Physiologic effects of nasopharyngeal administration of supplemental oxygen at various flow rates in healthy neonatal foals

David M. Wong Section of Equine Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Cody J. Alcott Section of Equine Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Chong Wang Department of Veterinary Clinical Sciences, and the Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.
Department of Statistics, College of Liberal Arts & Sciences, Iowa State University, Ames, IA 50011.

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Bonnie L. Hay-Kraus Section of Anesthesia, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Benjamin R. Buchanan Brazos Valley Equine Hospital, 6999 Hwy 6 Loop, Navasota, TX 77868.

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Charles W. Brockus Charles Rivers Laboratories, Preclinical Services, 6995 Longley Ln, Reno, NV 89511.

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Abstract

Objective—To evaluate the effects of various flow rates of oxygen administered via 1 or 2 nasal cannulae on the fraction of inspired oxygen concentration (Fio2) and other arterial blood gas variables in healthy neonatal foals.

Animals—9 healthy neonatal (3- to 4-day-old) foals.

Procedures—In each foal, a nasal cannula was introduced into each naris and passed into the nasopharynx to the level of the medial canthus of each eye; oxygen was administered at 4 flow rates through either 1 or both cannulae (8 treatments/foal). Intratracheal Fio2, intratracheal end-tidal partial pressure of carbon dioxide, and arterial blood gas variables were measured before (baseline) and during unilateral and bilateral nasopharyngeal delivery of 50, 100, 150, and 200 mL of oxygen/kg/min.

Results—No adverse reactions were associated with administration of supplemental oxygen except at the highest flow rate, at which the foals became agitated. At individual flow rates, significant and dose-dependent increases in Fio2, Pao2, and oxygen saturation of hemoglobin (Sao2) were detected, compared with baseline values. Comparison of unilateral and bilateral delivery of oxygen at similar cumulative flow rates revealed no differences in evaluated variables.

Conclusions and Clinical Relevance—Results indicated that administration of supplemental oxygen via nasal cannulae appeared to be a highly effective means of increasing Fio2, Pao2, and Sao2 in neonatal foals. These findings may provide guidance for implementation of oxygen treatment in hypoxemic neonatal foals. (Am J Vet Med 2010;71:1081–1088)

Abstract

Objective—To evaluate the effects of various flow rates of oxygen administered via 1 or 2 nasal cannulae on the fraction of inspired oxygen concentration (Fio2) and other arterial blood gas variables in healthy neonatal foals.

Animals—9 healthy neonatal (3- to 4-day-old) foals.

Procedures—In each foal, a nasal cannula was introduced into each naris and passed into the nasopharynx to the level of the medial canthus of each eye; oxygen was administered at 4 flow rates through either 1 or both cannulae (8 treatments/foal). Intratracheal Fio2, intratracheal end-tidal partial pressure of carbon dioxide, and arterial blood gas variables were measured before (baseline) and during unilateral and bilateral nasopharyngeal delivery of 50, 100, 150, and 200 mL of oxygen/kg/min.

Results—No adverse reactions were associated with administration of supplemental oxygen except at the highest flow rate, at which the foals became agitated. At individual flow rates, significant and dose-dependent increases in Fio2, Pao2, and oxygen saturation of hemoglobin (Sao2) were detected, compared with baseline values. Comparison of unilateral and bilateral delivery of oxygen at similar cumulative flow rates revealed no differences in evaluated variables.

Conclusions and Clinical Relevance—Results indicated that administration of supplemental oxygen via nasal cannulae appeared to be a highly effective means of increasing Fio2, Pao2, and Sao2 in neonatal foals. These findings may provide guidance for implementation of oxygen treatment in hypoxemic neonatal foals. (Am J Vet Med 2010;71:1081–1088)

Administration of supplemental oxygen is commonly performed to increase the oxygen content of blood in hypoxemic neonatal foals.1 In a neonatal foal, oxygen can be provided via a face mask, nasal cannula, or transtracheal catheter or by means of mechanical ventilation involving endotracheal intubation.1–3 Of these 4 methods of oxygen administration, a nasal cannula might perhaps cause the least discomfort and be the most practical, cost-effective, and frequently used method.1,3 Despite the frequent administration of supplemental oxygen in equine neonatal medicine, detailed investigation of the effects of flow rate (ie, dosage) of oxygen on arterial blood gas variables and Fio2 in foals has not been undertaken, to our knowledge. In previous studies,3,4 oxygen at a flow rate of 10 L/min was administered via a face mask or nasal catheter to foals at 30 minutes to 7 days after birth. The treatments resulted in significant increases in Pao2, compared with pretreatment values; however, effects on Fio2 and the use of different flow rates of oxygen were not investigated.3,4

Despite the obvious benefits gained from administration of supplemental oxygen, such as treatment of hypoxemia and reductions in ventilator requirements and myocardial effort necessary to maintain a given alveolar oxygen tension, awareness of potential detrimental effects of prolonged exposure to supraphysiologic concentrations of inspired oxygen administered to foals should be considered.3 Relatively minor complications associated with supplemental oxygen administration include nasal irritation and rhinitis, airway drying, and stimulation of excessive airway secretions.1 However, hyperoxemia may result in the generation of reactive oxygen species that are injurious to the lungs and other organs through oxidative stress.5,6 For example, it is known that fatal ALI develops in mice that are experimentally exposed to 100% oxygen for 4 days.7 Furthermore, hyperoxic conditions result in DNA damage in lung tissue of mice, and hyperoxia has been associated with direct toxic effects in the lungs and the development of bronchopulmonary dysplasia in premature infants.8–10 In general, to decrease the likelihood of oxidative stress and damage, it is recommended to maintain the Fio2 at ≤ 60% if supplemental oxygen is to be administered for a prolonged (> 24 hours) period.11,12 Thus, equine clinicians should attempt to maintain an Fio2 < 60% when administering supplemental oxygen to foals; however, the relationship between flow rate and Fio2 in neonatal foals is currently not known.

Knowledge of Fio2 in foals that are being administered supplemental oxygen also would be useful in grading pulmonary disease severity in affected foals. Acute lung injury and ARDS are syndromes of noncardiogenic respiratory failure that have been widely recognized in people and less well described in foals.13–17 These syndromes are characterized by diffuse alveolar damage. In horses, diagnosis of these syndromes requires that at least 4 of 5 criteria are met: acute onset of tachypnea and labored breathing at rest; presence of risk factors such as inflammation, infection, sepsis, or trauma; evidence of pulmonary capillary leakage without increased pulmonary capillary pressure (eg, radiographic evidence of diffuse pulmonary infiltrates); evidence of diffuse pulmonary inflammation; and evidence of inefficient gas exchange (derived via determination of the Pao2:Fio2 ratio).15 With regard to gas exchange, ALI in horses is characterized by a Pao2:Fio2 ratio < 300 mm Hg (but > 200 mm Hg), whereas ARDS is characterized by a Pao2:Fio2 ratio < 200 mm Hg.15,16 However, the Pao2:Fio2 ratio has not been specifically investigated in healthy neonatal foals, to our knowledge. In addition, the Fio2 must be assessed to determine whether a foal has ALI or ARDS. Although the Fio2 in foals that are breathing room air or being ventilated mechanically may be known, the Fio2 in foals that are receiving oxygen via intranasal administration has not been determined. The purpose of the study reported here was to evaluate the effects of different flow rates of oxygen administered via 1 or 2 nasal cannulae on the Fio2 and other arterial blood gas variables in healthy neonatal foals. We sought to establish a dosage protocol for supplemental oxygen delivery via nasal cannulae in foals. We hypothesized that increasing oxygen flow rates would increase Fio2 and Pao2 in a dose-dependent manner.

Materials and Methods

Foals—For the investigation, 9 healthy neonatal foals from Iowa State University's teaching herd were used. Each foal was considered healthy on the basis of physical examination findings, adequate passive transfer of maternal antibodies (plasma immunoglobulin concentration at 24 hours after birth, ≥ 800 mg/dL), and the absence of any disorders in the dam during pregnancy or parturition. The duration of gestation in all foals was considered normal. Breeds included Thoroughbreds (n = 5) and Quarter Horses and related breeds (4). There were 5 fillies and 4 colts. The foals’ ages ranged from 3 to 5 days (mean ± SD age, 3.9 ± 0.5 days), and weights ranged from 55 to 67 kg (mean weight, 60.4 ± 3.8 kg). The study protocol was approved by the Iowa State University Animal Care and Use Committee.

Instrumentation—On the day of the experimental procedure, each foal was weighed, a physical examination was performed, and rectal temperature, heart rate, and respiratory rate were recorded. The haired skin over the left dorsal metatarsal artery was clipped and prepared aseptically for catheter placement. A local anesthetic creama was applied liberally in the region of the dorsal metatarsal artery at least 10 minutes prior to catheter placement. The foal was sedated with diazepamb (0.16 mg/kg, IV) and placed in right lateral recumbency. Subsequently, 0.25 mL of 2% lidocainec was injected ID in the skin superficial to the dorsal metatarsal artery. A 20-gauge, 1.5-inch, over-the-needle intra-arterial catheterd was placed under aseptic conditions into the dorsal metatarsal artery, and a low-volume (0.9-mL) extension sete was attached; the apparatus was secured with adhesive and protected with a bandage.

While the foal was still sedated, a polyethylene sampling linef (outer diameter, 3 mm) was inserted through the left ventral meatus with the guidance of a preplaced nasotracheal tubeg (internal diameter, 8 mm); the sampling line was advanced into the trachea to a point just caudal to the thoracic inlet for measurement of Fio2 and Petco2. Placement of the tracheal catheter was confirmed radiographically. Additionally, a nasal cannula (internal diameter, 4 mm) that was made of soft plastic tubingh was inserted into each ventral meatus so that the tip of each cannula was positioned in the nasopharynx at the level of the medial canthus of the eye. Each cannula was secured in place with tape and sutures.

Experimental protocol—Baseline values of rectal temperature, heart rate, and respiratory rate were recorded at least 1 hour after administration of the sedative, while each foal was standing. Immediately after collection of those baseline data, a baseline arterial blood sample (2 mL) was collected anaerobically into syringes containing heparin; syringes were immediately placed in an ice bath, and samples were analyzed within 10 minutes by use of a blood gas analyzer.i The blood gas analyzer was calibrated with reagent packs and gas standards prior to and every hour during each experimental procedure. Arterial blood samples were evaluated in duplicate; findings were corrected to rectal temperature, and the mean value for each variable was calculated.

Following collection of the baseline blood sample, each nasal cannula was connected to an individual air humidifierj and flow meterk and then connected to a flow splitter and a high-pressure tank that contained medical-grade (100%) oxygen. The tracheal catheter was interfaced with an airway gas analyzerl that measured Fio2 and Petco2. The analyzer was calibrated prior to each procedure by use of gas supplied by the manufacturer. Each foal was observed for coughing, behavioral changes, or adverse effects during the approximately 3-hour experimental procedure period.

Each foal was manually restrained in a standing position in the stall with the mare present. Oxygen administration at the first predetermined rate was initiated, and a minimum of 5 minutes elapsed before measurements were made. A previous study3 in foals revealed that a 2-minute interval is adequate for equilibration. During the 5-minute equilibration period, the rate at which Fio2 changed along with the fluctuations in Fio2 was subjectively assessed until a stable reading was established. In 5 foals, oxygen was initially administered bilaterally (ie, through both nasal cannulae) and 4 rates of oxygen administration were evaluated. The flow rate for each cannula was initially 50 mL of oxygen/kg/min, which was adjusted to 100, 150, and 200 mL of oxygen/kg/min in sequence (total dosages of 100, 200, 300, and 400 mL of oxygen/kg/min, respectively). Those total dosages of supplemental oxygen corresponded to 6, 12, 18, and 24 L/min, respectively, in a 60-kg foal. In those 5 foals, oxygen was subsequently administered in the same sequence of increasing flow rates through only 1 randomly selected (ie, left or right) cannula (total dosages of 50, 100, 150, and 200 mL of oxygen/ kg/min). Those total dosages of supplemental oxygen corresponded to 3, 6, 9, and 12 L/min, respectively, in a 60-kg foal. In the other 4 foals, oxygen was initially administered bilaterally (ie, through both nasal cannulae) and the same 4 rates of oxygen administration were evaluated. However, the flow rate for each cannula was initially 200 mL of oxygen/kg/min, which was adjusted to 150, 100, and 50 mL of oxygen/kg/min in sequence (total dosages of 400, 300, 200, and 100 mL of oxygen/kg/min, respectively). In those 4 foals, oxygen was subsequently administered in the same sequence of decreasing flow rates through only 1 randomly selected (ie, left or right) cannula (total dosages of 200, 150, 100, and 50 mL of oxygen/kg/min). On the day that a foal was to be used in an experimental procedure, it was allocated to receive one or the other of the dosage regimens on an alternating schedule (ie, evaluated foals 1, 3, 5, 7, and 9 received the increasing flow rate regimen and evaluated foals 2, 4, 6, and 8 received the decreasing flow rate regimen).

For all foals, a minimum of 5 minutes was allowed to elapse before measurements were made at each flow rate; data collection at each flow rate was completed within 10 minutes. If a foal became excited during handling, it was allowed to regain a quiet demeanor with minimal restraint prior to collection of data. At each flow rate, measurements included assessments of rectal temperature, heart rate, and respiratory rate and the Fio2 and Petco2 values were obtained from a gas sample aspirated through the tracheal catheter; an arterial blood sample (2 mL) was collected and analyzed, as described. At the end of data collection at each oxygen flow rate, the foal was disconnected from all monitors and external devices and was allowed free access to the mare for at least 10 minutes. Prior to administration of oxygen at the various oxygen flow rates, the Fio2 was evaluated to ensure that no residual effects from previous oxygen administration were present.

Statistical analysis—All data are reported as mean ± SD. A repeated-measures ANOVA was applied to each of the response variables (rectal temperature, heart rate, respiratory rate, Fio2, pHa, Pao2, Paco2, Petco2, blood bicarbonate concentration, TCO2, Sao2, and Pao2:Fio2 ratio) by use of computer software.m For each response variable, an F test with Kenward and Roger adjustment to degrees of freedom was used to test for differences among the variable means of 9 data groups (baseline values and 8 treatment groups [bilateral administration of oxygen at rates of 50, 100, 150, or 200 mL/kg/min and unilateral administration of oxygen at rates of 50, 100, 150, and 200 mL/kg/min]) with significance set at a value of P < 0.05. When a significant F test was calculated, post hoc Tukey t tests were applied for pairwise comparisons between treatment means. To evaluate the effects of oxygen flow rate on 2 particular response variables, Fio2 and Pao2, a linear regression analysis with repeated measures was applied to each of the responses by use of computer software.m The coefficient of determination also was calculated for the regression model for each response variable. In addition, the correlation coefficient between Paco2 and Petco2 was estimated and testedn for significance. A value of P < 0.05 was considered significant.

Results

There were no complications associated with instrumentation or data collection in any foal. Most foals tolerated handling and restraint calmly, but some foals became excited; those foals were allowed to regain a quiet demeanor prior to collection of data. No adverse effects were observed during administration of oxygen at the lower flow rates (50, 100, and 150 mL/kg/min). However, foals developed signs of agitation during oxygen administration at the highest flow rate (200 mL/kg/min) exemplified by head tossing, rubbing of the muzzle, and hyperesthesia, regardless of whether oxygen was administered via 1 or both nasal cannulae. There were no significant differences among foals with regard to rectal temperature, heart rate, or respiratory rate at any oxygen flow rate, compared with baseline values (Table 1). Likewise, comparisons of data obtained at the various oxygen flow rates revealed no significant difference in rectal temperature, heart rate, or respiratory rate, with the exception of a significant (P = 0.04) difference in respiratory rate between unilateral administration of oxygen at a rate of 50 mL/kg/min and bilateral administration of oxygen at a rate of 100 mL/kg/min.

Table 1—

Mean ± SD respiratory rate, heart rate, and rectal temperature in 9 healthy neonatal foals before (baseline) and during administration of supplemental oxygen at various flow rates via 1 or 2 nasal cannulae (unilateral and bilateral oxygen delivery, respectively).

VariableBaselineOxygen delivery
Unilateral (mL/kg/min)Bilateral (mL/kg/min)
5010015020050100150200
Respiratory rate (breaths/min)39 ± 1252 ± 10a47 ± 1544 ± 1140 ± 1538 ± 1037 ± 11b44 ± 842 ± 12
Heart rate (beats/min)94 ± 10101 ± 6101 ± 8101 ± 1998 ± 1995 ± 1197 ± 1296 ± 1295 ± 10
Temperature (°C)38.4 ± 0.438.7 ± 0.338.6 ± 0.338.6 ± 0.438.6 ± 0.338.4 ± 0.338.6 ± 0.438.5 ± 0.438.5 ± 0.4

Within a row, mean values with different superscript letters differ significantly (adjusted P < 0.04).

Data regarding Fio2, pHa, Pao2, Paco2, Petco2, blood bicarbonate concentration, TCO2, Sao2, and Pao2: Fio2 ratio were obtained for all foals at each oxygen flow rate (Table 2). The Fio2 measurement fluctuated, depending on the foal's activity and respiratory rate, but generally increased and reached a plateau within 30 to 60 seconds of the commencement of oxygen administration at each flow rate. Compared with baseline values, significant (P < 0.001) increases in Fio2, Pao2, and Sao2 were detected at all oxygen flow rates. Other significant differences from baseline values included changes in pHa during unilateral delivery of oxygen at a rate of 200 mL/kg/min (P = 0.04) and in Paco2 during unilateral delivery at rates of 100 and 200 mL/kg/min and during bilateral delivery at a rate of 100 mL/kg/min (P < 0.04). Compared with baseline values, there were no significant differences in values of Petco2, blood bicarbonate concentration, and TCO2 at any oxygen flow rate, regardless of delivery method.

Table 2—

Mean ± SD arterial blood gas and tracheal gas variables in 9 healthy neonatal foals before (baseline) and during administration of supplemental oxygen at various flow rates via 1 or 2 nasal cannulae (unilateral and bilateral oxygen delivery, respectively).

VariableBaselineOxygen delivery
Unilateral (mL/kg/min)Bilateral (mL/kg/min)
5010015020050100150200
          
Fio2 (%)18.0 ± 0.7b23.0 ± 1.4b30.9 ± 2.1b44.2 ± 5.8b,c,d52.6 ± 8.3b,d,e30.9 ± 2.6b48.7 ± 6.2b,c56.4 ± 3.4b,e74.6 ± 4.2b
pHa7.435 ± 0.02a7.415 ± 0.027.417 ± 0.017.418 ± 0.017.411 ± 0.02b7.422 ± 0.017.412 ± 0.027.422 ± 0.037.426 ± 0.02
Pao2 (mm Hg)92.5 ± 8.2a135.9 ± 13.2b175.2 ± 14.6b219.6 ± 31.9b,e,f269.7 ± 40.8b,d,f174.3 ± 26.8b261.2 ± 38.3b,c,e307.8 ± 41.0b,c,d374.2 ± 58.2b
Paco2 (mm Hg)47.7 ± 2.8a49.7 ± 2.450.5 ± 2.3b50.1 ± 2.851.3 ± 3.1b49.8 ± 1.851.0 ± 2.2b49.8 ± 2.948.6 ± 3.6
Petco2 (mm Hg)253.9 ± 3.352.6 ± 4.952.8 ± 7.953.9 ± 7.954.6 ± 5.655.6 ± 2.855.3 ± 6.055.2 ± 5.155.3 ± 4.8
Bicarbonate (mmol/L)31.4 ± 2.730.7 ± 1.331.4 ± 1.231.2 ± 1.331.4 ± 1.230.8 ± 1.931.5 ± 1.431.4 ± 2.030.8 ± 2.2
TCO2 (mmol/L)32.3 ± 2.032.0 ± 1.532.8 ± 1.332.6 ± 1.332.8 ± 1.332.2 ± 2.032.9 ± 1.432.8 ± 2.132.2 ± 2.3
Sao2 (%)96.7 ± 0.7a98.5 ± 0.3b99.2 ± 0.1b99.4 ± 0.2b99.6 ± 0.1b99.1 ± 0.3b99.6 ± 0.1b99.7 ± 0.1b99.8 ± 0.1b
Pao2·FIO2 ratio514 ± 39594 ± 73g,h569 ± 61502 ± 75g517 ± 58563 ± 55540 ± 73547 ± 81501 ± 57h

Within a row, mean baseline value and and values at individual oxygen flow rates that have different superscript letters differ significantly [P < 0.05).

Within a row, FIO or Pao2 at individual oxygen flow rates that have different superscript letters differ significantly (P ≤ 0.02 and ≤ 0.03, respectively).

Witnin a row, mean ratio values at individual oxygen flow rates that have different superscript letters differ significantly [P < 0.05).

Administration of supplemental oxygen increased Fio2 and Pao2 in a dose-dependent manner. However, at any given flow rate, measured variables were not affected by delivery method (ie, unilateral or bilateral administration). More specifically, values of the measured variables obtained during unilateral administration of 100 mL of oxygen/kg/min did not differ significantly from those obtained during bilateral administration of 50 mL of oxygen/kg/min; similarly, values of the measured variables obtained during unilateral administration of 200 mL of oxygen/kg/min did not differ significantly from those obtained during bilateral administration of 100 mL of oxygen/kg/min.

In addition, comparisons among individual oxygen flow rates delivered by either method revealed significant (P ≤ 0.02) differences in Fio2, with the exception of 100 mL/kg/min administered bilaterally versus 150 mL/kg/min administered unilaterally, 150 mL/kg/min administered bilaterally versus 200 mL/kg/min administered unilaterally, and 150 mL/kg/min administered unilaterally versus 200 mL/kg/min administered unilaterally. Also, comparisons among individual oxygen flow rates delivered by either method revealed significant (P ≤ 0.03) differences in Pao2, with the exception of 100 mL/kg/min administered bilaterally versus 150 mL/kg/min administered bilaterally, 100 mL/kg/min administered bilaterally versus 150 mL/kg/min administered unilaterally, 150 mL/kg/min administered bilaterally versus 200 mL/kg/min administered unilaterally, and 150 mL/kg/min administered unilaterally versus 200 mL/kg/min administered unilaterally. With regard to the Pao2:Fio2 ratio, a significant difference between 200 mL of oxygen/kg/min administered bilaterally and 50 mL of oxygen/kg/min administered unilaterally (P = 0.03) and between 50 mL of oxygen/kg/min administered unilaterally and 150 mL of oxygen/kg/min administered unilaterally (P = 0.04) was detected. No significant differences in pHa, Paco2, Petco2, blood bicarbonate concentration, and TCO2 were identified among individual oxygen flow rates.

Linear regression analysis yielded equations for Fio2 and Pao2 associated with unilateral or bilateral oxygen delivery (Table 3). The coefficient of determination was 0.9223 for the regression model of Fio2 and 0.8632 for the regression model of Pao2. In other words, the linear regression model could explain 92.23% and 86.32% of the variation in Fio2 and Pao2, respectively. There was a significant correlation (r = 0.497; P < 0.001) between Paco2 and Petco2.

Table 3—

Linear regression analysis results for FIO2 and PaO2 in 9 healthy neonatal foals that were administered supplemental oxygen at various fow rates via 1 or 2 nasal cannulae (unilateral and bilateral oxygen delivery, respectively).

VariableDelivery methodDerived equationP value
Fio2UnilateralFio2 = 17.33 ± (0.1297 × oxygen flow/cannula)< 0.001
 BilateralFio2 = 17.33 ± (0.2665 × oxygen flow/cannula)< 0.001
Pao2UnilateralPao2o = 91.93 ± (0.8247 × oxygen flow/cannula)< 0.001
 BilateralPao2 = 91.93 ± (1.4513 × oxygen flow/cannula)< 0.001

Discussion

Results of the study reported here indicated that Pao2 and Fio2 increased in a dose-dependent manner as the flow of supplemental oxygen into the nasopharynx of healthy neonatal foals increased. Intuitively, this was an expected response to oxygen administration. Nevertheless, these findings support the rationale for nasopharyngeal administration of supplemental oxygen in hypoxemic foals and provide a dosage guide for oxygen administration as well as expected changes in Pao2 and Fio2 in response to treatment with oxygen in healthy neonatal foals. Also, data obtained in the present study indicated that measured variables did not differ when oxygen was administered at a specific flow rate through 1 or 2 nasal cannulae; this suggests that oxygen administration via 1 nasal cannula can provide adequate changes in Fio2 and Pao2, within certain flow rate limits. If a maximum increase in Fio2 in healthy neonatal foals is desired, nasopharyngeal administration of oxygen at a rate of 200 mL/kg/min simultaneously in each naris (400 mL/kg/min total) can increase the Fio2 to approximately 75%.

Physiologically, nasopharyngeal administration of oxygen increases the Fio2, thereby allowing higher concentrations of oxygen to reach the alveoli; consequently, this creates a higher concentration gradient of oxygen between the alveoli and arterial blood within the pulmonary vasculature. The increase in Fio2 is a result of direct flow of supplemental oxygen into the trachea and the capacity of the nasopharynx to act as a reservoir for inspired air (ie, oxygen).12 During supplemental oxygen administration, the nasopharynx is progressively filled with higher concentrations of oxygen, particularly during the pause in air movement between expiration and inspiration. The fixed volume of air contained within the nasopharynx is gradually filled with supraphysiologic concentrations of oxygen, thereby increasing the Fio2 upon inspiration.12 The pause between expiration and inspiration will vary with the respiratory rate; therefore, higher oxygen flow rates may be necessary to achieve anticipated Fio2 values in animals with higher respiratory rates.18 This is supported by the fact that Fio2 is inversely related to respiratory rate in infants receiving oxygen via intranasal administration.18,19 Other factors that affect the Fio2 in infants and foals include cannula flow rate, the Fio2 in the cannula gas flow, patency of cannula openings, placement of the nasal cannula, patient's body weight, minute ventilation, and the relative duration of inspiration and expiration.1,19

On the basis of the present study's results, it is apparent that there is a rapid change in Fio2 and Pao2 in response to administration of supplemental oxygen in healthy neonatal foals. Increases in Fio2 were observed within 30 to 60 seconds after commencement of oxygen administration, similar to findings in other species.12 In addition, based on the rapid decrease in Fio2 once supplemental oxygen administration was discontinued, clearance of oxygen was rapid—a factor that should be considered when administering supplemental oxygen in a clinical setting. Another point of interest was the irritation or discomfort caused by unilateral or bilateral intranasal administration of oxygen at a flow rate of 200 mL/kg/min in the foals in the present study. However, the authors have administered supplemental oxygen at flow rates > 200 mL/kg/min to ill neonatal foals without observing adverse effects. It is likely that ill neonatal foals are lethargic and less responsive to the irritation caused by high rates of oxygen administration. Nonetheless, if nasal irritation or discomfort develops during unilateral administration of oxygen at a specific flow rate, distribution of the same total flow rate through 2 nasal cannulae may be a viable alternative delivery method. Despite the high flow rates of oxygen, no retardation of exhalation or trapping of carbon dioxide was evident in the foals of the present study. Although there was a significant increase in Paco2 during unilateral administration of oxygen at flow rates of 100 and 200 mL/kg/min and during bilateral administration at a flow rate of 200 mL/kg/min, compared with baseline values, the degree of hypercapnea was considered clinically unimportant in the healthy study foals. Moreover, no significant differences were detected between baseline Petco2 and Petco2 values at the individual oxygen flow rates. However, in infant studies,20,21 the administration of oxygen via nasal cannula generated positive end-expiratory pressure, depending on the size of the nasal cannula (with respect to infant size) and flow rate. Therefore, it is possible that positive end-expiratory pressure can be generated in neonatal foals receiving supplemental oxygen via nasal cannula, particularly in ill foals that have decreased or weakened respiratory effort as a result of exhaustion or weak contraction of respiratory muscles.1 This can potentially result in elevated airway pressure with both positive (increased functional residual capacity, alveolar recruitment, and improvement in ventilation-perfusion matching) and negative (retention of carbon dioxide and hypercapnia) consequences, especially at high oxygen flow rates.1,21

The relationship and correlation between Paco2 and Petco2 has been examined in various studies22–24 in efforts to use Petco2 as a less invasive means of monitoring Paco2 in clinical cases such as emergency room admissions and during anesthesia; overall correlation between these 2 variables has been high in several studies22–24 in people. Likewise, a significant correlation between Paco2 and Petco2 was determined in the healthy neonatal foals used in the present study. However, the actual correlation between Petco2 and Paco2 was only moderate (r = 0.497). This can be partially explained by the fact that administration of supplemental oxygen had a significant effect on Paco2 but not on Petco2. Therefore, oxygen administration accounted for part of the variation in Paco2 that was not correlated with Petco2. Nevertheless, it is possible that Petco2 could be used to reflect and monitor changes in Paco2 in ill foals, although further studies are necessary. It should be noted that the gas sample used for measurement of Petco2 in the present study was aspirated from the intrathoracic portion of the trachea rather than from the nares or nasopharynx, which are more easily accessible locations and are more likely to be used for Petco2 measurement in ill foals. The possibility that the anatomic location at which Petco2 is measured may change Petco2 values slightly requires further investigation.

One important reason to attempt to estimate Fio2 is the ability to use the Pao2:Fio2 ratio to evaluate pulmonary gas exchange in hypoxemic patients and to assess respiratory tract disease severity. Acute lung injury is defined as a Pao2:Fio2 ratio < 300 mm Hg (but > 200 mm Hg), whereas ARDS is defined as a Pao2:Fio2 ratio < 200 mm Hg (along with other previously described criteria).14–16 Specific modifications to the definition of ALI and ARDS have been made to account for the documented changes in gas exchange efficiency that develop in neonatal foals (< 7 days old) as well as in infants.15,25 In the consensus definitions of ALI and ARDS in veterinary medicine, the threshold of equine neonatal ALI is defined as a Pao2:Fio2 ratio of < 250 mm Hg, whereas equine neonatal ARDS is defined as a Pao2:Fio2 ratio of < 160 mm Hg at 4 days after birth.15 The Pao2:Fio2 ratio that was considered normal in that report15 was a value > 400 mm Hg. In the study reported here, the mean Pao2:Fio2 ratio in healthy neonatal foals (mean age, 3.9 days) ranged from 501 to 594 mm Hg and was established in standing foals that were, at times, receiving intranasal administration of supplemental oxygen. The difference in the Pao2:Fio2 ratio between the present and previous studies15,26,27 may be explained, in part, by the fact that the consensus definitions were based on arterial blood gas values from foals that were breathing room air in lateral recumbency, a position that is known to decrease Pao2 values. Overall, only a few veterinary reports13,14 have documented the use of the Pao2:Fio2 ratio in foals, and accordingly, the use of the Pao2:Fio2 ratio in neonatal foals with pulmonary diseases is in its infancy. The information obtained from the study of this report confirmed that the mean Pao2:Fio2 ratio in healthy neonatal foals that are breathing room air should be approximately 500 mm Hg (range, 477 to 594 mm Hg). Furthermore, this information can be used to estimate the Fio2 in hypoxemic neonatal foals, which will facilitate the further investigation of the Pao2:Fio2 ratio in clinical cases. Clearly, additional studies are necessary to assess Pao2:Fio2 ratio values in foals with ALI or ARDS and evaluate the sensitivity and specificity of the extrapolated threshold ratios for diagnosis of ALI and ARDS in neonatal foals.

Another reason to be aware of the Fio2 induced by administration of supplemental oxygen in neonatal foals is to avoid development of oxygen toxicosis as a result of high flow rates of oxygen. On the basis of the findings of the present study, it is unlikely that the recommended maximum Fio2 (60%) during supplemental oxygen administration or mechanical ventilation11,12 would be exceeded, particularly with unilateral administration of the oxygen dosages investigated. However, in severely hypoxemic neonatal foals, bilateral nasal cannulae have been used to administer oxygen in combined flow rates of up to 30 L/min (eg, administration of 250 mL of oxygen/kg/min in each naris in a 60-kg foal).1 The maximum mean Fio2 measured in the present study was approximately 75% when foals received oxygen intranasally at a rate of 200 mL/kg/min bilaterally. Maintenance of a unilateral oxygen flow rate of ≤ 200 mL/kg/min or a bilateral flow rate of ≤ 150 mL/ kg/min should avoid excessively high Fio2 concentrations in neonatal foals, if prolonged intranasal administration of oxygen is necessary. The guidelines set forth by the Society of Critical Care Medicine recommend that the lowest possible Fio2 should be used at all times to achieve treatment goals and should not exceed 50% in patients with respiratory failure.28

Although it is important to be cognizant of the Fio2 to avoid development of oxygen toxicosis and to evaluate the efficacy of pulmonary gas exchange, the clinical endpoints of supplemental oxygen administration are improved Pao2 and Sao2. The value of Pao2 in foals receiving unilateral administration of oxygen intranasally at a flow rate of 200 mL/kg/min in the present study (mean Pao2, 269.7 mm Hg) was similar to the finding in slightly younger foals receiving unilateral administration of oxygen intranasally at a flow rate of 10 L/min in another study3 (mean Pao2, 268.5 mm Hg). At the flow rates used in the present study, the mean maximum Pao2 values that could be achieved via unilateral and bilateral intranasal oxygen administration in healthy neonatal foals are approximately 270 and 375 mm Hg, respectively. However, this information is of limited clinical use in ill neonatal foals with compromised cardiopulmonary function (ie, diffusion impairment, ventilation-perfusion mismatch, or intrapulmonary or intracardiac right-to-left shunting of blood) that results in impaired alveolar gas exchange and hypoxemia.29 For example, in 1 study,30 the mean Pao2 value in response to administration of supplemental oxygen via facemask was significantly decreased in abnormal neonatal foals, compared with the value in similarly treated healthy neonatal foals (mean Pao2, 129.4 and 312.8 mm Hg, respectively). Therefore, adjustment of the flow rate of supplemental oxygen in ill foals with cardiopulmonary disease should be based on evaluation of the response to supplemental oxygen administration (eg, measurement of Pao2 and Sao2). Physiologically, as Pao2 increases, Sao2 concomitantly increases. Not surprisingly, Sao2 increased from baseline (as Pao2 increased) during oxygen administration at all of the flow rates used in the present study. Recommended therapeutic goals of oxygen administration in neonatal foals include maintenance of Pao2 at 80 to 110 mm Hg and Sao2 > 90%.1,28

In the study reported here, other significant differences in measured variables were detected when findings at the individual oxygen flow rates were compared with baseline values or with one another. Compared with the baseline value, there was a significant decrease in pHa during unilateral administration of oxygen at a rate of 200 mL/kg/min, but the difference between the 2 values (0.024) is not likely to have any clinical importance. Furthermore, the exact reason why respiratory rate during unilateral administration of 100 mL of oxygen/kg/min and during bilateral administration of 100 mL of oxygen/kg/min differed significantly is unknown. Although restraint of the foals could have resulted in excitement, no specific explanation could be provided for this observation.

One distinct limitation of the present study that should be highlighted was the varied temperaments of the foals. Most foals tolerated handling and restraint without resentment. However, some foals became very excited upon handling, which increased heart and respiratory rates and potentially altered the variables being measured. In particular, Fio2 appeared to fluctuate the most, depending on the foal's activity and respiratory rate. If a foal was excited, the investigators allowed the foal to regain a quiet demeanor with minimal restraint prior to collection of data. Nonetheless, the few highly anxious foals may have provided skewed results. Another limitation of the study was that the foals were all in good health, and the response to nasopharyngeal administration of supplemental oxygen may be different in ill neonatal foals with pulmonary disease. Evaluation of the response to nasopharyngeal administration of oxygen at different flow rates in ill neonatal foals, including those with pulmonary diseases, is warranted.

Results of the present study have indicated that nasopharyngeal administration of supplemental oxygen effectively increases Fio2, Pao2, and Sao2 and allows clinicians to estimate Fio2 in neonatal foals. Previously recommended oxygen flow rates in foals vary from 2 to 15 L/min, depending on the size, needs, and response of the foal.1,31,32 Information obtained from the present study has provided linear regression equations to estimate the Fio2 (based on body weight) in neonatal foals in response to different oxygen flow rates and to predict the response (ie, Pao2) to a specific oxygen flow rate in healthy neonatal foals and subsequently compare this theoretical response with the response of an ill foal. It should be emphasized that the findings of the present study and the linear regression equations are estimates of Fio2 and Pao2 in response to nasopharyngeal administration of supplemental oxygen in healthy standing neonatal foals and should not be used as absolute therapeutic values or goals. Adequate response to oxygen administration is best evaluated by monitoring arterial blood gas variables such as Pao2 and Sao2 and the clinical response of the patient.

ABBREVIATIONS

ALI

Acute lung injury

ARDS

Acute respiratory distress syndrome

Fio2

Fraction of inspired oxygen concentration

Petco2

End-tidal partial pressure of carbon dioxide

pHa

Arterial blood pH

Sao2

Oxygen saturation of hemoglobin in arterial blood

TCO2

Total carbon dioxide concentration

a.

Xylocaine (2%) jelly, AstraZeneca, Wilmington, Del.

b.

Diazepam, Hospira, Lake Forest, Ill.

c.

Lidocaine 2%, Hospira, Lake Forest, Ill.

d.

Quickflash radial artery catheterization set, Arrow International, Reading, Pa.

e.

Minivolume extension set, Baxter Healthcare Corp, Deerfield, Ill.

f.

Criticare Systems, Waukesha, Wis.

g.

Smiths Medical, Dublin, Ohio.

h.

Duodenal tube, Rusch, Kernen, Germany.

i.

Rapidlab, Bayer Healthcare, Tarrytown, NY.

j.

Aquapak, Hudson Respiratory Care, Research Triangle Park, NC.

k.

Timeter flow meter, Allied Healthcare Products, St Louis, Mo.

l.

Poet IQ, Criticare Systems, Waukesha, Wis.

m.

Mixed procedure, SAS, version 9.1.3, SAS Institute Inc, Cary, NC.

n.

Correlation procedure, SAS, version 9.1.3, SAS Institute Inc, Cary, NC.

References

  • 1.

    Palmer JE. Ventilatory support of the critically ill foal. Vet Clin North Am Equine Pract 2005; 21:458461.

  • 2.

    Hoffman AM, Viel L. A percutaneous transtracheal catheter system for improved oxygenation in foals with respiratory distress. Equine Vet J 1992; 24:239241.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Stewart JH, Rose RJ, Barko AM. Response to oxygen administration in foals: effect of age, duration and method of administration on arterial blood gas values. Equine Vet J 1984; 16:329331.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Rose RJ, Hodgson DR, Leadon D, et al. Effect of intranasal oxygen administration on arterial blood gas and acid base parameters in spontaneously delivered, term induced and induced premature foals. Res Vet Sci 1983; 34:159162.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Sola A, Rogido MR, Deulofeut R. Oxygen as a neonatal health hazard: call for detente in clinical practice. Acta Paediatr 2007; 96:801812.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Mantell LL, Horowitz S, Davis JM, et al. Hyperoxia-induced cell death in the lung—the correlation of apoptosis, necrosis, and inflammation. Ann N Y Acad Sci 1999; 887:171180.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Smith LJ. Hyperoxic lung injury: biochemical, cellular, and morphologic characterization in the mouse. J Lab Clin Med 1985; 106:269278.

    • Search Google Scholar
    • Export Citation
  • 8.

    Barker GF, Manzo ND, Cotich KL, et al. DNA damage induced by hyperoxia: quantitation and correlation with lung injury. Am J Respir Cell Mol Biol 2006; 35:277288.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Varsila E, Pesonen E, Andersson S. Early protein oxidation in the neonatal lung is related to development of chronic lung disease. Acta Paediatr 1995; 84:12961299.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Weinberger B, Laskin DL, Heck DE, et al. Oxygen toxicity in premature infants. Toxicol Appl Pharmacol 2002; 181:6067.

  • 11.

    Hess D, Kacmarek R. Determining appropriate physiologic goals. In: Hess D, Kacmarek R, eds. Essentials of mechanical ventilation. 2nd ed. New York: McGraw-Hill, 2002;105112.

    • Search Google Scholar
    • Export Citation
  • 12.

    Dunphy E, Mann F, Dodam J, et al. Comparison of unilateral versus bilateral nasal catheters for oxygen administration in dogs. J Vet Emerg Crit Care 2002; 12:245251.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Dunkel B, Dolente B, Boston RC. Acute lung injury/acute respiratory distress syndrome in 15 foals. Equine Vet J 2005; 37:435440.

  • 14.

    Dunkel B. Acute lung injury and acute respiratory distress syndrome in foals. Clin Tech Equine Pract 2006; 5:127133.

  • 15.

    Wilkins P, Otto C, Baumgardner J, et al. Acute lung injury and acute respiratory distress syndromes in veterinary medicine: consensus definitions: The Dorothy Russell Havemeyer Working Group on ALI and ARDS in Veterinary Medicine. J Vet Emerg Crit Care 2007; 17:333339.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149:818824.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Wilkins PA, Seahorn T. Acute respiratory distress syndrome. Vet Clin North Am Equine Pract 2004; 20:253273.

  • 18.

    Kuluz JW, McLaughlin GE, Gelman B, et al. The fraction of inspired oxygen in infants receiving oxygen via nasal cannula often exceeds safe levels. Respir Care 2001; 46:897901.

    • Search Google Scholar
    • Export Citation
  • 19.

    Frey B, Shann F. Oxygen administration in infants. Arch Dis Child Fetal Neonatal Ed 2003; 88:F84F88.

  • 20.

    Locke RG, Wolfson MR, Shaffer TH, et al. Inadvertent administration of positive end-distending pressure during nasal cannula flow. Pediatrics 1993; 91:135138.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Frey B, McQuillan PJ, Shann F, et al. Nasopharyngeal oxygen therapy produces positive end-expiratory pressure in infants. Eur J Pediatr 2001; 160:556560.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Barton CW, Wang ES. Correlation of end-tidal CO2 measurements to arterial Paco2 in nonintubated patients. Ann Emerg Med 1994; 23:560563.

  • 23.

    Cheng KI, Tang CS, Tsai EM, et al. Correlation of arterial and end-tidal carbon dioxide in spontaneously breathing patients during ambulatory gynecologic laparoscopy. J Formos Med Assoc 1999; 98:814819.

    • Search Google Scholar
    • Export Citation
  • 24.

    McNulty SE, Roy J, Torjman M, et al. Relationship between arterial carbon dioxide and end-tidal carbon dioxide when a nasal sampling port is used. J Clin Monit 1990; 6:9398.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Rodriguez Martinez CE, Guzman MC, Castillo JM, et al. Evaluation of clinical criteria for the acute respiratory distress syndrome in pediatric patients. Pediatr Crit Care Med 2006; 7:335339.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Madigan JE, Thomas WP, Backus KQ, et al. Mixed venous blood gases in recumbent and upright positions in foals from birth to 14 days of age. Equine Vet J 1992; 24:399401.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Stewart JH, Rose RJ, Barko AM. Respiratory studies in foals from birth to seven days of age. Equine Vet J 1984; 16:323328.

  • 28.

    Task Force on Guidelines; Society of Critical Care Medicine. Guidelines for standards of care for patients with acute respiratory failure on mechanical ventilatory support. Crit Care Med 1991; 19:275278.

    • Search Google Scholar
    • Export Citation
  • 29.

    Wilkins PA. Lower respiratory problems of the neonate. Vet Clin North Am Equine Pract 2003; 19:1933.

  • 30.

    Rossdale PD. Some parameters of respiratory function in normal and abnormal newborn foals with special reference to levels of Pao2 during air and oxygen inhalation. Res Vet Sci 1970; 11:270276.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Dallap B, Orsini J. Respiratory system. In: Orsini J, Divers T, eds. Equine emergencies. 3rd ed. St Louis: Saunders, 2008;435472.

  • 32.

    Magdesian K, Wilkins P. Neonatology. In: Orsini J, Divers T, eds. Equine emergencies. 3rd ed. St Louis: Saunders, 2008;486521.

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