Conscious awareness with recall is a persistent complication of general anaesthesia (GA). Adequate application of technology with awareness of its limitations in order to reduce complications associated with GA is the keystone  . In order to achieve this, monitoring the depth of anaesthesia is of great importance  . Unlike the administration of adequate analgesia, the measureable end-points for adequate anaesthesia are not well described. The only reliable endpoint for consciousness is absence of response to a voice command, but this does not distinguish light from deep sleep  . Achieving adequate depth of anaesthesia during surgical procedures is desirable. Deep level of anaesthesia, resulting in cardiovascular depression (easy to detect) and prolonged awakening times (rather harmless), is of minor clinical interest, while light anaesthesia is difficult to detect and disturbing from the patients’ point of view. Therefore, assessment of the depth of anaesthesia is fundamental to anaesthetic practice  . Several monitoring devices based on the principle of passively processed EEG have been developed out of which the Bi-spectral index Scale™ (BIS) and the A-line ARX-In- dex (AAI) are two such scales. BIS shows good correlation with behavioural assessment of level of consciousness while studies have shown mid-latency auditory evoked potentials (MLAEP) in AAI to have high sensitivity and specificity with level of sedation during anaesthesia  . Volatile inhalational agents like Isofluorane reduce the amplitudes of MLAEPs and increase their latency in a dose-dependent fashion. AAI has been derived from auditory evoked potential (AEP) and represents as a single numerical variable of the depth of anaesthesia  . AAI is highly sensitive for distinguishing the transition from unconsciousness to consciousness. This study aimed at using AEP monitor/AAI scale to titrate depth of anaesthesia in neurosurgical population for reducing the utilization of isoflurane and concurrently demonstrating the cost sparing effect of AEP without jeopardizing the anaesthetic technique, the surgery or the patient outcome.
The study was conducted at a Tertiary care hospital which serves as a referral institution for a large number of hospitals in the region. The duration of the study was from 15 May 2007 to 14 May 2008. The study design was an observational analytical prospective cohort. The patient population was consecutively admitted neurosurgical patients aged more than 15 years requiring GA including intubation and neuromuscular blocking agents (NMBA).After obtaining written informed consent the enrolled patients were allocated to one of two groups: Group 1 or Group 2 and assessed for intra-operative awareness, Post-operative recovery and Utilisation of Isofluorane. (Figure 1) Exclusion criteria were patients with history of deafness, mental subnormality, alcohol or drug dependence, previous history of head injury, any other neurological disorder, ASA class III patients, duration of surgery < 90 min to >150 min or duration of maintenance period of anaesthesia < 45 min or >90 min. The study had been
Figure 1. Flow of participants.
approved by the institutional ethics committee. All enrolled patients underwent a detailed history and physical examination before being enrolled in the study. Patients in Group 1 were monitored for conventional parameters like Heart rate (HR), Pulse oximetry (SpO2), Non-invasive blood pressure (NIBP), End-tidal carbon-di-oxide (EtCO2), Temperature (Temp) and Electrocardiogramme (ECG). The fluid intake, urine output, presence of lacrimation and sweating were monitored. In addition the administered dose of Isofluorane was recorded throughout the anaesthesia which maintained the patient with stable haemodynamic status and lack of awareness. Patients in Group 2 were monitored additionally for
anaesthetic depth and for monitoring of intraoperative awareness, to describe the post-stimulus MLAEP latencies and amplitudes as waveforms and as
3. Sample Size and Statistical Analysis
In order to identify a clinically relevant and a statistically significant difference in the intra-operative awareness level and maintenance of depth of anaesthesia at a pre-determined value of end-tidal concentration of Isofluorane, a minimum number of 30 patients were required in each group. A total of 60 patients were enrolled in the study and equal numbers were randomly allotted to Group 1 or Group 2. To detect the ability of AEP monitor (AAI scale) to titrate the depth of anaesthesia and reduce the intra-operative awareness, the haemodynamic response of the 2 groups were pooled group and compared to each other (Group 1: control; Group 2: with AEP monitor). Post-operative variables (eye opening, head lift, motor activity, and post-operative recovery time) were recorded and the pooled data of Group 1 was compared with Group 2. For all numerical continuous variables the mean was recorded and variance was described as Standard Deviation (SD). For all dichotomous categorical variables median and inter-quartile ranges (IQR) were calculated. Haemodynamic responses as a measure of intra-operative awareness/ depth of anaesthesia were compared between the 2 groups using Student’s t-test, Chi-square test or the Fishers exact test as appropriate. Using two sample t-test cost analysis of expense of isoflurane was done. The pooled data of the concentration of Isofluorane given was used in Dions formula to derive per patient and per minute cost of Isoflurane  . Data was analysed using statistical software SPSS 17.0. P-value < 0.05 was considered statistically significant.
Sixty neurosurgical patients with anticipated duration of surgery between 90 - 150 min were enrolled for the study. Thirty patients were allocated to Group 1 and a similar number were allocated to Group 2. Males outnumbered the females in both groups [Group 1: males n = 25 (84%), females n = 5 (16%)] [Group 2: males n = 27 (89%), females n = 3 (11%)]. The age of the patients in Group 1 ranged from 18 yrs to 62 yrs while in Group 2 it ranged from ranged from 23 yrs to 65 yrs. All other operative and anaesthesia parameters are summarized (Table 1). There was no significant difference in the intraoperative haemodynamic responses measured between the two study groups (Table 2). There was no significant difference in the identification of intraoperative aware-
Table 1. Baseline and operative characteristics of the study groups.
SD = Standard deviation.
Table 2. Intra-operative haemodynamic responses measured between the two groups.
EtCO2 = End-tidal carbon-di-oxide, DBP = Diastolic blood pressure, SpO2 = Oxygen saturation, SBP = Systolic blood pressure, SD = Standard deviation.
ness using the conventional parameters between the two groups (Table 3(a)). There was no significant difference in the rate of fresh flow of gases between the 2 groups. However there was a significantly lesser consumption of Isofluorane in Group 2 as compared to Group 1 (Table 3(b)). There was also a significant difference in the post-operative recovery variables, with a significantly faster time to recovery for patients in Group 2 (Table 4).
Even though the knowledge about the mechanisms of general anaesthesia has increased considerably since its introduction in clinical practice, it is unknown how anaesthetics prevent consciousness  . This study was undertaken to study the usefulness of AEP monitoring in a neurosurgical population, with focus on intraoperative awareness by titrating the depth of anaesthesia and using it to reduce the patient Isofluorane consumption. In several studies AAI have been shown to reduce the amount of anaesthetics given and expedite immediate postoperative recovery as compared to standard practice   . A number of studies have also demonstrated that the sensitivity and specificity for AAI is not perfect   and fears have been raised that the incidence of awareness might even increase if the anaesthetist aims at an upper threshold value   .
In our study, in group 1, the effect of conventional monitoring on the incidence of awareness was investigated in clinical routine. In group 2, AEP hypnosis monitor using AAI was investigated and evaluated during general anaesthe-
Table 3. (a) Comparison of Intra-operative awareness between the study groups; (b) Comparison of Isofluoraneutilisation and cost between the study groups.
FGF = Fresh flow of gas.
Table 4. Post-operative recovery using the Aldrete scale in the study population.
sia. According to Kalkman and Drummond  , MLAEP are almost completely suppressed soon after loss of consciousness. Many studies have suggested that derivatives of MLAEP like AEP are better discriminators than BIS in tracing the transition from awake to the anaesthetized state   titrating depth of anaesthesia and detecting intra-operative awareness.
The absence of haemodynamic response in patients does not necessarily include absence of intra-operative awareness. Haemodynamic variables are known to be poor indicators of the hypnotic state  and our study also shows similar results. The relation of haemodynamic variables to arousal was also not found to be consistent similar to findings by other researchers     . Our study demonstrated that AEP reflected as the AAI scale is a valid tool for ascertaining the depth of anaesthesia and the AEP index is easy to calculate and all the calculations are real time. The present study was designed to evaluate the cost sparing effect of AEP monitor showing that its use resulted in a significantly lesser utilisation of Isofluorane as compared to intra-operative depth ascertainment by conventional technique. The cost analysis study carried out showed that the AEP monitor was not only useful in reducing the per patient cost of the anaesthetic agent used, isoflurane (Figure 2(a)), but also the per minute cost (Figure 2(b)). AEP use resulted in a significantly lesser utilisation of
Figure 2. (a) Cost per patient; (b) Cost per minute.
Isofluorane as compared to intra-operative depth ascertainment by conventional technique. The study also showed a significantly faster recovery time in patients given anaesthesia with AEP monitoring compared to control group. Using AEP/ AAI not only was there a better titration of anaesthesia but also significant reduction in the post-operative stay in the PACU. A significant difference (P < 0.05) in all the postoperative parameters was recorded in the PACU between the two groups with a significantly shorter post-operative recovery time in the patients of the group 2.
The limitation of this study was that using evoked potentials to monitor depth of anaesthesia entails technical, clinical and practical complexities and many confounding factors can alter these potentials such as stimulus characteristics (intensity, duration, inter-stimulus interval), electrode placement technique, age and gender of the subject and choice of anaesthetic drugs. Also since the overall incidence of awareness in the general population is very low, a larger sample size may be able to identify a statistically significant difference.
Our study showed that AAI reduced the amount of anaesthetics given and expedited the postoperative recovery as compared to standard practice. AEP monitoring during general anaesthesia including an NMBA reduced the incidence of awareness as compared to standard monitoring and has been used clinically to titrate the depth of anaesthesia and to reduce the risk of intraoperative awareness leading to less anaesthetic drug use and faster and improved recovery from PACU.
In conclusion, this study demonstrates that hypnosis monitoring can reduce the incidence of awareness with better titration of depth of anaesthesia, decrease the incidence of post-operative nausea and vomiting, and ensure faster recovery from post anaesthesia care unit without compromising on the anaesthetic technique, the surgery or the patient outcome.
KT conceived and designed the study. KT and TVSP acquired the data, managed the cases and analysed the data. KT drafted the article. All of the authors were involved in patient management. All authors approve the final manuscript.
The authors declare no source of financial support.
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