Haemodynamic and metabolic effects in diabetic ketoacidosis in rats of treatment with sodium bicarbonate or a mixture of sodium bicarbonate and sodium carbonate

Abstract

SummaryTo examine factors determining the haemodynamic and metabolic responses to treatment of diabetic ketoacidosis with alkali, groups of anaesthetised and ventilated rats with either diabetic ketoacidosis (mean arterial pH 6.86-6.96, mean arterial blood pressure 63-67 mmHg) or hypovolaemic shock due to blood withdrawal (mean pH a 7.25-7.27, mean arterial blood pressure 36-41mmHg) were treated with sodium chloride ('saline'), sodium bicarbonate or 'Carbicarb' (equimolar bicarbonate plus carbonate). In the diabetic ketoacidosis series, treatment with either alkali resulted in deterioration of mean arterial blood pressure and substantial elevation of blood lactate, despite a significant rise in myocardial intracellular pH determined by 31p-magnetic resonance spectroscopy. These effects were accompanied by falling trends in the ratios of myocardial phosphocreatine and ATP to inorganic phosphate. Erythrocyte 2,3-bisphosphoglycerate was virtually absent in animals with diabetic ketoacidosis of this severity and duration. In contrast, in shock due to blood withdrawal, infusion of saline or either alkali was accompanied by a transient elevation of mean arterial blood pressure and no significant change in the already elevated blood lactate; erythrocyte 2,3-bisphosphoglycerate was normal in these animals. The effect of alkalinization in rats with severe diabetic ketoacidosis was consistent with myocardial hypoxia, due to the combination of very low initial erythrocyte 2,3-bisphosphoglycerate, alkali-exacerbated left shift of the haemoglobin-oxygen dissociation curve and artificial ventilation. No evidence was found for any beneficial effect of 'Carbicarb' in either series of animals; 'Carbicarb' and sodium bicarbonate could be deleterious in metabolic acidosis of more than short duration. [Diabetologia (1995) 38: 889-898]

Sodium Bicarbonate for the Treatment of Lactic Acidosis

“…Lactate concentrations increased with sodium bicarbonate infusion (compared with control subjects) in animal studies of hypoxic lactic acidosis, 45,47,49 phenformin-induced lactic acidosis, 46,68 hemorrhagic shock, 48 and DKA. 55,57 This finding has also been reported in cases of chronic lactic acidosis associated with malignancies. 85 It is possible that lactate rises in these settings because of impaired oxygen delivery to tissues.…”

“…46,47 Most wholeanimal studies, however, have shown that pH can be raised and even normalized. 16,48,49,[53][54][55] Most relevant to clinical practice, in two studies of patients with lactic acidosis receiving mechanical ventilation, IV infusion of sodium bicarbonate in dosages of 2 mmol/kg for 15 min or 1 mmol/kg for 1 to 2 min raised the pH only 0.14 and 0.05 units, respectively. 2,56 Yet, the body has multiple compartments separated by membranes of differing permeabilities and systems of active transport.…”

“…59 Intracellular pH has been measured in cells or animals using nuclear magnetic resonance spectroscopy, pH-sensitive fluorescent dyes, intramuscular electrodes, and the distribution of carbon 14-labeled dimethadione (Table 1). The results are inconsistent, with intracellular pH rising in one study, 55 not changing in six studies, 11,34,49,53,60,61 falling in nine studies, 46,47,[62][63][64][65][66][67][68] and either rising or falling depending on the buffer used in two investigations. 69,70 In various studies, intracellular pH has been shown to fall with bicarbonate in RBCs, 46 muscle, 68 liver, 47 lymphocytes, 66 and brain.…”

“…Nevertheless, these studies uniformly fail to reveal any hemodynamic benefit for sodium bicarbonate when compared with iso-osmolar saline solution. 16,[45][46][47][48][49]53,55,62,64,[72][73][74] When it has been measured, cardiac output either does not change 48,49,74 or falls. 11,46,47 Right ventricular contractility 72,74 and hepatic blood flow 46,47 fall.…”

Treatment of lactic acidosis: Appropriate confusion

“…66 Other reports on outcomes of intracellular pH with bicarbonate therapy show variable effects. [67][68][69][70][71][72] Second, to the extent that bicarbonate administration raises extracellular pH, it is associated with a reduction in ionized calcium concentration, since the binding of calcium to albumin is pH dependent. 73 A sodium bicarbonate load administered to patients with LA was associated with a significant fall in ionized calcium concentration, whereas a sodium chloride load was not.…”