In 7 years, 301 patients met our inclusion criteria for the study (Figure 1, Table 1). Of the patients included, 152 (50.5%) were male, had a median age of 55 (IQR 41-69) years and had a BMI of 29.1 (24.2-36.9) kg/m2. Median preoperative vital signs included a mean arterial pressure of 86.5 mmHg (74-98.5), systolic blood pressure of 121 mmHg (106-137), heart rate of 97 beats/min (84-114), respiratory rate of 18 breaths/min (16-23), and a temperature of 98.4 °F (98.1-99.3). Median preoperative lab values included lactate 1.8 mmol/L (1.3-2.9), creatinine 1.1 mg/dL (0.8-1.8), platelet 230 x103/mcL (158-311), bilirubin 0.9 mg/dL (0.6-1.5), and a PaO2 130 mmHg (95-175). These patients presented with median SOFA scores of 2 (0-8), and qSOFA scores of 1 (0-2).
The cohort received a median pre-operative fluid resuscitation volume of 19.0 ml/kg (9.3-35.3), and 85 (28%) required pre-operative vasopressor use. All required an urgent operation, within 24 hours, with a median time to the OR of 5.8 hours (3.3-12.6). Post operatively, these patients experienced average ventilator days of 2 (0-7), intensive care length of stay of 3 d (0-12), and total hospital length of stay 9 d (3-20). Overall mortality was 14.6% (44 patients).
Table 1: Demographics, Vitals, Laboratory Values, Scoring systems, interventions and outcomes.
Variable
|
Median
|
Lower Quartile
|
Upper Quartile
|
Age (yr)
|
55
|
41
|
69
|
BMI (kg/m2)
|
29.1
|
24.2
|
36.9
|
HR (beats/min)
|
97
|
84
|
114
|
MAP (mmHg)
|
86.5
|
74
|
98.5
|
SBP (mmHg)
|
121
|
106
|
137
|
RR (breath/min)
|
18
|
16
|
23
|
Temp (°F)
|
98.4
|
98.1
|
99.3
|
FiO2 (%)
|
40
|
40
|
50
|
Bili (mg/dL)
|
0.9
|
0.6
|
1.5
|
Creatinine (mg/dL)
|
1.1
|
0.8
|
1.8
|
Lactate (mmol/L)
|
1.8
|
1.3
|
2.9
|
Plt (x103/mcL)
|
230
|
158
|
311
|
PaO2 (mkmHg)
|
130
|
95
|
175
|
SOFA
|
2
|
0
|
8
|
qSOFA
|
1
|
0
|
2
|
Time to OR (hour)
|
5.8
|
3.3
|
12.6
|
Fluids/Kg (mL/Kg)
|
19.0
|
9.3
|
35.3
|
Ventilator Days
|
2
|
0
|
7
|
ICU LOS (day)
|
3
|
0
|
12
|
LOS (day)
|
9
|
3
|
20
|
BMI – body mass index, MAP – mean arterial pressure, SBP – systolic blood pressure, FiO2 – fractional inspired oxygen, PaO2 – partial pressure of oxygen, SOFA – sequential organ failure assessment score, qSOFA – quick sequential organ failure assessment score.
Patients were grouped based upon pre-operative fluid volume in 10 mL/kg groups, up to greater or equal than 70 mL/kg (Figure 2). For fluid resuscitation, 80 patients (27%) received less than 10 mL/kg, 72 (24%) received 10-<20 mL/kg, 51 (17%) received 20-<30mL/kg, 36 (12%) received 30-<40 mL/kg, 20 (7%) received 40-<50 mL/kg, 10 (3%) received 50-<60mL/kg, 13 (4%) received 60-<70mL/kg, and 19 (6%) received greater than or equal to 70 mL/kg. Chi-square analysis indicated a significant trend of increasing mortality as fluids per kg increased, p=0.004. Percent mortality and totals in each group is demonstrated by table 2.
Figure 2: Percent Mortality with increasing 10ml/kg fluid resuscitation.
Table 2: Percent Mortality with increasing 10ml/kg fluid resuscitation
Fluids per Kg by Mortality
|
Fluid per Kg
|
Survived
|
Died
|
Total
|
< 10 mL/kg
|
73 (91.3%)
|
7 (8.8%)
|
80
|
10-<20 mL/kg
|
62 (86.1%)
|
10 (13.9%)
|
72
|
20-<30 mL/kg
|
45 (88.2%)
|
6 (11.8%)
|
51
|
30-<40 mL/kg
|
29 (80.6%)
|
7 (19.4%)
|
36
|
40-<50 mL/kg
|
18 (90.0%)
|
2 (10.0%)
|
20
|
50-<60 mL/kg
|
9 (90.0%)
|
1 (10.0%)
|
10
|
60-<70 mL/kg
|
8 (61.5%)
|
5 (38.5%)
|
13
|
70+ mL/kg
|
13 (68.4%)
|
6 (31.6%)
|
19
|
Total
|
257
|
44
|
301
|
|
Statistic
|
DF
|
Value
|
Prob
|
Mantel-Haenszel Chi-Square
|
1
|
8.4864
|
0.0036
|
There was no significant correlation between time to operative source control and mortality (p=0.08, Figure 3)
Figure 3: Mortality with Time to Operative Source Control
Patients were additionally grouped into less than and greater than or equal to 30 mL/kg of fluid resuscitation. There were 203 patients (67%) who received less than 30 mL/kg of fluid, and 98 patients (33%) who received greater than or equal to 30 mL/kg (Table 3). These patient groups were similar in age and gender. Each group had similar presenting heart rates, medians 96 and 101 (p=0.21), however, had significant differences in mean arterial pressure, 88 mmHg vs 82 mmHg (p<0.001), SBP, 124 mmHg vs 113 mmHg (p=0.001) and initial lactate, 1.8 vs 2.3 (p=0.002). These groups scored similar on qSOFA, 1 vs 1 (p=0.06). The patients in the <30mL/kg group received significantly less fluid, with median fluid/kg 12.9 vs 46.9 (p<0.001). Despite more resuscitation, patients ≥30mL/kg more frequently required vasopressors 37% vs 24% (p=0.02).
Mortality was significantly lower in patients who received less fluid, 11% vs 21% (p=0.02). Median Ventilatory days (1 vs 3), ICU LOS (2 vs 4) and hospital LOS (8 vs 9) were all lower with fewer fluids, however the differences were not statistically significant.
Table 3: < 30 mL/kg vs ≥ 30 mL/kg. Reported as standard deviations unless otherwise stated.
|
<30ml/kg
(n=203)
|
≥30ml/kg
(n=98)
|
|
|
Median (IQR)
|
Median (IQR)
|
p-value
|
Age
|
55 (41-68)
|
56 (44-71)
|
0.46
|
Male, n (%)
|
106 (52%)
|
46 (47%)
|
0.39
|
HR
|
96 (82-112)
|
101 (85-118)
|
0.21
|
MAP
|
88 (75-102)
|
82 (70-93)
|
<0.001
|
SBP
|
124 (109-140)
|
113 (102-129)
|
0.001
|
Lactate (n=166/81)
|
1.8 (1.2-2.6)
|
2.3 (1.5-4.4)
|
0.002
|
Total Fluids
|
12.9 (4.7-20.0)
|
46.9 (37.8-64.7)
|
<0.001
|
Preoperative Vasopressor
|
49 (24%)
|
36 (37%)
|
0.02
|
Time to OR (Hours)
|
6.1 (3.5-12.2)
|
4.9 (2.7-13.1)
|
0.11
|
Sofa
|
2 (0-7)
|
3 (1-10)
|
0.05
|
qSOFA
|
1 (0-1)
|
1 (0-2)
|
0.06
|
LOS (d)
|
8 (3-19)
|
9 (3-23)
|
0.57
|
ICU LOS (d)
|
2 (0-11)
|
4 (0-13)
|
0.22
|
Ventilator Days
|
1 (0-6)
|
3 (0-7)
|
0.08
|
Mortality
|
23 (11%)
|
21 (21%)
|
0.02
|
Further analyses compared patients who survived versus non-survivors (table 4). Survivors had a significantly lower average age 53 vs 65 (p<0.001) and presented with lower SOFA 2.0 vs 10.5, (p<0.001) and qSOFA (1.0 vs 2.0, p<0.001) scores. Survivors presented with better vital signs, including higher MAP (90 mmHg vs 72 mmHg, p<0.001), lower heart rates (96 bpm vs 105 bpm, p=0.02) and a lower respiratory rate (18 vs 22 breaths per minute, p=0.005). Survivors had better baseline physiology and renal function with a lower lactate (1.7 vs 3.2 mmol/L, p<0.001) and creatinine (1.0 vs 2.0 mg/dl, p<0.001). Patients who survived required on average lower volumes of fluid per kilogram (17.8 vs 27.4 mL/kg, p=0.007) and only 21% of survivors compared with 68% of non-survivors required pre-operative vasopressors (p<0.001). Lastly, non-survivors tended to have operative source control quicker than survivors (4.1 hours vs 6.2 hours, p=0.06).
Table 4: Comparison of variables of survivors vs non-survivors, expressed as medians and interquartile range, except otherwise noted.
Survivors vs Non-Survivors
|
|
Survived (n=257)
|
Died (n=44)
|
p-value
|
Demographics
|
Age (years)
|
53 (38-67)
|
65 (58-72)
|
<0.001
|
Vitals
|
HR (beats/minute)
|
96 (83-112)
|
105 (93-122)
|
0.02
|
MAP (mmHg)
|
90 (76-101)
|
72 (66-79)
|
<0.001
|
SBP (mmHg)
|
123 (109-139)
|
106 (91-116)
|
<0.001
|
RR (breaths/minute)
|
18 (16-22)
|
22 (18-29)
|
0.005
|
Temp (°F)
|
98.4 (98.1-99.3)
|
98.1 (96.6-99.9)
|
0.24
|
Laboratory Values
|
Bilirubin (mg/dL)
|
0.9 (0.6-1.4)
|
1.5 (1.1-2.5)
|
<0.001
|
Creatinine (mg/dL)
|
1.0 (0.8-1.4)
|
2.0 (1.4-3.2)
|
<0.001
|
Lactate(mmol/L)
|
1.7 (1.2-2.6)
|
3.2 (1.8-6.9)
|
<0.001
|
Platelet (x103/mcL)
|
240 (175-314)
|
167 (97-283)
|
0.001
|
Scoring Systems
|
SOFA
|
2.0 (0-6)
|
10.5(6-14)
|
<0.001
|
qSOFA
|
1.0 (0-1)
|
2.0 (1-3)
|
<0.001
|
Interventions
|
Pre-op Vasopressor
|
55 (21%)
|
30 (68%)
|
<0.001
|
Time to OR (hours)
|
6.2 (3.3-13.0)
|
4.1 (3.3-7.6)
|
0.06
|
Fluids per Kg (mL/kg)
|
17.8 (8.6-32.7)
|
27.4 (14.3-59.6)
|
0.007
|
A regression model measuring the unadjusted effect of binary fluid level on mortality on the cohort of 301 patients (Table 5) indicated that patients treated with 30 or more mL/kg were 1.89 times as likely to die than those treated with fluids below 30 mL/kg (95% CI 1.10-3.25, p=0.02). Upon adjustment by covariates (age, MAP, SBP, heart rate, lactate, creatinine and SOFA score), the amount of fluid administered was no longer statistically significant (p=0.59). Significant risk factors for mortality in the adjusted model included increasing age (p=0.001), increasing lactate (p<0.001), and increasing SOFA (p<0.001) levels. The inclusion of lactate in the latter model reduced the patient sample size in the model to 247. In a separate model without lactate (N=299), increasing age and SOFA remained as the only statistically significant risk factors for death.
Table 5: Relative risk regression model for mortality for those treated with <30 or ≥30 ml/kg, and adjusted for covariate risk factors.
Relative Risks for Risk Factors of Mortality
Effect of Fluid Volume 30+ ml/kg vs. < 30 ml/kg
|
|
|
95% CI for RR
|
|
Unadjusted Model (N=301)
|
RR
|
Lower
|
Upper
|
p-value
|
30+ ml/kg vs. < 30 ml/kg
|
1.89
|
1.10
|
3.25
|
0.02
|
|
|
95% CI for RR
|
|
Adjusted Model (N=247)
|
RR
|
Lower
|
Upper
|
p-value
|
30+ ml/kg vs. < 30 ml/kg
|
1.15
|
0.69
|
1.92
|
0.59
|
Age (years)
|
1.03
|
1.01
|
1.05
|
0.001
|
MAP (mmHg)
|
0.99
|
0.97
|
1.02
|
0.63
|
SBP (mmHg)
|
1.00
|
0.98
|
1.02
|
0.77
|
Heart rate (beats/minute)
|
1.01
|
1.00
|
1.02
|
0.20
|
Lactate (mmol/L)
|
1.09
|
1.05
|
1.14
|
<0.001
|
Creatinine (mg/dL
|
1.00
|
0.86
|
1.17
|
0.95
|
SOFA
|
1.13
|
1.07
|
1.19
|
<0.001
|
Similar results were found when analyzing the effect of increasing volume by 10 ml/kg intervals on mortality (Table 6). An unadjusted model indicated that mortality risk significantly increased by 14% for every 10 mL/kg increase in fluid volume (RR=1.14, 95% CI 1.07-1.21, p<0.001). Fluid volume was no longer significant (p=0.78) when adjusted by the covariates listed above, replaced by increasing age (p=0.002), lactate (p<0.001) and SOFA (p<0.001) levels as significant risk factors in a model with lactate and by increasing age and SOFA in a separate model without lactate.
Table 6: Relative risk regression model for mortality for those treated with increasing amounts of fluid by 10mL/kg and adjusted for covariate risk factors.
Relative Risks for Risk Factors of Mortality
Effect of Fluid Volume in Increasing 10 ml/kg Intervals
|
|
|
95% CI for RR
|
|
Unadjusted Model (N=301)
|
RR
|
Lower
|
Upper
|
p-value
|
10 ml/kg Increase in Fluid Volume
|
1.14
|
1.07
|
1.21
|
<0.001
|
|
|
95% CI for RR
|
|
Adjusted Model (N=247)
|
RR
|
Lower
|
Upper
|
p-value
|
10 ml/kg Increase in Fluid Volume
|
1.01
|
0.93
|
1.10
|
0.78
|
Age (years)
|
1.03
|
1.01
|
1.05
|
0.002
|
MAP (mmHg)
|
0.99
|
0.97
|
1.02
|
0.65
|
SBP (mmHg)
|
1.00
|
0.98
|
1.02
|
0.74
|
Heart rate (beats/minute)
|
1.01
|
1.00
|
1.02
|
0.20
|
Lactate (mmol/L)
|
1.10
|
1.05
|
1.15
|
<0.001
|
Creatinine (mg/dL
|
1.02
|
0.88
|
1.17
|
0.83
|
SOFA
|
1.12
|
1.07
|
1.19
|
<0.001
|