Ketamine vs Lidocaine in Traumatic Rib Fractures

A Prospective, Randomized, Single-Blinded Trial of Ketamine Versus Lidocaine Infusions for Multimodal Pain Management in Traumatic Rib Fracture Patients

Rib fractures continue to be a common occurrence in trauma patients of all ages. Traumatic rib fractures can cause severe pain in patients and lead to shallow breathing and further complications such as the need for mechanical ventilation, hospital or ventilator associated pneumonia, atelectasis, and acute respiratory distress syndrome. Effective multimodal pain management is needed to optimize a patient's respiratory status and can also play a role in early mobility, less pulmonary complications, shorter ICU and hospital length of stay, and decreased mortality. Current multimodal pain management options include opioids, muscle relaxants, gabapentin, acetaminophen, nonsteroidal anti-inflammatory drugs, and various regional/neuraxial anesthesia techniques. Both ketamine and lidocaine infusions for pain control have also been shown in studies to be safe and effective, with the benefit of minimizing the use of opioids. However, there have been very few studies that have used ketamine or lidocaine infusions for pain control specifically in patients with traumatic rib fractures. Therefore, the purpose of this study is to evaluate ketamine versus lidocaine infusions as an adjunctive therapy to reduce opioid consumption in the first 72 hours in patients with multiple traumatic rib fractures.

Study Overview

• Status: Recruiting
• Conditions: Rib Fractures; Rib Fracture Multiple; Rib Trauma
• Intervention / Treatment: Drug: Ketamine; Drug: Lidocaine

Detailed Description

Effective pain control plays a key role is optimizing a patient's respiratory status after suffering multiple rib fractures. Using multimodal pain management techniques and optimizing a patient's pain control regimen helps to minimize the complications associated with rib fractures, such as pneumonia and the need for mechanical ventilation. The benefit of using opioid-sparing options such as ketamine or lidocaine infusions would be to avoid the side effects associated with opioids, which include delirium, constipation, and depressed respiratory drive.

Ketamine and lidocaine infusions are both medications that have been used in numerous studies to effectively treat post-operative pain. Low dose ketamine infusions have also recently been shown to be a safe and effective adjunct option to help reduce pain scores and decrease opioid use in patients with traumatic rib fractures. Currently there is no published studies to assess lidocaine's effectiveness to reduce pain scores and opioid use in traumatic rib fracture patients. There is also only one study to date that has directly compared ketamine to lidocaine infusions for pain control. This study occurred in 60 patients undergoing elective nephrectomy and evaluated three 24-hour infusion groups: ketamine, lidocaine, or placebo. The primary outcome showed that both ketamine and lidocaine infusions significantly reduced 24-hour OME compared to placebo (33% ketamine, 42% lidocaine) and decreased overall pain scores.

This trial is a single center, prospective, randomized trial of adult patients with ≥ 3 traumatic rib fractures admitted to a Level 1 trauma center at Spectrum Health Butterworth Hospital. As part of the current rib fracture protocol all patients will receive the standard multimodal pain regimen at the investigator's institution, including acetaminophen, NSAIDS, muscle relaxants and gabapentin. Currently ketamine infusions and regional/neuraxial anesthesia techniques are added if the standard multimodal pain regimen is insufficient. Lidocaine infusions have also been used at the institution for post-surgical pain control to minimize opioid use. The objective of the study will be to compare ketamine versus lidocaine infusions on the effectiveness to optimize pain control as well as minimize the use of opioids in patients with traumatic rib fractures.

If consent is obtained the patient will be randomized 1:1 to receive either a ketamine or lidocaine infusion for pain control, along with standard of care, using a pre-designed randomization schedule. Patients must be enrolled within 16 hours of hospital admission and are expected to remain on the infusion for a minimum of 24 hours. The duration, titration, and stopping of study drug will be dependent on the progress of the patient's overall pain status and provider decision, with data being included for the study medication for up to 72 hours. If patients require surgery at any time the study medication will not be held unless signs of adverse events occur. Patients who are unable to remain on the study infusion or have a regional/neuraxial anesthetic placed before the 24-hour mark (decided based on the Trauma and Surgical Intensive Care Unit services) will be considered a screen fail and no data will be contributed to the study, however, the screen fail will be documented. If a patient is unable to remain on infusion or has a regional/neuraxial anesthetic placed ≥ 24 hours, their data will be included up until that point and analyzed. Adverse event and serious adverse events will be monitored throughout the entire study period, with continuous cardiac telemetry being required in both study groups and daily lidocaine levels drawn in the lidocaine group.

• Study Type: Interventional
• Enrollment (Estimated): 74
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Brittany Hoyte, PharmD; Email: brittany.hoyte@spectrumhealth.org
• Study Contact Backup: Name: Hannah R Wheeler; Phone Number: 616-486-9834; Email: hannah.wheeler@corewellhealth.org

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Spectrum Health Hospital
      • Contact: Brittany R Hoyte, PharmD; Phone Number: 616-352-2462; Email: brittany.hoyte@spectrumhealth.org
      • Sub-Investigator: Alistair J Chapman, MD
      • Sub-Investigator: Charles J Gibson, MD
      • Sub-Investigator: Gaby A Iskander, MD
      • Sub-Investigator: Benjamin N Gayed, MD
      • Sub-Investigator: Nicholas C Watson, MD
      • Sub-Investigator: Amy R Spencer, MD
      • Sub-Investigator: Richard S Hagelberg, MD
      • Sub-Investigator: Jess A Spradling, MD
      • Sub-Investigator: Elizabeth A Steensma, MD
      • Sub-Investigator: Amanda Y Yang, MD
      • Principal Investigator: Brittany R Hoyte, PharmD
      • Sub-Investigator: Cathryn L Chadwick, MD
      • Sub-Investigator: Patricia A Pentiak, MD
      • Sub-Investigator: Douglas R Kwazneski, MD
      • Sub-Investigator: Luke T Durling, MD
      • Sub-Investigator: Kailyn K Hing, MD
      • Sub-Investigator: Calvin J Ice, PharmD
      • Sub-Investigator: Laura A Krech, MPH
      • Sub-Investigator: Jessica L Parker, MS
      • Sub-Investigator: Matthew B Dull, MD
      • Sub-Investigator: Kailyn Kwong-Hing, MD
      • Contact: Hannah R Wheeler; Phone Number: 616-486-9834; Email: hannah.wheeler@corewellhealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults ≥ 18 years old
2. ≥ 3 traumatic blunt rib fractures
3. Enrollment within 16 hours of being admitted to the hospital
4. Patients whom in the investigator's clinical judgement, would require escalated pain control regiments in the future and would potentially benefit from participation in this study in terms of pain control.

Exclusion Criteria:

1. Patients receiving any regional/neuraxial anesthetic techniques or ketamine infusion before randomization
2. Adults with diminished decision-making capacity
3. Adults of limited English proficiency/non-English speakers
4. Prisoners
5. Pregnant or breastfeeding women
6. Patient admission weight greater than 120 kg

7. Patients with any of the following medical history:

   1. Active delirium (as defined by Confusion Assessment Method)
   2. Dementia
   3. Psychosis
   4. Glaucoma
   5. Heart block (except with patients with a functioning artificial pacemaker)
   6. Congestive heart failure (ejection fraction <20% recorded in last year)
   7. Adams-Stokes syndrome
   8. Wolff-Parkinson-White Syndrome
8. Patient is unable to communicate with staff for pain assessments at time of enrollment
9. Most recent documented Glasgow Coma Score <15 at the time of study enrollment
10. Severe bradycardia (heart rate <50 bpm based on last vital sign recorded at time of study enrollment)
11. Sustained hypertension (systolic blood pressure >180 mm Hg or diastolic blood pressure >100 mm Hg for at least 3 sets of vital signs in a row prior to study enrollment)
12. Any seizure suspected or identified during hospital admission
13. Patient with active acute coronary syndrome obtained from admission problem list

14. Patients with known hepatic disease or acute liver failure

    a. Acute liver failure on admission defined as either: i. International normalized ratio > 1.5, without being on home anticoagulation ii. Aspartate aminotransferase or Alanine aminotransferase greater than 120 IU/L (3 times upper limit of normal) b. Known hepatic disease defined as past medical history of Child Turcotte Pugh (Child's) score C

15. Patients with a history of end-stage renal disease or admission creatinine clearance (CrCl) ≤30 ml/min

    a. CrCl will be based on Cockcroft-Gault equation from admission labs

16. Use of antiarrhythmic medication therapy prior or during admission

    a. Amiodarone, sotalol, dofetilide, dronedarone, mexilitine

17. Patients with a known allergy/sensitivity to lidocaine or ketamine, amide anesthetics, or components of the solution
18. Patients who, in the investigator's opinion, should not be included in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ketamine; Infusion initiation: 0.1 mg/kg/hr Max: 0.3 mg/kg/hr Recommended titration: 0.1 mg/kg/hr* as needed every 4 hours based on pain scores ≥5 and physician order Dosing will be based on patient actual body weight (ABW) recorded as dosing weight on time of hospital admission.	Drug: Ketamine; Will receive titratable infusion.; Other Names: Ketalar
Active Comparator: Lidocaine; Infusion initiation: 1 mg/kg/hr Max: 2 mg/kg/hr Recommended titration:0.25 mg/kg/hr* as needed every 4 hours based on pain scores ≥5 and physician order Dosing will be based on patient actual body weight (ABW) recorded as dosing weight on time of hospital admission.	Drug: Lidocaine; Will receive titratable infusion, will have daily lidocaine level labs drawn daily.; Other Names: Xylocaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral Morphine Equivalent - Opioid Usage	Oral morphine equivalence is a way to track the amount of opioids used by standardizing all opioid utilizations and converting them to daily morphine equivalence in mg.	0-24 hours post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analogue Numeric Pain Score	Visual Analogue Numeric Pain Score are recorded as a scale of 1-10, with 0 being no pain and 10 as worst imaginable pain. Patient will be asked their pain score every 6 hours.	0-24; 24-48; 48-72 hours post infusion
Oral Morphine Equivalent - Opioid Usage	Oral morphine equivalence is a way to track the amount of opioids used by standardizing all opioid utilizations and converting them to daily morphine equivalence in mg.	24-48; 48-72 hours post infusion
Respiratory Failure	Respiratory failure was defined by need for mechanical intubation	0-30 days post-infusion
Use of Regional/Neuraxial anesthesia	Measure of regional/neuraxial anesthesia placement rates. Patient would need to be taken off study medication if decision made to place regional/neuraxial anesthetic.	0-30 days post infusion
Hospital Length of Stay	Total hospital length of stay up to 365 days	Will capture retrospectively after patient's medical discharge
Intensive Care Unit Length of stay	Total intensive care unit length of stay up to 365 days	Will capture retrospectively after patient's medical discharge
Incentive Spirometry	Measure of percent improvement in incentive spirometry level from baseline (before infusion). Incentive spirometry levels range from 0-4,000 mL.	0-24; 24-48; 48-72 hours post infusion
Adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	0-72 hours post infusion
In-Hospital mortality	Patient's death will be recorded if it occurs before discharge	Will capture retrospectively after patient's medical discharge

Collaborators and Investigators

• Sponsor: Brittany Hoyte

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: February 22, 2021
• First Submitted That Met QC Criteria: March 1, 2021
• First Posted (Actual): March 4, 2021

Study Record Updates

• Last Update Posted (Estimated): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Ketamine; Lidocaine; Rib Fracture; Traumatic Rib Fracture
• Additional Relevant MeSH Terms: Wounds and Injuries; Thoracic Injuries; Multiple Trauma; Fractures, Bone; Rib Fractures; Fractures, Multiple; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Ketamine; Lidocaine
• Other Study ID Numbers: 2019-508

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: Yes