Anaesthesia With or Without Rocuronium in Intubation and Intraoperative Nerve-monitoring During Thyroid Surgery.

• ClinicalTrials.gov Identifier: NCT03910504
• Recruitment Status: Completed
• First Posted: April 10, 2019
• Last Update Posted: November 3, 2020
• Sponsor: Federico Longhini
• Information provided by (Responsible Party): Federico Longhini, University Magna Graecia

Study Description

Brief Summary:

In this randomized controlled trial the investigators want to assess if, compared to controls, the administration of one single low-dose of rocuronium would increase the occurrence of absent or weak (i.e. amplitude <100 μV) signal at V1 and R1, indicating a residual NMBA activity. In addition, we also recorded: 1) the occurrence of difficult laryngoscopy; 2) the time-to-intubation; 3) the occurrence of difficult intubation; 4) the number of intubation attempts; 5) the intubation failure rate; 6) the need for oxygenation between intubation attempts; 7) the lowest peripheral saturation in oxygen (SpO2); 8) the number of severe desaturations; 9) the time-to-V1 and 10) the number of post-surgical complications.

Condition or disease	Intervention/treatment	Phase
Thyroid; Neuromuscular Blockade; Anesthesia Complication; Anesthesia Intubation Complication	Drug: Rocuronium 0.3 mg*kg; Drug: No Rocuronium	Not Applicable

Detailed Description:

The lesion of laryngeal nerves is one of the most severe complications, which could be observed during the thyroid and parathyroid surgery. The recent clinical review, relative the problem and based on 27 articles and 25000 patients involved, shows that the incidence of the temporary paralysis of the recurrent laryngeal nerve (RLN) was 9,8%, and the permanent paralysis of the nerve was 2,3%. In the most cases the typical reasons of lesions of RLN are: section, clamping, electrothermic damage, stretching or entrapment of the nerve. The lesions of the RLN could lead to voice disturbance, breathing and swallow alterations. It is also one of the most frequent reasons for legal medicine disputes.

The intraoperative nerve-monitoring (IONM) of the RLN and of the external branch of superior laryngeal nerve (EBSLN) has been suggested as an instrument to limit the risk of post-operative damaging. It was introduced in the 60's, and the method was accepted by surgical community with the great enthusiasm. This technique is based on employment of special electrode, which transmits electrical signal of low amperage and stimulates directly the RLN, evaluating the muscle response. The stimulation of the EBSLN is commonly identified by contractions of cricothyroid muscle. On the other hand, the stimulation of the RLN leads to the response of the relative vocal cord, which could be palpated or observed by means of electromyography (EMG).

For implementation of the good IONM the collaboration between the surgeons and the anaesthesiologists is strongly required, e.g. the vocal cords are been monitored during the operation by means of laryngoscopy or a special endotracheal tube.

The particular role for the anaesthesiologists during the operation is the way of using of muscle relaxants. In fact, long-action agents should be generally avoided to prevent the absence of adequate muscle response, during the IONM.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Anaesthesia With or Without Neuromuscular Blocking Agents in Intubation and Intraoperative Nerve-monitoring During Thyroid Surgery: a Feasibility and Safety Pilot Study.
• Actual Study Start Date: April 17, 2019
• Actual Primary Completion Date: December 30, 2019
• Actual Study Completion Date: December 30, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Rocuronium 0,3 mg/kg; One hour before the operation the patient will receive the midazolam from 1 to 5 mg intravenous. After the adequate preoxigenation and denitrogenation, the induction phase will be performed with the propofol 2 mg/kg intravenous bolus (for the sedation). At the same time continues infusion of remifentanyl (up to 1 mcg/kg/min) will guarantee the adequate anaesthesia. Patients, who have been randomized to this group, will be obtained single reduced dose of rocuronium (0,3 mg/kg) once intravenous bolus. The dose of rocuronium will be prepared by an external investigator, to leave the anesthesiologist blinded of the group treatment. The drug will be diluited in a syringe with 20 ml of solution.	Drug: Rocuronium 0.3 mg*kg; Patients randomized to the control group will receive rocuronium at 0.3 mg*kg ev bolus at the induction of anesthesia.; Other Name: Neuromuscular blockade
Experimental: No rocuronium; One hour before the operation the patient will receive the midazolam from 1 to 5 mg intravenous. After the adequate preoxigenation and denitrogenation, the induction phase will be performed with the propofol 2 mg/kg intravenous bolus (for the sedation). At the same time continues infusion of remifentanyl (up to 1 mcg/kg/min) will guarantee the adequate anaesthesia. Patients, who have been randomized to this group, will not receive rocuronium, but normal saline will be administered by the anesthesiologist in charge of the patients. The dose of normal saline (20 ml in one syringe) will be prepared by an external investigator, to leave the anesthesiologist blinded of the group treatment.	Drug: No Rocuronium; Patients randomized to the interventional group will not receive neuromuscular blockade at the induction of anesthesia.; Other Name: No neuromuscular blockade

Outcome Measures

Primary Outcome Measures :

1. Occurrence of absent or weak signal at V1 and R1 (i.e. amplitude <100 μV) [ Time Frame: Immediately after vagus and recurrent laryngeal nerve identification ]
   Record of the vagus (V1) and recurrent laryngeal nerve (R1) with the intraoperative neuromuscular monitoring before the dissection of the thyroid

Secondary Outcome Measures :

1. Time of intubation [ Time Frame: Immediately after successful endotrachel intubation ]
   The time of intubation is intended as the duration from the moment when the anaesthesiologist takes the laryngoscope till the first end-tidal carbon dioxide record
2. Rate of difficult intubation [ Time Frame: Immediately after successful endotrachel intubation ]
   Difficult orotracheal intubation is defined as an intubation, which requires more than 2 laryngoscopies, which continues more than 10 minutes, or whether it claims the use of alternative devices
3. Cormack Lehane scale value [ Time Frame: Immediately after successful endotrachel intubation ]
   Evaluation of laryngeal exposition according to Cormack-Lehane (1: Full view of glottis; 2a: Partial view of glottis; 2b: Only posterior extremity of glottis seen or only arytenoid cartilages; 3: Only epiglottis seen, none of glottis seen; 4: Neither glottis nor epiglottis seen)
4. V1 time [ Time Frame: Immediately after vagus identification ]
   The time passed from the cutaneous incision until the measurement of V1 (pre-dissection stimulation of vagus nerve)
5. incidence of post-operative complication [ Time Frame: At 48 hours from surgery ]
   The incidence of post-operative complication (paralysis of RLN, hyporparathyroidism, bleeding or infections of surgical site, dysphagia, post-operative lung complications).
6. Post-dissection vagus stimulation value [ Time Frame: Immediately after the complete removal of the thyroid ]
   Record of the vagus stimulation (V2) with the intraoperative neuromuscular monitoring after the dissection of the thyroid
7. Post-dissection recurrent nerve stimulation value [ Time Frame: Immediately after the complete removal of the thyroid ]
   Record of the recurrent nerve stimulation (R2) with the intraoperative neuromuscular monitoring at the end of the dissection of the thyroid
8. Pain assessment [ Time Frame: Immediately after the end of the surgery ]
   Evaluation of postoperative pain by means of the numeric pain rating scale from 0 (no pain) to 10 (maximal severe pain)
9. Predissection recurrent nerve stimulation value [ Time Frame: Immediately after recurrent nerve identification ]
   Record of the recurrent nerve stimulation (R1) with the intraoperative neuromuscular monitoring before the dissection of the thyroid
10. Predissection vagus stimulation value [ Time Frame: Immediately after vagus identification ]
    Record of the vagus stimulation (V1) with the intraoperative neuromuscular monitoring before the dissection of the thyroid

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Elective surgery of the thyroid with the use of Intra-Operative Neuromuscular Monitoring (IONM)

Exclusion Criteria:

• Patients who suffer from paralysis of vocal cords or diseases of neuromuscular system.
• Patients with a history of allergy to anaesthetic drugs.
• Patients who has a high possibility of difficult intubation due to one the following criteria: a) interdental distance < 20 mm; b) marked upper teeth protrusion (mandibular prognathism), which is not possible to correct; c) thyromental distance ≤ 60 mm; d) Mallampati class 4; e) macroglossia with marked micrognathia; f) fixed neck flection; g) severe scar tissue or post radiation fibrosis of the tongue.
• Patients who has a high possibility of difficult intubation due to two of the following criteria, associated with each other: a) interdental distance < 35 mm; b) moderate prognathism or retrgnathia; c) mentohyoid distance < 40 mm; d) thyromental distance ≤ 65 mm; e) Mallampati class 2-3; f) reduced head-neck flexion and extension; g) Body Mass Index (BMI) > 30 kg/m2.

Contacts and Locations

Locations

Italy

AOU Mater Domini

Catanzaro, Italy

Sponsors and Collaborators

Federico Longhini

Investigators

• Principal Investigator: Federico Longhini, MD; Dipartimento di Scienze Mediche e Chirurgiche, Università Magna Graecia

More Information

• Responsible Party: Federico Longhini, Associate Professor, University Magna Graecia
• ClinicalTrials.gov Identifier: NCT03910504
• Other Study ID Numbers: IONM
• First Posted: April 10, 2019
• Last Update Posted: November 3, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The full protocol, datasets used and analysed during the current study will be available on reasonable request at the corresponding author
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: Data will be available after publication
• Access Criteria: On reasonable request at the corresponding author

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Thyroid Diseases; Endocrine System Diseases; Rocuronium; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Neuromuscular Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs