TIVA WITH REMIFENTANIL OR FENTANYL COMBINED WITH PROPOFOL FOR CABG
SURGERY
T. Möllhoff, L.
Herregods, D. Blake, C. MacAdams, S. Shaikh‡
* University
Hospital of Münster, Münster, Germany
Co-ordinated by
Glaxo Wellcome Research & Development‡
Introduction Remifentanil hydrochloride
(REMI) is a unique potent m-opioid agonist which
does not accumulate following prolonged administration due to its metabolism by
non-specific blood and tissue esterases. REMI therefore offers the opportunity
to provide high-dose opioid analgesia via TIVA for cardiac surgery without requiring prolonged post-operative
mechanical ventilation. This study
investigated the safety and efficacy of a REMI infusion versus ’fast-track’
intermittent bolus doses of fentanyl (FEN) in patients with ejection fractions
of 0.3 or greater undergoing CABG
surgery.
Methods: Following Ethics
Committee approval and provision of informed consent, 24 open label
pilot-patients received REMI and a further 297 patients were randomised to
receive either REMI (n=148) or FEN (n=149) in a double blind manner. All
patients were premedicated with diazepam 10mg PO 1 hr before surgery. Following
propofol (0.5mg/kg) induction, pancuronium
was given to facilitate intubation. A propofol infusion was then started
(3mg/kg/hr) together with either REMI (Placebo bolus + 1mg/kg/min infusion) or FEN
(15mg/kg bolus +
placebo infusion).Vital signs were measured at regular intervals during the
induction and operative periods. At the end of
surgery REMI patients continued to received remifentanil until deemed
eligible to begin extubation. Responses
to intra-operative events were assessed.
Inadequate anaesthesia was defined as: Hypertension: SBP >15% above
pre-operative baseline or 140mmHg for > 1min pre and post-bypass (AP
>80mmHg > 1min during bypass); Tachycardia: HR > 90 bpm for >1
min pre-bypass, > 100 bpm for >1 min post-bypass; Somatic: gross
movement, swallowing, eye opening, grimacing;
Autonomic: sweating, lachrymation. Inadequate anaesthesia was treated
with bolus dose/infusion rate increase of opioid (2mg/kg FEN, 1.0mg/kg + 0.5-1mg/kg/min REMI), propofol,
vasodilators/b-blockers.
Excessive anaesthesia defined as: SBP <
80mmHg for >1 min; HR <40 bpm for >1min was prevented/treated with: 1.
fluids, 2. opioid and/or propofol infusion rate decrease (50%), 3. other
drugs. Analyses
of the proportion of patients requiring management of inadequate or excessive
anaesthesia and the median number of treatment interventions are presented
below.
|
Results Efficacy Population (n=
297) |
REMI (n=148) |
FEN
(n=149) |
P-value |
|
Pts with medication to prevent/treat inadequate anaesthesia¤ |
105 (71%) |
142 (95%) |
<0.001 |
|
Median no. of interventions to treat inadequate anaesthesia |
1 |
6 |
|
|
Pts with medication to prevent/treat excessive anaesthesia¤ |
138 (93%) |
120 (81%) |
0.002 |
|
Median no. of interventions to treat excessive anaesthesia |
3 |
1 |
|
|
Safety population (n=321) |
REMI (n= 172) |
FEN (n=149) |
P-value |
|
Patients with one or more adverse events # |
138 (80%) |
113 (76%) |
0.347 |
¤ = Logistic regression , # = Fisher's Exact Test,
Conclusions The higher incidence of treatment for
excessive anaesthesia was probably due to a
more profound level of analgesia in the remifentanil group. Remifentanil/propofol was as well tolerated as fentanyl / propofol in this patient population