Because desflurane has a low blood/gas solubility, it may be useful for neurosurgical procedures that require rapid induction, rapid emergence and quick adjustments of anaesthetic depth in response to surgical stimuli. However, in healthy volunteers, desflurane has been reported to cause sympathetic hyperactivity during induction resulting in tachycardia and hypertension . No comparable cardiovascular effects were measured in a group anaesthetized with isoflurane.
Fentanyl has been reported to blunt tachycardia and hypertension caused by desflurane . Sufentanil, with favourable pharmacokinetics for operations up to 5–6 h, has been demonstrated to attenuate haemodynamic responses to surgical stimuli. Furthermore sufentanil may decrease cerebral blood flow (CBF) as well as cerebral oxygen consumption [3,4]. The changes in CBF correlated with changes in CBF velocity, thus permitting acute monitoring of the effects of sufentanil using transcranial Doppler ultrasonography (TCD) .
Volatile anaesthetics such as isoflurane tend to increase CBF and CBF velocity at concentrations exceeding 1 MAC if arterial blood pressure is maintained constant [6,7]. Compared with other volatile anaesthetics, desflurane has a more rapid cerebral wash-in and wash-out as demonstrated by nuclear magnetic resonance spectroscopy . In dogs cerebrovascular resistance was reduced at desflurane concentrations exceeding 1 MAC . Accordingly CBF was increased at these concentrations if arterial blood pressure was maintained. These data suggest that desflurane is a cerebral vasodilator comparable with other volatile anaesthetics. However, it is not known whether the acute systemic haemodynamic effects of desflurane aggravate the cerebrovascular effects.
The aim of this study was to examine the effect of sufentanil and N2O as an adjunct to desflurane anaesthesia in a setting closely resembling that found in clinical practice. Our hypothesis was that sufentanil and N2O would reduce the systemic haemodynamic effects caused by induction with desflurane and would attenuate the effects of desflurane on CBF velocity as determined by TCD.
The study was performed after approval by the local ethics committee and after written informed consent was obtained from 18 patients scheduled for minor abdominal surgery. The patients ranged in age from 21 to 65 years and were physical status ASA Grade I or II. None of the patients had respiratory, cardiovascular, cerebrovascular, or intracranial pathology. Further exclusion criteria were pregnancy, predisposition to malignant hyperthermia, allergies and the pre-operative use of vasoactive or psychoactive medication. All patients were assigned to receive either desflurane in O2 without opioid (group 1; n = 9) or desflurane in O2/N2O plus sufentanil (group 2; n = 9) in a prospective randomized fashion.
Anaesthetic management was performed following a protocol previously published by Ebert and Muzi . Patients were premedicated with midazolam 7.5 mg p.o. 30 min before anaesthesia. After placing the patients in the supine position and obtaining baseline haemodynamic and TCD recordings a priming dose of vecuronium (0.03 mg kg−1 i.v.) was administered followed by induction of anaesthesia using etomidate (0.2 mg kg−1 i.v.) and vecuronium (0.07 mg kg−1 i.v.) (group 1) or etomidate (0.2 mg kg−1), sufentanil (0.3 μg kg−1) and vecuronium (0.07 mg kg−1) (group 2). A facemask was applied and patients were ventilated for 12 min before endotracheal intubation. Patients in group 1 were ventilated using O2 for 2 min before administration of desflurane. Then the concentration of desflurane was adjusted to 0.5 MAC (3.6 vol%) for 1 min, followed by 1.0 MAC (7.2 vol%) for 1 min and finally by 1.5 MAC (10.8 vol%) for another 7 min. In group 2, patients inhaled a mixture of N2O 67% and oxygen 33% for 2 min before administration of desflurane at the same MAC equivalents and time intervals. In the presence of nitrous oxide 0.5 MAC equalled 2.1 vol%; 1.0 MAC, 4.2 vol% and 1.5 MAC, 6.3 vol% desflurane. Care was taken to manually ventilate the patient's lungs so that the end-tidal CO2 (PETCO2) was maintained constant throughout the study period and was comparable between patients. Target PETCO2 for manual ventilation was 4.8 kPa. Infrared capnography was used to measure PETCO2 and N2O concentrations at the Y-piece of the anaesthetic circuit (AS/3™, Datex, Helsinki, Finland). All patients were normothermic. Routine monitoring included electrocardiogram (leads II and V5), noninvasive blood pressure and pulse oximetry. Continuous TCD of the middle cerebral artery (MCA) was performed by placing a 2 MHz Doppler monitoring probe (Neuroguard™, Medasonics, Fremont, CA) either at the right or left 'transtemporal window'. MCA insonation was started at a depth of 45 mm and confirmed by increasing insonation depth until a bidirectional flow signal could be detected, indicating the bifurcation of the internal carotid artery into the anterior communicating artery and the MCA. Insonation depth was then reduced until a maximum signal from the proximal segment of the MCA was received. The probe was placed while the patient was awake and was not changed thereafter, thus ensuring that the angle of insonation remained constant throughout the study period. The Doppler probe was fixed using a clamp provided by the manufacturer of the Doppler device.
Base-line readings included heart rate (HR), systolic, diastolic, and mean arterial blood pressure (SAP, DAP, MAP, respectively), peripheral oxygen saturation (SpO2), PETCO2, mean MCA blood flow velocity (VmMCA) and systolic MCA blood flow velocity (VsMCA). During the course of induction, haemodynamic data were obtained every minute. Base-line TCD recordings were determined within at least 3 min and averaged. To avoid the influence of endotracheal intubation and surgical stimulation, the study was completed before endotracheal intubation was performed.
For each minute, data were pooled and expressed as mean ± standard error of mean (SEM). Comparison of data was performed using analysis of variance for repeated measures (Anova), comparing the two treatment groups over time. Data within groups were then analysed by Student's t-test applying the Simes-Hochberg correction for reduction of type I errors . A P-value of less than 0.05 was considered significant. Intergroup differences were analysed using Student's t-test for unpaired samples.
The two groups of patients did not differ significantly in demographic data (Group 1: age: 47 ± 4.7 years; weight: 65 ± 2.5 kg; five female, four male; group 2: age: 48 ± 5.7 years; weight: 64 ± 2.7 kg; four female, five male). During desflurane administration, peak end-tidal concentrations were 9.2 ± 0.4 vol% in group 1 and 5.5 ± 0.2 vol% in group 2 (Fig. 1). In both groups, PETCO2 was maintained constant throughout the study period and mean PETCO2 did not differ between groups (group 1: 4.7 ± 0.1 kPa; group 2: 4.6 ± 0.2 kPa). Of the nine patients receiving just desflurane, five showed lacrimation as well as facial flush after desflurane was added whereas no patient in the desflurane, N2O and sufentanil group showed such symptoms. None of the patients in either group 1 or group 2 showed signs of upper airway obstruction or bronchospasm.
Base-line haemodynamic data were similar in both groups. After induction with etomidate and vecuronium in group 1, mean HR and MAP were slightly but not significantly higher in this group as compared with group 2 receiving etomidate, vecuronium and sufentanil (HR: group 1, 79 ± 4 b.p.m.; group 2, 72 ± 5 b.p.m.; MAP: group 1, 86 ± 4 mmHg; group 2, 82 ± 4 mmHg). In group 1 HR increased significantly in comparison with base-line 8 min after administration of desflurane (peak HR: 108 ± 2 b.p.m.) and remained different up to the end of the study period. However, no significant variations in HR occurred in group 2 (Fig. 2 a, b). Values of MAP, SAP, and DAP changed similar to HR. MAP increased significantly 6 min after desflurane administration in group 1 (peak MAP: 114 ± 6 mmHg) followed by a reduction after 8 min (Fig. 2) whereas no changes in MAP were seen in group 2.
It was possible to obtain TCD recordings in all subjects. Base-line values of both groups of patients did not vary significantly (VmMCA group 1: 51 ± 4 cm s−1; group 2: 46 ± 5 cm s−1). In both groups VmMCA increased after administration of desflurane. In group 1, the increase in VmMCA (peak VmMCA: 86 ± 7 cm s−1) paralleled the increase in HR and MAP (Fig. 3 and 4). However, although in group 2 HR and MAP did not increase, VmMCA demonstrated an increase compared with group 1 (peak VmMCA: 73 ± 5 cm s−1) being significantly different from base-line values after 7 min.
The present study examined the effects of desflurane induced haemodynamic changes on CBF velocity. Furthermore the effect of administration of sufentanil and N2O in addition to desflurane was determined by measuring systemic haemodynamic variables as well as CBF velocity. The results of the study demonstrate (1) that desflurane induced systemic haemodynamic changes can be reduced by addition of sufentanil and N2O under clinical conditions, (2) that desflurane induced tachycardia and hypertension are paralleled by an increase in CBF velocity, and (3) that administration of sufentanil and N2O blunts but does not abolish desflurane-induced increases in CBF velocity. However, the blunted CBF velocities in the group receiving sufentanil and N2O may be a result of the reduction in desflurane concentrations although similar MAC equivalents were used.
The pharmacokinetics of desflurane render this new volatile anaesthetic suitable for a wide variety of surgical procedures. Desflurane has been reported to provide haemodynamic control similar to isoflurane. Thus, the use of desflurane permits maintenance and quick adjustment of deliberate hypotension. However, during induction in healthy volunteers the administration of desflurane has been associated with tachycardia and hypertension, a reaction which is not seen during isoflurane induction and which may be because of activation of different sites in lung and systemic tissues [1,11]. The results of the present study confirm these findings even under clinical conditions. The patients studied varied in age from 21 to 65 years, including patients older than the volunteers studied by Ebert and Muzi . Furthermore the data show that the combination of sufentanil and N2O is a useful adjunct to desflurane anaesthesia since it effectively blunts the systemic haemodynamic responses induced by higher concentrations of desflurane. Thus greater haemodynamic stability is achieved during desflurane induction reducing risks associated with tachycardia and hypertension.
A variety of adjuvants including clonidine, esmolol and fentanyl, have been used to blunt desflurane induced tachycardia and hypertension [2,12]. Fentanyl reduced the peak HR increase by 70 ± 7% and the peak MAP increase by 46 ± 11%; however, no reduction in catecholamine levels was measured . Alfentanil effectively blunted the haemodynamic changes during desflurane administration but did not reduce desflurane induced sympathetic activity . Sufentanil allowed more rapid recovery than fentanyl and alfentanil especially in surgical procedures of 5–6 h in duration . The effect of sufentanil during anaesthesia maintained with desflurane has not been reported previously. In a study comparing the incidence of myocardial ischaemia during coronary artery bypass grafting in patients receiving either desflurane or sufentanil anaesthesia, desflurane was associated with more haemodynamic changes and myocardial ischaemia than sufentanil during induction . Opioids decrease central sympathetic outflow  and decrease HR during inhalational anaesthesia . These findings are consistent with data presented in this study showing a decrease in HR and MAP in the group receiving sufentanil before administration of desflurane (Fig. 2 a, b).
The central nervous system effects of desflurane have been reviewed extensively . Recently, it was shown that the ability of desflurane to produce suppression of the electroencephalogram (EEG) is similar to that of isoflurane . Results of various studies indicate that desflurane is a cerebral arteriolar vasodilator similar to other volatile anaesthetics. Cerebral oxygen consumption is reduced during desflurane anaesthesia and there is evidence that CO2 reactivity is maintained . Findings on the effect of desflurane on intracranial pressure (ICP) are still controversial. However, since desflurane is a cerebral vasodilator it is not an anaesthetic of first choice in patients presenting with increased ICP . In patients with intracerebral mass lesions, an increase of cerebrospinal fluid pressure (CSFP) was measured after administration of 1 MAC desflurane whereas no change in CSFP was determined using isoflurane .
The ability to assess CBF changes by noninvasive techniques, for example, measurement of CBF velocity by TCD, is still a matter for discussion. Several studies reported a close correlation between changes in CBF and VmMCA under various physiological and pharmacological conditions [5,22]. However, CBF values cannot be inferred using TCD because the diameter of the insonated vessel is unknown. Moreover the correlation of CBF and VmMCA may be altered by changes in vessel diameter. During isoflurane anaesthesia, increases in the diameter of basal cerebral arteries have been demonstrated, leading to an under-estimation of CBF increase . However, others have reported that CBF measures correlated well with CBF velocity during isoflurane anaesthesia . Recently, it was shown that cerebral autoregulation is impaired by isoflurane and desflurane. At a concentration of 0.5 MAC, isoflurane delayed the autoregulatory response of the cerebral vessels in reaction to a decrease in MAP whereas desflurane delayed and reduced autoregulation. At concentrations of 1.5 MAC, both isoflurane and desflurane ablated cerebral autoregulation . These data are consistent with the findings in the present study. The desflurane-induced increase in MAP in group 1 was associated with an increase in VmMCA up to the end of the study period although only transient changes would be expected if cerebral autoregulation was functional. Furthermore, addition of sufentanil and N2O did not ablate the effects of desflurane, although the systemic haemodynamic response to desflurane was blunted (Fig. 2 a, b). However, the increase in VmMCA was less in group 2 compared with group 1 (Fig. 4). A possible explanation is presented in Fig. 1. The desflurane induced increase in VmMCA may be concentration dependent. Although patients in group 2 received the same MAC equivalent of desflurane as did patients in group 1 the absolute concentration administered was about 1.7 times lower in this group. Further studies determining CBF velocity at various concentrations are needed in order to confirm this finding.
Data on the effect of sufentanil on CBF and CBF velocity are inconsistent. Sufentanil and fentanyl increased CBF velocity under clinical conditions without showing differences in the cerebral haemodynamic profiles of the two drugs . In contrast, CBF was not changed after administration of sufentanil in healthy volunteers . In patients with brain injury no differences in CBF velocity were determined in a group receiving sufentanil . Addition of N2O may have potentiated the increase in VmMCA in group 2, as demonstrated, for example, during isoflurane anaesthesia . N2O causes increases in CBF if administered alone , however, in combination with i.v. anaesthetics, opioids, or premedication with benzodiazepines the effect of N2O was reduced .
In conclusion the results of this study demonstrate that desflurane induced haemodynamic responses can be blunted by the administration of sufentanil and N2O. Thus patients at risk for myocardial ischaemia may benefit using this approach. However, desflurane increased CBF velocity and although an attenuation was observed by addition of sufentanil and N2O, desflurane should be used with care in patients with intracranial pathology.
1 Ebert TJ, Muzi M. Sympathetic hyperactivity during desflurane
anesthesia in healthy volunteers. A comparison with isoflurane. Anesthesiology
2 Weiskopf RB, Eger Ed, Noorani M, Daniel M. Fentanyl, esmolol, and clonidine blunt the transient cardiovascular stimulation induced by desflurane
in humans. Anesthesiology
3 Scholz J, Bause H, Schulz M et al.
Pharmacokinetics and effects on intracranial pressure of sufentanil
in head trauma patients. Br J Clin Pharmcol
4 Werner C, Kochs E, Bause H, Hoffman WE, Schulte am Esch J. Effects of sufentanil
on cerebral hemodynamics and intracranial pressure in patients with brain injury. Anesthesiology
5 Werner C, Hoffman WE, Baughman VL, Albrecht RF, Schulte am Esch J. Effects of sufentanil
on cerebral blood flow, cerebral blood flow velocity
, and metabolism in dogs. Anesth Analg
6 Kochs E, Hoffman WE, Werner C, Albrecht RF, Schulte am Esch J. Cerebral blood flow velocity
in relation to cerebral blood flow, cerebral metabolic rate for oxygen, and electroencephalogram analysis during isoflurane anesthesia in dogs. Anesth Analg
7 Schregel W, Schaefermeyer H, Sihle-Wissel M, Klein R. Transcranial Doppler sonography during isoflurane/N2O anaesthesia and surgery: flow velocity, 'vessel area' and 'volume flow'. Can J Anaesth
8 Lockhart SH, Cohen Y, Yasuda N et al.
Cerebral uptake and elimination of desflurane
, isoflurane, and halothane from rabbit brain: an in vivo
NMR study. Anesthesiology
9 Lutz LJ, Milde JH, Milde LN. The cerebral functional, metabolic, and hemodynamic effects of desflurane
in dogs. Anesthesiology
10 Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika
11 Weiskopf RB, Eger EI, Daniel M, Noorani M. Cardiovascular stimulation induced by rapid increases in desflurane
concentration in humans result from activation of tracheopulmonary and systemic receptors. Anesthesiology
12 Devcic A, Muzi M, Ebert TJ. The effects of clonidine on desflurane
-mediated sympathoexcitation in humans. Anesth Analg
13 Yonker-Sell AE, Muzi M, Hope WG, Ebert TJ. Alfentanil modifies the neurocirculatory responses to desflurane
. Anesth Analg
14 Shafer SL, Varvel JR. Pharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology
15 Helman JD, Leung JM, Bellows WH et al.
The SPI Research Group. The risk of myocardial ischemia in patients receiving desflurane
anesthesia for coronary artery bypass graft surgery. Anesthesiology
16 Flacke JW, Flacke WE, Bloor BC, Olewine S. Effect of fentanyl, naloxone, and clonidine on hemodynamics and plasma catecholamine levels in dogs. Anesth Analg
17 Cahalan MK, Lurz FW, Eger EI, Schwartz LA, Beaupre BN, Smith JS. Narcotics decrease heart rate during inhalational anesthesia. Anesth Analg
18 Young WL. Effects of desflurane
on the central nervous system. Anesth Analg
19 Hoffman WE, Edelman G. Comparison of isoflurane and desflurane
anesthetic depth using burst suppression of the electroencephalogram in neurosurgical patients. Anesth Analg
20 Strebel S, Lam AM, Matta B, Mayberg TS, Aaslid R, Newell DW. Dynamic and static cerebral autoregulation during isoflurane, desflurane
, and propofol anesthesia. Anesthesiology
21 Muzzi DA, Losasso TJ, Dietz NM, Faust RJ, Cucchiara RF, Milde LN. The effect of desflurane
and isoflurane on cerebrospinal fluid pressure in humans with supratentorial mass lesions. Anesthesiology
22 Dahl A, Lindegaard KF, Russell D et al.
A comparison of transcranial Doppler and cerebral blood flow studies to assess cerebral vasoreactivity. Stroke
23 Trindle MR, Dodson BA, Rampil IJ. Effects of fentanyl vs. sufentanil
in equianesthetic doses on middle cerebral artery blood flow velocity. Anesthesiology
24 Hansen T, Warner D, Todd M, Vust L. Effects of nitrous oxide and volatile anesthetics on cerebral blood flow. Br J Anaesth
25 Eng C, Lam AM, Mayberg TS, Lee C, Mathisen T. The influence of propofol with and without nitrous oxide on cerebral blood flow velocity
reactivity in humans. Anesthesiology