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Anesth Analg 2001;93:1489-1494
© 2001 International Anesthesia Research Society

ANESTHETIC PHARMACOLOGY

The Recovery of Cognitive Function After General Anesthesia in Elderly Patients: A Comparison of Desflurane and Sevoflurane

Xiaoguang Chen, MD*, Manxu Zhao, MD*, Paul F. White, PhD MD, FANZCA*, Shitong Li, MD*, Jun Tang, MD*, Ronald H. Wender, MD{dagger}, Alexander Sloninsky, MD{dagger}, Robert Naruse, MD{dagger}, Robert Kariger, MD{dagger}, Tom Webb, MD{dagger}, and Eve Norel, MD{dagger}

*Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, Texas; and {dagger}Department of Anesthesiology, Cedars-Sinai Medical Center, Los Angeles, California

Address all correspondence to Dr. Paul F. White, Professor and McDermott Chair of Anesthesiology, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, F2.208, Dallas, Texas 75390-9068. Address e-mail to paul.white{at}utsouthwestern.edu


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
We evaluated the cognitive recovery profiles in elderly patients after general anesthesia with desflurane or sevoflurane. After IRB approval, 70 ASA physical status I–III consenting elderly patients (>=65 yr old) undergoing total knee or hip replacement procedures were randomly assigned to one of two general anesthetic groups. Propofol and fentanyl were administered for induction of anesthesia, followed by either desflurane 2%–4% or sevoflurane 1%–1.5% with nitrous oxide 65% in oxygen. The desflurane (2.5 ± 0.6 MAC · h) and sevoflurane (2.7 ± 0.5 MAC · h) concentrations were adjusted to maintain comparable depths of hypnosis using the electroencephalogram bispectral index monitor. The Mini-Mental State (MMS) test was used to assess cognitive function preoperatively and postoperatively at 1, 3, 6, and 24-h intervals. The use of desflurane was associated with a more rapid emergence from anesthesia (6.3 ± 2.4 min versus 8.0 ± 2.8 min) and a shorter length of stay in the postanesthesia care unit (213 ± 66 min versus 241 ± 87 min). However, there were no significant differences between the Desflurane and the Sevoflurane groups when the MMS scores were compared preoperatively, and postoperatively at 1, 3, 6, and 24 h. Compared with the preoperative (baseline) MMS scores, the values were significantly decreased at 1 h postoperatively (27.8 ± 1.7 versus 29.5 ± 0.5 in the Desflurane group, and 27.4 ± 1.7 versus 29.2 ± 1.0 in the Sevoflurane group, respectively). However, the MMS scores returned to preoperative baseline levels within 6 h after surgery. At 1 h and 3 h after surgery, 51% and 11% (versus 57% and 9%) of patients in the Desflurane (versus Sevoflurane) Group experienced cognitive impairment. In conclusion, desflurane is associated with a faster early recovery than sevoflurane after general anesthesia in elderly patients. However, recovery of cognitive function was similar after desflurane and sevoflurane-based anesthesia.

IMPLICATIONS: Desflurane was associated with a faster early recovery than sevoflurane after general anesthesia in elderly patients. However, recovery of cognitive function was similar with both volatile anesthetics.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Cognitive impairment (e.g., delirium, confusion) is a significant problem in elderly patients during the early postoperative period (1). The incidence of transient postoperative neurologic impairment can be as frequent as 44%–61% in elderly patients undergoing orthopedic surgery (2,3). The occurrence of postoperative delirium in the elderly can result in increased morbidity, delayed functional recovery, and a prolonged hospital stay. The use of volatile anesthetics that are rapidly eliminated with minimal metabolic breakdown may reduce postoperative delirium and cognitive dysfunction in elderly surgical patients by facilitating a faster recovery from general anesthesia. The availability of volatile anesthetics with low blood-gas partition coefficients (e.g., sevoflurane [0.69] and desflurane [0.42]) (4,5) should also provide for shorter emergence times compared with traditional inhaled anesthetics (6–8). Thus, the use of shorter-acting anesthetic and analgesic drugs may contribute to less postoperative cognitive impairment and confusion in elderly patients (9,10).

Even though both desflurane and sevoflurane are widely used in clinical practice, there is no study directly comparing these drugs in elderly patients with respect to postoperative cognitive recovery. Therefore, we designed this randomized, double-blinded study to determine the speed of recovery, as well as the incidence and duration of cognitive impairment in elderly patients undergoing total knee or hip replacement procedures under general anesthesia with a sevoflurane or desflurane-based technique.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
After obtaining approval from the IRB at Cedars-Sinai Medical Center in Los Angeles and written, informed consent, 70 ASA physical status I–III patients over 65 yr of age (range from 66 to 86 yr; median age, 74 yr) undergoing total knee or hip replacement procedures were enrolled in this study. Patients were randomly assigned to one of two standardized general anesthetic groups using a computer-generated random number table. All patients were anesthetized by the same group (n = 6) of private practice anesthesiologists. Patients with clinically significant cardiovascular, respiratory, hepatic, renal, neurological, psychiatric, metabolic disease, or weighing >50% above ideal body weight were excluded from participating in this study. Those who had undergone a general anesthesia within the previous seven days were also excluded. All patients were asked to provide detailed medical histories and demographic information, including alcohol and drug consumption, as well as any history of neuropsychiatric disorders.

In the preoperative holding area, patients completed baseline visual analog scales (VAS) for sedation, fatigue, discomfort, pain and nausea using 100-mm scales (0 = none, 100 = maximum), as well as the Mini-Mental State (MMS) test (11). The MMS is a screening test that quantitatively assesses cognitive impairment by asking patients a variety of questions. The maximum MMS score is 30 points, with scores of 23 or less being indicative of cognitive impairment. The criterion used to define a decline in cognitive function was a decrease of 2 or more points on the MMS test (12).

All patients received midazolam 1 mg IV for preoperative medication. On arrival in the operating room, routine monitoring devices were placed, including an electroencephalogram (EEG) Bispectral index (BIS) monitor (A-2000; Aspect Medical Systems, Natick, MA). Baseline mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SpO2) values were recorded over a 2–3 min interval before induction of anesthesia. Subsequently, MAP, HR, SpO2, and end-tidal (ET) concentrations of nitrous oxide (N2O) and the volatile anesthetics were recorded every 1–2 min after induction for 15 min and then every 5 min from skin incision until the end of anesthesia. Volatile anesthetic concentrations were determined using an infrared gas analyzer (Criticare Poet IQ; Criticare Systems Inc., Waukesha, WI).

Anesthesia was induced with fentanyl, 1.0–1.5 µg/kg IV, and propofol, 1.0–2.0 mg/kg IV. Tracheal intubation was facilitated with succinylcholine, 1 mg/kg IV. Anesthesia was maintained with desflurane 2–4% ET or sevoflurane 1.0–1.5% ET in combination with N2O 65% in oxygen. Supplemental doses of fentanyl, 0.5–1.0 µg/kg IV (to maximum dose of 250 µg), and cisatracurium, 4–6 mg IV, were administered during the maintenance period. The initial inspired concentration of desflurane and sevoflurane were adjusted to achieve an ET concentration of 1.1 minimum alveolar anesthetic concentration (MAC) with both volatile anesthetics, and subsequently adjusted to maintain the EEG BIS value in the range of 55–65 and the MAP value within 20% of the patient’s baseline value. During the maintenance period, ventilation was controlled to maintain normocarbia using a semiclosed circle system with a total fresh gas flow rate of 3 L/min.

At the end of surgery, residual neuromuscular blockade was reversed using glycopyrrolate, 0.01 mg/kg IV, and neostigmine, 0.05 mg/kg IV, if the patient failed to maintain a sustained contraction in response to a tetantic electrical stimulus applied at the wrist. Sevoflurane or desflurane was discontinued at the start of skin closure, and N2O was discontinued at the end of surgery. The lungs were ventilated with 100% O2 at a fresh gas flow rate of 10 L/min. The times from discontinuing N2O to eye opening, tracheal extubation, obeying commands (e.g., squeeze the investigator’s hand), as well as the times to orientation to name and date of birth were assessed at 30–60 s intervals. The durations of anesthesia (from the start of induction to discontinuation of N2O) and surgery (from surgical incision to skin closure) were also recorded.

On arrival in the postanesthesia care unit (PACU), a patient-controlled analgesia (PCA) device (Abbott Lifecare PCA II; Abbott Park, IL) was connected to the patient’s IV catheter, and PCA therapy was initiated when the patient was sufficiently alert to understand how to operate the device. The PCA device was programmed to deliver hydromorphone 1 mL (0.2 mg) bolus doses, with a minimum lockout interval of 10 min. At 1, 3, 6, and 24 h after the end of anesthesia, an investigator who was unaware of the anesthetic group to which the patient was assigned evaluated the patient’s quality of recovery by asking them to repeat the MMS and VAS for sedation, fatigue, discomfort, pain, and nausea. The testing intervals were determined based on previous experience in a pilot study evaluating the ability of elderly patients to complete these assessment tools in the early postoperative period. Adverse side effects (e.g., dizziness, headache, drowsiness/sedation, and anxiety/restlessness) were recorded at the same time intervals. The length of the PACU stay, total amount of hydromorphone, and other medication administered within the 24-h postoperative study period were recorded. At 24 h after anesthesia, the patient’s satisfaction with their anesthetic experience was assessed by a blinded observer using a 4-point verbal rating scale with 0 = poor, 1 = fair, 2 = satisfied, and 3 = very satisfied.

A sample size of 35 was determined by using a power analysis based on the assumptions that a) the incidence of postoperative cognitive impairment at 1 h after anesthesia would be 50% (2,3), b) a 70% reduction (from 50% to 15%) would be of clinical significance, and c) {alpha} = 0.05, ß = 0.2. Student’s t-test was performed for continuous variables, and paired Student’s t-test was used to compare the intragroup differences in the MMS scores at different assessment points with their baseline values. Categorical data were analyzed by {chi}2 test or Fisher’s exact test, as appropriate. All tests were two-sided and a value of P < 0.05 was considered statistically significant. Data are presented as mean values ± SD, numbers or percentages.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
The two anesthetic groups were comparable with respect to demographic variables and durations of anesthesia and surgery, as well as doses of medications used for premedication, induction, and maintenance of anesthesia, and reversal of muscle relaxation (Table 1). Most importantly, equi-MAC hours of desflurane and sevoflurane were administered in both groups. In addition, there were no significant differences in the amounts of postoperative analgesic or antiemetic medications administered to the two study groups.


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  		Table 1. Patient Demographic Characteristics and Drug Requirements in the Two Anesthetic Groups
 
At the end of anesthesia, the mean ET concentrations of desflurane and sevoflurane were 1.52% ± 0.74% and 0.51% ± 0.31%, respectively. The emergence times from the end of anesthesia to eye opening, tracheal extubation, following verbal commands, and orientation were significantly shorter in the Desflurane (versus Sevoflurane) Group (Table 2). Although the duration of PACU stay was shorter in the Desflurane group (versus Sevoflurane), it failed to achieve statistical significance (P = 0.134) (Table 2).


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  		Table 2. Emergence and Intermediate Recovery Times After Discontinuation of Maintenance Anesthetics in the Two Anesthetic Groups
 
When compared with the preoperative baseline MMS values, the mean MMS scores were significantly decreased at 1 h postoperatively in both groups (27.8 ± 1.7 versus 29.5 ± 0.5 in the Desflurane and 27.4 ± 1.7 versus 29.2 ± 1.0 in the Sevoflurane group). Over 85% of the patients in both groups had returned to their preoperative baseline levels at 3 h postoperatively. At 24 h postoperatively, all the patients (except one in the Sevoflurane group) had returned to their baseline MMS scores. There were no differences between the Desflurane and the Sevoflurane groups with respect to their MMS score preoperatively and at 1, 3, 6, and 24 h postoperatively (Fig. 1).



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  		Figure 1. Perioperative Mini-Mental State (MMS) score in the Desflurane (—{blacklozenge}—) and Sevoflurane (—{blacksquare}—) Groups. Values are mean ± SEM. *P < 0.05 vs baseline values.

 
A total of 18 patients in the Desflurane group (51%) and 20 patients in the Sevoflurane group (57%) experienced significant decreases in cognitive function at 1 h postoperatively. At 3 h postoperatively, there were only 4 patients in the Desflurane group (11%) and 3 patients in the Sevoflurane group (9%) with persistent decreases in their MMS scores. Importantly, 97% of patients in the Desflurane group and 94% in the Sevoflurane group demonstrated completely normal cognitive function at 6 h postoperatively. However, there was one patient in the Sevoflurane group who manifested an abnormal MMS score at 24 h postoperatively (Table 3).


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  		Table 3. Patients with Pre- and Postoperative Cognitive Dysfunction (Abnormal Mini-Mental State Scores), and Degree of Satisfaction with their Anesthesia in the Two Anesthetic Groups
 
No significant differences were found between the two groups with respect to their VAS scores for sedation, fatigue, pain, discomfort, and nausea. Similarly, there were no differences between the two anesthetic groups with respect to postoperative side effects (Table 4). Finally, over 90% of the patients in both groups were highly satisfied with their anesthetic experience and would accept the same anesthetic in the future (Table 3).


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  		Table 4. Side Effects During the 24-h Postoperative Period in the Two Anesthetic Groups
 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Despite advances in surgical and anesthetic techniques, major surgery in the elderly population can still be associated with significant postoperative morbidity and mortality (13). Psychological dysfunction (e.g., postoperative delirium or confusional states) can contribute to postoperative morbidity in the elderly (14). Postoperative cognitive impairment is a condition characterized by impairment of memory and concentration, and the incidence has been reported to be extremely frequent in elderly patients undergoing major surgery. In addition to general anesthesia, patient predisposition, type of surgery, and postoperative factors (e.g., opioid analgesics) can also contribute to the development of cognitive impairment in the elderly.

The pathogenesis of postoperative cognitive dysfunction is unclear; however, age, alcohol abuse, low baseline cognition, hypoxia, hypotension, and type of surgery have been alleged to contribute to this problem (1). The choice of anesthetic drugs can also affect postoperative cognition because residual levels of volatile anesthetics can produce changes in central nervous system activity (15,16). Therefore, the use of anesthetics with a rapid clearance and negligible metabolism may offer advantages in this patient population. The volatile anesthetics desflurane and sevoflurane possess low blood-gas partition coefficients, contributing to a faster early recovery from anesthesia compared with the traditional volatile anesthetics (6–8).

Emergence from anesthesia was more rapid after desflurane compared with sevoflurane in our elderly population, consistent with previous studies involving younger patients (17). Although desflurane offered an advantage over sevoflurane with respect to the early recovery period, the intermediate recovery phase as measured by psychometric testing failed to demonstrate any significant differences between the two volatile anesthetics. These results are also consistent with our earlier findings in younger patients undergoing ambulatory surgery (17).

The clinical tools used to measure cognitive function after anesthesia have not been standardized, and the timing of the measurements has varied widely in earlier studies (5,8,10). Standard psychometric tests used to measure cognitive ability in adults require a considerable amount of time to administer, rendering them impractical in the perioperative period. In addition to the MMS, the Saskatoon Delirium Checklist (18), Digit-Symbol Substitution Test (16), Geriatric Mental State Examination (19), and the Confusion Assessment Method (20) have all been used to evaluate cognitive function in the elderly. These tests assess recovery of consciousness, perception, orientation, coherence, memory, and motor activity. The use of a more sensitive psychological test of cognitive dysfunction might have demonstrated more prolonged impairment of cognitive performance after discontinuing the anesthetics.

In the present study, the MMS was selected because it combined a high validity and reliability with brevity and ease of application (and completion) for elderly patients undergoing surgery with general anesthesia (21). This test concentrates on the cognitive aspect of mental function and excludes questions concerning mood and abnormal mental experiences. The MMS consists of 11 questions that assess orientation to time and place, registration, attention, calculation, short-term recall, language, and constructional ability (e.g., Bender-Gestalt design). The maximum score is 30 points, with scores of <23 indicative of cognitive impairment. According to Anthony et al. (22), the MMS test was 87% sensitive and 82% specific in detecting dementia and delirium. The present study found that 51% of elderly patients in the Desflurane group and 57% in the Sevoflurane group experienced a transient decline (lasting <3 h) in their cognitive function after anesthesia, consistent with previous reports (2,3).

Although postoperative mental dysfunction is well recognized in elderly patients (1–3), the duration of the impairment is controversial (23–28). Edwards et al. (25) found a progressive impairment in mental function from postoperative day 2 through day 7 that was maximal on days 4 and 5. A more recent study using shorter-acting anesthetic drugs found that elderly patients were impaired only on the first postoperative day (26). Interestingly, one published study using highly sensitive testing procedures found that cognitive dysfunction was present in 26% of elderly patients at one week after major noncardiac surgery and in 10% after 3 months (27). In this international multicenter study, increasing age and duration of anesthesia, limited education, a second operation, postoperative infections, and respiratory complications were risk factors for early postoperative cognitive dysfunction. However, only age was a risk factor for late postoperative cognitive dysfunction. In a follow-up study, Abildstrom et al. (28) reported that postoperative cognitive dysfunction was a reversible condition in the majority of cases, but may persist in approximately 1% of elderly patients. Of importance, cognitive dysfunction in the early postoperative period was a significant risk factor for long-term cognitive dysfunction.

Further studies are needed to evaluate the long-term effects of these anesthetics on cognitive function in the elderly. The absence of a significant difference in the two groups does not exclude the possibility that a more sensitive test of cognitive function might demonstrate a difference between the two volatile anesthetics. In addition, increasing the sample size to over 200 patients might have revealed a significant difference between the two anesthetic groups in the MMS scores at one hour postoperatively. However, a difference in the MMS scores between the two anesthetic groups at one hour after surgery is unlikely to be of any clinical significance with respect to facilitating the recovery process in this patient population.

The MAC of desflurane was estimated to be 5.2% in the elderly. However, the desflurane MAC is reduced to 1.7% by the addition of N2O 60% (29). The MAC of sevoflurane in the elderly is reported to be 1.5% (30). In the present study, the averaged ET concentrations of desflurane and sevoflurane were 1.9% and 0.9%, respectively, during the operation, and 1.5% ± 0.7% and 0.5% ± 0.3%, respectively, at the end of anesthesia. Therefore, the patients’ cognitive function recovery profiles were compared after equivalent MAC concentrations of the two volatile anesthetics during the operation and at the end of anesthesia.

In conclusion, desflurane was associated with a faster early recovery than sevoflurane in elderly patients after total knee or hip replacement procedures. However, postoperative recovery of cognitive function was similar with both volatile anesthetics. Most importantly, use of either desflurane or sevoflurane for maintenance of anesthesia in the elderly was associated with only transient cognitive impairment, even after anesthesia lasting 2–3 hours.


   Acknowledgments
 
An educational grant was made to the White Mountain Institute of Los Altos, California (Dr. P. F. White, President) by Baxter PPI, Chicago, Illinois.


   References
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 Introduction
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Accepted for publication August 17, 2001.




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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