Table 6 Articles included in the review analyzing the use of morphine in periarticular infiltrations

Han et al. [74]

RCT

90 TKA

1. Spinal anesthetic + synovial injection of Ropivacaine/epinephrine/morphine

2. Spinal anesthetic + synovial injection of Ropivacaine/epinephrine

3. Spinal anesthetic + synovial injection of saline

1. 40 ml 300 mg ropivacaine with 0.25 mL of 1:200,000 epi, 0.5 mL of 5 mg morphine, 9.25 mL 0.9% NS

2. 40 ml 300 mg ropivacaine with 0.25 mL of 1:200,000 epi, 9.75 mL 0.9% NS

3. 50 mL of 0.9% NS

In the context of epidural PCA, no difference in VAS pain scores at rest or exercise. No difference in rescue tramadol use for pain, no difference in booster PCA use before epidural catheter removal. No difference in range of motion observed

No statistical difference in nausea/vomiting. No other complications reported

Garcia et al. [71]

RCT

50 TKA

1. Intra-articular morphine injection

2. Intra-articular saline injection

1. 1 ml (10 mg) morphine in 19 mL NS

2. 20 mL NS

Intra-articular morphine had lower pain scores reported at 2 and 6 h in treatment group, but otherwise had similar pain scores. Treatment group also had decreased mean 24-h morphine consumption (12.2 mg vs 20.6 mg), decreased time to request of first rescue medication

No statistical difference in incidence of nausea, vomiting, somnolence

Kim et al. [32]

RCT

256 TKA

All patients received spinal anesthetic + PAI of

1. Saline, epinephrine, cefazolin

2. Ropivacaine

3. Ropivacaine, morphine

4. Ropivacaine, ketorolac

5. Ropivacaine, morphine, ketorolac

6. Ropivacaine, morphine, ketorolac, methylprednisolone

1. 1 g cefazolin (10 mL), and 0.6 mg epinephrine (1:1000, 0.6 mL), 49.4 mL NS

2. Ropivacaine 180 mg (24 mL) + 36 mL NS

3. Ropivacaine 180 mg (24 mL) + 5 mg (5 mL) morphine sulfate + 31 mL NS

4. Ropivacaine 180 mg (24 mL) + ketorolac 30 mg (1 mL) + 35 mL NS

5. Ropivacaine 180 mg (24 mL) + 5 mg (5 mL) morphine sulfate + ketorolac 30 mg (1 mL) 30 mL NS

6. Ropivacaine 180 mg (24 mL) + 5 mg (5 mL) morphine sulfate + ketorolac 30 mg (1 mL) + methylprednisolone 40 mg (1 mL) + 29 mL NS

All groups had lower pain scores compared to control for first 6 h after surgery. Combinations of Ropivacaine/ketorolac/morphine ± methylprednisolone showed improvement in pain scores for 12 h as well as lower opioid consumption over the first 24 h post-surgery. No statistical difference in total opioid consumption over the hospital stay between any group

No difference in nausea/vomiting/urinary retention/wound problems/deep infection

Heine et al. [72]

RCT

31 arthroscopic

1. IA (intra-articular bupivacaine

2. IA bupivacaine and morphine

3. IA bupivacaine and higher dose morphine

1. IA 100 mg bupivacaine

2. IA 100 mg bupivacaine, 1 mg morphine

3. IA 100 mg bupivacaine, 3 mg morphine

Bupivacaine + 3 mg morphine had improved pain at rest at 12 h and day 1, and improved at 12 h/day 1/day 2 on standing, improved walking scores. Both morphine groups had received less analgesia then bupivacaine alone

Report increased nausea and somnolence with addition of morphine, no statistical analysis reported

Li et al. [73]

RCT

120 TKA

1. Cocktail with morphine + epidural morphine 2. Cocktail with morphine 3. Cocktail without morphine

1. 100 mg ropivacaine, 6 mg dipropionate betamethasone, 15 mg betamethasone sodium phosphate, 8 mg morphine, saline to 60 ml + 2 mg epidural morphine

2. 100 mg ropivacaine, 6 mg dipropionate betamethasone, 15 mg betamethasone sodium phosphate, 8 mg morphine, saline to 60 ml

3. 100 mg ropivacaine, 6 mg dipropionate betamethasone, 15 mg betamethasone sodium phosphate, saline to 60 ml

Addition of morphine to cocktail had lower pain scores than cocktail without morphine although worse than morphine cocktail with epidural. Lower pain at rest, lower tramadol requirements. All groups had similar quadricep strength

No statistical significance in nausea, vomiting or metoclopramide usage

Wang et al. [75]

RCT

100 TKA

1. PAI of ropivacaine, epinephrine

2. PAI of ropivacaine, epinephrine, morphine

1. 0.2% ropivacaine and 2.0 μg/mL epinephrine

2. 2% ropivacaine, 2.0 μg/mL epinephrine, and 0.1 mg/mL morphine hydrochloride

Lower morphine use in first 24 h and total. No difference in VAS pain scores, knee ROM, quadricep strength, or daily ambulation distance

1 patient in morphine group developed 1 day of foot drop

Iwakiri et al. [76]

RCT

53 undergoing bilateral TKA (106 TKA total)

1. PAI with Ropivacaine/epinephrine/ketoprofen/methylprednisolone

2. Ropivacaine/epinephrine/ketoprofen/methylprednisolone/morphine

1. 0.5 mg/mL of ropivacaine [20 mL], 1:1000 epinephrine [adrenaline; 0.1 mL], 25 mg of ketoprofen [1.25 mL], 20 mg of methylprednisolone sodium [0.3 mL], and 8.35 mL of normal saline solution

2. 0.5 mg/mL of ropivacaine [20 mL], 1:1000 epinephrine [adrenaline; 0.1 mL], 25 mg of ketoprofen [1.25 mL], 20 mg of methylprednisolone sodium [0.3 mL], and 8.35 mL of normal saline solution, 0.1 mg/kg morphine

No difference in pain VAS scores at rest or in motion, no difference in ROM, thigh swelling

Comparison was made between TKA of a single patient so nausea/vomiting reported as aggregate. No surgical site infection, nerve palsy, DVT

Iwakiri et al. [77]

RCT

102 TKA

1. Ropivacaine/epinephrine/ketoprofen/methylprednisolone

2. Ropivacaine/epinephrine/ketoprofen/methylprednisolone/morphine

1. .5 mg/mL of ropivacaine [40 mL], 1:1000 epinephrine [0.1 mL], 50 mg of ketoprofen [2.5 mL], 40 mg of methylprednisolone sodium [0.6 mL], and 16.8 mL of normal saline solution

2. 0.5 mg/mL of ropivacaine [40 mL], 1:1000 epinephrine [0.1 mL], 50 mg of ketoprofen [2.5 mL], 40 mg of methylprednisolone sodium [0.6 mL], 10 mg morphine [1 ml] and 15.8 mL of normal saline solution

No difference in VAS pain scores at rest or in motion, use of rescue analgesia, ROM, thigh swelling

Morphine group had statistically significant increased nausea between 30 min to 9 h and significantly more vomiting episodes and anti-emetic usage

Tammachote et al. [47]

RCT

64 TKA

1. Levobupivacaine/ketorolac/morphine/epinephrine

2. Levobupivacaine only

1. levobupivacaine 150 mg, ketorolac 30 mg, morphine 5 mg, 0.6 mg epinephrine

2. Levobupivacaine 150 mg

Morphine group had decreased pain scores at rest over the first 4 h after surgery, less morphine consumption over the first 48 h with larger effect in the first 8 h. ROM, length of stay and re-admission were similar

No wound complications in either group. No other complications reported

Mauerhan et al. [78]

RCT

105 TKA

1. Saline

2. Morphine

3. Bupivacaïne

4. Morphine/Bupivacaine

1. 10 mL saline

2. 5 mg morphine sulfate

3. 50 mg bupivacaine

4. 5 mg morphine sulfate/50 mg bupivacaine

All intra-articular injections led to improved pain scores compared to placebo but no difference in pain scores between test groups. No difference in PCA usage. Analysis of combined morphine/bupivacaine groups shows some difference in pain scores only at 4/6 h group

No complications reported