Table 2. Hospital Course and Outcomesa in a Study of the Effect of Tranexamic Acid vs Placebo on Neurologic Outcomes in Patients With Traumatic Brain Injury.
| Outcome | Treatment group, No. (%) | ||
|---|---|---|---|
| Bolus maintenance (n = 312) | Bolus only (n = 345) | Placebo (n = 309) | |
| Fluids through 24 h | |||
| Median out-of-hospital and in-hospital crystalloid, median (IQR), L | 3.2 (1.9-5.1) | 3.5 (2.3-5.1) | 3.5 (2.2-5.1) |
| Any blood products administered | 65 (21) | 56 (16) | 72 (23) |
| Volume of blood products among patients with some blood products administered, median (IQR), L | 1.3 (0.6-2.2) | 0.8 (0.5-2.1) | 1.4 (0.6-2.4) |
| Any red blood cells administered | 54 (17) | 44 (13) | 62 (20) |
| Red blood cells among patients with some administered, median (IQR), U | 3.0 (2.0-4.5) | 2.0 (0.9-4.0) | 3.0 (1.4-4.8) |
| Outcome from admission blood draw | |||
| Percentage of clot lysed at 30 min following maximum amplitude, %b | (n = 246) | (n = 261) | (n = 240) |
| <0.8 (fibrinolysis shutdown) | 157 (64) | 165 (63) | 148 (62) |
| 0.8-3.0 (normal) | 61 (25) | 65 (25) | 56 (23) |
| >3.0 (hyperfibrinolysis) | 28 (11) | 3 (12) | 36 (15) |
| Outcomes from initial head computed tomographic imaging | |||
| Marshall Classificationc | (n = 290) | (n = 332) | (n = 291) |
| Diffuse injury I | 115 (40) | 134 (40) | 120 (41) |
| Diffuse injury II | 117 (40) | 135 (41) | 106 (36) |
| Diffuse injury III | 12 (4) | 12 (4) | 12 (4) |
| Diffuse injury IV | 4 (1) | 5 (2) | 7 (2) |
| Diffuse injury V/VI | 42 (14) | 46 (14) | 46 (16) |
| Rotterdam Scored | (n = 161) | (n = 187) | (n = 158) |
| 1 | 1 (1) | 5 (3) | 2 (1) |
| 2 | 28 (17) | 36 (19) | 32 (20) |
| 3 | 91 (57) | 98 (52) | 81 (51) |
| 4 | 24 (15) | 28 (15) | 17 (11) |
| 5 | 12 (7) | 17 (9) | 21 (13) |
| 6 | 5 (3) | 3 (2) | 5 (3) |
| Hospital discharge outcomes | (n = 294) | (n = 329) | (n = 292) |
| Glasgow Outcome Scale-Extended score >4e | 101 (34) | 101 (31) | 96 (33) |
| Disability Rating Scalef | (n = 294) | (n = 329) | (n = 291) |
| 0-1 (none to mild disability) | 84 (29) | 89 (27) | 90 (31) |
| 2-6 (partial to moderate) | 92 (31) | 122 (37) | 92 (32) |
| 7-11 (moderately severe) | 37 (13) | 41 (12) | 33 (11) |
| 12-21 (severe to extremely severe) | 23 (8) | 26 (8) | 17 (6) |
| >21 (vegetative to death) | 58 (20) | 51 (16) | 59 (20) |
| Mortality | 53 (18) (n = 294) | 39 (12) (n = 331) | 51 (17) (n = 295) |
| 28-d outcomes | |||
| Neurological procedures, No. (%)g | |||
| Any neurological intervention | 62 (20) | 75 (22) | 54 (17) |
| Craniotomy or craniectomy | 27 (9) | 39 (11) | 27 (9) |
| Intracranial pressure monitoring | 48 (15) | 55 (16) | 48 (16) |
| Adverse events, No. (%)h | |||
| Seizure or seizure-like activity | 5 (2) | 17 (5) | 7 (2) |
| Any thromboembolic event | 13 (4) | 31 (9) | 30 (10) |
| Myocardial infarction | 3 (1) | 2 (1) | 1 (<1) |
| Pulmonary embolism | 3 (1) | 6 (2) | 5 (2) |
| Thrombotic stroke | 3 (1) | 13 (4) | 10 (3) |
| Deep vein thrombosis | 3 (1) | 10 (3) | 9 (3) |
| Other thromboembolic eventi | 1 (<1) | 13 (4) | 9 (3) |
| Hospital-free days, mean (SD)j | 13.6 (10.7) | 14.1 (10.4) | 13.6 (10.7) |
| Intensive care unit–free days, mean (SD)k | 18.1 (10.8) | 19.1 (9.7) | 18.5 (10.6) |
| Ventilator-free days, mean (SD)l | 19.9 (10.8) | 20.9 (9.7) | 20.2 (10.5) |
| Mortality | 53 (19) (n = 285) | 40 (13) (n = 318) | 50 (18) (n = 285) |
| 6-mo outcomesm | |||
| Glasgow Outcome Scale-Extended score >4e | 153 (58) (n = 262) | 178 (62) (n = 289) | 163 (60) (n = 272) |
| Disability Rating Scale scoref | (n = 261) | (n = 287) | (n = 266) |
| 0-1 (none to mild disability) | 123 (47) | 143 (50) | 134 (50) |
| 2-6 (partial to moderate disability) | 64 (25) | 79 (28) | 53 (20) |
| 7-11 (moderately severe disability) | 12 (5) | 10 (3) | 12 (5) |
| 12-21 (severe to extremely severe disability) | 6 (2) | 6 (2) | 11 (4) |
| >21 (vegetative to death) | 56 (21) | 49 (17) | 56 (21) |
| Mortality | 55 (21) (n = 262) | 46 (16) (n = 289) | 54 (20) (n = 272) |
Abbreviation: IQR, interquartile range.
The table includes hospital process measures and outcomes. The sections are organized by chronology from early hospitalization to 6-month follow-up, with some overlap between the sections (eg, some hospital discharges occurred beyond 28 days or even 6 months).
Alterations in fibrinolysis based on fibrinolytic pathway mediators and degree of clot lysis based on kaolin-activated thromboelastography and defined as LY30 (the percent of lysis that occurs 30 minutes after maximum amplitude is achieved). Reasons for missing LY30 are presented in eTable 13 in Supplement 2.
The Marshall classification places patients into 1 of 6 categories of increasing severity based on findings of noncontrast computed tomographic imaging of the brain: I (no visible pathology), II (midline shift 0-5 mm, basal cisterns remain visible, no high or mixed density lesions >25 cm3), III (midline shift 0-5 mm, basal cisterns compressed or completely effaced, no high- or mixed-density lesions >25 cm3), IV (midline shift >5 mm, no high- or mixed-density lesions >25 cm3), V (any lesions evacuated surgically), VI (high- or mixed-density lesion >25 cm3 not surgically removed).
The Rotterdam classification includes 6 categories ranging from 1 (best prognosis) to 6 (worst prognosis). The score is derived from 4 components: basal cisterns (0 indicates normal; 1, compressed; 2, absent), midline shift (0 indicates ≤5 mm and 1 indicates >5 mm), epidural mass lesion (0 indicates present and 1 indicates absent), intraventricular blood or traumatic subarachnoid blood (0 indicates absent and 1 indicates present). The scores for each component are summed and then 1 is added to arrive at the overall score. Only participants with intracranial hemorrhage are included for this outcome. Participants with 1 or more components missing or indeterminant were also excluded.
The Glasgow Outcome Scale-Extended subdivides the categories of severe and moderate disability and good recovery using a scale of 1 to 8, where 1 indicates death; 2, vegetative state; 3, lower severe disability; 4, upper severe disability; 5, lower moderate disability; 6, upper moderate disability; 7, lower good recovery; and 8, upper good recovery. Structured telephone interviews have been developed and validated for the measure and these questions were incorporated into the follow-up survey. The measure was dichotomized into unfavorable (1-4) and favorable (5-8) outcomes for this trial.
The Disability Rating Scale is designed to classify patients based on their degree of function after brain injury, consisting of 8 components: eye opening, communication, motor response, feeding, toileting, grooming, dependence/level of functioning, and psychosocial adaptability/employability. The overall score ranges from 0 (complete recovery) to 30 (death).
Neurosurgical interventions include craniotomy, craniectomy, and placement of a neuromonitoring or drainage device. The follow-up period for interventions continued through hospital discharge or 28 days, whichever occurred first.
Adverse events listed in this section are events listed on the drug insert that are known to be associated with tranexamic acid. The follow-up period for adverse events continued through hospital discharge or 28 days, whichever occurred first. Fifteen patients in the placebo group received open-label tranexamic acid. Among these participants, 1 adverse event (pulmonary embolism) was reported. Each count indicates the number of patients with 1 or more events of the type described in the row label. One patient in the placebo group had 2 instances (or a recurrence) of thrombotic stroke and another patient in the placebo group had 2 instances of deep vein thrombosis.
Other includes cerebral venous sinus thrombosis (7 participants in the bolus only group and 5 in the placebo group), superficial venous thrombosis (2 in the bolus only group and 1 in the placebo group), internal jugular vein thrombus (1 in the bolus only group and 1 in the placebo group), disseminated intravascular coagulation (1 in the bolus maintenance group and 1 in the bolus only group), cerebral vascular emboli (1 in the bolus only group and 1 in the placebo group), left ventricular thrombus (1 in the placebo group), inferior vena cava thrombus (1 in the bolus only group), and “presumed embolic infarcts” (1 in the bolus only group). One patient in the bolus only group had 2 “other” thromboembolic events, thus counts in this footnote do not sum to the count in the table for that group.
Hospital-free days include any day from hospital admission through day 28 that the participant was alive and out of the hospital. Some participants, primarily those who withdrew before discharge, are missing this measure (20 in the bolus maintenance group, 14 in the bolus only group, and 14 in the placebo group).
Intensive care unit–free days include any day from hospital admission through day 28 that the participant is alive and not in the ICU. Participants who died prior to discharge (even if after 28 days) are assigned a value of 0. Some participants, primarily those who withdrew before discharge, are missing this measure (19 in the bolus maintenance group, 14 in the bolus only group, and 14 in the placebo group).
Ventilator-free days include any day from hospital admission through day 28 that the participant is alive and does not require mechanical ventilatory support. Participants who die prior to discharge (even if after 28 days) are assigned a value of 0. Some participants, primarily those who withdrew before discharge, are missing this measure (19 in the bolus maintenance group, 14 in the bolus only group, and 14 in the placebo group).
There were 9 participants for whom the Glasgow Outcome Scale-Extended was taken at 6 months but not the Disability Rating Scale score (1 in the bolus maintenance group, 2 in the bolus only group, and 6 in the placebo group).