Different Doses of Neostigmine for Reversal of Moderate Neuromuscular Blockade in Children

NCT ID: NCT05053594

Last Updated: 2021-09-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-01
• Study Completion Date: 2022-02-20

Brief 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.

Detailed 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.

Conditions

Neuromuscular Blockade; Neuromuscular Block, Residual; Neuromuscular Block Prolonged

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group N10

Reversal with neostigmine 10 mcg/kg and atropine 5 mcg/kg

Group Type: EXPERIMENTAL

Neostigmine 10 mcg/kg

Intervention Type: DRUG

Once the third response to TOF is obtained, neostigmine 10 mcg/kg will be administered

Group N20

Reversal with neostigmine 20 mcg/kg and atropine 10 mcg/kg

Group Type: EXPERIMENTAL

Neostigmine 20 mcg/kg

Intervention Type: DRUG

Once the third response to TOF is obtained, neostigmine 20 mcg/kg will be administered

Group N30

Reversal with neostigmine 30 mcg/kg and atropine 15 mcg/kg

Group Type: EXPERIMENTAL

Neostigmine 30 mcg/kg

Intervention Type: DRUG

Once the third response to TOF is obtained, neostigmine 30 mcg/kg will be administered

Group P

Spontaneous reversal (placebo)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Once the third response to TOF is obtained, saline will be administered

Interventions

Neostigmine 10 mcg/kg

Once the third response to TOF is obtained, neostigmine 10 mcg/kg will be administered

Intervention Type: DRUG

Neostigmine 20 mcg/kg

Once the third response to TOF is obtained, neostigmine 20 mcg/kg will be administered

Intervention Type: DRUG

Neostigmine 30 mcg/kg

Once the third response to TOF is obtained, neostigmine 30 mcg/kg will be administered

Intervention Type: DRUG

Placebo

Once the third response to TOF is obtained, saline will be administered

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Children physical status according to the American Society of Anesthesiologists I and II
• Submitted to general anesthesia to perform tonsillectomy associated or not with adenoidectomy

Exclusion Criteria

• Refusal to participate in the study
• Presence of kidney, liver or neuromuscular disease
• Contraindication to the use of any drug used in the study
• Body mass index (BMI) ≥ 30.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Pontificia Universidade Catolica de Sao Paulo

OTHER

Sponsor Role: lead

Responsible Party

Eduardo Toshiyuki Moro

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eduardo T Moro, MD

Role: PRINCIPAL_INVESTIGATOR

Pontificia Catholic University of São Paulo

Central Contacts

Eduardo T Moro, MD

Role: CONTACT

edumoro85@gmail.com

+5515997728015

Other Identifiers

CAAE 46436121.0.0000.5373

Identifier Type: -

Identifier Source: org_study_id