This study involved 532 patients who underwent spine surgery at Ehime University Hospital from 2012 to 2014. There were 283 males and 249 females, with an average age of 64.2 years (range, 10–89 years). None of the patients had delirium or a history of delirium preoperatively. None of the patients had a history of psychiatric diseases requiring the use of psychotropic drugs. All operations were performed by one of the four senior spine surgeons having >10 years of clinical experience. All operations were performed under general anesthesia with propofol and isoflurane, enflurane complex with fentanyl, and rocuronium bromide or vecuronium bromide, and all the patients were supplied with oxygen (3–5 L/min) through a mask for at least 24 postoperative hours. The study was approved by the institutional review board at Ehime University (IRB approval no., 1801010).

The presence of delirium was determined based on the diagnostic and statistical manual of mental disorders (DSM-IV) criteria [7], which are the gold standard for psychiatric evaluation [8]. Nurses were trained for the detection of symptoms, including hyperactivity, hypoactivity, disarray, hallucination, and delusion, in patients according to the DSM-IV criteria. Patients both with and without symptoms of delirium were observed during regular postoperative care from day 0 to 7. When a patient was suspected with symptoms of delirium, the nurse called two doctors to discuss whether the patient actually had delirium. Patients were finally diagnosed as having delirium when both the doctors confirmed the diagnosis. The presence of delirium and its symptoms were recorded in the medical records after the decision.

The clinical records of all 532 patients were retrospectively reviewed, and patients were divided into two groups: delirium positive and negative groups. The overall and age group-related incidences of delirium were calculated, and statistical analysis was performed to compare the age between the delirium positive and negative groups.

After the evaluation of incidence in all the patients, each patient with delirium (age-matched delirium positive group) was matched with two patients of the same age in the delirium negative group (age-matched delirium negative group). The selection of patients from the database of spine surgeries was carried out by one of the co-authors who was not informed of the patients’ backgrounds. If there was no patient of the same age, we selected patients within 2 years of age difference. Risk factors in the agematched delirium positive group were compared with those in the age-matched delirium negative group. Preoperative risk factors included age, sex, ambulatory status, number of medication, smoking history, habit of alcohol use, history of surgery under general anesthesia, comorbidities (diabetes mellitus, cardiovascular disease, and neurological disorder), white blood cell (WBC) count and C-reactive protein (CRP), Hb, Hct, Alb, and sodium (Na) levels. Intraoperative factors included cervical surgery, operative time, and intraoperative blood loss. Postoperative factors included WBC count and CRP, Hb, Alb, and Na levels on postoperative day 1 and highest body temperature until the delirium or within 7 postoperative days. All the data were obtained from medical or nursing records. No patient data was lost.

All the data were analyzed using JMP ver. 9.0.3 for Macintosh (SAS Institute Inc., Cary, NC, USA). The mean age of the delirium positive and negative groups is presented as a five-number summary, whereas other numerical variables are presented as the mean and standard deviation. The Mann–Whitney U-test was used for the statistical analysis of the difference in the mean values between the groups for non-normally distributed and ordinal variables. The Student t-test was employed for normally distributed variables. The chi-square test was used to compare categorical variables. A p-value of <0.05 was considered statistically significant. Multivariate logistic regression models, with backward elimination, were constructed to find independent risk factors associated with the occurrence (positive or negative) of postoperative delirium. Factors with p<0.05 in the previous univariate analysis were included. Odds ratios and their 95% confidence intervals were calculated. A p-value of <0.05 was considered statistically significant.

Delirium occurred after spine surgery in 59 of 532 patients (11.1%). The age-specific incidence of delirium and mean age at the onset of delirium (for age of 60–89 years presented in 5-year intervals) were calculated (Table 1). The incidence of delirium increased with increasing age. In the 80–84 and 85–89 years age groups, the incidence was 35.6% and 50.0%, respectively (Table 1). The mean age of the delirium positive group was significantly higher than that of the delirium negative group (77.6±6.6 versus 62.5±17.3 years, respectively; p<0.001) (Fig. 1). Almost all the cases of delirium were observed between the day of the surgery and three days after it. Two patients had delirium on postoperative days 4 and 5. All the patients recovered from the delirium by postoperative 1 week.

The age-matched delirium positive group included 59 patients, while the age-matched delirium negative group included 116 patients. Univariate analysis was initially performed. Regarding preoperative data, male sex, cervical operation, and nonambulatory status tended to be associated with delirium (p<0.1), but the association was not statistically significant. There was no significant difference in the number of medications, history of smoking and alcohol use, history of surgery under general anesthesia, and comorbidities (diabetes mellitus, cardiovascular disease, and neurological disease) (Table 2). Regarding the preoperative laboratory data, blood Na levels were significantly lower in the age-matched delirium positive group than in the age-matched delirium negative group (p=0.04). Other factors, including WBC count and CRP, Hb, Hct, and Alb levels, were not significant (Table 3). Regarding intraoperative data, blood loss was significantly higher in the age-matched delirium positive group than in the agematched delirium negative group (p=0.004). Longer operative times tended to be associated with delirium (p=0.055) (Table 2). Regarding postoperative data, high CRP levels, low Hct and Alb levels, and high body temperature on postoperative day 1 were identified as significant risk factors for delirium (p=0.002, 0.02, 0.004, and 0.009, respectively) (Table 3).

Subsequently, multivariate logistic regression analysis was performed. Preoperative Na levels; intraoperative blood loss; postoperative CRP, Hct, and Alb levels; and body temperature (detected as significant risk factors of delirium in the univariate analysis) were analyzed. Intraoperative blood loss was the only significant risk factor identified (odds ratio, 7.07; 95% confidence interval, 0.02–0.97) (Table 4).