6) aorta were lower than T4 but still higher than T(0). At T3 and T4, CK-MB levels in group I were significantly higher than those in II and III groups (P=0.0220, 0.0108 and 0.0202, 0.0295). At T6, the CK-MB level of group II was significantly higher than that of group III (P<0.0001). At T4 and T5, the MDA value of group I was higher than that of group II (P=0.0060 and 0.0364). Meanwhile, the SOD level in group I was also higher than that of group II and group III at the T4 point (P<0.0001 and 0.0084). There was a correlation between the CK-MB value and the aorta clamping time,correlation coefficient range being 0.55 - 0.81,(P<0.05). However, there was no correlation between the CK-MB and MDA, SOD. CONCLUSION: There is ischemia reperfusion injury during cardiac surgery CPB with the increase of OFR production and elevation of the antioxidant reserve. Inhalation of large dose of enflurane may result in increased myocardial ischemia reperfusion injury manifested by elevated levels of myocardial enzymes and OFR production.

Halogenated inhalational anaesthetics.

The halogenated inhalational anaesthetics halothane, enflurane, isoflurane and desflurane can produce metabolic hepatocellular injury in humans to a variable extent. During metabolism of these anaesthetics, tissue acetylation occurs due to the formation of reactive intermediates. Proteins modified by acetylation may constitute neo-antigens with a potential for triggering an antibody-mediated immune response. The likelihood of suffering post-operative immune hepatitis depends on the amount of the anaesthetic metabolized and is thereby considerably less with enflurane, isoflurane or desflurane compared with halothane. Plasma inorganic fluoride concentrations are regularly increased after sevoflurane. Elevated inorganic fluoride concentrations have been associated with nephrotoxicity following methoxyflurane anaesthesia but not after sevoflurane. Another source of concern is the products of degradation from reactions with carbon dioxide absorbents. Most important is compound A, which has been shown to exhibit nephrotoxicity in rodents. However, no significant changes in renal function parameters have been reported in surgical patients.

Degrees of aversion shown by rats and mice to different concentrations of inhalational anaesthetics.

The distress associated with the induction of anaesthesia with halothane, isoflurane, enflurane and carbon dioxide was investigated in rats and mice by measuring the level of aversion they displayed on exposure to low, medium and high concentrations of these agents. The animals were exposed to each agent in a test chamber containing air or gas mixtures, which they were able to enter and leave at will, and the level of aversion was assessed in terms of the initial withdrawal and total dwelling times in the chamber. Comparisons between the anaesthetic and air-control treatments indicated that concentrations of the agents recommended for the rapid and efficient induction of anaesthesia were associated with some degree of aversion. Carbon dioxide was by far the most aversive gas for both rats and mice, with the least aversive being halothane for rats, and halothane and enflurane for mice. With all the anaesthetics, the level of aversion increased as the concentration increased.

Pharmacodynamic interaction of nitrous oxide with sevoflurane, desflurane, isoflurane and enflurane in surgical patients: measurements by effects on EEG median power frequency.

BACKGROUND AND OBJECTIVE: This study investigates the interaction of sevoflurane and nitrous oxide on EEG median power frequency of 2.5 Hz during surgery. METHODS: Sevoflurane concentrations required for electroencephalographic median power frequency between 2 and 3 Hz were measured in 25 patients during gynaecological laparotomies. Nitrous oxide was randomly administered at 0, 20, 40, 60 and 75 vol%, subsequently two different concentrations in each patient. The data were analysed using isobolographic analysis together with previously published data on nitrous oxide-isoflurane, -enflurane, or -desflurane interaction. RESULTS: The interaction is described by the equation: C volatile anaesthetic/C0 volatile anaesthetic + C N2O/C0 N2O=1 (C is the concentrations for a drug combination to achieve the desired effect; C0 is the concentration for single drug use). The parameters are C0 isoflurane=1.11 vol% (95% CI 1.03-1.19), C0 enflurane=1.64 (1.52-1.77), C0 desflurane=5.31 (4.92-5.73), C0 sevoflurane=2.12 (1.96-2.29), C0 N2O=174 (153-202). These parameters decrease by 6% (2.5-10) for every 10 years of patients' age > 40 years. CONCLUSIONS: The interaction is compatible with additivity. The potency of nitrous oxide to substitute the volatile anaesthetics is less than anticipated from previously reported MAC values.

Sister chromatid exchanges and micronuclei in lymphocytes of operating room personnel occupationally exposed to enfluorane and nitrous oxide.

The objective of this article is to assess whether occupational exposure to anesthetics increases genotoxic risk. We investigated two cytogenetic biomarkers, sister chromatid exchanges (SCE) and micronuclei (MN), in the peripheral blood lymphocytes of 46 anesthesiologists (24 men), working in operating rooms and mostly exposed to enfluorane and nitrous oxide, and 66 controls (35 men), not exposed to chemicals and living in the same area. Contrary to what was expected, a lower frequency of SCE was found in male anesthesiologists than in controls. Smoking status was found to be positively associated with SCE frequency in each group, while no relation to age was evident. On the contrary, MN frequency was significantly higher in female, but not male, anesthesiologists than in controls. Age and smoking status did not modify the association. No relationship between MN frequency and duration of employment was found in anesthesiologists. Smoking status and mean number of cigarettes smoked per day in smokers were not associated with MN frequency in either anesthesiologists or in controls. MN analysis seems to be a sensitive index of possible genotoxic effects of occupational exposure to anesthesiologists, and women appear to be more susceptible to these effects than men.

Dexmedetomidine reduces seizure threshold during enflurane anaesthesia in cats.

Dexmedetomidine is an alpha 2 agonist and has been reported to have proconvulsant actions. To investigate the interaction of dexmedetomidine with convulsant anaesthetics, we studied effects on seizure threshold in cats during enflurane anaesthesia. Cats were prepared with chronic implantation of electrodes for recording of the cortical electroencephalogram (EEG) and midbrain reticular formation multi-unit activity (R-MUA). Seizure threshold, the reciprocal of the number of electrical stimuli required to induce generalized EEG seizure activity x 1000 (seizure induction index (SII)), was assessed. The effects of dexmedetomidine 1, 10 and 100 micrograms kg-1 i.v. and yohimbine 500 micrograms kg-1, an alpha 2 antagonist, on SII during 3.5% enflurane anaesthesia were investigated. Dexmedetomidine significantly increased SII at 10 and 100 micrograms kg-1, and this effect was reversed by yohimbine. We found that high-dose dexmedetomidine reduced seizure threshold during enflurane anaesthesia.

Vomiting, retching, headache and restlessness after halothane-, isoflurane- and enflurane-based anaesthesia. An analysis of pooled data following ear, nose, throat and eye surgery.

BACKGROUND: Isoflurane has exceeded halothane and enflurane in usage. A literature search, however, revealed no data comparing the effects on emesis, headache and restlessness of these three agents. METHODS: With hospital ethics committee approval and patient consent, a prospective, randomised, double-blind study of 556 patients undergoing ENT and eye surgery was undertaken to evaluate the effects of halothane, isoflurane and enflurane on vomiting, retching, headache and restlessness until 24 h after anaesthesia. Balanced general anaesthesia was administered comprising benzodiazepine premedication, induction with thiopentone-atracurium-morphine (ENT patients) or fentanyl (eye patients), controlled ventilation and maintenance with either halothane 0.4-0.6 vol% (n = 186), isoflurane 0.6-0.8 vol% (n = 184) or enflurane 0.8-1 vol% (n = 186) in nitrous oxide 67% and oxygen. RESULTS: The three study groups were comparable, and comprised comparable subgroups having ear, nose, throat, intraocular and non-intraocular surgery. During early recovery from anaesthesia, the respective requirements for halothane, isoflurane and enflurane for analgesia (7%, 9% and 10%), frequency of emesis (6%, 8% and 8%), antiemetic requirements (1%, 1% and 2%), restlessness-pain scores and time spent in the recovery ward (27 SD 10, 31 SD 12 and 26 SD 9 min) were similar. During the ensuing 24-h postoperative period, patients who had isoflurane experienced emesis less often than those who had halothane (36% vs 46%, P < 0.025) but did so with similar frequency to those who had enflurane (46% vs 41%). Antiemetic requirements were least in those given isoflurane (isoflurane 12%, halothane and enflurane 23% each, P < 0.005), but headache and analgesic requirements were similar. CONCLUSION: Isoflurane induces less postoperative emesis than halothane, but headache is similarly frequent after anaesthesia with any of these agents.

Effects of volatile anesthetics on respiratory activity and chemosensitivity in the isolated brainstem-spinal cord of the newborn rat.

To elucidate the various actions of volatile anesthetics on respiratory activity and chemosensitivity, we have studied the activities of the respiration-related structures in the medulla of the in vitro brainstem-spinal cord preparation of the newborn rat. Halothane decreased respiratory burst frequency (fR), inspiratory duration (Ti), integrated ventral C4 root activity (integral of C4) and respiratory minute activity (RMA) in a concentration-dependent fashion. Bicuculline counteracted the depressive effect of halothane on fR, integral of C4, and RMA. Inspiratory neuronal activity recorded at the rostral ventrolateral medulla (RVL) corresponded to these changes. Activities of Pre-Inspiratory (Pre-I) neurons and expiratory neurons in the RVL were also inhibited by halothane. The C4 activity did not always correspond to Pre-I neurons' discharge. In this comparative study of three volatile anesthetics, the inhibitory effect on fR appeared to be greater with enflurane than with halothane or isoflurane. The reversal effects of bicuculline on decreases in fR, integral of C4, and RMA also seemed to be greater with enflurane than with halothane or isoflurane. Hypercapnia (pH 7.0) induced a significant increase in fR and RMA, and a significant decrease in Ti. Although halothane inhibited overall activities, chemo-responsiveness to hypercapnia changed similarly even during halothane application. Hypocapnia (pH 7.8) significantly decreased fR, and increased integral of C4 and Ti. Hypocapnia during halothane application also induced a significant decrease in fR and RMA. These results suggest that the modification of GABAA receptor-mediated neurotransmission is in part responsible for the respiratory depression by volatile anesthetics, affecting especially fR, integral of C4, and RMA. Low respiratory rate by enflurane is associated with GABAergic modification. Prolongation of Ti by enflurane, seen clinically, does not seem to be either central or GABAergic. These findings demonstrate the responsiveness to CO2 and the respiratory compensation mechanism via respiratory frequency in the isolated preparation. It is, furthermore, indicated that halothane preserves the central chemosensitivity while its concentration is high enough to reduce the respiratory activities.

The site of airway irritation during induction of anaesthesia.

The aim of this investigation was to study the role of the nasal airway in mediating upper airway reflexes during induction of anaesthesia when the commonly used irritant inhalational anaesthetic agent enflurane is used. In a prospective randomised study, 40 ASA 1 & 2 day-case patients undergoing body surface surgery were recruited. Following intravenous induction using propofol, 20 patients received enflurane administered via a laryngeal mask airway (LMA), the anaesthetic vapour therefore bypassing the nasal airway. In the other group, 20 patients received enflurane anaesthesia administered using a face mask, the nasal airway therefore being exposed to inhalation anaesthetic. We were unable to demonstrate any significant (p < 0.05) differences between the two groups in relation to upper airway complications (cough, breath holding, laryngeal spasm, bronchospasm and excitement). Previous work has identified the nose as a possible important reflexogenic site for upper airway reflexes in humans during anaesthesia. We have been unable to demonstrate any difference in upper airway complications when the nasal airway was included or excluded from exposure to irritant anaesthetic vapours, when administered in a clinical setting.

Interactions between nicardipine and enflurane, isoflurane, and sevoflurane.

PURPOSE: During nicardipine induced hypotension, different inhalational anaesthetics may have different effects on haemodynamic variables, sympathetic function and drug metabolism. Therefore, the haemodynamic effects and pharmacokinetics of nicardipine were studied in the presence of the three inhalation anaesthetics enflurane, isoflurane and sevoflurane. METHODS: Thirty patients scheduled for neurosurgery were randomly assigned to one of three anaesthetic techniques: enflurane, isoflurane or sevoflurane. Nicardipine (0.017 mg.kg-1) was administered during stable anaesthesia and the following measurements made for 30 min: blood pressure, heart rate, and plasma concentration of norepinephrine, epinephrine and nicardipine. RESULTS: With sevoflurane, plasma concentrations of nicardipine, five minutes after administration, (39.8 +/- 3.5 ng.ml-1, mean +/- SEM) were higher (P < 0.05) than in the other two groups (28.3 +/- 2.9 ng.ml-1, 32.6 +/- 4.3 ng.ml-1, enflurane and isoflurane, respectively). With isoflurane, the approximated half-life of nicardipine (14 +/- 4 min) was shorter and clearance (2.1 +/- 0.3 l.min-1) more rapid. Peak heart rates were similar in all groups but elevated rates continued longer with isoflurane (> 30 min). Nicardipine-induced reduction in blood pressure was greater with sevoflurane but low pressures persisted for longer with isoflurane. Plasma catecholamine concentrations increased with isoflurane and enflurane, but not with sevoflurane: considerably higher epinephrine concentrations were seen with isoflurane. CONCLUSION: This study showed that the action of nicardipine is modified by different inhalational anaesthetic agents. Nicardipine has a prolonged duration of action in the presence of isoflurane and produces greater initial hypotension with sevoflurane.