To evaluate a patient for hypoxia, the physician is most likely to order which laboratory test

Traditional Assessment of Ventilation-Perfusion Inequality

A central question that has engaged the attention of physiologists and physicians for many years has been how best to assess the amount of ventilation-perfusion inequality. Ideally, we would like to know the actual distribution of ventilation-perfusion ratios (see next section), but theprocedure required for this is too complicated for many clinical situations. Traditionally, we rely on measurements of Po2 and Pco2 in arterial blood and expired gas.

The arterial Po2 certainly gives some information about the degree of ventilation-perfusion inequality. In general, the lower the Po2, the more marked is the mismatching of ventilation and blood flow. The chief merit of this measurement is its simplicity, but a disadvantage is that its value is sensitive to the overall ventilation and pulmonary blood flow, to inspired Po2, and to other potential causes of hypoxemia already discussed.

Arterial Pco2 is so sensitive to the level of ventilation that it gives little information about the extent of the ventilation-perfusion inequality. However, the most common cause of an increased Pco2 in chronic lung disease is mismatching of ventilation and blood flow, as explained later in the section on ventilation-perfusion inequality and carbon dioxide retention.

Because of these limitations, the alveolar-arterial Po2 difference is frequently measured and is more informative than the arterial Po2 alone because it is less sensitive to the level of overall ventilation. To understand the significance of this measurement, we need to look in more detail at how gas exchange is altered by the imposition of ventilation-perfusion inequality.

Figure 10.20 shows an oxygen–carbon dioxide diagram with the same ventilation-perfusion line as that inFigure 10.17. Suppose initially that this lung has no ventilation-perfusion inequality. The Po2 and Pco2 of the alveolar gas and arterial blood would then be represented by point i, known as the ideal point. This is at the intersection of the gas and bloodrespiratory exchange ratio (R) lines; these lines indicate the possible compositions of alveolar gas and arterial blood consistent with the overall respiratory exchange ratio (carbon dioxide output/oxygen uptake) of the whole lung. In other words, a lung in which R = 0.8 would have to have its mixedalveolar gas point (A) located somewhere on the line joining points i and I. A similar statement can be made for thearterial gas point (a).

What happens to the composition of mixed alveolar gas and arterial blood as ventilation-perfusion inequality is imposed on the lung? The answer is that both points diverge away from theideal point (i) along the gas and blood R lines. The more extreme the degree of ventilation-perfusion inequality, the further the divergence. Moreover, the type of ventilation-perfusion inequality determines how much each point will move. For example, a distribution containing a large amount of ventilation to units with high ventilation-perfusion ratio especially moves point A down and to the right, away from point i. By the same token, a distribution containing large amounts of blood flow to units with low ventilation-perfusion ratios predominantly moves point a leftward along the blood R line.

Acute Respiratory Failure

Acute respiratory failure with an increasing Paco2 from 40 to 80 mm Hg results in a corresponding decrease in pH from 7.40 to 7.20. In general, blood gas analysis from this type of patient shows a Pco2 greater than 45 mm Hg, a pH of less than 7.35, and HCO3− and BE within the normal range. This finding is the typical picture of acute respiratory acidosis. The reason for this condition can vary from drug-induced hypoventilation to acute neurologic conditions to pulmonary or cardiac dysfunction. Hypoxemia varies with the underlying cause. Symptoms depend on the presentation and on the degree of hypoxemia and hypercapnia. The typical presentation of hypoxemic respiratory failure is severe dyspnea with accessory muscle use, tachycardia, hypertension, diaphoresis, and mental status changes. Worsening status and arterial blood gases are often interpreted as impending ventilatory failure. Options for ventilatory support should be considered on an emergency basis.

Hyperventilation can occur in response to hypoxemia, but it is also seen without hypoxemia in pronounced metabolic acidosis (Kussmaul's breathing in diabetes) and in intracranial dysfunction. This condition leads to respiratory alkalosis with a pH greater than 7.45 and a Paco2 lower than 35 mm Hg. Additionally, the anxious or painful patient may show signs of treatable hyperventilation. Confounding clinical situations can be associated with tissue hypoxia related to a low amount of transported O2, such as in methemoglobinemia, carbon monoxide poisoning, and severe anemia. In chronic hyperventilation, pH normalizes over time as a result of renal compensation, but Paco2 remains lower than 35 mm Hg.

Ventilation and Blood Gases

During pregnancy, respiratory patterns remain relatively unchanged. Minute ventilation increases via an increase in tidal volume from 450 to 600 mL and a small increase in respiratory rate of 1 to 2 breaths/min.79 This occurs primarily during the first 12 weeks of gestation with a minimal increase thereafter. The ratio of total dead space to tidal volume remains constant during pregnancy, resulting in an increase in alveolar ventilation of 30% to 50% above baseline. The increase in minute ventilation results from hormonal changes and from an increase in CO2 production at rest by approximately 30% to 300 mL/min. The former is closely related to the blood level of progesterone,80 which acts as a direct respiratory stimulant. The progesterone-induced increase in chemosensitivity also results in a steeper slope and a leftward shift of the CO2-ventilatory response curve. This change occurs early in pregnancy and remains constant until delivery.69

Dyspnea is a common complaint during pregnancy, affecting up to 75% of women.81 Contributing factors include increased respiratory drive, decreased Paco2, increased oxygen consumption from the enlarging uterus and fetus, larger pulmonary blood volume, anemia, and nasal congestion. Dyspnea typically begins in the first or second trimester but improves as the pregnancy progresses. In a study in which 35 women were observed closely during pregnancy and postpartum, dyspnea was not caused by alterations in central ventilatory control or respiratory mechanical factors but rather to the awareness of the increased ventilation.82 Exercise has no effect on pregnancy-induced changes in ventilation or alveolar gas exchange.83 The hypoxic ventilatory response is increased during pregnancy to twice the normal level, secondary to elevations in estrogen and progesterone levels.84 This increase occurs despite blood and cerebrospinal fluid (CSF) alkalosis.

During pregnancy, Pao2 increases to 100 to 105 mm Hg (13.3 to 14.0 kPa) as a result of greater alveolar ventilation and a decline in Paco2 (Table 2.4).85–87 As pregnancy progresses, oxygen consumption continues to increase, and cardiac output increases to a lesser extent, resulting in a reduced mixed venous oxygen content and increased arteriovenous oxygen difference. After mid-gestation, pregnant women in the supine position frequently have a Pao2 less than 100 mm Hg (13.3 kPa). This occurs because the FRC may be less than closing capacity, resulting in closure of small airways during normal tidal volume ventilation.85 Moving a pregnant woman from the supine to the erect or lateral decubitus position improves arterial oxygenation and reduces the alveolar-to-arterial oxygen gradient. The increased oxygen tension facilitates the transfer of oxygen across the placenta to the fetus.

Introduction

Blood gas analysis is a common investigation used to assess and monitor the acid–base balance of patients. Depending on the source of the blood sample, the test may be either an arterial blood gas (ABG) or venous blood gas (VBG). ABGs provide a range of standard variables (e.g., pH, partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), and indirectly, HCO3− and base excess) which are useful in the investigation of acidosis or alkalosis and its underlying etiology (i.e., metabolic, respiratory, or mixed). VBGs can approximate pH, but venous pCO2 and pO2 are of little utility (Byrne et al., 2014). Technological developments have also enabled the simultaneous quantitation of key electrolytes (e.g., K, Na, Ca, Cl), metabolites (e.g., lactate, blood glucose, creatinine), and blood components (e.g., oxyhemoglobin, carboxyhemoglobin, methemoglobin (MetHb), oxygen saturation, etc.). Newer blood gas analyzers are also able to provide increasingly rapid and accurate results. Such information is critical in the evaluation and management of various life-threatening conditions (e.g., shock, respiratory failure). This has allowed blood gas analysis a wide range of applications especially in the intensive care and emergency department settings. This article will discuss the procedures of blood gas analysis and the interpretation of blood gas results in health and some common disease states.

Arterial Blood Gas Studies

The arterial Po2, arterial Pco2, and pH are the most informative laboratory indicators of gas exchange in patients with pulmonary edema. Arterial blood gas studies are not sensitive to early edema. Interstitial pulmonary edema does not usually affect oxygen uptake in the lungs beyond modest hypoxemia caused by ventilation-perfusion mismatching. In contrast, alveolar flooding seriously compromises gas exchange, resulting in right-to-left shunting of blood from ongoing perfusion of fluid-filled or collapsed alveoli. In two studies of groups of patients with increased permeability edema from lung injury, oxygenation appeared to depend more on the ability of the pulmonary circulation to mediate hypoxic pulmonary vasoconstriction—and thereby reduce perfusion to damaged and edematous areas of the lungs—than on the amount of edema present.109,110

In patients hospitalized for acute cardiogenic pulmonary edema, arterial Pco2 may be low, especially in the early stages, when tachypnea results in alveolar hyperventilation. Arterial Pco2 may also be within the normal range or elevated, the latter indicating alveolar hypoventilation, which can be caused by underlying lung disease, increased metabolic production of carbon dioxide (perhaps related to increased work of breathing), increased wasted ventilation (ventilation of poorly perfused alveoli), or mechanical impairment caused by weak respiratory muscles.111 An elevated pulmonary dead space fraction in the first 24 hours after development of severe increased permeability edema identifies patients with a higher risk for death, particularly if the dead space fraction is greater than 0.60.62

When pulmonary edema is severe or the lungs have been injured, many patients develop metabolic acidosis as a result of tissue hypoxia, increased work of breathing, intrinsic lung lactate production, or all of these.112 Attempts to correct acidosis with parenteral bicarbonate administration usually are not necessary; rather, the underlying cause must be identified and treated appropriately. Maintenance of a satisfactory systemic blood pressure is crucial. Respiratory acidosis caused by alveolar hypoventilation can be treated either bynoninvasive ventilation (NIV) or by invasive mechanical ventilation with endotracheal intubation. Metabolic acidosis can be partially corrected by alleviating hypoxemia and improving cardiac function; the possibility of underlying disease amenable to surgery (e.g., intestinal ischemia or infarction, perforation of a viscus) or pancreatitis should be considered.

Arterial Blood Gases

Blood gas analysis need not be undertaken in individuals with mild asthma. If the asthma is of sufficient severity to merit prolonged observation, however, blood gas analysis is indicated; in such cases, hypoxemia and hypocapnia are the rule. With the subject breathing ambient air, the Pao2 is usually between 55 and 70 mm Hg and the Paco2 between 25 and 35 mm Hg. At the onset of the attack, an appropriate pure respiratory alkalemia is usually evident; with attacks of prolonged duration, the pH returns toward normal as a result of a compensatory metabolic acidemia. A normal Paco2 in a patient with moderate to severe airflow obstruction is reason for concern because it may indicate that the mechanical load on the respiratory system is greater than can be sustained by the ventilatory muscles and that respiratory failure is imminent. When the Paco2 increases in such settings, the pH decreases quickly because the bicarbonate stores have become depleted as a result of renal compensation for the prolonged preceding respiratory alkalemia. Because this chain of events can take place rapidly, close observation is indicated for asthmatic patients with “normal” Paco2 levels and moderate to severe airflow obstruction.

Arterial Blood Gas

ABG measurements provide valuable information about the adequacy of oxygenation, ventilation, and acid‐base balance. An ABG analysis should be obtained within 15–30 minutes after intubation to evaluate the need for adjustment in ventilator settings. After each change on the ventilator, a new ABG check should be considered to evaluate the effectiveness of the adjustment. The PaO2 should verify the accuracy of the transcutaneous pulse oximetry readings. If the noninvasive pulse oximetry and PaO2 from the ABG correlate, the FiO2 can be adjusted based on the noninvasive pulse oximetry alone. The PaCO2 guides the need for adjustments in minute ventilation.

Abstract

Blood gas measurements provide the intensivist with diagnostic information on many organ systems. The anion gap (AG) and the strong ion gap (SIG) exploit the principle of electroneutrality to quantify the net balance of unmeasured ions in plasma. The AG should be corrected for abnormalities in plasma albumin and phosphate concentrations. The AG and SIG can be used to narrow the differential diagnosis of acid-base disorders, and an increased corrected AG or SIG is diagnostic of a metabolic acidosis (i.e., an acidifying process) irrespective of plasma pH or bicarbonate. The SIG is often perceived as more complex but frequently yields more precise results in critically ill patients. In addition, the strong ion model can be used to guide fluid management because it acknowledges that electrolyte changes are causal mechanisms of acid-base disorders.

Diagnosis

The diagnosis of blast lung is based on a high index of suspicion, clinical features (Table 3.3; Box 3.14) and radiological investigation (Box 3.15).

Blood gas analysis shows progressive hypoxaemia and carbon dioxide retention. Pulse oximetry may be helpful but should be used with caution, bearing in mind that it does not give any indication of carbon dioxide levels and may not demonstrate progressive respiratory failure if inspired oxygen levels are high.

Clinical and radiological features may occur almost immediately or their appearance may be delayed for up to 48 hours. Symptoms may not be seen until sudden deterioration has already occurred. A period of observation is therefore mandatory for all patients at risk of blast injury to the lungs.

Disseminated intravascular coagulation (DIC) and hypokalaemia (before intravenous fluid therapy) have both been associated with blast lung injury. Conventional therapy including fresh frozen plasma (FFP) should be used for the DIC. There is now evidence that recombinant factor VIIa may be of value in life-threatening pulmonary haemorrhage. Early recognition of a significantly reduced potassium followed by intravenous replacement may reduce the likelihood of arrhythmias.

Severity Score

Blood gas analysis, specifically oxygenation, is regarded as the standard for assessment of severity of ARDS. While the P/F ratio provides the threshold value for the definition of ARDS, the (A–a) O2 difference (difference between “alveolar” vs. arterial Po2) can express the degree of hypoxemia. Both indices should be used with caution because neither incorporates any measure of the respiratory system mechanics nor the ventilatory assistance being provided to the patient. In this regard, the OI = [(mean airway pressure × FiO2) × 100]/PaO2 attempts to correct that deficiency. However, even this may mislead if the ventilation strategy employed is not optimized, such as inappropriately high or low airway pressures or Fio2 in the case of an intrapulmonary shunt, which is minimally responsive to altered Fio2 or airway pressure.

Although death in ARDS is usually attributable to multiorgan failure41 rather than persistent hypoxemia, the severity of oxygenation failure, expressed as the OI,42 or to a lesser extent as the P/F ratio43 does correlate with the duration of mechanical ventilation and with mortality in children. In contrast to oxygenation, the ventilation index44: [Paco2 × peak airway pressure × respiratory rate]/1000 has been employed to reflect the difficulty involved in clearing CO2, (i.e., the pulmonary dead space). The magnitude of dead space in the first days of ARDS has been shown to predict outcome in adults45 and recently in children.46