Intra-operative

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PROSPECT Recommendations

  • Peripheral nerve blocks are not recommended to be performed intra-operatively (Grade D, LoE 4). PROSPECT definition of pre-operative, intra-operative and postoperative administration Click here for more information

Clinical practice

  • None cited

Transferable evidence

  • None cited

Total knee arthroplasty-specific evidence

  • Evidence suggests that the time of administration of femoral nerve blocks has no effect on postoperative pain outcomes after TKA. Therefore, included studies of such techniques have been pooled for analysis irrespective of the timing of administration. All of the procedure-specific evidence is presented in the Postoperative section

PROSPECT Recommendations

  • GA + femoral nerve block, or spinal anaesthesia (with LA) + femoral nerve block are recommended as first choices for anaesthesia/analgesia (Grade D, LoE 4) (see also Pre-operative Peripheral nerve block techniques for evidence and recommendations about femoral nerve block)
  • Spinal LA + morphine is recommended but not as the first choice of anaesthetic/analgesic technique (Grade D, LoE 4), because of a greater potential for adverse events compared with femoral nerve block (transferable evidence, LoE 3) (see also Pre-operative Spinal techniques)
  • GA or spinal anaesthesia without any local or regional analgesic technique is not recommended (Grade D, LoE 4)
  • Epidural anaesthesia is not recommended (Grade D, LoE 4) because postoperative epidural analgesia is not recommended

Clinical practice

  • It is considered that analgesic drugs should be administered in time to secure sufficient pain relief when the patient wakes
  • Spinal anaesthesia provides a more complete surgical block than epidural anaesthesia
  • Epidural analgesia is associated with a relatively high degree of patient monitoring and serious (although rare) major complications
  • Epidural analgesia is a relatively complicated and invasive technique compared with peripheral nerve blocks

Transferable evidence

  • Epidural analgesia was superior to systemic analgesia for postoperative pain outcomes following hip or knee replacement Choi et al 2003 Click here for more information
  • A combination of epidural local anaesthetic plus opioid produced superior analgesic benefits compared with either drug administered alone in three studies of hip or knee surgery Lorenzini et al 2002 Click here for more information
  • Epidural analgesia was associated with a lower incidence of sedation compared with systemic analgesia Choi et al 2003 Click here for more information
  • Epidural anaesthesia reduces the frequency of deep vein thrombosis and pulmonary embolism, and reduces intra-operative and postoperative blood loss, compared with general anaesthesia, particularly in total hip arthroplasty patients, as shown in a review
  • Two studies showed superior analgesic effects of spinal LA plus opioid compared with LA alone, following total hip or knee arthroplasty Drakeford et al 1991 Click here for more information
  • Bupivacaine administered via spinal infusion (0.5% at 0.4 ml/h or 0.2 ml/h) resulted in an increase in the incidence of sensory and motor block compared with saline infusion
  • Diamorphine administered spinally in combination with bupivacaine showed a significantly higher incidence of nausea and vomiting compared with the bupivacaine alone group (p<0.05) following knee or hip replacement surgery
  • Epidural infusion of ropivacaine (2 mg/ml) plus sufentanil (1 µg/ml) produced a significantly higher incidence of adverse events (pruritus, nausea and vomiting) than ropivacaine alone following major knee surgery (p<0.01; n=115)
  • Epidural administration of strong opioids is associated with side-effects including pruritus, PONV, urinary retention, and respiratory depression
  • Epidural analgesia was associated with more frequent urinary retention, pruritus and low blood pressure compared with systemic analgesia in hip or knee replacement Choi et al 2003 Click here for more information
  • Neuraxial opioids are associated with a greater risk of side-effects compared with continuous plexus and peripheral neural blockades after major orthopaedic surgery

Total knee arthroplasty-specific evidence

  • Pain scores during ROM were significantly lower in the epidural group compared with the spinal anaesthesia + IV PCA morphine group on postoperative days 1–10 (p<0.001, in all cases)
  • Pain scores at rest were significantly lower in the epidural group compared with the spinal anaesthesia + IV PCA morphine group on postoperative day 1 (p<0.001), but not on days 2–10
  • There was significantly less sedation in the epidural group compared with the spinal anaesthesia + IV PCA morphine group on postoperative day 1 (p=0.04), but not on day 2
  • VAS pain scores were significantly lower in the IV propofol + spinal anaesthesia group compared with the IV propofol + fentanyl group at 3–4 days postoperatively (p<0.05), but not at 8 h or 1–2 days following surgery (
  • IV propofol + spinal anaesthesia was associated with significantly reduced time to extubation, emergence, response to command, and orientation (p<0.001, in all cases) compared with IV propofol + fentanyl anaesthesia (
  • IV propofol + spinal anaesthesia was associated with significantly reduced requirement for antihypertensive therapy compared with IV propofol + fentanyl anaesthesia (p<0.01) (
  • The incidence of sore throat (p=0.002), hoarseness (p=0.009), and nausea (p=0.049) was significantly lower in the IV propofol + spinal anaesthesia group compared with the IV propofol + fentanyl group; the incidence of vomiting, dizziness and back pain was similar in both groups (
  • Significantly more patients reported feeling comfortable (p=0.01) and having good dreams (p<0.0001) in the IV propofol + spinal anaesthesia group than in the IV propofol + fentanyl group (
  • Postoperative pentazocine consumption was significantly higher in the IV propofol + spinal anaesthesia group compared with the IV propofol + fentanyl group in the first 8 h postoperatively (p<0.05); there were no significant differences between the two groups in the consumption of diclofenac sodium at 8 h postoperatively (postoperative analgesia was diclofenac sodium [50 mg] administered rectally every 6 h, and pentazocine, as required) (
  • Study Details Farag et al 2005 Click here for more information
  • Study Details Kudoh et al 2004 Click here for more information
  • Lumbar epidural versus spinal anaesthesia
  • Spinal versus IV anaesthesia

PROSPECT Recommendations

  • Intra-articular LA and/or morphine is not recommended at this time (Grade D, LoE 4) because of inconsistent analgesic efficacy in procedure-specific and transferable evidence (see Postoperative Intra-articular Analgesia)
  • Intra-articular NSAIDs, neostigmine, or clonidine are not recommended (Grade D, LoE 4) because there is no procedure-specific and inconsistent transferable evidence
  • Intra-articular corticosteroid is not recommended at this time (Grade D, LoE 4) because there is no procedure-specific evidence, despite positive transferable evidence from minor orthopaedic procedures (LoE 1)
  • After the cut-off date of the systematic literature search, additional studies of combined intra-articular and incisional LA have shown an analgesic benefit (procedure-specific evidence, LoE 1) (see Postoperative Intra-articular Analgesia)

Clinical practice

  • Doses of IA morphine in some studies (5–10 mg) represent systemic, not IA doses

Transferable evidence

  • A systematic review of knee joint surgery RCTs looked at the effects of IA morphine, compared with saline Kalso E et al 2002 Click here for more information
  • Several randomised studies in arthroscopic knee or ankle surgery have shown that intra-articular corticosteroid reduced pain after surgery
  • A second systematic review of RCTs examining the effects of IA morphine following knee joint surgery suggested that there were no significant analgesic effects of morphine compared with saline Rosseland LA 2005 Click here for more information

Total knee arthroplasty-specific evidence

  • There is no evidence that the timing of administration of intra-articular analgesia has a significant effect on postoperative pain outcomes. All studies of intra-articular analgesia are presented in the Postoperative Intra-articular section, except for studies comparing different times of administration.

PROSPECT Recommendations

  • After the cut-off date of the systematic literature search, additional studies of combined intra-articular and incisional LA have shown an analgesic benefit (procedure-specific evidence, LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • None cited

Total knee arthroplasty-specific evidence

PROSPECT Recommendations

  • Drains are not recommended (Grade A), as they do not provide analgesic or other recovery benefits (procedure-specific evidence, LoE 1) and are associated with pain on removal (LoE 4)

Clinical practice

  • Drains are associated with pain on removal

Transferable evidence

  • Wound drains without suction produced less postoperative pain intensity on removal compared with drains with suction in intra-articular procedures (n=126; p<0.05)
  • Several studies showed no significant benefit of drained compared with un-drained wounds for a range of postoperative pain outcomes, including postoperative pain scores, in orthopaedic surgery Parker et al 2003 Click here for more information
  • Wound drains were associated with higher pain scores than no drains (no statistical analysis) in one study of patients undergoing total hip arthroplasty (n=23)
  • A meta-analysis evaluating the effectiveness of closed suction drainage systems during orthopaedic surgery found no difference in the incidence of wound infection, haematoma or dehiscence between patients with drains and those with un-drained wounds, and concluded that the evidence was insufficient to support or refute the use of drains

Total knee arthroplasty-specific evidence

  • Three studies out of three showed that drainage was not associated with any significant difference compared with no drainage for VAS pain scores, see Table 5 for details ( Click here for more information
  • Only one study out of three reported analgesic use following the use of drainage or no drainage and showed no significant difference for the number of requests for analgesia (
  • Three studies out of three showed no significant difference between drainage and no drainage for knee flexion; see Table 5 for details Click here for more information
  • One of three studies showed that drainage significantly increased the circumference of the knee on day 3 (p<0.0096) compared with no drainage, but there was no significant difference at 1 week, 1 month or 4 months postoperatively, or for the circumference of the thigh or the calf ( Click here for more information
  • One out of one study showed that drainage significantly increased the time to regain active straight-leg raising (p=0.02) compared with no drainage (
  • Two studies comparing drainage with no drainage reported hospital stay and showed no significant difference between groups (
  • Two studies comparing drainage with no drainage reported blood loss and transfusion requirements, with mixed results: one study reported no significant difference for blood loss or incidence of blood transfusion, but drainage was associated with a significant increase in units of transfused blood (p=0.03) (
  • One study reported no significant difference between drainage and no drainage for postoperative complications ( Click here for more information
  • Study details and Table 5 Click here for more information

PROSPECT Recommendations

  • No recommendation can be made for tourniquet use, as this depends on surgical/anatomical requirements, rather than pain

Clinical practice

  • Tourniquet use provides a better intra-operative surgical overview of the anatomy and avoids nerve damage (med vastus approach). Decision to use rests with the surgeon, depending on the individual patient’s anatomy and the surgeon’s experience
  • Results are difficult to interpret, due to insufficient description of anaesthetic techniques

Transferable evidence

  • None cited

Total knee arthroplasty-specific evidence

  • Release of a pneumatic tourniquet around the thigh before suturing and bandaging was significantly superior to release after suturing and bandaging for reducing VAS pain scores at 4 h postoperatively (p<0.001) (
  • Use of tourniquet was not found to be associated with any significant effect on postoperative complications, except for a significant reduction in overall blood loss in one of the two studies ( Click here for more information
  • Release of a pneumatic tourniquet around the thigh before suturing and bandaging was significantly superior to release after suturing and bandaging for the time to achieve a straight leg (p<0.00001) (
  • Release of a pneumatic tourniquet around the thigh before suturing and bandaging was significantly superior to release after suturing and bandaging for reducing the incidence of minor wound complications (p=0.04) and excessive swelling (p=0.02) (
  • Two out of three studies found that surgery with tourniquet was associated with increased pain scores compared with no tourniquet; see Table 6 for details ( Click here for more information
  • Two out of three studies reported no differences between treatment groups in terms of supplemental analgesic use; see Table 6 for details ( Click here for more information
  • Three out of three studies reported that short-term functional outcomes were superior among patients who had not had a tourniquet (see Table 6 for details), although longer-term (>3 months) joint flexibility was not found to differ significantly according to tourniquet use ( Click here for more information
  • Release of a pneumatic tourniquet around the thigh after suturing and bandaging was not significantly different from release before suturing and bandaging for the mean range of flexion at 5 or 10 days or 6 weeks (
  • Two out of two studies reported no significant difference between use of tourniquet and no tourniquet for length of hospital stay (
  • Release of a pneumatic tourniquet around the thigh after suturing and bandaging was similar to release before suturing and bandaging for hospital stay (
  • Study details and Table 6 Barwell et al 1997 Click here for more information

PROSPECT Recommendations

  • No recommendation can be made for one type of approach over another, as use depends on individual patient factors and surgical requirements, rather than pain

Clinical practice

  • Type of approach depends on individual patient factors and surgical requirements, rather than pain

Transferable evidence

  • None cited

Total knee arthroplasty-specific evidence

  • The medial trivector approach and the parapatellar approach were associated with similar Knee Society pain scores at 6 weeks and 6 months postoperatively (
  • The subvastus and medial parapatellar approaches were not significantly different for postoperative VAS pain scores (
  • Patients in the posterior cruciate ligament (PCL) excised, PCL retained, posterior stabilised and valgus groups had significantly better Knee Society mean pain scores than those in the PCL released group (p=0.03); no significant differences were observed between the PCL excised, PCL retained and posterior stabilised groups (
  • The medial trivector approach was associated with a significant decrease in the number of days to achieve straight leg raising (p<0.05) compared with the parapatellar approach (
  • The subvastus approach was significantly superior to the medial parapatellar approach for the time to attainment of 90-degree flexion (p<0.01), but there was no significant difference for the time to attainment of full extension or active straight leg raising (
  • Patients in the PCL excised, PCL retained, posterior stabilised and valgus groups had significantly better knee scores than those in the PCL released group (p=0.002) (
  • No significant differences were observed between the PCL excised, PCL retained and posterior stabilised groups with regards to ROM, knee scores or function scores (
  • The medial trivector approach and the parapatellar approach were associated with similar quadriceps strength at 6 months, Knee Society function scores at 6 weeks and 6 months, and ROM at discharge, 6 weeks and 6 months (
  • The subvastus and medial parapatellar approaches were not significantly different for walking ability with full weight-bearing (
  • A meta-analysis evaluating the effects of retention and sacrifice of the posterior cruciate ligament (PCL) in total knee arthroplasty concluded that there was no basis for a decision regarding the benefits of either retaining or sacrificing the PCL, with or without posterior stabilisation, due to heterogeneity in study quality
  • Study details Fisher et al 1998 Click here for more information

PROSPECT Recommendations

  • No recommendation can be made for choice of prosthesis, as this depends on individual patient factors and surgical requirements, rather than pain

Clinical practice

  • The choice of prosthesis depends on factors such as patient’s age, activity level, bone quality and osteoporosis (leg position/axis, ligamentous knee stability), rather than pain

Transferable evidence

Total knee arthroplasty-specific evidence

  • A mobile-bearing knee replacement was significantly superior to a fixed-bearing prosthesis for reducing Oxford knee pain scores at 1 year postoperatively (p=0.009), and also American Knee Society pain score (p=0.015) (
  • Different designs of prosthesis (Tricon-M, Tricon stem, and PCA resurfacing) were similar for pain at rest or "first-step pain" at 6 months, and 1, 2 and 4 years; the Tricon stem design was significantly superior to the other designs for pain during activity at 4 years (p=0.04) (
  • Resurfacing of the patella was associated with superior pain control, for measures of pain other than Knee Society Pain Scores, and especially for anterior knee pain, compared with non-resurfacing ( Click here for more information
  • A meta-analysis of patellar resurfacing during total knee arthroplasty demonstrated that the incidence of anterior knee pain was significantly less in knees with resurfaced patellas compared with non-resurfaced patellas (p=0.00001), although functional outcomes improved regardless of whether or not the patella was resurfaced. Patients in the resurfaced patella group reported better satisfaction (p=0.00001) and a reduced risk of reoperation compared with those in the non-resurfaced patella group
  • A meta-analysis evaluating patellar resurfacing in total knee arthroplasty showed a reduced risk of anterior knee pain and reoperation with patellar resurfacing compared with knees without patellar resurfacing
  • A mobile-bearing knee replacement was similar to a fixed-bearing prosthesis for range of flexion postoperatively (
  • A meta-analysis of two studies evaluating mobile bearing versus fixed bearing prostheses for total knee arthroplasty found that ROM and functional performance were similar with both types of prosthesis
  • Different designs of prosthesis (Tricon-M, Tricon stem, and PCA resurfacing) were similar for Nottingham Health Profile scores e.g. sleep, pain, mobility, house work, hobbies (
  • A meta-analysis of patellar replacement during total knee replacement showed that the resurfaced patella performed better than the non-resurfaced patella (which had a higher risk for re-operation, significant anterior knee pain, and pain during stair climbing), although there were no differences observed between groups for knee scores or patient satisfaction, and the authors concluded that many confounding factors could influence the outcome (
  • Different designs of prosthesis (Tricon-M, Tricon stem, and PCA resurfacing) were similar for activity at 2 and 4 years postoperatively (
  • Patient preference was not significantly different between a mobile-bearing knee replacement and a fixed-bearing prosthesis (
  • Six out of six studies that used the Knee Society Pain Score to evaluate pain at follow-up after knee surgery (months to years) reported no significant difference in pain between patients with resurfaced patella versus retained patella Barrack et al 2001 Click here for more information
  • Different designs of prosthesis (Tricon-M, Tricon stem, and PCA resurfacing) were similar for Hospital for Special Surgery (HSS) clinical scores, except at 4 years postoperatively when HSS scores had deteriorated significantly with the Tricon stem compared with the other two designs (p=0.02) (
  • Pain scores (frequency, severity and pain at night, measured using the Nottingham scale) were not significantly different in the cemented and cementless groups at 5 years postoperatively (
  • Six studies out of six Click here for more information
  • Six studies out of six ( Click here for more information
  • One study out of one reported a significantly better Knee Society Clinical Rating Score 2 years postoperatively with the non-resurfaced patella group compared with the resurfaced group; however, the scores were not significantly different between groups at 1, 4, 6, 8 or 9 years postoperatively (
  • The degrees of flexion contracture and the total range of movement at 5 years after surgery were not significantly different beween the cemented and cementless groups (
  • Study details and Table 7 Barrack et al 2001 Click here for more information

Data are available from studies that assessed intra-operative analgesia versus intra-operative placebo, as well as those that assessed intra-operative analgesia versus the same analgesia given pre- or postoperatively. It is considered that analgesic medication needs to be initiated in time to ensure an adequate analgesic effect in the immediate postoperative period. This may necessitate administration prior to the postoperative period.

Where there is evidence that the time of administration of analgesics has no significant effect on postoperative pain outcomes, studies are presented in the Postoperative section only, except for those studies specifically comparing different times of administration.

Studies of analgesics that are given peri-operatively (pre-/intra- and postoperatively) are also presented in the Postoperative section only.

PROSPECT Recommendations

  • Intra-operative dextromethorphan is not recommended (Grade D, LoE 4) because of inconsistent analgesic effects in procedure-specific and transferable evidence
  • Intra-operative ketamine cannot be recommended at this time (Grade D, LoE 4) because there is limited procedure-specific evidence (LoE 1; see Postoperative NMDA receptor antagonists), despite analgesic efficacy in other procedures (transferable evidence, LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine
  • A quantitative systematic review found that dextromethorphan does not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases

Total knee arthroplasty-specific evidence

  • VAS scores at rest were significantly lower in the dextromethorphan + chlorpheniramine maleate (CPM) after skin incision group compared with the CPM alone before skin incision group at 8 (p<0.05) and 24 h (p<0.001) postoperatively only; there was no effect at 1, 2, 4, 48 and 72 h (
  • The time to first postoperative PCA analgesia was significantly increased in the dextromethorphan + CPM after skin incision group compared with the CPM alone before skin incision group (p<0.05) (
  • Total morphine consumption over days 1–3 and mean morphine consumption on each day was reduced in the dextromethorphan + CPM after skin incision group compared with the CPM alone before skin incision group (p<0.05) (
  • There were no significant differences in morphine-related side-effects between the dextromethorphan + CPM after skin incision and CPM alone before skin incision groups (
  • Study details Yeh et al 2000 Click here for more information

PROSPECT Recommendations

  • Intra-operative weak opioids are not recommended (Grade D, LoE 4) because there is no evidence that intra-operative administration is of greater analgesic benefit than postoperative administration

Clinical practice

  • It is considered that weak opioids are ineffective as a single therapy for postoperative pain following total knee arthroplasty, and are ineffective for treatment of high-intensity pain (VAS >/=50 mm)

Transferable evidence

  • Tramadol was more effective than placebo for pain relief in a meta-analysis of post-surgical patients
  • The combination of tramadol and paracetamol enhances analgesic efficacy compared with either agent alone (
  • Tramadol (50 or 100 mg orally) provided no benefit over placebo for postoperative pain scores up to 5 h after total hip arthroplasty (n=137)
  • Codeine (60 mg orally) provided no benefit over placebo for postoperative pain scores up to 6 h after total hip arthroplasty (n=121)
  • Tramadol (100 mg bolus IV) provided no benefit over placebo for postoperative pain scores after total hip or knee arthroplasty (n=48)
  • Two studies found that codeine 30 mg + paracetamol 300 mg was associated with a higher incidence of constipation and vomiting than tramadol 37.5 mg + paracetamol 325 mg following arthroscopy

Total knee arthroplasty-specific evidence

  • The VAS pain scores of the lowest dose tramadol group (1.25 mg/kg) were significantly higher than those of all the other groups (2.5 mg/kg, 3.75 mg/kg and 5 mg/kg) at 0 and 10 min (p<0.05, in both cases) after arrival in PACU, but there were no significant differences between groups at later time points (recorded every 10 min until 60 min post-PACU) (
  • The total number of patients requiring supplemental analgesic in PACU to achieve a VAS pain score </=3 was significantly higher in the low dose tramadol group compared with all the other groups (2.5 mg/kg, 3.75 mg/kg and 5 mg/kg) (p<0.05, in all cases) (
  • The frequency of PCA use was significantly higher in the low dose tramadol group compared with all other groups (2.5 mg/kg, 3.75 mg/kg and 5 mg/kg) (p<0.05, in all cases) (postoperative analgesia was tramadol 20 mg/ml PCA bolus doses, 5-min lockout) (
  • Study details Pang et al 2003 Click here for more information