Carbon Dioxide Tension

Pco₂ has been measured traditionally by exposing whole blood to a modified pH electrode contained in a jacket with a Teflon membrane at its tip (see Chapter 11). The jacket contains a bicarbonate buffer. As CO₂ diffuses through the membrane, it combines with water to form carbonic acid (H₂CO₃). The H₂CO₃ dissociates into H⁺ and HCO3−, thereby changing the pH of the bicarbonate buffer. The change in pH is measured by the electrode and is proportional to the Pco₂. Newer blood gas analyzers use a spectrophotometer to measure the absorbance of CO₂ in the infrared portion of the spectrum. The blood must be anticoagulated and kept in an anaerobic state until analysis. Pco₂ may also be estimated using a transcutaneous electrode. Measurement of end-tidal CO₂ (Petco₂) is sometimes used to track Pco₂ (see later section, Capnography).

The pH and Pco₂ are usually measured from the same sample, so bicarbonate can be easily calculated. Automated blood gas analyzers perform this calculation along with others to derive values such as total CO₂ (dissolved CO₂ plus HCO3−) and standard bicarbonate (i.e., HCO3− corrected to a Paco₂ of 40 mm Hg). If the hemoglobin (Hb) is measured or estimated, the base excess (BE) can be calculated. The normal buffer base at a pH of 7.40 is approximately 48 mmol/L. BE is the difference between the actual buffering capacity of the blood and the expected value. When the buffering capacity is less than the expected value, the difference is a negative value. This is sometimes referred to as a base deficit rather than a negative base excess. The main buffers that affect the BE are HCO3− and Hb.

Oxygen Tension

The Po₂ (arterial or mixed venous) has been traditionally measured by exposing whole blood, obtained anaerobically, to a platinum electrode covered with a thin polypropylene membrane. This type of electrode is called a polarographic electrode or Clark electrode. Oxygen molecules are reduced at the platinum cathode after diffusing through the membrane (see Chapter 11). Newer blood gas analyzers use an optical system that senses the ability of O₂ to change the intensity and duration of phosphorescence in a phosphorescent dye. Po₂ may also be measured using a transcutaneous electrode (see Chapter 11).

Blood gas values (pH, Pco₂, Po₂) are influenced by the patient’s temperature. Alteration of body temperature affects the partial pressure of dissolved CO₂, which influences pH as described in the previous equations. Table 6-1 describes the expected blood gas changes when the patient’s temperature is not 37°C. Although blood gas measurements are made at 37°C, the value reported is sometimes corrected to the patient’s temperature.

Technical problems with blood gas electrodes and related measuring devices include contamination by protein or blood products. In electrode-based analyzers, depletion of buffers in the electrodes may reduce accuracy and cause unacceptable drift. Tears or ruptures of the membranes used to cover the electrodes are also common malfunctions. Some newer analyzers use spectrophotometric methods that can be compromised by mechanical or electronic failure of the sampling cuvette, or by inadequate mixing of the specimen.

Specimen Collection for Blood Gases

Arterial samples are usually obtained from either the radial or brachial arteries via puncture or catheter in adults. Arterial specimens may also be drawn from the femoral, dorsalis pedis, posterior tibial, or umbilical arteries. The radial artery of the nondominant hand is usually the preferred site. A warmed capillary sample (arterialized) can also be obtained to approximate an arterial specimen.

Before a radial artery puncture, adequacy of collateral circulation to the hand from the ulnar artery should be established, using the modified Allen’s test (Figure 6-1). The original Allen’s test was described by Dr. Edgar Allen, a vascular surgeon at the Mayo Clinic in the 1920s, to assist in the diagnosis of thromboangiitis obliterans (e.g., Raynaud’s disease). A positive test in his description denoted reduced circulation; however, using the modified technique, a “positive test” demonstrates adequate collateral circulation. In performing the modified Allen’s test, the technologist occludes both the radial and ulnar arteries by pressing down over the wrist. The patient is instructed to make a fist, then open the hand and relax the fingers. The palm of the hand is pale and bloodless because both arteries are occluded. The ulnar artery is released while the radial remains occluded. The hand should be reperfused rapidly (5–15 seconds) if the ulnar supply is adequate. If perfusion is inadequate, an alternative site should be used.

Arterial puncture should not be performed through any type of lesion. Similarly, puncture distal to a surgical shunt (e.g., shunts used for dialysis) should be avoided. Infection or evidence of peripheral vascular disease should prompt selection of an alternative site. Some patients may be using anticoagulant drugs such as heparin, warfarin (Coumadin), or streptokinase. High doses of these drugs or a history of prolonged clotting times may be relative contraindications to arterial puncture. Box 6-1 lists some of the potential hazards associated with arterial puncture.

Success in obtaining an arterial specimen by radial puncture requires careful positioning of the patient’s wrist. The hand should be hyperextended with good support under the wrist (Figure 6-2, arterial puncture). A topical anesthetic may be useful for some patients, but is usually unnecessary. Always perform the modified Allen’s test to ensure adequate collateral circulation before puncturing the artery. The person drawing the sample should be in a comfortable position (i.e., sitting) to maximize control of the needle during insertion. It is recommended that the person drawing the sample use standard precautions and personal protective equipment, including gloves and eyewear. A vented syringe or similar device allows the blood to “pulse” into the syringe, ensuring that the needle is in the lumen of the artery.

Drawing a sample from a catheter–infusion system for an arterial or mixed venous sample from a pulmonary artery (Swan-Ganz) catheter has its own nuances. Contamination of the sample with flush solution is a common problem. Withdrawing a small volume of blood into a “waste” syringe ensures that the sample is not diluted by flush solution in the catheter. Care should be taken to limit the volume of blood removed in this process. Significant blood loss can occur with repetitive measurements. Another problem associated specifically with mixed venous specimen collection is displacement of the Swan-Ganz catheter tip. If the catheter is advanced too far, it may “wedge” into a pulmonary arteriole. Specimens drawn from this position often reflect arterialized pulmonary capillary blood. Similarly, if the catheter tip is withdrawn or “loops back,” it may be in the right ventricle or atrium rather than in the pulmonary artery. Specimens obtained from this location may not represent true mixed venous blood.

Venous samples from peripheral veins are not useful for assessing oxygenation. Venous blood reflects only the metabolism of the area drained by that particular vein. Venous samples may be used for measurement of pH or blood lactate during exercise.

Blood is usually collected in a syringe to which an anticoagulant (e.g., heparin) has been added, and sealed from the atmosphere immediately (Criteria for Acceptability 6-1). Blood gases are typically drawn using specially designed syringes containing a dry anticoagulant (i.e., a blood gas “kit”). Dry heparin is applied to the lumen of the needle and the interior of the syringe. A small heparin pellet is often placed in the syringe to provide additional anticoagulation. Care must be taken that heparin solution (sometimes used for flushing arterial catheters) does not contaminate the sample. Contamination by flush solution may affect Po₂ and Pco₂ values by dilution, but the buffering capacity of whole blood prevents large changes in pH.

After the syringe has been capped (see Chapter 12 for safe handling of blood specimens), the sample should be thoroughly mixed by rolling or gently shaking. Mixing helps prevent the sample from clotting, whether dry or liquid heparin is used. Mixing is also important for analyzers that use spectrophotometric methods for measuring blood gases. Lithium heparin or a similar preparation should be used for specimens that will also be used for electrolyte analysis.

Air contamination of arterial or mixed venous blood specimens can seriously alter blood gas values. Room air at sea level has a Po₂ of approximately 150 mm Hg, and a Pco₂ near 0. If air bubbles are present in a blood gas specimen, equilibration of gases between the sample and air occurs (Table 6-2). Contamination commonly occurs during sampling when air is left in the syringe after the sample is collected. Small bubbles may also be introduced if the needle does not connect tightly to the syringe. Other sources of air contamination include poorly fitting plungers and failure to properly cap the syringe. Use of a vented syringe or one in which the pulse pressure of the blood displaces the plunger can help prevent air bubble contamination.

Sample storage depends on the type of syringe used. If a glass syringe is used, the sample may be stored in ice-water slush if analysis is not done within a few minutes. Ice water reduces the metabolism of red and white blood cells in the sample. Specimens with O₂ tensions in the normal physiologic range (50–150 mm Hg) show minimal changes over 1–2 hours for glass syringes if kept in ice water. Changes in specimens held at room temperature are related to cellular metabolism in the blood, particularly in white blood cells and platelets. Specimens with Po₂ values above 150 mm Hg are most susceptible to alterations resulting from gas leakage or cell metabolism. When the Po₂ is 150 mm Hg or more, Hb is almost completely bound with O₂. In such cases, a small change in O₂ content results in a large change in Po₂.

If a plastic syringe is used, blood gas specimens should be analyzed within 30 minutes. Plastic syringes are not completely gas tight, so room air can contaminate the sample. The influx of O₂ may be counterbalanced by the consumption of O₂ if the sample is not iced. When a blood gas specimen is placed in an ice-water bath, the solubility of O₂ increases, as does the affinity of hemoglobin for oxygen. This lowers the partial pressure of O₂ in the sample and increases the gradient between the sample and the environment. This gradient exaggerates the leakage of O₂ into the specimen (as occurs with plastic syringes). When the sample is introduced into the analyzer at 37°C, solubility and Hb affinity return to their normal values, the oxygen that leaked in is released, and the Po₂ is falsely increased. Because of these phenomena, blood gas specimens in plastic syringes should not be placed in ice water. If specimens cannot be routinely analyzed within 30 minutes, glass syringes with ice-water storage may be preferable.

Capillary samples are useful in infants when arterial puncture is impractical. The area for collection (the heel is commonly chosen) should be heated by a warm compress and lanced. Blood is then allowed to fill the required volume of heparinized glass/plastic capillary tubes. Squeezing the tissue should be avoided because predominantly venous blood will be obtained. The capillary tubes should be carefully sealed to avoid air bubbles. Guidelines for quality control of blood gas analyzers and for the safe handling of blood specimens are included in Chapter 12.

pH

The pH of arterial blood in healthy adults averages 7.40 with a range of 7.35–7.45. Arterial pH below 7.35 constitutes acidemia. A pH above 7.45 constitutes alkalemia. Because of the logarithmic scale, a change of 0.3 pH units represents a twofold change in [H⁺] concentration. If the pH decreases from 7.40 to 7.10 with no change in Pco₂, the concentration of hydrogen ions has doubled. Conversely, if the concentration of [H⁺] is halved, the pH increases from 7.40 to 7.70, assuming the Pco₂ remains at 40 mm Hg. Changes of this magnitude represent marked abnormalities in the acid-base status of the blood and are almost always accompanied by clinical symptoms (e.g., cardiac arrhythmias) (Figure 6-3). If a metabolic acidemia is present, examination of the Anion Gap (AG) needs to be assessed. The anion gap is the difference between routinely measured cations (sodium) and anions (chloride and bicarbonate) in serum, plasma, or urine. The magnitude of the difference in serum is calculated to help identify the cause of a metabolic acidemia. The anion gap also reflects unmeasured cations (e.g., proteins, organic acids, phosphates) and anions (e.g., calcium, potassium, magnesium) (Table 6-3). The AG is expressed in units of mEg/L or mmol/L and is calculated by subtracting the serum concentrations of chloride and bicarbonate from the concentrations of sodium and potassium. However, in routine clinical practice, the potassium is frequently ignored, which leaves the following equation:

AG=[Na+]−[Cl-+HCO3−]AG=140−[105+24]AG=11 mEq/L

The normal range is 3 − 11 mEq/L; however, the reference range should be provided by the lab performing the tests.

Acid-base disorders arising from lung disease are often related to Pco₂ and its transport as carbonic acid. If the pH is outside of its normal range (i.e., acidemia or alkalemia) but Pco₂ is within normal limits, the condition is termed nonrespiratory or metabolic (Table 6-4). The calculated HCO3− is a useful indicator of the relationship between pH and Pco₂. In the presence of acidemia (pH less than 7.35) and normal CO₂ (Pco₂ 35–45 mm Hg), HCO3− will be low and a metabolic acidosis is present. A Pco₂ of less than 35 mm Hg in the presence of acidosis suggests that ventilatory compensation for acidemia is occurring. The acid-base status would be considered partially compensated nonrespiratory (i.e., metabolic) acidosis. Complete compensation occurs if pH returns to the normal range. This happens when ventilation reduces Pco₂ in proportion to the HCO3−.

Table 6-4

Acid-Base Disorders

Status	pH	Pco2	HCO3−
Simple Disorders
Metabolic acidosis	Low	Normal	Low
Metabolic alkalosis	High	Normal	High
Respiratory acidosis	Low	High	Normal
Respiratory alkalosis	High	Low	Normal
Compensated Disorders
Compensated respiratory acidosis, or metabolic alkalosis	Normal*	High	High
Compensated metabolic acidosis, or respiratory alkalosis	Normal*	Low	Low
Combined Disorders
Metabolic/respiratory acidosis	Low	High	Low
Metabolic/respiratory alkalosis	High	Low	High

^*Compensation cannot return values to within normal limits in severe acid-base disturbances. In addition, a normal pH may result in instances of respiratory and metabolic disturbances that occur together but are not compensatory.

In the presence of alkalemia (pH above 7.45) and normal Pco₂ (35–45 mm Hg), calculated bicarbonate will be increased and metabolic alkalosis is present. If ventilatory compensation occurs, Pco₂ will be slightly increased. However, decreased ventilation is required so that the CO₂ can increase. Reduced minute ventilation may interfere with oxygenation. For this reason, Paco₂ seldom increases above 50 mm Hg to compensate for nonrespiratory (i.e., metabolic) alkalosis. Compensation may be incomplete if the alkalosis is severe.

Abnormal Pco₂ and HCO3− characterize combined respiratory and nonrespiratory acid-base disorders. In combined acidosis, Pco₂ is elevated (more than 45 mm Hg) and HCO3−is low (less than 22 mEq/L). In combined alkalosis, HCO3−is elevated (more than 26 mEq/L) and Pco₂ is low (less than 35 mm Hg). The pH is more severely deranged (i.e., much higher or lower) than if just one disorder were present.

Carbon Dioxide Tension

The arterial carbon dioxide tension (Paco₂) in a healthy adult is approximately 40 mm Hg; it may range from 35–45 mm Hg. The Pco₂ of venous or mixed venous blood is seldom used clinically. Body temperature affects Paco₂, as described in Table 6-1.

Paco₂ is inversely proportional to alveolar ventilation (_A) (see Chapter 5). When _A decreases, CO₂ may not be removed by the lungs as fast as it is produced. This causes Paco₂ to increase. The pH falls (i.e., [H⁺] increases) as CO₂ is hydrated to form carbonic acid:

CO2+ H2O↔H2CO3↔H++ HCO3−

Increasing levels of CO₂ in the blood drive this reaction to the right. The patient has respiratory acidosis resulting from hypoventilation. Conversely, when alveolar ventilation removes CO₂ more rapidly than it is produced, Paco₂ decreases. The pH increases (i.e., [H⁺] falls) as the patient becomes alkalotic. This condition is called hyperventilation, or respiratory alkalosis.

If dead space increases, high-minute ventilation (_E) may be required to adequately ventilate alveoli and keep Paco₂ within normal limits. Respiratory dead space occurs because some lung units are ventilated but not perfused by pulmonary capillary blood. Pulmonary embolization is an example of dead space–producing condition. Emboli may block pulmonary arterioles, causing ventilation of the affected lung units to be “wasted.” To maintain normal Paco₂, total ventilation must be increased to compensate for wasted ventilation. Paco₂ may be normal, or decreased, even though significant pulmonary disease is present.

Patients who have disorders such as lobar pneumonia may increase their _E to provide more alveolar ventilation of functional lung units. This mechanism compensates for lung units that do not participate in gas exchange. Hypoxemia is a common cause of hyperventilation (i.e., respiratory alkalosis). Hyperventilation may be seen in patients with asthma, emphysema, bronchitis, or foreign body obstruction. Anxiety, stress or central nervous system disorders may also cause hyperventilation. Hyperventilation may also be an intentional or unintentional result of mechanical ventilation.

Increased Paco₂ (i.e., hypercapnia) commonly occurs in patients who have advanced obstructive or restrictive disease. These individuals are characterized by markedly abnormal ventilation-perfusion (/) patterns. They are unable to maintain adequate alveolar ventilation. Not all patients with advanced pulmonary disease retain CO₂. Those who do become hypercapnic often have a low ventilatory response to CO₂ (see Chapter 5). Their response to the increased work of breathing caused by obstruction or restriction is to allow CO₂ to increase rather than increase ventilation. When respiratory acidosis results from increased Pco₂, renal compensation usually occurs (see Table 6-4).

Increased Paco₂ may also be seen in patients who hypoventilate as a result of central nervous system or neuromuscular disorders. Whether CO₂ retention is the result of lung disease, central nervous system dysfunction, or neuromuscular disease, pH is usually maintained close to normal. The kidneys retain and produce bicarbonate (HCO3−) to match the increased Paco₂. This response may completely compensate for a mildly elevated Paco₂. However, it can seldom produce normal pH when the Paco₂ is greater than 65 mm Hg. If the disorder causing the increased Paco₂ is acute (e.g., foreign body aspiration), little or no renal compensation may be observed.

Some degree of hypoxemia is always present in patients who retain CO₂ while breathing air. As alveolar CO₂ increases, alveolar O₂ decreases. If the cause of hypercapnia is either obstructive or restrictive lung disease, hypoxemia may be severe because of /abnormalities. Because O₂ therapy is common in these patients, changes in Pco₂ while breathing supplementary O₂ must be carefully monitored. Some patients with chronic hypoxemia have a decreased ventilatory response to CO₂. O₂ administered to these patients may reduce their hypoxic stimulus to ventilation. As a result, Paco₂ may increase further. O₂ therapy is usually titrated to maintain Paco₂ values less than 60 mm Hg without hypercapnia and acidosis.

Oxygen Tension

The Pao₂ of healthy young adults at sea level ranges from 85–100 mm Hg and decreases slightly with age. Breathing room air at sea level results in an inspired Po₂ of approximately 150 mm Hg:

PIO2=FIO2(PB−47) =0.21(760−47) =0.21(713) =149.7

where:

F_IO₂= fractional concentration of inspired O₂

P_B= barometric pressure

47= partial pressure of water vapor at 37°C

The partial pressure of O₂ in alveolar gas is usually close to 100 mm Hg and can be calculated using the alveolar air equation:

PAO2=(FIO2×  [PB−47])−PaCO2 (FIO2+1−FIO2R)

where:

Paco₂= arterial CO₂ tension (presumed equal to alveolar CO₂ tension)

R= respiratory exchange ratio (co₂/o₂)

Substituting 40 mm Hg for Paco₂, and 0.8 for R:

PAO2=(0.21  ×   [760−47])−40  (0.21+1−0.210.8)

=(0.21  ×  713)−40(1.1975)