Br. J. Anaesth. (1976), 48, 195

ERRORS IN OXYGEN TENSION MEASUREMENTSCAUSED BY HALOTHANE

J. G. DENT AND K. J. NETTER

SUMMARY

Halothane, independent of oxygen tension, increased the signal of the gold/silver-silver chloridemicroelectrode. The output of microelectrodes at different oxygen tensions in the presence of in-creasing amounts of halothane has been measured. Halothane causes an increase in the electrodesignal which is proportional to its concentration. This effect results from the polarographic reductionof halothane. It is concluded that the gold/silver-silver chloride microelectrode cannot be used tomeasure oxygen tension during halothane anaesthesia.

A gold/silver-silver chloride microelectrode systemhas been developed by Erdmann, Kunke and Krell(1972) for measuring oxygen tension in micro-areas ofliving tissue during anaesthesia and has been usedalso to measure oxygen tension in actively metaboliz-ing liver microsomal preparations (Wolf et al., 1975).We observed that the addition of halothane to asolution increased the apparent oxygen tension. Thisphenomenon has been investigated to determine itscause and to assess the magnitude of the halothaneeffect.

METHODS

Electrodes were prepared by the method of Erdmann(1972) and were coated with a hydrophilic resin(Primal Ac-35 Doduco KG, Pforzheim, WestGermany). The electrode signal was amplified with amodel 1200 Chemical Microsensor (TransidyneGeneral Corp. Michigan, U.S.A.) and the micro-sensor output was recorded on a chart recorder.Measurements of oxygen tension were made at37 °C in a 1-cm square spectrophotometer cuvette.Halothane 2.5% v/v in dimethylformamide (DMF)was added to 2 ml of sample solution, usually 0.9%w/v sodium chloride. It was established that up to200 [jditre DMF gave no signal with the electrode.Solutions of known oxygen tension were prepared bybubbling 0.9% sodium chloride with 10% oxygenand 90% nitrogen, compressed air (20.8% oxygen),and pure nitrogen. The addition of a small amount ofglucose and glucose oxidase ensured the maintenanceof anaerobic conditions.

J. G. DENT, B.SC, PH.D. ; K. J. NETTER, DR.MED. ; Departmentof Pharmacology, Section of Toxicology, University ofMainz, Obere Zahlbacher Str. 67, D-65 Mainz, Germany.

RESULTS

Increasing amounts of halothane added to the salinesolutions resulted in an increase in the electrodesignal (fig. 1). The effects of halothane were indepen-dent of the initial oxygen concentration. Similarresults were obtained in other assay media (1.15%potassium chloride and diluted guineapig blood) andwhen halothane was added as a solution in ethanol.

2 4 6 8 10 12 14 16 18 20

Halothane Conctntration 19/100 ol 0.9 I Saline

FIG. 1. The influence of halothane at different concentra-tions on the response of a single electrode. Measurementswere made with a single electrode in two separate experi-ments, • and A. Halothane was added as a 2.5% v/vsolution to 0.9% sodium chloride. Halothane concentration(mg/100 ml) was calculated from the specific gravity ofhalothane (1.87 g/ml at 20 °C). Solutions of different oxygen

tension were prepared as described in the text.

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196 BRITISH JOURNAL OF ANAESTHESIA

It may be concluded that the increased electrodesignal did not result from a halothane-solvent orhalothane-assay medium interaction. Commerciallyavailable halothane has thymol (0.01% w/v) presentas a stabilizing agent; however, thymol in largequantities (100 mg/100 ml) did not affect the elec-trode signal.

As halothane is a highly volatile liquid, the pos-sibility of its evaporation from the saline solutionwas investigated by adding halothane to saline at aconcentration of 10 mg/100 ml. The electrode cur-rent was recorded immediately and remainedconstant for 30 min. This was taken to indicate thestability of halothane in saline, when added in DMF.If the effects of halothane were on the silver/silverchloride reference electrode its effect would not beimportant in anaesthesia as the reference electrode isfrequently a surface electrode applied to the skin.However, by separating the gold and silver/silverchloride electrodes in two saline solutions joined bya simple salt bridge, it was shown that the increasedsignal occurred only when halothane was added to thesolution containing the gold electrode.

Different electrodes exhibited different sensitivi-ties to halothane. This effect might be the resultof different thicknesses of the hydrophilic coating.Measurements of the signal produced by halothaneon electrodes which had not been coated with thehydrophilic resin revealed that uncoated electrodeswere more sensitive but equally variable in theirresponse to halothane. However, the response of agiven electrode decreased following coating. Theresponse of coated electrodes varied from 30 to140 mm Hg apparent oxygen tension per 10 mghalothane per 100 ml saline. These variable factorsmake it impossible to devise a universally applicablecorrection factor.

The fact that halothane affects the electrodesignal and that this effect is located at the cathodesuggested that halothane was being reduced polaro-graphically. The polarization profile for oxygen andhalothane is shown in figure 2. It is apparent that theprofiles overlap and that it is not possible to dis-tinguish between halothane and oxygen by an altera-tion in the electrode polarizing potential. Theplateaux for the first reductive step of oxygen andthat for halothane overlap substantially.

Halothane in the gas phase caused an increase inthe signal from a conventional Clark-type electrodefitted with a 25-ILIQ thick polyethylene membrane(Severinghaus et al., 1971). It was also reported thathalothane sensitized the electrode to oxygen. We

400

300

200

100

Oxygen Halothane

300 400 500 600 700 800Polarizing Voltage (-fflV)

900 1000

FIG. 2. The polarization curve for a single electrode. Pointswere obtained by measuring the electrode signal at differentpolarization voltages after equilibration for 2 min in 0.9%saline gassed with compressed air (• • ) , or anaerobic0.9% saline with approximately 15 mg/100 ml halothane

(x x) .

were unable to demonstrate an effect of halothaneon a Clark electrode (L. Eschweiler & Co., Kiel)fitted with a 12-pim thick polytetrafluoroethylene(PTFE) membrane when halothane was added at aconcentration of 500 mg/100 ml saline. However, athigher halothane concentrations (1500 mg/100 ml) orin the absence of the membrane, an increase inelectrode current was observed. These resultsindicate that the Clark-type electrode fitted with aPTFE membrane may be used to measure oxygentension in the presence of halothane concentrationsin the clinical range.

We found that halothane did not have a sensitizingeffect on the gold microelectrode. Furthermore, theobservation that the coating of gold microelectrodeswith hydrophilic resin decreased the sensitivity tohalothane indicates the possibility that the discoveryof a coating material permeable to oxygen butimpermeable to halothane may allow oxygen measure-ments with the microelectrode in the presence ofhalothane.

DISCUSSION

The results described here indicate that measure-ment of oxygen tension with the gold/silver-silverchloride electrode during halothane anaesthesia is

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HALOTHANE AND OXYGEN TENSION MEASUREMENT 197

likely to be inaccurate. The blood halothane con-centrations associated with clinical anaesthesia arestated as being between 9 and 22.5 mg/100 ml(Atallah and Geddes, 1972). With the electrode usedto obtain the data in figure 1, such concentrations ofhalothane would increase the apparent Po2 by60-150 mm Hg. Thus the error is very large. Thefact that halothane is reduced polarographically in-dicates the possibility of developing a polarographicmethod for the determination of halothane in bio-logical fluids. This is being investigated currently.

ACKNOWLEDGEMENTS

We acknowledge gratefully the Deutsche Forschungs-gemeinschaft for financial support and (J. G. D.) the RoyalSociety for a European Travelling Fellowship.

REFERENCES

Atallah, M. M., and Geddes, I. C. (1972). The gas chro-matographic estimation of halothane in blood using anelectron capture detection unit. Br.J. Anaesth., 44, 1035.

Erdmann, W. (1972). Anaesthesiology, Proc. Fifth WorldCongress of Anaesthesiologists, Kyoto, p. 203. Amster-dam: Excerpta Medica International Congress, Series292.

Kunke, S., and Krell, W. (1972). In Oxygen Work-shop, Dortmund 1971 (eds. N. Kessler, D. F. Bruley,L. C. Clark, W. Lubbers, J. A. Silver, and J. Strauss),p. 169. Munich and Berlin: Urban and Schwarzenberg.

Severinghaus, J. W., Weiskopf, R. B., Nishimura, M., andBradley, A. F. (1971). Oxygen electrode errors due topolarographic reduction of halothane. J. Appl. Physiol.,31, 640.

Wolf, C. R., Elcombe, C. R., Illing, H. P. A., Bridges,J. W., Nimmo-Smith, R. H., King, L. J., and Netter,K. J. (1975). Measurements of substrate-induced oxygenuptake during microsomal drug oxidation using a goldmicroelectrode. Xenobiotica, 5, 173.

ERREURS DANS LES MESURES DE LA TENSIOND'OXYGENE CAUSEES PAR L'HALOTHANE

RESUME

L'halothane augmente, independemment de la tensiond'oxygene, le signal de la microelectrode or/argent-chlorure

d'argent. On a mesure la production des microelectrodes adifferentes tensions d'oxygene en presence de quantitescroissantes d'halothane. L'halothane provoque dans lesignal de l'electrode une augmentation qui est proportion-nelle a sa concentration. Cet effet provient de la reductionpolarographique de l'halothane. On en conclut que l'onne peut pas utiliser les microelectrodes or/argent-chlorured'argent pour mesurer la tension de l'oxygene pendantles anesthesies obtenues par l'halothane.

HALOTHANINDUZIERTE FEHLER BEI DERPOLAGRAPHISCHEN MESSUNG DER

SAUERSTOFFSPANNUNG

ZUSAMMENFASSUNG

Es wurde die Beobachtung gemacht, dass Halothan denPolarisationsstrom de Gold/Ag-AgCl-Sauerstoff-Mikro-elektrode unabhangig von der tatsachlichen Sauerstoff-konzentration erhoht. Dieser Effekt wurde naher charakteri-siert durch Messung des Elektrodensignals bei vers-chiedenen Sauerstoffspanungen und ansteigenenden Halo-thankonzentrationen. Die Erhohung des Polarisations-stromes ist der Halothankonzentration proportional, wobeisolche Halothankonzentrationen gewahlt wurden, die imanasthetisch wirksamen Bereich liegen. Die Erhohung desElektrodensignals beruht auf einer polarographischenReduktion des Halothans. Diese Ergebnisse zeigen, dassdie Anwendung der Gold/Ag-AgCl-Mikroelektrode zurVerfolgung der Sauerstoffspannung im Blut wahrend einerHalothannarkose problematisch ist.

ERRORES EN LAS MEDICIONESDE LA TENSION DE OXIGENO PRODUCIDA

POR EL HALOTANO

SUMARIO

El halotano aumentd la serial del microelectrodo oro/plata-cloruro de plata, independiente de la tension de oxigeno.Se ha medido la potencia de los microelectrodos a diferentestensiones de oxigeno en presencia de crecientes cantidadesde halotano. El halotano produce un aumento en la serial delelectrodo que es proporcional a la concentration de halotano.Este efecto es el resultado de la reduction polarografica delhalotano. Se llega a la conclusi6n de que el microelectrodooro/plata-cloruro de plata no se puede usar para medir latensi6n de oxigeno durante la anestesia inducida porhalotano.

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ASSOCIATION OF ANAESTHETISTS OF GREAT BRITAIN & IRELAND

Joint Meeting with the Danish Society of Anaesthesiologists

Copenhagen June 11th & 12th 1976

Scientific ProgrammeSymposia:

Clinical use of relaxantsThe central circulationAcid-base balance problemsThe stress response to surgery

Social ProgrammeA reception will be provided by the Danish Society on Thursday, 10th June. TheAssociation will be host to the Danish Society on Friday evening, and there will be adinner-dance on Saturday 12th.TravelThe Association has arranged group travel to include air fare, and hotel accom-modation.

RegistrationApplication forms will be sent to all members of the Association or may be obtainedfrom the Honorary Secretary, Room 475, Tavistock House, Tavistock Square,London WC1H 9JP.

ASSOCIATION OF ANAESTHETISTS OF GREAT BRITAIN AND IRELAND

ANNUAL SCIENTIFIC MEETING in 1976

at the Tara Hotel, Kensington, London W.8 on Thursday and Friday, November 18-19.

Those wishing to submit papers for the scientific sessions are requested to send FOUR

COPIES of a summary of 300 words, not later than Friday, May 26th, 1976, to:-

The Hon. Secretary

Association of Anaesthetists of Great Britain and Ireland

Room 475 Tavistock House South

Tavistock Square

London WC1H 9JP.

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