Clinical trial NCT01932918: Antinociceptive Modalities on Ischemia Reperfusion Injury
Official title: The Interaction of Nociceptive Stimulation and Various Antinociceptive Modalities on Ischemia Reperfusion Injury
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: End Stage Liver Disease
Lung Cancer
Keywords: reactive oxygen species
ischemia reperfusion injury
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2013-08-30
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: End stage liver disease Lung cancer

Brief summary: Postoperative pain caused by surgery-associated tissue injury is a major concern for all the clinical practitioners. Because it affects multiple systems and induces physiological, immunological and psychological changes. Previous literature showed surgical injury induces a systemic inflammatory metabolic-endocrine response that is proportional to the severity of the surgical stress. In surgeries such as liver transplantation, the patients suffer not only from postoperative pain but also an additional oxidative stress caused by ischemia reperfusion. Previous report have proved that an adequate postoperative pain control improves the recovery and reduces the inflammatory cascade by suppression of physiological and psychological stresses. However, the effect of postoperative pain management on ischemia reperfusion injury is unclear so far. In this three year study, we plan to continue our previous study to test the following two hypothesis: (1) postoperative pain exacerbate remote organ injury caused by ischemia reperfusion, (2) the interaction of different antinociceptive modalities on ischemia reperfusion injury.

Detailed description: Our team focused on the study of reperfusion injury in liver transplantation, lung resection and open heart surgeries which need cardiopulmonary bypass. Previous clinical observation showed the increase of lung water in liver transplant recipients. Some patients may even develop pulmonary edema which not only lengthen intensive care unit stay and hospital stay, but also increase morbidity and mortality. In the hepatic ischemia reperfusion animal model, we proved that the release of large amount of reactive oxygen species play an important part in remote lung injury. If propofol, which possesses free radical scavenger property, is given adequately, the production of reactive oxygen species will decrease thus reducing the extent of remote lung injury. In another clinical study, we found that resuming two lung ventilation from one lung ventilation induces a massive superoxide production, which also could be reduced when using propofol for the maintenance of anesthesia.

Postoperative pain caused by surgery-associated tissue injury is a major concern for all the clinical practitioners. Because it affects multiple systems and induces physiological, immunological and psychological changes. Previous literature showed surgical injury induces a systemic inflammatory metabolic-endocrine response that is proportional to the severity of the surgical stress. In surgeries such as liver transplantation, the patients suffer not only from postoperative pain but also an additional oxidative stress caused by ischemia reperfusion. Previous report have proved that an adequate postoperative pain control improves the recovery and reduces the inflammatory cascade by suppression of physiological and psychological stresses. However, the effect of postoperative pain management on ischemia reperfusion injury is unclear so far. In this three year study, we plan to continue our previous study to test the following two hypothesis: (1) postoperative pain exacerbate remote organ injury caused by ischemia reperfusion, (2) the interaction of different antinociceptive modalities on ischemia reperfusion injury.

In the first part, we plan to use the animal model that we have already established to test if analgesics reduce inflammatory responses and remote lung injury caused by hepatic ischemia and to study if different antinociceptive modalities result in different consequences. In the second part, we will recruit patients receiving liver transplantation, lung resection and open heart surgeries needing cardiopulmonary bypass to study the interaction of nociception and various antinociceptive modalities on ischemia reperfusion injury.

Eligibility criteria: Inclusion Criteria:

* End stage liver disease patients scheduled for liver transplantation in National Taiwan University Hospital
* Lung cancer patients scheduled for thoracic surgery in National Taiwan University Hospital

Exclusion Criteria:

* preoperative pulmonary dysfunction

Primary outcomes:
measure: lung injury score
timeFrame: four days
Secondary outcomes:
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Department of Anesthesiology, NTUH, Taipei, Taiwan
Study officials:
affiliation: Department of Anesthesiology, NTUH, Taipei, Taiwan
name: Kuang Cheng Chan, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lin TF, Yeh YC, Lin FS, Wang YP, Lin CJ, Sun WZ, Fan SZ. Effect of combining dexmedetomidine and morphine for intravenous patient-controlled analgesia. Br J Anaesth. 2009 Jan;102(1):117-22. doi: 10.1093/bja/aen320. Epub 2008 Nov 5.