Acid-Base Disorders

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Chapter 124

Acid-Base Disorders

Emergency physicians often manage patients who have an acid-base disorder. Although it is not typically a chief complaint, an acid-base disturbance may be the cause of a patient’s symptoms and in some cases represents an immediate life threat. Unlike the supportive therapies for many physiologic derangements, which can be temporized by targeting the effects of the underlying lesion (e.g., supplemental oxygen for pneumonia), the treatment of many acid-base derangements is contingent on identification and treatment of the cause. Emergency physicians must therefore recognize when an acid-base disorder is present and have a diagnostic approach. This chapter presents the essential elements of acid-base physiology, describes the most important causes of acid-base derangements, and highlights key steps in their management.

Principles of Disease

Many basic cellular processes are sensitive to small changes in serum pH; the kidneys, lungs, and physiologic buffers therefore defend serum pH, which is normally between 7.36 and 7.44. Serum pH is determined by the relative concentrations of bicarbonate (HCO3−) and carbon dioxide (PaCO2); when two of these variables are known, the third may be calculated. Most blood gas analyzers measure pH and PaCO2 and report a calculated [HCO3−]; most laboratories, when they report a serum bicarbonate concentration, are reporting a measured total carbon dioxide concentration, which is the sum of the serum bicarbonate and dissolved carbon dioxide. The dissolved carbon dioxide usually contributes negligibly to total carbon dioxide concentration but can become significant in patients with hypercapnia.

An acidosis is a process that lowers HCO3− or raises PaCO2 and tends to create an acidemia, which exists when serum pH is below 7.36. An alkalosis conversely represents a process that raises HCO3− or lowers PaCO2 and tends to create an alkalemia, which is present when serum pH is above 7.44. The terms acidemia and acidosis are not interchangeable; acidosis (or alkalosis) describes a process that pushes serum pH down (or up); acidemia and alkalemia describe the serum pH itself. A patient who is acidemic has at least one acidosis but may have two or more acidoses and may also have one or more alkaloses. Patients with normal serum pH, that is, without acidemia or alkalemia, may have acidoses and alkaloses whose net effect is serum neutrality.

Bicarbonate concentration is predominantly regulated by the kidneys and PaCO2 by lung ventilation. Diseases that affect kidney function may therefore produce a metabolic acidosis or alkalosis, for which the lungs will try to compensate by decreasing or increasing PaCO2, respectively. Likewise, pulmonary insults cause a respiratory acidosis or alkalosis, for which the kidneys will try to compensate by raising or lowering serum HCO3−, respectively.

In the majority of acid-base disturbances, the role of the emergency physician is to identify and manage dangerous causes of the disturbance. Uncommonly, the acid-base disorder is severe enough that the resulting acidemia or alkalemia itself is dangerous; serum pH below 6.7 or higher than 7.6 is considered unsustainable and may cause cardiac hypocontractility and irritability, seizures, cerebral edema, and a variety of metabolic disturbances. In these cases, empirical therapy directed at normalization of serum pH may be warranted simultaneously with a search for the underlying process or processes.

A reduced serum bicarbonate concentration defines a metabolic acidosis, which may be the primary disorder or a compensation for a primary respiratory alkalosis; an elevated serum bicarbonate concentration defines a metabolic alkalosis, which may be the primary disorder or a compensation for a primary respiratory acidosis. Likewise, a reduced PaCO2 represents a respiratory alkalosis, and an elevated PaCO2 represents a respiratory acidosis. When only a primary disturbance and its corresponding compensation are present, it is described as a simple acid-base disorder. A mixed acid-base disorder exists when more than one primary disturbance occurs simultaneously.

Alterations in serum pH are resisted initially by intracellular and extracellular physiologic buffers, followed by specific responses from the lungs and the kidneys. Peripheral and central chemoreceptors adjust pulmonary minute ventilation in response to changes in serum pH. In a primary metabolic acidosis, an increase in minute ventilation lowers PaCO2 and pushes the serum pH closer to normal. A primary metabolic alkalosis likewise causes a reduction in minute ventilation to elevate PaCO2 in an attempt to restore physiologic serum pH.

The response of the kidneys to alterations in serum pH occurs over hours to days. A sustained acidemia promotes renal excretion of H+ and retention of HCO3−, whereas alkalemia causes renal HCO3− excretion and H+ retention. The kidney transports hydrogen ions in exchange for potassium, whose serum concentration must also be maintained within tight parameters. This may become clinically important when, for instance, correction of alkalemia is attempted: retention of H+ cannot occur unless potassium stores are sufficient to allow urinary K+ excretion. Potassium supplementation may therefore be necessary to alkalinize the urine in cases of, for example, heterocyclic antidepressant toxicity.

Diagnostic Strategies

An acid-base disturbance is often first identified when the results of laboratory tests ordered to evaluate the patient’s symptoms demonstrate alterations in bicarbonate, pH, or PaCO2. The possibility of an acid-base disorder is suggested by clinical events such as toxic ingestions, severe vomiting, or diarrhea as well as in patients with diseases affecting the organs responsible for maintenance of acid-base balance—primarily the lungs and kidney. All critically ill patients and certainly all patients being mechanically ventilated require an assessment of acid-base status.

When an acid-base disturbance is identified or suspected, elucidation of its underlying cause or causes is central to appropriate management. When the cause of an acid-base disturbance is not evident, the emergency evaluation begins with a full history and physical examination and proceeds with targeted laboratory studies.

Simple acid-base disorders are categorized by the serum pH, PaCO2, and HCO3− concentrations (Table 124-1). When the primary disturbance is identified, the next step is to determine its etiology and whether an appropriate compensation has occurred. An inappropriate compensation suggests that the process underlying the primary disturbance has hindered an appropriate response or that more than one primary disturbance is present. Simple formulas allow the calculation of an appropriate response once the primary disturbance has been categorized. Compensatory processes generally return pH toward normal but not to normal and never beyond normal; such an exaggerated “compensation” actually represents a second primary disorder.

Blood gas and serum chemistry analysis allows calculation and interpretation of the serum anion gap.

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Plasma must remain electrically neutral: the sum of anions and cations must be equal. Because routinely measured cations exceed routinely measured anions, the anion gap represents the concentration of anions other than chloride and bicarbonate in the blood. A variety of these anions are normally present, but serum albumin accounts for most of the physiologic (normal) anion gap, which is usually between 9 and 15. The higher the anion gap, the more likely that one or more unmeasured anions is generating a metabolic acidosis. Besides albumin, classic unmeasured anions such as lactate and ketones are now also routinely measured and can be incorporated into a diagnostic pathway (albumin concentration reported in grams per deciliter must be corrected by multiplying by 2.5 to be included in anion gap calculations). Unmeasured cations are also present and may account for an elevated anion gap in cases of hypomagnesemia or hypocalcemia, often in combination with hypokalemia (because serum potassium concentration varies so little, it is usually left out of anion gap calculations and is therefore functionally an unmeasured cation). Elevated concentrations of unmeasured cations may cause a low anion gap (<3 mEq/L), such as in cases of lithium toxicity and hypergammaglobulinemia seen in multiple myeloma. Bromide toxicity and hypertriglyceridemia may confound electrolyte measurements and also cause a low or negative anion gap.

Hypoalbuminemia is common and consequential from an acid-base perspective because as albumin is the primary contributor to the “normal” anion gap, significant depression of serum albumin will reduce the anion gap, which could mask the presence of an important unmeasured anion. For example, a chronically malnourished alcoholic may present with alcoholic ketoacidosis but also long-standing hypoalbuminemia, which causes a substantial increase in serum bicarbonate (hypoalbuminemia is in fact a state of metabolic alkalosis). The acute ketonemia therefore reduces serum bicarbonate to “normal,” and no anion gap is present. Patients at risk for hypoalbuminemia who present with any significant illness should have serum albumin measured, and if it is low, a normal serum bicarbonate concentration represents a metabolic acidosis. The anion gap can be adjusted to reflect hypoalbuminemia, when albumin is measured in grams per deciliter, by the following formula:

image

A normal anion gap does not exclude clinically significant acidosis or high concentrations of unmeasured anions. Direct measurement of compounds that often produce an elevated anion gap (e.g., lactate, ketones, toxic alcohols) should still be pursued when there is clinical concern despite a normal anion gap.

Independent of bicarbonate levels, sodium and chloride play an important role in acid-base status. When [Na+] − [Cl−], the so-called strong ion difference, is significantly less than 38, an acidosis is present. An alternative to using the anion gap to identify both the presence and cause of acid-base disorders has the clinician start with the base excess (as calculated by a blood gas analyzer), subtract the sodium chloride effect,* and subtract the albumin effect.† What remains is, in the case of metabolic acidosis, the unmeasured anions (e.g., lactate, ketones, uremic acids, toxic alcohols, or other toxins; see later).1

Painful arterial blood sampling is unnecessary for the evaluation of acid-base disturbances. PaCO2, HCO3−, and pH values taken from peripheral venous, central venous, intraosseous, and capillary blood are all suitable for acid-base assessment.2–4

Respiratory Acidosis

Respiratory acidosis occurs when hypoventilation leads to an inappropriately elevated PaCO2 and resulting acidemia. Any condition that reduces minute ventilation may cause respiratory acidosis (Box 124-1). This commonly occurs acutely in the setting of airway embarrassment, pulmonary insults, major trauma, intracranial catastrophe, or central nervous system (CNS) depressants and chronically in progressive lung disease, neurologic muscle weakness conditions, or obesity hypoventilation syndrome. Respiratory acidosis may be accompanied by hypoxemia, which, depending on its pace and severity, will cause end-organ effects such as headache, ischemic chest pain, altered mental status (usually agitation), bradycardia, and circulatory collapse. When tissue oxygenation is adequate, hypercapnia—which is better tolerated than hypoxemia—tends to produce somnolence and obtundation with cerebral vasodilation and resulting elevation of intracranial pressure.

BOX 124-1   Causes of Respiratory Acidosis

Beginning 6 to 12 hours after onset of the insult and progressing for 3 to 5 days, the kidneys respond to a respiratory acidosis by retaining bicarbonate; the resulting compensatory metabolic alkalosis, with an elevated serum bicarbonate level, partially corrects serum pH. Chloride ions are excreted in the urine to increase serum HCO3−; patients with chronic respiratory acidosis (e.g., as seen in chronic obstructive pulmonary disease) are therefore often noted to have hypochloremia. An appropriate metabolic compensation for respiratory acidosis is an increase of approximately 3.5 mEq/L in serum HCO3− concentration for every increase of 10 mm Hg in PaCO2; a patient with chronic respiratory disease resulting in a baseline PaCO2 of 60 mm Hg would therefore be expected to have a serum bicarbonate level of approximately 30 mEq/L (and a slight acidemia).

Acute respiratory acidosis is the most immediately dangerous of the acid-base disturbances; fortunately, it is usually also the most readily treatable, as pulmonary ventilation deficits are quickly addressed by therapies commonly used by emergency physicians. Relief of airway obstruction and provision of either noninvasive or mechanical ventilation will often correct imminently dangerous hypoxemia or hypercapnia as treatments directed at the underlying disorder are initiated.

Patients with chronic respiratory acidosis are often hypoxemic at baseline and may be susceptible to further hypoventilation if normal oxygen saturation levels are promptly restored.5 Typically, a patient with chronic obstructive pulmonary disease being treated for an acute exacerbation receives high-flow oxygen and is later found to be obtunded with profound hypercapnia. It is therefore prudent to target a lower than normal oxygen saturation in patients thought to be so habituated; SpO2 fractions in the low 90s and high 80s are usually well tolerated in this population.6 However, supplemental oxygen must not be withheld from patients with dangerously low oxygen saturation or patients with end-organ hypoxic insults, such as myocardial or cerebral ischemia. In these cases, aggressive oxygenation therapies must be instituted, with preparations made to initiate mechanical ventilation if it is needed.

Patients with chronic respiratory acidosis who have been intubated should receive frequent blood gas analyses; standard ventilator settings applied to patients who chronically hypoventilate may precipitate posthypercapnic metabolic alkalosis. Correction of PaCO2 to normal levels (40 mm Hg) in this group can cause dangerous alkalemia; clinicians should target a slightly acidemic serum pH (~7.35), which, depending on the severity and chronicity of the patient’s baseline respiratory acidosis, may correspond to remarkably high PaCO2 levels.

Respiratory Alkalosis

Respiratory alkalosis occurs when increased minute ventilation causes a decreased PaCO2 and subsequent increase in serum pH. It is often associated with hysterical hyperventilation; however, as always, the emergency physician must consider dangerous conditions before arriving at a psychiatric diagnosis (Box 124-2).

BOX 124-2   Causes of Respiratory Alkalosis

Of particular interest in the differential diagnosis of acute respiratory alkalosis is salicylate toxicity, a dangerous, treatable mixed acid-base disorder (described later) that may be manifested with hyperventilation as its most prominent feature. Suicidal aspirin ingestions often produce the classic syndrome of tinnitus, hyperthermia, confusion, and a variety of metabolic derangements ultimately leading to seizures, coma, and cardiovascular collapse. Chronic salicylism, however, is notoriously subtle in its presentation and occurs in older, sicker patients who have seemingly more likely explanations for their symptoms. Emergency physicians should have a low threshold to obtain a serum salicylate level in cases of unexplained respiratory alkalosis.

Patients with respiratory alkalosis classically complain of lip and extremity paresthesias and may also experience muscle cramps and lightheadedness or even syncope as well as hypocalcemia symptoms, such as carpopedal spasm. The homeostatic response to respiratory alkalosis first involves cellular secretion of H+ in exchange for K+; if respiratory alkalosis persists, the kidneys excrete bicarbonate and retain chloride, leading to a compensatory metabolic acidosis with reduced serum HCO3−, hypokalemia, and hyperchloremia.

Pregnant women hyperventilate throughout gestation and normally have a PaCO2 between 31 and 35 mm Hg, serum pH between 7.46 and 7.50, and serum bicarbonate concentration between 18 and 22 mEq/L. Clinicians should be mindful that eucapnia (PaCO2 ~40 mm Hg) in the pregnant patient may represent hypoventilation.7

As with other acid-base disorders, management of respiratory alkalosis is directed at the underlying cause. When organic causes of respiratory alkalosis have been excluded, hypocapnia symptoms can be relieved in patients with psychological hyperventilation by reassurance. The technique of using a paper bag to cause rebreathing probably works through the placebo effect rather than by changes in PaCO2 and carries the potential danger of inducing hypoxemia.8

Metabolic Acidosis

Metabolic acidosis is defined by a reduced serum bicarbonate concentration. It is a common disorder in emergency department patients and may be a diagnostic challenge for the emergency physician.

Etiology

Metabolic acidosis occurs when acids are added (either by intrinsic processes or from exogenous sources), acid excretion is impaired, or there is inappropriate loss of alkali. Metabolic acidoses are classically divided into normal anion gap and elevated anion gap to assist the clinician in determining their etiology.

Elevated Anion Gap Metabolic Acidosis

The causes of elevated anion gap metabolic acidosis are classically remembered by the mnemonic MUDPILES; however, it is more useful to focus on the identity of the unmeasured anion (Box 124-3). If the cause of an elevated anion gap metabolic acidosis is found to be lactate or ketones, the next step is to determine the cause of the high serum lactate or ketone concentration.

BOX 124-3   Causes of Elevated Anion Gap Metabolic Acidosis

Increased production of lactate is a common cause of elevated anion gap metabolic acidosis, and measurement of serum lactate is indicated when another cause is not apparent. When the elevation of the anion gap is accounted for by serum lactate concentration, the clinician next considers the causes of lactic acidosis; these may be divided into hypoxic or hypoperfusion states (most commonly shock) and exogenous cellular toxins, such as cyanide and carbon monoxide. Idiosyncratic causes of lactic acidosis include short gut syndrome (usually after bariatric surgery),9 reverse transcriptase inhibitor therapy for human immunodeficiency virus (HIV) infection,10 and metformin therapy. The likelihood of metformin causing lactic acidosis is thought to be enhanced by renal failure (serum creatinine > 1.5 mg/dL), congestive heart failure, coexisting metabolic acidosis, and exposure to intravenous radiologic contrast media.

Common unmeasured anions other than lactate that cause an elevated anion gap metabolic acidosis include keto acids (usually from diabetic ketoacidosis), acidic products of exogenous toxins (most importantly, the toxic alcohols), and organic acids that accumulate in renal failure.

Carbon Monoxide and Cyanide.: Exposure to carbon monoxide and cyanide causes lactic acidosis through tissue hypoxia; both are important elements of the differential diagnosis of an elevated anion gap of unknown cause. Although patients extricated from fires have a variety of reasons to have a high lactate concentration, most of these patients, especially if they are obtunded or in cardiac arrest, should be empirically treated for both carbon monoxide and cyanide toxicity. In treatment of cyanide toxicity with suspected coincident carbon monoxide exposure, the nitrite portions of the antidote kit are withheld for concern that the resultant methemoglobinemia will be poorly tolerated given the carboxyhemoglobin burden. Severity of carbon monoxide exposure and treatment requirements may be better predicted by the degree of initial acidemia than by carboxyhemoglobin level.11

Diabetic Ketoacidosis.: Diabetic ketoacidosis is a common acid-base disorder defined by hyperglycemia, ketonemia, and acidemia. It may occur in type 1 insulin-dependent diabetics or type 2 non–insulin-dependent diabetics. Patients with diabetic ketoacidosis classically complain of progressive polyuria, polydipsia, and malaise, but diabetic ketoacidosis may be manifested atypically with chief complaints of vomiting, abdominal pain, or altered mental status. Sodium concentration is not corrected for hyperglycemia when the anion gap is calculated because this dilutional hyponatremia affects other ions in the serum. Diabetic ketoacidosis is often caused by medication noncompliance but may complicate any physiologic stress; when diabetic ketoacidosis is diagnosed, identification of the precipitant is a management priority. Treatment focuses on volume expansion with intravenous fluids, insulin therapy, and careful attention to and replacement of electrolytes, particularly potassium.

Alcoholic Ketoacidosis.: Alcoholic ketoacidosis causes an elevated anion gap metabolic acidosis that may be mistaken for the more common diabetic ketoacidosis. Alcoholic ketoacidosis is usually seen when a long-standing ethanol user abruptly stops drinking; ketones are generated by a combination of malnutrition and dehydration. Patients with alcoholic ketoacidosis may demonstrate a high anion gap, but a mixed acid-base disorder can be due to concomitant ethanol withdrawal, which may cause a respiratory alkalosis, and vomiting, which produces a metabolic alkalosis. The resultant serum pH can therefore be acidemic, normal, or alkalemic. Like diabetic ketoacidosis, alcoholic ketoacidosis includes the symptoms of vomiting, abdominal pain, dehydration, altered mental status, prostration, and lethargy; however, alcoholic ketoacidosis patients generally do not demonstrate hyperglycemia or glycosuria. In alcoholic ketoacidosis, the ratio of the keto acid β-hydroxybutyrate to its metabolites acetoacetate and acetone is double the ratio seen in diabetic ketoacidosis. Urine dipsticks detect acetoacetate but not β-hydroxybutyrate; this causes an apparent worsening of ketonemia as the patient metabolizes β-hydroxybutyrate to acetoacetate, whereas the patient is actually recovering.12 The treatment of alcoholic ketoacidosis is dextrose-containing fluids; insulin is contraindicated.

Methanol and Ethylene Glycol.: Methanol and ethylene glycol, the toxic alcohols, represent an important element of the emergency differential for elevated anion gap metabolic acidosis because their considerable morbidity and mortality can be prevented by timely therapy, and the presence of a wide anion gap may be the most conspicuous sign that this dangerous ingestion has occurred. Toxic alcohols are typically consumed by alcoholics seeking a less expensive drink, by children as an accidental ingestion (usually ethylene glycol, which is sweet), or in a suicide attempt. The first measurable sign of toxic alcohol poisoning is an osmol gap, which precedes the elevated anion gap; as the parent compounds are converted to their toxic metabolites, the osmol gap closes and the anion gap widens. Treatment centers on prevention of the enzymatic conversion of methanol and ethylene glycol into their toxic metabolites by use of either ethanol or fomepizole. Many laboratories will report a spuriously elevated lactate concentration in the presence of glycolate, a byproduct of ethylene glycol poisoning. Isopropyl (rubbing) alcohol ingestion causes intoxication, ketosis, and an osmol gap but does not cause acidosis.

Isoniazid.: Grand mal seizures are associated with high lactate levels that typically resolve within 1 hour. Isoniazid (INH) toxicity is usually listed in the differential for metabolic acidosis, but consideration of INH toxicity should primarily be prompted by intractable seizures because it is the seizures that cause the lactic acidosis, not INH. INH toxicity is an important consideration in these cases because it causes seizures that do not respond to usual treatments of status epilepticus. Continuous seizure activity, in addition to cardiorespiratory embarrassment, causes a profound, life-threatening acidemia from lactate generation. The initial treatment of status epilepticus related to INH toxicity is the administration of vitamin B6 (pyridoxine). Specific therapies targeting nonepileptic causes of seizures, such as hypoglycemia, eclampsia, hyponatremia, and cyanide toxicity, should also be considered in the patient with seizures unresponsive to standard therapy.

Salicylate Toxicity.: Salicylate toxicity first produces a respiratory alkalosis, as described before. Untreated, the syndrome evolves into a complex acid-base disorder with paradoxical aciduria during the initial respiratory alkalosis, followed by an elevated anion gap metabolic acidosis and hyperthermia due to its interference with cellular metabolism. Serum pH can be normal during the initial phase of the disease—a false reassurance. Dehydration, electrolyte disturbances, fatigue, and lung injury ultimately lead to decompensation with respiratory acidosis—completing the so-called triple acid-base disturbance—followed by cardiovascular collapse. Management of aspirin toxicity includes gastrointestinal decontamination, urine alkalinization, meticulous supportive care, and hemodialysis.

Normal Anion Gap Metabolic Acidosis

Normal anion gap metabolic acidosis is less likely to be immediately dangerous or caused by an imminently dangerous condition and is therefore of less interest to the emergency physician. The majority of cases encountered in the emergency department are caused by gastric loss of bicarbonate in the setting of diarrhea. A variety of other conditions and medications may cause a normal anion gap metabolic acidosis (Box 124-4), including renal tubular acidosis and bladder-diverting urologic procedures. An important iatrogenic cause of normal anion gap metabolic acidosis is the rapid infusion of large volumes of normal saline; 0.9% normal saline contains 154 mEq/L of sodium and chloride without bicarbonate or any other buffer and is therefore acidic compared with serum. The hyperchloremic acidosis associated with normal saline therapy is generally well tolerated and causes less physiologic derangement than in acidoses of equal magnitude caused by other mechanisms; however, in patients with existing severe acidemia who require aggressive volume resuscitation, use of a more balanced fluid (lactated Ringer’s solution, Normosol, Plasma-Lyte), especially after the first several liters of normal saline, may be prudent.

BOX 124-4   Causes of Normal Anion Gap Metabolic Acidosis

Management

Management of metabolic acidosis is directed at identification and treatment of the underlying cause while appropriate resuscitative and supportive care is provided. An example of this paradigm is the management of generalized seizures; seizures often cause profound acidemia, but if they are terminated promptly, serum pH normalizes quickly and without sequelae. The treatment of acidemia from seizures is therefore not to treat the acidemia itself but to support the patient through the seizures and terminate the seizures.

When to treat acidemia by actively correcting serum pH, with use of intravenous sodium bicarbonate, is controversial. Theoretic harms of using intravenous sodium bicarbonate to correct acidemia include the following:

Many authors question the utility of bicarbonate therapy even in cases of severe acidemia, given these potential harms and the absence of demonstrated benefit.13 However, although evidence is lacking, it is commonly recommended to treat serum pH less than 7.1 empirically with sodium bicarbonate, 1 mEq/kg, unless the underlying acidosis is thought to be quickly responsive to therapy.14 Many experts will not treat pH above 6.7, however, especially in diabetic ketoacidosis, in which profound acidemia is usually well tolerated while the underlying lesion is corrected. Endpoints of therapy include pH above 7.1 and serum bicarbonate concentration above 10 mEq/L. A bicarbonate drip is prepared by adding 150 mEq sodium bicarbonate (three “crash cart ampules,” which are usually 50 mL of 8.4% solution) to 1 liter of 5% dextrose in water and infusing as slowly as the clinical situation permits. Sodium bicarbonate should generally not be added to normal saline for concern of hypertonicity.

An important clinical pitfall is the use of sodium bicarbonate to treat metabolic acidosis without recognizing a concomitant respiratory acidosis. For example, a severe diabetic ketoacidosis patient with profound metabolic acidosis, after hours of respiratory compensation, may tire; the respiratory alkalosis in this case becomes inadequate, which is then considered a primary respiratory acidosis. Providing ventilatory support to address the respiratory acidosis is much more important than bicarbonate therapy. In an appropriate respiratory compensation for metabolic acidosis, the PaCO2 drops by the same amount as the serum bicarbonate concentration. It is thought that spontaneous respiration cannot sustainably reduce PaCO2 beyond 10 to 12 mm Hg, which is the appropriate compensatory respiratory alkalosis for a metabolic acidosis that drives the pH down to about 7.10. Noninvasive or mechanical ventilation may be required to prevent a more severe acidemia, which is likely to result in multiorgan dysfunction.

Although administration of sodium bicarbonate is unlikely to be beneficial in most cases of acidemia caused by endogenous acid production (lactic acidosis, ketoacidosis), sodium bicarbonate therapy is theoretically more attractive in conditions in which the underlying problem is bicarbonate loss (which generally causes a hyperchloremic or normal anion gap metabolic acidosis) or impairment of acid secretion, such as renal failure. Many of the acidosis syndromes caused by exogenous toxins (aspirin, heterocyclic antidepressants) call for bicarbonate as a specific therapy; these cases are distinct from the empirical use of bicarbonate to treat the acidemia itself.

Bicarbonate has been variously recommended and used as an empirical therapy in cardiac arrest. However, most studies show either no benefit or poorer outcomes in this context, and the 2010 American Heart Association guidelines state that routine use of sodium bicarbonate is not recommended for patients in cardiac arrest.15

In summary, sodium bicarbonate should not routinely be used to treat undifferentiated acidemia or acidemia caused by lactic acidosis or ketoacidosis. If the serum pH is so severely depressed that the acidemia itself is thought to be an immediate life threat, bicarbonate therapy is an option. A lower treatment threshold is appropriate in acidemia caused by bicarbonate loss or renal failure, and bicarbonate should not be withheld when it is specifically indicated to treat the underlying cause of an acidosis.

Acidemia causes hyperkalemia as H+ is brought into cells in exchange for K+. Clinicians managing patients with acid-base disturbances should therefore carefully monitor serum potassium concentration; as the acidosis resolves, serum potassium level will fall and may require supplementation. This is classically seen in diabetic ketoacidosis patients, who are invariably potassium depleted irrespective of their initial serum potassium concentration.

Metabolic Alkalosis

Metabolic alkalosis occurs from the loss of H+ or retention of HCO3−. Emergency physicians encounter metabolic alkalosis usually as a consequence of prolonged vomiting or nasogastric suction or as a compensation for chronic respiratory acidosis. The differential diagnosis includes a variety of predominantly endocrine and electrolyte disorders (Box 124-5). Patients taking diuretic medications may reduce their plasma volume around a steady concentration of HCO3−, causing a contraction alkalosis. Contraction alkalosis is often coincident with hypokalemia, which itself causes a metabolic alkalosis as intracellular K+ is exchanged for H+.

BOX 124-5   Causes of Metabolic Alkalosis

In the acute phase, the lungs compensate for a metabolic alkalosis by decreasing minute ventilation and retaining carbon dioxide, although from the perspective of an emergency physician, an acute elevation in PaCO2 is a primary respiratory acidosis until dangerous causes of ventilatory insufficiency have been excluded. Prolonged metabolic alkalosis leads to compensatory renal HCO3− excretion.

Metabolic alkalosis rarely causes dangerous alkalemia, and the emergency management of metabolic alkalosis is directed at identification and treatment of dangerous underlying causes. Usual management of patients who have volume loss, vomiting, or hypokalemia will address the resulting saline-responsive metabolic alkalosis. Edematous or euvolemic patients with conditions that cause renal Na+ retention (and accompanying H+ loss) may have a saline-resistant metabolic alkalosis, but this generally does not require emergency therapy. In rare cases, severe metabolic alkalosis may cause hypocalcemic tetany, seizures, altered mental status, or dysrhythmias and require empirical therapy in the emergency department, usually in consultation with nephrology, with either acetazolamide or hydrochloric acid.

Mixed Disorders

A simple acid-base disorder is a combination of a primary disturbance and subsequent compensation. Mixed acid-base disorders occur when two or more primary acid-base lesions coincide. These simultaneous conditions may push the serum pH in the same or opposite directions, and each will generate its own compensatory responses; mixed disorders may therefore be difficult to recognize by either clinical or laboratory features. Most often in emergency department patients with mixed acid-base disorders, there is a dominant, precipitating problem that either complicates an existing disease or causes failure of compensatory mechanisms.

Detailed acid-bases analysis is not typically performed in the emergency department; however, knowledge of frequently used acid-base assessment concepts and common conditions that cause a mixed disturbance is valuable. The body usually does not fully compensate for a primary acid-base disorder, so, for example, a primary metabolic acidosis should generate a compensatory respiratory alkalosis, but the serum pH is expected to still be below 7.36. Whether an appropriate respiratory compensation to a metabolic acidosis has occurred can be approximated by comparing the PaCO2 to the last two digits of the serum pH. In a primary metabolic acidosis with appropriate respiratory compensation, these two values should be similar, that is, a patient with a serum pH of 7.20 should have a PaCO2 of 20 mm Hg. If the serum pH is 7.17 and the PaCO2 is 30 mm Hg, the respiratory compensation is less than expected and a primary respiratory acidosis is present. This is commonly seen in patients whose dominant condition causes a metabolic acidosis but also impairs respiration, such as sepsis.

The delta gap (ΔG) describes the difference between the deviation of the anion gap (AG) from normal and the deviation of the serum bicarbonate concentration from normal:

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Conceptually, calculation of the delta gap asks whether the anion gap is accounted for by the change in serum bicarbonate concentration. In patients with an elevated anion gap and a delta gap greater than +6, meaning that serum bicarbonate level is significantly higher than would be predicted by the number of unmeasured anions, a metabolic alkalosis in addition to a metabolic acidosis is likely to be present. This is commonly seen when the dominant acidosis condition causes severe vomiting (e.g., diabetic ketoacidosis). In patients with an elevated anion gap and delta gap more negative than −6, meaning that the serum bicarbonate level is significantly lower than expected given the anion gap, a normal anion gap metabolic acidosis is likely be present in addition to the elevated anion gap metabolic acidosis. This is seen most commonly when a lactic acidosis complicates severe diarrhea.

Key Concepts

image Patients with an acute severe metabolic acidosis rely on a robust respiratory compensation; in these cases the adequacy of the ventilatory response should be assessed and augmented, with noninvasive or invasive ventilation, if needed.

image Patients who have a chronic respiratory acidosis (e.g., in chronic obstructive pulmonary disease) are at risk for dangerous alkalemia if they are ventilated with routine parameters. Blood gas analysis in these cases should be performed frequently and settings titrated to serum pH.

image Alcoholic ketoacidosis may be manifested similarly to diabetic ketoacidosis but is much less common; insulin is considered contraindicated in alcoholic ketoacidosis.

image When an elevated anion gap is recognized, the initial assessment focuses on identifying its etiology as belonging to one of four causes: ketoacidosis, toxic ingestions, lactic acidosis, and renal failure (typically, only chronic renal failure causes significant acidosis).

image When the cause of an elevated anion gap is determined to be lactate or ketones, diagnostic efforts are directed at identifying the cause of the lactic acidosis or ketoacidosis.

image Sodium bicarbonate is not recommended for the empirical treatment of acidemia; it is an option in cases of severely depressed pH thought to pose an immediate life threat.

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*Sodium chloride effect = [Na+] − [Cl−] − 38.

†Albumin effect = 2.5(4.2 − [albumin]).

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