Dextromethorphan for Postoperative Pain

Overseen By Pui Yan, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Nathanael Heckmann

Disqualifiers: Bmi ≥ 35, Opioid abuse, others

Compensation: Varies

Number of Visits: 6

Duration: 48 hours

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether dextromethorphan, a common cough suppressant, can alleviate pain after knee replacement surgery. Researchers aim to determine if it is more effective than a placebo, which contains no active ingredients. They seek adults planning knee replacement surgery who do not have severe obesity or a history of opioid abuse. Participants will receive either dextromethorphan or a placebo to compare their effects on pain relief. As an unphased trial, this study allows participants to contribute to research that could enhance post-surgery pain management.

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

The trial information does not specify whether you need to stop taking your current medications.

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

Research has shown that dextromethorphan, a common ingredient in cough medicine, might help reduce pain after surgery. In a study with 30 patients, taking 90 mg of dextromethorphan before surgery lowered pain and drowsiness. Another review found that using dextromethorphan around the time of surgery could decrease the need for opioids (strong painkillers) and reduce pain levels in the first 24-48 hours after surgery.

While these results are promising for pain management, these studies mainly focus on the treatment's effectiveness, not just its safety. However, since dextromethorphan is already approved for treating coughs, it is generally considered safe when used as directed. Individual experiences can vary, so discussing any concerns with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard postoperative pain treatments that typically rely on opioids or NSAIDs, dextromethorphan is unique because it targets the brain's NMDA receptors, which are involved in pain perception. This mechanism is different from traditional options that primarily focus on blocking inflammation or opioid receptors. Researchers are excited about dextromethorphan for postoperative pain because it has the potential to reduce pain without the risk of addiction associated with opioids, offering a safer alternative for pain management after surgery.

What evidence suggests that dextromethorphan might be an effective treatment for postoperative pain?

Research has shown that dextromethorphan can help reduce pain after surgery. One study found that patients who took 90 mg before their operation experienced less pain and drowsiness. Another study discovered that dextromethorphan decreased the need for strong painkillers like opioids and lowered pain levels at various times post-surgery. In this trial, participants will receive either dextromethorphan or a placebo to evaluate its effectiveness in managing postoperative pain. These findings suggest that dextromethorphan could be a useful option for managing pain after surgery. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are about to have knee replacement surgery and are generally healthy or have mild to moderate systemic disease. It's not for those with a BMI of 35 or higher, a history of opioid abuse, or severe vomiting after past surgeries.

Inclusion Criteria

You are in good to moderate health according to the ASA classification.

I am 18 or older and planning to have knee replacement surgery.

Exclusion Criteria

I have experienced uncontrollable vomiting after surgery in the past.

You have a body mass index (BMI) of 35 or higher.

You have a history of misusing opioid drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 60 mg oral dextromethorphan (or matching placebo) preoperatively, as well as 30 mg 8- and 16-hours postoperatively

48 hours

Preoperative visit and postoperative monitoring at 6, 12, 24, and 48 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dextromethorphan Hydrobromide
• Placebo

Trial Overview The study is testing if Dextromethorphan, commonly used in cough medicines, can help manage pain after knee surgery better than a placebo. Participants will be randomly assigned to receive either the medication or an inactive substance.

How Is the Trial Designed?

Group I: Dextromethorphan Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Nathanael Heckmann

Lead Sponsor

Trials

1

Recruited

160+

Published Research Related to This Trial

In a study of 38 children undergoing tympanomastoid surgery, premedication with oral dextromethorphan significantly reduced the total doses of opioids needed during and after surgery compared to a placebo group.

Children who received dextromethorphan reported lower pain scores post-surgery, indicating that it effectively manages pain and decreases reliance on stronger opioids like morphine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral dextromethorphan reduces perioperative analgesic administration in children undergoing tympanomastoid surgery. Hasan, RA., Kartush, JM., Thomas, JD., et al.[2014]

In a study of 50 patients undergoing abdominal hysterectomy, oral dextromethorphan (150 mg) significantly reduced morphine consumption by 30% in the first 4 hours post-surgery compared to placebo, indicating its potential as an effective adjunct for pain management.

Despite the initial reduction in morphine use, dextromethorphan did not lead to significant differences in overall pain scores or hyperalgesia (increased sensitivity to pain) at 24 hours post-operation, suggesting that while it may help with immediate analgesic needs, it does not have lasting effects on pain sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of preoperative oral dextromethorphan on immediate and late postoperative pain and hyperalgesia after total abdominal hysterectomy. Ilkjaer, S., Bach, LF., Nielsen, PA., et al.[2019]

In a study of 100 patients undergoing abdominal hysterectomy, those receiving 30 mg of dextromethorphan (DEX) reported significantly lower pain scores in the post-anesthetic care unit compared to the placebo group.

While DEX did not reduce overall morphine consumption significantly, it did prolong the time to first morphine use, suggesting a potential benefit in managing postoperative pain with a lower incidence of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of pre- and postoperative oral dextromethorphan for reduction of intra- and 24-hour postoperative morphine consumption for transabdominal hysterectomy. Chau-In, W., Sukmuan, B., Ngamsangsirisapt, K., et al.[2013]

In a study of 75 patients undergoing oral surgery, dextromethorphan (DM) did not significantly reduce pain in the first 6 hours post-surgery, indicating it may not provide immediate analgesic effects.

However, at 48 hours post-surgery, patients taking DM reported lower pain intensity and unpleasantness, suggesting that DM may help reduce postoperative hyperalgesia by antagonizing NMDA receptors involved in pain signaling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antihyperalgesic effect of the N-methyl-D-aspartate receptor antagonist dextromethorphan in the oral surgery model. Gordon, SM., Dubner, R., Dionne, RA.[2019]

In a study of 60 patients undergoing total abdominal hysterectomy, dextromethorphan did not significantly reduce pain scores or morphine consumption compared to placebo, indicating it may not be effective for postoperative pain management.

Both the dextromethorphan and placebo groups showed similar levels of secondary hyperalgesia after surgery, suggesting that dextromethorphan does not prevent this condition following tissue trauma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan and pain after total abdominal hysterectomy. McConaghy, PM., McSorley, P., McCaughey, W., et al.[2019]

In a study of 30 patients undergoing surgery, taking 90 mg of dextromethorphan before the operation significantly reduced pain intensity and sedation levels compared to a placebo, leading to a better overall feeling of well-being.

Patients who received dextromethorphan also required about 55% less morphine and diclofenac for pain relief after surgery, indicating its effectiveness in reducing the need for postoperative analgesics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan attenuation of postoperative pain and primary and secondary thermal hyperalgesia. Weinbroum, AA., Gorodezky, A., Niv, D., et al.[2013]

In a double-blinded study of 50 patients undergoing abdominal hysterectomy, those who received oral dextromethorphan experienced significantly lower pain scores at rest 48 and 72 hours post-surgery compared to the placebo group.

Patients taking dextromethorphan also showed a trend towards reduced morphine consumption in the first 24 hours and significantly lower usage of codydramol over the next 48 hours, indicating its potential as an analgesia-sparing agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative dextromethorphan reduces postoperative pain after hysterectomy. Henderson, DJ., Withington, BS., Wilson, JA., et al.[2019]

In a study of 66 patients undergoing knee surgery, a high dose of dextromethorphan (200 mg every eight hours) resulted in a modest 29.3% reduction in morphine requirements, indicating some potential for opioid-sparing effects.

However, despite its NMDA antagonist properties, dextromethorphan did not significantly improve postoperative pain levels compared to lower doses used in previous studies, suggesting limited efficacy in enhancing pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large-dose oral dextromethorphan as an adjunct to patient-controlled analgesia with morphine after knee surgery. Wadhwa, A., Clarke, D., Goodchild, CS., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36991450/

A double-blinded, placebo-controlled, randomized study to ... The purpose of this study is to evaluate the efficacy of multi-dose dextromethorphan for postoperative pain control following TKA.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05278494?term=DEXTROMETHORPHAN&viewType=Table&rank=8

Dextromethorphan for Treatment of Postoperative Pain A randomized, placebo-controlled study to evaluate the efficacy of perioperative dextromethorphan compared to placebo for the treatment of postoperative pain.

3. withpower.com withpower.com/trial/phase-pain-postoperative-4-2022-d567f

Dextromethorphan for Postoperative Pain In a study of 30 patients undergoing surgery, taking 90 mg of dextromethorphan before the operation significantly reduced pain intensity and sedation levels ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4755866/

Perioperative Dextromethorphan as an Adjunct for ... This meta-analysis suggests dextromethorphan use perioperatively reduces postoperative opioid consumption at 24-48 hours and pain scores at 1, 4-6, and 24 hours ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S001078242200419X

Dextromethorphan as a novel nonopioid adjunctive agent ... Preemptive administration of DXM prior to surgery has been shown to decrease both intraoperative and postoperative opioid needs [10].

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40198711/

Dextromethorphan as an Opioid-Sparing Analgesic in ... This review explores dextromethorphan's multifaceted role in reducing postoperative pain and minimizing opioid consumption, thus optimizing patient recovery and ...