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 Normal 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 36:747752, 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 doesnt 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 proinflammatory 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.