Plasma Catecholamines
Accurate and sensitive techniques for measuring plasma catecholamines
have existed for 3 decades, but interpretation of the data they yield has been controversial.
Normal plasma epinephrine and norepinephrine levels are typically in the range of
100 to 400 pg/mL, and they can increase sixfold or more with stress.
Plasma concentrations of epinephrine, which reflect adrenal medullary
activity[450]
if not overall sympathetic activity,
are labile. The uncontrolled stress experienced by experimental subjects has clouded
the meaning of measured levels. Significant isolated adrenal medullary secretion
results from certain stressful situations, such as public speaking.[29]
Moreover, venous samples may reflect the epinephrine kinetics in the organ being
sampled rather than in the whole body, and arterial samples may be more reliable.
[451]
The significance of norepinephrine concentration in plasma is
even more controversial. Although the adrenal
medulla secretes some norepinephrine, levels in plasma generally reflect spillover
from sympathetic stimulation because most of the norepinephrine released at the nerve
ending is taken up again by the nerve terminal. Although reuptake may be tissue
specific and markedly influenced by alterations in physiology or diseases, this spillover
in humans is 10% to 20% of the norepinephrine synthesis rate at baseline and may
be greatly enhanced in periods of sympathetic activation.[452]
The most compelling argument for use of plasma norepinephrine as a marker for sympathetic
activity comes from animal studies in which plasma norepinephrine levels directly
mirrored nerve stimulation.[453]
Many important
studies have correlated elevations in plasma catecholamines with acute and chronic
stress and have led to the concept of stress-free anesthesia. A striking relationship
between mortality rates for patients with CHF and elevated plasma norepinephrine
levels resulted in the use of β-adrenergic antagonists to treat ventricular
dysfunction.[454]
[455]
The development of experimental radiotracer techniques to assess
the in vivo kinetics of catecholamines has provided additional information that is
of clinical importance, particularly in relation to regional kinetics. For example,
studies relying only on arterial and venous catecholamines suggested that the hepatomesenteric
bed contributed significantly to the total body clearance of catecholamines but only
minimally (<8%) to the spillover. However, later studies of regional norepinephrine
kinetics demonstrated that the gut release of norepinephrine (≤25% of the total
body) was largely obscured by efficient extraction (>80%) in the liver. Similarly,
selective elevations in norepinephrine release from the heart, which may be associated
with ischemia, the early onset of CHF, and tachyarrhythmias, may not be apparent
in measured arterial or venous levels.[456]
Observations
involving regional spillover led to the realization that although stress may activate
a generalized sympathetic response, there may be different patterns contingent on
the stimulus. It is possible that the lack of association of plasma norepinephrine
levels in the presence of clinically significant sympathetic activation may be a
function of the measurement technique or the particular stressor. Although many
anesthetic techniques, including inhaled, opiate, and regional anesthetics, can attenuate
the stress response, whether attenuation represents a benefit or liability in patient
care remains a matter of controversy.[457]
[458]
Until recently, there were few data to suggest that the attenuation of the stress
response altered outcome, with the exception of prolonged postoperative epidural
anesthesia or special surgical situations. However, results of several studies in
infants and adults undergoing heart surgery suggest that the use of high-dose opiates
or other strategies to diminish perioperative stress may improve outcome.[459]
[460]
[461]
[462]
In the past 5 to 10 years, studies have reported that neuraxial analgesia can decrease
ischemic and thrombotic complications by attenuating the sustained increase in perioperative
catecholamines associated with surgery and general anesthesia.[463]
[464]
[465]
It is our belief that, given the effects of age, posture, and
hydration, small changes in plasma catecholamine levels correlate poorly with hemodynamic
changes and merit cautious interpretation, whereas significant increases (>1000
pg/mL) in levels are good markers of sympathetic nervous system activation.
