Elective Open Thoracotomy Clinical Trial
Official title:
Target-Controlled Infusion of Remifentanil Without Muscle Relaxant Allows Acceptable Surgical Conditions During Thoracotomy
Although the administration of muscle relaxation is essential standard of care for thoracic
procedures, it could cause long-reversal times and postoperative residual curarization
(PORC) increasing length of post-anesthesia care unit (PACU) stay and hospital costs.
Sugammadex offers new perspectives to reduce the incidence of PORC. Unfortunately it is not
available in many countries because of its significantly high cost. We hypothesized that the
use of target-controlled remifentanil infusion (TCI) with the non-muscle relaxant (NMR)
would be associated with comparable surgical conditions and reduced total costs compared
with the use of neuromuscular blockers during thoracotomy.
After ethical approval, 66 patients scheduled for elective thoracotomy under sevoflurane
anesthesia with TCI remifentanil will be included in this prospective, randomized,
single-blind, controlled study.
Patients will be randomly assigned to receive cisatracurium or saline (n = 33 for each
group) throughout the procedure. Laryngoscopy and intubating conditions, intraoperative
modified thoracic surgery rating scale (Table below), incidence of light anesthesia, and use
of vasopressors and anesthetics, clinical recovery, incidence of PORC, PACU and hospital
stays, and total costs will be recorded.
Administration of muscle relaxation is essential standard of care in thoracic surgery as it
causes an improvement of surgical conditions. The concept of "Fast-track thoracic
anesthesia" requires the use of either short or intermediate-acting nondepolarising
neuromuscular blocking drugs, to provide a sufficient neuromuscular blockade during surgery
and to restore the normal neuromuscular transmission immediately at the end of surgery.1
However, long-reversal times and postoperative residual curarization (PORC) are still a
problem in 30%-60% of the anesthetized patients even with the use of new intermediate-acting
neuromuscular blockers.2-3 PORC could cause aspiration of the lungs and respiratory failure4
after thoracic surgery that may prolong the post anesthesia care unit (PACU) and hospital
stays.
Although, sugammadex, a modified gamma-cyclodextrin, offers new perspectives to reduce the
incidence of PORC,4 it is not available in many countries because of its significantly high
cost.5
Therefore, in fast-track cardiac surgery, it seems unnecessary to maintain paralysis by
repetitive bolus injection or continuous infusion of neuromuscular blockers with overall
surgeons' satisfaction.6
The use of remifentanil without muscle relaxants provides excellent intubating conditions
and short recovery duration.7 The effective concentration range of remifentanil for tracheal
intubation without muscle relaxant is 4.5-5.5 ng/ml.8 The use of non-muscle relaxant (NMR)
anesthetic techniques using remifentanil with either propofol or sevoflurane allows early
extubation after trans-sternal or video-assisted thymectomy in myasthenic patients.9-10
The use of NMR technique on the surgical conditions during thoracotomy in patients without
neuromuscular diseases has not yet been studied.
We hypothesizes that the use of NMR technique during thoracotomy will be associated with
comparable surgical conditions with the standard use of neuromuscular blockers.
The attending anesthesiologist is not blinded. All patients will be premedicated with 1-2 mg
oral lorazepam the night before surgery.
In all patients, standard monitors, and state and response entropy (SE and RE, respectively)
will be applied. Neuromuscular blockade is measured with a train-of-four (TOF) (Datex-Ohmeda
Division, Instrumentarium Corporation, Helsinki, Finland). The forearm is immobilized to
prevent interfering movements. The ulnar nerve will be stimulated supramaximally at the
wrist with a TOF stimuli (60 mA for 200 μsec) at 15-sec intervals. Baseline twitch amplitude
is established after induction of anesthesia. TOF ratio is recorded as ratio between the
fourth and the first twitch (T4/T1).
The radial artery is catheterized. Normothermia is maintained by using forced-air warming
blankets. A thoracic epidural or paravertebral catheter is inserted but no local anesthetics
are infused during the study to avoid their effects on the study outcomes.
Anesthetic technique is standardized in all studied patients. Anesthesiologists who give the
anesthetic will not be involved in the collection of outcome data.
After preoxygenation, anesthesia is induced using propofol 1.5-3 mg/kg and target-controlled
infusion (TCI) of remifentanil at an effect-site concentration (Ce) of 4 ng/mL using the TCI
system (Injectomat® TIVA Agilia, Fresenius Kabi, France), to achieve the SE values below 50
and the difference between RE and SE below 10 and the mean arterial blood pressure (MAP) and
heart rate are <20% of the baseline values. When the SE is >50 and the RE-SE difference is
>10, and the MAP and heart rate are >20%, propofol 0.5 mg/kg is administered followed with
gradual increases in remifentanil Ce by 0.5 ng/mL with a maximum Ce of 6 ng/ml.
Anesthesia is maintained with 0.7-1.5 minimum alveolar concentration (MAC) of sevoflurane to
maintain the SE values below 50 and the difference between RE and SE below 10.
Remifentanil Ce will be increased by 0.5 ng/mL when the SE values are > 50, the difference
between RE and SE >10, and the MAP and heart rate are >20% of the baseline values despite a
target sevoflurane MAC ≥ 1.5.
When the SE is <50 and the RE-SE difference is <10, the sevoflurane MAC will be gradually
decreased to a minimum of 0.7, followed with gradual decreases in remifentanil Ce by 0.5
ng/mL with a minimum Ce of 1.5 ng/ml.
Light anesthesia is defined as an episode with SE values that exceeds 50 and/or MAP and HR
values that exceeds the baseline by 20% and that lasted for more than 3 consecutive min.
Patients' two lungs (TLV) are mechanically ventilated with fraction of inspired oxygen
(FiO2) of 0.4 in air, tidal volume (VT) of 8 mL/kg, inspiratory to expiratory (I: E) ratio
of 1:2.5 and PEEP of 5 cm H2O, fresh gas flow (FGF) of 1.5-1.7 l/min, and respiratory rate
adjusted to achieve a PaCO2 of 35-45 mm Hg.
After pleurotomy, the patient's dependent lung is ventilated with a TV of 6 mL/kg and FiO2,
I: E ratio, PEEP, FGF, and respiratory rate, are maintained as during TLV and the lumen of
the nondependent lung is left open to air.
Hemodynamic control is standardized according to the authors' protocol.
During surgery, the authors will administer Lactated Ringer's solution at a rate of 2
mL/kg/h. If MAP drops down to 60 mmHg, 250 mL of plasma protein fraction 5% will be
administered, and, if this is not enough, repeated doses of intravenous of ephedrine 5 mg or
norepinephrine 5 µg, will be administered to maintain urine output to be equal or greater
than 0.5 ml/kg/hour. A hemoglobin concentration of 8 g/dL or greater is compensated with red
blood cell concentrates.
All surgical procedures will be performed by the same surgeons who are blinded for the
study.
In the case of clinically unacceptable laryngoscopy and intubating conditions, poor or
extremely poor surgical conditions, or a sudden deterioration of surgical conditions despite
the SE values below 50, the difference between RE and SE < 10, the MAP and heart rate are
<20% of the baseline values, cisatracurium is administered in a bolus dose of 0.1 mg/kg.
At the end of surgery, the nondependent lung is re-expanded, TLV is resumed as before
surgery. The remifentanil and sevoflurane will be discontinued after chest closure and skin
closure (T0), respectively. In the Muscle Relaxant group, during skin closure, when the TOF
ratio ranged between 0.3 and 0.5, the neuromuscular blockade is antagonized with 50 µg/kg
neostigmine and 10 µg/kg glycopyrrolate.
Tracheal extubation will be performed immediately when all extubation criteria were achieved
(TOF ratio ≥ 0.9, spontaneous ventilation, the ability to follow verbal commands, eyes
opening, head lift ≥ 5 s, and hand grip).
A pilot study showed that the proportion of the surgeons who rated their satisfaction with
surgical conditions as an excellent (Score 4) in anesthetized patients with cisatracurium
was 92.5%. A priori power analysis indicated that a sample size of 30 patients was
sufficiently large to detect a 30% difference in the proportion of the excellent operative
conditions, during the use of NMRT, a type-I error of 0.05 and a power of 90%. We added more
patients (10%) for a final sample size of 33 patients to compensate patients dropping out
during the study.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment