Effects of chloride content of intravenous crystalloid solutions in critically ill adult patients: a meta-analysis with trial sequential analysis of randomized trials

Annals of Intensive Care

Table 2 Effects of balanced crystalloids versus 0.9% saline fluid on mortality and renal outcomes

Outcomes	Balanced crystalloids	0.9% Saline	Risk ratio/standard mean difference (95% CI)
In-hospital mortality	Events/total	Events/total	Fixed models	Random models
Waters et al. [20]	1/33	1/33	1.00 [0.07, 15.33]	1.00 [0.07, 15.33]
Takil et al. [21]	0/15	0/15	Not estimable	Not estimable
Van Zyl et al. [22]	0/27	0/27	Not estimable	Not estimable
Young et al. [23]	3/22	4/24	0.82 [0.21, 3.25]	0.82 [0.21, 3.25]
Young et al. [9]	87/1152	95/1110	0.88 [0.67, 1.17]	0.88 [0.67, 1.17]
Verma et al. [24]	5/33	2/34	2.58 [0.54, 12.36]	2.58 [0.54, 12.36]
Semler et al. [25]	72/520	68/454	0.92 [0.68, 1.26]	0.92 [0.68, 1.26]
Semler et al. [10]	818/7942	875/7860	0.93 [0.85, 1.01]	0.93 [0.85, 1.01]
Summary	986/9744	1045/9557	0.92 [0.85, 1.00]	0.92 [0.85, 1.00]
Fixed model heterogeneity: χ² = 1.78, df = 5 (p = 0.88); I² = 0%; test for overall effect: Z = 1.88 (p = 0.06)
Random model heterogeneity: τ² = 0.00; χ² = 1.78, df = 5 (p = 0.88); I² = 0%; test for overall effect: Z = 1.89 (p = 0.06)

Outcomes	Balanced crystalloids	0.9% Saline	Risk ratio/standard mean difference (95% CI)
30-day mortality	Events/total	Events/total	Fixed models	Random models
Young et al. [23]	3/22	4/24	0.82 [0.21, 3.25]	0.82 [0.21, 3.25]
Semler et al. [25]	72/520	68/454	0.92 [0.68, 1.26]	0.92 [0.68, 1.26]
Semler et al. [10]	818/7942	875/7860	0.93 [0.85, 1.01]	0.93 [0.85, 1.01]
Summary	893/8484	947/8338	0.92 [0.85, 1.01]	0.92 [0.85, 1.01]
Fixed model heterogeneity: χ² = 0.03, df = 2 (p = 0.98); I² = 0%; test for overall effect: Z = 1.78 (p = 0.08)
Random model heterogeneity: τ² = 0.00; χ² = 0.03, df = 2 (p = 0.98); I² = 0%; test for overall effect: Z = 1.78 (p = 0.08)

Outcomes	Balanced crystalloids	0.9% Saline	Risk ratio/standard mean difference (95% CI)
60-day mortality	Events/total	Events/total	Fixed models	Random models
Semler et al. [25]	87/520	83/454	0.92 [0.70, 1.20]	0.92 [0.70, 1.20]
Semler et al. [10]	928/7942	975/7860	0.94 [0.87, 1.02]	0.94 [0.87, 1.02]
Summary	1015/8462	1058/8314	0.94 [0.87, 1.02]	0.94 [0.87, 1.02]
Fixed model heterogeneity: heterogeneity: χ² = 0.04, df = 1 (p = 0.84); I² = 0%; test for overall effect: Z = 1.51 (p = 0.13)
Random model heterogeneity: τ² = 0.00; χ² = 0.04, df = 1 (p = 0.84); I² = 0%; test for overall effect: Z = 1.52 (p = 0.13)

Outcomes	Balanced crystalloids	0.9% Saline	Risk ratio/standard mean difference (95% CI)
Development of stage 2 or higher AKI	Events/total	Events/total	Fixed models	Random models
Waters et al. [20]	4/33	5/33	0.80 [0.24, 2.72]	0.80 [0.24, 2.72]
Young et al. [23]	3/22	6/24	0.55 [0.15, 1.92]	0.55 [0.15, 1.92]
Young et al. [9]	105/1067	104/1025	0.97 [0.75, 1.25]	0.97 [0.75, 1.25]
Verma et al. [24]	1/33	3/34	0.34 [0.04, 3.14]	0.34 [0.04, 3.14]
Semler et al. [25]	97/520	87/454	0.97 [0.75, 1.26]	0.97 [0.75, 1.26]
Semler et al. [10]	807/7558	858/7458	0.93 [0.85, 1.02]	0.93 [0.85, 1.02]
Summary	1017/9233	1063/9028	0.93 [0.86, 1.01]	0.93 [0.86, 1.01]
Fixed model heterogeneity: χ² = 1.74, df = 5 (p = 0.88); I² = 0%; test for overall effect: Z = 1.71 (p = 0.09)
Random model heterogeneity: τ² = 0.00; χ² = 1.74, df = 5 (p = 0.88); I² = 0%; test for overall effect: Z = 1.69 (p = 0.09)

Outcomes	Balanced crystalloids	0.9% Saline	Risk ratio/standard mean difference (95% CI)
New RRT use	Events/total	Events/total	Fixed models	Random models
Takil et al. [21]	0/15	0/15	Not estimable	Not estimable
Young et al. [9]	38/1152	38/1110	0.96 [0.62, 1.50]	0.96 [0.62, 1.50]
Verma et al. [24]	5/33	3/34	1.72 [0.45, 6.62]	1.72 [0.45, 6.62]
Semler et al. [25]	24/520	14/454	1.50 [0.78, 2.86]	1.50 [0.78, 2.86]
Semler et al. [10]	189/7588	220/7458	0.84 [0.70, 1.02]	0.84 [0.70, 1.02]
Summary	256/9308	275/9071	0.91 [0.77, 1.07]	0.95 [0.75, 1.21]
Fixed model heterogeneity: χ² = 3.77, df = 3 (p = 0.29); I² = 20%; test for overall effect: Z = 1.16 (= 0.24)
Random model heterogeneity: τ² = 0.01; χ² = 3.77, df = 3 (p = 0.29); I² = 20%; test for overall effect: Z = 0.38 (p = 0.70)

Outcomes	Balanced crystalloids	0.9% Saline	Risk ratio/standard mean difference (95% CI)
RRT-free days	Mean ± SD, No.	Mean ± SD, No.	Fixed models	Random models
Semler et al. [25]	24.9 ± 9.7, 520	23.7 ± 10, 520	0.12 [− 0.00, 0.25]	0.12 [− 0.00, 0.25]
Semler et al. [10]	25.6 ± 8.6, 7942	24.8 ± 8.9, 7860	0.09 [0.06, 0.12]	0.09 [0.06, 0.12]
Summary			0.09 [0.06, 0.12]	0.09 [0.06, 0.12]
Fixed model heterogeneity: χ² = 0.38, df = 1 (p = 0.54); I² = 0%, test for overall effect: Z = 6.02 (p < 0.00001)
Random model heterogeneity: τ² = 0.00; χ² = 0.21, df = 1 (p = 0.65); I² = 0%; test for overall effect: Z = 6.03 (p < 0.00001)

CI confident interval, AKI acute kidney injury, RRT renal replacement therapy, SD standard difference, SMD standard mean difference