Measured and calculated variables of global oxygenation in healthy neonatal foals

David M. Wong Departments of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Kate L. Hepworth-Warren Departments of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Beatrice T. Sponseller Departments of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Joan M. Howard Departments of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Chong Wang Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Abstract

OBJECTIVE To assess multiple central venous and arterial blood variables that alone or in conjunction with one another reflect global oxygenation status in healthy neonatal foals.

ANIMALS 11 healthy neonatal foals.

PROCEDURES Central venous and arterial blood samples were collected from healthy neonatal foals at 12, 24, 36, 48, 72, and 96 hours after birth. Variables measured from central venous and arterial blood samples included oxygen saturation of hemoglobin, partial pressure of oxygen, lactate concentration, partial pressure of carbon dioxide, and pH. Calculated variables included venous-to-arterial carbon dioxide gap, estimated oxygen extraction ratio, ratio of partial pressure of oxygen in arterial blood to the fraction of inspired oxygen, bicarbonate concentration, base excess, and blood oxygen content.

RESULTS Significant differences between arterial and central venous blood obtained from neonatal foals were detected for several variables, particularly partial pressure of oxygen, oxygen saturation of hemoglobin, and oxygen content. In addition, the partial pressure of carbon dioxide in central venous blood samples was significantly higher than the value for corresponding arterial blood samples. Several temporal differences were detected for other variables.

CONCLUSIONS AND CLINICAL RELEVANCE Results of this study provided information about several variables that reflect global oxygenation in healthy neonatal foals. Values for these variables in healthy foals can allow for comparison with values for critically ill foals in future studies. Comparison of these variables between healthy and ill foals may aid in treatment decisions and prognosis of clinical outcome for critically ill foals.

Abstract

OBJECTIVE To assess multiple central venous and arterial blood variables that alone or in conjunction with one another reflect global oxygenation status in healthy neonatal foals.

ANIMALS 11 healthy neonatal foals.

PROCEDURES Central venous and arterial blood samples were collected from healthy neonatal foals at 12, 24, 36, 48, 72, and 96 hours after birth. Variables measured from central venous and arterial blood samples included oxygen saturation of hemoglobin, partial pressure of oxygen, lactate concentration, partial pressure of carbon dioxide, and pH. Calculated variables included venous-to-arterial carbon dioxide gap, estimated oxygen extraction ratio, ratio of partial pressure of oxygen in arterial blood to the fraction of inspired oxygen, bicarbonate concentration, base excess, and blood oxygen content.

RESULTS Significant differences between arterial and central venous blood obtained from neonatal foals were detected for several variables, particularly partial pressure of oxygen, oxygen saturation of hemoglobin, and oxygen content. In addition, the partial pressure of carbon dioxide in central venous blood samples was significantly higher than the value for corresponding arterial blood samples. Several temporal differences were detected for other variables.

CONCLUSIONS AND CLINICAL RELEVANCE Results of this study provided information about several variables that reflect global oxygenation in healthy neonatal foals. Values for these variables in healthy foals can allow for comparison with values for critically ill foals in future studies. Comparison of these variables between healthy and ill foals may aid in treatment decisions and prognosis of clinical outcome for critically ill foals.

Shock, broadly defined as a failure to meet cellular metabolic demands, can result from failure of blood delivery or maldistribution of blood flow within the cardiovascular system.1 If hypoperfusion persists, tissue oxygen consumption decreases, which results in cellular dysoxia, anaerobic cellular metabolism, cell death, and multiorgan dysfunction.1–3 Clinical monitoring of shock in critically ill patients encompasses evaluation of several subjective and objective assessments and targeted therapeutic decisions to facilitate adequate oxygen delivery and restore aerobic cellular activity. By improving tissue oxygenation, the risk of multiorgan dysfunction, a cause of increased morbidity and mortality rates among hospitalized patients, can potentially be avoided.4 Toward this goal, specific therapeutic endpoints have been used to estimate adequacy of resuscitation in shock states, ranging from evaluation of noninvasive physical examination variables (eg, heart rate, capillary refill time, urinary output, and mental status) to more invasive measurements (eg, cardiac output and So2).5–7 Prospective clinical studies support the use of more invasive monitoring to guide early goal-directed therapy in critically ill people.5,8,9 Those studies were conducted with the supposition that early hemodynamic assessment based on results of physical examination, vital signs, and urinary output would fail to detect persistent global tissue hypoxia, as might be observed during compensatory shock.1,5 Conversely, assessment and use of So2, BE, pH, and arterial lactate concentration as therapeutic endpoints are arguably more valuable than physical examination variables and might help guide specific early goal-directed therapy to more effectively manipulate cardiac preload, afterload, and contractility to attain optimal balance between oxygen delivery and demand.5,7,10 It was concluded that early goal-directed therapy improved patient outcome for severe sepsis and septic shock (in-hospital mortality rate with early goal-directed therapy was 30.5%, compared with 46.5% without early goal-directed therapy).5 Interestingly, some follow-up studies11–14 refuted the benefits of invasive monitoring and early goal-directed therapy on the basis of a lack of difference in outcomes when protocol-based (ie, measurement of So2 and early goal-directed therapy) and standard-based resuscitation were used for septic shock, which has provided controversy in regard to the benefits of invasive monitoring and early goal-directed therapy in critically ill people.11–14

Shock is commonly encountered in neonatal foals, primarily as a result of sepsis, but therapeutic endpoints in equine medicine are largely reliant on assessment of physical examination findings and blood lactate concentrations, which may fail to detect suboptimal oxygen delivery.15–18 Although the placement of a catheter in a pulmonary artery for measurement of So2 is impractical in most veterinary clinical settings, neonatal foals with sepsis or shock (or both) invariably require placement of a catheter in a jugular vein to initiate appropriate treatment. In these instances, a longer (35- to 40-cm) IV catheter routinely can be inserted to near the right atrium and used to collect central venous blood. Measurement of oxygen saturation in central venous blood is an acceptable replacement for measurement of oxygen saturation in mixed venous blood, although it overestimates So2 by 5%.10,19–22

Measurement of Scvo2 provides an estimate of the amount of oxygen that has been extracted from circulating hemoglobin by organs during the return of blood to the right side of the heart.19 In addition to Scvo2, several other variables investigated as markers of global oxygenation in humans may be applicable in foals. For example, Pcvco2 – Paco2 has been used to guide treatment of shock.19,23–25 Carbon dioxide is a normal terminal product of oxidative metabolism, and, in the absence of a vascular shunt, CO2 concentrations in the venous blood must be higher than those in the arterial blood.19,23–25 In situations that result in anaerobic metabolism from oxygen debt, hydrogen ions are generated from hydrolysis of ATP to ADP and increased production of lactate.25 Hydrogen ions are buffered by bicarbonate present in cells; during this process, CO2 is produced.26 The Paco2 is dependent on pulmonary gas exchange, whereas Pcvco2 is dependent on blood flow (ie, cardiac output) to remove CO2 from the tissues.19 An inverse relationship exists between cardiac output and Pcvco2 – Paco2, with increased Pcvco2 – Paco2 suggesting a decrease in blood flow.27,28 Other variables evaluated as markers of global oxygenation include Po2 or Pco2, blood lactate concentration, and O2ER as well as blood gas variables (pH, bicarbonate concentration, and BE).26,29–31

A paucity of clinical information currently exists with regard to basic global oxygen metabolism during sepsis and shock in equine neonates, and an equal lack of information exists with respect to monitoring foals with sepsis and shock. The objectives of the study reported here were to measure variables associated with global oxygen status as well as to compare results between central venous and arterial samples for several variables associated with systemic oxygenation. One or more of the evaluated variables subsequently may serve as a method for monitoring global oxygenation in ill foals.

Materials and Methods

Animals

Eleven university-owned Thoroughbred and Quarter Horse neonatal foals (5 colts and 6 fillies) were used in the study. Mean ± SD body weight was 52.2 ± 7.6 kg. All foals were considered healthy on the basis that the dam had an uncomplicated gestation and parturition and that physical examination variables of the foals were within acceptable limits. Foals were excluded if it was determined that they had inadequate passive transfer of immunity (serum IgG < 800 mg/dL, measured at 24 hours of age). Foals were kept with their dams during the entire study period; each dam and foal was housed in a box stall with access to small individual paddocks. The study protocol was reviewed and approved by the Iowa State University Institutional Animal Care and Use Committee.

Experimental design and sample collection

When foals were 12 hours old, anesthetic cream was topically placed on the lateral aspect of the left hind limb over the metatarsea dorsalis III artery. Foals then were sedated with diazepam (0.1 mg/kg, IV) and placed in right lateral recumbency on a padded mat. Hair over the left jugular vein was clipped, the skin was aseptically prepared, and 1 mL of lidocaine was administered SC over the jugular vein. A 16-gauge, 60-cm, single-lumen polyurethane catheter with a peel-away introducera was inserted into the jugular vein in the rostral third of the neck. Catheter length was estimated before insertion by measuring the distance from the catheter insertion site to the level of the caudal aspect of the scapula. The catheter was advanced until the tip of the catheter was located within 1 rib space of the cranial vena cava, which was confirmed by evaluation of a lateral thoracic radiograph. If the catheter was in the right atrium or cranial to the cranial vena cava, the catheter was repositioned and another radiograph was obtained to confirm proper placement. The catheter was held in place with sutures, and patency was maintained by flushing 5 mL of heparinized saline (0.9% NaCl) solution through the catheter every 6 to 8 hours.

Blood samples were collected 10 minutes after foals were positioned in lateral recumbency. Approximately 0.5 to 1 mL of arterial blood was collected by use of anaerobic conditions from the metatarsea dorsalis III artery with a blood gas syringe containing lyophilized heparin. Subsequently, 10 mL of central venous blood was obtained anaerobically by use of the catheter in the cranial vena cava. For the central venous sample, ≥ 3 times the dead space volume of the catheter was withdrawn before sample collection. Approximately 1 mL of the central venous blood sample was placed by use of anaerobic conditions into a blood gas syringe containing lyophilized heparin, and the remaining central venous blood was split between a tube containing EDTA and a serum separator tube. The precollection blood was administered back to each foal via the IV catheter, and the catheter was flushed with heparinized saline solution. Arterial and central venous blood samples were collected from each foal at 12, 24, 36, 48, 72, 96, and 120 hours after birth.

Both the central venous and arterial blood samples were analyzed within 15 minutes after collection. Blood variables measuredb were Pcvo2, Pao2, Scvo2, Sao2, central venous lactate concentration, arterial lactate concentration, Pcvco2, Paco2, central venous pH, and arterial pH. Variables calculatedb were Pcvco2 – Paco2, O2ER, Pao2:Fio2, O2Ctcv, O2Cta, HCO3cv, HCO3a, BEcv, and BEa. Equations used for calculation of some of these variables were as follows:

article image

where pK = 6.091 and α (ie, the solubility coefficient for CO2) = 0.0307.

Statistical analysis

All results were reported as mean ± SD. All measured and calculated blood variables (responses) were analyzed by use of repeated-measures ANOVAs. Sample, time, and the sample-by-time interaction were used as fixed effects, whereas foal was used as the subject of the repeated measures. Differences were assessed by use of the F test followed by the Tukey t test for multiple comparisons. For all analyses, values were considered significantly different at P < 0.05.

Results

No complications were associated with catheter placement or data collection, and vital signs remained within acceptable limits in all foals during the experimental period. Mean ± SD length of the central venous catheter (from catheter insertion site to the cranial vena cava) was 34.8 ± 2.5 cm. The Pao2 and Sao2 were significantly higher than the Pcvco2 and Scvo2, respectively, at all time points. Furthermore, Pao2 was significantly lower at 12, 24, 36, and 48 hours, compared with the Pao2 at later times (Table 1). The O2Cta was significantly higher than the O2Ctcv at all time points.

Table 1—

Mean ± SD values of oxygen saturation, partial pressure of oxygen, and oxygen content for blood samples obtained from 11 healthy foals at various times during the neonatal period.

Age (h)Scvo2 (%)Sao2 (%)Pcvo2 (mm Hg)Pao2 (mm Hg)O2Ctcv (mL of O2/dL)O2Cta (mL of O2/dL)
1273.9 ± 9.292.2 ± 4.7*40.0 ± 5.364.6 ± 11.6*12.8 ± 2.116.1 ± 1.8*
2476.5 ± 4.894.8 ± 1.7*40.9 ± 4.069.9 ± 6.6*12.3 ± 1.216.6 ± 0.9*
3675.2 ± 4.693.4 ± 5.4*40.4 ± 3.569.3 ± 12.3*12.4 ± 1.215.5 ± 1.3*
4874.8 ± 4.595.1 ± 1.8*40.9 ± 3.372.1 ± 7.7*12.9 ± 1.716.5 ± 3.6*
7274.1 ± 5.196.5 ± 1.3*40.1 ± 3.878.8 ± 8.8*§12.2 ± 1.416.3 ± 1.6*
9673.1 ± 8.996.3 ± 1.7*39.9 ± 6.078.2 ± 7.9*§11.9 ± 1.716.3 ± 1.7*
12073.7 ± 6.996.5 ± 1.2*39.8 ± 3.978.4 ± 5.9*§12.0 ± 2.016.1 ± 1.2*
All ages74.5 ± 1.195.0 ± 1.740.2 ± 0.612.4 ± 0.416.2 ± 0.4

When there was no significant (P ≥ 0.05) effect of time on a variable, the mean value over time (all ages) was calculated.

Within a row, value differs significantly (P < 0.05) from the corresponding value for the central venous variable.

Within a column, value differs significantly (P < 0.05) from the value at 12 hours.

Within a column, value differs significantly (P < 0.05) from the value at 24 hours.

Within a column, value differs significantly (P < 0.05) from the value at 36 hours.

Within a column, value differs significantly (P < 0.05) from the value at 48 hours.

— = Not determined.

The Pao2:Fio2 was significantly higher at 72, 96, and 120 hours, compared with the value at 12 or 24 hours (Table 2). There was no significant difference between arterial and central venous lactate concentrations at any time point. The arterial lactate concentration was significantly higher at 12 hours, compared with the arterial lactate concentration at 36, 48, 96, and 120 hours. The central venous lactate concentration was significantly higher at 12 hours, compared with the central venous lactate concentration at 24, 36, 48, 96, and 120 hours. At all times, Pcvco2 was significantly higher than the corresponding Paco2. The Paco2 was significantly higher at 12 hours, compared with Paco2 at 96 and 120 hours. No significant differences in Pcvco2 – Paco2 or O2ER were detected at any time.

Table 2—

Mean ± SD values of various measured and calculated variables for blood samples obtained from 11 healthy foals at various times during the neonatal period.

Age (h)Pcvco2 (mm Hg)Paco2 (mm Hg)Pcvco2 – Paco2 (mm Hg)O2ER (%) (mm Hg)Lactate-cv (mmol/L)Lactate-a (mmol/L)Pao2:Fio2
1245.2 ± 2.942.4 ± 2.9*2.9 ± 2.219.8 ± 9.62.5 ± 0.92.5 ± 0.9300 ± 57
2442.8 ± 3.539.4 ± 2.9*3.6 ± 2.919.3 ± 4.51.5 ± 0.31.6 ± 0.3336 ± 34
3644.4 ± 3.841.3 ± 4.0*4.1 ± 1.919.2 ± 7.01.4 ± 0.31.4 ± 0.4332 ± 59
4845.6 ± 3.441.0 ± 3.0*4.6 ± 2.120.9 ± 3.81.4 ± 0.41.4 ± 0.5345 ± 37
7246.2 ± 2.840.8 ± 2.8*5.3 ± 1.422.4 ± 4.31.6 ± 0.71.7 ± 0.7376 ± 42
9644.2 ± 2.538.8 ± 2.9*5.4 ± 3.024.1 ± 9.21.5 ± 0.61.5 ± 0.4374 ± 38
12043.9 ± 3.538.5 ± 2.4*5.4 ± 3.023.6 ± 6.81.4 ± 0.21.4 ± 0.2375 ± 28
All ages44.6 ± 1.14.5 ± 1.021.3 ± 2.0

Lactate-a = Arterial lactate concentration. Lactate-cv = Central venous lactate concentration.

See Table 1 for remainder of key.

Central venous pH was significantly lower than arterial pH at 48, 72, 96, and 120 hours. The HCO3cv was significantly higher than HCO3a at 96 hours (Table 3).

Table 3—

Mean ± SD values of BE, bicarbonate concentration, and pH for blood samples obtained from 11 healthy foals at various times during the neonatal period.

Age (h)BEcv (mEq/L)BEa (mEq/L)HCO3cv (mmol/L)HCO3 a (mmol/L)pHcvpHa
125.1 ± 1.94.5 ± 1.829.6 ± 2.028.6 ± 2.17.422 ± 0.0247.433 ± 0.015
244.7 ± 2.23.7 ± 2.028.8 ± 2.327.3 ± 2.17.432 ± 0.0257.445 ± 0.024
365.0 ± 2.13.9 ± 2.029.3 ± 2.327.8 ± 2.37.425 ± 0.0227.433 ± 0.022
484.7 ± 1.63.9 ± 1.829.3 ± 2.027.8 ± 2.07.416 ± 0.0257.435 ± 0.017*
725.3 ± 2.44.3 ± 2.630.0 ± 2.528.1 ± 2.77.416 ± 0.0227.441 ± 0.021*
964.2 ± 2.13.4 ± 2.028.6 ± 2.126.6 ± 2.6*7.415 ± 0.0207.452 ± 0.032*
1204.1 ± 1.73.4 ± 1.928.5 ± 1.926.7 ± 2.37.418 ± 0.0217.459 ± 0.020*
All ages4.7 ± 0.43.9 ± 0.429.2 ± 0.627.6 ± 0.77.421 ± 0.0067.442 ± 0.010

pHa = Arterial pH. pHcv = Central venous pH.

See Table 1 for remainder of key.

There was no significant effect of time on Pcvco2, O2Ctcv, O2Cta, Scvo2, Sao2, Pcvco2, Pcvco2 – Paco2, O2ER, central venous pH, arterial pH, HCO3cv, HCO3a, BEcv, and Bea. Therefore, a mean value over time for each variable was calculated (Tables 1–3).

Discussion

Clinical and hemodynamic variables such as heart rate, blood pressure, urine output, and central venous pressure can be unreliable or late indicators of inadequate tissue perfusion and, in some situations, may provide limited guidance for timely treatment.30 In the study reported here, investigation into the use of central venous and arterial blood variables associated with global oxygenation in healthy neonatal foals was conducted to establish baseline values. The subsequent objective will be to compare similar global oxygen variables for ill foals, with the intent of improving treatment and the ability to determine prognosis in situations such as sepsis and septic shock in neonatal foals.

In the present study, placement of a central venous catheter into the cranial vena cava in healthy neonatal foals was technically easy to accomplish, and the catheter was easy to maintain for the 5-day study period. Inflammation or skin irritation was not detected at the catheter insertion site, and adverse effects attributable to catheter placement were not encountered.

Mean body weight of the foals was 52.2 kg, and the mean length of the catheter from the insertion site to the cranial vena cava was 34.8 cm. Ideally, catheter placement in the cranial vena cava should be confirmed with radiography; however, if radiography is not available, we suggest (on the basis of subjective observation) that length of the catheter to reach the cranial vena cava can be reasonably estimated by measuring the distance from the catheter insertion site to the caudal aspect of the scapula.

The So2 reflects the amount of oxygen remaining in blood in the pulmonary artery, including blood from the cranial and caudal vena cava, coronary sinuses, and right side of the heart, after all the tissues of the body have consumed oxygen, and it is a representative index of global tissue oxygenation.32–35 The So2 has been used in critical care settings for people to aid in treatment decisions (eg, assessing resuscitation, cardiac function, and systemic oxygen balance) as well as for determining a prognosis.32–35 Moreover, assessment and monitoring of So2 can be more reliable than the use of physical examination variables in patients with compensated shock, whereby noninvasively measured variables can fail to detect the presence or severity of shock.36–39 However, collection of mixed-venous blood samples requires placement of a catheter in a pulmonary artery, which traverses 2 heart valves. This procedure is invasive and technically challenging and can be associated with complications, including catheter-associated infections, increased risk of arrhythmias, and, rarely, rupture of the pulmonary artery.40 Thus, measurement of So2 has become less popular in the human critical care field.35,40

In contrast, measurement of Scvo2 in samples obtained from the cranial vena cava has been advocated as a surrogate for So2.41,42 The main factors that influence Scvo2 are the concentration of hemoglobin, Sao2, cardiac output, and oxygen consumption. Theoretically, if hemoglobin concentration, Sao2, and oxygen consumption are kept constant, Scvo2 reflects cardiac output.24 In healthy people, Scvo2 ranges from 73% to 82%, with a high or low Scvo2 suggestive of potential pathological conditions.19 A low Scvo2 indicates increased oxygen extraction from hemoglobin and typically suggests inadequate oxygen delivery or increased oxygen consumption, whereas a high Scvo2 can result from impaired oxygen utilization and may represent an inability of cells to extract oxygen, mitochondrial defects, or microcirculatory shunting in sepsis.19,35,43–46 Evaluation of blood lactate concentrations and Pcvco2 – Paco2 may help differentiate the underlying cause of alterations in Scvo2.19,23,24

In the study reported here, no significant difference in Scvo2 was detected during the experimental period (12 to 120 hours); mean ± SD Scvo2 over all times was 74.5 ± 1.1% (range, 52% to 87%). Mean values of Scvo2 in healthy neonatal foals were similar to those measured in healthy people (76 ± 6%).47 In humans with sepsis, a target treatment endpoint of Scvo2 > 70% has been suggested, but prospective trials in ill foals will be necessary to evaluate the use of Scvo2 as a treatment endpoint.5,48 In dogs with experimentally induced hypovolemia, low or decreasing Scvo2 and high or increasing Pcvco2 – Paco2 were detected after administration of furosemide, which reflected changes in global oxygen balance and altered microcirculatory blood flow in hypovolemia.24 As expected in the present study, Sao2 was significantly higher at all times than was Scvo2; mean Sao2 over all times was 95 ± 1.7%, which is similar to measurements in healthy neonatal foals reported elsewhere.49

In relation to Scvo2 and Sao2, values for the partial pressure of oxygen in mixed-venous blood in recumbent neonatal (birth to 14 days of age) foals have been reported, with a mean ± SD value of 40.5 ± 0.5 mm Hg over the 14-day study period.50 Mean Pcvco2 reported in the present study (40.2 ± 0.6 mm Hg) for central venous blood was similar to that previously reported for mixed-venous blood.50 In the present study, mean Pao2 was significantly lower at 12 hours, compared with the Pao2 at several later time points (ie, 48, 72, 96, and 120 hours). This pattern has been observed in other studies and is attributed to the change in gas exchange efficiency that developmentally occurs in foals during the first week after birth.51

As would be expected in healthy foals, Pcvco2 was significantly higher than Paco2 during the study period, and values were similar to Pco2 measured in samples obtained from the pulmonary vein of neonatal foals50 and healthy adult dogs.52 The Pcvco2 – Paco2 has been used as a marker of global hemodynamic status and might have use for the detection of low blood flow states in ill neonatal foals.23 An increase in Pcvco2 results when cellular oxidation overwhelms the body's buffering systems.41 Although Paco2 is variable and dependent on pulmonary gas exchange, Pcvco2 is dependent on blood flow (ie, cardiac output) to remove CO2 from tissues.19,41 Thus, an increase in Pcvco2 – Paco2 can reflect decreased blood flow and has been reported in critically ill humans with severe sepsis, heart failure, hypovolemia, or other low-flow states.27,28,41,53,54 The complementary use of Scvo2 and Pcvco2 – Paco2 has been recommended for conditions in which oxygen uptake is insufficient because of microcirculatory or mitochondrial defects (ie, severe sepsis) that result in a falsely elevated Scvo2; in this situation, an increase in Pcvco2 – Paco2 may help clinicians detect inadequate oxygen delivery.19 No difference in Pcvco2 – Paco2 was noted over time in the healthy foals of the present study; mean ± SD Pcvco2 – Paco2 over all times was 4.5 ± 1.0 mm Hg, which is similar to the Pcvco2 – Paco2 in healthy people (< 5 mm Hg) and healthy dogs (5.8 mm Hg).26,28,52–54

The O2ER is the amount of oxygen removed from the blood by the tissues. Oxygen extraction increases in situations of decreased oxygen delivery (ie, shock), tissue hypoxia, or lactic acidosis or as a result of increased metabolic demand.31 A strong negative correlation between O2ER and Scvo2 has been detected in humans: as hemoglobin becomes more desaturated, an increase in oxygen extraction occurs, which results in a decrease in Scvo2.31 When oxygen delivery decreases below the threshold to maintain oxygen consumption via increased oxygen extraction, consumption becomes delivery dependent and tissues begin to produce lactate, with lactic acidosis typically accompanying an O2ER > 50%.10,31 Conversely, a decrease in O2ER can be observed if tissue oxygen consumption decreases or if tissues cannot use oxygen; this situation may be associated with an abnormal increase in Scvo2.31 If the tissues are not capable of extracting oxygen (ie, shunting of blood or cell death), venous blood may have a high oxygen content despite persistent cellular hypoxia.35 The O2ER has also been used to help identify patients with fatal conditions, especially those with Scvo2 > 70%.31 The mean O2ER for all times in the foals of the study reported here was 21.3%, which is comparable to that reported for dogs55 (20.5%) and healthy people31 (25%).

Lactate is the end product of glycolysis, with the arterial lactate concentration historically used as the reference value for assessment of tissue hypoxia or dysoxia.56 However, it has been suggested56–58 that venous and arterial lactate concentrations can be used interchangeably. Venous blood samples can typically be collected more rapidly and are technically easier to collect, compared with arterial blood samples, which has spurred investigation of the suitability of venous blood lactate concentrations as an early indicator of sepsis.56,58 In 1 study,58 the mean difference between venous and arterial lactate concentrations in people was 0.54 mmol/L, which suggests that lactate concentrations in peripheral venous blood can be an appropriate substitute in septic patients. In another study,56 investigators found a strong correlation (r = 0.96) between arterial and peripheral venous blood lactate concentrations, with venous blood lactate concentrations more effective than arterial lactate concentrations for use in detecting severe sepsis. Other investigators compared central venous and arterial blood lactate concentrations and reported a mean difference in central venous-to-arterial lactate concentrations of 0.08 mmol/L.59 Conversely, a difference between arterial and venous lactate concentrations has been found (mean venous lactate concentration was 1.1 mmol/L higher than the corresponding arterial lactate concentration in people admitted to an emergency department).57 In comparison, a slightly higher arterial lactate concentration, compared with the venous blood lactate concentration, was detected in people with sepsis.56 In the study reported here, the central venous lactate concentration was comparatively similar to values for peripheral venous samples obtained from healthy foals.60 A significant difference was not detected between the central venous and arterial lactate concentrations in the present study, which suggested that central venous and arterial lactate concentrations can be used interchangeably for healthy neonatal foals. Both arterial and venous lactate concentrations have been evaluated in neonatal foals with sepsis16–18; however, to our knowledge, no studies have been conducted to compare peripheral venous or central venous lactate concentrations with arterial lactate concentrations in ill foals.

Studies61,62 have also detected a relationship between the degree of acidosis and mortality rates in critically ill patients. Blood pH is commonly evaluated during blood gas analysis and is a cornerstone for assessment of acid-base status. In contrast to pH values measured in adult horses,63 in which no difference was detected between venous and arterial pH, the foals of the study reported here had a significantly lower central venous pH, compared with the arterial pH, at 48, 72, 96, and 120 hours. Other variables have been used to assess hemodynamic failure. For example, inadequate oxygen delivery to tissues during sepsis or other conditions associated with hypoperfusion may be identified by an increase in lactate concentrations, but a number of unmeasured acidic compounds can also be present during these conditions and perhaps better detected by assessment of BE or serum HCO3 concentration.c Base excess has been used as a marker of tissue perfusion and adequacy of resuscitation as well as a predictor of mortality rates.64,c Low (more negative) BE values at admission have been associated with higher mortality rates, and improvement of BE in patients with severe sepsis and septic shock has been a strong predictor of a better outcome.64,c In addition, BE has been suggested as a surrogate for blood lactate concentration when a lactometer is not available, with BE −4 mEq/L correlating with a lactate concentration > 3 mmol/L.65 In 1 study16 involving ill neonatal foals, BE < 3.9 mEq/L predicted hyperlactatemia (lactate concentration > 5 mmol/L) with good sensitivity and specificity.

Base excess also has been used as an indicator of metabolic acid-base disturbances.29 In the study reported here, a significant difference between BEcv and BEa was not detected, with mean values of 4.7 and 3.9 mmol/L, respectively. In addition to BE, serum HCO3 concentrations have also been suggested as a method for evaluation of acid-base status as well as a surrogate for BE.29,66 Measurement of serum HCO3 concentration is more readily available because these concentrations are routinely measured during serum biochemical analysis, whereas blood gas analysis is not always available. In studies29,66 that involved evaluation of human patients in intensive care units, serum HCO3 concentration had a strong correlation (r = 0.857) with BE and was a reliable indicator of metabolic acidosis. In many ways, these variables (lactate concentration, BE, and HCO3 concentration) are different facets of the same process (ie, perturbation of the acid-base equilibrium as a result of the nonvolatile acid load originating from dysfunctional cells [lactate] or dead cells [intracellular strong acid content higher than plasma content]).61 However, depending on the degree of perturbation during critical illness and availability of diagnostic testing, one or more of these specific variables may help guide future resuscitation efforts in ill foals and could potentially aid in determining prognosis.64

The Pao2:Fio2 was implemented in the 1990s to improve standardization of research and criteria for more accurate determination of disease severity and prognosis as it relates to acute respiratory distress syndrome.67 This ratio facilitates evaluation of the respiratory system by comparing Pao2 with the amount of inspired oxygen and is part of the inclusion criterion for acute lung injury and acute respiratory distress syndrome.51,67,68 Consensus definitions have been developed for veterinary use and specifically to address acute lung injury and acute respiratory distress syndrome in neonatal foals and to account for recognized changes in gas exchange efficiency that occur in newborn foals during the first week after birth.51 The suggested Pao2:Fio2 values in clinically normal animals are similar to those in the study reported here, although the mean Pao2:Fio2 at 24 hours in the present study was 300 mm Hg, whereas the suggested ratio in the consensus statement was > 350 mm Hg.51 This difference may in part have been attributable to the fact that data used to calculate Pao2:Fio2 in the consensus statement were based on values from foals in a standing position (compared with recumbent foals in the present study) or differences in instrumentation.51 Data for the study reported here will help to validate the recommended consensus values for Pao2:Fio2 in neonatal foals and provide additional time points (36, 72, and 120 hours) for evaluation of Pao2:Fio2.

Oxygen content in blood is needed to calculate other variables associated with global oxygenation, such as oxygen delivery and oxygen consumption. In the present study, there was no effect of time on O2Cta and O2Ctcv; thus, the mean value over time for these 2 variables was 16.2 and 12.4 mL/dL, respectively. These values in healthy foals are similar to, but slightly less than, those measured in healthy humans34 (O2Cta, 18 to 20 mL/dL; O2Ctcv, 13 to 16 mL/dL) and dogs55 (O2Cta, 18.5 mL/dL; O2Ctcv, 14.7 mL/dL). Oxygen content is greatly impacted by hemoglobin concentration, which differs among reports. The hemoglobin content factor used to estimate hemoglobin oxygen content differs from 1.31 to 1.39, with a mid-range value of 1.34 used in many studies; in the study reported here, a value of 1.39 was used.

One limitation of the present study was that only 11 healthy foals were used to investigate the variables associated with systemic oxygenation. Ideally, data for a larger number of healthy foals would have been collected. In addition, foals were sedated with diazepam at 12 hours of age to facilitate catheter placement. Although foals appeared to regain normal mentation and activity by the time catheter placement was complete (approx 30 to 45 minutes), it is possible that residual effects of diazepam may have impacted some of the variables to a slight degree. Finally, it has been reported50,69 that collection of blood from recumbent foals alters results for some of the variables (eg, venous partial pressure of O2, venous partial pressure of CO2, and Pao2). In the study reported here, both central venous and arterial blood samples were collected while foals were recumbent because this would most likely be the position of ill foals in a clinical situation. In addition, collection of arterial blood samples from a foal in a standing position would be extremely difficult. Despite these limitations, this study provided values for central venous and arterial blood variables that can be used for comparison with measurements obtained in future research investigations and clinical patients. Many of the variables investigated in this report interact or impact one another; thus, it is unlikely that a single variable will be a panacea. However, future investigation and use of one or more of these variables for ill foals may facilitate early detection of critical clinical conditions (ie, shock or sepsis), help guide treatment decisions (eg, when to initiate provision of supplemental oxygen, vasopressors, or IV fluids), and provide prognostic information.

ABBREVIATIONS

BE

Base excess

BEa

Base excess in arterial blood

BEcv

Base excess in central venous blood

HCO3a

Bicarbonate concentration in arterial blood

HCO3cv

Bicarbonate concentration in central venous blood

O2Cta

Oxygen content in arterial blood

O2Ctcv

Oxygen content in central venous blood

O2ER

Oxygen extraction ratio

Pao2:Fio2

Ratio between arterial partial pressure of oxygen and fraction of inspired oxygen

Pcvco2

Partial pressure of carbon dioxide in central venous blood

Pcvco2 – Paco2

Central venous–arterial difference in partial pressure of carbon dioxide

Pcvo2

Partial pressure of oxygen in central venous blood

Sao2

Arterial oxygen saturation

Scvo2

Central venous oxygen saturation

So2

Mixed-venous oxygen saturation

Footnotes

a

Long-term catheter with peel-away introducer, Mila International, Erlanger, Ky.

b.

pHOx Ultra analyzer, Nova Biomedical, Waltham, Mass.

c.

Palma LC, Ferreira GF, Amaral ACKB, et al. Acidosis and mortality in severe sepsis and septic shock evaluated by base excess variation (abstr). Crit Care 2003;7(suppl 3):39.

References

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  • 1. Prittie J. Optimal endpoints of resuscitation and early goal-directed therapy. J Vet Emerg Crit Care 2006; 16: 329339.

  • 2. Nelson DP, Beyer C, Samsel RW, et al. Pathological supply dependence of O2 uptake during bacteremia in dogs. J Appl Physiol 1987; 63: 14871492.

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    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345: 13681377.

  • 6. Butler AL, Campbell VL. Assessment of oxygen transport and utilization in dogs with naturally occurring sepsis. J Am Vet Med Assoc 2010; 237: 167173.

  • 7. Elliott DC. An evaluation of the end points of resuscitation. J Am Coll Surg 1998; 187: 536547.

  • 8. de Oliveira CF, de Oliveira DSF, Gottschald AFC, et al. ACCM/PALS haemodynamic support guidelines for paediatric septic shock: an outcomes comparison with and without monitoring central venous oxygen saturation. Intensive Care Med 2008; 34: 10651075.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9. Donati A, Loggi S, Preiser JC, et al. Goal-directed intraoperative therapy reduces morbidity and mortality and length of hospital stay in high-risk surgical patients. Chest 2007; 132: 18171824.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Joshi R, de Witt B, Mosier JM. Optimizing oxygen delivery in the critically ill: the utility of lactate and central venous oxygen saturation (ScvO2) as a roadmap of resuscitation in shock. J Emerg Med 2014; 47: 493500.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11. Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 2010; 303: 739746.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12. Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation or septic shock. N Engl J Med 2015; 372: 13011311.

  • 13. ARISE Investigators; ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014; 371: 14961506.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14. ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014; 370: 16831693.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15. Palmer J. Update on the management of neonatal sepsis in horses. Vet Clin North Am Equine Pract 2014; 30: 317336.

  • 16. Corley KTT, Donaldson LL, Furr MO. Arterial lactate concentration, hospital survival, sepsis and SIRS in critically ill neonatal foals. Equine Vet J 2005; 37: 5359.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17. Borchers A, Wilkins PA, Marsh PM, et al. Admission L-lactate concentration in hospitalised equine neonates: a prospective multicenter study. Equine Vet J Suppl 2012;(41): 5763.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18. Borchers A, Wilkins PA, Marsh PM, et al. Sequential L-lactate concentration in hospitalised equine neonates: a prospective multicenter study. Equine Vet J Suppl 2013;(45): 27.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19. Tánczos K, Nemeth M, Molnar Z. The multimodal concept of hemodynamic stabilization. Front Public Health 2014; 2: 34.

  • 20. Chawla LS, Zia H, Gutierrez G, et al. Lack of equivalence between central and mixed venous oxygen saturation. Chest 2004; 126: 18911896.

  • 21. Varpula M, Karlsson S, Ruokonen E, et al. Mixed venous oxygen saturation cannot be estimated by central venous oxygen saturation in septic shock. Intensive Care Med 2006; 32: 13361343.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22. Reid M. Central venous oxygen saturation: analysis, clinical use and effects on mortality. Nurs Crit Care 2013; 18: 245250.

  • 23. Du W, Wang XT, Long Y, et al. Combining central venous-to-arterial partial pressure of carbon dioxide difference and central venous oxygen saturation to guide resuscitation in septic shock. J Crit Care 2013; 28: 1110.e11110.e5.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24. Kocsi A, Demeter G, Erces D, et al. Central venous-to-arterial CO2 gap is a useful parameter in monitoring hypovolemiacaused altered oxygen balance: animal study. Crit Care Res Pract 2013; 2013: 583598.

    • Search Google Scholar
    • Export Citation
  • 25. Weil MH, Rackow EC, Trevino R, et al. Difference in acid-base state between venous and arterial blood during cardiopulmonary resuscitation. N Engl J Med 1986; 315: 153156.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26. Vallet B, Teboul JL, Cain S, et al. Venoarterial CO2 difference during regional ischemic or hypoxic hypoxia. J Appl Physiol 2000; 89: 13171321.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27. Adrogué HJ, Rashad MN, Gorin AB, et al. Assessing acid-base status in circulatory failure. Differences between arterial and central venous blood. N Engl J Med 1989; 320: 13121316.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28. Mecher CE, Rackow EC, Astiz ME, et al. Venous hypercarbia associated with severe sepsis and systemic hypoperfusion. Crit Care Med 1990; 18: 585589.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29. Surbatovic M, Radakovia S, Jevtic M, et al. Predictive value of serum bicarbonate, arterial base deficit/excess and SAPS III score in critically ill patients. Gen Physiol Biophys 2009; 28: 271276.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30. Allen M. Lactate and acid base as a hemodynamic monitor and markers of cellular perfusion. Pediatr Crit Care Med 2011; 12(suppl): S43S49.

  • 31. Park JS, Kim SJ, Lee SW, et al. Initial low oxygen extraction ratio is related to severe organ dysfunction and high in-hospital mortality in severe sepsis and septic shock patients. J Emerg Med 2015; 49: 261267.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32. Kandel G, Aberman A. A mixed venous oxygen saturation: its role in the assessment of the critically ill patient. Arch Intern Med 1983; 143: 14001402.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33. Kasnitz P, Druger GL, Yorra F, et al. Mixed venous oxygen tension and hyperlactatemia. Survival in severe cardiopulmonary disease. JAMA 1976; 236: 570574.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34. Powner DJ, Doshi PB. Central venous oxygen saturation monitoring: role in adult donor care? Prog Transplant 2010; 20: 401405.

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