Awareness during general anesthesia: An Indian viewpoint.

BACKGROUND AND AIMS: The incidence of intra-operative awareness with explicit recall in the Western world has been reported to be between 0.1% and 0.2% in the general surgical population and up to 1-2% of patients at high risk for this complication. Awareness in the Indian population has never been studied; we therefore wanted to detect the incidence of awareness in patients who were at high risk of experiencing awareness during surgery in our population.
MATERIAL AND METHODS: We conducted a prospective single-center observational study at a 600-bedded tertiary cancer care referral hospital. We recruited adult patients posted for major cancer surgery who were considered to be at high risk for awareness. These patients were interviewed at three time-points using the structured modified Brice interview questionnaire. The primary outcome studied was the incidence of definite intra-operative awareness.
RESULTS: A total of 934 patients were included in the final analysis of which none reported awareness. Using the rule of three (Hanley and Lippman-Hand) we conclude that the upper 95% confidence interval for the incidence of awareness in this population is <1 in 300 (0.33%).
CONCLUSION: Awareness under anesthesia is a distressing complication with a potential for long-term psychological consequences, and every effort should be undertaken to prevent it. It is reassuring though that our data in Indian cancer patients at high risk for intra-operative awareness suggests that it is an uncommon occurrence.

Introduction

Awareness during general anesthesia is an infrequent but serious problem with potential long-term psychological consequences for the patient and medico-legal implications for the anesthetist.[1] The incidence of awareness has been reported to be between 0.1% and 0.2% in the general surgical population in the Western world.[23] Patients undergoing cesarean section, cardiothoracic surgery or emergency surgery, patients with a difficult airway and those developing intra-operative hypotension are among those considered to have increased chances of awareness and the incidence in this group may be as high as 1–2%.[4] Cancer patients undergoing major surgery may have many of these risk factors (for example, difficult airway in head and neck cancer patients and radical surgery with massive blood loss) predisposing them for awareness under anesthesia. The incidence of awareness may vary among patient population due to differences in genetic make-up and anesthesia technique.[5] Awareness in the Indian population has never been studied; hence, we prospectively evaluated the incidence of awareness in cancer patients population would be no higher than 3%, which is the reported incidence in the Western world.

Material and Methods

We conducted a prospective single-center observational study at a 600-bedded tertiary cancer care referral hospital. The Institutional Review Board approved this study prior to commencement.

We recruited adult patients posted for major cancer surgery who were considered to be at high risk for awareness. These included patients receiving one lung ventilation (thoracic surgery, use of high oxygen concentrations), patients undergoing emergency surgery (hemodynamically unstable), receiving air/oxygen intra-operatively (avoiding nitrous oxide), unanticipated difficult airway (difficulty in maintaining adequate depth of anesthesia), and intra-operative hypotension (requiring reduction of anesthetic depth).[3678] In all the patients recruited in this study, an additional common and significant risk factor for accidental awareness under general anesthesia was the use of neuromuscular blockade.[9] Exclusion criteria for this study were refusal of consent, ongoing psychiatric medication, altered sensorium, and language barrier.

This was a pragmatic study with no change in routine clinical practice. The choice of anesthetic agents, muscle relaxants, and perioperative analgesia was left to the discretion of the theater anesthetist. Being a tertiary care cancer center, all the cases in our institution are managed by anesthesia residents in training supervised by qualified anesthesia consultants. All patients received balanced anesthesia (induction with induction agents, opioids and muscle relaxant with maintenance of anesthesia with opioids, muscle relaxants and halogenated agents) with or without regional technique depending on the surgery and the theatre anesthetist. Over the whole study period, anesthesia technique remained consistent. Mandatory intra-operative monitoring included continuous electrocardiogram monitoring, pulse oximetry, capnography and noninvasive blood pressure; in addition, invasive blood pressure monitoring was instituted where considered necessary. None of the patients had bispectral index (BIS) monitoring; however, respiratory gas monitors were available in most cases to measure end-tidal anesthetic concentration (ETAC). Based on the inclusion criteria, patients at high risk for awareness were identified at the end of the surgery by questioning theater anesthetists. These patients were interviewed by our project nurse at three time-points, immediate postoperative, at 24 h and on day 7 postoperative or on discharge (whichever was earlier) during their postoperative hospital stay using a simple structured questionnaire (modified from Brice et al. Appendix 1).[10] Evaluation of awareness was based upon these three interviews. The primary outcome measure was the incidence of confirmed awareness, which was defined by the patient's recollection of intra-operative events during any of the interviews using the structured questionnaire. Consent was taken at the 24-h interview (delayed consent), and any patient who refused consent was excluded, in the final analysis. All patients who were suspected to have awareness as per interview were to be re-interviewed by an independent reviewer to confirm the diagnosis of awareness. Definite awareness was defined as occurring when the patient was certain of having been aware at any time during the operation. Awareness was considered as possible in those cases where the patient thought he had been awake during surgery, but was not completely sure. These definitions were based on a previous study by Errando et al.[4] In case of awareness being detected, there was support arranged from in-hospital psychologist for counseling of affected patients.

Patients who were mechanically ventilated/died in the postoperative period which resulted in a missed interview were excluded in the final analysis.

Statistical considerations

The incidence of awareness in high-risk population has been reported to be between 1% and 2%.[4] A sample size of 850 would allow us to detect an incidence of 3% (with a 1.1% margin of error) with 95% confidence. To account for protocol deviations and losses to follow-up, we planned to accrue 1000 patients. Data were entered into statistical software (SPSS 18.0, SPSS Inc., Chicago, IL, USA) for analysis. Descriptive statistics was used to report results.

Results

Between March 2009 and September 2011, a total of 15,554 patients underwent surgeries of which 1030 patients were eligible to participate in this study. Of these, 934 patients were included in the final analysis. Of the 96 patients that were excluded, 63 refused consent, and 33 could not complete all the three interviews as they were either ventilated in the postoperative period or did not survive.

Figure 1 and Table 1 summarize the characteristics and the details of the included patients. None of the 934 patients reported awareness. Using the rule of three (Hanley and Lippman-Hand) we conclude that the upper 95% confidence interval for the incidence of awareness in this population is <1 in 300 (0.33%).[11] In statistical analysis, the rule of three (as proposed by Hanley) states that if a certain event did not occur in a sample with n subjects, 0–3/n is the 95% confidence interval for the rate of occurrences in the population. The accuracy of this estimation is more when the sample size (n) is more than 30.

Figure 1

Study flow chart of included patients

Table 1

Patient characteristics

Discussion

Awareness is caused by the administration of general anesthesia that is inadequate to maintain unconsciousness. This could be due to various factors, patient and surgical factors which necessitate a deliberate reduction in depth of anesthesia. Another contributory mechanism could be pharmacogenetic factors resulting in variability in anesthetic dose requirement among patients. Patients undergoing major surgery for cancer would be expected to have an increased incidence of awareness because of multiple predisposing factors such as extensive surgery with major blood loss, one-lung ventilation in thoracic surgery and unanticipated difficult airway in head and neck cancer.[4] However, our study failed to demonstrate awareness under general anesthesia in this patient group.

Within this population, sub-groups of patients who were considered to be having independent risk factors for awareness such as sicker patients (American Society of Anesthesiologists physical status III-V), female gender and younger patients (age <40 years) also did not report awareness.[41213]

We found that the incidence of awareness in this group of patients is likely to be <0.33% and would therefore possibly be even lower in patients without these risk factors. Previous studies on awareness among Caucasian patients have determined the incidence to be between 1 and 2 in 1000 in the general population to as high as 1–2 in 100 patients in high risk for awareness.[234] One possible explanation for this difference between our study and the published data could be a variation in anesthetic techniques. All the patients in our study received inhalation-based balanced anesthesia and in most, respiratory gas monitor with ETAC measurement formed a close alternative measure of the pharmacodynamic effect of general anesthesia. The inter-patient variability with respect to adequate dose requirement might be less with the use of inhalational anesthetics with ETAC, when compared to total intravenous anesthesia (TIVA).[14] There is also evidence that TIVA may predispose patients to awareness compared to inhalational anesthetics with measurement of ETAC.[2491516] In addition, there has been speculation about the influence of genetics and ethnic differences on anesthetic requirements; this may have also contributed to the low incidence of awareness in our study as compared to western population.[517]

One of the difficulties in identifying the true incidence of awareness is that it is a patient-reported outcome and, therefore, the detection of awareness can be subjective and also depends on the timing and structure of the interview. To minimize bias, we used a structured interview that has been utilized in prior studies to detect awareness.[2410] We also planned for re-interviews of potential cases of awareness by an independent investigator. We chose three time-points for interviews as approximately 35% of cases are detected only at a delayed postoperative interview.[18] The strength of this study is that the study design involved no change in routine anesthetic care. This ensured that the results of the study would be applicable to day-to-day practice. An important consideration is that although some patients are able to report awareness immediately postsurgery, others may not realize that they were aware until days or even weeks after the event. One of the limitations of this study is that for logistic reasons, we were not able to follow patients beyond hospital discharge. In addition though ETAC measurement was available in most cases, their values (ETAC below the recommended levels) were not recorded in the case report form, as our aim was to determine only the incidence of awareness in our population. As this study was conducted in a highly selected group of cancer patients at a tertiary care cancer center, the results of this study cannot be extrapolated to all surgical patients.

Over the past years, techniques to monitor depth of anesthesia have evolved. Several brain-function monitors based on the processed electroencephalogram or evoked potentials have been developed to assess anesthetic depth. It has been recommended that BIS monitoring should be used in patients at increased risk of awareness undergoing general anesthesia with muscle relaxant to decrease the incidence of awareness.[3] A large randomized controlled trial conducted in over 20,000 unselected surgical patients demonstrated that BIS monitoring may decrease intra-operative awareness when compared with routine care.[19] In contrast, in the B-Unaware and the BAG-RECALL trials, the superiority of BIS over ETAC monitoring for the prevention of awareness was not established.[2021]

We conclude that despite concerns among anesthetists about under-reporting of awareness, our data in Indian cancer patients at high risk for intra-operative awareness suggests that it is an uncommon occurrence.