Reduced Cancer Risk, Improved Survival With Neuraxial Anesthesia

Neuraxial anesthesia (NA) appears to be associated with improved overall survival (OS) in patients undergoing surgery for tumor resection, particularly in those with colorectal cancer. According to a recent meta-analysis published in Oncotarget(2016;7:15262-15273), the authors identified a correlation between the use of NA and reduced risk for cancer recurrence.

The authors found significantly improved OS and reduced cancer recurrence with NA versus general anesthesia (GA). This finding is among those that show that anesthetic technique correlates with clinically important outcomes, including mortality and morbidity. “Specifically, we found a positive association between neuraxial anesthesia and improved OS in colorectal cancer (HR [hazard ratio] 0.653; 95% CI 0.430-0.991,P=0.045, the random-effects model),” they explained.

“Our results suggest that … the use of [NA] has been found to be associated with improved OS after colorectal cancer, prostate cancer, gastro-oesophageal cancer, laryngeal and hypopharyngeal cancer, and ovarian cancer surgery,” the researchers wrote.

This finding does not come as a surprise. “Increasing evidence in the medical literature suggests that the type of anesthesia and, more specially, the choice of perioperative analgesia may affect both intermediate- and longer-term clinical outcomes after cancer surgery,” wrote Paul White, PhD, MD, in an email interview with Anesthesiology News. “For example, several retrospective studies, and many in vitro studies, have been published over the last 10 years suggesting an association between perioperative opioid use and recurrence of cancer after initial surgery for tumor removal.”

Dr. White is a consultant at Cedars-Sinai Medical Center, in Los Angeles, and the Rizzoli Institute at the University of Bologna, Italy, and is on the editorial advisory board ofAnesthesiology News.

“Despite the lack of prospective clinical outcome data,” Dr. White advised, “it would be my recommendation to:

• utilize aggressive multimodal analgesic techniques during the perioperative period (e.g., local anesthetics [IV and epidural, TAP block, wound infiltration]), NSAIDs [nonsteroidal anti-inflammatory drugs] (e.g., ibuprofen, celecoxib), acetaminophen, dexamethasone, α-2 agonists [clonidine, dexmedetomidine], ketamine and sympatholytic drugs (e.g., β-blockers [esmolol, labetalol]) to supplement general anesthetics for controlling acute autonomic responses during surgery;
• avoid the use of either IV or epidural infusions of opioid analgesics; and
• encourage early ambulation and resumption of normal activities of daily living after surgery.”

Meta-Analysis Design

The reviewers conducted a meta-analysis of 21 studies identified in the PubMed, Web of Science, Embase and Cochrane Database of Systematic Reviews. After data abstraction, adjusted HRs with 95% CIs were used to assess the effects of NA, NA with or without GA, and GA alone on outcomes in patients after surgery for tumor resection. The reviewers detected an association between improved OS with NA versus GA (HR, 0.853; 95% CI, 0.741-0.981; P=0.026, the random-effects model).

“For recurrence-free survival (RFS), a significant association between neuraxial anesthesia and improved RFS (HR 0.846, 95% CI 0.718-0.998, P=0.047, the random-effects model) was detected compared with GA. Our meta-analysis suggests that neuraxial anesthesia may be associated with improved OS in patients with cancer surgery, especially for those patients with colorectal cancer,” the reviewers wrote.

In the analyzed studies, “Most general anesthesia was induced with propofol, opioids and a muscle relaxant, and maintained with a continuous infusion of propofol, isoflurane, sevoflurane or desflurane in an oxygen-air mixture,” said first author Meilin Weng, MD, in an interview via email with Anesthesiology News. However, the reviewers did not distinguish the OS with IV GA and that of inhaled GA, he said. Dr. Weng practices in both the Department of Anesthesiology at Fudan University Shanghai Cancer Centre and the Department of Oncology at Shanghai Medical College of Fudan University.

Dr. Weng recommended that NA be used in all cases of tumor resection. “Our results are especially applicable to colorectal cancer surgery,” he noted, but added, “We also use NA combined with GA for other types of surgery for tumor resection, such as lung cancer, esophageal cancer, abdominal cancer, ovarian cancer, cervical cancer, prostate cancer, etc. During these operations, neuroendocrine stress and surgical trauma are relatively high. NA combined with GA can greatly preserve immune function and patients can get more benefits.” He said NA is not required for removal of precancerous neoplasia.

“Neuraxial anesthesia can attenuate neuroendocrine stress by cutting off afferent neural transmission from reaching the central nervous system and blocking descending efferent activation of the sympathetic nervous system,” Dr. Weng explained. “It can reduce anesthetic requirements, decrease the release of endogenous opioids, improve tissue oxygenation and promote innate antitumor factors through the effects of local anesthetic. It can also bring early survival benefit by reducing the incidence of thrombotic events, infection, cardiovascular and pulmonary complications.”