Hypoxemia Silverstein's Chapter PDF

CHAPTER 15 HYPOXEMIA † Steve C. Haskins, DVM, MS, DACVAA, DACVECC KEY POINTS • Hypoxemia is defined as a partial pressure of oxygen of less than 80 mm Hg or arterial blood hemoglobin saturation of less than 95%. • When cyanosis is manifested as a sign of hypoxemia, it is always a late sign of sev...

CHAPTER 15 HYPOXEMIA † Steve C. Haskins, DVM, MS, DACVAA, DACVECC KEY POINTS • Hypoxemia is defined as a partial pressure of oxygen of less than 80 mm Hg or arterial blood hemoglobin saturation of less than 95%. • When cyanosis is manifested as a sign of hypoxemia, it is always a late sign of severe hypoxemia. • There are three causes of hypoxemia: low inspired oxygen concentration, hypoventilation, or venous admixture. • There are four causes of venous admixture: low ventilationperfusion regions; small airway and alveolar collapse (atelectasis); diffusion defects; and anatomic right-to-left shunts. Hypoxemia is generally defined as an arterial partial pressure of oxygen (PaO2) of less than 80 mm Hg or arterial blood hemoglobin saturation (SaO2 or SpO2) of less than 95%. Serious, potentially lifethreatening hypoxemia is generally defined as a PaO2 less than 60 mm Hg or an SaO2 or SpO2 of less than 90%. Atmospheric oxygen is normally ventilated into the alveoli; it then diffuses across the respiratory membrane along partial pressure gradients into the plasma. Anything that interferes with one or more of these processes will decrease the plasma PO2. Oxygen diffuses from the plasma into the red blood cell and binds to hemoglobin. Both the PaO2 and SaO2 are affected by the same pulmonary processes, and SaO2 or SpO2 are often used as a surrogate marker of PaO2. Blood oxygen can also be expressed as a concentration or content (milliliters of oxygen per 100 ml of whole blood), but this parameter is primarily determined by hemoglobin concentration and is not considered, per se, to be a marker of hypoxemia. COLLECTION OF BLOOD SAMPLES FOR IN VITRO MEASUREMENT Arterial blood must be used for an assessment of pulmonary function. Venous blood comes from the tissues and is more a reflection of tissue function than lung function. The details of blood sampling and storage before analysis have been detailed elsewhere.1-3 The blood sample must be taken as anaerobically as possible (exposure to air will change the partial pressures of both oxygen and carbon dioxide) and analyzed as soon as possible. (In vitro metabolism and diffusion of gases into and through the plastic of the syringe will change the partial pressures of both oxygen and carbon dioxide.4) Excessive dilution with anticoagulant should be avoided.5 RECOGNITION OF HYPOXEMIA PaO2 The PaO2 is the partial pressure (the vapor pressure) of oxygen dissolved in solution in the plasma of arterial blood and is measured with a blood gas analyzer, usually with a silver anode/platinum cathode system in an electrolyte solution (polarography) separated † Deceased. from the unknown solution (the blood) by a semipermeable (to oxygen) membrane. The arterial PO2 (PaO2) is a measure of the ability of the lungs to move oxygen from the atmosphere to the blood. The normal PaO2 at sea level ranges between 80 and 110 mm Hg. SpO2 Hemoglobin saturation with oxygen (SaO2) is the inevitable consequence of the increase in PaO2 during the arterialization of venous blood as it traverses the lung; PaO2 and SaO2 are directionally (though not linearly) related. Hemoglobin saturation with oxygen can be measured with a bench-top oximeter (SaO2) using many wavelengths of red to infrared light. Pulse oximeters use only two wavelengths (660 and 940 nm) and are designed to measure only oxygenated hemoglobin (SpO2) (see Chapters 109 and 186).6,7 SpO2 is directionally, but not linearly, associated with PaO2 (Figure 15-1) and therefore can be used as a surrogate marker of PaO2 (Table 15-1). The SO2/PO2 relationship is described by a sigmoid curve, the oxygen-hemoglobin dissociation curve (see Figure 15-1 and Table 15-1). There are several important clinical implications of this relationship. Most importantly, the difference between normoxemia and hypoxemia is only a few saturation percentage points (see Table 15-1), and severe hypoxemia is only a few saturation percentage points below that. Small changes in SpO2 represent large changes in PaO2 in this region of the oxyhemoglobin dissociation curve. Second, severe hypoxemia is defined at a level when the hemoglobin is still 90% saturated. This may not seem fair, but it is the partial pressure of oxygen in the plasma, not hemoglobin saturation, that drives oxygen diffusion down to the mitochondria. PO2 is the driving force; SO2 (more specifically oxygen content) is the reservoir that prevents the rapid decrease in PO2 that would otherwise occur when oxygen diffuses out of the blood. Third, saturation measurements cannot detect the difference between a PaO2 of 100 and 500. This difference is important when monitoring and tracking the progress of animals breathing an enriched oxygen mixture. With these, and a few additional caveats, pulse oximeters noninvasively, continuously, and automatically monitor very well the parameter they were designed to measure—hypoxemia (see Chapter 186). Pulse oximeter readings are prone to error, and suspected hypoxemia should be corroborated with other clinical signs and an arterial blood gas analysis if necessary. Cyanosis Grayish to bluish discoloration of mucous membranes commonly signals the presence of deoxygenated hemoglobin in the observed tissues. The observation of cyanosis is dependent on the visual acuity of the observer (some individuals can see it earlier than others), lighting (it is more readily detected in a well-lit room than in the shadows of a cage), and the type of lighting used (it is more readily detectable with incandescent as opposed to fluorescent lighting).12 In general, it requires an absolute concentration of deoxygenated hemoglobin to manifest sufficient cyanosis that everyone agrees to its 81 PART II • RESPIRATORY DISORDERS existence; 5 gm/dl is the commonly cited figure.13 This is important for two reasons. First, if a dog had a hemoglobin concentration of 15 gm/dl, cyanosis would manifest when the arterial blood saturation decreased to 67% (equivalent to a PaO2 of about 37 mm Hg (see Figure 15-1). When cyanosis is manifested as a sign of hypoxemia, it is always a late sign of severe hypoxemia. Second, if an animal is anemic—for instance, having a hemoglobin concentration of 5 gm/ dl—it would die of hypoxemia and the resultant tissue hypoxia long before manifesting cyanosis. MECHANISMS OF HYPOXEMIA Oxyhemoglobin dissociation curves of different species Hemoglobin saturation (%) 82 There are three causes of hypoxemia: low inspired oxygen concentration, hypoventilation, and venous admixture (Figure 15-2; Tables 15-2 and 15-3). A fourth cause of hypoxemia can be a reduced venous oxygen content14-18 secondary to low cardiac output or sluggish peripheral blood flow (shock) or high oxygen extraction by the tissues (seizures). When venous oxygen content is very low, it takes Table 15-1 Correlation Between PaO2 and SaO2* Partial pressure of oxygen (PO2) Horse P5023.8 Dog P5028.7 Man Cat P5026.8 PaO2 SaO2 Severe hyperoxemia 500 100 Hyperoxemia 125 99 Normoxemia 100 98 Hypoxemia <80 <95 Severe hypoxemia <60 <90 29 50 P50 P5034.1 FIGURE 15-1 Oxyhemoglobin dissociation curves for the horse, man, dog, and cat.8-11 *This chart represents rounded approximations of the relationship between PaO2 and SaO2 in people and dogs. Cats have a right-shifted curve, in comparison, and the corresponding SaO2 values are lower (see Figure 15-1). Table 15-2 Primary Physiologic Causes of Hypoxemia Causes of Hypoxemia Recognition and Examples Treatment Low inspired oxygen Inspection of the apparatus Improper functioning apparatus to which the animal is attached Depleted oxygen supply; altitude Oxygen supplementation if at altitude Disconnect patient from mechanical apparatus and repair/replace apparatus Global hypoventilation Elevated PaCO2, end-tidal CO2, or PvCO2 Neuromuscular dysfunction; airway obstruction, abdominal distention, chest wall dysfunction, pleural space filling defect Oxygen supplementation; positive pressure ventilation; remove/bypass obstruction; decompress abdomen; close or stabilize chest wall; provide thoracocentesis Venous admixture See Table 15-3 See Table 15-3. CO2, Carbon dioxide; PvCO2, venous PCO2. Hypoxemia Decreased efficiency of transport of oxygen from the alveoli to the pulmonary capillaries Low alveolar oxygen due to reduced delivery of oxygen to the alveoli Low V/Q regions Low inspired oxygen Zero V/Q regions Hypoventilation Diffusion impairment Right-to-left A-V shunt FIGURE 15-2 Categorical causes of hypoxemia. Low alveolar oxygen due to increased extraction of oxygen from the alveoli (see text) Low venous oxygen content CHAPTER 15 • Hypoxemia Table 15-3 Venous Admixture Mechanisms of Venous Admixture Causes Notes Low V/Q regions Moderate to severe diffuse lung disease (edema, pneumonia, hemorrhage) Common; responsive to oxygen therapy Atelectasis (No V/Q regions) Severe to very severe diffuse lung disease (edema, pneumonia, hemorrhage) Common; not responsive to oxygen but responsive to PPV Diffusion defects Moderate to severe, diffuse lung disease (oxygen toxicity, smoke inhalation, ARDS) Uncommon; partially responsive to oxygen Right-to-left shunts Right-to-left PDA and VSD; intrapulmonary A-V anatomic shunts Uncommon; not responsive to oxygen or PPV; surgery possible A-V, Arterial to venous; ARDS, acute respiratory distress syndrome; low V/Q ratio, low ventilation compared with blood flow because of either low regional ventilation or high regional perfusion; PDA, patent ductus arteriosus; PPV, positive pressure ventilation; Q, perfusion; V, ventilation; VSD, ventricular septal defect. more oxygen and more time for the capillary blood to be arterialized. This lowers alveolar PO2 (PAO2) and therefore PaO2 will be lowered. In practice, the impact of low venous oxygen and blood flow is often offset by a decrease in shunt fraction, which offsets the decrease in PaO2.14,19 Low venous oxygen is verified by measuring central or mixed venous oxygen. Low Inspired Oxygen Low inspired oxygen must be considered any time an animal is attached to mechanical apparatus such as a face mask, anesthetic circuit, or ventilator or is in an enclosed environment such as an oxygen cage. Inspired or ambient oxygen concentration can be measured with a variety of commercially available oxygen meters. The problem can often be identified by inspection and verification of the improper operation of the mechanical device and remedied by replacing the device with one that is operating properly. The decrease in inspired oxygen concentration decreases the alveolar oxygen concentration and subsequently arterial blood oxygenation. High altitude is another cause of low inspired oxygen. Atmospheric oxygen concentration is 21% at any altitude, but as altitude increases, barometric pressure decreases and the partial pressure of oxygen in the atmosphere (PatmO2) represented by 21% also decreases. Normal individuals living at higher altitudes have lower PaO2 values and compensate to some extent by hyperventilating. Hypoventilation Hypoventilation is defined by an elevated PaCO2 (≥45 mm Hg) or one of its surrogate markers: end-tidal CO2 (usually about 5 mm Hg lower than PaCO2) or central venous PCO2 (usually about 5 mm Hg higher than PaCO2). See Chapter 16 for further discussion of this topic. Alveolar oxygen is the balance between the amount of oxygen being delivered to the alveoli (inspired oxygen concentration and alveolar minute ventilation) and the amount of oxygen being removed from the alveoli by the arterialization of venous blood (ultimately, tissue metabolism). A decrease in alveolar minute ventilation (hypoventilation) decreases the delivery of oxygen to the alveoli and subsequently to the blood leading to hypoxemia. Increasing the inspired oxygen concentration is very effective in preventing hypoxemia secondary to hypoventilation. There are only four gases of note in alveoli: oxygen, carbon dioxide, water vapor, and nitrogen. The partial pressure of alveolar oxygen (PAO2) can be determined by the alveolar air equation. The normal alveolar composition of gases when breathing room air at sea level is water vapor 50 mm Hg (fixed; alveolar gases are always 100% saturated at body temperature); carbon dioxide 40 mm Hg (regulated by the brainstem respiratory control center); oxygen 105 mm Hg; and nitrogen 560 mm Hg.19 If an animal was to hypoventilate to a PaCO2 of 80 mm Hg, the water vapor pressure and nitrogen levels would remain unchanged but the oxygen would fall to about 65 mm Hg and the patient would become hypoxemic. When breathing 100% oxygen for a time to allow the elimination of nitrogen from the readily mobilized stores (alveoli, blood, and vessel-rich tissues), the alveolar water vapor and carbon dioxide levels would not change but nitrogen would decrease to near 0 and oxygen would increase to near 665. If an animal were to severely hypoventilate while breathing 100% oxygen, the alveolar carbon dioxide could theoretically rise to about 550 mm Hg before the alveolar oxygen decreased to a level that would lead to hypoxemia (PaO2 < 80 mm Hg). Hence hypoventilation is a cause of hypoxemia in patient’s breathing room air but not in patients breathing enriched oxygen mixtures. Further hypoxemia as a result of hypoventilation is readily resolved with oxygen therapy. Venous Admixture Venous admixture is all the ways in which venous blood can get from the right side to the left side of the circulation without being properly oxygenated. Blood flowing through some regions of the lung may be suboptimally oxygenated or may not be oxygenated at all. When this “venous” blood admixes with optimally arterialized blood flowing from the more normally functioning regions of the lung, the net oxygen content and PaO2 are reduced. There is typically a small amount of venous admixture in the normal lung (<5%).20 An increase in venous admixture represents a reduced blood-oxygenating efficiency of the lung and implies the presence of intrinsic pulmonary parenchymal disease. There are four causes of venous admixture (see Table 15-2): (1) low ventilation-perfusion regions, (2) small airway and alveolar collapse (atelectasis or zero ventilation but perfused lung units), (3) diffusion defects, and (4) anatomic right-to-left shunts. Most diffuse lung disease will have a variable combination of each of these mechanisms; however, one often predominates. These mechanisms have important therapeutic implications. It is also inappropriate to use the term ventilation-perfusion (V/Q) mismatch as a cause of hypoxemia without some adjective (i.e., “high” or “low”) because not all types of V/Q mismatch contribute to hypoxemia (Table 15-4). Regions of low ventilation-perfusion (V/Q) ratio Alveoli with a low ventilation-perfusion (V/Q) ratio occur secondary to small airway narrowing, which impairs ventilation. Because it is a ratio, a low V/Q could also be caused by an increased Q, such as occurs in pulmonary thromboembolism. Small airway narrowing may be caused by bronchospasm, fluid accumulation along the walls of the lower airways, or epithelial edema. Like global hypoventilation, regional hypoventilation results in the reduced delivery of oxygen to alveoli (compared with that removed by the circulation) and a 83 84 PART II • RESPIRATORY DISORDERS Table 15-4 Categories of Ventilation-Perfusion Mismatching and Their Contribution to PaO2 Category Impact Example Ventilated but unperfused lung units Alveolar dead space ventilation; no impact on net PaO2 because there is no blood flow to or from these regions Pulmonary thromboembolism Higher than average ventilation/perfusion ratio lung units Regional hyperventilation; tends to increase PaO2 Hypovolemia; high tidal volumes Average ventilation-perfusion ratio lung units Normal situation; normal PaO2 Normal Lower than average ventilation-perfusion ratio lung units Regional hypoventilation; tends to decrease PaO2 Small airway narrowing secondary to lower airway disease; hypoxemia is oxygen responsive No ventilation but perfused lung units Physiologic shunt; tends to decrease PaO2 Small airway and alveolar collapse; hypoxemia is not oxygen responsive but is responsive to PPV PPV, Positive pressure ventilation. reduction in alveolar and arterial PO2. Poorly oxygenated blood from these capillary beds admixes with blood from more normally functioning regions of the lung, diluting and reducing the net oxygen concentration. This is a common mechanism of hypoxemia in moderate pulmonary disease. Like global hypoventilation, regional hypoventilation is very responsive to oxygen therapy. Regions of zero V/Q Small airway and alveolar collapse (regions of zero V/Q) occurs in diseases associated with the accumulation of airway fluids (transudate, exudates, or blood). Small airway and alveolar collapse is common in the dependent regions of the lung if animals are recumbent for prolonged periods of time (e.g., general anesthesia or coma) in the absence of an occasional deep (sigh) breath. Blood flowing through these areas will not be arterialized. This condition has been referred to as “physiologic shunt” (blood flowing past nonfunctional alveoli) to differentiate it from a “true or anatomic shunt,” where blood completely bypasses all alveoli (be they functional or not). Hypoxemia due to zero V/Q regions is not responsive to oxygen therapy because oxygen cannot get to the gas exchange surface. Collapsed small airways and alveoli can only be “reactivated” by increasing airway or transpulmonary pressure, by taking a deep spontaneous breath, or by augmentation of airway pressure. This is a common mechanism of hypoxemia in severe pulmonary disease as proven by the fact that positive pressure ventilation and positive end-expiratory pressure (PEEP) are usually very effective at improving lung oxygenating efficiency. Diffusion impairment Diffusion impairment as a result of a thickened respiratory membrane is an uncommon cause of hypoxemia. Capillaries meander through the interstitial septae, between alveoli, bulging first into one alveolus and then into the adjacent alveolus. The interstitium between the endothelium and the epithelium on the “bulge side” or “thin side” of the capillary (encompassing two thirds to three fourths of the circumference of the capillary) is either nonexistent (the endothelial and epithelial basement membranes are one in the same) or is functionally nonexistent, and no fluid accumulates here. Transcapillary fluid leaks occur on the thick (“service”) side of the capillary but do not accumulate here either. Fluid is forced (by the low compliance of the interstitial tissues and lymphatics) upward toward the loose interstitial tissues surrounding the medium-sized arterioles, venules, and bronchioles toward the hilus of the lung.21 Eventually these interstitial fluids build up enough pressure that they break into the airways and distribute along the airway surfaces, causing first airway narrowing (low V/Q) and then small airway and alveolar collapse (0 V/Q), as discussed earlier and without a diffusion defect per se. In order for a diffusion defect to occur, the flat type I alveolar pneumocytes have to be damaged by inhalation or inflammatory injury. In the healing process, the thick, cuboidal type II alveolar pneumocytes proliferate across the surface of the gas exchange surface. This can occur with oxygen toxicity or during progression of the acute respiratory distress syndrome.22 Such thickening of the gas exchange membrane represents a substantial diffusion defect until such time as the type II pneumocytes mature to type I pneumocytes. Diffusion defects are partially responsive to oxygen therapy. Anatomic Shunts Anatomic shunts that cause hypoxemia are vascular abnormalities where the blood flows from the right side to the left side of the circulation, bypassing all alveoli in the process. This is not a common mechanism of hypoxemia and most commonly found in young animals with congenital defects. This cause of hypoxemia is not responsive to either oxygen therapy or positive pressure ventilation. Some are amenable to surgical intervention. ESTIMATING THE MAGNITUDE OF THE VENOUS ADMIXTURE In pulmonary parenchymal disease, lungs often fail in their ability to get oxygen in before failing their ability to get carbon dioxide out. This is apparent from the rather common co-occurrence of hypocapnia and hypoxemia and is attributed to the fact that alveolarcapillary units that are working relatively well can easily compensate for those that are working relatively poorly with respect to carbon dioxide elimination but not for oxygen intake. It is for this reason that it is important to evaluate PaCO2 and PaO2 separately. PaCO2 defines alveolar minute ventilation; PaO2 defines blood oxygenation. Given the specifics of the situation, any combination of ventilation (normo-, hypo-, or hyper-) and oxygenation (normo-, hypo-, or hyper-) can coexist in a patient at a given time, and different combinations mandate different therapeutic strategies. Although PaO2 defines the status of blood oxygenation, the clinical significance of the measurement (the status of lung function; the magnitude of the venous admixture) can only be fully appreciated when PaO2 is referenced to the PaCO2 and the inspired oxygen at the time of measurement. Because factors including FiO2 and the nature of ventilator settings can alter PaO2, in general it is recommended to estimate venous admixture under some arbitrary conditions (such as “always while breathing room air” or “always while breathing 100% oxygen” or “always off ventilator support” or “always at a certain mean airway CHAPTER 15 pressure”). Although the latter approach may provide a more consistent evaluation of the underlying pathophysiology, the former approach indexes therapeutic effectiveness and guides the withdrawal of such support. PaCO2 + PaO2 Added Value (“The 120 rule”) When breathing 21% oxygen at sea level, the PaCO2 + PaO2 added value calculation will give the clinician some idea about lung function. A normal PaCO2 of 40 mm Hg and a minimum PaO2 value for normoxemia of 80 mm Hg add to 120. An added value of less than 120 mm Hg suggests the presence of venous admixture, and the greater the discrepancy, the worse the lung function. If PaCO2 increases from 40 mm Hg to 60 mm Hg by hypoventilation, the PaO2 should decrease from 80 mm Hg to about 60 mm Hg if the animal does not have lung disease, and the addition of the two values will still equal 120. The conclusion is that the cause of the hypoxemia in this situation was purely hypoventilation. If instead the animal has a PaCO2 of 60 mm Hg and a PaO2 of 40 mm Hg, the added value is 100 (less than 120) and it can be concluded that the animal has lung dysfunction in addition to hypoventilation. This added value rule or “120 rule” can only be used when the patient is breathing 21% oxygen at near-sea level conditions. At altitude, atmospheric and alveolar and arterial PO2, and the “added value rule,” need to be proportionately decreased. Alveolar-Arterial PO2 Gradient The alveolar-arterial PO2 gradient (A-a gradient) is the difference between the calculated alveolar partial pressure of oxygen (PAO2) and the measured arterial partial pressure of oxygen (PaO2) and is described in further detail in Chapter 186. At sea level, breathing 21%, the alveolar air equation can be shortened to PA O2 = 150 − PaCO2 At different altitudes and inspired oxygen concentrations, the complete formula must be used. Once PAO2 has been calculated, the A-a gradient is calculated by subtracting the measured PaO2 from the calculated PAO2. When breathing room air, the usual A-a gradient is less than 10 mm Hg; values above 20 mm Hg are considered to represent decreased oxygenating efficiency (venous admixture). Unfortunately the normal A-a gradient increases at higher inspired oxygen concentrations and may be as high as 100 to 150 mm Hg at an inspired oxygen concentration of 100%. As a result the A-a gradient is of most value when assessing room air blood gases. PaO2/FiO2 Ratio Many approaches have been suggested that could be used to compensate for the variation in A-a gradient associated with variation in inspired oxygen. The PaO2/FiO2 (or P/F) ratio is the easiest to calculate and is further described in Chapter 186. The P/F ratio can be very misleading when used at 21% inspired oxygen concentrations if PaCO2 values are elevated. PaCO2 values have been ignored in this calculation, but when breathing room air, changes in PaCO2 can have a significant impact on PaO2. It is recommended to use the “120 rule” or A-a gradient when evaluating room air blood gases and to use the P/F ratio if evaluating arterial blood gases from patients on supplemental oxygen. Venous Admixture (Shunt) Calculation If a mixed venous blood sample (pulmonary artery) can be obtained, then venous admixture can be calculated as Q S /Q T = (CcO2 − CaO2 )/(CcO2 − Cv- O2 ) where QS is shunt fraction; QT, cardiac output; QS/QT, venous admixture expressed as a percent of cardiac output; CcO2, oxygen content • Hypoxemia of end-capillary blood; CaO2, oxygen content of arterial blood; and Cv- O2 , oxygen content of mixed venous blood. Jugular venous blood is sometimes used as a surrogate for pulmonary arterial blood. Arterial and mixed venous PO2 is measured and oxygen content (ml/dl) is calculated as (1.34 × Hb × SO2 ) + (0.003 × PO2 ) where SO2 is percent hemoglobin saturation with oxygen. Capillary PO2 is assumed to be equal to calculated PAO2 and is used to calculate capillary oxygen content. PO2 is measured and SO2 is either measured (accuracy mandates a bench-top oximeter) or extrapolated from a standard oxyhemoglobin dissociation curve (which is the value reported on the printout from some blood gas analyzers, or can be derived by hand from an oxyhemoglobin dissociation curve such as in Figure 15-1. Venous admixture is normally less than 5%.20 Values greater than 10% are considered to be increased and may increase to more than 50% in severe, diffuse lung disease. Although the equation shown earlier seems like a lot of math, it is considered to be the most accurate way to estimate venous admixture.23 If blood samples are taken while the patient is breathing room air, all the previously discussed categorical mechanisms of venous admixture are assessed. If blood samples are taken while the patient is breathing 100% oxygen, the low V/Q mechanism of hypoxemia is eliminated from the assessment and diffusion defects are minimized. In this usage, the formula is referred to as the “shunt” formula because it assesses the magnitude of the remaining two causes of venous admixture: “physiologic” shunts secondary to atelectasis and true “anatomic” shunts. Intermediate inspired oxygen concentrations and particularly changes in inspired oxygen concentration will change the venous admixture calculated by this formula by virtue of the impact of the FiO2 on the low V/Q regions.24-26 Like P/F ratio, venous admixture will also be impacted by changes in mean airway pressure by virtue of its impact on the open/closed status of alveoli. It is usually recommended to determine the venous admixture at the current inspired oxygen and ventilator settings, whatever they might be, depending on the needs of the patient.26 REFERENCES 1. Haskins SC: Sampling and storage of blood for pH and blood gas analysis, J Am Vet Med Assoc 170:429-433, 1977. 2. Gray S, Powell LL: Blood gas analysis. In Burkitt-Creedon JM, Davis H: Advance monitoring and procedures for small animal emergency and critical care, Oxford, UK, 2012, John Wiley & Sons, Ch 22, pp 286-292. 3. Kennedy SA, Constable PD, Sen I, Couetil L: Effects of syringe type and storage conditions on results of equine blood gas and acid-base analysis, Am J Vet Res 73:979-987, 2012. 4. Rezende ML, Haskins SC, Hopper K: The effects of ice-water storage on blood gas and acid-base measurements, J Vet Emerg Crit Care 17:67-71, 2006. 5. Hopper K, Rezende ML, Haskins SC: Assessment of the effect of cilution of blood samples with sodium heparin on blood gas, electrolyte, and lactate measurements in dogs, Am J Vet Res 65:656-660, 2005. 6. Biebuyck JF: Pulse oximetry, Anesthesiology 70:98-108, 1989. 7. Ayres DA: Pulse oximetry and CO-oximetry. In Burkitt-Creedon JM, Davis H, editors: Advanced monitoring and procedures for small animal emergency and critical care, Oxford, UK, 2012, John Wiley & Sons, pp 274-285. 8. Smale K, Anderson LS, Butler PJ: An algorithm to describe the oxygen equilibrium curve for the Thoroughbred racehorse, Equine Vet J 26:500502, 1994. 9. Kelman GR: Digital computer subroutine for the conversion of oxygen tension into saturation, J Appl Physiol 21:1375-1376, 1966. 10. Cambier C, Wierinckx M, Clerbaux T, Detry B, Liardet MP, Marville V, Frans A, Gustin P: Haemoglobin oxygen affinity and regulating factors of the blood oxygen transport in canine and feline blood, Res Vet Sci 77:83-88, 2004. 85 86 PART II • RESPIRATORY DISORDERS 11. Clerbaux T, Gustin P, Detry B, Cao ML, Frans A: Comparative study of the oxyhaemoglobin dissociation curve of four mammals: man, dog, horse, and cattle, Comp Biochem Physiol 106:687-694, 1993. 12. Kelman GR, Nunn JF: Clinical recognition of hypoxaemia under fluorescent lamps, Lancet 1:1400-1403, 1966. 13. Martin L, Khalil H: How much reduced hemoglobin is necessary to generate central cyanosis? Chest 87:182-185, 1990. 14. Bishop MJ, Cheney FW: Effects of pulmonary blood flow and mixed venous O2 tension on gas exchange in dogs, Anesthesiology 58:130-135, 1983. 15. Giovannini I, Boldrini G, Sganga G, et al: Quantification of the determinants of arterial hypoxemia in critically ill patients, Crit Care Med 11:644645, 1983. 16. Huttemeier PC, Ringsted C, Eliasen K, Mogensen T: Ventilationperfusion inequality during endotoxin-induced pulmonary vasoconstriction in conscious sheep: mechanisms of hypoxia, Clin Physiol 8:351-358, 1988. 17. Santolicandro A, Prediletto R, Formai E, et al: Mechanisms of hypoxemia and hypocapnia in pulmonary embolism, Am J Respir Crit Care Med 152:336-347, 1995. 18. Cooper CB, Celli B: Venous admixture in COPD: pathophysiology and therapeutic approaches, J Clin Obst Pulm Dis 5:376-381, 2008. 19. Lumb AB: Nunn’s applied respiratory physiology, ed 6, Oxford, 2005, Butterworth Heinemann. 20. Haskins SC, Pascoe PJ, Ilkiw JE, et al: Reference cardiopulmonary values in normal dogs, Comp Med 55:158-163, 2005. 21. Staub NC: The pathogenesis of pulmonary edema, Prog Cardiovasc Dis 23:53-80, 1980. 22. Ware LB, Matthay MA: The acute respiratory distress syndrome, N Engl J Med 342:1334-1349, 2000. 23. Wandrup JH: Quantifying pulmonary oxygen transfer deficits in critically ill patients, Act Anaesth Scand 107:37-44, 1996. 24. Gowda MS, Klocke RA: Variability of indices of hypoxemia in adult respiratory distress syndrome, Crit Care Med 25:41-45, 1997. 25. Whiteley JP, Gavaghan DJ, Hahn DEW: Variation of venous admixture, SF6 shunt, PaO2, and the PaO2/FIO2 ratio with FIO2, Brit J Anaesth 88:771-778, 2002. 26. Oliven A, Abinader E, Bursztein S: Influence of varying inspired oxygen tensions on the pulmonary venous admixture (shunt) of mechanically ventilated patients, Crit Care Med 8:99-101, 1980.