Cerebral Blood Flow and Cerebral Metabolic Rate
Opioids generally produce modest decreases in cerebral metabolic
rate (CMR) and intracranial pressure (ICP), although the changes are influenced by
the concomitant administration of other agents and anesthetics, as well as by patient
conditions (also see Chapter 21
).
When vasodilatation is produced by co-administered anesthetics, opioids are more
likely to cause cerebral vasoconstriction. Opioids also decrease cerebral blood
flow (CBF) when combined with N2
O. When opioids are administered alone
or when the co-administered anesthetics cause cerebral vasoconstriction, opioids
usually have no influence or result in a small increase in CBF.
Endogenous opioid activity is present in cerebral arteries, although
exogenously administered opioids were found to exert little effect on pial artery
diameter in several animal models.[90]
Morphine
and enkephalins produced dose-dependent pial arterial dilatation.[91]
Fentanyl (100 µg/kg) causes dose-related reductions in CBF and CMRO2
in rats receiving N2
O. In the piglet, fentanyl, alfentanil, and sufentanil
decrease arteriolar diameter in a dose-dependent naloxone-reversible manner.[92]
Fentanyl alone causes little change in CBF in the dog.[93]
In human volunteers, positron emission tomography demonstrates that CBF changes
induced by fentanyl are regionally heterogeneous.[94]
The effect of sufentanil on CBF in the dog may be dose- and time-dependent.
It was reported that sufentanil (20 µg/kg IV) produced 30% to 40% decreases
in CBF 5–10 minutes after opioid administration.[95]
Another study showed that sufentanil (10–200 µg/kg) produced transient
increases in CBF that peaked 2 minutes after drug administration in the dog.[96]
In humans, both fentanyl and sufentanil can increase middle cerebral artery blood
flow velocity by ∼25%.[97]
In other reports,
it was shown that in healthy volunteers, sufentanil (0.5 µg/kg IV) had no significant
effect on CBF.[97]
Alfentanil (25 or 50 µg/kg
IV), administered to patients receiving isoflurane (0.4%–0.6%)-N2
O
anesthesia, produced minimal reductions in middle cerebral artery flow velocity.
[98]
In the dog, alfentanil and remifentanil both decreased regional
blood flow by 40% to 50% in the cortex, hippocampus, and caudate.[99]
A positron emission tomography study in human volunteers showed that remifentanil
induced dose-dependent changes in relative regional CBF in areas involved in pain
processing, such as lateral prefrontal cortex, inferior parietal cortex, and supplementary
motor area.[100]
In patients scheduled to undergo
supratentorial tumor surgery receiving N2
O, both remifentanil (1 µg/kg/min)
and similarly fentanyl (2 µg/kg/min), reduced CBF and did not significantly
affect cerebrovascular reactivity to carbon dioxide.[101]
Opioids usually produce mild to moderate decreases in CMR that
remain coupled to CBF. However, opioid-induced neuroexcitation and focal seizure
activity can cause regional increases in brain metabolism. Regional increases in
glucose utilization induced by high doses of alfentanil in the rat were associated
not only with epileptiform activity but also with neuropathic lesions.[102]
In humans, positron emission tomography evaluation demonstrated that 1–3 µg/kg/min
infusions of remifentanil induce significant increases in CMR for glucose.[103]
