Efficacy of Multimodal Opioid Therapy During Hepatic Resection Surgery

Study Overview
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Brief Summary
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The patient population requiring hepatic resection can demonstrate an unpredictable risk of exhibiting peri-operative coagulopathy resulting either from the pre-operative hepatic pathophysiology or volume of parenchymal resection. Choice of analgesia can be severely limited. Currently, the most commonly described use of combined remifentanil infusion and intrathecal morphine has been in fast-track cardiac surgery. To date, there are no published data describing its use in the context of major hepatobiliary where the investigators predict it may provide adequate analgesia with a lower rate of adverse effects over the first 24 hours after surgery.

Detailed Description
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Choice of analgesia in hepatic resection surgery can be severely limited. This can depend upon on the pre-operative hepatic pathophysiology or the extent of parenchymal resection, both of which will affect peri-operative hepatic function, capacity for drug handling and risk of coagulopathy. Use of IV morphine during hepatic resection can result in high plasma levels post-operatively due to a reduced rate of morphine metabolism, risking a higher rate of morbidity. However, this remains a mainstay of peri-operative analgesia in combination with controversial non-opioid supplementation (paracetamol, non-steroidal anti-inflammatory drugs). This study compares the efficacy of IV morphine only versus a combination of pre-incisional intrathecal morphine and intra-operative IV remifentanil. Intrathecal morphine provides the mainstay of post-operative analgesia for 12-24 hours and remifentanil provides profound, titratable intra-operative analgesia until the delayed onset of the intrathecal morphine. We hypothesise that this combination might provide desirable intra-operative haemodynamic conditions and eliminate the post-operative additive effects of long-acting, intra-operative IV opioid and intrathecal morphine. Further, if the dose of intrathecal morphine is adequate, this would result in a low rate of post-operative analgesic supplementation and fewer side effects. The titratable dose range of remifentanil is limited to the lower range found to risk post-operative hyperalgesia.

Official Title
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Efficacy Of IV Morphine vs Remifentanil-Intrathecal Morphine Analgesia During Hepatic Resection Surgery

Conditions
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Liver Dysfunction, Pain

Intervention / Treatment
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* Drug: Morphine sulphate
* Drug: Morphine hydrochloride, remifentanil hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult ASA I, II or stable III Undergoing primary elective hepatic resection of < 50% predicted parenchymal resection Exclusion Criteria: Previous major upper GI surgery: liver resection or transplant gastrectomy oesophagectomy Whipple's procedure Contraindications to dural puncture: coagulopathy uncorrected anti-coagulant therapy spinal deformity neurological disorder psychiatric disorder Morphine allergy Co-morbidity predisposing to failure of extubation at conclusion of surgery: severe cardiopulmonary pathology scoring ASA III (unstable) IV V sleep apnoea morbid obesity (BMI > 35) Failure to proceed with resection, emergency resection or conversion to > 50% parenchymal resection Chronic/intractable pain conditions: requiring long-term high dose analgesia implanted analgesic devices Predisposition to severe post-operative nausea and vomiting: motion sickness previous PONV Anatomical or physiological indication for rapid sequence induction (relative)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>IV morphine group | Drug: Morphine sulphate<br>* Intravenous morphine titrated up to 0.25 milligrams/kilogram prior to end of resection phase or within first 2 hours of surgery<br>|
| Experimental: 2<br>Remifentanil-intrathecal morphine group | Drug: Morphine hydrochloride, remifentanil hydrochloride<br>* Pre-induction intrathecal morphine HCl (< 3 attempts), single shot via 25 G pencil point spinal needle at 10 micrograms/kilogram Intra-operative intravenous remifentanil HCl at titratable dose range 0.1-0.25 micrograms/kilogram/minute until start of wound closure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid-related side effects |  | First 24 hours post-operatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IV opioid analgesic supplementation |  | First 24 hours post-operatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intrathecal morphine ITM intravenous morphine remifentanil hepatic resection, Adult, ASA I-III (stable), Liver dysfunction requiring primary parenchymal resection