Bicarbonate Therapy in Severe Metabolic Acidosis

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Bicarbonate Therapy in Severe Metabolic Acidosis

• Neil A. Kurtzman, MD
• Department of Internal Medicine,
• Texas Tech University Health Sciences Center,
• Lubbock, Texas 79430

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• 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

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Gain of Acid

• Exogenous (eg, NH4Cl)
  
• Endogenous
• Abnormal lipid metabolism DKA
• Abnormal CHO metabolism Lactic acidosis
• Normal protein metabolism Uremic acidosis

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• Kraut and Kurtz did an online (Clin Exp Neprol
  10111-117, 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 lt 0.01)

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• More than 80 of nephrologists consider the pCO2
  in making their decision to treat
• Only 59 of intensivists do (plt0.02)
• In patients with lactic acidosis, 86 of
  nephrologists treat with bicarbonate
• Two-thirds of intensivists give bicarbonate (plt
  0.05)

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• 60 of nephrologists treat DKA with bicarbonate
• 28 of intensivists give bicarbonate to patients
  with DKA (plt0.01)
• 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

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• 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

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• 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

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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?

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• 3. How much bicarbonate should be given and
  how is that amount calculated?
• 4. What are the deleterious effects of
  bicarbonate therapy?

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Deleterious effects of acidemia

• Decreased myocardial contractility
• Fall in cardiac output
• Fall in BP
• Pulmonary venoconstriction

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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

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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

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• tolbutamide
• methotrexate
• phenobarbital
• phenytoin

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• Optimal extracelluar pH 7.4
• Optimal intracellular pH 7.1
• Deviations from normal pH will obviously decrease
  the efficiency of all reactions

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• Acidemia protects the central nervous system
  against seizures, it sensitizes the myocardium to
  arrhythmias
• Extracellular pH is a surrogate for intracellular
  pH

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When is acidemia severe enough to warrant therapy?

• Most authorities in acid-base physiology would
  give bicarbonate to a patient with an arterial pH
  lt 7.1
• Not a hard and fast rule
• More on this later

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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

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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 36747-752,
  1989)
• (0.4 2.6 / pHCO3) (body weight)

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• 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

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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)

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• 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

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• 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

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• 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

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• 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

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• 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

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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

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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

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DKA

• Bicarbonate therapy delays the removal of ketone
  bodies from the blood
• Bicarbonate therapy markedly increases blood
  acetoacetate and beta-hydroxybutyrate levels

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• 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

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• 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.

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• 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.

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• 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.

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• 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.

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• Case 1 got no bicarbonate even though his pH was
  lt 7.0
• Case 2 received bicarbonate though he had a
  higher pH
• Bicarbonate therapy must be individualized

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• Desired HCO3 observed HCO3
• Use total body water
• Assume pCO2 will not change
• Give that amount which will raise the pH to 7.2

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• Reevaluate in two hours
• Make new plan based on the new data
• Correct the underlying cause(s)

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