Prolonged mivacurium infusion in young and elderly adults

Abstract

Prolonged mivacurium infusion in young and elderly adultsPurpose: This study was designed to evaluate pharmacoclynamically and pharmacokinetically if the ds-cis isomer of mivacurium contributed to neuromuscular block during prolonged infusions lasting more than four hours in young adult and elderly (> 60 yr) patients. Methods: The mechanomyogramic neuromuscular response of the adductor potlids was recorded in 32 adults 18-59 yr. and 19 elderly (> 60 yr.) patients during N20:O2:opioid anaesthesia. The mivacudum infusion rate was adjusted to maintain single twitch depression at 95 --+-496 of control. Blood samples were taken every 30 min to determine the plasma concent~tion of ds-cis isomer of mivacufium. At the end of the surgical procedure, patients were allowed to recover spontaneously to at least 25% of control twitr~ response. gemflts: The mean mivacurium infusion requirement to maintain 97 +_ I (mean +__ SD)% depression of the twitch response was 6.0 -+ 0.4 pg.kg-l-min -t in young adults, and 4.3 +_ 0.3 pg-kgUmin -~ in elderly paEents (P < 0.001), The infusion requirement in patients with low plasma cholinesterase activity was the lowest 2.4 _.+ 1.2 /Jg.kg -~.min -j. Plasma ds-cis isomer concentrations reached peak levels wi~in one-two hours and remained relatively constant throughout the duration of infusion even in patients with low cholinesterase actMty. There was no relationship between duration of infusion, plasma concentrations of ds-ds isomer and the early recovery indices of mivacurium (up to 25%). Neuromuscular transmission recovered adequately with or without antagonism in all patients. Condusiom When the mivacudum infusion was ~ to maintain 95 ---4% twitch deprmsion, the plasma concentration of the ds-cis isomer did not increase during prolonged infusions (four hours) and neuromuscular transmission recovers satisfactorily.Objectif : Cette Etude pharmacoclynamique et pharmacocinEtique visait A determiner si risomEre dc-cis du mivacurium contribualt au bloc neuromusculalre pendant des perfusions de quatre heures et plus, chez des jeunes adultes el: chez des sujets plus ~gEs (>60 ans). M6thodes : La r6ponse m6canomyographique neuromusculaire a 6t6 enregistr~ae ,~ I'adducteur du pouce chez 32 patients adultes de 18 ~ 59 ans et chez 19 patients plus ~g6s (>60 ans) pendant une anesth~ie associant N20/O2 un morphinique. La vitesse de peffusion du mivacurium 6talt r~glEe de fagon ~ maintenir un twitch sous 95 -496 du contr61e. La concentration plasmatique de I'isorn6re cis-cis du mivacurium 6tait d6termin6e sur des ~-hantillons de sang pr~lev~s aux 30 min. Une fois la chirurgie termir~,e, on laissait les patients r6cup~rer spontan6ment jusqu',~ une r6ponse d'au moins 25% au twitch. ll~ultats : [. perfusion moyenne de mivacurium n~cessaire pour maintenir la r~ponse au twitch sous 97 + 1% (moyenne + El') ~talt de 6,0 + 0,4 pg-kg -~.min -~ chez les jeunes adultes et de 4,3 _+ 0,3 #g'kg -~-min -~ chez les patients plus ~s (P < 0,001). Les patients dont I'activit6 de la cholinest~rase plasmatique ~ faible avai...

Pharmacokinetics and pharmacodynamics of mivacurium in young adult and elderly patients

“…(8) all found lower infusion requirements in elderly compared with young adult patients, and also found that the necessary infusion rate seemed to decrease with time. The duration of infusion was, however, longer (4 h) (8, 17). A correlation was found between the pChe activity and the infusion rate of mivacurium both in the young adult and elderly patients; the higher the pChe activity the higher the infusion rate.…”

“…(17) and Goudsouzian et al . (8) all found lower infusion requirements in elderly compared with young adult patients, and also found that the necessary infusion rate seemed to decrease with time. The duration of infusion was, however, longer (4 h) (8, 17).…”

“…The infusion requirement found in young adults is comparable to data from other studies in adults during narcotic anesthesia (3, 4, 6, 16), but slightly higher than reported by Goudsouzian et al . (8). This can be explained by differences in methodology as Goudsouzian et al .…”

“…Several papers have described the pharmacodynamics of mivacurium following bolus doses and continuous infusions. Most of these studies were performed in young adults (1–5), with only a few in elderly patients (6–8). The pharmacokinetics of mivacurium has been described in young healthy adults (9, 10), whereas pharmacokinetic data of elderly patients are sparse (11).…”