Recovery of elderly patients from two or more hours of desflurane or sevoflurane anaesthesia{dagger}

J. E. Heavner1,2, A. D. Kaye1,3, B.-K. Lin1 and T. King1

1 Department of Anesthesiology, 2 Department of Physiology and 3 Department of Pharmacology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA

Corresponding author. E-mail: james.heavner@ttmc.ttuhsc.edu
{dagger}Declaration of interest: This lab has participated in several studies sponsored by Baxter Healthcare, the sponsor of the study reported in this manuscript. Dr Alan Kaye is a paid speaker on Baxter’s speakers bureau.

Accepted for publication: April 29, 2003


    Abstract
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Background. The solubility of desflurane compared with sevoflurane suggests more rapid recovery from desflurane anaesthesia. This could be important after prolonged anaesthesia and fast recovery may be advantageous in the elderly where slow recovery of mental function is a concern. We compared emergence from desflurane vs sevoflurane in elderly patients undergoing two or more hours of anaesthesia.

Methods. Fifty ASA physical status I, II, or III patients, 65 yr of age or older, undergoing anaesthesia expected to last two or more hours were randomly assigned to receive desflurane/nitrous oxide or sevoflurane/nitrous oxide anaesthesia. Patients were given 1–2 µg kg–1 fentanyl i.v. and anaesthesia was induced with propofol 1.5–2.5 mg kg–1 i.v. and maintained with either desflurane 2–6% or sevoflurane 0.6–1.75% with nitrous oxide 65% in oxygen. Inspired anaesthetic concentrations were adjusted to obtain adequate surgical anaesthesia and to maintain mean arterial pressure within 20% of baseline values. Early and intermediate recovery times were recorded. Digit-Symbol Substitution Test (DSST) scores and Visual Analog Scale (VAS) scores for pain and nausea were recorded before pre-medication and every 15 min in the Post Anaesthesia Care Unit (PACU) until patients were discharged.

Results. Early recovery times are given as median, quartiles. The times to extubation (5 (4–9); 9 (5–13) min), eye opening (5 (3–5); 11 (8–16) min), squeezing fingers on command (7 (4–9); 12 (8–17) min); and orientation (7 (5–9); 16 (10–21) min) were significantly less (P<0.05) for desflurane than for sevoflurane. Intermediate recovery, as measured by the DSST and time to ready for discharge from the PACU (56 (35–81); 71 (61–81) min) was similar in the two groups.

Conclusions. Early but not intermediate recovery times of elderly patients undergoing a wide range of surgical procedures requiring two or more hours of anaesthesia is significantly (P<=0.05) faster after desflurane.

Br J Anaesth 2003; 91: 502–6

Keywords: anaesthesia, general; anaesthesia, geriatric; anaesthetics volatile, desflurane; anaesthetics volatile, sevoflurane; recovery


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Sevoflurane and desflurane have pharmacokinetic properties that favour rapid emergence from anaesthesia. Recovery is more rapid after desflurane than after sevoflurane.14 This is a result of differences in blood:gas (0.45 vs 0.65) and fat:blood partition (27 vs 48) coefficients of desflurane vs sevoflurane, respectively.5 The lower partition coefficients of desflurane favour its more rapid elimination from the body. Eger and colleagues4 speculated that additional factors such as effects of degradation products of sevoflurane might delay recovery from sevoflurane after longer anaesthesia. More rapid recovery from prolonged anaesthesia may be an advantage in the elderly in whom cognitive impairment (e.g. delirium, confusion) is a problem during recovery.6 Chen and colleagues7 found that compared with sevoflurane, desflurane gave a faster emergence from anaesthesia and less time in the PACU in elderly patients undergoing total knee or hip replacement. However, recovery of cognitive function, measured by the Mini-Mental State test, was no different between desflurane and sevoflurane. We report results that confirm and extend Chen and colleagues’s7 observations in patients 65 yr of age or older undergoing a wide range of surgical procedures requiring two or more hours of general anaesthesia with desflurane/nitrous oxide or sevoflurane/nitrous oxide.


    Methods
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Fifty male and female patients were studied after approval of the Institutional Review Board for the Protection of Human Subjects and with their written, informed consent. Patients were ASA physical status I, II, or III; 65 yr of age or older; having non-emergency surgery under general anaesthesia, expected to last approximately 2 h. The patients were expected to remain in the hospital for at least 24 h after surgery. The procedures included orthopaedic, abdominal, urogenital, skin graft, eye, lymph node dissection, and breast surgery.

We excluded patients with significant coronary disease or chronic pulmonary disease; renal failure and/or hepatic dysfunction; morbid obesity (body weight >110 kg); a recent (within 12 months) history of alcohol or drug abuse; haematocrit <25%; a personal or family history of malignant hyperthermia; exposure to general anaesthetic agents within the previous 7 days, and if use of nitrous oxide was not appropriate.

Subjects were randomly assigned to receive either desflurane/nitrous oxide (n=25) or sevoflurane/nitrous oxide (n=25). Group assignment was made using computerized randomization. Data were recorded by an observer masked to the anaesthetic allocation. Before pre-medication, subjects were asked to take a Digit-Symbol Substitution Test (DSST)8 and indicate their current pain and nausea on a 10 cm Visual Analog Scale (VAS; 0=no pain, 10=excruciating pain; 0=no nausea, 10=excruciating nausea). In the DSST, patients were given 2 min to replace digits with appropriate symbols located in a legend at the top of the page.

Anaesthesia was induced with fentanyl (1–2 µg kg–1 i.v.) and propofol (1.5–2.5 mg kg–1 i.v.) and muscle paralysis obtained with vecuronium (0.1 mg kg–1 i.v.).

Desflurane group
Anaesthesia was maintained with desflurane 2–6% in combination with nitrous oxide 60% in oxygen. Inspired desflurane concentration (gas flow rate of 2.0 litre min–1) was adjusted as necessary to maintain pulse and arterial pressure within 15% of pre-induction values. If acute increases occurred, the inspired concentration of desflurane was increased by up to 50%. Fentanyl (50 µg i.v.) was used to control acute changes that did not respond to two consecutive 50% increases in the inspired concentration of desflurane or if there were other signs of inadequate analgesia (i.e. tearing, purposeful movements, diaphoresis).

Sevoflurane group
Anaesthesia was maintained with sevoflurane 0.6–1.75% and nitrous oxide 60% plus oxygen. Inspired sevoflurane concentration (gas flow rate of 2.0 litre min–1) was adjusted as necessary to maintain haemodynamic variables within 15% of pre-induction values. Similar treatments were used for signs of inadequate anaesthesia, using increased anaesthetic concentrations and doses of fentanyl.

In both groups of patients, if hypertension and tachycardia (an increase of 20% above the baseline values) persisted despite these measures, esmolol was given i.v.. If the response was inadequate, nitroprusside was given according to usual clinical practice. If hypotension and bradycardia (a decrease of >20% of the baseline values) occurred, the subject’s position was adjusted and i.v. fluid administration was increased, inspired concentration of anaesthetic agent was decreased or, if needed, stopped. Phenylephrine, ephedrine, dopamine, or epinephrine were used as necessary according to usual clinical practice. Bradycardia (HR <40 beats min–1 or causing haemodynamic compromise) was treated with ephedrine or atropine as clinically indicated.

Arterial pressure, ECG, and arterial oxygen saturation were recorded before induction of anaesthesia then, along with end-tidal carbon dioxide, nitrous oxide, and volatile anaesthetic concentrations, every 2 min after induction of anaesthesia for 15 min and then every 5 min until the end of surgery. End-tidal carbon dioxide was maintained between 32 and 35 mm Hg using assisted or controlled ventilation. Doses of vecuronium (0.5–1.0 mg increments) were given to maintain a single twitch in the train of four. Bispectral Index was continuously monitored. Total anaesthetic time (from administration of induction agent to stopping the volatile anaesthetic agent); total surgical duration (from skin incision to placement of last suture); time to extubation (discontinuation of volatile agent); early recovery (time to awakening (eyes open); time to verbal command (squeeze finger); time to orientation (place, time, date); time to discharge from operating room; post-operative analgesic use; incidence of vomiting; antiemetic use and dose; and time to meet PACU discharge criteria (Post Anaesthesia Recovery Score >=9; Table 1) were recorded. While in the PACU, the subjects were asked to take a DSST and indicate their pain and nausea on VAS every 15 min until discharge.


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Table 1 Post-anaesthetic recovery score
 
Neuromuscular block was antagonized with glycopyrrolate (6–8 µg kg–1, i.v.) and neostigmine (40–80 µg kg–1, i.v.). Inhalation agent administration was discontinued abruptly after administration of reversal agents. Ventilation of the lungs was continued with oxygen 100% at a fresh gas flow rate of 6 litre min–1 until the subject was extubated.

Statistics
Time to ready for discharge from the PACU was the primary outcome measure. Power analysis ({lambda}=0.05 and (1–ß)=0.8) showed that 45 patients would be required to demonstrate a difference of 5 min. Numerical data are given as median (interquartile range). DSST scores were expressed as per cent of baseline for each subject. Student’s two-tailed t-test for unpaired data was used to determine if differences were significantly different (P<0.05 duration of surgery, duration of anaesthesia, induction dose of propofol and fentanyl, time to eyes open, time to squeeze finger, time to extubation, time to orientation, time to meet PACU discharge criteria). Fisher’s exact test was used to determine if significant difference (P<0.05) existed between the number of patients receiving intraoperative fentanyl and analgesic in the PACU. Statistical computations were done using Pharmacologic Calculation System version 4.2(c) and graphing was done using STATA v8.0(c) on an IBM compatible PC using Windows 2000.


    Results
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
There were no significant differences in the duration of surgery or anaesthesia or time to ready for PACU discharge between the two groups (Tables 2 and 3). On the other hand, times to extubation, eyes opening, squeeze finger, and orientation were significantly less for desflurane than for sevoflurane (Table 3).


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Table 2 Patients details, surgery and anaesthesia (median and interquartile values)
 

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Table 3 Recovery measurements (min:median (interquartile range)). *Significantly different (P<0.05) t-test between groups
 
Pain and nausea VAS scores and DSST scores did not vary significantly (no P value correction for multiple comparisons) between the two groups at any of the times data (Figs 13). Intraoperative and postoperative analgesic use did not differ significantly between desflurane and sevoflurane patients. The DSST scores showed an initial decrease from baseline values in both groups and progressively improved during recovery.



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Fig 1 Pain VAS scores in patients receiving desflurane or sevoflurane before anaesthetic induction and at 15 min intervals after arrival in the PACU. The horizontal line in the interior of each box is median. The height of the box is the interquartile distance, which is the difference between the third and first quartile. The whiskers extend to the maximum and minimum values. No significant difference (P>0.05) between scores for the two study groups at any time (t-test for unpaired data). Desflurane is shaded, sevoflurane is in white.

 


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Fig 3 DSST per cent of baseline score in patients receiving desflurane or sevoflurane before anaesthetic induction and at 15 min intervals after arrival in the PACU. The horizontal line in the interior of each box is median. The height of the box is the interquartile distance, which is the difference between the third and first quartile. The whiskers extend to the maximum and minimum values. No significant difference (P>0.05) between scores for the two study groups at any time (t-test for unpaired data). Desflurane is shaded, sevoflurane is in white.

 

    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
We found that early but not intermediate recovery from desflurane is faster than from sevoflurane in elderly patients undergoing prolonged general anaesthesia. These results confirm and extend the findings of Chen and colleagues7 who compared recovery from desflurane and sevoflurane anaesthesia in elderly patients (>=65 yr of age) undergoing total knee or hip replacement. That study was very similar to ours, except for assessment of cognitive recovery (DSST vs MMS) and type of surgery.

There is remarkably good agreement, qualitative and quantitative, between early outcome results in the two studies. For example, Chen and colleagues7 reported average time to eye opening following discontinuation of desflurane exactly equal to the average time we found for eye opening (6.3 min). This shows that the type of surgery usually is not a major determinant of early recovery.

We concur with Chen and colleagues7 that further studies of the recovery of cognitive function in the elderly following anaesthesia are needed, but such assessment is not easy. The Saskatoon Delirium Checklist,9 Geriatric Mental State Examination,10 and the Confusion Assessment Method,11 in addition to the DSST and MMS, have all been used to evaluate cognitive function in the elderly, to measure return of consciousness, perception, orientation, coherence, memory, and motor activity. To our knowledge, the sensitivity and selectivity of these tests for assessment of cognitive impairment recovery following anaesthesia has not been demonstrated. It is therefore possible that recovery of cognitive function is indeed different following desflurane vs sevoflurane anaesthesia but a difference was not detected by the DSST in our study or the MMS in the study by Chen and coworkers.7

The DSST scores we obtained (expressed as per cent of pre-anaesthetic value-baseline) were variable. We found that this could indicate at least in part, the distraction of patients by factors such as nausea, pain, and emotional distress that influenced their ability or willingness to perform the test.

In summary, we found in elderly patients after a variety of surgical interventions that early recovery is faster following desflurane vs sevoflurane anaesthesia. However, intermediate recovery as measured by DSST did not differ. Assessment of intermediate and longer recovery could be limited by the lack of sensitive and selective measures.


    Acknowledgement
 
Baxter Healthcare Corporation provided financial support for this study.



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Fig 2 Nausea VAS scores in patients receiving desflurane or sevoflurane before anaesthetic induction and at 15 min intervals after arrival in the PACU. The horizontal line in the interior of each box is median. The height of the box is the interquartile distance, which is the difference between the third and first quartile. The whiskers extend to the maximum and minimum values. No significant difference (P>0.05) between scores for the two study groups at any time (t-test for unpaired data). Desflurane is shaded, sevoflurane is in white.

 

    References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
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2 Nathanson MH, Fredman B, Smith I, White PF. Sevoflurane versus desflurane for outpatient anesthesia: a comparison of maintenance and recovery profiles. Anesth Analg 1995; 81: 1186–90[Abstract]

3 Welborn LG, Hannallah RS, Norden JM, et al. Comparison of emergence and recovery characteristics of sevoflurane, desflurane, and halothane in pediatric ambulatory patients. Anesth Analg 1996; 83: 917–20[Abstract]

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5 Evers AS, Crowder CM. General anesthetics. In: Hardman JG, Limbird LE, eds. The Pharmacological Basis of Therapeutics, 10th Edn. New York: McGraw-Hill, 2001; 337–65

6 Parikh SS, Chung F. Postoperative delirium in the elderly. Anesth Analg 1995; 80: 1223–32[Abstract]

7 Chen X, Zhao M, White PF, et al. The recovery of cognitive function after general anesthesia in elderly patients: a comparison of desflurane and sevoflurane. Anesth Analg 2001; 93: 1489–94[Abstract/Free Full Text]

8 Drummond GB. The assessment of postoperative mental function. Br J Anaesth 1975; 47: 130–42[ISI][Medline]

9 Miller PS, Richardson JS, Jyu CA, et al. Association of low serum anticholinergic levels and cognitive impairment in the elderly presurgical patients. Am J Psych 1988; 145: 342–5[Abstract]

10 Duckworth GS. The reliability of G.E.M.S. Proc Ont Psychogeriatric Assoc 1976; 54–9

11 Inouye SK, van Dyck Ch, Alessi CA, et al. Clarifying confusion: the confusion assessment method: a new method for detection of delirium. Ann Intern Med 1990; 113: 941–8[ISI][Medline]