The Effects of Anesthetics on an In-vivo Oxygen Electrode MARY L O U I S E B A T E S , B.A., A L F R E D F E I N G O L D , M.S., M.D., AND M A R T I N I. G O L D ,
M.D.
Department of Anesthesiology, University of Miami, School of Medicine, and Veterans Administration Hospital, 1201 N. W. 16th Street, Miami, Florida 33125
ABSTRACT
have been shown to be electrochemically reduced by the standard Clark oxygen electrode 6 at polarizing voltages greater than 0.5 volts. T h e IBC Universal in-vivo Oxygen Electrode* described by Harris 3 and Strauss 7 uses a polarizing voltage of 0.7 volts and may be subject to this phenomenon. The IBC electrode in vitro was shown to be at least as accurate and precise as the Radiometer in a previous study from the authors' laboratory, in which methods of comparison, calibration and maintenance were described. 2 However, since IBC electrodes are used during anesthesia, 2,3 anesthetic agents might falsely increase the measured oxygen tension. This possibility was tested
ANESTHETIC AGENTS
in vitro with three inhalation anesthetic agents: halothane, enflurane and methoxyflurane.
Received January 13, 1975; received revised manuscript March 20, 1975; accepted for publication March 20, 1975. Address reprint requests to M. L. Bates, Assistant to Martin I. Gold, M.D., Department of Anesthesiology, University of Miami School of Medicine, P.O. Box 875, Biscayne Annex, Miami, Florida 33152. * International Biophysics Corporation, Irvine, California.
448
Method The IBC electrode was equilibrated with heparinized blood in a tonometer cuvette at 37 C. with an 0 2 tension of 150 torr for one hour before each study. Oxygen tensions in the tonometer ranging from 0 to 250 torrf were achieved using a gas-mixing p u m p (Instrumentations Associates) and medical-grade oxygen and nitrogen. T h e gas mixture from the pump was directed through a vaporizer previously calibrated by gas chromatography 4 (Microtek 2700) into a tonometer. (Instrumentation Laboratories 237). Drager, Ethrane, and Pentec vaporizers were used for halothane, enflurane, and methoxyflurane, respectively. The tonometer spin-mixes the cuvette t Corroborated by macro Scholander analysis.
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Bates, Mary Louise, Feingold, Alfred, and Gold, Martin I.: T h e effects of anesthetics on an in-vivo oxygen electrode. Am J Clin Pathol 64: 4 4 8 - 4 5 1 , 1975. T h e IBC in-vivo oxygen electrode may be used during anesthesia. T h e possibility that three common inhalation anesuietics—halothane, enflurane, and methoxyflurane—might be reduced at the electrode, thereby changing the Po, value, was tested. Enflurane and methoxyflurane do not affect die current produced at the electrode; halothane significantly increases P02 readings at oxygen tensions below 105 torr. It is suggested that Pao2 readings below 105 torr be confirmed by the standard bench method. (Key words: Halothane; Oxygen tension; Electrode; Tonometry; Anesthetics.)
October
1975
449
ANESTHETIC EFFECTS ON OXYGEN ELECTRODE
Table 2. Effect of Halothane on IBC Oxygen Electrode Tonometered Halothane Gas Concentration Tonometer Gas 02 Tension (Torr)
Radiometer Blood 02 Tension (Torr) Mean ± S.D. n = 8
0%
1.5% IBC Blood 0 2 Tension (Torr)
0 (100% N2)
11 ± 1.4
24
42
63
67
70
45
55 ± 1.4 57 ± 1.4
54* 65
60 70
70 76
74 80
74 82
75
83 ± 2.6 82 ± 1.8
75* 75
80
85 88
108 88
117 88
105
108 ± 1.3
113
110
116
115
114
150
148 ± 2.4
155
153
158
155
154
250
231 ± 1.5
248
255
255
260
260
* Two different IBC electrodes.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
for 2 sec. and rests 2 sec. T h e cathode Table 1. Effect of Enflurane and Methoxyand anode of the IBC electrode were flurane on IBC Oxygen Tension at a threaded through plastic tubing into the Tonometered Tension of 75 T o r r blood through the port in the lid of the IBC Blood 02 tonometer. T h e tonometer mixed for 9 Tension* (Torr) minutes, then was stopped for 1 minute Mean ± S.D. n = 4 before each measurement. Following the IBC reading, 1 ml. of blood was withdrawn 1. After calibration of IBC from the tonometer and analyzed by a electrode 76 ± 0.5 standard bench oxygen electrode (Radiom- 2. After 20 min. exposure eter E 5046) calibrated at known baroto 2% enflurane 75 ± 0.5 metric pressure wim room air and a zero 3. After 12 min. washout 74 ± 0 Po2 solution of sodium sulfite and Borax. 20 min. exposure Small increments of blood were added to 4. After to 1.5% methoxyflurane 74 ± 0 the cuvette to maintain a level of 5 ml. 5. After 16 min. washout 73 ± 0.5 throughout the study. ' Four readings were taken 2 min. apart after equilibration. Two protocols were followed for analyzing anesthetic effect on measured oxygen tension. First, the response time was determined at a single tonometered Poj by reSecond, halothane was introduced in incording IBC PQJ every 2 minutes after creasing concentrations of 0.4, 1.0, 1.5, to exposure to the agent. At the same times 2.0 vol % at the following oxygen tensions: blood samples were analyzed for halothane 0, 45, 75, 105, 150 and 250 torr. Twenty content by gas chromatography following minutes passed before halothane was inhexane extraction. A 6 ft., 10% diiso- creased to the next concentration. Six decylphthalate on Chromosorb P column different IBC electrodes were used, one for was used with the electron-capture de- enflurane and methoxyflurane and five tector. for halothane.
450
BATES, FEINGOLD, AND GOLD Results
Discussion and Conclusion T h e IBC micro 0 2 electrode utilizes the polarographic principle. Oxygen dissolved in the blood diffuses through a hydrophilic
64
membrane, Hydron, and is reduced electrochemically at a gold cathode. T h e current produced is proportional to the amount of oxygen arriving at the cathode. A polarizing voltage of 0.7 volts is used in both IBC electrodes and Radiometer E5046 electrodes. Severinghaus 6 reported that halothane, a brominated hydrocarbon, can be reduced at a voltage greater than 0.4 volts. He also reported that the Radiometer response is slower to halothane than to oxygen, and reduction takes place only when blood is allowed to remain in the cuvette for several minutes. In our bench Pos analyses the blood remained in the Radiometer cuvette for 3 0 - 6 0 sec, so no reduction was evident. T h e presence of halothane neither decreases erythrocytic oxygen utilization significantly 1 n o r changes the affinity of hemoglobin for oxygen, 8 so increase in PQJ can be reasonably attributed to reduction of anesthetic agent. Presumably, at P^'s above 105 torr enough oxygen is reduced to minimize current resulting from reduction of halothane; the electrode seems to preferentially reduce 0 2 . Methoxyflurane and enflurane are chlorinated hydrocarbons containing no bromine. T h e voltage required to reduce a chlorinated hydrocarbon is much more than that required for brominated ones such as halothane, and the polarizing voltage of the IBC electrode is not sufficient to cause this reduction. Our data indicate that at oxygen tensions less than 105 torr halothane elevates current in the IBC electrode. This is concentration-dependent, greater at low Paoj, and minimal at high Pa^. T h e IBC electrode responds within 4 minutes to the presence of halothane in clinical concentrations, and the increase in current seems to parallel the increase in halothane content in the blood. When the IBC electrode is used for measurement of Pa 02 during halothane anesthesia, any Pa 02 below 105 torr should be confirmed by other methods.
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Neither enflurane nor methoxyflurane altered the IBC-measured oxygen tension in blood (Table 1). Halothane, however, produced a significant concentration-dependent effect (Table 2). Current due to halothane reduction increased with greater halothane concentrations: 0.4% halothane increased the IBC P 02 reading from 54 to 60 torr at a tonometered tension of 45 torr; 1.0% increased the reading to 70 torr; 1.5 and 2.0% increased it to 74 torr. As tonometered P 0 j increased, the increment due to halothane decreased. When 100% N2 was used to achieve zero P 02 the IBC electrode read 24 torr (released from hemoglobin) at 0% halothane. After equilibration with 2.0% halothane this increased to 70 torr. At a tonometered P 02 of 75 torr the addition of 2.0% halothane increased the measured P 02 only from 75 to 88 torr. These increases were not evident in concurrent measurements with the Radiometer electrode. Readings were taken eight times after equilibration at each 0 2 tension; mean and standard deviation of these measurements are indicated in Table 2. No consistent change in IBC or Radiometer P 02 occurred at tonometered oxygen tensions of 105 torr or greater, regardless of halothane concentration. T h e time required to achieve maximum halothane effect was approximately 18 minutes. Fourteen minutes were required for halothane equilibration in blood as measured by gas chromatography. T h e difference, 4 minutes, represents the IBC electrode response time to halothane. At very low concentrations of halothane (0.4%) this response time of the IBC was slower, about 10 minutes.
A.J.C.P.—Vol.
October 1975
ANESTHETIC EFFECTS ON OXYGEN ELECTRODE References
Bergman NA: Changes in Po, with time in human blood containing anesthetic agents. Anesthesiology 32:357-58, 1970 Gold MI, Diaz PM, Feingold A, et al: A disposable in vivo oxygen electrode for the continuous measurement of arterial tension. Surgery (in press, August 1975) Harris TR, Hugent M: Continuous arterial oxygen tension monitoring in the newborn infant. J Pediatr 82:929-939, 1973 Lowe HJ: Flame ionization detection of volatile anesthetics in blood, gases and tissues. Anesthesiology 25:808-814, 1964
451
5. Park WY, Balingit P, Kenmore PI, et al: Changes in arterial oxygen tension during total hip replacement. Anesthesiology 39:642-644, 1973 6. Severinghaus J, Weiskopf RB, Nishimura M, et al: Oxygen electrode errors due to polaroraphic reduction of halothane. J Appl Physiol 1:640-42, 1971 7. Strauss AW, Escobedo M, Goldring O: Continuous monitoring of arterial oxygen tension in the newborn infant. J Pediatr 85:254—61, 1974 8. Weiskopf RB, Nishimura M, Severinghaus JW: The absence of an effect of halothane on blood hemoglobin 0 2 equilibrium in vitro. Anesthesiology 35:579-81, 1971
f
Third International Symposium on Detection and Prevention of Cancer April 26 to May 1, 1976 Americana Hotel, New York City Thirteen Conferences, 33 Panels, 56 Symposia, 15 Courses and 23 Workshops deal with cancer prevention, impact of occupational and environmental risk factors on clinical oncology, manifestations of occult cancer and tumor susceptibility, identification of high-risk groups, multiple-factor etiology and detection and management of early cancer in specific sites. This Continuing Medical Education Activity is acceptable for Credit Hours on an hour-for-hour basis in Category No. 1 for T h e Physician's Recognition Award of The American Medical Association. Sponsored by T h e International Study Group for the Detection and Prevention of Cancer (DePCa), and co-sponsored by T h e Mount Sinai School of Medicine of CUNY and by T h e International Agency for Research on Cancer." Proffered Paper Abstracts: Deadline, November 15, 1975. For information, write: Herbert E. Nieburgs, M.D., Mount Sinai School of Medicine of CUNY, Fifth Avenue at 100th Street, New York, N.Y. 10029, U.S.A., Tel. (212)-534-4991.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
N e w s and N o t i c e s
M.D.
Department of Anesthesiology, University of Miami, School of Medicine, and Veterans Administration Hospital, 1201 N. W. 16th Street, Miami, Florida 33125
ABSTRACT
have been shown to be electrochemically reduced by the standard Clark oxygen electrode 6 at polarizing voltages greater than 0.5 volts. T h e IBC Universal in-vivo Oxygen Electrode* described by Harris 3 and Strauss 7 uses a polarizing voltage of 0.7 volts and may be subject to this phenomenon. The IBC electrode in vitro was shown to be at least as accurate and precise as the Radiometer in a previous study from the authors' laboratory, in which methods of comparison, calibration and maintenance were described. 2 However, since IBC electrodes are used during anesthesia, 2,3 anesthetic agents might falsely increase the measured oxygen tension. This possibility was tested
ANESTHETIC AGENTS
in vitro with three inhalation anesthetic agents: halothane, enflurane and methoxyflurane.
Received January 13, 1975; received revised manuscript March 20, 1975; accepted for publication March 20, 1975. Address reprint requests to M. L. Bates, Assistant to Martin I. Gold, M.D., Department of Anesthesiology, University of Miami School of Medicine, P.O. Box 875, Biscayne Annex, Miami, Florida 33152. * International Biophysics Corporation, Irvine, California.
448
Method The IBC electrode was equilibrated with heparinized blood in a tonometer cuvette at 37 C. with an 0 2 tension of 150 torr for one hour before each study. Oxygen tensions in the tonometer ranging from 0 to 250 torrf were achieved using a gas-mixing p u m p (Instrumentations Associates) and medical-grade oxygen and nitrogen. T h e gas mixture from the pump was directed through a vaporizer previously calibrated by gas chromatography 4 (Microtek 2700) into a tonometer. (Instrumentation Laboratories 237). Drager, Ethrane, and Pentec vaporizers were used for halothane, enflurane, and methoxyflurane, respectively. The tonometer spin-mixes the cuvette t Corroborated by macro Scholander analysis.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
Bates, Mary Louise, Feingold, Alfred, and Gold, Martin I.: T h e effects of anesthetics on an in-vivo oxygen electrode. Am J Clin Pathol 64: 4 4 8 - 4 5 1 , 1975. T h e IBC in-vivo oxygen electrode may be used during anesthesia. T h e possibility that three common inhalation anesuietics—halothane, enflurane, and methoxyflurane—might be reduced at the electrode, thereby changing the Po, value, was tested. Enflurane and methoxyflurane do not affect die current produced at the electrode; halothane significantly increases P02 readings at oxygen tensions below 105 torr. It is suggested that Pao2 readings below 105 torr be confirmed by the standard bench method. (Key words: Halothane; Oxygen tension; Electrode; Tonometry; Anesthetics.)
October
1975
449
ANESTHETIC EFFECTS ON OXYGEN ELECTRODE
Table 2. Effect of Halothane on IBC Oxygen Electrode Tonometered Halothane Gas Concentration Tonometer Gas 02 Tension (Torr)
Radiometer Blood 02 Tension (Torr) Mean ± S.D. n = 8
0%
1.5% IBC Blood 0 2 Tension (Torr)
0 (100% N2)
11 ± 1.4
24
42
63
67
70
45
55 ± 1.4 57 ± 1.4
54* 65
60 70
70 76
74 80
74 82
75
83 ± 2.6 82 ± 1.8
75* 75
80
85 88
108 88
117 88
105
108 ± 1.3
113
110
116
115
114
150
148 ± 2.4
155
153
158
155
154
250
231 ± 1.5
248
255
255
260
260
* Two different IBC electrodes.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
for 2 sec. and rests 2 sec. T h e cathode Table 1. Effect of Enflurane and Methoxyand anode of the IBC electrode were flurane on IBC Oxygen Tension at a threaded through plastic tubing into the Tonometered Tension of 75 T o r r blood through the port in the lid of the IBC Blood 02 tonometer. T h e tonometer mixed for 9 Tension* (Torr) minutes, then was stopped for 1 minute Mean ± S.D. n = 4 before each measurement. Following the IBC reading, 1 ml. of blood was withdrawn 1. After calibration of IBC from the tonometer and analyzed by a electrode 76 ± 0.5 standard bench oxygen electrode (Radiom- 2. After 20 min. exposure eter E 5046) calibrated at known baroto 2% enflurane 75 ± 0.5 metric pressure wim room air and a zero 3. After 12 min. washout 74 ± 0 Po2 solution of sodium sulfite and Borax. 20 min. exposure Small increments of blood were added to 4. After to 1.5% methoxyflurane 74 ± 0 the cuvette to maintain a level of 5 ml. 5. After 16 min. washout 73 ± 0.5 throughout the study. ' Four readings were taken 2 min. apart after equilibration. Two protocols were followed for analyzing anesthetic effect on measured oxygen tension. First, the response time was determined at a single tonometered Poj by reSecond, halothane was introduced in incording IBC PQJ every 2 minutes after creasing concentrations of 0.4, 1.0, 1.5, to exposure to the agent. At the same times 2.0 vol % at the following oxygen tensions: blood samples were analyzed for halothane 0, 45, 75, 105, 150 and 250 torr. Twenty content by gas chromatography following minutes passed before halothane was inhexane extraction. A 6 ft., 10% diiso- creased to the next concentration. Six decylphthalate on Chromosorb P column different IBC electrodes were used, one for was used with the electron-capture de- enflurane and methoxyflurane and five tector. for halothane.
450
BATES, FEINGOLD, AND GOLD Results
Discussion and Conclusion T h e IBC micro 0 2 electrode utilizes the polarographic principle. Oxygen dissolved in the blood diffuses through a hydrophilic
64
membrane, Hydron, and is reduced electrochemically at a gold cathode. T h e current produced is proportional to the amount of oxygen arriving at the cathode. A polarizing voltage of 0.7 volts is used in both IBC electrodes and Radiometer E5046 electrodes. Severinghaus 6 reported that halothane, a brominated hydrocarbon, can be reduced at a voltage greater than 0.4 volts. He also reported that the Radiometer response is slower to halothane than to oxygen, and reduction takes place only when blood is allowed to remain in the cuvette for several minutes. In our bench Pos analyses the blood remained in the Radiometer cuvette for 3 0 - 6 0 sec, so no reduction was evident. T h e presence of halothane neither decreases erythrocytic oxygen utilization significantly 1 n o r changes the affinity of hemoglobin for oxygen, 8 so increase in PQJ can be reasonably attributed to reduction of anesthetic agent. Presumably, at P^'s above 105 torr enough oxygen is reduced to minimize current resulting from reduction of halothane; the electrode seems to preferentially reduce 0 2 . Methoxyflurane and enflurane are chlorinated hydrocarbons containing no bromine. T h e voltage required to reduce a chlorinated hydrocarbon is much more than that required for brominated ones such as halothane, and the polarizing voltage of the IBC electrode is not sufficient to cause this reduction. Our data indicate that at oxygen tensions less than 105 torr halothane elevates current in the IBC electrode. This is concentration-dependent, greater at low Paoj, and minimal at high Pa^. T h e IBC electrode responds within 4 minutes to the presence of halothane in clinical concentrations, and the increase in current seems to parallel the increase in halothane content in the blood. When the IBC electrode is used for measurement of Pa 02 during halothane anesthesia, any Pa 02 below 105 torr should be confirmed by other methods.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
Neither enflurane nor methoxyflurane altered the IBC-measured oxygen tension in blood (Table 1). Halothane, however, produced a significant concentration-dependent effect (Table 2). Current due to halothane reduction increased with greater halothane concentrations: 0.4% halothane increased the IBC P 02 reading from 54 to 60 torr at a tonometered tension of 45 torr; 1.0% increased the reading to 70 torr; 1.5 and 2.0% increased it to 74 torr. As tonometered P 0 j increased, the increment due to halothane decreased. When 100% N2 was used to achieve zero P 02 the IBC electrode read 24 torr (released from hemoglobin) at 0% halothane. After equilibration with 2.0% halothane this increased to 70 torr. At a tonometered P 02 of 75 torr the addition of 2.0% halothane increased the measured P 02 only from 75 to 88 torr. These increases were not evident in concurrent measurements with the Radiometer electrode. Readings were taken eight times after equilibration at each 0 2 tension; mean and standard deviation of these measurements are indicated in Table 2. No consistent change in IBC or Radiometer P 02 occurred at tonometered oxygen tensions of 105 torr or greater, regardless of halothane concentration. T h e time required to achieve maximum halothane effect was approximately 18 minutes. Fourteen minutes were required for halothane equilibration in blood as measured by gas chromatography. T h e difference, 4 minutes, represents the IBC electrode response time to halothane. At very low concentrations of halothane (0.4%) this response time of the IBC was slower, about 10 minutes.
A.J.C.P.—Vol.
October 1975
ANESTHETIC EFFECTS ON OXYGEN ELECTRODE References
Bergman NA: Changes in Po, with time in human blood containing anesthetic agents. Anesthesiology 32:357-58, 1970 Gold MI, Diaz PM, Feingold A, et al: A disposable in vivo oxygen electrode for the continuous measurement of arterial tension. Surgery (in press, August 1975) Harris TR, Hugent M: Continuous arterial oxygen tension monitoring in the newborn infant. J Pediatr 82:929-939, 1973 Lowe HJ: Flame ionization detection of volatile anesthetics in blood, gases and tissues. Anesthesiology 25:808-814, 1964
451
5. Park WY, Balingit P, Kenmore PI, et al: Changes in arterial oxygen tension during total hip replacement. Anesthesiology 39:642-644, 1973 6. Severinghaus J, Weiskopf RB, Nishimura M, et al: Oxygen electrode errors due to polaroraphic reduction of halothane. J Appl Physiol 1:640-42, 1971 7. Strauss AW, Escobedo M, Goldring O: Continuous monitoring of arterial oxygen tension in the newborn infant. J Pediatr 85:254—61, 1974 8. Weiskopf RB, Nishimura M, Severinghaus JW: The absence of an effect of halothane on blood hemoglobin 0 2 equilibrium in vitro. Anesthesiology 35:579-81, 1971
f
Third International Symposium on Detection and Prevention of Cancer April 26 to May 1, 1976 Americana Hotel, New York City Thirteen Conferences, 33 Panels, 56 Symposia, 15 Courses and 23 Workshops deal with cancer prevention, impact of occupational and environmental risk factors on clinical oncology, manifestations of occult cancer and tumor susceptibility, identification of high-risk groups, multiple-factor etiology and detection and management of early cancer in specific sites. This Continuing Medical Education Activity is acceptable for Credit Hours on an hour-for-hour basis in Category No. 1 for T h e Physician's Recognition Award of The American Medical Association. Sponsored by T h e International Study Group for the Detection and Prevention of Cancer (DePCa), and co-sponsored by T h e Mount Sinai School of Medicine of CUNY and by T h e International Agency for Research on Cancer." Proffered Paper Abstracts: Deadline, November 15, 1975. For information, write: Herbert E. Nieburgs, M.D., Mount Sinai School of Medicine of CUNY, Fifth Avenue at 100th Street, New York, N.Y. 10029, U.S.A., Tel. (212)-534-4991.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
N e w s and N o t i c e s
