Heat Stress Disorders
Conditions
Keywords
firefighter, heat stress, platelet activation, aspirin
Brief summary
The purpose of this study is to determine if aspirin taken by firefighters prevents platelets from becoming sticky when body temperature rises during work in protective clothing.
Detailed description
Firefighters have the highest rate of line-of duty death (LODD) in the United States. More than half of these LODD are cardiovascular related occurring disproportionately around fire suppression activities. In addition, shift work, lifestyle factors, and the exposures associated with fire suppression (e.g. smoke, chemicals) may predispose the firefighter to earlier onset of heart disease or cause a pro-inflammatory state leading to endothelial dysfunction. Fire suppression activities exacerbate cardiovascular strain and endothelial dysfunction and provide potential triggers for ischemic events (e.g. myocardial infarction, stroke). There is a rapid rise in heart rate following the activation of a fire company which may persist for as long as 20 minutes. Even in cases where heavy work is not being performed, the repetitive upper body exercise associated with tool use raises heart rate disproportionately to oxygen consumption. Finally, there is a rapid rise in core body temperature from increased physical activity, environmental heat and impaired thermoregulation that has been shown to cause vasoconstriction and activate coagulation during heat stress (12, 13). This has recently been demonstrated in firefighters working in thermal protective clothing. The combination of triggers created during fire suppression may result in heart attack or stroke, especially in firefighters with risk factors for cardiovascular disease. Interventions beyond basic fireground rehab may be required to minimize the effect of these triggers and enhance a firefighter's health and wellness. Fireground rehab typically focuses on cooling and rehydration of the firefighter following fire suppression or training with the assumption that these interventions will correct the underlying pathophysiology. Effective fireground rehab must deliver appropriate interventions and monitor the progress of the firefighter. While correcting hyperthermia and hypohydration are essential for continued performance, it is not clear if these therapies correct alterations in platelet or endothelial function or if other interventions are necessary to correct these physiological disturbances. Furthermore, the options for monitoring the firefighter beyond simply measuring heart and respiratory rate are limited. In our FEMA-funded Fireground Rehab Evaluation (FIRE) Trial, we demonstrated that five commercially available thermometers did not reliably measure or estimate core temperature following uncompensable heat stress (UHS) making it impossible to gauge the effectiveness of rehab interventions.
Interventions
Two weeks 82 mg aspirin taken orally prior to exercise protocol
OTHERActive cooling
Active cooling to remediate heat stress following exercise by placing hands and forearms into cold water
DRUGAcute aspirin (ASA)
325 mg chewable aspirin administered immediately following exercise
OTHERPassive cooling
Removing protective garments for passive cooling following exercise
DRUGDaily placebo
Placebo comparator for daily aspirin therapy
DRUGAcute placebo
Placebo comparator for acute aspirin therapy
Sponsors
Federal Emergency Management Administration
Eyemarker Systems, Inc
Dave Hostler
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
1\. Apparently healthy males and females aged 18-49 years
Exclusion criteria
1. History of heart disease, vascular disease, or sudden death including prior MI, coronary revascularization, congenital heart disease or history of stroke 2. Hypertension during screening: SBP\>139 or DBP\>89 3. Those who are taking medications that may be expected to blunt the physiologic response to a treadmill exercise test (e.g. beta blockers) 4. Prescription medication with known side effect of impaired thermoregulation 5. Positive pregnancy test at any time during the study 6. Resting ECG with clinical presentation suggesting coronary heart disease (e.g. pathologic Q wave) 7. Known history of gastrointestinal disease or disorder i.e. diverticulitis which creates a theoretical risk of the core temperature capsule becoming lodged in the digestive tract 8. Medications and supplements known to alter endothelial function (e.g. arginine, omega 3 fatty acids, NSAIDS, tobacco products. This exclusion may be disregarded for subjects willing to stop taking the supplement for the duration of the study 9. At the discretion of the study physician for any other medical condition or prescription medication 10. Known history of platelet dysfunction 11. Aspirin allergy or intolerance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Platelet Closure Time | 0, 30, 60, and 90 minutes post exercise | — |
| Vascular Function Measured by Peripheral Arterial Tonometry | Baseline, 30, 60, and 90 minutes post exercise | Reactive Hyperemia Index |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Activation of Coagulation | 0, 30, 60, and 90 minutes post exercise | This measure was not collected. Equipment was not available. |
| Hyperthermia and Hemoconcentration Identified by Retinal Imaging | 0, 30, 60, and 90 minutes post exercise | This measure was not collected. Equipment was not available. |
Countries
United States
Participant flow
Pre-assignment details
Active Cooling Arm not completed - insufficient number of subjects were recruited to complete these arms of the trial, and the Passive Cooling arms were the only ones conducted.
Participants by arm
| Arm | Count |
|---|---|
| Daily ASA, Passive Cool, Acute ASA Two weeks of daily aspirin therapy prior to exercise, passive cooling following exercise, aspirin immediately post exercise
Daily aspirin (ASA): Two weeks 82 mg aspirin taken orally prior to exercise protocol
Acute aspirin (ASA): 325 mg chewable aspirin administered immediately following exercise
Passive cooling: Removing protective garments for passive cooling following exercise | 25 |
| Daily ASA, Passive Cool, Acute Placebo Two weeks of daily aspirin therapy prior to exercise, passive cooling following exercise, placebo immediately post exercise
Daily aspirin (ASA): Two weeks 82 mg aspirin taken orally prior to exercise protocol
Passive cooling: Removing protective garments for passive cooling following exercise
Acute placebo: Placebo comparator for acute aspirin therapy | 29 |
| Daily Placebo, Passive Cool, Acute ASA Two weeks of daily placebo prior to exercise, passive cooling following exercise, aspirin immediately post exercise
Acute aspirin (ASA): 325 mg chewable aspirin administered immediately following exercise
Passive cooling: Removing protective garments for passive cooling following exercise
Daily placebo: Placebo comparator for daily aspirin therapy | 25 |
| Daily Placebo, Passive Cool, Acute Placebo Two weeks of daily placebo prior to exercise, passive cooling following exercise, placebo immediately post exercise
Passive cooling: Removing protective garments for passive cooling following exercise
Daily placebo: Placebo comparator for daily aspirin therapy
Acute placebo: Placebo comparator for acute aspirin therapy | 23 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 3 | 8 | 8 |
Baseline characteristics
| Characteristic | Daily ASA, Passive Cool, Acute ASA | Daily ASA, Passive Cool, Acute Placebo | Daily Placebo, Passive Cool, Acute ASA | Daily Placebo, Passive Cool, Acute Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 33.2 years STANDARD_DEVIATION 10.1 | 29.3 years STANDARD_DEVIATION 8.6 | 30.5 years STANDARD_DEVIATION 8.5 | 34.5 years STANDARD_DEVIATION 9.3 | 31.8 years STANDARD_DEVIATION 8.6 |
| Region of Enrollment United States | 25 participants | 29 participants | 25 participants | 23 participants | 102 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 4 Participants | 0 Participants | 8 Participants |
| Sex: Female, Male Male | 24 Participants | 26 Participants | 21 Participants | 23 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 25 | 0 / 29 | 0 / 25 | 0 / 23 |
| serious Total, serious adverse events | 0 / 25 | 0 / 29 | 0 / 25 | 0 / 23 |
Outcome results
Primary
Platelet Closure Time
Time frame: 0, 30, 60, and 90 minutes post exercise
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Daily ASA, Passive Cool, Acute ASA | Platelet Closure Time | 30 minutes post | 300 seconds |
| Daily ASA, Passive Cool, Acute ASA | Platelet Closure Time | Immediate post exercise | 275.5 seconds |
| Daily ASA, Passive Cool, Acute ASA | Platelet Closure Time | 60 minutes post | 300 seconds |
| Daily ASA, Passive Cool, Acute ASA | Platelet Closure Time | 90 minutes post | 300 seconds |
| Daily ASA, Passive Cool, Acute Placebo | Platelet Closure Time | 60 minutes post | 300 seconds |
| Daily ASA, Passive Cool, Acute Placebo | Platelet Closure Time | 90 minutes post | 275 seconds |
| Daily ASA, Passive Cool, Acute Placebo | Platelet Closure Time | Immediate post exercise | 207 seconds |
| Daily ASA, Passive Cool, Acute Placebo | Platelet Closure Time | 30 minutes post | 300 seconds |
| Daily Placebo, Passive Cool, Acute ASA | Platelet Closure Time | 90 minutes post | 300 seconds |
| Daily Placebo, Passive Cool, Acute ASA | Platelet Closure Time | Immediate post exercise | 95 seconds |
| Daily Placebo, Passive Cool, Acute ASA | Platelet Closure Time | 30 minutes post | 300 seconds |
| Daily Placebo, Passive Cool, Acute ASA | Platelet Closure Time | 60 minutes post | 300 seconds |
| Daily Placebo, Passive Cool, Acute Placebo | Platelet Closure Time | 30 minutes post | 105 seconds |
| Daily Placebo, Passive Cool, Acute Placebo | Platelet Closure Time | 60 minutes post | 105 seconds |
| Daily Placebo, Passive Cool, Acute Placebo | Platelet Closure Time | Immediate post exercise | 90 seconds |
| Daily Placebo, Passive Cool, Acute Placebo | Platelet Closure Time | 90 minutes post | 105 seconds |
Primary
Vascular Function Measured by Peripheral Arterial Tonometry
Reactive Hyperemia Index
Time frame: Baseline, 30, 60, and 90 minutes post exercise
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Daily ASA, Passive Cool, Acute ASA | Vascular Function Measured by Peripheral Arterial Tonometry | Baseline | 1.89 ratio (Reactive Hyperemia Index) | Standard Deviation 0.38 |
| Daily ASA, Passive Cool, Acute ASA | Vascular Function Measured by Peripheral Arterial Tonometry | 30 minutes post | 1.97 ratio (Reactive Hyperemia Index) | Standard Deviation 0.56 |
| Daily ASA, Passive Cool, Acute ASA | Vascular Function Measured by Peripheral Arterial Tonometry | 60 minutes post | 2.18 ratio (Reactive Hyperemia Index) | Standard Deviation 0.48 |
| Daily ASA, Passive Cool, Acute ASA | Vascular Function Measured by Peripheral Arterial Tonometry | 90 minutes post | 2.09 ratio (Reactive Hyperemia Index) | Standard Deviation 0.31 |
| Daily ASA, Passive Cool, Acute Placebo | Vascular Function Measured by Peripheral Arterial Tonometry | 30 minutes post | 1.77 ratio (Reactive Hyperemia Index) | Standard Deviation 0.38 |
| Daily ASA, Passive Cool, Acute Placebo | Vascular Function Measured by Peripheral Arterial Tonometry | 60 minutes post | 1.92 ratio (Reactive Hyperemia Index) | Standard Deviation 0.48 |
| Daily ASA, Passive Cool, Acute Placebo | Vascular Function Measured by Peripheral Arterial Tonometry | 90 minutes post | 1.98 ratio (Reactive Hyperemia Index) | Standard Deviation 0.45 |
| Daily ASA, Passive Cool, Acute Placebo | Vascular Function Measured by Peripheral Arterial Tonometry | Baseline | 1.77 ratio (Reactive Hyperemia Index) | Standard Deviation 0.51 |
| Daily Placebo, Passive Cool, Acute ASA | Vascular Function Measured by Peripheral Arterial Tonometry | 60 minutes post | 1.56 ratio (Reactive Hyperemia Index) | Standard Deviation 0.68 |
| Daily Placebo, Passive Cool, Acute ASA | Vascular Function Measured by Peripheral Arterial Tonometry | 30 minutes post | 1.77 ratio (Reactive Hyperemia Index) | Standard Deviation 0.71 |
| Daily Placebo, Passive Cool, Acute ASA | Vascular Function Measured by Peripheral Arterial Tonometry | 90 minutes post | 1.91 ratio (Reactive Hyperemia Index) | Standard Deviation 0.66 |
| Daily Placebo, Passive Cool, Acute ASA | Vascular Function Measured by Peripheral Arterial Tonometry | Baseline | 2.16 ratio (Reactive Hyperemia Index) | Standard Deviation 0.74 |
| Daily Placebo, Passive Cool, Acute Placebo | Vascular Function Measured by Peripheral Arterial Tonometry | 90 minutes post | 1.98 ratio (Reactive Hyperemia Index) | Standard Deviation 0.51 |
| Daily Placebo, Passive Cool, Acute Placebo | Vascular Function Measured by Peripheral Arterial Tonometry | 30 minutes post | 1.73 ratio (Reactive Hyperemia Index) | Standard Deviation 0.3 |
| Daily Placebo, Passive Cool, Acute Placebo | Vascular Function Measured by Peripheral Arterial Tonometry | Baseline | 1.72 ratio (Reactive Hyperemia Index) | Standard Deviation 0.34 |
| Daily Placebo, Passive Cool, Acute Placebo | Vascular Function Measured by Peripheral Arterial Tonometry | 60 minutes post | 1.83 ratio (Reactive Hyperemia Index) | Standard Deviation 0.4 |
Secondary
Activation of Coagulation
This measure was not collected. Equipment was not available.
Time frame: 0, 30, 60, and 90 minutes post exercise
Population: This measure was not collected. Equipment was not available.
Secondary
Hyperthermia and Hemoconcentration Identified by Retinal Imaging
This measure was not collected. Equipment was not available.
Time frame: 0, 30, 60, and 90 minutes post exercise
Population: This measure was not collected. Equipment was not available.