Chapter 21. Acid–Base Disorders

The assessment of an emergency patient's acid–base status must begin with a clinical suspicion that an underlying acid–base disorder exists. That an acid–base disorder might exist in a patient presenting obtunded, hypotensive, hypoperfused, or obviously in extremis is rarely surprising. Patients with more subtle presentations or chronic, well-compensated acid–base disorders often elude clinicians in today's busy and overtasked emergency departments. One must remain diligent for clinical signs, astutely reviewing basic electrolyte panels, and remain open to the possibility that a patient may be or become more ill than he or she first appears. Knowing when to investigate for the possibility of an acid–base disorder or evaluate for complex mixed acid–base disorders requires astute clinical acumen. Unfortunately, many emergency providers today lack the ability to perform mixed acid–base assessments with facility, and many mixed or complex disorders, no doubt, go undiagnosed or undertreated.

In this chapter, we hope to review the measures of acid–base status routinely available to the emergency medicine critical care practitioner, their utility, as well as their liabilities. Using these measures, this chapter will provide a rational guide to the interpretation and initial management of a patient's acid–base status.

The Henderson–Hasselbalch equation in its original form IS of limited clinical utility AND is given as follows:

The Kassirer–Bleich equation is obtained by inserting known constants into the Henderson–Hasselbalch equation and then taking the antilog of each side.1 The resultant equation is much more conceptually useful in understanding clinical acid–base interactions:

The Kassirer–Bleich equation makes clear the interactions between the Pco2, the bicarbonate concentration, and the free hydrogen ion concentration. If any two of these values are known, the other can be calculated.

Serum Bicarbonate

The serum bicarbonate concentration is often one of the first pieces of measured laboratory data available for clinical assessment of acid–base status. Regardless of how it is labeled when reported, this value is actually a measured total CO2 concentration.2 The total CO2 concentration is a combination of bicarbonate, carbonic acid, and dissolved carbon dioxide. The amount of dissolved carbon dioxide can be calculated if the measured Pco2 is known by multiplying the Pco2 by the solubility coefficient of CO2 in the blood, 0.03. Hence:

Most of the time, the relative contribution of the Pco2 to this value is negligible, and as such is commonly ignored. It can become a significant factor in the hypercapnic patient, leading to reported total bicarbonate levels higher than would be reflected by a true assessment of the [HCO3].

The reported serum bicarbonate can be a good initial indicator of the presence of an uncomplicated metabolic acidosis. As we can see from the Kassirer–Bleich equation, a rise in [H+] (decreasing pH) will necessitate an increase in the ratio of Pco2 to [Hco3−], and this will usually show up as a decreased serum bicarbonate measure. Following repeated serum bicarbonate measures is often performed to record the response to treatment for simple organic metabolic acidoses, such as ketoacidosis or lactic acidosis, when simple and relatively noninvasive measures are desired, and when complex mixed acid–base disorders have been excluded.

The serum bicarbonate is, however, not a very sensitive measure, and does not allow on its own for an analysis of the underlying disorder. In the presence of hypercapnia, as mentioned above, it can be higher than anticipated with an underlying acidemia due to the contribution of the Pco2 and respiratory compensation. Patients with chronic lung disease or metabolic compensation can have markedly elevated serum bicarbonates at baseline, and without an appreciation for that baseline, a “normal” value can be falsely reassuring. Primary respiratory acidosis or alkalosis will produce a compensatory change in the bicarbonate levels, and can mask a mixed acid–base disorder. Reliance on the measured serum bicarbonate as a solitary measure of acid–base status should only be entertained in a simple patient without suspicion for underlying compensation and an unambiguous clinical picture.

Arterial Blood Gas

The arterial blood gas (ABG) remains the mainstay for acid–base interpretation. While not always necessary for the identification and management of an acid–base disorder, a thorough understanding of the reported values and how to interpret them is essential. Laboratories will report values for pH, Pco2, Po2, [HCO3], base excess (BE) (or deficit), and percent oxygen saturation.

The pH of the blood, normally between 7.35 and 7.45, is an assessment of the free hydrogen ion concentration in the blood. A blood pH of less than 7.35 is called acidemia; a blood pH of greater than 7.45 is called alkalemia. The pH is measured in the lab with an electrode permeable only to hydrogen ions.

The Pco2 and Po2 are the partial pressure of dissolved CO2 and O2 in the blood, respectively. They are also measured values obtained by using electrodes specific to the respective gasses.

The [HCO3] as reported with a blood gas is calculated by using the measured pH and the measured Pco2 using the Henderson–Hasselbalch equation. While some advocate that the measured [HCO3] (or total CO2 concentration) as reported in an electrolyte panel is a more reliable figure, that measured value can be flawed for the reasons discussed above. It is doubtful that either the calculated or measured [HCO3] can uniformly be considered a more “true” assessment of the serum [HCO3]. One should be aware of the liabilities of each approach when attempting to interpret discrepancies between the two.

The BE is an estimation of the amount of acid it would take to titrate 1 L of blood back to a normal pH of 7.40, assuming the Pco2 were adjusted to a normal of 40 mm Hg. The BE is usually reported in units of milliequivalent per liter. It is calculated from the measured pH and the calculated [HCO3−] according to the following equation3:

In an acidosis, the BE is a negative value, and is often referred to as a base deficit. The BE is often used as a marker for metabolic acidosis, and is more reliable than the serum bicarbonate concentration as such, as it is adjusted for the effect of a concomitant respiratory disorder.

The oxygen saturation reported on a blood gas analysis is also a calculated value using the measured Po2 and pH, based on the anticipated hemoglobin oxygen dissociation curve for that given pH.

There is an important distinction to be made between acidemia and acidosis, as well as between alkalemia and alkalosis. Acidemia and alkalemia refer to the relative abnormalities in the blood pH. Acidosis and alkalosis refer to an underlying disease process. It is possible in mixed acid–base disorders to have a low pH, hence be acidemic, while having a concurrent metabolic alkalosis. An example of this might be an acidemic diabetic ketoacidosis patient with a low pH and a primary metabolic acidosis, who also has a concurrent metabolic alkalosis (but not alkalemia) brought about by vomiting and resultant hydrogen ion depletion.

What follows is a five-step approach to the interpretation of acid–base status2,4–8 (see Table 21-1). Whether this approach or another is used by an individual provider is not as important as is the practice that every assessment of acid–base status go through a sequenced and methodical analysis, every time.

Step 1: Is there a primary acidemia or alkalemia? Look at the pH as determined by the blood gas. A pH of less than 7.35 demonstrates acidemia, while a pH of greater than 7.42 demonstrates alkalemia. The direction in which the pH is deviated from normal is the effect of the primary acid–base disorder affecting the patient. While compensation for the primary disorder will decrease the effect of the primary disorder, it will never bring the pH back entirely to a normal range.

Step 2: Is the primary disorder respiratory or metabolic? Look at the Pco2 from the blood gas and the serum HCO3. Whether to use the measured total bicarbonate from an electrolyte profile or the calculated HCO3 from a blood gas analysis remains a debate, although these authors, as a matter of routine practice, use the measured value from the electrolyte profile. In acidemia, a high Pco2 suggests a primary respiratory acidosis, usually accompanied by an elevated [HCO3] representing metabolic compensation. A low [HCO3] suggests a primary metabolic acidosis, usually accompanied by a low Pco2, representing a partial respiratory compensation. In alkalemia, a low Pco2 suggests a primary respiratory alkalosis, usually accompanied by a low [HCO3] representing a partial metabolic compensation. A high [HCO3] suggests a primary metabolic alkalosis, usually accompanied by a high Pco2, representing a partial respiratory compensation (see Table 21-2).

Step 3: Is there appropriate compensation for the primary disorder? In primary metabolic disorders, there should be rapid compensation for the resultant acidemia or alkalemia by the respiratory system.

Metabolic acidosis: In primary metabolic acidosis, the body will attempt to normalize the acidemia by “blowing off” CO2. The formula of Winters and coworkers is used to calculate the predicted Pco2 given the [HCO3]9:

If the measured Pco2 is less than expected, then the patient is blowing off his or her CO2 more than would be required to compensate for the primary metabolic acidosis, and a concomitant respiratory alkalosis is present. If the measured Pco2 is higher than expected, then the patient is failing to blow off enough CO2 to compensate for the primary metabolic acidosis, and a concomitant respiratory acidosis is present.

Metabolic alkalosis: In primary metabolic alkalosis, the body will attempt to normalize the alkalemia by retaining CO2. The expected increase in Pco2 should be approximately 0.6 times the increase in the [HCO3]:

If the measured Pco2 is less than expected, then a concomitant respiratory alkalosis is present. If the measured Pco2 is greater than expected, then a concomitant respiratory acidosis is present. A caveat to this rule is the fact that even in profound metabolic alkalosis, the Pco2 will rarely rise above 50 mm Hg, which represents the upper limit of normal respiratory compensation.10 If the expected Pco2 is greater than 50 mm Hg, failure to compensate fully is likely due to exceeding the limits of the respiratory compensatory mechanism rather than to a concomitant underlying respiratory alkalosis.

Respiratory alkalosis/acidosis: In primary respiratory acid–base disorders, the metabolic compensation for the primary disorder increases over time. The acute compensation occurs as a result of the bicarbonate buffering system, and occurs over the first 24–48 hours. Chronic compensation comes about as the result of the kidneys' ability to increase or decrease production of bicarbonate and to increase bicarbonate resorbtion or excretion. Chronic compensatory changes are usually seen from 72 hours and beyond. The clinician must decide, based on the history and clinical presentation, how acute the primary respiratory disorder is likely to be before being able to assess the appropriateness of the metabolic compensation. Likewise, a metabolic compensation greater or less than expected may prompt a reassessment of the acuity of the primary disorder.

In acute primary respiratory acidosis, the [HCO3] should increase by 1 mEq/L for every 10 mm Hg increase in the Pco2. In a chronic primary respiratory acidosis, the [Hco3] should increase by 4 mEq/L for every 10 mm Hg increase in the Pco2.

In acute primary respiratory alkalosis, the [HCO3] should decrease by 2 mEq/L for every 10 mm Hg decrease in the Pco2. In a chronic primary respiratory alkalosis, the [HCO3] should decrease by 5 mEq/L for every 10 mm Hg decrease in Pco2.

If the [HCO3] is lower than expected, then a concomitant metabolic acidosis may be present. If the [HCO3] is higher than expected, then a concomitant metabolic alkalosis may be present. It is clearly not possible for a respiratory acidosis and a respiratory alkalosis to coexist.

Step 4: Calculate the anion gap. Regardless of the primary acid–base disturbance, the anion gap (AG) should be calculated. Although the AG has limitations as a screening tool, an elevated AG should be presumed to indicate the presence of an AG acidosis. Metabolic compensation for a primary respiratory alkalosis should not elevate the AG.

Step 5: If there is a metabolic acidosis, is there another concomitant metabolic disturbance? This step is key to recognizing mixed metabolic acid–base disorders. Regardless of the primary acid–base disorder, if either step two or three identified a metabolic acidosis, proceed with the following calculations:

If there is an AG metabolic acidosis (an AG >12), then calculate the delta gap (Δgap). The Δgap is a tool that will help to reveal a concomitant metabolic alkalosis or non-AG acidosis when an AG metabolic acidosis has been found.11 In a simple AG metabolic acidosis, the increase in the AG above normal should be matched millimolar for millimolar by a fall in the [HCO3]. Let us assume the upper normal of the AG to be 12 mmol/L, and the lower normal of the [HCO3] to be 22 mmol/L. If we ascribe the ΔAG to be the rise in the AG above the upper limit of normal, that is:

and the Δ[HCO3] to be the fall of the [HCO3] below normal, that is:

then the Δgap can be calculated as follows:

Given that in a straightforward AG acidosis, the rise in an AG should be perfectly matched by a fall in the [HCO3], we should expect a Δgap of zero. In practice, a 2 standard deviation from the mean variation in the Δgap would give us normal values ranging from −6 to +6.11

If the Δgap is less than −6, it suggests a loss of [HCO3] greater than should be anticipated by the AG acidosis known to exist. This suggests a concomitant non-AG acidosis. If the Δgap is greater than +6, the reduction in bicarbonate is not as great as should be expected by the known AG acidosis, and a concomitant metabolic alkalosis exists.

If there is a non-AG metabolic acidosis, then for every unit increase in the [Cl], there should be a unit decrease in the [HCO3]. Remembering the discussion of electroneutrality when we looked at the AG, a decrease in the [HCO3] must be accompanied by an increase in the [Cl] or in another unmeasured anion. If the increase is in an unmeasured anion, then an increase in the AG results. Since in a non-AG metabolic acidosis, we have already established a normal AG, the [Cl] must increase proportional to the decrease in [HCO3]. If we assume a normal chloride to be 100 mmol/L, then for every 1 mmol/L increase in the chloride, we should expect a 1 mmol/L decrease in the [HCO3], that is:

If the measured [HCO3] is more than 5 mmol/L greater than expected (to allow for a 2 standard deviation range) based on the chloride concentration, then a concomitant metabolic alkalosis is present.

Respiratory Acidosis

Any etiology that limits the effective minute ventilation will result in decreased ventilation and in turn an increase in Pco2, leading to a respiratory acidosis. A list of possible causes of respiratory acidosis is shown in Table 21-3.

Treatment of a primary respiratory acidosis should be aimed at correcting the lack of respiratory drive, reducing the effective dead space, or increasing the minute ventilation. Remember that respiratory acidosis, if not the primary acid–base disorder, may be an appropriate compensation for a metabolic alkalosis! Make sure to rule out a mixed acid–base disorder before correcting it.

Respiratory Alkalosis

Respiratory alkalosis results from excessive minute ventilation and a resultant decrease in the Pco2. Potential causes of a respiratory alkalosis are shown in Table 21-4. Hypocapnic patients are not always alkalemic, and a respiratory alkalosis is a common compensation for metabolic acidosis. As in a respiratory acidosis, respiratory alkalosis may be an appropriate compensation, and caution should be entertained in ascribing a respiratory alkalosis to psychogenic hyperventilation until an underlying mixed acid–base disorder has been ruled out. Salicylate toxicity in particular can result in severe metabolic acidosis, and any treatment that removes or inhibits respiratory compensation, which can at times seem severe, may rapidly worsen the underlying acidemia.

Metabolic Alkalosis

Metabolic alkalosis is characterized by an increase in the [HCO3]. It is brought about by the excess loss of hydrogen ions, the endogenous administration of bicarbonate or another anion such as lactate, acetate, or citrate, or, most commonly, the increased reabsorption of bicarbonate.

A metabolic alkalosis is classified as chloride responsive or chloride resistant based on the spot urine chloride concentration. A chloride-responsive metabolic alkalosis presents with a low urinary chloride concentration of less than 15 mEq/L, suggesting total body chloride depletion and in turn renal retention of chloride. In order to maintain electrical neutrality, low [Cl−] is accompanied by a retention of HCO3−, and it is this retention of HCO3− that brings about the resultant alkalosis. As such, chloride-responsive metabolic alkalosis is more of a problem of chloride balance than of bicarbonate balance, and restoration of chloride is what is needed to allow the kidneys to normalize the [HCO3−] and in turn the alkalosis. Chloride-responsive metabolic alkaloses are due to gastrointestinal losses of chloride because of gastric suctioning (direct loss of hydrochloric acid [HCl]), volume depletion (reduction in space of distribution of HCO3−), or diuretic therapy (loss of NaCl and reduction in space of distribution of HCO3−).12 Chloride-responsive metabolic alkalosis is almost always associated with a volume deficit as well, and treatment should be aimed at correcting both the volume deficit and the chloride deficit, something which is most easily accomplished with normal saline (0.9% NaCl).13 The total deficit of chloride can be calculated according to the following equation:

The volume of saline, in liters to be infused, necessary to correct the chloride deficit can then be calculated by taking the chloride deficit and dividing by 154 mEq/L (the chloride concentration of normal saline). Infusion of dilute concentrations of HCl can also be utilized to replete both hydrogen ion and chloride stores in severe cases of chloride-responsive metabolic alkalosis, although normalization of volume status with isotonic saline is recommended first.

Chloride-resistant metabolic alkalosis is characterized by a high urinary spot chloride concentration greater then 25 mEq/L. It can be brought about by either mineralocorticoid excess or profound hypokalemia.

In a state of mineralocorticoid excess, such as Cushing's syndrome or excessive mineralocorticoid administration, the kidneys inappropriately retain HCO3− via an aldosterone-mediated pump in the proximal tubule. The workup should be aimed at identifying and correcting the underlying cause of the mineralocorticoid excess. Acetazolamide, by blocking carbonic anhydrase, can inhibit the reabsorption mechanism in the proximal tubule and help promote appropriate renal excretion of HCO3−, as well as facilitate diuresis of the fluid overload that typically accompanies this state.

Hypokalemia causes an intracellular shift of hydrogen ions resulting, by means of a shift of the bicarbonate buffering equation to the left, in a relative excess of HCO3−. In this case, repletion of potassium along with volume repletion, if required, should correct the alkalemia.

In all cases of metabolic alkalosis, careful consideration should be made to the potential exogenous sources of alkali in the patient's medications and fluids. Acetate, citrate, or lactate in parenteral infusions, blood transfusions, or IV fluids should be considered. One of the most common causes of metabolic alkalosis, as mentioned below, is an inadvertent “overshoot” metabolic alkalosis that results from overly aggressive or inappropriate administration of alkali as treatment for metabolic acidosis.

See Table 21-5 for a review of the common causes of metabolic alkalosis.

Metabolic Acidosis

Metabolic acidosis is brought about due to the loss of extracellular bicarbonate (diarrhea, renal loss of bicarbonate, enterocuteneous fistulae), the accumulation of an endogenously produced organic acid (lactic acidosis, ketoacidosis), or the administration of an acid (salicylate, methanol, ethylene glycol, etc.).

The Anion Gap

The AG is utilized to evaluate patients with a metabolic acidosis. Metabolic acidosis can come about either due to an increase in hydrogen ion concentration or due to a loss of bicarbonate. The AG helps differentiate between these two possibilities.

The concept of electroneutrality dictates that the charge of all positively charged ions in the body must be matched by an equivalent charge of negatively charged ions. The AG is the difference between the total concentration of the predominant cation (Na+) and the total concentration of the predominant anions (Cl−, HCO3−):

The value of the AG represents the normal difference between the concentrations of cations and anions not included in the AG calculation. The cations and anions that normally contribute to the AG are shown in Table 21-6. Normal values for the AG vary slightly depending on the techniques of an individual lab. The original normal range for the AG was 8–16 mEq/L, although newer laboratory techniques have resulted in a lower normal range of 3–11 mEq/L.14 This value represents the value of the relative charge superiority of unmeasured anions relative to unmeasured cations.

A metabolic acidosis that results in the accumulation of excess hydrogen ions will cause an increased AG. We will refer to this as an AG metabolic acidosis. This comes about because the excess hydrogen ions bind with free bicarbonate ions to form carbonic acid, driving the carbonic acid buffering equation to the right, resulting in a decreased concentration of bicarbonate:

This reduced bicarbonate concentration results in a reduced measured anion concentration, and in turn a larger AG. Caution is advised in relying too heavily on the AG as a screening measure of acidosis, especially in a clinical context where strong suspicion for organic acidosis exists. While elevated lactic acid levels should bring about a corresponding large AG, multiple studies have shown that the AG fails to predict lactate levels in both critically ill medical and trauma patients.15–17 In the event that an organic acidosis is strongly suspected, measuring blood levels of the organic acid directly (lactate in lactic acidosis, acetate or β-hydroxybutyrate in ketoacidosis) more reliably detects or excludes the underlying disorder.

In contrast, a metabolic acidosis that comes about as a result of a loss of bicarbonate from the extracellular fluid does not result in an increase in the AG. At first, this might seem counterintuitive. When a metabolic acidosis is brought about by bicarbonate loss, however, the kidneys maintain electroneutrality by retaining chloride ions. Since both chloride and bicarbonate are measured anions, the total contribution of measured anion concentration to the AG remains unchanged, although the relative ratio of chloride to bicarbonate will increase. We will refer to this as a non-AG metabolic acidosis, although because of the elevated relative chloride concentration you may see non-AG metabolic acidosis sometimes referred to as hyperchloremic metabolic acidosis.18

Anion Gap Metabolic Acidosis

As mentioned above, an AG metabolic acidosis is brought about by the accumulation of excess hydrogen ions and the subsequent reduction in the bicarbonate concentration by means of the carbonic acid buffering system. Since the extracellular fluid must remain electrically neutral, the reduction in bicarbonate concentration must occur concurrently with an increase in another anion. The unmeasured anion that replaces bicarbonate in maintaining electrical neutrality is the conjugate base to the acid that gave off the excess hydrogen ion. In the case of lactic acidosis, lactic acid gives off its hydrogen ion, leaving behind lactate, a negatively charged ion:

Acids causing an AG metabolic acidosis can be inorganic (sulfate, phosphate), organic (lactate or ketoacids), or exogenous (salicylates). The most common causes of an AG metabolic acidosis can be remembered by the acronym A CAT MUDPILES (see Table 21-7).4,19 A careful history and exam combined with confirmatory tests will help narrow the differential diagnosis.

Nonanion Gap Metabolic Acidosis

Non-AG metabolic acidosis is caused not by the addition or accumulation of an acid, but by the loss, through either renal or gastrointestinal means, of bicarbonate. Causes of non-AG metabolic acidosis are shown in Table 21-8.19

The urine AG can be utilized to distinguish between renal and gastrointestinal etiologies for a non-AG metabolic acidosis.5 The urine anion gap (UAG) is calculated by obtaining the spot urine electrolyte values for Na, K, and Cl as follows:

In the event of renal loss of HCO3, the UAG would be large, as bicarbonate is not measured in the UAG and would account for a large amount of the urinary ions. In the event of gastrointestinal loss of bicarbonate, the kidneys would be retaining HCO3, and the UAG would approximate zero.

Bicarbonate does not function well as a buffer, in the strictest sense of the word, at near-physiologic pH.13 The dissociation constant or pK of the carbonic acid–bicarbonate buffering system is 6.1. If we assume that the effective range of a buffering system is within 1 pH unit of its dissociation constant (the pH level at which the acid is 50% dissociated), then the carbonic acid–bicarbonate buffering system should work effectively between a pH of 5.1 and 7.1, but would clearly not be an effective buffer at near-physiologic pH. This would be true under laboratory conditions were we simply titrating an acid. In the body, however, the respiratory system has the ability to remove CO2. As H2CO3 is formed by the buffering of excess H+ by HCO3−, the subsequent increased CO2 can be removed via increased ventilation, pulling the buffering equation to the right, and significantly extending the effective buffering range of the system.10

The administration of NaHCO3 solutions in an attempt to increase serum pH has been a long-standing practice and one that, on the surface, would appear to make empirical sense. The principal concern for a patient in severe acidosis (pH <7.10) is for impaired cardiac contractility.20 Other effects of severe acidosis include centralization of blood volume, cardiac sensitization to dysrhythmias, hyperkalemia, respiratory fatigue, increased metabolic demands, insulin resistance, and obtundation or coma.21 Clinicians often are confronted by a desire to normalize a severely acidotic pH, and the tool in our armamentarium that has been used for that purpose has been NaHCO3. Arguments in favor of directly correcting an acidosis with alkali therapy hinge on two presumptions: (1) correction of the acidosis independent of addressing the underlying cause is beneficial and (2) administration of sodium bicarbonate solutions effectively corrects or improves acidosis. Neither is necessarily the case.

The administration of NaHCO3 solutions has not been associated with decreased mortality, and can cause significant complications. In laboratory conditions, acidosis has been shown to be protective for ATP-deprived liver cells, delaying the onset of cell death.22 If we presume this to be true in vivo, then correction of acidosis without normalization of the underlying causative disorder would be harmful. The exogenous administration of NaHCO3 also pushes the carbonic acid buffering equation to the right:

This increases the Pco2, increasing the respiratory burden for clearing CO2. In the absence of capability to increase respiratory excretion of CO2, the net effect of NaHCO3 administration may be to paradoxically lower the pH due to the increased Pco2. In an intact organism, a severe acidemia may have already brought about a maximal respiratory effort at compensation, making the lungs unable to accommodate the increased CO2 burden. In a patient with fixed ventilation, as on a ventilator, the administration of NaHCO3 often produces a paradoxical acidosis as the patient is unable to accommodate the increased CO2 burden.

The objective when treating an organic acidosis, where an acidotic pH is almost always a marker for an underlying derangement in need of correction and not a problem itself in need of normalization, should be to correct the underlying cause of the acidosis. Restoration of tissue perfusion in lactic acidosis and of nutritional substrate in alcoholic ketoacidosis, and the administration of insulin in diabetic ketoacidosis should completely correct the underlying acidosis.23 The administration of alkali solutions to these patients concomitant with the correction of the underlying disorder almost universally causes an overshoot alkalosis.

If a severe acidosis (pH <7.10) is present, the administration of alkali therapy may be required in bicarbonate-loosing metabolic acidosis such as profound diarrhea or renal tubular acidosis, where the body's production of HCO3 cannot keep pace with losses. Alkali therapy can also provide a temporizing measure in the renal failure patient who develops a metabolic acidosis while hemodialysis is arranged, as such a patient will be incapable of renal compensation and increased bicarbonate production or acid excretion. Alkali therapy may also be considered in the event of massive exogenous acid ingestion that exceeds the capabilities of compensatory mechanisms, such as occurs in salicylate or toxic alcohol ingestion. In this case, the additional CO2 transport capability supplied by sodium bicarbonate may prove a temporizing measure while arranging for hemodialysis in order to remove the exogenous acid.

If the decision is made to administer sodium bicarbonate, the goal should be to partially correct a severe acidosis to no greater a pH than 7.2, so as to prevent a reflex alkalosis after overcorrection. Inherent in the administration of sodium bicarbonate is the administration of a not insignificant amount of sodium. While commercially produced solutions are available, in practice an infusion is usually made by mixing 150 mEq (three standard 50-mEq ampoules) in 1 L of 5% dextrose in water (D5W) or 100 mEq (two standard 50-mEq ampoules) in 1 L of 0.25% sodium chloride (0.25% NaCl), yielding a near-isotonic solution.21 The distribution of bicarbonate varies depending on the degree of acidosis, and is about 50% of lean body weight at normal pH, but increases upwards of 70% lean body weight in severe acidosis (pH <7.10).10 If we presume to only be utilizing the administration of sodium bicarbonate in the presence of severe acidosis, and without correction upwards of a pH of 7.20, we can use 60%, or 0.6, as an estimation of the distribution of bicarbonate. Our goal should be to correct the pH to no greater than 7.20, which according to the Henderson–Hasselbalch equation should correspond to a [HCO3] of 10 mmol/L. The bicarbonate deficit can be calculated according to the following equation:

The total calculated deficit should be given slowly as an infusion. The net effect of the infusion will not be manifest until upwards of 30 minutes following the infusion. It is important to stress that continuing a bicarbonate infusion until normalization of pH is observed will uniformly result in an often poorly tolerated “overshoot” alkalosis. As such, only the calculated dose should be infused, and further alkali therapy directed by subsequent blood gas and electrolyte analysis.

Alternate alkali infusions have been developed that have theoretical advantages over sodium bicarbonate including carbicarb (a 1:1 solution of sodium bicarbonate and disodium carbonate) and THAM (0.3N tromethamine). No clinical trial has demonstrated either agent to be superior to sodium bicarbonate, and their clinical use is not indicated.10,23