Dexmedotomidine for Acute Pain Control in Patients With Multiple Rib FracturesRandomized Controlled Trial

Study Overview
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Brief Summary
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Blunt chest trauma is the second most common form of unintentional trauma in the US and is associated with significant morbidity and mortality. Thoracic injuries are the third most common cause of death in trauma patients. Rib fractures have an increased associated risk of pneumonia, prolonged hospitalization, and cost. The associated severe pain leads to poor pulmonary mechanics, which contributes to additional complications. Treatment for rib fractures is focused on optimizing analgesia and intense pulmonary hygiene. Most common strategies utilize early mobilization, incentive spirometry (IS), and multimodal pain regimens. A variety of techniques for analgesia after blunt chest trauma exist. Epidural analgesia is one of the best-studied methods and can often provide significant pain relief. However, this method is invasive, has associated complications, and often can be contraindicated due to coagulopathy or other injuries. Most often a form of multimodal pain strategy is utilized which incorporates acetaminophen, Nonsteroidal anti-inflammatory drugs (NSAIDs), trans-dermal lidocaine, and muscle relaxants. Opioids remain an important adjunct to control severe pain, however, narcotics have their own associated complications. The aim of our study is to use an infusion of dexmedetomidine (Precedex) to aid in pain management in patients presenting with 3 or more rib fractures. The investigators hypothesize that dexmedetomidine will decrease patient pain and opioid use.

Detailed Description
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This is a prospective, randomized, double-blinded, placebo-controlled trial. Patients will be identified as they present to the trauma bay and meet eligibility criteria. Following informed consent patients will be randomized to either the intervention or control arm. Randomization and allocation concealment will be managed by a nominated independent individual(s) not involved in patient care or data extraction/analysis. The consenting physician will contact the randomization individual by phone. They will use a random number generator to assign group in a 1:1 ratio and then maintain a password-protected randomization database that is only accessible to the principal investigator and randomization individual(s). The intervention arm will receive an infusion of dexmedetomidine (precedex) at 0.4-0.6 mcg/kg/h (Based off ideal body weight). The control arm will receive an infusion of normal saline. Medication distribution and management will be handled by the Investigational Drug Service (IDS) at UCI medical center. A pharmacist who does not participate in the rest of the study will encode the study drug accordingly. Dexmedetomidine is approved for ICU and procedural sedation, and its use in this study for analgesics is off-label. A baseline pain assessment will be performed using a numerical pain score (NPS). Infusions will start within 12 hours of arrival to the ICU and will continue for 24 hours. Infusion will stop once the patient is transferred out of the ICU or at 24 hours, whichever is first. In the scenario of possible adverse events (as listed below) the physician can hold or stop the study medication at their discretion. All enrolled patients will also receive a multimodal pain regimen with acetaminophen, NSAIDs, lidocaine patch, gabapentin, and muscle relaxants. For moderate and severe pain (5-10) patients will receive 5-10mg oxycodone every 4-6 hours upon request. Nursing staff will assess pain per the unit standard of care. NPS and opiate administration will be documented in the EMR by the nursing staff. All participants, providers, and staff will be blinded unless medical necessity requires patients to be unblinded. Data will be collected prospectively from the EMR by blinded researchers and entered into a REDCap database. Data collection will include demographics, mechanism of injury, injury severity score (ISS), imaging, pain scores, pain medications, incentive spirometry, pulmonary complications, ICU LOS, hospital LOS, discharge disposition, and any other clinically relevant data. Criteria for drop out include: Participant withdrawal of consent Ordered to drop-out by the investigators or attending physician Cases of unmasked blinding Since both injury severity and age can be confounding variables with pain, the study team plans to do a subgroup analysis after the completion of data collection. Injury severity Score (ISS) ≥ 15 and < 15 will be used to stratify injury severity. Age ≥ 65 and <65 will be used to stratify patient age.

Official Title
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Dexmedotomidine for Acute Pain Control in Patients With Multiple Rib Fractures

Conditions
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Rib Fractures, Pain, Acute

Intervention / Treatment
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* Drug: Dexmedetomidine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Blunt trauma patients > 3 rib fractures Admission to the ICU Exclusion Criteria: Exclusion criteria: Younger than 18 Pregnant Prisoners History of adverse reaction to dexmedetomidine GCS < 14 Acute CHF exacerbation Bradycardia or heart block (HR <55) Hypotension (SBP < 90mmHg or MAP < 65mmHg) Current opioid use (>30mg OME/day) Inability to communicate with staff (dementia) Cirrhosis or chronic liver dysfunction (Child Pugh class C)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a prospective, randomized, double-blinded, placebo-controlled trial. Patients will be identified as they present to the trauma bay and meet eligibility criteria. Following informed consent patients will be randomized to either the intervention or control arm. Randomization and allocation concealment will be managed by a nominated independent individual(s) not involved in patient care or data extraction/analysis. The consenting physician will contact the randomization individual by phone. They will use a random number generator to assign group in a 1:1 ratio and then maintain a password protected randomization database that is only accessible to the principal investigator and randomization individual(s).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Precedex arm<br>The intervention arm will receive an infusion of dexmedetomidine (precedex) at 0.4-0.6 mcg/kg/h (Based off ideal body weight). | Drug: Dexmedetomidine<br>* Dexmedotomidine for Acute Pain Control in Patients with Multiple Rib Fractures<br>|
| Placebo Comparator: Control arm<br>The control arm will receive an infusion of normal saline. Medication distribution and management will be handled by the Investigational Drug Service (IDS) at UCI medical center. | Other: Placebo<br>* The control arm will receive an infusion of normal saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Pain | Numerical pain score (NPS): a score of 1-10 that will be recorded by the nurse in charge of the patients as standard of care. | through study completion of index hospitalization (up to 6 months) | 
| Use of morphine and morphine equivalents. | 2. Oral morphine equivalents (OME) - A study team member will do a chart review and collect morphine used by the patients. | through study completion of index hospitalization (up to 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epidural administration | Epidural use - patients that fail pain management will be offered an epidural | through study completion of index hospitalization (up to 6 months) | 
| Time in the hospital | ICU length of stay - number of days in the ICU Hospital length of stay - number of days admitted to the acute care hospital | through study completion of index hospitalization (up to 6 months) | 
| Respiratory complications | Respiratory complications - include events such as unplanned intubation, pneumonia, pneumothorax and incentive spirometry | through study completion of index hospitalization (up to 6 months) | 
| Mortality | Mortality - in-hospital mortality rate and 30-day mortality | through study completion of index hospitalization (up to 6 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rib Fracture, Pain, Dexmedotomidine