Desflurane, a new fluorinated ether, is chemically similar to isoflurane except for the substitution of a fluorine for a chlorine atom on the alpha-ethyl carbon. Although the irritant effects of desflurane are recognized [1,2], it has been accepted generally that the cardiovascular changes are mild and similar to those of isoflurane [3-5].
Recently, inspired concentrations of desflurane greater than 1 minimum alveolar anesthetic concentration (MAC) have been shown to produce significant tachycardia and hypertension, with a marked increase in plasma catecholamines [6,7]. A study by Ebert and Muzi  showed a significant difference in cardiovascular response between isoflurane and desflurane upon increasing the inspired drug concentration from 1.0 to 1.5 MAC. At 1.5 MAC, desflurane produced greater sympathetic nerve activity, tachycardia, and hypertension compared with isoflurane. In patients undergoing coronary artery bypass graft surgery, a significant increase in heart rate and systemic and pulmonary arterial pressures was shown in patients exposed to desflurane compared with sufentanil . In the same study, myocardial ischemia was significantly more common at induction in the desflurane group.
After a rapid increase in concentration, desflurane appears to cause profound sympathetic stimulation by a mechanism as yet unknown. It has been suggested that the pungent and irritant properties of desflurane may cause airway irritation thus stimulating a sympathetic response [6-8]. Intravenous lidocaine suppresses coughing and the cardiovascular response to airway stimulation [10-12]. The aim of this study was to determine the effects of intravenous lidocaine on the cardiovascular and catecholamine response to a rapid increase in desflurane concentration.
After permission from the local ethics committee, 20 unpremedicated patients were studied. Patients conformed to ASA grades I and II, with body weights between 50 and 100 kg and between 18 and 60 yr old. After we obtained written, informed consent, patients were randomly allocated into a control group (C), and a lidocaine group (L) using a sealed envelope technique. Those taking regular medication or drugs known to modify catecholamine metabolism or uptake were excluded. Patients were not allowed to smoke or to drink coffee or alcohol for 24 h before anesthesia.
Thirty minutes before induction of anesthesia, an 18-gauge cannula was inserted into a forearm vein and a 22-gauge cannula into a radial artery. After this period of quiet, supine acclimatization, a blood sample was taken for catecholamine analysis through the arterial cannula. This consisted of 10 mL of blood taken into a lithium heparin glass tube containing 5 mg of sodium metabisulphite as an antioxidant. The sample bottles were placed in a container of ice and delivered to the laboratory where they were centrifuged. The plasma was then decanted into a plastic tube and stored at -70 degrees C. Analysis by high-pressure liquid chromatography was performed within 8 wk.
Monitoring included electrocardiogram, peripheral oxygen saturation, end-tidal carbon dioxide, end-tidal desflurane, and arterial blood pressure recorded every half minute for the duration of the study. Anesthesia was induced using intravenous propofol 2 mg/kg and muscle relaxation produced by intravenous vecuronium bromide 0.1 mg/kg. Using a face mask, ventilation of the patient to normocarbia was achieved with desflurane 0.7 MAC and oxygen FIO2 1.0. This was continued until an end-tidal desflurane concentration of 0.7 MAC was achieved. A blood sample was then taken for catecholamine analysis. In Group L, lidocaine 1.5 mg/kg was given intravenously over 1 min. This dose results in plasma lidocaine levels greater than 3 micro gram/mL for 5 min after administration . These levels significantly suppress cough reflexes after tracheal irritation and intubation [10,12], while a lower dose of 1 mg/kg suppresses cardiovascular responses to tracheal intubation . Group C received a similar volume of 0.9% sodium chloride solution intravenously. These solutions were prepared and coded by a colleague who took no further part in the study. The concentration of desflurane was then abruptly increased to 1.5 MAC. Every minute for 5 min after the increase in desflurane concentration, arterial blood samples were taken for catecholamine analysis. Other observations, such as lacrimation, salivation, bronchospasm, and airway obstruction were noted. Having completed the study period, the trachea was intubated, and anesthesia continued in the normal fashion.
Patient characteristics were compared using unpaired t-test. Catecholamine responses between groups were compared using Mann-Whitney U-test. Changes over time within each group were analyzed using one-way analysis of variance for repeated measurements, and paired t-test for specific times. A P value of less than 0.05 was considered significant.
Each group consisted of 10 patients with no significant differences found between them with regard to gender, age, or weight. The mean +/- SD age was 33 +/- 11 yr in Group C and 40 +/- 11 yr in Group L. The mean +/- SD weight was 63 +/- 11 kg in Group C and 72 +/- 16 kg in Group L. There was no significant difference between groups in the end-tidal concentration of desflurane, with 1.5 MAC achieved 2 min after the increase in drug concentration. A significant increase in heart rate and mean arterial pressure occurred in both groups upon increasing desflurane concentration to 1.5 MAC (P < 0.05) Table 1. In Group L, the increase in heart rate was significantly less compared to Group C from 0.5 until 2.5 min after the increase in desflurane concentration (P < 0.05). The mean arterial pressure was significantly different between groups only at 4.5 and 5 min, with higher values recorded in Group L (P < 0.05).
Compared with the value at 0.7 MAC, plasma epinephrine was significantly increased at 1 and 3 min in group C (P < 0.05), and at 3, 4, and 5 min in Group L (P < 0.01). Plasma norepinephrine was significantly increased in both groups, compared with the value at 0.7 MAC, throughout the 5-min period after increased desflurane concentration (P < 0.05). However, there was no significant difference in plasma catecholamines between the groups at any time Figure 1 and Figure 2.
Lacrimation occurred in seven patients (three in Group C and four in Group L), and salivation occurred in 12 patients (five in Group C and seven in Group L).
The cardiovascular response to an increase in desflurane concentration has been obtunded by fentanyl, clonidine, and esmolol [13-15]. However, this merely represents action on the efferent limb of the reflex and fails to elucidate the cause. By anesthetizing the airways, a potential afferent pathway could be interrupted. Muzi et al.  have attempted this in a study involving nerve blocks, transtracheal injection and nebulized lidocaine. Sympathetic activity was estimated using peroneal nerve microneurography. They found no attenuation of the sympathetic response and suggested that more distal (unanesthetized) airway sites or direct central nervous system stimulation was the cause. By producing a more predictable increase in plasma levels of local anesthetic, intravenous lidocaine provides a more reliable method of anesthetizing the distal airways.
The increase in heart rate, mean arterial pressure, and catecholamines, which we found after the introduction of desflurane 1.5 MAC, confirms the sympathetic response observed in previous studies [6-8]. The increase in heart rate in Group L was significantly less than in Group C. These observations may be due to the fact that lidocaine has a bradycardic effect. In addition, intravenous lidocaine produces a decrease in myocardial contractility at a dose of 2 mg/kg and an increase at a dose of 1 mg/kg . This may explain the significantly higher mean arterial pressure in Group L at 4.5 and 5 min. There was no statistically significant difference between the groups with regard to plasma catecholamines. These observations would indicate that anesthesia of the airways does not attenuate the sympathetic response to a rapid increase in desflurane concentration. The results are in keeping with those observed by Muzi et al. .
We recognize that the number of patients studied is relatively small. However, the nature of the cardiovascular changes observed prompted early analysis of the results and conclusion of the study.
In conclusion, this study does not show any attenuation of the potent sympathetic activity after a rapid increase in desflurane concentration. It is therefore unlikely that airway irritation represents the afferent limb of this response. One possible explanation of these effects is a direct action on the vasomotor center itself. Further research should be directed toward the discovery of this unknown mechanism.
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