Lidocaine + Ketamine for Postoperative Pain

Overseen By Steven Minear, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: The Cleveland Clinic

Must not be taking: Gabapentin, Magnesium, Nitrous oxide, others

Disqualifiers: Pregnancy, Morbid obesity, Cardiac failure, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Surgery duration (2+ hours)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if using lidocaine and ketamine (an anesthetic) during and after surgery can reduce opioid use and lower pain levels for those recovering from abdominal surgery. Participants will receive one of the following: lidocaine and ketamine, lidocaine and a placebo, ketamine and a placebo, or a placebo only. The goal is to find a safer and more effective method for managing post-surgical pain. This trial suits adults planning elective abdominal surgery under general anesthesia for at least two hours. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking pain management solution.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you use gabapentin, magnesium, or nitrous oxide around the time of surgery. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In past studies, both lidocaine and ketamine have shown promise in managing post-surgical pain. Research shows that lidocaine can reduce pain and lessen the need for opioids after an operation. Ketamine, when used in low doses, has also effectively managed pain without causing additional side effects.

When used together, lidocaine and ketamine have worked well. One study found that using both can improve pain relief during and after surgery. Importantly, this combination did not lead to more side effects.

However, while lidocaine is generally safe, it can be dangerous if not used correctly. Proper administration is crucial. Overall, evidence suggests that the combination of lidocaine and ketamine is well-tolerated and effective for managing pain. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore the combination of lidocaine and ketamine for managing postoperative pain. Unlike traditional pain relief methods, which often rely on opioids or NSAIDs, this approach leverages ketamine's unique ability to block certain pathways in the brain that process pain, potentially offering faster and more effective pain relief. Lidocaine, known for its local anesthetic properties, complements ketamine by stabilizing nerve activity and reducing inflammation. Together, they could provide a powerful alternative that minimizes the risk of side effects associated with long-term opioid use, making them a promising option for patients recovering from surgery.

What evidence suggests that this trial's treatments could be effective for reducing postoperative pain?

Research has shown that both lidocaine and ketamine can reduce pain and the need for opioids after surgery. In this trial, participants may receive either lidocaine and ketamine together, lidocaine with a placebo, or ketamine with a placebo. Studies indicate that adding ketamine to lidocaine can decrease the amount of pain medication needed during and after surgery. This combination also relieves pain more effectively than using either one alone. Ketamine alone has been shown to lessen pain and reduce opioid use. It also aids recovery by lowering the risk of nausea and vomiting. Together, these treatments offer promising benefits for managing pain after surgery. ^{6 7 8 9 10}

Who Is on the Research Team?

Steven Minear, MD

Principal Investigator

Cleveland Clinic Florida

Are You a Good Fit for This Trial?

Adults aged 18-80 undergoing elective inpatient abdominal surgery with general anesthesia lasting over 2 hours can join. Excluded are pregnant or breastfeeding individuals, those needing post-op ventilation, using certain drugs like gabapentin, obese patients (BMI ≥35), people with severe heart failure or communication issues, and those allergic to the study meds.

Inclusion Criteria

You had surgery with general anesthesia that lasted 2 hours or more.

Elective inpatient open or laparoscopic abdominal surgery

Exclusion Criteria

Pregnancy or breastfeeding

You are scheduled to need a breathing machine after surgery.

You are planning to have regional anesthesia or pain relief.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive perioperative infusions of lidocaine and/or ketamine during abdominal surgery

Surgery duration (2+ hours)

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for opioid consumption, pain scores, and other outcomes for 48 hours post-surgery

48 hours

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine
• Lidocaine

Trial Overview The trial is testing if lidocaine and/or ketamine given during surgery can reduce opioid use and pain after abdominal operations. Patients will receive either both drugs, just one of them, or a placebo in a randomized manner to compare their effects on postoperative recovery.

How Is the Trial Designed?

Group I: Lidocaine and placebo Experimental Treatment 1 Intervention

Lidocaine and placebo

Group II: Lidocaine and ketamine Experimental Treatment 1 Intervention

Lidocaine and ketamine

Group III: Ketamine and placebo Experimental Treatment 1 Intervention

Ketamine and placebo

Group IV: Placebo and placebo Placebo Group 1 Intervention

Placebo and placebo

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4606413/

Role of Ketamine in Acute Postoperative Pain Management In a number of limited situations, ketamine has shown some efficacy in controlling postoperative pain and decreasing opioid consumption.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11679605/

The Impact of Ketamine on Outcomes in Acute Pain ... Evidence shows that intravenous ketamine reduces the pain intensity, postoperative opioid use, and the risk of vomiting and nausea while improving analgesia.

3. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1394219/full

The impact of ketamine on pain-related outcomes after ... Additionally, a review found that using low-dose ketamine along with morphine after thoracic surgery can lessen postoperative pain and is safer ...

4. nature.com nature.com/articles/s41380-023-01945-z

Efficacy and safety of perioperative application of ketamine ... In conclusion, perioperative application of ketamine reduces postoperative depression and pain scores with increased risk of adverse effects.

5. journals.lww.com journals.lww.com/ijsopen/fulltext/2025/08000/effectiveness_of_preemptive_intravenous_ketamine.7.aspx

Effectiveness of preemptive intravenous ketamine on ... We conclude that preemptive intravenous ketamine decreases pain score, prolongs postoperative analgesia requests, and decreases analgesia consumption when ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03391427

Study Details | NCT03391427 | Ketamine, Lidocaine and ... Perioperative lidocaine infusion has been shown to reduce postoperative pain and opioid consumption. Perioperative low dose Ketamine has shown improved ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1089947224001084

Efficacy and Safety of Adding Ketamine to Lidocaine in ... The addition of K to L in IVRA shortened the onset time, prolonged the block time, and reduced intraoperative and postoperative pain without increasing ...

8. associationofanaesthetists-publications.onlinelibrary.wiley.com associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/anae.15270

The use of intravenous lidocaine for postoperative pain and ... Intravenous lidocaine is used widely for its effect on postoperative pain and recovery but it can be, and has been, fatal when used inappropriately and ...

9. rapm.bmj.com rapm.bmj.com/content/47/Suppl_1/A244.1

B334 Lidocaine and ketamine infusion for intraoperative ... Our pilot study concluded that Ketamine/Lidocaine infusion significantly decreases the pain scores in recovery and the doses of opioids used postoperatively in ...

10. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/48/NCT04084548/Prot_SAP_000.pdf

Ketamine and/or lidocaine analgesia for abdominal surgery Single preoperative doses of lidocaine and ketamine also did not reduce postoperative pain or opioid consumption after gynecological laparotomies (53).