BJA Advance Access originally published online on April 30, 2004
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British Journal of Anaesthesia, 2004, Vol. 92, No. 6 865-869
© 2004 The Board of Management and Trustees of the British Journal of Anaesthesia
Laboratory Investigations |
Medical aerosol propellant interference with infrared anaesthetic gas monitors
The Department of Anesthesia and Critical Care Medicine, Hebrew University Hadassah School of Medicine, Jerusalem, Israel
*Corresponding author: Department of Critical Care Medicine, Room B7 08, Sunnybrook and Women’s College Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5 Canada. 
This study was performed with the assistance of internal departmental funding only.
Accepted for publication: February 11, 2004
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Abstract |
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Background. 1,1,1,2 Tetrafluoroethane is a hydrofluoroalkane (HFA) that is replacing chlorofluorocarbons (CFC) as a medical aerosol propellant in an attempt to reduce damage to the ozone layer. This study compared the effects of HFA- and CFC-based inhalers on four anaesthetic gas monitoring systems.
Methods. The HFA- and CFC-based inhalers were activated in close proximity to the sample line of two Datex Ohmeda, an Agilent and a Siemens infrared anaesthetic agent monitoring systems. The effects were recorded on each system for five common anaesthetic agents.
Results. The HFA inhaler caused either maximal false positive readings (with the exception of desflurane) or transient measurement failure on all systems. The Datex Ohmeda AS/3 system misidentified the HFA inhaler as carbon dioxide at low concentration (2 ± 0 mm Hg). The CFC-based inhaler caused a minor false-positive reading (0.4 ± 0%) for halothane only on the Datex Ohmeda AS/3 system only and was misidentified as carbon dioxide at 33.3 (SD 2.1) mm Hg and 22.4 (8.9) mm Hg by the Agilent and Siemens systems.
Conclusions. The HFA inhaler adversely affected all equipment tested. The infrared spectra of HFA and the common anaesthetic gases have considerable overlap at the 8–12 µm range that is not shared by the CFCs. The differences in spectral overlap explain the different effects of the HFA and CFC propellants. Anaesthetic gas concentration data may be erroneous using the HFA-based inhalers.
Br J Anaesth 2004; 92: 865–9
Keywords: anaesthesia; complications, inhalation anaesthesia; equipment, inhalers; pharmacology, salbutamol
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Introduction |
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In an attempt to decrease emission of substances that cause damage to the ozone layer, the Montreal Protocol of 1987 encouraged the cessation of use of chlorofluorocarbons (CFCs).1 A contribution to this effort has come from some pharmaceutical companies that have changed the propellant in their inhaler medications. Propellants based on CFCs (such as difluorodichloromethane, monofluorotrichloroethane and tetrafluorodichloroethane) are being phased out and replaced with more ‘ozone friendly’ agents, including a hydrofluoroalkane (HFA): 1,1,1,2-tetrafluoroethane, also known as Norflurane, Dymel® 134a/P and HFA 134a (DuPont Fluorochemicals, Wilmington, DE, USA). This substance does not contain the carbon–chlorine functionality associated with ozone depletion in the upper atmosphere. The change in propellant has led to some minor changes in inhaler function (including smaller particle size for example2 3), but in general has not been of clinical significance.4–7 Following the observation that during anaesthesia the use of a salbutamol inhaler with the newer propellant led to a sudden rise in the anaesthetic agent measurement on the infrared gas monitor (Fig. 1), this bench study set out to explore and explain this phenomenon.
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Methods |
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An HFA-based inhaler (Salbutamol 100 µg per puff, Ventolin, GlaxoSmithKline, UK) and a CFC-based inhaler (ipratropium bromide 20 µg per puff, Aerovent, Teva Pharmaceutical Industries Ltd, Israel) were compared for their effects on four anaesthetic gas monitoring systems: the Datex Ohmeda G-AO gas analyser with AS/3 monitor (Datex Ohmeda, Finland), the Datex Ohmeda M CAiOV gas analyser with the Datex Ohmeda S/5 monitor (Datex Ohmeda, Finland), the Hewlett Packard M1026A gas analyser with Agilent monitor (Agilent Patient Care System, Andover, MA, USA) and the Siemens SC7000 ENG monitor and gas analyser (Siemens Medical Systems, Danvers, MA, USA).
For both inhalers and all systems, the inhaler was activated once into an open tube about 1.5 cm from the open end of the sampling tube of the infrared gas monitoring equipment. For the systems that employed automatic agent identification (Datex Ohmeda M CAiOV S/5, Siemens SC7000 and Agilent/Hewlett Packard M1026A), this was tested first, starting from a situation where no anaesthetic gas had been identified. For the systems where the anaesthetic agent either could or had to be set manually (all systems besides the Datex Ohmeda M CAiOV S/5), the system was tested when set to each of the gases to be tested (halothane, enflurane, isoflurane, sevoflurane and desflurane). The starting anaesthetic concentration was allowed to return to zero before commencing each measurement. The peak concentration was recorded for both inhalers and for each anaesthetic agent setting three times; in addition, a descriptive record was made of the graphical representation of agent measurement. The effect of the inhalers on end tidal carbon dioxide measurement was also recorded.
Nebulized solutions of salbutamol 2.5 mg and ipratropium bromide 0.125 mg were also tested in all systems as a control to ascertain the effects of the drug substances in the absence of propellant.
The time course of the interference effect of HFA 134a was also investigated. The monitor selected for this investigation was the Datex Ohmeda AS/3, set to measure halothane. The breathing circuit of an anaesthetic machine (North American Drager Narcomed GS, Drager Medical Inc., USA), including the inhaler adaptor, was attached to a bag. The ventilator was set at a rate of 10 bpm, I:E ratio of 1:2 and tidal volume of 600 ml. The fresh gas flow (using air) was set sequentially at 2, 5 and 10 litre min–1. At each setting, one puff of the inhaler was released into the circuit. The inspiratory concentration of halothane for each breath that appeared on the monitor was recorded until the concentration dropped to zero. The zero measurement was observed for at least 2 min, before a subsequent measurement series was made. Four series were performed at each fresh gas flow setting. Results are presented as mean (SD).
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Results |
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Each of the four systems examined responded in a different manner to inhaler exposure. None of the systems responded at all to the nebulized drugs. No false-positive readings were recorded for nitrous oxide.
Datex Ohmeda systems
The Datex Ohmeda AS/3 equipment does not have automated anaesthetic agent identification, but does allow user selection of each of the five anaesthetic agents. When set to all agents besides desflurane, the HFA inhaler caused a maximal graphical and numerical monitor reading (the maximum being 15%). When set to desflurane, the monitor’s response was sub-maximum, reaching 28.1 (0.1)%. In contrast, the CFC inhaler caused a response only when the monitor was set to halothane, for which the monitor uses the highest gain (with a reading of 0.4 (0)%). The end tidal carbon dioxide response was similar for both inhalers: 2 (0) mm Hg. These results are summarized in Table 1.
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On testing the newer Datex Ohmeda S/5 with automated gas identification, if the system had not previously identified an anaesthetic gas, the HFA inhaler produced no response; the CFC inhaler was identified as halothane. If the monitor had previously identified another anaesthetic gas, such as isoflurane, the use of the HFA inhaler led to measurement failure for up to a few seconds. This equipment does not allow user selection of the anaesthetic agent. The effect on the carbon dioxide measurements was similar to that described above.
Hewlett Packard Agilent system
When started in the automatic agent identification mode, exposure to the HFA inhaler caused an initial downwards deflection of the graph followed by measurement failure and auto-zero of the anaesthetic agent, carbon dioxide and oxygen measurements. No agent identification was made. The CFC inhaler had no effect at all. Similar results were achieved when the monitor was set to each individual agent.
The HFA inhaler was not identified as carbon dioxide, while the CFC inhaler caused a reading of 33.3 (2.1) mm Hg over three measurements.
Siemens system
Exposure to the HFA inhaler caused a maximal deflection of the graphic representation of all five anaesthetic agents, transient measurement failure and subsequently unstable numerical readings until returning to zero. There was a smaller response on the carbon dioxide tracing, without generation of a numerical value. No agent was identified by the automatic agent identification system.
Exposure to the CFC inhaler had no effect on any of the gas measurements, but produced a marked effect on the carbon dioxide measurement: 22.4 (8.9) mm Hg over five measurements.
Time course measurements
The time course for the effect of the HFA inhaler was dependent on fresh gas flow and is shown in Figure 2. The effect disappeared within ten breaths at all fresh gas flow settings.
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Discussion |
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This study has shown that the HFA inhaler can cause short-lived, but clinically significant, false-positive readings for all five commonly used potent anaesthetic gases in various monitoring systems. These findings are significantly different from those produced by a CFC-containing inhaler. The small effect of CFCs on infrared gas monitors has been described previously,8–10 but on less technologically advanced equipment in some cases.
Modern infrared gas monitors function by measuring the absorption of infrared light by the sampled gas at up to five wavelengths in the 3.3 or 8–12 µm areas of the infrared spectrum and then solving a series of simultaneous equations to calculate the concentration of the anaesthetic agent or carbon dioxide. Multiple wavelengths are required in order to distinguish between the different anaesthetic gases, and the 8–12 µm range is used as this represents the area of the infrared spectrum where anaesthetic gases show maximum absorbance (Fig. 3). Figure 4 shows the infrared absorbance spectrum of HFA 134a. As can be seen, HFA 134a demonstrates significant infrared absorbance across the whole 8–12 µm wavelength range. This high absorbance completely overlaps the peaks on the anaesthetic gas spectra in the 8–12 µm range and presumably accounts for the interference in monitoring function. In contrast, CFCs show only isolated peaks of infrared absorption in the 8–12 µm range,11 accounting for their lesser effect on anaesthetic gas concentration measurement (Fig. 5).
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The similarities in absorption spectra between HFA 134a and the anaesthetic gases can in part be predicted from the similarity in their molecular structure (Fig. 6), and from a historical point of view it is interesting to note that 1,1,1,2-tetrafluoroethane was tested as an anaesthetic agent in animals as early as 1967. It was found to have moderate potency, requiring approximately 50 vol% to induce anaesthesia,12 but was not developed for use in humans. In doses associated with inhaler use, the propellant has been shown to be safe and non-anaesthetic.13 14
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HFA 134a is by no means unique in its ability to interfere with infrared gas analysis. Many other gases (including alcohol and methane for example) have been reported to have similar effects,15–17 and monitoring technology has been developed to overcome most of these interference patterns. Salbutamol itself is not the cause of the interference described as: (i) nebulized salbutamol had no effect on the infrared analysis and (ii) salbutamol is an aerosol of fine particles and not a gas and is therefore unlikely to affect infrared gas analysis.
The methodology of this study was designed to maximize the effect of the inhaler propellant on the infrared gas monitors, the propellant being released almost directly into the monitor sample line. As shown in Figures 1 and 2, however, in clinical and simulated clinical situations, the effects are similar.
This study was performed to verify and explain the clinical finding that, when administered to a patient, the newer inhaler produced a sudden peak in the measured anaesthetic concentration on infrared gas monitoring equipment. The findings above demonstrate that this change was likely to be due to the inhaler propellant and that an explanation for it can be found in the similarity of the infrared spectra between the propellant agent and the anaesthetic gases.
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References |
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1 www.epa.gov/ozone/science/sc_fact.html
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