Reply: We are happy to respond to Dr. Zhou's considerations on our study comparing 15% hypertonic sodium pyruvate (HPY) with 8% hypertonic NaCl (HS) in the treatment of sheep with multiple hemorrhages (1). Dr Zhou's main contention is that the conclusion of our study should be the opposite, that is, HPY offers benefits over HS in the initial phase of hemorrhagic shock resuscitation, although he states that according to the conditions of our study, on the surface, no initial advantage of HPY was seen.
Based on our data, we rejected our first hypothesis: a small volume of HPY is superior to osmotically and volume-matched HS for improving acute metabolic dysfunction, base deficit, and lactate/pyruvate (L/P) ratio imbalance. In addition, we rejected our second hypothesis: HPY improves hemodynamics and reduces fluid volume for similar hemodynamics. These are the only reasonable conclusions that can be reached based on the data. We do appreciate that any animal study is limited by certain model considerations. Conclusions must be considered with respect to the model used. Our study only addressed the acute effects of fluid resuscitation in a moderate hemorrhagic hypovolemia, a common clinical presentation requiring fluid therapy.
We used a closed-loop resuscitation system with a physiological target end point of 90 mmHg to infuse the first 4 mL/kg of HPY or HS, followed by lactate Ringer, in both groups. In the discussion, we state, "It may be that our conscious model of shock was not severe enough to see a benefit of pyruvate." Dr. Zhou misquotes us, "the shock model was not severe enough to show benefit of pyruvate." Dr. Zhou also wrote, "if the MAP further dropped and remained at 40 mmHg as shown in the Mongan et al. hemorrhagic model (2), the prospective cardiovascular benefits of pyruvate: less hemodynamic decompensation, a higher cardiac output level, and lowered lactate/pyruvate (L/P) ratio would be predictable to appear in this experiment." This is conjecture. In our study, after the first hemorrhage of 25 mL/kg, MAP decreased to 40 mmHg, and there was no observed cardiovascular benefit of HPY resuscitation. In addition, oxygen delivery was lower with HPY than that with HS resuscitation. No hemodynamic and systemic oxygenation advantages were apparent with HPY.
It is a reach to extrapolate from our data that HPY offered benefits over HS for resuscitation based on the transient variations in pH, lactate, and HCO3−. Our study shows that shock increased lactate similarly in both groups, and with the HS, it slowly recovered but increased 3-fold with the pyruvate. This is a consequence of how pyruvate is metabolized, and we do not think that this is a particular advantage or disadvantage. There was rapid alkalinization using HPY in our model. However, we do not consider this to be of benefit in shock because an increased hydrogen ion concentration is an important stimulus for several compensatory mechanisms for both cardiovascular and pulmonary function. The L/P ratio is an indicator of the metabolic status (2, 3) and was not suggestive of benefit for HPY because L/P was significantly higher than HS 120 min after the beginning of treatment.
Dr. Zhou said that HPY not only avoids hyperchloremia-induced renal dysfunction but also protects kidney function in ischemia and oxidative stress and pointed this as an advantage in our study. We did not evaluate renal function in our model. However, based on similar models in which renal function has been studied, resuscitation with either hypertonic saline or lactated Ringer in euhydrated and dehydrated sheep, no renal dysfunction was found due to hyperchloremia (4).
Finally, references to support Dr. Zhou's several contentions would have been helpful, for example:
"Evidently, in order to prevent HPY from alkalosis, it is essential to reduce the dosage or concentration of HPY from 15% to 11.0% (1.0 M, or less) of NaPyr in shock resuscitation."
"Substitution of 1/2 NaCl in 7.2% HS with equimolar NaPyr: 3.5% NaCl/7.0% NaPyr (the ratio may vary) would be superior to current HS solutions."
"In ischemia or hypoxia, the new pyruvate-containing HS in resuscitation would not only prevent iatrogenic hyperchloremic acidosis in addition to the improvement of disturbed glucose metabolic pathways, but also correct original metabolic (lactic) acidosis induced by severe shock, and provide the protection of vital organ function as well."
We wait to read the peer-reviewed results of the experimental or clinical use of such solutions.
Paulo do Nascimento, Jr
George C. Kramer
Resuscitation Research Laboratory
Department of Anesthesiology, UTMB
1. do Nascimento P Jr, Vaid SU, Hoskins SL, Espana JM, Kinsky MP, Kramer GC: Hypertonic 15% sodium pyruvate offers no initial resuscitation advantage compared with 8% hypertonic NaCl in sheep with multiple hemorrhages. Shock
2. Mongan PD, Fontana JL, Chen R, Bunger R: Intravenous pyruvate prolongs survival during hemorrhagic shock in swine. Am J Physiol
3. Mongan PD, Capacchione J, Fontana JL, West S, Bunger R: Pyruvate improves cerebral metabolism during hemorrhagic shock. Am J Physiol Heart Circ Physiol
4. Ho HS, Sondeen JL, Dubick MA, Wade CE, Gunther RA: The renal effects of 7.5% NaCl-6% dextran-70 versus lactated Ringer's resuscitation of hemorrhage in dehydrated sheep. Shock