Ketamine for Hemorrhoids

Recruiting at1 trial location

Overseen by Steven Carter, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Oklahoma

Must not be taking: Narcotics

Disqualifiers: Schizophrenia, Psychosis, others

No Placebo Group

Prior Safety Data

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests if ketamine can help reduce pain in patients having surgery for severe hemorrhoids. Ketamine is given during the operation to block pain signals in the brain. The study compares patients who receive ketamine with those who do not. Ketamine has been studied for its potential to reduce postoperative pain and opioid consumption, but results have been mixed.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are using narcotics regularly, you must stop at least one month before the hemorrhoidectomy.

What data supports the effectiveness of the drug ketamine for treating hemorrhoids?

Research shows that ketamine can reduce pain and depression in various medical settings, such as surgery and cancer treatment, which suggests it might help with pain management in hemorrhoids. However, there is no direct evidence specifically for hemorrhoids. ^{1 2 3 4 5}

Is ketamine generally safe for humans?

Ketamine is generally safe for humans, but it can cause side effects like a sense of detachment from reality and increased blood pressure. Chronic use may lead to bladder and bile duct issues. ^{6 7 8 9 10}

How does the drug ketamine differ from other treatments for hemorrhoids?

Ketamine is unique because it is typically used as an anesthetic and pain reliever, often administered through injections or oral forms like gels or lollipops, which is different from standard hemorrhoid treatments that usually involve topical creams or surgical procedures. Its use for hemorrhoids is novel, as it leverages ketamine's pain-relieving properties in a new context. ^{1 11 12 13 14}

Research Team

Steven Carter, MD

Principal Investigator

University of Oklahoma

Eligibility Criteria

This trial is for adults aged 18-100 who are having surgery (hemorrhoidectomy) for severe hemorrhoids (Grade III or IV). They must be able to have general anesthesia and not use strong painkillers regularly. People with a history of schizophrenia, other hallucinatory psychiatric illnesses, or psychosis cannot participate.

Inclusion Criteria

Adults aged 18-100

You recently had surgery to remove severe hemorrhoids (Grade III or IV).

Exclusion Criteria

Inability to undergo general anesthesia

Chronic narcotic usage defined as either having a pain contract with a pain management specialist and no narcotic usage for one month prior to hemorrhoidectomy.

You have medical conditions that make it unsafe for you to have a hemorrhoidectomy (surgical removal of hemorrhoids).

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo hemorrhoidectomy with either intraoperative ketamine infusion or standard anesthesia

1 day

1 visit (in-person, surgery)

Post-operative Monitoring

Participants' post-operative pain is assessed using a numeric rating scale and the Wong-Baker FACES pain scale

2 weeks

1 visit (in-person), multiple contacts (phone)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of narcotic usage

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Ketamine (NMDA Receptor Antagonist)

Trial Overview The study is testing if ketamine can help with pain after hemorrhoid surgery. About 100 patients will either receive ketamine or no ketamine while under anesthesia, without knowing which group they're in; however, the researchers will know.

Participant Groups

Group I: Intraoperative ketamine infusion Active Control 1 Intervention

Subjects in this group will receive standard anesthesia during surgery and a dose of ketamine at 0.3 mg/kg IV bolus prior to surgical incision. If the procedure lasts more than 1 hour, an additional bolus dose will be given.

Group II: Control group Active Control 1 Intervention

This group will only receive the standard anesthesia during surgery with no ketamine.

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Dr. Scott Rollins

University of Oklahoma

Chief Executive Officer since 2016

PhD in Immunology from the University of Oklahoma

Dr. Ondria Gleason

University of Oklahoma

Chief Medical Officer

MD from the University of Oklahoma College of Medicine

Findings from Research

In a study of 268 procedures involving 35 children with leukemia, the combination of thiamylal plus pentazocine (TP) provided faster sedation compared to ketamine plus midazolam (KM) during bone marrow aspirations and intrathecal chemotherapy.

While TP was associated with a higher incidence of transient desaturation events, these were manageable with oxygen supplementation, indicating that TP can be a safe and effective alternative for sedation in pediatric oncology procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiamylal Plus Pentazocine Shows Similar Efficacy as Ketamine Plus Midazolam for Painful Procedures in Children With Leukemia. Nakagawa, S., Okamoto, Y., Kodama, Y., et al.[2019]

Adding ketamine to caudal local anaesthetics significantly prolongs the time before children need their first pain relief after surgery, with an average increase of 5.60 hours compared to local anaesthetics alone, based on a review of 13 randomized controlled trials involving 584 patients.

While ketamine reduces the need for additional pain relief (rescue analgesia), concerns about potential neurotoxicity and the appropriate dosing in children remain, indicating that further research is needed before widespread clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and adverse effects of ketamine as an additive for paediatric caudal anaesthesia: a quantitative systematic review of randomized controlled trials. Schnabel, A., Poepping, DM., Kranke, P., et al.[2022]

A meta-analysis of 15 studies involving 1697 patients showed that perioperative intravenous ketamine significantly reduces postoperative depression scores, with the most substantial effects observed on the first day after surgery (SMD -0.97).

While ketamine also decreased pain scores on the first postoperative day, it was associated with a higher risk of adverse effects, including nausea, vomiting, headaches, hallucinations, and dizziness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies. Guo, J., Qiu, D., Gu, HW., et al.[2023]

A 49-year-old woman with severe treatment-resistant major depression experienced significant improvement after receiving 36 sessions of ketamine intravenous therapy over 10 months, resulting in nearly a 50% reduction in her depressive symptoms.

The case suggests that long-term repeated ketamine therapy could be a viable option for patients with treatment-resistant depression, but further research is needed to determine the best treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketamine infusion for a patient with treatment-resistant major depression: a 10-month follow-up. Kwon, JH., Sim, WS., Hong, JP., et al.[2018]

Ketamine is recognized for its excellent pain-relieving properties and safety, making it a valuable option for short-term sedation and chronic pain management in children with cancer, although more research is needed to fully establish its efficacy in this area.

Various administration routes for ketamine, including intravenous, intramuscular, and intranasal, have been shown to be effective, and it generally does not lead to significant long-term neurological side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the clinical applications of ketamine in pediatric oncology. Prakash, S., Gupta, AK., Meena, JP., et al.[2021]

A review of 41 treatment arms from 21 studies found that ketamine formulations that maximize first pass metabolism and delay the time to peak concentration (Tmax) are associated with better safety and tolerability, particularly in reducing side effects like dissociation and increased blood pressure.

The study revealed strong correlations between the ketamine:norketamine ratio and both dissociation ratings and blood pressure changes, suggesting that careful formulation can help minimize adverse effects while maintaining the antidepressant efficacy of ketamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. Glue, P., Russell, B., Medlicott, NJ.[2021]

A new subcutaneous formulation of ketamine was developed using Captisol® to achieve a balanced pH and osmolality close to physiological levels, which may reduce injection site irritation and sterile abscesses commonly seen with current formulations.

This innovative formulation strategy allows for a buffered ketamine solution that maintains high concentration while minimizing adverse reactions, suggesting potential for broader application in other amine-based medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three Birds, One Excipient: Development of an Improved pH, Isotonic, and Buffered Ketamine Formulation for Subcutaneous Injection. Wallach, J., Gamrat, J., Jauhola-Straight, R., et al.[2022]

There is currently no standardized safety monitoring protocol for off-label use of generic ketamine, and safety monitoring for intranasal esketamine varies by jurisdiction, leading to potential gaps in patient safety.

The Ketamine Side Effect Tool (KSET) is recommended as a comprehensive tool for monitoring both acute and long-term side effects of ketamine and esketamine treatments, addressing the lack of agreed frameworks for safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. Bayes, A., Short, B., Zarate, CA., et al.[2023]

Ketamine use more than three times a week is linked to lower bladder function, as indicated by reduced voided volumes and higher scores on the Pelvic Pain, Urgency and Frequency questionnaire, especially in users with over 24 months of use.

After one year of abstinence from ketamine, individuals showed significant improvements in bladder function, with lower symptom scores and higher voided volumes, suggesting that some urinary tract changes may be reversible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lower urinary tract changes in young adults using ketamine. Mak, SK., Chan, MT., Bower, WF., et al.[2022]

Chronic use of ketamine can lead to serious health issues, including biliary duct damage (cholangiopathy) and bladder dysfunction (ulcerative cystitis), which are becoming more recognized in medical settings.

A case report of a teenage patient illustrates the rare occurrence of both conditions occurring simultaneously, highlighting the need for increased awareness among emergency physicians as recreational ketamine use rises.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recreational ketamine-induced cholangiopathy and ulcerative cystitis. Vu, DM., Freyre, K., Opsha, O., et al.[2021]

A study involving 12 children aged 1 year 7 months to 6 years found that a ketamine lollipop (50 mg) was well-tolerated, with participants showing a relatively good emotional state during premedication.

The results indicate that ketamine lollipops could be a promising option for premedication in pediatric patients, as they did not exhibit typical side effects associated with ketamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ketamine lollipop for pediatric premedication]. Horiuchi, T., Kurehara, K., Kitaguchi, K., et al.[2013]

In a study of 55 children aged 2-6 years, oral transmucosal ketamine (50 mg) was found to be less effective than oral midazolam (0.5 mg/kg) for premedication before minor surgery, as indicated by lower sedation scores and higher rates of agitation.

Children receiving ketamine had more difficulty with separation from parents and showed poorer cooperation with the anesthesia mask compared to those receiving midazolam, suggesting that ketamine may not be a beneficial alternative to midazolam in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of relatively low dose of oral transmucosal ketamine premedication in children: a comparison with oral midazolam. Horiuchi, T., Kawaguchi, M., Kurehara, K., et al.[2022]

A new oral gel formulation of ketamine was developed to provide an alternative to the bitter-tasting injectable solution, making it easier and more palatable for patients to take.

The gel maintained its effectiveness and stability over 12 weeks, with the release rate of ketamine being adjustable through the addition of flavoring and other additives, which could enhance patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preparing oral dosage form of ketamine in the hospital for simplicity and patient compliance--preparations using agar]. Kaneuchi, M., Kohri, N., Senbongi, K., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Thiamylal Plus Pentazocine Shows Similar Efficacy as Ketamine Plus Midazolam for Painful Procedures in Children With Leukemia. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and adverse effects of ketamine as an additive for paediatric caudal anaesthesia: a quantitative systematic review of randomized controlled trials. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Intravenous ketamine infusion for a patient with treatment-resistant major depression: a 10-month follow-up. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

A review of the clinical applications of ketamine in pediatric oncology. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Three Birds, One Excipient: Development of an Improved pH, Isotonic, and Buffered Ketamine Formulation for Subcutaneous Injection. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Lower urinary tract changes in young adults using ketamine. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Recreational ketamine-induced cholangiopathy and ulcerative cystitis. [2021]

11. Japan pubmed.ncbi.nlm.nih.gov

[Ketamine lollipop for pediatric premedication]. [2013]

12. France pubmed.ncbi.nlm.nih.gov

Evaluation of relatively low dose of oral transmucosal ketamine premedication in children: a comparison with oral midazolam. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Influence of premedication with xylazine on the distribution and metabolism of intramuscularly administered ketamine in cats. [2016]

14. Japan pubmed.ncbi.nlm.nih.gov

[Preparing oral dosage form of ketamine in the hospital for simplicity and patient compliance--preparations using agar]. [2019]