Refining Extracorporeal Support Strategy: Oxygen Pressure Field Theory IX

OPFT Part IX:   Using OPFT to Refine Extracorporeal Support Strategy.

The anion gap is the difference in the measured cations and the measured anions in serum, plasma, or urine. The magnitude of this difference (i.e. “gap”) in the serum is often calculated in medicine when attempting to identify the cause of metabolic acidosis. If the gap is greater than normal, then high anion gap metabolic acidosis is diagnosed.

The term “anion gap” usually implies “serum anion gap”, but the urine anion gap is also a clinically useful measure.

Refining Extracorporeal Support Strategy


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Authored by:  Gary Grist,  BS, RN, CCP, LCP   

To View all of Gary Grist”s Posts Regarding OPFT-  click here

Mr Gary Grist delivered a seminar on this topic at The Missouri Perfusion Society 16th Annual Meeting titled “Beyond The Fick Equation”  on June 10-12, 2011

Using The Anion Gap And Venoarterial Carbon Dioxide Gradient To Refine Extracorporeal Support Strategy.

Oxygen Pressure Field Theory suggests that two markers, the anion gap [AG] and the venoarterial carbon dioxide gradient [ p(V-A)CO2] , may be useful in assessing the mircrocirculation to determine relative  changes in intracellular oxygen, CO2 and pH.  Interpretation of the AG has been discussed in detail in Part 8.  The p(V-A)CO2 has also been discussed in earlier postings, however, actual clinical values have yet to be presented.

That will be done now.

The text book value for p(V-A)CO2 in healthy people is about 5 mmHg.

However, this cannot be verified in the clinical setting because healthy patients do not have arterial and central venous lines from which simultaneous blood gas samples can be drawn.  In a study of over 100 venoarterial ECMO patients, the  average p(V-A)CO2  was calculated from blood samples taken  from the ECMO pump venous return line and from indwelling arterial lines in the patient (not from the post-oxygenator blood line).  The average p(V-A)CO2  was 9 +/- 3 mmHg.  This means that approximately 2/3rds of this sick ECMO population had p(V-A)CO2  values ranging from 6 – 12 mmHg.  The median value was also 9 mmHg.  This is higher than the text book value, which is expected since this is a sick population requiring  mechanical cardiopulmonary support.

The patients with  p(V-A)CO2  less than 9 mmHg had a survival rate of  87% and those with p(V-A)CO2 of 9 mmHg or greater  had a survival rate of only 65%.  There is  statistical significance between the two groups (p = 0.0126).  The larger the p(V-A)CO2 the greater the mortality.  No patients with a p(V-A)CO2 over 15 mmHg for a sustained period survived.   Like the AG, the p(V-A)CO2 is a value determined by calculation from two separate test results , the pvCO2 and the paCO2.  Accordingly, the p(V-A)CO2 will have a greater inaccuracy [roughly 10% of all values will be inaccurate].  Therefor, the p(V-A)CO2 values should be averaged over a period of time to reduce the inaccuracy.

Drawing samples  every 6 – 8 hours from a patient on long-term extracorporeal support is adequate.This means that the p(V-A)CO2 is most effective as a long-term indicator. For example, in my ECMO patient # 195, the daily p(V-A)CO2 values were as follows:

  • Day  One: 6, 5, 5, 5, 4, 7 with the daily average being 5 mmHg.
  • Day Two: 5, 4, 1, 3, 4 with the daily average being  3 mmHg.
  • Day Three: 3, 4, 4, 3, 2, 4 with the daily average being 3 mmHg.
  • Day Four: 3, 3, 4, 3, 13, 8 with the daily average being 6 mmHg.
  • Day Five: 5, 6, 5, 3, 10, 7 with the daily average being  6 mmHg.
  • Day Six: 8, 10, 11, 8 with the daily average being 9 mmHg.

Overall average p(V-A)CO2  was 5 mmHg. As you can see, the average daily  started out at 5 mmHg and then dropped in the first half of the ECMO treatment to 3 mmHg.  On Day Four, the ECMO blood flow was reduced to idling when a cardiac echo was performed.  A p(V-A)CO2 was also taken at this time.  Can you tell which measurement occurred during the echo?

The ECMO blood flow was increased after the echo to the previous level. The blood flow was then weaned to idling over the next 2 days and the child taken off ECMO.

The p(V-A)CO2  can be very unstable, particularly in the patient with a cardiogenic diagnosis.  This is often reflected in wide swings of the p(V-A)CO2 during the initial period of extracorporeal support.  The p(V-A)CO2 values sometime seem circadian in nature during long-term extracorporeal support [ECS].  Often during weaning of ECS, the p(V-A)CO2 will increase a small amount.  This  probably reflects a slight overall decrease of cardiac output.

This may be because the ECS is reduced by a certain volume and the heart does not automatically compensate for this amount of lost  blood flow , thus the p(V-A)CO2  increases. [ The AG also often increases slightly during weaning for a similar reason. ] The AG and p(V-A)CO2  represent two different mechanisms of assessment for the microcirculation.  Together they give the best idea of what is occurring at the capillary level inside the tissue cells.

The AG assesses the relative amount of abnormal metabolism, usually intracellular metabolic acidosis.  The abnormal metabolism originates in the lethal corner which is the area of the capillary bed receiving the least oxygen and having the worst waste product removal.In a worst case scenario, PCD is poor and thus the lethal corner becomes very large.  The AG increases as abnormal metabolism increases in the enlarged lethal corner.  As the AG rises , survival plummets.

The p(V-A)CO2 represents the intracapillary velocity of blood.  In healthy people, intracapillary velocity remains stable at about 200 microns/second. Increased cardiac output as a result of increased oxygen demand is handled by increasing PCD.The intracapillary velocity remains about the same even though the CO has greatly increased.

If intracapillary velocity decreases, the p(V-A)CO2 increases.  For every 1 point that the p(V-A)CO2 increases, intracellular pCO2 increases by 2-4 mmHg , depending on PCD.In a worst case scenario, a patient with a paCO2 of 40 mHg and a pvCO2 of 60 mmHg would have a p(V-A)CO2 of 20 mmHg.

If PCD is poor, the intracellular pCO2 could be as high as 60 mHg ABOVE the arterial paCO2 of 40 mmHg.  This would result in a intracellular pCO2 of 100 mmHg and an intracellular pH of less than 7.  This, of course, is incompatible with life.

  • ECMO patients with an average AG of  11 mEq/L or less have a survival rate of 88%.
  • Patients with an average AG greater than 11 mEq/L have a survival rate of only  57% (p < 0.0005).
  • ECMO patients with an average p(V-A)CO2 of less than 9 mmHg have a survival rate of 87%.
  • Patients with an average p(V-A)CO2 of 9 mmHg or greater have a survival rate of 65% (p < 0.02).

Theoretically, if the ECMO patient can keep both the AG and the p(V-A)CO2 low, then survival should be optimized regardless of the diagnosis.

In fact, that is the case.

This low AG, low p(V-A)CO2  group of patients has a survival rate of 93% . Likewise, patients who are unable to optimize these two markers, theoretically, will have a very low survival.  That is, in fact, the case. This high AG, high p(V-A)CO2  group of patients has a survival rate of only 44%.

Theoretically, patients who can maintain one of the markers at a low value while the other marker remains elevated should have an intermediate survival rate.  Patients with a low AG and a high p(V-A)CO2  have a survival rate of 83%.  Patients with a low p(V-A)CO2  and a high AG have a 76% survival rate. Both these rates represent intermediate survival between the low AG, low p(V-A)CO2  group and the high AG, high p(V-A)CO2  group.

Again, theoretically, patients in the low AG, low p(V-A)CO2 group should also have the shortest ECMO time. This is because the intracellular environment is optimized and healing proceeds unhindered.  In fact, the average ECMO time for these survivors is 100 +/- 37 hours. The high AG, high p(V-A)CO2 group survivors should have the longest  ECMO time, since healing is impaired by  abnormal intracellular conditions.  This group is on ECMO 190 +/- 105 hours.

Likewise, the intermediate groups are on ECMO for intermediate periods of time [ 159 +/- 98 and 127 +/-53 hours, respectively].

The goal of the perfusionist taking care of a patient on long-term ECS should be to manipulate the AG and p(V-A)CO2  with interventions which seek to keep both markers as low as possible.  Even if only one marker is successfully reduced, this will have a significant impact on morbidity and survival.  In other words, the low marker helps to ameliorate the effects of the elevated marker.

But, there are limits. 

For example, regardless of how low the p(V-A)CO2 is kept, if the average AG is 20 mEq/l or greater, the ECMO  patient will expire on ECMO or soon after being weaned off.

Alternately, no matter how low the average AG is kept, patients with an average p(V-A)CO2 of 15 mmHg or greater will also expire.

To Summarize

Patients have a low AG (<= 11 mEq/L) or a high AG ( 11 mEq/L) and a low p(V-A)CO2  (<9mmHg) or a high p(V-A)CO2 (=/9mmHg):

1 – Low AG, low p(V-A)CO2 = high survival, short ECS support time.

2 – High AG, high p(V-A)CO2 = low survival, long ECS support time.

3 – High AG, low p(V-A)CO2or  low AG, high p(V-A)CO2  = intermediate survival, intermediate ECS support time.

The next posting will describe specific interventions which may result in the manipulation of the AG and p(V-A)CO2  markers.