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December
1996
Small, oral dose of clonidine reduces the incidence
of intraoperative myocardial ischemia in patients having vascular surgery.
Stuehmeier K-D, Mainzer B, Cierpka J, et al; Anesthesiology 1996;85:706-712.
[ see abstract below ]
Ischemic cardiac complications remain an important concern in the patient
undergoing major vascular surgery. Some years ago the Cleveland Clinic
performed cardiac catheterization on 1,000 consecutive patients undergoing
vascular surgery - a feat which will probably never be repeated! They
found that significant coronary artery disease existed in about 65% of
patients, and in about 18%, surgically correctable coronary artery disease
was found without any cardiac symptoms, resting ECG changes or history
of congestive heart failure (Hertzer N: Clinical experience with preoperative
coronary angiography. J Vasc Surg 2:510-514, 1985). Subsequently there
has been an enormous amount of investigation performed on defining the
most sensitive, specific and cost-effective means of evaluating risk for
perioperative cardiac events in patients scheduled for vascular surgery.
In the October 1996 edition of ANESTHESIOLOGY, Stuehmeier and colleagues
report the remarkable finding that a single 2 g/kg dose (about 0.15 mg
for the average sized adult) of clonidine taken orally before surgery
reduced the incidence of perioperative myocardial ischemic episodes by
nearly 40%. Four patients in the placebo group went on to develop acute
myocardial infarction after surgery compared with none in the treatment
group, but the study size (297 patients) was of insufficient size for
this to reach statistical significance. The greatest reduction in reversible
ischemic episodes coincided with surgical stimulation. Moreover, this
apparent myocardial protection occurred without overt differences in hemodynamic
function or requirement for vasoactive drugs between the two groups.
Although this study probably raises more questions than it answers, it
again draws attention to the unique pharmacologic profile of the alpha-2
adrenoreceptor agonists. These agents act centrally to decrease sympathetic
outflow and norepinephrine levels, as well as providing anxiolysis, analgesia,
antiemetic and antisialogogic actions - all of which would seem to be
eminently desirable in a premedicant. The dose of clonidine given in this
study appears almost homeopathic - and yet it appeared to confer significant
myocardial protection.
The reader is also referred to another recently published study on the
use of larger doses of clonidine in hypertensive patients undergoing major
vascular surgery, in which it decreased anesthetic requirements and improved
circulatory stability (Quinton L et al.: Clonidine for major vascular
surgery in hypertensive patients: a double-blind, controlled, randomized
study. Anesthesia and Analgesia 83:687-695, 1996). In fact, an increasing
number of studies are presently being performed with newer, more potent
and selective parenteral alpha-2 adrenoreceptor agonists such as dexmedetomidine
and mefanazole. The next decade promises to launch this group of drugs
into a permanent and important niche in the anesthesiologists' pharmacopoeia.
Return to the Current Literature Review Front
Page, or read the abstract:
ABSTRACT
Background:
Most new perioperative myocardial ischemic episodes occur in the absence
of hypertension or tachycardia. The ability of a 8-adrenoceptor agonists
to inhibit central sympathetic outflow may benefit patients with coronary
artery disease by increasing the myocardial oxygen supply-and-demand ratio.
Methods:
A randomized double-blind study design was used in 297 patients scheduled
to have elective vascular surgical procedures to evaluate the effects of
2 ug/kg-1 oral clonidine (n=145) or placebo (n=152) on the incidence of
perioperative myocardial ischemic episodes, myocardial infraction, and cardiac
death. Continuous real-time S-T segment trend analysis (lead II and V5)
was performed during anesthesia and surgery and correlated with arterial
blood pressure and heart rate before and during ischemic events. Does requirements
for vasoactive and antiischemic drugs to control blood pressure and heart
rate as well as episodes of myocardial ischemia (i.e., catecholamines, 8-adrenoceptor
antagonists, nitrates, and systemic vasodilators) and fluid volume load
were recorded.
Results:
Administration of clonidine reduced the incidence of perioperative myocardial
ischemic episodes from 39% (59 of 152) to 24% (35 of 145) (P < 0.01).
Hemodynamic patterns, percentage of ischemic time, and the number of ischemic
episodes per patient did not differ. Nonfatal myocardial infraction developed
after operation in four patients receiving placebo compared with none receiving
clonidine (day 2 to 21; P = 0.07). The incidence of fatal cardiac events
(1 vs. 2) was not different. Dose requirements for vasoactive and antiischemic
drugs did not differ between the groups, but the amount of presurgical fluid
volume was slightly greater in patients receiving clonidine (951 + 388 vs.
867 + 391 ml; P < 0.03).
Conclusion:
A small oral dose of clonidine, given prophylactically,
can reduce the incidence of perioperative myocardial ischemic episodes without
affecting hemodynamic stability in patients with suspected or documented
coronary artery disease.
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