Healthy
Conditions
Brief summary
This study will examine how sufentanil (a commonly used pain medication) will alter responses to simulated blood loss in humans. To simulate blood loss in the research laboratory, participants will complete a test with their lower body in a custom-designed vacuum chamber for a brief period of time.
Detailed description
Pain management on the battlefield is critical for the wellbeing of the soldier. Given that a hemorrhagic injury on the battlefield is virtually always associated with pain, it is paramount that the selected pain medication does not disrupt appropriate physiological mechanisms that are beneficial towards the maintenance of blood pressure and vital organ blood flow during that hemorrhagic insult. Current guidelines for the selection of pain medications of a hemorrhaging soldier are based upon limited scientific evidence, with the vast majority of supporting studies being conducted on anesthetized animals. Thus, the interaction between hemorrhagic shock and pain medications commonly employed on the battlefield is yet to be determined in the conscious humans. This study will test the hypothesis that sufentanil will impair the capacity for a conscious human to tolerate a hemorrhagic insult. The obtained data will provide the necessary scientific evidence in humans to support the Committee on Tactical Combat Casualty Care (CoTCCC) guidelines on the analgesic of choice for moderate to severe injuries where the casualty is in hemorrhagic shock. Notably, such data will identify the analgesic that least compromises a human's ability to tolerate a hemorrhagic insult, ultimately providing critical information to the combat medic on which analgesic should be employed for such an injury.
Interventions
DRUGSufentanil
Subjects will receive Sufentanil while the effects of this drug on tolerance to a hemorrhagic insult will be assessed.
OTHERPlacebo
Subjects will receive a placebo pill while the effects of this placebo on tolerance to a hemorrhagic insult will be assessed.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* 18-45 years of age * Healthy * Non-obese (body mass index less than 30 kg/m2) * Body mass greater than or equal to 65 kg * Speak English
Exclusion criteria
* Subjects not in the defined age range * Subjects who have cardiac, respiratory, neurological and/or metabolic illnesses * Any known history of renal or hepatic insufficiency/disease * Pregnancy or breast feeding * Body mass less than 65 kg * Current smokers, as well as individuals who regularly smoked within the past 3 years * Subjects who cannot speak or read English * Positive urine drug screen * Currently taking pain modifying medication(s)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerance to Simulated Hemorrhage | 6 hours | Tolerance to a simulated hemorrhagic challenge will be assessed, for both the placebo and sufentanil limbs, by causing progressive central hypovolemia via lower-body negative pressure. This progressive lower-body negative pressure (LBNP) challenge will be performed until the onset of syncopal symptoms (defined as: profound bradycardia, a precipitous drop in arterial blood pressure and accompanying narrowing of pulse pressure, a sustained systolic blood pressure less than 80 mmHg, and/or subjective symptoms such as light-headedness, sweating, nausea, or dizziness). The primary variable will be the quantification of lower-body negative pressure that is required to cause these symptoms. This quantification will be objectively measured via a cumulative stress index which is calculated as the sum of the product of the LBNP level and the duration of each level, until test termination (i.e., 40 mmHg x 3 min + 50 mmHg x 3 min, etc). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Assessment | 6 hours | Pain assessments will be conducted using a digital algometer to obtain maximum pain thresholds caused by pressure. This pain assessment technique is conducted by applying the tip of a hand-held digital algometer on the subject's digit. Force is gradually increased and the peak force is recorded when the subject first reports a painful sensation. Removal of the pressure from the algometer immediately relieves the painful sensation and the subject can voluntarily stop the test at any time. This assessment will be performed when the subject has received placebo and sufentanil. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enrolled Participants in Crossover Design Participants received both placebo and sufentanil in a randomized crossover model. Thus, the reported baseline characteristics reflect those individuals who participated in both limbs. | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | Enrolled Participants in Crossover Design |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age, Continuous | 29 years STANDARD_DEVIATION 4 |
| Body-Mass Index | 25 kg/m^2 STANDARD_DEVIATION 2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 29 |
| other Total, other adverse events | 0 / 29 | 0 / 29 |
| serious Total, serious adverse events | 0 / 29 | 0 / 29 |
Outcome results
Primary
Tolerance to Simulated Hemorrhage
Tolerance to a simulated hemorrhagic challenge will be assessed, for both the placebo and sufentanil limbs, by causing progressive central hypovolemia via lower-body negative pressure. This progressive lower-body negative pressure (LBNP) challenge will be performed until the onset of syncopal symptoms (defined as: profound bradycardia, a precipitous drop in arterial blood pressure and accompanying narrowing of pulse pressure, a sustained systolic blood pressure less than 80 mmHg, and/or subjective symptoms such as light-headedness, sweating, nausea, or dizziness). The primary variable will be the quantification of lower-body negative pressure that is required to cause these symptoms. This quantification will be objectively measured via a cumulative stress index which is calculated as the sum of the product of the LBNP level and the duration of each level, until test termination (i.e., 40 mmHg x 3 min + 50 mmHg x 3 min, etc).
Time frame: 6 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil | Tolerance to Simulated Hemorrhage | 599 min*mmHg | Standard Deviation 412 |
| Placebo | Tolerance to Simulated Hemorrhage | 651 min*mmHg | Standard Deviation 271 |
Secondary
Pain Assessment
Pain assessments will be conducted using a digital algometer to obtain maximum pain thresholds caused by pressure. This pain assessment technique is conducted by applying the tip of a hand-held digital algometer on the subject's digit. Force is gradually increased and the peak force is recorded when the subject first reports a painful sensation. Removal of the pressure from the algometer immediately relieves the painful sensation and the subject can voluntarily stop the test at any time. This assessment will be performed when the subject has received placebo and sufentanil.
Time frame: 6 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil | Pain Assessment | 1.04 kg | Standard Deviation 0.43 |
| Placebo | Pain Assessment | 1.16 kg | Standard Deviation 0.4 |