Description of Entire Cohort and Characteristics of the Resuscitation Groups
A total of 333 patients were included (Figure 2). Demographics, comorbidities, injury characteristics, care prior to ICU admission, and outcomes are shown in Table 1. Subjects were typically male, middle-aged, and suffering blunt trauma. Prior to ICU admission, subjects received 2 (0, 6) units of packed red blood cells (PRBCs), 2 (0, 5) units of fresh frozen plasma (FFP), and 0 (0, 1) units of platelets; 37% were taken to the operating room. Whole blood was not available during the study period.
Table 1: Subject Characteristics and Acute ICU Resuscitation
Subject Characteristics
|
Subjects 2016-2019 (n = 333)
|
Age (years)
|
41 (28, 55)
|
Male
|
257 (77%)
|
Obesity
|
92 (28%)
|
Diabetes
|
27 (8%)
|
Smoker
|
68 (20%)
|
CHF
|
7 (2%)
|
CKD
|
0 (0%)
|
Blunt trauma
|
266 (80%)
|
AIS
|
|
Head ≥ 3
|
111 (33%)
|
Chest ≥ 3
|
189 (57%)
|
Abdomen ≥ 3
|
99 (30%)
|
Spine ≥ 3
|
47 (14%)
|
Lower extremity ≥ 3
|
156 (47%)
|
ISS
|
29 (17, 41)
|
Pre-ICU Care
|
|
Transfer
|
73 (22%)
|
Initial lactate (mmol/L)
|
5.8 (4.6, 7.8)
|
RBCs transfused (units)
|
2 (0, 6)
|
FFP transfused (units)
|
2 (0, 5)
|
Platelets transfused (units)
|
0 (0, 1)
|
To OR from ED
|
124 (37%)
|
Acute ICU Resuscitation
|
|
Lactate at ICU admission (mmol/L)
|
4.1 (3, 5.2)
|
Received PRBCs
|
89 (27%)
|
Received FFP
|
69 (21%)
|
Received platelets
|
62 (19%)
|
Operative intervention
|
91 (27%)
|
Vasopressors used
|
85 (26%)
|
Volume of IVF (L)
|
2.2 (1, 4.4)
|
Duration of acute ICU resuscitation (hours)
|
12 (6, 25)
|
Outcomes
|
|
ICU length of stay (days)
|
6 (4, 13)
|
Duration of mechanical ventilation (days)
|
4 (2, 8)
|
ARDS
|
18 (5%)
|
AKI
|
89 (27%)
|
AKI onset from ICU admission (hours)
|
11 (1, 24)
|
Discharge home
|
165 (50%)
|
Deceased
|
40 (12%)
|
The median time to lactate normalization was 12 (6, 25) hours and subjects received a median 2.2 (1, 4.4) L of crystalloid. A total of 1084 resuscitative boluses were given, with hypotension (50%), oliguria without hypotension (31%), and elevated lactate without hypotension (31%) being the most common indications. Approximately one third of subjects were taken to the operating room during this period. The most common reason for operative intervention was extremity fixation (53; 16%), while 26 subjects (8%) underwent operative intervention for new or recurrent hemorrhage. Subjects had a median ICU LOS of 6 (4, 13) days and were mechanically ventilated for 4 (2, 8) days. AKI occurred in 89 subjects (27%) while 40 subjects (12%) died prior to discharge.
Patient characteristics, pre-ICU care, acute ICU resuscitation, and outcomes for the four resuscitation groups are presented in Table 2. Approximately half of the subjects were in the extended resuscitation group (47%), while the remainder were evenly distributed amongst the other three groups. Demographics and comorbidities were similar between all four groups. The extended resuscitation group was more severely injured and received more operative interventions, vasoactive medications, blood products, and crystalloid during acute ICU resuscitation. In contrast, the minimal resuscitation group was less severely injured and required lower rates of operative intervention, infrequent vasopressors, and the least amount of blood products and crystalloid to normalize lactate.
Resuscitation Timing, Crystalloid Volume, and Outcomes
Here, we focus on comparing the early resuscitation group and the late resuscitation group (Table 2). The two groups had similar injury characteristics based upon their AIS and ISS scores. Prior to ICU admission, the late resuscitation group received more blood products; otherwise, the groups were similar. Upon ICU arrival, the two groups had similar blood lactate concentrations. The early resuscitation group reached a normal blood lactate concentration by 9 (6, 19) hours while the late group achieved a normal blood lactate by 13 (5, 25) hours. Blood product and vasopressor use during this period was similar in the two groups.
Table 2: Subject Characteristics, Acute ICU Resuscitation, and Outcomes by Bolus Group
|
Min. Resus. (n = 46)
|
Early Resus. (n = 64)
|
Late Resus. (n = 68)
|
Extended Resus. (n = 155)
|
Patient Characteristics
|
|
|
|
|
Age (years)
|
41 (26, 57)
|
43 (32, 58)
|
38 (27, 54)
|
43 (28, 53)
|
Male
|
36 (78%)
|
49 (77%)
|
51 (75%)
|
121 (78%)
|
AIS
|
|
|
|
|
Head ≥ 3
|
11 (24%)
|
25 (39%)
|
19 (28%)
|
56 (36%)
|
Chest ≥ 3
|
24 (52%)
|
30 (47%)
|
39 (57%)
|
96 (62%)
|
Abdomen ≥ 3
|
6 (13%)
|
12 (19%)
|
23 (34%)
|
58 (37%)
|
Spine ≥ 3
|
4 (9%)
|
8 (12%)
|
10 (15%)
|
25 (16%)
|
Lower extremity ≥ 3
|
15 (33%)
|
25 (39%)
|
37 (54%)
|
79 (51%)
|
Blunt trauma
|
31 (67%)
|
50 (78%)
|
55 (81%)
|
130 (84%)
|
ISS
|
22 (17, 34)
|
24 (17, 35)
|
29 (17, 43)
|
29 (22, 43)
|
Pre-ICU Care
|
|
|
|
|
Transfer
|
10 (22%)
|
12 (19%)
|
20 (29%)
|
31 (20%)
|
Initial lactate (mmol/L)
|
5.3 (4.4, 6.8)
|
5.8 (4.6, 8.5)
|
6.1 (4.8, 7.7)
|
5.9 (4.7, 8)
|
RBCs transfused (units)
|
2 (0, 4)
|
1 (0, 4)
|
3 (0, 7)**
|
3 (0, 6)
|
FFP transfused (units)
|
1.5 (0, 4)
|
1 (0, 3.2)
|
3 (0, 8)**
|
3 (0, 5)
|
Platelets transfused (units)
|
0 (0, 1)
|
0 (0, 0)
|
0 (0, 1)***
|
0 (0, 1)
|
To OR from ED
|
17 (37%)
|
16 (25%)
|
25 (37%)
|
66 (43%)
|
Acute ICU Resuscitation
|
|
|
|
|
Lactate at ICU admission (mmol/L)
|
3.7 (2.4, 4.7)
|
4.2 (3.3, 5.4)
|
3.8 (2.7, 5)
|
4.2 (3.1, 5.4)
|
RBCs transfused (units)
|
0 (0, 0)
|
0 (0, 0.2)
|
0 (0, 1)
|
0 (0, 1)
|
FFP transfused (units)
|
0 (0, 0)
|
0 (0, 0)
|
0 (0, 0)
|
0 (0, 1)
|
Platelets transfused (units)
|
0 (0, 0)
|
0 (0, 0)
|
0 (0, 0.2)
|
0 (0, 0)
|
Operative intervention
|
8 (17%)
|
16 (25%)
|
21 (31%)
|
46 (30%)
|
Vasopressors used
|
5 (11%)
|
10 (16%)
|
16 (24%)
|
54 (35%)
|
Volume of IVF (L)
|
0.6 (0.1, 1.3)
|
1.7 (1.3, 2.6)
|
1.1 (0.3, 2.7)**
|
3.7 (2.1, 6.6)
|
Duration of acute ICU resuscitation (hours)
|
7 (5, 13)
|
9 (6, 19)
|
13 (5, 25)
|
17 (8, 28)
|
Outcomes
|
|
|
|
|
ICU length of stay (days)
|
5 (3, 7)
|
5 (3, 8)
|
9 (5, 18)***
|
7 (4, 14)
|
Duration of mechanical ventilation (days)
|
2 (1, 4)
|
2 (1, 6)
|
5 (3, 11)***
|
5 (2, 10)
|
ARDS
|
1 (2%)
|
2 (3%)
|
5 (7%)
|
10 (6%)
|
AKI
|
5 (11%)
|
7 (11%)
|
26 (38%)***
|
51 (33%)
|
AKI onset from ICU admission (hours)
|
22 (1, 44)
|
16 (11, 34)
|
18 (11, 33)
|
12 (5, 21)
|
Discharge home
|
32 (70%)
|
36 (56%)
|
33 (49%)
|
64 (41%)
|
Deceased
|
2 (4%)
|
7 (11%)
|
7 (10%)
|
24 (15%)
|
Comparing the early resus. group to late resus. group, * indicates p < 0.05, ** indicates p < 0.01,*** indicates p ≤ 0.001
Figure 3 shows the median and IQR of the cumulative volume given over the first 48 hours of ICU admission. At 24 hours, subjects in both groups received similar volumes (3.1 L vs 3.3 L). By 48 hours, subjects in the late group had received more crystalloid than subjects in the early group (5.5 L vs 4.1 L, p ≤ 0.001).
Next, we looked at the indications for initial crystalloid resuscitation and whether they differed between these groups. Subjects in both groups received roughly half of their first boluses in the setting of hypotension: 45% for the early resuscitation group and 47% for the late resuscitation group. Vasopressors dose changes prior to a bolus were rare, occurring in 2% of the early group and 7% of the late group. Outside of hypotension, the early resuscitation group tended to receive boluses in the setting of elevated lactate (60% vs 25%) or upon return to the ICU from the operating room (14% vs 3%) compared with the late resuscitation group. The late resuscitation group received more fluid in the setting of tachycardia (25% vs 6%) or oliguria (53% vs 3%) compared with the early resuscitation group. Crystalloid was rarely given in the setting of biochemical renal dysfunction (0% in the early group vs 6% in the late group).
Subjects in the late resuscitation group had a longer ICU LOS than the early resuscitation group (9 vs 5 days, p ≤ 0.001). After adjusting for important covariates, late resuscitation remained associated with longer ICU LOS (β 6.49, 95% CI [3.11, 9.87], p ≤ 0.001). Similarly, for the secondary outcomes, the late resuscitation group had a longer duration of mechanical ventilation (5 vs 2 days, p ≤ 0.001), and a higher incidence of AKI (38% vs 11%, p ≤ 0.001). After adjusting for covariates, the duration of mechanical ventilation was longer (β 6.02, 95% CI [2.6, 9.44], p ≤ 0.001), and risk of AKI was higher (aOR 7.99, 95% CI [2.56, 25.03], p ≤ 0.001) in the late resuscitation group (Table 3).
Table 3: Regression Analyses
Independent Variable
|
Coeff/OR
|
95% CI
|
p
|
ICU length of stay (days)
|
|
|
|
Chest AIS ≥ 3
|
5.28
|
[1.9, 8.65]
|
0.002
|
RBCs before ICU admission (units)
|
0.34
|
[0.04, 0.63]
|
0.026
|
Vasopressor use during acute ICU resuscitation
|
9.64
|
[0.31, 18.96]
|
0.043
|
Late resus.
|
6.04
|
[2.59, 9.5]
|
≤ 0.001
|
Duration of mechanical ventilation (days)
|
|
|
|
Chest AIS ≥ 3
|
4.19
|
[0.69, 7.69]
|
0.019
|
Late resus.
|
5.56
|
[2.05, 9.06]
|
0.002
|
AKI
|
|
|
|
Age (years)
|
1.04
|
[1.01, 1.07]
|
0.008
|
Initial lactate (mmol/L)
|
1.19
|
[1.07, 1.34]
|
0.002
|
Platelets during acute ICU resuscitation (units)
|
2.23
|
[1.09, 4.53]
|
0.027
|
Late resus.
|
9.58
|
[2.95, 31.19]
|
≤ 0.001
|
Volume during acute ICU resuscitation (L)
|
1.29
|
[1.03, 1.63]
|
0.03
|
For our two sensitivity analyses in which we replaced crystalloid volume during acute ICU resuscitation as an independent variable with either volume or boluses over the first 48 hours of ICU admission, we found delayed resuscitation remained associated with longer ICU LOS, increased duration of mechanical ventilation, and higher risk of AKI. Similarly, when transfer patients were excluded from our regression models, we continued to see an association between late resuscitation and longer ICU LOS, increased duration of mechanical ventilation, and higher risk of AKI. The results of our sensitivity analyses are provided in the supplementary material.