Table 4 Articles included in the review analyzing the use of ketorolac in periarticular infiltrations

Nikhar et al. [2]

RCT

75 total knee arthroplasty patients

(1) (D) Ropivacaine/Epinephrine + Dexmedetomidine

(2) (K) Ropivacaine/Epinephrine + Ketorolac

(3) (C) CONTROL –Ropivacaine/Epinephrine

30 mg periarticular infiltration

343.00 min ± 144.45 min pain relief

Ketorolac demonstrated better postoperative pain score, duration of analgesia, and decreased epidural opioid use compared to control and ropivacaine + dexmedetomidine

No complications

Andersen et al. [37]

RCT

60 total knee arthroplasty patients

(1) Intraoperative 150 mL ropivacaine + 30 mg Ketorolac with 8 intra-articular injections postoperatively containing 15 mg Ketorolac q6h

(2) Intraoperative 150 mL ropivacaine + 1 mL saline with 8 intra-articular injections postoperatively containing 0.5 mL Saline (CONTROL)

30 mg periarticular infiltration

24–48 h with statistically significant change

Ketorolac demonstrated decreased PCA opioid use and prolonged time to first use of PCA, decreased postoperative pain intensity score while walking and at rest, and decreased time to home readiness in the ropivacaine + ketorolac group vs. control

1 × patient with postoperative hematoma in ketorolac group

Hannon et al. [38]

Meta-analysis

Meta-analysis of 60 studies

Inclusion criteria included English, human studies that included the use of PAI in patients receiving either TKA or THA, containing a control group and providing quantitative outcomes. Meta-analysis included 3 high-quality studies [31, 52, 67] with ketorolac as an additive to PAI in TKA only

30 mg periarticular infiltration

Various

Intraoperative PAI with Ketorolac leads to decrease postoperative pain, but effect on opioid usage is unclear – 2/3 studies found no difference in opioid usage with the addition of ketorolac. The addition of Ketorolac to PAI contain long-acting analgesics provides additional benefit compared to PAI without ketorolac

Various

Apinyankul et al. [39]

RCT

56 patients receiving TKA

1. 60 mg Ketorolac as an additive to unspecified PAI cocktail

2. 80 mg triamcinolone acetonide as an additive to unspecified PAI cocktail

60 mg periarticular infiltration

no significant difference in pain relief in comparison at 0, 24, 48, 72 h postop

Ketorolac showed no significant difference in morphine consumption, VAS scores, postoperative knee extension or straight leg tests immediately after surgery, 24 h, 48, or 72 h postoperatively when compared to the triamcinolone additive. Postoperative knee flexion was decreased in the ketorolac injection group compared to the triamcinolone group

Not documented

Hinzpeter et al. [40]

RCT

48 patients receiving TKA

1. Periarticular infiltration receiving 40 µg of gonyautoxin 2/3 (GTX 2/3) in saline (study group)

2. Periarticular infiltration using 300 mg levobupivacaine, 1 mg epinephrine, and 60 mg Ketorolac

60 mg periarticular infiltration

no significant difference in pain relief in comparison at 0, 6, 12, 36 and 60 h postop

Ketorolac showed no significant difference in morphine consumption although median PCA use in the control group was 9 mg (range 0–54 mg) comparted to 16 mg (range 0–62 mg) to the GTX 2/3 group (p = 0.40). Ketorolac showed improvement of range of motion at 6 and 12 h, no change after 36 h

No difference in complications, side effects or length of stay in hospital

Kopitko et al. [41]

RCT

161 patients receiving TKA

1. Nerve blockade using bupivacaine completed after completion of surgery n = 50

2. (LAI) PAI performed during surgery including 10–10 mL 20 mg lidocaine with 0.01 mg adrenaline and 100 mg ropivacaine, 500 mg tranexamic acid, and 30 mg Ketorolac n = 52

3. Control group receiving neither PAI or nerve blockade n = 59

30 mg periarticular infiltration

significant decrease in pain at 4–8 h, 24–36 h postop

42% of patients receiving PAI had tolerable pain between 4 and 8 h postop, 0% had severe pain based on numerical rating scores (NRS). 3% of PAI patients displayed tolerable pain compared to 19% in the nerve blockade group and 10% in the control group with 0% of patients showing severe NRS scores. PAI groups also showed significantly lower decreases in hemoglobin. The PAI group showed increased use of 100 mg IV Tramadol at 4–8 h and increased use of 50 mg IV Tramadol at 24–36 h, but no significant increases in other medications

No complications

Laoruengthana et al. [42]

RCT

54 patients receiving simultaneous bilateral TKA

1. 1^st Knee would receive 50 mg bupivacaine + 30 mg Ketorolac, 2^nd Knee another unspecified mixture

2. 1^st Knee would receive 50 mg bupivacaine only, 2nd Knee another unspecified mixture

30 mg intraoperative periarticular infiltration plus 30 mg IV q8h for the first 48 h

Decreased pain for 96 h postoperatively

Ketorolac group showed statistically improved postoperative VAS pain scores from 12 to 96 h. Ketorolac group showed higher degrees of knee flexion and straight leg raise. 61.11% of patients favored the knee receiving the Ketorolac compared to the contralateral knee

No complications

Laoruengthana et al. [43]

RCT

100 patients receiving TKAs

1. Patients received PAI containing 100 mg Bupivacaine and 30 mg Ketorolac and postoperative IV Ketorolac (n = 50)

2. Patients received PAI containing 100 mg of bupivacaine with 20 mg of parecoxib and postoperative IV parecoxib (n = 50)

30 mg intraoperative periarticular infiltration plus 30 mg IV q12h for the first 48 h

pain was decreased in the ketorolac group 6 h postop

Ketorolac group showed significantly decreased VAS scores comparted to the parecoxib group at 6 h postoperative. Levels of total morphine consumption at 24–48 h were comparable. Total perioperative blood loss and hemoglobin change was increased in the ketorolac group but showed no difference in blood transfusion

1 × DVT in Ketorolac group, 1 × PJI in parecoxib group. No statistical difference in complications between groups

Liu et al. [44]

RCT

134 patients receiving TKAs

1. (A) patients receiving PAI cocktail containing 400 mg ropivacaine, 30 mg ketorolac, 0.3 mg adrenaline, 5 mg morphine, diluted in normal saline

2. (B) patients receiving PAI with 200 mg bupivacaine, 40 mg methylprednisone, 0.3 mg adrenaline, 5 mg morphine, diluted in normal saline

30 mg periarticular infiltration

Group A displayed lower VAS scores improved over 72 h and improved range of motion over 14 days

Group A (PAI containing ketorolac) showed significantly decreased VAS scores at 6 h, 24 h, 48 h, and 72 h compared to group B. Group A also displayed improved joint range of motion on the 3rd, 7th, 10th, and 14th days

No complications

Danoff et al. [45]

RCT

26 patients receiving simultaneous bilaterally TKA

Patients receiving bilateral TKA with one knee receiving 266 mg liposomal bupivacaine 30 mL of 0.25% and bupivacaine (EXP), and the contralateral knee receiving 250 mg ropivacaine, 0.5 mg epinephrine, 30 mg ketorolac, and 0.08 mg clonidine (ROP)

30 mg periarticular infiltration

No statistical difference during the first two days postoperatively

There was no difference in visual analog scales or functional recovery between groups

No complications

Tammachote et al. [47]

RCT

64 patients receiving TKA

1. (M) Group receiving multimodal PAI containing 150 mg levobupivacaine, 30 mg ketorolac, and 5 mg morphine

2. (S) Group receiving PAI with 150 mg levobupivacaine only

30 mg periarticular infiltration

(M) showed decreased pain level in first 4 h and less morphine consumed in 8 h. (M) demonstrated 254 ± 155 min pain relief vs 148 ± 82 min pain relief in (S) group

Significantly decrease VAS score in group containing levobupivacaine, ketorolac, and morphine (M) group compared to single analgesic (S). (M) also showed decrease morphine use in first 8 h, and approximately 2 h longer until the first request of analgesia

No complications

Motififard et al. [46]

RCT

110 patients receiving TKA

1. Patients receiving PAI cocktail containing 50 mg bupivacaine hydrochloride, 1 mL morphine sulfate 10 mg/mL, 3 mcg epinephrine (1:1000), and 30 mg ketorolac. (n = 57)

2. Patients receiving PAI containing 300 mcg epinephrine (1:1000) only (n = 53)

30 mg periarticular infiltration

VAS scores obtained at 24 h, 48 h, and 6 weeks postop

Bupivacaine + morphine + epinephrine + Ketorolac group showed increase Knee Society Score after 6 weeks. There was significantly lower VAS scores and significantly higher ROM in the PAI cocktail group compared to the epinephrine control at 24 h, 48 h and six weeks

No complications related to intervention