1 Department of Anaesthesiology, Intensive Care and Emergency, 2 Department of Medical Imaging and 3 Department of Ophthalmology and Ophthalmo-Paediatry, Fondation Ophtalmologique Adolphe de Rothschild, 2529 rue Manin, F-75940 Paris Cedex 19, France
* Corresponding author. E-mail: jmdevys{at}fo-rothschild.fr
Accepted for publication September 10, 2004.
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Methods. Thirteen mechanically ventilated children () were included. Blood flow velocities of central retinal artery, ophthalmic artery, and middle cerebral artery were measured by Doppler ultrasound during 1 and 2 age-adjusted minimal alveolar concentration (MAC) sevoflurane anaesthesia. Intra-ocular pressure and non-invasive haemodynamic parameters were also measured. End-tidal carbon dioxide tension was controlled during all the study period.
Results. Mean arterial pressure decreased from 1 to 2 age-adjusted MAC sevoflurane (58 [12] vs 54 [12] mm Hg, P=0.01). In the ophthalmic artery, end diastolic velocity (EDV) decreased significantly at 2 MAC (1 MAC: 4.4 [4] cm s1 vs 2 MAC: 1.4 [2.4] cm s1; P=0.04) and resistivity index (RI) increased significantly (1 MAC: 0.83 [0.11] vs 2 MAC: 0.93 [0.09]; P=0.007). Systolic velocity, EDV, and RI remained constant in the central retinal artery and in the middle cerebral artery.
Conclusion. High alveolar concentration of sevoflurane decreased blood flow velocity in the ophthalmic artery, but not in the central retinal and the middle cerebral arteries in children ventilated in hyperoxic condition. This effect was related to a decrease in mean arterial pressure. This vessel-dependant effect may be explained by the different autoregulatory mechanisms of these arteries. In the present hyperoxic conditions, the vascular effect of sevoflurane may have been limited in the central retinal artery and not in the ophthalmic artery.
Keywords: anaesthetics volatile, sevoflurane ; blood, flow, velocity ; blood, retrobulbar circulation ; children
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
As well as the middle cerebral artery, the ophthalmic artery is a branch of the internal carotid artery. The central retinal artery is a division of the ophthalmic artery. These vessels are involved in the blood supply of the posterior segment, and particularly of the retina. Altered retrobulbar circulation is a frequent finding in ophthalmologic pathology as glaucoma, and these haemodynamic alterations seem to be correlated with the severity of the disease.7 Little is known about variations of ocular blood flow during anaesthesia, and case reports of postoperative blindness lead us to consider the importance of the oculo-vascular effect of anaesthetic agents.8 9
In children with ocular disorders, ocular examination and ultrasound exploration required complete eye immobility and therefore a general anaesthesia. We hypothesized that, in children, sevoflurane could induce retrobulbar haemodynamic variations. This study was therefore designed to evaluate the effect of sevoflurane at 1 and 2 MAC on retrobulbar circulation blood flow velocity in children.
![]() |
Patients and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Blood flow velocities of retrobulbar vessels were assessed by colour Doppler imaging using a Sonoline AntaresTM ultrasound system (Siemens Medical System Inc., Issaquah, WA, USA). The B-mode frequency was 11.4 MHz and the Doppler frequency 7.3 MHz. A thick layer of gel was applied over the closed superior eyelid. In order not to modify the orbital pressure and therefore the blood vessels haemodynamic characteristics, the probe was not directly applied to the skin. The central retinal vessels were recognized with the colour mode, within the shadow of the optic nerve, and then a small Doppler gate (1.5 or 1.0 mm of width) was positioned 1.5 mm behind the papilla. The ophthalmic artery was recognized with the colour mode at its third portion (before the origin of the central retinal artery) as it runs close to the medial wall of the orbit (posterior and inferior to the superior ophthalmic vein). The same small Doppler gate (1.5 mm of width) was positioned at the most posterior visible part of the vessel. The Doppler gate was not positioned too close to a sinuosity of the vessel.
Cerebral blood flow was assessed by middle cerebral artery flow velocity measurement using a 2 MHz pulsed transcranial Doppler ultrasound (Basic TCDTM, Atys Medical, Soucieu en Jarrest, France). The Doppler probe was positioned at the temporal scalp surface, and the M1 segment of the middle cerebral artery was detected as is standard protocol.10 Repetitive measurements during both anaesthesia levels were performed at the same location of the vessels by the same investigator.
IOP, retrobulbar, and cerebral blood flow Doppler ultrasound were always performed at the side considered as healthy, respectively, by the same ophthalmologist (P.D.), radiologist (O.B.), and anaesthesiologist (T.G.). Peak systolic velocity (PSV) and end diastolic velocity (EDV) were obtained from the spectral mode for ophthalmic, central retinal, and middle cerebral arteries. Resistivity index (RI) was calculated as follow: RI=(PSVEDV)/PSV. IOP, haemodynamic, and Doppler parameters were measured and recorded by investigators blinded to the MAC value.
Based on a preliminary study showing a 25% decrease of EDV in the ophthalmic artery under 2 MAC sevoflurane anaesthesia compared with 1 MAC, a sample size of 12 patients should be enrolled in the study to show a statistical significant difference with =0.05 and ß=0.9 for a two-sided test. After verifying the normal distribution of continuous data, differences between the mean values were analysed using a paired Student's t-test. P<0.05 was considered to be statistically significant. All values are expressed as mean (SD).
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Mean arterial pressure decreased significantly (P=0.01) at 2 MAC compared with 1 MAC sevoflurane (Table 1). Heart rate and IOP remained unchanged at both sevoflurane concentrations. All patients exhibited an anterograde direction of blood flow in the ophthalmic artery. Blood flow velocities and RI did not change in the middle cerebral and the central retinal arteries. In opposite to these two vessels, EDV decreased (P=0.04) and RI increased (P=0.007) significantly at 2 MAC compared with 1 MAC sevoflurane in the ophthalmic artery. Variations of RI, EDV, and PSV for all children are presented in Figure 1. We did not observe any effect of the order of application of the different MAC levels.
|
|
Changes of local blood flow in this circulation have been used to quantify vascular disorders in pathologies such as glaucoma, diabetes, or carotid artery stenosis.12 In glaucomatous optics neuropathy, many clinical studies confirmed a reduced EDV associated with an elevated RI in the central retinal7 11 13 14 and in the ophthalmic arteries.14 In the absence of intra-ocular hypertension, a high RI value in the ophthalmic artery could be interpreted as a vascular contribution in glaucomatous neuropathy. Doppler examination could be dependent on the investigator, especially for the retrobulbar circulation. However, retrobulbar Doppler examination has shown a good short-term reproducibility for the same examiner,15 and in our study, it was always performed by the same senior investigator. In this condition, the expected reproducibility coefficient for repeated Doppler measurements in the different orbital arteries is less than 5% for the RIs and about 10% for velocity measurements.12 15 Moreover, there are variables that could potentially influence ocular circulation and particularly EDV as IOP and carbon dioxide partial pressure. Therefore, carbon dioxide partial pressure was controlled and IOP exhibited no change throughout the application of the different alveolar concentration of sevoflurane.
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Effect of inhaled anaesthetic agents on cerebral blood flow are considered as equivalent for all agents. Inhaled anaesthetic agents affect the cerebral circulation in two different ways: a cerebral vasodilation occurs first by direct effect on vascular smooth muscles of cerebral arteries resulting in increasing blood flow. Secondly, vasoconstriction occurs in relation to the reduction in metabolism. Sevoflurane has the less intrinsic cerebral vasodilatory effect of volatile agents.3 At 1.5 MAC, sevoflurane may have a cerebral vasodilatory effect, but human studies using transcranial Doppler showed small changes in cerebral blood flow.3 Moreover, sevoflurane maintains cerebral blood flow velocity as constant with increasing MAC in adults and children.16 Our study is in accordance with these results even for a high alveolar concentration of sevoflurane as shown by unchanged velocities in the middle cerebral artery despite a decrease in the mean arterial pressure with 2 MAC of sevoflurane.
Ophthalmic artery is the first major branch of the internal carotid artery. The central retinal artery is a subdivision of the ophthalmic artery, and is involved in the blood supply of the posterior segment. Anatomical description of the retrobulbar circulation is presented in Figure 2. Although the ocular circulation does not have any autonomic nerve supply, the ophthalmic and central retinal arteries have an autoregulation of their own blood flow.17 18 Preservation of this autoregulation is important not only from a physiologic approach, but also for its clinical implications in glaucoma and retinal ischemia.19 20 In the ophthalmic artery, previous data suggested a specific and different autoregulative response from the middle cerebral artery: in the case of a non-significant stenosis of the internal carotid artery, vasoreactivity of the ophthalmic artery seems to be lower than in the middle cerebral artery.21 In a healthy patient, blood flow velocities of the ophthalmic artery decrease significantly after acetazolamide treatment, in contrast to the middle cerebral or internal carotid arteries.19 These results suggest that autoregulation in the ophthalmic artery is different from other cerebral arteries. In the present study, we show a decreased diastolic blood flow velocity in the ophthalmic artery associated with a decrease in the mean arterial pressure induced by sevoflurane anaesthesia. The data suggest that blood flow autoregulation of the ophthalmic artery is impaired by sevoflurane.
|
Transcranial Doppler ultrasound was used to measure the effect of sevoflurane on cerebral blood flow velocity, as a comparison for ocular blood flow. This non-invasive method is reproducible and has shown a good correlation with a direct measure of cerebral blood flow by xenon clearance or radioactive microsphere.23 24 Moreover, transcranial Doppler ultrasound has been validated for the study of cerebral autoregulation in children.2527
In the present study, patients were ventilated in hyperoxic conditions (). In animal experimental models in pigs and monkeys, these conditions were associated with the central retinal artery vasocontriction.28 29 The vasoconstriction induced by these hyperoxic conditions may have limited the magnitude of change in blood flow velocity of the central retinal artery. In humans, the hyperoxia-induced retinal vasoconstriction is probably related to endothelin-1 retinal secretion, and is not observed in choroidal circulation.30 In young healthy patients, this hyperoxia-induced vasoconstriction is not observed in the ophthalmic artery.31 In the present hyperoxic conditions, the vascular effect of sevoflurane may have been limited in central retinal artery but not in ophthalmic artery. A further study concerning the oculo-vascular effects of different
levels on these three vessels in anaesthetized children could answer this question.
Effects of i.v. anaesthetic agents (as midazolam or propofol) or of other inhaled agents on retrobulbar circulation are unknown. It could be of interest to study their effects in patients with altered ocular circulation, in whom anaesthesia-related hypotension may severely compromise ocular blood flow.
We concluded that high alveolar concentration of sevoflurane with may enhance alterations of ophthalmic artery blood flow diastolic velocity in children but do not alter haemodynamic parameters in central retinal artery. In consequence, interpretation of blood flow velocity values in the retrobulbar circulation (especially in ophthalmic artery) should consider anaesthesia procedure to avoid excessive diagnosis of vascular disorders in ophthalmic pathologies as glaucoma.
![]() |
Footnotes |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2 Monkhoff M, Schwarz U, Gerber A, Fanconi S, Banziger O. The effects of sevoflurane and halothane anesthesia on cerebral blood flow velocity in children. Anesth Analg 2001; 92: 8916
3 Matta BF, Heath KJ, Tipping K, Summors AC. Direct cerebral vasodilatory effects of sevoflurane and isoflurane. Anesthesiology 1999; 91: 67780[CrossRef][ISI][Medline]
4 Cho S, Fujigaki T, Uchiyama Y, et al. Effects of sevoflurane with and without nitrous oxide on human cerebral circulation. Transcranial Doppler study. Anesthesiology 1996; 85: 75560[ISI][Medline]
5 Summors AC, Gupta AK, Matta BF. Dynamic cerebral autoregulation during sevoflurane anesthesia: a comparison with isoflurane. Anesth Analg 1999; 88: 3415
6 Fairgrieve R, Rowney DA, Karsli C, Bissonnette B. The effect of sevoflurane on cerebral blood flow velocity in children. Acta Anaesthesiol Scand 2003; 47: 122630[CrossRef][ISI][Medline]
7 Plange N, Remky A, Arend O. Colour Doppler imaging and fluorescein filling defects of the optic disc in normal tension glaucoma. Br J Ophth 2003; 87: 7316[CrossRef][ISI]
8 Williams EL. Postoperative blindness. Anesth Clin North Am 2002; 20: 36784
9 Benumof JL, Mazzei W, Roth S, et al. Multifactorial etiology of postoperative vision loss. Anesthesiology 2002; 96: 15312
10 Lam AM. Intraoperative transcranial Doppler monitoring. Anesthesiology 1995; 82: 15367[CrossRef][ISI][Medline]
11 Guthoff RF, Berger RW, Winkler P, Helmke K, Chumbley LC. Doppler ultrasonography of the ophthalmic and central retinal vessels. Arch Ophth 1991; 109: 5326[Abstract]
12 Tranquart F, Berges O, Koskas P, et al. Color Doppler imaging of orbital vessels: personal experience and literature review. J Clin Ultrasound 2003; 31: 25873[CrossRef][ISI][Medline]
13 Galassi F, Nuzzaci G, Sodi A, Casi P, Vielmo A. Color Doppler imaging in evaluation of optic nerve blood supply in normal and glaucomatous subjects. Int Ophthal 1992; 16: 2736[CrossRef][ISI]
14 Kaiser HJ, Schoetzau A, Stumpfig D, Flammer J. Blood-flow velocities of the extraocular vessels in patients with high-tension and normal-tension primary open-angle glaucoma. Am J Ophthal 1997; 123: 3207[ISI][Medline]
15 Senn BC, Kaiser HJ, Schotzau A, Flammer J. Reproducibility of color Doppler imaging in orbital vessels. Ger J Ophthal 1996; 5: 38691
16 Heath KJ, Gupta S, Matta BF. The effects of sevoflurane on cerebral hemodynamics during propofol anesthesia. Anesth Analg 1997; 85: 12847[Abstract]
17 Best M, Gerstein D, Wlad N, Rabinovitz AZ, Hiller GH. Autoregulation of ocular blood flow. Arch Ophth 1973; 89: 1438[CrossRef][ISI][Medline]
18 Tachibana H, Gotoh F, Ishikawa Y. Retinal vascular autoregulation in normal subjects. Stroke 1982; 13: 14955[Abstract]
19 Kerty E, Horven I, Dahl A, Nyberg-Hansen R. Ocular and cerebral blood flow measurements in healthy subjects. A comparison of blood flow velocity and dynamic tonometry measurements before and after acetazolamide. Acta Ophthalmol 1994; 72: 4018[Medline]
20 Kerty E, Horven I. Ocular hemodynamic changes in patients with high-grade carotid occlusive disease and development of chronic ocular ischaemia. I. Doppler and dynamic tonometry findings. Acta Ophthalmol Scand 1995; 73: 6671[ISI][Medline]
21 Bornstein NM, Gur AY, Geyer O, Almog Y. Vasomotor reactivity in the ophthalmic artery: different from or similar to intracerebral vessels? Eur J Ultrasound 2000; 11: 16[CrossRef][Medline]
22 Delaey C, Van De Voorde J. Regulatory mechanisms in the retinal and choroidal circulation. Ophthal Res 2000; 32: 24956[CrossRef][ISI]
23 Bishop CC, Powell S, Rutt D, Browse NL. Transcranial Doppler measurement of middle cerebral artery blood flow velocity: a validation study. Stroke 1986; 17: 91315[Abstract]
24 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 1993; 76: 12226[Abstract]
25 Larsen FS, Olsen KS, Hansen BA, Paulson OB, Knudsen GM. Transcranial Doppler is valid for determination of the lower limit of cerebral blood flow autoregulation. Stroke 1994; 25: 19858[Abstract]
26 Strebel S, Lam AM, Matta B, et al. Dynamic and static cerebral autoregulation during isoflurane, desflurane, and propofol anesthesia. Anesthesiology 1995; 83: 6676[CrossRef][ISI][Medline]
27 Vavilala MS, Lee LA, Lee M, et al. Cerebral autoregulation in children during sevoflurane anaesthesia. Br J Anaesth 2003; 90: 63641
28 Eperon G, Johnson M, David NJ. The effect of arterial PO2 on relative retinal blood flow in monkeys. Invest Ophthal 1975; 14: 34252[ISI][Medline]
29 Riva CE, Pournaras CJ, Tsacopoulos M. Regulation of local oxygen tension and blood flow in the inner retina during hyperoxia. J Appl Physiol 1986; 61: 5928
30 Dallinger S, Dorner GT, Wenzel R, et al. Endothelin-1 contributes to hyperoxia-induced vasoconstriction in the human retina. Invest Ophthalmol Vis Sci 2000; 41: 8649
31 Evans DW, Harris A, Danis RP, Arend O, Martin BJ. Altered retrobulbar vascular reactivity in early diabetic retinopathy. Br J Ophth 1997; 81: 27982[ISI]