Isoflurane Preconditioning for Liver Resections

This study has been terminated.
(We no longer had an appropriate patient population.Study closed)
Sponsor:
Information provided by (Responsible Party):
Anesthesia, Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier:
NCT01031550
First received: December 10, 2009
Last updated: December 11, 2013
Last verified: December 2013
  Purpose

The objective is to examine the efficacy of isoflurane (inhaled anesthetic gas) to induce clinically effective preconditioning in patients undergoing elective hepatic surgery.


Condition Intervention
Liver Disease
Drug: isoflurane
Other: standard of care

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Isoflurane Induced Anesthetic Preconditioning in Elective Liver Resection

Resource links provided by NLM:


Further study details as provided by Rutgers, The State University of New Jersey:

Primary Outcome Measures:
  • Post Operative Complications Grade IIIb or Greater According to Clavien's Classification [ Time Frame: first 7 post operative days ] [ Designated as safety issue: No ]
    Post operative complications grade IIIB or greater according to Clavien's classification


Secondary Outcome Measures:
  • Peak Postoperative AST, ALT and T Bili [ Time Frame: first 7 post operative days ] [ Designated as safety issue: No ]
  • Length of ICU and Hospital Stay [ Time Frame: first 7 post operative days ] [ Designated as safety issue: No ]
  • Decrease in Liver Lipid Peroxidation and Apoptosis [ Time Frame: first 7 post operative days ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: January 2010
Study Completion Date: June 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: standard anesthetic management
standard anesthetic management
Other: standard of care
standard of care
Experimental: preconditioning with 2 MAC isoflurane group
preconditioning with isoflurane
Drug: isoflurane
isoflurane an anesthetic gas agent administered at specific times at a flow of 2 MAC

  Hide Detailed Description

Detailed Description:

Elective liver resection is performed primarily for the treatment of benign and malignant liver tumors1. In addition, with the increasing use of living donor liver transplantation to supplement the inadequate pool of cadaveric organs available, liver resection is performed also in live liver donors2.

Postoperative complications are common following liver resections. Occurrence of complications increases ICU and hospital stay, and resource utilization. The most serious postoperative complication after a liver resection is post-resectional liver failure (PLF)3. Risk factors for the development of PLF are preexisting liver disease, especially cirrhosis, excessive blood loss during liver resection, and liver ischemia and reperfusion injury4-5. Several strategies have been developed to combat excessive intra-operative blood loss including: lowering the central venous pressure6, hypoventilation7, and hepatic inflow occlusion using an atraumatic clamp8 (Pringle's maneuver)9; While inflow occlusion is the most important of these steps, hepatic ischemia and reperfusion is an important sequel to the inflow occlusion. Therefore, interventions which decrease hepatic ischemia reperfusion injury to the liver have the potential to improve outcomes following liver resection.

A strategy that directly modulates the hepatic response to ischemia is ischemic preconditioning (IPC). Classically, IPC has been induced by exposing an organ to brief periods of ischemia and reperfusion before exposing the organ to a more prolonged ischemic insult. In patients undergoing liver resection, IPC decreases postoperative aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels15. IPC is also associated with decreased histological evidence of apoptosis as well as immunohistochemical evidence of increased protective gene expression16 in the liver.

The primary disadvantage of IPC is the direct stress to the target organ as well as the mechanical trauma to major vasculature.

More recently, it has been found that inhaled volatile anesthetics such as Desflurane, Sevoflurane and Isoflurane induce similar preconditioning effects19 without causing any significant direct organ damage. While several animal studies exist, which demonstrate the hepatoprotective effect of volatile anesthetics on the liver23, there is only limited clinical data examining their effect in humans. One recent small clinical study, examining the preconditioning effect of volatile anesthetic on patients undergoing liver surgery, showed that anesthetic pre conditioning (APC) using Sevoflurane significantly decreased the several measures of liver dysfunction postoperatively24.

However, Sevoflurane is partially metabolized by the liver and may increase plasma fluoride concentration. Also, it may react with CO2 absorbent and can produce Compound-A, which in turn has been linked to nephrotoxicity. On the other hand, isoflurane, another inhalational anesthetic agent commonly used during liver surgery also has been shown to have a preconditioning effect in experimental animals, and does not carry the potential side effects of sevoflurane.

Therefore, the primary objective of this study is to examine the efficacy of isoflurane to induce clinically effective preconditioning in patients undergoing elective hepatic surgery.

Study Design:

In this prospective study, patients undergoing elective liver resection with inflow occlusion (Pringle maneuver) at UH, Newark will be randomized (1:1) to either standard anesthetic management with Propofol (No APC group) or anesthetic preconditioning with 2 minimum alveolar concentration (MAC) of isoflurane (APC group). Because preexisting liver disease, especially cirrhosis, is an important determinant of post operative outcomes, and to balance the randomization of subjects regarding this important variable randomization will be stratified into those with and without preexisting liver disease. The primary endpoint is the occurrence of postoperative complications grade IIIb or greater (Clavien's classification). The secondary endpoints are peak postoperative aspartate and alanine aminotransferase (AST and ALT) and total bilirubin (T Bili), length of ICU and hospital stay, and a decrease in liver lipid peroxidation and apoptosis

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients with liver tumors undergoing liver resection of > 1 segment liver resection must be performed with inflow occlusion > 30 min

Exclusion Criteria:

  • patients undergoing liver resection of one segment or less
  • patients undergoing laparoscopic liver resection
  • patients in whom the liver resection is performed with no inflow occlusion or inflow occlusion of < 30 min
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01031550

Locations
United States, New Jersey
UMDNJ-University Hospital
Newark, New Jersey, United States, 07101
Sponsors and Collaborators
Rutgers, The State University of New Jersey
Investigators
Principal Investigator: Yuriy Gubenko, MD Rutgers, The State University of New Jersey
  More Information

No publications provided

Responsible Party: Anesthesia, Investigator Intiated Dept of Anesthesia, Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier: NCT01031550     History of Changes
Other Study ID Numbers: 0120090226
Study First Received: December 10, 2009
Results First Received: September 16, 2013
Last Updated: December 11, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Rutgers, The State University of New Jersey:
liver resection for liver disease

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases
Anesthetics
Isoflurane
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Inhalation
Anesthetics, General

ClinicalTrials.gov processed this record on September 16, 2014