Epidural Morphine for Postoperative Analgesia After Total Knee Arthroplasty

Study Overview
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Brief Summary
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Single femoral nerve blockade combined with patient-controlled intravenous analgesia are used for postoperative analgesia for patients after TKA in the hospital of the investigators. Although this method provides acceptable analgesia, the incidence of opioid-associated side effects is relatively high. Low-dose epidural morphine is commonly used in postoperative analgesia after cesarean section, and the effect of single dose morphine lasts more than 20 hours, with low incidences of itching, nausea, vomiting, and respiratory depression. The investigators hypothesize that, for patients undergoing TKA, the addition of low-dose epidural morphine to single femoral nerve block and intravenous opioids can improve the postoperative analgesia, reduce the consumption of intravenous opioids and decrease opioid-associated side effects.

Detailed Description
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Total knee arthroplasty (TKA) is an important therapy for patients with serious knee osteoarthritis in order to improve quality of life and relieve pain. But a large number of patients who undergo this surgery experience moderate to severe postoperative pain. Previously, the investigators used single femoral nerve blockade combined with patient-controlled intravenous analgesia for postoperative analgesia for patients after TKA. Although this method provides acceptable analgesia, the incidence of opioid-associated side effects is relatively high. Low-dose epidural morphine is commonly used in postoperative analgesia after cesarean section, and the effect of single dose morphine lasts more than 20 hours, with low incidences of itching, nausea, vomiting, and respiratory depression. The investigators hypothesize that, for patients undergoing TKA, the addition of low-dose epidural morphine to single femoral nerve block and intravenous opioids can improve the postoperative analgesia, reduce the consumption of intravenous opioids and decrease opioid-associated side effects.

Official Title
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Effect of Low-dose Epidural Morphine Combined With Single-injection Femoral Nerve Block on Postoperative Analgesia in Patients After Total Knee Arthroplasty

Conditions
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Adult Patients, Total Knee Arthroplasty, Epidural Analgesia, Femoral Nerve Block, Analgesic Adverse Reaction

Intervention / Treatment
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* Procedure: Epidural morphine
* Procedure: Epidural placebo
* Procedure: Single femoral nerve block
* Drug: Intravenous morphine analgesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (age of 18 years or older); American Society of Anesthesiologists classification I-III; Scheduled to undergo unilateral TKA under combined spinal and epidural anesthesia. Exclusion Criteria: Age higher than 90 years old; Presence of any contraindication to neuraxial block or peripheral nerve block; Continuous use of opioid analgesics during the last month; Unable to understand Numeric Rating Scale for pain evaluation or existence of language barrier; Severe renal insufficiency (requirement of renal replacement therapy); History of asthma; Recruited in another clinical trials.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epidural morphine<br>Epidural morphine (2 mg morphine in 5 ml normal saline) is administered through the epidural catheter at the end of surgery. Single femoral nerve block is performed with 20 ml of 0.5% ropivacaine under the guidance of ultrasonography and nerve stimulator after surgery. Intravenous morphine analgesia is provided with a patient-controlled analgesia pump which is established with 100 ml of 0.5 mg/mL morphine, programmed to deliver a 2 ml bolus with a lockout interval of 8-10 min and a background infusion of 0.5 mL/h. | Procedure: Epidural morphine<br>* 2 mg of morphine (0.4 mg/ml morphine in 5 ml normal saline) is administered through the epidural catheter at the end of surgery.<br>Procedure: Single femoral nerve block<br>* Single femoral nerve block is performed with 20 ml 0.5% ropivacaine under the guidance of ultrasonography and nerve stimulator after surgery.<br>Drug: Intravenous morphine analgesia<br>* Intravenous morphine analgesia is provided with a patient-controlled analgesia pump which is established with 100 ml of 0.5 mg/ml morphine, programmed to deliver a 2 ml bolus with a lockout interval of 8-10 min and a background infusion of 0.5 ml/h.<br>|
| Placebo Comparator: Epidural placebo<br>Epidural placebo (5 ml normal saline) is administered through the epidural catheter at the end of surgery. Single femoral nerve block is performed with 20 ml of 0.5% ropivacaine under the guidance of ultrasonography and nerve stimulator after surgery. Intravenous morphine analgesia is provided with a patient-controlled analgesia pump which is established with 100 ml of 0.5 mg/mL morphine, programmed to deliver a 2 ml bolus with a lockout interval of 8-10 min and a background infusion of 0.5 mL/h. | Procedure: Epidural placebo<br>* 5 ml normal saline is administered through the epidural catheter at the end of surgery.<br>Procedure: Single femoral nerve block<br>* Single femoral nerve block is performed with 20 ml 0.5% ropivacaine under the guidance of ultrasonography and nerve stimulator after surgery.<br>Drug: Intravenous morphine analgesia<br>* Intravenous morphine analgesia is provided with a patient-controlled analgesia pump which is established with 100 ml of 0.5 mg/ml morphine, programmed to deliver a 2 ml bolus with a lockout interval of 8-10 min and a background infusion of 0.5 ml/h.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of patients with moderate to severe pain (Numeric Rating Scale pain score of 4 or higher) | Pain severity is evaluated with Numeric Rating Scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) both at rest and with movement. | Until 48 hours after surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NRS pain scores (at rest and with movement) at various timepoints after surgery | Pain severity is evaluated with Numeric Rating Scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) both at rest and with movement. | At 6, 12, 24, 36 and 48 hours after surgery. | 
| Cumulative morphine consumption | Cumulative morphine consumption during 48 hours after surgery. | Until 48 hours after surgery. | 
| Recovery of motor function of the lower limb from blockade | Modified Bromage scale (0 = no blockade: extended limb lift off the bed; 1 = flexion/extension at knee and ankle joint; 2 = no flexion/extension at knee or ankle joint; 3 = complete blockade). | At the end of the surgery and at 0.5, 6, 12, 24, 36, 48 hours after surgery. | 
| Time to begin functional exercise and ground walking | Time to begin functional exercise and ground walking | During hospital stay, up to 1 week after surgery. | 
| Patient's satisfaction with analgesia | Evaluated in 5 scale, i.e., very satisfactory, satisfactory, neither satisfactory nor unsatisfactory, unsatisfactory, and very satisfactory. | At 48 hours after surgery. | 
| Length of stay in hospital after surgery | Length of stay in hospital after surgery | Until hospital discharge up to 30 days after surgery. | 
| Incidence of postoperative complication | Incidence of postoperative complication within 30 days after surgery. | Until 30 days after surgery. | 
| The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index | Evaluated with the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. | At 30 days after surgery. | 
| Quality of life (SF-12) at 30 days after surgery | Evaluated with Short-Form Health Survey-12 (SF-12) at 30 days after surgery. | At 30 days after surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adults, Unilateral TKA, Single femoral nerve block, Low-dose epidural morphine, Effect of postoperative analgesia, Quality of life