Læknablaðið - 15.08.1995, Side 43

LÆKNABLAÐIÐ 1995; 81
619
Nýr doktor í læknisfræði
Vigdís Hansdóttir læknir við svæfinga- og
gjörgæsludeild Sahlgrenska sjúkrahússins í
Gautaborg varði doktorsritgerð í læknisfræði
við Háskólann í Gautaborg 21. apríl síðastlið-
inn. Ritgerðin heitir Epidural Sufentanil Anal-
gesia; a pharmacokinetic and pharmacodynamic
study in patients after thoracotomy. Fer ágrip
doktorsritgerðarinnar hér á eftir:
Safe and optimal administration of epidural
sufentanil requires information on analgesic
and adverse effects and needs to be related to
the disposition of sufentanil in both CSF and
plasma.
Methods: Postthoracotomy analgesia with
epidural sufentanil was studied in 97 patients.
After intrathecal administration (15 pg) the
sufentanil concentration was measured in plas-
ma and CSF and the pharmacokinetics calcu-
lated. Epidural morphine (4 mg) and sufenta-
nil (75 pg) given at the lumbar or thoracic level
were compared by means of pharmacokinetics
in CSF and plasma. During epidural infusion
of sufentanil (1 pg/ml) analgesia, sedation,
CSF and plasma pharmacokinetics, and venti-
latory response to CO, rebreathing were com-
pared after administration at the thoracic and
lumbar level and when combined with bupiva-
caine and administered at the thoracic level.
Morphine and sufentanil concentrations were
assayed by gaschromatography and radioim-
munoassay respectively. CÓ2 rebreathing re-
sponses were assessed ad modum Read and
Whitelaw.
Results: After intrathecal administration of
sufentanil, clearance from CSF (27±5 pl/
kg*min) was about ten times that of morphine.
After intrathecal and epidural administration
sufentanil concentrations were higher in CSF
than in plasma, but CSF concentrations de-
Key words: Anaesthetic technique, intrathecal, epidurat,
bolus, infusion; pain, postoperative; opioid, morphine, su-
fentanil; local anaesthetic, bupivacaine; pharmacokinetics,
cerebrospinal fluid, plasma; ventilation, carbon dioxide re-
breathing, mouth occlusion pressure.
clined more
rapidly com-
pared with
morphine. The
availability in
CSF after epid-
ural adminis-
tration was 3%
and 0.6% after
bolus dose ad-
ministration
and infusion
respectively.
The terminal
half-lives were
10 and 7 h in
plasma and CSF respectively after epidural su-
fentanil infusion, which is shorter than after
bolus dose administration. The lumbar CSF
concentrations after thoracic epidural adminis-
tration of morphine and sufentanil were 50%
and 20% respectively of the concentrations af-
ter lumbar epidural administration. During su-
fentanil infusion, pain scores were similar but
the infusion rate, sedation and ventilatory im-
pairments less when administered at the tho-
racic compared with the lumbar level. Thorac-
ic sufentanil analgesia was further optimised
when combined with bupivacaine; analgesia
was superior, the infusion rate and ventilatory
impairments less, and sedation negligible.
Steady state was reached after almost 2 days of
epidural infusion, but the extent of accumu-
lation was low due to high total clearance. CSF
concentrations were higher than in plasma at
steady state. Plasma half life was 9.9± 1.7 h,
the distribution volume of 15.5±2.12 1/kg, and
clearance 17.4±1.11 pl/kg*min.
Conclusions: After thoracotomy epidural
sufentanil analgesia is optimal and safe when
administered epidurally at the surgical level
and combined with bupivacaine, and when su-
pervision of the patients is continued until
steady state. The infusion rate seems low
enough to avoid major side effects but clearly
sufficient for effective analgesia.