|
Catecholamine
activation in the vasomotor center on emergence from anesthesia: the effects
of alpha-2 agonists.
Bruandet N, Rentero N, Debeer L, Quintin L; Anesthesia and Analgesia
1998; 86:240-5
[ see abstract below ]
Through the development of anesthesiology as a specialty an enormous amount
of attention has been given to techniques of anesthetic induction and
maintenance, and much less to the emergence and recovery phase. Yet this
may be the most critical period of the entire anesthetic, as patients
go from a controlled, protected, tightly monitored situation, to a situation
where their airway is no longer protected, pain control is mitigated by
the fear of causing respiratory depression, and monitoring is progressively
less intense. There is increasing evidence that sympathoadrenal activation,
catecholamine surge, tachycardia and hypertension are greatest at emergence
and extubation - even greater, as shown in studies on patients undergoing
major vascular surgery, than application or release of the aortic cross-clamp.
More recently, it has been demonstrated that in patients with coronary
artery disease, the risk of acute myocardial ischemia is greatest on emergence
from anesthesia and in the early postoperative period.
In the March issue of Anesthesia and Analgesia, Bruandet et alreport
on the ability of the administration of alpha-2 agonists to modify catecholamine
activation on emergence from anesthesia. In a laboratory study on halothane-anesthetized
rats, these authors studied the effect of the alpha-agonists clonidine
and mivazerol on the rostral ventrolateral medulla (RVLM). The RVLM contains
adrenergic neurons which control the spinal sympathetic preganglionic
neurons, which in turn control the peripheral circulation and therefore
may be responsible for the hypertensive response seen during anesthetic
emergence.
Using the technique of in vivo electrochemistry, a catechol signal was
recorded during anesthesia and on emergence with the administration of
saline (control), clonidine or mivazerol. Both alpha-agonists significantly
depressed the catecholamine response of the RVLM to emergence from anesthesia;
clonidine had more effect on preventing hypertension whereas mivazerol
was more effective against tachycardia.
What is the clinical implication of these studies? The alpha-2 agonists
are attractive agents to be used to blunt the hypertensive and tachycardiac
response to emergence from anesthesia, and thereby possibly decreasing
the incidence and consequences of acute postoperative myocardial ischemia.
A long acting alpha-2 agonist such as clonidine may be given as a premedication
and still have some protective effect on emergence after relatively short
procedures. The more specific alpha-agonists, mivazerol and dexmedetomidine,
although still undergoing investigation prior to FDA approval, may be
given by continuous infusion throughout the operative period. This, together
with their analgesic properties with minimal respiratory depression, makes
them potentially the first "emergence agents" - administered specifically
to control pain, anxiety and the catecholamine response to anesthetic
emergence.
Return to the Current Literature Review Front
Page , or read the abstract:
ABSTRACT
The rostral
ventrolateral medulla (RVLM) controls the vascular system and may contribute
to postoperative hypertension. It comprises adrenergic cardiovascular neurons,
a site for action of alpha2-adrenergic agonists. Because alpha2 agonists
minimize perioperative circulatory activation, we asked the following question:
do alpha2 agonists, such as clonidine and mivazerol, blunt the catecholamine
activation observed in the RVLM on emergence from anesthesia?
Halothane-anesthetized, paralyzed rats had their ventilatory, circulatory,
and acid-base stability controlled. All pressure points and incisions were
infiltrated with local anesthetics. With in vivo electrochemistry, a catechol
signal was recorded in the RVLM during 150 min of stable halothane anesthesia
(saline-halothane group); for 120 min after halothane discontinuation (saline-emergence
group); after emergence and administration of the reference alpha2 agonist,
clonidine 7 microg/kg or 21 microg/kg I.V. (50% or 90% effective dose [ED50
or ED90, respectively); and after emergence and administration of a new
alpha2 agonist, mivazerol 20 microg/kg or 150 microg/kg I.V. (ED50 or ED90).
Under halothane, dose-response curves for the RVLM catecholamine signal
were constructed for mivazerol and an alpha2 antagonist, idazoxan (ED50
2.3 mg/kg I.V.).
Stable halothane anesthesia (n = 5) led to no change in mean arterial pressure
(MAP), heart rate (HR), or catechol signal (CAOC). During emergence from
anesthesia, the MAP, HR, and CAOC increased (n = 5). Clonidine led to a
near total suppression of the RVLM catecholamine activation noticed on emergence
from anesthesia (n = 5). Hypertension was partially blunted with clonidine
7 microg/kg (n = 5). Tachycardia was partially blunted with mivazerol 20
microg/kg (n = 5). Pretreatment with idazoxan suppressed all the effects
of mivazerol (n = 5).
Implications: On emergence from anesthesia, alpha2 agonists modify
the activity of adrenergic cardiovascular neurons located within the vasomotor
center, as assessed by in vivo electrochemistry. We provide a rationale
for the use of alpha2 agonists on emergence from anesthesia in coronary/hypertensive
patients.
|
