Several advances are likely to benefit the intensive care unit (ICU) patient requiring sedation, analgesia and anxiolysis. Sedatives continue to be used on a routine basis in critically ill patients and they require continuous reassessment of the level of sedation. The routine use of standardized and validated sedation scales and monitors are needed.
The bispectral index (BIS™) which is a monitor of cortical suppression may be used to maintain the optimal level of sedation and hypnosis . In a study by Rubenstein  the BIS monitor  was found to be a useful monitoring guide for the titration of propofol to achieve deep sedation for children. Assessing the degree of sedation can be difficult in mechanically-ventilated patients with whom communication is invariably limited. The use of sedation scales is the most frequently used method of quantifying the sedative effect. More than 25 sedation instruments have been described, yet none is universally accepted. The Richmond agitation sedation scale (RASS)  has been validated in ICU patients. The ideal agent should satisfy the physician's desire for an effective, safe, titratable, cheap and rapidly acting drug that has both sedative and analgesic properties, and should also prevent anxieties and unpleasant memories for the patient . The α2 agonist dexmedetomidine is a new sedative and analgesic agent which is being used for sedation in ICU for up to 24 h after surgery. Dexmedetomidine provides haemodynamic stability and appears to have no clinically important adverse effect on respiration . We aimed to assess the correlation of BIS with RASS during dexmedetomidine sedation and evaluate the use of BIS to monitor levels of sedation in ICU patients.
Our hospital Ethics Committee approved the study and written informed consent was obtained from each patient. Eleven adult patients (18-yr or older) were investigated. Patients who were expected to undergo a minimum of 8 h artificial ventilation after thyroidectomy with sternotomy were included in the study. On arrival at the ICU, patients received a loading infusion of dexmedetomidine 1 μg kg−1 over 10 min followed by a maintenance infusion of 0.5 μg kg−1 h−1 for 8 h. The efficacy of sedation was assessed and recorded hourly using the RASS  (Table 1) and continuously monitored with BIS. The BIS electrodes were placed on the forehead and were connected to an A-2000 BIS monitoring system (Aspect Medical Systems, Framingham, MA, USA). Electrode sites were abraded using conventional alcohol swabs. A BIS of 60–80 was considered the target range for sedation. Clinical data including age and gender were recorded. Heart rate (HR), arterial pressure (systolic), respiratory rate and SPO2 were also monitored. Clinical and laboratory data were collected for the 24 h period and APACHE II and SOFA scores were determined. No other sedative or analgesic agent was given, and no patient received spinal or epidural analgesia in the perioperative period. Patients were ventilated mechanically with oxygen-enriched air to attain blood gases in the following ranges: pH 7.35–7.55, PO2 11.3–26.6 kPa, PCO2 3.72–5.32 kPa. Following discontinuation of the sedative infusion and when the patient was alert, cardiovascularly stable, normothermic with an arterial oxygen tension ≥11.3 kPa while inspiring an oxygen concentration below 40%, positive end-expiratory pressure <5 cmH2O, a tidal volume of >6 mL kg−1, and a respiratory rate between 10–20 breaths min−1 extubation was undertaken.
Statistical analysis was undertaken with SPSS for Windows version 10.0 paired t-tests were used for the comparison of the data. RASS and BIS data are shown as mean (±SD) as well as interquartile range and comparisons were made using the Wilcoxon signed rank sum test. The Spearman's rank correlation was used for the correlation analysis between RASS and BIS. P < 0.05 was accepted as statistically significant.
Eleven mechanically-ventilated critically ill patients, aged 50.1 ± 17.8 (17–82) (mean ± SD (range)) years, 3 males and 8 females, APACHE II score 12.6 ± 3.9 (7–20) and SOFA score 3.3 ± 1.7 (0–6) were studied. The range of RASS score was between 0.9 and −1.7. BIS varied from 65 to 75. Significant correlations between RASS and BIS values were found (r = 0.9; P = 0.0001) (Fig. 1).
A fall in HR was significant at 2 h (P < 0.05) and very significant at the other study times (P < 0.001) when compared with baseline HR. A fall in systolic arterial pressure was significant in all measurements with one exception baseline (P < 0.05) (Table 2). No significant change was detected in HCO3, PO2, base excess, PCO2 and SaO2 (Table 3). FiO2, tidal volume, plateau and peak pressures and respiratory rate did not change significantly between the first and eighth hours (Table 4).
Sedatives continue to be used on a routine basis in critically ill patients. We mostly use dexmedetomidine for sedating our patients in ICU. It has proved to be a good sedating agent in critically ill patients requiring mechanical ventilation but it may cause sympatholysis via central and peripheral mechanisms . Patients receiving a dexmedetomidine infusion at 1 μg kg−1 h−1 had significantly lower HRs compared to control . We used dexmedetomidine at 1 μg kg−1 h−1 for 10 min and then lowered it to 0.5 μg kg−1 h−1. As in other previously published data, it caused a significant fall in HR and blood pressure but no detrimental effect on haemodynamics.
Sedation therapy should be guided by subjective or objective assessment in order to avoid over or undersedation . Oversedation may cause prolongation of mechanical ventilation or disturbance of haemodynamics, whereas inadequate sedation may also be detrimental [4,9].
Inadequate monitoring of sedation and analgesia may contribute to adverse outcomes and complications. Assessment of sedation and agitation is useful to allow more accurate titration of sedation and to evaluate agitated behaviour but existing sedation scales have limitations. Most sedation scoring systems use responses to stimuli and/or patient appearance and physiological variables to estimate the level of sedation. These scores must be interpreted subjectively or, in case of physiological parameters, can be influenced by ICU therapy. In a recent review of sedation scoring systems, De Jonghe and colleagues  identified 25 instruments designed to measure consciousness in the ICU settings. New guidelines recommend that the benefit of protocols might be enhanced by using patient-specific sedation targets as the relative need for sedation can vary widely among patients as well as over time for an individual patient . The RASS  which was developed recently is a 10-point scale. RASS has five levels of sedation in addition to level 0 (calm) . The Ramsay sedation scale  has three ‘asleep’ levels and three ‘awake’ levels, whereas the Sedation–Agitation Scale  and the Motor Activity Assessment Scale  have three sedation levels plus one level for a calm state. As a target of light to moderate sedation is common for mechanically-ventilated patients, RASS was designed to offer multiple levels (0 to −3) within this range. This important range of responses is condensed into one or two sedation levels in other scales .
But there are, however, several limitations to RASS. It relies on patient auditory and visual acuity and is not suitable for patients with severe impairments. Secondly some patients may be sleeping or sedated but respond to auditory or physical stimulation violently. Although such patients would receive a RASS score on the sedation range, nurses note the excessive response and consider it in their medication titration . Therefore, objective tools to measure the level of sedation are urgently needed so that oversedation can be avoided and the level of sedation be adjusted if muscle relaxants are given. The BIS monitor was initially designed to measure the level of consciousness in adults during anaesthesia  but may have benefits over subjective clinical monitoring of sedation. BIS is a processed electroencephalographic parameter that provides a measure of sedative levels on a relative scale. For various agents (e.g. propofol and midazolam) it has been shown that BIS may correlate with dose-dependent levels of anaesthesia [15–17] and ICU sedation [18,19]. Recently, McDermott and colleagues  investigated the use of BIS during sedation in children undergoing elective diagnostic or therapeutic procedures. They found good correlation between BIS and the various sedation scales which was parallel to our data. A statistically significant correlation existed between BIS values and the RASS, SAS and Glasgow coma scale in critically ill brain-injured patients . Simmons and colleagues stated that SAS and BIS levels work well to describe the depth of sedation for ventilated ICU patients . BIS correlated with clinically assessed sedation levels and was useful for differentiating adequate from inadequate sedation, which would be of value when the clinical examination is unavailable  Triltsch and colleagues  compared BIS with the COMFORT score to determine the level of sedation in a paediatric ICU. They found significant correlation for deeply sedated patients whereas no correlation was found in the group with light sedation. But in our study strong correlation was present between BIS and RASS in light sedation. This controversy might be due to the difference of the patients' age (paediatric vs. adult) or method. Ely and colleagues [24,25] also demonstrated a strong correlation between RASS and the Glasgow Coma Scale (r = 0.93) as well as modified bispectral array electroencephalography (r = 0.70).
Mondello and colleagues  demonstrated the utility of BIS to track levels of consciousness in ICU patients while still maintaining the use of scoring systems to care for them. We also used both BIS monitoring and scoring system. BIS is useful and shows the alert state but is incapabable of measuring agitation. RASS contains several levels of agitation.
In conclusion, for achieving a more appropriate sedation range, the development and application of sedation guidelines or protocols should be explored. RASS correlates with BIS monitoring during dexmedetomidine sedation in ICU patients and their use together for monitoring sedation in ICU may be advantageous.
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