Spinal Anesthesia for Enhanced Recovery After Liver Surgery
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 128
- 试验地点
- 1
- 主要终点
- Cumulative 72-hour volume of intravenous fluids and blood products administered
研究概览
简要总结
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.
详细描述
Hepatic resection surgery (hepatectomy) for primary or metastatic malignancy is a major operation involving large, painful upper abdominal incisions, as well as considerable postoperative physiological derangements.
Uncontrolled postoperative incisional pain results in significant respiratory impairment, delayed mobilization, and augmentation of the surgically-induced stress response, placing patients at increased risk of postoperative complications and chronic post-surgical pain. Acute pain management with high-dose parenteral opioids further compounds this risk. Multimodal opioid-sparing therapy, and regional anesthesia in particular, is therefore an essential component of enhanced recovery after surgery (ERAS) pathways and patient-centred care.
Regional anesthesia using neuraxial block (intraoperative spinal anesthesia or thoracic epidural anesthesia) followed by postoperative continuous thoracic epidural analgesia (CTEA; postoperative administration of epidural local anesthetic and/or opioid) is the best method for treating pain following large abdominal surgeries, including liver resection, and has been shown to improve postoperative respiratory function and decrease respiratory complications in other surgeries.
However, the effects of intraoperative neuraxial block and postoperative CTEA on fluid balance, systemic hemodynamics, and functional recovery after hepatic resection surgery remain controversial. CTEA is frequently associated with postoperative hypotension, resulting in increased perioperative intravenous (IV) fluid administration, red blood cell transfusion, and vasopressor use in liver resection patients. For major hepatectomies, CTEA may also be an independent risk factor for postoperative acute kidney injury (AKI), presumably due to impairment of renal autoregulation. Excessive IV fluid administration in the postoperative period is associated with significant weight gain, often necessitating diuretic therapy; delayed return of gastrointestinal function; increased need for packed red blood cell (pRBC) transfusion due to hemodilution; increased infective complications due to this increased pRBC transfusion rate; and increased length of hospital stay.
In addition, concerns remain about the use of CTEA following liver resection surgery due to the potentially increased risk of epidural hematoma formation in the setting of postoperative coagulopathy. This concern has resulted in unplanned delays in epidural catheter removal postoperatively, due to persistent coagulation abnormalities, prolonging hospitalization by 1-3 d in up to 15% of patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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)
干预措施: Spinal anesthesia with intrathecal morphine (Procedure)
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)
干预措施: Bupivacaine 0.75% in Dextrose Inj 8.25% (Drug)
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)
干预措施: Morphine (Drug)
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).
干预措施: Continuous thoracic epidural analgesia (Procedure)
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).
干预措施: Bupivacaine 0.25% Preservative-Free Injectable Solution (Drug)
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).
干预措施: Bupicavaine 0.125% epidural solution (Drug)
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).
干预措施: Hydromorphone 10 mcg/mL epidural solution (Drug)
结局指标
主要结局
Cumulative 72-hour volume of intravenous fluids and blood products administered
时间窗: 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
Cumulative 72-hour opioid consumption (OC_0-72h)
时间窗: 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).
Area under the curve over 72 hours of the summed pain intensity difference scores at rest (AUC-SPID-PAR_0-72h)
时间窗: 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.
次要结局
- Cumulative perioperative vasopressor and/or inotrope consumption(Intraoperatively and during the first 7 days after surgery or until hospital discharge, whichever occurs earlier)
- Cumulative incidence (proportion) of rescue analgesia (parenteral opioid) use (%)(72 hours after surgery or until hospital discharge, whichever occurs earlier)
- Cumulative fluid balance (CFB) at 72 hours(72 hours after surgery or until hospital discharge, whichever occurs earlier)
- Percentage fluid overload (% FO) at 72 hours(72 hours 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)
- 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))
- 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(72 hours after surgery or until hospital discharge, whichever occurs earlier)
- Time to mobilization (h)(7 days after surgery or until hospital discharge, whichever occurs earlier)
- Time to gastrointestinal (GI) recovery (h)(7 days after surgery or until hospital discharge, whichever occurs earlier)
- Time to removal of urinary catheter (h)(7 days after surgery or until hospital discharge, whichever occurs earlier)
- Time to adequate pain control with PO medications (h)(7 days after surgery or until hospital discharge, whichever occurs earlier)
- 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(7 days after surgery or until hospital discharge, whichever occurs earlier)
- Overall Benefit of Analgesia Score (OBAS) at 72 hours(72 hours after surgery or until hospital discharge, whichever occurs earlier)
- Index hospitalization length of stay(During index hospital admission (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively))
- Analgesic-related adverse events: incidence rate ratio of severe respiratory depression(During index hospital admission (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively))
- Analgesic-related adverse events: incidence rate ratio of sedation(During index hospital admission (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively))
- Analgesic-related adverse events: cumulative incidence (proportion) of postoperative delirium(During index hospital admission (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively))
- Number (count) of surgical complications with Clavien-Dindo grade ≥ III(During index hospital admission (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively))
- Number (count) of non-surgical complications based on the Postoperative Morbidity Survey (POMS)(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.)
- Comprehensive Complication Index (CCI) score Comprehensive Complication Index (CCI) score Comprehensive Complication Index (CCI) score(During index hospital admission (censored at the earliest of hospital discharge, in-hospital death, or 30 days 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)
- Volume-related weight gain (VRWG) at 72 hours(72 hours after surgery or until hospital discharge, whichever occurs earlier)
研究者
Alex Grunfeld
Principal Investigator
University of Manitoba