Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05053594 |
| Other study ID # |
CAAE 46436121.0.0000.5373 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2021 |
| Est. completion date |
February 20, 2022 |
Study information
| Verified date |
September 2021 |
| Source |
Pontificia Universidade Catolica de Sao Paulo |
| Contact |
Eduardo T Moro, MD |
| Phone |
+5515997728015 |
| Email |
edumoro85[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
There is no recent information on the required dose of neostigmine for the reversal of
cisatracurium-induced moderate neuromuscular blockade (NMB) [Train-of-four (TOF) count =
1-3)] in children. The aim of this study will be to evaluate by means of a prospective,
randomized and double-blinded clinical trial, the time required for reversal of moderate NMB
(TOFc 3) to T4/T1 (TOF ratio, TOFr) > 0.9 and TOFr = 1.0 after administration of different
doses of neostigmine (10, 20 or 30 mcg/kg) or placebo in children undergoing inhalational
(sevoflurane) general anesthesia. In addition, the probability of NMB reversal in less than
10 minutes, the presence of bradycardia, respiratory complications and postoperative vomiting
will be evaluated. The time for reversal is expected to be inversely proportional to the
administered dose of neostigmine.
Description:
Children aged between 2 and 10 years old submitted to general anesthesia to perform
tonsillectomy associated or not to adenoidectomy and will be evaluated in this prospective
and randomized study. Patients will be randomly distributed into one of 4 groups according to
the dose of neostigmine used for NMB reversal:
- Group N10: reversal with neostigmine 10 mcg/kg and atropine 5 mcg/kg
- Group N20: reversal with neostigmine 20 mcg/kg and atropine 10 mcg/kg
- Group N30: reversal with neostigmine 30 mcg/kg and atropine 15 mcg/kg
- Group P: spontaneous reversal (placebo)
For each patient, an opaque envelope will be prepared, sealed and numbered sequentially
containing the group to which the patient will be allocated. A list of randomized
computer-generated numbers (www.random.org) will be used for this purpose. No surgeon,
assistant nursing, and anesthesiologist involved in anesthesia control or data collection
will be aware of the dose of neostigmine to be administered. An anesthesiologist not involved
in the study will be responsible for preparing the solution containing neostigmine and
atropine (diluted with saline solution until complete 10mL) according to the group to which
each patient belongs. The syringes will be similar and identified only with a label with the
word "reversal".
STUDY SEQUENCE
Anaesthesia No child will receive preanesthetic medication. After entry into the operating
room, all patients will be monitored with cardioscope, noninvasive blood pressure, pulse
oximetry and, after tracheal intubation, with capnography. In all children, venous access
will be obtained in one of the upper limbs after induction under facial mask with sevoflurane
(6%) in mixture with O2 5 L/min. After pre-oxygenation, tracheal intubation will be performed
after intravenous fentanyl (3 mcg/kg) and cisatracurium (0.1 mg/kg). Anesthesia maintenance
will be based on sevoflurane (1 to 2 CAM) diluted in O2/air flow (60%) 2 L/min. Ventilation
will be controlled, with tidal volume and respiratory rate adjusted for the maintenance of
PETCO2 between 30 and 40 mmHg. When there is a suspicion of inadequate anesthesia plan the
concentration of sevoflurane will be increased and if adequacy is not sufficient, additional
fentanyl bolus (1 mcg/kg) will be administered. Repeated doses of cisatracurium (0.02 mg/kg)
will be used to maintain TOFc < 4. All patients will receive clonidine 2 mcg/kg
intravenously, dexamethasone 0.1 mg/kg, ondansetron 0.1 mg/kg, dipyrone 30 mg/kg and morphine
0.1 mg/kg. Hydration will be performed with 0.9% saline (2 mL/kg/h). The central temperature
will be kept above 36 degrees Celsius and peripheral (tenar eminence of the monitored palm)
above 32 degrees Celsius. The NMB reversal will be performed when TOFc 3.
Monitoring of neuromuscular blockade NMB will be monitored by the acceleromyography method
(TOF Watch ®; Schering-Plough) as recommended for use in clinical research. The acceleration
transducer will be fixed on the volar side of the distal phalanx of the thumb. Venous access
and blood pressure cuff will be positioned on the opposite arm to the limb used for NMB
monitoring. After cleaning the skin in the path of the ulnar nerve in the forearm, the
electrodes will be positioned at the height of the wrist with a distance between 3 to 6 cm
between them. Calibration will be performed after automatically after a 50 Hz tetanic
stimulation for 5 seconds. The stimulation (Train-of-Four, TOF) will be applied every 15
seconds for 2 minutes before cisatracurium administration. No additional doses of NMB will be
given. Once the third response to TOF is obtained, a dose of neostigmine (10, 20 or 30
mcg/kg) will be administered and the time until the TOF reaches values equal to 0.9 and 1.0
will be recorded. The primary outcome will be the time required for the reversal of moderate
NMB (TOFc 3) up to TOFr 0.9 and TOFr 1.0. In addition, the probability of reversal of NMB in
less than 10 minutes after administration of different doses of neostigmine will be
evaluated. The sample size will be based on a previous study that determined the need for 12
patients per group to detect a difference of 4 minutes and a standard deviation of 3 minutes
with a power of 80% and alpha error of 5%. 9 Considering the possible losses, a total of 60
children will be randomized.
