Dexamethasone in Pain Control After Total Knee Replacement
Condition: Acute Pain
MeSH terms: Acute Pain
Study type: Interventional
Phase: Phase 4

Summary: 
      The primary aims of total knee replacement are improvement in functional activities and
      reduce pain due to degenerated knee joints. However, there are around 20-30% of patients
      would develop significant pain problem despite uncomplicated total knee replacement. It
      accounts for major post-operative problems and burdens.

      Dexamethasone is glucocorticoid which is associated with anti-inflammatory response. It is
      well known to have prophylaxis effect for post-operative nausea and vomiting. Perioperative
      single dose of systemic dexamethasone have shown to be useful for reduction in pain and
      cumulative opioid consumption. Meta-analysis from De Oliveira et al supports that
      dexamethasone (up to 0.2 mg/kg) is a safe and effective multimodal pain strategy after
      surgical procedures. However, this dose recommendation is not surgery specific. It is
      essential to have more RCTs evaluating the optimal dose of steroid for pain management after
      hip and knee surgery.
    

Detailed description: 
      Patients will be approached at the preadmission clinic or in the general ward before
      operation. The analgesic methods will be explained and s/he will be recruited into the study
      if s/he agrees. There are standardized preoperative, intraoperative and postoperative
      analgesic regimes for patients undergoing total knee replacement.

      For preoperative analgesic regime, pregabalin 50mg are given the night before operation. Same
      analgesic regime is used on the day before operation. For intraoperative regime, standardized
      intraarticular local anaesthetic infiltration is used. For postoperative analgesic regime,
      PCA using morphine is used. In addition to PCA using morphine, standardized analgesic regime
      is used -- regular pregabalin 50mg nocte, paracetmal 1g QID, Celebrex 200mg BD will be given
      for 5 days.

      Patients will be randomized into one of three groups. Patients in the first group (D1) will
      receive standardized oral analgesic regime pre-operatively, intraoperatively and
      postoperatively. In addition to the above, they will be given preoperative intravenous 8mg
      dexamethasone. Patients in the second (D2) group will be given preoperative intravenous 16mg
      dexamethasone, in addition to same pre-operative, intraoperative and post-operative analgesic
      regimes. Patients in the third (C) group will be given preoperative intravenous 4ml 0.9%
      saline, in addition to same pre-operative, intraoperative and post-operative analgesic
      regimes.

      Preoperative Care Assessment will be done at the preadmission clinic or at the general ward.
      Pre-operative pregabalin will be given before operation and on the day before operation.
      Fasting will start six hours before operation.

      Range of movement of the operating knee, quadriceps function, pain scores of the affecting
      knee will be assessed on day before operation.

      Pre-operative inflammatory marker (e.g. CRP, ESR, tumour necrosis factor α, interleukin IL-6)
      and H'stix will be taken on day of admission.

      Anaesthetic and intraoperative care

      All patients will be anaesthetized according to the following protocol:

      On arrival to the operation theatre, a 18 or 16 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.

      Patients will be provided with spinal anaesthesia for the operation with 2.4 ml 0.5% heavy
      Marcaine will be administrated into spinal space after position confirmed with spinal needle.
      No intrathecal opioid will be given during the procedure. Patient will be sedated with TCI
      propofol (0.3 -1 ug/ml) throughout the whole total knee replacement after successful spinal
      anaesthesia.

      Intravenous antibiotic will be given before skin incision. Hypotension will be managed with
      intravenous phenylephrine or ephedrine at the discretion of the anaesthesiologist.
      Intra-operative fluid 8-10ml/kg/hr will be infused as maintenance. Also intravenous bolus of
      fluid will be given for replacement of blood loss. Infusion fluid warmer and thermal blanket
      will be used with the aim of keeping a core temperature of 35.5-37.5 degrees Celsius.

      Local anaesthetic infiltration of 40ml 0.75% ropivacaine, 0.5ml 1:200,000 adrenaline, 30mg
      ketorolac in 60ml normal saline will be administrated by orthopaedic surgeons after implant
      insertion and wound closure.

      Patients will subsequently be transferred to the post anaesthetic care unit (PACU) for
      monitoring for at least 1 hour. H'stix and H'cue will be checked 2 hours and 4 hours after
      preoperative injection of dexamethasone.

      Analgesic modalities and pain assessment

      Procedures for the all analgesic modalities are described below:

      Group D1 Patients from group D will be given a bolus injection of 2 ml saline with 2 ml
      dexamethasone (4mg/ml) before skin incision.

      Group D2 4ml bolus injection of dexamethasone (4mg/ml) will be given intravenously prior to
      incision.

      Group C 4ml bolus injection of 0.9% saline will be given intravenously prior to incision.

      For all groups In the recovery room after surgery, boluses of 2mg intravenous morphine will
      be given every 5 minutes until numerical rating pain score (NRS) is less than 4/10. A PCA
      machine will then be connected. The machine will be configured to give 1mg of morphine at a
      time and the lockout duration will be set to 5 minutes. No background infusion will be given
      and the maximum dose limit will be 0.1mg/kg per hour of morphine sulphate.

      Intramuscular morphine sulphate at a dose of 0.1mg/kg will be prescribed every 4 hours if
      necessary for breakthrough beginning from postoperative day 0. Intravenous 4mg ondansetron is
      used every 4 hours if necessary if there is any nausea or vomiting.

      On postoperative day 0, patient will resume oral diet if not contraindicated. Oral
      paracetamol and COX-2 inhibitor will be given for 5 days. Oral pregabalin will be given for 7
      days.

      While on PCA morphine, the patient's respiratory rate, SpO2 and sedation score will be
      monitored every hour. Heart rate and blood pressure will be checked every 4 hours. NRS pain
      scores at rest, during knee movement, during sleep, cumulative PCA morphine doses, and number
      of PCA demands/goods delivered, and side effects (nausea, vomiting, dizziness) will be
      recorded every 4 hours. Patients will be assessed by pain team everyday.

      Patients will be on PCA morphine for at least 2 days. If NRS pain scores during knee movement
      on postoperative day 2 is less than 4/10 or clinically low morphine consumption, PCA morphine
      will be stopped. PCA morphine will be continued if NRS is equal or greater than 4, or if the
      patient remains on a high PCA consumption.

      After PCA morphine has stopped, NRS pain scores at rest and during knee movement, as well as
      the dose and frequency of rescue analgesia used will be charted once a day until discharge.

      Surgical technique/Prosthesis The surgery will be performed by the same surgical team with
      standardized surgical technique. All the patients will have posterior stabilized knee
      prosthesis. Tranexamic acid will be given according to our protocol. Standardized regimen and
      technique of local infiltration of analgesic at the end of the surgery will be given as part
      of the multi-modal pain control protocol

      Postoperative care and assessment Day zero mobilization or early mobilization with PT and OT
      rehabilitation is encouraged after operation. Fluid diet will be allowed on postoperative day
      0.

      The surgical team will assess for occurrences of postoperative surgical complications,
      suitability for discharge (good pain control, ambulation, normal bowel function, and ability
      to eat properly without vomiting. Urinary retention will be documented as well.

      Range of movement of the operating knee and other rehabilitation parameters will be
      assessment by allied health staffs from Day 0 till day of discharge.

      Side effects of steroid are documented e.g. gastrointestinal bleeding, hyperglycaemia, wound
      infection (Southampton wound assessment scale), or other systemic infections are documented.

      Glucose level will be measured in 7am and 5pm on Day 1 and Day 2. Insulin will be used to
      keep glucose <15 mmol/dl. Blood investigations will also be performed. Inflammatory marker
      e.g. ESR, CRF, tumour necrosis factor α, interleukin IL-6 will be taken on Day 0, Day 1 and
      Day 2. Haemoglobin level and the need of transfusion will be documented.
    

Intervention name(s): Dexamethasone; Saline
Intervention type(s): Drug; Drug
Intervention description(s): Bolus injection of different dose of dexamethasone will be given intravenously prior to incision.; Bolus injection of 4ml 0.9% saline will be given intravenously prior to incision.
Intervention MeSH terms: Dexamethasone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment