Clinical trial NCT03391427: Ketamine, Lidocaine and Combination for Postoperative Analgesia in Open Liver Resection
Official title: Ketamine, Lidocaine and Combination for Postoperative Analgesia in Open Liver Resection: A Prospective, Randomized, Four-arm, Double Blind, Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hepatectomy
Keywords: Lidocaine
Ketamine
postoperative analgesia
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2018-01-05
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Lidocaine, ketamine, combination and placebo are being evaluated for treating postoperative pain in major liver resection
Primary purpose: TREATMENT

Brief summary: Lidocaine and ketamine both are being used for perioperative analgesia. Perioperative lidocaine infusion has been shown to reduce postoperative pain and opioid consumption. Perioperative low dose Ketamine has shown improved postoperative pain and reduced opioid usage. We therefore tested the hypothesis that the combination would provide better analgesia in the milieu of intrathecal morphine.

Detailed description: All study participants were monitored according to American Society of Anesthesiologists guidelines. All received intrathecal morphine (300 to 400 mcg) at L3-4 interspace via 25 G Whitacre needle. Participants were then randomized (computer generated) into one of four groups.

General anesthesia was induced and endotracheal intubation was done. Immediately, after intubation, Lidocaine group (L) received a Lidocaine infusion at 0.33 mg/kg/h.

The Ketamine group (K) received a ketamine infusion at 70 mcg/Kg/h. The Lidocaine-Ketamine group (LK) received a Lidocaine infusion at 0.33 mg/kg/h plus a Ketamine infusion at 70 mcg/Kg/h.

The control group (P) received a normal saline infusion to keep the blind. The infusions were stopped approximately 30-45 minute before the completion of surgery.

All participants received a hydromorphone patient-controlled analgesia (PCA) via a pump. All were given acetaminophen 650 mg every 6 hrs for 4 days.

Postoperatively, participants were monitored for nausea, vomiting, sedation, respiratory depression, light-headedness, perioral numbness, pruritus, disturbed dreams and hallucinations.

Postoperative Hydromorphone consumption for the first, second and third day was recorded from the chart maintained by acute pain service team who were blinded to the group assignment.

After the operation, study participants were interviewed at regular intervals by a blinded investigator about their current pain level, as well as satisfaction with pain management. They were also be questioned regarding the presence and severity of opioid-related side effects (nausea, vomiting, sedation, respiratory depression and, pruritus) and light-headedness, perioral numbness, disturbed dreams and hallucinations. Hospital charts were reviewed and data collected to analyze time to request for additional analgesia and total consumption of opioids, non-opioid analgesics, anti-emetics, and antipruritics within the first 72 hours postoperatively.

Eligibility criteria: Inclusion Criteria:

* ASA physical status 2-4
* Elective major liver resection
* Signed informed consent

Exclusion Criteria:

* ICU admission after surgery
* tracheal extubation not planned after surgery
* language barrier
* mental impairment
* severe coagulopathy
* chronic pain or opioid dependance or both
* alcohol/substance abuse
* allergy to the study drugs
* refusal for spinal
* infection at site of spinal

Primary outcomes:
measure: Opioid consumption
timeFrame: 24 hr
Secondary outcomes:
measure: Opioid consumption
timeFrame: 48 hrs
measure: Opioid related side effects
timeFrame: 72 hrs
measure: Chronic pain
timeFrame: 6 weeks
measure: Patient satisfaction
timeFrame: 72 hrs
measure: Chronic pain
timeFrame: 12 weeks
measure: Opioid consumption
timeFrame: 72 hrs
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
Study officials:
affiliation: Lawson
name: Achal Dhir
role: PRINCIPAL_INVESTIGATOR
References:
citation: Harvey KP, Adair JD, Isho M, Robinson R. Can intravenous lidocaine decrease postsurgical ileus and shorten hospital stay in elective bowel surgery? A pilot study and literature review. Am J Surg. 2009 Aug;198(2):231-6. doi: 10.1016/j.amjsurg.2008.10.015. Epub 2009 Mar 12.
citation: Rakic AM, Golembiewski J. Low-dose ketamine infusion for postoperative pain management. J Perianesth Nurs. 2009 Aug;24(4):254-7. doi: 10.1016/j.jopan.2009.05.097. No abstract available.
citation: Ko JS, Choi SJ, Gwak MS, Kim GS, Ahn HJ, Kim JA, Hahm TS, Cho HS, Kim KM, Joh JW. Intrathecal morphine combined with intravenous patient-controlled analgesia is an effective and safe method for immediate postoperative pain control in live liver donors. Liver Transpl. 2009 Apr;15(4):381-9. doi: 10.1002/lt.21625.