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.

Disclosures

Anesthesiology. 2020;133(4):764-773. 

In This Article

Results

We selected 255,330 patients who had cancer surgery during the study period. We then excluded 52,209 patients who had anesthesia multiple times during the study period, 5,905 patients diagnosed with a benign tumor or a malignant potential tumor, 227 patients who had spinal anesthesia, and 686 patients who received nitrous oxide without volatile anesthesia. In total, 196,303 patients who met the inclusion criteria were divided into those who had volatile anesthesia using desflurane, sevoflurane, or isoflurane with/without nitrous oxide (volatile anesthesia group, n = 166,966) and those who had propofol-based total intravenous anesthesia (total intravenous anesthesia group, n = 29,337; Figure 1).

Figure 1.

Flow chart of patient selection.

Table 1 shows the baseline characteristics of the patients, hospitals, and procedures for the overall study cohort and each of the two groups. Overall, 63,678 (32.4%) patients had colectomy and 61,056 (31.1%) had gastrectomy. The standardized differences for all variables suggested no differences between the volatile anesthesia and total intravenous anesthesia groups with the exception of male sex, academic hospital, year of surgery, and high hospital volume. The BMI data were missing for 1,856 (0.9%) patients, the cancer stage was missing for 39,342 (20.0%) patients, and the Barthel Index at admission was missing for 5,795 (3.0%) patients.

The median postoperative follow-up period was 639 days (interquartile range, 234 to 1,301 days) in the volatile anesthesia group and 768 days (interquartile range, 286 to 1,525 days) in the total intravenous anesthesia group.

The overall mortality rates in the volatile anesthesia and total intravenous anesthesia groups were 10.4% and 11.4%, respectively. The proportions of recurrence or death in the volatile anesthesia and total intravenous anesthesia groups were 18.3% and 18.8%, respectively.

The results of the Kaplan–Meier analysis are shown in Figure 2 (overall survival) and Figure 3 (recurrence-free survival). The 1-yr overall survival was 89.8% in the volatile anesthesia group and 90.0% in the total intravenous anesthesia group. The 1-yr recurrence-free survival was 80.8% in the volatile anesthesia group and 81.9% in the total intravenous anesthesia group.

Figure 2.

Kaplan–Meier analysis of overall survival.

Figure 3.

Kaplan–Meier analysis of recurrence-free survival.

Figure 4 shows the association between total intravenous anesthesia and overall survival or recurrence-free survival by Cox regression analyses. We found no significant difference 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) between the volatile anesthesia and total intravenous anesthesia groups. Variables that were significantly associated with worse overall survival and recurrence-free survival were an age of older than 60 yr, male sex, underweight (BMI of less than 18.5 kg/m2), Charlson Comorbidity Index score of 3 or 4, cancer stage, preoperative adjuvant therapy, postoperative adjuvant therapy, preoperative renal replacement therapy, smoking, preoperative or intraoperative blood transfusion, preoperative use of morphine or oxycodone, academic hospital, Barthel Index, and at least one postoperative complication.

Figure 4.

Results of Cox regression analyses for recurrence-free survival and overall survival.

Figure 5 shows the association between total intravenous anesthesia and overall survival or recurrence-free survival by instrumental variable analyses. The F statistic was 27,416 (P < 0.001), suggesting that the instrumental variable was strongly associated with the treatment assignment (volatile anesthesia or total intravenous anesthesia). Compared with volatile anesthesia, total intravenous anesthesia was not significantly associated with better overall survival (hazard ratio, 1.02; 95% CI, 0.95 to 1.09; P = 0.65), but was significantly associated with better recurrence-free survival (hazard ratio, 0.92; 95% CI, 0.87 to 0.98; P = 0.01).

Figure 5.

Results of instrumental variable analyses for recurrence-free survival and overall survival, in which the instrumental variable was defined as the proportion of total intravenous anesthesia at each hospital.

Table 2 shows the results of the subgroup analyses for each type of cancer surgery. There was no significant difference in overall survival or recurrence-free survival between the volatile anesthesia and total intravenous anesthesia groups in any type of surgery.

Supplemental Digital Content, table 1 (https://links.lww.com/ALN/C420) shows the patients' characteristics after propensity score matching. The distribution was well-balanced between the volatile anesthesia and total intravenous anesthesia groups. Supplemental Digital Content, table 2 (https://links.lww.com/ALN/C421) shows that total intravenous anesthesia was not significantly associated with improved overall survival (hazard ratio, 1.01; 95% CI, 0.79 to 1.21; P = 0.77) or recurrence-free survival (hazard ratio, 1.00; 95% CI, 0.96 to 1.05; P = 0.94) in the propensity score-matched cohort.

The results of the instrumental variable analyses using the proportion of total intravenous anesthesia in each of 47 prefectures as another instrumental variable were similar to those in the main analyses; total intravenous anesthesia was significantly associated with improved recurrence-free survival, but not significantly associated with improved overall survival, compared with volatile anesthesia (Supplemental Digital Content, table 3, https://links.lww.com/ALN/C422).

processing....