Non-Particulate Steroids (Betamethasone Sodium Phosphate, Dexamethasone Sodium Phosphate, and Dexamethasone Palmitate) Combined with Local Anesthetics (Ropivacaine, Levobupivacaine, Bupivacaine, and Lidocaine): A Potentially Unsafe Mixture

Figures & data

Table 1 Particulate Size Distribution in Mixed Solutions (Normal Saline or Local Anesthetics and Non-Particulate Steroids)

Non-Particulate Steroids	Normal Saline or Local Anesthetics	Dilution	No. of Particulates (%)	Particulate Distribution				>100 μm	>500 μm	P-value
				0–10 μm	11–20 μm	21–50 μm	51–100 μm
Betamethasone sodium phosphate 5.2 mg/mL	0.9% Normal saline	1:1	0	0	0	0	0
		1:2	0	0	0	0	0
		1:3	0	0	0	0	0
	0.75% ropivacaine HCl	1:1	183	15(8.2)	29(15.3)	47(25.4)	66(36.6)	14(7.8)	12(6.7)	0.84
		1:2	176	11(6.3)	26(14.8)	50(28.4)	64(36.4)	12(6.8)	13(7.3)
		1:3	169	12(7.1)	25(14.9)	49(29.9)	52(30.8)	19(11.2)	10(6.1)
	0.75% levobupivacaine HCl	1:1	104	8(7.7)	13(12.5)	38(36.5)	27(26)	18(17.3)	0(0)	0.99
		1:2	100	7(7)	14(14)	36(36)	28(28)	15(15)	0(0)
		1:3	94	5(5.3)	15(16)	35(37.2)	22(23.4)	17(18.1)	0(0)
	0.5% bupivacaine HCL	1:1	93	83(89.2)	10(10.8)	0	0	0	0	0.05
		1:2	81	78(96.3)	3(3.7)	0	0	0	0
		1:3	75	73(97.3)	2(2.7)	0	0	0	0
	1% lidocaine HCl	1:1	3	1	2	0	0	0	0	0.7
		1:2	2	1	1	0	0	0	0
		1:3	0	0	0	0	0	0	0
Dexamethasone disodium phosphate 4 mg/mL	0.9% Normal saline	1:1	0	0	0	0	0	0	0
		1:2	0	0	0	0	0	0	0
		1:3	0	0	0	0	0	0	0
	0.75% ropivacaine HCl	1:1	756	452(59.8)	296(39.2)	8(1)	0	0	0	0.36
		1:2	708	421(59.5)	281(39.7)	6(0.8)	0	0	0
		1:3	641	387(60.4)	253(39.5)	1(0.1)	0	0	0
	0.75% levobupivacaine HCl	1:1	565	398(70.4)	142(25.1)	25(4.5)	0	0	0	0.56
		1:2	501	362(72.3)	121(24.2)	18(3.5)	0	0	0
		1:3	472	345(73.1)	115(24.4)	12(2.5)	0	0	0
	0.5% bupivacaine HCL	1:1	51	48(94.1)	3(5.9)	0	0	0	0	0.65
		1:2	43	42(97.7)	1(2.3)	0	0	0	0
		1:3	31	30(96.8)	1(3.2)	0	0	0	0
	1% lidocaine HCl	1:1	7	6	1	0	0	0	0	0.58
		1:2	5	5	0	0	0	0	0
		1:3	2	2	0	0	0	0	0
Dexamethasone palmitate 5 mg/mL	0.9% Normal saline	1:1	0	0	0	0	0	0	0
		1:2	0	0	0	0	0	0	0
		1:3	0	0	0	0	0	0	0
	0.75% ropivacaine HCl	1:1	0	0	0	0	0	0	0
		1:2	0	0	0	0	0	0	0
		1:3	0	0	0	0	0	0	0
	0.75% levobupivacaine HCl	1:1	0	0	0	0	0	0	0
		1:2	0	0	0	0	0	0	0
		1:3	0	0	0	0	0	0	0
	0.5% bupivacaine HCL	1:1	0	0	0	0	0	0	0
		1:2	0	0	0	0	0	0	0
		1:3	0	0	0	0	0	0	0
	1% lidocaine HCl	1:1	0	0	0	0	0	0	0
		1:2	0	0	0	0	0	0	0
		1:3	0	0	0	0	0	0	0

Figure 1 Non-particulate steroids were pure liquid with no identifiable particle. (A) Microscopic findings of betamethasone sodium phosphate (BSP) (× 200), (B) dexamethasone sodium phosphate (DSP) (× 200), (C) dexamethasone palmitate (DPA) (× 200).

Figure 2 (A) Microscopic findings of betamethasone sodium phosphate (BSP) mixed with 0.75% ropivacaine HCl (ropivacaine) (× 100). (B) High density and extremely large particulates (>500 µm) in BSP mixed with ropivacaine (× 200). (C) BSP mixed with 0.75% levobupivacaine HCl (levobupivacaine) (× 100). (D) High density and large particulates (>100 µm) in BSP mixed with levobupivacaine (× 200). (E) BSP mixed with hyperbaric bupivacaine HCl (× 100). This shows dot-shaped particulates (<10 µm). (F) BSP mixed with 1% lidocaine HCl (× 100). No identifiable particulate is observed.

Figure 3 (A) Microscopic findings of dexamethasone sodium phosphate (DSP) mixed with 0.75% ropivacaine HCl (ropivacaine) (× 100). (B) Small and short rod-like shaped particulates (≤10 µm) in DSP mixed with ropivacaine (× 200). (C) DSP mixed with 0.75% levobupivacaine HCl (levobupivacaine) (× 100). (D) Small and short particulates in DSP mixed with levobupivacaine (× 200). (E) DSP mixed with hyperbaric bupivacaine HCl (× 100). (F) DSP mixed with 1% lidocaine HCl (× 100). No identifiable particulate is observed.

Figure 4 Microscopic findings of dexamethasone palmitate (DPA) mixed with 0.75% ropivacaine HCl (ropivacaine) (× 100).

Figure 5 Insoluble particulates after heating (36–37 °C) (× 400). These particulates were produced from betamethasone sodium phosphate (BSP) mixed with 0.75% ropivacaine HCl (ropivacaine).

Table 2 The pH of Non-Particulate Steroids, Normal Saline, and Local Anesthetics

Non-Particulate Steroids and Local Anesthetics	pH
Betamethasone sodium phosphate 5.2 mg/mL	8.5
Dexamethasone disodium phosphate 4 mg/mL	7.6
Dexamethasone palmitate 5 mg/mL	7.1
0.75% ropivacaine HCl	6.1
0.75% levobupivacaine HCl	5.8
0.5% bupivacaine HCl	6.4
1% lidocaine HCl	6.3

Table 3 Measurement of pH in Mixed Solutions (Normal Saline or Local Anesthetics and Non-Particulate Steroids)

Non-Particulate Steroids	Normal Saline or Local Anesthetics	Dilution	pH
Betamethasone sodium phosphate 5.2 mg/mL	0.9% Normal saline	1:1	7.83
		1:2	7.83
		1:3	7.83
	0.75% ropivacaine HCl	1:1	7.01
		1:2	6.62
		1:3	6.46
	0.75% levobupivacaine HCl	1:1	6.92
		1:2	6.35
		1:3	6.13
	0.5% bupivacaine HCL	1:1	7.41
		1:2	7.23
		1:3	7.11
	1% lidocaine HCl	1:1	7.31
		1:2	7.16
		1:3	7.03
Dexamethasone disodium phosphate 4 mg/mL	0.9% Normal saline	1:1	7.12
		1:2	6.95
		1:3	6.94
	0.75% ropivacaine HCl	1:1	6.66
		1:2	6.45
		1:3	6.32
	0.75% levobupivacaine HCl	1:1	6.53
		1:2	6.33
		1:3	6.23
	0.5% bupivacaine HCL	1:1	6.79
		1:2	6.67
		1:3	6.59
	1% lidocaine HCl	1:1	6.57
		1:2	6.38
		1:3	6.22
Dexamethasone palmitate 5 mg/mL	0.9% Normal saline	1:1	6.42
		1:2	6.21
		1:3	6.14
	0.75% ropivacaine HCl	1:1	5.4
		1:2	5.21
		1:3	5.08
	0.75% levobupivacaine HCl	1:1	4.87
		1:2	4.71
		1:3	4.65
	0.5% bupivacaine HCL	1:1	5.17
		1:2	5.11
		1:3	5
	1% lidocaine HCl	1:1	5.36
		1:2	5.46
		1:3	5.51