Blood gas interpretation (Proceedings)

Disturbances of acid-base equilibrium occur in a wide variety of critical illnesses and are among the most commonly encountered disorders in the intensive care unit (ICU). In addition to reflecting the seriousness of the underlying disease, disturbances in hydrogen ion concentration ([H+]) have important physiologic effects.

A blood pH less than normal is called acidemia; the underlying process causing the acidemia is called acidosis. Similarly, alkalemia and alkalosis refer to an increased pH and the underlying process, respectively. Acidosis and alkalosis can be further classified based on whether it is a primary change in PCO2 (respiratory) or HCO3 - (metabolic) that alters the extracellular [H+]. Although an acidosis and alkalosis may coexist, there can be only one resulting pH. Therefore, acidemia and alkalemia are mutually exclusive conditions, where as acidosis and alkalosis are not.

The approach to acid-base derangements should emphasize a search for a cause, rather than an immediate attempt to normalize the pH. Many disorders are mild and do not require treatment. Further, treatment may be more detrimental than the acid-base disorder itself. More importantly, the clinician must fully consider the possible underlying pathologic state(s). This approach may facilitate a directed intervention that will benefit the patient more than normalization of the pH.'

Physiologic effects of acidemia and alkalemia

Precise H+ regulation is essential because the activities of almost all enzyme systems in the body are influenced by [H+]. Therefore, perturbations in [H+] may alter virtually all cell and body functions, leading to widespread physiologic change of clinical importance. However, in any given patient, the effects of acidemia and alkalemia may be difficult to discern because any physiologic consequences may be influenced by the underlying illness causing the acid-base disorder.

Metabolic acidemia causes stimulation of the sympathetic-adrenal axis (increasing vascular resistance), decrease the affinity of hemoglobin for oxygen (shift the oxyhemoglobin dissociation curve to the left) and increases the free concentration (and potential for toxicity) of many drugs by decreasing their protein binding. In severe acidemia, stimulation of the sympathetic-adrenal axis is countered by a depressed responsiveness of adrenergic receptors to circulating catecholamines. Severe acidemia typically causes a decrease in cardiac output and vasodilation, despite sympathetic stimulation. Additional influences of severe acidemia include altered renal and hepatic blood flow, altered enzymatic function, promotion of cardiac arrhythmias, depressed mental status, as well as induction of hyperkalemia and increased ionized calcium levels.

Acute respiratory acidemia causes marked increases in cerebral blood flow. As PCO2 increases, patients may become confused, irritable, anxious (symptoms difficult to differentiate from hypoxemia), with possible loss of consciousness and seizures. Acute hypercapnia causes depression of diaphragmatic contractility, which may contribute to the downward spiral of respiratory failure in patients with acute CO2 retention.

Acidemia is better tolerated than is alkalemia. While a pH of 7.2 is typically well tolerated, a pH of 7.6 is associated with significant mortality. Respiratory alkalosis lowers blood pressure and calculated systemic vascular resistance. Most vascular beds demonstrate vasodilation but vasoconstriction predominates in the cerebral circulation. Both respiratory and metabolic alkalemia can lead to seizures. The clinical effect of alkalemia-induced changes in oxygen delivery is small but in patients with ongoing tissue hypoxia the increased hemoglobin oxygen affinity (shift of the oxyhemoglobin dissociation curve to the right) may be detrimental and clinically significant. Alkalemia may decrease ionized calcium levels, due to increased calcium binding to proteins, and hypokalemia due to transcellular exchange with H+.

Approach to acid-base disturbances

This discussion will generally follow the more widely accepted "bicarbonate-based" approach to understanding acid-base disturbances, although a method developed by Peter Stewart, is considered superior for a select subgroup of patients. The Stewart method identifies the true determinants of the pH: the strong ion difference, the total concentration of weak acids, and the PCO2. Using any method, diagnosing disorders of acid-base homeostasis in the ICU can be challenging. Many critically ill patients have combinations of disorders (mixed acid-base disorders). In addition, patients admitted to the ICU often have pre-existing disturbances – such as metabolic acidosis in patients with chronic renal failure and metabolic alkalosis in patients on loop diuretics – that must be taken into account when one is evaluating subsequent changes.

A stepwise, conventional approach to identify the primary acid-base disorder follows:

• Step 1:Were there any factors (collection, storage or processing) that may

• invalidate the results obtained?

• Step 2:Determine whether an acidemia (pH < 7.36) or an alkalemia (pH > 7.44) is present. (In mixed disorders, the pH may be in the normal range, but the bicarbonate level, the PCO2, or the anion gap will signal the presence of an acid- base disturbance.)

• Step 3:Is the primary disturbance metabolic or respiratory? (That is, does any change in the PCO2 account for the direction of the change in pH?)

• Step 4:Is compensation appropriate for the primary disturbance (Table 1)?

• Step 5:Is the anion gap (AG) elevated? If so, is the Δ gap = Δ HCO3-? If not, there is an additional non-gap acidosis or a metabolic alkalosis.

• Step 6:Put it all together; what is the most likely diagnosis?

Blood has a tremendous capacity to buffer acids, which is the first line of defense against perturbations in systemic pH. A buffer can be thought of as a substance that, when present in solution, takes up [H+] and therefore resists change in pH when [H+] is added. The overall buffering system of the body is complex and includes several components. The most important system is the CO2 - HCO3 -, which is the principal buffer in the extracellular fluid. While buffers allow the body to resist changes in pH, buffering capacity can become depleted. Compensatory responses to a primary acid-base disturbance also act to reduce the severity of the change in pH, but are never strong enough to normalize the pH. Respiratory compensation occurs within minutes to hours, however, renal compensation occurs more slowly, typically over the course of hours to days. Because of this delay in renal compensation, respiratory acid-base disorders are classified as acute and chronic. Where acute is before renal compensation has occurred, while chronic is after. Therefore, one must consider whether enough time has passed for compensation to have occurred. When calculating compensation, specific terminology has been adopted. If the measured PCO2 is equivalent to the expected PCO2, then the respiratory compensation is adequate, and the condition is called a compensated metabolic acidosis. If the PCO2 is higher than the calculated value, hence insufficiently compensated, then the disturbance is called a primary metabolic acidosis with a superimposed respiratory acidosis. If the PCO2 is lower than the calculated value, then there is a respiratory alkalosis also present. This acid-base disturbance is called a primary metabolic acidosis with a superimposed respiratory alkalosis. Lastly, if either of the latter two conditions occur, but the pH is normal, then you have a combined metabolic acidosis and respiratory alkalosis. This last statement emphasizes that there is no primary disorder, but that both disorders are equivalent in severity (which is why the pH is normal).

Metabolic acidosis

Metabolic acidosis is characterized by a primary decrease in [HCO3 -], either by the loss of HCO3 - (as in gastrointestinal losses or impaired renal acid secretion) or by a gain of acid associated with an unmeasured anion, and compensatory reduction in the PCO2. The etiologies of metabolic acidosis are therefore divided into those that cause an increase in the AG (organic acidosis) and those associated with a normal gap (hyperchloremic acidosis). The AG is the difference between measured cations and measured anions, defined as [Na+] – ([Cl-] + [HCO3 -]). Under normal conditions, unmeasured anions are accounted for by plasma proteins, primarily albumin, while the remainder consists of phosphate, sulfates, lactate and other organic anions. The unmeasured anions that may, under pathologic conditions, lead to an increased AG can be either endogenous substances (ketones, lactate) or exogenous substances (salicylates, ethylene glycol). It is important to understand however, that a substantial organic acidosis can be present despite a normal measured AG, typically because of the hypoalbuminemia of critical illness.

Normal AG acidosis occurs from the loss of HCO3 -, through the kidney or through the gut, or from the addition of an acid with chloride as the accompanying anion. Etiologies of a normal-gap acidosis are listed in Table 2, while etiologies if an increased AG metabolic acidosis are given in Table 3. Bicarbonate therapy may be indicated for normal-gap acidosis, however, for most AG acidoses, correction of the underlying cause will typically suffice.

Metabolic alkalosis

Metabolic alkalosis is characterized by a primary increase in the [HCO3 -] and a compensatory increase in the PCO2. Respiratory compensation for severe metabolic alkalosis has practical limits, as respirations can only be suppressed to a certain degree before hypoxemia becomes the primary respiratory stimulus. For a metabolic alkalosis to persist there must be both a process that elevates serum [HCO3 -] (generally gastric or renal acid loss) and a stimulus for renal HCO3 - reabsorption (typically hypovolemia, hypochloremia, renal failure or mineralocorticoid excess). The major causes of metabolic alkalosis in the ICU – vomiting, nasogastric suction, loop diuretics, corticosteroids, and over ventilation of patients with chronically increased bicarbonate levels – are obvious from a patient's history and medication list. If the etiology is not clear, a trial of volume and chloride replacement, as well as correction of hypokalemia, can be attempted. In patients who require continued diuresis but exhibit rising HCO3 - levels, acetazolamide can be used to reduce the HCO3 - level. The etiologies of metabolic alkalosis are listed in Table 4.

Respiratory acidosis

Respiratory acidosis is characterized by a primary increase in the arterial PCO2 and a compensatory increase in the [HCO3 -]. Respiratory acidosis represents ventilatory failure or disordered central control of ventilation, the pathophysiology, etiology and treatment of which are described in detail elsewhere. However, initial treatment of clinically significant respiratory acidosis consists of capturing the patient's airway and providing positive pressure ventilatory support, pending treatment of the specific pathologic etiology (see Table 5.)

Respiratory alkalosis

Respiratory alkalosis is characterized by a primary reduction in arterial PCO2. Respiratory alkalosis is very common in the ICU and its causes range from benign (simple anxiety) to life-threatening (pulmonary embolism). Distinguishing those respiratory alkaloses that are manifestations of serious disease requires a thorough clinical review. Etiologies of respiratory alkalosis are listed in Table 6.

The primary treatment of respiratory alkalosis is treating the underlying cause of hyperventilation. The alkalemia itself does not require treatment. In cases where a severe alkalemia is present – generally, when a respiratory alkalosis is superimposed on a metabolic alkalosis – sedation may be necessary. In sepsis, where a substantial portion of cardiac output can go to the respiratory muscles, intubation and muscle relaxation may be used to control hyperventilation and redirect blood flow.

Mixed acid-base disturbances

Mixed acid-base disorders, defined as independently coexisting disorders, not merely compensatory responses. Mixed acid-base disorders can lead to very dangerous extremes of pH. Several key facts can be helpful in determining the presence of a mixed acid-base disorder. First, if the pH is normal, but the HCO3 - and the PCO2 are abnormal, then a mixed acid-base disturbance is present. This is explained by the fact that compensation is never sufficient to achieve a normal pH. Secondly, if the pH is abnormal and the changes in HCO3 - and the PCO2 occur in the opposite direction, then a mixed acid-base disturbance is present. Lastly, the presence of normal pH, PCO2 and HCO3 - does not eliminate the presence of a mixed acid-base disturbance, especially if an elevated AG exists (indicative of a mixed metabolic acidosis and metabolic alkalosis).

Arterial vs venous sampling

The evaluation of an arterial blood gas (ABG) has traditionally been the sample of choice for acid-base interpretation. It has been increasingly understood that although an ABG is great for evaluating the respiratory aspect of the patient, it is unlikely to reflect the acid-base status of the peripheral tissues, particularly in the hemodynamically unstable patient. Therefore, a venous blood gas may be the preferred site of sampling for a more accurate representation of what is occurring at the tissue level.

Whether you obtain an arterial sample or venous sample, it is important to obtain a sample that minimizes sampling errors. One of the most common technical mistakes is excessive heparin in the syringe, diluting the sample size. This dilution can dramatically change the measured values. Additional considerations are prompt removal of air bubbles from the syringe. Analysis should be performed promptly – generally within 15 minutes.

References Available Upon Request