Awakening, Clinical Recovery, and Psychomotor Effects After Desflurane and Propofol Anesthesia

Abstract

We compared postanesthetic and residual recovery of desflurane versus propofol anesthesia.Twenty volunteers were anesthetized for 1 h at 1-wk intervals with either propofol (induction) plus desflurane (1.25 minimum alveolar anesthetic concentration) in O₂ (PD), propofol plus desflurane in N₂ O-O₂ (PDN), propofol plus propofol infusion with N₂ O-O₂ (PPN), or desflurane (induction) plus desflurane in O₂ (DD). Awakening and clinical recovery were measured. Psychomotor skills (attention, coordination, reactive skills, and memory) were tested before and 1, 3, 5, and 7 h after anesthesia. Awakening was fastest in Group PDN. At 1 h after anesthesia, the subjects given desflurane for maintenance (PD, PDN, and DD) performed significantly (P < 0.05-0.01) better in several psychomotor tests compared with those whose anesthesia was maintained with propofol (PPN). However, subjects met criteria for home readiness as fast after PPN as after PDN anesthesia (mean times +/- SE until fitness for discharge were 126 +/- 20, 81 +/- 14, 70 +/- 7, and 106 +/- 14 min after PD, PDN, PPN, and DD, respectively). Awakening and early psychomotor recovery for as long as 1 h after anesthesia is faster after desflurane than after propofol, but there was no difference in time to home readiness or in residual effects thereafter between propofol and desflurane with N₂ O in O₂.

(Anesth Analg 1996;83:721-5)

Within 10 years, more than 75% of all elective operations performed in the United States will be done on an outpatient (ambulatory) basis. In ambulatory surgery, anesthetic techniques enabling rapid recovery without side effects are of utmost importance ^[1]. Propofol is used in anesthesia for ambulatory surgery with expectations of rapid recovery ^[2] and fast discharge of patients with few residual effects ^[3,4]. Desflurane is also well suited for outpatient anesthesia ^[5,6].

Many studies have examined recovery after desflurane and propofol, but few have actually compared these two and long-term effects have not been compared. It appears that awakening and initial recovery from desflurane may be faster than from propofol ^[7]. In one study ^[8], psychomotor scores of the patients who received desflurane for induction and maintenance of anesthesia or maintenance only were better than the scores of those who were given propofol for the same purpose.

We hypothesized that the immediate postanesthetic and residual recovery is more rapid after desflurane than after propofol. We tested this hypothesis in volunteers not undergoing surgery, because more accurate emergence and recovery data can be obtained; we compared only anesthetics in the absence of adjuvant medications and other factors that are present in a surgical setting.

Methods

This study was designed as a randomized, prospective, cross-over investigation. Institutional review board approval was obtained prior to the enrollment of volunteers. Informed, written consent was obtained from volunteers prior to their initiation into the study. An anesthesiologist performed a history and physical examination in order to determine the suitability of subjects for the study. Only healthy males 18-39 yr old were eligible. On testing days, subjects were not allowed to eat or drink after midnight prior to each anesthetic. Subjects were instructed to refrain from drinking alcohol for 24 h prior to sessions. They were told not to drive a car, operate heavy machinery, or cook until the day after each anesthetic, and they were required to have an escort accompany them home after sessions. Subjects were paid for their participation upon completion of the study.

Twenty volunteers were anesthetized for 1 h at 1-wk intervals with either propofol (induction) plus desflurane (1.25 minimum alveolar anesthetic concentration [MAC]) in O₂ (PD), propofol plus desflurane in N₂ O-O₂ (PDN), propofol plus propofol infusion with N₂ O-O₂ (PPN), or desflurane (induction) plus desflurane in O₂ (DD). Prior to anesthesia, subjects received 0.5-1 mL/kg lactated Ringer's solution for each hour the subject was non per os. Subjects then breathed 100% O₂ and were given 3 mg d-tubocurarine intravenously (IV). Those subjects randomized to Groups PD, PDN, and PPN received propofol 2.5 mg/kg IV in a bolus injection for induction of anesthesia. Subjects in Group DD had anesthesia induced with desflurane. Desflurane was administered initially at 3% and increased gradually every two to three breaths by 3% until the eyelid reflex was lost. For all groups, after loss of eyelid reflex, succinylcholine 1.0 mg/kg IV bolus was administered followed by laryngoscopy and tracheal intubation. For the purpose of this study, endotracheal intubation was considered the end of induction and the beginning of the maintenance of anesthesia.

After intubation, anesthesia was maintained for 1 h and titrated to effect in each group. Subjects in Groups PD and DD received 1.25 MAC desflurane (7.5%) in O₂, and those in Group PDN received 1.25 MAC desflurane (3.5%) in N₂ O (60%) and O₂. Subjects in Group PPN received a continuous propofol infusion (9 mg centered dot kg^-1 centered dot h^-1) and N₂ O (60%) in O₂ as an adjunct. Ventilation was assisted to produce a PETCO₂ of 30-40 mm Hg. During maintenance, light anesthesia or hypertension (>20% of baseline) was treated by increasing by 20% the end-tidal concentration of desflurane or the propofol infusion rate. Hypotension (<20% of baseline) was treated first by infusion of fluids and then by decreasing by 20% the end-tidal concentration of desflurane or the propofol infusion rate.

Blood pressure, heart rate, O₂ saturation, end-tidal CO₂, and temperature were measured and recorded prior to induction of anesthesia, every minute during induction until 10 min after induction, and every 5 min thereafter until consciousness ensued. In patients receiving desflurane, the end-tidal concentration of desflurane was measured and recorded by an infrared DATEX analyzer (Datex Division of Instrumentarium Corp., Helsinki, Finland). For group PPN, propofol was infused by a Baxter AS20GH-2 pump (Baxter Healthcare Corp., Hooksett, NH).

After 1 h of maintenance anesthesia, desflurane, propofol, and N₂ O were discontinued. Before discontinuation, no tapering of the administration of the anesthetics was carried out. When the subjects were breathing to maintain a PETCO₂ of 30-50 mm Hg and had a gag reflex, their tracheas were extubated. Emergence from anesthesia was assessed by a blinded observer. The times elapsed from the discontinuation of anesthesia for the subject to open his eyes and to respond to the commands "squeeze my fingers," "tell me your name," and "tell me your date of birth" were recorded as well as the time elapsed until the subject could orient himself to the date and his present location. Subjects were also asked to sit, stand, walk, urinate, drink liquids, and dress themselves as soon as they were able to do so. Those times were recorded by a blinded observer, and, after the subjects were able to do all, they were considered home ready, i.e., suitable for discharge. These variables are commonly used postoperatively to assess patients' suitability for discharge from the hospital after ambulatory surgery ^[2,9].

Before the first session of the experiment, subjects were trained (in three practice sessions) to use the psychomotor test apparatuses in order to prevent further learning of the tasks during the actual testing. Psychomotor tasks were performed before anesthesia and 1, 3, 5, and 7 h after anesthesia. A snack was served approximately 2 h after anesthesia, and lunch was served approximately 4 h after anesthesia.

The Maddox wing test ^[10] was used to measure eso- and exophoria and motor function of the eyes. An action judgment test, similar to a driving test, was used to measure sustained eye-hand coordination: using a steering wheel, subjects attempted to keep two pointers on a moving track without striking objects. Simple auditory and visual reaction times were determined by measuring the time it took the subject to press a button after hearing a sound or seeing a letter on the computer screen. Eye-hand coordination was measured by having the subject track a randomly moving circle on a computer screen with a cross controlled by a mouse. Mistakes were measured by counting the number of times that the cross exceeded 1 cm from the target. In the multiple reaction test, subjects pressed the appropriate button in response to different visual and auditory stimuli presented simultaneously. Reaction time and mistakes (i.e., the number of incorrect or missed responses) were recorded. For more detailed description of the tests, see Nuotto and Korttila ^[11]. In the Digit Symbol Substitution Test, subjects were given 1 min to replace digits with appropriate symbols located in a legend at the top of the page ^[12].

Immediate recall was tested by presenting 20 words, one at a time, from a preselected list; immediately after the list was presented, the subject was asked to write, in any order, as many of the words as he could remember in 2 min ^[13]. Long-term recall was tested at 3 and 7 h after anesthesia. Three hours after anesthesia, the subject was asked to write as many words as possible from the lists already used to test immediate recall (20 words presented at baseline and 20 words presented 1 h after sedation). Seven hours after sedation, the subject was again asked to write as many words as possible from the 20-word lists presented at baseline and 1 and 5 h after sedation (a maximum of 60 words).

For the emergence from anesthesia criteria, analysis of variance was used to compare group means and post-hoc comparisons were made of individual means when appropriate. For the psychomotor tests, repeated measures analysis of variance was used to compare results at different times after anesthesia and post-hoc comparisons were used to compare individual means when appropriate. Statistical significance was assumed at P < 0.05.

Results

Twenty subjects were eligible for the study and completed all four of the anesthetic regimens. Their average (+/- SE) age, height, and weight was 24 +/- 1 yr, 178 +/- 2 cm, and 79 +/- 2 kg, respectively. Five subjects were eligible for the study but did not complete all four of the anesthetic regimens; therefore, they were not included in the analysis.

The average +/- SD desflurane concentration (end-tidal) used during maintenance for Group PD was 7.1% +/- 0.6%; that for Group PDN was 3.5% +/- 0.2%; and that for Group DD was 7.4% +/- 0.4%. The average propofol infusion rate for Group PPN was 8.6 +/- 2.2 mg centered dot kg^-1 centered dot h^-1. When the subjects were receiving desflurane for induction, 20% held their breath, 55% coughed, 45% had excessive secretions, and 5% developed laryngospasm.

Initial emergence from anesthesia with a propofol anesthetic (Group PPN) was significantly slower than that from anesthesia in the three desflurane maintenance groups Table 1. Subjects receiving propofol for maintenance took longer to open their eyes, squeeze fingers, state their name, state their birth date, and become oriented to the date and their present location than when they received desflurane for maintenance. In addition, subjects in Group DD were oriented more quickly than subjects in Group PD (P < 0.05). Subjects receiving N₂ O in addition to O₂ and desflurane for maintenance (Group PDN) were able to open their eyes, squeeze fingers, state their name, state their birth date, and orient themselves more quickly than subjects who received only desflurane and O₂ for maintenance (pooled Groups PD and DD; all P < 0.01 except squeeze fingers, P < 0.05).

Table 1: Emergence and Clinical Recovery after 1 h of Anesthesia in 20 Volunteers

Concerning the variables of home readiness, including subjects' ability to sit, stand, walk, tolerate oral fluids, urinate, dress themselves, and be judged fit for discharge, there were few significant differences between groups Table 1. Subjects receiving N₂ O in addition to desflurane and O₂ for maintenance (Group PDN) were able to sit significantly (P < 0.05) sooner than subjects who received only desflurane and O₂ for maintenance (Groups PD and DD pooled). Subjects receiving propofol for maintenance (Group PPN) were able to urinate sooner and were judged fit for discharge sooner than subjects in all the other groups who received desflurane for maintenance Table 1. However, times to fitness for discharge were similar in Groups PDN and PPN.

Psychomotor impairment was relatively transient for all four groups. There was no significant difference between the four treatment groups beyond 1 h after anesthesia. Table 2 presents the change from baseline in psychomotor performance measurements obtained 1 h after anesthesia for the four treatment groups. One hour after anesthesia, subjects who had received propofol for maintenance (PPN) had greater exophoria (Maddox wing), made more mistakes on the action judgment, coordination, and multiple reaction, and remembered fewer words for immediate recall than subjects in the other groups who had received desflurane for maintenance. There was no significant difference in psychomotor performance at any time between the three groups receiving desflurane for maintenance.

Table 2: Mean +/- SE Difference from Baseline to 1 h After the End of 1 h of Anesthesia for Various Psychomotor Tests in 20 Healthy Volunteers

At 3, 5, and 7 h after anesthesia, there were no differences between the groups in any parameter of psychomotor skills tested. The impaired performance seen 1 h after anesthesia in the Maddox wing, action judgment, and coordination tests in subjects given propofol (PPN) had returned to baseline by the 3-h time point.

Discussion

The hypothesis tested was true in that subjects woke up faster (e.g., eye-opening and orientation) and were able to sit earlier after desflurane than after propofol anesthesia. Similarly, subjects performed significantly better in many psychomotor tests one hour after desflurane anesthesia when compared with propofol anesthesia. However, time to fitness for discharge home from recovery room was as fast after propofol as after desflurane when N₂ O was used to supplement anesthesia. Also, no differences between the groups were noted three hours or later after anesthesia.

In the absence of a reliable measure of the depth of anesthesia for both inhaled and intravenous anesthetics, all attempts were made to produce and maintain equivalent depth of anesthesia in all groups. Certainly, toleration of the endotracheal tube was maintained and blood pressures and heart rates were no different between the groups. No tapering of either desflurane or propofol anesthesia was done at the end of the anesthesia in order to maintain the tolerance of the endotracheal tube to the very end of anesthesia in the absence of adjuvants drugs (e.g., narcotic analgesics and neuromuscular blocking agents). Early recovery times in our study after propofol maintenance were similar to recovery times that have been previously reported after propofol maintenance infusions. For example, in one study ^[14] where propofol was administered for two hours to 11 volunteers by an adaptive feedback control algorithm based on quantitative electroencephalogram analysis, the time to orientation to time and place was 18 minutes, which was statistically less than 40 minutes after methohexital, using a similar technique. In 25 patients undergoing ambulatory oral surgery and conservative dentistry who were given propofol for induction and maintenance over three hours, the mean time until patients became reorientated with respect to time and place was 11 minutes ^[15].

Can these results be generalized to patients who undergo surgery and who may experience pain or postoperative nausea and vomiting? Unfortunately, the influence of pain on psychomotor and cognitive function in humans has not been extensively studied. In the only study of which we are aware, psychomotor performance was not affected by acute pain ^[16]. Nausea and vomiting, which were not problems in this study, are in clinical practice known factors causing delays in recovery and admissions to the hospital after ambulatory surgery ^[17].

We have developed and earlier found the psychomotor tests to be sensitive in assessing residual effects after alcohol ^[12], intravenous sedatives, and anesthetics ^[3,18] as well as after analgesics ^[14] and sedative/analgesic combinations ^[19]. Impairment in coordination, divided attention, and reaction time tests have been used to estimate driving skills as well as to determine the duration of hospital stay necessary after surgery and/or anesthesia ^[20].

Induction with desflurane alone (DD) was not ideal. A majority of the subjects coughed and had excessive secretions. This problem, though, is not unique and has been reported by other investigators and in large part led the Food and Drug Administration not to approve desflurane for induction of anesthesia ^[21].

Our study has shown that awakening and clinical recovery are faster after desflurane combined with N₂ O compared with desflurane administered with O₂. Recovery of cognitive and psychomotor function is faster after desflurane used for maintenance of anesthesia for one hour than after propofol anesthesia, although recovery for both drugs is rapid enough so that even three hours after the discontinuation of propofol anesthesia no difference from baseline was evident.

As is indicated in times to toleration of oral fluids Table 1, nausea and vomiting were not problems in our subjects, except in one subject in the DD group who had difficulties performing the one-hour tests because of sickness, and in two, one, and two subjects in Groups PD, PPN, and DD, respectively, whose oral fluid intake was delayed because of nausea. Actually, when propofol was used for induction and desflurane with N₂ O in O₂ for maintenance (PDN), subjects tolerated oral fluids as early as 17 minutes after anesthesia. In clinical practice, nausea and vomiting may delay discharge home after ambulatory surgery ^[2]. Earlier clinical studies indicate that desflurane anesthesia may be associated with more postoperative nausea and vomiting than propofol anesthesia ^[6,7,22].

We conclude that, after maintenance of anesthesia for one hour, both awakening and psychomotor recovery are distinctly faster after desflurane than after propofol anesthesia for as long as one hour after anesthesia. In addition, fitness for discharge is achieved as fast after desflurane as after propofol if N₂ O is used to supplement anesthesia, and recovery of psychomotor skills was complete at three hours after anesthesia.