IV vs Epidural Opioids for Laparotomy Pain

Overseen By Melinda Seering, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Yair Rubin

Must not be taking: Opioids, Anticoagulants, Marijuana, others

Disqualifiers: Chronic pain, Substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 10

Duration: 4-5 days

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two methods of administering opioids (strong painkillers) to manage pain after open abdominal surgery. It compares opioids mixed with an epidural (a type of pain relief given through the back) to opioids delivered through an IV (a drip into a vein). The goal is to determine if both methods provide equally effective pain control. Individuals planning to undergo open abdominal surgery and receive an epidural might be suitable candidates for this trial. As a Phase 2, Phase 3 trial, the research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval. Participants have the opportunity to contribute to significant advancements in pain management.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are using opioids or have a history of chronic pain, you may not be eligible to participate.

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

Research has shown that hydromorphone, administered either through an epidural or an IV, has been studied for safety. For the epidural method, studies found that doses of 0.5 mg and 0.6 mg effectively reduce labor pain without harming newborns. These studies also reported no negative effects on bowel function or newborn health.

For intravenous use, hydromorphone provides strong pain relief with few side effects, such as nausea. One study showed that pain levels dropped significantly from 10 to 1 within just five minutes after administering 2 mg of IV hydromorphone, and none of the patients required additional medication for side effects.

Overall, these findings suggest that hydromorphone, whether given through an epidural or IV, is generally well-tolerated and effective for managing pain after surgery. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments for laparotomy pain because they explore different methods of delivering opioids, which can enhance pain management. Unlike the standard intravenous opioid administration, which relies on a patient-controlled analgesia (PCA) system, the study compares this with an epidural method. The epidural treatment uses hydromorphone combined with bupivacaine, delivered directly to the spine, which may provide more effective pain relief with potentially fewer side effects. This method could result in better pain control and improved patient comfort during recovery.

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

This trial will compare the effectiveness of epidural versus intravenous opioids for managing pain after laparotomy. Research has shown that both methods can effectively manage post-surgical pain. Participants may receive epidural opioids, which can help the bowel resume function sooner after surgery, addressing a common concern in abdominal operations. Patients have reported high satisfaction with epidural hydromorphone for pain relief. Alternatively, participants may receive intravenous opioids, such as hydromorphone, which provide quick pain relief and may reduce the need for additional medication later. Some studies suggest that intravenous opioids might control pain better than certain epidural methods. Both options are effective, but their success can depend on the patient and the type of surgery. ^{1 3 6 7 8}

Who Is on the Research Team?

Melinda Seering, MD

Principal Investigator

Univeristy of Iowa

Are You a Good Fit for This Trial?

This trial is for individuals undergoing laparotomy surgery who need pain control after the operation. Specific eligibility criteria are not provided, so it's important to contact the study organizers for detailed inclusion and exclusion factors.

Inclusion Criteria

Patient is able to use a patient controlled pump

I can speak and understand English.

I am scheduled for an abdominal surgery that includes a cut above my belly button and will have an epidural.

Exclusion Criteria

I have a liver condition that affects how drugs are processed.

I have used opioids before surgery.

Routine use of marijuana

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either intravenous PCA or epidural PCEA opioids combined with local anesthetic for post-operative pain management

4-5 days

Daily visits for pain and satisfaction assessment

Follow-up

Participants are monitored for safety, effectiveness, and recovery post-treatment, including bowel function and discharge readiness

10 days

Daily assessments until discharge or maximum 10 days post-operatively

What Are the Treatments Tested in This Trial?

Interventions

• Epidural administered opioid
• Intravenous administered opioid

Trial Overview The study is testing two common methods of delivering extra opioids for post-surgery pain relief: mixing them in an epidural solution or giving them separately through an IV. The goal is to see which method controls pain better.

How Is the Trial Designed?

Group I: Control Active Control 1 Intervention

Hydromorphone administered intravenous PCA combined with a continuous bupivacaine epidural infusion

Group II: Treatment Active Control 1 Intervention

Hydromorphone combined with bupivacaine in the epidural and administered as a continuous infusion with a PCEA bolus as necessary

Who Is Running the Clinical Trial?

Yair Rubin

Lead Sponsor

Trials

1

Recruited

80+

University of Iowa

Lead Sponsor

Trials

486

Recruited

934,000+

Published Research Related to This Trial

A novel multimodal analgesic approach using continuous bilateral rectus sheath catheters, along with gabapentin, clonidine, and nonsteroidal anti-inflammatories, effectively managed postoperative pain without the need for opioids or epidural analgesia in a patient after laparotomy.

The patient experienced minimal discomfort, was able to ambulate early, quickly advanced her diet, and had a short hospital stay, indicating high satisfaction and effective pain management with this alternative method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rectus sheath catheters for continuous analgesia after laparotomy--without postoperative opioid use. Malchow, R., Jaeger, L., Lam, H.[2012]

Epidural opioids provide effective postoperative pain relief in veterinary patients, offering prolonged analgesia with less sedation compared to traditional injectable opioids.

The technique is considered safe, with minimal associated risks, making it a favorable option for managing pain in veterinary surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative epidural analgesia. McMurphy, RM.[2019]

Intravenous lignocaine-fentanyl and epidural ropivacaine-fentanyl provide similar levels of pain relief after major abdominal oncosurgery, as indicated by comparable rescue fentanyl consumption and pain scores in a study of 60 patients.

However, the epidural group experienced a significantly higher rate of intraoperative hypotension, suggesting that intravenous lignocaine-fentanyl may be a safer option with fewer hemodynamic complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Lignocaine-Fentanyl Versus Epidural Ropivacaine-Fentanyl for Postoperative Analgesia After Major Abdominal Oncosurgery: A Pilot Prospective Randomised Study. Nandi, R., Mishra, S., Garg, R., et al.[2022]

Opioid analgesics, while effective for treating acute pain in hospitalized patients, carry significant risks such as sedation, respiratory depression, and even death, highlighting the need for careful monitoring.

Nurses play a crucial role in patient safety by assessing risk factors for opioid-related adverse effects and utilizing evidence-based recommendations and technology for effective monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring Hospitalized Adult Patients for Opioid-Induced Sedation and Respiratory Depression. Jungquist, CR., Smith, K., Nicely, KL., et al.[2018]

Epidural analgesia significantly reduces the risk of postoperative mortality and various complications, such as atrial fibrillation and respiratory depression, in adults undergoing surgery with general anesthesia, based on a review of 125 trials involving 9044 patients.

While epidural analgesia offers substantial benefits, it also carries risks, including increased chances of arterial hypotension and urinary retention, highlighting the need for careful risk-benefit assessments for each patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of epidural analgesia on mortality and morbidity after surgery: systematic review and meta-analysis of randomized controlled trials. Pöpping, DM., Elia, N., Van Aken, HK., et al.[2022]

In a clinical trial involving 20 patients undergoing upper abdominal surgery, those receiving fentanyl via the epidural route required significantly less medication compared to those receiving it intravenously, consuming more than twice as much fentanyl.

Both groups reported similar levels of pain, sedation, and nausea in the first 24 hours post-surgery, indicating that the method of administration did not adversely affect overall comfort or side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-controlled on-demand epidural fentanyl. A comparison of patient-controlled on-demand fentanyl delivered epidurally or intravenously. Welchew, EA., Breen, DP.[2019]

In a study of 40 patients undergoing major abdominal surgery, epidural sufentanil combined with bupivacaine resulted in a 50% reduction in sufentanil consumption compared to intravenous administration, indicating enhanced analgesic efficacy.

The findings suggest that epidural sufentanil works through spinal mechanisms, providing effective pain relief without increasing side effects or altering pain scores compared to the IV route.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal mechanisms contribute to analgesia produced by epidural sufentanil combined with bupivacaine for postoperative analgesia. Joris, JL., Jacob, EA., Sessler, DI., et al.[2021]

Epidural analgesia provided better pain relief in the acute postoperative phase compared to intravenous analgesia, with lower Visual Analog Scale (VAS) scores at 24 hours (3.29 vs 3.93).

Both epidural and intravenous analgesia showed similar effectiveness in managing chronic postoperative pain at 6 months, with no significant difference in VAS scores (2.03 for epidural vs 2.53 for intravenous).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of epidural and intravenous route for acute and chronic postoperative pain control in patients with gynecological malignancy. Balkan, B., Demirayak, G., Çetingök, H., et al.[2021]

In a study of 30 elderly patients undergoing laparoscopic cholecystectomy, intravenous (IV) anesthesia techniques provided better hemodynamic stability, with significantly lower rates of intraoperative hypotension and bradycardia compared to epidural (EPI) techniques.

Patients receiving IV anesthesia reported higher satisfaction levels than those with EPI, primarily due to discomfort and anxiety associated with the epidural procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of intravenous-based and epidural-based techniques for anesthesia and postoperative analgesia in elderly patients undergoing laparoscopic cholecystectomy. Nishikawa, K., Kimura, S., Shimodate, Y., et al.[2018]

In a study of 87 patients undergoing minimally invasive colorectal surgery, thoracic epidural analgesia (EA) did not show any clinical advantage over conventional intravenous analgesia (IA) in terms of pain relief or quality of life after surgery.

However, patients receiving EA experienced a higher incidence of hypotensive episodes and tended to use more narcotics, suggesting potential complications and increased medication use without improved outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Clinical Trial of Epidural Compared with Conventional Analgesia after Minimally Invasive Colorectal Surgery. Hanna, MH., Jafari, MD., Jafari, F., et al.[2017]

In a study involving 20 patients undergoing major surgery, epidural fentanyl administration resulted in a lower incidence of significant heart rate reduction compared to intravenous administration, suggesting a potential safety benefit.

However, overall hemodynamic stability, plasma fentanyl levels, and other physiological markers showed no significant differences between the two methods, indicating that epidural fentanyl does not provide a clear clinical advantage over intravenous administration for postoperative analgesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidural and intravenous fentanyl produce equivalent effects during major surgery. Guinard, JP., Carpenter, RL., Chassot, PG.[2019]

Epidural analgesia provided significantly better pain relief compared to intravenous morphine patient-controlled analgesia (PCA) in patients undergoing major surgery, with lower pain scores recorded up to four days post-operation.

Patients receiving epidural analgesia had a shorter hospital stay, averaging 101 hours compared to 126 hours for those on PCA, indicating a potential benefit in recovery time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidural analgesia compared with intravenous morphine patient-controlled analgesia: postoperative outcome measures after mastectomy with immediate TRAM flap breast reconstruction. Correll, DJ., Viscusi, ER., Grunwald, Z., et al.[2019]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0007091222002860

Current approaches to acute postoperative pain ... A number of systematic reviews have reported a significant reduction in time to return of bowel function with the use of epidural analgesia, with no impact on ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3747287/

Postoperative Pain Control - PMC - PubMed Central - NIH A recent observational study showed that single-dose intrathecal opioid followed by IV PCA resulted in better pain control than CEA in patients undergoing ...

3. nature.com nature.com/articles/s41598-024-75610-y

Epidural injection of hydromorphone for postoperative pain ... The epidural injection of 0.5 mg hydromorphone proved to be effective in alleviating pain caused by maternal episiotomy and did not negatively affect neonatal ...

4. bmcanesthesiol.biomedcentral.com bmcanesthesiol.biomedcentral.com/articles/10.1186/s12871-024-02420-0

The 50% effective dose of hydromorphone and morphine for ... Effective hemorrhoidectomy analgesia requires a 3:1 ratio of epidural morphine to epidural hydromorphone. Both drugs provide excellent patient satisfaction.

5. academic.oup.com academic.oup.com/bja/article-pdf/89/3/409/909767/89-3-409.pdf

Effectiveness of acute postoperative pain management This review examines the evidence from published data concerning the incidence of moderate-severe and of severe pain after major surgery, with three analgesic.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6513588/

Epidural analgesia versus patient‐controlled intravenous ... Pain scores were 7.0 to 8.0 points lower with epidural analgesia in these trials (mean scores with IVPCA 34 and 53, respectively). 7 to 24 hours, ‐, 103 (2 RCTs) ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1155/2019/9054538

Postoperative Analgesic Effects of Different Doses ... Our study showed that 0.6 mg epidural hydromorphone could be an appropriate dose for the treatment of acute postoperative pain after cesarean ...

8. link.springer.com link.springer.com/article/10.1007/s00228-020-02880-6

Single dose epidural hydromorphone in labour pain All newborn outcomes were uneventful. Hydromorphone's distribution and elimination after single epidural dose seem similar to that reported for ...