Regional Anesthesia for Back Surgery

Overseen By John O'Toole, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: John O'Toole

Must not be taking: Opioids, Local anesthetics

Disqualifiers: Opioid tolerance, Indwelling pain device, Allergy to anesthetics, Chronic kidney disease, others

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

Compensation: Varies

Number of Visits: 15

Duration: Up to 30 days

125 Participants Needed

Trial Summary

What is the purpose of this trial?

Opioid overuse is a widespread public health crisis in the United States with increasing rates of addiction and overdose deaths from prescription opioids. Reducing the need for opiate analgesics in the post-operative setting has become a high priority in minimizing long-term opioid use in surgical patients. This study will serve to demonstrate the efficacy of the addition of regional analgesic techniques in reducing post-operative opioid requirements in patients undergoing common lumbar spinal surgical procedures.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are opioid tolerant, meaning you take more than 30mg of morphine equivalents daily.

What data supports the effectiveness of the drug Bupivacaine-Epinephrine 0.25%-1:200,000 Injectable Solution plus clonidine for back surgery?

Research shows that adding epinephrine to bupivacaine can significantly prolong the duration of anesthesia, making it more effective for surgeries. Additionally, clonidine combined with bupivacaine and epinephrine has been shown to improve pain relief during procedures, suggesting potential benefits for back surgery. ^{1 2 3 4 5}

Is the combination of bupivacaine and epinephrine generally safe for use in humans?

The combination of bupivacaine and epinephrine, sometimes with clonidine, has been studied for various types of anesthesia and is generally considered safe, though it can cause changes in blood pressure and heart rate. Clonidine may cause sedation and has a different safety profile compared to epinephrine, which acts as a vasoconstrictor (narrows blood vessels). ^{4 6 7 8 9}

How does regional anesthesia for back surgery differ from other treatments?

Regional anesthesia for back surgery, such as using bupivacaine, is unique because it provides targeted pain relief by blocking nerve signals in a specific area, unlike general anesthesia which affects the whole body. Bupivacaine is a long-acting local anesthetic that can be used with or without a vasoconstrictor like epinephrine to prolong its effects, making it a reliable option for surgeries requiring extended pain control. ^{3 10 11 12 13}

Research Team

John O'Toole, M.D., M.S.

Principal Investigator

Rush University Medical Center

Eligibility Criteria

This trial is for adults aged 18-80 undergoing specific lumbar spinal surgeries, who can consent to participate. It's not for those with advanced kidney or liver disease, opioid tolerance, pregnancy, ongoing worker's comp cases, allergies to local anesthetics like bupivacaine or clonidine, other surgical indications besides degenerative disease, pain devices in place, or conditions affecting pain evaluation.

Inclusion Criteria

I am between 18 and 80 years old.

I am scheduled for a specific spine surgery involving 1 to 3 levels of my spine.

Willing and able to give consent

Exclusion Criteria

Active pregnancy

I have advanced kidney disease or liver failure.

Presence of an indwelling pain device (e.g., intrathecal opioid pump, spinal cord stimulator, dorsal root ganglion stimulator)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative

Patients receive either a placebo or ESPB with bupivacaine plus clonidine immediately prior to surgery

1 day

1 visit (in-person)

Treatment

Participants undergo minimally invasive lumbar spine surgery with perioperative pain management

Up to 30 days

Daily monitoring during inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including opioid consumption and complications

90 days

Multiple follow-up assessments at 14, 56, and 90 days postoperatively

Treatment Details

Interventions

• Bupivacaine-Epinephrine 0.25%-1:200,000 Injectable Solution plus clonidine
• Normal Saline

Trial Overview The study tests if adding regional anesthesia (Bupivacaine-Epinephrine plus clonidine) reduces the need for opioids after minimally invasive lumbar spine surgery. The goal is to see if this approach can help manage post-operative pain and lower long-term opioid use.

Participant Groups

Group I: Investigational Experimental Treatment 1 Intervention

Patients will undergo regional ESPB with bupivacaine plus clonidine in the holding area of the OR immediately prior to surgery. 30mL of 0.25% bupivacaine/1:200,000 epinephrine/50mcg clonidine will be administered bilaterally (total 60ml) to the lumbar paraspinal erector spine plane using ultrasound-guidance.

Group II: Control Placebo Group 1 Intervention

Patients will receive a placebo injection of normal saline via the same ESPB technique. 30ml of normal saline will be administered bilaterally (total 60ml) to the lumbar paraspinal erector spine plane using ultrasound-guidance.

Who Is Running the Clinical Trial?

John O'Toole

Lead Sponsor

Trials

1

Recruited

130+

Findings from Research

In a study of 96 elderly patients undergoing lower extremity surgery, adding 0.3 mg of epinephrine to bupivacaine significantly prolonged the duration of spinal anesthesia, enhancing the regression time to the L-2 level by 29%.

The addition of epinephrine also increased the motor blockade, indicating that it can effectively enhance the anesthetic effects of bupivacaine without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of increasing amounts of epinephrine during isobaric bupivacaine spinal anesthesia in elderly patients. Racle, JP., Benkhadra, A., Poy, JY., et al.[2013]

In a study involving 29 ASA II-III patients undergoing peripheral vascular surgery, the addition of epinephrine or clonidine to spinal bupivacaine significantly prolonged the duration of sensory blockade compared to bupivacaine alone, with sensory blockade lasting approximately 230 minutes in the combination groups versus 170 minutes in the bupivacaine-only group.

Despite the prolonged sensory blockade, the study found no significant differences in the plasma concentrations of bupivacaine among the three groups, indicating that epinephrine and clonidine do not reduce the absorption of bupivacaine into the bloodstream.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of epinephrine and clonidine on plasma concentrations of spinal bupivacaine. Boico, O., Bonnet, F., Mazoit, JX.[2019]

In a study of 435 patients, bupivacaine (0.75% in 8.25% dextrose) demonstrated superior efficacy compared to tetracaine for spinal anesthesia, with only one unsatisfactory anesthesia case in the bupivacaine group versus 19 in the tetracaine group for the lower dose.

Bupivacaine was found to be a safe and reliable option for spinal anesthesia, although tetracaine provided longer motor blockade; adding epinephrine to either anesthetic significantly extended their duration of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal anesthesia: bupivacaine compared with tetracaine. Moore, DC.[2013]

In a study of 100 healthy parturients, adding a low dose of clonidine to an epidural mixture of bupivacaine, epinephrine, and sufentanil significantly improved the quality and duration of labor analgesia compared to other combinations.

The side effects associated with clonidine were minimal, with manageable hypotension and mild sedation that did not cause fetal distress, indicating it is a safe addition to epidural analgesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clonidine added to bupivacaine-epinephrine-sufentanil improves epidural analgesia during childbirth. Claes, B., Soetens, M., Van Zundert, A., et al.[2019]

In a study of 44 patients undergoing lumbar disc surgery, the combination of epinephrine with clonidine and bupivacaine in epidural anesthesia resulted in less decrease in arterial pressure and heart rate compared to clonidine alone.

The use of low-dose epidural epinephrine helps stabilize arterial pressure during combined epidural and general anesthesia, suggesting it may enhance the safety profile of the anesthesia technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic effects of epinephrine associated to an epidural clonidine-bupivacaïne mixture during combined lumbar epidural and general anesthesia. Senard, M., Ledoux, D., Darmon, PL., et al.[2013]

In a study of 50 patients with moderate hypertension undergoing tooth extraction, the combination of lidocaine with clonidine provided similar anesthetic effects to lidocaine with epinephrine, but with better hemodynamic stability.

Patients receiving lidocaine with clonidine experienced significantly less postoperative pain and required fewer analgesics compared to those receiving lidocaine with epinephrine, suggesting clonidine may be a safer alternative for hypertensive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is clonidine an adequate alternative to epinephrine as a vasoconstrictor in patients with hypertension? Patil, PM., Patil, SP.[2013]

In a study of 33 patients receiving either clonidine or epinephrine mixed with lidocaine for brachial plexus block, clonidine resulted in higher pain scores and fewer patients being pain-free for over 12 hours compared to epinephrine, indicating less effective postoperative analgesia.

Clonidine led to higher peak plasma concentrations of lidocaine occurring earlier than with epinephrine, suggesting a reduced safety margin for local anesthetic toxicity, although it may still be useful when epinephrine is contraindicated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between clonidine and epinephrine admixture to lidocaine in brachial plexus block. Gaumann, D., Forster, A., Griessen, M., et al.[2022]

In a study of 92 women undergoing surgery, adding clonidine to lidocaine for epidural anesthesia did not significantly change the number of segments of analgesia compared to plain lidocaine or epinephrine.

Clonidine at 10 micrograms/ml resulted in a significant decrease in heart rate, while patients receiving epinephrine experienced a notable increase in heart rate, indicating that clonidine may provide a more stable cardiovascular profile during anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of clonidine added to lidocaine solution for epidural anesthesia. Nishikawa, T., Dohi, S.[2022]

Adding low-dose clonidine to hyperbaric ropivacaine significantly prolongs the duration of sensory and motor blockade as well as postoperative pain relief in patients undergoing lower limb or abdominal surgeries, based on a study of 90 patients.

While the combination improves anesthesia duration, it also increases the risk of intra-operative hypotension and bradycardia, which can be managed with standard clinical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of adding low-dose clonidine to intrathecal hyperbaric ropivacaine: A randomized double-blind clinical trial. Kakunje, R., Sethuramachandran, A., Parida, S., et al.[2020]

Bupivacaine, used in various concentrations (0.25%, 0.5%, 0.75%) for different types of anesthesia, consistently provided complete sensory anesthesia for a wide range of surgical procedures, with onset times of 4 to 10 minutes and maximum effect in 15 to 35 minutes.

While there were 15 reported systemic toxic reactions, none led to lasting harm, indicating that Bupivacaine can be used safely in clinical settings, although careful monitoring is necessary, especially with higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine: a review of 11,080 cases. Moore, DC., Bridenbaugh, LD., Thompson, GE., et al.[2019]

Bupivacaine with a vasoconstrictor has a shorter onset time for local anesthesia compared to bupivacaine without a vasoconstrictor, but the duration of anesthesia is longer without the vasoconstrictor.

Using bupivacaine without a vasoconstrictor resulted in lower postoperative pain levels and better blood circulation, which is beneficial for the osseointegration of dental implants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical parameters of the local anesthetic effects of bupivacaine applied with and without a vasoconstrictor in oral implantology. Duka, M., Lazić, Z., Stamatović, N., et al.[2019]

In a study involving 20 patients undergoing elective urologic surgery, the addition of epinephrine to bupivacaine did not change the maximum level of sensory blockade achieved, which was similar in both groups (T7 and T8).

However, the group receiving bupivacaine with epinephrine experienced significant increases in cardiac output, stroke volume, and end diastolic volume shortly after administration, highlighting the systemic effects of epinephrine, while the plain bupivacaine group showed a significant decrease in ejection fraction after 15 minutes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic monitoring in epidural blockade: cardiovascular effects of 20 ml 0.5% bupivacaine with and without epinephrine. Kerkkamp, HE., Gielen, MJ.[2013]

The combination of perioperative clonidine and bupivacaine for pain management during and after above-knee amputation resulted in very low postoperative pain scores (mean of 1.2 out of 10) and minimal opioid use (only 10 mg of oxycodone required).

Importantly, the patient did not experience any incidents of hypotension, bradycardia, or sedation during the infusion, and there was no report of stump or phantom limb pain for 12 months following the surgery, suggesting a safe and effective pain management strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of postoperative perineural infusion of bupivacaine and clonidine after lower extremity amputation in preventing phantom limb and stump pain. Madabhushi, L., Reuben, SS., Steinberg, RB., et al.[2013]

References

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

Effect of increasing amounts of epinephrine during isobaric bupivacaine spinal anesthesia in elderly patients. [2013]

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

Effects of epinephrine and clonidine on plasma concentrations of spinal bupivacaine. [2019]

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

Spinal anesthesia: bupivacaine compared with tetracaine. [2013]

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

Clonidine added to bupivacaine-epinephrine-sufentanil improves epidural analgesia during childbirth. [2019]

5. Belgium pubmed.ncbi.nlm.nih.gov

Hemodynamic effects of epinephrine associated to an epidural clonidine-bupivacaïne mixture during combined lumbar epidural and general anesthesia. [2013]

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

Is clonidine an adequate alternative to epinephrine as a vasoconstrictor in patients with hypertension? [2013]

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

Comparison between clonidine and epinephrine admixture to lidocaine in brachial plexus block. [2022]

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

Clinical evaluation of clonidine added to lidocaine solution for epidural anesthesia. [2022]

9. India pubmed.ncbi.nlm.nih.gov

Effects of adding low-dose clonidine to intrathecal hyperbaric ropivacaine: A randomized double-blind clinical trial. [2020]

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

Bupivacaine: a review of 11,080 cases. [2019]

11. Serbia pubmed.ncbi.nlm.nih.gov

Clinical parameters of the local anesthetic effects of bupivacaine applied with and without a vasoconstrictor in oral implantology. [2019]

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

Hemodynamic monitoring in epidural blockade: cardiovascular effects of 20 ml 0.5% bupivacaine with and without epinephrine. [2013]

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

The efficacy of postoperative perineural infusion of bupivacaine and clonidine after lower extremity amputation in preventing phantom limb and stump pain. [2013]