Table 3 The confounding factors of included studies

El-Emam2020

Egypt

I/II:50/6

(IPACK + SACB)

SACB: 10 mL of 0.125 bupivacaine plus 40 mg methylprednisolone

IPACK: 10 mL of 0.125 bupivacaine plus 40 mg methylprednisolone;

(SACB)

SACB: 10 mL of 0.125 bupivacaine plus 40 mg methylprednisolone

N/A

N/A

N/A

N/A

N/A

Hu2020

China

I/II/III: 25/39/16

(IPACK + SACB)

IPACK: 0.2% ropivacaine 15 ml

SACB:0.2% ropivacaine 20 ml;

(SACB)

SACB:0.2% ropivacaine 20 ml;

VAS > 5, 20–40 mg Parecoxib sodium was given via Intravenous injection

General anesthesia

N/A

Propofol 3–5 mg/(kg h), Remifentanil 10–15 g/ (kg h) and other medications were adjusited by patients' situation

PCA: the analgesic formula was sufentanil 2 μg/kg, dezocine 10 mg, and Ondansetrone 16 mg + 0.9% sodium chloride injection diluted to 100 ml, the basic dose was 2 ml/h, the additional dose was 2 ml/time, and the locking time was 15 min

Kim2019

America

I/II/III: 1/81/4

IPACK + SACB + mPAI

IPACK: 25 mL of 0.25% bupivacaine; SACB: 15 mL of bupivacaine 0.25% with 2 mg of preservative-free dexamethasone; mPAI: bupivacaine 0.25% with 1:300,000 epinephrine at a volume of 30 mL; methylprednisolone, 40 mg/mL in 1 mL; cefazolin, 500 mg in 10 mL; and normal saline, 22 ml; note:mPAI: modified PAI

PAI

PAI: bupivacaine 0.5% with 1:300,000 epinephrine at a volume of 30 Ml, methylprednisolone, 40 mg/mL in 1 mL; cefazolin, 500 mg in 10 mL; and normal saline, 22 mL; 20 mL of 0.25% bupivacaine; 2 mg IV dexamethasone and ensure 10 mg dexamethasone via all route

NRS > 6 for 2 h, an IV hydromorphone PCA was ordered

spinal epidural anesthetic

Meloxicam: 7. 5 mg per os if age ≥ 75 or older

15 mg otherwise; Extended-release oxycodone (10 mg per os) in the holding area

Combined spinal epidural anesthetic with 60 mg mepivcaine spinal IV sedation: 2–5 mg with midazolam and propofol infusion; Ondansetron: 4 mg IV

Famotidine: 20 mg IV

Fentanyl: up to 100 mcg;

1. Acetaminophen: 1000 mg IV every 6 h for 4 doses. Then, 1 g PO every 8 h

2. Ketorolac: 30 mg IV every 6 h for 4 doses. If patient is 75 or older, 15 mg IV every 6 h for 4 doses

3. Oxycodone (IR): 5 mg (for NRS pain 0–4) or 10 mg (for NRS 5–10) every 3 h PRN; 4. Meloxicam: 15 PO to start after ketorolac is finished (7.5 mg PO if age > 75 years old); 5. Hydromorphone: 0. 5 mg IV every 10 min × 4 doses for breakthrough pain (NRS > 6,rescue analgesia);

Kertkiatkachorn2020

Thailand

I/II/III: 3/58/6

(IPACK + SACB + CACB)

IPACK: 20 mL of 0.25% levobupivacaine with ketorolac (15 mg) and epinephrine (0.1 mg)

SACB: 20 mL of 0.25% levobupivacaine with ketorolac (15 mg) and epinephrine (0.1 mg) with intermittent negative aspirations

CACB: 0.15% levobupivacaine (5 mL/h for 60 h)

CACB + PAI

CACB: 0.15% levobupivacaine (5 mL/h for 60 h)

PAI: 20 mL of 0.5% levobupivacaine, 30 mg of ketorolac, 0.3 mg of epinephrine combined with isotonic saline for a total volume of up to 80 mL into the posterior capsule, medial and lateral collateral ligament insertions, medial and lateral meniscus remnant, anterior capsule, suprapatellar pouch, fat pad, and soft tissue;

VAS score ≥ 4 during their stay in PACU, 2 mg of IV morphine was administered every 30 min

spinal anesthesia(3 mL of 0.5% hyperbaric bupivacaine without intrathecal morphine)

All patients received oral acetaminophen (2 × 375-g tablets) and oral celecoxib (400-g tablet) 30 min before surgery

Dexamethasone (10 mg) and ondansetron (4 mg) were administered for postoperative nausea and vomiting prophylaxis

Parecoxib (40 mg IV every 12 h; 2 doses)

Acetaminophen (orally, 650 mg per dose every 6 h)

Pregabalin (orally, 75 mg per dose once a day), and Celecoxib (orally, 400 mg per dose once a day; started after the last dose of parecoxib)

Kampitak2020(Comparison A)

Thailand

I/II/III: 1/62/2 1

(Proximal IPACK + CACB)

Proximal IPACK: 5 mL 0.25% levobupivacaine with 1:200,000 epinephrine; simultaneously, the needle was slowly withdrawn, and 15 mL of local anesthetic was injected until the tip of the needle reached the end of the medial aspect of the femur

CACB: 15 mL of 0.25% levobupivacaine was injected with intermittent negative aspirations, 0.15% levobupivacaine was continuously dripped at 5 mL/hour via a disposable infusion pump

LIA: 20 mL of 0.5% levobupivacaine, 0.3 mL of 1:1000 epinephrine, 30 mg of ketorolac, and 40 mL of isotonic sodium chloride solution;

TNB + CACB

TNB:15 ml 0.25% levobupivacaine were injected in divided doses of 5 mL, aspirating frequently to avoid intravascular injection

CACB: same with intervention group

LIA: same with intervention group

NRS > 4, 2 mg of intravenous morphine was administered every 30 min; Continued NRS > 4 for up to 1 h, PCA was administered using

Morphine (no basal rate, PCA dose 2 mg, lockout 10 min);

spinal anesthesia (3 mL of 0.5% hyperbaric bupivacaine)

Lorazepam (0.5 mg) was administered orally on the night before surgery(mild or worse anxiety); Paracetamol (650 mg orally) 30 min prior to surgery as premedication;

Intravenous dexamethasone (10 mg) and ondansetron (4 mg) for postoperative nausea and vomiting prophylaxis

20 mg of intravenous parecoxib every 12 h on postoperative day (POD) 0–1; 650 mg of acetaminophen orally every 6 h; 75 mg of pregabalin orally once daily; After the last dose of parecoxib, 400 mg of celecoxib and half a tablet of tramadol hydrochloride/acetaminophen were administered, followed by 650 mg of acetaminophen orally every 6 h as needed

Kampitak2020(Comparison B)

Thailand

I/II/III: 1/62/2

(Distal IPACK + CACB)

Distal IPACK: 20 mL of 0.25% levobupivacaine with 1:200 000 epinephrine was injected while slowly withdrawing the needle until the tip of the needle reached the medial femoral condyle; CACB: same with intervention group;

(TNB + CACB)

TNB: same with intervention group

CACB: same with intervention group

same as Comparison A

same as Comparison A

same as Comparison A

same as Comparison A

same as Comparison A

Li2019

China

I/II/III: 6/38/16

IPACK + SACB

IPACK: 0.33% ropivacaine 15 ml

SACB: 0.33% ropivacaine 20 ml;

SACB

SACB: 0.33% ropivacaine 20 ml

NRS > 5, Nalbuphine was injected at 0.08 mg/kg(intravenously)

Combined spinal and epidural anesthesia(0.5% bupivacaine 1.6–2 ml, lidocaine was added as needed);

Flurbiprofen 50 mg(Intravenous injection)

N/A

Celecoxib 200 mg, bid, po

Li2020(Comparison A)

China

I/II/III: 17/52/31

IPACK + SACB + LFCNB

SACB: 20 ml AV

IPACK: 20 ml AV

LFCNB: 10 ml AV

LIA: 60 ml AV

note: AV, 0.2% ropivacaine and 2.0 ug/ mL of epinephrine

SACB + LFCNB

SACB: 20 ml AV

IPACK: 20 ml placebo

LFCNB: 10 ml AV

LIA: 60 ml AV

Morphine hydrochloride (10 mg) was intramuscularly administered with untolerate pain reported by patients

N/A

N/A

Tranexamic acid (first dose of 20 mg/kg IV used during surgery; another dose used 8 h later); Elastic bandage to reduce the blood loss;

Postoperatively, ice compression devices were applied. Loxoprofen (60 mg, 1 tablet, b.i.d) was prescribed to control postoperative pain and alprazolam (0.4 mg, 1 tablet, qn) was given as a sleep aid; Tourniquet was used; After hospital discharge, patients were given rivaroxaban orally (10 mg, qd) to prevent venous thromboembolism for 2 weeks, loxoprofen orally for pain control (60 mg twice a day) until patients felt no pain, and were introduced to functional recovery methods

Li2020(Comparison B)

China

I/II/III: 22/43/35

IPACK + SACB

SACB: 20 ml AV

IPACK: 20 ml AV

LFCNB: 10 ml placebo

LIA: 60 ml AV

SACB

SACB: 20 ml AV

IPACK: 20 ml placebo

LFCNB: 10 ml placebo

LIA: 60 ml AV;

See in Li (comparison A)

See in Li (comparison A)

See in Li (comparison A)

See in Li (comparison A)

See in Li (comparison A)

Ochroch2020

America

I/II/III: 1/65/53

IPACK + CACB

CACB: ropivacaine 0.2% at a basal rate of 8 mL/ hour with a PCA of 5 mL every 30 min;

IPACK: 20 ml of ropivacaine 0.5%;

CACB

CACB: ropivacaine 0.2% at a basal rate of 8 mL/ hour with a PCA of 5 mL every 30 min

Sham IPACK: superficial injection of local anesthetic to create a skin weal of the medial side of the knee;

Spinal (99,75%)/General (30,25%); Spinal anesthesia: bupivacaine 10–15 mg; Ketamine 0. 3–0. 5 mg/kg intravenously;

Acetaminophen 1000 mg PO

Gabapentin 300 mg PO

Celecoxib 200 mg PO

Adductor canal catheter, ropivacaine 0. 5%20 mL

All patients received prophylaxis for postoperative nausea and vomiting: including 4 mg of dexamethasone; 4 mg of ondansetron 20 min before recovery from anesthesia; (dexamethasone was withheld in patients with blood glucose above 250 mg/dL)

Adductor canal catheter, ropivacaine 0. 2%8 mL/hour with demand bolus of 5 mL, lockout interval 30 min in 2 days

Acetaminophen 1000 mg PO every 8 h in 3 days

Celecoxib 200 mg PO every 12 h in 3 days

Gabapentin 300 mg PO every 12 h in 7 days

Oxycodone 5–10 mg PO every 4 h per registered nurse;

N/A

Patterson2020

America

I/II/III: 3/44/22

IPACK + CACB

CACB: 20 mL ropivacaine 0.25% with epinephrine 3 mcg/ml; 8 mL/h continuous infusion of ropivacaine 0.2% was initiated through the adductor canal catheter; IPACK: 15 ml ropivacaine 0.25% with epinephrine 3 mcg/mL with an additional 5 ml of local anesthesia, a total of 20 mL of local anesthetic

CACB

CACB: 20 mL ropivacaine 0.25% with epinephrine 3 mcg/ml; 8 mL/h continuous infusion of ropivacaine 0.2% was initiated through the adductor canal catheter; sham IPACK: 2 ml 0.9% saline for sham IPACK;

Oxycodone immediate-release tablets, IV morphine, and/or IV hydromorphone were available for breakthrough pain not relieved by oral medications

Neuraxial block or general anesthesia

All patients received 150 mg pregabalin (75 mg for patients aged > 70 years)

Patients received intravenous (IV) ketamine 0.25 mg/kg (up to 50 mg) and dexamethasone 8 mg IV

Patients were prescribed 1 g IV acetaminophen followed by 1 g oral acetaminophen every 6 h while in the hospital, 400 mg oral celecoxib followed by 200 mg daily, and 75 mg or 150 mg oral pregabalin daily in the evening

Sankineani2018

India

N/A

IPACK + SACB

IPACK: 15 ml of 0.2% ropivacaine

SACB:20 ml of 0.2% ropivacaine;

SACB

SACB:20 ml of 0.2% ropivacaine

If patients have breakthrough pain, Intravenous diclofenac 75 mg along with a transdermal buprenorphine patch (5 mcg/h)

Spinal anesthesia(2.5 ml 0.5% hyperbaric bupivacain)

N/A

N/A

Postoperative analgesic regimen: paracetamol 1 g intravenously every 8 h for 3 days followed by oral paracetamol 1 g every 8 h for 1 month, gabapentin 300 mg given orally once daily for a period of 4 weeks

Tak2020(Comparison A)

India

II/III: 106/7

IPACK + SACB

SACB:0.2% ropivacaine 20 ml

IPACK: 0.2% ropivacaine 20 ml

CACB

CACB: 0.2% ropivacaine via catheter at 5 ml/h for 48 h

Oxycodone immediate release tablets or intravenous morphine was considered in the form of rescue analgesia

spinal anesthesia

oral celecoxib 200 mg and gabapentin 300 mg preoperatively 10 h before surgery

N/A

intravenous paracetamol 1 g was given every 8 h for 3 days followed by oral paracetamol 1 g every 8 h along with Gabapentin 300 mg given orally once daily for a period of 4 weeks

Tak2020(Comparison B)

India

II/III: 106/8

IPACK + SACB

SACB:0.2% ropivacaine 20 ml

IPACK: 0.2% ropivacaine 20 ml

SACB

SACB:0.2% ropivacaine 20 ml

see in TAK(Comparison A)

see in TAK(Comparison A)

see in TAK(Comparison A)

see in TAK(Comparison A)

see in TAK(Comparison A)

Vichainarong2020

Thailand

I/II/III: 3/59/3

IPACK + CACB + LIA

IPACK: 5 mL of 0.25% levobupivacaine with 1:200,000 epinephrine

CACB: 20 mL 0.25% levobupivacaine, Levobupivacaine 0.15% was continuously dripped at 5 mL/hour via a disposable infusion pump for 60 h postoperatively

LIA: levobupi vacaine 100 mg, ketorolac 30 mg, epinephrine 0.3 mg diluted with isotonic sodium chloride solution to a total volume of 80 mL;

CACB + LIA

CACB: 20 mL 0.25% levobupivacaine, Levobupivacaine 0.15% was continuously dripped at 5 mL/hour via a disposable infusion pump for 60 h postoperatively

LIA: levobupi vacaine 100 mg, ketorolac 30 mg, epinephrine 0.3 mg diluted with isotonic sodium chloride solution to a total volume of 80 mL;

If patients presented with persisting pain and NRS ≥ 4, the patient would receive 2 mg of intravenous morphine as rescue therapy

spinal anesthesia: 15 mg of 0.5% hyperbaric bupivacaine;

All patients received 650 mg of acetaminophen and 400 mg of celecoxib orally 30 min before surgery

All patients received 10 mg of dexamethasone and 4 mg of ondansetron intravenous for postoperative nausea and vomiting prophylaxis;

Two consecutive doses of 15 mg ketorolac intravenous, 650 mg oral acetaminophen every 6 h, and 75 mg oral pregabalin (Lyrica) daily; After the last dose of ketorolac intravenous, 400 mg oral celecoxib (Celebrex) daily and half a tablet of tramadol hydrochloride/acetaminophen (Ultracet) were administered every 8 h; 40 mg intravenous esomeprazole daily for preventing upper gastrointestinal bleeding and 4 mg intravenous ondansetron every 6 h to prevent nausea and vomiting

Zheng2020

China

I/II: 17/33

IPACK + SACB

IPACK: 0.375% ropivacaine 15 ml

SACB: 0.375% ropivacaine 25 ml;

FNB + SNB

FNB: 0.375% ropivacaine 20 ml

SNB: 0.375% ropivacaine 20 ml;

VAS > 3, Intravenous sufentanyl was used as 0.1 μg/kg

N/A

Intravenous Administration: Midazolam 0.02 mg/kg

Sufentanil 0.2–0.3 g/kg

Etomidate 0.2 mg/kg

Aquarium sulfonate 0.6 mg/kg

Intravenous Administration: sufentanil 2 μg/kg; Ondansetron 8 mg and sterile saline all 100 ml; The background infusion rate is 2 ml/h and the lock time is 15 min

N/A

El-Emam2020

Egypt

I/II:50/6

N/A

N/A

N/A

Only OA patients included

No

12w

0

Hu2020

China

I/II/III: 25/39/16

N/A

N/A

N/A

N/A

No

2d

0

Kim2019

America

I/II/III: 1/81/4

Coinvestigator surgeons

N/A

N/A

Tourniquet was used

Yes

2d

0

Kertkiatkachorn2020

Thailand

I/II/III: 3/58/6

performed by or under the supervision of two senior surgeons

tricompartmental prostheses; hand-mixed cementing techniques

minimally invasive minimidvastus approach

N/A

Yes

2 m

2

Kampitak2020(Comparison A)

Thailand

I/II/III: 1/62/2 1

Performed by three orthopedic surgeons

hand-mixed cementing techniques; tricompartmental prostheses

minimally invasive minimidvastus approach

Tourniquet was used

Yes

6w

5

Kampitak2020(Comparison B)

Thailand

I/II/III: 1/62/2

same as Comparison A

same as Comparison A

same as Comparison A

same as Comparison A

same as Comparison A

S same as Comparison A

same as Comparison A

Li2019

China

I/II/III: 6/38/16

senior surgeons

N/A

N/A

N/A

No

2d

0

Li2020(Comparison A)

China

I/II/III: 17/52/31

performed by 2 senior surgeons

Prostheses: DePuy P.F.C; Stryker Triathlon;

standard medial parapatellar approach

LIA was used in every group

No

3 m

0

Li2020(Comparison B)

China

I/II/III: 22/43/35

See in Li (comparison A)

See in Li (comparison A)

See in Li (comparison A)

See in Li (comparison A)

See in Li (comparison A)

see in Li (Comparison A)

see in Li (Comparison A)

Ochroch2020

America

I/II/III: 1/65/53

N/A

N/A

N/A

N/A

No

2w

1

Patterson2020

America

I/II/III: 3/44/22

Performed by one of three fellowship-trained total joint surgeons

posterior stabilized prosthesis

medial parapatellar approach

tourniquet was used

No

2d

2

Sankineani2018

India

N/A

performed by a single surgeon (AVGR)

Posterior stabilized knee prosthesis

medial parapatellar approach

All patients were discharged in POD 3

No

2d

0

Tak2020(Comparison A)

India

II/III: 106/7

Two fellowship trained joint replacement surgeons

Posterior stabilized knee prosthesis without patellar resurfacing

medial parapatellar approach

All patients had a standard supervised rehabilitation program and were discharged on POD 3; Adductor canal catheter was removed on POD2;

No

2d

0

Tak2020(Comparison B)

India

II/III: 106/8

see in TAK(Comparison A)

see in TAK(Comparison A)

see in TAK(Comparison A)

see in TAK(Comparison A)

No

2d

0

Vichainarong2020

Thailand

I/II/III: 3/59/3

performed by or under the supervision of two senior surgeons

minimally invasive minimidvastus approach

N/A

N/A

Yes

2 m

1

Zheng2020

China

I/II: 17/33

N/A

N/A

N/A

N/A

No

2d

0