Volatile Versus Total Intravenous Anesthesia for Cancer Prognosis in Patients Having Digestive Cancer Surgery

A Nationwide Retrospective Cohort Study

Kanako Makito, M.D., M.P.H.; Hiroki Matsui, M.P.H.; Kiyohide Fushimi, M.D., Ph.D.; Hideo Yasunaga, M.D., Ph.D.


Anesthesiology. 2020;133(4):764-773. 

In This Article

Abstract and Introduction


Background: Previous experimental and clinical studies have shown that anesthetic agents have varying effects on cancer prognosis; however, the results were inconsistent among these studies. The authors compared overall and recurrence-free survival in patients given volatile or intravenous anesthesia for digestive tract cancer surgery.

Methods: The authors selected patients who had elective esophagectomy, gastrectomy, hepatectomy, cholecystectomy, pancreatectomy, colectomy, and rectal cancer surgery from July 2010 to March 2018 using the Japanese Diagnosis Procedure Combination database. Patients were divided into a volatile anesthesia group (desflurane, sevoflurane, or isoflurane with/without nitrous oxide) and a propofol-based total intravenous anesthesia group. The authors hypothesized that total intravenous anesthesia is associated with greater overall and recurrence-free survival than volatile anesthesia. Subgroup analyses were performed for each type of surgery.

Results: The authors identified 196,303 eligible patients (166,966 patients in the volatile anesthesia group and 29,337 patients in the propofol-based total intravenous anesthesia group). The numbers (proportions) of death in the volatile anesthesia and total intravenous anesthesia groups were 17,319 (10.4%) and 3,339 (11.4%), respectively. There were no significant differences between the two groups in overall survival (hazard ratio, 1.02; 95% CI, 0.98 to 1.07; P = 0.28) or recurrence-free survival (hazard ratio, 0.99; 95% CI, 0.96 to 1.03; P = 0.59), whereas instrumental variable analyses showed a slight difference in recurrence-free survival (hazard ratio, 0.92; 95% CI, 0.87 to 0.98; P = 0.01). Subgroup analyses showed no significant difference in overall or recurrence-free survival between the groups in any type of surgery.

Conclusions: Overall and recurrence-free survival were similar between volatile and intravenous anesthesia in patients having digestive tract surgery. Selection of the anesthetic approach for these patients should be based on other factors.


Volatile and intravenous anesthetic agents are commonly used for maintenance of anesthesia. Laboratory and animal studies have suggested that volatile anesthetic drugs are more likely to enhance the activity of cancer cells through suppression of immune cell function, modulation of the neuroendocrine stress response to surgery, and cancer cell signaling.[1–3] In contrast, intravenous anesthetic agents (e.g., propofol) have antiinflammatory and antioxidative effects that may protect against perioperative immune suppression. Previous experimental studies have demonstrated antitumor effects by direct regulation of key ribonucleic acid pathways and signaling in cancer cells in patients with gastric cancer, non–small cell lung cancer, breast cancer, and endometrial and esophageal squamous cell carcinoma.[4–9]

Several studies have compared overall survival or recurrence-free survival of patients with cancer who had volatile anesthesia versus total intravenous anesthesia. A meta-analysis of 10 studies (nine retrospective studies and one small randomized controlled trial) involving patients having breast, esophageal, gastric, colon, rectal, or non–small cell lung cancer surgery showed that total intravenous anesthesia was not associated with improved recurrence-free survival, but was associated with improved overall survival, compared to volatile anesthesia.[10] However, all studies in the meta-analysis were limited because of their small sample sizes and possibility of residual confounders.

We therefore conducted a large-scale study to compare overall survival and recurrence-free survival between volatile anesthesia and total intravenous anesthesia using a national inpatient database in Japan. The objective of the study was to evaluate the association of volatile anesthesia versus total intravenous anesthesia with cancer prognosis among patients having digestive cancer surgery. We hypothesized that total intravenous anesthesia is associated with a greater overall survival and recurrence-free survival than is volatile anesthesia.