Non-interventional study evaluating exposure to inhaled, low-dose methoxyflurane experienced by hospital emergency department personnel in France.

OBJECTIVES: Low-dose methoxyflurane is a non-opioid, inhaled analgesic administered via the Penthrox inhaler and was recently licensed in Europe for emergency relief of moderate-to-severe trauma-associated pain in conscious adults. This non-interventional study investigated occupational exposure to methoxyflurane in the hospital emergency department (ED) personnel during routine clinical practice. SETTING AND PARTICIPANTS: The study was conducted in two hospital ED triage rooms in France over a 2-week and 3-week period, respectively. Low-dose methoxyflurane analgesia was self-administered by patients via the inhaler under the supervision of nursing staff, per routine clinical practice. An organic vapour personal badge sampler was attached to the uniform of the nurses working in the treatment rooms throughout an 8-hour shift (total of 140 shifts during the study period). Seven-day ambient air monitoring of each treatment room was also performed. Methoxyflurane levels adsorbed in each badge sampler were measured by a central laboratory. The primary objective was to evaluate methoxyflurane exposure experience by the hospital ED nurses during an 8-hour shift. RESULTS: In 138 badge samplers, the median (range) concentration of methoxyflurane present following 8-hour nursing shifts was 0.017 (0.008, 0.736) ppm. This level was almost 900-fold lower than the previously reported 8-hour-derived maximal exposure level of 15 ppm; methoxyflurane exposure approaching this threshold was not documented in any badges. There was no correlation between the number of applications of low-dose methoxyflurane administered during a shift (range 0-5) and the vapour exposure measured on the personal badge samplers. CONCLUSIONS: This study indicates that nurses working in hospital EDs experience very low levels of occupational exposure to methoxyflurane vapour during routine clinical practice. These real-world data can provide reassurance to healthcare providers supervising patients receiving low-dose methoxyflurane analgesia via a Penthrox inhaler; further studies may inform exposure in other hospital ED settings.

Pharmacokinetics of inhaled anesthetics in humans: measurements during and after the simultaneous administration of enflurane, halothane, isoflurane, methoxyflurane, and nitrous oxide.

To determine the relative washin and washout characteristics of isoflurane, enflurane, halothane, and methoxyflurane, we administered all four anesthetics simultaneously (total = 1.1 MAC) to nine healthy patients for 2 hr. Concentrations of anesthetics in end-tidal gases were measured during washin and for 5-9 days during washout. Multiexponential (multicompartment) models were fit to the washin and washout curves using least-squares analysis. Slowly equilibrating compartments could only be identified during washout. For 27 of the 36 data sets, five-compartment models fit the washout curves significantly better than four-compartment models. The time constant for our first compartment is consistent with that predicted for washout of the lungs. Time constants for the second, third, and fifth compartments were consistent with current data for blood flows and solubilities of vessel-rich, muscle, and fat tissue groups, respectively. The fourth compartment has a time constant that lies between the time constants predicted for muscle and fat.

Leakage of volatile anaesthetics from agent-specific keyed vapourizer filling devices.

Agent-specific keyed vapourizer filling devices were designed to ensure that an anaesthetic vapourizer is filled with the correct agent. Since there appear to be no reports of possible loss of volatile agent or operating room pollution resulting from either the design or patterns of use of these devices, measurements were made with three anaesthetic agents and two methods of use. First, two bottles each of methoxyflurane, enflurane and halothane were fitted with a suitable filling device and the weight of agent lost from each bottle over six weeks was measured. Bottle #1 of each agent remained without agitation between weighings; bottle #2 was tipped to mimic filling of a vapourizer. Weight loss over the six week period was 2.76 and 3.15 per cent of the halothane, 2.22 and 2.43 per cent of the enflurane, and 0.58 and 0.96 per cent of the methoxyflurane, for bottles #1 and #2, respectively. Second, pollution was measured with an infra-red analyser for halothane, using bottles #1 and #2, as described above, and a third bottle on which the filling device was replaced by the screw-on cap after each filling of the vapourizer. Vapour loss was undetectable for bottle #1, between 25 and 30 ppm for bottle #2, and between 350 and 400 ppm for bottle #3. Thus, although the design of the filling devices results in loss of the anaesthetic agent, this loss represents potential pollution only when the device is replaced by the screw-on cap between use. Therefore, when using filling devices, these should be left on the bottle of volatile agent between fillings to decrease operating room pollution.

Concentrations of methoxyflurane and nitrous oxide in veterinary operating rooms.

The surgical rooms of 14 private veterinary practices were monitored to determined methoxyflurane (MOF) concentrations during surgical procedure under routine working conditions. The average room volume for these 14 rooms was 29 m3. The average MOF value for all rooms was 2.3 ppm, with a range of 0.7 to 7.4 ppm. Four of the 14 rooms exceeded the maximum recommended concentration of 2 ppm. Six rooms which had 6 or more air changes/hr averaged 1.1 ppm, whereas 8 rooms with less than 6 measurable air changes/hr averaged 3.2 ppm. Operating rooms that had oxygen flows of more than 1,000 cm3/min averaged 4.4 ppm, whereas those with flows of less than 1,000 cm3/min averaged 1.5 ppm. The average time spent during a surgical procedure using MOF, for all 14 facilities, was 2 hours. Nitrous oxide (N2O) concentrations were determined in 4 veterinary surgical rooms. The average N2O concentration for 3 rooms without waste anesthetic gas scavenging was 138 ppm. Concentration of N2O in the waste anesthetic gas-scavenged surgical room was 14 ppm, which was below the maximum recommended concentration of 25 ppm.

Waste anesthetic gas exposures to veterinarians and animal technicians.

A survey of veterinarians was conducted in an 11-county region of eastern Colorado to determine the extent of usage of inhalation anesthetics and to measure exposures of veterinarians and their assistants to waste anesthetic gases. The survey indicated that inhalation anesthetics were used in 80.8% of the 210 practices. Exposures to waste anesthetics in veterinary practices were far less than reported in human hospitals. Waste anesthetic concentrations were affected by size of the patient, type of breathing system, and use of scavenging systems. Dilution ventilation had no effect on breathing zone concentrations. The endotracheal tube and occasionally the anesthetic machine were the major sources of leakage of anesthetic gases.

Pollution of delivery ward air by nitrous oxide--methoxyflurane.

Pollution of delivery ward atmosphere by analgesic gases and vapors has not been studied as extensively as pollution of operating theaters. This study shows that delivery room atmosphere is polluted by methoxyflurane (0.5--0.8 ppm) and nitrous oxide (300--540 ppm) and that a local gas exhaust system reduces the concentration by half.

[Gas chromatographic determination of the solubility coefficient for volatile anaesthetics (author's transl)]. / Gaschromatographische Bestimmung des Verteilungskoeffizienten für volatile Anaesthetika.

For the determination of the solubility coefficient of volatile anaesthetics in Schindler's liquid culture, modified by Karzel, a gas-chromatographic analysis with direct-injection-method was used. A well defined volume with a known concentration of the anaesthetic was added to a vessel with known volume. After equilibration the concentration of the inhalational anaesthetics was determined in the liquid at various temperatures. The solubility coefficient and the temperature coefficient were then calculated from these data. We obtained the following solubility coefficients at -4 degrees C (37 degrees): for halothane 1,07 (0,77), for enflurane 1,14 (0,70), for methoxyflurane 4,92 (3,23) and for isoflurane 1,13 (0,82). In Schindler's liquid culture modified by Karzel the values at 24 degrees (37 degrees) were: for halothane 1,33 (0,92), for enflurane 1,32 (0,87), for methoxyflurane 6,61 (4,48) and for isoflurane 1,19 (0,98). The temperature coefficient for this temperature range were in water (in Schindler's liquid culture) for halothane: -2,31 . 10(-2) K(-1) (-3,15 . 10(-2) K(-1)), for methoxyflurane: -13,0 . 10(-2) K(-1) (-16,48 . 10(-2) K(-1)), for enflurane: -3,38 . 10(-2) K(-1) (-3,46 . 10(-2) K(-1)) and for isoflurane: -2,38 . 10(-2) K(-1) (-1,62 . 10(-2) K(-1)).

Some characteristics of an exceptionally potent inhaled anesthetic: thiomethoxyflurane.

The authors sought to test whether a deviation existed for the correlation between anesthetic potency and the oil/gas partition coefficient at an extreme of lipid solubility. For thiomethoxyflurane, the sulfur analog of methoxyflurane, the oil/gas partition coefficient was 7230 +/- 50 SEM, and MAC (minimum alveolar concentration of thiomethoxyflurane required for anesthesia) in 4 dogs was 0.035 +/- 0.008 percent of 1 atm. This agrees with the potency predicted by the lipid solubility, although thiomethoxyflurane is 7 1/2 times more potent than methoxyflurane, to date the most potent available anesthetic. Thiomethoxyflurane water/gas and blood/gas partition coefficients were 5.4 +/- 0.3 and 68.1 +/- 1.5, respectively. The latter coefficient accords with the prolonged recovery associated with this agent. Renal and hepatic blood chemistries measured on the 1st and 7th days following anesthesia showed only small changes from preanesthetic values.

Response time of the Narkotest anesthetic gas monitor.

Response time (RT) of the Narkotest anesthetic gas monitor was measured for 7 inhalation anesthetics, using a 5 L/min fresh gas flow (FGF). Time to 63 percent of maximum response (RT63) and to 95 percent of maximum response (RT95) was directly related to rubber/gas and oil/gas partition coefficients. RT95 ranged from 7 seconds for N2O to 843 seconds for methoxyflurane. RT measured at 0.5 L/min FGF was markedly prolonged over RT at 5 L/min. When the Narkotest was placed on the expiratory limbs of circle-absorber breathing circuits, the difference between the calibrated Narkotest reading (Fn) and the mixed expired circuit concentration (Fc) was shown to depend on the rate of increase of the circuit concentration.

Pertinence and precision in pollution measurements.

A new approach for the study of the pollution of operating theatre atmospheres by volatile anaesthetic agents is described. Disadvantages of earlier work are discussed together with ways in which they may be overcome. Some pitfalls in analysis, sampling and standardization are indicated and some hazards of incorrect data interpretation are shown. The need for a cautious and critical attitude is emphasized.

Adsorption of anaesthetic vapours on charcoal beds.

The adsorptive properties of four charcoals have been examined in relation to their value as adsorbents in filters attached to an anaesthetic trolley. Data for four anaesthetics have been obtained. The test conditions (flow rate, concentration, humidity) were those relevant to the application, and the effect of variation of these conditions was also studied. The air flow resistance of the charcoals was measured. Basic data are thus provided for the design of suitable adsorbers. The performance of two prototype anaesthetic adsorbers has been measured.

Minimum blood concentration--a universal concept of anaesthetic potency.

Although brain concentration of anaesthetic agents is attractive as a method of expressing anaesthetic potency, both theoretical and practical considerations limit the usefulness of this index. Therefore, the MAC concept has been utilized to develop another expression of potency: the minimum blood concentration. This takes into account the blood/gas solubility coefficient, and the fact that at equilibrium the amount of anaesthetic agent present in brain is reflected in the blood concentration, and it is applicable to both parenteral and to inhalation anaesthetic agents.