Spinal Anesthesia For Enhanced Recovery After Liver Surgery

NCT03715517 | Recruiting

• 1 other identifier: B2018:048
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatectomy; Pain, Postoperative; Liver Neoplasms

Keywords

Injections, Spinal; Analgesia, Epidural; Anesthesia, Spinal; Patient Reported Outcome Measures; Postoperative Period

Outcome Measures

Primary Outcomes (3)

• Cumulative 72-hour volume of intravenous fluids and blood products administered

  Intraoperative plus cumulative postoperative intravenous (IV) fluid volume administered, total (mL) = sum of volumes of IV crystalloid, IV colloid, and non-albumin blood products (packed red blood cells \[pRBC\], fresh-frozen plasma \[FFP\], and platelets) administered

  Intraoperatively and during the first 72 hours postoperatively or until hospital discharge, whichever occurs earlier

• Area under the curve over 72 hours of the summed pain intensity difference scores at rest (AUC-SPID-PAR_0-72h)

  Numerical Rating Scale (NRS) Summed Pain Intensity Difference at rest (SPID-PAR) (calculated as Area Under the Curve \[AUC\] using the trapezoidal rule) over 0 to 72 hours (AUC-SPID-PAR\_0-72h) after surgery. Pain intensity (PI) is assessed preoperatively and at 2, 6-12, 24, 36, 48, 60, and 72 hours after surgery or until hospital discharge, whichever came first, using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is the "worst possible pain". Pain intensity difference (PID\_t) is calculated as the difference in pain intensity from time 0 to each time point t. SPID\_t is calculated using the trapezoidal rule as the area under the curve (AUC) for Pain Intensity Difference over the time interval 0 to t hours, respectively, divided by the length of the time interval (t hours). A positive value is a decrease (improvement) of the pain.

  72 hours after surgery or until hospital discharge, whichever occurs earlier

• Cumulative 72-hour opioid consumption (OC_0-72h)

  Total perioperative epidural, intravenous, and oral opioid requirements measured in oral morphine equivalents (OME, mg).

  Intraoperatively and during the first 72 hours postoperatively or until hospital discharge, whichever occurs earlier

Secondary Outcomes (23)

• Vasopressor-free days to day 30

  During index hospital admission (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively)

• Cumulative intraoperative vasopressor and/or inotrope consumption

  Intraoperatively (from anesthesia start time to anesthesia end time)

• Cumulative perioperative vasopressor and/or inotrope consumption

  Intraoperatively and during the first 7 days after surgery or until hospital discharge, whichever occurs earlier

• Cumulative 72-hour volume of intravenous fluids administered

  Intraoperatively and during the first 72 hours postoperatively

• Area under the curve over 72 hours of the summed pain intensity difference scores of movement-evoked pain (MEP) (AUC-SPID-MEP_0-72h)

  72 hours after surgery or until hospital discharge, whichever occurs earlier

Other Outcomes (6)

• Cumulative 24-hour volume of intravenous fluids and blood products administered

  Intraoperatively and during the first 24 hours postoperatively

• Area under the curve (AUC) over 24 hours of the summed pain intensity difference (SPID) scores at rest (AUC-SPID-PAR_0-24h)

  24 hours after surgery

• Cumulative 24-hour (IV) opioid consumption (OC_0-24h)

  Intraoperatively and during the first 24 hours postoperatively or until hospital discharge, whichever occurs earlier

Study Arms (2)

Intrathecal morphine

EXPERIMENTAL

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)

Procedure: Spinal anesthesia with intrathecal morphine; Drug: Bupivacaine 0.75% in Dextrose Inj 8.25%; Drug: Morphine

Thoracic epidural analgesia

ACTIVE COMPARATOR

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).

Procedure: Continuous thoracic epidural analgesia; Drug: Bupivacaine 0.25% Preservative-Free Injectable Solution; Drug: Bupicavaine 0.125% epidural solution; Drug: Hydromorphone 10 mcg/mL epidural solution

Interventions

Continuous thoracic epidural analgesia PROCEDURE

Needle/catheter: 17 Ga. × 80 mm Tuohy epidural needle (Perican®, B. Braun Medical Inc., Bethlehem, PA, USA); Arrow FlexTip Plus® 19 Ga. epidural catheter (Arrow International Inc., Reading, PA, USA) Level of insertion and patient positioning: T6-T8, upright sitting position for insertion of needle and catheter (to 5 cm beyond loss-of-resistance point) and for injection of test dose (3 mL 2% lidocaine with epinephrine 1:200,000); supine for injection of bolus dose Confirmation of correct placement: Loss of resistance to air or saline; negative aspiration of the epidural catheter; negative test dose; and ease of injection of an initial bolus dose

Thoracic epidural analgesia

Spinal anesthesia with intrathecal morphine PROCEDURE

Needle/catheter: 25 Ga. × 90 mm high-flow Whitacre spinal needle (Becton-Dickinson, Franklin Lakes, NJ, USA) Level of insertion and patient positioning: L2-L3, lateral decubitus position during injection; immediately post-injection, patient is placed supine in \<5% degree of Trendelenburg Confirmation of correct placement: Aspiration of cerebrospinal fluid

Intrathecal morphine

Bupivacaine 0.75% in Dextrose Inj 8.25% DRUG

0.25 mg⋅kg-¹ hyperbaric bupivacaine 0.75%

Also known as: Spinal heavy bupivacaine

Intrathecal morphine

Morphine DRUG

3 mcg⋅kg-¹ intrathecal morphine (preservative-free)

Also known as: Intrathecal morphine

Intrathecal morphine

Bupivacaine 0.25% Preservative-Free Injectable Solution DRUG

0.25 mg⋅kg-¹ bupivacaine 0.25%

Also known as: Bupivacaine 0.25% epidural solution

Thoracic epidural analgesia

Bupicavaine 0.125% epidural solution DRUG

Epidural solution, bupivacaine 0.125% with hydromorphone 10 mcg·mL-¹, infusion range 0.075-0.125 mL⋅kg-¹⋅h-¹

Also known as: Bupivacaine 0.125% preservative-free injectable solution

Thoracic epidural analgesia

Hydromorphone 10 mcg/mL epidural solution DRUG

Epidural solution, bupivacaine 0.125% with hydromorphone 10 mcg·mL-¹, infusion range 0.075-0.125 mL⋅kg-¹⋅h-¹

Thoracic epidural analgesia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, Adults aged ≥ 18 years (there will be no upper age restriction);
• American Society of Anesthesiologists Physical Status classification (ASA-PS) of I to III;
• Undergoing subcostal or midline laparotomy for elective liver resection surgery under general anesthesia; if the planned procedure is a combined operation (i.e., concomitant extrahepatic surgery) , the associated procedure should not add more than one hour to the surgical time of the primary hepatic resection procedure alone;
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Provision of signed and dated informed consent form
• Body mass index (BMI) between 17 and 40 kg·m-², inclusive;
• Negative result on serum pregnancy test at Screening and negative urine pregnancy test at Baseline (for women of childbearing potential, defined as those who have not undergone a hysterectomy or been postmenopausal for at least 12 consecutive months); and not currently breastfeeding, or planning to do so within 7 d following surgery;
• Stated willingness and ability to comply with all study and/or follow-up evaluations and communicate clearly with the Investigator and staff; and
• Voluntary participation and ability to provide written informed consent prior to any study procedures.

You may not qualify if:

• Emergency surgery;
• Age \< 18 years;
• Planned laparoscopic hepatic resection;
• Planned laparotomy incision other than (right) subcostal, midline, or extended midline;
• Patients with obvious non-resectable disease prior to signing informed consent;
• Liver transplant recipient or previous hepatic resection or living-donor hepatectomy surgery;
• Major surgery (open abdominal and/or thoracic) under general anesthesia ≤ 30 d preoperatively;
• Contraindications to neuraxial (spinal or epidural) anesthesia: (a) anticipated difficult intubation; (b) coagulation or hemostatic abnormalities within 30 d of surgery (defined as thrombocytopenia \[platelet count \< 100 × 10⁹ L-¹\]; INR \> 1.4; or activated partial thromboplastin time \[aPTT\] \> 40 s); (c) bleeding diathesis; (d) ongoing use (≤ 7 d before surgery) or planned perioperative use of antiplatelet agents (apart from acetylsalicylic acid 81 mg) or anticoagulants (excluding deep-vein thrombosis prophylaxis); (e) recent (≤ 30 d preoperatively) systemic infection or current (≤ 48 h) fever (≥ 38.4 °C), or evidence of infection (including superficial cutaneous infection in the thoracic and/or lumbar regions); (f) history of neurologic disorder affecting the spinal cord or the hemithorax or below; or impaired bladder/bowel function; (g) acute or subacute (≤ 90 d preoperatively) intracranial hemorrhage; or (h) technical contraindications to epidural placement: (i) local skin or soft tissue infection at proposed site for thoracic epidural insertion; (ii) previous cervicothoracic, thoracic, or thoracolumbar spinal surgery; (iii) history of spinal tumor, fracture or infection; or (iv) recent (≤ 14 d preoperatively) epidural corticosteroid injection;
• Significant cardiac arrhythmias (including pacemaker-dependence) or clinically significant cardiovascular disease (New York Heart Association \[NYHA\] functional classification III-IV);
• Volume overload (hyperhydration), particularly in cases of pulmonary edema or acute decompensated congestive heart failure (CHF);
• Acute kidney injury (AKI) and/or chronic kidney disease (CKD) based on the 2012 Kidney Disease Improving Global Outcomes (KDIGO) AKI (excluding the oliguria criterion) and CKD guideline definitions: AKI: increase in serum creatinine (SCr) (≥ 26.5 μmol·L-¹ within 48 h or ≥ 1.5× baseline within 7 d); CKD: abnormalities of kidney structure or function, present for \> 3 mo, defined as either of the following present for \> 3 mo: (1) ≥ 1 marker(s) of kidney damage: (a) albuminuria (24-h albumin-creatinine ratio \[ACR\] ≥ 30 mg·g-¹ \[≥ 3 mg·mmol-¹\]), (b) urine sediment abnormalities, (c) electrolyte and other abnormalities due to tubular disorders, (d) abnormalities detected by histology, (e) structural abnormalities detected by imaging, (f) history of kidney transplantation; and/or decreased glomerular filtration rate (GFR \< 60 mL-¹·min-¹·1.73 m-², estimated using the 2009 CKD-EPI creatinine equation \[eGFR\_creat\]);
• Severe hypernatremia (\[Na⁺\] ≥ 155 mmol·L-¹) and/or hyperchloremia (\[Cl-\] ≥ 125 mmol·L-¹);
• Chronic pain; current (≤ 30 d preoperatively) and/or prior chronic (for a period of ≥ 90 d) opioid use; or history of alcohol, opiate, and/or other drug abuse or dependence;
• Use of supraphysiologic glucocorticoid (GC) doses (≥ 7.5 mg·day-¹ of prednisone or equivalent): recent (≤ 30 d), prolonged (\> 2 consecutive weeks), or multiple courses totalling \> 3 weeks in the preceding 6 months;
• Known allergy or sensitivity (e.g., glucose-6-phosphate dehydrogenase \[G6PD\] deficiency) to amide local anesthetics, opioids, or acetaminophen, or hypersensitivity to other materials to be used in the study (e.g., latex \[epidural catheter adapter\], epidural dressing or tape); or

Sponsors & Collaborators

• University of Manitoba: lead

Study Sites (1)

University of Manitoba

Winnipeg, Manitoba, R3E 0Z2, Canada

RECRUITING

MeSH Terms

Conditions

Pain, Postoperative; Liver Neoplasms; Agnosia

Interventions

Anesthesia, Spinal; Bupivacaine; Morphine; Hydromorphone

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Anesthesia, Conduction; Anesthesia; Anesthesia and Analgesia; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Alex Grunfeld, MD

  University of Manitoba

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alex Grunfeld, MD

CONTACT

204-787-1125; alexander.grunfeld@umanitoba.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: October 23, 2018
• Study Start: October 4, 2018
• Primary Completion (Estimated): July 31, 2031
• Study Completion (Estimated): December 31, 2031
• Last Updated: February 5, 2026

Record last verified: 2026-02

Locations

CA (1)