Bicarbonate Therapy in Severe

Metabolic Acidosis
Neil A. Kurtzman, MD
Department of Internal Medicine,
Texas Tech University Health Sciences Center,
Lubbock, Texas 79430
• Metabolic acidosis: A primary fall in the
bicarbonate concentration

• Due to either a gain of acid or a loss of base

(usually HCO3)

• Acidemia refers solely to a fall in pH

 Gain of Acid
• Exogenous (eg, NH4Cl)
• Endogenous

• Abnormal lipid metabolism

DKA

• Abnormal CHO metabolism

Lactic acidosis

• ANormal protein metabolism

Uremic acidosis
• Kraut and Kurtz did an online (Clin Exp Neprol
10:111-117, 2006) survey of how intensivists and
nephrologists gave HCO3 to patients with metabolic
acidosis

• Forty percent of the intensivists would not give

bicarbonate unless the pH was less than 7.0

• Only 6% of nephrologists wait until pH gets this

low (p < 0.01)
• More than 80% of nephrologists consider the
pCO2 in making their decision to treat

• Only 59% of intensivists do (p<0.02)

• In patients with lactic acidosis, 86% of

nephrologists treat with bicarbonate

• Two-thirds of intensivists give bicarbonate

(p< 0.05)
• 60% of nephrologists treat DKA with bicarbonate

• 28% of intensivists give bicarbonate to patients

with DKA (p<0.01)

• Both would administer bicarbonate by constant

infusion, targeting an arterial pH of 7.2

• Seventy-five percent of nephrologists calculate

the amount of bicarbonate required, while only
one-third of intensivists do so
• Metabolic acidosis results from a loss of bicarbonate
(eg diarrhea)

• Or from its titration to an anionic base that often can

be converted back to bicarbonate (eg DKA or lactic
acidosis)

• This non-bicarbonate base anion is commonly

termed “potential” bicarbonate
• Giving bicarbonate to a patient with a true
bicarbonate deficit is not controversial

• Controversy arises when the decrease in

bicarbonate concentration is the result of its
conversion to another base which, given time,
can be converted back to bicarbonate
In considering acute bicarbonate replacement four
questions should be considered

1. What are the deleterious effects of acidemia

and when are they manifest?

2. When is acidemia severe enough to warrant

therapy?
3. How much bicarbonate should be given and
how is that amount calculated?

4. What are the deleterious effects of bicarbonate

therapy?
 Deleterious effects of
acidemia

• Decreased myocardial contractility

• Fall in cardiac output

• Fall in BP

• Pulmonary venoconstriction
 Deleterious effects of
acidemia

• Decreased binding of norepinephrine to its

receptors

• Acidemia may adversely affect cell functions

such as enzymatic reactions, ATP generation,
fatty acid biosynthesis, and bone
formation/resorption
 Deleterious effects of
acidemia
• Drugs which are salts of weak acids are more
active during acidemia

• More receptor binding

• More entry to cells

• Best example is ASA

• tolbutamide

• methotrexate

• phenobarbital

• phenytoin
• Optimal extracelluar pH 7.4

• Optimal intracellular pH 7.1

• Deviations from normal pH will obviously

decrease the efficiency of all reactions
• Acidemia protects the central nervous system
against seizures, it sensitizes the myocardium
to arrhythmias

• Extracellular pH is a surrogate for intracellular

pH
When is acidemia severe enough to warrant therapy?

• Most authorities in acid-base physiology

would give bicarbonate to a patient with an
arterial pH < 7.1

• Not a hard and fast rule

• More on this later

How much bicarbonate should be given and
how is that amount calculated?

• The volume of distribution of bicarbonate is

approximately that of total body water

• In patients with metabolic acidosis it is said to

vary from 50% to greater than 100%,
depending on the severity of the acidemia
How much bicarbonate should be given and how is
that amount calculated?

• Any calculated amount is approximate

• Fernandez et al have derived a formula for

calculating the bicarbonate space (KI 36:747-
752, 1989)

• (0.4 + 2.6 / pHCO3) (body weight)

 How much bicarbonate should be given and
how is that amount calculated?

• At a pCO2 of 13 mm Hg and HCO3 of 4 mEq/l,

the arterial pH is 7.1

• Raise the HCO3 to only to 8 mEq/L the blood

pH will increase to 7.4

• This assumes the pCO2 doesn’t change

 How much bicarbonate should be given
and how is that amount calculated?

• If the bicarbonate concentration rises only 1

mEq/L the pH would be above 7.2

• Arterial pCO2 typically however does not

remain the same after bicarbonate infusion

• In severely acidotic patients it rises 6.7 ± 1.8

mm Hg when an infusion of sodium
bicarbonate is given (1.5 mmol/kg over 5min)
What are the deleterious effects of bicarbonate
therapy?

• Bicarbonate therapy is associated with an

increase in mortality

• True in humans and experimental animals

under a variety of acidemic conditions

• Fall in blood pressure and cardiac output

What are the deleterious effects of bicarbonate
therapy?

• Shifts in ionized calcium

• In strong acid acidosis potassium also shifts

out of the cell

• Sensitizes the heart to abnormal electrical

activity and subsequent arrhythmias
What are the deleterious effects of bicarbonate
therapy?

• “Paradoxical” intracellular acidosis – CO2 shifts

into cells

• Both volume expansion and hypernatremia can

occur

• Fulminate congestive heart failure with flash

pulmonary edema may result
What are the deleterious effects of bicarbonate
therapy?

• In vitro studies show that intracellular

alkalinization hastens cell death following anoxia

• Stimulates superoxide formation, increases pro-

inflammatory cytokine release, and enhances
apoptosis

• Relationship to human disorders unknown

What are the deleterious effects of bicarbonate
therapy?

• Rebound alkalemia – especially with low arterial

pCO2

• Blood lactate and ketone bodies increase

• This “potential” bicarbonate will be converted

back to actual bicarbonate unless it lost in the
urine
 DKA

• Acetoacetate and beta-hydroxybutyrate are lost

in the urine before the patient arrives at the
hospital

• The patient is truly bicarbonate deficient

• More urinary loss of ketone bodies occurs

following fluid administration and volume
repletion
 DKA
• Hyperchloremic metabolic acidosis the day
after insulin therapy

• Almost never necessary to give bicarbonate

even though the patient is bicarbonate deficient
unless renal function is permanently impaired

• Bicarbonate therapy markedly increases blood

acetoacetate and beta-hydroxybutyrate levels
 DKA

• Bicarbonate therapy delays the removal of

ketone bodies from the blood

• Bicarbonate therapy markedly increases blood

acetoacetate and beta-hydroxybutyrate levels
 Lactic Acidosis

• Mortality greater than 80%

• Outcome depends on the treatment of its cause

• Cardiogenic or hemorrhagic shock

• Exogenous toxins such as cyanide or metformin

CASE #1: A 20 year-old man with a five-year
history of type 1 diabetes mellitus was admitted
for the ninth time in diabetic ketoacidosis. He
was poorly responsive and had Kussmaul
respirations. Before any therapy he had a
plasma Na of 140 mEq/L, K 4 mEq/L, Cl 109
mEq/L, CO2 3 mEq/L, and his creatinine was 1
mg/dL. The arterial pH was 6.95, pCO2 14 mm
Hg, and the calculated HCO3 was 3 mEq/L.
Urine and blood ketones were strongly
positive. He was treated with insulin and
appropriate fluid and electrolyte replacement.
He was not given bicarbonate. The next day
he was fully oriented. His plasma Na was 142,
K 4, Cl 114 and his CO2 was 18 mEq/L. The
remainder of his clinical course was
unremarkable.
CASE #2: An 80 year old man was admitted
with severe congestive heart failure. He was
hypotensive and oliguric. He had both
pulmonary and peripheral edema. His baseline
creatinine was known to be 1.6 mg/dL. On
arrival at the emergency room his plasma Na
was 135 mEq/L, K 4 mEq/L, Cl 97 mEq/L,
CO2 7 mEq/L, and his creatinine was 2.5
mg/dl. His arterial pH was 7.1, pCO2 20 mm
Hg, and the calculated HCO3 was 6 mEq/l.
The blood lactate level was 20 mmol/L .
The patient was intubated and placed on a
respirator keeping his pCO2 at 20 mmHg.
CVVHD was begun with a bath containing 14
mEq/L of bicarbonate. He was given an
infusion of 300 mEq of bicarbonate over two
hours; with a total body water of 43 liters, one
would aim for a HCO3 of 14 mEq/L: (7 mEq/L
X 43 L = 301 mEq). At the end of that time his
pH was 7.2 and the HCO3 was 13 mEq/L. Five
days later he was transferred out of the
intensive care unit, his lactic acidosis resolved.
• Case #1 got no bicarbonate even though his
pH was < 7.0

• Case #2 received bicarbonate though he had a

higher pH

• Bicarbonate therapy must be individualized

• Desired HCO3 – observed HCO3

• Use total body water

• Assume pCO2 will not change

• Give that amount which will raise the pH to 7.2

• Reevaluate in two hours

• Make new plan based on the new data

• Correct the underlying cause(s)

Sandra Sabatini and Neil A. Kurtzman: Bicarbonate
Therapy in Severe Metabolic Acidosis, JASN in
press.