Prolonged mivacurium infusion in young and elderly adults.
OBJECTIVE
This study was designed to evaluate pharmacodynamically and pharmacokinetically if the cis-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 pollicis was recorded in 32 adults 18-59 yr. and 19 elderly (> 60 yr.) patients during N2O:O2:opioid anaesthesia. The mivacurium infusion rate was adjusted to maintain single twitch depression at 95 +/- 4% of control. Blood samples were taken every 30 min to determine the plasma concentration of cis-cis isomer of mivacurium. At the end of the surgical procedure, patients were allowed to recover spontaneously to at least 25% of control twitch response.


RESULTS
The mean mivacurium infusion requirement to maintain 97 +/- 1 (mean +/- SD)% depression of the twitch response was 6.0 +/- 0.4 micrograms.kg-1.min-1 in young adults, and 4.3 +/- 0.3 micrograms.kg-1.min-1 in elderly patients (P < 0.001). The infusion requirement in patients with low plasma cholinesterase activity was the lowest 2.4 +/- 1.2 micrograms.kg-1.min-1. Plasma cis-cis isomer concentrations reached peak levels within one-two hours and remained relatively constant throughout the duration of infusion even in patients with low cholinesterase activity. There was no relationship between duration of infusion, plasma concentrations of cis-cis isomer and the early recovery indices of mivacurium (up to 25%). Neuromuscular transmission recovered adequately with or without antagonism in all patients.


CONCLUSIONS
When the mivacurium infusion was titrated to maintain 95 +/- 4% twitch depression, the plasma concentration of the cis-cis isomer did not increase during prolonged infusions (four hours) and neuromuscular transmission recovers satisfactorily.
Goudsouzian
N
N
Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Chakravorti
S
S
Denman
W
W
Schwartz
A
A
Yang
H S
HS
Cook
D R
DR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D000762:Anesthesia Recovery Period; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D000779:Anesthetics, Local; D002802:Cholinesterases / Q000097:blood; D003992:Dibucaine; D006801:Humans; D007262:Infusions, Intravenous; D007536:Isomerism; D007546:Isoquinolines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008875:Middle Aged; D000077590:Mivacurium; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D009294:Narcotics / Q000008:administration & dosage; D019148:Neuromuscular Blockade; D009469:Neuromuscular Junction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D009609:Nitrous Oxide / Q000008:administration & dosage; D010100:Oxygen / Q000008:administration & dosage; D009435:Synaptic Transmission / Q000187:drug effects; D013933:Thumb; D013997:Time Factors
D018685:Anesthetics, Inhalation; D000779:Anesthetics, Local; D007546:Isoquinolines; D009294:Narcotics; D003473:Neuromuscular Nondepolarizing Agents; D000077590:Mivacurium; D002802:Cholinesterases; D009609:Nitrous Oxide; D003992:Dibucaine; D010100:Oxygen