Out of 183 patients with septic shock referring to ED during the study period, 109 (59.56%) completed the study, and their data were analyzed (Fig. 2). The mean age of the 109 patients was 67.62 ± 14.67 years, and 65 (59.1%) were males. Besides, 41 (37.3%) subjects died, and the mean scores of the subjects in APACHE II and SAPS were 23.46 ± 21.76 and 50.54 ± 21.76, respectively, which had a significant difference between non-survival and survival groups. In addition, 34 (30.9%) subjects had urinary tract infections, 48 (43.6%) respiratory infections, 13 (11.8%) abdominal infections, and 14 (12.7%) other causes of septic shock, of which the prevalence of urinary tract infections was significantly higher in those who died. Moreover, 54 (49.1%) subjects had diabetes (DM), 26 (23.6) chronic obstructive disease (COPD), 44 (40%) cancer, 28 (25.5%) were smoker, 33 (30%) had hypertension (HTN), and six (5.5%) used corticosteroids. The prevalence of underlying diseases, such as diabetes, cancer, and hypertension, were significantly higher in the non-survival group. Totally, 46 (42.2%) patients underwent mechanical ventilation, the majority belong to the non-survival group; 43 (39.45%) subjects underwent packed-cell infusion during the study period. The mean MAP of patients on arrival and six hours after the treatment onset was 73.05 ± 8.84 and 15.23 ± 93.67, respectively, which had a significant increase over time (P-value = 0.00). Systolic blood pressure increased from 80.82 ± 12.63 on arrival to 107.75 ± 17.62 mmHg during the treatment (P-value = 0.01), and their heart rate had no significant changes over time (115.18 ± 11.3 on arrival versus 95.21 ± 8.62 beat/minute after six hours of treatment onset) (P-value = 0.63). RRI increased from 0.71 ± 0.03 on arrival to 0.70 ± 0.1 after six hours of treatment onset (P-value = 0.05); RRI value was significantly higher in the non-survival group until the 30 minutes of treatment onset, compared to survivals (Table 1).
Table 1
Characteristics of the Study Participants
Variable
|
Total
|
(95%confidenc interval)
|
P-value
|
Survived (n = 75)
|
Non-survived (n = 75)
|
Gender
|
Male
|
41(37.6%)
|
24(22%)
|
(0.9997–1)
|
1.000
|
Female
|
27(24.8%)
|
17(15.6%)
|
Age, yr.
|
66.29(14.6)
|
69.83(14.704)
|
(-9.273 - 2.203)
|
0.225
|
SAPS IIa, mean (SD)
|
47.26(23.40)
|
55.97(17.70)
|
(-17.12–0.30)
|
0.042
|
APACHE IIb, mean (SD)
|
21.53(9.79)
|
26.68(11.16)
|
(-9.20 -1.11)
|
0.013
|
Origin of sepsis
|
Urinary, n (%)
|
16(23.5)
|
18(43.9)
|
(1.10–5.85)
|
0.026
|
Respiratory, n (%)
|
34(50.7)
|
14(34.1)
|
(0.225–1.12)
|
0.092
|
Abdominal, n (%)
|
8(11.8)
|
5(12.2)
|
(0.32–3.43)
|
0.946
|
Other, n (%)
|
10(14.7)
|
4(9.8)
|
(0.18–2.15)
|
0.454
|
Past medical history
|
Diabetes, n (%)
|
28(41.2)
|
26(63.4)
|
(1.11–5.50)
|
0.024
|
Chronic obstructive disease, n (%)
|
13(19.1)
|
13(31.7)
|
(0.80–4.80)
|
0.135
|
Cancer, n (%)
|
11(16.2)
|
33(80.5)
|
(7.18–58.49)
|
0.000
|
Tobacco use, n (%)
|
14(20.6)
|
14(34.1)
|
(0.83–4.79)
|
0.117
|
Hypertension, n (%)
|
16(23.5)
|
17(41.5)
|
(1.00 -5.31)
|
0.048
|
Corticosteroids use, n (%)
|
2(2.9)
|
4(9.8)
|
(0.62–20.42)
|
0.131
|
Patients requiring mechanical ventilation
|
16(14.7%)
|
30(27.5%)
|
(0.000–0.000)
|
0.000
|
Patients undergoing blood transfusion
|
23(21.1%)
|
20(18.3%)
|
(0.156–0.170)
|
0.163
|
mean SBP, mmHg
|
97.088 (8.011)
|
87.445(12.436)
|
(5.762–13.523)
|
0.000
|
SBP on arrival, mmHg
|
83.79(9.412)
|
75.88(15.576)
|
(3.177–12.655)
|
0.001
|
SBP at 30 min, mmHg
|
89.56(9.763)
|
84.15(10.66)
|
(1.451–9.374)
|
0.008
|
SBP at 120 min, mmHg
|
101.62(8.913)
|
91.34(18.132)
|
(5.126–15.427)
|
0.000
|
SBP after 6 h, mmHg
|
113.38(7.891)
|
98.41(24.301)
|
(7.085–22.85)
|
0.000
|
Mean MAP
|
85.433(6.663)
|
77.896(10.995)
|
(4.188–10.886)
|
0.000
|
MAP on arrival
|
75.191(7.827)
|
69.512(9.375)
|
(2.371–8.987)
|
0.001
|
MAP at 30 min
|
79.176(8.343)
|
74.683(9.078)
|
(1.112–7.874)
|
0.010
|
MAP at 120 min
|
89.353(7.521)
|
80.927(15.685)
|
(4.002–12.85)
|
0.000
|
MAP after 6 h
|
98.015(6.888)
|
86.463(21.479)
|
(4.588–18.513)
|
0.002
|
Mean PR
|
100. 180(8.244)
|
102.006(12.391)
|
(-6.181–2.528)
|
0.405
|
PR on arrival
|
114.44(11.327)
|
116.41(11.28)
|
(-6.407–2.46)
|
0.379
|
PR at 30 min
|
104.56(8.773)
|
105.44(17.641)
|
(-5.908–4.147)
|
0.729
|
PR at 120 min
|
94.6(7.249)
|
97.78(18.85)
|
(-9.357–3.002)
|
0.306
|
PR after 6 h
|
87.12(12.311)
|
88.39(22.065)
|
(-8.798–6.253)
|
0.736
|
Mean RRI
|
0.693(0.025)
|
0.718(0.063)
|
(-0.041–0.007)
|
0.006
|
RRI on arrival
|
0.699(0.020)
|
0.733(0.024)
|
(-0.041–0.024)
|
0.000
|
RRI at 30 min
|
0.699(0.021)
|
0.732(0.023)
|
(-0.042–0.025)
|
0.000
|
RRI at 120 min
|
0.683(0.086)
|
0.712(0.116)
|
(-0.068–0.009)
|
0.141
|
RRI after 6 h
|
0.692(0.024)
|
0.694(0.161)
|
(-0.053–0.049)
|
0.936
|
a SAPS: Simplified Acute Physiology Score |
b APACHE II: Acute Physiology and Chronic Health Evaluation II; IQR: interquartile range; |
Treatment was based on the early goal-directed resuscitation (13), and the treatment goal was set to MAP ≥ 65mmHg and CVP ≥ 8mmHg; RRI was determined accordingly at different time points (Fig. 3).
There was no significant difference in RRI values between the two groups on arrival and 30 minutes and six hours after treatment onset. For a more detailed evaluation, the Mann-Whitney nonparametric test was used, in which the P-value of 0.413 indicated the same mean RRI on arrival and P-value = 0.172 for RRI30, P-value = 0.405 for RRI6h. But in the second hour of treatment, a significant difference was found between RRI120 values (P-value = 0.05). RRI values were generally compared in Fig. 4.
To compare RRI levels at different time points, the Friedman nonparametric test (given that the normality of the data was rejected) was used. The mean RRI rank at different time points is given in Table 2.
Table 2
Patients’ RRI during the study
|
Mean (SD)
|
Mean Rank
|
P-value
|
RRI0
|
0.7124(0.27)
|
2.88
|
0.00
|
RRI30
|
0.7119(0.27)
|
2.86
|
RRI120
|
0.6948(0.1)
|
2.30
|
RRI6h
|
0.6931(0.1)
|
1.97
|
a. Fridman test |
The mean rating value decreased overtime from 0 minutes to six hours. In other words, the RRI level decreased over time. There was a significant difference among RRI levels at four time points (0, 30, and 120 minutes, as well as six hours). The Wilcoxon post hoc test was utilized to examine RRI level variability across time points, the results are shown in Table 3.
Table 3. RRI Changes at Different Time Points
RRI6h-RRI120
|
RRI6h-RRI30
|
RR120-RRI30
|
RR6h-RRI0
|
RRI120-RRI0
|
RRI30-RRI0
|
|
.013
|
.000
|
.000
|
.000
|
.000
|
.305
|
P-value
|
a. Wilcoxon signed ranks test
To calculate the significance level, the Bonferroni correction was used as\(\frac{0.05}{6}=0.008\). Therefore, in Table 3, differences between the groups with a P-value of < 0.008 were considered significant. Therefore, there was a significant difference in RRI levels between the time points of (0 and 120), (0 and six hours), (30 and 120 minutes), (30 minutes and six hours), which the RRI level decreased at 120 minutes compared to zero minutes, at six hours compared to zero minutes, at 120 minutes compared to 30 minutes, and at six hours compared to 30 minutes. Using logistic regression, the Omnibus tests of model coefficients showed that RRI had no significant effect on achieving the treatment goal of MAP ≥ 65 mmHg and CVP ≥ 8 mmHg and P-values were 0.54 on arrival, 0.26 at 30 minutes, 0.40 at 120 minutes, and 0.54 after six hours.