Search results
In the recent study, a total of 1,313 research were identified based on the inclusion criteria. After removing 366 duplicates, 947 records remained. From these, 902 articles were excluded based on the title and abstract screening. 36 RCTs were ultimately enrolled after browsing the whole text and 9 studies were excluded for specific reasons (Figure 1).
The sample size of the included studies ranged from 23 to 323 participants. Among the included studies, a total of 3,048 patients who underwent primary unilateral TKA were represented in thirty-one RCTs. Additionally, one study by Morales-Munoz et al. included 54 patients who underwent knee replacement surgery, and four studies encompassed 211 patients who underwent bilateral TKA. The follow-up period across the studies varied from 24 hours to 1 year. In terms of glucocorticoid administration, 1,188 patients received systemic glucocorticoid administration either before anesthesia induction or after surgery, while 663 patients had been implemented with glucocorticoid in the cocktail protocol for intraoperative periarticular infiltration. The specific drugs utilized in the studies included dexamethasone in twenty studies, methylprednisolone in six studies, triamcinolone acetonide in five studies, hydrocortisone in three studies, betamethasone in two studies, and prednisone in one study. The basic characteristics of the studies are described in the Table 1[17-52]. The risk of bias assessment of RCT studies is presented in Figure 2.
Table 1. Characteristic of the included studies.
|
Study
|
Year
|
country
|
Sample size
|
Mean age
|
Gender (M:F) (I/C)
|
Anesthesia
|
Intervention
|
Pain Manage
|
Relevant outcome
|
Follow-up
|
(I/C)
|
Gasbjerg et al.17
|
2022
|
Danish
|
161/162
|
69/68
|
80:81/74:88
|
S/G
|
24mg DXM prior surgery
|
Oral paracetamol and ibuprofen prior and after surgery, LIA, PCA (morphine), Morphine for rescue analgesia.
|
VAS and adverse effects
|
3 months
|
Lei et al.18
|
2021
|
China
|
62/63
|
66.0 /66.0
|
12:50/8:55
|
G
|
10mg DXM prior to induction
|
LIA, oral diclofenac or an IM of morphine as required.
|
VAS, ROM, Inflammatory cytokines and adverse effects
|
3 months
|
Cheng et al.19
|
2021
|
China
|
49/49#
|
63.7/64.8
|
10:45/12:43
|
S
|
Oral prednisone (10 mg qd, from pod1, for 2 weeks).
|
Oral celecoxib prior surgery, LIA, celecoxib on pod1 and tramadol for 2 weeks.
|
VAS and adverse effects
|
3 months
|
Zhang et al.20
|
2020
|
China
|
31/32
|
66.3/67.3
|
6:25/4:28
|
G
|
20 mg DXM after anesthesia, 10 mg DXM at 24 and 48 h.
|
PIA, enteric-coated diclofenac sodium bid.
|
Inflammatory cytokines and adverse effects
|
1 year
|
Tammachote and Kanitnate.21
|
2020
|
Thailand
|
50/50
|
67 /69
|
8:42/6:44
|
S
|
0.15 mg/kg DXM after anesthesia
|
PIA, IV ketorolac or morphine as required during the pod2, oral naproxen, oral tramadol as required on pod3. Extended-released acetaminophen, nortriptyline and pregabalin at bedtime.
|
VAS, ROM and adverse effects
|
3 months
|
Kim et al.22
|
2020
|
Korea
|
45/44
|
69.3 /68.2
|
4:41/3:41
|
S
|
10 mg DXM 1 hour prior surgery
|
PIA, PCA (fentanyl and Acupan), oral celecoxib, tramadol/acetaminophen, oral oxycodone, IV pethidine or fentanyl patches as emergency required.
|
VAS and adverse effects
|
1 week
|
Chan et al.23
|
2020
|
China
|
46/45
|
75.5/75.3
|
11:35/13:32
|
S
|
8 mg DXM prior induction
|
LIA, PCA morphine, oral analgesic regimen (pregabalin, paracetamol and celecoxib).
|
VAS, ROM, Inflammatory cytokines and adverse effects
|
1 year
|
Yu et al.24
|
2019
|
China
|
45/43
|
65.1/64.2
|
19:26/17:26
|
G
|
10mg DXM after the anesthesia and repeated at 24h.
|
Oral oxycodone or an IM of pethidine hydrochloride as required.
|
VAS, ROM, Inflammatory cytokines and adverse effects
|
3 months
|
Chen et al.25
|
2019
|
China
|
30/30
|
66.7/68.1
|
8:22/8:22
|
S
|
125 mg MP on the induction.
|
LIA, PCA Morphine, Oral or IV medications (Gabapentin, Esomeprazole, Paracetamol, Cefazolin, Tranexamic acid, Etoricoxib, Bisacodyl, Metoclopramide, Dihydrocodeine).
|
Inflammatory cytokines and adverse effects
|
1 year
|
Xu et al.26
|
2018
|
China
|
60/61
|
64.5/65.8
|
11:49/8:53
|
G
|
20mg DXM prior induction
|
PAI, oral diclofenac, oxycodone HCl or IM of morphine as required.
|
VAS, ROM, Inflammatory cytokines and adverse effects
|
3 months
|
Wu et al.27
|
2018
|
China
|
50/50
|
66.9/67.4
|
17:33/18:32
|
G
|
10 mg DXM 1h prior surgery
|
MOAG from 1day prior operation (celecoxib, pregabalin), oral oxycodone or an IM of pethidine hydrochloride as required.
|
VAS, ROM, Inflammatory cytokines and adverse effects
|
3 months
|
Li et al.28
|
2018
|
China
|
36/32
|
63.9 /64.7
|
7:29/5:27
|
NR
|
100 mg HC, 2 hours prior and 8 hours after surgery
|
Oral celecoxib, LIA, PCA, IM of pethidine hydrochloride as required.
|
VAS, ROM and adverse effects
|
30 days
|
Dissanayake et al.29
|
2018
|
Australia
|
41/40
|
NR
|
NR
|
S/G
|
8mg DXM at induction and at 24 hour.
|
LIA, paracetamol, gabapentin for 2,3 days post-surgery, oxycodone/naloxone for 4,5 days, ibuprofen or celecoxib, oxycodone and tramadol slow release as required.
|
VAS and adverse effects
|
6 weeks
|
Study
|
Year
|
country
|
Sample size
|
Mean age
|
Gender (M:F) (I/C)
|
Anesthesia
|
Intervention
|
Pain Manage
|
Relevant outcome
|
Follow-up
|
(I/C)
|
Xu et al.30
|
2018
|
China
|
54/54
|
63.6 /63.6
|
8:46/9:45
|
G
|
10 mg DXM after anesthesia, 10 mg DXM returned to the inpatient unit.
|
PIA, MOAG from 1day prior operation (diclofenac, pregabalin), oral oxycodone or an IM of parecoxib as required.
|
VAS, ROM, Inflammatory cytokines and adverse effects
|
3 days
|
Lindberg-Larsen et al.31
|
2017
|
Denmark
|
33/30
|
65.0/67.7
|
13:20/15:15
|
S
|
125 mg MP after anesthesia
|
Oral paracetamol, naproxen 1h prior surgery, LIA, oral paracetamol and naproxen. Opioids as request.
|
VAS, Inflammatory cytokines and adverse effects
|
24 hours
|
Lee et al.32
|
2018
|
Canada
|
60/60
|
64.6/67
|
18:42/23:37
|
S
|
8 mg DXM over 10 minutes after block
|
Oral acetaminophen before surgery, LIA, PCA hydromorphone, oral acetaminophen, oral opioids (hydromorphone or oxycodone), IV ketorolac or subcutaneous opioids as needed,
|
VAS and adverse effects
|
48 hours
|
Morales-Munoz et al.33
|
2015
|
Spain
|
27/27
|
68.8/68.8
|
8:19/6:21
|
S
|
8 mg DXM
|
0.5% ropivacaine (20ml) for FNB
|
VAS and adverse effects
|
48 hours
|
McLawhorn et al.34
|
2015
|
America
|
11/12
|
68/66
|
3:8/3:9
|
S
|
100mg HSS 2h prior surgery, 2 more doses given 8 h.
|
PECA till day 2, acetaminophen and oral narcotic analgesics as needed
|
Adverse effects
|
hospital stay
|
Backes et al.35
|
2013
|
America
|
28/20
|
NR
|
NR
|
G
|
10 mg DXM prior to induction
|
Oral extended release oxycodone, celecoxib prior surgery, intraarticular pain pumps of 0.5% bupivacaine, PCA hydromorphone, oral extended release oxycodone, hydrocodone/acetaminophen and/or IV hydromorphone as request.
|
ROM
|
48 hours
|
Koh et al.36
|
2013
|
Korea
|
135/134
|
72.0/72.0
|
38:117/35:119
|
S
|
10 mg DXM 1 hour prior surgery
|
MOAG prior surgery (sustained-release oxycodone, celecoxib, pregabalin and acetaminophen), Continuous FNB, PIA, PCA fentanyl, Oral celecoxib, pregabalin and acetaminophen or IM of ketoprofen as required.
|
VAS and adverse effects
|
1 year
|
Lunn et al.37
|
2011
|
Denmark
|
24/24
|
66/67
|
13:11/8:16
|
S
|
125mg MP prior anesthesia.
|
LIA, IV sufentanil in PACU, oral oxycodone, celecoxib and slow-release acetaminophen, oral gabapentin and from the night of surgery up to the 6th.
|
VAS, Inflammatory cytokines and adverse effects
|
30 days
|
Jules-Elysee et al.38
|
2011
|
America
|
15/15
|
64 /71
|
6:9/9:6
|
S
|
100 mg HC prior surgery, 2 dose eight hours apart.
|
PECA(bupivacaine and hydromorphone ), bilateral FNBs, oxycodone and acetaminophen as needed
|
VAS, Inflammatory cytokines and adverse effects
|
6 months
|
Peng et al.39
|
2021
|
China
|
60/60
|
65.1/65.1
|
4:56/4:56
|
NR
|
7 mg betamethasone.
|
PIA, PCA (morphine), parecoxib after for 3 days and oral Loxoprofen Sodium, aminophenol oxycodone sed as emergency.
|
VAS, ROM and adverse effects
|
3 months
|
Wang et al.40
|
2021
|
China
|
52/50
|
65.1/63.9
|
17:35/15:35
|
G
|
10 mg DXM
|
LIA, celecoxib, morphine hydrochloride injected subcutaneously as required.
|
VAS, ROM, Inflammatory cytokines and adverse effects
|
3 months
|
El-Boghdadly et al.41
|
2021
|
United Kingdom
|
68/72#
|
63.1/65.8
|
34:34/25:47
|
S
|
8 mg DXM
|
Oral acetaminophen and celecoxib preoperatively, LIA, IV fentanyl or hydromorphone at PACU, oral acetaminophen celecoxib. Oral oxycodone, hydromorphone or PCA with hydromorphone or morphine as request.
|
VAS, ROM and adverse effects
|
1 month
|
Study
|
Year
|
country
|
Sample size
|
Mean age
|
Gender (M:F) (I/C)
|
Anesthesia
|
Intervention
|
Pain Manage
|
Relevant outcome
|
Follow-up
|
(I/C)
|
Chan et al.b, 42
|
2020
|
China
|
45/45
|
66/66
|
31:14:/31:14
|
S
|
40 mg TA
|
LIA, PCA.
|
VAS, ROM and adverse effects
|
1 year
|
Tsukada et al.43
|
2016
|
Japan
|
40/37
|
75 /72
|
5:35/5:32
|
S
|
40 mg MP
|
LIA, IV flurbiprofen axetil, oral loxoprofen, diclofenac sodium as request.
|
VAS, ROM and adverse effects
|
1 year
|
Kim et al.44
|
2015
|
Korea
|
43/43
|
71.4/70.6
|
2:41/4:39
|
S
|
40 mg MP
|
Oral celecoxib and tramadol/acetaminophen for pre 1day, LIA, PCA (fentanyl), Ketorolac and fentanyl patch for 3 - 6 day. Oral celecoxib, tramadol/acetaminophen. IM of pethidine or oral oxycodone was used on rescue. .
|
VAS, ROM, Inflammatory cytokines and adverse effects
|
7 days
|
Ikeuchi et al.45
|
2014
|
Japan
|
20/20
|
77 /76
|
2:18/4:16
|
G
|
6.6 mg DXM
|
LIA, PCA (Fentanyl), oral loxoprofen tablets until POD5 and as needed.
|
VAS, Inflammatory cytokines and adverse effects
|
3 months
|
Kwon et al.46
|
2014
|
Korea
|
76/76
|
69.3/69.3
|
0:76/0:76
|
S
|
40 mg TA
|
Oral celecoxib, ultracet and pregabalin prior operation, LIA, PCA (fentanyl and bupivacaine), oral celecoxib and ultracet bid. IM of ketoprofen as request.
|
Adverse effects
|
6 months
|
Yue et al.47
|
2013
|
China
|
36/36
|
70.2/69.3
|
4:32/4:32
|
G
|
1 ml betamethasone
|
Oral celecoxib preoperatively and postoperatively, LIA, PCA (morphine), IM of morphine as required.
|
VAS, ROM and adverse effects
|
1 year
|
Chia et al.48
|
2013
|
Australia
|
39/40
|
68.9 /65.1
|
NR
|
S
|
40 mg triamcinolone acetate
|
LIA, celecoxib for 2 weeks. .
|
VAS, ROM and adverse effects
|
3 months
|
Seah et al.49
|
2011
|
Singapore
|
50/50
|
67.9/65.4
|
NR
|
S/G
|
40 mg TA
|
LIA, oral naproxen and PCA (morphine).
|
VAS, ROM and adverse effects
|
2 year
|
Christensen et al.50
|
2009
|
America
|
39/37
|
65.8/65.2
|
16:23/7:30
|
G
|
40 mg MP acetate
|
Oral celecoxib, oxycodone and acetaminophen preoperatively, FNB, LIA,
|
VAS, ROM and adverse effects
|
3 months
|
Li et al.51
|
2021
|
china
|
45/45
|
66.1/68.2
|
15:30/8:37
|
G
|
10 mg DXM at the induction, 10 mg DXM, 100ml
|
Oral loxoprofen or celecoxib after hospital admission, LIA, oral Loxoprofen, IM parecoxib until hospital discharge, IM Morphine hydrochloride as required.
|
VAS, ROM, Inflammatory cytokines and adverse effects
|
3 months
|
Hatayama et al.52
|
2021
|
Japan
|
50/50
|
71.6 /72.3
|
12:38/5:45
|
G
|
10 mg DXM 1h prior, 24h after surgery, 40mg TA
|
PIA, FNB, oral acetaminophen on pod1, IM pentazocine and transrectal administration of diclofenac as request.
|
VAS, Inflammatory cytokines and adverse effects
|
1 week
|
Note: #, final analyzed; a, knee replacement surgery; b, bilateral TKA; I/C, Interventional group/Control group; M/F, Male/Female; NR, not rated; S/G, Intraspinal anesthesia/General anesthesia; DXM, dexamethasone; MP, methylprednisolone; HC, hydrocortisone; TA, triamcinolone acetonide; HSS, hydrocortisone sodium succinate; LIA, local infiltration analgesia; PIA, periarticular infiltration analgesia; PCA, patient-controlled intravenous analgesia; PCEA, patient-controlled epidural analgesia; MOAG, multimodal oral analgesic drugs; IM, muscular injection; IV, intravenous injection; FNB, femoral nerve block; VAS, Visual analgesia score; ROM, Range of Motion.
Postoperative VAS
In the analysis, twenty-five studies reported the VAS on postoperative day 1 (POD1) following TKA, including 1,302 patients in the glucocorticoid group and 1,292 patients in the control group. Furthermore, twenty-three trials recorded the VAS on postoperative day 2 (POD2), with 1,243 patients in the glucocorticoid group and 1,236 patients in the control group. Six studies measured the VAS score on postoperative 3 months (POM3), including 272 patients in the glucocorticoid group and 271 patients in the control group. The results indicated that the use of glucocorticoids significantly reduced the postoperative VAS (Figure 3, POD1: MD = -0.59; 95%CI: -0.78, -0.39; P < 0.000; Figure 4, POD2: MD = -0.18; 95%CI: -0.31, -0.05; P = 0.006; Figure 5, POM3: MD = -0.09; 95%CI: -0.14, -0.04; P = 0.001).
Morphine consumption
Eleven records provided data of morphine consumption on POD1 following TKA. These studies involved 475 patients in the glucocorticoid group and 473 patients in the control group. Morphine consumption was significantly reduced in the glucocorticoid group (Figure 6, MD = -2.61; 95% CI: -4.57, -0.66; P = 0.009) compared to the control group.
Postoperative Range of Motion
ROM in the knee joint was assessed on POD1 and postoperative days 3 (POD3). Eleven studies provided ROM data on POD1 with 481 patients in the glucocorticoid group and 467 patients in the control group. Ten studies assessed ROM on POD3, with 479 patients in the glucocorticoid group and 473 patients in the control group. The overall analysis demonstrated that systemic administration (SA) and periarticular injection analgesia (PIA) of glucocorticoids improved the ROM comparing to the control group after TKA (Figure 7, POD1: MD = 5.22; 95%CI: 3.40, 7.04; P < 0.000; Figure 8, POD3: MD = 3.50; 95%CI: 0.86, 6.15; P = 0.009).
Postoperative inflammatory response
Eleven trials evaluated the C-reactive protein (CRP) concentration on POD1, involving 487 patients in the glucocorticoid group and 482 patients in control group. Additionally, eleven trials recorded the CRP concentration on POD2, with 526 patients vs. 521 patients in two groups respectively. Seven studies reported the CRP concentration on POD3, encompassing 322 patients in the glucocorticoid group and 323 patients in the control group. The results showed a significant reduction of CRP in the glucocorticoid group compared to the control group (Supplementary figure 1, POD1: MD = -18.75; 95% CI: -23.36, -14.15; P<0.000; Supplementary figure 2, POD2: MD: -47.05; 95% CI: -59.80, -34.29; P<0.000; Supplementary figure 3, POD3: MD = -37.79; 95% CI: -49.45, -26.12; P<0.000).
In addition, eight trials assessed the Interleukin-6 (IL-6) concentration on POD1, with 369 patients in the glucocorticoid group and 368 patients in the control group. The IL-6 concentration was significantly lower in the glucocorticoid group on POD1 (Supplementary figure 4, MD = -60.02; 95% CI: -71.02, -49.02; P<0.000).
Postoperative adverse effects
Data from six studies were analyzed to investigate the incidence of postoperative nausea and vomiting (PONV) on POD1, while fourteen studies reported the PONV incidence during the entire postoperative period. The results showed that perioperative systemic or periarticular injection glucocorticoid reduced the incidence of PONV not only on POD1 but also during total postoperative period (Supplementary figure 5, POD1: RR = 0.49; 95% CI: 0.35, 0.67; P<0.000; Supplementary figure 6, Total: RR = 0.63; 95% CI: 0.51, 0.77; P<0.000).
Eight records provided data on blood glucose concentration on POD1, and five of them reported the blood glucose concentration on POD2 as well. The analysis showed that blood glucose concentration was significantly increased in the glucocorticoid group on POD1 compared with the control group (Supplementary figure 7, MD = 0.47; 95%CI: 0.25, 0.68; P<0.000). However, the difference in blood glucose concentration between the two groups was reduced on POD2 (Supplementary figure 8, MD = -0.16; 95%CI: -0.55, 0.23; P = 0.42).
Fourteen studies evaluated the occurrence of wound infection postoperatively, while two studies reported the occurrence of venous thrombosis. The analysis did not show a significant increase in the risk of postoperative wound infection (Supplementary figure 9, RR= 0.98; 95% CI: 0.64, 1.51; P=0.93) and venous thrombosis in the glucocorticoid group (Supplementary figure 10, RR= 1.47; 95% CI: 0.25, 8.68; P=0.67).
Length of Hospital Stay
Nineteen trails reported the duration of hospitalization after TKA which including 807 patients in the glucocorticoid group and 801 patients in the control group. The overall pooled outcomes showed that perioperative glucocorticoid administration significantly decreased the LOS comparing to the control group (Supplementary figure 11, MD =-0.27; 95% CI: -0.44, -0.09; P = 0.003).
Comparison of efficacy between systemic administration and periarticular infiltration in glucocorticoid group
In the comparison between systemic administration and periarticular infiltration of glucocorticoids, two studies with 95 patients in each group were included. The results showed that the postoperative VAS was significantly lower in periarticular infiltration group compare to the systemic administration group on POD2 (Supplementary figure 12, MD = -0.16; 95% CI: -0.29, -0.02; P=0.02). However, the plasma CRP level was significantly lower in the systemic administration group compare to the periarticular infiltration group on POD1 and POD2 (Supplementary figure 13, POD1: MD = 10.30; 95% CI: 4.74, 15.85; P=0.0003; Supplementary figure 14, POD2: MD =13.62; 95% CI: 2.19, 25.05; P=0.02).
Publication bias
Publication bias was evaluated using funnel plots and Begg’s and Egger’s tests for VAS on POD1, 2, 3, which showed no evidence of publication bias (Supplementary figure 15, 16 and 17, Begg: Pr > |z| = 0.624, 0.635, 0.976, Egger’s: P = 0.491, 0.251, 0.733). And the publication bias for VAS on POM3 and morphine consumption were not assessed due to the small number of included studies.