Site(s) mediating sympathetic activation with desflurane.
BACKGROUND
Three strategies were employed to better define the afferent site(s) at which desflurane initiates its neurocirculatory activation.


METHODS
Young (aged 19-28 yr) healthy volunteers were employed in three separate studies. Monitoring included electrocardiography, radial artery blood pressure, and direct recordings of sympathetic outflow to skeletal muscle blood vessels by microneurography. In each study, anesthesia was established with 2.5 mg/kg propofol, and in studies 1 and 2 was maintained with 5.4% desflurane via a double-lumen tube. In study 1 (n = 7) a double-lumen tube was placed with the bronchial cuff just below the vocal cords to selectively give 14.5% desflurane or 2.4% isoflurane to the upper airway (via the tracheal lumen) or lower airway (via the bronchial lumen). Study 2 (n = 14) consisted of standard placement of a left side double-lumen tube to selectively increase the inspired desflurane concentration of either right or left lung to 11% while decreasing the inspired concentration in the opposite lung to 0%, thereby maintaining constant systemic concentrations of desflurane (gas chromatography). Study 3 consisted of lidocaine or placebo airway treatment before anesthetic induction and administration of 11% inspired desflurane by mask: group A-n = 9, topical and nebulized lidocaine, glossopharyngeal and superior laryngeal nerve blocks, and transtracheal administration of lidocaine; group B-n = 7, similar treatment as group A with placebo (saline); and group C-n = 8, systemic infusions of 2% lidocaine to match plasma concentrations of lidocaine in group A.


RESULTS
In study 1, significant increases in heart rate, mean arterial pressure, and sympathetic neural activity (26%, 23%, and 62%, respectively) occurred when desflurane was directed to the upper airway. These responses were approximately twofold to sixfold larger when desflurane was given to the lower airway (lungs). There were no significant increases in these variables when isoflurane was administered to the upper airways, and a significant increase in heart rate occurred only when isoflurane was delivered to the lower airways. In study 2, separate right or left lung increases in desflurane did not change the blood concentration of desflurane or sympathetic neural activity but led to significant increases in heart rate (44%) and mean arterial pressure (32%). The simultaneous administration of desflurane to both lungs increased the millimolar (mM) concentration of desflurane in the blood from 1.17 to 2.39 mM and led to increases in sympathetic neural activity (750%), heart rate (90%), and mean arterial pressure (63%). In study 3, neither regional nor systemic administration of lidocaine reduced the significant neurocirculatory activation caused by the rapid increase in the inspired concentration of desflurane by mask.


CONCLUSIONS
There are sites in the upper airway (larynx and above) that respond with sympathetic activation during rapid increases in desflurane concentration independent of systemic anesthetic changes. These responses, while lesser than those seen with rapid increases to the lung, may represent direct irritation of airway mucosa. Heart rate and mean arterial pressure responses to desflurane can be initiated by selectively increasing concentrations to either right or left lung without altering systemic levels of desflurane. From this it is inferred that there are sites within the lungs, separate from systemic sites, that mediate this response. Neither systemic lidocaine nor attempted blockade of upper airway sites with cranial nerve blocks combined with topical lidocaine was effective in attenuating the neurocirculatory activation associated with desflurane.
Muzi
M
M
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, USA.
Ebert
T J
TJ
Hope
W G
WG
Robinson
B J
BJ
Bell
L B
LB
D000293:Adolescent; D000328:Adult; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D000077335:Desflurane; D004594:Electrophysiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007530:Isoflurane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects* / Q000294:innervation*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
D018685:Anesthetics, Inhalation; D000779:Anesthetics, Local; D008012:Lidocaine; D000077335:Desflurane; D007530:Isoflurane