To the Editor:
We deeply appreciated Dr. Coppola et al.’s thorough yet concise review of acid-base physiology and the clinical indications for sodium bicarbonate. One more complication of acidosis deserves mention: coagulopathy. Although acidosis is often a secondary effect of injury and frequently occurs alongside other derangements such as hypothermia, low pH has independent effects on clotting. These include decreased fibrinogen concentration decreased activity of factors V, VII, and X decreased thrombin generation prolonged splenic bleeding times thrombocytopenia and the induction of disseminated intravascular coagulopathy. In fact, even the modest acidosis of pH 7.35 is associated with increased blood loss and reoperation for bleeding. Acidosis-associated coagulopathy is detectable in a range of laboratory derangements including increased prothrombin time and activated partial thromboplastin times increased activated clotting time and hypocoagulability in all parameters of viscoelastic tests.
As in so many of the other injuries discussed by the authors, acidosis-associated coagulopathy is not reversed by sodium bicarbonate. Retrospective analysis of surgical patients who experienced acidosis that was intraoperatively normalized found increased postoperative blood loss compared to patients whose pH remained normal during surgery. Surgical models in swine that maintained a constant core temperature and then used either hydrochloric acid infusions or hemorrhage and hypoventilation to induce acidosis found broad impairments of coagulation that were not corrected when pH was restored to 7.4 with sodium bicarbonate. This suggests that the acidosis-associated coagulopathy is not just an excursion outside the optimal operating pH of a particular set of enzymes. It is likely a complicated process where acidosis is both a cause and consequence of injury. Moreover, All acidosis is not equal: lactic acidosis often implies not just low pH but mitochondrial energy production failure, and therefore cellular dysfunction may be added to the coagulopathic milieu.
Sodium bicarbonate’s lack of efficacy leaves perioperative clinicians bereft of a clear solution to a common and serious problem. In the absence of strong data, a multimodal strategy seems best: maintaining euthermia, avoiding gratuitous crystalloid infusions, correcting electrolyte abnormalities, institution of judicious ventilatory support, and treating coagulopathy deliberately with laboratory-guided, algorithm-based transfusion strategies or fixed-ratio protocols. As the authors note, we should always aim to treat the underlying state, and sodium bicarbonate is not enough.