Perineural Methylprednisolone Depot Formulation Decreases Opioid Consumption After Total Knee Arthroplasty

Figures & data

Table 1 Patient Demographics and Clinical Characteristics

Variables	DEX (N = 50)	DEX/MPA (N = 50)	P-value
Age	65.42 ± 8.40	66.82 ± 9.09	0.43
Sex, Male	16 (32%)	18 (36%)	0.67
Weight (kg)	91.04 ± 19.10	88.76 ± 17.31	0.53
Height (inches)	65.40 ± 4.92	64.81 ± 4.35	0.52
BMI (kg/m^2)	33.23 ± 6.91	32.76 ± 5.79	0.72
Ethnicity			0.18
African American	6 (12%)	10 (20%)
Caucasian	41 (82%)	33 (66%)
Hispanic	3 (6%)	7 (14%)
Alcohol use	30 (60%)	30 (60%)	>0.99
Smoker			>0.99
Active	3 (6%)	2 (4%)
Former	20 (40%)	20 (40%)
Never	27 (54%)	28 (56%)
ASA status			0.55
1–2	26 (52%)	23 (46%)
3–4	24 (48%)	27 (54%)
Comorbid diseases
Anxiety medications*	16 (32%)	7 (14%)	0.032
Neuropathy	7 (14%)	9 (18%)	0.55
Diabetes mellitus	11 (22%)	16 (32%)	0.26
Peripheral Vascular Disease	4 (8%)	3 (6%)	>0.99
Renal insufficiency**	1 (2%)	3 (6%)	0.62
Hepatic insufficiency^†	2 (4%)	4 (8%)	0.68
White Blood cell (WBC) preoperative^‡	6.4 (5.9–8.0)	6.4 (5.0–7.9)	0.54
Fasting Serum Glucose (FSG) preoperative	96.0 (87.0–117.0)	95.0 (91.0–125.0)	0.96
ACLP preoperative	4.05 ± 1.29	3.51 ± 0.82	0.028
Periarticular Injection	19 (38%)	18 (36%)	0.84
Surgical Duration (min)	105.08 ± 25.04	108.24 ± 22.39	0.51
Tourniquet Duration (min)	49.81 ± 25.28	54.38 ± 25.58	0.38
PACU Stay (min)	138.28 ± 57.16	138.58 ± 70.26	0.98

Notes: data are presented as mean ± SD, median (interquartile range: q25-q75), n (%). *Included antidepressants and anxiolytics **GFR<50 or creatinine clearance less than 50mL/min. ^†Past medical history or 2–3 times upper limit of hepatic enzyme. ^‡44 of 50, 38 of 50 patients were missing in the DEX and DEX/MPA group, respectively 44 of 50, 39 of 50 patients were missing in the DEX and DEX/MPA group, respectively.

Abbreviations: DEX, dexamethasone sodium phosphate; MPA, methylprednisolone acetate; BMI, body mass index; ASA, American Society of Anesthesiologists; ACLP, acceptable/comfortable level of pain; PACU, post-anesthesia care unit.

Table 2 Summary of Postoperative Outcomes

Variables	DEX (n = 50)	DEX/MPA (n = 50)	Difference (95% CI)	P-value
Primary outcome
Total oral morphine milligram equivalent (OME)	172 (117.5–250.0)	122.5 (74.0–181.0)	−45.3 (−80.5 to −10)	0.011
Secondary outcomes
Daily OME*
POD 1	50.6 (39.7 to 61.6)	49.7 (38.7 to 60.6)	−0.9 (−16.6 to 14.7)	0.90
POD 2	64.2 (53.3 to 75.1)	48.7 (37.7 to 59.7)	−15.5 (−31.2 to 0.2)	0.053
POD 3	51.8 (39.5 to 64.0)	37.8 (24.7 to 51.0)	−14.0 (−32.0 to 4.1)	0.13
Perioperative OME	21.3 (10.0–30.2)	15.0 (10.0–24.3)	−5 (−10 to 0)	0.044
Postoperative OME	145.0 (85.0–188.0)	101.0 (61.0–300.0)	−38.0 (−72.0 to −4.0)	0.024
Highest Active Pain Score*
POD 1	7.0 (6.4 to 7.6)	6.6 (6.0 to 7.2)	−0.4 (−1.2 to 0.5)	0.37
POD 2	7.4 (6.8 to 8.0)	6.5 (5.9 to 7.1)	−0.9 (−1.8 to −0.1)	0.031
POD 3	6.7 (6.0 to 7.4)	5.3 (4.6 to 6.1)	−1.4 (−2.4 to −0.4)	0.008
Highest Rest Pain Score*
POD 1	6.7 (6.0 to 7.3)	6.2 (5.6 to 6.8)	−0.5 (−1.4 to 0.4)	0.28
POD 2	7.0 (6.4 to 7.7)	5.7 (5.0 to 6.4)	−1.3 (−2.3 to −0.4)	0.005
POD 3	6.1 (5.3 to 6.8)	5.1 (4.3 to 5.9)	−1.0 (−2.1 to 0.1)	0.082
ACLP POD 1	3.66 ± 0.99	3.89 ± 0.74	0.23 (−0.15 to 0.61)	0.23
ACLP POD 2	4.13 ± 1.05	3.71 ± 1.03	−0.42 (−0.94 to 0.11)	0.12
PO acetaminophen (mg)^†
POD 1	2925.0 (1950.0–2925.0)	2925.0 (2925.0–2925.0)	0 (0 to 0)	0.18
POD 2	2925.0 (1950.0–3900.0)	2925.0 (1950.0–3900.0)	−487.5 (−975 to 0)	0.53
POD 3	1950.0 (975.0–2925.0)	975.0 (0.0–2925.0)	−487.5 (−975 to 0)	0.06
Ketorolac (mg)^†
POD 1	0.0 (0.0–0.0)	0.0 (0.0–15.0)	0 (0 to 0)	0.31
POD 2	0.0 (0.0–0.0)	0.0 (0.0–0.0)	0 (0 to 0)	0.61
POD 3	0.0 (0.0–0.0)	0.0 (0.0–0.0)	0 (0 to 0)	0.84
Celecoxib (mg)^†
POD 1	200.0 (0.0–400.0)	200.0 (0.0–400.0)	0 (0 to 0)	0.38
POD 2	200.0 (0.0–400.0)	200.0 (0.0–400.0)	0 (0 to 0)	0.63
POD 3	0.0 (0.0–400.0)	0.0 (0.0–200.0)	0 (0 to 0)	0.66
Active Range of Movement (AROM)^‡
POD 1	85.0 (72.0–100.0)	90.0 (82.0–99.0)	5.5 (−2.0 to 13.0)	0.16
POD 2	96.5 (85.0–107.0)	94.0 (89.0–100.0)	1.5 (−5.0 to 8.0)	0.56
POD 3	91.5 (83.0–99.0)	92.0 (88.0–98.0)	2.0 (−5.0 to 9.0)	0.63
Hospital length of stay (Days)	2.46 ± 0.84	2.22 ± 0.79	−0.24 (−0.56 to 0.08)	0.14
Revision surgery	2 (4%)	2 (4%)	NA	>0.99
Disposition				0.32
Home	38 (76%)	42 (84%)	NA
Short term rehabilitation	12 (24%)	8 (16%)
6 weeks opioids	14 (28%)	16 (32%)	NA	0.66
3 months opioids	6 (12%)	7 (14%)	NA	0.77

Notes: continuous data are presented as mean ± SD and mean difference (95% CI); median (interquartile range: p25 – p75) and median difference by Hodges-Lehman estimator (95% CI); least square mean (LSM) (95% CI) and LSM difference (95% CI) from repeated measures analysis. Categorical data were presented as n (%). *Perioperative OME or preoperative pain score was adjusted as a covariate in the repeated measures analysis, respectively. ^†In the DEX/MPA group, 1 of 50 patients were missing on POD 2 and 19 of 50 patients were missing on POD 3; In the DEX group, 13 of 50 patients were missing on POD 3. ^‡In the DEX/MPA group, 11 of 50 patients were missing on POD 1, 13 of 50 patients were missing on POD 2, 31 of 50 patients were missing on POD 3; In the DEX group, 7 of 50 patients were missing on POD 1, 18 of 50 patients were missing on POD 2, 24 of 50 patients were missing on POD 3.

Abbreviations: DEX, dexamethasone sodium phosphate; MPA, methylprednisolone acetate; ACLP, acceptable comfort level of pain; POD, postoperative day.

Figure 1 This STROBE flowchart shows patient inclusion.

Abbreviation: STROBE, Strengthening the Reporting of Observational studies in Epidemiology.

Figure 2 Progression of opioid consumption throughout the immediate postoperative period in DEX and DEX/MPA group.

Abbreviations: POD, postoperative day; OME, oral milligram morphine equivalent.

Table 3 Summary of Results for Laboratory Values

Variables	DEX (n = 50)	DEX/MPA (n = 50)	Difference (95% CI)	P-value
White blood cell count (WBC)
POD 0	8.0 (7.2 to 8.7)	8.6 (7.8 to 9.3)	0.6 (−0.5 to 1.7)	0.29
POD 1	12.6 (11.8 to 13.3)	11.5 (10.8 to 12.3)	−1.1 (−2.1 to 0.1)	0.062
POD 2	10.4 (9.6 to 11.2)	9.5 (8.7 to 10.4)	−0.8 (−2.0 to 0.3)	0.16
POD 3	9.2 (8.0 to 10.4)	8.8 (7.8 to 9.8)	−0.4 (−1.9 to 1.1)	0.59
Fasting Serum Glucose (FSG)
POD 0	147.0 (137.6 to 156.4)	140.0 (130.3 to 149.7)	−7.0 (−20.5 to 6.5)	0.31
POD 1	160.8 (151.4 to 170.2)	138.3 (128.6 to 148.0)	−22.5 (−36 to −8.9)	0.001
POD 2	123.9 (113.9 to 133.9)	114.9 (104.7 to 125.1)	−9.0 (−23.3 to 5.3)	0.22
POD 3	128.6 (115.0 to 142.3)	114.5 (102.7 to 126.4)	−14.1 (−32.2 to 4.0)	0.13

Notes: Data are presented as least square mean (LSM) and 95% CI, LSM difference (95% CI). Baseline lab value was not adjusted in the repeated measures analysis due to a significant amount of missing data.

Abbreviations: DEX, dexamethasone sodium phosphate; MPA, methylprednisolone acetate.