Analgesics in the Pre-hospital Setting: Implications on Hemorrhage Tolerance - Fentanyl

The purpose of this project is to test how fentanyl, an analgesic currently employed in the pre-hospital setting by the US Army, alters the capacity to tolerate a hemorrhagic insult in humans.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Fentanyl; Other: Placebo

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.

With this background, we will test the hypothesis that fentanyl 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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy
• Non-obese (body mass index less than 30 kg/m2)
• Body mass greater than or equal to 65 kg

Exclusion Criteria:

• Subjects who have cardiac, respiratory, neurological and/or metabolic illnesses
• Any known history of renal or hepatic insufficiency/disease
• Pregnancy or breast feeding
• Current smokers, as well as individuals who regularly smoked within the past 3 years
• Positive urine drug screen
• Currently taking pain modifying medication(s)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fentanyl; Fentanyl will be administered intravenously during one visit.	Drug: Fentanyl; Subjects will receive 75 ug Fentanyl while the effects of this drug on tolerance to a hemorrhagic insult will be assessed.
Placebo Comparator: Placebo; Placebo (saline) will be administered intravenously during one visit.	Other: Placebo; Subjects will receive saline while the effects of this drug on tolerance to a hemorrhagic insult will be assessed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Stress Index	Tolerance to a simulated hemorrhagic challenge will be assessed, for both the placebo and fentanyl limbs, by causing progressive central hypovolemia via lower-body negative pressure (LBNP). This progressive lower-body negative pressure 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).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pressure Pain Tolerance	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 after the subject has received placebo and fentanyl.	12 months

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Craig G Crandall, PhD, Institute for Exercise and Environmental Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): November 18, 2020
• Study Completion (Actual): November 18, 2020

Study Registration Dates

• First Submitted: October 21, 2019
• First Submitted That Met QC Criteria: October 21, 2019
• First Posted (Actual): October 23, 2019

Study Record Updates

• Last Update Posted (Actual): January 24, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Fentanyl
• Other Study ID Numbers: STU 092017-069

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The individual participant data (IPD) from this study are available from the principal investigator upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No