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Risk factors associated with postoperative delirium after surgery for oral cancer
Journal of Cranio-Maxillo-Facial Surgery 43 (2015) 1094e1098
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Risk factors associated with postoperative delirium after surgery for oral cancer Takumi Hasegawa*, Izumi Saito, Daisuke Takeda, Eiji Iwata, Natsuki Yonezawa, Yasumasa Kakei, Akiko Sakakibara, Masaya Akashi, Tsutomu Minamikawa, Takahide Komori Department of Oral and Maxillofacial Surgery (Chief: Prof. T. Komori), Kobe University Graduate School of Medicine, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Paper received 16 March 2015 Accepted 8 June 2015 Available online 17 June 2015
Objective: The purpose of this study was to retrospectively investigate the multivariate relationships among the various risk factors for postoperative delirium in patients undergoing oral cancer surgery. Material and methods: The medical records of all patients with oral cancer who underwent curative head and neck surgery between April 2011 and March 2013 at our institution were retrospectively reviewed. There was a total of 188 patients, including 110 males and 78 females. Results: We found that older age, extensive surgical procedure, longer operation, excessive hemorrhage, blood transfusion, longer postoperative management in the intensive care unit, longer postoperative hospital stay, lower albumin level in the preoperative blood test, and lower total protein, albumi, n and hemoglobin levels and a higher C-reactive protein (CRP) level in the postoperative blood tests were significant variables in the univariate analysis (p < 0.05). We also determined that an older age (odds ratio [OR] ¼ 6.83), intraoperative lower hemoglobin levels (OR ¼ 6.82), and excessive hemorrhage (OR ¼ 3.62) during surgery were significant variables in the multivariate analysis. Conclusion: Clinicians should pay special attention to preventing delirium during the postoperative management of older patients with these risk factors. Furthermore, increasing the hemoglobin levels during surgery may be able to prevent postoperative delirium. © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
Keywords: Delirium Postoperative Oral cancer Risk factor Surgery
1. Introduction Postoperative delirium is a major complication after surgical procedures. Most postoperative delirium arises within a few days after surgery, and patients usually recover rapidly. However, continuous delirium complicates postoperative management. In addition, postoperative delirium is occasionally associated with higher morbidity, prolonged hospital stays, higher costs, and increased mortality (Koolhoven et al., 1996; Inouye et al., 1999; Schneider et al., 2002). Therefore, preventing postoperative delirium may contribute to reducing these problems. Many
* Corresponding author. Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 6500017, Japan. Tel.: þ81 78 382 6213; fax: þ81 78 351 6229. E-mail address: [email protected] (T. Hasegawa).
investigators have reported the risk factors associated with postoperative delirium for many types of surgery (van der Mast et al., 1999; Zakriya et al., 2002; Merchant et al., 2005; Kazmierski et al., 2006). However, the factors leading to postoperative delirium remain unclear because of its complex etiology. In previous studies, the incidence of postoperative delirium was 17%e26% after head and neck surgery (Weed et al., 1995; Yamagata et al., 2005; Shiiba et al., 2009). In a multivariate analysis study, there were numerous risk factors, including the age, gender, length of operation, pain control, and use of minor tranquilizers. However, only a few studies to date have evaluated the multivariate relationships among the various risk factors and postoperative delirium associated with oral cancer (Yamagata et al., 2005; Shiiba et al., 2009). Moreover, their studies did not demonstrate symptoms of delirium. In this study, we retrospectively investigated the symptoms of delirium and the multivariate relationships among
http://dx.doi.org/10.1016/j.jcms.2015.06.011 1010-5182/© 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
T. Hasegawa et al. / Journal of Cranio-Maxillo-Facial Surgery 43 (2015) 1094e1098
the various risk factors for postoperative delirium in patients undergoing oral cancer surgery. 2. Material and methods This was a nonrandomized, retrospective (historical) cohort study of patients. Thus, this study was granted exemption from institutional review board approval by our institution. Between April 2011 and March 2013, a total of 188 patients with oral cancer underwent major head and neck surgery at the Department of Oral and Maxillofacial Surgery, Kobe University Hospital. Patients were diagnosed with postoperative delirium when symptoms corresponded to one of the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) definition (American Psychiatric Association, 1997). These criteria focus on four key features: 1) acute changes in mental status with a fluctuating course; 2) inattention; 3) disorganized thinking; and 4) an altered level of consciousness. The symptoms of delirium were classified as Type 1: disturbance of consciousness and attention; Type 2: psychomotor behavior; Type 3: changes in cognition (perception); Type 4: orientation disturbance; and Type 5: hallucinations. We investigated the following variables: age, gender, medical history, history of alcohol consumption, history of smoking, surgical procedure, length of operation, blood loss, blood transfusion, existence of tracheotomy, postoperative management in the intensive care unit (ICU), perioperative blood tests (total protein [TP], albumin [ALB], creatinine [Cre], sodium [Na], chlorine [Cl], hemoglobin [Hb], and C-reactive protein [CRP]) and the postoperative hospital stay. The surgical procedures were classified into four categories: only tumor resection (TR), only neck dissection (ND), TR þ ND, and TR þ ND þ immediate reconstruction (R). Preoperative blood tests were performed within 5 days of surgery, and postoperative tests were performed 3 and 7 days after surgery. All factors are listed in Table 1. When the data were introduced into a multiple logistic regression model, the patients were divided according to surgical procedure (Only TR and Only NR vs TR þ ND and TR þ ND þ R). Patients were similarly divided into two groups based on age (<75 years old and 75 years old), into two groups based on blood loss (<800 mL and 800 mL), and into two groups based on the intraoperative Hb levels (<10 g/dL and 10 g/dL). Data collection and statistical analyses were carried out with SPSS 15.0 (SPSS Inc, Chicago, IL, USA) and Stat-View-J-4.5 software (Abacus Concepts, Berkeley, CA, USA). The association of each variable with the postoperative delirium was tested by using the ManneWhitney U nonparametric test for ordinal variables and the Fisher exact test for categorical variables. A value of p < 0.05 was considered statistically significant. All of the variables associated with postoperative delirium were introduced into a multiple logistic regression model. Forward selection methods were used, with the rejection of those variables that did not fit the model significantly. The postoperative blood tests on postoperative days 3 and 7 were also excluded, because 21 patients (72.4%) were diagnosed with postoperative delirium before postoperative day 3. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were also calculated for the significant signs. A value of p < 0.05 was considered statistically significant. 3. Results Postoperative delirium occurred in 29 of the 188 patients (15.4%), who included 19 males and 10 females. Most cases of delirium (86.2%) were observed between 1 and 5 days after surgery, at a mean of 3.0 days (Fig. 1).
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With regard to the types of symptoms, in the female patients with delirium, there were two cases (20.0%) of Type 1, five cases (50.0%) of Type 2, four cases (40.0%) of Type 3, no cases (0%) of Type 4, two cases (20.0%) of Type 5, and two cases (20.0%) of unknown type. In terms of the types of symptoms in male patients with delirium, there were two cases (10.5%) of Type 1, 13 cases (68.4%) of Type 2, three cases (15.8%) of Type 3, four cases (21.1%) of Type 4, three cases (15.8%) of Type 5, and three cases (15.8%) of unknown type (Table 2). There were no significant differences in the types between males and females. The patients with postoperative delirium had a mean age of 79.0 ± 8.9 years (range: 52e92 years). The patients without postoperative delirium had a mean age of 67.4 ± 12.9 years (range: 24e92 years). The patients with postoperative delirium were significantly older than those without postoperative delirium in the univariate analysis (p < 0.05) (Table 1). There were no significant differences between the sexes in the patients with and without postoperative delirium (Table 1). There were also no significant differences between other demographic factors, such as medical history, alcohol consumption history, and chronic smoking history in the patients with and without postoperative delirium (Table 1). There were seven cases of only TR, one case of only ND, three cases of TR þ ND, and 18 cases of TR þ ND þ R in the patients with postoperative delirium. There were 78 cases of only TR, 12 cases of only ND, five cases of TR þ ND, and 64 cases of TR þ ND þ R in the patients without postoperative delirium. There was a significant difference between the only TR or ND and the TR þ ND or TR þ ND þ R rates in the patients with and without postoperative delirium in the univariate analysis (p < 0.05) (Table 1). There were significant differences between intraoperative factors such as blood loss, intraoperative Hb levels, blood transfusion, and length of operation in the patients with and without postoperative delirium (p < 0.05) (Table 1). There was no significant difference in the performance of tracheotomy between the patients with and without postoperative delirium. The mean duration of ICU stay was 4.5 ± 2.3 days for the patients with postoperative delirium and 2.9 ± 3.1 days for the patients without postoperative delirium. There was a significant difference in the ICU stay between the patients with and without postoperative delirium (p < 0.05) (Table 1). The postoperative hospital stay of the patients with postoperative delirium was significantly longer than that of the patients without postoperative delirium. An analysis of the results of preoperative blood tests demonstrated that only the albumin (ALB) levels of patients who developed delirium were significantly lower than those of patients who did not develop delirium. An analysis of the postoperative blood tests demonstrated that the total protein (TP), ALB, and hemoglobin (Hb) levels of the patients with delirium were significantly decreased compared to those of the patients without delirium. In addition, the C-reactive protein (CRP) level of patients with delirium was significantly increased compared to that of the patients without delirium. Applying a logistic regression model and forward stepwise algorithms, we determined that older age, lower intraoperative Hb levels, and excessive hemorrhage during surgery were significant variables (Table 3). The patients' gender, medical history and existence of tracheotomy, and preoperative blood test results (TP, Cre, Na, Cl, and Hb) were excluded from this model, because these factors were not significant in the univariate analysis. The multivariate adjusted ORs and 95% CIs of the included factors were calculated. The discriminant hitting ratio (84.6%) was considered to be excellent in this study.
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Table 1 Characteristics and incidence rates of postoperative delirium after oral cancer surgery. Variables Demographic factors Sample size Gender Male Female Age (y) Range Mean ± SD Medical history (overlapping distribution) Cerebrovascular disease Diabetes mellitus Hypertension Coronary heart disease Renal dysfunction Psychosis or dementia Others Nothing particular Alcoholism Chronic smoking Peri- or intraoperative factors Type of surgery Only TR or ND TR þ ND or TR þ ND þ R Length of operation (hours; mean ± SD) Blood loss (mL; mean ± SD) Intraoperative hemoglobin (Hb) (g/dL) Blood transfusions Tracheotomy Postoperative management in ICU (days) Postoperative hospital stay (days) Preoperative blood test (mean ± SD) Total protein (TP) (g/dL) Albumin (ALB) (g/dL) Creatinine (Cre) (mg/dL) Sodium (Na) (mEq/L) Chlorine (Cl) (mEq/L) Hemoglobin (Hb) (g/dL) Postoperative blood test (POD 3) (mean ± SD) Total protein (TP) (g/dL) Albumin (ALB) (g/dL) Creatinine (Cre) (mg/dL) Sodium (Na) (mEq/L) Chlorine (Cl) (mEq/L) Hemoglobin (Hb) (g/dL) C-reactive protein (CRP) (mg/dL) Postoperative blood test (POD 7) (mean ± SD) Total protein (TP) (g/dL) Albumin (ALB) (g/dL) Creatinine (Cre) (mg/dL) Sodium (Na) (mEq/L) Chlorine (Cl) (mEq/L) Hemoglobin (Hb) (g/dL) C-reactive protein (CRP) (mg/dL)
Delirium, number (%)
No delirium, number (%)
p Value
29 (15.4)
159 (84.6)
19 (66.5) 10 (34.5)
91 (57.2) 68 (42.8)
n.s.
52e92 49.0 ± 8.9
24e92 67.4 ± 12.9
<0.05a
8(27.6) 2(6.9) 8(27.6) 6(20.7) 5(17.2) 1(3.4) 3(10.3) 6(20.9) 8(27.6) 13(44.8)
44(42.3) 8(7.7) 25(24.0) 42(40.4) 16(15.4) 9(8.7) 4(3.8) 63(60.6) 64(40.3) 84 (52.8)
n.s. n.s. n.s.
8 (27.6) 21 (72.4) 9.2 ± 4.6 967.0 ± 1113.4 9.4 ± 1.8 14 (48.3) 19 (65.5) 4.5 ± 2.3 54.6 ± 27.3
90 (56.6) 69 (43.4) 6.3 ± 5.1 392.7 ± 537.7 11.4 ± 1.7 29 (18.2) 71 (44.7) 2.9 ± 3.1 39.9 ± 32.3
<0.05b <0.05a <0.05a <0.05a <0.05b n.s. <0.05a <0.05a
6.6 ± 0.7 3.7 ± 0.5 1.0 ± 0.7 140.3 ± 2.0 106.5 ± 2.0 12.4 ± 2.6
7.0 ± 3.2 4.0 ± 0.4 0.9 ± 1.1 140.5 ± 2.5 106.1 ± 2.7 13.0 ± 1.6
n.s. <0.05a n.s. n.s. n.s. n.s.
5.0 ± 0.9 2.6 ± 0.5 0.8 ± 0.6 138.4 ± 2.8 105.9 ± 3.5 9.5 ± 1.8 9.3 ± 5.3
5.5 ± 0.9 3.1 ± 0.7 0.8 ± 1.1 139.6 ± 2.7 105.9 ± 3.4 10.7 ± 2.2 5.0 ± 4.5
<0.05a <0.05a n.s. n.s. n.s. <0.05a <0.05a
5.4 ± 0.7 2.6 ± 0.4 0.9 ± 0.5 139.7 ± 3.5 105.0 ± 3.8 9.7 ± 1.4 4.8 ± 4.8
5.8 ± 0.8 3.1 ± 0.6 3.5 ± 30.4 140.1 ± 2.6 104.4 ± 3.3 10.9 ± 1.8 3.1 ± 3.9
<0.05a <0.05a n.s. n.s. n.s. <0.05a <0.05a
n.s., Not significant; TR, tumor resection; ND, neck dissection; R, immediate reconstruction. a ManneWhitney U test. b Fisher exact test.
4. Discussion In previous reports, the incidence of delirium after cardiovascular surgery ranged from 30% to 73% (Hammeke and Hastings, 1988; Smith and Dimsdale, 1989; Rudolph et al., 2005). Dyer et al. reported that the incidence of postoperative delirium was 0%e 73.5% after various surgeries (Dyer et al., 1995). However, only a few studies performed to date have evaluated the multivariate relationships among the various risk factors and postoperative delirium following surgery for oral cancer (Yamagata et al., 2005; Shiiba et al., 2009). These studies reported that the incidence of postoperative delirium after head and neck surgery was 17%e26% (Weed et al., 1995; Yamagata et al., 2005; Shiiba et al., 2009). In the
present study, the incidence of postoperative delirium after oral cancer surgery was 15.4%. This result was similar to those of previous studies (Weed et al., 1995; Yamagata et al., 2005; Shiiba et al., 2009). In this study, most cases of delirium (86.2%) were observed between 1 and 5 days after surgery. Takeuchi et al. reported that most of the delirium developed by day 7 after surgery, and suggested that clinicians should pay particular attention to the possibility of delirium during the first postoperative week (Takeuchi et al., 2012). We agree with their opinion. No reports have shown that female gender was a risk factor for postoperative delirium, whereas some reports have suggested that male gender could be a risk factor for delirium (Dyer et al., 1995; Shiiba et al., 2009; Takeuchi et al., 2012). Several investigators
T. Hasegawa et al. / Journal of Cranio-Maxillo-Facial Surgery 43 (2015) 1094e1098
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Table 3 Results of multivariate logistic regression analysis of risk factors for postoperative delirium. Variable
p Value
Older age (75 years) Intraoperative hemoglobin (<10 g/dL) Excessive hemorrhage (800 ml)
<0.001 <0.001 0.016
Odds ratio
6.83 6.82 3.62
95% CI Lower
Upper
2.47 2.57 1.27
18.90 18.12 10.30
CI, confidence interval.
Fig. 1. Time of postoperative onset of delirium.
have reported that no correlations were observed between gender and postoperative delirium (Weed et al., 1995; Yamagata et al., 2005). In this study, there were no significant differences between the sexes in the patients with and without postoperative delirium. However, the incidence of postoperative delirium in the male patients (17.3% of all male patients) was higher than that in female patients (12.8% of all female patients). In addition, the rate of Type 2 (psychomotor behavior) symptoms was 13/19 (68.4%) of males, which was higher than the rate of 5 and 10 females (50%). It may be possible that males are more prone to develop hyperactive or agitated delirium, such as Type 2, compared to females. Type 2 delirium is associated with patients turning over, falling down or climbing out of bed, and self-removal of drip infusion, etc., and such activity complicates the postoperative management. We should therefore focus particular attention on Type 2 delirium to prevent severe medical errors. This study indicated that there was a significantly higher incidence of postoperative delirium in elderly patients, similar to that in a previous study (Dyer et al., 1995; Schneider et al., 2002; Shiiba et al., 2009; Sasajima et al., 2012; Takeuchi et al., 2012). Shiiba et al. speculated that elderly patients were less able to adapt physically and psychologically to drastic alterations during the surgical period than younger patients, and that this might induce postoperative delirium (Shiiba et al., 2009). This is likely closely related to the higher incidence of postoperative delirium after extensive operations. Weed et al. reported that many patients after major head and neck cancer surgery had a high risk of developing postoperative delirium, because the age of many patients was advanced, and time-intensive surgeries, such as immediate reconstruction with free flaps, are often performed (Weed et al., 1995). In this study, older age (OR ¼ 6.83) was also associated with a higher risk of postoperative delirium after oral cancer surgery in a multivariate analysis (Table 3). In contrast, an extensive surgical procedure history was associated with a higher risk according to a univariate analysis (Table 1).
An analysis of the preoperative blood tests demonstrated that only the ALB level of patients who developed delirium was significantly lower than that of the patients who did not. This result suggested that an appropriate preoperative nutritional status may prevent postoperative delirium. In the postoperative blood tests, the TP, ALB, Hb, and CRP levels were all related to the incidence of postoperative delirium. This suggests that undernutrition (lower TP and ALB), anemia (lower Hb), and inflammation (higher CRP) may promote postoperative delirium. The relationship between the blood test results and postoperative delirium has been controversial in various studies (Morse and Litin, 1969; Weed et al., 1995; Marcantonio et al., 1998; Schneider et al., 2002; Yamagata et al., 2005; Shiiba et al., 2009). However, excessive hemorrhage and postoperative hematocrit values have been reported as postoperative factors predicting the development of delirium in several studies (Marcantonio et al., 1998; van der Mast et al., 1999; Schneider et al., 2002; Yamagata et al., 2005; Shiiba et al., 2009; Sasajima et al., 2012). Schneider et al. demonstrated that a trend for greater intraoperative blood loss with a subsequent need for increased transfusions was heavily associated with postoperative delirium, and with the severity and duration of the delirium (Schneider et al., 2002). Furthermore, Marcantonio et al. demonstrated that postoperative delirium was associated with a reduced hematocrit value of less than 30% and intraoperative blood loss requiring a greater number of transfusions (Marcantonio et al., 1998). van der Mast et al. speculated that massive hemorrhaging during an operation reduced the cerebral oxygen supply, a condition similar to cerebral ischemia, and might play a role in postoperative mental disorders (van der Mast et al., 1999). In this study, lower intraoperative Hb levels (OR ¼ 6.82) and excessive hemorrhage (OR ¼ 3.62) were also associated with a higher risk of postoperative delirium after oral cancer surgery in a multivariate analysis (Table 3). The performance of blood transfusion, however, was associated with a higher risk only by univariate analysis (Table 1). Therefore, the increasing of Hb levels during surgery through active blood transfusion may be able to prevent postoperative delirium. However, we need to carefully consider this point because of the negative side effects of blood transfusion. Postoperative delirium is generally treated by the administration of haloperidol, droperidol, or benzodiazepine for symptomatic treatment (O'Keeffe and Ní Chonchubhair, 1994; Dyer et al., 1995; Parikh and Chung, 1995; Moller et al., 1998). The association between the use of mild sedatives and delirium has been controversial
Table 2 Types of symptoms of delirium after oral cancer surgery. Types of symptom of delirium (overlapping distribution)
Males (n ¼ 19)
Females (n ¼ 10)
Type 1: disturbance of consciousness and attention Type 2: psychomotor behavior Type 3: change in cognition (perception) Type 4: orientation disturbance Type 5: hallucination Unknown
2 13 3 4 3 3
2 5 4 0 2 2
(10.5 (68.4 (15.8 (21.1 (15.8 (15.8
%) %) %) %) %) %)
(20.0 (50.0 (40.0 (0 %) (20.0 (20.0
%) %) %) %) %)
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(Marcantonio et al., 1994; Yamagata et al., 2005; Takeuchi et al., 2012). Some reports have shown that use of these agents increased delirium (Marcantonio et al., 1994; Takeuchi et al., 2012). Benzodiazepines have been shown to potentially cause delirium via central nervous system sedation and withdrawal mechanisms (Takeuchi et al., 2012). However, other reports have found a decrease in delirium with the medication (Schor et al., 1992; Yamagata et al., 2005). We used mainly mild sedatives for sleep disturbance and used major sedatives (tranquilizers), such as haloperidol (44.8% of the patients with delirium), risperidone (41.4%), and quetiapine (24.1%) to treat delirium. Schrader et al. demonstrated that the preoperative administration of haloperidol resulted in a positive effect on the severity and duration of delirium (Schrader et al., 2008). Regardless, the appropriate management of the sleep cycle and environmental improvement is important. We are planning a future study to investigate these preventive strategies and early treatments on the development of postoperative delirium. 5. Conclusion In this study, we successfully demonstrated multivariate relationships among the various risk factors for postoperative delirium in patients undergoing oral cancer surgery. We determined that older age, lower intraoperative Hb levels, and excessive hemorrhage during surgery were significant factors associated with the development of delirium in a multivariate analysis. Therefore, clinicians should pay special attention to preventing delirium during the postoperative management of older patients with these risk factors. Finally, increasing the hemoglobin levels during surgery may be able to prevent postoperative delirium. Conflict of interest There are no financial or personal relationships with other people or organizations that can inappropriately influence the work of the authors. We did not receive any sources of study funding, including those of an institutional or departmental nature. Acknowledgments No study funding was received, including any of an institutional or departmental nature. References American Psychiatric Association: Diagnostic, and statistical manual of mental disorders, 4th ed. Washington, DC: American Psychiatric Association, 1997 Dyer CB, Ashton CM, Teasdale TA: Postoperative delirium. A review of 80 primary data-collection studies. Arch Intern Med 155(5): 461e465, 1995 Hammeke TA, Hastings JE: Neuropsychologic alterations after cardiac operation. J Thorac Cardiovasc Surg 96(2): 326e331, 1988
Inouye SK, Bogardus Jr ST, Charpentier PA, Leo-Summers L, Acampora D, Holford TR, et al: A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med 340(9): 669e676, 1999 Kazmierski J, Kowman M, Banach M, Pawelczyk T, Okonski P, Iwaszkiewicz A, et al: Preoperative predictors of delirium after cardiac surgery: a preliminary study. Gen Hosp Psychiatry 28(6): 536e538, 2006 Koolhoven I, Tjon-A-Tsien MR, van der Mast RC: Early diagnosis of delirium after cardiac surgery. Gen Hosp Psychiatry 18(6): 448e451, 1996 Marcantonio ER, Juarez G, Goldman L, Mangione CM, Ludwig LE, Lind L, et al: The relationship of postoperative delirium with psychoactive medications. JAMA 272(19): 1518e1522, 1994 Marcantonio ER, Goldman L, Orav EJ, Cook EF, Lee TH: The association of intraoperative factors with the development of postoperative delirium. Am J Med 105(5): 380e384, 1998 Merchant RA, Lui KL, Ismail NH, Wong HP, Sitoh YY: The relationship between postoperative complications and outcomes after hip fracture surgery. Ann Acad Med Singapore 34(2): 163e168, 2005 Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, et al: Longterm postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet 351(9106): 857e861, 1998 Morse RM, Litin EM: Postoperative delirium: a study of etiologic factors. Am J Psychiatry 126(3): 388e395, 1969 O'Keeffe ST, Ní Chonchubhair A: Postoperative delirium in the elderly. Br J Anaesth 73(5): 673e687, 1994 Parikh SS, Chung F: Postoperative delirium in the elderly. Anesth Analg 80(6): 1223e1232, 1995 Rudolph JL, Babikian VL, Birjiniuk V, Crittenden MD, Treanor PR, Pochay VE, et al: Atherosclerosis is associated with delirium after coronary artery bypass graft surgery. J Am Geriatr Soc 53(3): 462e466, 2005 Sasajima Y, Sasajima T, Azuma N, Akazawa K, Saito Y, Inaba M, et al: Factors related to postoperative delirium in patients with lower limb ischaemia: a prospective cohort study. Eur J Vasc Endovasc Surg 44(4): 411e415, 2012 € hner H, Habel U, Salloum JB, Stierstorfer A, Hummel TC, et al: Risk Schneider F, Bo factors for postoperative delirium in vascular surgery. Gen Hosp Psychiatry 24(1): 28e34, 2002 Schor JD, Levkoff SE, Lipsitz LA, Reilly CH, Cleary PD, Rowe JW, et al: Risk factors for delirium in hospitalized elderly. JAMA 267(6): 827e831, 1992 Schrader SL, Wellik KE, Demaerschalk BM, Caselli RJ, Woodruff BK, Wingerchuk DM: Adjunctive haloperidol prophylaxis reduces postoperative delirium severity and duration in at-risk elderly patients. Neurologist 14(2): 134e137, 2008 Shiiba M, Takei M, Nakatsuru M, Bukawa H, Yokoe H, Uzawa K, et al: Clinical observations of postoperative delirium after surgery for oral carcinoma. Int J Oral Maxillofac Surg 38(6): 661e665, 2009 Smith LW, Dimsdale JE: Postcardiotomy delirium: conclusions after 25 years? Am J Psychiatry 146(4): 452e458, 1989 Takeuchi M, Takeuchi H, Fujisawa D, Miyajima K, Yoshimura K, Hashiguchi S, et al: Incidence and risk factors of p ostoperative delirium in patients with esophageal cancer. Ann Surg Oncol 19(12): 3963e3970, 2012 van der Mast RC, van den Broek WW, Fekkes D, Pepplinkhuizen L, Habbema JD: Incidence of and preoperative predictors for delirium after cardiac surgery. J Psychosom Res 46(5): 479e483, 1999 Weed HG, Lutman CV, Young DC, Schuller DE: Preoperative identification of patients at risk for delirium after major head and neck cancer surgery. Laryngoscope 105(10): 1066e1068, 1995 Yamagata K, Onizawa K, Yusa H, Wakatsuki T, Yanagawa T, Yoshida H: Risk factors for postoperative delirium in patients undergoing head and neck cancer surgery. Int J Oral Maxillofac Surg 34(1): 33e36, 2005 Zakriya KJ, Christmas C, Sr Wenz JF, Franckowiak S, Anderson R, Sieber FE: Preoperative factors associated with postoperative change in confusion assessment method score in hip fracture patients. Anesth Analg 94(6): 1628e1632, 2002
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Risk factors associated with postoperative delirium after surgery for oral cancer Takumi Hasegawa*, Izumi Saito, Daisuke Takeda, Eiji Iwata, Natsuki Yonezawa, Yasumasa Kakei, Akiko Sakakibara, Masaya Akashi, Tsutomu Minamikawa, Takahide Komori Department of Oral and Maxillofacial Surgery (Chief: Prof. T. Komori), Kobe University Graduate School of Medicine, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Paper received 16 March 2015 Accepted 8 June 2015 Available online 17 June 2015
Objective: The purpose of this study was to retrospectively investigate the multivariate relationships among the various risk factors for postoperative delirium in patients undergoing oral cancer surgery. Material and methods: The medical records of all patients with oral cancer who underwent curative head and neck surgery between April 2011 and March 2013 at our institution were retrospectively reviewed. There was a total of 188 patients, including 110 males and 78 females. Results: We found that older age, extensive surgical procedure, longer operation, excessive hemorrhage, blood transfusion, longer postoperative management in the intensive care unit, longer postoperative hospital stay, lower albumin level in the preoperative blood test, and lower total protein, albumi, n and hemoglobin levels and a higher C-reactive protein (CRP) level in the postoperative blood tests were significant variables in the univariate analysis (p < 0.05). We also determined that an older age (odds ratio [OR] ¼ 6.83), intraoperative lower hemoglobin levels (OR ¼ 6.82), and excessive hemorrhage (OR ¼ 3.62) during surgery were significant variables in the multivariate analysis. Conclusion: Clinicians should pay special attention to preventing delirium during the postoperative management of older patients with these risk factors. Furthermore, increasing the hemoglobin levels during surgery may be able to prevent postoperative delirium. © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
Keywords: Delirium Postoperative Oral cancer Risk factor Surgery
1. Introduction Postoperative delirium is a major complication after surgical procedures. Most postoperative delirium arises within a few days after surgery, and patients usually recover rapidly. However, continuous delirium complicates postoperative management. In addition, postoperative delirium is occasionally associated with higher morbidity, prolonged hospital stays, higher costs, and increased mortality (Koolhoven et al., 1996; Inouye et al., 1999; Schneider et al., 2002). Therefore, preventing postoperative delirium may contribute to reducing these problems. Many
* Corresponding author. Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 6500017, Japan. Tel.: þ81 78 382 6213; fax: þ81 78 351 6229. E-mail address: [email protected] (T. Hasegawa).
investigators have reported the risk factors associated with postoperative delirium for many types of surgery (van der Mast et al., 1999; Zakriya et al., 2002; Merchant et al., 2005; Kazmierski et al., 2006). However, the factors leading to postoperative delirium remain unclear because of its complex etiology. In previous studies, the incidence of postoperative delirium was 17%e26% after head and neck surgery (Weed et al., 1995; Yamagata et al., 2005; Shiiba et al., 2009). In a multivariate analysis study, there were numerous risk factors, including the age, gender, length of operation, pain control, and use of minor tranquilizers. However, only a few studies to date have evaluated the multivariate relationships among the various risk factors and postoperative delirium associated with oral cancer (Yamagata et al., 2005; Shiiba et al., 2009). Moreover, their studies did not demonstrate symptoms of delirium. In this study, we retrospectively investigated the symptoms of delirium and the multivariate relationships among
http://dx.doi.org/10.1016/j.jcms.2015.06.011 1010-5182/© 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
T. Hasegawa et al. / Journal of Cranio-Maxillo-Facial Surgery 43 (2015) 1094e1098
the various risk factors for postoperative delirium in patients undergoing oral cancer surgery. 2. Material and methods This was a nonrandomized, retrospective (historical) cohort study of patients. Thus, this study was granted exemption from institutional review board approval by our institution. Between April 2011 and March 2013, a total of 188 patients with oral cancer underwent major head and neck surgery at the Department of Oral and Maxillofacial Surgery, Kobe University Hospital. Patients were diagnosed with postoperative delirium when symptoms corresponded to one of the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) definition (American Psychiatric Association, 1997). These criteria focus on four key features: 1) acute changes in mental status with a fluctuating course; 2) inattention; 3) disorganized thinking; and 4) an altered level of consciousness. The symptoms of delirium were classified as Type 1: disturbance of consciousness and attention; Type 2: psychomotor behavior; Type 3: changes in cognition (perception); Type 4: orientation disturbance; and Type 5: hallucinations. We investigated the following variables: age, gender, medical history, history of alcohol consumption, history of smoking, surgical procedure, length of operation, blood loss, blood transfusion, existence of tracheotomy, postoperative management in the intensive care unit (ICU), perioperative blood tests (total protein [TP], albumin [ALB], creatinine [Cre], sodium [Na], chlorine [Cl], hemoglobin [Hb], and C-reactive protein [CRP]) and the postoperative hospital stay. The surgical procedures were classified into four categories: only tumor resection (TR), only neck dissection (ND), TR þ ND, and TR þ ND þ immediate reconstruction (R). Preoperative blood tests were performed within 5 days of surgery, and postoperative tests were performed 3 and 7 days after surgery. All factors are listed in Table 1. When the data were introduced into a multiple logistic regression model, the patients were divided according to surgical procedure (Only TR and Only NR vs TR þ ND and TR þ ND þ R). Patients were similarly divided into two groups based on age (<75 years old and 75 years old), into two groups based on blood loss (<800 mL and 800 mL), and into two groups based on the intraoperative Hb levels (<10 g/dL and 10 g/dL). Data collection and statistical analyses were carried out with SPSS 15.0 (SPSS Inc, Chicago, IL, USA) and Stat-View-J-4.5 software (Abacus Concepts, Berkeley, CA, USA). The association of each variable with the postoperative delirium was tested by using the ManneWhitney U nonparametric test for ordinal variables and the Fisher exact test for categorical variables. A value of p < 0.05 was considered statistically significant. All of the variables associated with postoperative delirium were introduced into a multiple logistic regression model. Forward selection methods were used, with the rejection of those variables that did not fit the model significantly. The postoperative blood tests on postoperative days 3 and 7 were also excluded, because 21 patients (72.4%) were diagnosed with postoperative delirium before postoperative day 3. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were also calculated for the significant signs. A value of p < 0.05 was considered statistically significant. 3. Results Postoperative delirium occurred in 29 of the 188 patients (15.4%), who included 19 males and 10 females. Most cases of delirium (86.2%) were observed between 1 and 5 days after surgery, at a mean of 3.0 days (Fig. 1).
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With regard to the types of symptoms, in the female patients with delirium, there were two cases (20.0%) of Type 1, five cases (50.0%) of Type 2, four cases (40.0%) of Type 3, no cases (0%) of Type 4, two cases (20.0%) of Type 5, and two cases (20.0%) of unknown type. In terms of the types of symptoms in male patients with delirium, there were two cases (10.5%) of Type 1, 13 cases (68.4%) of Type 2, three cases (15.8%) of Type 3, four cases (21.1%) of Type 4, three cases (15.8%) of Type 5, and three cases (15.8%) of unknown type (Table 2). There were no significant differences in the types between males and females. The patients with postoperative delirium had a mean age of 79.0 ± 8.9 years (range: 52e92 years). The patients without postoperative delirium had a mean age of 67.4 ± 12.9 years (range: 24e92 years). The patients with postoperative delirium were significantly older than those without postoperative delirium in the univariate analysis (p < 0.05) (Table 1). There were no significant differences between the sexes in the patients with and without postoperative delirium (Table 1). There were also no significant differences between other demographic factors, such as medical history, alcohol consumption history, and chronic smoking history in the patients with and without postoperative delirium (Table 1). There were seven cases of only TR, one case of only ND, three cases of TR þ ND, and 18 cases of TR þ ND þ R in the patients with postoperative delirium. There were 78 cases of only TR, 12 cases of only ND, five cases of TR þ ND, and 64 cases of TR þ ND þ R in the patients without postoperative delirium. There was a significant difference between the only TR or ND and the TR þ ND or TR þ ND þ R rates in the patients with and without postoperative delirium in the univariate analysis (p < 0.05) (Table 1). There were significant differences between intraoperative factors such as blood loss, intraoperative Hb levels, blood transfusion, and length of operation in the patients with and without postoperative delirium (p < 0.05) (Table 1). There was no significant difference in the performance of tracheotomy between the patients with and without postoperative delirium. The mean duration of ICU stay was 4.5 ± 2.3 days for the patients with postoperative delirium and 2.9 ± 3.1 days for the patients without postoperative delirium. There was a significant difference in the ICU stay between the patients with and without postoperative delirium (p < 0.05) (Table 1). The postoperative hospital stay of the patients with postoperative delirium was significantly longer than that of the patients without postoperative delirium. An analysis of the results of preoperative blood tests demonstrated that only the albumin (ALB) levels of patients who developed delirium were significantly lower than those of patients who did not develop delirium. An analysis of the postoperative blood tests demonstrated that the total protein (TP), ALB, and hemoglobin (Hb) levels of the patients with delirium were significantly decreased compared to those of the patients without delirium. In addition, the C-reactive protein (CRP) level of patients with delirium was significantly increased compared to that of the patients without delirium. Applying a logistic regression model and forward stepwise algorithms, we determined that older age, lower intraoperative Hb levels, and excessive hemorrhage during surgery were significant variables (Table 3). The patients' gender, medical history and existence of tracheotomy, and preoperative blood test results (TP, Cre, Na, Cl, and Hb) were excluded from this model, because these factors were not significant in the univariate analysis. The multivariate adjusted ORs and 95% CIs of the included factors were calculated. The discriminant hitting ratio (84.6%) was considered to be excellent in this study.
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Table 1 Characteristics and incidence rates of postoperative delirium after oral cancer surgery. Variables Demographic factors Sample size Gender Male Female Age (y) Range Mean ± SD Medical history (overlapping distribution) Cerebrovascular disease Diabetes mellitus Hypertension Coronary heart disease Renal dysfunction Psychosis or dementia Others Nothing particular Alcoholism Chronic smoking Peri- or intraoperative factors Type of surgery Only TR or ND TR þ ND or TR þ ND þ R Length of operation (hours; mean ± SD) Blood loss (mL; mean ± SD) Intraoperative hemoglobin (Hb) (g/dL) Blood transfusions Tracheotomy Postoperative management in ICU (days) Postoperative hospital stay (days) Preoperative blood test (mean ± SD) Total protein (TP) (g/dL) Albumin (ALB) (g/dL) Creatinine (Cre) (mg/dL) Sodium (Na) (mEq/L) Chlorine (Cl) (mEq/L) Hemoglobin (Hb) (g/dL) Postoperative blood test (POD 3) (mean ± SD) Total protein (TP) (g/dL) Albumin (ALB) (g/dL) Creatinine (Cre) (mg/dL) Sodium (Na) (mEq/L) Chlorine (Cl) (mEq/L) Hemoglobin (Hb) (g/dL) C-reactive protein (CRP) (mg/dL) Postoperative blood test (POD 7) (mean ± SD) Total protein (TP) (g/dL) Albumin (ALB) (g/dL) Creatinine (Cre) (mg/dL) Sodium (Na) (mEq/L) Chlorine (Cl) (mEq/L) Hemoglobin (Hb) (g/dL) C-reactive protein (CRP) (mg/dL)
Delirium, number (%)
No delirium, number (%)
p Value
29 (15.4)
159 (84.6)
19 (66.5) 10 (34.5)
91 (57.2) 68 (42.8)
n.s.
52e92 49.0 ± 8.9
24e92 67.4 ± 12.9
<0.05a
8(27.6) 2(6.9) 8(27.6) 6(20.7) 5(17.2) 1(3.4) 3(10.3) 6(20.9) 8(27.6) 13(44.8)
44(42.3) 8(7.7) 25(24.0) 42(40.4) 16(15.4) 9(8.7) 4(3.8) 63(60.6) 64(40.3) 84 (52.8)
n.s. n.s. n.s.
8 (27.6) 21 (72.4) 9.2 ± 4.6 967.0 ± 1113.4 9.4 ± 1.8 14 (48.3) 19 (65.5) 4.5 ± 2.3 54.6 ± 27.3
90 (56.6) 69 (43.4) 6.3 ± 5.1 392.7 ± 537.7 11.4 ± 1.7 29 (18.2) 71 (44.7) 2.9 ± 3.1 39.9 ± 32.3
<0.05b <0.05a <0.05a <0.05a <0.05b n.s. <0.05a <0.05a
6.6 ± 0.7 3.7 ± 0.5 1.0 ± 0.7 140.3 ± 2.0 106.5 ± 2.0 12.4 ± 2.6
7.0 ± 3.2 4.0 ± 0.4 0.9 ± 1.1 140.5 ± 2.5 106.1 ± 2.7 13.0 ± 1.6
n.s. <0.05a n.s. n.s. n.s. n.s.
5.0 ± 0.9 2.6 ± 0.5 0.8 ± 0.6 138.4 ± 2.8 105.9 ± 3.5 9.5 ± 1.8 9.3 ± 5.3
5.5 ± 0.9 3.1 ± 0.7 0.8 ± 1.1 139.6 ± 2.7 105.9 ± 3.4 10.7 ± 2.2 5.0 ± 4.5
<0.05a <0.05a n.s. n.s. n.s. <0.05a <0.05a
5.4 ± 0.7 2.6 ± 0.4 0.9 ± 0.5 139.7 ± 3.5 105.0 ± 3.8 9.7 ± 1.4 4.8 ± 4.8
5.8 ± 0.8 3.1 ± 0.6 3.5 ± 30.4 140.1 ± 2.6 104.4 ± 3.3 10.9 ± 1.8 3.1 ± 3.9
<0.05a <0.05a n.s. n.s. n.s. <0.05a <0.05a
n.s., Not significant; TR, tumor resection; ND, neck dissection; R, immediate reconstruction. a ManneWhitney U test. b Fisher exact test.
4. Discussion In previous reports, the incidence of delirium after cardiovascular surgery ranged from 30% to 73% (Hammeke and Hastings, 1988; Smith and Dimsdale, 1989; Rudolph et al., 2005). Dyer et al. reported that the incidence of postoperative delirium was 0%e 73.5% after various surgeries (Dyer et al., 1995). However, only a few studies performed to date have evaluated the multivariate relationships among the various risk factors and postoperative delirium following surgery for oral cancer (Yamagata et al., 2005; Shiiba et al., 2009). These studies reported that the incidence of postoperative delirium after head and neck surgery was 17%e26% (Weed et al., 1995; Yamagata et al., 2005; Shiiba et al., 2009). In the
present study, the incidence of postoperative delirium after oral cancer surgery was 15.4%. This result was similar to those of previous studies (Weed et al., 1995; Yamagata et al., 2005; Shiiba et al., 2009). In this study, most cases of delirium (86.2%) were observed between 1 and 5 days after surgery. Takeuchi et al. reported that most of the delirium developed by day 7 after surgery, and suggested that clinicians should pay particular attention to the possibility of delirium during the first postoperative week (Takeuchi et al., 2012). We agree with their opinion. No reports have shown that female gender was a risk factor for postoperative delirium, whereas some reports have suggested that male gender could be a risk factor for delirium (Dyer et al., 1995; Shiiba et al., 2009; Takeuchi et al., 2012). Several investigators
T. Hasegawa et al. / Journal of Cranio-Maxillo-Facial Surgery 43 (2015) 1094e1098
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Table 3 Results of multivariate logistic regression analysis of risk factors for postoperative delirium. Variable
p Value
Older age (75 years) Intraoperative hemoglobin (<10 g/dL) Excessive hemorrhage (800 ml)
<0.001 <0.001 0.016
Odds ratio
6.83 6.82 3.62
95% CI Lower
Upper
2.47 2.57 1.27
18.90 18.12 10.30
CI, confidence interval.
Fig. 1. Time of postoperative onset of delirium.
have reported that no correlations were observed between gender and postoperative delirium (Weed et al., 1995; Yamagata et al., 2005). In this study, there were no significant differences between the sexes in the patients with and without postoperative delirium. However, the incidence of postoperative delirium in the male patients (17.3% of all male patients) was higher than that in female patients (12.8% of all female patients). In addition, the rate of Type 2 (psychomotor behavior) symptoms was 13/19 (68.4%) of males, which was higher than the rate of 5 and 10 females (50%). It may be possible that males are more prone to develop hyperactive or agitated delirium, such as Type 2, compared to females. Type 2 delirium is associated with patients turning over, falling down or climbing out of bed, and self-removal of drip infusion, etc., and such activity complicates the postoperative management. We should therefore focus particular attention on Type 2 delirium to prevent severe medical errors. This study indicated that there was a significantly higher incidence of postoperative delirium in elderly patients, similar to that in a previous study (Dyer et al., 1995; Schneider et al., 2002; Shiiba et al., 2009; Sasajima et al., 2012; Takeuchi et al., 2012). Shiiba et al. speculated that elderly patients were less able to adapt physically and psychologically to drastic alterations during the surgical period than younger patients, and that this might induce postoperative delirium (Shiiba et al., 2009). This is likely closely related to the higher incidence of postoperative delirium after extensive operations. Weed et al. reported that many patients after major head and neck cancer surgery had a high risk of developing postoperative delirium, because the age of many patients was advanced, and time-intensive surgeries, such as immediate reconstruction with free flaps, are often performed (Weed et al., 1995). In this study, older age (OR ¼ 6.83) was also associated with a higher risk of postoperative delirium after oral cancer surgery in a multivariate analysis (Table 3). In contrast, an extensive surgical procedure history was associated with a higher risk according to a univariate analysis (Table 1).
An analysis of the preoperative blood tests demonstrated that only the ALB level of patients who developed delirium was significantly lower than that of the patients who did not. This result suggested that an appropriate preoperative nutritional status may prevent postoperative delirium. In the postoperative blood tests, the TP, ALB, Hb, and CRP levels were all related to the incidence of postoperative delirium. This suggests that undernutrition (lower TP and ALB), anemia (lower Hb), and inflammation (higher CRP) may promote postoperative delirium. The relationship between the blood test results and postoperative delirium has been controversial in various studies (Morse and Litin, 1969; Weed et al., 1995; Marcantonio et al., 1998; Schneider et al., 2002; Yamagata et al., 2005; Shiiba et al., 2009). However, excessive hemorrhage and postoperative hematocrit values have been reported as postoperative factors predicting the development of delirium in several studies (Marcantonio et al., 1998; van der Mast et al., 1999; Schneider et al., 2002; Yamagata et al., 2005; Shiiba et al., 2009; Sasajima et al., 2012). Schneider et al. demonstrated that a trend for greater intraoperative blood loss with a subsequent need for increased transfusions was heavily associated with postoperative delirium, and with the severity and duration of the delirium (Schneider et al., 2002). Furthermore, Marcantonio et al. demonstrated that postoperative delirium was associated with a reduced hematocrit value of less than 30% and intraoperative blood loss requiring a greater number of transfusions (Marcantonio et al., 1998). van der Mast et al. speculated that massive hemorrhaging during an operation reduced the cerebral oxygen supply, a condition similar to cerebral ischemia, and might play a role in postoperative mental disorders (van der Mast et al., 1999). In this study, lower intraoperative Hb levels (OR ¼ 6.82) and excessive hemorrhage (OR ¼ 3.62) were also associated with a higher risk of postoperative delirium after oral cancer surgery in a multivariate analysis (Table 3). The performance of blood transfusion, however, was associated with a higher risk only by univariate analysis (Table 1). Therefore, the increasing of Hb levels during surgery through active blood transfusion may be able to prevent postoperative delirium. However, we need to carefully consider this point because of the negative side effects of blood transfusion. Postoperative delirium is generally treated by the administration of haloperidol, droperidol, or benzodiazepine for symptomatic treatment (O'Keeffe and Ní Chonchubhair, 1994; Dyer et al., 1995; Parikh and Chung, 1995; Moller et al., 1998). The association between the use of mild sedatives and delirium has been controversial
Table 2 Types of symptoms of delirium after oral cancer surgery. Types of symptom of delirium (overlapping distribution)
Males (n ¼ 19)
Females (n ¼ 10)
Type 1: disturbance of consciousness and attention Type 2: psychomotor behavior Type 3: change in cognition (perception) Type 4: orientation disturbance Type 5: hallucination Unknown
2 13 3 4 3 3
2 5 4 0 2 2
(10.5 (68.4 (15.8 (21.1 (15.8 (15.8
%) %) %) %) %) %)
(20.0 (50.0 (40.0 (0 %) (20.0 (20.0
%) %) %) %) %)
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(Marcantonio et al., 1994; Yamagata et al., 2005; Takeuchi et al., 2012). Some reports have shown that use of these agents increased delirium (Marcantonio et al., 1994; Takeuchi et al., 2012). Benzodiazepines have been shown to potentially cause delirium via central nervous system sedation and withdrawal mechanisms (Takeuchi et al., 2012). However, other reports have found a decrease in delirium with the medication (Schor et al., 1992; Yamagata et al., 2005). We used mainly mild sedatives for sleep disturbance and used major sedatives (tranquilizers), such as haloperidol (44.8% of the patients with delirium), risperidone (41.4%), and quetiapine (24.1%) to treat delirium. Schrader et al. demonstrated that the preoperative administration of haloperidol resulted in a positive effect on the severity and duration of delirium (Schrader et al., 2008). Regardless, the appropriate management of the sleep cycle and environmental improvement is important. We are planning a future study to investigate these preventive strategies and early treatments on the development of postoperative delirium. 5. Conclusion In this study, we successfully demonstrated multivariate relationships among the various risk factors for postoperative delirium in patients undergoing oral cancer surgery. We determined that older age, lower intraoperative Hb levels, and excessive hemorrhage during surgery were significant factors associated with the development of delirium in a multivariate analysis. Therefore, clinicians should pay special attention to preventing delirium during the postoperative management of older patients with these risk factors. Finally, increasing the hemoglobin levels during surgery may be able to prevent postoperative delirium. Conflict of interest There are no financial or personal relationships with other people or organizations that can inappropriately influence the work of the authors. We did not receive any sources of study funding, including those of an institutional or departmental nature. Acknowledgments No study funding was received, including any of an institutional or departmental nature. References American Psychiatric Association: Diagnostic, and statistical manual of mental disorders, 4th ed. Washington, DC: American Psychiatric Association, 1997 Dyer CB, Ashton CM, Teasdale TA: Postoperative delirium. A review of 80 primary data-collection studies. Arch Intern Med 155(5): 461e465, 1995 Hammeke TA, Hastings JE: Neuropsychologic alterations after cardiac operation. J Thorac Cardiovasc Surg 96(2): 326e331, 1988
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