Dexmedetomidine and HIPEC

Inflammation is associated with an increased risk of cancer recurrence. Various methods have been used to decrease the inflammatory response induced by the cancer and surgery. In this study the investigators would like determine if a commonly used sedative drug (dexmedtomidine) has an impact on this inflammatory state when used as part of the anesthetic. The investigators will conduct a pilot study with 20 patients undergoing a Hyperthermic Intraperitoneal Chemotherapy (HIPEC) procedure as part of their cancer treatment. 10 patients will receive the standard of care for anesthesia during the cancer surgery and a placebo infusion of normal saline at a rate consistent to that of the study drug. 10 additional patients will receive the same standard of care anesthetic plan with the addition of an infusion of dexmeditomidine during the procedure. The investigators will measure the degree of inflammation before, during and after the surgical procedure by looking at the levels of inflammatory markers in blood samples. The goal is to determine if the addition of dexmodtomidine affects the inflammatory state of patients undergoing a HIPEC procedure. This information will be used to guide future studies aiming at decreasing cancer recurrence and improve patient outcomes.

Purpose: To investigate the use of intra-operative dexmedetomidine infusions to reduce the inflammatory and stress response of cytoreductive treatment and hyperthermic intra-peritoneal chemotherapy (HIPEC). Hypothesis: HIPEC surgery patients who receive an intra-operative infusion of dexmedetomidine in addition to the current standard of care, consisting of parenteral and enteral opioids and thoracic epidural will have a reduction in their inflammatory markers intra-operatively, in PACU, POD1 and POD5 and a reduction in oral morphine equivalent opioid consumption in PACU and POD1, in comparison to those who receive a placebo infusion. Justification: Surgical tumor excision is a cornerstone of primary cancer treatment, but is also recognized as one of the greatest risk factors for metastatic spread. The perioperative period, characterized by the surgical stress response and pharmacologic-induced angiogenesis and immunomodulation, results in a physiologic environment that supports tumor spread and distant reimplantation. There is potential for anesthesiologists to modulate the unwanted consequences of the stress response on the immune system and minimize residual disease by altering their anesthetic plan. Dexmedtomidine is a commonly used sedative that can be used as part of an anesthetic during surgery. In vitro and animal studies have shown that dexmedtomidine decreases the inflammatory response but no research has been conducted with cancer-related conditions. Objective: To determine if dexmedtomidine, when used intraoperatively, can decrease the levels of inflammation in patients a Hyperthermic Intraperitoneal Chemotherapy (HIPEC) procedure as part of their cancer treatment. Primary Objective: Reduction in inflammatory markers: CRP, ESR, NLR, PLR, plasma viscosity, lactate. Secondary Objectives Reduction in Cancer markers: CEA (carcinoembyronic antigen] and CA19-9 Reduction in opioid use Reduction in volatile usage (average sevoflurane end-tidal level) Research Design: In this pilot study, 20 patients undergoing a HIPEC procedure as part of their cancer treatment will be randomized into 2 groups. One group (controls) will receive the current anesthetic standard of care. The second group (experimental) will also receive the current anesthetic standard of care with the addition of an infusion of dexmedtomidine during the surgical procedure. Biomarkers of inflammation (Lactate, CRP, ESR, plasma viscosity, NLR, PLR, and procalcitonin) and cancer markers (CEA and CA19-9) will be measured at 5 time points: pre-operatively, intra-opertatively prior to chemotherapy, post-operatively in the post-anaesthetic care unit, post-operative day 1, and post-operative day 5. Quantitative analysis of the inflammatory markers will be used to compare the two groups. Statistical Analysis: Data will be summarized and t-tests will be used to compare the data from the 2 groups.

1 group will receive placebo drug delivery (Normal Saline infusion). The 2nd group will receive the study drug infusion (Dexmedetomidine)

A blinded syringe with either the placebo or study drug will be given to the anesthesiologist involved in that patient's care. All other care providers will be blinded to the study group

Inclusion Criteria: Patients undergoing a Hyperthermic Intraperitoneal Chemotherapy (HIPEC) procedure as part of their cancer treatment at Vancover General Hospital 18 years of age or older Able to provide informed consent Expected stay 5 days or greater in hospital Presenting for HIPEC with Colon or Appendix Cancer Exclusion Criteria: Contraindication to dexmedtomidine use including allergy or sensitivity to the drug Pregnancy Dementia ASA greater than or equal to 4 Significant liver disease Current use of steroid or immunosuppressive medication Mesothelioma tumour origin Current use of clonidine Current opioid use exceeding 30mg of oral morphine equivalents Patient not eligible or patient refusal to have a thoracic epidural