Pharmacokinetic
Analysis for Epidural Ropivacaine Induced Cardiac Arrest
Tomoko
Takeda, M.D., Kenichi Masui, M.D., Ryuji Yonamine, M.D., Isao Fukuda, M.D.,
Takehiko Ikeda, M.D. and Tomiei Kazama, M.D..
Department
of Anesthesiology, National Defense Medical College, Tokorozawa, Saitama,
Japan.
Case
The
patient was 39-year-old primigravida who complicated with Takayasu disease.
She was scheduled for caesarean section with epidural anesthesia. An epidural
catheter was inserted at level L3-4. After negative aspiration tests for blood
or cerebrospinal fluid, 20ml of ropivacaine 1% was injected. Eight min after
injection, upper level of sensory block was Th8. Heart rate was 150/min (sinus
rhythm) and electrocardiogram showed slightly ST depression. Then, she was
suffering from shortness of breath and garrulous. Because convulsion occurred
at 13 min after injection, tracheal intubation was performed followed by
thiopental sodium and vecuronium bromide. And then 14 ,17, and 22 min after
injection, electrocardiogram showed pulseless ventricular tachycardia, but
immediately returned to sinus rhythm by hitting on her sternum or
defibrillation. After the end of operation, newborn and she left the operating
room without severe side effects.
Pharmacokinetic
analysis
A
compartment model was developed for analyzing the time course of plasma
ropivacaine concentration by using nonlinear least-square curve fitting. Model
contained epidural space (Cepi) and central compartment (Ccent), absorption
half-life from Cepi to Ccent (ka), and elimination half-life of Ccent (kel).
Calculated parameters were followings: ka=14min, Kel=13.3min, maximum drug
concentration time (Tmax)=13.3min, and maximum drug concentration (Cmax)=3.66mg/l.
Discussion
Because
of short time onset of local anesthetic toxicty, intravascular injection was
suspected. However, pharmacokinetic analysis suggested few ropivacaine was
injected directly into the vessels. A previous study reported that it
estimated ka=14min, Tmax=21.6min, and Cmax=2.06mg/l in healthy volunteer. In
our case, the cause of high plasma concentration of ropivacaine might be that
smaller epidural space and overswelling of vessel might shorten absorption
half-life of ropivacaine.
Conclusions
At
the time of epidural drug administration, local anesthetics might be absorbed
from epidural space to vessel more rapidly in pregnant than in nonpregnant.
Pharmacokinetic analysis suggested that it might increase the risk of local
anesthetic toxicity in pregnant patient.