YIJOM-1518; No of Pages 5

Int. J. Oral Maxillofac. Surg. 2009; xxx: xxx–xxx

doi:10.1016/j.ijom.2009.01.011, available online at http://www.sciencedirect.com

Clinical Paper
Head and Neck Oncology

M. Shiiba*, M. Takei, M. Nakatsuru,

Clinical observations of H. Bukawa, H. Yokoe, K. Uzawa,
H. Tanzawa

postoperative delirium after Department of Dentistry and Oral Surgery,

Chiba University Hospital, Chiba University,
1-8-1 Inohana, Chiba city, Chiba 260-8677,
Japan

surgery for oral carcinoma

M. Shiiba*M. Takei, M. Nakatsuru, H. Bukawa, H. Yokoe, K. Uzawa, H. Tanzawa:
Clinical observations of postoperative delirium after surgery for oral carcinoma. Int.
J. Oral Maxillofac. Surg. 2009; xxx: xxx–xxx. # 2009 International Association of
Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Abstract. The aim of the present study was to clarify the clinical characteristics of
postoperative delirium and to determine appropriate postoperative management for
its prevention. The authors analysed 132 cases of primary surgery for oral
carcinoma and observed 24 (18%) cases of postoperative delirium. Univariate
analysis revealed that significant risk factors for postoperative delirium were older
age, male gender, extensive surgery and morphine pain control. Logistic regression
analysis showed that older age and male gender were significant risk factors for
postoperative delirium, while patient-controlled analgesia with fentanyl was
effective for prevention of postoperative delirium. There was a trend for
postoperative delirium to be associated with extensive surgery. In those who had
delirium, blood tests revealed that alkaline phosphatase, total protein, sodium,
chlorine, red blood cell count, haemoglobin and haematocrit were significantly Keywords: delirium; oral carcinoma; patient-
diminished after surgery. These results indicate that general condition is closely controlled analgesia; fentanyl.
related to the onset of postoperative delirium, and suggest that appropriate
postoperative management can reduce the incidence of this complication. Accepted for publication 21 January 2009

Postoperative delirium is a major compli-
cation that usually develops in the acute
postoperative period (usually within hours
to a few days) after comparatively exten-
sive surgical procedures2. The condition is
characterised by a disturbance of con-
sciousness accompanied by a change in
cognition. Most delirious patients recover
rapidly, but delirium can cause problems
during postoperative management.
Much research has aimed to clarify the
risk factors for postoperative delirium;
however, the details of postoperative delir-
ium remain unclear due to its complex
morbidity1,3,4,14,15. Postoperative delirium
has been reported in many types of surgery
and its incidence varies6,8,12,17. According
to previous studies concerning head and
neck operations, the incidence of post-
operative delirium was 17–26%, and risk
factors were age, anaesthesia, massive hae-
morrhage7, stage, flap reconstruction,
operative time, blood transfusion, infusion,
minor tranquiliser use16, living alone,
white blood cell count, ASA class and
anaesthesia time14. The present study
aimed to clarify the clinical characteristics
of postoperative delirium and to investigate
practical approaches that can contribute to
its prevention.
Materials and methods
Subjects
The authors retrospectively analysed 132
cases of oral carcinoma. All patients
underwent primary surgery under general
anaesthesia between January 2001 and
September 2006.
Patients were diagnosed with post-
operative delirium when symptoms corre-

0901-5027/000001+05 $30.00/0 # 2009 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: M.. Shiiba, et al., Clinical observations of postoperative delirium after surgery for oral carcinoma, Int
J Oral Maxillofac Surg (2009), doi:10.1016/j.ijom.2009.01.011
YIJOM-1518; No of Pages 5
2 Shiiba et al.
sponded to one of the criteria outlined in
the Diagnostic and Statistical Manual of
Mental Disorders, 4th edition (DSM-IV)
definition2: disturbance of consciousness
(i.e. reduced clarity of awareness of the
environment) with reduced ability to
focus, sustain or shift attention; a change
in cognition (such as memory deficit, dis-
orientation or language disturbance) or the
development of a perceptual disturbance
that is not better accounted for by a pre-
existing, established, or evolving demen-
tia; the disturbance develops during a short
period of time (usually hours to days) and
tends to fluctuate during the course of the
day; there is evidence from the history,
physical examination or laboratory find-
ings that the disturbance is caused by the
direct physiological consequences of a
general medical condition.
Factors for postoperative delirium
The authors analysed the following vari-
ables: age, gender, history of respiratory
disease and BMI (preoperative factors);
surgical procedure, anaesthesia time,
operation time, blood loss and volume
of transfusion fluid (intraoperative fac-
tors); and tracheotomy, postoperative
management in the intensive care unit
(ICU) and pain control management (post-
operative factors). Surgical procedure was
classified into three categories: tumour
resection; tumour resection and neck dis-
section; and tumour resection, neck dis-
section and immediate reconstruction.
Postoperative pain was treated with
patient-controlled analgesia with either
morphine hydrochloride (PCA-morphine)
or fentanyl citrate (PCA-fentanyl).
Laboratory data were analysed to clarify
the association between general condition
Table 1. Patient profiles.
Age (years meanSD)
BMI (kg/m2; meanSD)
Respiratory disease
Surgical procedure
Tumour resection
Tumour resection + ND*
Tumour resection + ND + R**
Operative duration (min; mean  SD)
Anaesthetic duration (min; mean  SD)
Blood loss (g; median)
Volume of transfusion fluid (ml; mean  SD)
Pain control
PCA-morphine
PCA-fentanyl
Postoperative management in ICU
Tracheotomy
* ND: neck dissection.
** R: immediate reconstruction.
Please cite this article in press as: M.. Shiiba, et al., Clinical observations of postoperative delirium after surgery for oral carcinoma, Int
J Oral Maxillofac Surg (2009), doi:10.1016/j.ijom.2009.01.011
and the onset of postoperative delirium.
Preoperative blood tests were performed
within 5 days of surgery and postoperative
tests on the day after surgery.
Statistical analysis
All statistical analyses were performed
using SPSS statistical software (Chicago,
IL, USA). Statistical categorical data were
analysed with Fisher’s exact test. Compar-
isons of continuous quantitative variables
were performed with Student’s t-test or
Mann–Whitney U-test. The independent
association of significant factors deter-
mined by the univariate analyses was
examined using stepwise regression ana-
lysis and logistic regression analysis. P
values less than 0.05 were considered
significant.
Results
Incidence of postoperative delirium
A total of 132 patients who underwent
primary surgery for oral carcinoma were
studied. Patient profiles are summarised in
Table 1 and no significant gender-related
differences were observed. Postoperative
delirium occurred in 24 (18%) of 132
patients.
Risk factors revealed by univariate
analyses
Univariate analyses revealed that older
age (Student’s t-test; p = 0.0023), male
gender (Fisher’s exact test; p = 0.0237),
more extensive surgical procedure (Fish-
er’s exact test; p = 0.0072) and postopera-
tive pain control with morphine (Fisher’s
exact test; p = 0.0225) were risk factors
Total (n = 132)
63.0  12.6
22.5  3.6
24
6 4
18
108
472.8  134.3
564.2  134.1
518.0
3458.1  660.4
69
63
11
28
for postoperative delirium (Table 2).
There was a non-significant trend towards
longer operative duration, longer anaes-
thetic duration and greater blood loss in
patients who developed delirium com-
pared with those who did not. Surgical
procedure was strongly correlated with
operative duration (correlation analysis;
correlation coefficient: 0.525) and anaes-
thetic duration (correlation analysis; cor-
relation coefficient: 0.506). These data
suggest that postoperative delirium tends
to be associated with extensive surgery.
Multivariate analyses
Stepwise regression analysis was per-
formed to determine risk factors for post-
operative delirium. Age, gender and
postoperative pain control were found to
be crucial factors. These three factors were
subjected to logistic regression analysis to
clarify the association between them and
the development of postoperative delir-
ium. The results showed older age (logis-
tic regression analysis; OR: 1.097, 95%CI:
1.037–1.159) and male gender to be sig-
nificant risk factors for postoperative
delirium (logistic regression analysis;
OR: 5.486, 95%CI: 1.582–19.017), while
pain control with fentanyl-PCA was effec-
tive for preventing postoperative delirium
(logistic regression analysis; OR: 0.220,
95%CI: 0.070–0.694) (Table 3).
Analysis of laboratory data after/before
surgery
Analysis of blood tests revealed that alka-
line phosphatase (ALP; Mann–Whitney
U-test; p = 0.0072), total protein (TP;
Mann–Whitney U-test; p = 0.0112),
sodium (Na; Mann–Whitney U-test;
Female (n = 55) Male (n = 77)
63.1  14.6 63.0  11.0
23.1  4.1 22.1  3.8
10 14
2
10 8
41 67
458.5  143.8 485.7  124.2
552.0  145.9 576.4  121.7
498.0 519.0
3327.0  673.6 3577.3  656.6
30 39
25 38
4 7
11 17
YIJOM-1518; No of Pages 5

Clinical observations of postoperative delirium after surgery for oral carcinoma 3

Table 2. Association between risk factors and postoperative delirium.

Not delirious n = 108 (81.8%) Delirious n = 24 (18.2%) P value
Age (mean  SD) 61.2  12.6 69.7  8.9 0.0023 *1
Gender: male 58 (53.7%) 19 (79.2%) 0.0237 *2
BMI (kg/m2; mean  SD) 22.3  3.5 22.5  3.9 0.8473 *1
Respiratory disease 21 (19.4%) 3 (12.5%) 0.7044 *2

Surgical procedure
Tumour resection alone or with ND 24 (22.2%) 0 (0.0%) 0.0072 *2
Tumour resection + ND + R 84 (77.8%) 24 (100%)
Operative duration (min; mean  SD) 466.5  134.4 506.9  122.7 0.1934 *1
Anaesthetic duration (min; mean  SD) 558.8  137.3 597.1  105.5 0.2144 *1
Blood loss (g; median) 511.5 561.0 0.3424 *3
Volume of transfusion fluid (ml; mean  SD) 3407.5  686.5 3620.0  608.9 0.5438 *1

Pain control
PCA-morphine 51 (47.2%) 18 (75.0%) 0.0225 *2
PCA-fentanyl 57 (52.8%) 6 (25.0%)
Postoperative management in ICU 8 (7.4%) 3 (12.5%) 0.4580 *2
Tracheotomy 21 (19.4%) 7 (28.0%) 0.2838 *2
*1 Student’s t-test.
*2 Fisher’s exact test.
*3 Mann–Whitney U-test.

Table 3. Logistic regression analysis for postoperative delirium.

95% CI
Factor Coefficient P value Odds ratio
Lower Upper
4 6
Constant 8.128 0.0001 2.9  10 4.8  10 0.018
Age 0.092 0.0011 1.097 1.037 1.159
Gender: Male 1.702 0.0073 5.486 1.582 19.017
Pain control: Fentanyl 1.514 0.0098 0.220 0.070 0.694

p = 0.0386), chlorine (Cl; Mann–Whitney
U-test; p = 0.0053), red blood cell count
(RBC; Mann–Whitney U-test;
p = 0.0104), haemoglobin (HGB; Mann–
Whitney U-test; p = 0.0139), haematocrit
(HCT; Mann–Whitney U-test; p = 0.0078)
were significantly diminished after sur-
gery (Table 4). TP, RBC, HGB and
HCT were significantly correlated (corre-
lation analysis; correlation coefficient:
>0.6) and were also correlated with blood
loss (correlation analysis; correlation
coefficient: >0.4). These results indicate
that general condition is closely related to
the onset of postoperative delirium, and
that alterations of general condition might
be mainly due to blood loss.
Discussion
The incidence of postoperative delirium
was 18% in the present study; this is
similar to previous reports describing an
incidence of 17–26% in patients under-
going resections of malignant head and
neck tumours7,14,16. The present study
showed a significant gender-related differ-
ence in the incidence of postoperative
delirium, whereas previous studies have
shown only a trend in this direction. No
reports have shown female gender to be a
risk factor for postoperative delirium, so it
is reasonable to suggest that male gender
could be a risk factor for delirium after
surgery for oral carcinoma. This risk fac-
tor might have been revealed in the present
study owing to adequate numbers of sub-
jects.
In agreement with previous studies, the
present study indicated a significantly
higher incidence of postoperative delirium
in elderly patients10,12,13. The authors
speculate that elderly patients are less able
to adapt physically and psychologically to
drastic alterations during the surgical per-
iod than younger patients, and that this
might induce postoperative delirium. This
is likely to be closely related to the higher
incidence of postoperative delirium in
extensive operations.
The data revealed a statistically signifi-
cant association between postoperative
pain management with morphine and the
incidence of postoperative delirium. PCA
is widely used because of its safety and
efficacy in the management of acute post-
operative pain9; however, the present data
showed no suppression of postoperative
delirium in the PCA-morphine group. This
might be due to the complications of
morphine: confusion, delirium and cogni-
tive impairment. In contrast, the PCA-
fentanyl group had a significant advantage
in avoiding postoperative delirium com-
pared with the PCA-morphine group. HER-
5
RICK et al. investigated the safety and
cognitive impact of PCA with fentanyl
compared with morphine among elderly
postoperative patients following hip or
knee arthroplasty. They reported that fen-
tanyl produced less postoperative cogni-
tive depression compared with morphine.
These findings suggest that PCA-fentanyl
is preferable to morphine in the manage-
ment of postoperative pain, as it is less
likely to lead to postoperative delirium.
Previous studies have indicated that inap-
propriate pain control or sleep cycle dis-
turbance contribute to delirium onset;
accordingly PCA-fentanyl might have
played a critical role in both pain control
and sleep cycle11.
Analysis of blood tests showed close
association between general condition and

Please cite this article in press as: M.. Shiiba, et al., Clinical observations of postoperative delirium after surgery for oral carcinoma, Int
J Oral Maxillofac Surg (2009), doi:10.1016/j.ijom.2009.01.011
YIJOM-1518; No of Pages 5

4 Shiiba et al.

Table 4. Comparison of laboratory data after/before surgery (%) between patients with and without delirium.
Ratio of laboratory data after/before surgery (%)
P value*
Not delirious (mean  SD) Delirious (mean  SD)
Aspartate aminotransferase (AST) 120.3  42.6 119.9  41.3 0.7697
Alanine aminotransferase (ALT) 90.9  41.7 79.7  26.2 0.1191
Lactate dehydrogenase (LDH) 91.7  16.9 88.2  16.5 0.2731
Alkaline phosphatase (ALP) 75.4  14.8 69.1  11.3 0.0072**
Total protein (TP) 79.3  9.2 75.9  7.9 0.0112**
Albumin (ALB) 78.0  9.1 76.5  8.5 0.2941
Uric acid (UA) 73.3  16.4 74.7  19.4 0.5417
Urea nitrogen (UN) 82.3  28.6 81.3  24.1 0.9066
Creatinine (Cre) 93.7  20.3 95.5  17.0 0.2990
Total bilirubin (T-Bil) 146.5  50.6 146.0  52.7 0.9147
Sodium (Na) 97.4  2.6 98.2  2.1 0.0386**
Potassium (K) 93.2  11.5 90.2  7.7 0.0717
Chlorine (Cl) 98.1  3.4 99.5  3.2 0.0053**
White blood cell count (WBC) 221.8  70.7 201.1  43.7 0.1162
Red blood cell count (RBC) 87.5  11.8 83.8  10.8 0.0104**
Haemoglobin (HGB) 88.3  12.0 84.4  11.0 0.0139**
Haematocrit (HCT) 88.3  11.7 83.3  10.5 0.0078**
Mean corpuscular volume (MCV) 99.9  1.9 99.4  1.3 0.1871
Mean corpuscular haemoglobin (MCH) 100.9  3.0 100.7  2.4 0.8260
Mean corpuscular haemoglobin concentration (MCHC) 101.0  2.4 101.2  2.4 0.6918
Red blood cell distribution width (RDW) 101.5  7.0 100.6  5.7 0.7758
Platelet (PLT) 85.7  36.8 82.1  14.3 0.4907
Platelet crit (PCT) 86.8  12.0 82.6  11.0 0.4878
Mean platelet volume (MPV) 100.7  5.4 100.5  4.9 0.6178
Platelet distribution width (PDW) 100.4  3.0 100.1  2.7 0.8295
*P values were calculated with Mann–Whitney U-test.
**Statistically significant difference.

postoperative delirium. Among the chan-
ged laboratory data, TP, RBC, HGB and
HCT appeared to be correlated with blood
loss, suggesting that blood loss is a crucial
risk factor for postoperative delirium.
In conclusion, the present study
strongly indicates that age and gender
are significant risk factors for postopera-
tive delirium, and that delirium tends to
develop in parallel with increased surgical
stress. Postoperative pain control with
fentanyl using a PCA system had an
advantage in prevention of postoperative
delirium. Accordingly, surgeons should
take these risk factors into consideration
and pay closer attention to managing the
patient’s condition throughout the peri-
operative period.
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YIJOM-1518; No of Pages 5

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1632 table of contents.

Please cite this article in press as: M.. Shiiba, et al., Clinical observations of postoperative delirium after surgery for oral carcinoma, Int
J Oral Maxillofac Surg (2009), doi:10.1016/j.ijom.2009.01.011