RIB PAIN (Rib Fractures Treated With Parental Analgesia With Infused LidocaiNe)

Study Overview
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Brief Summary
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Traumatic rib fractures (RF) are a relatively common occurrence in patients of all ages, with a 10% incidence in all trauma patients and are associated with significant morbidity and mortality. Adequate analgesia is paramount for preventing pulmonary complications and can reduce morbidity and mortality. There is longstanding evidence of lidocaine's effectiveness and safety in the post-operative patient and the investigators hypothesize that this modality may prove to be ideal in trauma patients with RF. Therefore, it is imperative that intravenous lidocaine be investigated to ascertain if there is significant benefit for pain reduction in patients who have sustained rib fractures. A single-centre, double-blind, randomized control trial to evaluate the analgesic efficacy of a 72-96 hour IV lidocaine infusion plus standard analgesics versus placebo infusion plus standard analgesics will be performed on patients (age 18 or older) diagnosed with two or more traumatic rib fractures ,from blunt thoracic trauma, requiring hospital admission at Victoria Hospital. The primary outcome is mean pain score, as measured on the Visual Analog Scale (VAS) when the patient is at rest and with movement. Secondary outcomes are protocol adherence, patient satisfaction as measured on the VAS, incidence of respiratory failure requiring mechanical ventilation, hospital length of stay, ICU length of stay, mortality, incidence of lidocaine toxicity, treatment regimens (use of additional non-opioid analgesics) and total morphine equivalents used (including breakthrough doses). This trial will serve to quantify the analgesic efficacy of intravenous lidocaine for patients with traumatic rib fractures. Successful completion of a single centre trial will inform the development of a multi-centre trial powered to demonstrate a reduction in respiratory failure in the trauma population.

Detailed Description
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This trial will use a randomized double blind design. All patients (age 18 or older) diagnosed with two or more traumatic rib fractures requiring hospital admission at Victoria Hospital will be identified at the time of admission by trauma team members and / or ICU research assistants. Patients unable to understand or follow instructions in English or French, and those unable to complete the Visual Analog Scale (VAS) for pain for any reason, will be excluded. Any physician member of the inpatient trauma service team, trauma nurse practitioner, or ICU research assistants may approach patients and their families to discuss participation in the trial. Research assistants will be responsible for providing the Letter of Information and Consent Form to families, and storing them once complete. Consented patients will be randomized at admission using the online randomization tool, like REDCAP, by pharmacy. Once randomized, research assistants will contact pharmacy to order Study Drug, but will remain blinded to study arm Consented patients will receive either standard care (acetaminophen, NSAIDs, opioids) plus IV placebo or standard care plus IV lidocaine using a fixed strategy with variable blocks and a 1:1 allocation ratio. The pharmacy will be the only party unblinded to randomization and will distribute the Study Drug [either IV lidocaine or Lactated Ringer's (a clear colourless solution that is indistinguishable from Lidocaine)] to study participants. All patients will be followed throughout their hospital stay by our research assistants to assess pain and secondary outcomes. IV lidocaine will be administered as a bolus dose of 2 mg/kg (maximum dose 100 mg) followed by a 2 mg/kg/hr infusion for 72-96 hrs. Lactated Ringer's will be administered at the same overall rate to the control group. Patient pain scores will be accessed at the bedside using the VAS at time 0hrs and every six hours for the duration of study drug infusion. Daily monitoring of the patient will be performed by the trauma team and bedside nurses. Clinical care will be conducted as usual with the exception of the provision of study drug, the recording of pain Q6 hours, and the assessment of patient satisfaction at the end of the 72-96 hour infusion. All other patient data will be collected from the patient's EMR and bedside chart. In accordance with LHSC hospital Lidocaine policy, all study patients will be on telemetry to monitor for arrhythmias resulting from lidocaine toxicity. As the use of IV lidocaine is already common in the LHSC patient population, all nursing staff are trained to detect signs and symptoms of lidocaine toxicity, and will contact the treatment and research teams if these develop. The study drug infusions will be stopped if any signs of toxicity are seen. The treating team will be unblinded to randomization group in any cases of suspected Lidocaine toxicity. The primary outcome will be mean pain score calculated from the multiple VAS measures performed during Lidocaine infusions when the patient is at rest and with movement. Secondary outcomes are protocol adherence, patient satisfaction as measured on the VAS, incidence of respiratory failure requiring mechanical ventilation, hospital length of stay, ICU length of stay, mortality, incidence of lidocaine toxicity, treatment regimens (use of additional non-opioid analgesics) and total morphine equivalents used (including breakthrough doses). Secondary outcomes will be recorded by the ICU research assistants on a daily basis during each patient's index stay. Research assistants will help administer the satisfaction survey to patients as soon as possible following completion of the 72-96 hour Lidocaine infusion. The methodology, pain and satisfaction reporting with VAS is very similar to the investigator's previous work. A sample size of 26 patients is required to find a difference between two independent group means using the following parameters: (1) a 20% reduction in VAS score (20mm), (2) 90% power, (3) probability of a Type I error = 5%, and s stand deviation of 15% (15mm). An anticipated attrition rate of 20% will be used to ensure enough patients are included for adequate power. Therefore a minimum of 32 patients will be enrolled in the study. Continuous data will be reported as mean +/- standard deviation or median and interquartile range, depending on the distribution of each data point. Categorical data will be reported as percentages with corresponding 95% confidence intervals. The mean pain score will be compared between treatment groups using Student's T-test. Findings with a Type I error rate < 5% will be considered statistically significant. Analyses of secondary outcomes will be primarily descriptive. Any significance testing of these outcomes will be strictly hypotheses-generating.

Official Title
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A Randomized Control Trial of Intravenous Lidocaine for the Management of Traumatic Rib Fractures: a Single Trauma Centre Trial

Conditions
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Rib Fracture Multiple, Pain, Chest, Pain, Acute, Respiratory Failure, Thoracic Injuries, Trauma Chest

Intervention / Treatment
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* Drug: Intervention: Lidocaine
* Drug: Control: Standard Care + Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All adult patients, 18 years or older, admitted to Victoria Hospital's Trauma Service with two or more traumatic rib fractures. Exclusion Criteria: Patients under 18 years old Patients who sustained complex trauma with multiple other injuries or have decreased LOC or required intubation at admission Patients with a known allergy/sensitivity to Lidocaine or other local anesthetic, amide anesthetics or components of the solution Patients with a known history of hypersensitivity to methylparaben and/or propylparaben (preservatives used in multidose solutions), or to their metabolite para amino benzoic acid Patients who do not speak English with adequate fluency to consent or participate in the VAS survey Patients receiving epidural analgesia for another reason Patients with pre-existing cardiac arrhythmias including Adam-Stokes syndrome; Wolff- Parkinson-White syndrome; and severe degrees of sinoatrial, atrioventricular, or intraventricular heart block (except in patients with a functioning artificial pacemaker) Patients who are known to be pregnant or breast feeding, as identified on Past Medical History, or by initial laboratory investigations performed as a part of standard trauma team assessment Patients with known hepatic/renal disease, as identified on Past Medical History, or by initial laboratory investigations performed as a part of standard trauma team assessment Patients who refuse inclusion

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: RCT, single site, double blinded
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control: Standard Care + Placebo<br>Standard care (acetaminophen, NSAIDs, opioids, gabapentin) as directed by MRP care team plus IV placebo (Lactated Ringers). Lactated Ringers will be delivered as a initial bolus and then run as a continuous infusion to mimic the volume (as per Kg) of study drug for 72-96 hours. Standard care will be determined by the care team with no limitations introduced by the research team. Medications utilized and dosing regimes will be recorded after the intervention. | Drug: Control: Standard Care + Placebo<br>* Placebo IV bolus and infusion. Weight based to mimic lidocaine volume.<br>* Other names: Ringer's Lactate;|
| Experimental: Intervention: Lidocaine<br>Standard care (acetaminophen, NSAIDs, opioids, gabapentin) as directed by MRP care team plus IV lidocaine. IV lidocaine will be administered as a bolus dose of 2 mg/kg (maximum dose 100 mg) followed by a 2 mg/kg/hr infusion for 72-96 hrs. | Drug: Intervention: Lidocaine<br>* IV Lidocaine bolus plus infusion. Weight based.<br>* Other names: Lidocaine Hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Visual Analogue Scale (VAS) Score for Pain | The primary outcome will be mean pain score calculated from the multiple VAS measures performed during Lidocaine infusions when the patient is at rest and with movement. The VAS for pain is a continuous numerical scale, demonstrated by a horizontal or vertical line, 10 cm long, with verbal descriptors at each end demonstrating the extremes, +/- a central descriptor. It is a scale essentially from 1 to 10, with one being no pain and 10 being the worst pain possible. Subjects mark on the line their approximate pain score by drawing a transecting line. This will be measured with a ruler from the start point on the line and recorded as a data point. | Pain score to be measured before treatment initiation and every 6 hours thereafter until 72-96 hours. Scores will be performed by bedside nursing. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Protocol Non-adherence | Incidence of protocol violations with corresponding 95% confidence intervals. Descriptions of the deviations will be recorded. Types include, number of patients who received lidocaine that were not assigned to that group; number of patients who were assigned lidocaine and never received the study drug; non-weight based dosages of lidocaine; etc. | Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period. | 
| Patient satisfaction as measured on the Visual Analogue Scale for Satisfaction | The VAS for pain is a continuous numerical scale, demonstrated by a horizontal or vertical line, 10 cm long, with verbal descriptors at each end demonstrating the extremes, +/- a central descriptor. It is measured from one, representing not satisfied at all to ten, representing completely satisfied. Subjects mark on the line their approximate pain score by drawing a transecting line. This will be measured with a ruler from the start point on the line and recorded as a data point. Score will be performed on a VAS at the end of the treatment period. | Research assistants will help administer the satisfaction survey to patients as soon as possible following completion of the 72-96 hour Lidocaine infusion. | 
| Incidence of respiratory failure requiring mechanical ventilation | Categorical data will be reported as percentages with corresponding 95% confidence intervals. | Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period. | 
| Hospital length of stay | Continuous data will be reported as mean +/- standard deviation or median and interquartile range, depending on the distribution of each data point. | Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period. | 
| ICU length of stay | Continuous data will be reported as mean +/- standard deviation or median and interquartile range, depending on the distribution of each data point. | Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period. | 
| Incidence of Mortality | Categorical data will be reported as percentages with corresponding 95% confidence intervals. | Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period or when the mortality occurs. | 
| Incidence of lidocaine toxicity/adverse events | Categorical data will be reported as percentages with corresponding 95% confidence intervals. Toxic symptoms will also be recorded. | Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period. | 
| Treatment regimens (use of additional non-opioid analgesics): Medication type | Any non-opioid analgesic medications used will be recorded. Incidence of each medications' use will be reported as percentages with corresponding 95% confidence intervals. | Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period. | 
| Treatment regimens (use of additional non-opioid analgesics): Dosages | Dosages of any non-opioid analgesic medications used will be recorded. | Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period. | 
| Treatment regimens (use of additional non-opioid analgesics): Frequency | Dosing frequency of any non-opioid analgesic medications used will be recorded. | Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period. | 
| Treatment regimens (use of additional non-opioid analgesics): Delivery Route | Route of delivery of any non-opioid analgesic medications used will be recorded. Categories include by mouth (PO); subcutaneously (SubQ); Intravenously (IV); and other. | Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period. | 
| Total morphine equivalents used (including breakthrough doses) | Dose will be the cumulative opioid dose over the 72-96 hour period. Conversion to Morphine Equivalents will be calculated. Continuous data will be reported as mean +/- standard deviation or median and interquartile range, depending on the distribution of each data point. | Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lidocaine Infusions, Thoracic trauma, Analgesic Management, Rib Fractures, Pain