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J Korean Neurosurg Soc 43 : 143-148, 2008 Incidence and Risk Factors of Acute
Yoon-Sik Oh, M.D.1 Postoperative Delirium in Geriatric
Dong-Won Kim, M.D.2 Hyoung-Joon Chun, M.D.1 Hyeong-Joong Yi, M.D.1 Objective : Postoperative delirium (POD) is characterized by an acute change in cognitive function and can
result in longer hospital stays, higher morbidity rates, and more frequent discharges to long-term care facilities.
In this study, we investigated the incidence and risk factors of POD in 224 patients older than 70 years of
age, who had undergone a neurosurgical operation in the last two years.
Methods : Data related to preoperative factors (male gender, >70 years, previous dementia or delirium, alcohol
abuse, serum levels of sodium, potassium and glucose, and co-morbidities), perioperative factors (type of
surgery and anesthesia, and duration of surgery) and postoperative data (length of stay in recovery room,
severity of pain and use of opioid analgesics) were retrospectively collected and statistically analyzed.
Results : POD appeared in 48 patients (21.4%) by postoperative day 3. When we excluded 26 patients with
Departments of Neurosurgery1 previous dementia or delirium, 17 spontaneously recovered by postoperative day 14, while 5 patients recovered Anesthesia and Pain Medicine,2 by postoperative 2 months with medication, among 22 patients with newly developed POD. The univariate Hanyang University risk factors for POD included previously dementic or delirious patients, abnormal preoperative serum glucose Medical Center, Seoul, Korea level, pre-existent diabetes, the use of local anesthesia for the operation, longer operation time (>3.2 hr) or
recovery room stay (>90 min), and severe pain (VAS>6.8) requiring opioid treatment (p<0.05). Backward
regression analysis revealed that previously dementic patients with diabetes, the operation being performed
under local anesthesia, and severe postoperative pain treated with opioids were independent risk factors
for POD.
Conclusion : Our study shows that control of blood glucose levels and management of pain during local
anesthesia and in the immediate postoperative period can reduce unexpected POD and help preventing
unexpected medicolegal problems and economic burdens.
KEY WORDS : Anesthesia∙Diabetes∙Geriatric∙Pain∙Postoperative delirium.
Delirium is an acute confusional state characterized by fluctuating symptoms such as inattention, disturbances of consciousness, or disorganized thinking. Other importanthallmarks of this syndrome include disorientation, memory impairment, perceptual disturbances,altered psychomotor activity, and disturbed sleep-wake cycles12). Postoperative delirium(POD), one of the most unexpected and perplexing complications encountered in theperioperative period, is relatively well reported and investigated in the field of cardiac andmajor non-cardiac orthopedic surgery. According to these reports, POD is associated withgreater cost, longer length of hospital stays or institutionalization, more frequent dischargeto long-term care facilities, additional complications aside from POD, poor recovery, andmortality8,19,26). Although reversible in nature, POD precedes with some cognitive deficitsremaining for up to months after surgery, particularly in the elderly4,21). The main differencesbetween POD and dementia are the potential for reversibility, length of morbidity, and �Received：January 7, 2008 presence of an initiating event. For this reason, clinicians sometimes encounter unexpectedly �Accepted：March 18, 2008 intriguing situations, if uninformed or unprepared prior to the surgical intervention. Therefore, �Address for reprints： Hyeong-Joong Yi, M.D.
prevention and early cognition of POD are most important. Department of Neurosurgery However, it is little known about the incidence of POD and risk factors in populations with Hanyang University Medical Center neurosurgical illness, regardless of the specific disease category including brain, spine or Haengdang-dong, Seongdong-guSeoul 133-792, Korea peripheral nervous system. Moreover, as the population becomes older as a whole, the incidence of POD is also likely to increase accordingly, as proven by previous literature1,4). In this study, we investigated the real incidence and risk factors of POD in elderly neurosurgical patients.
J Korean Neurosurg Soc 43｜March 2008
MATERIALS AND METHODS
with or without diabetes7,19,22). Operative factors includedlocation of surgery (brain, spine, or peripheral nervous system), type of surgery (emergency vs. elective), type of In this retrospective study, we collected pertinent demo- anesthesia (general vs. local, neuroleptic or regional) and graphic and laboratory data of patients who had been duration of surgical procedures. Types of brain surgery were admitted to the neurosurgical department for operative further subdivided by traumatic, cerebrovascular, neoplastic, procedures during 2 consecutive years between November and others. Those of spine surgery were categorized by 2004 and October 2006. During the study period, a total of degenerative, traumatic, and others. Types of surgery were 1762 consecutive patients were admitted and underwent divided according whether they were performed at working surgical procedures. Among these, 292 patients were older time (8 A.M. to 6 P.M.) or not. The types of anesthesia than 70 years at the time of surgery, and 68 patients were were divided as followings : general endotracheal endocircle excluded for the following reasons : moribund state or semiclosed anesthesia attended by anesthesiologists; local decreased consciousness upon admission or surgery not infiltration of lidocaine conducted by neurosurgeons aided amenable to command order; incomplete data gathering by midazolam, benzodiazepine and other parenteral analgesics due to in-hospital death, and lost follow-up due to discharge injection; neuroleptic anesthesia with intravenous propofol, to recuperating facilities. In total, 224 patients were enrolled midazolam and fentanyl conducted by anesthesiologists, and regional nerve blockade conducted by anesthesiologists2,20).
For patients with acute postoperative cognitive impairment, Postoperative factors were mainly related to pain and its detected either by caregivers or medical personnel, we management such as the time spent in the recovery room, immediately obtained radiographic images of the brain, either postoperative pain measured by a 10-cm visual analogue by computed tomogram (CT) or magnetic resonance scale (VAS), and narcotic usage to control pain18,23).
imaging (MRI), to exclude the possibility of an organiclesion. For the patients without an organic brain lesion, resident physicians and attending nurses measured the Univariate comparisons for categorical variables and cognitive status using the mini-mental status examination continuous variables were performed using χ2-tests and (Korean version (MMSE))6) and the confusion assessment Student's t-tests, respectively. Continuous variables were also method (CAM) score12) on postoperative day 1, 2, and 3.
dichotomized according to their respective mean values; pre- Each interviewer had previously been trained on the interview existent co-morbidities (2.4), duration of surgery (3.2 hr), contents and had a uniform structural written checklist. The recovery room stay (90 min), VAS score (6.8). Multivariate interviewers conducted daily interviews with the patients association was conducted using the backward regression and completed the checklist form as well as medical records method with factors having univariate significance. In doing denoting the mental state as "agitated", "confused", "diso- so, we analyzed the association between potential risk factors riented", "delirious", "unable to sleep", or "looks something and the emergence of POD. Finally, we assessed the relative weird". POD was confirmed when the recorded MMSE risk (odds ratio : OR) and corresponding 95% confidence score was less than 23 points or relevant features were eminent interval (CI) for each risk factor. We also assessed the in the CAM score (1. acute onset and fluctuating course discriminative power of the last multivariate test using the of cognitive and behavioral impairment, 2. inattention or area under the curve for the respective receiver operating distractibility, 3. disorganized thinking, 4. altered level of characteristic curve10). An area under the curve generally consciousness; the test was positive if both of the first two ranges from 0.5 (no discriminative power) to 1.0 (perfect features were present or if 1 and either 3 or 4 were present).
prediction). Statistical significance was considered if the pvalue was less than 0.05.
Assessment of risk factors
We selected various known risk factors to verify their applicability to our cohort. Preoperative factors included male,older age (＞65 years), patients already suffering dementia For the patients included in our study, the mean age (SD) or delirium regardless of underlying conditions, history of was 70.5±4.26 years (range 65 to 89 years) and 55.5% were alcohol abuse (＞10 yr), abnormal serum level of sodium male (n=123). Among 224 patients, 48 showed evidence (＜130 or ＞150 mmol/L), potassium (＜3.0 or ＞6.0 of POD (21.4%) by postoperative day 3 (Table 1). POD mmol/L), and glucose (fasting ＜60 or postprandial 2hr appeared on postoperative day 1 in 35 patients (72.9%), on ＞300 mg/dL), and co-morbidities of more than 2 diseases postoperative day 2 in 11 patients, and on postoperative day Postoperative Delirium in Geriatric Patients｜YS Oh, et al.
Table 1. Clinical summary of elderly patients undergoing neurosurgical
Table 2. Results of univariate risk factors for POD*
operation (n=224)* Odds ratio (95% CI) Preoperative factor Preoperative factor Alcohol abuse (+) Abnormal serum sodium Alcohol abuse (+) Abnormal serum potassium Abnormal serum sodium Abnormal serum glucose Abnormal serum potassium Pre-existent co-morbidities (≥2.4) 0.085 Abnormal serum glucose Pre-existent diabetes (+) Pre-existent co-morbidities (≥2.4) 87 Brain/spine/PNS surgery Traumatic brain injury Emergency surgery General/local anesthesia Duration of surgery (≥3.2 hr) Duration of surgery (≥3.2 hr) Postoperative factor Postoperative factor Recovery room stay (≥90 min) Recovery room stay (≥90 min) VAS score (>6.8) VAS score (>6.8) Analgesic usage (+) *POD : postoperative delirium, CI : confidence interval, abnormal serum *POD : postoperative delirium, abnormal serum sodium : Na<130 or >150 sodium : Na<130 or >150 mmol/L, abnormal serum potassium : K<3.0 mmol/L, abnormal serum potassium, : K<3.0 or >6.0 mmol/L, abnormal or >6.0 mmol/L, abnormal serum glucose : fasting blood sugar <60 or serum glucose : fasting blood sugar <60 or blood sugar 2 hr postprandial blood sugar 2 hr postprandial>300 mg/dL, VAS : 10-cm visual analogue >300 mg/dL, PNS : peripheral nervous system, VAS : 10-cm visual analogue scale, analgesic usage : narcotic usage to control postoperative pain.
scale, analgesic usage : narcotic usage to control postoperative pain �Statistically significant, by χ2 tests and Student's t-tests 3 in 2 patients. Except 26 patients with preoperative dementia the type of operation being performed under local anesthesia or delirium, all 22 POD patients showed recovery until the (95% CI OR, 1.34-3.47), and severe postoperative pain 8th postoperative week; 17 patients (77.3%) recovered either requiring opioid analgesics (95% CI OR, 1.45-4.16, and spontaneously (n=12) or with conventional haloperidol/ 1.06-2.14, respectively) were independent risk factors of gabapentin medication (n=5) until postoperative day 14.
POD, irrespective of the patients' neurosurgical diagnoses Donepezil HCl (Aricept; Eisai Co, Japan) was empirically (Table 3). The area under the curve was 0.72 (OR, 0.64-0.81).
prescribed (5 mg to 10 mg), once a day, to 5 patients whoshowed POD beyond postoperative day 1425). Of the 5 patients with persistent POD, 2 recovered by postoperativeday 28, and 3 patients recovered by post-operative day 56.
Because the presentation of POD varies and can often be Of twenty-six patients with preoperative dementia or delirium, vague and multifaceted in a majority of cases, only a high postoperative recovery was found only in 6 patients during Table 3. Results of multivariate risk factors for POD*
hospitalization, ranges from 25 days to 251 days. Odds ratio 95% CI Univariate analyses showed that postoperative occurrence of 289.2-852.4 <0.0001 POD correlated with factors such as previous dementia or Abnormal preoperative delirium (p＜0.0001), abnormal serum glucose level (p=0.020), serum glucose (+) pre-existent diabetes (p=0.017), operation performed under Pre-existent diabetes (+) a local or regional anesthesia (p=0.012), longer operation Local or regional anesthesia (+) time (＞3.2 hr) (p=0.021), severe pain score (VAS＞6.8) Duration of surgery (≥3.2 hr) (p=0.005), postoperative usage of narcotic analgesics Recovery room stay (≥90 min) (+) (p=0.040), and longer stay in the recovery room (＞90 min) VAS score (> 6.8) (+) (p=0.035; Table 2). Analgesics usage (+) *POD : postoperative delirium, CI : confidence interval, abnormal serum Multivariate analyses using the backward regression method glucose : fasting blood sugar <60 or blood sugar 2hr postprandial >300 revealed that previous dementia or delirium (95% CI OR, mg/dL, VAS : 10-cm visual analogue scale, analgesic usage : narcoticusage to control postoperative pain. �Statistically significant, by multivariate 289.2-852.4), pre-existent diabetes (95% CI OR, 1.17-2.45), analysis using backward regression method J Korean Neurosurg Soc 43｜March 2008
index of suspicion makes the patient approach, diagnosis, in our study were similar to those identified in previous and ongoing management amenable. If patients already reports1-4,7,13-18,27). Surprisingly, we could not obtain any have dementia or delirium preoperatively, occurrence of significant relationship between brain surgery and POD, POD is very likely and moreover, recovery from POD is also regardless of disease category or surgery, such as performed very unlikely to happen irrespective of treatment provided.
on microscope or by naked-eye. The incidence of POD Once POD is strongly suspected, swift initial action should was not different between patients who underwent surgery be attempted either by close patient interview with psychiatric on the brain and spine diseases. Our findings reaffirm the tools (MMSE, CAM, etc), radiographic images (CT, MRI), predominant role of systemic, extracerebral factors on the or by any other method to confirm POD or to rule out occurrence of POD.
the presence of an organic brain lesion. One major findingin this study was that we were able to reduce the incidence of Pathophysiology and treatment of POD
POD by identifying at-risk patients earlier in the preoperative As for the pathophysiology of POD, reversible neuronal period and by managing blood sugar levels, pain, and anxiety dysfunction is likely the cause, following toxic or metabolic during the perioperative period, albeit only to limited extent.
disturbances. Systemic inflammatory response and adhesion, Effective control of postoperative pain plays the most crucial activation and degranulation of some vasoactive substances role in reducing POD, and this finding is compatible with and the consequent development of perivascular edema, result that of previous reports, although we did not provide details from the interaction between leukocytes and endothelial on the methods of analgesia9,18).
cells. This reversible edema presents as a conduction disabilityof the nerve and decreased cerebral perfusion in certain Incidence and risk factors of POD
brain areas. Acetylcholine also seems to play a crucial role The incidence of POD varies between 5.1% and 52.5% in the development of POD due to its various roles in the in elderly patients undergoing major surgery, and certain regulation of cerebral functions, including motor activity, procedures such as hip fracture or aortic surgery having higher rapid eye movement (REM) sleep, mood, attention, and risk of POD4,5,7,8,21,22,27). Because there has been practically memory. Thus, the lack of acetylcholine or relative excess no neurosurgical literature on the incidence of POD, we of dopaminergic transmission seems to be connected to could not compare the 21.4% incidence in our study with the development of POD. The age-dependent decrease of that from similar studies. We could only assume that the acetylcholine transmission is a physiologic process, and incidence was not much higher than expected. Several reduced "cholinergic reserve" may be responsible for the contributing factors such as exclusion of a certain percentage significantly higher incidence of POD among geriatric of decreased consciousness due to brain lesions and in- patients8,11,16). These findings normally do not appear on hospital mortality could result in a lower incidence. Unless conventional radiographic images as organic brain lesions, these factors had been excluded, the incidence would have since only sophisticated targeted images can display such been increased further more. For patients with preoperative tiny chemical abnormalities. delirium or dementia, the assessment of new onset POD The primary treatment of delirium involves focusing on the was not easy and straightforward, but the literature strongly underlying cause and factors, but severe behavioral, environ- supported this association4,19,21,27). Persistence, alteration or mental, and psychiatric symptoms also require treatment.
aggravation of prior symptoms might be culprits to suspect If non-pharmacological interventions are ineffective, psych- POD. With strong suspicion, close attention and cautious otropic medication may be needed. Neuroleptics such as patient monitoring, prompt detection can be achieved. haloperidol or droperidol, and benzodiazepine are generally With regard to length of time for POD emergence, the employed to control symptoms like agitation, restlessness, and findings of our study are comparable with those of previous altered perception. Vitamins may be useful for alcoholics reports. In our cohort, 72.9% of patients exhibited POD and melatonin has been suggested to prevent and treat on postoperative day 1, 22.9% on postoperative day 2, and delirium by normalizing alterations in the sleep-wake cycle.
the remainder on postoperative day 3. POD usually occurs by Physostigmine and metrifonate are also considered break- the third postoperative day and becomes worse at night4,18,23).
through pharmaceuticals for treating behavioral problems This fact suggests that intensive postoperative management associated with POD by ameliorating cholinesterase activity4,9).
of pain, blood sugar levels, and patient discomfort should Successful use of donepezil, an effective regimen against be conducted as soon as the patient leaves the operating dementia that lowers serum anticholinergic activity, has room and should be sustained until at least postoperative been recently reported in a delirious patient19). Most POD day 3. The factors associated with the development of POD patients improve spontaneously or with medical treatment Postoperative Delirium in Geriatric Patients｜YS Oh, et al.
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