Clinical trial NCT02449720: Intraperitoneal Local Anaesthetic in Bowel Surgery
Official title: The Effect of Intraperitoneal Local Anaesthetic on Functional Recovery Following Bowel Resection: A Prospective Randomised Blinded Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Colorectal Disorders
Keywords: intraperitoneal
ropivacaine
bowel resection
local anaesthetic
recovery
Lead sponsor: Royal Adelaide Hospital
Sponsor class: OTHER
Collaborators: name: University of Adelaide
name: University of South Australia
name: Saint Andrew's Hospital
name: Calvary North Adelaide Hospital
First posted: 2015-05-20
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the addition of a local anaesthetic infusion into the abdomen to patient controlled analgesia in the management of postoperative pain and recovery after bowel surgery. Half of the patients will have an infusion of a local anaesthetic called ropivacaine and half will have an infusion of placebo in addition to their normal pain relief.

Detailed description: The purpose of this randomised controlled blinded trial is to determine the effectiveness in every day practice of intraperitoneal local anaesthetic (IPLA) infusion on postoperative recovery following bowel resection in an optimised Enhanced Recovery After Surgery (ERAS) setting.

The investigators hypothesise that, in an optimised ERAS setting, intraperitoneal instillation and infusion of the local anaesthetic ropivacaine to the site of maximal visceral dissection for 48 hrs will result in an improved functional postoperative recovery following both open and laparoscopic bowel surgery.

This research will provide evidence to allow recommendation on the routine inclusion of IPLA into the multimodal analgesia component of ERAS programs for bowel surgery.

Eligibility criteria: Inclusion Criteria:

* The study population will include adults from the Central Adelaide Local Health network catchment area, South Australia.
* Patients known to the Colorectal Surgical Unit who have provided informed consent to undergo elective large bowel resection for any indication or undergoing reversal of Hartmann's Procedure will be invited to participate in this study.
* Potential participants will then be provided with an Information Sheet and encouraged to take the time to read it, discuss it with anyone they like, and ask any questions they have prior to deciding if they wish to participate. They will be reassured that participation is voluntary and there is no disadvantage to them if they decide not to participate.
* After obtaining informed consent, eligibility for inclusion will be determined based on health questions and blood results.

Exclusion Criteria:

* Under 18 years of age or over age 90.
* Allergy to local anaesthetic.
* Underlying medical conditions requiring deviation from the proposed anaesthetic protocol i.e., use of spinal or epidural anaesthesia rather than general anaesthesia.
* American Society of Anesthesiologists (ASA) \>=4 due to the higher likelihood or morbidity and mortality, which may confound resulting data.
* Severe underlying cardiovascular disease including conduction abnormalities, ischaemic heart disease or congestive heart failure, or use of amiodarone as a regular medication due to a higher risk or cardiac arrest under general anaesthetic or during use of local anaesthesia.
* Chronic Renal Failure (CRF) Stage 3 (GFR \> 60 based on two samples a minimum 90d apart).
* The pharmacokinetics of ropivacaine is not affected by renal failure although the renal clearance of its main metabolite (S)-2',6'-pipecoloxylidide (PPX) correlates with creatinine clearance, non-renal clearance compensates for reduced renal clearance in most patients.
* GFR will be calculated using the Cockcroft Gault equation for creatinine clearance (CrCl) : CrCl ml/min = \[140-age(years)\] x bodyweight (kg) / R x serum creatinine (micromol/L)
* R = 0.815 for males, 0.85 for females
* Hepatic dysfunction of Child-Pugh class B or C. Patients with end-stage liver disease have about a 60% lower mean ropivacaine clearance than healthy subjects and are thus expected to have over two-fold higher steady-state ropivacaine plasma concentrations during a continuous ropivacaine infusion.
* Concurrent or recent (within 3 months) use of fluvoxamine, enoxacin, ketoconazole, or cimetidine. These are potent CYP (cytochrome P450) 1A2, 2E1, or 3A4 inhibitors that have been shown to reduce ropivacaine clearance in vivo or in in vitro models. Potential participants concurrently using other potent CYP1A2, 2E1, or 3A4 inhibitors, where it is unclear if there is an effect on ropivacaine clearance, will be included or excluded from the study at the discretion of their study specialist anaesthetist.
* Abdominal-perineal resections (APR) due to the greater area of dissection and skin incision which will increase the level of baseline somatic pain felt by a patient.
* Requirement for postoperative drain in-situ, as this will drain the experimental solution out of the abdomen.
* Preoperative systemic steroid dependence due to derangement of the inflammatory response.
* Preoperative chronic pain illness including fibromyalgia, chronic regional pain syndrome, chronic fatigue syndrome, non specific chronic pain requiring daily opiate use, and history of alcohol or drug dependence due to the impact these have on subjective interpretation of pain and tolerance to opioid requiring significantly higher dosing regimens.
* Inability to consent or complete data scores in the study questionnaires due to cognitive impairment and/or language barrier.
* Pregnancy or breastfeeding.

Primary outcomes:
measure: Change from Baseline of the Surgical Recovery Scale to Day 45
timeFrame: Baseline (preoperative), and postoperative days 1, 3, 7, 30 and 45
Secondary outcomes:
measure: Change in Pain Over Time to Day 7 (Subjective)
timeFrame: At postoperative hours 3, 6, 12, 24, 48, and 72, and at day 7
measure: Change in Pain Over Time to day 3 (Objective)
timeFrame: Postoperative day 1, 2, and 3
measure: Recovery of Normal Bowel Function
timeFrame: Inpatient postoperative period (variable), and expected duration of 3-7 days.
measure: Time to Readiness for Discharge
timeFrame: up to 30 days
measure: Operative Complications
timeFrame: 30 days post operation
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
Study officials:
affiliation: Royal Adelaide Hospital, Colorectal Surgical Unit Research Registrar
name: Jaime A Duffield, BMBS PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Paddison JS, Sammour T, Kahokehr A, Zargar-Shoshtari K, Hill AG. Development and validation of the Surgical Recovery Scale (SRS). J Surg Res. 2011 May 15;167(2):e85-91. doi: 10.1016/j.jss.2010.12.043. Epub 2011 Jan 31.
citation: Kahokehr A, Sammour T, Zargar Shoshtari K, Taylor M, Hill AG. Intraperitoneal local anesthetic improves recovery after colon resection: a double-blinded randomized controlled trial. Ann Surg. 2011 Jul;254(1):28-38. doi: 10.1097/SLA.0b013e318221f0cf.
citation: Duffield JA, Thomas ML, Moore JW, Hunter RA, Wood C, Gentili S, Lewis M. Intraperitoneal Local Anesthetic Instillation and Postoperative Infusion Improves Functional Recovery Following Colectomy: A Randomized Controlled Trial. Dis Colon Rectum. 2018 Oct;61(10):1205-1216. doi: 10.1097/DCR.0000000000001177.