Vet Clin Small Anim 32 (2002) 1031–1048

Blood gas analysis

Thomas K. Day, DVM, MS
Louisville Veterinary Specialty and Emergency Services, 12905 Shelbyville Road,
Suite 3, Louisville, KY 40243, USA

Analysis of blood gases from an artery or central vein can provide valua-
ble information on the cardiopulmonary and acid-base status of a critically
ill veterinary patient. Arterial blood samples provide information primarily
regarding pulmonary function, whereas a jugular or mixed venous sample
can provide information on overall cardiac performance (perfusion) and
whole-body acid-base status. Traditionally, arterial samples have been used
primarily to assess blood gases and make judgments regarding perfusion
and overall metabolic status of the tissues. There has been recent interest
and evidence suggesting that central venous blood (jugular or pulmonary
artery) can be used to monitor trends in overall perfusion and acid-base sta-
tus in small animals with cardiovascular compromise. There also is evidence
in human medicine that jugular venous oxygen saturation (SjVO2) can pro-
vide evidence regarding cerebral oxygenation when combined with other
oxygen delivery variables.

Sample collection
The first step of blood gas analysis is obtaining an appropriate sample.
Equipment that can be used consists of a 1- or 3-mL syringe with a small-
gauge needle (23–29 gauge). A small amount of heparin should be collected
to coat the hub of the needle. Too much heparin can result in dilution of the
sample and the possibility of inaccurate results, such as low pH, low PCO2,
and low bicarbonate (HCO3
) [1]. The sample needs to be stored in an anae-
robic environment as soon as collection is completed. Any air bubbles with-
in the sample should be evacuated, and the needle should be occluded by
placing a rubber stopper over the needle. Another method to maintain an
anaerobic environment would be to remove the needle after sample collec-
tion and place a syringe plug over the tip of the syringe. There is evidence

E-mail address: lvses@earthlink.net (T.K. Day).

0195-5616/02/$ - see front matter Ó 2002, Elsevier Science (USA). All rights reserved.
PII: S 0 1 9 5 - 5 6 1 6 ( 0 2 ) 0 0 0 3 5 - 9
1032 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048

that a tight-fitting syringe cap is superior to a rubber stopper over the needle
in maintaining an anaerobic environment [2]. Air bubbles that are contained
within the blood sample can alter the blood gas values. The PCO2 of room air
is extremely low, and the PO2 of room air is much higher compared with the
blood sample. Therefore, prolonged exposure to an air bubble, especially
one that occupies more than 10% of the sample volume, can result in a
decrease in PCO2 and an increase in PO2 [2].
The sample should be analyzed as soon as possible, usually within 15 to
20 minutes of collection. The sample should be placed on a rocker or be con-
stantly mixed if there is a delay in analysis. Blood that is permitted to stand
before analysis results in an increased PCO2, decreased pH, decreased glu-
cose, and increased lactate. These changes are attributed to glycolysis by
white blood cells, red blood cells, and platelets, and they occur much more
slowly at 4°C versus 25°C (room temperature) [3]. A delay in analysis neces-
sitates that the sample be placed in the refrigerator or on ice for no more
than 2 hours before analysis [3].
Arterial blood samples can be collected via occasional percutaneous
punctures or via an indwelling catheter. Arteries that can be used in the dog
include the femoral, dorsal pedal, and dorsal auricular artery in large
breeds. Indwelling catheters can be maintained most efficiently in the dorsal
pedal and dorsal auricular arteries. Obtaining an arterial sample in cats can
be more difficult, and the only site that can be used without difficulty is the
femoral artery. The dorsal pedal artery can be used in some instances. An
indwelling catheter is much more difficult to insert and maintain in cats and
usually requires a cutdown procedure of the femoral artery.

Equipment
Blood gas analyzers
The technologic advances in bedside blood gas analyzers have resulted in
an accurate and cost-effective manner of evaluating blood gases and acid-
base status in veterinary patients. One of the more popular and affordable
units is the i-STAT (Sensor Devices Incorporated; Waukesha, WI). The
i-STAT has been evaluated in dogs and horses and corresponds accurately
with more expensive laboratory-based units that can cost tens of thousands
of dollars [4,5]. Other bedside units that are available and have been eval-
uated include the Stat-Pal II (PPG Industries, La Jolla, CA). Development
of an accurate and reliable bedside monitor can decrease the amount of time
from sample collection to sample analysis, resulting in the most accurate
results. The blood gas variables PCO2 and PO2 are measured directly as is
blood pH. Oxygen saturation (SO2), total blood carbon dioxide (TCO2), base
excess, and HCO3
are all calculated variables. Recently, blood lactate
determination (see details below) has been incorporated as a routine vari-
able that is determined concurrently with the blood gas analysis.
 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048 1033

Co-oximeters
SO2 is dependent on several variables, including PaO2, temperature of the
blood, the concentration of hydrogen ion (pH), and the quantity of 2,3-
diphosphoglycerate. The bedside blood gas analyzers do not take these var-
iables into consideration when reporting SO2. The analyzer also does not
consider abnormal concentrations of dysfunctional hemoglobin (methemo-
globin, carboxyhemoglobin, and sulfhemoglobin).
A co-oximeter directly measures percentages of carboxy- and methemo-
globin, and SO2. Fortunately, clinical conditions that result in increased
methemoglobin are uncommon in veterinary emergency medicine. Methe-
moglobinemia results in poor arterial blood oxygen saturation (SaO2),
although PaO2 can be normal. The PaO2 is of primary interest in veterinary
patients rather than the associated SaO2. Therefore, purchasing a co-oxi-
meter for routine use in veterinary medicine is not necessary.

Pulse oximetry
Pulse oximeters are common noninvasive devices used to monitor veteri-
nary patients while they are under anesthesia and during advanced respira-
tory support (mechanical ventilation). The principle of pulse oximetry is
that the saturation of pulsed arterial blood (SpO2) can be determined on a
beat by beat basis. Beer’s law is used to determine the amount of absorption
of two wavelengths of light by hemoglobin to differentiate oxygenated from
deoxygenated hemoglobin [6].
Pulse oximetry must be used with caution when determining the SaO2 in
critically ill veterinary patients, especially those with cardiovascular com-
promise and poor perfusion. A detectable pulsation at the site of probe
placement is required for a pulse oximeter to report SpO2. Poor perfusion
of the site of probe placement (usually the tongue) results in low SpO2 values
despite the possibility of adequate SpO2. Rising PaCO2 values can occur even
with normal PaO2, SaO2, and SpO2 values. Other factors that can result in
poor SpO2 values in spite of normal SaO2 include excessive room light, dry
area at the site of probe placement, and excessive movement. Unfortunately,
in some critically ill veterinary patients, an arterial blood sample should be
collected to determine if a low SpO2 value is real.

Capnometry
Capnometers are noninvasive devices used to measure expired carbon
dioxide. The end-tidal carbon dioxide (ETCO2) equates closely to PaCO2 [7].
The primary use of capnometry is to monitor the adequacy of ventilation.
Hypoventilation (see below) is defined as an increase in PaCO2. Any increase
in ETCO2 correlates with an increase in PaCO2 in patients with normal cardio-
vascular function. An increase in the difference between PaCO2 and ETCO2
(PaCO2
ETCO2) usually is a sign of increased dead space ventilation and
1034 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048

altered ventilation-perfusion of the lung. The most common cause of an

increase in PaCO2
ETCO2 is poor perfusion of the lungs (ie, poor cardiac
output) [8]. Therefore, the cardiovascular status of a patient should be inves-
tigated when there is a sudden decrease in ETCO2 during anesthesia or mon-
itoring of ventilator patients. Pulmonary thromboembolism is another
example of a clinical scenario that results in an increase in the PaCO2
ETCO2
value. Monitoring of ETCO2 during cardiopulmonary resuscitation (CPR)
can aid in assessing lung perfusion and cardiac output and can predict CPR
outcome [9].

Arterial or venous sample?

The first question to ask before collection of a blood sample for analysis
is the goal of the information to be obtained. Analysis of pulmonary func-
tion requires an arterial blood sample. Proper assessment of the PaO2 value
obtained from the arterial blood sample also requires knowledge of the frac-
tion of inspired oxygen (FiO2) and the partial pressure of oxygen in the
alveoli (PAO2). Calculation of the alveolar-arterial difference (PAO2
PaO2)
and other indices of oxygenation (PaO2/FiO2) helps to determine states of
hypoxemia (see below).
Analysis of tissue perfusion and overall acid-base status, conversely,
requires evaluation of a mixed venous (pulmonary artery) blood sample
[10]. The value of venous blood gas analysis was not considered strongly
until a large disparity between arterial and venous blood gases was deter-
mined in human patients during CPR [11]. The partial pressure of oxygen
in venous blood (PVO2) is also an important variable that is used to help
determine global tissue perfusion. It is possible to have normal or higher
than normal PaO2 and severely compromised PVO2 in dogs with normal pul-
monary function and poor tissue perfusion [10].
A true mixed venous blood sample is collected from the pulmonary artery.
Catheterization of the pulmonary artery is not a routine technique in veteri-
nary patients, although catheterization of the jugular vein is technically easier
and less expensive to perform. Arterial, jugular, and mixed venous oxygen
values have been determined in normal dogs [12]. A comparison of jugular
and mixed venous oxygen did not correlate well in a swine model of endotoxic
shock, although the acid-base variables did correlate well between the two
samples [13]. The use of jugular venous blood to assess venous oxygenation
has been advocated in veterinary critical care, however [14,15].
The recent addition of lactate analysis with blood gas values using the
i-STAT bedside analyzer has provided information on variables that affect
lactate production. Two types of lactic acidosis (production of lactate
exceeds utilization by kidneys and liver) occur [16,17]. Type A (hypoxic) lac-
tic acidosis occurs when mitochondrial function is normal but oxygen deliv-
ery to tissues is inadequate. Type B (nonhypoxic) lactic acidosis occurs when
 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048 1035

oxygen delivery is adequate but there is a defect in mitochondrial function.

Type A is most common in veterinary patients, especially those with cardio-
vascular disease. Type B is not discussed here.
Hypoxic lactic acidosis occurs whenever oxygen delivery is impaired
because of poor tissue perfusion or reduced oxygen content. Clinical exam-
ples include CPR, shock, cardiac failure, hypovolemia, hypoxemia, and
severe anemia. Lactate concentrations greater than 2 to 2.5 mEq/L are con-
sidered elevated in dogs and cats [16]. Venous lactate concentrations are of
greater value than arterial lactate concentrations, because the venous sample
implies tissue perfusion.

Arterial blood gas analysis

Arterial blood samples provide information primarily related to the pul-
monary system using the true blood gas variables of PaO2, SaO2, and PaCO2.
Proper evaluation of the blood gas variables can only occur with an arterial
sample, although, traditionally, overall acid-base status and decisions on
therapy have also been based on arterial samples. Recent information, espe-
cially that related to the critically ill patient, has directed overall acid-base
status to central venous samples and not to arterial samples because of the
potential for large disparities between the two [11]. The following discussion
on arterial blood gas analysis has two sections. The first discusses the blood
gases. The second discusses the acid-base disturbances. A separate section
discusses venous blood gas analysis. The reader is reminded of the disparity
between arterial and venous samples in the critically ill patient. For continu-
ity purposes, however, all the acid-base disturbances are discussed in the
arterial blood gas analysis section. Pertinent emphasis is applied where nec-
essary to alert the reader to the proper interpretation of arterial and venous
samples.

Blood gas analysis

The only blood gases that are included in the blood gas analysis are PaO2
and PaCO2. The SaO2 is a derived value that may not be as reliable based on
the method of calculation by the blood gas analyzer. A co-oximeter is
required to measure SaO2 directly. The PaCO2 provides information on ven-
tilation whereas the PaO2 provides information regarding oxygenation. A
complete description and explanation of the physiology of PaO2 and PaCO2
are found elsewhere [18].

Ventilation
Alveolar ventilation is indirectly proportional to PaCO2 based on the
alveolar ventilation equation:
Paco2 ¼ Vco2  0:863=VA
1036 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048

where VCO2 is the amount of carbon dioxide produced by the metabolism

and delivered to the lungs, VA is alveolar ventilation, and 0.863 is a constant
that equates dissimilar units for VCO2 and VA.
Hyperventilation is defined as a decrease in PaCO2 (hypocapnia), and hypo-
ventilation is defined as an increase in PaCO2 (hypercapnia). The respiratory
rate and effort determine alveolar ventilation; however, a clinician is not able
to describe hyperventilation by observing an increased respiratory rate. Anal-
ysis of PaCO2 is required to determine hyperventilation. Common causes of
hyperventilation in critically ill veterinary patients include pain, hypoxemia
of any cause, pulmonary disease, and central nervous system (CNS)–medi-
ated hypocapnia (liver disease, sepsis, heatstroke, and CNS disease).

Oxygenation
Measurement of PaO2 is the basis to determine oxygenation. Two terms
have been used interchangeably that are somewhat different in definition:
hypoxemia and hypoxia. Hypoxemia refers to a decrease in PaO2 (<60 mm
Hg), whereas hypoxia refers to a general reduction in oxygen delivery
whether by hypoxemia or decreased cardiac output [7]. PaO2 is primarily
determined by PAO2, which is described by the alveolar gas equation:
Pao2 ¼ Pio2
1:2 ðPaco2 Þ
where PIO2 is the partial pressure of inspired oxygen and 1.2 represents the
respiratory quotient. The PIO2 is determined by the following equation:
Pio2 ¼ Fio2 ðPB
47Þ
where FIO2 is the fraction of inspired oxygen, PB is the barometric pressure,
and 47 represents water vapor pressure in millimeters of mercury, which is
subtracted as dry gases are measured.
Any evaluation of PaO2 must include other variables to describe
adequately the hypoxemia. The FIO2 must be presented (especially when
supplemental oxygen is administered), PAO2 should be calculated, and the
difference between PAO2 and PaO2 must also be calculated. The PAO2
PaO2
is an important variable that helps to determine the severity of arterial
hypoxemia (described below).
There are five common causes of hypoxemia: hypoventilation, decreased
FIO2, diffusion impairment, ventilation-perfusion (V-Q) mismatch, and
right-to-left pulmonary shunt. Hypoventilation, by definition, is hypoxemia
because of an increased PaCO2 and is usually resolved with ventilation.
Hypoxemia caused by low FIO2 is resolved by providing supplemental oxy-
gen. Diffusion impairment in veterinary patients can be caused by diffuse
interstitial disease, severe emphysema, or vasculitis. Supplemental oxygen
may help to resolve hypoxemia in addition to treatment of the primary dis-
order. V-Q mismatch implies that ventilation and perfusion of alveoli are
not proportional. An increase in ventilation without appropriate perfusion
results in a V-Q ratio greater than 1, commonly referred to as increased
 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048 1037

alveolar dead space. Clinical examples include pulmonary thromboembo-

lism and severe emphysema. A decrease in ventilation to alveoli that are still
perfused results in a V-Q ratio less than 1. Examples include pulmonary
edema, pneumonia, and pulmonary contusions. Supplemental oxygen may
improve hypoxemia depending on the severity of the V-Q mismatch. A
V-Q ratio that approaches zero or little to no ventilation in areas of the lung
with adequate perfusion is referred to as right-to-left pulmonary shunt.
There is no ventilation of a large area of lung, but perfusion still occurs
(ie, a more severe V-Q mismatch). Pulmonary arterial blood delivered to the
lung to be oxygenated returns to the pulmonary veins and left atrium unoxy-
genated, resulting in severe arterial hypoxemia. Common causes of right-to-
left shunt are similar to those of V-Q mismatch but include more severe pre-
sentations, such as severe pulmonary edema, consolidation of a lung lobe
due to pneumonia, atelectasis, and extrapulmonary shunts (eg, reverse pat-
ent ductus arteriosis, severe ventricular septal defects). Supplemental oxygen
does not resolve hypoxemia caused by right-to-left shunts.
The PAO2
PaO2 difference is used to determine whether or not a V-Q
mismatch is present. The PAO2
PaO2 difference is a variable that should
be calculated whenever PaO2 is evaluated. Large PAO2
PaO2 values repre-
sent the severity of hypoxemia. The normal PAO2
PaO2 is 5 to 15 mm
Hg depending on whether or not supplemental oxygen is administered [7].
The variability of PAO2
PaO2 during supplemental oxygen administration
may necessitate calculation of another variable to help determine the
severity of hypoxemia. The PaO2/FIO2 ratio is a more reliable method of
determining the severity of hypoxemia when FIO2 is greater than 0.5 and
PaO2 is less than 100 mm Hg [19]. In other words, the PaO2/FIO2 ratio indi-
cates the responsiveness of hypoxemia to oxygen supplementation and may
also indicate how much of the hypoxemia is a result of right-to-left intrapul-
monary shunt. The normal PaO2/FIO2 value while breathing room air is 100/
0.2 ¼ 500 mm Hg. PaO2/FIO2 ratios less than 300 indicate acute lung injury,
and values less than 200 indicate acute respiratory distress syndrome [20].
Calculation of these variables may help to determine whether or not the
patient requires mechanical ventilation [21].
The PAO2
PaO2 has been used and found to correlate with outcome in
veterinary patients [22]. Although PAO2
PaO2 is primarily a pulmonary
variable, cardiovascular function can affect the value obtained. Also, sur-
vival in patients with a large PAO2
PaO2 was not influenced by the disease
process. Therefore, PAO2
PaO2 and PaO2/FIO2 can be extremely valuable
calculations to determine the severity of hypoxemia.
One definition of hypoxemia also includes calculation of the content of
oxygen in arterial blood (CaO2) [7]. The CaO2 equation is as follows:
Cao2 ¼ ðHb  Sao2  1:34Þ þ ðPao2  0:003Þ
where Hb is the hemoglobin concentration, 1.34 is the amount of oxygen
carried by 1 g of hemoglobin, and 0.003 is the percentage of dissolved
1038 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048

oxygen in plasma (0.3%) expressed as a decimal. The final units of CaO2 are
expressed as milliliters of oxygen per deciliter of blood. The equation shows
that the bulk of the CaO2 calculation is based on the amount of hemoglobin.
Anemia affects CaO2 more than hypoxemia alone.
The importance of PaO2, SaO2, and CaO2 revolves around one of the pri-
mary cardiovascular variables called oxygen delivery (DO2). The equation
for DO2 is as follows:
Do2 ¼ CO  Cao2
where CO is cardiac output. Therefore, a ‘‘simple’’ blood gas variable such
as PaO2 can lead to the calculation of many variables that provide valuable
information about the critically ill patient.

Acid-base status
A complete discussion of acid-base balance is beyond the scope of this
review. The reader is referred elsewhere for an in-depth discussion of acid-
base balance [23]. The discussion that follows concentrates on major points
regarding acid-base status so that important variables can be obtained and
appropriate decisions can be made in the critically ill veterinary patient.
The basis for the traditional approach to acid-base balance revolves
around hydrogen ion concentration (expressed as pH), PCO2, and HCO3
.
Carbon dioxide combines with water to form carbonic acid, which further
dissociates to hydrogen ion and bicarbonate. The Henderson-Hasselbalch
(H-H) equation describes the interactions:
pH þ pK þ log ½HCO3
=½H2 CO3 :
This equation can be substituted with a clinically applicable index of
HCO3
, which results in the more useful form of the equation:
pH þ pK þ log ½HCO3
=0:03ðPco2 Þ:
Simplified, changes in HCO3
and PCO2 dictate the four primary acid-
base disturbances as well as the direction of compensation in an attempt
to maintain pH (see details below). Compensation can be acute, involving
the lungs, liver, and extracellular fluid, and chronic, primarily involving the
kidneys.
Normal values of the arterial blood gas can follow the ‘‘rule of 4’’: pH of
7.40, PaO2 of 80 to 100 mm Hg (based on FIO2 ¼ 0.21), PaCO2 of 40 mm Hg,
and HCO3
of 24 mEq/L.
Acid-base analysis should follow a logical series to determine abnormal-
ities that actually follow the previous order of presentation. First, examine
the pH; second, the PaCO2; and third, the HCO3
. Then, based on the
expected compensatory changes (see below), determine if you have a pri-
mary disorder with an appropriate compensatory response, a mixed dis-
order (actually two or three primary disorders occurring simultaneously), or
a compensated disorder. A compensated disorder can only be identified by a
 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048 1039

normal pH with abnormal PaCO2 and HCO3
values that have changed
appropriately based on the primary disorder. Performing an analysis out
of this order can introduce confusion. One other important point is that
electrolytes, physical examination, discovery of an underlying cause, and
other diagnostic techniques must be evaluated concurrently with the blood
gas analysis to determine the appropriate definitive therapy for the disorder.
Like any diagnostic tool, blood gas analysis should be used as one ‘‘piece of
the puzzle’’ and should not be relied on as an exclusive diagnostic test.

Metabolic acidosis
Metabolic acidosis is a common acid-base disturbance in critically ill
patients. The primary event in metabolic acidosis is a decrease in the HCO3

concentration. The H-H equation states that a decrease in HCO3
results in
a compensatory decrease in PaCO2 or hyperventilation. The amount of
decrease in PCO2 in relation to a decrease in HCO3
is a 1.2-mm Hg decrease
in PaCO2 for every 1.0-mEq/L decrease in HCO3
.
The anion gap can be used to help differentiate potential causes of meta-
bolic acidosis. The calculation of anion gap is most practical with the fol-
lowing equation:
ðNaþ þ Kþ Þ
ðCl
þ HCO3
Þ:

There are two broad categories of metabolic acidosis that combine the
concept of anion gap. An increased anion gap metabolic acidosis usually
involves normochloridemia. The cause of the increased anion gap, although
the chloride is normal, is attributed to unmeasured anions (those that do not
contain chloride). Common causes of increased anion gap (normochlore-
mic) metabolic acidosis include ethylene glycol toxicosis, diabetic ketoacido-
sis, uremic acidosis, lactic acidosis, and salicylate intoxication [24].
Metabolic acidosis characterized by a normal anion gap usually has
hyperchloridemia as a component. In most instances, HCO3
is lost in
excess of chloride, resulting in hyperchloridemia. Common causes of normal
anion gap (hyperchloremic) metabolic acidosis include acute small bowel
diarrhea, dilutional acidosis (rapid administration of 0.9% sodium chloride),
and posthypocapnic metabolic acidosis [24].
Treatment of metabolic acidosis primarily involves identification and
treatment of the underlying cause. In many instances, treatment of the pri-
mary cause corrects the metabolic acidosis. Administration of sodium bicar-
bonate has been a controversial issue in veterinary medicine. Most agree
that if the pH is below 7.1 or 7.2, bicarbonate therapy to raise the pH higher
than 7.2 is indicated along with therapy of the underlying cause of the met-
abolic acidosis. Blood pH less than 7.1 or 7.2 may lead to life-threatening
cardiovascular complications, including impaired cardiac contractility, poor
pressor response to catecholamines, and sensitization to ventricular arrhyth-
mias [24]. A common formula that is used to calculate total HCO3
deficit is
1040 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048

as follows:
HCO3
dose ðmEqÞ ¼ 0:3  body weight ðkgÞ  base excess
ðdeficitÞ ðmEqÞ:

An arbitrary administration of one fourth to one third of the total dose

over 20 to 30 minutes should correct the pH to higher than the desired 7.2.
Repeat blood gas analysis is required to determine the desired pH.
Sodium bicarbonate is not an innocuous drug, and there are potential
complications of administration. Volume overload can occur as a result of
the amount of sodium, decreased serum ionized calcium, increased affinity
of hemoglobin for oxygen with potential to decrease oxygen delivery to tis-
sues, paradoxic cerebrospinal fluid acidosis, and increased PaCO2.

Respiratory acidosis
The primary event in respiratory acidosis is an increase in the PaCO2 con-
centration (also called hypercapnia). The H-H equation states that an
increase in PaCO2 results in a compensatory increase in HCO3
. The amount
of increase in HCO3
in relation to an increase in PaCO2 is a 0.15-mEq/L
increase in HCO3
for every 1-mm Hg increase in PaCO2 in an acute respi-
ratory acidosis. The amount of increase in HCO3
is higher in chronic res-
piratory acidosis, because the kidneys have had time to provide a
compensatory effect. The amount of increase in HCO3
in relation to an
increase in PaCO2 is a 0.35-mEq/L increase in HCO3
for every 1-mm Hg
increase in PaCO2 in chronic respiratory acidosis [25].
Common causes of respiratory acidosis in critically ill veterinary patients
include any pulmonary disease (acute or chronic), neurologic disease, drugs
(eg, anesthetic agents, opioid analgesics), neuromuscular disease, and pleu-
ral disease [25]. Acute hypercapnia increases cerebral blood flow (CBF) and
intracranial pressure, which can have detrimental effects in the patient with
brain injury. When the PaCO2 concentrations reach approximately 100 mm
Hg, a state of severe cerebral depression results. The sympathetic nervous
system is also stimulated by hypercapnia, predisposing patients to arrhyth-
mias. Finally, elevations in PaCO2 cause vasodilation that is signified
by ‘‘brick red’’ mucous membranes. Extreme vasodilation can result in
hypotension.
Therapy for respiratory acidosis in nonanesthetized patients usually is
related to providing mechanical ventilation. Analysis of arterial blood gases
can help to determine the definition of respiratory failure, especially in rela-
tion to concurrent hypoxemia. One definition of respiratory failure is PaCO2
greater than 50 mm Hg in the nonsedated and nonanesthetized patient [21].
Other definitions of respiratory failure include PaO2 less than 50 mm Hg
with FIO2 of 0.21 or a poor response of PaO2 less than 50 mm Hg with FIO2
greater than 0.5 [21]. Hypercapnia and hypoxemia concurrently should be
treated aggressively with mechanical ventilation.
 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048 1041

Metabolic alkalosis
The primary event in metabolic alkalosis is an increase in the HCO3

concentration. The H-H equation states that an increase in HCO3
results
in a compensatory increase in the PaCO2 or hypoventilation. The amount
of increase in PCO2 in relation to an increase in HCO3
is a 0.6-mm Hg
increase in PaCO2 for every 1.0-mEq/L increase in HCO3
[24]. Note that the
PaCO2 response to metabolic alkalosis is usually not as marked as in meta-
bolic acidosis.
Metabolic alkalosis is usually the result of the hydrogen ion (H+) loss that
occurs with pure gastric vomiting. Two other causes of metabolic alkalosis
are diuretic therapy and judicious administration of sodium bicarbonate.
Loss of H+ in pure gastric vomiting (pyloric obstruction) also involves loss
of Cl
. Renal regulation of electrolytes is important in the creation and
maintenance of excess HCO3
. Loss of hydrogen chloride in pure gastric
vomiting usually results in excessive loss of extracellular volume as well. The
kidney attempts to retain as much sodium as possible, usually retaining Cl

with Na+. The concurrent loss of chloride results in the retention of the next
most abundant negative ion in the body, HCO3
. The result is an excess of
HCO3
and metabolic alkalosis with pH values commonly greater than
7.50. Hypochloridemia and hypokalemia can also occur with excessive
hydrogen chloride loss. In many instances, ‘‘hypoelectrolytemia’’ can result
(decreased Na+, K+, Cl
) in patients with metabolic alkalosis caused by gas-
tric hydrogen chloride loss.
Clinical signs of metabolic acidosis usually involve the underlying cause
and the clinical effects of electrolyte disturbances. Severe hypokalemia
(<2.5 mEq/L) can result in weakness and changes on the ECG. A decrease
in ionized calcium as a result of metabolic alkalosis can contribute to weak-
ness and muscle twitching [24].
Metabolic alkalosis is a secondary event, and therapy must be directed to
the primary cause. The acid-base changes in metabolic alkalosis are not cor-
rected until adequate chloride is replaced. Concurrently, deficits in sodium
and potassium should be replaced as well. Commonly, administration of
0.9% sodium chloride with potassium supplementation is the fluid of choice
to replace electrolyte deficits and help correct metabolic alkalosis. Antiemet-
ics, surgery for pyloric obstruction, and other specific therapy to correct the
underlying cause help to reduce further losses of Cl
and Hþ.

Respiratory alkalosis
The primary event in respiratory alkalosis is a decrease in the PaCO2 con-
centration (also called hypocapnia). The H-H equation states that a decrease
in PaCO2 results in a compensatory decrease in HCO3
. The amount of
decrease in HCO3
in relation to a decrease in PaCO2 is a 0.25-mEq/L
decrease in HCO3
for every 1-mm Hg decrease in PaCO2 in acute respira-
tory alkalosis. The amount of decrease in HCO3
is higher in chronic respi-
ratory alkalosis, because the kidneys have had time to provide a
1042 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048

compensatory effect. The amount of decrease in HCO3
in relation to a

decrease in PaCO2 is a 0.55-mEq/L decrease in HCO3
for every 1-mm Hg
decrease in PaCO2 in chronic respiratory acidosis [25].
Common causes of respiratory alkalosis in critically ill patients include
stimulation of peripheral chemoreceptors in response to hypoxemia, any
pulmonary disease, and direct stimulation of the respiratory center (eg, heat-
stroke, drugs, sepsis, CNS disease). Clinical signs of respiratory alkalosis in
veterinary patients have not been recognized aside from obvious signs of the
underlying disease process. Anesthetized patients can have decreases in car-
diac output and blood pressure in response to hypocapnia, but this effect has
not been observed in awake veterinary patients.
Therapy is directed to treatment of the underlying disease process,
because no other therapy is effective.

Mixed acid-base disturbances

Discussion of mixed acid-base disturbances has involved entire chapters,
because the concepts of multiple acid-base disorders occurring simultane-
ously are complex. The reader is referred elsewhere for a detailed description
of mixed acid-base disorders [26,27]. Mixed acid-base disorders are ex-
tremely common in critically ill veterinary patients.
Diagnosis of a mixed acid-base disorder can be difficult. Therefore, guide-
lines exist that can help the clinician to establish a logical approach to blood
gas analysis [27]. The nontraditional approach to acid-base balance can be
helpful in a mixed disorder. There is a difference between a mixed disorder
and expected compensation for a simple disorder. First, follow the diagnosis
of simple disorders as described previously. If the calculations are not com-
patible with a simple disorder, the following steps may be helpful in deter-
mining the presence of a mixed disorder [27]:
1. The presence of a normal pH and abnormal PaCO2 and HCO3
implies a
mixed disorder.
2. A change in pH in the opposite direction than that predicted for a pri-
mary disorder requires a diagnosis of a mixed disorder.
3. When PaCO2 and HCO3
change in opposite directions than those pre-
dicted, there is a mixed disorder.
4. Values that are obtained within the expected compensatory effect do not
prove that a simple disorder is present; they just suggest the possibility if
supported by the clinical data.
Laboratory or collection errors could result in the diagnosis of a mixed
disorder. Analysis of a venous blood gas for pulmonary values (PaCO2)
results in miscalculation of compensation. Too much heparin in the syringe,
storage of the blood sample for longer than 15 to 20 minutes at room tem-
perature, and miscalculation of HCO3
could result in the diagnosis of a
mixed disorder when one is not present. Mixed disorders fall into the follow-
 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048 1043

ing categories: mixed disorders with neutralizing effects on pH, mixed disor-
ders with additive effects on pH, and triple disorders [27]. Clinical examples
of these three categories are briefly described below with emphasis only on
common problems in critically ill patients. Every possibility of a mixed dis-
order is not presented.

Neutralizing effect on pH
A mixed respiratory alkalosis and metabolic acidosis can occur in many
clinical situations. Most of these patients have acute respiratory alkalosis in
the presence of a high anion gap metabolic acidosis. The blood gas analysis
is characterized by low PaCO2 and low HCO3
in the face of a pH that may
be close to normal. The only simple disorder that can result in these same
findings is chronic respiratory alkalosis that has completely compensated.
Clinical findings can help to differentiate between the two, and direct ther-
apy for the acid-base disturbance is not warranted. Therapy is centered
on correcting the clinical cause of the acid-base disorder.
Gastric dilatation–volvulus (GDV) is a common example. The metabolic
acidosis is usually a result of lactic acidosis secondary to poor perfusion, and
the acute respiratory alkalosis is a result of pain-induced hyperventilation.
Therapy would include gastric decompression, aggressive fluid therapy, and
analgesia. Dogs or cats with low-output heart failure (lactic acidosis) that
develop acute pulmonary edema (hypoxemia with secondary hyperventila-
tion) is another common clinical presentation of this mixed disorder. Ther-
apy would include increasing cardiac output and providing oxygen support
and diuretic therapy. CPR can result in this mixed disorder as well. Caution
is advised when analyzing arterial or venous samples only, however. Arterial
samples can reveal respiratory alkalosis caused by hyperventilation (usually
by the clinician performing CPR), yet the central venous sample can reveal
increased partial pressure of carbon dioxide in jugular venous blood (PVCO2)
as a result of poor perfusion (see below).
Metabolic acidosis and metabolic alkalosis can occur simultaneously.
Most of these patients have a chronic disorder, resulting in metabolic acido-
sis (eg, renal failure, diarrhea, uncomplicated ketoacidosis), and they begin
vomiting pure gastric contents (metabolic alkalosis). The importance of
making the diagnosis of this mixed disorder is that if one disorder is treated
without recognition of the second, the second can appear unopposed. The
opposite can also occur when metabolic alkalosis caused by pure gastric loss
leads to severe volume depletion, resulting in lactic acidosis. Vomiting and
diarrhea are important causes of hyperchloremic metabolic acidosis and
metabolic alkalosis (parvovirus enteritis). Caution is advised in this sce-
nario; serum electrolytes and results of blood gas analysis may be within
the normal range in this setting, because these disturbances have opposite ef-
fects on HCO3
and Cl
. A physical examination and history are important
factors in making this diagnosis.
1044 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048

Additive effect on pH
Disorders with an additive effect on pH can have dramatically high or
low values. A mixed acidosis (metabolic and respiratory) can occur in many
clinical situations, including cardiopulmonary arrest and severe pulmonary
edema secondary to low-output cardiac failure and lactic acidosis as a result
of poor tissue perfusion. The PaCO2 is usually normal or high, the HCO3
is
low, and the pH can be dangerously low. Therapy is directed to improving
tissue perfusion with the possibility of providing mechanical ventilation,
especially if hypoxemia is present.
A mixed alkalosis (metabolic and respiratory) is uncommon in veterinary
patients. The PaCO2 is low, the HCO3
is low, and the pH is high. This type
of disorder can occur in the GDV complex (hydrogen chloride loss and
pain) and in patients with congestive heart failure that have been treated
with diuretics. Therapy consists of providing a source of chloride to correct
the metabolic component and treating the underlying cause of the respira-
tory component.

Triple disorders
Triple disorders usually occur when a mixed metabolic disorder (acidosis
and alkalosis) is complicated by an acute respiratory disturbance [27]. The
pH and HCO3
may be increased, decreased, or normal. The PaCO2 is increased
when the mixed metabolic disturbance is complicated by acute respiratory
acidosis, and PaCO2 is decreased when acute respiratory alkalosis occurs.
Applying the nontraditional approach to blood gas analysis (see below) may
help in clarifying a triple disorder, although the calculation can be tedious.
Two examples of triple acid-base disorders are low-output heart failure
[28] and GDV syndrome [29]. Low-output heart failure patients treated with
diuretics can have metabolic acidosis secondary to lactic acidosis and meta-
bolic alkalosis caused by hypochloridemia. Acute pulmonary edema can
result in increased ventilation and decreased PaCO2 (respiratory alkalosis).
Conversely, if the edema becomes severe, hypoventilation and increased
PaCO2 (respiratory acidosis) can occur. GDV syndrome is one of the com-
mon disorders that can have any acid-base disturbance and a triple disturb-
ance. Metabolic acidosis occurs because of poor perfusion, metabolic
alkalosis can occur secondary to hypochloridemia, and distention of the
torsed stomach can decrease ventilation (respiratory acidosis). Patients with
minimal distention can have pain-induced hyperventilation and decreased
PaCO2 (respiratory alkalosis) in addition to the two metabolic disturbances.

Venous blood gas analysis

The ability to adequately assess oxygenation is limited and usually
involves measuring some aspect of global oxygenation compared with indi-
vidual organ oxygenation. The ability to examine a measure of global
 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048 1045

oxygenation is limited in some situations, such as sepsis, in which global mea-

sures of oxygenation may be normal, yet individual organs become hypoxic.
Evidence of poor oxygenation of organs usually is recognized after the
organ has been damaged and begins to fail. Analysis of venous blood gas
can provide global information on tissue perfusion and tissue acid-base bal-
ance but provides no information on pulmonary variables (PaO2 and PaCO2).

Tissue perfusion
There are similarities in arterial blood gas values and mixed (pulmonary
artery) venous blood gas values, with the exception of oxygen and SO2 in
normal dogs [12]. An investigation in people seems to have first brought
to attention the concept of using venous oxygen and venous oxygen satura-
tion (SVO2) as measures of global tissue perfusion during cardiopulmonary
arrest [11]. Pulmonary artery catheterization is limited in veterinary medi-
cine, although a jugular venous sample can provide similar information
regarding perfusion.
The PVO2 and associated SVO2 can provide base information to calculate the
content of oxygen in venous blood (CVO2) similar to that of the calculation of
CaO2. The difference in the two values, referred to as the a-v O2 difference, can
be used as a measure of total body oxygen oxygenation. The PVO2 from a jug-
ular venous or pulmonary artery catheter can provide evidence of tissue per-
fusion. A low PVO2 indicates that the maximum amount of oxygen is being
extracted from the tissues, thus widening the a-v O2 difference. Normal PVO2
values range from 35 to 50 mm Hg. When the PVO2 falls between 28 and 35 mm
Hg, there is limited oxygen reserve in the tissues and a state of anaerobic
metabolism is pending [30]. Aggressive therapy with colloids, crystalloids,
inotropes, or other methods of increasing perfusion is necessary to prevent
further decreases. A PVO2 value below 27 mm Hg indicates the presence of
an anaerobic metabolism and production of lactic acidosis. This value is so
low that it is considered a preterminal event. Elevation in PVO2 higher than
60 mm Hg in an animal breathing room air suggests decreased tissue uptake
of oxygen such that the tissues do not receive the oxygen because of shunting
of blood at the capillary level. Sepsis is a common clinical entity in which ele-
vations in PVO2 occur because of shunting of blood away from the tissues [14].
Venous lactate can also provide evidence of poor tissue perfusion,
although the venous value would be expected to be similar to the arterial
value. Lactate concentrations higher than 2 to 2.5 mEq/L indicate abnormal
accumulation in critically ill dogs and cats [14,16]. The i-STAT blood gas
analyzer currently has the capability to provide lactate concentrations with
the blood gas information.

Acid-base status
Venous acid-base analysis can be important in scenarios of poor tissue
perfusion. There was a large disparity between arterial and venous acid-base
1046 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048

values during CPR such that the arterial blood indicated an adequate pH
but the venous blood indicated severe acidosis with elevated PCO2 [11]. An
elevation in PVCO2 usually indicates inadequate ventilation in the patient
with normal tissue perfusion, yet during poor tissue perfusion, elevated
PVCO2 indicates poor perfusion. Therapy in a patient with such disparity
between arterial and venous blood consists of providing perfusion with col-
loids, crystalloids, or inotropes, for example.

Cerebral oxygenation
An interesting concept in the monitoring of cerebral oxygenation has
been suggested in human patients with brain injury. Although many var-
iables have been proposed to monitor brain-injured human patients, SjVO2
has been suggested as measuring the adequacy of CBF [31]. The following
equation has been proposed as providing the most accurate information on
global CBF:
CMRO2 ¼ CBFðCao2
Cjvo2 Þ
where CMRO2 is the cerebral metabolic rate for oxygen and CjVO2 is the
content of oxygen in jugular venous blood, which is calculated from the par-
tial pressure of oxygen in jugular venous blood (PjVO2) and SjVO2 similar to
the calculations for CaO2 and CVO2 noted previously. An abnormally low
SjVO2 (<50% [normal ¼ 65%]) suggests the possibility of cerebral ischemia.
Collection of jugular venous blood and calculation of CBF are within the
realms of veterinary critical care, and the previous formula may be used
to monitor veterinary patients with traumatic brain injury.

Nontraditional approach to acid-base analysis

The traditional approach to acid-base balance gives the impression that
PaCO2 and HCO3
are independent variables that affect [H+]. Only PaCO2
is an independent variable, however. An increase in PaCO2 results in an
increase in hydrogen ions, which are buffered primarily by proteins, and the
HCO3
concentration increases secondarily. The traditional approach also
does not take into account the effects of electrolytes (Na+, K+, Cl
) and
plasma proteins on acid-base balance.
Stewart [32] developed a method of acid-base analysis that is directed by
three physical laws: maintenance of electroneutrality, satisfaction of dissoci-
ation equilibrium for incompletely dissociated solutes, and conservation of
mass. The nontraditional approach identifies three independent variables:
PaCO2, the strong ion difference, and the total concentration of weak acids
(proteins).
A complete and extensive explanation of the nontraditional approach to
acid-base balance is provided elsewhere [33]. The Stewart approach was
modified to extend the traditional assessment in acid-base disturbances and
 T.K. Day / Vet Clin Small Anim 32 (2002) 1031–1048 1047

can be useful in the assessment of mixed acid-base disturbances, including

triple disturbances.

Summary
Evaluation of both arterial and central venous blood can be valuable in
monitoring the critically ill veterinary patient. The traditional approach,
which concentrates on arterial blood analysis only, may miss important
aspects of oxygen delivery to tissues, especially in patients with poor perfu-
sion. The advances that have resulted in affordable bedside blood gas ana-
lyzers have created a clinical situation in which blood gas analysis should
be an integral part of critical care monitoring. Following basic principles
of interpretation, blood gas analysis, which has traditionally been viewed
as a complex method of monitoring, should become more useful. Assessing
both the arterial and central venous samples should result in more efficient
and higher quality care for veterinary patients.

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