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

We are examining how morphine (a commonly used pain medication) will alter responses to simulated blood loss in humans. To simulate blood loss in our research laboratory, participants will complete a test with their lower body in a custom-designed vacuum chamber for a brief period of time.

Study Overview

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

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 morphine 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): 44
• 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: 18 years to 45 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: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Morphine; Morphine will be administered intravenously	Drug: Morphine; Subjects will receive Morphine while the effects of this drug on tolerance to a hemorrhagic insult will be assessed.
Placebo Comparator: Placebo; Saline will be administered intravenously	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
Tolerance to Simulated Hemorrhage	Tolerance to a simulated hemorrhagic challenge will be assessed, for both the placebo and morphine limbs, by causing progressive central hypovolemia via lower-body negative pressure (LBNP). This progressive 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 LBNP 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). A larger cumulative stress index represents a greater tolerance	30 minutes from the onset of applying lower-body negative pressure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Assessment - Algometer	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 morphine.	30 minutes from the onset of the protocol

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2019
• Primary Completion (Actual): January 4, 2022
• Study Completion (Actual): January 4, 2022

Study Registration Dates

• First Submitted: October 21, 2019
• First Submitted That Met QC Criteria: October 23, 2019
• First Posted (Actual): October 24, 2019

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2022
• Last Verified: December 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; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: STU 092017-070

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

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