Horses placed in dorsal recumbency during general anesthesia often develop a large Pao2 - Pao2 that can lead to hypoxemia, despite ventilation with oxygen-rich gas.1,2 This scenario is caused by ventilation-perfusion mismatching and atelectasis formation in dependent lung areas that result in right-to-left shunting of blood.3,4 Pulmonary atelectasis occurs to a greater or lesser extent in nearly all subjects. Similar to the situation in humans,5 horses may develop marked alveolar collapse during anesthesia.4,6 Compression and absorption atelectases are the main pathogenic mechanisms underlying lung collapse.7
As the Fio2 increases, the nitrogen component of air is reduced, which abolishes the alveolar scaffold that helps alveoli remain open. As a result, the alveoli become more prone to collapse in atelectatic areas, which results in increased ventilation-perfusion mismatching.8,9 The density of helium is one-seventh that of air. Thus, when helium is added to inspired gas, it reduces turbulent flow and resistance in the airways and improves ventilation and gas exchange.10 Because helium is less dense than air and oxygen, it will move through narrow bronchioles more easily than other gases. Thus, use of a fresh gas mixture of helium and oxygen might offer 3 important advantages: inspired gas will more readily reach the alveoli, which will allow easier diffusion; breathing effort will be substantially reduced because of a lower resistance to airway flow; and carbon dioxide will be eliminated more rapidly.11 Studies12,13 indicate that human patients with obstruction of the bronchi and bronchioli benefit from use of a helium-oxygen mixture during mechanical ventilation. In those studies,12,13 use of a helium-oxygen mixture was associated with a significantly lower mean PIP and better Cdyn. Furthermore, in addition to enhancing carbon dioxide elimination, helium-oxygen mixtures may also improve oxygenation, compared with effects of an oxygen-nitrogen mixture.14
Reopening (recruiting) nonventilated lung areas with an ARM and subsequent application of sufficient PEEP to preserve ventilation of reopened alveoli (ie, open lung strategy) are used to minimize pulmonary complications15,16 while improving pulmonary gas exchange and thus arterial oxygenation. A high inspiratory pressure is often necessary to open nonaerated alveoli.4 Two approaches for achieving alveolar recruitment have been proposed. One entails use of higher pressures with sustained inflation of the lungs at a prescribed PIP for 5 to 30 seconds.17–19 The other approach involves stepwise increases in the PEEP and the PIP while maintaining a constant pressure difference and therefore constant tidal volume.20,21
The objective of the study reported here was to examine the efficacy of an ARM with incremental and decremental changes in PEEP in anesthetized horses ventilated with a helium-oxygen mixture or oxygen. We hypothesized that improvements in lung mechanics (evident as an increase in Cdyn with a reduction in PIP) would be greater with an ARM performed when horses were ventilated with the helium-oxygen mixture than when ventilated with oxygen.
Materials and Methods
Animals
Six healthy (as determined on the basis of results of preanesthetic physical examination) horses (3 Standardbreds and 3 Thoroughbreds; 3 mares and 3 geldings) owned by the Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine were included in the study. Mean ± SD body weight was 585 ± 51 kg, and mean age was 5 ± 1 years. An a priori power analysis (type II error, 0.2; type I error, 0.05; and SD, 15%) indicated that 6 animals would be necessary to detect clinically relevant changes in Pao2 and Cdyn. Horses were moved into stalls 12 to 24 hours before each anesthetic episode, and hay and water were provided. Hay, but not water, was withheld for 8 hours before each experiment. The study was approved by the Institutional Animal Care and Use Committee of the University of Pennsylvania (No. 806212-aadaghi).
Study design
A prospective crossover study was conducted. Horses were assigned by use of a computer-generated randomization list to receive a ventilation gas of helium-oxygen or pure oxygen. After a minimum washout period of 2 weeks, the experiment was repeated, and horses received the other ventilation gas.
Anesthesia
Lidocaine was infiltrated into the subcutaneous tissues over the left jugular vein, and a 14-gauge catheter was placed aseptically into the vein. Xylazine hydrochloridea (0.8 mg/kg, IV) was administered as the premedication, and anesthesia was induced by IV administration of midazolamb (0.05 mg/kg) and ketamine hydrochloridec (2.2 mg/kg). After anesthesia was induced, all horses were intubated with a cuffed Murphy tube (internal diameter, 24 mm) and then positioned in dorsal recumbency on a thick foam mattress. Anesthesia was maintained with isofluraned administered in heliox (70% helium and 30% oxygen) or pure oxygen. The end-tidal isoflurane concentration was targeted at 1.3%. A crystalloid solutione was administered IV at a rate of 5 mL/kg/h; dobutaminef was administered IV at a rate of 0.75 μg/kg/min (adjusted as necessary) to maintain MAP > 60 mm Hg during anesthesia. A 20-gauge catheter was inserted in a transverse facial artery and used to monitor blood pressure and for collection of arterial blood samples. The catheter was connected to a calibrated pressure transducerg via a fluid-filled (heparinized saline [0.9% NaCl] solution) rigid extension line and calibrated to zero atmospheric pressure at the level of the shoulder joint.
At the end of anesthesia, horses were administered a sedative dose of xylazine (0.2 mg/kg, IV) and allowed to recover without assistance. The orotracheal tube was removed, and horses were nasotracheally intubated to allow nasal insufflation of oxygen (15 L/min) during the recovery period.
Ventilation strategy
An anesthesia workstationh operating with an electronically driven piston ventilator was used; the volume delivered was determined by the diameter of the piston and the distance it traveled. Before each experiment, the y-piece of the rebreathing circuit was occluded, and the workstation performed a computer-controlled assessment (leak and self-evaluation program). This involved evaluation of system compliance measurements necessary to ensure proper compensation for any compressed gas volume within the breathing circuit during positive-pressure ventilation and, hence, constant delivery of the tidal volume selected by the operator.
After intubation was performed, the endotracheal tube was connected to the ventilator, and the horses were immediately ventilated with a volume-controlled ventilation mode and inspiratory-to-expiratory ratio of 1:2. Tidal volume was set to 14 mL/kg throughout each experiment, whereas respiratory rate was adjusted to maintain Petco2 at 35 to 40 mm Hg. Airway pressures and Cdyn were measured by use of a pitot-based flowmeter.22,i The flowmeter was calibrated with a 3-L calibration syringej by use of room air and subsequently by use of oxygen and heliox to confirm that there was not a significant difference in determined calibration factors. Results for 15 test runs for each ventilation gas yielded mean calculated calibration factors of 5.98 ± 0.11, 5.95 ± 0.13, and 6.05 ± 0.16 for room air, oxygen, and heliox, respectively.
Baseline measurements (PEEP, 0 cm H2O) were obtained 60 minutes after the start of mechanical ventilation. Subsequently, a PEEP-based ARM (steps of 5 cm H2O every 5 minutes up to a maximum PEEP of 30 cm H2O, followed by incremental decreases of PEEP back to 0 cm H2O) was performed while maintaining a constant tidal volume. Four minutes after increasing (or decreasing) each PEEP, MAP, heart rate, respiratory rate, Petco2, Fio2, PIP, plateau airway pressure, and Cdyn were recorded. An arterial blood sample (2 mL) was obtained anaerobically and immediately analyzed with a blood gas analyzerk to measure Pao2 and Paco2 without temperature correction. The inspiratory oxygen concentration was measured continuously by use of a paramagnetic analyzer that was calibrated on a regularly scheduled basis. The Pao2 was calculated as follows:
where Patm is the atmospheric pressure (which was measured the morning of each experiment), Ph2o is the partial pressure of water, and R is the respiratory exchange ratio (which has a value of 0.8). The Pao2 - Pao2 was calculated by use of the alveolar gas equation, and the Pao2-to-Fio2 ratio and Pao2-to-Pao2 ratio were also calculated. Alveolar dead space was calculated as (Paco2 - Petco2)/Paco2
Statistical analysis
Data analysis was performed with statistical software.l,m Visual assessment of QQ plots and the Shapiro-Wilk test were used to confirm normal distribution of model residuals of dependent variables. All data were reported as mean ± SD. Variables were compared with baseline values (PEEP, 0 cm H2O) and between ventilation gases. Statistical analysis was conducted as a 2-factorial repeated-measure ANOVA with Bonferroni correction for multiple comparisons and mixed-effects linear regression analysis. Significance was set at values of P < 0.05.
Results
An increase in PEEP resulted in a significant and linear decrease in MAP, whereas heart rate remained stable with no significant differences between ventilation gases (Table 1). There was no significant difference between ventilation gases with regard to respiratory rate (5 to 7 breaths/min for heliox and 6 to 7 breaths/min for oxygen). Both PIP and plateau airway pressure increased and decreased linearly with increasing and decreasing PEEP, respectively, for both ventilation gases. However, PIP was consistently lower for heliox than for oxygen, with significant differences between the gases at high PEEP (≥ 15 cm H2O). Throughout the entire ARM, Cdyn was significantly higher for heliox than for oxygen.
Mean ± SD values for cardiovascular function and respiratory mechanics of 6 anesthetized horses ventilated with heliox (70% helium and 30% oxygen) or pure oxygen during an ARM involving incremental and decremental PEEP.
| MAP (mm Hg) | Heart rate (beats/min) | PIP (cm H2O) | Plateau airway pressure (cm H2O) | Cdyn (mL/cm H2O) | Alveolar dead space (%) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PEEP (cm H2O) | Heliox | Oxygen | Heliox | Oxygen | Heliox | Oxygen | Heliox | Oxygen | Heliox | Oxygen | Heliox | Oxygen |
| 0 | 106 ± 17 | 104 ± 13 | 44 ± 2 | 40 ± 4 | 22 ± 2 | 26 ± 4 | 20 ± 2 | 23 ± 3 | 336 ± 50 | 239 ± 38* | 12.4 ± 8 | 12.1 ± 6 |
| 5 | 95 ± 27 | 102 ± 14 | 46 ± 10 | 40 ± 3 | 27 ± 3 | 31 ± 4 | 26 ± 3 | 27 ± 3 | 369 ± 71 | 243 ± 30* | 11.8 ± 9 | 12.6 ± 5 |
| 10 | 102 ± 14 | 101 ± 10 | 46 ± 9 | 40 ± 3 | 32 ± 2 | 36 ± 4 | 29 ± 2 | 32 ± 2 | 361 ± 42 | 247 ± 35* | 16.9 ± 5 | 11.0 ± 5 |
| 15 | 95 ± 13 | 95 ± 15 | 45 ± 8 | 42 ± 9 | 36 ± 2† | 40 ± 2† | 35 ± 2† | 37 ± 3† | 378 ± 33 | 260 ± 32* | 16.3 ± 6 | 11.7 ± 6 |
| 20 | 85 ± 13 | 90 ± 17 | 43 ± 5 | 41 ± 9 | 42 ± 2† | 45 ± 2† | 40 ± 3† | 42 ± 2† | 380 ± 38 | 264 ± 21* | 17.4 ± 6† | 15.9 ± 4† |
| 25 | 80 ± 11† | 75 ± 14† | 41 ± 4 | 39 ± 5 | 46 ± 1† | 49 ± 1*† | 45 ± 2† | 47 ± 2*† | 382 ± 29 | 273 ± 36* | 20.1 ± 4† | 18.0 ± 7† |
| 30 | 71 ± 6† | 74 ± 9† | 42 ± 7 | 39 ± 3 | 52 ± 2† | 56 ± 2*† | 50 ± 2† | 52 ± 1*† | 378 ± 43 | 265 ± 40* | 21.1 ± 5† | 19.1 ± 6† |
| 25 | 82 ± 14† | 83 ± 14† | 39 ± 8 | 39 ± 6 | 41 ± 2† | 46 ± 2*† | 39 ± 1† | 43 ± 2*† | 449 ± 44† | 319 ± 42*† | 18.6 ± 4† | 17.9 ± 7† |
| 20 | 88 ± 18† | 89 ± 17† | 37 ± 7 | 37 ± 5 | 34 ± 1† | 38 ± 3† | 32 ± 2† | 37 ± 3*† | 499 ± 37† | 361 ± 44*† | 17.8 ± 4† | 17.3 ± 7† |
| 15 | 97 ± 23 | 95 ± 23 | 35 ± 5 | 35 ± 3 | 30 ± 2† | 34 ± 2*† | 28 ± 2† | 31 ± 2*† | 500 ± 37† | 382 ± 47*† | 15.0 ± 5 | 14.4 ± 8 |
| 10 | 115 ± 19 | 102 ± 19 | 36 ± 6 | 35 ± 4 | 25 ± 2 | 30 ± 4* | 22 ± 2 | 27 ± 3*† | 506 ± 35† | 357 ± 50*† | 15.4 ± 5 | 14.7 ± 4 |
| 5 | 114 ± 16 | 106 ± 15 | 37 ± 8 | 36 ± 4 | 23 ± 1 | 25 ± 3 | 21 ± 3 | 22 ± 3 | 432 ± 46† | 319 ± 48*† | 15.6 ± 7 | 14.9 ± 7 |
| 0 | 105 ± 21 | 100 ± 19 | 37 ± 6 | 36 ± 4 | 20 ± 2 | 23 ± 4 | 19 ± 2 | 20 ± 3 | 378 ± 51 | 281 ± 45* | 13.8 ± 9 | 17.6 ± 4 |
Sixty minutes after the start of mechanical ventilation, an ARM with PEEP (0 to 30 cm H2O in steps of 5 cm H2O every 5 minutes, followed by incremental steps back to 0 cm H2O) was performed.
Within a variable, value differs significantly (P < 0.05) from the value for heliox.
Within a column, value differs significantly (P < 0.05) from the baseline value (PEEP = 0 cm H2O).
For both ventilation gases, the ARM resulted in a significant increase in Pao2 and thus in the Pao2-to-Pao2 ratio and Pao2-to-Fio2 ratio, whereas the Pao2 - Pao2 decreased significantly. However, in accordance with an Fio2 that was consistently much lower for heliox, Pao2 - Pao2 values were always significantly lower for heliox than for oxygen (Table 2). During decremental PEEP, significantly higher Pao2-to-Pao2 and Pao2-to-Fio2 ratios were maintained for heliox, compared with ratios for oxygen, when PEEPs of 10 and 5 cm H2O were reached.
Mean ± SD values of blood gas variables for 6 anesthetized horses ventilated with heliox (70% helium and 30% oxygen) or pure oxygen during an ARM involving incremental and decremental PEEP.
| Fio2 (%) | Pao2 (mm Hg) | Pao2-to-Fio2 ratio | Pao2 - Pao2 (mm Hg) | Pao2-to-Pao2 ratio | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| PEEP (cm H2O) | Heliox | Oxygen | Heliox | Oxygen | Heliox | Oxygen | Heliox | Oxygen | Heliox | Oxygen |
| 0 | 30 ± 1 | 94 ± 2* | 82 ± 9 | 220 ± 90* | 274 ± 31 | 232 ± 95 | 88 ± 9 | 407 ± 90* | 0.48 ± 0.1 | 0.35 ± 0.1 |
| 5 | 30 ± 1 | 94 ± 2* | 80 ± 10 | 212 ± 87* | 267 ± 33 | 223 ± 92 | 90 ± 10 | 415 ± 87* | 0.47 ± 0.1 | 0.34 ± 0.1 |
| 10 | 31 ± 1 | 94 ± 2* | 77 ± 11 | 220 ± 91* | 257 ± 35 | 231 ± 96 | 93 ± 11 | 407 ± 91* | 0.45 ± 0.1 | 0.35 ± 0.1 |
| 15 | 32 ± 2 | 94 ± 2* | 80 ± 8 | 197 ± 79* | 267 ± 27 | 208 ± 83 | 90 ± 8 | 430 ± 79* | 0.47 ± 0.1 | 0.32 ± 0.1 |
| 20 | 30 ± 1 | 94 ± 2* | 82 ± 7 | 241 ± 99* | 272 ± 23 | 254 ± 104 | 88 ± 7 | 386 ± 99* | 0.48 ± 0.2 | 0.38 ± 0.1 |
| 25 | 32 ± 1 | 95 ± 2* | 85 ± 12 | 272 ± 119* | 283 ± 40 | 286 ± 125 | 85 ± 12 | 355 ± 119* | 0.50 ± 0.2 | 0.43 ± 0.1 |
| 30 | 30 ± 1 | 96 ± 2* | 95 ± 17† | 330 ± 131*† | 316 ± 57† | 347 ± 138 | 75 ± 17 | 297 ± 131* | 0.56 ± 0.2 | 0.53 ± 0.1 |
| 25 | 30 ± 1 | 96 ± 2* | 122 ± 15† | 420 ± 109*† | 406 ± 49† | 442 ± 114† | 48 ± 15† | 207 ± 109*† | 0.72 ± 0.2† | 0.67 ± 0.1*† |
| 20 | 30 ± 1 | 96 ± 3* | 129 ± 8† | 443 ± 55*† | 429 ± 25† | 466 ± 58† | 41 ± 8† | 184 ± 55*† | 0.76 ± 0.1† | 0.71 ± 0.1*† |
| 15 | 30 ± 1 | 96 ± 2* | 133 ± 10† | 434 ± 63*† | 442 ± 33† | 457 ± 66† | 37 ± 10† | 193 ± 63*† | 0.78 ± 0.1† | 0.69 ± 0.1*† |
| 10 | 30 ± 1 | 96 ± 3* | 132 ± 11† | 361 ± 136*† | 439 ± 36† | 380 ± 92*† | 38 ± 11† | 266 ± 88*† | 0.77 ± 0.1† | 0.58 ± 0.1*† |
| 5 | 31 ± 1 | 96 ± 2* | 109 ± 15† | 307 ± 116* | 363 ± 50† | 324 ± 61* | 61 ± 15† | 320 ± 58*† | 0.64 ± 0.1† | 0.49 ± 0.1*† |
| 0 | 31 ± 1 | 96 ± 3* | 86 ± 8 | 242 ± 90* | 286 ± 27 | 254 ± 94 | 84 ± 8 | 385 ± 90 | 0.50 ± 0.1 | 0.39 ± 0.1 |
See Table 1 for key.
Discussion
The objective of the study reported here was to examine the efficacy of an ARM in horses ventilated with heliox and oxygen. Results indicated that performing an ARM with increasing and decreasing PEEP increments in dorsally recumbent anesthetized horses improved compliance and oxygenation and that when horses breathed heliox, they had better respiratory mechanical function associated with higher compliance and lower airway pressures.
The Pao2-to-Fio2 ratio is one of the clinical variables most commonly used to assess the quality of pulmonary oxygen exchange.23 It also is used to evaluate the efficacy of alveolar recruitment, with a ratio of > 300 considered to indicate success.24 Similarly, an increase in Pao2 to at least 400 mm Hg when using pure oxygen as the ventilation gas has been considered a target for successful recruitment in dorsally recumbent horses undergoing an ARM.25 Because the ARM resulted in a significant increase in both Pao2 and the Pao2-to-Fio2 ratio in all horses, it can be concluded that the ARM was successful. Disadvantages for the use of the Pao2-to-Fio2 ratio are that it is noncontinuous and that multiple blood gas analyses are necessary.
The Cdyn is a variable that is useful for determining the optimum PEEP, and it can be measured noninvasively and continuously. The PEEP that induces the highest compliance is usually considered the ideal PEEP26 and is accompanied by the highest Pao2.21 In the present study, PEEP between 10 and 15 cm H2O was associated with the highest Cdyn and therefore should have been ideal for these horses. This finding was consistent with results of other studies20,21,25 conducted to examine alveolar recruitment and PEEP in anesthetized horses. However, investigators for another study27 of anesthetized horses conducted by use of the electric impedance tomography technique found that changes in compliance mainly reflect changes in the dependent portions of the lungs but not the nondependent portions of the lungs, whereas the Pao2 reflects changes in dependent and nondependent portions of the lungs and is therefore the more accurate variable. The Cdyn of horses when ventilated with heliox reached a plateau that was higher than that for the horses when ventilated with oxygen, and it also was reached earlier (ie, at a lower PEEP) during the ARM and then maintained for a longer period, which indicated that the presence of helium in the respiratory system helped small airways and alveoli to open more easily and to remain open. Functionally, these respiratory mechanical changes translated into better pulmonary gas exchange as the significantly higher Pao2-to-Fio2 and Pao2-to-Pao2 ratios for heliox during decremental PEEP (< 15 cm H2O) clearly indicated. This difference between the 2 ventilation gases could have been ascribed to the property of helium as an inert gas that allowed the terminal bronchioli and alveoli to open more easily at lower PEEPs. Further studies to compare lower Fio2 values will be necessary to evaluate the influence of helium in more detail.
Administration of helium-oxygen mixtures to mechanically ventilated horses preserves gas exchange better than does administration of pure oxygen.28,29 The reason is that the rate of absorption of gas, especially from nonventilated areas of the lungs, increases with increases in Fio2.8 If the oxygen concentration in the lungs is progressively increased, the rate of absorbed gas will at some point exceed the rate of gas inflow and a progressive collapse of the alveoli can occur.9 In the horses of the present study, ventilation with heliox caused a significantly lower Pao2 - Pao2 and Pao2-to-Pao2 ratio throughout anesthesia, compared with results when horses were breathing oxygen. Therefore, it can be assumed that use of an inert gas such as helium can help to reduce the extent of gas absorption and hence collapse of small airways and alveoli, particularly in dependent areas of the lungs and from the beginning to the end of anesthesia. Heliox administration during mechanical ventilation and at the same tidal volume resulted in a significantly higher Cdyn, which in turn resulted in lower airway pressure, compared with results for oxygen administration. Because of the physical and, thus, flow properties of helium, a gas mixture with a high helium concentration will induce a low resistance to flow and therefore allow the airway pressure to be lower and gas to flow more constantly, compared with results for gas mixtures that yield a high Fio2, even at a high gas velocity as occurs during positive-pressure ventilation.10 In human patients with airway obstruction, mechanical ventilation with helium gas mixtures results in a lower PIP.12,13 In a study29 of anesthetized horses in lateral recumbency, it was not possible to detect differences in PIP when ventilating with helium-oxygen mixtures or with pure oxygen. The authors of that study29 ventilated the horses with a PIP between 25 and 30 cm H2O and without PEEP. In the horses of the present study, differences were most relevant when reaching high airway pressures during the ARM but not during baseline ventilation with lower PIPs. Therefore, we concluded that the advantages of helium as a low-density inert gas are more important for situations that involve the high gas velocities and airway pressures necessary during PEEP-driven alveolar recruitment.
If the ARM was solely considered to be a lung-opening procedure for the study reported here, then presence of helium in the inspired gas did not make a difference in alveolar recruitment, compared with effects of oxygen. This was not surprising because it is the PIP during the inspiratory phase of mechanical ventilation that is the driving force for opening closed small airways and collapsed alveoli, whereas PEEP prevents reopened lung tissue from recollapsing.15 Because volume-controlled ventilation was used in the horses of the present study, airway pressure was dependent on lung compliance. The greater compliance in horses when receiving heliox resulted in a lower PIP. A significant increase in Pao2 was observed at a high PIP of > 50 cm H2O, which occurred only at a PEEP of 30 cm H2O. A pressure range of 40 to 80 cm H2O has been considered necessary for opening collapsed lung areas in dorsally recumbent horses.20,21,25,27,30 In the present study, the steps for PEEP and PIP were probably too large to identify the threshold opening pressure. Increasing PEEP in smaller intervals might have helped identify differences between ventilation gases.
Increasing the PEEP and consequently the inspiratory airway pressure resulted in a progressive decrease in arterial blood pressure in all horses. A negative impact of PEEP on hemodynamic function has been described21,31 and is mainly caused by marked impairment of venous return as a result of elevated intrathoracic pressures, which leads to reduced cardiac output. A decline in cardiac output and tissue perfusion pressures during high positive-pressure ventilation will also negatively affect peripheral tissue blood supply21 and could explain the increase in alveolar dead space in horses of the present study. Although the airway pressures were lower in horses when breathing heliox, we did not detect differences in hemodynamic function between ventilation gases. During the ARM, use of PEEP was the same for all horses and thus accounted for most of the negative impact on systemic cardiovascular function for both ventilation gases.
A limitation of the study was the lack of another ventilation gas mixture with a low Fio2 (eg, oxygen plus nitrogen). Inclusion of such a gas in future studies will help identify key properties of helium that are responsible for the greater efficacy of the ARM observed for heliox-ventilated horses in this study (ie, whether inertia or the more favorable gas flow characteristics were key factors). Given that the primary purpose of the study reported here was to investigate the efficacy of an ARM performed when horses were ventilated with heliox versus pure oxygen, PEEP was not maintained for additional time beyond the end of the successful alveoli recruitment. Thus, we cannot comment on whether alveolar collapse would have recurred to a lesser degree with a lower PEEP for heliox, compared with oxygen. Further studies are needed to address the long-term benefits of an ARM in animals ventilated with heliox versus oxygen.
Two technical limitations of the study must be mentioned. First, the pitot tube used for compliance measurements was calibrated with a 3-L calibration syringe and room air. Density and viscosity of delivered gases affect measurement accuracy of various types of flowmeters,32 but specific data for heliox or other helium-oxygen mixtures were not available. Furthermore, use of low-density gases such as xenon may cause overestimation of gas volumes by approximately 2.5% to 4.0%.32,33 In the present study, this could have led to an overestimation of the measured tidal volume, and therefore the compliance, for heliox-ventilated horses. A post hoc approach was used to compare calibration of the syringe and room air with the calibration factor determined for pure oxygen and heliox, and no significant difference was found among these measurements. This finding is consistent with results of a study34 conducted to compare calibrations of human intensive care unit ventilators with various gas mixtures, including helium-oxygen. Second, the tidal volume delivered by the piston-driven ventilator was not measured per se. However, evaluation of mechanical ventilators used in human anesthesia has revealed that owing to their technical design, piston-driven ventilators are the most accurate because they consistently deliver the volume over a wide range of volumes and gas flows and under various airway and lung compliance or resistance conditions. Results of 1 study35 indicate that piston-driven ventilators operate with the highest precision and deliver tidal breaths with a volume error consistently less than the threshold of 5% allowed by the manufacturers and completely independent of fresh gas flow rates. Considering that all horses in the present study were ventilated with the same tidal volume and that significant differences in peak and plateau airway pressures were detected, it was likely that the differences in compliance between the ventilation gases were attributable to differences in respiratory mechanics and not to measurement errors.
An ARM performed in isoflurane-anesthetized horses ventilated with heliox instead of oxygen was significantly more efficient at improving pulmonary oxygen exchange and respiratory mechanics. The advantages for the use of helium gas mixtures, compared with other inert gases such as nitrogen, to facilitate better oxygen exchange remain unclear. Future studies with other gas mixtures are needed to elucidate whether use of heliox results in better oxygenation variables than can be achieved with other oxygen-enriched mixtures of inert gases (eg, oxygen-nitrogen mixtures).
Acknowledgments
Supported by intramural funds from the Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pa.
The authors declare that there were no conflicts of interest.
Presented in abstract form at the Association of Veterinary Anaesthetists' Fall Meeting, Berlin, November 2017.
The authors thank Dr. Hannah Chapman, Sara Hyman, and Dr. Kelly Varner for technical assistance during the study; Hilary Randall Goff and Dr. Mary Robinson for care of the horses between experiments; and Dr. Darko Stefanovski for assistance with the statistical analysis.
ABBREVIATIONS
| ARM | Alveolar recruitment maneuver |
| Cdyn | Dynamic lung compliance |
| Fio2 | Fraction of inspired oxygen |
| MAP | Mean arterial blood pressure |
| Pao2 - Pao2 | Alveolar-arterial difference in partial pressure of oxygen |
| PEEP | Positive end-expiratory pressure |
| Petco2 | End-tidal partial pressure of carbon dioxide |
| PIP | Peak inspiratory pressure |
Footnotes
X-ject, Henry Schein Inc, Dublin, Ohio.
Akorn Medical, Vernon Hills, Ill.
Ketathesia, Henry Schein Inc, Dublin, Ohio.
Isothesia, Henry Schein Inc, Dublin, Ohio.
Normosol, Abbott Laboratories, Abbott Park, Ill.
Hospira Inc, Lake Forest, Ill.
PressureTrans, Henry Schein Inc, Dublin, Ohio.
Tafonius, Hallowell EMC, Pittsfield, Mass.
H-Lite, Morpheus Engineering, Wenum Wiesel, Netherlands.
Ohio Cal-check 3-L calibration syringe, Ohio Medical Products, Gurnee, Ill.
Opti CCA-TS2 blood gas analyzer, Opti Medical Systems Inc, Roswell, Ga.
SAS, version 9.3, SAS Institute Inc, Cary, NC.
GraphPad Prism, version 7, GraphPad Software Inc, San Diego, Calif.
References
1. Hall LW, Gillespie JR. Alveolar-arterial oxygen tension differences in anaesthetized horses. Br J Anaesth 1968;40:560–568.
2. Auckburally A, Nyman G. Review of hypoxaemia in anaesthetized horses: predisposing factors, consequences and management. Vet Anaesth Analg 2017;44:397–408.
3. Nyman G, Hedenstierna G. Comparison of conventional and selective mechanical ventilation in the anaesthetized horse. Effects on central circulation and pulmonary gas exchange. Zentralbl Veterinarmed A 1988;35:299–314.
4. Nyman G, Funkquist B, Kvart C, et al. Atelectasis causes gas exchange impairment in the anesthetized horse. Equine Vet J 1990;22:317–324.
5. Brismar B, Hedenstierna G, Lundquist H, et al. Pulmonary densities during anesthesia with muscular relaxation—a proposal of atelectasis. Anesthesiology 1985;62:422–428.
6. Hedenstierna G, Lundquist H, Lundh B, et al. Pulmonary densities during anaesthesia. An experimental study on lung morphology and gas exchange. Eur Respir J 1989;2:528–535.
7. Duggan M, Kavanag BP. Pulmonary atelectasis: a pathogenic perioperative entity. Anesthesiology 2005;102:838–854.
8. Dale WA, Rahn H. Rate of gas absorption during atelectasis. Am J Physiol 1952;170:606–613.
9. Dantzker DR, Wagner PD, West JB. Instability of lung units with low Va/Q ratios during O2 breathing. J Appl Physiol 1975;38:886–895.
10. Papamoschou D. Theoretical validation of the respiratory benefits of helium-oxygen mixtures. Respir Physiol 1995;99:183–190.
11. Hurford WE, Cheifetz IM. Should Heliox be used for mechanically ventilated patients? Respir Care 2007;52:582–591.
12. Gross MF, Spear RN, Peterson BM. Helium-oxygen mixture does not improve gas exchange in mechanically ventilated children with bronchiolitis. Crit Care 2000;4:188–192.
13. Abd-Allah SA, Rogers MS, Terry M, et al. Helium-oxygen therapy for pediatric acute severe asthma requiring mechanical ventilation. Pediatr Crit Care Med 2003;4:353–357.
14. Katz A, Gentile MA, Craig DM, et al. Heliox improves gas exchange during high frequency ventilation in a pediatric model of acute lung injury. Am J Respir Crit Care Med 2001;164:260–264.
15. Lachmann B. Open up the lung and keep the lung open. Intensive Care Med 1992;18:319–321.
16. Barbas CS, de Matos GF, Pincelli MP, et al. Mechanical ventilation in acute respiratory failure: recruitment and high positive end-expiratory pressure are necessary. Curr Opin Crit Care 2005;11:18–28.
17. Rothen HU, Neumann P, Berglund JE, et al. Dynamics of re-expansion of atelectasis during general anaesthesia. Br J Anaesth 1999;82:551–556.
18. Celebi S, Koner O, Menda F, et al. The pulmonary and hemodynamic effects of two different recruitment maneuvers after cardiac surgery. Anesth Analg 2007;104:384–390.
19. Cakmakkaya OS, Kaya G, Altintas F, et al. Restoration of pulmonary compliance after laparoscopic surgery using a simple alveolar recruitment maneuver. J Clin Anesth 2009;21:422–426.
20. Wettstein D, Moens Y, Jaeggin-Schmucker F, et al. Effects of an alveolar recruitment maneuver on cardiovascular and respiratory parameters during total intravenous anesthesia in ponies. Am J Vet Res 2006;67:152–159.
21. Hopster K, Wogatzki A, Geburek F, et al. Effects of positive end-expiratory pressure titration on intestinal oxygenation and perfusion in isoflurane anesthetized horses. Equine Vet J 2017;49:250–256.
22. Moens YP, Gootjes P, Ionita JC, et al. In vitro validation of a Pitot-based flow meter for the measurement of respiratory volume and flow in large animal anaesthesia. Vet Anaesth Analg 2009;36:209–219.
23. Araos JD, Larenza MP, Boston RC, et al. Use of the oxygen content-based index, Fshunt, as an indicator of pulmonary venous admixture at various inspired oxygen fractions in anesthetized sheep. Am J Vet Res 2012;73:2013–2020.
24. Pintado MC, de Pablo R, Trascasa M, et al. Individualized PEEP setting in subjects with ARDS. Respir Care 2013;58:1416–1423.
25. Hopster K, Kästner SB, Rohn K, et al. Intermittent positive pressure ventilation with constant positive end-expiratory pressure and alveolar recruitment maneuver during inhalation anesthesia in horses undergoing surgery for colic, and its influence on the early recovery period. Vet Anaesth Analg 2011;38:169–177.
26. Suter PM, Fairley B, Isenberg MD. Optimum end-expiratory airway pressure in patients with acute pulmonary failure. N Engl J Med 1975;292:284–289.
27. Ambrisko TD, Schramel J, Hopster K, et al. Assessment of distribution of ventilation and regional lung compliance by electrical impedance tomography in anaesthetized horses undergoing alveolar recruitment manoeuvres. Vet Anaesth Analg 2017;44:264–272.
28. Driessen B, Nann L, Klein L. Use of a helium/oxygen carrier gas mixture for inhalation anesthesia during laser surgery in the airway of the horse. In: Steffey EP, ed. Recent advances in anesthetic management of large domestic animals. Ithaca, NY: International Veterinary Information Service, 2003.
29. Staffieri F, Bauquier SH, Moate PJ, et al. Pulmonary gas exchange in anesthetized horses mechanically ventilated with oxygen or a helium/oxygen mixture. Equine Vet J 2009;41:747–752.
30. Ambrósio AM, Ida KK, Souto MT, et al. Effects of positive end-expiratory pressure titration on gas exchange, respiratory mechanics and hemodynamics in anesthetised horses. Vet Anaesth Analg 2013;40:564–572.
31. Wilson DV, Soma LR. Cardiopulmonary effects of positive end-expiratory pressure in anesthetized, mechanically ventilated ponies. Am J Vet Res 1990;51:734–739.
32. Goto T, Saito H, Nakata Y, et al. Effects of xenon on the performance of various respiratory parameters. Anesthesiology 1999;90:555–563.
33. Miyaji T, Fukakura Y, Usuda Y, et al. Effects of gas composition on the delivered tidal volume of the Avance Carestation. J Anesth 2015;29:690–695.
34. Tassaux D, Jolliet P, Thouret JM, et al. Calibration of seven ICU ventilators for mechanical ventilation with helium-oxygen mixtures. Am J Respir Crit Care Med 1999;160:22–32.
35. Wallon G, Bonnet A, Guérin C. Delivery of tidal volume from four anaesthesia ventilators during volume-controlled ventilation: a bench study. Br J Anaesth 2013;110:1045–1051.
