(Stroke. 2000;31:2266-f.)
© 2000 American Heart Association, Inc.
Letters to the Editor |
Is the Acetazolamide Test Valid for Quantitative Assessment of Maximal Cerebral Autoregulatory Vasodilation?
Neuroradiology Section, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri
To the Editor:
I read with great interest the article by Demolis and colleagues1 and the short editorial by Dr Alkayed that followed. The study by Demolis et al is an important contribution to the literature. Although the acetazolamide is commonly used to assess the vasodilatory capacity of the cerebral circulation, the physiological significance of an abnormal blood flow or blood velocity response to this stimulus is not known. As Dr Alkayed correctly states, the degree to which blood flow responses to this agent indicate autoregulatory capacity is unclear. The results from the study of Demolis et al serve to further underscore this fact. I am writing to point out 2 minor, but important, errors in the thoughtful editorial by Dr Alkayed that followed.
First, the vasodilatory effects of acetazolamide are complex and very likely caused by different mechanisms that PCO2-induced vasodilation.2 3 Hemodynamic studies of patients with carotid occlusive disease comparing the vasodilatory effects acetazolamide to hypercapnia or physiological activation have reported striking discordances.4 5 Kazumata and colleagues5 measured an increase in cerebral blood flow with hypercapnia in 10 of 11 patients with an absent increase or paradoxical reduction in cerebral blood flow after acetazolamide. The study by Nishimura and coworkers6 reported an association between PCO2 effects (not acetazolamide) and the effects of induced hypotension using PET measurements of cerebral blood flow. The findings of Demolis and colleagues and the study by Nishimura are therefore not contradictory.
Second, indirect methods of hemodynamic assessment such as these require empiric validation as predictors of stroke risk.7 Dr Alkayed cited 2 studies as reporting an association between stroke risk and impaired blood flow responses to acetazolamide. The first, a pioneering study by Yonas and colleagues,8 suffered from several methodological flaws, including mixed patient populations and a retrospectively defined hemodynamic threshold to identify normal and abnormal acetazolamide responses.7 The second study, by Yokota et al,9 is mistakenly cited as supporting an association between stroke risk and impaired blood flow responses to acetazolamide, when, in fact, it found just the opposite. This was a well-designed, prospective study of 105 patients. Over a mean follow-up period of 2.7 years, the risk of stroke in patients with normal acetazolamide-induced blood flow responses (6 in 39 patients) was the same as the risk for patients with abnormal response (7 of 39 patients).9
The study by Demolis and colleagues supports the hypothesis that the vasodilatory effects of acetazolamide are mediated by a different mechanism than vasodilation due to autoregulation. The physiological and clinical significance of an absent increase or paradoxical reduction in cerebral blood flow after acetazolamide remains to be determined.
References
1.
Demolis P, Florence G, Thomas L, Dinh YRT,
Giudicelli J-F, Seylaz J. Is the acetazolamide test valid
for quantitative assessment of maximal cerebral autoregulatory
vasodilation? An experimental study. Stroke.. 2000;31:508–515.
2. Hauge A, Nicolaysen G, Thoresen M. Acute effects of acetazolamide on cerebral blood flow in man. Acta Physiol Scand.. 1983;117:233–239.[Medline] [Order article via Infotrieve]
3. Cotev S, Lee J, Severinghaus JW. The effects of acetazolamide on cerebral blood flow and cerebral tissue pCO2. Anesthesiology.. 1968;29:471–477.[Medline] [Order article via Infotrieve]
4. Inao S, Tadokoro M, Nishino M, Mizutani N, Terada K, Bundo M, Kuchiwaki H, Yoshida J. Neural activation of the brain with hemodynamic insufficiency. J Cereb Blood Flow Metab.. 1998;18:960–967.[Medline] [Order article via Infotrieve]
5.
Kazumata K, Tanaka N, Ishikawa T, Kuroda S, Houkin K,
Mitsumuri K. Dissociation of vasoreactivity to
acetazolamide and hypercapnia: comparative study in
patients with chronic occlusive major cerebral artery disease.
Stroke.. 1996;27:2052–2058.
6. Nishimura S, Suzuki A, Hatazawa J, Nishimura H, Shirane R, Yasui N, Yoshimoto T. Cerebral blood flow responses to induced hypotension and to CO2 inhalation in patients with major cerebral artery occlusive disease: a positron emission tomography study. Neuroradiology.. 1999;41:73–79.[Medline] [Order article via Infotrieve]
7.
Derdeyn CP, Grubb RL Jr, Powers WJ. Cerebral
hemodynamic impairment: methods of measurement and
association with stroke risk. Neurology.. 1999;53:251–259.
8. Yonas H, Smith HA, Durham SR, Pentheny SL, Johnson DW. Increased stroke risk predicted by compromised cerebral blood flow reactivity. J Neurosurg.. 1993;79:483–489.[Medline] [Order article via Infotrieve]
9.
Yokota C, Hasegawa Y, Minematsu K, Yamaguchi T. Effect
of acetazolamide reactivity and long-term outcome in
patients with major cerebral artery occlusive disease.
Stroke.. 1998;29:640–644.
Response
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine
Key Words: acetazolamide • cerebral blood flow
Whether CO2 and acetazolamide cause vasodilation by the same mechanism is unclear. Clinically, a dissociation between hypercapnic and acetazolamide vasoreactivities has been reported.R1 I agree with Dr Derdeyn that evidence for or against an association between stroke risk and abnormal response to CO2 and acetazolamide should be considered separately. The study by Yokota et alR2 was mistakenly used as supportive of an association between impaired vasodilator capacity and stroke risk. The clinical significance of an abnormal response to acetazolamide, as Dr Derdeyn points out, remains unclear.
References
1. Kazumata K, Tanaka N, Ishikawa T, Kuroda S, Houkin K, Mitsumori K. Dissociation of vasoreactivity to acetazolamide and hypercapnia: comparative study in patients with chronic occlusive major cerebral artery disease. Stroke.. 1996;27:2052–2058.
2. Yokota C, Hasegawa Y, Minematsu K, Yamaguchi T. Effect of acetazolamide reactivity and long-term outcome in patients with major cerebral artery diseases. Stroke.. 1998;29:640–644.
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