Horacio J. Adrogué

Assessing acid-base status in circulatory failure. Differences between arterial and central venous blood.

Abstract To assess arteriovenous differences in acid-base status, we measured the pH and partial pressure of carbon dioxide (PCO2) in blood drawn simultaneously from the arterial and central venous circulations in 26 patients with normal cardiac output, 36 patients with moderate and 5 patients with severe circulatory failure, and 38 patients with cardiac or cardiorespiratory arrest. The patients with normal cardiac output had the expected arteriovenous differences: venous pH was lower by 0.03 unit, and venous PCO2 was higher by 0.8 kPa (5.7 mm Hg). These differences widened only slightly in those with moderate cardiac failure. Additional simultaneous determinations in mixed venous blood from pulmonary arterial catheters were nearly identical to those in central venous blood. In the five hypotensive patients with severe circulatory failure there were substantial differences between the mean arterial and central venous pH (7.31 vs. 7.21) and PCO2 (5.8 vs. 9.0 kPa [44 vs. 68 mm Hg]). Large arteriovenous diff...

Changes in plasma potassium concentration during acute acid-base disturbances☆

Abstract It has been widely held that the changes in plasma potassium concentration observed during acute acid-base disorders are solely determined by the associated changes in blood acidity. However, a critical examination of the literature uncovers wide differences among the four cardinal acid-base disorders with respect to the associated changes in plasma potassium concentration. In fact, the data suggest that a host of factors other than the attendant changes in plasma hydrogen ion concentration may well modulate the intercompartmental distribution of body potassium during acid-base disorders. In this study we review the qualitative, quantitative and mechanistic aspects of the plasma potassium response to acute alterations in blood acidity.

Plasma Acid-Base Patterns in Diabetic Ketoacidosis

In a study of the types of plasma acid-base patterns present at 196 admissions for diabetic ketoacidosis we found no relation between the initial level of serum total carbon dioxide and the plasma anion gap; instead, there was a broad spectrum of acid-base patterns, ranging from pure anion-gap acidosis to pure hyperchloremic acidosis. Although the degree of renal dysfunction on admission, which reflected the magnitude of volume depletion, was independent of the severity of metabolic acidosis, it was responsible for the variable retention of plasma ketones: the more severe the volume depletion on admission, the greater the ketone retention and the less prominent the hyperchloremic acidosis. Recovery from acidosis was significantly slower in patients admitted with pure hyperchloremic acidosis. After therapy, hyperchloremia developed in most patients at four to eight hours after admission, because of the retention of chloride in excess of sodium and the excretion of ketones by the kidney.

Consequences of Inadequate Management of Hyponatremia

Dilutional hyponatremia is a commonly observed disorder in hospitalized patients. It represents an excess of water in relation to prevailing sodium stores and is most often associated with a high plasma level of arginine vasopressin, including that found in patients with the syndrome of inappropriate antidiuretic hormone secretion. Hyponatremia may be classified as either acute or chronic depending on the rate of decline of serum sodium concentration, and can lead to a wide range of deleterious changes involving almost all body systems. Serious complications of dilutional hyponatremia most frequently involve the central nervous system. In fact, acute severe hyponatremia is potentially life-threatening and must be treated promptly and aggressively. Chronic hyponatremia often develops in patients with nonrenal diseases and is associated with increased morbidity and mortality. In patients hospitalized for congestive heart failure, hyponatremia is linked to a poor prognosis and increased length of hospital stay. Prompt recognition and optimal management of hyponatremia in hospitalized patients may reduce in-hospital mortality and symptom severity, allow for less intensive hospital care, decrease the duration of hospitalization and associated costs, and improve the treatment of underlying comorbid conditions and patients’ quality of life. The proper treatment of dilutional hyponatremia, especially when chronic, must avoid increasing serum sodium too rapidly, which can lead to permanent or fatal neurologic sequelae. The treatment of hyponatremia may be facilitated by emerging therapies that block the actions of arginine vasopressin at V2 and V1a receptors to promote aquaresis, the electrolyte-sparing elimination of free water, and elevate serum sodium concentrations.

Determinants of plasma potassium levels in diabetic ketoacidosis.

The classic proposal of intracellular K+ for extracellular H+ exchange as responsible for the hyperkalemia of diabetic ketoacidosis (DKA) has been questioned because experimentally induced organic anion acidosis fails to produce hyperkalemia. It has been suggested, instead, that the elevated serum [K+] of DKA might be the result of the compromised renal function, secondary to volume depletion, that usually accompanies DKA. However, several metabolic derangements other than volume depletion and acidosis, which are known to alter potassium metabolism, also develop in DKA. This study of 142 admissions for DKA examines the possible role of alterations in plasma pH, bicarbonate, glucose (G), osmolality, blood urea nitrogen (BUN) and plasma anion gap (AG) on the levels of [K+]p on admission. Significant (p less than 0.01) correlations of [K+]p with each of these parameters were found that could individually account for 8 to 15 percent of the observed variance in the plasma potassium levels; however, the effects of some or all of these parameters on the [K+]p could be independent and therefore physiologically additive. Since the parameters under study are themselves interrelated, having statistically significant correlations with each other, their possible independent role on [K+]p was evaluated by multiple regression analysis. Only plasma pH, glucose and AG emerged as having a definite independent effect on [K+]p, with no independent role found for bicarbonate, BUN and osmolality. The equation that best describes [K+]p on admission for DKA was: [K+]p = 25.4 - 3.02 pH + 0.001 G + 0.028 AG, (r = 0.515). These results indicate that the endogenous ketoacidemia and hyperglycemia observed in DKA, which result primarily from insulin deficit, are the main determinants of increased [K+]p. Since exogenous ketoacidemia and hyperglycemia in the otherwise normal experimental animal do not increase [K+]p, it is postulated that insulin deficit itself may be the major initiating cause of the hyperkalemia that develops in DKA. Renal dysfunction by enhancing hyperglycemia and reducing potassium excretion also contributes to hyperkalemia.

Systemic Calciphylaxis Revisited

A syndrome characterized by rapidly progressive ischemic necrosis involving large areas of the skin and muscle, and by peripheral gangrene associated with extensive vascular calcifications was observed in a patient with end-stage renal failure on chronic hemodialysis. In an effort to control the disease, parathyroidectomy was performed which resulted in rapid improvement of tissue perfusion. However, the patient eventually died from sepsis within 2 months after admission. This case presents the typical features of the syndrome of systemic calciphylaxis. The literature is reviewed searching for similar cases of this poorly recognized, but life-threatening, clinical syndrome. The pathogenesis, clinical manifestations, and therapy of this unusual and rapidly progressive, but potentially reversible, condition are reviewed with emphasis on its prompt recognition and appropriate management.

Aiding fluid prescription for the dysnatremias.

AbstractObjective: The goal of the present study was to develop a novel approach that facilitates the prescription of fluid therapy in patients with abnormal serum sodium concentration. Methodology and results: The novel approach is based on a simple equation, derived from established principles on the distribution of sodium in body fluids, that estimates the impact of a unit dose, i. e., 1 l of any infusate on the patients serum sodium concentration. In accordance with the equation, the expected change in the patients serum sodium concentration in response to 1 l of any infusate (Δ[Na+]s) is obtained by subtracting the sodium concentration of the patients serum from the sodium concentration of the infusate, each expressed in mEq/l, and dividing the result by the patients estimated total body water expressed in liters (adding 1 l to account for the volume of the infusate). The amount of the particular infusate to be administered over the course of any given time period can be easily computed by dividing the desired Δ[Na+]s at the end of the period by the calculated Δ[Na+]s effected by 1 l of the infusate. The utility and limitations of the proposed approach are presented. Conclusions: The novel equation is not a means for formulating therapy. Rather, it provides, simply and expeditiously, quantitative projections that can assist the physician in implementing the selected treatment plan for patients with dysnatremias.

Influence of steady-state alterations in acid-base equilibrium on the fate of administered bicarbonate in the dog.

Previous workers have shown that metabolic acidosis increases the apparent space through which administered bicarbonate is distributed. This finding has been ascribed to the accompanying acidemia and to the consequent availability of a large quantity of hydrogen ion that accumulates on nonbicarbonate tissue buffers during the development of acidosis. To test this hypothesis, bicarbonate space was measured in dogs with a broad range of steady-state plasma [HCO-3] in association with alkalemia as well as with acidemia. Appropriate combinations of pH and plasma [HCO-3] were achieved by pretreating the animals to produce graded degrees of each of the four cardinal, chronic acid-base disorders. Metabolic acidosis (n = 15) was produced by prolonged HCl-feeding; metabolic alkalosis (n = 17) by diuretics and a chloride-free diet; and respiratory acidosis (n = 9) and alkalosis (n = 8) by means of an environmental chamber. Animals with normal acid-base status (n = 4) were also studied. Sodium bicarbonate (5 mmol/kg) was infused over 10 min to the unanesthetized animals; observations were carried out over 90 min. The results obtained from animals with metabolic acid-base disturbances demonstrated an inverse relationship between bicarbonate space and initial plasma pH, confirming the previous findings of others. By contrast, the results obtained in animals with respiratory acid-base disturbances demonstrated a direct relationship between bicarbonate space and initial plasma pH. The pooled data revealed that bicarbonate space is, in fact, quite independent of the initial pH but is highly correlated with the initial level of extracellular [HCO-3]; dogs with low extracellular [HCO-3] (congruent to 10 meq/liter) whether acidemic or alkalemic, have a bicarbonate space that is 25% larger than normal and some 50% larger than in dogs with high extracellular [HCO-3] (congruent to 50 meq/liter). We conclude from these results that the increased bicarbonate space in metabolic acidosis (and respiratory alkalosis) does not reflect the availability of more hydrogen ions for release during bicarbonate administration, but merely evidences the wider range of titration (delta pH) of nonbicarbonate buffers that occurs during alkali loading whenever plasma [HCO-3] is low.

Assessing acid-base disorders

Effective management of acid-base disorders depends on accurate diagnosis. Three distinct approaches are currently used in assessing acid-base disorders: the physiological approach, the base-excess approach, and the physicochemical approach. There are considerable differences among the three approaches. In this review, we first describe the conceptual framework of each approach, and comment on its attributes and drawbacks. We then highlight the application of each approach to patient care. We conclude with a brief synthesis and our recommendations for choosing an approach.

The Challenge of Hyponatremia

Treatment of hypotonic hyponatremia often challenges clinicians on many counts. Despite similar serum sodium concentrations, clinical manifestations can range from mild to life threatening. Some patients require active management, whereas others recover without intervention. Therapeutic measures frequently yield safe correction, yet the same measures can result in osmotic demyelination. To address this challenge, we present a practical approach to managing hyponatremia that centers on two elements: a diagnostic evaluation directed at the pathogenesis and putative causes of hyponatremia, the case-specific clinical and laboratory features, and the associated clinical risk; and a management plan tailored to the diagnostic findings that incorporates quantitative projections of fluid therapy and fluid losses on the patients serum sodium, balances potential benefits and risks, and emphasizes vigilant monitoring. These principles should enable the clinician to formulate a management plan that addresses expeditiously three critical questions: Which of the determinants of the serum sodium are deranged and what is the underlying culprit? How urgent is the need for intervention? What specific therapy should be instituted and which are the associated pitfalls?