Dr. DuBose:
Our next speaker is Dr. Ravindra Mehta, who is known for his investigations into acute renal failure, particularly acute renal failure in the critical care setting. Certainly one area he has been identified with is as an advocate for a better understanding of the effects and application of continuous therapy. In addition to introducing a whole new set of initials into the nephrologic and critical care lexicon, continuous therapy also introduces a peculiar set of acid-base and electrolyte problems. That is the subject of Ravi's talk. Ravi, welcome.

Dr. Ravindra Mehta
I would like to thank the program committee for giving me the opportunity to be here.

00:00

Introduction and overview
I have structured my talk in terms of trying to cover for you a brief consideration of the operational characteristics of continuous therapies just to orient you to what you are more familiar with; defining the nature of the problems, management strategies, and prevention in this area.

00:00

Case history: CRRT in a 76-year-old ICU patient
I will start with a case which is representative of some of the types of cases you are likely to see. This was a 76-year old woman who was referred to our center for regional citrate CRT. She was in one of the local hospitals. She had had an unfortunate postoperative course following a 7-vessel coronary artery bypass graft.

She had multiple complications immediately postop surgery, notably a right ventricle dilation while she was on the table. This required her to have a very prolonged bypass time. She was hypotensive and was thought to have developed a right ventricle infarct.

She recovered just briefly and 12 hours later had to be taken back to the operating room because she had a bleeding saphenous vein graft. This was fixed with a bradycardial patch.

Following this, unexpectedly she developed respiratory failure with dense air space opacities. She had persistent hypotension and bleeding and she had profound thrombocytopenia requiring massive blood transfusions.

Over the course of about the next five days, she had gained about 20 liters of fluid. On Postoperative Day #4, she was on a Bumex drip. But despite these measures, she was oliguric and was not able to make any urine. So she was referred to us. On transfer, she had cardiogenic shock, DIC, thrombocytopenia anemia; she had an acute lung injury; there was a possibility of pneumonia; she was in renal failure; and there was an obvious myocardial injury which had been recent.

00:00

Case history: Further course
As an outpatient she had had a history of arrhythmias and was on amiodarone. Her physical examination was significant for a fair amount of edema. She had a soft murmur, she had a rancorous chest, her blood pressures were 85/50 on a variety of pressor agents, and her oxygen saturation or 100 percent FIO₂ was 86 percent.

As you can see, she was on four pressors. And despite this, her pressure was still in this range. She had an O₂ sat of 86 percent and a pH of 7.33, PO₂ of 59, PCO₂ of 38, and a base excess of -6.4. She had a hypokinetic right ventricle wall, and her ejection fraction was less than 30 percent. We started her on continuous venovenous hemodiafiltration using citrate anticoagulation because of her renal insufficiency and to support her other organs.

00:00

Our approach to citrate anticoagulation with CVV-HDF
Just to give you a preview of how we approach CVVHDF and lead you into some of the subsequent things, I am just going to spend a moment on this conceptual diagram. This represents our approaches using the Prisma system.

In essence we use citrate anticoagulation with a 4 percent dry sodium citrate, which has 140 mmol of citrate per liter, and 420 of sodium. This is delivered right at the access site. We use a predilution fluid simply to reduce the filtration fraction--that means reduce the viscosity of blood going through.

We set the blood pump flow rate at 100 ml/minute. The citrate flow rate starts at 160 to 200 ml/hr. That is approximately 3 percent of the blood flow rate. We have a specific dialysate, which is hypotonic with respect to sodium, has no base, no calcium. And since we are chelating calcium, we will give calcium chloride back in a separate circuit through a central vein. In addition, this is intended because the Prisma system does not allow you to set the effluent pump speed specifically. And as a consequence, what we want to do is minimize the interface where the nurses have to interfere with the machine. As a consequence, we deliver the substitution fluid post-filter so it goes directly to the patient. The only thing they are interacting with is the IV fluid.

Notice that we are using sodium chloride here, because with the hypotonic sodium here, you will be removing and facilitating the removal of sodium chloride which is delivered from the citrate. The citrate flow rate is adjusted to maintain a post-filter ionized calcium. The calcium chloride is adjusted to maintain a proper peripheral ionized calcium. So this being the general sequence of how we do things, let me take you through and do a comparison of how these techniques work.

00:00

Comparison of IHD and CRRT
If you think about it, we are very familiar with intermittent dialysis where using variable permeable membranes you are used to using blood flow rates which are less than the dialysate flow rates. As a consequence, the dialysate never gets saturated. The ultrafiltration rates depend upon what you are trying to achieve, but it is from 0 to 2 liters per hour. The dialysate base has 4 mg of acetate and 35 mg of bicarbonate per liter. There is no substitution fluid. You do this procedure over a few hours. The major force is diffusion with urea clearances of 180 to 200 ml/min.

In contrast, amongst the CRRT techniques, one has to recognize that the operational characteristics will largely determine what you are going to see. If you use a hemofiltration technique, the only force for removing things is convection. As a consequence, it is the amount and composition of the substitution fluid which will influence your overall metabolic status. When you use a hemodialysis technique, such as CVVHD, diffusion is the main force; however, notice that the blood flow rate is significantly higher than your dialysate flow rate. As a consequence, your dialysate is saturated. And here most of the solutions used have been lactate, bicarbonate, or you can use citrate to provide the base. When you use a combination technique (such as CVV-HDF), you use both diffusion and convection in this method.

00:00

Source: Feriani M et al, Nephrol Dial Transplant. 1998;13 Suppl 6:62-5. Review. No abstract available.

Predicted serum bicarbonate changes during IHD
Theoretically this is a theoretical aspect of seeing what would happen there. This is the bicarbonate flux going into the blood. This is the bicarbonate levels rising. Over a period of time as you approach a period of equilibration, there is no longer a major change in the blood bicarbonate level. Usually the time of dialysis around which this occurs is about 2.5 to 3 hours, and you can see that there is a rapid rise and then there is a plateau of the serum bicarbonate level.

00:00

Source: Kumar VA et al, Am J Kidney Dis. 2000 Aug;36(2):294-300.

Serum bicarbonate changes during EDD (Extended Daily Dialysis
If you take the dialysis duration longer, for say 7 to 8 hours, as you would do with a SLED (slow, low efficiency dialysis) or an EDD or an extended daily dialysis technique, you start seeing in comparison to CVVH, that the bicarbonate goes up, comes down, goes up, comes down, but it tends to stay higher because you have had more opportunity to deliver bicarbonate over time. If you take this sort of parallel-thought process, if you are going to give it for an even longer period of time with continuous therapies, you would expect to find that you are now reaching steady state where the bicarbonate uptake is equivalent to the amount of acid generation so that you reach a steady state bicarbonate.

00:00

Acid-base balance in CRRT
In essence, in CRRT, one of the things you have to consider is what is your base source and how is it being delivered? It could be acetate, lactate, bicarbonate or citrate. And the delivery site could be the substitution fluid, the dialysate, or both. And how you manipulate those will influence what you are likely to see.

00:00

Composition of typical replacement fluids / dialysis solutions
This is just a depiction of some of the various concoctions of replacement fluids which have been available, as well as dialysates. In the U.S. to a large extent people who use heparin-based continuous therapies have been dependent upon using the PD solutions, which notice have a sodium of 132, have lactate as the base, and because of this-- there have been some problems with this--there is now a solution which has a sodium 140 with again lactate as a base. In contrast, most of the substitution fluids have ranged from Ringer lactate, have ranged from half-normal saline with bicarbonate -- many combinations can be used.

00:00

Source: Levraut J et al, Crit Care Med. 1997 Jan;25(1):58-62.

Lactate removal with CRRT
There is a very nicely done study that was published about three years ago which looked at the ability of continuous therapies to remove lactate in relation to the total plasma clearance of lactate. We all know, as Dr. Szerlip pointed out--lactic acidosis is sort of an epiphenomenon. However, if you are giving lactate exogenously from your therapy, then you at some point have to be concerned whether you are contributing to a relative over-production of lactate, which in the setting of impaired metabolism of lactate might contribute to a problem.

This was a study that looked at lactate elimination in 10 patients with acute renal failure. They measured the lactate concentration in serum and ultradiafiltrate and to calculate the clearance and then also looked at the area under the curves in these patients given the lactate.

00:00

Source: Levraut J et al, Crit Care Med. 1997 Jan;25(1):58-62.

Lactate disappearance curves in ICU patients
This is just to show you that they gave a lactate infusion over a short period of time. Notice that the majority of that lactate disappears in less than an hour. These are in sick patients; however, these were not patients who had lactic acidosis as defined by the definition before.

00:00

Source: Levraut J et al, Crit Care Med. 1997 Jan;25(1):58-62.

Filter lacatate levels and sieving coefficiencts
As you see here, at time points during the lactate infusion--these are the blood lactate levels--this is the lactate which appears in the ultrafiltrate. This is the lactate sieving coefficient, simply a ratio of what is in the ultrafiltrate to the blood. That suggests that the membrane is very permeable to a small molecule, as expected, as lactate. This is the filter lactate clearance, which is about 24 ml/minute. This was CVVHDF, where they had one liter of dialysate and about 700 of ultrafiltrate. So this equates to what you would expect it to be.

00:00

Source: Levraut J et al, Crit Care Med. 1997 Jan;25(1):58-62.

Total plasma and CVVHDF lactate clearances
However, when you look at the total area under the curve analysis, this is the actual plasma clearance of lactate which is going on in the tissues. So in comparison to what you are doing with CVVHDF, you can see only about 2 to 3 percent of the total plasma clearance is being provided by the filter. This makes it a very important aspect of things. In other words, if you are trying to correct lactic acidosis, it is not because you will be able to remove lactate. It is because you will be able to provide buffer back and dissociate the side effects of the buffer in terms of the sodium overload and the fluid. And I will demonstrate that in a minute.

00:00

Source: Heering et al, J Am Soc Nephrol 8:159, 1997

Lactate, acetate, or bicarbonate for CVVH replacement fluid
In terms of CVVH, the hemofiltration guys... they would choose substitution fluid. There has been this ongoing controversy, "Which base is better?" And while there are some studies out from Germany--this is from Dr. Heering's data, looking at comparison of patients with acetate, bicarbonate, or lactate. You can see that over time there really is no significant difference in terms of correction of bicarbonate levels.

00:00

Source: Zimmerman D et al, Nephrol Dial Transplant. 1999 Oct;14(10):2387-91.

Acid-base balance in CVVHD
The same has been done with CVVHD techniques. This is a study from Dr. Zimmerman and Tobe in Toronto, looking at two group comparisons, the same patients serving as their own controls. The first period of lactate was a bicarbonate. And you can see that there really is no difference in terms of the levels of bicarbonate which are generated from these two bases. So it is not that you can't use lactate, but it is just simply a question of are you contributing to any other aspects of lactic accumulation?

00:00

This is our own study. We had a small group of patients. We were doing a metabolic comparison where we looked at patients on citrate, CRRT, and we were looking at the oxygen consumption and CO₂ production to look at the respiratory quotient. What I would just like to simply point out to you is that these are the times when they were not on any therapy. You can see the mean bicarbonate was 22.5. The times they are on therapy, the bicarbonate goes up. This is not with any base other than citrates. So they are not getting exogenous bicarbonate or lactate. By metabolism itself, citrate can provide an equivalent amount of base, and that becomes sort of an opportunity to utilize citrate in that manner.

To go to PART TWO click here

Back to Topic Index
Topic Index  Chronic Renal Failure -- Continuous Renal Replacement Therapies