Remifentanil Tapering and Post-adenotonsillectomy Pain in Children

NCT ID: NCT03994146

Last Updated: 2023-08-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-16
• Study Completion Date: 2023-08-18

Brief Summary

Tonsillectomy is the commonest operation of childhood and results in considerable pain.

Remifentanil is a potent, ultra short acting opioid with a long- established safety record in paediatric anaesthesia that is used to provide intraoperative analgesia.

There is evidence from adult studies that remifentanil increases postoperative pain, although this may be ablated if propofol (rather than inhalational anaesthesia) is used or if the remifentanil is tapered rather than abruptly discontinued at the end of surgery.

The analgesic effect of gradual withdrawal of remifentanil at the end of surgery has not been studied in children and may have significant clinical implications.

The primary measure of efficacy will be the dose of fentanyl rescue analgesia in the peri-operative period (1 mcg.kg-1 bolus for >20% increase in pulse, blood pressure or movement intraoperatively or a FLACC(Face, Legs, Arms, Cry, Consolablity) score of >5 in recovery).

Detailed Description

Tonsillectomy is one of the commonest childhood operations in the world; approximately 9200 children have their tonsils removed every year in Norway alone.

Postoperative pain following the procedure is significant and notoriously difficult to mange. It´s management is potentially complicated by nausea and the risk of tonsillar infection or re-bleeding. Post-tonsillectomy pain in children is persistent, with 75% of children experiencing significant pain for the first three days and 50% still suffering with significant pain one week after the procedure. As well as delaying recovery, reducing oral intake of food and drink and disturbing sleep, post tonsillectomy pain has been shown to result in more than 50% of patients and their parents consulting their primary care physician in the post operative period, with the ensuing costs to the families and healthcare providers.

It is worth noting, that despite significant postoperative pain and potential complications, recovery after adeno / tonsillectomy is excellent.

The operative nature of tonsillectomy and adenotonsillectomy necessitates the provision of general anaesthesia to the child. The technique must ensure sufficient depth of anaesthesia and analgesia and protection of the airway from blood and surgical debris. Whilst there are a wide variety of anaesthetic techniques employed to achieve these goals,Total Intra Venous Anaesthesia (TIVA) with propofol and remifentanil has been shown in previous studies to be superior to volatile based (gas) anaesthesia, resulting in less post operative nausea and vomiting, less long term adverse behavioural changes, improved quality of emergence from anaesthesia, and less environmental pollution.

The use of remifentanil and propofol TIVA in children is well established and has been in use since at least the year 2000 for children undergoing tonsillectomy. Despite this the effects of remifentanil dosing on post-operative pain has not been studied in children undergoing tonsillectomy, though it may play a significant role.

Conditions

Child, Only; Pain; Tonsillectomy; Remifentanil

Study Design

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

Study Groups

Remifentanil tapering / Placebo abrupt cessation

Syringe one contains Remifentanil 2 mg in 40 ml NaCl 9 mg.ml-1 = 50 µg.ml-1 which will be infused at a rate of 0.9 µg.kg-1.min-1 and Syringe two contains 40 ml NaCl 9 mg.ml-1 at an identical infusion rate. According to randomisation syringe one will then be tapered towards the end of surgery and syringe two abruptly stopped.

Group Type: EXPERIMENTAL

Remifentanil

Intervention Type: DRUG

Syringe containing 40 ml of Remifentanil 50 µg/ml for intravenous administration.

In order to maintain double blinding two identical syringes, prepared by pharmacy according to randomisation, will be simultaneously infused. One of the syringes will be abruptly stopped at the end of the operation whilst the other is tapered by stepwise decreases in infusion rate prior to the end of surgery.

Sodium Chloride 9mg/mL

Intervention Type: DRUG

Syringe containing 40 ml of Sodium Chloride 9 mg/ml for intravenous administration.

In order to maintain double blinding two identical syringes, prepared by pharmacy according to randomisation, will be simultaneously infused. One of the syringes will be abruptly stopped at the end of the operation whilst the other is tapered by stepwise decreases in infusion rate prior to the end of surgery.

Placebo tapering / Remifentanil abrupt cessation.

Syringe one contains 40 ml NaCl 9 mg.ml-1 and Syringe two contains Remifentanil 2 mg in 40 ml NaCl 9 mg.ml-1 = 50 µg.ml-1 which will be infused at a rate of 0.9 µg.kg-1.min-1. According to randomization syringe one will be tapered towards the end of surgery and syringe two abruptly stopped.

Group Type: PLACEBO_COMPARATOR

Remifentanil

Intervention Type: DRUG

Syringe containing 40 ml of Remifentanil 50 µg/ml for intravenous administration.

In order to maintain double blinding two identical syringes, prepared by pharmacy according to randomisation, will be simultaneously infused. One of the syringes will be abruptly stopped at the end of the operation whilst the other is tapered by stepwise decreases in infusion rate prior to the end of surgery.

Sodium Chloride 9mg/mL

Intervention Type: DRUG

Syringe containing 40 ml of Sodium Chloride 9 mg/ml for intravenous administration.

In order to maintain double blinding two identical syringes, prepared by pharmacy according to randomisation, will be simultaneously infused. One of the syringes will be abruptly stopped at the end of the operation whilst the other is tapered by stepwise decreases in infusion rate prior to the end of surgery.

Interventions

Remifentanil

Syringe containing 40 ml of Remifentanil 50 µg/ml for intravenous administration.

In order to maintain double blinding two identical syringes, prepared by pharmacy according to randomisation, will be simultaneously infused. One of the syringes will be abruptly stopped at the end of the operation whilst the other is tapered by stepwise decreases in infusion rate prior to the end of surgery.

Intervention Type: DRUG

Sodium Chloride 9mg/mL

Syringe containing 40 ml of Sodium Chloride 9 mg/ml for intravenous administration.

In order to maintain double blinding two identical syringes, prepared by pharmacy according to randomisation, will be simultaneously infused. One of the syringes will be abruptly stopped at the end of the operation whilst the other is tapered by stepwise decreases in infusion rate prior to the end of surgery.

Intervention Type: DRUG

Other Intervention Names

Ultiva; Normal saline; Placebo

Eligibility Criteria

Inclusion Criteria

• American Society Anaesthesiology I-II children 1 to 10 years
• Weight over 10.0 Kg
• Presenting for tonsillotomy / tonsillectomy or adenotonsillectomy at Akershus Universitetssykehus, Lørenskog and Lovisenberg Diakonale Hospital, Norway

Exclusion Criteria

• Children who have had airway surgery previously.
• Children who have had any type of surgery in the previous 12 months.
• Children using chronic pain medication or who have used analgesia in the 24 hours preceding surgery.
• Children who are known to suffer from NSAID sensitive asthma.
• Children with a known allergy to propofol or remifentanil.
• Pre-existing cardiac, renal, liver dysfunction.
• Children or parents who are not fluent in Norwegian or English.
• Children in whom more than three attempts at intravenous cannulation are required or in those who request an inhalational induction or premedication

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Akershus

OTHER

Sponsor Role: lead

Responsible Party

William James Morton

Principle Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Signe Søvik, MD. PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Akershus

Locations

Akershsus Universitetssykehus

Lørenskog, Akershus, Norway

Lovisenberg Diakonale Sykehus

Oslo, , Norway

Countries

Norway

Other Identifiers

2019-001677-81

Identifier Type: -

Identifier Source: org_study_id