Clinical trial NCT02909322: Epidural Versus Paravertebral Block Analgesia After Hepatectomy
Official title: Analgesic and Hemodynamic Effects of Continuous Epidural Analgesia Compared to Paravertebral Block in Liver Resection Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pain Control After Elective Hepatectomy
Lead sponsor: Queen's University
Sponsor class: OTHER
First posted: 2016-09-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Opioid consumption
timeFrame: 0-72 hours after surgery
measure: Time to first request for opioids
timeFrame: 0-72 hours after surgery
measure: Pain scores
timeFrame: 30min, 4, 8, 24, 48, and 72 hours after surgery
Secondary outcomes:
measure: Nausea
timeFrame: 30min, 4, 8, 24, 48, and 72 hours after surgery
measure: Satisfaction with analgesia
timeFrame: 72 hours after surgery
measure: Success rates of CEA and PVB
timeFrame: 0-72 hours after surgery
measure: Failure rates of CEA and PVB
timeFrame: 0-72 hours after surgery
measure: Mean arterial pressure
timeFrame: 0-72 hours after surgery
measure: Central venous pressure
timeFrame: 0-72 hours after surgery
measure: Urine output
timeFrame: 0-72 hours after surgery
measure: Acid-base
timeFrame: 0-72 hours after surgery
measure: Intravenous fluid volume
timeFrame: 0-72 hours after surgery
measure: Vasopressor volume
timeFrame: 0-72 hours after surgery
measure: Resumption of full oral diet
timeFrame: 0-72 hours after surgery
measure: Hospital length of stay
timeFrame: 0-72 hours after surgery
measure: Adverse events
timeFrame: 0-72 hours after surgery
measure: Demographic data
timeFrame: Upon enrollment up to 72 hours after surgery
Other outcomes:
Locations:
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
Study officials:
affiliation: Queen's University/ Kingston Health Sciences Centre
name: Anthony MH Ho, MD,FRCPC
role: PRINCIPAL_INVESTIGATOR
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