Effectiveness of Bupivacaine, Ketorolac, Ketamine, vs Bupivacaine Alone in Reducing Postoperative Pocket Pain

Study Overview
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Brief Summary
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Bupivacaine is the most widely used local anesthetic agent across majority of the Cardiac Implantable Electronic device (CIED) implant procedures in the United States. It is hypothesized that the combination of Bupivacaine-Ketorolac-Ketamine (BKK) is more effective in alleviating perioperative and postoperative pain as compared to the use of bupivacaine alone. A few studies have been done to look for the effectiveness of BKK in abdominal surgical procedures. However, no study has been done to evaluate its efficacy and effectiveness in patients undergoing CIED insertion.

Detailed Description
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Bupivacaine is a widely used local anesthetic and is often administered by spinal injection prior to major surgical procedures. Ketorolac is a potent NSAID which is used for the short-term relief of moderate to severe pain. It's used for long term duration is generally limited due to its potential to cause GI ulcers/perforation and renal failure. A single dose of perioperative Ketorolac has been found to be effective in reducing opioid consumption. Ketamine is NMDA receptor antagonist and is used for its anesthetic, analgesic, and psychotomimetic effects. It is primarily used for induction and maintenance of anesthesia and induces a trance like state providing pain relief, sedation, and amnesia. Although an effective local anesthetic agent, bupivacaine has weak analgesic effect and is used in combination with several analgesic agents for effective perioperative and postoperative analgesia. A common drug used in this analgesic regimen usually includes opioids such as morphine, oxycodone, and fentanyl. Over the last few decades the United States has witnessed an opioid epidemic and post-surgical opioid prescription is one of the major contributors of this epidemic. An opioid free combination of Bupivacaine-Ketorolac-Ketamine (BKK) is thought to be effective in alleviating perioperative and postoperative pain.

Official Title
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Pain Management in Cardiac Implantable Electronic Device Insertion; Effectiveness of Bupivacaine, Ketorolac, Ketamine, vs Bupivacaine Alone in Reducing Postoperative Pocket Pain

Conditions
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Pain Management

Intervention / Treatment
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* Drug: Bupivacaine alone OR Bupivacaine-Ketorolac-Ketamine (BKK) Combination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both male and female patients Patients older than 18 years of age Patients undergoing new CIED (ICD, pacemaker, CRT-D or CRT-P) Patients willing to participate in the study Exclusion Criteria: Patients with prior history of allergic reaction to any component of the drug; bupivacaine, ketorolac, or ketamine Pregnant or breastfeeding patients Prisoners Patients younger than 18 years of age Patients not willing to participate in the study Patients deemed not suitable or unstable for the study as per physician's discretion

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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Accepts Healthy Volunteers

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Bupivacaine Alone<br>This is the control group of patients receiving 20 cc of 0.5% bupivacaine (Bupivacaine HCL 100 mg [5mg/ml] alone. The dose and number of doses of the medicines will be adjusted as per discretion of the operator. | Drug: Bupivacaine alone OR Bupivacaine-Ketorolac-Ketamine (BKK) Combination<br>* The plan will be to stratify patients in two groups: intervention group receiving 20 cc combination of BKK (Bupivacaine HCl 60 mg [3 mg/mL], Ketorolac Tromethamine 24 mg [1.2mg/mL], Ketamine HCl 24 mg [1.2 mg/mL]) vs the control group receiving 20 cc of 0.5% bupivacaine (Bupivacaine HCL 100 mg [5mg/ml]. The dose can be repeated multiple times during the procedure as per operator's discretion. The patients will be further stratified into sub-groups based on type of procedure they had undergone. Analgesia/anesthesia strategy will be local infiltration of the drug along with a sedating agent based on institutional standard of care. The dose of the medicines will be adjusted as per discretion of the operator to maintain adequate anesthesia/analgesia during and after the procedure.<br>|
| Experimental: Bupivacaine-Ketorolac-Ketamine (BKK) Combination<br>This is the intervention group of patients receiving 20 cc combination of BKK (Bupivacaine HCl 60 mg [3 mg/mL], Ketorolac Tromethamine 24 mg [1.2mg/mL], Ketamine HCl 24 mg [1.2 mg/mL]).The dose and number of doses of the medicines will be adjusted as per discretion of the operator. | Drug: Bupivacaine alone OR Bupivacaine-Ketorolac-Ketamine (BKK) Combination<br>* The plan will be to stratify patients in two groups: intervention group receiving 20 cc combination of BKK (Bupivacaine HCl 60 mg [3 mg/mL], Ketorolac Tromethamine 24 mg [1.2mg/mL], Ketamine HCl 24 mg [1.2 mg/mL]) vs the control group receiving 20 cc of 0.5% bupivacaine (Bupivacaine HCL 100 mg [5mg/ml]. The dose can be repeated multiple times during the procedure as per operator's discretion. The patients will be further stratified into sub-groups based on type of procedure they had undergone. Analgesia/anesthesia strategy will be local infiltration of the drug along with a sedating agent based on institutional standard of care. The dose of the medicines will be adjusted as per discretion of the operator to maintain adequate anesthesia/analgesia during and after the procedure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparative efficacy/superiority of BKK compared to bupivacaine alone in reducing the pain intensity | The goal of this prospective open label study is to demonstrate a comparative efficacy/superiority of BKK compared to bupivacaine alone in reducing the pain intensity. Patient's pain will be assessed using a Visual Analog Scale either through a telephone call from the research team or via clinic follow-up visit. The visual analog scale (VAS) determines pain from 0 to 10 with 0 indicating no pain (Better outcome) and 10 indicating worse pain in their life indicating (worse outcome). | Upto 1 week | 
| Comparative efficacy/superiority of BKK compared to bupivacaine alone in providing comfort | The goal of this prospective open label study is to demonstrate a comparative efficacy/superiority of BKK compared to bupivacaine alone in providing comfort. Patient's comfort will be assessed using a verbal rating score either through a telephone call from the research team or via clinic follow-up visit. The comfort score determines patients comfort from 0 to 100 with 0 indicating extremely uncomfortable (Worse outcome) and 100 indicating extremely comfortable (Better outcome). | Upto 1 week | 
| Comparative efficacy/superiority of BKK compared to bupivacaine alone in Quality of Life (QoL) | The goal of this prospective open label study is to demonstrate a comparative efficacy/superiority of BKK compared to bupivacaine alone in Quality of Life. Patient's Quality of Life will be assessed using a QoL score (EQ5-5D-5L) either through a telephone call from the research team or via clinic follow-up visit. The Quality of life questionnaire (EQ-5D-5L) has five response levels : no problems (Level 1); slight; moderate; severe; and extreme problems (Level 5), with low values suggesting better outcomes and higher values suggesting worse outcomes. | Upto 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital readmission rates | Hospital readmission rates due to device implantation related pain or surgical site infection will be analyzed. | Until 7 days (Until the end of the sutdy) | 
| Adverse Effects | Rates of adverse effects, including allergic reaction, worsening of the renal function, presyncope/syncope, HTN, drug-drug interaction or any patient reported side effects will be analyzed. | Until 7 days (Until the end of the sutdy) | 
| Cost comparison of medications | Cost of medications will be compared. | Upto 1 week | 
| Amount of pain medication used | Amount of pain medication used will be analyzed | Upto 1 week |