Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03597776 |
| Other study ID # |
UW18-276 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
January 3, 2019 |
| Est. completion date |
September 14, 2020 |
Study information
| Verified date |
May 2024 |
| Source |
The University of Hong Kong |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Osteoarthritis of knees and hips is a common medical problem present in elderly, which poses
significant impairment to their mobility, independence, and quality of life. Despite the
availability of conservative treatment, such as simple analgesics and physiotherapy, total
joint replacement is the only curative option for this disease entity.
The latter, however, is not without risk. A study by Poulakka has demonstrated that patients
with poor pain control in the postoperative period were three to ten times more likely to
develop chronic pain, which may significantly impair the patients' functional status and
quality of life.
Optimal pain control is therefore essential in facilitating rehabilitation and in preventing
long-term morbidities.
Lidocaine [2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide] is an amide local anaesthetic
that is characteristically fast in onset and short in duration of action. As such, it has
long been used for providing regional anaesthesia for operation, but with limited role in
terms of post operative analgesia.
Recently, intravenous infusion of lidocaine has been shown to be safe and effective in
reducing post operative pain (resting and dynamic), opioid consumption, and chronic
post-surgical pain. The mechanism of action involves both peripheral and central actions. In
addition to blockade of the Voltage-gated Sodium Channel of the peripheral nerves, lidocaine
also inhibits priming of the PolyMorphoNuclear granulocyte (PMN) by inducing a time-dependent
inhibition of intracellular G-protein signalling molecule (Gq); thus reducing release of
cytokines and Reactive Oxygen Species Centrally, lidocaine also causes blockade of NMDA
receptors and Neurokinin Receptors of the Wide-Dynamic Range Neurons in the dorsal horn of
spinal cord; thus reduces glutamate activity.
We therefore hypothesize that the use of intravenous lidocaine may reduce acute pain and
improve the range of knee flexion after total knee replacement. Currently, there is strong
evidence supporting its use in laparoscopic and open abdominal surgeries. There is, however,
a paucity of studies in orthopedic surgeries. To date, there is no randomized controlled
trial that studied its effect in total knee replacement.
Description:
OBJECTIVE:
The aim of this study is to estimate the effectiveness of a preemptive bolus of intravenous
lidocaine on reduction in acute pain, improvement on the range of movement, other
rehabilitation parameters and functional scoring in the post-operative period after total
knee replacement.
DESIGN:
This is a double-blinded, randomized, placebo-controlled trial.
RECRUITMENT & SAMPLE SIZE:
Over a one-year period, suitable patients will be approached at the pre-admission clinic and
in the general ward before their operation. Informed consent will be obtained before
enrollment.
The sample size required is calculated to be 45 subjects per group.
PATIENT CHARACTERISTICS:
In order to minimize potential confounding factors, the demographic data of each subject will
be collected during preoperative assessment, including: age, gender, duration of preoperative
pain duration, preoperative NRS (movement) and NRS (rest). Both active and passive ROM of the
knee will be assessed by the attending physiotherapist.
RANDOMIZATION & BLINDING:
Each subject will be assigned to either Lidocaine Group or Placebo Group. A randomization
list will be established by a computer-generated random sequence before the study begins. An
envelope containing the group assignment will be prepared, sealed, sequentially numbered, and
allocated for each subject. A "blinded" anaesthetist will then prepare lidocaine or saline
according to the group assigned for the attending anaesthetist. The subjects, the
investigators, and all the parties involved in patient management or data collection will be
blinded throughout the study period.
INTERVENTION:
For Lidocaine Group: a bolus of intravenous lidocaine of 2mg/kg over 5 mins will be given
before skin incision.
For Placebo Group: Normal Saline of equal volume will be given as bolus before skin incision.
ANAESTHESIA & ANALGESIA:
(I) PRE-OPERATIVE: Routine preoperative assessment will be taken at the pre-admission clinic
or at the general ward; and standard fasting times (6 hours for solid food and 2 hours for
clear liquid) will be ordered.
No analgesics or sedatives will be given as pre-medication. Holter machine will be used to
document any arrhythmia preoperatively and will be attached to patient till Day 1
postoperatively.
(II) INTRA-OPERATIVE: In addition to continuous ECG monitoring, BP, heart rate and SpO2 will
be monitored at no longer than every 5 mins throughout the operation. Signs and symptoms of
local anaesthetic toxicity will be assessed at 30 minute intervals.
After establishing at least one patent intravenous cannula and ensuring the monitors are
properly applied, Spinal Anaesthesia will be given by the attending anaesthetist under
aseptic technique.
The choice of equipment (Whitacre or Quincke Needle), technique (landmark or
ultrasound-guided), and approach (midline or paramedical) are at the discretion of the
attending anaesthetist.
An intrathecal dose of 2.2-2.6ml 0.5% Heavy Bupivacaine with 15mcg of fentanyl will be given
depending on the height of the patient. Vasopressors and intravenous fluids will be given as
necessary to keep the patient's blood pressure within 20% of his/her baseline, and to keep
the heart rate within normal range.
Bolus of lidocaine or placebo will then be given over 5 minutes before skin incision.
No Sedation will be given during operation in order to facilitate monitoring of systemic
toxicity.
No Systemic Analgesics will be given, including Paracetamol, NSAIDS, Ketamine and Opioids.
The surgeries will be performed by the same team of orthopedic surgeons experienced in total
knee replacement at a tertiary level university teaching hospital, using standardized
surgical techniques. All patients will undergo posterior stabilized knee prosthesis.
Standardized dose of LIA (40ml 0.75% Ropivacaine, 0.5ml 1 in 200,000 Adrenaline, 30mg
Ketorolac in 60ml Normal Saline) will be administered by the orthopedic team.
(III) POST-OPERATIVE (PHASE I RECOVERY IN PACU): Upon completion of surgery, the patient will
be transferred to PACU for further monitoring for at least 30 minutes. BP, heart rate, and
SpO2 will be monitored every 5 minutes in addition to continuous ECG monitoring. Signs and
symptoms of local anaesthetic toxicity will be assessed at 15 minute intervals.
Pain will be evaluated every 5 mins using NRS. If the score is greater than 4/10, 2mg
morphine will be given intravenously every 5 mins provided the patient has a respiratory rate
of > 12/min and a sedation score of <1 until a NRS of < 4/10 is achieved. At which point, a
patient-controlled analgesia (PCA) device will be connected to deliver morphine under a
standardized regime: 1mg bolus with 5 mins lockout, an hourly maximum of 0.1mg/kg, and no
background infusion.
(IV) POST-OPERATIVE (PHASE II RECOVERY IN WARD): Continuous ECG monitoring will continually
be applied until Day 1 postoperatively.
Signs and symptoms of local anaesthetic toxicity will be assessed clinically at 1-hour
intervals for 12 hours after operation.
BP, heart rate, SpO2, and sedation score will be monitored at 1-hour intervals while on PCA
morphine; BP and heart rate will be monitored at 4-hour intervals once PCA morphine is
terminated.
Postoperative analgesics will consist of:
PCA Morphine for at least 2 days postoperatively, and will be terminated on postoperative Day
3 once NRS (movement) is less than 4/10 or when 24-hour morphine consumption is less than
10mg.
Standardized analgesic regime, depending on body weight, will be started immediately after
operation. For body weight > 50kg, Oral paracetamol 1gram QID, and pregabalin 75mg nocte for
1 week celecoxib 200mg BD for 5 days. For body weight < 50kg, Oral paracetamol 1gram TDS, and
pregabalin 50mg nocte for 1 week. celecoxib 200mg daily for 5 days.
0.1mg/kg of intramuscular Morphine will be provided as necessary as rescue analgesic for any
breakthrough pain. Intravenous Ondansetron of 0.1mg/kg will be given as necessary for nausea
and vomiting.
Diet will be resumed on Postoperative Day 0. The rehabilitation programme will be
standardized for all patients and be carried out by the same team of physiotherapists and
occupational therapists with the goal of early mobilization on Postoperative Day 0.
