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Spinal Anesthesia For Enhanced Recovery After Liver Surgery (SAFER-L)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03715517
Recruitment Status : Recruiting
First Posted : October 23, 2018
Last Update Posted : October 23, 2018
Sponsor:
Information provided by (Responsible Party):
Alex Grunfeld, University of Manitoba

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.

Condition or disease Intervention/treatment Phase
Hepatectomy Pain, Postoperative Liver Neoplasms Procedure: Continuous thoracic epidural analgesia Procedure: Spinal anesthesia with intrathecal morphine Drug: Bupivacaine 0.75% in Dextrose Inj 8.25% Drug: Morphine Drug: Bupivacaine 0.25% Preservative-Free Injectable Solution Drug: Bupicavaine 0.125% epidural solution Drug: Hydromorphone 10 mcg/mL epidural solution Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 128 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Spinal Anesthesia for Enhanced Recovery After Liver Surgery
Actual Study Start Date : October 4, 2018
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : December 2019

Arm Intervention/treatment
Experimental: Intrathecal morphine

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

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


Drug: Bupivacaine 0.75% in Dextrose Inj 8.25%
0.25 mg⋅kg⁻¹ hyperbaric bupivacaine 0.75%
Other Name: Spinal heavy bupivacaine

Drug: Morphine
3 mcg⋅kg⁻¹ intrathecal morphine (preservative-free)
Other Name: Intrathecal morphine

Active Comparator: Thoracic epidural analgesia

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

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


Drug: Bupivacaine 0.25% Preservative-Free Injectable Solution
0.25 mg⋅kg⁻¹ bupivacaine 0.25%
Other Name: Bupivacaine 0.25% epidural solution

Drug: Bupicavaine 0.125% epidural solution
Epidural solution, bupivacaine 0.125% with hydromorphone 10 mcg·mL⁻¹, infusion range 0.075-0.125 mL⋅kg⁻¹⋅h⁻¹
Other Name: Bupivacaine 0.125% preservative-free injectable solution

Drug: Hydromorphone 10 mcg/mL epidural solution
Epidural solution, bupivacaine 0.125% with hydromorphone 10 mcg·mL⁻¹, infusion range 0.075-0.125 mL⋅kg⁻¹⋅h⁻¹




Primary Outcome Measures :
  1. Cumulative 72-hour volume of intravenous fluids and blood products administered [ Time Frame: Intraoperatively and during the first 72 hours postoperatively or until hospital discharge, whichever occurs earlier ]
    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

  2. Area under the curve over 72 hours of the summed pain intensity difference scores at rest (AUC-SPID-PAR_0-72h) [ Time Frame: 72 hours after surgery or until hospital discharge, whichever occurs earlier ]
    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.

  3. Cumulative 72-hour opioid consumption (OC_0-72h) [ Time Frame: Intraoperatively and during the first 72 hours postoperatively or until hospital discharge, whichever occurs earlier ]
    Total perioperative epidural, intravenous, and oral opioid requirements measured in oral morphine equivalents (OME, mg).


Secondary Outcome Measures :
  1. Vasopressor-free days to day 30 [ Time Frame: During index hospital admission (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively) ]
    Vasopressor-free days to 30 days after surgery will be defined as the number of days alive and not on vasopressors before 30 days. If the patient is on vasopressors at day 30 or dies prior to day 30, vasopressor-free days will be 0.

  2. Cumulative intraoperative vasopressor and/or inotrope consumption [ Time Frame: Intraoperatively (from anesthesia start time to anesthesia end time) ]
    Cumulative norepinephrine (NE)-equivalent time-weighted dose (mcg·kg⁻¹·min⁻¹ of anesthesia time) of vasopressors and/or inotropes (phenylephrine, norepinephrine, dopamine, and/or epinephrine).

  3. Cumulative perioperative vasopressor and/or inotrope consumption [ Time Frame: Intraoperatively and during the first 7 days after surgery or until hospital discharge, whichever occurs earlier ]
    Cumulative norepinephrine (NE)-equivalent time-weighted dose (mcg·kg⁻¹·min⁻¹ of vasopressor and/or inotrope infusion duration) of vasopressors and/or inotropes (phenylephrine, norepinephrine, dopamine, and/or epinephrine).

  4. Cumulative 72-hour volume of intravenous fluids administered [ Time Frame: Intraoperatively and during the first 72 hours postoperatively ]
    Intraoperative plus cumulative postoperative intravenous (IV) fluid volume administered, excluding non-albumin blood products, total (mL) = sum of volumes of IV crystalloid and IV colloid administered

  5. Area under the curve over 72 hours of the summed pain intensity difference scores of movement-evoked pain (MEP) (AUC-SPID-MEP_0-72h) [ Time Frame: 72 hours after surgery or until hospital discharge, whichever occurs earlier ]
    Numerical Rating Scale (NRS) Summed Pain Intensity Difference of movement-evoked pain (SPID-MEP) (calculated as Area Under the Curve [AUC] using the trapezoidal rule) over 0 to 72 hours after surgery (AUC-SPID-MEP_0-72h)

  6. Cumulative incidence (proportion) of rescue analgesia (parenteral opioid) use (%) [ Time Frame: 72 hours after surgery or until hospital discharge, whichever occurs earlier ]
    Rescue analgesia (parenteral opioid) use is defined as receipt of supplemental (i.e., in addition to that defined by the intervention protocols) doses of fentanyl, morphine, and/or hydromorphone via the intravenous (IV) route, either via patient-controlled analgesia (PCA) or nurse/physician administration.

  7. Cumulative fluid balance (CFB) at 72 hours [ Time Frame: 72 hours after surgery or until hospital discharge, whichever occurs earlier ]
    Cumulative fluid balance (CFB) is defined as the sum of current daily fluid balance (DFB) and the sum of DFB from all preceding days. DFB (mL) = (total daily fluid input - total daily fluid output). Daily fluid input includes: (1) resuscitation fluids (isotonic crystalloid [at a rate >1 L/6 h]; colloids [albumin, hydroxyethyl starch]); (2) blood products (packed red blood cells; frozen plasma; platelets; cryoprecipitate); (3) maintenance and replacement fluids (dextrose-containing crystalloid; isotonic crystalloid [at a rate ≤1 L/6 h]); (4) nutrition (enteral nutrition [i.e., tube feeds]; parenteral nutrition; oral fluid intake); and (5) fluid creep (volume due to concentrated electrolytes; volume used to keep venous access open; intermittent and continuous medication). Daily fluid output includes: (1) blood loss; (2) urine output; (3) dialysis ultrafiltrate (if applicable); (4) losses through drains; and (5) losses through enteric (e.g., nasogastric) tubes.

  8. Percentage fluid overload (% FO) at 72 hours [ Time Frame: 72 hours after surgery or until hospital discharge, whichever occurs earlier ]
    Percentage fluid overload (% FO) is defined as the ratio between cumulative fluid balance and the initial body weight, in percentage: % FO = [(total fluid in (L) - total fluid out (L)) / admission body weight (kg) × 100].

  9. Volume-related weight gain (VRWG) at 72 hours [ Time Frame: 72 hours after surgery or until hospital discharge, whichever occurs earlier ]
    Volume-related weight gain at time t (VRWG_t) is defined as the percentage body weight gain at time t, calculated as the difference between the baseline body weight and body weight at time t divided by baseline body weight (t = 0): VRWG_t (%) = [(body weight [kg]_t - body weight [kg]_0) / body weight [kg]_0 × 100%].

  10. Quality of recovery, as measured by the change from baseline 15-item Quality of Recovery (QoR-15) scale score over the first 72 hours postoperatively [ Time Frame: 72 hours after surgery or until hospital discharge, whichever occurs earlier ]
    Patient-reported quality of recovery (QoR), as assessed using the 15-item Quality of Recovery (QoR-15) scale, with the change from baseline in the total QoR-15 score (range 0-150) at 72 hours postoperatively defining the analysis endpoint. The QoR-15 is a 15-item patient-completed questionnaire including items measuring pain, physical comfort, psychological support, emotional state, and independence in activities of daily living over the preceding 24 hours. Items are rated on a 10-point scale, with higher subscale (item) and total scale values indicating a better outcome. The scale's validity (content, criterion, and construct), reliability (test-retest and internal consistency [inter-item and split-half coefficients]), responsiveness (minimal clinically important difference [MCID] = 8.0), acceptability, and feasibility properties have been well-established.

  11. Time to mobilization (h) [ Time Frame: 7 days after surgery or until hospital discharge, whichever occurs earlier ]
    Defined as time to first out-of-bed mobilization (sitting out of bed, standing or walking).

  12. Time to gastrointestinal (GI) recovery (h) [ Time Frame: 7 days after surgery or until hospital discharge, whichever occurs earlier ]
    Defined as the later of (1) time to solid diet tolerance (recovery of upper GI function), and (2) time to first flatus or bowel movement.

  13. Time to removal of urinary catheter (h) [ Time Frame: 7 days after surgery or until hospital discharge, whichever occurs earlier ]
  14. Time to adequate pain control with PO medications (h) [ Time Frame: 7 days after surgery or until hospital discharge, whichever occurs earlier ]
  15. Sleep disturbance, as measured by the change from baseline Patient-Reported Outcomes Measurement Information System (PROMIS®) Short Form v1.0 - Sleep Disturbance 8a scale T-score over the first 7 days postoperatively [ Time Frame: 7 days after surgery or until hospital discharge, whichever occurs earlier ]
    The Patient-Reported Outcomes Measurement Information System (PROMIS®) Short Form v1.0 - Sleep Disturbance (SD) 8a scale assesses self-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep. The 8-item self-report version (Short Form [SF]) of the PROMIS® SD 8a scale included in this study queries sleep disturbance symptomatology based on the past 7 days, with each item rated on a 5-point Likert scale ranging from 1 (never) to 5 (almost always). All item scores are summed to calculate a total raw score where higher scores indicate more severe sleep disturbance symptomatology. Psychometric evaluations of the 8-item PROMIS® SF SD 8a in a wide range of patient populations have provided support for its high reliability (test-retest, internal consistency) and validity (convergent, divergent, face, construct). A smaller between-group increase from baseline (preoperative) to 7-day postoperative PROMIS® SF SD 8a T-scores indicates a better outcome.

  16. Overall Benefit of Analgesia Score (OBAS) at 72 hours [ Time Frame: 72 hours after surgery or until hospital discharge, whichever occurs earlier ]
    The Overall Benefit of Analgesia Score (OBAS) is a patient-reported outcome measure of seven pain-related quality-of-life indicators: (1) pain intensity at rest (scored 0-4, 0 = minimal pain, to 4 = maximum imaginable pain); patient-reported distress with respect to five opioid-related adverse effects (each scored 0-4, 0 = not at all, to 4 = very much): (2) vomiting, (3) itching, (4) sweating, (5) freezing, and (6) dizziness; and (7) patient satisfaction with pain treatment (scored 0-4, 0 = not at all, to 4 = very much). To calculate the OBAS score, the scores for items 1-6 and 4 minus the score for item 7 are summed for a total scale score range of 0 to 28, with lower values indicating a better outcome.

  17. Index hospitalization length of stay [ Time Frame: During index hospital admission (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively) ]
    Duration (days) of index hospitalization from date of index operation to date of hospital discharge (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively).

  18. Analgesic-related adverse events: incidence rate ratio of severe respiratory depression [ Time Frame: During index hospital admission (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively) ]
    Severe respiratory depression is defined as respiratory rate (RR) < 8 and/or hypoxemia (Spo2 < 90%) related to excessive somnolence and/or alveolar hypoventilation.

  19. Analgesic-related adverse events: incidence rate ratio of sedation [ Time Frame: During index hospital admission (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively) ]
    Severe opioid-induced sedation, as defined by Pasero-McCaffery Opioid-induced Sedation Scale (POSS) score of 3 or 4. The POSS is graded on a 5-point scale (S = sleep, easy to arouse; 1 = awake and alert; 2 = slightly drowsy, easily aroused; 3 = frequently drowsy, arousable, drifts off to sleep during conversation; 4 = somnolent, minimal or no response to verbal or physical stimulation), with scores of S, 1, and 2 considered acceptable levels of sedation, and scores of 3 or 4 considered unacceptable levels of sedation.

  20. Analgesic-related adverse events: cumulative incidence (proportion) of postoperative delirium [ Time Frame: During index hospital admission (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively) ]
    Delirium will be evaluated via trained nursing assessments using the 3-min Confusion Assessment Method (3D-CAM). The diagnosis of delirium by 3D-CAM requires a positive response to (1) acute onset or fluctuating course; and (2) inattention; and either (3) disorganized thinking or (4) altered level of consciousness. To reduce the likelihood of fluctuations or temporal changes, all assessments were completed between 11:00 AM and 2:00 PM and for each participant, within a 2-hour time period.

  21. Number (count) of surgical complications with Clavien-Dindo grade ≥ III [ Time Frame: During index hospital admission (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively) ]
    Postoperative surgical complications are assessed using the Clavien-Dindo classification (none, I, II, III, IV, or V) and classified by system.

  22. Number (count) of non-surgical complications based on the Postoperative Morbidity Survey (POMS) [ Time Frame: Postoperative non-surgical complications are assessed using the Postoperative Morbidity Survey (POMS) based on retrospective review of medical charts and patient telephone follow-up at 30 days. ]
    Postoperative non-surgical complications are assessed using the Postoperative Morbidity Survey (POMS) based on retrospective review of medical charts and patient telephone follow-up at 30 days.

  23. Comprehensive Complication Index (CCI) score Comprehensive Complication Index (CCI) score Comprehensive Complication Index (CCI) score [ Time Frame: During index hospital admission (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively) ]
    Postoperative surgical and non-surgical complications are graded using the Comprehensive Complication Index (CCI), a continuous scale ranking the severity of any combination of postoperative complications from 0 to 100 in each patient.


Other Outcome Measures:
  1. Cumulative 24-hour volume of intravenous fluids and blood products administered [ Time Frame: Intraoperatively and during the first 24 hours postoperatively ]
    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

  2. Area under the curve (AUC) over 24 hours of the summed pain intensity difference (SPID) scores at rest (AUC-SPID-PAR_0-24h) [ Time Frame: 24 hours after surgery ]
    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 24 hours (AUC-SPID-PAR_0-24h) after surgery

  3. Cumulative 24-hour (IV) opioid consumption (OC_0-24h) [ Time Frame: Intraoperatively and during the first 24 hours postoperatively or until hospital discharge, whichever occurs earlier ]
    Total perioperative epidural, intravenous, and oral opioid requirements measured in oral morphine equivalents (OME, mg).

  4. Time to first parenteral opioid dose administration (min) [ Time Frame: 72 hours after surgery or until hospital discharge, whichever occurs earlier ]
    Parenteral opioid administration is defined as receipt of fentanyl, morphine, and/or hydromorphone via the intravenous (IV) route, either via patient-controlled analgesia (PCA) or nurse/physician administration.

  5. Cumulative incidence (proportion) of patient-controlled analgesia (PCA) utilization postoperatively (%) [ Time Frame: 7 days after surgery or until hospital discharge, whichever occurs earlier ]
    Patient-controlled analgesia (PCA) utilization is defined as use of PCA with intravenous opioids (morphine, fentanyl, and/or hydromorphone).

  6. Cumulative incidence (proportion) of postoperative vasopressor and/or inotrope dependency (%) [ Time Frame: 7 days after surgery or until hospital discharge, whichever occurs earlier ]
    Requirement for postoperative vasopressor and/or inotrope therapy (phenylephrine, norepinephrine, dopamine, and/or epinephrine) to maintain mean arterial pressure (MAP) ≥ 65 mm Hg and/or to treat signs and/or symptoms of systemic hypoperfusion.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • Altered mental status or educational, psychiatric, or communication (language, literacy) barriers that would impede accurate assessment of postoperative pain and/or ability to complete questionnaire instruments.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03715517


Contacts
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Contact: Alex Grunfeld, MD 204-787-1125 alexander.grunfeld@umanitoba.ca

Locations
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Canada, Manitoba
University of Manitoba Recruiting
Winnipeg, Manitoba, Canada, R3E 0Z2
Contact: Alex Grunfeld, MD    204-787-1125    alexander.grunfeld@umanitoba.ca   
Sponsors and Collaborators
University of Manitoba
Investigators
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Principal Investigator: Alex Grunfeld, MD University of Manitoba
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Responsible Party: Alex Grunfeld, Principal Investigator, University of Manitoba
ClinicalTrials.gov Identifier: NCT03715517    
Other Study ID Numbers: B2018:048
First Posted: October 23, 2018    Key Record Dates
Last Update Posted: October 23, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alex Grunfeld, University of Manitoba:
Injections, Spinal
Analgesia, Epidural
Anesthesia, Spinal
Patient Reported Outcome Measures
Postoperative Period
Additional relevant MeSH terms:
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Liver Neoplasms
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Neurologic Manifestations
Signs and Symptoms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Morphine
Hydromorphone
Bupivacaine
Pharmaceutical Solutions
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Analgesics, Opioid
Narcotics
Analgesics