BASIC CONCEPTS

Hydrogen Ion Concentration and pH

The hydrogen ion concentration [H+] in aqueous solutions is traditionally expressed by the
pH, which apparently means the power of hydrogen, and is a logarithmic function of the
[H+]; i.e.,

The physiological range of pH and corresponding [H+] is shown in Table 31.1. The normal
pH of plasma is indicated as 7.40, which corresponds to a [H+] of 40 nEq/L.
Features of the pH
The relationships in Table 31.1 illustrate 3 unfortunate features of the pH: (a) it is a
dimensionless number, which has no relevance in chemical or physiological events, (b) it
varies in the opposite direction to changes in [H+], and (c) changes in pH are not linearly
related to changes in [H+]. Note that as the pH decreases, the changes in [H+] become
gradually larger with each change in pH. This means that changes in pH will have different
implications for acid-base balance at different points along the pH spectrum.
Although it is unlikely that the pH will be abandoned, it is not a representative measure
of the acid-base events in the body.

Hydrogen Ions as a Trace Element

Also evident in Table 31.1 is the fact that [H+] is expressed as nanoequivalents per liter
(nEq/L). One nanoequivalent is one-millionth of a milliequivalent (1 nEq = 1×10-6 mEq), so
hydrogen ions are about a million times less dense than the principal ions in extracellular
fluid (sodium and chloride), whose concentration is expressed in mEq/L. This gives hydrogen
ions the status of a trace element. How can such a small quantity of an ion have all the effects
attributed to acidosis and alkalosis? Other trace elements certainly have important biological
effects, but it is also possible that changes in the [H+] are just one of several physicochemical
changes that are taking place in the extracellular fluid.
This would explain why the same degree of acidosis is more life-threatening in lactic acidosis
than in ketoacidosis (as described in the next chapter); i.e., the acidosis is not the problem.
Classification of Acid-Base Disorders
According to traditional concepts of acid-base physiology, the [H +] in extracellular fluid is
determined by the balance between the partial pressure of carbon dioxide (PCO2) and the
concentration of bicarbonate (HCO3) in the fluid. This relationship is expressed as follows
(1):

The PCO2/HCO3 ratio identifies the primary acid-base disorders and secondary responses,
which are shown in Table 31.2.
Primary Acid-Base Disorders
According to equation 31.2, a change in either the PCO2 or the HCO3 will cause a change in
the [H+] of extracellular fluid. When a change in PCO2 is responsible for a change in [H+],
the condition is called a respiratory acid-base disorder: an increase in PCO2 is a respiratory
acidosis, and a decrease in PCO2 is a respiratory alkalosis. When a change in HCO3 is
responsible for a change in [H+], the condition is called a metabolic acid-base disorder: a
decrease in HCO3 is a metabolic acidosis, and an increase in HCO3 is a metabolic alkalosis.
Secondary Responses
Secondary responses are designed to limit the change in [H+] produced by the primary acid-
base disorder, and this is accomplished by changing the other component of the
PaCO2/HCO3 ratio in the same direction. For example, if the primary problem is an increase
in PaCO2 (respiratory acidosis), the secondary response will involve an increase in HCO3,
and this will limit the change in [H+] produced by the increase in PaCO2. Secondary
responses should not be called “compensatory responses” because they do not completely
correct the change in [H+] produced by the primary acid-base disorder (2). The specific
features of secondary responses are described next. The equations described in the next
section are included in Figure 31.1.
Responses to Metabolic Acid-Base Disorders
The response to a metabolic acid-base disorder involves a change in minute ventilation that is
mediated by peripheral chemoreceptors located in the carotid body at the carotid bifurcation
in the neck.
Metabolic Acidosis
The secondary response to metabolic acidosis is an increase in minute ventilation (tidal
volume and respiratory rate) and a subsequent decrease in PaCO2. This response appears in
30–120 minutes, and can take 12 to 24 hours to complete (2). The magnitude of the response
is defined by the equation below (2).

EXAMPLE: For a metabolic acidosis with a plasma HCO3 of 14 mEq/L, the ∅HCO3 is 24 –
14 = 10 mEq/L, the ∅PaCO2 is 1.2×14 = 17 mm Hg, and the expected PaCO2 is 40 – 17 = 23
mm Hg. If the PaCO2 is >23 mm Hg, there is a secondary respiratory acidosis. If the PaCO2
is <23 mm Hg, there is a secondary respiratory alkalosis.
Metabolic Alkalosis
The secondary response to metabolic alkalosis is a decrease in minute ventilation and a
subsequent increase in PaCO2. This response is not as vigorous as the response to metabolic
acidosis because the peripheral chemoreceptors are not very active under normal conditions,
so they are easier to stimulate than inhibit. The magnitude of the response to metabolic
alkalosis is defined by the equation below (2)
EXAMPLE: For a metabolic alkalosis with a plasma HCO3 of 40 mEq/L, the ∅HCO3 is 40
– 24 = 16 mEq/L, the ∅PaCO2 is 0.7×16 = 11 mm Hg, and the expected PaCO2 is 40 + 11 =
51 mm Hg. This is only a borderline elevation in PaCO2, and it demonstrates the relative
weakness of the response to metabolic alkalosis.
Responses to Respiratory Acid-Base Disorders
The secondary response to changes in PaCO2 occurs in the kidneys, where HCO3 absorption
in the proximal tubes is adjusted to produce the appropriate change in plasma HCO3. This
renal response is relatively slow, and can take 2 or 3 days to reach completion. Because of the
delay in the secondary response, respiratory acid-base disorders are separated into acute and
chronic disorders.
Acute Respiratory Disorders
Acute changes in PaCO2 have a small effect on the plasma HCO3, as indicated in the
following two equations (2).

EXAMPLE: For an acute increase in PaCO2 to 60 mm Hg, the ∅HCO3 is 0.1×20 = 2 mEq/L
for an acute respiratory acidosis, and 0.2×20 = 4 mEq/L for an acute respiratory alkalosis.
Neither of these changes would be recognized as significant.
Chronic Respiratory Disorders
The renal response to an increase in PaCO2 is an increase in HCO3 reabsorption in the
proximal renal tubules, which raises the plasma HCO3 concentration. The response to a
decrease in PaCO2 is a decrease in renal HCO3 reabsorption, which lowers the plasma HCO3
concentration. The magnitude of this response is similar, regardless of the directional change
in PaCO2, so the equation below applies to both chronic respiratory acidosis and alkalosis.
Using a normal PaCO2 of 40 mm Hg and a normal HCO3 of 24 mEq/L, the above equation
can be rewritten as follows:

STEPWISE APPROACH TO ACID-BASE ANALYSIS

The following is a structured, rule-based approach to the diagnosis of primary, secondary,
and mixed acid-base disorders using the relationships between the [H+], PCO2, and HCO3
concentration described previously. Several examples are included as instructional aids. The
reference ranges for arterial pH, PCO2, and HCO3 are shown below.
pH = 7.36–7.44
PCO2 = 36–44 mm Hg
HCO3 = 22–26 mEq/L
Stage I: Identify the Primary Acid-Base Disorder
In the first stage of the approach, the PaCO2 and pH are used to identify the primary acidbase
disorder.
Rule 1: If the PaCO2 and/or the pH is outside the normal range, there is an acid-base
disorder.
Rule 2: If the PaCO2 and pH are both abnormal, compare the directional change.
2a. If the PaCO2 and pH change in the same direction, there is a primary metabolic acid-base
disorder.
2b. If the PaCO2 and pH change in opposite directions, there is a primary respiratory acid-
base disorder.
EXAMPLE: Consider a case where the arterial pH = 7.23 and the PaCO 2 = 23 mm Hg. The
pH and PaCO2 are both reduced (indicating a primary metabolic disorder) and the pH is low
(indicating an acidosis), so the diagnosis is a primary metabolic acidosis.
Rule 3: If only the pH or PaCO2 is abnormal, the condition is a mixed metabolic and
respiratory disorder (i.e., equal and opposite disorders).
3a. If the PaCO2 is abnormal, the directional change in PaCO2 identifies the type of
respiratory disorder (e.g., high PaCO2 indicates a respiratory acidosis), and the opposing
metabolic disorder.
3b. If the pH is abnormal, the directional change in pH identifies the type of metabolic
disorder (e.g., low pH indicates a metabolic acidosis) and the opposing respiratory disorder.
EXAMPLE: Consider a case where the arterial pH = 7.38 and the PaCO 2 = 55 mm Hg.
Only the PaCO2 is abnormal, so there is a mixed metabolic and respiratory disorder. The
PaCO2 is elevated, indicating a respiratory acidosis, so the metabolic disorder must be a
metabolic alkalosis. Therefore, this condition is a mixed respiratory acidosis and metabolic
alkalosis. Both disorders are equivalent in severity because the pH is normal.
Stage II: Evaluate the Secondary Responses
The second stage of the approach is for cases where a primary acid-base disorder has been
identified in Stage I. (If a mixed acid-base disorder was identified in Stage I, go directly to
Stage III). The goal in Stage II is to determine if there is an additional acidbase disorder.
Rule 4: For a primary metabolic disorder, if the measured PaCO2 is higher than expected,
there is a secondary respiratory acidosis, and if the measured PaCO2 is less than expected,
there is a secondary respiratory alkalosis.
EXAMPLE: Consider a case where the PaCO2 = 23 mm Hg, the pH = 7.32, and the HCO3 =
16 mEq/L. The pH and PCO2 change in the same direction, indicating a primary metabolic
disorder, and the pH is acidemic, so the disorder is a primary metabolic acidosis. Using
equations 31.3 and 31.4, the ∅PaCO2 is 1.2×(24 – 16) = 10 mm Hg (rounded off), and the
expected PaCO2 is 40 – 10 = 30 mm Hg. The measured PaCO2 (23 mm Hg) is lower than the
expected PaCO2, so there is an additional respiratory alkalosis. Therefore, this condition is a
primary metabolic acidosis with a secondary respiratory alkalosis.
Rule 5: For a primary respiratory disorder, a normal or near-normal HCO3 indicates that the
disorder is acute.
Rule 6: For a primary respiratory disorder where the HCO3 is abnormal, determine the
expected HCO3 for a chronic respiratory disorder.
6a. For a chronic respiratory acidosis, if the HCO3 is lower than expected, there is an
incomplete renal response, and if the HCO3 is higher than expected, there is a secondary
metabolic alkalosis.
6b. For a chronic respiratory alkalosis, if the HCO3 is higher than expected, there is an
incomplete renal response, and if the HCO3 is lower than expected, there is a secondary
metabolic acidosis.
EXAMPLE: Consider a case where the PaCO2 = 23 mm Hg, the pH = 7.54, and the HCO3 =
38 mEq/L. The PaCO2 and pH change in opposite directions, indicating a primary respiratory
disorder, and the pH is alkaline, so the disorder is a primary respiratory alkalosis. The HCO3
is abnormal, indicating that this is not an acute respiratory alkalosis.
Using Equations 31.9 and 31.11 for a chronic respiratory alkalosis, the ∅PCO2 is 40 – 23 =
17 mm Hg, the ∅HCO3 is 0.4×17 = 7 mEq/L, and the expected HCO3 is 24 + 7 = 31 mEq/L.
The measured HCO3 is the same as expected for a chronic respiratory alkalosis, so this
condition is a chronic respiratory alkalosis with an appropriate (completed) renal response. If
the measured HCO3 was less than 31 mEq/L, this condition would be a chronic respiratory
alkalosis with an incomplete renal response, and if the measured HCO3 was higher than 31
mEq/L, this would indicate a secondary metabolic alkalosis.

Stage III: Use The “Gaps” to Evaluate a Metabolic Acidosis

The final stage of this approach is for patients with a metabolic acidosis, where the use of
measurements called gaps can help to uncover the underlying cause of the acidosis. These are
described in the next section.

THE GAPS
There are numerous potential sources of a metabolic acidosis in critically ill patients, and the
measurements described in this section are designed to help in the search for the culprit.
The Anion Gap
The anion gap is a rough estimate of the relative abundance of unmeasured anions, and is
used to determine if a metabolic acidosis is due to an accumulation of non-volatile acids (e.g.,
lactic acid) or a primary loss of bicarbonate (e.g., diarrhea) (6,7).
Determinants
To achieve electrochemical balance, the concentration of negatively charged anions must
equal the concentration of positively charged cations. This electrochemical balance is
expressed in the equation shown below using electrolytes that are routinely measured,
including sodium (Na), chloride (CL), and bicarbonate (HCO3), as well as the unmeasured
cations (UC) and unmeasured anions (UA).
Rearranging the terms in this equation yields the following relationships:

Influence of Albumin
The unmeasured anions and cations that normally contribute to the anion gap are shown in
Table 31.3 . Note that albumin is the principal unmeasured anion, and the principal
determinant of the anion gap. Albumin is a weak (i.e., poorly dissociated) acid that
contributes about 3 mEq/L to the AG for each 1 g/dL of albumin in plasma (at a normal pH)
(3). A low albumin level in plasma will lower the AG, and this could mask the presence of an
unmeasured anion (e.g., lactate) that is contributing to a metabolic acidosis. Since
hypoalbuminemia is present in as many as 90% of ICU patients (9), the following formula for
the “corrected AG” (AGc) has been proposed to include the contribution of albumin:
(4.5 represents the normal concentration of albumin in plasma). For a patient with an AG of
10 mEq/L and a plasma albumin of 2 g/dL, the AGc is 10 + (2.5×2.5) = 16 mEq/L, which
represents a 60% increase in the AG.
Using the Anion Gap
The AG can be used to identify the underlying mechanism of a metabolic acidosis, which
then helps to identify the underlying clinical condition. An elevated AG occurs when there is
an accumulation of fixed or non-volatile acids (e.g., lactic acidosis), while a normal AG
occurs when there is a primary loss of bicarbonate (e.g., diarrhea) ( 7). Table 31.4 shows the
causes of metabolic acidosis grouped according to the AG.
HIGH AG: Common causes of high AG metabolic acidosis are lactic acidosis, diabetic
ketoacidosis, and advanced renal failure (where there is loss of H+ secretion in the distal
tubules of the kidneys). Also included are toxic ingestions of methanol (which produces
formic acid), ethylene glycol (which produces oxalic acid), and salicylates (which produce
salicylic acid)

NORMAL AG: Common causes of a normal AG metabolic acidosis are diarrhea, saline
infusion (see Figure 12.3), and early renal failure (where there is loss of bicarbonate
reabsorption in the proximal tubules). The loss of HCO3 is counterbalanced by a gain of
chloride ions to maintain electrical charge neutrality; hence the term hyperchloremic
metabolic acidosis is used for normal AG metabolic acidoses. (In high AG metabolic
acidoses, the remaining anions from the dissociated acids balance the loss of HCO3, so there
is no associated hyperchloremia.)
RELIABILITY The AG has shown a limited ability to detect non-volatile acids, and there
are several reports where the AG was normal in patients with lactic acidosis (11,12). The
poor performance of the AG may be due to the confounding influence of albumin, which was
not considered in early studies of the AG. A recent study shows that the albumincorrected
AG (AGc) provides a more accurate assessment of metabolic acidosis than the AG (13).
The Gap-Gap Ratio
In the presence of a high AG metabolic acidosis, it is possible to detect another metabolic
acid-base disorder (a normal AG metabolic acidosis or a metabolic alkalosis) by comparing
the AG excess (the difference between the measured and normal AG) to the HCO3 deficit
(the difference between the measured and normal HCO3 in plasma). This is accomplished
with the equation shown below, which includes 12 mEq/L for the normal AG and 24 mEq/L
for the normal HCO3 in plasma.
This ratio is sometimes called the gap-gap ratio because it involves two gaps (the AG excess
and the HCO3 deficit). Some applications of the gap-gap ratio are described next.
Mixed Metabolic Acidoses
In metabolic acidoses caused by non-volatile acids (high AG metabolic acidosis), the
decrease in serum HCO3 is equivalent to the increase in AG, and the gap-gap (AG
Excess/HCO3 deficit) ratio is unity or 1. However, if there is a second acidosis that has a
normal AG, the decrease in HCO3 is greater than the increase in AG, and the gap-gap ratio
falls below unity (<1). Therefore, in the presence of a high AG metabolic acidosis, a gap-gap
ratio <1 indicates the co-existence of a normal AG (hyperchloremic) metabolic acidosis
(6,14).
DIABETIC KETOACIDOSIS: A popular question on the medicine boards is a case where
the management of a patient with diabetic ketoacidosis (DKA) is associated with
improvement in the blood glucose and the clinical condition of the patient, but the acidosis
persists, and you are asked what to do (more insulin, more fluids, etc). The answer lies in the
gap-gap ratio; i.e., DKA presents with a high AG metabolic acidosis, but the aggressive
infusion of isotonic saline during the initial management creates a hyperchloremic (normal
AG) metabolic acidosis, which replaces the high AG acidosis as the ketoacids are cleared. In
this situation, the serum bicarbonate remains low, but the gap-gap ratio falls below 1 as the
acidosis switches from a high AG to a normal AG acidosis (15). Therefore, monitoring the
serum HCO3 alone will create a false impression that the DKA is not resolving, while the
gap-gap ratio provides an accurate measure of the acid-base status of the patient.
Metabolic Acidosis and Alkalosis
When alkali is added in the presence of a high AG acidosis, the decrease in serum
bicarbonate is less than the increase in AG, and the gap-gap is greater than unity (>1).
Therefore, in the presence of a high AG metabolic acidosis, a gap-gap >1 indicates the co-
existence of a metabolic alkalosis. This is an important consideration because metabolic
alkalosis is common in ICU patients (from the frequent use of nasogastric suction and
diuretics).

KETOACIDS
Ketogenesis
When carbohydrates are not available for metabolic energy production, there is a breakdown
of triglycerides in adipose tissue (lipolysis) to generate fatty acids, which are transported to
the liver and metabolized to form 3 ketone bodies; i.e., acetoacetate, β- hydroxybutyrate, and
acetone. This is illustrated in Figure 32.3. These ketones are released from the liver and can
be used as oxidative fuels by vital organs such as the heart and central nervous system. The
oxidative metabolism of ketones yields 4 kcal/g, which is slightly in excess of the energy
yield from the oxidative metabolism of glucose (3.7 kcal/g).
FIGURE 32.3 Ketogenesis in the liver, which occurs in response to diminished availability
of glucose. Acetone is a ketone, but is not a ketoacid.
Ketoacids in Blood
The normal concentration of ketones in the blood is negligible (0.1 mmol/L), but blood
ketone levels increase tenfold (to 1 mmol/L) after just 3 days of starvation. Acetone is not a
ketoacid, but is responsible for the “fruity” odor of breath in patients with ketoacidosis.
Acetoacetate (AcAc) and β-hydroxybutyrate (β-OHB) are strong acids (i.e., readily
dissociate), and they promote a decrease in plasma pH when their plasma concentrations
reach 3 mmol/L (43). The balance of AcAc and β-OHB in blood is determined by the
following redox reaction (see Figure 32.3):

The balance of this reaction favors the formation of β-OHB. In conditions of enhanced ketone
production, the β-OHB:AcAc ratio ranges from 3:1 in diabetic ketoacidosis, to as high as 8:1
in alcoholic ketoacidosis. The concentration of ketoacids in the blood in diabetic and
alcoholic ketoacidosis is shown in Figure 32.4. Note the preponderance of β- OHB in both
conditions. Because of this preponderance, ketoacidosis is more accurately called β-
hydroxybutyric acidosis.
The Nitroprusside Reaction
The nitroprusside reaction is a colorimetric method for detecting AcAc and acetone in blood
and urine. The test can be performed with tablets (Acetest) or reagent strips (Ketostix,
Labstix, Multistix). A detectable reaction requires a minimum AcAc concentration of 3
mmol/L. Because this reaction does not detect the predominant ketoacid, β-hydroxybutyrate
(43), it is an insensitive method for monitoring the severity of ketoacidosis. This is illustrated
in Figure 32.4. In alcoholic ketoacidosis, the total concentration of ketoacids in blood is 13
mmol/L, which represents more than a hundredfold increase over the normal concentration of
blood ketones, yet the nitroprusside reaction will be negative because the AcAc concentration
is below 3 mmol/L.
ß-hydroxybutyrate Testing
There are portable “ketone meters” that can provide reliable measurements of β-OHB
concentrations in fingerstick (capillary) blood, and results are available in about 10 seconds
(44). (Available devices include Precision Xtra meter from Abbot Laboratories and Nova
Max PLUS from Nova Biomedical.) The American Diabetes Association considers
measurements of plasma β-OHB with these meters as the preferred method for monitoring
patients with diabetic ketoacidosis (45).
DIABETIC KETOACIDOSIS
Diabetic ketoacidosis (DKA) is usually seen in insulin-dependent diabetic patients, but there
is no previous history of diabetes mellitus in 27–37% of cases (46). The most common
precipitating factors in DKA are inappropriate insulin dosing and concurrent illness (e.g.,
infection). The mortality rate of DKA is 1–5% (46).
Clinical Features
The definition of DKA proposed by the American Diabetes Association includes a blood
glucose >250 mg/dL, plasma [HCO3] <18 mEq/L, plasma pH ″7.30, an elevated anion gap,
and evidence of ketones in blood or urine (45). However, there are exceptions:
1. The blood glucose is only mildly elevated (<250 mg/dL) in about 20% of cases of
DKA(47).
2. The anion gap can be normal in DKA (48). The renal excretion of ketones is accompanied
by an increase in chloride reabsorption in the renal tubules, and the resulting hyperchloremia
limits the increase in the anion gap.
Additional clinical features of interest in DKA are summarized below.
1. Leukocytosis is not a reliable marker of infection in DKA because ketonemia produces a
leukocytosis, which is proportional to the concentration of ketones in plasma (45). However,
an increase in immature neutrophils (band forms) can be a reliable marker of infection in
patients with DKA (49).
2. Elevated troponin I levels without evidence of an acute coronary event has been reported in
27% of patients with DKA (50).
3. Dehydration is almost universal in DKA, but this may not be reflected in the plasma
sodium concentration because hyperglycemia has a dilutional effect on plasma sodium;i.e.,
the plasma sodium concentration decreases by 1.6–2 mEq/L for every 100 mg/dL increase in
the plasma glucose concentration (51,52).
Management
The management of DKA is summarized in Table 32.2 . The following are some of the
details.
Intravenous Fluids
Volume deficits in DKA average 50–100 mL/kg (4–8 L for an 80 kg adult) (45). Volume
resuscitation begins with isotonic (0.9%) saline infused at a rate of 1 liter per hour (or 15–20
mL/kg/hr) (45). When the patient stabilizes (e.g., blood pressure returns to normal), the
infusion rate can be decreased to 250–500 mL/hr (4–14 mL/kg/hr). When the blood glucose
falls to 250 mg/dL, change the intravenous fluid to 5% dextrose in 0.45% saline and decrease
the infusion rate to 150–250 mL/hr.
Insulin
Insulin therapy is started with regular insulin given intravenously, starting with a bolus dose
of 0.15 units per kilogram body weight and followed with a continuous infusion at 0.1
units/kg/hr. Because insulin adsorbs to intravenous tubing, the initial 50 mL of infusate
should be run through the IV setup before the insulin drip is started. The blood glucose levels
should decrease by 50 to 75 mg/dL per hour (46), and the insulin infusion should be adjusted
to achieve this goal. When the blood glucose level falls to 200 mg/dL, the insulin infusion
should be decreased to 0.05 to 0.1 units/kg/hr, and dextrose should be added to the
intravenous fluids. Thereafter, the blood glucose levels should be maintained between 150–
200 mg/dL (45,46). Achieving euglycemia is not recommended because of the risk of
hypoglycemia.
AFTER DKA RESOLVES: When DKA has resolved (i.e., glucose <200 mg/dL, plasma
[HCO3] >18 mEq/L, plasma pH >7.3) and the patient can tolerate oral fluids, subcutaneous
insulin can be started. Patients who were insulin-dependent prior to admission can be placed
on their usual outpatient regimen. Patients who are new to insulin should receive 0.5–0.8
Units/kg per day in divided doses (46).
Potassium
Potassium depletion is universal in DKA, and the average deficit is 3 to 5 mEq/kg (47).
However, the initial serum K + is often normal (74% of patients) or even elevated (22% of
patients) (47). The serum K+ can fall dramatically during insulin therapy (transcellular shift),
so if the initial serum K+ is low (<3.3 mEq/L), the insulin should be withheld until the serum
K+ can be normalized (by giving 40 mEq KCL hourly). If the serum K+ is high (≥5 mEq/L),
no potassium is given initially, and when the serum K+ is normal, 20–30 mEq of KCL should
be added to each liter of IV fluid (45). Regardless of the initial potassium regimen, the serum
K+ should be checked every 1–2 hours for the first 4–6 hours.
Phosphate
Phosphate depletion is also common in DKA, and serum phosphate levels are typically 1– 1.5
mmol/kg (47). However, phosphate replacement has no documented benefit in DKA, and is
not recommended unless the hypophosphatemia is severe (45–47). If the serum PO4 is <1
mg/dL, give 20–30 mEq potassium phosphate with each liter of IV fluid (45).
Bicarbonate
Bicarbonate therapy does not improve the outcome in DKA, and is not recommended as a
routine measure (45–47). However, in patients who are in extremis with a pH <7.0, the
bicarbonate regimen presented earlier can be used as a desperation measure.
Monitoring Acid-Base Status
The serum [HCO3] is not a reliable measurement for following the acid-base status during
the management of DKA because the isotonic saline produces a hyperchloremic acidosis that
prevents the bicarbonate from rising despite a resolving ketoacidosis. In this situation,
monitoring the gap-gap ratio is more informative. The gap-gap ratio is the ratio of the anion
gap excess to the bicarbonate deficit, and is described at the end of the last chapter (see pages
596–597). This ratio is unity (1.0) in pure ketoacidosis, and it decreases as the ketoacidosis
resolves and is replaced by the hyperchloremic acidosis. When the ketones have been cleared
from the bloodstream, the ratio approaches zero.