The impact of Bispectral Index monitoring on sedation administration in mechanically ventilated patients.
The aim of this prospective randomised controlled trial was to assess the effectiveness of the Bispectral Index (BIS) monitor in supporting clinical sedation management decisions in mechanically ventilated intensive care unit patients Fifty adult mechanically ventilated surgical and general intensive care unit patients receiving sedative infusions of morphine and midazolam were randomly allocated to receive BIS monitoring (n=25) or standard sedation management (n= 25). In the BIS group, sedation was titrated to maintain a BIS value of greater than 70. In the standard management group, sedative needs were titrated based on subjective assessment and clinical signs
There was no statistically significant difference in the amount of sedation administered (morphine P= 0.67 and midazolam P= 0.85). However, there was a statistically significant difference in sedation administration over time. Patients in the BI S group received increasing amounts of sedation over time whilst those in the control group received decreasing amounts of sedation over time. The same inverse relationship existed for both sedative agents (morphine P= 0.005, midazolam P= 0.03). Duration of mechanical ventilation was comparable in the two groups We conclude that the use of BIS monitoring did not reduce the amount of sedation used, the length of mechanical ventilation time or the length of ICU stay.
Key Words: bispectral index, sedation, intensive care, critical care, nursing, mechanical ventilation
Sedation is used in almost all mechanically ventilated patients to minimise perceptions of and stress responses to anxiety and pain. Optimal sedation for critically ill patients however, remains a challenge and many intensive care unit (ICU) patients are at risk of being under- or oversedated (1). Several sedation scoring systems have been developed to assess depth of sedation and promote optimal management (2-4). Sedation scoring systems however, contain some inherent limitations. Considering their subjective nature, they are prone to inconsistencies with inter-rater reliability and many have not been rigorously tested and validated (4,5). Their effectiveness may also be limited in the more deeply sedated patients and those receiving neuromuscular blockade (5). To optimally monitor sedation levels, Bispectral Index (BIS) monitoring has been gaining increasing interest and may be useful, given its objectivity and replicability (6-8). The BIS is a continuous, processed electroencephalographic (EEG) measurement designed to measure cerebral activity and monitors the electrophysiological effects of sedatives and anaesthetics (9). As such, the BIS monitor provides a numeric value (0-100, with lower values indicating a lower level of consciousness) that reflects the patient's level of sedation and allows clinicians to titrate and manage sedation based on the desired objective value. Studies of ICU patients show that BIS values below 60 indicate the presence of deep sedation (11) and an average BIS score with a mean value of 66 correlated to a Sedation Agitation Scale (SAS) score of 1-2 (unarousable to very sedated) while an average BIS score with a mean value of 81 correlated to an SAS score of 3-5 (sedated to agitated) (P=0.001) (6).
We performed a prospective randomised control trial to assess the effectiveness of the BIS monitor in supporting clinical sedation management decisions in mechanically ventilated ICU patients. The study aimed to investigate the impact of BIS monitoring on the amount and timing of sedative administration in ventilated patients. We hypothesised that patients receiving BIS monitoring would receive less sedation than those receiving standard ICU sedation assessment and management, and that this would lead to a reduction in duration of mechanical ventilation.
MATERIAL AND METHODS
After obtaining institutional research ethics committee approval and delayed written informed consent from the patient's next of kin, 50 eligible patients were enrolled. Participants randomised to the intervention group (n=25) received BIS monitoring and the control group (n=25) received the standard ICU sedation assessment and management. Patients in the BIS group had their sedative requirements titrated based on the BIS readings. Sedation was adjusted to maintain a BIS value of greater than 70. Patients randomised to receive BIS monitoring were continuously monitored until they were extubated or a tracheostomy was performed. Patients randomised to the control intervention received standard care. This was based on conducting twice daily clinical ward rounds where sedative needs were assessed and prescribed by physicians and nurses were responsible for titrating sedation according to the goal of sedation and the patient's response to medication. Nurses in this group adjusted the sedation primarily based on subjective clinical assessments, utilising traditional clinical signs (heart rate, blood pressure, conscious level, pupillary size). Sedation scoring using the Motor Activity Assessment Scale is also recommended as part of standard practice within the unit; however, prior to commencing the study we observed poor compliance among clinicians in utilising this assessment tool. Hence, its use in the control arm was not mandated.
Patients were randomised using sealed opaque pre-coded envelopes. Enrolment criteria were: intubated and mechanically ventilated; likely to be ventilated for greater than 12 hours and receiving continuous intravenous sedation of morphine and midazolam. Exclusion criteria were intracranial injury or neurological disorder and facial burns. These exclusion criteria were chosen because the EEG is affected by neurologic derangements (13) and BIS readings can decrease with neurological disorders (14), and it is difficult to apply a sensor to a patient with facial burns. All eligible patients were recruited within 24 hours of admission to ICU.
The BIS was measured using an Aspect XP 3.0 monitor connected to a BIS sensor (Aspect, U.S.A.). The sensor (Quatro ZIP Prep four electrode) was applied to the patient's forehead based on the manufacturer's recommendations. Before starting recording, we verified that the electrical impedance was within the valid range. Signal Quality Index (SQI) was continuously monitored and maintained greater than 50% and electromyographic activity was also continuously monitored and maintained at less than 55 db. The BIS readings were continuously displayed on the monitoring screen. To ensure the accurate and consistent use of BIS monitoring equipment among nurses, an intervention tool was developed, based on recommendations from the manufacturers (10). The tool specified how BIS should be used (impedance tests, change of contacts etc), when to record the BIS score and what the readings reflect. A value of 0-40 is considered to reflect a deep hypnotic state, 40-60 general anaesthesia, 70 deep sedation, 80-90 light to moderate sedation and 100 is an awake state (10). BIS readings were recorded hourly until the participants were extubated or received a tracheostomy.
The following demographic data items were recorded for all participants: APACHE II on admission: diagnostic category; body mass index; gender; age; sedative agent administration; analgesia administration (dose, mode and time of delivery). In addition, duration of mechanical ventilation and duration of ICU stay were recorded for all study participants.
With 25 subjects per group, this study had an 80% power to detect a difference in any continuously normally distributed outcome, equivalent to 80% of one standard deviation with a two-sided P value of 0.05. A difference of this magnitude was considered likely to be of clinical importance.
Statistical analysis was conducted using SAS version 8.2 (SAS Institute Inc., Cary, NC, U.S.A.) Comparisons of proportions between groups were made using chi square tests for equal proportion, whilst continuous variables were compared using Student's t test and validated using Wilcoxon rank sum tests. The distribution of sedative agents (morphine and midazolam) was found to be well approximated by a log-normal distribution and was log-transformed prior to analysis, with results presented as geometric means with a 95% confidence interval. The relationship between sedation over time was assessed using generalised linear modelling accounting for repeat measures and adjusted for confounding variables. Results for normally distributed outcomes are presented as mean (standard deviation), log-normally distributed outcomes as geometric mean (95% confidence interval) and non-parametric outcomes presented as median (interquartile range). A two-sided P value of 0.05 was considered to be statistically significant.
Fifty patients were enrolled in the study, of whom 33 (66%) were male. Two patients' next of kin refused to provide assent for the study and one patient withdrew consent. The mean age was 53 years and the median APACHE score was 14. Patients were classified into one of four diagnostic categories: trauma (40%), medical (30%), surgical (16%) and cardiothoracic (14%). The demographics for both groups were well matched, revealing no significant difference between variables (Table 1).
There was no significant difference in the amount of sedation administered to the BIS and non BIS patients (Table 2). However, there was a significant difference in sedation administered over time. Patients in the BIS group received increasing amounts of sedation over time whilst those in the control group received decreasing amounts of sedation over time. The same inverse relationship existed for both agents--morphine P=0.005 (Figure 1) and midazolam P=0.03 (Figure 2).
There was no significant difference in the length of time patients were mechanically ventilated in the BIS and non BIS groups. The mean time of ventilation in the BIS group was 7.0 days (SD 0.6) compared with 7.0 days (SD 0.8) in the non BIS group (P=0.71).
There was no significant difference in ICU length of stay between the BIS and non BIS groups. The median ICU length of stay in the BIS group was 12 days (6-18) compared with 8 days (4-14) in the non BIS group (P=0.20).
Using generalised linear modelling, patient age and APACHE score had some impact on the amount of sedation administered (age P<0.0001, APACHE P=0.03). As the age of the patient increased, the amount of sedation decreased. The greater the APACHE score, the greater the amount of sedation.
The primary aim of this study was to investigate the impact of BIS monitoring on the amount of sedative administered in mechanically ventilated patients in the ICU. We were unable to demonstrate a significant difference in the amount of sedation (morphine and midazolam) administered to patients in each study group. However, there was a significant difference in the trend of sedative administration over time. Perhaps worryingly, patients in the BIS group received a relative increase in morphine and midazolam the longer they were in ICU, while those in the clinical assessment group received decreasing amounts of morphine and midazolam over time. Mechanical ventilation time and length of ICU stay were comparable in the two groups.
Several factors, including the presence of high electromyographic activity and subsequent EEG signal pollution, may account for the oversedation of BIS patients in ICU (8,15-17), however, we are unable to provide an adequate explanation for patients in the non BIS group receiving less sedation over time. There may be three issues underlying this finding: (1) increased drug tolerance over time (18), resulting in requirement for greater sedation when level of sedation is measured using BIS; (2) clinician concerns about drug dependence (19), resulting in under-sedation (in the non-BIS group) in the absence of an objective sedation score; and (3) clinicians' concerns about accumulation of sedative agents and their metabolites.
Our results suggest that BIS monitoring may be no better than subjective clinical assessments in the management of sedation administration. In fact, placing the emphasis on an objective score may diminish the importance of subjective assessments. While BIS monitoring assesses the depth of sedation, it does not account for patient need. For instance, patients whose condition is improving need less sedation: monitoring sedation with BIS would not take this into account.
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Previous research utilising BIS monitoring in the ICU has focused on correlation studies comparing clinical sedation scales with BIS readings. Such correlation studies have produced variable results with an overall modest correlation with clinical sedation scales such as the Ramsey sedation scale and SAS (6-8,16). There is a paucity of data available regarding the actual impact of BIS monitoring on sedation management and patient outcomes in the ICU. Olsen (20) examined the impact of BIS monitoring on rates of propofol administration in neurologically impaired patients and found that BIS monitoring led to an overall decrease in rates of propofol administration. It is difficult, however, to compare findings considering the methodological/sample differences between the two studies.
There are two main limitations in this study. The nature of BIS monitoring meant that we excluded patients with neurological conditions or intracranial injury. Similarly we excluded a subset of patients who often require greater levels of sedation (burns patients). We do not know how an objective score would have influenced sedation management in these groups of patients. Sedation management for patients in the control group could also be considered variable. However, discussion with colleagues in different ICUs confirms our belief that this variation in sedation management is indeed common practice for most Australian ICUs.
In conclusion, we demonstrate that the use of BIS monitoring was not helpful in allowing reduced sedative drug requirements in a heterogenous group of ICU patients and in fact may increase the use of these drugs over time. Perhaps future studies need to target specific groups of ICU patients that typically require larger amounts of sedation, such as burns patients.
This study received funding from the Australian College of Critical Care Nursing Ltd. and Abbott Australasia. Sensors were provided by Aspect Medical Systems (U.S.A.). BIS monitors were loaned by Philips Medical Systems and were returned at the end of the trial. The supporters of this study had no role in the study concept, design, data collection, data analysis, data interpretation or writing of the reports.
We would like to thank Carlos Scheinkestal for assistance with study design and manuscript review. We would also like to thank Andrew Davies, Lisa Higgins, Daryl Jones and Jamie Cooper for manuscript review.
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C. Weatherburn *, R. Endacott ([dagger]), P. Tynan ([double dagger]), M. Bailey ([section]) Intensive Care Unit, The Alfred Hospital and Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
* C.C.R.N., M.A., Research Co-ordinator and Critical Care Nurse, Intensive Care Unit, The Alfred Hospital.
([dagger]) M.A, Ph.D., Professor of Critical Care Nursing, Intensive Care Unit, The Alfred Hospital.
([double dagger]) C.C.R.N., B.N., ICU Clinical Educator, Intensive Care Unit, The Alfred Hospital.
([section]) Ph.D., M.Sc. (Statistics), B.Sc. (Rons.), Statistical Consultant and Senior Research Fellow, Department of Epidemiology and Preventive Medicine, Monash University.
Address for reprints: C. Weatherburn, Intensive Care Unit, The Alfred Hospital, 89 Commercial Road, Melbourne, Vic. 3181.
TABLE 1 Patient demographics BIS Non BIS P value (n=25) (n=25) Mean age (SD) 56.8 (20.7) 49.8 (21.8) 0.26 Median APACHE II (IQR) 14 (11-19) 14 (11-20) 0.82 Male (%) 64% 68% 0.78 Cardiothoracic (%) 8% 20% 0.23 Medical (%) 36% 24% 0.36 Surgical (%) 24% 8% 0.13 Trauma (%) 32% 48% 0.26 Body mass index (SD) (kg/[m.sup.2]) 28.5 (6.5) 27.1 (6.1) 0.4 BIS=Bispectral Index, IQR=interquartile range. TABLE 2 Total sedative amount in the BIS and non BIS patients (n= 50) Group Sedative Total daily dosage, mg P value mean (range) BIS Morphine 22.6 (14.9-34.5) 0.67 No BIS Morphine 26.6 (17.5-40.4) BIS Midazolam 18.4 (10.9-30.9) 0.85 No BIS Midazolam 14.6 (8.8-24.0) Data are presented as geometric mean with 95% confidence intervals (CI). BIS =Bispectral Index.
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|Author:||Weatherburn, C.; Endacott, R.; Tynan, P.; Bailey, M.|
|Publication:||Anaesthesia and Intensive Care|
|Article Type:||Clinical report|
|Date:||Apr 1, 2007|
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