Antinociceptive Modalities on Ischemia Reperfusion Injury
Condition: End Stage Liver Disease; Lung Cancer
MeSH terms: Liver Diseases; End Stage Liver Disease; Reperfusion Injury; Ischemia
Study type: Observational

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.
    

Intervention name(s): Patient controlled analgesia
Intervention type(s): Drug
Intervention description(s): PCA with morphine in liver transplant:
Intravenous patient controlled analgesia with morphine was used for postoperative pain control in liver transplant recipients.
PCA with morphine and ketorolac:
Patient controlled analgesia with morphine and ketorolac was used for postoperative pain control in liver transplant and thoracic surgery patients.
Intravenous PCA in thoracic surgery Intravenous patient controlled analgesia was used for postoperative pain control in thoracic surgery patients.
PCEA in thoracic surgery Patient controlled epidural analgesia was used for postoperative pain control in thoracic surgery patients.
Other intervention name(s): morphine; ketorolac; marcaine
Intervention MeSH terms: Ketorolac; Morphine
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        End stage liver disease Lung cancer
      
Biospecimen description: 
      plasma
    
Keywords: reactive oxygen species; ischemia reperfusion injury