Anesth Analg 2008; 107:343-344
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e3181758cd5
LETTER TO THE EDITOR
Section Editor:
: Lawrence Saidman
Etomidate, Nitric Oxide, and Cerebral Vasospasm
Stephen M. Howell, MD, and
Richard P. Driver, MD
West Virginia University Department of Anesthesiology; Morgantown, West Virginia; howells2{at}rcbhsc.wvu.edu
In Response:
The patient described in our case report1 had a deteriorating neurologic examination and angiographically demonstrated vasospasm before the medication administration error. As such, it is impossible to differentiate on-going vasospasm from injectate-induced vasospasm. We do however agree that intracerebroventricular etomidate could influence this process by a variety of mechanisms.
As Dr. Mashour notes,2 IV-infused etomidate appears to produce direct cerebral vasoconstriction independent of changes in cerebral metabolism in a canine model.3 For completeness, we must note that propofol and thiobarbiturates also induce direct vasoconstriction in isolated canine cerebral arteries.4,5
The utility of etomidate as a cerebral protective agent during focal cerebral ischemia has been appropriately questioned. Several studies have demonstrated that etomidate can increase cerebral injury in a rat model of forebrain ischemia.6,7 These studies involved the IV infusion of etomidate to burst suppression for a total of 6 h, with 3 h of mechanically induced ischemia. One can certainly debate the merit of extrapolating these data to a single IV bolus dose of etomidate used to secure a human airway in the setting of cerebral vasospasm.
We agree that nitric oxide synthase inhibition appears to play a role in the lack of cerebral protection of etomidate7 and that loss of nitric oxide synthase immunoreactivity seems to correlate clinically with subarachnoid hemorrhage induced vasospasm.8 As Dr. Mashour has alluded, IV etomidate could conceivably exacerbate existing cerebral vasospasm via reduction in nitric oxide synthase activity. Alternatively, and perhaps more likely, etomidate may not effect the vasomotor tone of cerebral blood vessels already in vasospasm because nitric oxide production is already deranged. Hence, etomidate could theoretically increase cerebral blood flow to an ischemic territory via vasoconstriction of normal cerebral arteries. This effect could not be seen in a model of ischemia produced by complete mechanical vessel occlusion. More importantly, nitric oxide synthase inhibition may be short-lived following a typical IV induction dose of etomidate because the mechanism appears to be competitive.7
It is known that etomidate affords greater systemic hemodynamic stability when compared with other induction agents such as propofol or barbiturates, which clearly favors cerebral perfusion in patients at risk for hemodynamic embarrassment. To the best of our knowledge, the changes in cerebral blood flow that occur with IV induction agents have not been extensively studied in animal models of cerebral vasospasm. Hopefully, future research will improve our understanding of this complicated physiology and pharmacology.
REFERENCES
- Howell S, Driver, RP. Unintentional intracerebroventricular administration of etomidate and rocuronium. Anesth Analg 2008;106:520–2[Abstract/Free Full Text]
- Mashour GA. Etomidate, nitric oxide, and cerebral vasospasm. Anesth Analg 2008;107:343[Free Full Text]
- Milde LN, Milde JH, Michenfelder JD. Cerebral functional, metabolic, and hemodynamic effects of etomidate in dogs. Anesthesiology 1985;63:371–7[Web of Science][Medline]
- Nakamura K, Hatano Y, Hirakata H, Nishiwada M, Toda H, Mori K. Direct vasoconstrictor and vasodilator effects of propofol in isolated dog arteries. Br J Anaesth 1992;68:193–7[Abstract/Free Full Text]
- Hatano Y, Nakamura K, Moriyama S, Mori K, Toda N. The contractile responses of isolated dog cerebral and extracerebral arteries to oxybarbiturates and thiobarbiturates. Anesthesiology 1989;71:80–6[Web of Science][Medline]
- Drummond JC, Cole DJ, Patel PM, Reynolds LW. Focal cerebral ischemia during anesthesia with etomidate, isoflurane, or thiopental: a comparison of the extent of cerebral injury. Neurosurgery 1995;37:742–9[Web of Science][Medline]
- Drummond JC, McKay LD, Cole DJ, Patel PM. The role of nitric oxide synthase inhibition in the adverse effects of etomidate in the setting of focal ischemia in rats. Anesth Analg 2005;100:841–6[Abstract/Free Full Text]
- Pluta RM, Thompson BG, Dawson TM, Snyder SH, Boock RJ, Oldfield EH. Loss of nitric oxide synthase immunoreactivity in cerebral vasospasm. J Neurosurg 1996; 84:648–54[Web of Science][Medline]
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