Effect of Total Intravenous Anaesthesia With Propofol on Postoperative Pain After Bilateral Third Molar Surgery

The Effect of Total Intravenous Anaesthesia With Propofol on Postoperative Pain After Third Molar Surgery: A Double-Blind Randomized Controlled Trial

Propofol is one of the most commonly used intravenous anaesthetic drugs both for induction and maintenance of general anaesthesia. Some of the advantages of total intravenous anaesthesia (TIVA) with propofol include reduced nausea and vomiting, reduced atmospheric pollution, better wake up profile and a more favourable intracranial physiology. However, the need for a reliable intravenous access, specialized pumps, pain on injection and potential concerns regarding awareness are some reasons that preclude more common use.

Postoperative dental pain produces an inflammatory pain model. Since propofol has anti-inflammatory effects, it may have significant analgesic effects in patients undergoing dental surgery. To the best of our knowledge, there are no randomized controlled trials comparing the effects of TIVA propofol and inhalational anaesthetic on postoperative dental pain. The aim of this study is to investigate the effect of TIVA propofol on postoperative pain scores, analgesic consumption, and adverse effects in patients undergoing dental surgery. This will help determine whether propofol may be a useful analgesic adjunct in dental surgery.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Sevoflurane; Drug: propofol

Detailed Description

Preoperative care

Assessment will be done at the preadmission clinic or at the general ward. Fasting for patients will start at midnight before operation. Sedative premedication will not be prescribed.

Anaesthesia and intraoperative care

Group S

Patients from group S will be anaesthetized according to the following protocol:

On arrival to the operation theatre, a 20 or 22 gauge intravenous cannula will be inserted. Standard monitoring with pulse oximeter, non-invasive blood pressure, and three lead electrocardiogram will be applied prior to induction. Non-invasive blood pressure will be checked at least every 5 minutes throughout the operation.

Propofol 1.5-3mg/kg, remifentanil 0.5-1mcg/kg, and rocuronium 0.6-1mg/kg or atracurium 0.5mg/kg will be used intravenously (IV) for induction of general anaesthesia. Otrivin can be applied nasally at the discretion of the anaesthetist. Intubation would be performed after induction of general anaesthesia. General anaesthesia monitoring will be used. Sevoflurane, air and oxygen will be used for maintenance of general anaesthesia. FiO2 will be kept between 35-50%. BIS monitoring will be applied and level of anaesthetia will be titrated to keep a BIS value of 40-60. Intravenous remifentanil infusion between 0.1-0.25mcg/kg/min will be given and this will be titrated to optimal haemodynamic parameters. Muscle relaxants can be given during the operation as required.

Intravenous phenylephrine, ephedrine or fluid administration with colloid or crystalloid will be given at the discretion of the anaesthesiologist for management of hypotension. Hypertension or tachycardia will be managed by titrating the remifentanil infusion up to 0.25mcg/kg/min or sevoflurane up to 1.5 MAC. Intravenous anti hypertensive agents such as beta blockers (eg. esmolol, labetolol), hydralazine, glyceryl trinitrate, and phentolamine can be given if hypertension persists.

Thermal blanket will be used with the aim of keeping a core temperature of 35.5-37.5 degrees Celsius. Ondansetron 4mg IV can be given 30 minutes before end of surgery.

Sevoflurane and remifentanil infusion will be switched off at the end of the procedure. Reversal of muscle relaxation can be obtained if required with neostigmine 50mcg/kg IV and atropine 20mcg/kg IV after the operation. Patients will subsequently be transferred to the post anaesthetic care unit (PACU) for monitoring for at least 30 minutes.

Group P

Patients in group P will be anaesthetized according to the following protocol:

Monitoring and other anaesthetic procedures including the management of hypertension and hypotension will be the same as group S. The only difference is that induction and maintenance of general anaesthesia will be conducted using total intravenous infusion of propofol. Sevoflurane will not be used, and oxygen and air would be given to provide a FiO2 of 30-50%.

Target controlled infusion (TCI) with modified Marsh effect site model (Fresenius Kabi) will be used for induction and maintenance of general anaesthesia. Level of anaesthesia will be titrated to produce a BIS value of between 40-60. As with patients in group S, remifentanil will be infused at a rate of between 0.1-0.25mcg/kg/min.

Analgesic modalities and pain assessment

Both groups (Groups S and P)

Dental surgeon will provide local infiltration with 2.7ml of 2% lignocaine with 1:80,000 adrenaline around the base of the gum of each third molar tooth. Morphine sulphate at a bolus dose of 0.025-0.075 mg/kg will be given intravenously before skin incision.

Resting pain scores will be checked every 5 minutes in the post anaesthetic care unit. 2mg boluses of intravenous morphine sulphate will be given every 5 minutes until the NRS pain score is less than 4/10. Respiratory rate, oxygen saturation, Ramsay sedation scores, blood pressure and heart rate will be monitored every 5 minutes while the patient is in the post anaesthetic care unit.

When the patient resumes fluid diet on postoperative day 0, oral paracetamol 500mg q6h and oral dihydrocodeine 30mg q6h will be prescribed on an as needed basis when NRS pain score is more than 3/10 for three days. Both analgesics will be given together.

In the ward, pain related parameters like the numerical rating scales (NRS) pain scores at rest and mouth opening, and side effects will also be recorded every 1 hour for 6 hours, and then once every 4 hours. Patients will be given a diary to record NRS pain scores at rest and with mouth opening, analgesic consumption, and side effects at 24th, 48th and 72nd hour after operation. Global pain satisfaction using a scale of 0-10 (0 being least satisfied and 10 being most satisfied) will be recorded on postoperative day 3.

Monitoring of vital signs will be at the discretion of the attending dental surgeon once the patient returns to ward, and final hospital discharge will also be determined by the attending dental surgeon.

A brief home telephone interview will be conducted at 3 months to assess the incidence of chronic pain. The severity of pain, if present, would be recorded using NRS at rest and on mouth opening from 0-10.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 4

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • The University of Hong Kong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA I to III
• Age 18 to 80 years old
• Scheduled for elective extraction of impacted bilateral third molar teeth under general anaesthesia in Queen Mary hospital.

Exclusion Criteria:

• Known drug allergy to propofol, opioids, non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors, paracetamol.
• Alcohol or drug abuse
• Impaired renal function, defined as preoperative serum creatinine level over 120µmol/L
• Patients with liver dysfunction (Plasma bilirubin over 34 micromol/L, INR over 1.7, ALT and AST over 100U/L)
• Impaired or retarded mental state
• BMI > 35kg/m2
• History of chronic pain
• Pregnancy
• Local infection
• Patient refusal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Group S; Patients will be anaesthetized by inhalational anaesthesia using sevoflurane.	Drug: Sevoflurane; Propofol 1.5-3mg/kg, remifentanil 0.5-1mcg/kg, and rocuronium 0.6-1mg/kg or atracurium 0.5mg/kg will be used intravenously (IV) for induction of general anaesthesia. Otrivin can be applied nasally at the discretion of the anaesthetist. Intubation would be performed after induction of general anaesthesia. General anaesthesia monitoring will be used. Sevoflurane, air and oxygen will be used for maintenance of general anaesthesia. FiO2 will be kept between 35-50%. BIS monitoring will be applied and level of anaesthetia will be titrated to keep a BIS value of 40-60. Intravenous remifentanil infusion between 0.1-0.25mcg/kg/min will be given and this will be titrated to optimal haemodynamic parameters. Muscle relaxants can be given during the operation as required.
Experimental: Group P; Patients will be anaesthetized using total intravenous propofol.	Drug: propofol; Monitoring and other anaesthetic procedures including the management of hypertension and hypotension will be the same as group S. The only difference is that induction and maintenance of general anaesthesia will be conducted using total intravenous infusion of propofol. Sevoflurane will not be used, and oxygen and air would be given to provide a FiO2 of 30-50%.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pain score	measure pain scores at rest and mouth opening using numeral rating scale	up to postoperative day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
analgesic consumption	record analgesic consumption base on patient drug record	up to postoperative day 3
side effects of analgesics used	pruritus, dizziness, nausea, vomiting, constipation etc.	up to postoperative day 3
intraoperative vital signs	blood pressure	during surgery
intraoperative vital signs	heart rate	during surgery
intraoperative vital signs	oxygen saturation	during surgery
presence of persistent pain	presence of chronic pain after surgery (Yes or No), and severity of pain using NRS 0-10 if pain is present	3 months after surgery
severity of persistent pain	severity of pain using NRS 0-10 if pain is present	3 months after surgery

Collaborators and Investigators

• Sponsor: The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2016
• Primary Completion (Actual): March 30, 2018
• Study Completion (Actual): March 30, 2018

Study Registration Dates

• First Submitted: February 7, 2017
• First Submitted That Met QC Criteria: February 15, 2017
• First Posted (Actual): February 20, 2017

Study Record Updates

• Last Update Posted (Actual): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 1, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: TIVA; propofol; postoperative pain
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Hypnotics and Sedatives; Anesthetics, Inhalation; Propofol; Sevoflurane
• Other Study ID Numbers: UW16-554

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No