Clinical trial NCT02552875: Shortening of the Twitch Stabilization Period by Tetanic Stimulation in Acceleromyography in Children and Young Adults
Official title: Shortening of the Twitch Stabilization Period by Tetanic Stimulation in Acceleromyography in Children and Young Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Train-of-Four-Monitoring
Keywords: Acceleromyography
staircase phenomenon
tetanic stimulation
Lead sponsor: University of Regensburg
Sponsor class: OTHER
First posted: 2015-09-17
Enrollment: 80
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Repetitive nerve stimulation is used to monitor the neuromuscular transmission function in infants, children and adults after the application of muscle relaxants. During repetitive stimulation of a motor nerve, amplitude of contractions of the corresponding muscle will increase to a plateau (twitch potentiation), which is known as the staircase phenomenon.

There is no systematic information about the staircase phenomenon of the adductor pollices muscle (ulnar nerve) in children between 1 month and 18 years .

In adults , a 50-Hz tetanus administered before initial twitch stabilization is able to shorten the twitch stabilization period and to eliminate this staircase phenomenon.

The purpose of this study is to investigate the characteristics of twitch potentiation in children between 1 month and 18 years by using acceleromyography.

In addition we investigate whether application of a 50-Hz tetanic stimulation is able to eliminate the twitch potentiation like in adults.

Detailed description: 1. Background:

   Acceleromyography at the adductor pollices muscle (ulnar nerve stimulation) is used to monitor the neuromuscular transmission function in infants, children and adults after the application of muscle relaxants. During repetitive stimulation of a motor nerve, amplitude of contractions of the corresponding muscle will increase to a plateau (twitch potentiation), which is known as the staircase phenomenon. This effect may influence the onset time and duration of twitch depression after the application of muscle relaxants. The staircase effect during the baseline stabilization period presents in a shorter time course and at lower degrees in smaller infants. In older infants, staircase effect presents in a longer period and is able to influence duration of twitch depression after the administration of muscle relaxants.

   There is no information about the staircase phenomenon at the adductor pollices muscle (ulnar nerve stimulation) in children between 1 month and 21 years.

   In adults , a 50-Hz tetanus administered before initial twitch stabilization is able to shorten the twitch stabilization period and to eliminate this phenomenon.
2. Aim of the study:

   The purpose of this controlled, randomised, pragmatic study is to investigate the characteristics of twitch potentiation (T1%, first twitch of TOF-stimulation; TOFR, Train-of-Four-ratio) in children between 1 month and 21 years by using acceleromyography. In addition we stimulate the right and the left arm simultaneously with acceleromyography (TOF-stimulation). At the one hand a 50 Hz tetanus will be administered before twitch stabilization (TOF-stimulation). At the other hand TOF-stimulation for twitch stabilization will be started without tetanic stimulation
3. Methods:

   Anaesthesia will be induced and maintained without muscle relaxants by propofol and remifentanil. After this acceleromyography will be performed simultaneously at the right and the left arm (adductor pollices muscle, ulnar nerve). At the one hand a 50 Hz tetanus will be administered before twitch stabilization (TOF-stimulation). At the contralateral side TOF-stimulation for twitch stabilization will be started without tetanus. TOF measurements will be collected by 2 TOF Watch SX and two notebooks for the course of 30 minutes.
4. Inclusion criterions/ groups

   -general anesthesia (total intravenous anaesthesia)

   Groups (total amount= 80)
   * group A: 18-21 years; n= 10
   * group B: 12-18 years; n= 10
   * group C: 6-12 years; n= 10
   * group D: 3-6 years; n= 10
   * group E: 25-60 months; n= 10
   * group F: 12-24 months; n= 10
   * group G: 6-11 months; n= 10
   * group H: 1-5 months; n= 10.
5. Exclusion criterions

   * participation in another trial
   * refusal of participation
   * state after burns
   * diabetes mellitus
   * reflux disease
   * difficult airway
   * pregnancy

Medications:

* volatile anesthetics
* antibiotics (aminoglycosides, polymyxin, clindamycin, lincomycin, tetracyclines)
* local anesthetics
* magnesium
* lithium
* Ca-chanel-blockers
* furosemide
* theophylline
* phenytoin
* cyclophosphamide
* metoclopramide
* β-blockers

Eligibility criteria: Inclusion Criteria:

* general anesthesia

Exclusion Criteria:

* participation in another trial
* refusal of participation
* state after burns
* diabetes mellitus
* reflux disease
* difficult airway
* pregnancy

Medications:

* volatile anesthetics
* antibiotics (Aminoglykoside, Polymyxin, Clindamycin, Lincomycin, Tetrazykline)
* local anesthetics
* magnesium
* Litium
* Ca-chanel-blockers
* furosemid
* theophyllin
* phenytoin
* cyclophosphamide
* metoclopramide
* β-blockers

Primary outcomes:
measure: T1% measurement
timeFrame: 30 minutes
Secondary outcomes:
measure: TOFR% maesurement
timeFrame: 30 minutes
Other outcomes:
Locations:
city: Regensburg
country: Germany
facility: University Medical Center Regensburg, Department of Anaesthesiology
Study officials:
affiliation: University Medical Center Regensburg, Germany
name: Christoph Unterbuchner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Saldien V, Vermeyen KM. Neuromuscular transmission monitoring in children. Paediatr Anaesth. 2004 Apr;14(4):289-92. doi: 10.1046/j.1460-9592.2003.01152.x. No abstract available.
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citation: Zhou ZJ, Wang X, Zheng S, Zhang XF. The characteristics of the staircase phenomenon during the period of twitch stabilization in infants in TOF mode. Paediatr Anaesth. 2013 Apr;23(4):322-7. doi: 10.1111/pan.12041. Epub 2012 Oct 17.
citation: Kopman AF, Kumar S, Klewicka MM, Neuman GG. The staircase phenomenon: implications for monitoring of neuromuscular transmission. Anesthesiology. 2001 Aug;95(2):403-7. doi: 10.1097/00000542-200108000-00023.
citation: Driessen JJ, Robertson EN, Booij LH. Acceleromyography in neonates and small infants: baseline calibration and recovery of the responses after neuromuscular blockade with rocuronium. Eur J Anaesthesiol. 2005 Jan;22(1):11-5. doi: 10.1017/s0265021505000037.
citation: Goudsouzian NG, Standaert FG. The infant and the myoneural junction. Anesth Analg. 1986 Nov;65(11):1208-17. No abstract available.
citation: Fuchs-Buder T, Claudius C, Skovgaard LT, Eriksson LI, Mirakhur RK, Viby-Mogensen J; 8th International Neuromuscular Meeting. Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision. Acta Anaesthesiol Scand. 2007 Aug;51(7):789-808. doi: 10.1111/j.1399-6576.2007.01352.x.
citation: Unterbuchner C, Werkmann M, Ziegleder R, Kraus S, Seyfried T, Graf B, Zeman F, Blobner M, Sinner B, Metterlein T. Shortening of the twitch stabilization period by tetanic stimulation in acceleromyography in infants, children and young adults (STSTS-Study): a prospective randomised, controlled trial. J Clin Monit Comput. 2020 Dec;34(6):1343-1349. doi: 10.1007/s10877-019-00435-4. Epub 2019 Nov 30.