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Effect of temperature on the oxyhemoglobin dissociation curve
LETTERS TO THE EDITOR
655
REFERENCES 1. Welte M, Haimerl E, Groh J, et al: Effect of interpleural morphine on postoperative pain and pulmonary function after thoracotomy. Br J Anaesth 69:637-639, 1992 2. Kreitzer JM, Reuben SS: Central nervous system toxicity in a patient receiving continuous intrapleural bupivacaine. J Clin Anesth 8:666-668, 1996 3. Symreng T, Gomez MN, Rossi N: Intrapleural bupivacaine versus saline after thoracotomy Effects on pain and lung function. A doubleblind study. J Cardiothorac Anesth 3:144-149, 1989 4. Mc Ilvaine WB, Knox RE Fennessey PV, Goldstein M: Continuous infusion of bupivacaine via intrapleural catheter for analgesia after thoracotomy in children. Anesthesiology 69:261-264, 1988
5. Rademaker BMP, Sih IL, Kalkman CJ, et al: Effects of intrapleurally administered bupivacaine 0.5% on opioid analgesic requirements and endocrine response during and after cholecystectomy. A randomized double-blind controlled study. Acta Anaethesiol Scand 35:108- i 12, 1991 6. Heres EK, Marquez J, Malkowski MJ, et al: Minimally invasive direct coronary artery bypass. Anesthetic, monitoring, and pain control considerations. J Cardiothorac Vasc Anesth 12:385-389, 1998 7. Mishra Y, Mehta Y, Mittal S, et al: Mammary coronary artery anastamosis without cardiopulmonary bypass through minithoracotomy. One-year clinical experience. Eur J Cardiothorac Surg 14:$31$37, 1998 (suppl 1)
Effect of Temperature on the O x y h e m o g l o b i n Dissociation Curve To the Editor:
In the original article by Leone et al, 1 "Effect of mild hypothermia during cardiopulmonary bypass on erythrocytic hemoglobin oxygen delivery," the investigators come to a remarkable conclusion regarding the effect of temperature on the oxyhemoglobin dissociation during cardiopulmonary bypass (CPB), because they were unable to show such an effect. They conclude " . . . it has been shown that mild hypothermic [extracorporeal circulation] ECC does not significantly alter the dissociation of oxygen from hemoglobin in patients presenting for cardiac surgery" (discussion), and "mild hypothermia to 32°C during ECC does not result in in vivo alterations in oxyhemoglobin dissociation" (abstract). As mentioned by the investigators, this is contrary to that found in earlier studies during CPB. The factors influencing the oxyhemoglobin dissociation curve were identified in the beginning of this century; PCO2 through its effect on pH 2 and the marked influence of temperature) Since that time, these effects have been included in every textbook of physiology. It would certainly be a sensation to find one patient with hemoglobin so atypical that the position of the dissociation curve was not influenced by temperature, and the investigators claim to have made the observation consistently in 17 patients. When I read the report, I suspected an error with the methods. The investigators claim they used e~-stat acid-base management during CPB and say, "all oxygen tensions are reported from temperature-corrected values" (Methods), and "values reported are temperature corrected for arterial gas tensions" (legend to Table 2). Arterial PCO 2 remained unchanged at 38 lmnHg during and after CPB. The same PCO2 at 37°C and 32°C (corrected for the difference in temperature between the patient and measuring device) appears to me to be pH-stat. Also, the pH was stable at 7.39 to 7.41, but it is not clear if pH is regarded as a gas tension. The correct definition of a-stat is that pH (temperature-corrected) increases with hypothermia from 7.40 to 7.48 at 32°C and consequently, PCO2 (temperature-corrected) decreases from 40 to 32 mmHg. 4 With pH-stat, temperature-corrected values for pH and PCO2 do not change with temperature. A peculiar finding in Table 2 is that in the mean values for PCO2 at "off ECC," the mixed venous value is less than the arterial value. Is it a printing mistake? The finding is presented without comment by the investigators. However, the important question is which Ps0 value, ie, oxygen tension at 50% oxyhemoglobin saturation, was determined by the investigators, Ps0 for the dissociation curve has been defined in many different ways. A commonly used definition is the PO2 at 50% saturation measured at or corrected to pH 7.40 and 37°C. A more refined definition includes PCO2 at 40 mmHg because it was shown earlier, that PCO2 changed the position of the dissociation curve, also through a mechanism that was not pH dependent; the so-called Haldane effect. Another definition includes a normal erythrocytic concentration of 2,3-diphospho-glycerate (2,3-DPG), a factor that markedly influences the position of the curve. Also, ionic strength and the concentration of chloride have an influence, although small, and if these factors are also normal or corrected for and included in the definition, then Ps0 probably would describe only the properties of the type of hemoglobin under study; adult, fetal, chemically manipulated, or belonging to a species other than humans. Finally, one more definition is the direct uncorrected or actual relation between the venous tension and saturation, which defines the actual position of the curve in the studied venous blood sample. The actual Ps0 decreases with a decrease in temperature if not counteracted by acidosis, but it would need a pH of approximately 7.16 to balance the effect of a temperature of 32°C. It is not easy to understand which technique the investigators used. First they say the venous oxygen tensions were temperature corrected, then they state they determined the Hill equation "without factoring changes in temperature or p H . . . assuming that standard temperature and pH existed, ie, a temperature of 37°C and a normal pH." In this context, normal venous pH is a misnomer because it is not 7.40, but 7.35, and in blood with 50% saturation, as in the coronary sinus, it is normally even less. How were the venous oxygen tensions first corrected for the temperature difference between the patient (32°C) and the measuring device (37°C) and then assumed to be at 37°C? This is far from clear. The corrected mean venous PO2 values varied between 42 and 45 mmHg. Unfortunately, corresponding values for the measured venous saturation were not published. Also, the terminology used by the investigators when they state that an in vivo determination of Ps0 was performed could be questioned because the blood samples were analyzed in ordinary devices for the analysis of blood gases and oxyhemoglobin saturation, a technique usually called in vitro. The investigators wanted to study the effect of cooling to 32°C. In my opinion, it would have been appropriate to correct for the
656
LETTERS TO THE EDITOR
difference in mixed venous pH and PCO2 compared with 7.40 and 40 mmHg before comparing the Pso values obtained. The other factors, 2.3-DPG, chloride concentration, and ionic strength, are probably not influenced in an important way by CPB. In conclusion, the methods used by the investigators are not described in enough detail, and I don't believe the conclusion is valid. I suspect the investigators, after corrections and assumptions, did not determine the appropriate Ps0 in the blood from their patients.
GOran Settergren, MD, PhD Department of Cardiothoracic Anaesthetics and Intensive Care Karolinska Hospital Stockholm, Sweden REFERENCES
1. Leone BJ, Watke CM, Osgood CF, et al: Effect of mild hypothermia during cardiopulmonary bypass on erythrocytic hemoglobin oxygen delivery. J Cardiothorac Vasc Anesth 12:393-396, 1998 2. Bohr C, Hasselbalch KA, Krogh A: Ueber einen in biologischer Beziehung wichtigen Einfluss, den die Kohlensaurespannung des Blutes auf dessert SauerstofPoindungtibt. SkandArch Physinl 16:402-412, 1904
3. Barcroft J: The Respiratory Functions of the Blood (ed 1). London, England, Cambridge, 1914 4. Rahn H, Reeves RB: Hydrogen ion regulation during hypothermia: From the Amazon to the operating room, in Omar Prakash (ed): Applied Physiology in Clinical Respiratory Care. Hague, The Netherlands, Martinus Nijhoff, 1982, p 1-15
Intra-Aortic Balloon Pump May Cause Arterial Blood Pressure Discrepancy Independently of Cardiopulmonary Bypass To the Editor: We read with interest the recent case report by Lennon and Gilfeather 1 in the Journal of Cardiothoracic and Vascular Anesthesia. The investigators described a case of arterial blood pressure (ABP) discrepancy related to an intra-aortic balloon pump (IABP) during cardiopulmonary bypass (CPB). Radial artery and aortic pressures were greater than femoral artery pressure. This discrepancy was caused by intermittent obstruction of the continuous CPB flow from the proximal to the distal aorta. We observed a similar ABP discrepancy related to an IABR but in contrast to the case of Lennon and Gilfeather, the patient was not on CPB. The patient was a 60-year-old man with triple-vessel coronary artery disease and a ventricular ejection fraction of 20%. He was admitted to the operating room for coronary artery bypass graft surgery. An 18 G left femoral artery catheter and a pulmonary artery catheter were inserted under local anesthesia. Vascular pressure transducers were positionned at the level of the right atrium. Pressure waveforms and values were displayed by an electronic monitor (Hellige SMU 611, Freiburg, Germany). Femoral ABP was 90/50
Fig 1.
Femoral ABP waveform with a functioning IABR
Radial ABP waveform with a functioning IABP.
~D
420
40
Fig 2.
...........................................................
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
,
,,
,
,,
,,
,,
,,
.........................................................................
Fig 3.
Femoral ABP waveform after discontinuation of the IABR
Fig 4.
Radial ABP waveform after discontinuation of the IABP.
655
REFERENCES 1. Welte M, Haimerl E, Groh J, et al: Effect of interpleural morphine on postoperative pain and pulmonary function after thoracotomy. Br J Anaesth 69:637-639, 1992 2. Kreitzer JM, Reuben SS: Central nervous system toxicity in a patient receiving continuous intrapleural bupivacaine. J Clin Anesth 8:666-668, 1996 3. Symreng T, Gomez MN, Rossi N: Intrapleural bupivacaine versus saline after thoracotomy Effects on pain and lung function. A doubleblind study. J Cardiothorac Anesth 3:144-149, 1989 4. Mc Ilvaine WB, Knox RE Fennessey PV, Goldstein M: Continuous infusion of bupivacaine via intrapleural catheter for analgesia after thoracotomy in children. Anesthesiology 69:261-264, 1988
5. Rademaker BMP, Sih IL, Kalkman CJ, et al: Effects of intrapleurally administered bupivacaine 0.5% on opioid analgesic requirements and endocrine response during and after cholecystectomy. A randomized double-blind controlled study. Acta Anaethesiol Scand 35:108- i 12, 1991 6. Heres EK, Marquez J, Malkowski MJ, et al: Minimally invasive direct coronary artery bypass. Anesthetic, monitoring, and pain control considerations. J Cardiothorac Vasc Anesth 12:385-389, 1998 7. Mishra Y, Mehta Y, Mittal S, et al: Mammary coronary artery anastamosis without cardiopulmonary bypass through minithoracotomy. One-year clinical experience. Eur J Cardiothorac Surg 14:$31$37, 1998 (suppl 1)
Effect of Temperature on the O x y h e m o g l o b i n Dissociation Curve To the Editor:
In the original article by Leone et al, 1 "Effect of mild hypothermia during cardiopulmonary bypass on erythrocytic hemoglobin oxygen delivery," the investigators come to a remarkable conclusion regarding the effect of temperature on the oxyhemoglobin dissociation during cardiopulmonary bypass (CPB), because they were unable to show such an effect. They conclude " . . . it has been shown that mild hypothermic [extracorporeal circulation] ECC does not significantly alter the dissociation of oxygen from hemoglobin in patients presenting for cardiac surgery" (discussion), and "mild hypothermia to 32°C during ECC does not result in in vivo alterations in oxyhemoglobin dissociation" (abstract). As mentioned by the investigators, this is contrary to that found in earlier studies during CPB. The factors influencing the oxyhemoglobin dissociation curve were identified in the beginning of this century; PCO2 through its effect on pH 2 and the marked influence of temperature) Since that time, these effects have been included in every textbook of physiology. It would certainly be a sensation to find one patient with hemoglobin so atypical that the position of the dissociation curve was not influenced by temperature, and the investigators claim to have made the observation consistently in 17 patients. When I read the report, I suspected an error with the methods. The investigators claim they used e~-stat acid-base management during CPB and say, "all oxygen tensions are reported from temperature-corrected values" (Methods), and "values reported are temperature corrected for arterial gas tensions" (legend to Table 2). Arterial PCO 2 remained unchanged at 38 lmnHg during and after CPB. The same PCO2 at 37°C and 32°C (corrected for the difference in temperature between the patient and measuring device) appears to me to be pH-stat. Also, the pH was stable at 7.39 to 7.41, but it is not clear if pH is regarded as a gas tension. The correct definition of a-stat is that pH (temperature-corrected) increases with hypothermia from 7.40 to 7.48 at 32°C and consequently, PCO2 (temperature-corrected) decreases from 40 to 32 mmHg. 4 With pH-stat, temperature-corrected values for pH and PCO2 do not change with temperature. A peculiar finding in Table 2 is that in the mean values for PCO2 at "off ECC," the mixed venous value is less than the arterial value. Is it a printing mistake? The finding is presented without comment by the investigators. However, the important question is which Ps0 value, ie, oxygen tension at 50% oxyhemoglobin saturation, was determined by the investigators, Ps0 for the dissociation curve has been defined in many different ways. A commonly used definition is the PO2 at 50% saturation measured at or corrected to pH 7.40 and 37°C. A more refined definition includes PCO2 at 40 mmHg because it was shown earlier, that PCO2 changed the position of the dissociation curve, also through a mechanism that was not pH dependent; the so-called Haldane effect. Another definition includes a normal erythrocytic concentration of 2,3-diphospho-glycerate (2,3-DPG), a factor that markedly influences the position of the curve. Also, ionic strength and the concentration of chloride have an influence, although small, and if these factors are also normal or corrected for and included in the definition, then Ps0 probably would describe only the properties of the type of hemoglobin under study; adult, fetal, chemically manipulated, or belonging to a species other than humans. Finally, one more definition is the direct uncorrected or actual relation between the venous tension and saturation, which defines the actual position of the curve in the studied venous blood sample. The actual Ps0 decreases with a decrease in temperature if not counteracted by acidosis, but it would need a pH of approximately 7.16 to balance the effect of a temperature of 32°C. It is not easy to understand which technique the investigators used. First they say the venous oxygen tensions were temperature corrected, then they state they determined the Hill equation "without factoring changes in temperature or p H . . . assuming that standard temperature and pH existed, ie, a temperature of 37°C and a normal pH." In this context, normal venous pH is a misnomer because it is not 7.40, but 7.35, and in blood with 50% saturation, as in the coronary sinus, it is normally even less. How were the venous oxygen tensions first corrected for the temperature difference between the patient (32°C) and the measuring device (37°C) and then assumed to be at 37°C? This is far from clear. The corrected mean venous PO2 values varied between 42 and 45 mmHg. Unfortunately, corresponding values for the measured venous saturation were not published. Also, the terminology used by the investigators when they state that an in vivo determination of Ps0 was performed could be questioned because the blood samples were analyzed in ordinary devices for the analysis of blood gases and oxyhemoglobin saturation, a technique usually called in vitro. The investigators wanted to study the effect of cooling to 32°C. In my opinion, it would have been appropriate to correct for the
656
LETTERS TO THE EDITOR
difference in mixed venous pH and PCO2 compared with 7.40 and 40 mmHg before comparing the Pso values obtained. The other factors, 2.3-DPG, chloride concentration, and ionic strength, are probably not influenced in an important way by CPB. In conclusion, the methods used by the investigators are not described in enough detail, and I don't believe the conclusion is valid. I suspect the investigators, after corrections and assumptions, did not determine the appropriate Ps0 in the blood from their patients.
GOran Settergren, MD, PhD Department of Cardiothoracic Anaesthetics and Intensive Care Karolinska Hospital Stockholm, Sweden REFERENCES
1. Leone BJ, Watke CM, Osgood CF, et al: Effect of mild hypothermia during cardiopulmonary bypass on erythrocytic hemoglobin oxygen delivery. J Cardiothorac Vasc Anesth 12:393-396, 1998 2. Bohr C, Hasselbalch KA, Krogh A: Ueber einen in biologischer Beziehung wichtigen Einfluss, den die Kohlensaurespannung des Blutes auf dessert SauerstofPoindungtibt. SkandArch Physinl 16:402-412, 1904
3. Barcroft J: The Respiratory Functions of the Blood (ed 1). London, England, Cambridge, 1914 4. Rahn H, Reeves RB: Hydrogen ion regulation during hypothermia: From the Amazon to the operating room, in Omar Prakash (ed): Applied Physiology in Clinical Respiratory Care. Hague, The Netherlands, Martinus Nijhoff, 1982, p 1-15
Intra-Aortic Balloon Pump May Cause Arterial Blood Pressure Discrepancy Independently of Cardiopulmonary Bypass To the Editor: We read with interest the recent case report by Lennon and Gilfeather 1 in the Journal of Cardiothoracic and Vascular Anesthesia. The investigators described a case of arterial blood pressure (ABP) discrepancy related to an intra-aortic balloon pump (IABP) during cardiopulmonary bypass (CPB). Radial artery and aortic pressures were greater than femoral artery pressure. This discrepancy was caused by intermittent obstruction of the continuous CPB flow from the proximal to the distal aorta. We observed a similar ABP discrepancy related to an IABR but in contrast to the case of Lennon and Gilfeather, the patient was not on CPB. The patient was a 60-year-old man with triple-vessel coronary artery disease and a ventricular ejection fraction of 20%. He was admitted to the operating room for coronary artery bypass graft surgery. An 18 G left femoral artery catheter and a pulmonary artery catheter were inserted under local anesthesia. Vascular pressure transducers were positionned at the level of the right atrium. Pressure waveforms and values were displayed by an electronic monitor (Hellige SMU 611, Freiburg, Germany). Femoral ABP was 90/50
Fig 1.
Femoral ABP waveform with a functioning IABR
Radial ABP waveform with a functioning IABP.
~D
420
40
Fig 2.
...........................................................
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
,
,,
,
,,
,,
,,
,,
.........................................................................
Fig 3.
Femoral ABP waveform after discontinuation of the IABR
Fig 4.
Radial ABP waveform after discontinuation of the IABP.