RITM-IVM: Efficacy of Multimodal Opioid Therapy During Hepatic Resection Surgery

Sponsor

St Vincent's University Hospital, Ireland (Other)

Overall Status

Unknown status

CT.gov ID

NCT00553553

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Dysfunction Pain	Drug: Morphine sulphate Drug: Morphine hydrochloride, remifentanil hydrochloride	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2007

Anticipated Primary Completion Date :

May 1, 2008

Anticipated Study Completion Date :

Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 IV morphine group	Drug: Morphine sulphate Intravenous morphine titrated up to 0.25 milligrams/kilogram prior to end of resection phase or within first 2 hours of surgery
Experimental: 2 Remifentanil-intrathecal morphine group	Drug: Morphine hydrochloride, remifentanil hydrochloride 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

Arm

Intervention/Treatment

Active Comparator: 1

IV morphine group

Drug: Morphine sulphate

Intravenous morphine titrated up to 0.25 milligrams/kilogram prior to end of resection phase or within first 2 hours of surgery

Experimental: 2

Remifentanil-intrathecal morphine group

Drug: Morphine hydrochloride, remifentanil hydrochloride

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

Outcome Measures

Primary Outcome Measures

Opioid-related side effects [First 24 hours post-operatively]

Secondary Outcome Measures

IV opioid analgesic supplementation [First 24 hours post-operatively]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)