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Abstract |
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• Methods Patients receiving mechanical ventilation in a medical intensive care unit were evaluated prospectively. Level of sedation was assessed with the Sedation-Agitation Scale (range 1–7, unarousable to dangerous agitation) and the Bispectral Index (range 0–100, flat line to awake waveform) recorded before and after stimulation. Patients were classified as receiving continuous infusions if an infusion had been administered within 24 hours preceding assessment.
• Results Nineteen patients were evaluated on 80 occasions. Scores on the Sedation-Agitation Scale ranged from 1 to 5 (mean 2.6 and median 2) and correlated highly with values for the Bispectral Index (R2 = 0.48 before and 0.44 after stimulation, P < .001). Patients receiving continuous infusions were more deeply sedated than were patients receiving boluses or no medication (mean [SD] scores, Sedation-Agitation Scale: 2.1 [1.2] vs 3.3 [1.0], P < .001; Bispectral Index before stimulation: 63 [24] vs 86 [13], P < .001). Patients receiving continuous infusions were more likely to have a score of 2 or less on the Sedation-Agitation Scale (32/44 vs 8/35, P < .001).
• Conclusion Objective and subjective assessments of sedation are highly correlated. Use of continuous infusions is associated with deeper levels of sedation, and patients receiving continuous infusions are more likely to be oversedated. Sedation therapy should be guided by subjective or objective assessment.
When sedatives are delivered as bolus doses, on an as-needed basis, drugs are principally given when patients are agitated. This strategy may prevent accumulation of sedatives by allowing the drugs to be eliminated between doses. In contrast, once a continuous infusion of sedative is started, a reduction in the dose of medications infused may be less likely unless mandated by one of the strategies just mentioned. Under these circumstances, the drug may be more likely to accumulate, and oversedation may occur.
| Use of continuous infusions of sedatives/hypnotics prolongs duration of mechanical ventilation.
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To assess the level of sedation, investigators have used a number of subjective clinical scoring systems and objective assessment with the Bispectral Index (BIS).4–8 Few studies9,10 included correlations between results obtained with subjective and objective assessment techniques, especially in patients receiving mechanical ventilation in medical ICUs.
We hypothesized that continuous infusions of sedatives would be associated with deeper levels of sedation. We therefore compared the level of sedation in patients managed with continuous infusions with the level in patients managed with boluses or no medication. We also compared the use of 2 distinct sedation assessment tools: the Sedation-Agitation Scale (SAS) and the BIS.5
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Methods |
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Exclusion criteria included the following: severe neurological disease (stroke with resultant aphasia, paresis, or paralysis), severe dementia or mental retardation (requiring placement in a skilled nursing facility or assistance with most activities of daily living), anoxic encephalopathy, and paralysis including that due to neuromuscular blockade. All patients were studied while they received full ventilatory support.
| Using the Sedation-Agitation Scale and the Bispectral Index, investigators compared daily sedation assessments of patients receiving mechanical ventilation and continuous infusions of sedatives/hypnotics with patients who were not receiving continuous infusions.
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Assessment of Sedation
Sedation was assessed by using both the SAS (Table 1
) and the BIS (BIS A-2000, Aspect Medical Systems, Newton, Mass).5 The BIS is a calculation of depth of sedation. Completely awake patients have scores from 90 to 100 on the BIS; consciously sedated patients, 70 to 89; patients under general anesthesia, 50 to 69; and deeply sedated and comatose patients, 0 to 50.10
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Definitions
A patient was classified as having received continuous intravenous sedation if an infusion of a sedative/hypnotic or narcotic, with or without additional sedative boluses, had been administered at any point during the 24 hours preceding evaluation. All other patients were classified as receiving bolus or no sedation. Oversedation was defined as a score of 2 or less on the SAS, and undersedation (or agitation) was defined as a score of 5 or greater on the SAS. Sedation was considered optimal when the SAS score was 3 or 4. No protocol based on a sedation score was used during the study.
Analysis
The relationships between scores on the SAS and BIS values and between mean scores on the BIS before and after stimulation were analyzed by using Pearson correlation. To compare patients studied while receiving continuous intravenous sedation with patients studied while receiving boluses or no sedation, we used the t test (continuous variables, data normally distributed), the Wilcoxon test (continuous variables, data not normally distributed), or the 
2 test with the Fisher 2-tailed exact test (dichotomous variables). The statistical software used for the analysis was SPSS, version 6.1 (SPSS Inc, Chicago, Ill).
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Results |
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. Reasons for mechanical ventilation were acute lung injury (8 patients), chronic obstructive pulmonary disease (4), cardiac disease (2), acute central nervous system events (2), sepsis (1), gastrointestinal bleeding (1), and pulmonary hypertension (1).
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Patients were studied on a total of 80 separate occasions. On 1 occasion, the SAS score was inadvertently not recorded. Sixty-eight BIS measurements were made; on 3 of these occasions, mean BIS scores after stimulation could not be determined because of poor signal quality.
The SAS scores ranged from 1 to 5; no patient had a score of 6 or 7 (Figure 1). The mean SAS score was 2.6 (SD 1.3) with a median of 2. The BIS values were from 29 to 98, with a mean of 73 (SD 23) before stimulation (median 78, quartiles 50 and 96) and a mean of 76 (SD 23) after stimulation (median 86, quartiles 58 and 95). The mean BIS values before and after stimulation were highly correlated (R2 = 0.79, P < .001; Figure 2).
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). For SAS scores of 1 or 2, the range of observed BIS values was very wide (range before stimulation 29–98, after stimulation 31–97). Nevertheless, the SAS scores and the BIS values were significantly correlated (before stimulation R2 = 0.48, P < .001, and after stimulation R2 = 0.44, P < .001; Figure 3).
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To ascertain if the goals of sedation might explain the significant differences between the groups, we analyzed the severity of respiratory failure by examining the level of positive end-expiratory pressure (PEEP) and the ratio of PaO2 to fraction of inspired oxygen (FIO2) at the time of study. Patients managed with boluses had slightly lower PEEP levels (mean [SD] 6 [1] vs 7 [2], P < .001) and higher PaO2/FIO2 ratios than did patients receiving continuous infusions (202 [93] vs 255 [72], P = .01). Nevertheless, when we compared sedation level (assessed by using either SAS or BIS) with PEEP and PaO2/FIO2, only relatively weak correlations were found for mean scores both before and after stimulation: SAS score with PEEP, R2=0.05; SAS score with PaO2/FIO2, R 2=0.11; BIS value with PEEP, R2 = 0.02. Between the PaO2/FIO2 and the BIS value, correlations (R2) were 0.17 (mean before stimulation) and 0.15 (mean after stimulation).
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Discussion |
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We found that patients receiving continuous infusions were more deeply sedated than were patients managed with boluses or no sedation, as indicated by both lower SAS scores and lower BIS values. Patients managed exclusively with boluses or no sedation at the time of the study were more likely to be sedated to the target level used in our ICU, an SAS score of 3 or 4. In contrast, nearly 75% of the time, patients who had received a continuous infusion for sedation had an SAS score of 2 or less.
One explanation for the variability in sedation level may be that the goals of sedation differed between patients managed with boluses and patients treated with continuous infusions. That is, in some patients, a higher level of sedation may have been desirable, and this level could be achieved only with continuous intravenous sedation. To address this possibility, we examined the relationship between mode of sedation and the degree of respiratory failure as reflected by PaO2/FIO2 and the level of PEEP required to achieve this degree of oxygenation. Patients receiving continuous infusions required higher levels of PEEP and had a lower PaO2/FIO2, but the differences (compared with boluses or no sedation) were small, and the correlations between these variables and SAS scores and BIS values were weak. Therefore, we do not think that different sedation goals completely explain the greater level of sedation observed in patients receiving continuous intravenous infusions of sedatives.
When we compared the SAS scores and the BIS values, we found a strong correlation (R2 = 0.48 and 0.44 for BIS values before and after stimulation) in a cohort of patients receiving mechanical ventilation in the medical ICU, stronger than that reported by other investigators. Simmons et al9 compared the BIS values with SAS scores in 63 ICU patients receiving mechanical ventilation and found a stronger correlation for trauma patients (R2 = 0.52) than for medical patients (R2 = 0.10). Riker et al10 noted a good correlation between SAS scores and BIS values (R2=0.37) in 39 patients who had cardiac surgery.
| Patients managed with bolus or no sedation had significantly higher scores on the Sedation-Agitation Scale (more agitated) and higher scores on the Bispectral Index (more alert) than did patients receiving continuous infusions of sedatives/hypnotics.
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For low SAS scores, the range of BIS values was wide. Therefore, some patients deemed to be quite sedated as indicated by a clinical score might actually have had higher levels of awareness. Alternatively, some patients with low SAS scores and high BIS values were sedated but had alpha intrusions (high-frequency electrical activity) due to pain; with the BIS, it may not be possible to distinguish such intrusions from the awake state.11
In summary, use of continuous intravenous infusions of sedative/hypnotic or narcotic agents is associated with deeper levels of sedation, and these patients are more likely to be oversedated (SAS score 2). Continuous infusions may lead to deeper levels of sedation because of higher drug levels and/or changes in context-sensitive half-life, although the mechanism is unknown because the pharmacokinetic data on sedatives/hypnotics in medical ICU patients are limited. In addition, objective and subjective assessments of sedation, as measured by the SAS and BIS, are highly correlated. These data reinforce the need to guide sedation therapy by using some method of assessing sedation; our results suggest that either subjective or objective techniques can be used.
| Patients receiving continuous infusions of sedatives were more deeply sedated than were patients receiving sedatives by bolus. Although the need for greater levels of sedation was desired in some patients because of the degree of respiratory failure, differing sedation goals did not completely explain all of the differences found.
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ACKNOWLEDGMENTS |
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REFERENCES |
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This article has been cited by other articles:
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  J. M LeBlanc, J. F Dasta, and S. L Kane-Gill Role of the Bispectral Index in Sedation Monitoring in the ICU Ann. Pharmacother., March 1, 2006; 40(3): 490 - 500. [Abstract] [Full Text] [PDF]
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 K. J. Lafleur Will Adequate Sedation Assessment Include the Use of Actigraphy in the Future? Am. J. Crit. Care., January 1, 2005; 14(1): 61 - 63. [Full Text] [PDF]
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B. D Watson and S. L Kane-Gill Sedation Assessment in Critically Ill Adults: 2001-2004 Update Ann. Pharmacother., November 1, 2004; 38(11): 1898 - 1906. [Abstract] [Full Text] [PDF]
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