Part V: The Role of Carbon Dioxide
Which of these unlikely bypass candidates- ” Ain’t Gonna Make It? “
Authored by: Gary Grist, BS, CCP, LCP
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Carbon Dioxide Pressure Field Theory
The term Oxygen Pressure Field Theory is a misnomer if the perfusionist is concerned about all the aspects of gas exchange at the microvascular level. Perhaps the term should be Vital Gas Pressure Field Theory because of the importance that CO2 plays in cellular function. CO2 is 30 times more soluble than O2. For this reason the assumption is made that if oxygenation is adequate the CO2 removal must also be adequate in the microvascular bed. However, this assumption can be incorrect and deadly. Because of the greater solubility of CO2 only small pressure gradients are needed to transfer large volumes of the gas in a liquid.
A CO2 pressure field exists, but it does not normally have the wide range of values seen in an oxygen pressure field. In a normal air breathing human the average tissue pCO2 is 1-2 mmHg higher than the intracapillary pCO2. As long a intracapillary blood velocity and perfused capillary density remain normal adequate amounts of CO2 will be removed. However, a change in either of these parameters beyond normal compensation mechanisms (that is, exponential changes) will result in a CO2 imbalance which has the potential to change intracellular pH.
The CO2 pressure field has its highest concentration in the area of the lethal corner. The CO2 concentration is less in areas closer to the capillary and nearest the arterial-end tissues. Like oxygen transfer, the efficiently of CO2 transfer can be impaired by two main factors; a reduction in intracapillary velocity and a reduction in perfused capillary density. If intracapillary blood flow velocity falls the efficiency of CO2 removal from the tissue cylinder also falls.
This is demonstrated by the venoarterial CO2 gradient [p(V-A)CO2]. The p(V-A)CO2 is the difference between the mixed venous pCO2 and the arterial pCO2. The normal gradient is about 5 mmHg. The p(V-A)CO2 increases as the intracapillary blood velocity falls. In fact, an increase in the average p(V-A)CO2 can be used to assess the cardiac index [CI] in adults.
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The formula is simple; divide the p(V-A)CO2 into the constant of 12.9 to get the CI. For example, if the average venoarterial CO2 gradient is 5 the formula would be CI = 12.9/5 = 2.6 L/min/M2. If the p(V-A)CO2 is 10 the CI would be 12.9/10 = 1.3 L/min/M2. The correlation for the formula is 0.76. An increase in the p(V-A)CO2 results in a selective venous respiratory acidosis.
For example, if the ABG =7.40/40/100 and the mixed VBG = 7.25/55/35 the high mixed VBG pCO2 is a reflection of reduced intracapillary blood velocity and an increase in the CO2 in the lethal corner tissues. Intracapillary blood flow functions just like the sweep gas through an oxygenator in terms of CO2 removal. With an oxygenator, if the sweep gas is too low CO2 will be retained in the blood even though oxygenation may be more than adequate. This will result in a respiratory acidosis in the blood. At the microvascular level, if capillary blood flow is too low the CO2 will be retained primarily in the venous-end tissues causing intracellular acidosis.
The amount of CO2 retained intracellularly depends on perfused capillary density. As discussed in an earlier posting, each capillary has a limitation on how much gas it can exchange. This includes oxygen and CO2. If perfused capillary density is low each capillary will be overloaded with the increased tissue volume surrounding it. The net result will be intracellular CO2 retention.
In animal and human experiments testing intracellular pCO2, the amount of CO2 retained varied. For each 1 mmHg increase in the p(V-A)CO2 above 5 mmHg, the intracellular pCO2 increases by 2 to 4 mmHg. The variation is probably caused by variances in the PCD. If a changing p(V-A)CO2 demonstrates a selective mixed venous respiratory acidosis, the intracellular pH change is 2 to 4 times greater because the intracellular CO2 retention is 2 to 4 times greater. This can cause disaster for the patient and failure for the perfusionist trying to keep the patient alive.
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Experiments have shown that in the fibrillating heart the intracellular pH is most affected by retained CO2 due to poor intracapillary blood flow and not metabolic acidosis. Once intracellular pCO2 reaches 400 mmHg the damage is irreversible even if intracapillary blood flow and PCD are returned to normal, i.e. the patient cannot be resuscitated successfully. Reducing the arterial pCO2 will not correct the situation very much. If an increased p(V-A)CO2 persists, reducing the arterial pCO2 by 10 mmHg has little affect because the magnitude of the intracellular change is 2 to 4 times greater than the changes in the blood alone. For example, if the arterial pCO2 is 40 mmHg and the mixed venous pCO2 is 60 mmHg, the p(V-A)CO2 is 20 mmHg.
This means that within the lethal corner the pCO2 will be equivalent to the base line pCO2 of at least 40 mmHg PLUS 2 to 4 times the amount of the increased gradient, or 30 to 60 mmHg. So, the lethal corner pCO2 will be 70 to 100 mmHg and the lethal corner pH will be 7.10 to 6.8 approximately. If the arterial pCO2 is reduced from 40 mmHg to 30 mmHg and the p(V-A)CO2 persists the mixed venous pCO2 will be 50 mmHg and the lethal corner pCO2 will be at least 30 mmHg PLUS 30 to 60 mmHg. So, the lethal corner pCO2 will be 60 to 90 mmHg and the lethal corner pH will be 7.20 to 6.9, not a significant improvement.
Theoretically, the most effective way to reduce intracellular pCO2 is to increase intracapillary blood flow and improve perfused capillary density. The evidence of success will be a reduced p(V-A)CO2.
Conceivably, intracellular pH can be alkalinized by increasing overall blood flow in an attempt to increase intracapillary velocity and improve PCD as well as reducing the arterial pCO2. Reducing overall intracellular pCO2 in this fashion when the patient is in metabolic acidosis may counteract the intracellular pH changes being caused by metabolic acidosis. At least one study has shown that patients who can sustain an above normal cardiac index after major surgery have less morbidity and mortality that patients limited to a normal CI.
The use of NaHCO3 to affect changes in blood pH may have contradictory effects intracellularly. If the intracellular pH change is due primarily to CO2 retention, NaHCO3 may aggravate the problem by increasing the overall CO2 in the cells. On the other hand, NaHCO3 may be beneficial if there is little intracellular retention of CO2 and the pH change is primarily metabolic.
Knowing the difference involves understanding the role the p(V-A)CO2 plays. There is no question that NaHCO3 affects blood pH, but its overall benefit has been questioned by many. According to O2/CO2 Pressure Field Theory the benefits of NaHCO3 may be circumstantial based on intracapillary blood flow and perfused capillary density. Obviously, a lot depends on intracapillary blood flow velocity and perfused capillary density. The mechanism that controls these variables is called Microvascular Redistribution. MR will be the subject of the next posting.
The p(V-A)CO2 is an important concept for the perfusionist to understand. The intracellular pH changes occurring in the lethal corner as a result of CO2 retention can be life threatening. The status of 3 hypothetical ICU patients is listed below. The intracellular pH of the venous -end tissues is based on the assumption that tissue pCO2 increases 3 times the p(V-A)CO2 increase.
The Suspects !
p(V-A): CO2 5 mmhg
Increase in gradient : 0 mmHg
Est. venous-end tissue pCO: 247mmHg
Est. venous-end tissue pH: 7.33
p(V-A): CO2 10 mmHg
Increase in gradient : 5 mmHg
Est. venous-end tissue pCO: 62 mmHg
Est. venous-end tissue pH: 7.18
p(V-A): CO2 20 mmhg
Increase in gradient : 15 mmHg
Est. venous-end tissue pCO: 92 mmHg
Est. venous-end tissue pH: 6.88
How does the perfusionist deal with each of these patients?
Mr. Green is OK.
Whatever interventions the perfusionist is using are working because his p(V-A)CO2 is low and estimated pH in the lethal corner is within normal limits for tissue function.
Prof. Plum is on a rocky road.
Intracellular pH is low in the lethal corner. He needs to be closely watched. A p(V-A)CO2 increase signals that the intervention is not working and the patient is getting worse, in spite of a normal ABG. If the p(V-A)CO2 decreases then the intervention is working and the patient will start to get better.
Col. Mustard is in serious shape.
Whatever intervention is being used is inadequate and a new plan needs to be implemented or he will soon die. An intracellular pH less than 7.00 is incompatible with life. Even with adequate oxygenation, normal metabolism cannot work because enzyme function is stilted by the low pH.
Notice that all these patients have a normal arterial blood gas and no base deficit….yet.
It is only a matter of time before Col Mustard develops metabolic acidosis even though he seemingly is receiving adequate oxygenation based on the pvO2. He will become unstable, go into multiple organ failure, arrest and die.
Col. Mustard was done-in, in the ICU, with an increased p(V-A)CO2, by an unwitting perfusionist who did not know what the hell was happening.
Another example of how the perfusionist can use the p(V-A)CO2 to assess a patient’s status would be during an open heart procedure involving deep hypothermia and circulatory arrest. In an earlier posting a formula which estimates the amount of oxygen stored in cold tissues was presented. Using the formula the perfusionist can estimate the “safe” arrest time before the tissues run out of oxygen and anaerobic metabolism begins.
For example, at 18 C, O2 has a solubility of 0.12 cc/mmHg/L. The average tissue pO2 can be estimated at 1.5 x the pvO2. So, a patient at 18C with a pvO2 of 200 mmHg would have an approximate oxygen store of 200 mmHg x 1.5 x 0.12 cc/mmHg/L = 36 ccO2/L of body tissue. If the patient is a child with a normal metabolic rate of 6ccO2/min/kg at 37C, the metabolic rate at 18C would be 0.6ccO2/min/kg or 1/10th normal. To complete the formula divide the oxygen store of 36 ccO2/L by 0.6 cc/O2/min/kg (or L). The “safe” arrest time period would be no greater than 60 minutes.
However, after an arrest period of only 45 minutes the perfusionist has the following uncorrected blood gases within 3 minutes of going back on bypass: ABG = 7.40/40/400 , VBG = 7.00/80/50.
The p(V-A)CO2 is 35 mmHg above the normal gradient of 5 mmHg. At 18C CO2 is much more soluble that at 37C. So, the amount of CO2 in the lethal corner will be very high based not only on an increased p(V-A)CO2 but also on the basis that more CO2 is dissolved in the tissues.
The perfusionist notices an increasing base deficit as the temperature is returned to normal even though the oxygen delivery has been more than adequate based on pvO2. Upon reaching normal temperature and correcting the base deficit with NaHCO3 the blood gases are: ABG = 7.40/40/250 and VBG 7.30/50/35. The p(V-A)CO2 is still elevated just prior to coming off bypass. The cause of the metabolic acidosis during rewarming is most likely the result of a very low tissue pH in the lethal corner caused by CO2 retention occurring during the hypothermic arrest.
This low tissue pH impaired the enzymes controlling normal oxygen metabolism in the lethal corner cells. During rewarming if intracapillary velocity was too slow and perfused capillary density was poor, the intracellular pH was not completely corrected by adequate removal of retained CO2. This impaired oxygen utilization resulted in the development of a base deficit. The patient is unstable coming of bypass but soon improves. After coming off bypass the intracellular pH improves as the body re-establishes its own mechanisms for correcting intracellular pH, the so-called Microvascular Redistribution System.
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