Epidural Versus Paravertebral Block Analgesia After Hepatectomy

Study Overview
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Brief Summary
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The best mode of analgesia delivery after hepatectomy is currently unknown. Many institutions routinely use continuous epidural analgesia (CEA) for pain control in this patient population. A functioning CEA provides adequate analgesia, but is associated with high failure rates (20-30%) and sometimes significant hemodynamic disturbances (hypotension) requiring an increased amount of intravenous fluid and blood products to maintain homeostasis. Furthermore, its safety has been the subject of debate in liver resection patients due to the elevated risk of epidural hematoma and its serious neurological consequences. These limitations highlight the need to explore other options for analgesic control after hepatectomy, such as paravertebral block (PVB). PVB has been shown to provide similar analgesia with a lower incidence of pulmonary complications, side effects (pruritis, urinary retention, nausea and vomiting, hypotension), and failure rates (6.1%) when compared to CEA in thoracic surgery, and therefore has been suggested as a safer alternative in hepatectomy patients. Despite this, there are no studies comparing the efficacy of CEA and PVB as analgesic techniques after hepatectomy. The investigators propose a randomized controlled trial to compare the analgesic efficacy, side effects, and complications associated with CEA and PVB in patients undergoing elective hepatectomy through a right subcostal incision.

Detailed Description
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The best mode of analgesia delivery after hepatectomy is currently unknown. Many institutions routinely use continuous epidural analgesia (CEA) for pain control in hepatectomy patients. However, its safety has been the subject of debate. Paravertebral block (PVB) has been suggested as a safer alternative in this patient population. Despite this, there are no studies comparing the efficacy of CEA and PVB as analgesic techniques after hepatectomy. Although CEA provides high quality analgesia, and reduces cardiovascular and respiratory complications and the incidence of postoperative thromboembolic events, it is associated with hypotension and complications such as epidural hematoma, epidural abscess, and spinal cord injury, which are serious concerns in hepatectomy patients. Furthermore, patients given CEA are more likely to need blood transfusions, and transfused patients have significantly higher mortality rates, complications related to infection, and hospital length of stay. PVB is a less popular technique that involves injecting local anesthetic (LA) into the paravertebral space. This technique has been successfully used for pain relief after several surgical procedures, including ablation of hepatic tumours and hepatectomy. Although CEA and PVB have never been compared in hepatectomy patients, they have been compared in thoracotomy patients; in this patient population, PVB and CEA provide similar levels of pain control, but CEA is associated with more complications and side effects such as hypotension, nausea, vomiting, and urinary retention, and PVB is associated with better pulmonary function. Both CEA and PVB are reasonably effective for post-hepatectomy analgesia compared to placebo, and have their own strengths and weaknesses. The gold standard CEA provides excellent analgesia at the expense of more intense hypotension, significant failure rates (20-30%), and a higher risk of epidural hematoma and its serious neurological consequences. These limitations highlight the need to explore other options for analgesic control after hepatectomy such as PVB. Therefore, the investigators propose a randomized controlled trial to compare the analgesic efficacy, hemodynamic changes, and side effects in CEA and PVB in patients undergoing elective hepatectomy through a right subcostal incision. Since CEA is currently the gold standard for analgesia after hepatectomy, the investigators propose a non-inferiority trial to determine whether PVB produces a similar analgesic profile to CEA in hepatectomy patients, while being associated with fewer adverse side effects. This is a randomized, controlled, pilot study. It will consist of two groups of participants undergoing hepatectomy: those receiving CEA, and those receiving PVB for analgesic control. CEA and PVB protocols will follow the usual standard of care at Kingston General Hospital (KGH). Participants in the CEA group will receive bupivacaine with hydromorphone infusion after induction of general anesthesia for surgery. Participants in the PVB group will receive a bolus dose of ropivacaine, and then ropivacaine infusion after induction of general anesthesia. Upon emergence from anesthesia, all participants will be transferred to the post-anesthetic care unit (PACU). Here, CEA participants will be started on patient-controlled epidural analgesia (PCEA) of bupivacaine and hydromorphone plus a self-administered bolus dose with a lockout period of 30 min if participants require additional pain relief, and PVB participants will be started on a patient-controlled paravertebral analgesia (PCPA) of ropivacaine plus a self-administered bolus dose with a lockout period of 30 min if participants require additional pain relief. All participants will receive oral hydromorphone every 4 hours as required for breakthrough pain relief starting on the morning of the second postoperative day. A member of the research team will assess the presence and severity of pain and nausea during the postoperative period. The assessments will be performed at 30 minutes after arrival to the PACU, and thereafter at 4, 8, 24, 48, and 72 hours after surgery. Investigators will ask all participants to score their pain at rest and with coughing on a numeric rating scale (NRS, where 0=no pain and 10=worst pain imaginable), and nausea scores (0=none, 1=mild, 2=moderate, 3=vomiting) at each of the above listed time points. At 72 hours after surgery, participant satisfaction with regard to analgesia will be assessed (1=very poor, 2=poor, 3=satisfactory, 4=good, 5=excellent). The requirement for breakthrough pain relief, the time of first breakthrough pain relief request, and cumulative opioid consumption will be recorded during the postoperative 72 hours.

Official Title
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Analgesic and Hemodynamic Effects of Continuous Epidural Analgesia Compared to Paravertebral Block in Liver Resection Patients

Conditions
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Pain Control After Elective Hepatectomy

Intervention / Treatment
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* Procedure: Bupivacaine and Hydromorphone
* Procedure: Ropivacaine and Hydromorphone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-80 years of age ASA I-III Undergoing elective liver resection through right subcostal incision Proficient in English Competent to give consent Exclusion Criteria: Not given informed consent Not competent to give informed consent Dementia or neurological impairment Jaundice (bilirubin > 50μmol/L) Liver resection combined with secondary surgical procedure Contraindication to either epidural or paravertebral block (INR ≥ 1.6, platelet count < 100,000/mm3, fever, previous back surgery) Anticipated significant coagulopathy post-liver resection (as indicated by a Model for End-Stage Liver Disease score >8 or predicted liver resection of more than 500g) Contraindications to any of the study medications Remain intubated in the postoperative period, due to inability to assess pain scores Midline incision and/or any type of extended incision that is not restricted to the standard right subcostal incision Body mass index < 18 or > 40 Pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Continuous Epidural Analgesia<br>Analgesic medications will be given via epidural, the standard of care. | Procedure: Bupivacaine and Hydromorphone<br>* Patients receive bupivacaine and hydromorphone infusion and bolus doses during surgery and 3 days after surgery.<br>|
| Experimental: Paravertebral Block Analgesia<br>Analgesic medications will be given via the paravertebral space. | Procedure: Ropivacaine and Hydromorphone<br>* Patients receive ropivacaine and hydromorphone infusion and bolus doses during surgery and 3 days after surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid consumption | Cumulative opioid consumption during the postoperative period will be recorded. | 0-72 hours after surgery | 
| Time to first request for opioids | The first time after surgery each participant asks for opioid medication for pain will be recorded. | 0-72 hours after surgery | 
| Pain scores | At the specified time points, participants will rate their pain on a scale from 0 to 10. | 30min, 4, 8, 24, 48, and 72 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nausea | At the specified time points, participants will rate their nausea. | 30min, 4, 8, 24, 48, and 72 hours after surgery | 
| Satisfaction with analgesia | Participants will rate their satisfaction with their analgesia. | 72 hours after surgery | 
| Success rates of CEA and PVB | The number of successful CEA and PVB procedures will be recorded. | 0-72 hours after surgery | 
| Failure rates of CEA and PVB | The number of therapeutic failures of CEA and PVB procedures will be recorded. | 0-72 hours after surgery | 
| Mean arterial pressure | Mean arterial pressure will be recorded. | 0-72 hours after surgery | 
| Central venous pressure | Central venous pressure will be recorded. | 0-72 hours after surgery | 
| Urine output | Urine output will be recorded. | 0-72 hours after surgery | 
| Acid-base | pH, bicarbonate, partial pressure of carbon dioxide, and partial pressure of oxygen in the blood will be recorded. | 0-72 hours after surgery | 
| Intravenous fluid volume | Total volume of crystalloids, colloids, and blood products given perioperatively and during the 72 hours after surgery will be recorded. | 0-72 hours after surgery | 
| Vasopressor volume | Total volume of vasopressors given perioperatively and during the 72 hours after surgery will be recorded. | 0-72 hours after surgery | 
| Resumption of full oral diet | The number of days taken to resume a full oral diet will be recorded. | 0-72 hours after surgery | 
| Hospital length of stay | The number of days until participants are discharged will be recorded. | 0-72 hours after surgery | 
| Adverse events | Any postoperative adverse events will be recorded. | 0-72 hours after surgery | 
| Demographic data | Descriptive demographic data will be recorded. | Upon enrollment up to 72 hours after surgery |