Ketamine vs Lidocaine in Traumatic Rib Fractures

• ClinicalTrials.gov Identifier: NCT04781673
• Recruitment Status: Recruiting
• First Posted: March 4, 2021
• Last Update Posted: April 8, 2021
• Sponsor: Brittany Kiracofe
• Information provided by (Responsible Party): Brittany Kiracofe, Spectrum Health Hospitals

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Rib Fractures; Rib Fracture Multiple; Rib Trauma	Drug: Ketamine; Drug: Lidocaine	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 74 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Prospective Randomized Trial, Single-blinded
• Masking: Single (Participant)
• Masking Description: Medication infusion and medication IV bag will be covered with brown protect from light bag
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized, Single-Blinded Trial of Ketamine Versus Lidocaine Infusions for Multimodal Pain Management in Traumatic Rib Fracture Patients
• Actual Study Start Date: April 1, 2021
• Estimated Primary Completion Date: January 2023
• Estimated Study Completion Date: January 2023

Arms and Interventions

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 Name: 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 Name: Xylocaine

Outcome Measures

Primary Outcome Measures :

1. Oral Morphine Equivalent - Opioid Usage [ Time Frame: 0-24 hours post infusion ]
   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.

Secondary Outcome Measures :

1. Visual Analogue Numeric Pain Score [ Time Frame: 0-24; 24-48; 48-72 hours post infusion ]
   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.
2. Oral Morphine Equivalent - Opioid Usage [ Time Frame: 24-48; 48-72 hours post infusion ]
   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.
3. Respiratory Failure [ Time Frame: 0-30 days post-infusion ]
   Respiratory failure was defined by need for mechanical intubation
4. Use of Regional/Neuraxial anesthesia [ Time Frame: 0-30 days post infusion ]
   Measure of regional/neuraxial anesthesia placement rates. Patient would need to be taken off study medication if decision made to place regional/neuraxial anesthetic.
5. Hospital Length of Stay [ Time Frame: Will capture retrospectively after patient's medical discharge ]
   Total hospital length of stay up to 365 days
6. Intensive Care Unit Length of stay [ Time Frame: Will capture retrospectively after patient's medical discharge ]
   Total intensive care unit length of stay up to 365 days
7. Incentive Spirometry [ Time Frame: 0-24; 24-48; 48-72 hours post infusion ]
   Measure of percent improvement in incentive spirometry level from baseline (before infusion). Incentive spirometry levels range from 0-4,000 mL.
8. Adverse events [ Time Frame: 0-72 hours post infusion ]
   Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
9. In-Hospital mortality [ Time Frame: Will capture retrospectively after patient's medical discharge ]
   Patient's death will be recorded if it occurs before discharge

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Adults ≥ 18 years old
2. ≥ 3 traumatic blunt rib fractures
3. Enrollment within 16 hours of being admitted to the hospital

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.

Contacts and Locations

Contacts

Contact: Steffen J Pounders, BS; 616-486-0461; steffen.pounders@spectrumhealth.org

Contact: Brittany Kiracofe, PharmD; brittany.kiracofe@spectrumhealth.org

Locations

United States, Michigan

Spectrum Health Hospital; Recruiting

Grand Rapids, Michigan, United States, 49503

Contact: Steffen J Pounders, BS 616-486-0461 Steffen.Pounders@spectrumhealth.org

Contact: Brittany R Kiracofe, PharmD 616-352-2462 brittany.kiracofe@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 Yand, MD

Principal Investigator: Brittany R Kiracofe, 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

Sponsors and Collaborators

Brittany Kiracofe

More Information

• Responsible Party: Brittany Kiracofe, Principal Investigator, Spectrum Health Hospitals
• ClinicalTrials.gov Identifier: NCT04781673
• Other Study ID Numbers: 2019-508
• First Posted: March 4, 2021
• Last Update Posted: April 8, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Brittany Kiracofe, Spectrum Health Hospitals:

Lidocaine; Ketamine; Rib Fracture; Traumatic Rib Fracture

Additional relevant MeSH terms:

Fractures, Bone; Rib Fractures; Fractures, Multiple; Wounds and Injuries; Thoracic Injuries; Multiple Trauma; Lidocaine; Ketamine; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Analgesics; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents