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

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

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.

Study Overview

• Status: Unknown
• Conditions: Pain; Liver Dysfunction
• Intervention / Treatment: Drug: Morphine sulphate; Drug: Morphine hydrochloride, remifentanil hydrochloride

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 Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Debbie A. D'Oyley, MB BS; Phone Number: +3531 2094262; Email: doyleyda@aol.com
• Study Contact Backup: Name: Neil J. McDonald, MB BCh; Phone Number: +3531 2094262; Email: n.mcdonald@svuh.ie

Study Locations

• Ireland
  • County Dublin
    • Dublin, County Dublin, Ireland, 4
      • Recruiting
      • St. Vincent's University Hospital
      • Principal Investigator: Neil J. McDonald, MB BCh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: St Vincent's University Hospital, Ireland
• Investigators: Principal Investigator: Neil J. McDonald, MB BCh, St Vincent's University Hospital, Ireland

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Anticipated): May 1, 2008
• Study Completion (Anticipated): June 1, 2008

Study Registration Dates

• First Submitted: November 2, 2007
• First Submitted That Met QC Criteria: November 2, 2007
• First Posted (Estimate): November 4, 2007

Study Record Updates

• Last Update Posted (Estimate): December 31, 2008
• Last Update Submitted That Met QC Criteria: December 30, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: Adult; Intrathecal morphine ITM intravenous morphine remifentanil hepatic resection; ASA I-III (stable); Liver dysfunction requiring primary parenchymal resection
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Remifentanil; Morphine
• Other Study ID Numbers: St. Vincent's Hospital Ireland