The oral cavity is important for pronunciation, swallowing, and digestion, and its function is essential for daily living. Advanced oral cancer entails a substantial loss of tissue after resection, which often leads to decreased quality of life postoperatively; therefore, reconstruction after tumor resection is important for quality of life in these patients. However, tumor resection and reconstructive surgery requires comparatively long operating and anesthesia times, which can lead to pneumonia, deep vein thrombosis, pressure areas, and postoperative delirium associated with prolonged bed rest. These complications can impede medical treatment and postoperative recovery (1,2). Postoperative delirium is a common and serious surgical complication that is defined as a change in mental status caused by a physical problem associated with surgery. Postoperative delirium is characterized by impaired consciousness, including a reduced ability to focus attention, changes in cognitive function, altered perception, and disturbed sleep-wake cycles. In addition, it has an acute onset and a fluctuating course (3).

Delirium is classified into three motor subtypes: Hyperactive/agitated (e.g. self-removal of intravenous line or gastric tube, rampage without self-control), hypoactive/somnolent (e.g. disorientation, hallucination), and mixed; the mixed type fluctuates between the hyperactive and hypoactive types during the course of the illness (3,4). Most patients with postoperative delirium recover rapidly; however, the condition is associated with increased morbidity, a prolonged hospital stay, higher economic costs, and increased mortality (3,5-8).

Many researchers have sought to clarify the risk factors for postoperative delirium but the specific features and risk factors are difficult to identify because of its complex morbidity (9-11). There are few reports on postoperative delirium in patients undergoing tumor resection and reconstructive surgery for oral cancer. Thus, the aim of this study was to identify the clinical risk factors associated with postoperative delirium in patients undergoing tumor resection and reconstructive surgery for oral cancer.

Postoperative delirium often leads to pneumonia, deep vein thrombosis, and pressure areas that impede medical treatment and postoperative recovery. The risk of postoperative delirium depends on the type of surgery (12). The rates reported for major surgical procedures are comparatively high at 21-60% for those undergoing hip fracture surgery (13) and 30-73% for those undergoing open heart surgery (3,8,14-17). Postoperative delirium has been reported to occur in 15-33.3% of patients undergoing surgery for oral cancer (18-21). Makiguchi et al reported the incidence of postoperative delirium to be 33.3% in patients undergoing free flap reconstruction for oral cancer (21). In the present study, 21.2% of patients underwent reconstructive surgery for oral cancer, which is a slightly lower proportion than in previous studies (21). The reason for this is that our study included not only patients undergoing free flap surgery but also those in whom a pedicle flap was used; of note, there was a significant difference in the incidence of postoperative delirium between these two groups of patients (10.2 vs. 30.9%, P=0.008).

We investigated the preoperative, intraoperative, and postoperative factors associated with the occurrence of postoperative delirium. There is some evidence indicating that older age, male sex, and tobacco and alcohol consumption are risk factors for postoperative delirium (7,22-24). Kuo et al showed that the flap survival rate decreased significantly in 1,364 patients with alcohol-induced psychiatric disorders who had undergone microsurgical tissue transfer after resection of head and neck cancer. They concluded that treatment requires a multidisciplinary approach and intensive medical care (25). In our study, there were no significant correlations between any of the above-mentioned risk factors and postoperative delirium in the univariate analysis, which is consistent with some earlier reports (16,20).

The univariate analysis of intraoperative and postoperative risk factors revealed a significant correlation between postoperative delirium and operating time (P=0.033), duration of anesthesia (P=0.039), amount of blood loss (P=0.027), method of reconstruction (P=0.008), type of flap used (P=0.009), and time to ambulation after surgery (P=0.0008); however, there was no significant correlation with blood transfusion, tracheotomy, or flap engraftment. Yamagata et al performed multivariate analyses and found that the risk increased significantly when the operating time was longer than 10 h (18). Our results are similar to those of earlier studies showing that longer operating and anesthesia times increase the risk of postoperative delirium. In this study, we found a significantly higher incidence of postoperative delirium in patients undergoing free flap reconstruction (30.9%) than in those undergoing pedicle flap reconstruction (10.0%); the highest rate was in patients undergoing forearm flap (37.5%) or scapular osteocutaneous flap (33.3%) reconstruction. Unlike other types of flap reconstruction, a forearm flap procedure involves multiple surgical sites, including the site on the forearm from which the skin is harvested for the graft, so patient mobility is restricted postoperatively. The longest operating and anesthesia times in our study were for scapular osteocutaneous flap reconstruction. In general, compared with patients undergoing a pedicle flap reconstruction, those undergoing free flap reconstruction tended to require prolonged bed rest to protect the anastomosed vessels. This might explain why postoperative delirium was so common in patients who underwent forearm flap and scapular osteocutaneous flap reconstruction, and may also explain why postoperative delirium occurs more often in patients undergoing free flap reconstruction than in those undergoing pedicle flap reconstruction.

Since 2009, our department has promoted ambulation on the second postoperative day for patients with oral cancer undergoing tumor resection with reconstruction. The mean number of days until postoperative ambulation has decreased from 4.6 to 3.1 days, and as a result, the occurrence of postoperative delirium has decreased from 29.2 to 14.0%. Moreover, multivariate logistic regression analysis in our study showed a significant correlation between early postoperative ambulation and a decreased risk of postoperative delirium. Early postoperative ambulation may be the reason our incidence of postoperative delirium is lower than that reported by Makiguchi et al (21). It is noteworthy that the rate of postoperative delirium in our non-early ambulation group was similar to that reported previously (21). In the past, bed rest after reconstructive surgery for oral cancer was considered important; however, recent reports have indicated that admission to the ICU after reconstructive surgery for head and neck cancer does not contribute to flap survival (26). In support of this, the promotion of early ambulation did not affect the flap survival in this study. Postoperative delirium has a temporal and etiologic relationship with surgery and usually develops between postoperative days 2 and 7(27). Consistent with previous reports (3,6,20), our results showed that the mean onset of postoperative delirium was 2.5±1.0 days after surgery, and it developed in less than 3 days in 86.4% of cases. Therefore, promoting early postoperative ambulation is critical for the prevention postoperative delirium. There have been several recent reports on the benefits of early postoperative ambulation across a number of surgical disciplines (28-32). These benefits include a reduced risk of respiratory complications, improved circulation, prevention of deep vein thrombosis and pulmonary embolism, and improved psychologic well-being. Consequently, early postoperative ambulation decreases the perioperative complications and contributes to a reduction in medical costs (4).

We found a close association between certain hematologic parameters and the risk of postoperative delirium. Patients with postoperative delirium had more hemorrhage than those without delirium, and as a result, postoperative blood tests revealed a decrease in hemoglobin, red blood cells, and hematocrit. Previous reports have similarly shown a relationship between decreased red blood cell count, hemoglobin, and hematocrit values as a result of blood loss and increased risk of postoperative delirium (18-20,23-25). Blood loss during surgery decreases the oxygen supply to the brain, which causes cerebral ischemia. There has been a suggestion that a decreased oxygen supply plays an important role in certain types of mental illness (33). However, the relationship between hematologic parameters and the risk of postoperative delirium remains controversial.

Our study has some limitations. First, it was retrospective in nature, so we cannot exclude the possibility of confounding factors. Second, the sample size was small. Third, it was not possible to compare the results of our study with those of others because there have been few previous reports specifically focusing on the risk of postoperative delirium, or other postoperative complications such as aspiration pneumonia and deep vein thrombosis, in patients undergoing tumor resection with reconstruction for oral cancer. Prospective multicenter randomized investigations in larger numbers of patients with longer follow-up durations are required to confirm our results. Fourth, this study did not examine in detail the benefits of early postoperative ambulation other than preventing delirium. The length of hospital stay varied depending on the presence or absence of postoperative treatment, such as chemotherapy and/or radiotherapy. Moreover, because the discharge criteria for swallowing, pronunciation, and neck and upper limb rehabilitation were not clear, we did not examine the length of hospital stay. Fifth, the study examined the patients' history of mental disorders, but not of other systematic diseases such as hypertension, diabetes, or obesity. Further, we were unable to finish the character analysis and psychoanalysis of every patient before surgery. We would like to examine these points in our future research.

This study is an early attempt to identify clinical risk factors for postoperative delirium in patients who have undergone tumor resection and reconstruction for oral cancer. Our findings indicate that delayed postoperative ambulation is a significant risk factor for postoperative delirium. We advocate the promotion of early postoperative ambulation because it enhances recovery and prevents a number of postoperative complications.