• View in gallery

    Mean Pao2 (diamonds), blood flow (as determined by measurement of CO; gray bars), and minute ventilation (VE; white bars) for 4 groups of anesthetized horses: SB with low (< 70 mm Hg) MAP (group SB-L; n = 7); SB with physiologically normal (≥ 70 mm Hg) MAP (group SB-N; 8), MV with low MAP (group MV-L; 6), and MV with physiologically normal MAP (group MV-N; 6). Horses were anesthetized and allowed a 60-minute equilibration period. At the end of that period (time 0; baseline), PiNO was delivered for 30 minutes. Variables were determined at baseline and 15 and 30 minutes after the start of PiNO.

  • View in gallery

    Percentage change in Qs/Qt (A), Pao2 - Pao2 (B), and Pao2 (C) in anesthetized horses before (baseline) and 15 and 30 minutes after the start of PiNO for 7 horses in group SB-L (gray diamonds and dashed line), 8 horses in group SB-N (gray squares and solid line), 6 horses in group MV-L (black diamonds and dashed line), and 6 horses in group MV-N (black squares and solid line). See Figure 1 for remainder of key.

  • View in gallery

    Box-and-whisker plots of Do2 (A) and So2 (B) at baseline and 15 and 30 minutes after the start of PiNO for 7 horses in group SB-L, 8 horses in group SB-N, 6 horses in group MV-L, and 6 horses in group MV-N. The lower and upper boundaries of each box represent the 25th and 75th percentiles of the data, respectively; the horizontal line in each box represents the median; and the whiskers represent the minimum and maximum values. See Figure 1 for remainder of key.

  • 1. Johnston GM, Eastment JK, Wood JLN, et al. The confidential enquiry into perioperative equine fatalities (CEPEF): mortality results of phases 1 and 2. Vet Anaesth Analg 2002;29:159170.

    • Search Google Scholar
    • Export Citation
  • 2. Dugdale AH, Obhrai J, Cripps PJ. Twenty years later: a single-centre, repeat retrospective analysis of equine perioperative mortality and investigation of recovery quality. Vet Anaesth Analg 2016;43:171178.

    • Search Google Scholar
    • Export Citation
  • 3. Whitehair KJ, Willits NH. Predictors of arterial oxygen tension in anesthetized horses: 1,610 cases (1992–1994). J Am Vet Med Assoc 1999;215:978981.

    • Search Google Scholar
    • Export Citation
  • 4. Hubbell JAE, Muir WW. Oxygenation, oxygen delivery and anaesthesia in the horse. Equine Vet J 2015;47:2535.

  • 5. Schauvliege S, Gasthuys F. Drugs for cardiovascular support in anesthetized horses. Vet Clin North Am Equine Pract 2013;29:1949.

  • 6. de Vries A, Brearly JC, Taylor PM. Effects of dobutamine on cardiac index and arterial blood pressure in isoflurane-anaesthetized horses under clinical conditions. J Vet Pharmacol Ther 2009;32:353358.

    • Search Google Scholar
    • Export Citation
  • 7. Swanson CR, Muir WW III, Bednarski RM, et al. Hemodynamic responses in halothane-anesthetized horses given infusions of dopamine or dobutamine. Am J Vet Res 1985;46:365370.

    • Search Google Scholar
    • Export Citation
  • 8. Swanson CR, Muir WW III. Dobutamine-induced augmentation of cardiac output does not enhance respiratory gas exchange in anesthetized recumbent healthy horses. Am J Vet Res 1986;47:15731576.

    • Search Google Scholar
    • Export Citation
  • 9. Briganti A, Portela DA, Grasso S, et al. Accuracy of different oxygenation indices in estimating intrapulmonary shunting at increasing infusion rates of dobutamine in horses under general anaesthesia. Vet J 2015;204:351356.

    • Search Google Scholar
    • Export Citation
  • 10. Hopster K, Wogatzki A, Geburek F, et al. Effects of positive end-expiratory pressure titration on intestinal oxygenation and perfusion in isoflurane anaesthetised horses. Equine Vet J 2017;49:250256.

    • Search Google Scholar
    • Export Citation
  • 11. Cournand A, Motley HL, Werko L, et al. Physiologic studies on the effects of intermittent positive pressure breathing on cardiac output in man. Am J Physiol 1948;152:162174.

    • Search Google Scholar
    • Export Citation
  • 12. Tyler DC. Positive end-expiratory pressure: a review. Crit Care Med 1983;11:300308.

  • 13. Shekerdemian L, Bohn D. Cardiovascular effects of mechanical ventilation. Arch Dis Child 1999;80:475480.

  • 14. Heinonen E, Hedenstierna G, Meriläinen P, et al. Pulsed delivery of nitric oxide counteracts hypoxaemia in the anaesthetised horse. Vet Anaesth Analg 2001;28:311.

    • Search Google Scholar
    • Export Citation
  • 15. Heinonen E, Nyman G, Meriläinen P, et al. Effect of different pulses of nitric oxide on venous admixture in the anaesthetized horse. Br J Anaesth 2002;88:394398.

    • Search Google Scholar
    • Export Citation
  • 16. Nyman G, Grubb TL, Heinonen E. Pulsed delivery of inhaled nitric oxide counteracts hypoxaemia during 2.5 hours of inhalation anaesthesia in dorsally recumbent horses. Vet Anaesth Analg 2012;39:480487.

    • Search Google Scholar
    • Export Citation
  • 17. Grubb T, Frendin JHM, Edner A, et al. The effects of pulse-delivered inhaled nitric oxide on arterial oxygenation, ventilation-perfusion distribution and plasma endothelin-1 concentration in laterally recumbent isoflurane-anaesthetized horses. Vet Anaesth Analg 2013;40:e19e30.

    • Search Google Scholar
    • Export Citation
  • 18. Grubb TL, Lord PF, Berger M, et al. Effects of pulse-delivered inhaled nitric oxide administration on pulmonary perfusion and arterial oxygenation in dorsally recumbent isoflurane-anesthetized horses. Am J Vet Res 2014;75:949955.

    • Search Google Scholar
    • Export Citation
  • 19. Wiklund M, Granswed I, Nyman G. Pulsed inhaled nitric oxide improves arterial oxygenation in colic horses undergoing abdominal surgery. Vet Anaesth Analg 2017;44:11391148.

    • Search Google Scholar
    • Export Citation
  • 20. Berggren SM. Oxygen deficit of arterial blood by non ventilating parts of the lung. Acta Physiol Scand 1942;4(suppl II):792.

  • 21. West JB. Ventilation-perfusion relationships. In: Respiratory physiology: the essentials. 9th ed. Philadelphia: Lippincott Williams & Wilkins, 2012;5676.

    • Search Google Scholar
    • Export Citation
  • 22. Day TK, Gaynor JS, Muir WW III, et al. Blood gas values during intermittent positive pressure ventilation and spontaneous ventilation in 160 anesthetized horses positioned in lateral or dorsal recumbency. Vet Surg 1995;24:266276.

    • Search Google Scholar
    • Export Citation
  • 23. Hodgson DS, Steffey EP, Grandy JL, et al. Effects of spontaneous, assisted, and controlled ventilatory modes in halothane-anesthetized geldings. Am J Vet Res 1986;47:992996.

    • Search Google Scholar
    • Export Citation
  • 24. Edner A, Nyman G, Essén-Gustavsson B. The effects of spontaneous and mechanical ventilation on central cardiovascular function and peripheral perfusion during isoflurane anaesthesia in horses. Vet Anaesth Analg 2005;32:136146.

    • Search Google Scholar
    • Export Citation
  • 25. Nyman G, Hedenstierna G. Ventilation-perfusion relationships in the anaesthetised horse. Equine Vet J 1989;21:274281.

  • 26. Cairo JM. Effects of positive-pressure ventilation on the pulmonary system. In: Pilbeam SP, ed. Pilbeam's mechanical ventilation—physiological concepts and clinical applications. 5th ed. St Louis: Elsevier, 2012;327352.

    • Search Google Scholar
    • Export Citation
  • 27. Neumann P, Wrigge H, Zinserling J, et al. Spontaneous breathing affects the spatial ventilation and perfusion distribution during mechanical ventilatory support. Crit Care Med 2005;33:10901095.

    • Search Google Scholar
    • Export Citation
  • 28. Wrigge H, Zinserling J, Neumann P, et al. Spontaneous breathing with airway pressure release ventilation favors ventilation in dependent lung regions and counters cyclic alveolar collapse in oleic-acid-induced lung injury: a randomized controlled computed tomography trial. Crit Care 2005;9:R780R789.

    • Search Google Scholar
    • Export Citation
  • 29. Mosing M, Senior JM. Maintenance of equine anaesthesia over the last 50 years: controlled inhalation of volatile anaesthetics and pulmonary ventilation. Equine Vet J 2018;50:282291.

    • Search Google Scholar
    • Export Citation
  • 30. Kelman GR, Nunn JF, Prys-Roberts C, et al. The influence of cardiac output on arterial oxygenation: a theoretical study. Br J Anaesth 1967;39:450458.

    • Search Google Scholar
    • Export Citation
  • 31. Gasthuys F, de Moor A, Parmentier D. Influence of dopamine and dobutamine on the cardiovascular depression during a standard halothane anaesthesia in dorsally recumbent ventilated ponies. Zentralbl Veterinarmed A 1991;38:494500.

    • Search Google Scholar
    • Export Citation
  • 32. Mizuno Y, Aida H, Fujinaga T. Effects of dobutamine infusion in dorsally recumbent isoflurane-anesthetized horses. J Equine Sci 1994;5:8794.

    • Search Google Scholar
    • Export Citation
  • 33. Young LE, Blissitt KJ, Clutton RE, et al. Temporal effects of an infusion of dobutamine hydrochloride in horses anesthetized with halothane. Am J Vet Res 1998;59:10271032.

    • Search Google Scholar
    • Export Citation
  • 34. Bryan TL, van Diepen S, Bhutani M, et al. The effects of dobutamine and dopamine on intrapulmonary shunt and gas exchange in healthy humans. J Appl Physiol 2012;113:541548.

    • Search Google Scholar
    • Export Citation
  • 35. Rennotte MT, Reynaert M, Clerbaux T, et al. Effects of two inotropic drugs, dopamine and dobutamine, on pulmonary gas exchange in artificially ventilated patients. Intensive Care Med 1989;15:160165.

    • Search Google Scholar
    • Export Citation
  • 36. Manohar M, Goetz TE. Intrapulmonary arteriovenous shunts of > 15 μm in diameter probably do not contribute to arterial hypoxaemia in maximally exercising Thoroughbred horses. J Appl Physiol 2005;99:224229.

    • Search Google Scholar
    • Export Citation
  • 37. Vizza CD, Della Rocca G, Di Roma A, et al. Acute hemodynamic effects of inhaled nitric oxide, dobutamine and a combination of the two in patients with mild to moderate secondary pulmonary hypertension. Crit Care 2001;5:355361.

    • Search Google Scholar
    • Export Citation
  • 38. Bradford KK, Bhaskar D, Pearl RG. Combination therapy with inhaled nitric oxide and intravenous dobutamine during pulmonary hypertension in the rabbit. J Cardiovasc Pharmacol 2000;36:146151.

    • Search Google Scholar
    • Export Citation

Advertisement

Effects of ventilation mode and blood flow on arterial oxygenation during pulse-delivered inhaled nitric oxide in anesthetized horses

Adam Auckburally BVSc1, Tamara L. Grubb DVM, PhD2, Maja Wiklund DVM3, and Görel Nyman DVM, PhD4
View More View Less
  • 1 Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, 75007 Uppsala, Sweden.
  • | 2 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.
  • | 3 Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, 75007 Uppsala, Sweden.
  • | 4 Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, 75007 Uppsala, Sweden.

Abstract

OBJECTIVE To determine the impact of mechanical ventilation (MV) and perfusion conditions on the efficacy of pulse-delivered inhaled nitric oxide (PiNO) in anesthetized horses.

ANIMALS 27 healthy adult horses.

PROCEDURES Anesthetized horses were allocated into 4 groups: spontaneous breathing (SB) with low (< 70 mm Hg) mean arterial blood pressure (MAP; group SB-L; n = 7), SB with physiologically normal (≥ 70 mm Hg) MAP (group SB-N; 8), MV with low MAP (group MV-L; 6), and MV with physiologically normal MAP (group MV-N; 6). Dobutamine was used to maintain MAP > 70 mm Hg. Data were collected after a 60-minute equilibration period and at 15 and 30 minutes during PiNO administration. Variables included Pao 2, arterial oxygen saturation and content, oxygen delivery, and physiologic dead space-to-tidal volume ratio. Data were analyzed with Shapiro-Wilk, Mann-Whitney U, and Friedman ANOVA tests.

RESULTS Pao 2, arterial oxygen saturation, arterial oxygen content, and oxygen delivery increased significantly with PiNO in the SB-L, SB-N, and MV-N groups; were significantly lower in group MV-L than in group MV-N; and were lower in MV-N than in both SB groups during PiNO. Physiologic dead space-to-tidal volume ratio was highest in the MV-L group.

CONCLUSIONS AND CLINICAL RELEVANCE Pulmonary perfusion impacted PiNO efficacy during MV but not during SB. Use of PiNO failed to increase oxygenation in the MV-L group, likely because of profound ventilation-perfusion mismatching. During SB, PiNO improved oxygenation irrespective of the magnitude of blood flow, but hypoventilation and hypercarbia persisted. Use of PiNO was most effective in horses with adequate perfusion.

Abstract

OBJECTIVE To determine the impact of mechanical ventilation (MV) and perfusion conditions on the efficacy of pulse-delivered inhaled nitric oxide (PiNO) in anesthetized horses.

ANIMALS 27 healthy adult horses.

PROCEDURES Anesthetized horses were allocated into 4 groups: spontaneous breathing (SB) with low (< 70 mm Hg) mean arterial blood pressure (MAP; group SB-L; n = 7), SB with physiologically normal (≥ 70 mm Hg) MAP (group SB-N; 8), MV with low MAP (group MV-L; 6), and MV with physiologically normal MAP (group MV-N; 6). Dobutamine was used to maintain MAP > 70 mm Hg. Data were collected after a 60-minute equilibration period and at 15 and 30 minutes during PiNO administration. Variables included Pao 2, arterial oxygen saturation and content, oxygen delivery, and physiologic dead space-to-tidal volume ratio. Data were analyzed with Shapiro-Wilk, Mann-Whitney U, and Friedman ANOVA tests.

RESULTS Pao 2, arterial oxygen saturation, arterial oxygen content, and oxygen delivery increased significantly with PiNO in the SB-L, SB-N, and MV-N groups; were significantly lower in group MV-L than in group MV-N; and were lower in MV-N than in both SB groups during PiNO. Physiologic dead space-to-tidal volume ratio was highest in the MV-L group.

CONCLUSIONS AND CLINICAL RELEVANCE Pulmonary perfusion impacted PiNO efficacy during MV but not during SB. Use of PiNO failed to increase oxygenation in the MV-L group, likely because of profound ventilation-perfusion mismatching. During SB, PiNO improved oxygenation irrespective of the magnitude of blood flow, but hypoventilation and hypercarbia persisted. Use of PiNO was most effective in horses with adequate perfusion.

Mortality rates associated with general anesthesia of horses are unacceptably high (approx 0.9% to 1.1% in healthy horses).1,2 A deficiency in tissue Do2 may be associated with morbidity and fatalities.3 The Do2, which is dependent on both perfusion and ventilation, is commonly decreased in anesthetized horses as a direct result of the cardiovascular and respiratory depressant effects of volatile anesthetics and the physical effect of recumbency.4

Decreased tissue perfusion, which may be a consequence of reduced CO (a determinant of blood flow), is identified clinically as hypotension (defined as an MAP < 70 mm Hg in horses5). In anesthetized horses, hypotension is often treated with an infusion of dobutamine6 (a nonselective β-adrenoceptor agonist that has positive inotropic effects) to increase ventricular output.7 Although blood pressure attributable to increased blood flow is increased with dobutamine, an infusion of dobutamine in horses does not ensure improved arterial oxygenation.8,9

Hypoventilation, identified clinically by the presence of hypercarbia, is commonly treated by initiating MV. Although this is effective for treating hypercarbia, hypoxemia and Do2 can be worsened by MV10 as a result of numerous factors, including a positive intrathoracic pressure-mediated decrease in CO via prevention of efficient venous return11 and an increase in lung volume that impedes cardiac filling owing to chamber and pericardial compression effects.12,13

Administration of PiNO improves arterial oxygenation in SB anesthetized horses.14–19 This effect does not occur through changes in ventilation or CO; instead, it is a result of redistribution of pulmonary blood from atelectatic to aerated areas of the lungs.17 Spontaneously breathing horses anesthetized for abdominal exploratory surgery that receive PiNO require dobutamine infusion for maintenance of normotension.19 Hypercarbia with subsequent respiratory acidosis commonly develops in horses receiving PiNO that do not receive ventilatory support.16–19 In healthy research horses, PiNO delivered by MV improved oxygenation; however, PiNO was delivered for only 5 minutes.14 To fully support anesthetized horses, a combination of PiNO, MV, and dobutamine administration may be necessary, but the combined impact of MV and PiNO during clinically relevant durations of anesthesia is unknown.

The objective of the study reported here was to determine the impact of 2 ventilation modes (MV and SB) and 2 perfusion conditions (MAP < or ≥ 70 mm Hg) on PiNO-mediated oxygenation in anesthetized horses. Our hypothesis was that MV and increased blood flow would optimize the effect of PiNO on arterial oxygenation.

Materials and Methods

Animals

Twenty-seven healthy Standardbreds were used in the study. Age ranged from 1 to 25 years, and body weight ranged from 375 to 610 kg. Horses were randomly (computer-generated numbers) assigned to 4 groups: SB with low (< 70 mm Hg) MAP (group SB-L; n = 7), SB with physiologically normal (≥ 70 mm Hg) MAP (group SB-N; 8), MV with low MAP (group MV-L; 6), and MV with physiologically normal MAP (group MV-N; 6). The experiment was approved by the local Ethical Committee on Animal Experiments in Uppsala, Sweden (C 201/14).

Anesthesia

Food, but not water, was withheld for 12 hours prior to anesthesia. Acepromazine (0.03 mg•kg−1) was administered IM approximately 30 minutes before induction of anesthesia. The subcutaneous tissues over the jugular veins were infiltrated with lidocaine. The left jugular vein was catheterized with a 14-gauge catheter, and the right jugular vein was catheterized with two 8.5F sheath introducers (one positioned distally in the vein and the other positioned proximally in the vein).

Additional premedication consisted of xylazine hydrochloride (1.1 mg•kg−1, IV) and butorphanol tartrate (0.025 mg•kg−1, IV). When sedation was apparent, anesthesia was induced by rapid IV administration of a bolus of ketamine hydrochloride (2.2 mg•kg−1) and diazepam (0.05 mg•kg−1). After each horse was recumbent, the trachea was intubated with a cuffed endotracheal tube (internal diameter, 26 mm). The horse was hoisted onto a padded surgical table, positioned in dorsal recumbency, and connected to a large-animal breathing system and anesthetic machine.a Anesthesia was maintained with isoflurane vaporized in oxygen. The Fio2 was maintained at approximately 0.9 by the computer-controlled Fio2 technology of the anesthetic machine. Ventilatory mode was SB or continuous mandatory MV. The MAP was allowed to decrease to < 70 mm Hg or was maintained at ≥ 70 mm Hg by administration of a variable rate infusion of dobutamine.

Instrumentation

After a horse was positioned on the surgical table, an 18-gauge catheter was inserted in the transverse facial or mandibular branch of the facial artery for measurement of blood pressure and collection of arterial blood samples for analysis. The catheter was connected via a 3-way stopcock to a pressure-monitoring line and transducer, which was connected to the multiparameter monitor integrated in the anesthetic machine. A 7.5F Swan-Ganz catheter was inserted via the distal introducer in the right jugular vein and guided into the pulmonary artery by use of pressure guidance from another multiparameter monitor.b This catheter was used to measure mean pulmonary arterial pressure as well as CO (determined by thermodilution) and to enable collection of mixed-venous blood samples. By use of a similar technique, a 7.5F pigtail multiple-hole catheter was inserted through the proximal introducer in the right jugular vein and guided into the right atrium. This catheter was used to measure right atrial pressure and to inject ice-cold saline (0.9% NaCl) solution for CO measurement. Both catheters were secured by use of the Luer-lock adaptor on the introducers. The ECG was monitored during placement of the catheters. All pressure transducers were calibrated to zero at the level of the shoulder joint.

Hemodynamic analysis

Thermodilution was used to measure CO. The Swan-Ganz catheter was connected to the multiparameter monitor,b and a 20-mL bolus of ice-cold (0°C) saline solution was manually injected through the pigtail catheter. A minimum of 3 boluses were injected, and the mean value was calculated and recorded.

Systolic arterial blood pressure, diastolic arterial blood pressure, and MAP were recorded from the arterial catheter; HR, RR, minute volume, peak inspired pressure, Petco2, end-tidal isoflurane concentration, and Fio2 were recorded from the calibrated multiparameter monitora integrated with the anesthetic machine.

Arterial and mixed-venous blood samples were simultaneously aspirated over a period of 3 breaths from the arterial and pulmonary artery catheters, respectively. Samples were analyzed immediately (arterial pH, mixed-venous pH, Pao2 mixed-venous partial pressure of oxygen, Sao2, So2, PaCo2, mixed-venous partial pressure of carbon dioxide and hemoglobin concentration) by use of a standard electrode technique.c

Calculated variables

The Do2 was calculated as Cao2 × CO. Venous admixture was calculated by use of the Berggren shunt formula20 as follows:

article image

where Cć o2 is the pulmonary end-capillary oxygen content and Co2 is the mixed-venous oxygen content. The CI was calculated as CO/body weight. Minute ventilation was calculated as RR × Vt. Values for Vd/Vt were calculated as (Paco2 - Petco2)/Paco2. The Pao2 was calculated by use of the alveolar gas equation21 as follows:

article image

where Paco2 is the alveolar partial pressure of carbon dioxide (the value for Paco2 was used for Paco2) and the respiratory quotient is 0.8. The Pao2 - Pao2 was calculated as Pao2 minus Pao2. The OER was calculated as the arterial-mixed-venous of oxygen content divided by Cao2.

PiNO

Anesthetized horses were allowed a 60-minute equilibration period. At the end of that period (time 0; baseline), PiNO was delivered for 30 minutes. Nitric oxide was delivered via the endotracheal tube by use of a specially designed device.d The device delivered a pulse of NO at the beginning of inspiration, and the flow sensor was triggered by the negative pressure generated by SB or the positive pressure generated by the ventilator during MV. The device was connected to a cylinder containing 2,000 ppm of NO in nitrogen.e The NO was delivered during the first 45% of inspiration (controlled by the device). The most effective timing and duration of delivery have been determined in previous studies.14,16,17

Data collection

Arterial and mixed-venous blood gas samples were collected at 0, 15, and 30 minutes (ie, before and 15 and 30 minutes after the start of PiNO) and analyzed to determine Pao2, Sao2, mixed-venous partial pressure of oxygen, Svo2, Paco2, pH, hemoglobin concentration, and venous lactate concentration. At the same time points, HR, RR, systolic and diastolic arterial blood pressures, MAP, mean pulmonary arterial pressure, right atrial pressure, Petco2, end-tidal isoflurane concentration, Fio2, oxygen saturation measured by use of pulse oximetry, CO, and Vt were recorded, and CI, Pao2, Cao2, mixed-venous oxygen content, Do2, Qs/Qt, minute ventilation, Vd/Vt, and OER were calculated. At the end of the procedure, horses were moved to a padded recovery stall and allowed to recover from anesthesia or were euthanized (IV administration of a barbiturate overdose), as determined by requirements of concurrent projects.

Statistical analysis

Raw data were entered into a spreadsheet programf for processing. For all statistical calculations, a statistical packageg was used. Data were tested for a Gaussian distribution by use of the Shapiro-Wilk normality test. Mann-Whitney tests were used to compare differences between SB and MV in hypotensive and normotensive horses, and a Friedman ANOVA and Dunn multiple comparisons post hoc test were used to compare differences over time within each group. Differences were considered significant at P < 0.05. Data were reported as mean ± SD.

Results

Animals

Age and body weight did not differ significantly among the groups.

Blood flow

Heart rate was higher in horses with physiologically normal MAP than in horses with low MAP at all time points for MV horses and at 30 minutes for SB horses (Table 1). The MAP was significantly higher in horses with physiologically normal MAP than in horses with low MAP for both MV groups and both SB groups and significantly higher in the SB-L group than the MV-L group at 15 and 30 minutes. There were no significant changes in mean pulmonary arterial pressure. The CO (measured as CI) was significantly higher in the SB-N group and MV-N group than the SB-L group and MV-L group, respectively, at all time points, but there were no differences between the MV-N and SB-N groups or between the MV-L and SB-L groups (Figure 1). The Qs/Qt decreased during PiNO in all groups, but there were no differences among groups (Figure 2).

Table 1—

Mean ± SD values for blood flow variables at various time points for anesthetized horses with SB with low (< 70 mm Hg) MAP (group SB-L; n = 7), SB with physiologically normal (≥ 70 mm Hg) MAP (group SB-N; 8), MV with low MAP (group MV-L; 6), and MV with physiologically normal MAP (group MV-N; 6).

VariableGroupBaseline15 minutes30 minutesP value*
HR (beats•min−1)SB-L38 ± 736 ± 535 ± 6NS
 SB-N48 ± 1545 ± 1442 ± 12NS
 MV-L35 ± 333 ± 332 ± 30.002
 MV-N45 ± 1049 ± 1150 ± 12NS
MAP (mm Hg)SB-L53 ± 1066 ± 768 ± 60.004
 SB-N72 ± 580 ± 780 ± 80.018
 MV-L53 ± 955 ± 8§56 ± 9§NS
 MV-N77 ± 1182 ± 481 ± 3NS
MPAP (mm Hg)SB-L13 ± 413 ± 314 ± 3NS
 SB-N16 ± 415 ± 414 ± 4NS
 MV-L15 ± 314 ± 313 ± 3NS
 MV-N12 ± 312 ± 311 ± 3NS
CI (mL•kg−1•min−1)SB-L45 ± 950 ± 1050 ± 110.027
 SB-N84 ± 3081 ± 2379 ± 22NS
 MV-L45 ± 643 ± 746 ± 5NS
 MV-N72 ± 1080 ± 881 ± 10NS
Qs/QtSB-L0.35 ± 0.100.29 ± 0.120.28 ± 0.12< 0.001
 SB-N0.38 ± 0.100.28 ± 0.090.28 ± 0.110.005
 MV-L0.46 ± 0.070.37 ± 0.090.36 ± 0.09< 0.001
 MV-N0.39 ± 0.100.36 ± 0.100.32 ± 0.07< 0.001
Hemoglobin (g•L−1)SB-L101 ± 696 ± 4097 ± 40.004
 SB-N113 ± 17110 ± 17108 ± 17NS
 MV-L105 ± 4105 ± 3§106 ± 3§NS
 MV-N117 ± 9122 ± 12123 ± 9NS
Lactate (mmol•L−1)SB-L0.7 ± 0.30.7 ± 0.20.8 ± 0.2NS
 SB-N0.6 ± 0.20.6 ± 0.20.6 ± 0.2NS
 MV-L0.9 ± 0.31.0 ± 0.31.1 ± 0.4NS
 MV-N0.7 ± 0.20.7 ± 0.30.7 ± 0.2NS

Horses were anesthetized and allowed a 60-minute equilibration period. At the end of that period (time 0; baseline), PiNO was delivered for 30 minutes. Variables were determined at baseline and 15 and 30 minutes after the start of PiNO.

Within a group, values differ significantly (P < 0.05; Friedman ANOVA with the Dunn multiple comparison test) among time points.

Within a time point within a ventilation mode (SB or MV), value differs significantly (P < 0.05) from the value for SB-N or MV-N.

Within a group, value differs significantly (P < 0.05) from the baseline value.

Within a time point, MV value differs significantly (P < 0.05) from the corresponding value for SB-L or SB-N.

Represents results for only 3 horses.

Represents results for only 4 horses.

MPAP = Mean pulmonary arterial pressure. NS = Not significant (P ≥ 0.05).

Figure 1—
Figure 1—

Mean Pao2 (diamonds), blood flow (as determined by measurement of CO; gray bars), and minute ventilation (VE; white bars) for 4 groups of anesthetized horses: SB with low (< 70 mm Hg) MAP (group SB-L; n = 7); SB with physiologically normal (≥ 70 mm Hg) MAP (group SB-N; 8), MV with low MAP (group MV-L; 6), and MV with physiologically normal MAP (group MV-N; 6). Horses were anesthetized and allowed a 60-minute equilibration period. At the end of that period (time 0; baseline), PiNO was delivered for 30 minutes. Variables were determined at baseline and 15 and 30 minutes after the start of PiNO.

Citation: American Journal of Veterinary Research 80, 3; 10.2460/ajvr.80.3.275

Figure 2—
Figure 2—

Percentage change in Qs/Qt (A), Pao2 - Pao2 (B), and Pao2 (C) in anesthetized horses before (baseline) and 15 and 30 minutes after the start of PiNO for 7 horses in group SB-L (gray diamonds and dashed line), 8 horses in group SB-N (gray squares and solid line), 6 horses in group MV-L (black diamonds and dashed line), and 6 horses in group MV-N (black squares and solid line). See Figure 1 for remainder of key.

Citation: American Journal of Veterinary Research 80, 3; 10.2460/ajvr.80.3.275

Minor clinically unimportant changes were evident at various time points. Hemoglobin concentration was higher in horses with physiologically normal MAP than in horses with low MAP. Lactate concentration was higher in the MV-L group than the MV-N group, but no changes in lactate concentration were detected between the SB groups.

Ventilation

Minute ventilation and RR were higher in the MV groups than in the SB groups. However, there were no differences between the SB-L and SB-N groups or between the MV-L and MV-N groups and no change over time in the MV or SB groups (Table 2). The Paco2 was lower in the MV groups than the SB groups at 15 and 30 minutes. There were no differences in Paco2 between the SB-N and SB-L groups or between the MV-N and MV-L groups, and there were no changes over time except for the SB-L group, in which Paco2 was higher at 15 and 30 minutes than at baseline. The Vd/Vt was higher in the MV-L group than the MV-N group at 15 and 30 minutes.

Table 2—

Mean ± SD values for ventilation variables at various time points for 4 groups of anesthetized horses (7 horses in group SB-L, 8 horses in group SB-N, 6 horses in group MV-L, and 6 horses in group MV-N).

VariableGroupBaseline15 minutes30 minutesP value*
Minute ventilation (L•min−1)SB-L29.5 ± 12.524.1 ± 8.623.6 ± 2.6NS
 SB-N28.5 ± 10.524.3 ± 14.125.5 ± 9.1NS
 MV-L44.8 ± 4.7§48.9 ± 5.8§47.6 ± 4.7§NS
 MV-N47.2 ± 11.7§47.1 ± 7.7§49.6 ± 10. 1§NS
RR (breaths•min−1)SB-L4.9 ± 2.03.6 ± 1.53.6 ± 1.3NS
 SB-N4.2 ± 2.13.6 ± 1.73.3 ± 1.6NS
 MV-L7.7 ± 0.8§8.0 ± 0.6§8.0 ± 0.6§NS
 MV-N8.2 ± 1.0§7.8 ± 0.4§8.0 ± 0.6§NS
PIP (cm H2O)SB-LNANANANA
 SB-NNANANANA
 MV-L27.2 ± 3.426.7 ± 2.227.7 ± 3.9NS
 MV-N20.8 ± 3.823.0 ± 3.623.3 ± 3.60.008
Paco2 (mm Hg)SB-L63.0 ± 7.569.8 ± 11.369.0 ± 8.30.001
 SB-N76.5 ± 1874.3 ± 10.576.5 ± 13.5NS
 MV-L63.0 ± 7.555.5 ± 4.5§55.5 ± 3.8§NS
 MV-N60.0 ± 9.860.8 ± 11.3§58.5 ± 8.3§NS
Vd/VtSB-L0.29 ± 0.070.25 ± 0.100.24 ± 0.13NS
 SB-N0.30 ± 0.060.24 ± 0.120.22 ± 0.10NS
 MV-L0.29 ± 0.080.28 ± 0.080.29 ± 0.07NS
 MV-N0.22 ± 0.04§0.18 ± 0.040.18 ± 0.06NS

NA = Not applicable. PIP = Peak inspiratory pressure.

See Table 1 for remainder of key.

Oxygenation

The Pao2 - Pao2 decreased during PiNO administration in all groups, except for the MV-L group (Table 3; Figure 2). The Pao2, Sao2, and Cao2 increased significantly during PiNO in the SB-L, SB-N, and MV-N groups, compared with respective baseline values (Figure 1). There were no differences between the SB groups, but Pao2, Sao2, and Cao2 were significantly lower in the MV-L group than the MV-N group at all time points. The Sao2 was significantly lower in the MV-L group than the SB-L group at all time points. The Pao2 changed over time. The Do2 increased significantly during PiNO in all groups, except for the MV-L group. The Do2 was significantly higher at all time points for the SB-N group and MV-N group than for the SB-L group and MV-L group, respectively (Figure 3). There were no differences in So2 between SB groups. The So2 was significantly lower in the MV-L group than the MV-N group at all time points. The OER was significantly higher in the MV-L group than the MV-N group, but there were no other differences among groups.

Table 3—

Mean ± SD values for oxygenation variables at various time points for 4 groups of anesthetized horses (7 horses in group SB-L, 8 horses in group SB-N, 6 horses in group MV-L, and 6 horses in group MV-N).

VariableGroupBaseline15 minutes30 minutesP value*
Fio2SB-L0.90 ± 0.070.92 ± 0.030.91 ± 0.03NS
 SB-N0.90 ± 0.020.90 ± 0.030.90 ± 0.02NS
 MV-L0.85 ± 0.05§0.84 ± 0.05§0.85 ± 0.05§NS
 MV-N0.90 ± 0.010.88 ± 0.020.88 ± 0.02NS
Pao2 - Pao2 (mm Hg)SB-L495.0 ± 42.8390.8 ± 69.8377.3 ± 60.80.003
 SB-N402.0 ± 129.8318.8 ± 112.5306.0 ± 99.80.038
 MV-L474.0 ± 45.8465.0 ± 48.8466.5 ± 45.8§NS
 MV-N349.5 ± 142.5264.0 ± 139.5253.5 ± 133.50.006
Pao2 (mm Hg)SB-L97.5 ± 28.5189 ± 57.8199.5 ± 59.3< 0.001
 SB-N153.0 ± 120.8237.0 ± 122.3250.5 ± 97.5< 0.001
 MV-L69.0 ± 55.575.8 ± 46.5§75.8 ± 40.5§NS
 MV-N217.5 ± 145.5293.3 ± 151.5301.5 ± 142.50.002
Sao2 (%)SB-L95.7 ± 2.298.6 ± 1.398.8 ± 1.2< 0.001
 SB-N94.7 ± 2.797.9 ± 1.197.8 ± 1.7< 0.001
 MV-L85.0 ± 7.4§89.3 ± 6.2§89.8 ± 71§NS
 MV-N95.5 ± 1.296.3 ± 0.796.7 ± 0.4< 0.001
Cao2 (mL•L−1)     
 SB-N146.3 ± 24.5153.2 ± 21.4153.5 ± 20.0< 0.001
 MV-L120.6 ± 14.9126.8 ± 15.4127.0 ± 16.7NS
 MV-N169.4 ± 15.6176.2 ± 16.3178.8 ± 20.90.002
Do2 (mL•kg−1•min−1)SB-L6.0 ± 1.26.9 ± 1.57.0 ± 1.6< 0.001
 SB-N12.8 ± 6.412.6 ± 4.912.3 ± 4.3NS
 MV-L5.5 ± 0.85.2 ± 1.05.6 ± 1.0NS
 MV-N12.2 ± 2.814.5 ± 2.115.1 ± 3.90.008
Po2 (mm Hg)SB-L39.8 ± 7.541.3 ± 5.342.8 ± 5.3NS
 SB-N51.8 ± 12.052.5 ± 9.854.0 ± 12.8NS
 MV-L31.5 ± 3.8§31.5 ± 3.8§30.8 ± 3.8§NS
 MV-N51.0 ± 9.057.0 ± 7.557.0 ± 10.50.012
So2 (%)SB-L67 ± 1273 ± 1473 ± 130.004
 SB-N74 ± 1077 ± 1178 ± 9NS
 MV-L60 ± 1160 ± 1158 ± 10NS
 MV-N82 ± 686 ± 485 ± 50.029
Cao2 - Co2 (mL•L−1)SB-L40.3 ± 15.238.2 ± 16.738.8 ± 16.50.004
 SB-N32.4 ± 9.835.5 ± 13.634.5 ± 12.8NS
 MV-L36.4 ± 3.641.9 ± 4.9§44.7 ± 6.5§NS
 MV-N28.3 ± 6.125.2 ± 4.227.3 ± 4.3NS
OER (%)SB-L31 ± 1232 ± 829 ± 13NS
 SB-N23 ± 924 ± 1123 ± 10NS
 MV-L31 ± 734 ± 736 ± 7NS
 MV-N17 ± 515 ± 416 ± 4NS

Cao2 - Co2 = Arterial-mixed-venous difference in oxygen content. Po2 = Mixed-venous partial pressure of oxygen.

See Table 1 for remainder of key.

Figure 3—
Figure 3—

Box-and-whisker plots of Do2 (A) and So2 (B) at baseline and 15 and 30 minutes after the start of PiNO for 7 horses in group SB-L, 8 horses in group SB-N, 6 horses in group MV-L, and 6 horses in group MV-N. The lower and upper boundaries of each box represent the 25th and 75th percentiles of the data, respectively; the horizontal line in each box represents the median; and the whiskers represent the minimum and maximum values. See Figure 1 for remainder of key.

Citation: American Journal of Veterinary Research 80, 3; 10.2460/ajvr.80.3.275

Discussion

Results of the present study supported the hypothesis that MV in combination with adequate blood flow promoted optimal gas exchange during PiNO by improving arterial oxygenation and managing hypercarbia. During MV, the degree of PiNO-mediated improvement in oxygenation, Do2, and Qs/Qt was related to an increase in blood flow as measured by an increase in CI. It was obvious that MV had a negative impact on the degree of improvement in oxygenation in horses with low blood flow. Interestingly, during SB, arterial oxygenation increased with PiNO regardless of the magnitude of blood flow. However, hypoventilation commonly developed in SB horses, which led to hypercarbia.

The lack of impact of PiNO on oxygenation for the MV-L group was unexpected because PiNO reportedly has a positive effect on oxygenation during short-term use.14 On the basis of the increase in Vd/Vt for the MV-L group, compared with results for the MV-N group, we speculate that this lack of effect was attributable to profound mismatching and a lack of perfusion to some ventilated lung regions. There is optimal gas exchange when ventilation and perfusion are equally matched, but MV can have deleterious effects on matching in a number of ways. First, CO is reduced during MV because of a reduction in cardiac filling pressure.11 If Do2 decreases below tissue oxygen demand, then So2 decreases and Pao2 is reduced.22 In the present study, OER was higher and So2 was lower in the MV-L group. Thus, a larger fraction of oxygen was extracted from the blood when capillary beds were perfused. This indicated that when hemoglobin saturation with oxygen was adequate, blood flow was proportionately more important than oxygen content for tissue oxygen supply, which agrees with results of other studies.23,24 In those studies,23,24 oxygen uptake did not differ between SB and MV, but Do2 decreased during controlled ventilation, which is a reflection of lower blood flow. Second, the matching was disturbed because the areas of lung normally ventilated became overventilated. This situation, compounded by the decrease in CO, increases alveolar dead space by reducing perfusion of the overventilated alveoli.12,22 More importantly, during periods of positive intrathoracic pressure, blood is forced from nondependent areas of the lungs (ie, those that are normally ventilated) and driven toward dependent areas of the lungs, a large proportion of which are atelectatic.25,26 Conventional MV will not recruit dependent atelectatic areas of the lungs because the alveolar pressure produced is insufficient. Additionally, the compressive effect on the pulmonary capillaries increases pulmonary vascular resistance and thereby further reduces perfusion. Overall, these effects will worsen mismatching, increase Qs/Qt and Vd/Vt, and reduce Pao2. These negative effects of MV were not detected in horses with sufficient CO during PiNO, presumably because of concomitant improvements of perfusion and vasodilation in well-ventilated pulmonary regions. Analysis of results of the study reported here suggested that the deterioration in CO induced by MV affected blood pressure as well as matching and gas exchange in the lungs.

In the present study, SB did not have a negative impact on oxygenation, and relative increases in oxygenation and a reduction in Qs/Qt were greatest in these horses. The respiratory mechanics during SB favors the distribution of gas in the lungs and improves ventilation of dependent juxtadiaphragmatic lung regions.27,28 The negative intrathoracic pressure during inspiration also promotes alveolar recruitment and counteracts cyclic alveolar collapse in dependent lung regions.28 Furthermore, arterial blood pressure is better preserved during SB through better cardiac preload and higher systemic vascular resistance attributable to acidemia associated with hypoventilation and subsequent hypercarbia.29 These combined effects likely contributed to improved matching in the study reported here. The similar effects of PiNO on arterial oxygenation for both the SB-L and SB-N groups suggested that the mode of ventilation played an integral role in the distribution of pulmonary perfusion, rather than being reliant on total blood flow.

Increased oxygenation with increased blood flow is attributable to an increase in pulmonary perfusion with subsequent uptake of oxygen from the lungs.30 Infusions of dobutamine increase CO and systemic and pulmonary pressure in anesthetized horses.31–33 However, dobutamine can also have a negative impact on oxygenation. In healthy awake humans, dobutamine infusion results in the recruitment of intrapulmonary shunt vessels owing to increasing CO, with a subsequent increase in Qs/Qt and Pao2 - Pao2.34 Furthermore, in critically ill mechanically ventilated humans, dobutamine adversely affects Pao2 by increasing shunting.35 However, intrapulmonary shunt vessels have not been described in the lungs of horses, and there is unlikely to be recruitment in situations of increased CO; consequently, there is little impact on arterial oxygenation.36 In the present study, Qs/Qt and Pao2 - Pao2 decreased in both MV and SB horses, likely because of the simultaneous administration of dobutamine during PiNO. Dobutamine administered alone to humans with pulmonary hypertension worsens shunting, but administration of a combination of NO and dobutamine has complementary effects on the pulmonary circulation.37 In the present study, selective pulmonary vasodilation attributable to NO was augmented by an increase in CO, with the deleterious effects of dobutamine on gas exchange being offset by the NO.37,38 The same mechanism likely contributed to the increase in Pao2 with PiNO and concurrent dobutamine administration. However, it is possible that this could have been an effect of dobutamine alone because a control group that received dobutamine without PiNO was not included. The greatest decrease in Pao2 - Pao2 was in the MV-N group because the nondependent portion of the lungs was better ventilated in combination with an increase in pulmonary perfusion as a result of dobutamine infusion and PiNO.

Other results of the present study can be explained by the interventions intended to support ventilation and perfusion. The use of MV led to significant differences in respiratory variables (RR and Paco2), and the administration of dobutamine resulted in significant differences in some cardiovascular variables (HR, MAP, hemoglobin concentration, and CI).

The present study revealed that the magnitude of blood flow had an impact on the efficacy of PiNO during MV. The use of PiNO failed to increase indices of oxygenation when blood flow was low, likely because of decreased perfusion of ventilated lung regions. Administration of dobutamine during PiNO resulted in dramatic improvements in arterial oxygenation and Do2 during MV. In SB horses, PiNO improved arterial oxygenation irrespective of the magnitude of blood flow, but hypoventilation and hypercarbia persisted.

Acknowledgments

This manuscript represents a portion of a thesis submitted by Dr. Auckburally to the Swedish University of Agricultural Sciences as partial fulfilment of the requirements for a Doctor of Philosophy degree.

Supported by a grant from the Swedish-Norwegian Foundation for Equine Research. Funding sources were not involved in the study design, data analysis and interpretation, or writing and publication of the manuscript.

The authors declare that there were no conflicts of interest.

Presented in abstract form at the Association of Veterinary Anaesthetists Spring Meeting, Grenada, West Indies, March 2018.

ABBREVIATIONS

Cao2

Arterial oxygen content

CI

Cardiac index

CO

Cardiac output

Do2

Oxygen delivery

Fio2

Fraction of inspired oxygen

HR

Heart rate

MAP

Mean arterial blood pressure

MV

Mechanical ventilation

NO

Nitric oxide

OER

Oxygen extraction ratio

Pao2

Alveolar partial pressure of oxygen

Pao2 - Pao2

Alveolar-arterial difference in partial pressure of oxygen

Petco2

End-tidal partial pressure of carbon dioxide

PiNO

Pulsed-delivered inhaled nitric oxide

Qs/Qt

Pulmonary shunt fraction

RR

Respiratory rate

Sao2

Arterial oxygen saturation

SB

Spontaneous breathing

So2

Mixed-venous oxygen saturation

Vd/Vt

Physiologic dead space-to-tidal volume ratio

Ventilation-perfusion ratio

Vt

Tidal volume

Footnotes

a.

Tafonius, Vetronic Services, Devon, England.

b.

Datex-Ohmeda AS/3-AM, Datex-Ohmeda, Helsinki, Finland.

c.

ABL 90 flex, Radiometer, Brønshøj, Denmark.

d.

NOrse, Datex-Ohmeda, Helsinki, Finland.

e.

AGA AB, Lidingö, Sweden.

f.

Microsoft Excel, version 2010, Microsoft, Redmond, Wash.

g.

GraphPad Prism, version 5, GraphPad Software Inc, La Jolla, Calif.

References

  • 1. Johnston GM, Eastment JK, Wood JLN, et al. The confidential enquiry into perioperative equine fatalities (CEPEF): mortality results of phases 1 and 2. Vet Anaesth Analg 2002;29:159170.

    • Search Google Scholar
    • Export Citation
  • 2. Dugdale AH, Obhrai J, Cripps PJ. Twenty years later: a single-centre, repeat retrospective analysis of equine perioperative mortality and investigation of recovery quality. Vet Anaesth Analg 2016;43:171178.

    • Search Google Scholar
    • Export Citation
  • 3. Whitehair KJ, Willits NH. Predictors of arterial oxygen tension in anesthetized horses: 1,610 cases (1992–1994). J Am Vet Med Assoc 1999;215:978981.

    • Search Google Scholar
    • Export Citation
  • 4. Hubbell JAE, Muir WW. Oxygenation, oxygen delivery and anaesthesia in the horse. Equine Vet J 2015;47:2535.

  • 5. Schauvliege S, Gasthuys F. Drugs for cardiovascular support in anesthetized horses. Vet Clin North Am Equine Pract 2013;29:1949.

  • 6. de Vries A, Brearly JC, Taylor PM. Effects of dobutamine on cardiac index and arterial blood pressure in isoflurane-anaesthetized horses under clinical conditions. J Vet Pharmacol Ther 2009;32:353358.

    • Search Google Scholar
    • Export Citation
  • 7. Swanson CR, Muir WW III, Bednarski RM, et al. Hemodynamic responses in halothane-anesthetized horses given infusions of dopamine or dobutamine. Am J Vet Res 1985;46:365370.

    • Search Google Scholar
    • Export Citation
  • 8. Swanson CR, Muir WW III. Dobutamine-induced augmentation of cardiac output does not enhance respiratory gas exchange in anesthetized recumbent healthy horses. Am J Vet Res 1986;47:15731576.

    • Search Google Scholar
    • Export Citation
  • 9. Briganti A, Portela DA, Grasso S, et al. Accuracy of different oxygenation indices in estimating intrapulmonary shunting at increasing infusion rates of dobutamine in horses under general anaesthesia. Vet J 2015;204:351356.

    • Search Google Scholar
    • Export Citation
  • 10. Hopster K, Wogatzki A, Geburek F, et al. Effects of positive end-expiratory pressure titration on intestinal oxygenation and perfusion in isoflurane anaesthetised horses. Equine Vet J 2017;49:250256.

    • Search Google Scholar
    • Export Citation
  • 11. Cournand A, Motley HL, Werko L, et al. Physiologic studies on the effects of intermittent positive pressure breathing on cardiac output in man. Am J Physiol 1948;152:162174.

    • Search Google Scholar
    • Export Citation
  • 12. Tyler DC. Positive end-expiratory pressure: a review. Crit Care Med 1983;11:300308.

  • 13. Shekerdemian L, Bohn D. Cardiovascular effects of mechanical ventilation. Arch Dis Child 1999;80:475480.

  • 14. Heinonen E, Hedenstierna G, Meriläinen P, et al. Pulsed delivery of nitric oxide counteracts hypoxaemia in the anaesthetised horse. Vet Anaesth Analg 2001;28:311.

    • Search Google Scholar
    • Export Citation
  • 15. Heinonen E, Nyman G, Meriläinen P, et al. Effect of different pulses of nitric oxide on venous admixture in the anaesthetized horse. Br J Anaesth 2002;88:394398.

    • Search Google Scholar
    • Export Citation
  • 16. Nyman G, Grubb TL, Heinonen E. Pulsed delivery of inhaled nitric oxide counteracts hypoxaemia during 2.5 hours of inhalation anaesthesia in dorsally recumbent horses. Vet Anaesth Analg 2012;39:480487.

    • Search Google Scholar
    • Export Citation
  • 17. Grubb T, Frendin JHM, Edner A, et al. The effects of pulse-delivered inhaled nitric oxide on arterial oxygenation, ventilation-perfusion distribution and plasma endothelin-1 concentration in laterally recumbent isoflurane-anaesthetized horses. Vet Anaesth Analg 2013;40:e19e30.

    • Search Google Scholar
    • Export Citation
  • 18. Grubb TL, Lord PF, Berger M, et al. Effects of pulse-delivered inhaled nitric oxide administration on pulmonary perfusion and arterial oxygenation in dorsally recumbent isoflurane-anesthetized horses. Am J Vet Res 2014;75:949955.

    • Search Google Scholar
    • Export Citation
  • 19. Wiklund M, Granswed I, Nyman G. Pulsed inhaled nitric oxide improves arterial oxygenation in colic horses undergoing abdominal surgery. Vet Anaesth Analg 2017;44:11391148.

    • Search Google Scholar
    • Export Citation
  • 20. Berggren SM. Oxygen deficit of arterial blood by non ventilating parts of the lung. Acta Physiol Scand 1942;4(suppl II):792.

  • 21. West JB. Ventilation-perfusion relationships. In: Respiratory physiology: the essentials. 9th ed. Philadelphia: Lippincott Williams & Wilkins, 2012;5676.

    • Search Google Scholar
    • Export Citation
  • 22. Day TK, Gaynor JS, Muir WW III, et al. Blood gas values during intermittent positive pressure ventilation and spontaneous ventilation in 160 anesthetized horses positioned in lateral or dorsal recumbency. Vet Surg 1995;24:266276.

    • Search Google Scholar
    • Export Citation
  • 23. Hodgson DS, Steffey EP, Grandy JL, et al. Effects of spontaneous, assisted, and controlled ventilatory modes in halothane-anesthetized geldings. Am J Vet Res 1986;47:992996.

    • Search Google Scholar
    • Export Citation
  • 24. Edner A, Nyman G, Essén-Gustavsson B. The effects of spontaneous and mechanical ventilation on central cardiovascular function and peripheral perfusion during isoflurane anaesthesia in horses. Vet Anaesth Analg 2005;32:136146.

    • Search Google Scholar
    • Export Citation
  • 25. Nyman G, Hedenstierna G. Ventilation-perfusion relationships in the anaesthetised horse. Equine Vet J 1989;21:274281.

  • 26. Cairo JM. Effects of positive-pressure ventilation on the pulmonary system. In: Pilbeam SP, ed. Pilbeam's mechanical ventilation—physiological concepts and clinical applications. 5th ed. St Louis: Elsevier, 2012;327352.

    • Search Google Scholar
    • Export Citation
  • 27. Neumann P, Wrigge H, Zinserling J, et al. Spontaneous breathing affects the spatial ventilation and perfusion distribution during mechanical ventilatory support. Crit Care Med 2005;33:10901095.

    • Search Google Scholar
    • Export Citation
  • 28. Wrigge H, Zinserling J, Neumann P, et al. Spontaneous breathing with airway pressure release ventilation favors ventilation in dependent lung regions and counters cyclic alveolar collapse in oleic-acid-induced lung injury: a randomized controlled computed tomography trial. Crit Care 2005;9:R780R789.

    • Search Google Scholar
    • Export Citation
  • 29. Mosing M, Senior JM. Maintenance of equine anaesthesia over the last 50 years: controlled inhalation of volatile anaesthetics and pulmonary ventilation. Equine Vet J 2018;50:282291.

    • Search Google Scholar
    • Export Citation
  • 30. Kelman GR, Nunn JF, Prys-Roberts C, et al. The influence of cardiac output on arterial oxygenation: a theoretical study. Br J Anaesth 1967;39:450458.

    • Search Google Scholar
    • Export Citation
  • 31. Gasthuys F, de Moor A, Parmentier D. Influence of dopamine and dobutamine on the cardiovascular depression during a standard halothane anaesthesia in dorsally recumbent ventilated ponies. Zentralbl Veterinarmed A 1991;38:494500.

    • Search Google Scholar
    • Export Citation
  • 32. Mizuno Y, Aida H, Fujinaga T. Effects of dobutamine infusion in dorsally recumbent isoflurane-anesthetized horses. J Equine Sci 1994;5:8794.

    • Search Google Scholar
    • Export Citation
  • 33. Young LE, Blissitt KJ, Clutton RE, et al. Temporal effects of an infusion of dobutamine hydrochloride in horses anesthetized with halothane. Am J Vet Res 1998;59:10271032.

    • Search Google Scholar
    • Export Citation
  • 34. Bryan TL, van Diepen S, Bhutani M, et al. The effects of dobutamine and dopamine on intrapulmonary shunt and gas exchange in healthy humans. J Appl Physiol 2012;113:541548.

    • Search Google Scholar
    • Export Citation
  • 35. Rennotte MT, Reynaert M, Clerbaux T, et al. Effects of two inotropic drugs, dopamine and dobutamine, on pulmonary gas exchange in artificially ventilated patients. Intensive Care Med 1989;15:160165.

    • Search Google Scholar
    • Export Citation
  • 36. Manohar M, Goetz TE. Intrapulmonary arteriovenous shunts of > 15 μm in diameter probably do not contribute to arterial hypoxaemia in maximally exercising Thoroughbred horses. J Appl Physiol 2005;99:224229.

    • Search Google Scholar
    • Export Citation
  • 37. Vizza CD, Della Rocca G, Di Roma A, et al. Acute hemodynamic effects of inhaled nitric oxide, dobutamine and a combination of the two in patients with mild to moderate secondary pulmonary hypertension. Crit Care 2001;5:355361.

    • Search Google Scholar
    • Export Citation
  • 38. Bradford KK, Bhaskar D, Pearl RG. Combination therapy with inhaled nitric oxide and intravenous dobutamine during pulmonary hypertension in the rabbit. J Cardiovasc Pharmacol 2000;36:146151.

    • Search Google Scholar
    • Export Citation

Contributor Notes

Address correspondence to Dr. Auckburally (Adam.Auckburally@scvetspecialists.co.uk).