Spinal Anesthesia for Liver Surgery

(SAFER-L Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Alex Grunfeld, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

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

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This project proposes to compare epidural versus spinal anesthesia in patients having liver resection surgery. The investigators hypothesize that spinal anesthesia will result in improved blood pressure control postoperatively and reduce the amount of intravenous fluids required after surgery. Spinal anesthesia is expected to provide the same pain control benefits as epidurals, with faster recovery of function. Spinal anesthesia may be a simple and effective way to improve and enhance the recovery in the increasing number of patients requiring liver resection.

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 evidence supports the effectiveness of the drug used in spinal anesthesia for liver surgery?

Research shows that intrathecal morphine, when used with spinal anesthesia, provides effective and long-lasting pain relief after surgery. Studies indicate that it can significantly extend the time before patients need additional pain medication, with minimal side effects when used in low doses.

^{1 2 3 4 5}

Is spinal anesthesia with intrathecal morphine safe for humans?

Spinal anesthesia with intrathecal morphine is generally safe when used in low doses, as it provides effective pain relief with minimal side effects. However, higher doses can lead to serious adverse events, such as respiratory depression, nausea, vomiting, and itching. Careful dosing is important to ensure safety.

^{1 2 4 6 7}

How does the drug 'Spinal anesthesia with intrathecal morphine' differ from other treatments for liver surgery?

Spinal anesthesia with intrathecal morphine is unique because it combines a spinal block with morphine directly injected into the spinal fluid, providing powerful and prolonged pain relief with minimal disturbance to brain function. This method is particularly effective for postoperative pain control, offering long-lasting analgesia with lower doses of morphine, which reduces the risk of side effects like respiratory depression.

^{1 2 3 4 8}

Eligibility Criteria

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.

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

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

Trial Timeline

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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Manitoba Winnipeg, Canada

Who Is Running the Clinical Trial?

University of Manitoba Lead Sponsor

References

1. Thailand pubmed.ncbi.nlm.nih.gov

Nausea, vomiting and pruritus induced by intrathecal morphine. [2013] Presently, in Siriraj Hospital, intrathecal morphine is routinely used in spinal anesthesia for postoperative pain control in more than 600 cases per month with doses lower than 0.3 mg. However, the incidence of side effects is high. This retrospective data review was performed to identify incidence and risk factors of postoperative nausea, vomiting, and pruritus.

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

Low dose intrathecal morphine effects on post-hysterectomy pain: a randomized placebo-controlled study. [2022] Spinal anesthesia with different doses of intrathecal morphine has been shown to relieve post-operative pain. We studied in a prospective randomized, double-blind fashion the effects of morphine 0, 100, 200, or 300 μg added to intrathecal bupivacaine on first post-operative 24 h patient-controlled analgesia morphine (PCA-morphine) consumption after abdominal hysterectomy under general anesthesia.

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

Postoperative pain control with intrathecal morphine. [2019] A clinical study of the use of intrathecal morphine in two groups of surgical patients, 32 in all, showed that the morphine provided very powerful and prolonged analgesia with little disturbance of cerebral function. When combined with a spinal block it did not interfere with the action of the spinal anaesthetic. When combined with a relaxant technique of anaesthesia some persistent curarisation was seen. The only complication to emerge from the study was respiratory depression which could be very delayed in its offset. The depression was sufficient to induce carbon dioxide narcosis in two patients. It is suggested that the dose of intrathecal morphine in the very elderly should be very severely restricted as they appeared to be unduly sensitive to the respiratory depressant effect of morphine when given intrathecally.

4. Germany pubmed.ncbi.nlm.nih.gov

[Intrathecal morphine for postoperative pain]. [2013] At the beginning, the way intrathecal morphine was used for postoperative pain relief was quite unfortunate, because the doses derived from experience with morphine-tolerant cancer patients were considerably too high and respiratory depression occurred frequently. Subsequent dose-finding studies showed that the doses of morphine used initially could be reduced by a factor of ten without loss of the analgesic effect and with a marked reduction in side-effects. No respiratory depression has been reported when doses below 0.1 mg morphine are used. METHOD. In this prospective study the effect of 0.06 to 0.08 mg intrathecal morphine, mixed with the local anaesthetic for spinal anesthesia, was investigated in surgical patients aged 21 to 81 years, ASA grade I or II, scheduled for orthopaedic operations or herniorraphies. Thirty unpremedicated patients were enrolled in the study and were, after informed consent, randomly allocated to a control group without morphine or to a morphine group. The analgesic effect was assessed by the time interval between the administration of the spinal anaesthesia and the first demand for an analgesic medication. The mood state was evaluated with the adjective checklist of Janke and Debus 6 h after the spinal anaesthesia. RESULTS AND DISCUSSION. In the control group half of the patients asked for an analgesic medication within 275 min (median) after the spinal anaesthesia, and all patients within 420 min, whereas in the morphine group half of the patients asked for an analgesic within 1170 min (median). Seven patients had not required an analgesic at the termination of the observation period 20 h after the spinal anaesthesia. The mood status showed no difference between the two groups, in particular, no dizziness or drowsiness after morphine. There was no difference in the incidence of side-effects such as nausea or urinary retention between the two groups. Pruritus was not reported spontaneously but was found upon questioning in five patients. It was in no case disturbing. CONCLUSIONS. Morphine (0.06 to 0.08 mg) mixed with the local anaesthetic for spinal anaesthesia provided for an analgesia of more than 20 h duration in half of the patients. This technique is safe, simple, reliable and virtually free of side-effects. No particular supervision due to the administration of intrathecal morphine is necessary in this dose range if systemic opiates are avoided. If the analgesia is unsatisfactory, a non-opioid analgesic is recommended.

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

Intrathecal morphine: dosage and efficacy in younger patients for control of postoperative pain following spinal fusion. [2022] Intrathecal morphine in an average dose of 0.01 mg/kg was given to 33 patients between ages 11 and 16 years who had spinal arthrodesis for idiopathic scoliosis. The morphine was administered intrathecally as a 10-cc bolus at the conclusion of the arthrodesis, but before closure. The goal was to study safety in terms of respiratory depression and pain relief. Respirations occurred spontaneously in 30 of the 33 patients within 15 minutes of cessation of anesthesia. Respiratory depression occurred in five patients, four of whom had arterial blood pCO2 levels greater than 60 mm Hg. Thirty-one patients had relief of pain for 8 to greater than 40 hours, averaging 18 hours. Two patients had no noticeable pain relief. There appeared to be no relation between dose and pain relief in this limited dose range. We were unable to duplicate the long duration of pain relief reported elsewhere. We also were unable to decrease the side effects of respiratory depression and nausea to a level reported by others. It may be that the 10 cc bolus injected intrathecally circulates to the brain and ventricles faster than desired, or that factors relating to type of anesthesia or dose need to be considered. Low-dose intrathecal morphine does provide noticeable pain relief in younger patients undergoing spinal fusion. The side effects of nausea and respiratory depression can be managed safely with medication.

6. United States 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. [2014] The administration of single dose intrathecal (IT) morphine with local anesthetics during spinal anesthesia produces an effective postoperative analgesia. In this study, we evaluated the efficacy and safety of two different doses of IT morphine with bupivacaine for postoperative analgesia after transurethral resection of prostate (TURP).

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

Serious Adverse Events after a Single Shot of Intrathecal Morphine: A Case Series and Systematic Review. [2022] Label="Background">The dose of intrathecal morphine is important because of its narrow therapeutic range. Due to a compounding error, pharmacy-compounded, ready-to-use syringes contained 1 mg ml-1 morphine instead of the intended 50 mcg ml-1. Six patients consequently received this twenty-fold dose. This study aims to describe the serious adverse events in these six patients and a systematic review is added to describe the characteristics of serious adverse events after intrathecal morphine.

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

Intrathecal Morphine in the Presence of a Syrinx in Pediatric Spinal Deformity Surgery. [2021] Intrathecal morphine (IM) is a popular adjunct for pain relief during pediatric spinal deformity surgery. There is no literature regarding its usefulness and safety in the presence of a spinal cord syrinx for patients undergoing spinal instrumentation. Anesthesiologists have previously been reluctant to use IM in the presence of any syrinx.