Reply: Should Acidosis during Liver Transplantation Be Treated?

In Reply:--Bogdonoff and Spiekermann raise an interesting point regarding the use of NaHCO₃ in the operating room, particularly during liver transplantation. They rarely use NaHCO₃, employing a less aggressive protocol than that used in our study. ^[1] The data fully support a less aggressive approach, and since our original study, we have relaxed our criteria for the administration of NaHCO₃ as well. We found there are no apparent hemodynamic consequences to allowing the arterial pH to decrease to 7.2, although liver transplantation is not the ideal setting in which to evaluate the effects of incremental changes in arterial pH. We also noticed that hyperkalemia may be exacerbated at lower arterial pH. On the other hand, the use of dichloroacetate has continued to ameliorate the acid-base changes during liver transplantation, in part by stimulating pyruvate dehydrogenase activity in the native liver before hepatectomy. ^[2] Thus, dichloroacetate still may be beneficial in moderating the severity of lactic acidosis during liver transplantation.

We agree that the mechanism of lactic acidosis during liver transplantation does not necessarily reflect tissue hypoperfusion but more typically represents an exogenous lactic acid challenge and excess nonanaerobic peripheral lactic acid production in response to a glucose challenge. ^[1] Two animal studies on the effect of metabolic acid challenge on cardiac function are germane. ^[3,4] First, Teplinsky et al. induced lactic acidosis in anesthetized dogs by infusing 0.5 N lactic acid to obtain arterial pH of 7.3. 7.2, or 7.1. ^[3] They found that, compared to controls maintained at pH 7.4, cardiac output decreased at pH 7.3 (by 14%), 7.2 (by 20%), and 7.1 (by 29%), which occurred secondary to decreased stroke volume and impaired contractility (dP/dt_max). Further, there was an accompanying pulmonary hypertension at pH 7.2 and 7.1 and an increase in right atrial pressure at pH 7.1, indicating that the lactic acid-induced decrease in cardiac output is not the result of hypovolemia but rather a direct effect on pump function.

Zhou et al. expanded on these findings in an isolated perfused rat heart model. ^[4] These authors induced metabolic acidosis by employing an HCO₃-depleted perfusate (pH 6.8, HCO₃ 6; analogous to our transfused reservoir blood ^[1]) and used nuclear magnetic resonance spectroscopy to evaluate metabolic function coincidentally with hemodynamic measurements. They noted a marked decrease in dP/dt (by 70% by 30 min) and intracellular pH, followed by decreases in creatine phosphate and oxygen consumption and a 50% increase in inorganic phosphate. Further, reperfusion of acidotic hearts with "normal" perfusate led to recovery of dP/dt and intracellular pH, followed by repletion of creatine phosphate from inorganic phosphate. Similar changes were observed when the acidotic perfusate pH was neutralized with Carbicarb (International Medication Systems, South El Monte, CA). Thus, correction of an acidotic extracellular pH has a direct positive inotropic effect on the myocardium.

The reasoning behind the treatment of pH 7.3 is that, until the graft liver is reperfused, the acidosis is not self-limited and is likely to get worse before it improves. This approach is comparable to treating hypotension after spinal anesthesia at a mean arterial pressure above that considered critical for end-organ perfusion. We agree that it is not necessary to choose pH 7.3 as the value to begin NaHCO₃ therapy. However, our experience has been that, regardless of the pH used as the threshold at which NaHCO₃ therapy is begun, dichloroacetate decreases NaHCO₃ utilization because it stabilizes arterial pH.

Robert E. Shangraw, M.D., Ph.D.; Department of Anesthesiology; Oregon Health Sciences University; 3181 SW Sam Jackson Park Road, UHS-2; Portland, Oregon 97201-3098.

(Accepted for publication on March 22, 1995.)