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Anesth Analg 2002;94:1628-1632
© 2002 International Anesthesia Research Society

GENERAL ARTICLES

Preoperative Factors Associated with Postoperative Change in Confusion Assessment Method Score in Hip Fracture Patients

Khwaja J. Zakriya, MD*, Colleen Christmas, MD{dagger}, James F. Wenz, Sr, MD{ddagger}, Shawn Franckowiak, BS{dagger}, Ross Anderson, PhD{dagger}, and Frederick E. Sieber, MD*

*Department of Anesthesiology, {dagger}School of Medicine, Division of Geriatrics and Gerontology, and {ddagger}Department of Orthopedics, Johns Hopkins Medical Institutions, Baltimore, Maryland

Address correspondence and reprint requests to Khwaja J. Zakriya, MD, Department of Anesthesiology, Johns Hopkins Bayview Medical Center, 4940 Eastern Ave., Baltimore, MD 21224. Address e-mail to kzakriya{at}jhmi.edu


   Abstract
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 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Postoperative delirium is a major problem in elderly patients undergoing surgical repair of hip fracture. It is imperative to identify potentially treatable preoperative factors associated with the onset of postoperative delirium to optimize outcome. We sought to determine what preoperative variables are associated with postoperative delirium in geriatric patients undergoing surgical repair of hip fracture. In a prospective, IRB-approved study, patients admitted to the geriatric hip fracture service were examined daily in the hospital for the occurrence of postoperative delirium. All patients with a preoperative diagnosis of dementia or delirium were eliminated. A positive confusion assessment method score ([+]CAM) was used to determine the presence of postoperative delirium during the acute hospital stay. To determine the association between preoperative variables (demographics, laboratory values, and comorbidities) and postoperative (+)CAM scores, {chi}2 and logistic regression analysis were performed with calculation for the odds ratios (OR). One-hundred-sixty-eight patients (72% women) were included in the analysis. Twenty-eight percent (n = 47) of patients had a (+)CAM score. Three variables were significant predictors of a (+)CAM score: (a) normal white blood cell count (OR, 2.2), (b) abnormal serum sodium (OR, 2.4); and (c) ASA physical status >II (OR, 11.3). The results suggest that preoperative medical conditions (abnormal serum sodium and ASA physical status >II) and an inability to mount a stress response (normal white blood cell count) may influence the patient’s postoperative mental status. In particular, two of the risk factors we identified may be amenable to therapy and are abnormal serum sodium and lack of an increase in white blood cell count during the stress of trauma and surgery.

IMPLICATIONS: This prospective study investigated preoperative variables that are predictive of postoperative delirium in geriatric patients undergoing surgical repair of hip fracture. The results suggest that the patient’s preoperative medical condition and inability to mount a stress response influence postoperative delirium.


   Introduction
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 Abstract
 Introduction
Methods
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 Discussion
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Delirium (acute confusional state) is defined as an acute disorder of attention and cognition (1). Postoperative delirium in hip fracture patients has a reported incidence of 28%–50% (2,3). Delirium has negative effects such as delaying postoperative mobilization, prolonging treatment on the ward, and preventing early rehabilitation (4,5).

Previous studies of postoperative delirium examined coronary artery bypass or mixed surgical populations (6,7). However, these study designs make it difficult to identify and interpret how preoperative factors are associated with neurologic dysfunction. First, the physiologic trespass that occurs with extracorporeal circulation is significant and has its own effects on neurologic function. Second, mixed populations of surgical procedures have different degrees of physiologic derangement. This makes the identification of preoperative factors associated with delirium more difficult. The current study investigates preoperative factors associated with delirium in a homogeneous surgical population (hip fracture). In addition, the surgical procedure is less traumatic than those involving extracorporeal circulation or major vascular/ thoracic surgery yet is highly associated with the development of postoperative delirium.

It is hoped that identification of preoperative factors associated with delirium will assist both the geriatrician and anesthesiologist in optimizing perioperative care. With this in mind, we sought to determine what preoperative variables (possibly amenable to therapy) are predictive of postoperative delirium in patients undergoing hip fracture repair.


   Methods
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 Abstract
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Results
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The IRB of Johns Hopkins Bayview Medical Center (JHBMC) approved this study, and written informed consent was obtained from all study participants. At JHBMC, a hip fracture service operates as a multidisciplinary team consisting of members from the geriatric, orthopedic, anesthesia, and rehabilitation services. Two-hundred-thirteen consecutive patients admitted to the hip fracture service were prospectively studied from March 1999 until December 2000.

We sought to determine what preoperative variables are predictive of postoperative delirium. The variables analyzed included demographics, ASA physical status, comorbid disease, and routine admission laboratory values.

The presence of postoperative delirium was defined by the use of the confusion assessment method (CAM) score (1). However, the CAM score does not provide information concerning the severity of the delirium. The CAM score is determined by examining the patient for (a) acute and fluctuating changes in mental status, (b) inattention, (c) disorganized or incoherent thinking, and (d) altered level of consciousness. A CAM score is considered to be positive ([+]CAM) if the patient displays a, b, and c, or a, b, and d, or a, b, c, and d. A patient was considered to have a (+)CAM score if these criteria were fulfilled by postoperative examination of the attending geriatrician. The postoperative time period of interest included 24 h after surgery until hospital discharge. The CAM score determination was performed each day during the mid-morning. To define risk factors that precede the development of delirium, prevalent cases of delirium occurring on admission were eliminated, and only postoperative incident cases were included. Preexisting dementia is a major predictor of postoperative delirium (2,7) but is not remediable; therefore, individuals with an admission diagnosis of dementia or delirium (n = 45) were eliminated from the study.

To test for the association of preoperative variables with delirium, we used a two-step process. First, we tested each preoperative variable independently with {chi}2 analysis using (+) or (-)CAM scores as the grouping variable. Second, those variables with P <= 0.1 from {chi}2 analysis were entered in a multiple logistic regression model. A cutoff value of P < 0.05 was set to determine significance.

Laboratory values were cataloged as normal or abnormal using the normal values of the clinical laboratory at JHBMC. Specifically, these normal ranges are: white blood cell count (4500–11,000 cells x 109/L), hematocrit (36%–46%), serum sodium (135–148 mEq/L), serum creatinine (0.5–1.2 mg/dL), blood urea nitrogen (7–22 mg/dL), and serum albumin (3.5–5.3 g/dL).


   Results
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Discussion
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After eliminating those patients with an admission diagnosis of dementia or delirium, 168 patients were included in the analysis. Twenty-eight percent (n = 47) of these patients had a (+)CAM score. The demographics of the patient population are shown in Table 1. Age was similar in both groups (79 ± 1 yr and 77 ± 1 yr in the [+]CAM and [-]CAM groups, respectively).


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  		Table 1. Patient Demographics (%)
 
Table 2 shows the results of univariate analysis ({chi}2) of preoperative variables. Comorbidities with a P <= 0.1 that were included in the multiple logistic regression model consisted of patients with ASA physical status >II, history of congestive heart failure, history of atrial fibrillation, and history of peripheral vascular disease. Preoperative laboratory values with a P <= 0.1 that were included in the multiple logistic regression model consisted of normal white blood cell count and abnormal serum sodium concentration.


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  		Table 2. Association of Preoperative Variable with (+)CAM by Univariate Analysis ({chi}2)
 
Logistic regression analysis of preoperative variables demonstrating an association with a (+)CAM score is shown in Table 3. Three variables were significant predictors of a (+)CAM score. These included normal white blood cell count, abnormal serum sodium, and ASA physical status >II.


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  		Table 3. Logistic Regression Analysis of Variables Independently Associated with (+)CAM
 

   Discussion
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 Methods
 Results
 Discussion
References
 
This study shows that the preoperative predictors of (+)CAM scores in patients undergoing hip fracture repair are normal white blood cell count, abnormal serum sodium, and ASA physical status >II. The results suggest that preoperative medical conditions (abnormal serum sodium and ASA physical status >II) and an inability to mount a stress response (normal white blood cell count) may influence the patient’s postoperative mental status.

Acute confusion in the elderly occurs in 15%–25% of hospitalized patients (8–10). Variables that have been associated with acute confusional states in the hospitalized elderly include dementia, alcoholism, severe medical illness, vision impairment, and depression (8,10,11). Predictors of postoperative delirium in cardiac surgery patients include old age, small level of albumin, poor physical condition, and alterations in serum amino acids (12,13). In addition, there may be a component of brain injury, as evidenced by increases in serum markers of acute brain injury (protein S-100ß and neuron-specific enolase) (6). Predictors of postoperative delirium in the noncardiac surgical population include age >70 years, history of alcohol abuse, cognitive impairment, poor physical function, markedly abnormal preoperative sodium, potassium, or glucose laboratory values, and aortic or thoracic surgery (7). Niermann and Zakrewski (14) echo these same risk factors as well as comorbidity, drugs with anticholinergic effects, male sex, and visual or hearing impairment. Types of anesthesia (regional versus general) and intraoperative hemodynamic complications have not been associated with delirium (15,16). However, delirium has been associated with greater intraoperative blood loss, more postoperative blood transfusions, and postoperative hematocrit <30% (15). These data suggest that occult hypoxemia may play an important role as a mechanism of postoperative delirium in the elderly (17,18). However, other large multicenter studies have not found hypoxemia to be a significant risk factor for postoperative cognitive dysfunction (19). It is unclear whether brain injury is an important mechanism of postoperative delirium in the noncardiac surgical patient. Blood concentrations of protein S-100ß increase after abdominal surgery and seem to be related to postoperative delirium (20). Of importance to the current study, one series has shown that cerebral microemboli do occur during total hip arthroplasty (21). Our study focused on preoperative predictors of delirium; therefore, we cannot assess mechanisms of delirium from our data.

The recognition and treatment of any variables that predispose a patient to delirium are important. Postoperative delirium in hip fracture patients has a reported incidence of 28%–50% (2,3). In studies specific to hip fracture, delirium is associated with advanced age, cognitive and functional impairment, comorbid conditions, and institutionalization (22). The incidence of delirium in our study (28%) was in the lower range in comparison with previous reports. This result may be secondary to the elimination of patients with preexisting dementia from the analysis. The current study agrees with other studies that suggest that the preoperative comorbid state is a primary determinant of development of delirium.

The fact that no relationship with age was found may be secondary to the population studied (age range, 50–98 years in [-]CAM group and age range, 51–91 years in [+]CAM group). Alternatively, at our institution, the hip fracture service operates as a multidisciplinary team consisting of members from the geriatric, orthopedic, anesthesia, and rehabilitation medicine specialties. Some risk factors may be modifiable, as demonstrated by studies showing that geriatric programs reduce the incidence of delirium in hip fracture patients (3,23). A normal white blood cell count was predictive of postoperative delirium. Leukocytosis has been weakly associated with the development of delirium in hospitalized patients (11). Catecholamine-induced leukocytosis has been demonstrated in numerous clinical studies (24). However, the current study did not meascure blood catecholamine levels. Thus, the possibility of an altered leukocyte response to catecholamines in those patients with postoperative delirium remains speculative.

Studies clearly show that delirium in the hip fracture population is an important predictor of poor long-term outcome even in patients without previous cognitive impairment (22,25). Patients who develop delirium have increased rates of major complications and more frequent discharge to long-term care or rehabilitative facilities (7). We are currently investigating outcomes related to delirium in this population.

The strength of this study is that it is prospective, examines a homogeneous surgical population in which the confounding variable of preexisting dementia has been eliminated, and distinguishes between prevalent cases of delirium at admission and postoperative incident cases. In this manner, we were better able to determine predictors of postoperative delirium. The weaknesses of the study are that we may have excluded or overlooked important variables in our analysis and that we were unable to distinguish the severity or duration of delirium related to these factors. In addition, the CAM score served as our sole means of detecting the presence of delirium. Other investigators have used tests in addition to the CAM score to provide a more refined approach to the diagnosis of delirium (3,26).

In summary, after eliminating patients exhibiting preoperative delirium or dementia, this study determined the preoperative variables that are predictive of delirium after hip fracture repair. The best predictors of delirium concern the patient’s preoperative medical condition. It is hoped that identification of preoperative factors associated with delirium will help in optimizing perioperative care. The results underscore the need for further studies to determine the effect of optimizing preoperative medical conditions on the incidence of postoperative delirium. In particular, two of the risk factors we identified may be amenable to therapy and are abnormal serum sodium and normal white blood cell count. Further intervention studies are warranted to investigate whether modification of sodium, blood count, or both alters the incidence of postoperative delirium.


   Acknowledgments
 
Supported, in part, by John A. Hartford Foundation grant #97214-G and the Johns Hopkins Geriatrics/Nursing Fund.

The authors would like to thank Kim Sigai for her expert preparation of this manuscript.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication January 28, 2002.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press