Metabolic Alkalosis in the ICU

Metabolic alkalosis – a plasma pH > 7.5 caused by an increased plasma concentration of bicarbonate (HCO₃) – is a common occurrence in the ICU. And while this type of acid-base disturbance accounts for more than 30% of all acid-base abnormalities, the pathophysiology and the work-up it requires is often the least understood. Below is a brief review and of metabolic alkalosis and a suggested diagnostic approach.

To begin, here are a few statements about metabolic alkalosis that should help:

1. In order for patients to develop metabolic alkalosis there has to be BOTH an event that initiates the alkalosis AND a process that maintains that it. (Experiments involving the exogenous injection of HCO₃ into normal, healthy subjects – subjects whose lungs and kidneys are able to appropriately buffer and excrete HCO₃ – fail to produce an alkalosis.)
2. The ability for the kidney to effectively handle HCO₃ is intimately tied to the serum concentrations of chloride (Cl) and potassium (K). It is also tied to sodium (Na) and magnesium (Mg), but to a lesser degree.

Like most acid-base disturbances, clinically significant metabolic alkalosis can affect almost any organ system as the cells try to carry out their normal functions in a non-physiologic pH. The most profound effects are usually neurological (e.g. depressed consciousness, seizures), respiratory (i.e. left-shift oxy-hemoglobin dissociation curve, increased O₂ consumption, and in more severe cases, respiratory depression) and cardiovascular (i.e. decreased cardiac output, hypertension or hypotension).

Clinically, metabolic alkalosis can be divided into two categories: “chloride-responsive” and “chloride-resistant.”[i] Finding which category applies to your patient will help treatment and further work-up, if necessary. A simple, spot urine chloride (U_Cl) level will help differentiate these categories. In the following way:

U_Cl < 20 = Chloride-responsive and is caused loss of GI fluid, hypovolemia or diuretics. And as the name suggests, can be treated with chloride-containing intravenous fluid, usually saline (see note below).

U_Cl  > 20 = Chloride-resistant. These patients require further evaluation into their volume status to help identify the underlying cause. Although less common in the ICU, the usual causes of chloride-resistant metabolic alkalosis. The usual causes are mineralocorticoid excess or hypokalemia, but the complete differential diagnosis for this group is much longer and failure to identify the cause for this group may require a more extensive work-up.

Because the incidence of metabolic alkalosis is so frequent, having an effectively diagnosing and treating metabolic alkalosis is essential to caring for patients in the ICU. Background knowledge of what factors affect how the kidney filters, secretes, and reabsorbs HCO₃ and a systematic approach to this complex process increases the likelihood of successful patient outcomes.

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[i] Sometimes referred to as “Saline-responsive” or “Saline-resistant.’ But, because treatment is often tied to specifically replacing the anion chloride, there is something lost when replacing the word ‘chloride’ in the nomenclature. The clinical significance of chloride is true even for contraction alkalosis -- one of the most common causes of chloride-responsive metabolic alkalosis we encounter in the Trauma ICU. Even in these cases, when the alkalosis is thought to form from a loss of intravascular volume, the key to effective treatment is to replace the chloride, and not just replacing volume. In fact, experiments have shown that chloride replacement without volume replacement is sufficient to correct the alkalosis and other experiments have shown that volume replacement without chloride (e.g. albumin) is not effective.

Thanks to Dr. Allan Peetz for this post.