Guidelines

For the Management of

Metabolic Alkalosis

By

Dr. Sinan Butrus

F.I.C.M.S

Clinical Standards & Guidelines

Kurdistan Board
For Medical Specialties
Metabolic alkalosis is a primary increase in serum bicarbonate (HCO3-) concentration as a
result of loss of H+ from the body or a gain in HCO3- manifests as alkalemia (pH >7.40);
usually compensated by alveolar hypoventilation with a rise in arterial carbon dioxide tension
(PaCO2) to decrease change in pH.
Elevated HCO3- can also represent a compensatory response to primary respiratory acidosis,
however; a bicarbonate concentration > 35 mEq/L is almost always caused by primary
metabolic alkalosis.
Normally, arterial PaCO2 increases by 0.5-0.7 mm Hg for every 1 mEq/L increase in plasma
bicarbonate concentration. If the change in PaCO2 is not within this range, this results to a
mixed acid-base disturbance. For example, if the increase in PaCO2 is more than 0.7 times the
increase in bicarbonate, then metabolic alkalosis coexists with primary respiratory acidosis.
Likewise, if the increase in PaCO2 is less than the expected change, then a primary
respiratory alkalosis is also present

Presentation:
The patient may experience weakness, myalgia, polyuria, hypoventilation and cardiac
arrhythmias.
Signs of hypocalcemia (tetany, Chvostek sign, Trousseau sign, seizures & mental changes)
Physical examination should include an evaluation for hypertension and for volume status
(orthostatic changes in blood pressure and heart rate, mucous membranes, presence or
absence of edema, skin turgor, weight change, urine output).

Work up:
• Measure serum electrolytes, HCO3- and arterial blood gases as the only definitive way to
diagnose metabolic alkalosis is with a simultaneous blood gases analysis that shows elevation
of both pH and PaCO2 and increased calculated bicarbonate.
Serum bicarbonate concentration can be calculated from a blood gas sample:
HCO3- = 24 × PaCO2 ÷ [H+]
The H+ can be estimated by subtracting the last 2 digits (hundredths value) of the pH value from 80
when the pH is 7.0 – 7.55, e.g. if the pH is 7.25 then the H+ concentration will be 80-25
• Measure serum anion gap to differentiate between primary metabolic alkalosis and
metabolic compensation for respiratory acidosis. AG = (Na+ + K+) – (Cl- + HCO3-).
The anion gap is frequently elevated to a modest degree in metabolic alkalosis because of the
increase in the negative charge of albumin and the enhanced production of lactate.
• If the etiology of metabolic alkalosis is not clear from the clinical history and physical
examination, including drug use and the presence of hypertension, then a urine chloride ion
concentration can be obtained to differentiate between
Chloride-responsive metabolic alkalosis (low urine chloride ion concentration < 20 mEq/L)
Chloride-resistant metabolic alkalosis(high urine chloride ion concentration > 20 mEq/L)
• Measuring the plasma renin activity and aldosterone level to find the etiology of metabolic
alkalosis, especially in patients with hypertension, hypokalemic (renal potassium wasting)
without diuretic use as low renin activity and high plasma aldosterone levels are found in
primary hyperaldosteronism, including glucocorticoid-remediable hyperaldosteronism.

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Management
depends primarily on the underlying etiology and on the patient’s volume status.
In the case of vomiting, administer antiemetic, if possible.
If continuous gastric suction is necessary, gastric acid secretion can be reduced with
H2-blockers or more efficiently with proton-pump inhibitors.
In patient on thiazide or loop diuretics, the dose can be reduced or the drug can be stopped if
appropriate. Alternatively, potassium-sparing diuretics or acetazolamide can be added.
Chloride-responsive alkalosis
• Volume depletion: treat the alkalosis with an intravenous infusion of isotonic sodium
chloride solution and as this type of alkalosis is usually associated with hypokalemia, use
potassium chloride to correct the hypokalemia.
• Edematous states (e.g., congestive heart failure CHF), use potassium chloride instead of
sodium chloride to correct the alkalosis and avoid volume overload.
If diuresis is needed, a carbonic anhydrase inhibitor (acetazolamide) or a potassium-sparing
diuretic (spironolactone, amiloride, triamterene) can be used to correct the alkalosis.
Chloride-resistant metabolic alkalosis
Management is based on the specific cause. Aldosterone antagonist (spironolactone,
amiloride, triamterene) is helpful in hyperaldosteronism.
Intravenous HCl is indicated (0.1N HCL at a rate < 2 mEq/Kg/hr or < 125 mEq/hr)
• Severe metabolic alkalosis (pH >7.55).
• Unable to administer sodium or potassium chloride because of volume overload or
advanced renal failure.
• Rapid correction of severe metabolic alkalosis is warranted (cardiac arrhythmias, hepatic
encephalopathy, and digoxin cardiotoxicity).
Hemodialysis & peritoneal dialysis
The main indication of dialysis in metabolic alkalosis is in patients with advanced renal
failure, who usually have volume overload and are resistant to acetazolamide.
Dialysis can be used to correct metabolic alkalosis with certain modifications of the dialysate.
In hemodialysis; use a low-bicarbonate dialysate (bicarbonate can be as low as 18 mmol/L).
Otherwise, sue acetate-free biofiltration (buffer-free dialysate) in which bicarbonate is not
present in the dialysate but is infused separately as needed, may be used.
In peritoneal dialysis; use isotonic sodium chloride solution as the dialysate.

Take home message:

 The most common causes are volume depletion (particularly when involving loss of
gastric acid and Cl from recurrent vomiting or nasogastric suction) and diuretic use.
 Metabolic alkalosis involving loss or excess secretion of Cl is termed Cl-responsive
managed by treating the cause and give patients with Cl-responsive metabolic
alkalosis 0.9% saline IV.
 Cl-resistant metabolic alkalosis is due to increased aldosterone effect so management
involves the correction of hyperaldosteronism.

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 Further reading
Two factors are needed to establish metabolic alkalosis generation & maintenance
Generation of metabolic alkalosis through one of the following mechanisms:
• Loss of hydrogen ions either through the GI tract (vomiting or nasogastric NG suction) or
through renal tract when the distal delivery of sodium increases in the presence of excess
aldosterone.
• Shift of hydrogen ions into the intracellular space mainly develops with hypokalemia
• Alkali administration in amounts that exceed the capacity of the kidneys to excrete as
observed in renal failure or in volume depletion.
• Contraction alkalosis: contraction of extracellular fluid volume caused by diuretic therapy
or chloride diarrhea.
Maintenance of metabolic alkalosis through one of the following mechanisms:
• Decreased perfusion to the kidneys caused by either volume depletion or a reduction in
effective circulating blood volume (eg, edematous states such as heart failure or cirrhosis)
which stimulates the renin-angiotensin-aldosterone system leading to increased renal sodium
ion reabsorption and enhanced hydrogen ion secretion. Aldosterone may also independently
increase the activity of the apical proton pump in the collecting duct. Whenever a hydrogen
ion is secreted into the tubular lumen, a bicarbonate ion is gained into the systemic
circulation.
• Chloride depletion may occur through the GI tract by loss of gastric secretions or through
the kidneys with loop diuretics or thiazides. Chloride depletion, even without volume
depletion, enhances bicarbonate reabsorption
• Many of the causes of metabolic alkalosis are also associated with hypokalemia. In turn,
hypokalemia maintains metabolic alkalosis by 5 different mechanisms.
1. Hypokalemia results in the shift of hydrogen ions intracellularly. The resulting
intracellular acidosis enhances bicarbonate reabsorption in the collecting duct.
2. Hypokalemia stimulates the apical H+/K+ ATPase in the collecting duct leading to
appropriate potassium ion reabsorption but a corresponding hydrogen ion secretion with net
gain of bicarbonate, maintaining systemic alkalosis.
3. Hypokalemia stimulates renal ammonia genesis, reabsorption and secretion which generate
bicarbonate that is returned to the systemic circulation.
4. Hypokalemia leads to impaired chloride ion reabsorption in the distal nephron with
enhancement of hydrogen ion secretion.
5. Hypokalemia reduces the glomerular filtration rate (GFR) which decreases the filtered load
of bicarbonate. In the presence of volume depletion, this impairs renal excretion of the excess
bicarbonate.
Causes of metabolic alkalosis
Chloride-responsive alkalosis (urine chloride < 20 mEq/L):
 Loss of gastric secretions - Vomiting, NG suction
 Loss of colonic secretions - Congenital chloridorrhea, villous adenoma
 Thiazides and loop diuretics (after discontinuation)
 Posthypercapnia
 Cystic fibrosis

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 Chloride-resistant alkalosis (urine chloride >20 mEq/L) with hypertension:
 Primary hyperaldosteronism - Adrenal adenoma, bilateral adrenal hyperplasia, adrenal
carcinoma, glucocorticoid-remediable hyperaldosteronism
 11B-HSD2 - Genetic, licorice, chewing tobacco, carbenoxolone
 CAH - 11-Hydroxylase or 17-hydroxylase deficiency
 Current use of diuretics in hypertension
 Cushing syndrome
 Exogenous mineralocorticoids or glucocorticoids
 Liddle syndrome
 Renovascular hypertension
Chloride-resistant alkalosis (urine chloride >20 mEq/L) without hypertension:
 Bartter syndrome
 Gitelman syndrome
 Severe potassium depletion
 Current use of thiazides and loop diuretics
 Hypomagnesemia
Other causes:
 Exogenous alkali administration - Sodium bicarbonate therapy in the presence of
renal failure, metabolism of lactic acid or ketoacids
 Milk-alkali syndrome
 Hypercalcemia
 Intravenous penicillin
 Re-feeding alkalosis
 Massive blood transfusion
Low plasma renin activity and aldosterone levels are found in:
 Cushing syndrome
 Exogenous steroid use
 Congenital adrenal hyperplasia (CAH)
 Liddle syndrome
High plasma renin activity and aldosterone levels are found in:
 Renal artery stenosis
 Diuretic use
 Renin-secreting tumors
 Bartter syndrome
 Gitelman syndrome

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 Algorithm for Metabolic Alkalosis

History - Physical examination -

S. bicarbonate - Arterial blood gas: No cause detected

Urine chloride
< 20 mEq/L > 20 mEq/L

Loss of gastric secretion Hypertension No Hypertension

Diuretic therapy Plasma renin activity Bartter's syndrome
Post-hypercapnea
Gitelman's syndrome
Villous adenoma
Diuretic therapy
Congenital chloridorrhea
Potassium or
magnesium depletion

High Low

Diuretics (current use) Plasma aldosterone

Renal artery stenosis Low High
Renin secreting tumor
Accelerated hypertension Licorice Primary hyperaldosteronism
Cushing's syndrome, Adrenal adenoma
exogenous steroids Bilateral adrenal hyperplasia
11-Hydroxylase or 17- Adrenal carcinoma
Hydroxylase deficiency Glucocorticoid-remediable
Liddle's syndrome hyperrtension

http://img.medscape.com/pi/emed/ckb/gps1/large/1339ALKALG.PD

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 Management of Metabolic Alkalosis

http://www.med-online.ro/eng/clinical/eng_005/eng_005_e.php
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References:
1. Christie P Thoma Metabolic Alkalosis Treatment & Management. Dec 26, 2014
http://emedicine.medscape.com/article/243160-treatment
2. James L. Lewis. Metabolic Alkalosis. February 2013
www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/acid-base-
regulation-and-disorders/metabolic-alkalosis#
3. Metabolic Alakalosis. University of Connecticut.2006
uhttp://fitsweb.uchc.edu/student/selectives/TimurGraham/Metabolic_Alkalosis_diagnosis_an
d_treatment.html
4. N Shah, C Shaw, LG Forni. Metabolic alkalosis in the Intensive Care Unit.
neth j crit care. volume 12 No 3. June 2008
http://njcc.nl/sites/default/files/pdf/NJCC_03%20Forni.pdf
5. Arterial blood gas analysis workshop. 2012
http://www.resus.org.uk/pages/alsabgGd.pdf
6. www.med-online.ro/eng/clinical/eng_005/eng_005_e.php
7. Hypokalaemic Alkalosis. 29/8/2014
http://www.patient.co.uk/pdf/1847.pdf.