Materials and Methods

Calves—Eight 8- to 12-week-old male Holstein calves that weighed (mean ± SD) 64 ± 15.7 kg were studied. The calves were determined to be healthy on the basis of results of physical examination, PCV, and total serum protein values. Calves were housed in facilities accredited by the Association for Laboratory Animal Care. Feed, but not water, was withheld the morning before anesthesia. The study was approved by the Washington State University Institutional Animal Care and Use Committee.

Study design—Cardiovascular variables were measured during 45 minutes of desflurane-induced anesthesia immediately prior to surgical placement of a duodenal canula and thymectomy in calves not administered preanesthetic medications. Anesthesia was induced by face mask administration of 18% desflurane^a delivered from an agent-specific vaporizer^b in O₂ with a circle breathing circuit connected to a small animal anesthesia machine^c and an O₂ flow rate of 6 L/min. The time from application of the face mask until tracheal intubation was accomplished was recorded. After tracheal intubation with a cuffed endotracheal tube, the O₂ flow rate was decreased to 2 L/min and the calf was connected to a mechanical ventilator^c that was adjusted to maintain ETCO₂ from 35 to 45 mm Hg and the peak inspiratory pressure at < 20 cm H₂O. End-tidal desflurane concentration and ETCO₂ were measured with a manually calibrated Raman scattering spectroscopic monitor.^d The calf was positioned in right lateral recumbency, and the vaporizer output was adjusted to administer 10% end-tidal concentration of desflurane for 30 minutes to permit catheterization of the auricular artery by use of an indwelling catheter^e and placement of a Swan-Ganz thermodilution catheter^f into the pulmonary artery. The 10% ET_DES was chosen because this concentration had provided a light plane of anesthesia that was suitable for catheter placement in pilot studies. All catheters were placed in the anesthetized calf without the aid of local anesthetic and by observation of strict aseptic protocol. Blood pressure was measured with a mercury-calibrated pressure transducer^g connected to a pressure module^h and monitor.ⁱ The thermodilution catheter was connected to a cardiac output module^j and monitor.ⁱ Proper positioning of the tip of the Swan-Ganz catheter within the pulmonary artery was confirmed by observation of the characteristic wave forms on the pressure monitor. Cardiac output was determined as the mean of 3 measurements at each time point by use of 5 mL of 5% dextrose maintained at 0°C. After instrumentation was completed, administration of desflurane was temporarily discontinued until mean arterial pressure increased to at least 100 mm Hg, at which time baseline values for direct systolic, diastolic, and mean arterial blood pressures; cardiac output; mean pulmonary artery pressure; pulmonary arterial occlusion pressure; central venous pressure; heart rate; and pulmonary arterial temperature were recorded. Arterial blood was collected and stored on ice for subsequent temperature-corrected measurement of pH, PCO₂, and PO₂ and calculation of HCO₃, total CO₂ concentration, and base excess by use of a blood gas machine^k that was validated for use in ruminants. After baseline values were recorded, vaporizer output was increased to administer 10% ET_DES.

Cardiovascular variables were recorded at 5, 10, 15, 30, and 45 minutes after collection of baseline data. Arterial blood was collected and stored on ice 15 and 45 minutes after baseline data collection. Cardiac index was calculated as follows:

View Expanded

where CO is cardiac output (L/min). Systemic and pulmonary vascular resistances were calculated as follows:

SVR (dynes•seconds•cm⁻⁵) = (mean arterial pressure [mm Hg] – central venous pressure [mm Hg]/CO) × 80

PVR (dynes•seconds•cm⁻⁵) = (mean PAP [mm Hg]) – pulmonary capillary wedge pressure [mm Hg]/CO) × 80

After data collection, desflurane administration was discontinued and anesthesia was maintained with isoflurane during the surgical preparation and procedure. Butorphanol (0.125 mg/kg, IM) was administered prior to recovery to provide postoperative analgesia.

Statistical analysis—Data are reported as mean ± SD values. Differences from baseline values were determined via 1-way ANOVA for repeated measures; post hoc differences between mean values were identified via the Bonferroni method. Values of P < 0.05 were considered significant.^l

Results

Mean time from the start of desflurane anesthesia until tracheal intubation was 151 ± 32.8 seconds. The rapid induction of anesthesia observed with administration of 18% desflurane was uniformly smooth and not accompanied by struggling. The ET_DES during recording of baseline values was 3.4 ± 2.48%, and mean ET_DES throughout the remainder of the study period was 10.0 ± 0.76%. Mean ETCO₂ ranged from 34 ± 3.6 mm Hg to 43 ± 8.4 mm Hg. All calves recovered from anesthesia and surgery without complications. Times to sternal recumbency and standing after termination of desflurane administration were not recorded.

Systolic, mean, and diastolic arterial blood pressures decreased significantly from 5 through 30 minutes after administration of 10.0% ET_DES, compared with baseline (Table 1). Arterial pressures decreased precipitously 5 minutes after collection of baseline values and reinstitution of 10% ET_DES, before gradually returning to baseline values at 45 minutes. Systemic vascular resistance decreased significantly from a baseline value of 1,085 ± 116 dynes•seconds•cm⁻⁵ to a low of 720 ± 84 dynes•seconds•cm⁻⁵ at 15 minutes, before returning to baseline values at 30 minutes. Pulmonary arterial blood temperature was decreased from 15 through 45 minutes relative to baseline. Arterial bicarbonate concentration was decreased at 45 minutes, compared with baseline values. Heart rate, PAP, pulmonary arterial occlusion pressure, pulmonary vascular resistance, central venous pressure, CI, arterial pH, P_aCO₂, PaO₂, and base excess were not significantly altered during administration of 10.0% ET_DES, compared with baseline.

Discussion

Induction of anesthesia was rapid and quite smooth in these calves. Face mask induction was easily accomplished because struggling or breath holding was not observed. The induction technique afforded excellent conditions for intubation; laryngospasm was not observed, and tracheal intubation was easily accomplished. Despite the low blood solubility of desflurane, there was adequate time to perform tracheal intubation and repeated application of the face mask was not necessary. Maintenance of anesthesia with 10% desflurane was associated with hemodynamic stability and lack of response to placement of the arterial catheter, jugular vein introducer set, and Swan-Ganz catheter. Although 10% ET_DES provided adequate conditions for instrumentation, it must be noted that the MAC value for desflurane has not been reported for calves or adult cattle and that desflurane MAC was not determined in this study. The ET_DES selected in this study (10%) was chosen on the basis of the presence of a slight palpebral reflex, lack of movement, and lack of blood pressure responses to surgical stimulation during pilot studies. Reported values for desflurane MAC range from 7.2% in dogs⁵ and 7.6% in horses⁶ to 9.5% in sheep^m and 10.0% in pigs.⁷ Halothane MAC for calves (0.76%)⁸ is lower than that for sheep (0.97%),⁹ so it is not unreasonable to speculate that the MAC value of desflurane for calves might be lower than the comparable value for sheep and might be similar to the values reported for dogs and horses. Because the MAC value for an inhalant anesthetic represents the alveolar concentration at which half the population is nonresponsive to a noxious stimuli, alveolar concentrations that permit surgical manipulations are usually 20% to 40% greater than the MAC.¹⁰ The 10% end-tidal concentration chosen in this study to provide a light plane of anesthesia in calves not administered preanesthetic sedation is approximately 30% greater than the MAC value of desflurane for horses or dogs and thus appears to substantiate this reasoning.

Baseline values were recorded after administration of desflurane had been temporarily discontinued and calves had partially recovered as indicated by their mean arterial blood pressure reaching at least 100 mm Hg. This criterion for collection of baseline values was chosen because it appeared to be an acceptable alternative during an experimental surgical procedure, compared with allowing calves to recover fully from the effects of desflurane followed by a second induction of anesthesia, and because precedent for this technique exists in the literature.^11,12

Observed changes in cardiopulmonary variables were reported in comparison to baseline values obtained when calves were allowed to awaken from desflurane anesthesia under conditions of spontaneous ventilation. Calves were in a very light plane of anesthesia during the baseline recordings as indicated by spontaneous movement and the need to lightly restrain the calf to prevent self-injury and dislodgement of instruments. Because baseline recordings were obtained during recovery from desflurane anesthesia and not during a constant ET_DES, it is possible that the baseline values were influenced by increased circulating catecholamine concentrations. However, cardiovascular values recorded during recovery from desflurane anesthesia in this study were quite similar to values recorded from healthy awake calves of a similar age.¹³ The mode of ventilation (controlled vs spontaneous) is known to have a profound impact on recorded cardiovascular variables. In a recent study³ conducted in desflurane-anesthetized horses, values of cardiovascular variables during conditions of controlled ventilation were always less than that during spontaneous ventilation. In addition to the effect on baseline cardiovascular data, the addition of controlled ventilation to desflurane anesthesia may be expected to suppress cardiovascular variables to a greater degree than would occur with spontaneous ventilation.

Mean arterial pressure decreased from 107 ± 15.4 mm Hg at baseline to 70 ± 11.4 mm Hg 5 minutes after reinstitution of 10% ET_DES, before gradually increasing to 89 ± 19.4 mm Hg at 45 minutes. A similar hypotensive effect has been observed during face mask induction of calves with sevoflurane¹¹ and dogs with isoflurane.ⁿ In both studies, arterial pressure decreased precipitously during the first 5 minutes of the mask induction and then increased toward baseline. This immediate hypotensive effect is consistent with that reported in rats administered isoflurane.¹⁴ The effect reported in rats is biphasic; a precipitous initial decrease is followed by a rapid return toward baseline. The initial rapid decline is prevented by pretreatment with the narcotic antagonist naloxone, suggesting that release of endogenous opioids is a mechanism by which isoflurane induces hypotension. Whether or not release of endogenous opioids is associated with the initial hypotensive effect of inhalant anesthetics in calves and dogs remains to be studied. In addition to the possible involvement of endogenous opioid release during induction of anesthesia, reduction of CNS sympathetic outflow is likely a contributing factor to the initial period of hypotension. A study investigating the cardiovascular effects of desflurane and sevoflurane in dogs determined that both agents were associated with reductions in left ventricular afterload, albeit by different mechanisms. Desflurane reduces left ventricular afterload by decreasing peripheral arteriolar tone, whereas sevoflurane causes a reduction in left ventricular afterload by reduction in aortic compliance.¹⁵

Cardiac index decreased from 124 ± 40.6 mL/kg/min at baseline to 107 ± 32.6 mL/kg/min 5 minutes after reinstitution of 10% ET_DES, before returning to baseline values (124 ± 41.7 mL/kg/min) at the 15-minute recording. Similar to the pattern observed with mean arterial pressure, the lowest values for CI were recorded during the period immediately after reinstitution of 10% ET_DES. Unlike values for mean arterial pressure, however, the changes in CI were not significant. These values were higher than those reported for calves anesthetized with 1.5 MAC halothane⁸ and in calves anesthetized with 3.7% end-tidal concentration of sevoflurane.¹¹ In humans, desflurane does change cardiac index, left ventricular ejection fraction, or the velocity of left ventricular circumferential fiber shortening, as assessed by echocardiography,¹⁶ suggesting that desflurane induces less suppression of myocardial contractility than other halogenated agents.¹⁷ Further evidence for the maintenance of cardiac output during desflurane anesthesia is given in a study by Steffey et al,³ who reported that the CI recorded from horses at 1.0 MAC of desflurane during conditions of controlled ventilation was near values reported for awake horses breathing O₂.

A decrease in mean arterial pressure coupled with no significant decrease in CI suggests a decrease in SVR. Indeed, 10% ET_DES was associated with a decrease in SVR, compared with baseline values at 5, 10, and 15 minutes. The reduction in SVR is consistent with a report in long-term–instrumented swine in which a decrease in SVR occurred as the MAC of desflurane was increased.¹⁸ The reduction in SVR most likely reflects decreased arteriolar tone resulting from decreased central sympathetic activity.

Mean values for PAP remained similar to baseline values throughout the study. The PAP values recorded in these calves anesthetized with 10% ET_DES were similar to values obtained from calves anesthetized with 1.5 MAC halothane.⁸

It is interesting to compare results obtained in this study with results of a study in which calves of similar age were anesthetized with 3.7% end-tidal concentration of sevoflurane by use of an identical protocol in the same laboratory.¹¹ It is important to note that when making comparisons between these 2 studies, the MAC values for desflurane and sevoflurane are not known in calves. It is therefore not possible to state that equivalent depths of anesthesia were achieved with 10% and 3.7% end-tidal concentrations of desflurane and sevoflurane, respectively, although similar methodology was used in both studies.

Heart rates of the calves in the sevoflurane study¹¹ ranged from 69 ± 10.6 beats/min to 74 ± 11.3 beats/min, whereas heart rates of calves in this desflurane study were higher and ranged from 84 ± 23.2 beats/min to 90 ± 33.1 beats/min. In long-term–instru-mented swine, 1.0 MAC of desflurane was associated with a higher heart rate, compared with 1.0 MAC of isoflurane.¹⁷ The differences in heart rates between the 2 studies may be related to the changes in blood pressure or may reflect an effect of the inhalants on the sympathetic nervous system. In healthy, young human volunteers, 1.0 to 1.5 MAC of desflurane was associated with hypertension and tachycardia, leading to the suggestion that, in humans, desflurane may have an effect on the sympathetic nervous system.¹⁹ Lastly, it must be remembered that because the MAC values of sevoflurane and desflurane in calves are unknown, the depths of anesthesia in the sevoflurane study and present study were likely different and thus would be expected to have an effect on the arterial pressures.

Mean arterial pressure in the sevoflurane study¹¹ ranged from 112 ± 16.1 mm Hg at baseline to 88 ± 10.5 mm Hg at 5 minutes after reinstitution of 3.7% end-tidal concentration of sevoflurane. Mean arterial pressures recorded from calves in the present study were lower and ranged from 107 ± 15.4 mm Hg at baseline to 70 ± 11.4 mm Hg at the 5-minute recording. Although values for arterial pressures were lower in this study, the lowest values recorded were within a clinically acceptable range.

The CI of calves administered 3.7% end-tidal concentration of sevoflurane remained stable during the study and ranged from 91 ± 30.8 mL/kg/min at baseline to a low of 89 ± 23.5 mL/kg/min at 5 minutes. Cardiac indices measured from the calves in the present study were higher and ranged from 124 ± 40.6 mL/kg/min at baseline to 107 ± 32.6 mL/kg/min. Although CI values were higher in calves administered desflurane, the actual percentage decrease from the peak value at baseline to the lowest value recorded was greater in this desflurane study (14%), compared with the sevoflurane study (2%). Values for SVR, PAP, pulmonary capillary wedge pressure, and PVR were similar between the 2 studies.

Although 10% ET_DES provided a light plane of anesthesia that was adequate for jugular and auricular catheter placement, surgical procedures were not attempted because anesthesia was maintained with isoflurane for the surgical procedure that followed data collection. This change of inhalant anesthetics was made for economic reasons. Because the MAC value for desflurane in calves is unknown and was not determined during this study, it is possible that the calves were at a lighter plane of anesthesia than is required to permit invasive surgical procedures. As the inspired concentration of desflurane is increased to deeper planes of surgical anesthesia, one would expect an increased suppression of cardiovascular performance. Although measurement of end-tidal anesthetic agents is an accepted method of assessing delivered anesthetic concentrations, increased dead-space ventilation or substantial mismatching of ventilation to perfusion within the lung can be a source of measurement error. However, significant differences in ETCO₂ or P_aCO₂ values were not detected during the study, and differences between values for ETCO₂ and P_aCO₂ were similar throughout the study. Although consistency between measured values for ETCO₂ and P_aCO₂ throughout the study does not eliminate the possibility of ventilation-perfusion mismatching as a source of measurement error for an inhalant anesthetic, this consistency does provide some measure of reassurance that substantial dead-space ventilation did not occur during the study period.

In the present study, administration of desflurane was associated with rapid and smooth induction of anesthesia and afforded excellent conditions for tracheal intubation. The lower blood solubility of desflurane results in a more rapid face mask–induction-intubation sequence, compared with other inhalant anesthetics such as halothane or even sevoflurane. Cardiovascular effects in calves were similar to those of other inhalant anesthetics such as sevoflurane and halothane. In addition, desflurane is highly inert and undergoes the least biodegradation of any currently available inhalant anesthetic. Low biodegradation is important in animals with impaired hepatic function and may be critical in many research applications.