SITE(S) MEDIATING SYMPATHETIC ACTIVATION WITH DESFLURANE

Background: Three strategies were employed to better define the affere nt site(s) at which desflurane initiates its neuro-circulatory activat ion. Methods: Young (aged 19-28 yr) healthy volunteers were employed i n three separate studies. Monitoring included electrocardiography, rad ial artery blood pressure, and direct recordings of sympathetic outflo w 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 ai rway (via the bronchial lumen). Study 2 (n = 14) consisted of standard placement of a left side double-lumen tube to selectively increase th e 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 airwa y treatment before anesthetic induction and administration of 11% insp ired desflurane by mask: group A-n = 9, topical and nebulized Lidocain e, glossophargngeal and superior laryngeal nerve blocks, and transtrac heal administration of lidocaine; group B-n = 7, similar treatment as group A with placebo (saline); and group C-n = 8, systemic infusions o f 2% lidocaine to match plasma concentrations of lidocaine in group A. Results: In study 1, significant increases in heart rate, mean arteri al pressure, and sympathetic neural activity (26%, 23%, and 62%, respe ctively) occurred when desflurane was directed to the upper airway. Th ese responses were approximately twofold to sixfold larger when desflu rane was given to the lower airway (lungs). There mere no significant increases in these variables when isoflurane was administered to the u pper airways, and a significant increase in heart rate occurred only w hen isoflurane was delivered to the lower airways. In study 2, separat e 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 incr eased the millimolar (mM) concentration of desflurane in the blood fro m 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 th e significant neurocirculatory activation caused by the rapid increase in the inspired concentration of desflurane by mask. Conclusions Ther e are sites In the upper airway (larynx and above) that respond with s ympathetic activation during rapid increases in desflurane concentrati on 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 pres sure responses to desflurane can be initiated by selectively increasin g concentrations to either right or left lung without altering systemi c levels of desflurane. From this it is inferred that there are sites within the lungs, separate from systemic sites, that mediate this resp onse. Neither systemic lidocaine nor attempted blockade of upper airwa y sites with cranial nerve blocks combined with topical lidocaine was effective in attenuating the neurocirculatory activation associated wi th desflurane.