Spinal Anesthesia for Liver Surgery

(SAFER-L Trial)

Overseen By Alex Grunfeld, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Manitoba

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

Disqualifiers: Emergency surgery, Liver transplant, Cardiovascular disease, Kidney disease, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

128 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares spinal and epidural anesthesia for individuals undergoing liver surgery. Researchers aim to determine if spinal anesthesia, specifically with intrathecal morphine, offers better blood pressure control and faster recovery, using less IV fluids while effectively managing pain. This study may suit adults planning elective liver surgery who can adhere to the study procedures and have no major heart or kidney issues. As an unphased trial, it provides an opportunity to contribute to medical knowledge and potentially enhance anesthesia practices for future patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using antiplatelet agents or anticoagulants (except for low-dose aspirin), you may need to stop them before surgery.

What prior data suggests that spinal anesthesia with intrathecal morphine is safe for liver surgery?

Research has shown that spinal anesthesia with intrathecal morphine is usually well-tolerated. Studies have found it effectively lowers pain levels and reduces the need for additional pain medication after surgery. However, some individuals might experience side effects like nausea, itching, or difficulty urinating within the first day post-surgery.

For the epidural option, past studies suggest it can also provide strong pain relief. It might have similar side effects, but these can vary among individuals.

Both treatments have been safely used in various surgeries, but each has its own potential side effects. Discussing with the trial team is important to determine which option might be best. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about spinal anesthesia with intrathecal morphine for liver surgery because it offers a potentially less invasive and more targeted approach to pain management compared to traditional methods like general anesthesia or continuous thoracic epidural analgesia. This technique uses a specific delivery method, injecting morphine directly into the spinal fluid, which could lead to more effective and longer-lasting pain relief with possibly fewer side effects. By focusing on a high-spinal anesthesia approach combined with intrathecal morphine, this method may also reduce the need for extensive postoperative opioid use, addressing a significant concern with current pain management practices.

What evidence suggests that spinal anesthesia with intrathecal morphine is effective for liver surgery?

Research has shown that spinal anesthesia with morphine injected into the spinal canal, a treatment arm in this trial, effectively reduces post-surgery pain. Studies have found that it lowers pain levels and decreases the need for additional strong painkillers without causing major side effects. Specifically, one study found that patients receiving this type of morphine used fewer opioids the day after surgery. This method is also cost-effective and reliable, with a low risk of technical problems. Overall, spinal anesthesia with morphine appears to be a promising option for managing pain and aiding recovery after liver surgery. Another treatment arm in this trial involves thoracic epidural analgesia, which will be compared to assess effectiveness and outcomes. ^{1 2 3 6 7}

Who Is on the Research Team?

Alex Grunfeld, MD

Principal Investigator

University of Manitoba

Are You a Good Fit for This Trial?

This trial is for adults over 18 who need elective liver resection surgery and can consent to the study. They should have a BMI between 17-40, be in stable physical condition (ASA-PS I to III), and not be pregnant or breastfeeding. The surgery shouldn't include extra procedures adding more than an hour.

Inclusion Criteria

I am having liver surgery through a cut near my belly, and any extra surgery won't extend the time by more than an hour.

You have signed and dated a form saying you understand and agree to be in the study.

I am willing and able to follow all study rules and be available for its duration.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo liver resection surgery with either spinal anesthesia or thoracic epidural analgesia

1 week

Intraoperative and postoperative monitoring

Postoperative Monitoring

Participants are monitored for fluid balance, pain intensity, and opioid consumption for 72 hours post-surgery

72 hours

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including vasopressor-free days and complications

30 days

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Bupicavaine 0.125% epidural solution
• Bupivacaine 0.25% Preservative-Free Injectable Solution
• Bupivacaine 0.75% in Dextrose Inj 8.25%
• Hydromorphone 10 mcg/mL epidural solution
• Morphine
• Spinal anesthesia with intrathecal morphine

Trial Overview The study compares spinal anesthesia with intrathecal morphine against continuous thoracic epidural analgesia for pain control after liver surgery. It aims to see if spinal anesthesia leads to better blood pressure control, less fluid needed post-surgery, and quicker recovery.

How Is the Trial Designed?

Group I: Intrathecal morphine Experimental Treatment 3 Interventions

Spinal anesthesia with intrathecal morphine Bolus (pre-induction): High-spinal anesthesia with 0.25 mg⋅kg-¹ hyperbaric bupivacaine 0.75% plus 3 mcg⋅kg-¹ intrathecal morphine (preservative-free) Postoperative analgesia: IV-PCA hydromorphone (bolus: 0.2 mg \[range: 0.1-0.4 mg\]; 5 min lockout; no infusion)

Group II: Thoracic epidural analgesia Active Control 4 Interventions

Continuous thoracic epidural analgesia Bolus (pre-induction): 0.25 mg⋅kg-¹ bupivacaine 0.25% plus 1 mcg⋅kg-¹ hydromorphone (0.1 mL⋅kg-¹) Infusion (initial): 0.25 mg⋅kg-¹⋅h-¹ bupivacaine 0.25% plus 1 mcg⋅kg-¹⋅h-¹ hydromorphone (0.1 mL⋅kg-¹⋅h-¹) Infusion (range): 0.19-0. 3 mg⋅kg-¹⋅h-¹ bupivacaine 0.25% plus 0.75-1.25 mcg⋅kg-¹⋅h-¹ hydromorphone (0.075-0.125 mL⋅kg-¹⋅h-¹) (3-10 mL⋅h-¹) Postoperative analgesia: (1) Epidural solution, bupivacaine 0.125% with hydromorphone 10 mcg·mL-¹, infusion range as above (0.075-0.125 mL⋅kg-¹⋅h-¹) (3-10 mL⋅h-¹), continued for a maximum of 72 h postoperatively; (2) IV-PCA hydromorphone (bolus: 0.2 mg \[range: 0.1-0.4 mg\]; 5 min lockout; no infusion).

Spinal anesthesia with intrathecal morphine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Spinal anesthesia with intrathecal morphine for:

• Pain management for surgical procedures
• Anesthesia for liver resection surgery

Approved in European Union as Spinal anesthesia with intrathecal morphine for:

• Pain management for surgical procedures
• Anesthesia for various surgeries including liver resection

Approved in Canada as Spinal anesthesia with intrathecal morphine for:

• Pain management for surgical procedures
• Anesthesia for liver resection and other surgeries

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

Published Research Related to This Trial

A prospective study involving 30 surgical patients demonstrated that low doses of intrathecal morphine (0.06 to 0.08 mg) mixed with local anesthetic provided effective pain relief for over 20 hours, significantly delaying the need for additional analgesics compared to a control group.

The use of these low doses was found to be safe, with no reported cases of respiratory depression or significant side effects, making it a reliable option for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intrathecal morphine for postoperative pain]. Schaer, H., Baasch, K., Prochacka, K.[2013]

Intrathecal morphine at an average dose of 0.01 mg/kg provided significant pain relief for 31 out of 33 patients undergoing spinal arthrodesis, lasting an average of 18 hours.

While low-dose intrathecal morphine was effective for pain management, there were concerns about respiratory depression in some patients, indicating the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal morphine: dosage and efficacy in younger patients for control of postoperative pain following spinal fusion. Blackman, RG., Reynolds, J., Shively, J.[2022]

Intrathecal morphine provided strong and long-lasting pain relief in a study of 32 surgical patients, with minimal impact on brain function, making it an effective analgesic option.

However, the study highlighted a significant risk of delayed respiratory depression, particularly in elderly patients, suggesting that lower doses should be used for this population to avoid serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative pain control with intrathecal morphine. Gjessing, J., Tomlin, PJ.[2019]

In a study of 60 patients undergoing transurethral resection of the prostate (TURP), a single dose of 150 μg intrathecal morphine combined with bupivacaine significantly reduced the need for additional pain relief compared to a 75 μg dose.

The higher dose (150 μg) was associated with a slightly increased incidence of mild pruritis in 20% of patients, but overall, both doses provided effective analgesia with high patient satisfaction and low rates of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of 75 and 150 μg doses of intrathecal morphine for postoperative analgesia after transurethral resection of the prostate under spinal anesthesia. Ozbek, H., Deniz, MN., Erakgun, A., et al.[2014]

Intrathecal morphine is effective for postoperative pain control but is associated with high rates of side effects, including nausea (21.5%), vomiting (14.8%), and pruritus (59.5%) in a study of 1,306 patients.

The incidence and severity of these side effects are significantly correlated with factors such as female gender, cesarean section, and higher doses of morphine (over 0.2 mg), indicating a need for careful dosing and consideration of alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nausea, vomiting and pruritus induced by intrathecal morphine. Chinachoti, T., Nilrat, P., Samarnpiboonphol, P.[2013]

In a study of 144 women undergoing abdominal hysterectomy, adding intrathecal morphine to bupivacaine significantly reduced the amount of morphine needed for pain relief in the first 24 hours after surgery, with the most effective dose being 200 μg.

No serious side effects were reported, and while pruritus was noted in morphine groups, overall side effects like nausea were similar across all groups, indicating that intrathecal morphine is a safe option for post-operative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose intrathecal morphine effects on post-hysterectomy pain: a randomized placebo-controlled study. Hein, A., Rösblad, P., Gillis-Haegerstrand, C., et al.[2022]

In a study of 42 pediatric patients undergoing spinal deformity surgery, intrathecal morphine (IM) was administered safely to most patients with spinal cord syrinxes, showing no neurological complications in the IM group.

While one patient experienced respiratory depression after surgery, the overall incidence of complications like pruritus and nausea/vomiting was mild and similar between those who received IM and those who did not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal Morphine in the Presence of a Syrinx in Pediatric Spinal Deformity Surgery. Ina, J., Poe-Kochert, C., Hardesty, CK., et al.[2021]

In a case series of six patients who received an incorrect dose of intrathecal morphine (1 mg/ml instead of 50 mcg/ml), four experienced serious adverse events, primarily respiratory depression and somnolence, highlighting the risks associated with dosing errors in pain management.

A systematic review of 63 cases indicated that serious adverse events after intrathecal morphine typically occur within 2 to 24 hours post-injection, with respiratory depression being life-threatening at doses exceeding 900 mcg, but naloxone did not compromise analgesia, suggesting a need for careful monitoring and dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious Adverse Events after a Single Shot of Intrathecal Morphine: A Case Series and Systematic Review. Koning, MV., Reussien, E., Vermeulen, BAN., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1365182X21001787

Evaluation of the addition of bupivacaine to intrathecal ... The aim of the present study was to retrospectively evaluate the potential benefits of the addition of hyperbaric 0.75% (11.25 mg) bupivacaine to IT morphine ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8879321/

Analgesic Effect of Intrathecal Morphine Combined with Low ... A lower dose of 5 mg combined with morphine was compared against saline and shown to be effective in lowering pain scores and opioid consumption without adverse ...

3. bmcanesthesiol.biomedcentral.com bmcanesthesiol.biomedcentral.com/articles/10.1186/s12871-020-01113-8

Intrathecal morphine is associated with reduction in ... The primary outcome - cumulative oMEDD on POD1 - was significantly reduced in the ITM group. Postoperative pain scores up to 24 h post-surgery ...

4. wjgnet.com wjgnet.com/2218-6182/full/v3/i3/191.htm

Intrathecal morphine for postoperative analgesia IT morphine for postoperative pain relief is cost-effective, moderately safe and reliable technique with low risk of technical failure.

5. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.814538/full

Analgesic Efficacy of Spinal Morphine in Comparison With ... The aim of the current study is to compare spinal morphine (SM) and bilateral landmark oriented transversus abdominis plane (TAP) block for postoperative pain ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0007091224004161

Non-pulmonary complications of intrathecal morphine ... Primary outcomes were rates of postoperative nausea and vomiting, pruritus, and urinary retention within the first 24 postoperative hours, analysed according to ...

7. brieflands.com brieflands.com/articles/aapm-94441

A Literature Review of Intrathecal Morphine Analgesia in ... Intrathecal morphine may be a better first-line analgesic modality than epidural analgesia in the context of major open hepato-pancreatic-biliary surgery.