Anisodamine hydrobromide in the treatment of critically ill patients with septic shock: a multicenter randomized controlled trial

Figures & data

Figure 1. CONSORT flowchart of patient recruitment.

Table 1. Baseline characteristics in the treated and control groups.

Variable	Total ($n=404$)	Treated ($n=203$)	Control ($n=201$)	p-value
Age (years, $\overline{x}\pm s$)	$58.75\pm 11.31$	$59.19\pm 10.56$	$58.31\pm 12.03$	0.436
Male ($\#$ of cases (%))	255 (63.12%)	128 (63.05%)	127 (63.18%)	0.978
BMI ($kg/m^2,\overline{x}\pm s$)	$22.95\pm 3.50$	$22.83\pm 3.51$	$23.07\pm 3.49$	0.492
Comorbidity ($\#$ of cases (%))				0.174
Hypertension	117 (27.34%)	54 (25.71%)	63 (28.90%)
Diabetes	101 (23.60%)	51 (24.29%)	50 (22.94%)
Coronary heart disease	33 (7.71%)	23 (10.95%)	10 (4.60%)
Cerebral infarction	37 (8.64%)	15 (7.14%)	22 (10.09%)
COPD	13 (3.04%)	9 (4.30%)	4 (1.83%)
Hyperlipidemia	121 (28.27%)	56 (26.67%)	65 (29.82%)
Malignancy	3(0.70%)	1 (0.48%)	2 (0.92%)
Renal failure	3 (0.70%)	1 (0.48%)	2 (0.92%)
Source of admission ($\#$ of cases (%))				0.072
Emergency room	240 (59.41%)	111 (54.68%)	129 (64.18%)
Intensive care unit	58 (14.36%)	38 (18.72%)	20 (9.95%)
Ward	83 (20.54%)	42 (20.69%)	41 (20.40%)
Transfer from other hospitals	23 (5.69%)	12 (5.91%)	11 (5.47%)
Infection sites ($\#$ of cases (%))				0.231
Respiratory system	207 (51.24%)	110 (54.19%)	97 (48.26%)
Urinary system	74 (18.32%)	40 (19.70%)	34 (16.92%)
CNS	11 (2.72%)	2 (0.99%)	9 (4.48%)
Digestive system	100 (24.75%)	44 (21.67%)	56 (27.86%)
Bloodstream	3 (0.74%)	2 (0.99%)	1 (0.50%)
Skin	31 (7.67%)	17 (8.37%)	14 (6.97%)
Unknown	3 (0.74%)	2 (0.99%)	1 (0.50%)
Vital signs at enrollment
Temperature (${}^{°}C,\overline{x}\pm s$)	$37.56\pm 1.10$	$37.54\pm 1.08$	$37.58\pm 1.12$	0.694
Heart rate ($\text{beats/min},\overline{x}\pm s$)	$114.15\pm 17.55$	$114.17\pm 16.85$	$114.12\pm 18.28$	0.969
Respiration rate ($\text{breaths/min},\overline{x}\pm s$)	$27.24\pm 7.38$	$27.37\pm 7.65$	$27.10\pm 7.10$	0.709
MAP ($\text{mmHg},\overline{x}\pm s$)	$59.18\pm 3.93$	$59.28\pm 3.88$	$59.08\pm 3.98$	0.601
SpO2 ($\%,\overline{x}\pm s$)	$91.88\pm 7.29$	$92.20\pm 7.30$	$91.56\pm 7.29$	0.382
Lactate ($\text{mmol/L},\overline{x}\pm s$)	$6.06\pm 2.79$	$6.14\pm 2.82$	$5.98\pm 2.77$	0.558
PCT (ng/mL, M ($P_{25},P_{75}$))	25.86 (2.31, 94.27)	22.51 (2.33, 81.95)	29.51 (2.20, 100.00)	0.619
WBC ($\times {10}^9/L,\overline{x}\pm s$)	$19.50\pm 9.49$	$19.63\pm 9.21$	$19.36\pm 9.79$	0.767
PLT ($\times {10}^9/L,\overline{x}\pm s$)	$161.93\pm 110.71$	$166.02\pm 116.11$	$157.81\pm 105.11$	0.456
HCT ($\%,\overline{x}\pm s$)	$34.28\pm 7.75$	$34.53\pm 7.40$	$34.03\pm 8.09$	0.513
SOFA score ($\overline{x}\pm s$)	$9.64\pm 4.07$	$9.54\pm 3.86$	$9.73\pm 4.28$	0.640
APACHE II score ($\overline{x}\pm s$)	$18.48\pm 6.41$	$18.39\pm 6.42$	$18.57\pm 6.41$	0.780
GCS ($\overline{x}\pm s$)	$8.33\pm 3.14$	$8.32\pm 3.26$	$8.35\pm 3.02$	0.903

BMI body mass index, COPD chronic obstructive pulmonary disease, CNS central nervous system, MAP mean arterial pressure, SpO₂ peripheral capillary oxygen saturation, PCT procalcitonin, WBC white blood cell, PLT platelet, HCT hematocrit, SOFA sequential organ failure assessment, APACHE acute physiology and chronic health evaluation, GCS Glasgow coma scale, CRRT continuous renal replacement therapy.

Figure 2. Kaplan-Meier estimates of the probability of survival to day 28. The p value for the log-rank test is 0.026.

Table 2. Stratified analysis of 28-day mortality.

		Variables	Total	Treated	Control	p-value
SOFA	$<8$	# of patients	125	64	61	0.558
		28-day mortality, n (%)	24 (19.2)	11 (17.2)	13 (21.3)
	$\ge 8$	# of patients	279	139	140	0.038*
		28-day mortality, n (%)	101 (36.2)	42 (30.2)	59 (42.1)
Lactate	(2,4)	# of patients	102	46	56	0.780
		28-day mortality, n (%)	28 (27.5)	12 (26.1)	16 (28.6)
	$\ge 4$	# of patients	302	157	145	0.020*
		28-day mortality, n (%)	97 (32.1)	41 (26.1)	56 (38.6)

* $p<0.05$ means the difference is statistically significant.

Table 3. Comparison of secondary clinical outcomes between the treated and control groups.

Variables	Total ($n=404$)	Treated ($n=203$)	Control ($n=201$)	p-value
7-day mortality, n(%)	41 (10.15)	14 (6.90)	27 (13.43)	0.030*
Hospital mortality, n(%)	108 (26.73)	43 (21.18)	65 (32.34)	0.011*
Hospital LOS, median (Q1, Q3)	9 (7, 12)	10 (7, 13)	9 (6, 12)	0.068
Vasopressor free days in 7 days, median (Q1, Q3)	5 (0, 6)	5.5 (1, 6)	4 (0, 5.5)	0.001*

* $p<0.05$ means the difference is statistically significant. LOS length of stay.

Figure 3. Comparisons of secondary outcomes between the treated and control groups. The error bar in (a)-(e) indicates the standard deviations. The box plots in (f) and (g) show the median, P25 and P75 (whiskers are at P5 and P95).

Table 4. Characteristics of the four adverse events in the treated group.

Symptoms	Total dosage (mg)	Pumping speed (mg/kg/h)	Age	BMI ($kg/m^2$)	Gender
Tachycardia	900	0.096	53	24.49	M
Tachycardia	820	0.084	63	18.31	F
Distended abdomen	800	0.046	56	25.71	M
Urine retention	500	0.065	58	19.15	M.

Availability of data and materials

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