This randomized clinical trial showed the effect of PCA with epidural bupivacaine–morphine compared with the effect of PCA with intravenous morphine in patients undergoing D2 radical gastrectomy for gastric cancer. The PCEA group, with thoracic epidural anesthesia using bupivacaine and morphine, had superior pain control both at rest and on coughing compared with the PCIA group, who received intravenous morphine. The patients in the PCEA group had better FBG control, which meant these patients experienced less postoperative stress compared with those in the PCIA group. The recovery of gastrointestinal activity was faster and the length of hospital stay was shorter in the PCEA group compared with these parameters in the PCIA group. Of note, we did not see any difference in the incidence of operation-related complications between the two groups.
The application of opioids by epidural analgesia delivers the drug close enough to the spinal cord so that the opioids can inhibit pain transmission from afferent nerves to the central nervous system through interaction with pre- and postsynaptic opioid receptors in the dorsal horn [10, 11]. Many doctors assume that when the same amount of an opioid is used, epidural application of PCA should achieve more effective analgesia than systemic administration. In the present study, though PCA with both epidural bupivacaine–morphine and intravenous morphine provided good analgesia after gastrectomy for gastric cancer, in the first 2 days after the operation we saw lower VAS scores, both at rest and on coughing, in the PCEA group. These results were similar to the results of other prospective randomized controlled studies in different patient populations [4, 6]. Based on previously published literature, epidural analgesia using a local anesthetic combined with an opioid was not only superior in relieving pain at rest and on coughing, but also led to a higher rating of well-being or satisfaction after operation than intravenous opioid analgesia in a wide range of patient populations [5, 12].
Gastrointestinal motility is increased by parasympathetic stimulation. Surgical trauma activates noncholinergic, nonadrenergic spinal reflex mechanisms that block excitatory vagal efferents via bulbar-mediated reflexes . Because of the blocking of this inhibitory reflex when patients use local analgesia with PCEA , the combination of an epidural opioid plus bupivacaine may help the recovery of gastrointestinal motility and reduce postoperative ileus [15, 16]. A large retrospective study of 726 Chinese patients after cesarean section showed that the time to first flatus passage in women with epidural PCA was 1.33 days, while the time in women who used intravenous PCA was 1.51 days, which means a quicker recovery of gastrointestinal motility with PCEA . However, that study did not include operations with gastrointestinal excision or anastomosis, and these factors may affect gastrointestinal motility more seriously. The use of opioids has a potential disadvantage because of their adverse effect on gastrointestinal function. Epidural analgesia with bupivacaine, via a low thoracic catheter, inhibits sympathetic outflow from the T5–L2 levels while sparing sacral parasympathetic stimulation. This method of analgesia may increase gastrointestinal motility after an operation and therefore lead to less ileus . Bradshaw et al.  demonstrated that standardized perioperative care protocols, including epidural analgesia with bupivacaine or/and morphine, in patients undergoing colon surgery led to a faster return of bowel activity and reduced length of stay in hospital. In our present study, the first time of flatus after gastrectomy for gastric cancer in the patients who used PCEA (with bupivacaine and morphine) was 3.1 days, which was shorter than the time in the patients who used PCIA (with morphine), and there was no significant difference between the two groups in the complications of gastrointestinal obstruction after the operation.
Surgical injury provokes a stress response that leads to a high catabolic state with hyperglycemia and increased oxidation of body protein , which is characterized by a state of insulin resistance  and can interfere with the postoperative recovery process [22, 23]. In recent years, some perioperative protocols, including preoperative oral carbohydrate , epidural analgesia, early nasogastric tube removal, and early feeding with a low-fat liquid diet, have all aimed at suppressing perioperative stress to achieve a faster recovery from surgery and a quicker hospital discharge of patients . Epidural blockade with local anesthetics can facilitate glucose utilization  and lessen the loss of body proteins . Yardeni et al. , in their randomized controlled trial comparing postoperative pain management techniques, reported an attenuated postoperative increase in serum cortisol and prolactin levels in their PCEA group, which meant that there was diminished activation of the hypothalamic–pituitary–adrenal axis response and a smaller surgery-associated neuroendocrine stress response in the PCEA group. In our study, a lower FBG level was found in patients with PCEA on the first day after gastrectomy for gastric cancer. This meant that there was a smaller stress response in the PCEA group, and this could have contributed to their faster recovery from surgery.
Urine retention is the most common complication with epidural analgesia after surgery. Weiniger et al.  reported that 83 % of women with lumbar epidural analgesia for labor required bladder catheterization. Capdevila et al.  reported that 53 % of patients with lumbar patient-controlled epidural anesthesia after reconstructive knee surgery had urinary retention in the early postoperative period. In a review of 7357 patients with epidural analgesia in 83 study groups from 1980 to 1999 reported by Dolin et al. , 21.5–38.1 % of patients experienced urinary retention. However, the incidence of urinary retention in patients with PCEA seemed to be lower in some recent studies. In a study by Ferguson et al. , a prospective randomized trial comparing PCEA with intravenous analgesia after major open gynecologic cancer surgery, only about 10 % of patients experienced urinary retention. Their results were similar to ours. Ladak et al.  found that, in patients with thoracic patient-controlled epidural analgesia (TPCEA) undergoing thoracotomy, the incidence of postoperative urine retention was about 10 %, which was also similar to the results of our study. Their study also showed that the incidence of urine retention did not have an association with catheter level (T3–T6 vs. T6–T8), drug type (bupivacaine 0.1 % + hydromorphone 0.015 mg/mL vs. ropivacaine 0.2 %), or infusion rate, nor did the incidence of urine retention have an association with the age, gender, or weight of the patients. An interesting trial was done by Chia et al. , comparing the incidence of urine retention after thoracotomy under postoperative PCEA in patients for whom the transurethral catheter was removed on the first postoperative day and those for whom the catheter was removed after the discontinuation of PCEA. They found that after removal of the bladder catheter, no patient in either group required re-catheterization for urinary retention and no patient had a catheter-related infection and they concluded that routine continuous bladder catheterization might not necessarily be required after thoracotomy in patients undergoing continuous thoracic epidural analgesia. In our study, we removed the catheter 24 h after the end of the PCA, and we did not find any difference in the incidence of urine retention between the PCEA and the PCIA groups.
In our study, the length of stay in hospital after gastrectomy in the PCEA group was 10.7 ± 1.7 days, which was significantly shorter than that in the PCIA group (11.9 ± 1.8 days). Less postoperative pain, a lower stress response, and a quicker return of bowel activity may all have contributed to the faster recovery from surgery in the PCEA group compared with the PCIA group.
In conclusion, our findings reveal that PCEA is safe and effective in patients undergoing gastrectomy for gastric cancer. PCEA results in a lower pain VAS score, a lower stress response, a quicker return of bowel activity, and a faster recovery than PCIA after gastrectomy for gastric cancer.