Clinical trial NCT02647047: Spinal Versus Epidural Analgesia in Laparotomic Liver Surgery
Official title: Spinal Analgesia Versus Epidural Analgesia in Minor Laparotomic Liver Surgery in an Enhanced Recovery Programme: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Secondary Malignant Neoplasm of Liver
Liver Diseases
Liver Neoplasms
Keywords: spinal analgesia
epidural analgesia
laparotomic liver resection
ERAS
length of stay
Lead sponsor: Ospedale San Raffaele
Sponsor class: OTHER
First posted: 2016-01-06
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of spinal analgesia for minor laparotomic hepatectomy compared with epidural analgesia, monitoring visual analog scale (VAS). The investigators expect at least the same post-operative pain control in the two groups (non inferiority of pain control with spinal analgesia compared to epidural analgesia). Second endpoint is to verify whether after spinal analgesia there is a decrease in patient's length of hospitalization according to enhanced recovery after surgery (ERAS) principles.

Detailed description: Liver surgery is performed under general anesthesia. Loco-regional analgesia is generally performed before general anesthesia induction to obtain the best post-operative pain control,in association with intravenous analgesic drug administration.

For minor laparotomic surgery (defined as the resection of up to three hepatic segments), if not contraindicated, in our hospital loco-regional analgesia is performed through the placement of a thoracic (T7-T8 or T8-T9) epidural catheter in which a local anesthetic (usually ropivacaine) and an opioid (usually sufentanil) are administered for the first three post-operative days. This is still considered the gold-standard for pain management in this surgery. In our institute, there is a dedicated acute pain service (APS) for pain management in the post-operative period. APS is also responsible for monitoring, registering and treating all side effects related to both the procedure and the drugs used.

In laparoscopic abdominal surgery, instead of epidural analgesia, if not contraindicated, spinal analgesia with low dose morphine before general anesthesia induction is performed. This technique is actually considered efficacy and safe in these type of surgeries.

The investigators therefore decided to test the efficacy of spinal analgesia versus epidural analgesia for minor liver surgery since anterior hepatic segments resection is less painful than major liver surgery because it requires less liver manipulation without significant involvement of the Glisson's capsule. This might imply a less incidence of procedure-related side effects such as post-dural puncture headache or site infections. Moreover, spinal analgesia may allow a earlier post-operative patients mobilization and thus a earlier hospital discharge.

In this randomized controlled trial, the investigators therefore aim to randomize 40 consecutive patients into 2 arms. The experimental group will receive spinal analgesia (morphine 0.2 mg) for post-operative pain control while the control group will receive epidural analgesia (bolus of ropivacaine 0.2% 4-6 mL followed by continuous epidural infusion of ropivacaine 0.2%: 99 mL + sufentanil 50 mcg/mL: 1 mL).

Randomization will be performed with closed opaque envelopes. During surgery, patients will be monitored as usual. Intraoperative blood losses and fluids administration will be recorded.

Patients randomized into the epidural group will not receive local anesthetic administration through the epidural catheter during the hepatic resection phase to avoid hemodynamic instability. Once the hepatic resection phase is finished and euvolemic status is recovered, epidural analgesia will be administered as mentioned before.

In patients in the spinal group, transversus abdominis plane (TAP) block with ropivacaine 0.375% 20 mL bilaterally or surgical wound infiltration with ropivacaine 0.75% 10- 20 mL will also be performed before anesthesia recovery.

In both groups, post-operative pain control will be managed with intravenous acetaminophen 1000 mg 40 minutes before ending of surgery followed by intravenous administration of acetaminophen 1000 mg every 8 hours and a non-steroidal antinflammatory drug (ketorolac 30 mg) as a rescue therapy in the post-operative period if not contraindicated.

Patients will be monitored every 24 hours until the achievement of the "ready to discharge" status defined as:

* appropriate oral alimentation;
* optimal pain control with drugs administered orally;
* adequate ability in walking and personal care;
* clinical, laboratory and instrumental absence of any post-operative complication;
* intestinal function recovery;
* patient consent to discharge.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years old
* Hospitalized patients
* Surgical indication for minor laparotomic anterior liver resection (II, III, IV and V hepatic segment resection)
* Surgical indication for laparotomic liver metastasectomy
* Ability to provide an informed consent

Exclusion Criteria:

* Patient refusal to provide informed consent
* Chronical therapy with opioids
* Pregnancy or breastfeeding
* Alcohol or drug abuse
* Planned or unplanned post-operative intensive care unit admission
* Contraindication to spinal/epidural analgesia
* Severe liver or renal failure
* Cognitive disorders, mental retard or psychiatric disorders
* Allergy to any drug used

Primary outcomes:
measure: Assessment of postoperative pain control by mean of the visual analog scale early after surgery
timeFrame: Within 1 hour after surgery
measure: Assessment of postoperative pain control by mean of the visual analog scale six hours after surgery
timeFrame: 6 hours after surgery
measure: Assessment of postoperative pain control by mean of the visual analog scale one day after surgery
timeFrame: 24 hours after surgery
measure: Assessment of postoperative pain control by mean of the visual analog scale two days after surgery
timeFrame: 48 hours after surgery
measure: Assessment of postoperative pain control by mean of the visual analog scale three days after surgery
timeFrame: 72 hours after surgery
measure: Assessment of postoperative pain control by mean of the visual analog scale at hospital discharge
timeFrame: Up to 30 days after surgery
Secondary outcomes:
measure: Ready to discharge status
timeFrame: Up to 30 days after surgery
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Ospedale San Raffaele
state: MI
Study officials:
affiliation: Ospedale San Raffaele
name: Raffaella Reineke, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tzimas P, Prout J, Papadopoulos G, Mallett SV. Epidural anaesthesia and analgesia for liver resection. Anaesthesia. 2013 Jun;68(6):628-35. doi: 10.1111/anae.12191.
citation: Revie EJ, Massie LJ, McNally SJ, McKeown DW, Garden OJ, Wigmore SJ. Effectiveness of epidural analgesia following open liver resection. HPB (Oxford). 2011 Mar;13(3):206-11. doi: 10.1111/j.1477-2574.2010.00274.x.
citation: Kasivisvanathan R, Abbassi-Ghadi N, Prout J, Clevenger B, Fusai GK, Mallett SV. A prospective cohort study of intrathecal versus epidural analgesia for patients undergoing hepatic resection. HPB (Oxford). 2014 Aug;16(8):768-75. doi: 10.1111/hpb.12222. Epub 2014 Jan 28.
citation: Ntinas A, Kardassis D, Konstantinopoulos I, Kottos P, Manias A, Kyritsi M, Zilianiaki D, Vrochides D. Duration of the thoracic epidural catheter in a fast-track recovery protocol may decrease the length of stay after a major hepatectomy: a case control study. Int J Surg. 2013;11(9):882-5. doi: 10.1016/j.ijsu.2013.07.014. Epub 2013 Aug 4.
citation: Koea JB, Young Y, Gunn K. Fast track liver resection: the effect of a comprehensive care package and analgesia with single dose intrathecal morphine with gabapentin or continuous epidural analgesia. HPB Surg. 2009;2009:271986. doi: 10.1155/2009/271986. Epub 2009 Dec 15.
citation: Hughes MJ, McNally S, Wigmore SJ. Enhanced recovery following liver surgery: a systematic review and meta-analysis. HPB (Oxford). 2014 Aug;16(8):699-706. doi: 10.1111/hpb.12245. Epub 2014 Mar 24.