The Effect of Adding Intraoperative Regional Anesthesia on Natural Killer Cell Function in Patients Undergoing Lung Cancer Resection

2014-07-24 14:11:09 | BioPortfolio


The investigators propose to compare the effect of combined epidural general anesthesia-analgesia versus only general anesthesia-analgesia on the immune function and inflammatory response of patients with lung cancer undergoing lung surgery. Regional anesthesia and analgesia help maintain perioperative immune function by reducing general anesthesia requirements, by ameliorating the stress response to surgery, and by sparing postoperative opioids. We propose a prospective randomized trial to determine the effects of epidural anesthesia and analgesia on the perioperative immune function and inflammatory response associated to lung cancer surgery. Primary Hypothesis: Perioperative immune function (NK cell activity) in patients undergoing tumor resection of stage I - III primary non-small cell lung cancers is better preserved in patients randomized to combine general-epidural anesthesia & analgesia than those randomized to only general balanced anesthesia and postoperative epidural analgesia.

Secondary Hypothesis: The profile of pro-inflammatory versus anti-inflammatory and lymphocyte stimulating cytokines after localized tumor resection of stage I - III primary non-small cell lung cancers is better preserved in patients randomized to combined general-epidural anesthesia and analgesia than to only general balanced anesthesia and postoperative epidural analgesia.


Surgery is the primary treatment of lung cancer, but surgery releases tumor cells into the systemic circulation. Whether this minimal residual disease results in clinical metastases is a function of host defense. At least three perioperative factors shift the balance toward initiation and progression of minimal residual disease. (1) Surgery per se depresses cell-mediated immunity, reduces concentrations of tumor-related anti-angiogenic factors (e.g., angiostatin and endostatin), and increases concentrations of pro-angiogenic factors such as VEGF. (2) Anesthesia impairs numerous immune functions, including neutrophil, macrophages, dendritic cells, T-cell, and NK-cell functions. (3) Opioid analgesics inhibit both cellular and humoral immune function in humans, and promote tumor growth in rodents. Regional analgesia attenuates each of these adverse effects. For example, regional anesthesia largely prevents the neuroendocrine stress response to surgery by blocking afferent neural transmission. With combined regional and general anesthesia/analgesia, the amount of general anesthetic required is much reduced — as is, presumably, immune suppression. And finally, regional analgesia provides superb pain relief, essentially obliterating the need for postoperative opioids. Animal studies show that regional anesthesia improves natural kill cell function and reduces the metastatic burden in animals inoculated with carcinoma cells. Preliminary retrospective data in cancer patients showed, that paravertebral analgesia for breast cancer surgery reduced risk of recurrence or metastasis by 40% during a 2.5 to 4-year follow-up period.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care


Lung Cancer


bupivacaine and fentanyl, bupivacaine


Cleveland Clinic Foundation
United States




Outcomes Research Consortium

Results (where available)

View Results


Published on BioPortfolio: 2014-07-24T14:11:09-0400

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Medical and Biotech [MESH] Definitions

A widely used local anesthetic agent.

A local anesthetic with rapid onset and long action, similar to BUPIVACAINE.

A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine.

A local anesthetic that is chemically related to BUPIVACAINE but pharmacologically related to LIDOCAINE. It is indicated for infiltration, nerve block, and epidural anesthesia. Mepivacaine is effective topically only in large doses and therefore should not be used by this route. (From AMA Drug Evaluations, 1994, p168)

A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)

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Anesthesia is the loss of feeling or sensation in all or part of the body. It may result from damage to nerves or can be induced by an anesthetist (a medical professional) using anesthetics such as thiopental or propofol or sevoflurane during a surgical ...

An anesthesiologist (US English) or anaesthetist (British English) is a physician trained in anesthesia and perioperative medicine. Anesthesiologists are physicians who provide medical care to patients in a wide variety of (usually acute) situations. ...

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