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Muscle surface pH: Comparison with cardiac output and arterial pH in the critically III subject
Muscle Surface pH : Comparison with Cardiac Output and Arterial pH in the Critically Ill Subject By William H. Weintraub, Stacy A. Roback, Mohandas Devadas, Joe Rysavy, and Arnold S. Leonard
A
METHOD for measuring muscle surface pH was described by Couch et al. in 1968.l Filler and Das adapted this concept by miniaturization of the pH probe, thus enabling its use in pediatric patients.24 Investigations from both of these groups have confirmed the surface pH of skeletal muscle as a sensitive, but indirect, indicator of peripheral muscle blood flow. The proposed mechanism for this relationship is hypothesized as follows: Increased hydrogen ion activity is a consequence of anaerobic glycolysis that results in the formation of lactic acid. Anaerobic glycolysis is presumed the result of reduced tissue perfusion. It is the purpose of this paper to correlate, under a variety of experimental shock states, peripheral muscle pH with central changes in cardiac output. Two different model systems were used. Hemorrhagic shock was produced by repeated bleeding in the dog, and endotoxin shock was initiated by the intravenous injection of gram-negative endotoxin. MATERIALS AND METHODS
Forty healthy mongrel dogs weighing 5-21 kg were used. Each dog was anesthetized with 30 mg/kg sodium pentobarbital. An endotracheal tube was inserted. No artificial ventilation was undertaken, as initial studies demonstrated that this means of support affected the animal’s ability to alter his own metabolic state. (Preeumably, a fixed-rate respirator does not allow necessary respiratory compensations.) The right femoral artery and vein were cannulated for measurement of cardiac output, and the catheters were advanced above the diaphragm. The left femoral artery was also cannulated for pressure readings and pulse contour evaluation, using a Microdot MS-5 pressure transducer with a range of O-300 mm Hg. A Corning Filler-Das in vivo pH electrode was rinsed with distilled water and standardized at pH 7, and at pH 4, using fresh known buffer solutions. An incision was made just above the joint in the right front leg, using cautery to produce a bloodless field. The pH probe was inserted under the muscle fascia, which was then sutured over the probe. After skin closure, the probe was taped tightly to ensure constant niuscle contact. The probe was attached to a Beckman expanded-scale pH meter, model No. 76. Dye dilution cardiac output as well as blood pressure readings and pressure contour cardiac output were measured in a manner previously described.5 After a period of stabilization, control readings of cardiac output, blood gases, muscle, and arterial pH were taken every 15 min. Four groups of ten dogs each were then treated in the followFrom the Department
of Surgery, University
of Minnesota
Hospitals,
Minneapolis,
Minn.
Presented at the Third Annual Meeting of the American Pediatric Surgical Association, Hot Springs, Vu., April 13-15, 1972. William H. Weintraub, M.D.: Department of Surgery, University of Minnesota Hospitals, Minneapolis, Minn. Stacy A. Roback, M.D.: Department of Surgery, Utiiversity of Minnesota Hospitals, Minneapolis, Minn. Mohandas Devadas, M.D.: Department of Surgery, University of Minnesota Hospifals, Minneapolis, Minn. Joe Rysavy, B.A.: Junior Scientist, Department of Surgery, University of Minnesota, Minneapolis, Minn. Arnold S. Leonard, M.D., Ph.D.: Head, Pediatric Surgery Section, Department of Surgery, University of
Minnewfa
Hospitals,
Journel of Pediatric
Minneapolis,
Minn.
Surgery, Vol. 7, No. 5 (October-November),
1972
505
506
WEINTRAUB ET AL.
ing manner: (1) Some 6% of the estimated blood volume was withdrawn every 15 min until the dog was depleted of approximately 40% of its blood volume. (2) Dogs were treated as in group 1, except that the entire volume was reinfused after approximately 40% of the blood volume had been withdrawn. (3) After the control period each dog was given a LD-50 dose of gram-negative endotoxin, (calculated at 2.5 mglkg) as a bolus. (4 These dogs were treated similarly to group 3, except for administration of 100 cc of plasma and 30 mg/kg of Solu-Medrol 1 hr after injection of the endotoxin. The pH probes were checked for accuracy with standard buffer solutions at the termination of every experiment.
RESULT’S
In group 1 (see Fig. 1) after 6% of the blood volume had been withdrawn, no noticeable change in mean blood pressure or arterial pH became evident. However, cardiac output and muscle pH both started an early downward trend. Blood lactate levels did not begin to iise significantly until more than 25% of the blood had been withdrawn. In group 2 (Fig. 2) after reinfusion of the shed blood, cardiac output, mean blood pressure, and muscle pH levels returned toward normal simultaneously. Blood lactate levels rose but no defineable changes occurred to arterial pH levels. In group 3 (Fig. 3) muscle pH, arterial pH, and cardiac output, as ivell as mean blood pressure, all fell shortly after the injection of endotoxin. Blood lactate levels began a slow, but continuous, rise throughout the experiment. The ranges of arterial and muscle pH were quite wide. In group 4 (Fig. 4), after entering the treatment phase of endotoxin shock, there was no statistically significant alteration in muscle or arterial pH. Group No. I -
Withdrawal
Time lminutesl
Fig. 1. Average values including ranges of ten dogs successively bled 6% of their estimated blood volume (group 1).
MUSCLE SURFACE pH Group No. 2 - Wifhdrowal, f?einhsion
Time (minutes)
to
Fig. 2. Average values including ranges of ten dogs successively bled down volume loss then reinfused (group 2).
36%
Group No. 3 -
E. coli Whout Treotmenf
Fig. 3. Average values including ranges of ten aogs given an LD-50 dose of endotoxin (group 3).
508
WEINTRAUB ET AL.
There was, however, a rise in cardiac output. The blood lactate rose slowly and maintained high levels throughout the course of this experiment also. DISCUSSION
Since skeletal muscle represents 40%~50% of body weight,s knowledge of its acid base status should be of importance to the clinician. Similarly, 30% of the oxygen consumption of the body at rest is accounted for by muscle, and during exercise its share can rise to 90%. In contrast, during shock states, organs other than muscle receive a larger share of the cardiac output. In conditions of normal tissue perfusions Duff and Smith’*s have shown that muscle pH is directlv related to arterial pH as far as charmes in acid-base balance are concerned. The control periods of our studies reaffirm this fact. In situations of hypovolemic shock, as demonstrated by groups 1 and 2, there is decreased tissue perfusion. This results in muscle converting from oxidative phosphorylation to anaerobic glycolysis, with buildup of lactic acid at the surface of the skeletal muscle cells. This increased hydrogen ion activity occurs early and is the explanation for the early fall in muscle pH noted in experiments I and 2. No significant changes were noted in blood lactate levels or arterial pH early in these experiments because the decreased tissue perfusion did not allow the lactate to be washed from the surface of the cells into the central circulation. Cardiac output has not been monitored during experiments GroupNo. 4 - E. co/i Jreofment with Solu -Medrol@ ond Plosmonote
i
E.col~
injected
I
treatment
E Solu-Medrol@
and plasma
M9Ofl B.P. (mmHg) 0
30
43
60
73
90
135
221
Fig. 4. Average values including ranges of ten dogs given an LD-50 dose of endotoxin and after 1 hr treated with 30 mg/kg of Sob-Medrol and 100 cc plasma (group 4).
MUSCLESURFACEpH
509
of this nature by previous investigators. It is apparent in these states of acute blood-volume change that muscle surface pH changes parallel those of cardiac output quite closely. The sequence would appear to be as follows: A decreased blood volume causes a decrease in cardiac output, which results in decreased muscle perfusion, subsequent buildup of lactate, and eventual lowering of muscle surface pH values. These alterations seem to occur well before more standard parameters such as blood pressure and arterial pH are affected. Our experiments differ from previous investigators in one area. Instead of one large bleed, repetitive small bleeds were used because this is more typical of bleeding seen in the clinical situation. This difference in experimental methods may explain the slow rise and fall of blood lactate levels in our experiments whereas others have noted a more rapid rise. Q~loIn fact, our lactate levels did not return to normal until some hours after the other parameters had returned to prebleed levels. In the endotoxin shock model, our findings were similar to those of prior studies.” Mean blood pressure, muscle surface pH, and arterial pH fell, whereas blood lactate levels rose. Cardiac output also fell. These experiments suggest that muscle pH is not more useful than other parameters for following endotoxin shock, and the clinician should use a more central means of monitoring. The dogs in group 4, after treatment with volume and large doses of steroids, did undergo a significant rise in cardiac output, with no appreciable change in any of the other parameters. The explanation of this phenomenon is not clear. However, diversion of this increased cardiac output to organs more important than skeletal muscle may explain why this higher cardiac output was not reflected in muscle surface pH readings. Other explanations, such as increased A-V shunting, are also plausible. Cardiac output was low throughout the endotoxin shock experiments and we were not able to measure any A-V shunting or vasoconstriction as postulated by Couch et al.11e12 CONCLUSION
Muscle pH would appear to have several areas of usefulness in the clinical situation. In states of completely normal muscle perfusion, muscle surface pH is a direct indicator of arterial pH and has the advantage of being a continuous measurement. This could be used for monitoring of patients on respirators or undergoing drug treatment for metabolic alkalosis or acidosis. In patients with acute hypovolemia, which would include many pediatric surgical problems, muscle pH detects changes of volume much earlier than arterial pH or blood pressure, and in fact parallels cardiac output closely. It thus can be used as an inexpensive and continuous indicator of cardiac output. In endotoxin shock or other severe shock states, muscle surface pH monitoring does not appear to have any clear advantage over other methods of monitoring. Where severe metabolic alterations have occurred, these experiments suggest muscle pH may be a useful indicator only as to when the subject goes into or comes out of this state. More central means of monitoring such cardiac output must be employed to govern therapeutic modalities.
510
WEINTRAUB ET AL.
REFERENCES 1. Lemieux, M. D., Smith, R. N., and Couch, N. P.: Effect of hemorrhage and reinfusion on electrometric surface hydrogen ion activity and redox potential of skeletal muscle. Surg. Forum 19:1,1968. 2. Filler, R. M., and Das, J. B.: Muscle pH: A new parameter in the monitoring of a critically ill child. Pediatrics 47:880,1971. 3.- -, Haase, G. M., and Donhoe, P. K.: Muscli pH as a monitor of tissue perfusion and acid base status. J. Pediat. Surg. 6:535, 1971. 4. - -, and Espinosa, H. M.: Clinical experience with continuous muscle pH monitoring as an index of tissue perfusion and oxygenation, and acid base status. Presented at the meeting of the Society of University Surgeons, Feb., 1972. 5. Weintraub, W. H., Cuderman, B. S., Hunt, C. E., Stauffer, W. M., Roback, S. A., and Leonard, A. S.: Computer monitoring of cardiodynamics in the newborn. J. Pediat. Surg. 6:372,1971. 6. Lemieux, M. D., Smith, R. N., and Couch, N. P.: Electrometric surface pH of skeletal muscle and hypovolemia. Amer. J. Surg. 117:627, 1969.
7. Duff, J. H., Groves, A. C., McLean, A. P. H., LaPointe, R., and MacLean, L. D.: Effective oxygen consumption in septic shock. Surg. Gynec. Obstet. 128:1051,1969. 8. Smith, R. N., Lemieux, M. D., and Couch, N. P.: Effects of acidosis and alkalosis on surface skeletal muscle hydrogen ion activity. Surg. Gynec. Obstet. 128:533, 1969. 9. Dmochowski, J. R., Couch, N. P., Kempf, R. N., and Appleton, D. R.: Electrometric surface pH of the ischemic kidney and the effect of hypothermia. J. Surg. Res. 6~4.5, 1966. 10.Couch, N. P., Maginn, R. R., Middleton, M. K., Appleton, D. R., and Dmochowski, J. R.: Effect of ischemic intervals and temperature on renal surface hvdrogen ion concentration. Surg. Gynec. Obstet. 125: 521,1967. 11.Dmochowski] J. R., and Couch, N. P.: Skeletal muscle hydrogen ion activity in endotoxin shock. Surg. Gynec. Obstet. 131: 669,197O. 12. Anas, P., Neely, W. A., and Hardy, J. B.: Effects of vasoactive drugs on oxygen consumption in endotoxin shock. Arch. Surg. (Chicago) 98:189,1969.
Discussion Dr. R. M. Filler (Boston): This paper clearly demonstrates the relation between cardiac output and muscle pH, at least in these experimental circumstances. I think there are other times when it is very dift?cuIt to know exactly what the correlation is. For example, in hypovolemic shock there is a clear correlation between muscle pH and cardiac output, but peripheral vasoconstriction is an additional factor influencing what is measured at the muscle level. It would be helpful in all these situations to have a way of measuring peripheral resistance continuously to evaluate completely the effect of this parameter on muscle PH. Nevertheless, although physiologic mechanisms for a low muscle pH are not known, muscle acidosis is a good indication that a child is not doing well and should trigger a search for causes of the abnormality. Therefore as a meaningful monitor of the total vital physiologic functions, muscle pH monitoring works out quite well.
A
METHOD for measuring muscle surface pH was described by Couch et al. in 1968.l Filler and Das adapted this concept by miniaturization of the pH probe, thus enabling its use in pediatric patients.24 Investigations from both of these groups have confirmed the surface pH of skeletal muscle as a sensitive, but indirect, indicator of peripheral muscle blood flow. The proposed mechanism for this relationship is hypothesized as follows: Increased hydrogen ion activity is a consequence of anaerobic glycolysis that results in the formation of lactic acid. Anaerobic glycolysis is presumed the result of reduced tissue perfusion. It is the purpose of this paper to correlate, under a variety of experimental shock states, peripheral muscle pH with central changes in cardiac output. Two different model systems were used. Hemorrhagic shock was produced by repeated bleeding in the dog, and endotoxin shock was initiated by the intravenous injection of gram-negative endotoxin. MATERIALS AND METHODS
Forty healthy mongrel dogs weighing 5-21 kg were used. Each dog was anesthetized with 30 mg/kg sodium pentobarbital. An endotracheal tube was inserted. No artificial ventilation was undertaken, as initial studies demonstrated that this means of support affected the animal’s ability to alter his own metabolic state. (Preeumably, a fixed-rate respirator does not allow necessary respiratory compensations.) The right femoral artery and vein were cannulated for measurement of cardiac output, and the catheters were advanced above the diaphragm. The left femoral artery was also cannulated for pressure readings and pulse contour evaluation, using a Microdot MS-5 pressure transducer with a range of O-300 mm Hg. A Corning Filler-Das in vivo pH electrode was rinsed with distilled water and standardized at pH 7, and at pH 4, using fresh known buffer solutions. An incision was made just above the joint in the right front leg, using cautery to produce a bloodless field. The pH probe was inserted under the muscle fascia, which was then sutured over the probe. After skin closure, the probe was taped tightly to ensure constant niuscle contact. The probe was attached to a Beckman expanded-scale pH meter, model No. 76. Dye dilution cardiac output as well as blood pressure readings and pressure contour cardiac output were measured in a manner previously described.5 After a period of stabilization, control readings of cardiac output, blood gases, muscle, and arterial pH were taken every 15 min. Four groups of ten dogs each were then treated in the followFrom the Department
of Surgery, University
of Minnesota
Hospitals,
Minneapolis,
Minn.
Presented at the Third Annual Meeting of the American Pediatric Surgical Association, Hot Springs, Vu., April 13-15, 1972. William H. Weintraub, M.D.: Department of Surgery, University of Minnesota Hospitals, Minneapolis, Minn. Stacy A. Roback, M.D.: Department of Surgery, Utiiversity of Minnesota Hospitals, Minneapolis, Minn. Mohandas Devadas, M.D.: Department of Surgery, University of Minnesota Hospifals, Minneapolis, Minn. Joe Rysavy, B.A.: Junior Scientist, Department of Surgery, University of Minnesota, Minneapolis, Minn. Arnold S. Leonard, M.D., Ph.D.: Head, Pediatric Surgery Section, Department of Surgery, University of
Minnewfa
Hospitals,
Journel of Pediatric
Minneapolis,
Minn.
Surgery, Vol. 7, No. 5 (October-November),
1972
505
506
WEINTRAUB ET AL.
ing manner: (1) Some 6% of the estimated blood volume was withdrawn every 15 min until the dog was depleted of approximately 40% of its blood volume. (2) Dogs were treated as in group 1, except that the entire volume was reinfused after approximately 40% of the blood volume had been withdrawn. (3) After the control period each dog was given a LD-50 dose of gram-negative endotoxin, (calculated at 2.5 mglkg) as a bolus. (4 These dogs were treated similarly to group 3, except for administration of 100 cc of plasma and 30 mg/kg of Solu-Medrol 1 hr after injection of the endotoxin. The pH probes were checked for accuracy with standard buffer solutions at the termination of every experiment.
RESULT’S
In group 1 (see Fig. 1) after 6% of the blood volume had been withdrawn, no noticeable change in mean blood pressure or arterial pH became evident. However, cardiac output and muscle pH both started an early downward trend. Blood lactate levels did not begin to iise significantly until more than 25% of the blood had been withdrawn. In group 2 (Fig. 2) after reinfusion of the shed blood, cardiac output, mean blood pressure, and muscle pH levels returned toward normal simultaneously. Blood lactate levels rose but no defineable changes occurred to arterial pH levels. In group 3 (Fig. 3) muscle pH, arterial pH, and cardiac output, as ivell as mean blood pressure, all fell shortly after the injection of endotoxin. Blood lactate levels began a slow, but continuous, rise throughout the experiment. The ranges of arterial and muscle pH were quite wide. In group 4 (Fig. 4), after entering the treatment phase of endotoxin shock, there was no statistically significant alteration in muscle or arterial pH. Group No. I -
Withdrawal
Time lminutesl
Fig. 1. Average values including ranges of ten dogs successively bled 6% of their estimated blood volume (group 1).
MUSCLE SURFACE pH Group No. 2 - Wifhdrowal, f?einhsion
Time (minutes)
to
Fig. 2. Average values including ranges of ten dogs successively bled down volume loss then reinfused (group 2).
36%
Group No. 3 -
E. coli Whout Treotmenf
Fig. 3. Average values including ranges of ten aogs given an LD-50 dose of endotoxin (group 3).
508
WEINTRAUB ET AL.
There was, however, a rise in cardiac output. The blood lactate rose slowly and maintained high levels throughout the course of this experiment also. DISCUSSION
Since skeletal muscle represents 40%~50% of body weight,s knowledge of its acid base status should be of importance to the clinician. Similarly, 30% of the oxygen consumption of the body at rest is accounted for by muscle, and during exercise its share can rise to 90%. In contrast, during shock states, organs other than muscle receive a larger share of the cardiac output. In conditions of normal tissue perfusions Duff and Smith’*s have shown that muscle pH is directlv related to arterial pH as far as charmes in acid-base balance are concerned. The control periods of our studies reaffirm this fact. In situations of hypovolemic shock, as demonstrated by groups 1 and 2, there is decreased tissue perfusion. This results in muscle converting from oxidative phosphorylation to anaerobic glycolysis, with buildup of lactic acid at the surface of the skeletal muscle cells. This increased hydrogen ion activity occurs early and is the explanation for the early fall in muscle pH noted in experiments I and 2. No significant changes were noted in blood lactate levels or arterial pH early in these experiments because the decreased tissue perfusion did not allow the lactate to be washed from the surface of the cells into the central circulation. Cardiac output has not been monitored during experiments GroupNo. 4 - E. co/i Jreofment with Solu -Medrol@ ond Plosmonote
i
E.col~
injected
I
treatment
E Solu-Medrol@
and plasma
M9Ofl B.P. (mmHg) 0
30
43
60
73
90
135
221
Fig. 4. Average values including ranges of ten dogs given an LD-50 dose of endotoxin and after 1 hr treated with 30 mg/kg of Sob-Medrol and 100 cc plasma (group 4).
MUSCLESURFACEpH
509
of this nature by previous investigators. It is apparent in these states of acute blood-volume change that muscle surface pH changes parallel those of cardiac output quite closely. The sequence would appear to be as follows: A decreased blood volume causes a decrease in cardiac output, which results in decreased muscle perfusion, subsequent buildup of lactate, and eventual lowering of muscle surface pH values. These alterations seem to occur well before more standard parameters such as blood pressure and arterial pH are affected. Our experiments differ from previous investigators in one area. Instead of one large bleed, repetitive small bleeds were used because this is more typical of bleeding seen in the clinical situation. This difference in experimental methods may explain the slow rise and fall of blood lactate levels in our experiments whereas others have noted a more rapid rise. Q~loIn fact, our lactate levels did not return to normal until some hours after the other parameters had returned to prebleed levels. In the endotoxin shock model, our findings were similar to those of prior studies.” Mean blood pressure, muscle surface pH, and arterial pH fell, whereas blood lactate levels rose. Cardiac output also fell. These experiments suggest that muscle pH is not more useful than other parameters for following endotoxin shock, and the clinician should use a more central means of monitoring. The dogs in group 4, after treatment with volume and large doses of steroids, did undergo a significant rise in cardiac output, with no appreciable change in any of the other parameters. The explanation of this phenomenon is not clear. However, diversion of this increased cardiac output to organs more important than skeletal muscle may explain why this higher cardiac output was not reflected in muscle surface pH readings. Other explanations, such as increased A-V shunting, are also plausible. Cardiac output was low throughout the endotoxin shock experiments and we were not able to measure any A-V shunting or vasoconstriction as postulated by Couch et al.11e12 CONCLUSION
Muscle pH would appear to have several areas of usefulness in the clinical situation. In states of completely normal muscle perfusion, muscle surface pH is a direct indicator of arterial pH and has the advantage of being a continuous measurement. This could be used for monitoring of patients on respirators or undergoing drug treatment for metabolic alkalosis or acidosis. In patients with acute hypovolemia, which would include many pediatric surgical problems, muscle pH detects changes of volume much earlier than arterial pH or blood pressure, and in fact parallels cardiac output closely. It thus can be used as an inexpensive and continuous indicator of cardiac output. In endotoxin shock or other severe shock states, muscle surface pH monitoring does not appear to have any clear advantage over other methods of monitoring. Where severe metabolic alterations have occurred, these experiments suggest muscle pH may be a useful indicator only as to when the subject goes into or comes out of this state. More central means of monitoring such cardiac output must be employed to govern therapeutic modalities.
510
WEINTRAUB ET AL.
REFERENCES 1. Lemieux, M. D., Smith, R. N., and Couch, N. P.: Effect of hemorrhage and reinfusion on electrometric surface hydrogen ion activity and redox potential of skeletal muscle. Surg. Forum 19:1,1968. 2. Filler, R. M., and Das, J. B.: Muscle pH: A new parameter in the monitoring of a critically ill child. Pediatrics 47:880,1971. 3.- -, Haase, G. M., and Donhoe, P. K.: Muscli pH as a monitor of tissue perfusion and acid base status. J. Pediat. Surg. 6:535, 1971. 4. - -, and Espinosa, H. M.: Clinical experience with continuous muscle pH monitoring as an index of tissue perfusion and oxygenation, and acid base status. Presented at the meeting of the Society of University Surgeons, Feb., 1972. 5. Weintraub, W. H., Cuderman, B. S., Hunt, C. E., Stauffer, W. M., Roback, S. A., and Leonard, A. S.: Computer monitoring of cardiodynamics in the newborn. J. Pediat. Surg. 6:372,1971. 6. Lemieux, M. D., Smith, R. N., and Couch, N. P.: Electrometric surface pH of skeletal muscle and hypovolemia. Amer. J. Surg. 117:627, 1969.
7. Duff, J. H., Groves, A. C., McLean, A. P. H., LaPointe, R., and MacLean, L. D.: Effective oxygen consumption in septic shock. Surg. Gynec. Obstet. 128:1051,1969. 8. Smith, R. N., Lemieux, M. D., and Couch, N. P.: Effects of acidosis and alkalosis on surface skeletal muscle hydrogen ion activity. Surg. Gynec. Obstet. 128:533, 1969. 9. Dmochowski, J. R., Couch, N. P., Kempf, R. N., and Appleton, D. R.: Electrometric surface pH of the ischemic kidney and the effect of hypothermia. J. Surg. Res. 6~4.5, 1966. 10.Couch, N. P., Maginn, R. R., Middleton, M. K., Appleton, D. R., and Dmochowski, J. R.: Effect of ischemic intervals and temperature on renal surface hvdrogen ion concentration. Surg. Gynec. Obstet. 125: 521,1967. 11.Dmochowski] J. R., and Couch, N. P.: Skeletal muscle hydrogen ion activity in endotoxin shock. Surg. Gynec. Obstet. 131: 669,197O. 12. Anas, P., Neely, W. A., and Hardy, J. B.: Effects of vasoactive drugs on oxygen consumption in endotoxin shock. Arch. Surg. (Chicago) 98:189,1969.
Discussion Dr. R. M. Filler (Boston): This paper clearly demonstrates the relation between cardiac output and muscle pH, at least in these experimental circumstances. I think there are other times when it is very dift?cuIt to know exactly what the correlation is. For example, in hypovolemic shock there is a clear correlation between muscle pH and cardiac output, but peripheral vasoconstriction is an additional factor influencing what is measured at the muscle level. It would be helpful in all these situations to have a way of measuring peripheral resistance continuously to evaluate completely the effect of this parameter on muscle PH. Nevertheless, although physiologic mechanisms for a low muscle pH are not known, muscle acidosis is a good indication that a child is not doing well and should trigger a search for causes of the abnormality. Therefore as a meaningful monitor of the total vital physiologic functions, muscle pH monitoring works out quite well.