IPACK (Interspace between the Popliteal Artery and the Capsule of the Posterior Knee) Block Combined with SACB (Single Adductor Canal Block) Versus SACB for Analgesia after Total Knee Arthroplasty

Abstract

Objectives

To evaluate the combination of the infiltration between the popliteal artery and the posterior capsule of the knee (iPACK) block and single adductor canal block (SACB) versus SACB for motor‐sparing knee analgesia effects after total knee arthroplasty (TKA).

Methods

PubMed, Ovid, Cochrane Library, and other databases were searched from the inception to January 2021. Randomized controlled trials (RCTs) comparing patients receiving iPACK plus SACB with patients receiving SACB after TKA were included. The included studies were assessed by two reviewers according to the Cochrane risk of bias criteria. Meta‐analysis was performed with STATA 13.0 software, the risk ratios (RR) and mean differences (MD) were used to compare dichotomous and continuous variables. The primary outcome was ambulation pain and secondary outcomes were rest pain, opioid consumption, function ability, clinical outcomes, and complications.

Results

Seven RCTs (304 knees in iPACK + SACB group; 305 knees in SACB group) were included. The follow‐up periods ranged from 2 days to 3 months. Pooled data indicated lower pain scores at ambulation (p < 0.0001) for iPACK + SACB. When comparing the pain scores of subgroups analyzed at specific periods, lower scores in subgroups within 12 h (at rest and ambulation) and after 48 h (at ambulation) were observed in the iPACK + SACB group. Analysis demonstrated greater reduction in morphine consumption (p = 0.007) in the iPACK + SACB group. The iPACK + SACB group is also superior to the SACB group regarding function ability, which included range of motion (ROM) (p = 0.001), time up to go (TUG) test (p = 0.030), and ambulation distance (p < 0.0001). No difference was found in clinical outcomes or complications.

Conclusions

With the iPACK added to SACB, pain scores, morphine consumption, functional ability were improved. Additional high‐quality studies are required to further address this topic.

Our study confirmed that with the addition of IPACK, SACB could significantly reduce the pain scores, morphine consumption, as well as to improve functional ability.

Introduction

Total knee arthroplasty (TKA) is regarded as an effective treatment that provides pain relief, deformity correction, and function reconstruction for patients with end‐stage knee arthritis. ¹ The rate of patients who experienced moderate to severe postoperative pain was reported from 23% to 54%. ¹ , ² , ³ Effective analgesia is of paramount importance for post‐TKA patients because it could decrease pain scores, facilitate recovery, and reduce the rates of immobility‐related complications. ⁴

The adductor canal block (ACB) is a widely accepted motor‐sparing ultrasound‐guided modality and could provide a blockade of the saphenous nerve and vastus medialis nerve with greater preservation of the quadriceps muscle strength than the femoral nerve block (FNB). ¹ , ⁵ ACB can be administered as single or as continuous form (administered in the form of repeated boluses at specific predetermined intervals). ⁶ Single‐shot ACB (SACB) has shown efficacy in pain control. ⁴ However, the anteromedial part of the knee could be covered by SACB while the posterior knee pain still troubles patients. To compensate for this, SACB is usually combined with sciatic nerve block or multimodal drug periarticular injection (PAI). ⁴ , ⁷ , ⁸ Recently, a procedure using ultrasound‐guided local anesthetic infiltration between the popliteal artery and the capsule of the knee (iPACK) has been shown to provide promising motor‐sparing posterior knee analgesia with a lower probability of nerve or vascular injury. ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ This novel approach anesthetizes terminal branches of genicular nerves and popliteal plexus that innervate the posterior capsule of the knee joint without affecting the main trunks of the tibial and common peroneal nerves (CPN). ⁸ , ¹⁵

Several randomized controlled trials (RCT) have compared SACB combined with iPACK block with SACB. ⁶ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ , ²¹ Many of these trials contained relatively small cohorts and demonstrated inconsistent outcomes. This uncertainty leads to the determination of which method to adopt by the surgeons. The purpose of this meta‐analysis was to elucidate whether iPACK plus SACB is superior to SACB with respect to pain score, morphine consumption, function ability, clinical outcomes, and complications.

Methods

This meta‐analysis was performed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA Checklist guidelines (Appendix S1). ²² , ²³

Search Strategy

A search was conducted in January 2021, in the PubMed, Ovid, Cochrane Library, and other databases. The search terms were as follows: (IPACK OR “interspace between the popliteal artery and posterior capsule of the knee”) AND (total knee arthroplasty OR knee arthroplasty OR total knee replacement OR knee replacement OR TKA OR TKR) AND ((randomize* control* trial*) OR RCT)). The manual search was used to identify proper results in published studies (Appendix S2).

Eligibility Criteria

The titles and abstracts were initially appraised by two reviewers when met inclusions. The full text was checked, and any disagreement was settled by discussion among the research team. The inclusion criteria followed PICO principle: P, participant; I, intervention; C, comparison; O, outcome. Participants were people undergoing TKA without age limitations; intervention was the regional anesthesia utilized iPACK + SACB; comparison was the regional anesthesia utilized SACB; and outcomes were pain scores, opioid consumption, function ability, clinical outcomes, and complications. Articles were excluded if they (i) used a continuous nerve block, (ii) were studies of basic or animal science, or economics, (iii) abstracts without full text.

Quality Assessment

Methodology quality was independently evaluated by two reviewers using the Cochrane Collaboration's tool for assessing risk of bias in randomized trials. ²⁴ It is a validated and reliable scoring tool used to assess the quality of RCT. The risk of bias included random sequence generation, allocation concealment, blinding of participants and personnel, blinding of assessors, incomplete outcome data, selective reporting, and other bias. The overall quality could be evaluated as “low risk of bias”, “high risk of bias”, or “unclear risk of bias”.

Data Extraction

Data were independently extracted by two authors via a standardized spreadsheet, including: first author, publication year, number of knees in each treatment arm, age, women percentage, body mass index, inclusion and exclusion criteria, conclusions. Anesthesia modality (types, dosages of anesthesia drugs, rescue anesthesia method, perioperative analgesia protocols), surgeons, prosthesis, surgical approach, follow‐up duration, and the number of patients lost to follow were also collected. We also attempted to contact study authors by email for additional information if needed. Data in other forms (e.g. median, confidence intervals, or range of values) were converted to mean and standard deviation based on Cochrane Handbook.

Outcomes

The primary outcome was ambulation pain score as measured by visual analogue scale (VAS) (scale 0–10, 0 = no pain and 10 = worst imaginable pain) and secondary outcomes included (i) pain score at rest; (ii) morphine consumption (oral); (iii) function ability: range of motion (ROM), time up to go test (TUG), quadriceps muscle strength (QMS), ambulation distance; (iv) clinical outcomes: length of hospital stay, surgery time; and (v) complications: risk of falls, vomiting, and nausea, etc.

Statistical Analysis

In our study, STATA 13.0 (StataCorp, College Station, Texas, US) was used for data synthesizes. Subgroup analysis based on follow‐up time points were used in our analysis. Mean difference (MD) for continuous variables and risk ratios (RR) for dichotomous variables with 95% confidence intervals (95% CIs) was reported. A p‐value of 0.05 was considered statistically significant. Data was pooled by random‐effects model. Statistical heterogeneity was detected by both Q statistics and I² statistics, and p‐value of 0.10 or I² > 60% was considered substantially heterogenous. Sensitivity analysis was applied to compare the effect of deleting either single study on the overall results. To assess publication bias, the funnel plots were used (number of studies >10) and the Egger test was performed when observed asymmetry in funnel plots. When p < 0.01 in the Egger test, the trim and filling method will be used to assess the stability of the results.

Results

Search Results

Our search yielded 165 results after duplicates. After title and abstract screening, 17 relevant papers remained for full‐text selection. Ultimately, seven RCTs ⁶ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ , ²¹ were included for qualitative analysis with the remainder excluded for various reasons as outlined in the PRISMA flow diagram (Figure 1).

Fig. 1.

PRISMA flow chart showing study identification, inclusion, and exclusion

Study Characteristics

Seven trials presented data from 609 patients (304 in iPACK + SACB group; 305 in SACB group). All included RCTs were published between 2018 and 2020 with the follow‐up periods ranging from 2 days to 3 months. There was no difference in age, sex, and BMI between two groups. Detailed study characteristics of included studies were presented in Table 1. Five studies ⁶ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ enrolled patients with osteoarthritis (OA), one study enrolled traumatic arthritis and rheumatoid arthritis patients. ²⁰ The type of analgesia drug used was variable, with six studies using ropivacaine, ⁶ , ¹⁶ , ¹⁷ , ¹⁸ , ²⁰ , ²¹ two using epinephrine, ¹⁶ , ¹⁸ and one using methylprednisolone and bupivacaine. ¹⁹ TKA was performed under general anesthesia in four studies ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ and spinal anesthesia in two studies. ⁶ , ²¹ One study used combined spinal and epidural anesthesia. ²⁰ The detailed interventions in each group can be seen in Table 2.

TABLE 1.

The basic information of included studies

Study (year)	Recruit period	Patients (n)		Age†		Women‡		BMI†
		I	C	I	C	I	C	I	C	Outcomes	Inclusion	Exclusion	Conclusions
El‐Emam (2020)	N/A	28	28	52 (15)	54 (13)	8 (28.57%)	9 (32.14%)	29.1 (2.7)	28.5 (3)	(1) VAS (2 weeks, 4 weeks, 8 weeks, 12 weeks); (2) WOMAC Index;	(1) Age > 45 years, ASA I–III; (2) Able to understand the study protocol; (3) Radiographic evidence of knee OA of the second degree or more; (4) Chronic pain prior to study entry for at least 6 months; (5) Pain did not respond to conservative therapies during the last 6 months.	(1) Patient refusal; (2) Bleeding or coagulation disorders; (3) Local skin infection or any other medical problem in the affected limb; (4) Psychiatric problems lead to difficult communication with	Combined SACB and iPACK block provide more effective analgesia and better functional outcome compared to the SACB alone.
												the patient; (5) Previous chronic opioid use; (6) Contraindications to steroid injection as diabetes or hypertension.
Hu (2020)	N/A	40	40	74.7 (6.3)	73.9 (4.9)	N/A	N/A	21.2 (1.9)	20 (4.2)	(1) VAS (rest VAS at 2 h, 6 h, 12 h, 24 h, 48 h; ambulation VAS at 2 h, 6 h, 12 h, 24 h, 48 h); (2) Time to rescue analgesic treatment and frequency; (3) Muscle strength, Daily walking distance; (3) Time for initial mobilization; (4) ROM at 48h; (5) Complications (Nausea, vomiting, bleeding, infection, falls et al)	(1) Primary unilateral TKA; (2) ASA I‐III.	(1) Severe cardiovascular disease; pulmonary dysfunction; central nervous system diseases; (2) Fail to communicate and cooperate with the medical staff; (3) Coagulation disorders;	Ultrasound‐guided SACB combined with IPACK block can be safely applied in TKA in the elderly patients, and the analgesia effect is more complete, and contributing to promote the early rehabilitation.
												(4) Puncture site infection;
												(5) Allergic to local anesthetic drugs.
Li (2019)	2017.11–2018.04	30	30	66 (6)	69 (6)	21 (70%)	16 (53.33%)	21.9 (2.2)	21.7 (2)	(1) Rescue nalbuphine consumption (IV, mg); (2) NRS (6 h, 8 h, 12 h, 24 h, and 48 h at rest and at ambulation); (3) Walking distance at POD 1 and POD; (4) ROM; (5) Complications (narcotic intoxication, hematoma, infection, muscle weakness, fall); (6) Hospital length.	(1) Primary unilateral TKA; (2) ASA I‐III; (3) Not allergic to narcotic drugs; (4) No history of mental diseases, neurological disorders, low compliance, no vital organ dysfunction, no history of epilepsy, drinking, drugs or in pregnancy.	N/A	SACB combined with iPACK block can provide a relatively perfect efficacy when used for multimodal analgesia after TKA and is helpful for patients' recovery.
Li (2020)	2018.05–2019.04	50	50	66.82 (6.17)	65.56 (6.34)	40 (80%)	31 (62%)	24.68 (2.60)	24.97 (3.18)	(1) VAS (at rest,2 h, 8 h, 12 h, 24 h, 48 h, and discharge; VAS (at ambulation, 2 h, 8 h, 12 h, 24 h, 48 h, and discharge); (2) Opioid consumption (within 24 h, 24–48 h, 48‐discharge), number of patients with no morphine requirement; (3) Knee flexion and extension at 24 h, 48 h, and discharge; (4) Quadriceps strength, mobilization distance at 24 h, 48 h, and discharge; (5) TUG, KSS, WOMAC at discharge and 3 months; (6) Complications.	(1) Aged between 50 and 80 years with BMI between 19 and 30 kg/m2; (2) ASA I‐III; (3) Primary unilateral TKA for OA.	(1) Knee flexion or varus‐valgus deformity >30°, inability to walk; (2) allergy to morphine or had a history of opioid consumption; (3) had any contraindications to regional anesthesia, local infiltration, general anesthesia, and the drugs used in study; (4) diagnosed with septic arthritis, rheumatic arthritis, traumatic arthritis, and other non‐OA diseases; and (5) patients with a medical history of psychiatric illness, cognitive impairment, recognized neuromuscular disorder, narcotic dependency, knee infection, knee surgery, or thromboembolic event including myocardial infarction, cerebrovascular accident, deep vein thrombosis, and pulmonary embolus. Additionally, patients with a language barrier, or those who refused to sign informed consent.	Combining SACB with iPACK is an effective method for decreasing early postoperative pain in TKA without increasing the complications or affecting the early rehabilitation.
Sankineani (2018)	2016.09–2017.03	60	60	60	61	38 (63.33%)	42 (70%)	29.36	28.88	(1) VAS at 8 h, on POD1, and on POD2; (2) ROM; (3) ambulation distance;	N/A	(1) Patients undergoing bilateral or revision TKA, with history of bleeding diathesis or prior vascular surgery on femoral vessels on operated site, severe renal insufficiency, arrhythmia or seizures, sepsis, preexisting lower extremity neurological abnormality and difficulties in comprehending VAS pain scores, were excluded from the study.	SACB + iPACK is a promising technique that offers improved pain management in the immediate postoperative period without affecting the motor function around the knee joint, resulting in better ROM and ambulation compared to SACB alone.
Tak (2020)	2019.03–2019.06	56	57	65.5	64.1	29 (51.8%)	37 (63.8%)	26	26.6	(1) VAS at rest, at ambulation every 8h up to 48 h; (2) opioids consumption in morphine equivalents; (3) ambulation distance (feet) on POD2, TUG, 30 s chair stand test, sitting active extension lag test and maximal knee flexion at discharge.	(1) Unilateral tricompartmental TKA for primary OA; (2) age between 45 and 80 years with an ASA of I–III.	(1) Bilateral or revision TKA; (2) Knee flexion, varus, valgus deformity ≥30°; (3) arthritis due to rheumatoid disease or trauma or septic arthritis; (4) creatinine >1.2, renal or hepatic dysfunction, known allergy to any study medication, chronic opioid use; (5) BMI > 40 kg/m2, chronic pain unrelated to knee joint, pre‐existing neuropathy, arrhythmia, epilepsy, had a history of bleeding diathesis or prior vascular surgery on femoral vessels on operated site and difficulty in comprehending VAS scores.	The addition technique of iPACK to SACB may not add any additional benefit in postoperative pain control, ambulation, opioid consumption or rehabilitation compared to SACB alone.
Wang (2020)	2019.01–2020.01	40	40	65.3 (7.11)	64.1 (8.01)	14 (35%)	9 (22.5%)	25.1 (3.4)	25.6 (3.9)	(1) VAS (at rest, 2 h, 8 h, 12 h, 24 h, 48 h, 72 h; at ambulation, 12 h, 24 h, 48 h, 72 h); (2) ROM; (3) muscle strength; (4) daily walking distance; (5) complications (nausea, vomiting, swelling, bleeding, delayed healing of wound, VTE, neurovascular injury, infection, falls).	(1) Primary TKA; (2) ASA I‐III;	(1) Deformity with flexion, valgus, varus >30°; (2) non‐OA diseases (including rheumatoid arthritis; traumatic arthritis; suppurative arthritis); (3) Allergic to analgesia drugs; (4) narcotic drug dependence; (5) psychopaths; (6) a history of knee surgery; (7) cannot communicate or unwilling to sign the informed consent.	SACB combined with iPACK block is more effective than SACB on analgesia after TKA.

^† The data was presented as mean and standard difference;

^‡ The data was presented as number and percentages; I represented intervention group (IPACK + SACB); C represented control group (SACB).

Abbreviations: ASA, American Society of Anesthesiologists; iPACK, interspace between the popliteal artery and the capsule of the posterior knee; KSS, Knee Society Score; NRS, Numeric Rating Scales; OA, osteoarthritis; POD, postoperative day; ROM, range of motion; SACB, single adductor canal block; TKA, total knee arthroplasty; TUG, Time up and go test; VAS, Visual Analog Scale; WOMAC, Western Ontario and McMaster Universities Arthritis Index.

TABLE 2.

The confounding factors of included studies

Author	ASA	Diseases	I	C	Rescue Method	Anesthesia	Pre‐operative	Intraoperative	Postoperative	Surgeons	Approach	Prothesis	Follow‐up
El‐Emam (2020)	I/II:50/6	OA (KL II, III)	(1) iPACK: 10 mL of 12.5% bupivacaine +40 mg methylprednisolone; (2) SACB: 10 mL of 12.5% bupivacaine +40 mg methylprednisolone.	SACB: 10 mL of 12.5% bupivacaine +40 mg methylprednisolone.	N/A	General	N/A	N/A	N/A	N/A	N/A	N/A	12 weeks
Hu (2020)	I/II/III: 25/39/16	OA	(1)iPACK: 15 ml of 0.2% ropivacaine; (2) SACB: 20 ml of 0.2% ropivacaine;	SACB: 20 ml of 0.2% ropivacaine;	When VAS > 5, 20 to 40 mg Parecoxib sodium was given (IV).	General	N/A	(1)Propofol 3–5 mg/(kg.h); (2) Remifentanil 10–15 mg/(kg.h);	(1) PCA: the analgesic formula: Sufentanil (2 μg/kg) + Dezocine (10 mg) + 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	N/A	N/A	N/A	2 days
								(3) other medications were given by patients' situation.
Li (2019)	I/II/III: 6/38/16	OA 39; Traumatic arthritis 16; RA 5.	(1) iPACK: 15 ml of 0.33% ropivacaine; (2) SACB: 20 ml of 0.33% ropivacaine.	(1) SACB: 20 ml of 0.33% ropivacaine.	When NRS > 5, nalbuphine was injected at 0.08mg/kg (IV)	Combined spinal and epidural anesthesia (0.5% bupivacaine 1.6–2 ml, lidocaine was added as needed)	Flurbiprofen 50 mg (IV)	N/A	Celecoxib 200mg, bid, po	Senior surgeons	N/A	N/A	2 days
Li (2020)	I/II/III: 22/43/35	OA	(1)iPACK: 20 ml AV; (2) SACB: 20 ml AV; AV: Anesthetic volume, consisted of 0.2% ropivacaine and 2.0 mg/mL of epinephrine.	SACB: 20 ml AV.	Morphine hydrochloride (10 mg) was intramuscularly administered with unbearable pain reported by patients.	General	N/A	Tranexamic acid (first dose of 20 mg/kg IV used during surgery; another dose used 8 h later); Elastic bandage was used to reduce the blood loss.	(1)Ice compression devices were applied; (2) loxoprofen (60 mg, 1 tablet, bid) was prescribed to control postoperative pain; (3) alprazolam (0.4 mg, 1 tablet, qn) was given as a sleep aid; (4) tourniquet was used;	Two senior surgeons	Standard medial parapatellar approach	Prostheses: DePuy P.F.C; Stryker Triathlon;	3 months
Sankineani (2018)	N/A	N/A	(1) iPACK: 15 ml of 0.2% ropivacaine; (2) SACB:20 ml of 0.2% ropivacaine.	SACB:20 ml of 0.2% ropivacaine.	If patients have breakthrough pain, diclofenac 75 mg along with a transdermal buprenorphine patch (5 mcg/h) were given (IV).	Spinal (2.5 ml of 0.5% hyperbaric bupivacaine)	Celecoxib 200 mg and gabapent300 mg were given 12 h before the surgery.	N/A	(1) Paracetamol 1 every 8 h for 3 days (IV) followed by oral paracetamol 1 g every 8 h for 1 month; (2) gabapentin 300 mg was given orally once daily for 4 weeks.	One surgeon (AVGR)	Medial parapatellar approach	Posterior stabilized knee prosthesis	2 days
Tak (2020)	II/III: 106/8	OA	(1) iPACK: 20ml of 0.2% ropivacaine; (2) SACB: 20 ml of 0.2% ropivacaine.	SACB: 20 ml of 0.2% ropivacaine.	Oxycodone immediate release tablets (oral); morphine (IV).	Spinal	Oral celecoxib 200 mg and gabapent300 mg 10 h before the surgery	N/A	(1)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 4 weeks.	Two surgeons	Medial parapatellar approach	Posterior stabilized knee prosthesis without patellar resurfacing	2 days
Wang (2020)	I/II/III: 3/48/29	OA	(1) iPACK: 20 ml of mixed analgesic drugs (0.2% ropivacaine +2.0 μg/ml epinephrine); (2) SACB: 20 ml of mixed analgesic drugs (0.2% ropivacaine +2.0 μg/ml epinephrine).	SACB: 20 ml mixed analgesic drugs (0.2% ropivacaine +2.0 μg/ml epinephrine);	Morphine hydrochloride (10 mg, IV)	General	Oral Celecoxib (200 mg) bid	N/A	(1) Oral celecoxib (200 mg, bid); (2) oral oxycodone sustained release tablets (10 mg, bid)	One surgeon	Medial approach	Cemented, P.F.C DePuy Synthes, Johnson & Johnson, USA	3 days

C represented control group (SACB); I represented intervention group (IPACK + SACB).

Abbreviations: ASA, American Society of Anesthesiologists; interspace between the popliteal artery and the capsule of the posterior knee; KL, Kellgren–Lawrence Classification; NRS, Numeric Rating Scales; OA, osteoarthritis; RA, Rheumatoid Arthritis; SACB, single adductor canal block; VAS, Visual Analog Scale.

Risk of Bias

The random sequence generation was described fairly well in five studies, and allocation concealment in five studies; in the remainder, this risk of bias was high or unclear. ¹⁶ , ¹⁷ , ²¹ Three studies described the blinding of participants and personnel explicitly, and the blinding method was not described in one study. ²¹ The dropout rate was lower than 20% in all studies and we did not find any other apparent bias. In general, the risk of bias in five studies was low, one study was unclear, and one study was high (Figures 2 and 3). Funnel plots were applied on the VAS score at rest and ambulation. The asymmetrical distribution of funnel plots was observed. The Egger test showed p < 0.01, thus we did the trim and filling test, and the results were not changed (Appendix S3).

Fig. 2.

Risk of bias graph

Fig. 3.

Risk of bias summary; (“+” indicates a low risk of bias, “−” indicates a high risk of bias, “?” indicates unclear or unknown risk of bias)

Sensitivity Analysis

To validate our results, the sensitivity analysis was performed by excluding one trial at a time and recalculating the pooled MD for the remaining trials, which showed that the conclusions remained unchanged in all outcomes, suggesting the stability of our meta‐analysis (Appendix S4).

Primary Outcome

Pain at Ambulation

When comparing the ambulation VAS scores of subgroups analyzed at specific periods in time, there was a trend toward lower VAS scores in the iPACK + SACB group in subgroups of 0–6 h, 8–12 h, 48 h, and after 72 h (Figure 4).

Fig. 4.

Forest plot of pain at ambulation between iPACK + SACB and SACB

Secondary Outcomes

Pain at Rest

We examined the combined VAS scores for each group, it demonstrated more reduction in VAS scores for the iPACK + SACB group versus the SACB group, and the difference was statistically significant (p < 0.001). Considering that the duration of follow‐up may be the origin of heterogeneity, subgroup analysis was conducted based on different follow‐up times. The iPACK + SACB group had lower VAS scores at 8 h (p = 0.002) and 12 h (p = 0.001) postoperatively (Figure 5).

Fig. 5.

Forest plot of pain at rest between iPACK + SACB and SACB

Morphine Consumption

Data on 354 patients from 4 trials were analyzed for morphine consumption. A significant difference was identified and the result showed decreased morphine usage in the iPACK + SACB group (MD = −0.451, p = 0.007) (Table 3.).

TABLE 3.

The results of meta‐analysis

Variables	N(Study)	Intervention group (IPACK+SACB)	Control group (SACB)	Pooled data		Heterogeneity
				MD/RR (95%CI)	P (Z test)	I2 (%)	p (Q test)
Clinical Outcomes
Hospital length (min)	3	120	120	−0.286 (−0.615, 0.043)	0.088	38.6%	0.196
Surgery time (min)	5	237	236	0.073 (−0.226, 0.373)	0.631	49.8%	0.113
Pain
Pain at rest, overall (VAS)	21	970	975	−0.958 (−1.313, −0.602)	<0.0001*	92.7%	<0.0001*
By subgroup (follow‐up time)
Pain at rest (at 2 h)	3	130	130	−1.309 (−2.742, 0.123)	0.073	96.2%	<0.0001*
Pain at rest (at 8 h)	4	186	187	−1.900 (−3.117, −0.684)	0.002*	95.8%	<0.0001*
Pain at rest (at 12 h)	3	130	130	−1.411 (−2.263, −0.559)	0.001*	89.4%	<0.0001*
Pain at rest (at 24 h)	4	186	187	−0.352 (−0.813, 0.108)	0.134	79.7%	0.002*
Pain at rest (at 48 h)	4	186	187	−0.296 (−0.704, 0.112)	0.155	74.3%	0.009*
Pain at ambulation (VAS)	22	958	960	−1.020 (−1.300, −0.741)	<0.0001*	87.9%	<0.0001*
By subgroup (follow‐up time)
Pain at ambulation (<6 h)	3	130	130	−1.378 (−2.464, −0.292)	0.013*	93.4%	<0.0001*
Pain at ambulation (8–12 h)	5	240	240	−1.170 (−1.826, −0.514)	<0.0001*	90.9%	<0.0001*
Pain at ambulation (at 24 h)	4	190	190	−0.795 (−1.612, 0.022)	0.057	93.1%	<0.0001*
Pain at ambulation (at 48 h)	4	186	188	−0.911 (−1.697, −0.125)	0.023*	92.3%	<0.0001*
Pain at ambulation (>72 h)	5	152	152	−0.858 (−1.132, −0.585)	<0.0001*	24.8%	0.256
Morphine consumption (mg, oral)	4	176	178	−0.451 (−0.778, −0.125)	0.007*	56.8%	0.074
Function Ability
Range of motion (°)	5	220	220	1.032 (0.462, 1.602)	<0.0001*	87.3%	<0.0001*
ROM (POD1)	2	100	100	0.906 (0.537, 1.275)	<0.0001*	36.4%	0.210
ROM (POD2)	2	80	80	1.523 (−0.100, 3.147)	0.066	94.9%	<0.0001*
Time up to go (s)	3	156	158	−0.247 (−0.469, −0.024)	0.030*	0%	0.487
Quadriceps muscle strength (MVIC)	6	270	270	−0.225 (−0.394, −0.055)	0.009*	0%	0.6
By subgroup (follow‐up time)
QMS (On POD1)	2	90	90	−0.163 (−0.561, 0.234)	0.420	44.9%	0.178
QMS (On POD2)	2	90	90	−0.176 (−0.469, 0.117)	0.240	0%	0.494
QMS (On POD3)	2	90	90	−0.347 (−0.641, −0.052)	0.021*	0%	0.570
Ambulation distances (m)	9	386	388	0.296 (0.131, 0.460)	<0.0001*	24.8%	0.223
By subgroup (follow‐up time)
Ambulation distances (POD1)	3	120	120	0.301 (0.000, 0.601)	0.050*	26.8%	0.255
Ambulation distances (POD2)	4	176	178	0.377 (0.087, 0.668)	0.011*	46%	0.135
Ambulation distances (POD3)	2	90	90	0.132 (−0.161, 0.425)	0.377	0%	0.440
Complications
Nausea	3	130	130	0.760 (0.554, 1.043)	0.089	0%	0.980

Abbreviations: MVIC, maximum voluntary isometric contraction; POD, postoperative day; QMS, Quadriceps muscle strength; ROM, Range of motion.

Function Ability

Range of Motion

ROM refers to the main movement when the knees are flexion and extension. When knee movement is limited, it causes pain, impairs function, and makes us predisposed to knee injuries. Data on 440 patients were analyzed and the results favored the iPACK + SACB group (MD = 2.686, p = 0.001).

Time Up and Go Test

TUG test is a simple evaluative test by measuring the time a patient takes to stand up from a chair, walk a distance of three meters without any support, and return to the chair. It could be used to estimate the risk of falling and the ability to maintain balance while walking. Data on 540 patients were pooled and the result suggested that the iPACK + SACB group performed better (MD = −0.247, p = 0.030).

Quadriceps Muscle Strength

The strength of the quadriceps muscle determined the ability of mobilization and could reduce falling. Pooled results showed that the SACB group was better in quadriceps muscle strength recovering (MD = −0.225, p = 0.009).

Ambulation Distance

Data on 774 patients suggested that patients with iPACK block had longer ambulation distances (MD = 0.296, p < 0.0001). Subgroup analysis showed similar benefits on postoperative day 1 (POD1) and on POD 2 while there was no difference on POD 3.

Clinical Outcomes

Data on 475 primary TKAs were pooled from 5 trials for the surgery time and 240 patients from three trials for hospital length. The difference was not statistically significant between the two groups.

Complications

Only three studies reported complications, therefore, limited data can be used for analysis. The nausea rate was similar between the two groups (RR = 0.760, p = 0.089).

Discussion

Key Findings

The key findings of this meta‐analysis were that iPACK plus SACB provided better results in terms of pain control, morphine use, and function recovery when compared with SACB. The results of pain scores (at rest, at ambulation) reached the minimally clinical importance (MCID) within 12 h. However, the other results lacked clinical importance.

Discussion over Results

TKA is associated with moderate‐to‐severe postoperative knee pain. The poor management of pain usually results in prolonged rehabilitation time, increased complications, and diminished patient satisfaction. Effective analgesia is of paramount importance. ⁴ The ideal analgesia regime should balance optimal pain control and best early recovery in fast‐track TKA management. ¹ ACB is an effective peripheral nerve block, which could replace FNB with better motor preservation ability and adequate analgesia effect. ¹ ACB could also reduce the risk of quadriceps weakness and falling risk. ²⁵ ACB had both single and continuous techniques, but the advantages of each technique are debatable. ²⁶ By blocking the saphenous nerve and the posterior branch of the obturator nerve, SACB provided satisfied analgesic effects on the anteromedial part of the knee. However, the posterior part was not covered. Ultrasound‐guided iPACK was introduced in 2012 as an alternative analgesic method for sciatic nerve block on the posterior part without causing any common peroneal nerve damage, foot drop, or numbness. ⁴ , ¹⁵ Several RCTs that compared SACB plus iPACK to SACB found inconclusive outcomes in terms of pain scors. ⁶ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ , ²¹ Therefore, our study was performed to assess whether iPACK plus SACB had superiority over SACB after TKA.

Our results showed that iPACK plus SACB was better than SACB regarding rest pain, activity pain, and morphine consumption. A significant difference was observed in pain relief after surgery and the results of pain scores (at rest and at ambulation) measured within 12 h all reached the MCID. Though high heterogeneity was found, the results were not changed by sensitivity analysis. Factors such as patient characteristics (sex, weight, height), local anesthetic formulation (dosage, volume), surgeon techniques (nerves or muscle damage, tourniquet use, and length), prothesis (cement, type), anesthesiologist techniques, and perioperative protocols (rehabilitation, analgesia, blood management, sleep, and emotion management) may explain for the stubborn heterogeneity. The rising demand for TKA also mandates strategies to minimize opioid consumption and prevent patients from adverse events such as nausea, vomiting, respiratory depression, or chronic opioid dependency. ²⁷ Rescue opioids were used for breakthrough pain in several studies and we found decreased opioids use with the addition of iPACK. The incidence of postoperative nausea or vomiting was low without significant difference in our review. This is most likely due to the effective blockade that reduced morphine consumption and minimized associated side effects. None of the included studies reported severe complications such as death, intoxication, puncture, or injury, and proved the safety of both interventions. However, it is important to closely monitor patients after administration of the anesthetic. As for function ability, we adopted four indicators (ROM, TUG test, ambulation distances, and quadriceps muscle strength) for assessment. There were significantly better outcomes in the iPACK plus SACB group comparing with the SACB group. However, these results all lack MCID and the interpretation must be made with caution due to the relatively small sample size and other confounding factors. However, the outcome of quadriceps muscle strength was better in the SACB group, which we cannot explain now. For clinical outcomes, multiple factors could affect the length of hospital stay or surgery time, for instance, sex, age, and physiological status. Prolonged hospitalization may lead to several complications, including deep vein thrombosis, muscle atrophy, and increased cost. No difference was found with hospital stay or surgery time and this may reveal the possibility of applying iPACK as it did not increase time–cost.

Recently, many researchers designed different trials by the combinations of ACB and iPACK. And the results were consistent with ours. Kertkiatkachorn et al. found iPACK plus SACB block may be a suitable alternative to CACB plus periarticular injection (PAI) under the condition that the surgeons cannot perform PAI. ²⁸ However, iPACK is more complicated, requiring the regional anesthesiologist with expertise. Kim et al. found the iPACK plus SACB significantly improved analgesia and reduced opioid consumption compared to PAI and strongly supported it within the multimodal analgesic pathway. ²⁹ Jung et al. reported that iPACK plus SACB may be a better option than PAI for controlling acute phase pain. ¹⁴ Similarly, Eccles et al. found iPACK plus SACB demonstrated improved early ambulation with decreased opioid use, and shortened length of stay compared with FNB plus sciatic nerve block. ¹¹

The strengthens of our study are that we adhere to the strict inclusion and exclusion criteria and only selected SACB plus iPACK with SACB for analysis to make sure the precision of our results.

Limitations

The review also has several limitations. First, the heterogeneous of several outcomes cannot be solved by subgroup analysis, however, we did sensitivity analysis and the results were not changed. Second, the included studies only had a small number of participants and short‐term follow‐up lengths, which indicates the paucity of large population and long‐term reports. Third, as the analgesic effects of iPACK mainly influence the posterior part pain, the assessment of pain on different knee parts should be specified in future studies. Further high quality and multicentral studies should be undertaken to refine the technique (ie, optimal place, injection pressure, anesthetic formulation and et al.).

Conclusions

With the iPACK added to SACB, pain scores, morphine consumption, function ability were improved. Additional high‐quality studies are required to further address this topic.

Abbreviations

The interspace between the popliteal artery and capsule of the knee (iPACK); Single adductor canal block (SACB); Total Knee Arthroplasty (TKA); Randomized controlled trials (RCTs); Femoral nerve block (FNB); risk ratio (RR); mean difference (MD); Visual analog scale (VAS); 95% confidence interval (95% CI); PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses); Periarticular injection (PAI); Range of motion (ROM); Time up to go test (TUG); Quadriceps muscle strength (QMS); Postoperative day (POD); Common peroneal nerve (CPN); Postoperative day (POD); minimally clinical importance (MCID).

Funding (information that explains whether and by whom the research was supported)

Supported by

1. West China Nursing Discipline Development Special Fund Project, Sichuan University(HXHL20003)

2. 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYJC18040)

3. The Key Research & Development program of Science & Technology Department of Sichuan Province 2021YFS0167

4. Post‐Doctor Research Project, West China Hospital, Sichuan University (2020HXBH080)

5. Sichuan University Postdoctoral Interdisciplinary Innovation Fund

Conflicts of interest/Competing interests (include appropriate disclosures)

The authors declare no competing interests.

Availability of data and material

All data are fully available without restriction.

Code availability (software application or custom code)

Not applicable.

Authors' contributions

TXM, JXL conceived the methods of the study, performed the database search, the article selection, and data extraction processes, LL, ZWT, and FZM performed the statistical analysis, and drafted the manuscript. CJL, NN conceived the methods of the study, performed the database search, the article selection, and data extraction processes, and drafted the manuscript. NN and ZZK helped to draft the manuscript. All authors read and approved the manuscript.

Ethical approval

This meta‐analysis and all the included studies meet all the ethical standards described in the declaration of Helsinki. No ethical committee approval was required for this study.

Consent to participate (include appropriate statements)

Not applicable.

Consent for publication (include appropriate statements)

All authors have stated for consents of publications.

Availability of data and material (data transparency)

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Supporting information

Appendix S1. Supplementary Tables.

Appendix S2. Supporting Information.