A study of psycho-behavioral patterns in patients emerging from general anesthesia using sevoflurane, propofol and their combination in early, intermediate and late post-operative period: A randomized controlled trial.

BACKGROUND: It has been contended the general anesthetic agents also may affect the psycho-social behavior of the patients, especially during the emergence from GA. This assumes much significance in day cases where, patients have to be roadworthy and mentally stable before discharge. AIMS: We compared the psycho-behavioral effects of propofol, sevoflurane and their combination, while emerging from anesthesia. SETTINGS AND
DESIGN: The patients coming for short duration day care anesthesia were studied in a prospective randomized controlled comparison.
MATERIALS AND METHODS: The psycho-behavioral changes in early, intermediate and late recovery period were studied in 60 consenting patients undergoing Total Intra Venous Anesthesia (TIVA) using Propofol, Volatile Induction and Maintenance Anesthesia (VIMA) using Sevoflurane and the combination of these two agents. STATISTICAL ANALYSIS: Statistical Analysis of the data and application of various statistical tests was carried out with help of Statistical Package for Social Services (SPSS version 18). Data were compiled, analyzed and presented as frequency, proportions, mean and standard deviation. The tests of significance, like Chi-square test, percentages, independent sample t test, paired t test, and P value were used in the study. RESULTS AND
CONCLUSIONS: Both the modalities of GA, viz; TIVA and VIMA, do produce significant psycho-behavioral changes in the patients after GA, though transiently. So it is imperative for the Clinicians to anticipate the entire aspect of Psycho-behavioral patterns before discharging the day cases from the Post anesthesia Care Unit (PACU).

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

To achieve the advantages of ‘Day Care/Ambulatory anesthesia, use of very potent, short and rapidly acting intravenous as well as inhalational anesthetic agents are the preference of anesthesiologists.[123] Amongst the available drugs, Propofol as Total Intra Venous Anesthesia (TIVA) and Sevoflurane as Volatile Induction and Maintenance Anesthesia (VIMA) fulfill the criteria for ambulatory anesthesia because of their unique pharmacokinetics, thus providing fast recovery after anesthesia. These drugs are frequently administered and their systemic effects have been elaborately studied but their psychological and behavioral side effects in the postoperative period are not well studied. With this primary outcome in mind, we started observing and assessing the psycho-behavioral changes in the patients emerging from general anesthesia, using one of these methods or their combination.

MATERIALS AND METHODS

Present study was conducted in randomly selected 60, American Society of Anesthesiologists (ASA) I or II consenting adult patients of both sexes, in the age range of 18-55 years after the approval of Institutional Ethical Committee (IEC). The patients with psychiatric diagnosis or on medication were excluded. Only patients posted for planned short duration elective surgeries (<90 min) under general anesthesia (GA) were included. Equal number of cases was chosen to compare the results. The power analysis was done to meet the end points of the study and was found to be 0.78, which was powered.

They were randomly allocated into 3 groups of 20 each, by a computer generated model.

Group S: Patients receiving Sevoflurane as induction and maintenance agent.

Group P: Patients receiving Propofol as induction and maintenance agent.

Group PS: Patients receiving Propofol as induction and Sevoflurane as maintenance agent.

Anesthetic procedure was explained to the patients, consent was obtained and they were kept fasting overnight. Pre-operative heart rate (HR), systolic and diastolic blood pressures (SBP, DBP), and saturation of Oxygen (SpO2) were recorded. Intravenous (I.V.) access was secured and patients were preloaded with 10 ml/kg of Ringer's lactate. Patients were premedicated with Inj. Atropine 0.01 μg/kg body weight + Inj. Fentanyl 2 mg/kg body weight + Inj. Midazolam 0.02 mg/kg body weight.

After this, the management varied as per the group to which the patient was allocated.

Group S (VIMA)

Mask induction was carried out using Bain's circuit with O2+ N2O (2 liters + 4 liters, respectively; in the ratio of 1:2). Sevoflurane was added up to 7.5% for first 2 min. and then reduced to 5% for next 2 min. and, thereafter, patients were maintained on 2-2.5% of sevoflurane to achieve adequate depth of anesthesia i.e., to maintain the vitals within 20% of baseline.

Group P (TIVA)

Induction was carried out with I.V. Propofol in bolus dose of 2.5 mg/kg body weight till initially loss of verbal contact and loss of eyelash reflex. Thereafter, patients were maintained on I.V infusion of propofol, the rate titrated to maintain adequate depth of anesthesia i.e., to maintain the vitals within 20% of baseline.

Group PS (Combination)

Induction was carried out by I.V. Propofol in bolus dose of 2.5 mg/kg body weight. Thereafter, patients were maintained on 2-2.5% of sevoflurane to achieve adequate depth of anesthesia i.e., to maintain the vitals within 20% of baseline.

Intra-operative monitoring of heart Rate/Systolic BP/Diastolic BP/SpO2 was continued.

After completion of surgery, I.V. and inhalational anaesthetic agents were stopped and patients were given 100% O2 for 5 minutes and recovered.

Recovery time T0 (time from stopping of anesthetic agent till achievement of Standard Aldrete Score (S.A.S.)[4] of 8 was recorded.

The patients were shifted to recovery room and vital parameters were monitored continuously. The psycho-behavioral assessment was done with help of SAS[4] [Annexure I] and Behavioral Pattern Scoring System (BPSS) [Annexure II] by same anesthesiologist, who was blinded to the modality of anesthesia being used, after 2 hours (T1).

Annexure I

Standard Aldrete score

Annexure II

Behavior pattern scoring system

After this evaluation, the patients were shifted to the wards and were followed up after exactly 24 hrs (T2) and 48 hrs (T3), when the BPSS were recorded. The last BPSS was carried out on follow up visit after 7 days after the anesthesia (T4). Any side effects, even the trivial ones, which the patient mentioned were recorded and treated, if required.

Data was compiled and statistical analysis of the data and application of various statistical tests was carried out with help of Statistical Package for Social Services (SPSS version 18). It was presented as frequency; proportions, mean, standard deviation, and percentages. The significance tests, Chi-square test, independent sample t test, paired t test, and P value were used in the study.

A P of less than 0.05 was considered as statistically significant. Continuous covariates (age) were compared using independent sample t test, with the p- being reported at the 95% confidence interval. Categorical covariates (sex, ASA grade,) were explained using Chi-square test as comparisons amongst the three groups. The results were expressed as Mean ± SD and P.

RESULTS

Demographic profile (Age/Sex/Weight) and duration of surgery were comparable in all the groups. Comparison of vital parameters showed that (within the groups):

In patients receiving only sevoflurane (Group S), there was significant increase in heart rate from pre-operative value of (81.15 ± 12.33) to immediate post-op value of (97.8 ± 20.3), but no significant changes in Blood pressures.

In patients receiving only propofol (group P), there was fall in systolic and diastolic BP, from pre-op value of (118.8 ± 9.05 and 72.95 ± 5.71) to post-op value of (113.1 ± 12.06 and 66.95 ± 9.82), respectively, but no significant changes in heart rate.

Coincidentally, in patients receiving the combination (Group PS), there was an increase in heart rate from pre-op value of (81.15 ± 10.7) to post-op value of (103 ± 16) and fall in both the systolic and diastolic blood pressures viz. pre-op (121 ± 10.67 and 73.6 ± 8.36) and post-op (115.6 ± 12.77 and 70 ± 11.04).

Other vital parameters did not show any statistically significant difference.

Recovery time was earliest in Group P followed by Group PS and delayed in Group S, but this difference was not statistically significant (P = 0.138) [Table 1].

Table 1

Comparison of time taken to reach T0

Comparison of SAS at various intervals

In the present study, SAS was used to assess subjective patient's state after anesthesia. Time taken to reach T0 (SAS > 8) between the three groups was comparable. But when compared at different time intervals i.e., T0 and T1 (after 2 hrs in early recovery phase); there was a statistically significant difference between the various groups. The Aldrete score of 8 was achieved earlier in Group S and Group P as compared to Group PS. At T0-SAS in Group PS was lower than other two Groups (P = 0.048), but at T1 there was no significant difference in SAS (P = 0.773) [Figure 1].

Figure 1

Comparison of S. A. S. at various intervals T0-SAS in Group PS was lower than other two Groups. (P= 0.048), T1-No significant difference in SAS (P= 0.773)

Comparison of BPSS at various intervals

On comparing the BPSS in the three groups at various time intervals i.e., (T1 - 2 hrs, T2 - 24 hrs, T3 - 48 hrs, T4 - 7 days) no statistically significant difference was found [Figure 2].

Figure 2

Comparison of B.P.S.S. at various intervals applying ANOVA test-There was no significant difference in B.P.S.S. among the three

Side effects

On comparing the various side effects between the three groups, we found:

Increased muscle tone in 70% of patients in Group S, 60% of patients in Group PS and only 35% in Group P

Shivering in 80% of patients in Group S, 30% of patients in Group P and only 25% in Group PS

Sedation in 70% of patients in Group PS, 55% of patients in Group S and P

Hypotension in 15% of patients in Group P and PS and 10% in Group S

Pain along I.V. line in 30% of patients in Group PS, 25% of patients in Group P, and none in Group S

25% of patients emerged crying after operation in Group P, but only 10% of patients in Group S and PS had similar incidence

Headache was complained by 80% of patients in Group PS, whereas about 60% of patients had similar complaints in Group S and P

60% of patients in Group S and PS and 40% in Group P complained of bodyaches

The incidence of early amnesia was higher in Group PS (75%), than in Group P (65%) and least in Group S (55%)

Similarly, the incidence of late amnesia was seen in 10% of patients in Group PS but only 5% of patients in Group S and P.

Various sleep disturbances and psychological changes

Hallucinations: In 15% of patients in Group P and 10% in Group S and PS

Nightmares: In 20% of patients in Group S only

Restlessness: In 10% of patients in Group S and PS, none in P

Disturbed sleep: In 20% of patients in Group PS and 5% in Group P

Sexual fantasies: In 25% of patients in Group P and 10% in Group PS, but none of the patients in Group S.

Other side effects observed were nausea, vomiting, giddiness, peri-orbital swelling, tingling numbness, generalized tonic clonic seizure (GTCS), and recall of intra-operative memory in occasional patients in all the three groups [Table 2].

Table 2

Side effects

Gender variability in recovery time

There was no difference in recovery time (awakening) between males and females in Group S. Recovery time in females in Group P was earlier than in males, whereas, in Group PS, the recovery time in females was delayed as compared to males [Table 3].

Table 3

Gender variability in recovery time

Summary of the results

Propofol, as a sole induction and maintenance agent:

In lower doses (13-15 ml/upto 150 mg), it causes no changes in psycho-behavioral pattern either in immediate or late post-operative period

In higher doses (>150 mg), it causes unpleasant intra-operative dreams, sedation, crying, headache, body aches, amnesia, nightmares, hallucinations, disturbed sleep, and sexual fantasies in females

Sevoflurane, as a sole induction and maintenance agent, in early post-operative period: it causes, Shivering, restlessness, increased muscle tone, sedation, and amnesia in intermediate post-operative period: it causes headache, bodyaches, and hallucinations

Propofol as induction and sevoflurane as maintenance agent (combination group): it causes, in early post-operative period, shivering, sedation, increased muscle tone, crying, headache, body aches and amnesia. In intermediate post-operative period, it causes, amnesia, disturbed sleep, hallucinations, restlessness, generalized tonic clonic, seizures, and sexual fantasies in females

DISCUSSION

Well-being represents the subjective patient condition, measured and analyzed by various methods.[567] Also, it has been proposed as a useful surrogate end point in anesthetic quality assessment.[8] However, in the context of general anesthesia, attempts to evaluate possible difference of quality, as related to patients behavioral effects between the different anaesthetic techniques have not been made very often. Also, with these general anesthetic agents used via I.V. as well as inhalational routes, the changes in vital parameters during anesthesia and their recovery criteria have been extensively studied in the recent years, but their psycho-behavioral changes on the patients have frequently been overlooked. These aspects are especially important since these patients are going to be discharged on the same day. There have been few reports of these changes in the literature but these are not properly studied and compared between TIVA and VIMA.

In this study, we have found that there are no psycho-behavioral changes either in the immediate or late post-operative period on administration of propofol in lower doses for TIVA (<150 mg). This concurs with some of the other studies.[910] Also, there were no complaints of nausea and vomiting, as is seen in other studies,[11] most likely due to anti-emetic property of propofol. But when it is given in higher doses (>150 mg), it produced various side effects like unpleasant intra-operative dreams, crying, headache, body ache, amnesia, sedation, nightmares, hallucinations, disturbed sleep in the early, and intermediate post-operative period. This compares well with various findings in some of the studies.[12131415] The finding of gender variability with these drugs also compares well with available evidence.[161718] The female gender does seem to require less recovery time from propofol rather than as compared to the sole volatile agents, which does not seem to have any relation with the gender. However in combination (PS) group the males required less recovery time, as compared to the females; also, a significant percentage of female patients receiving propofol, had dreams of sexual fantasies in the intra-operative period; whereas, most of the previous studies have reported that there is no evidence of intra-operative recall with propofol anesthesia.[19]

When sevoflurane was administered as VIMA, various side effects were observed in the early post-operative period i.e., shivering, restlessness, increased muscle tone, sedation, and amnesia, whereas, in intermediate post-operative period, patients presented with headache, body aches, and hallucinations. These findings compare with those of various authorities.[202122] There was no difference observed in the recovery time (awakening) between males and females. However, a study by Tercan and colleagues[23] showed that early recovery times were longer for female patients than for male patients after anesthesia based on sevoflurane or desflurane. Some efforts have also been made to find the quality of recovery after anesthesia and use it as a measure of the early postoperative health status of patients,[24] but still much needs to be done.

There has been synergism of psycho-behavioral changes in early and intermediate post-operative period when propofol was administered as induction and sevoflurane as maintenance agent (combination group PS). In same group, GTCS and sexual fantasies (female patient) were noted in a few patients in intermediate post-operative period. But there was delayed recovery of the female patients in the early post-operative period as compared to propofol. No psycho-behavioral changes have been noted in the late post-operative period in any of the three groups.

CONCLUSION

From our study, we conclude that:

Propofol as a sole anesthetic agent leads to faster recovery (awakening) in females but in combination with sevoflurane shows synergism for hypnotic effect causing delayed recovery in females

Sevoflurane, propofol, and their combination have various effects on the psychological profile and behavioral pattern of the patients in the early and intermediate post-operative period but not in the late post operative period

In the combination group i.e., Group PS, though there is synergism of desired anesthetic effect leading to reduced dose requirement but there is also synergism of hypnotic and other side effects

As a result of significant number of female patients having psycho-behavioral effects, especially of sexual nature, after administration of propofol, counseling may be required in these patients.