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September 29, 2019
Veverimer: A Promising Investigational Agent for Long-Term Treatment of Metabolic Acidosis in Chronic Kidney Disease: Veverimer is an oral non-absorbed acid binder that sequesters hydrochloric acid in the gastrointestinal tract, preventing its absorption and thereby raising serum bicarbonate concentrations. In a randomized one-year clinical trial in CKD patients with metabolic acidosis, patients taking veverimer achieved greater increases in serum bicarbonate and were more likely to achieve increases ≥4 mmol/L and/or into the reference range than patients taking placebo. Overall, veverimer was well tolerated, with adverse event rates similar to placebo. Veverimer effectively raises serum bicarbonate levels in stage IIIb–IV CKD patients via a sodium-independent mechanism. If approved by the U.S. FDA, it may provide a new option for patients with severe CKD and sodium- or volume-dependent comorbidities who may otherwise require renal replacement therapy for acidosis control.
Upon completion of the chapter, the reader will be able to:
Compare and contrast the four primary acid–base disturbances within the human body.
Apply simple formulas in a systematic manner to determine the etiology of simple acid–base disturbances and the adequacy of compensation.
Integrate the supplemental concepts of the anion gap and the excess gap to further assess for complex acid–base disturbances.
Discuss the most common clinical causes for each primary acid–base abnormality.
Describe the potential clinical complications of altered acid–base homeostasis.
Propose an appropriate treatment plan for patients with deranged acid–base physiology.
Given its reputation for complexity and the need to memorize innumerable formulas, acid–base analysis intimidates many health care providers. In reality, acid–base disorders always obey well-defined biochemical and physiological principles. The pH determines a patient’s acid–base status and an assessment of the bicarbonate (HCO3−) and arterial carbon dioxide (PaCO2) values identifies the underlying process. Rigorous use of a systematic approach to arterial blood gases (ABGs) increases the likelihood that derangements in acid–base physiology are recognized and correctly interpreted. This chapter outlines a clinically useful approach to acid–base abnormalities and then applies this approach in a series of increasingly complex clinical scenarios.
Disturbances of acid–base equilibrium occur in a wide variety of illnesses and are among the most frequently encountered disorders in critical care medicine. The importance of a thorough command of this content cannot be overstated given that acid–base disorders are remarkably common and may result in significant morbidity and mortality. Although severe derangements may affect virtually any organ system, the most serious clinical effects are cardiovascular (arrhythmias, impaired contractility), neurologic (coma, seizures), pulmonary (dyspnea, impaired oxygen delivery, respiratory fatigue, respiratory failure), and/or renal (hypokalemia). Changes in acid–base status also affect multiple aspects of pharmacokinetics (clearance, protein binding) and pharmacodynamics.
PHYSIOLOGY OF ACID–BASE HOMEOSTASIS
Acid–base homeostasis is ...