The exchange of approximately 30 l plasma water per day is necessary to achieve adequate control of uremia and acid–base disorders in ARF [14]. During continuous RRT, according to conventional acid–base thinking, there is a substantial loss of endogenous bicarbonate, which must be substituted by the addition of 'buffer' substances. (According to the Stewart–Figge approach, the explanation for this is that there is loss of a fluid with an SID of approximately 40 mEq/l, which must be replaced by a fluid with a similar SID.)
Lactate, acetate, and bicarbonate have been used as 'buffers' (or SID generators according to Stewart [7]) during RRT. Citrate has been used as a 'buffer' and for anticoagulation. These 'buffers' affect acid–base balance, and therefore we must understand their physiologic characteristics.
Bicarbonate has the major advantage of being the most physiologic anion equivalent. However, the production of a commercially available bicarbonate-based solution is not easy because of the formation of calcium and magnesium salts during long-term storage. Furthermore, the cost of this solution is approximately three times greater than that of other 'buffer' solutions. Accordingly, acetate and lactate have been used widely for RRT. Under normal conditions, acetate is rapidly converted on a 1:1 basis to carbon dioxide and then bicarbonate by both liver and skeletal muscle. Lactate is also rapidly converted in the liver on a 1:1 basis [15].
Studies of acetate-based solutions appear to exert a negative influence on the mean arterial blood pressure and cardiac function in the critically ill [16–18]. Morgera and coworkers [19] compared acid–base balance between acetate-buffered and lactate-buffered replacement fluids, and reported that the acetate-buffered solution was associated with a significant lower pH and bicarbonate levels than was the lactate-buffered solution. However, the acetate-buffered solution had 9.5 mmol/l less 'buffer' than the lactate-buffered one. Therefore, the difference is probably simply a matter of dose rather than choice of 'buffer'. From the Stewart–Figge perspective, the acetate-buffered solution contained 8 mmol/l chloride more than the lactate-buffered solution to achieve electrical equilibrium. This reduces the SID of the replacement fluid and acidifies blood more.
Thomas and coworkers [20] compared the effects of lactate-buffered versus bicarbonate-buffered fluids. Hemofiltration fluids contained either 44.5 mmol/l sodium lactate or 40.0 mmol/l sodium bicarbonate with 3 mmol/l lactate (43 mmol/l). Lactate-buffered fluids contained 142 mmol/l sodium and 103 mmol/l chloride (SID 39 mEq/l), and bicarbonate-buffered fluids contained 155 mmol/l sodium and 120 mmol/l chloride (SID 35 mEq/l). Lactate rose from approximately 2 mmol/l to 4 mmol/l when lactate-based fluids were given but not with bicarbonate. Both therapies resulted in a similar improvement in metabolic acidosis. Potentially, the lactate-buffered fluid could have had a more alkalinizing effect. However, the accumulation of lactate in blood might have offset this effect and attenuated the trend toward a higher base excess with the lactate-buffered fluids.
Tan and coworkers [21] studied the acid–base effect of CVVH with lactate-buffered and bicarbonate-buffered solutions. The lactate-buffered solution had an SID of 46 mEq/l, as compared with 35 mEq/l for the bicarbonate fluid. From the Stewart–Figge point of view, the lactate-buffered solution should have led to a greater amount of alkalosis. However, that study found a significant increase in plasma lactate levels and a decrease in base excess with the lactate-buffered solution (Figs 5 and 6). Lactate, if not metabolized and still present in blood, acts as a strong anion, which would have the same acidifying effect of chloride. Accordingly, iatrogenic hyperlactatemia can cause a metabolic acidosis (Fig. 7). The controversy can, of course, also be resolved by failure to convert exogenous lactate into bicarbonate.
Most commercially available replacement fluids are buffered with approximately 40–46 mmol/l lactate. In the vast majority of patients, the administration of such replacement fluid maintains a normal serum bicarbonate level without any significant increase in blood lactate concentration. Because the ability of the liver to metabolize lactate is in the region of 100 mmol/hour [22], even aggressive CVVH at 2 l/hour exchange would still deliver less than the normal liver can handle.
However, if lactate-based dialysate or replacement fluids are used in some patients with liver dysfunction or shock, then the administration of lactate-buffered fluids can induce significant hyperlactatemia and acidosis because the metabolic rate is insufficient to meet the additional lactate load. Although lactate normally acts as a 'buffer' by being removed from the circulation and thereby lowering the SID, if lactate is only partly metabolized and accumulates in plasma water then it acts like a strong anion. Thus, hyperlactatemia decreases the apparent SID, which results in increased dissociation of plasma water and thereby lowers the pH.
Citrate has been used for regional anticoagulation. During this procedure, citrate is administered to the circuit before the filter and chelates calcium, thus impeding coagulation. Once citrate enters the circulation, it is metabolized to carbon dioxide and then bicarbonate on a 1: 3 basis; thus, 1 mmol citrate yields 3 mmol carbon dioxide and then bicarbonate.
Under these circumstances, citrate acts as the 'buffer' as well as the anticoagulant. If the method described by Mehta and coworkers [23] is applied, then approximately 48 mmol/hour 'bicarbonate equivalent' is given as citrate. This rate of alkali administration may result in metabolic alkalosis (in up to 25% of cases). Caution is warranted in patients with liver disease, who may not be able to metabolize citrate. In these patients, citrate may accumulate and result in severe ionized hypocalcemia and metabolic acidosis because the citrate anion (C6H5O7
3-) acts as an unmeasured anion and increases the SIG, which has acidifying effects.
When oxidizable anions are used in the replacement fluids, the anion (acetate, lactate, and citrate) must be completely oxidized to carbon dioxide and water in order to generate bicarbonate. If the metabolic conversion of nonbicarbonate anions proceeds without accumulation, then their buffering capacity is equal to that of bicarbonate. Thus, the effect on acid–base status depends on the 'buffer' concentration rather than on the kind of 'buffer' used [15]. When the metabolic conversion is impaired, the increased blood concentration of the anions leads to an increased strong anion in lactate or unmeasured anions for acetate and citrate. All lower the apparent SID and acidify blood. The nature and extent of these acid–base changes is governed by the intensity of plasma water exchange/dialysis, by the 'buffer' content of the replacement fluid/dialysate, and by the metabolic rate for these anions.