(Chest. 2005;128:303-307.)
© 2005
American College of Chest Physicians
Concomitant Assessment of Depth of Sedation by Changes in Bispectral Index and Changes in Autonomic Variables (Heart Rate and/or BP) in Pediatric Critically Ill Patients Receiving Neuromuscular Blockade*
Randi M. Trope, DO;
Peter C. Silver, MD, FCCP and
Mayer Sagy, MD, FCCP
* From the Division of Pediatric Critical Care Medicine, North Shore-Long Island Jewish Medical Center, Schneider Children’s Hospital, New Hyde Park, NY.
Correspondence to: Mayer Sagy, MD, FCCP, Division of Pediatric Critical Care Medicine, North Shore-Long Island Jewish Medical Center, Schneider Children’s Hospital, 269–01 76th Ave, New Hyde Park, NY 11040; e-mail: msagy{at}lij.edu
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Abstract
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Objective: We evaluated whether or not changes in bispectral index (BIS) are associated with concomitant changes in autonomic variables that are in agreement with the different level of sedation that the changes in BIS indicate.
Design: A retrospective chart review.
Setting: A pediatric ICU of a children’s hospital.
Methods and main results: Charts of patients who were receiving mechanical ventilation and IV sedation, neuromuscular blockade, and continuous BIS monitoring were enrolled in the study. Changes in BIS values 
30% from previous readings were evaluated to determine whether or not concomitant changes of 10% in autonomic variables, in the same direction, coexisted. Forty-seven patients (35 male and 12 female) were enrolled in our study; ages ranged from 10 days to 18 years (mean, 4.2 ± 6.2 years [± SD]). Twenty-five patients were < 1 year of age (53%). All patients were sedated and pharmacologically paralyzed. Overall, 387 BIS readings (15%) showed a 30% change from the previously documented BIS number. These BIS changes were in agreement with heart rate (HR) changes, mean arterial pressure (MAP) changes, and both HR and MAP changes in 10.6%, 23.8%, and 5.7% of the time, respectively. The same analysis of agreement was done for patients 
1 year old, and results were no different from those of older patients. Among 21 patients who were not receiving any vasoactive drugs (
- and/or ß-adrenergic agonists) during the study period, 157 BIS recordings (15%) showed a 30% change from the previously documented BIS number. The percents of agreement with HR, MAP, and HR and MAP for these patients were 14.6%, 17.2%, and 7.6%, respectively. In 26 patients who were receiving vasoactive medications during the study, 230 BIS recordings (15%) showed a 30% change from the previously documented BIS number. For these patients, the percentages of agreement were 7.8%, 28.3%, and 4.3%, respectively. Agreement with MAP was significantly better than with HR for this group of patients (p < 0.05; Fisher Exact Test).
Summary: While significant changes in BIS are thought to reflect significant changes in depth of sedation, they have a very low rate of agreement with changes in vital signs. In the absence of BIS, the level of sedation of chemically paralyzed pediatric patients can be better guided by changes in MAP than in HR, particularly in patients receiving vasoactive drug treatment.
Key Words: agitation • autonomic variables • bispectral index • neuromuscular blockade • pediatric sedation
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Introduction
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Patients receiving mechanical ventilation while receiving neuromuscular blockade (NMB) require sedation to ensure an optimal level of comfort.1 For patients who do not require NMB, there are numerous scales available for the evaluation of depth of sedation.234 However, these scales rely on certain parameters of observable behavior that are not applicable to the paralyzed patient.
Traditionally, assessment of depth of sedation in critically ill children receiving NMB agents (NMBAs) has been linked to changes in their autonomic variables such as heart rate (HR) and BP.5 Despite the fact that the clinical significance of changes in vital signs is not specific and their sensitivity as markers for depth of sedation in the critically ill patient has never been established, in the absence of better alternatives, changes in autonomic variables are nevertheless commonly utilized.5
The advent of an objective monitor for assessment of depth of sedation, the bispectral index (BIS), has provided clinicians with a necessary tool for this purpose.6 The BIS monitor obtains raw EEG information from monitored patients and processes it to generate a number from 0 to 100. These BIS numbers correlate with depth of sedation, where a BIS value of 100 indicates a state of full awareness and a BIS value of 0 indicates absence of brain activity (Table 1
). Adjusting the dose of sedatives to achieve a BIS value between 40 and 50 ensures a state of deep hypnosis, whereas values > 65 and those < 35 would indicate inadequate sedation or oversedation, respectively.78
The BIS monitor has been validated in various clinical scenarios for assessing depth of sedation.78910111213 Based on these previous validations, we sought to verify the efficacy of the use of autonomic variable changes as an acceptable alternative method for evaluation of sedation in patients receiving NMBAs. We hypothesized that in patients receiving NMBAs, changes of large magnitude in BIS numbers reflect significant changes in their level of sedation and thus should also produce meaningful changes in HR and mean arterial pressure (MAP).
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Materials and Methods
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Patient Selection
The study met the institutional review board criteria for exempt determination as per Federal regulation 45CFR46.101b.4 A retrospective chart review of consecutive patients admitted to our pediatric ICU over a period of 30 months was conducted. Patients who were receiving mechanical ventilation while receiving IV sedation, NMB, and continuous BIS monitoring were considered for enrollment in the study. We excluded patients with cardiac pacing, heart block, and patients receiving any ß-blocking agents. Patients with a known encephalopathy or seizure disorder were also excluded.
Patient Monitoring and Management
All patients underwent continuous BIS monitoring (A-1000; Aspect Medical Systems; Natick, MA), MAP monitoring via an indwelling arterial catheter, and HR monitoring by ECG. The BIS sensor, composed of three Ag-AgCl electrodes (Zipprep; Aspect Medical Systems), was used for all patients. Clinical guidelines for sedation of patients receiving mechanical ventilation in the pediatric ICU during the period of the study suggested a combination of analgesia and sedation with IV-administered opiates (fentanyl or morphine) with or without benzodiazepines (midazolam or lorazepam). Vecuronium was the most commonly used agent for NMB when no contraindication to this drug existed. The targeted BIS was between 40 and 50.
Data Analysis
Data regarding BIS numbers and vital signs were evaluated only if they were concomitantly documented in the flow charts at a frequency of no less than every 4 h. Changes in BIS values of 30% from previous readings, occurring spontaneously or secondary to changes in the dose of administered sedatives, were evaluated to determine whether or not concomitant changes in autonomic variables coexisted. A minimum change of 10% in autonomic variables from the prior recording was required to define an agreement with the aforementioned changes in BIS as specified in Table 2 . We counted the number of times BIS changes were in agreement with changes in HR, with changes in MAP, and with changes in both HR and MAP together.
Results are presented as a percentage of agreement (see Formula 1). Percentages of agreement for all studied patients, for patients 1 year old, and for patients > 1 year old were calculated and analyzed separately for comparison. A similar, separate data analysis was done for patients who were receiving vasoactive drugs (- and/or ß-adrenergic agonists) during the period of BIS monitoring and compared with those who were not receiving them.
where n = number of times an agreement was found, and f = number of times an agreement was not found.
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Results
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Forty-seven patients, 35 male and 12 female, were enrolled in our study. The ages ranged from 10 days to 18 years (mean, 4.2 ± 6.2 years [± SD]). Twenty-five patients were < 1 year of age (53%). All patients were sedated with IV administration of opiates and benzodiazepines. Vecuronium, pancuronium, and cis-atracurium were administered for NMB to 40 patients (85%), 5 patients (11%), and 2 patients (4%), respectively. A total of 2,574 BIS recordings were eligible for analysis. BIS numbers ranged from 9 to 97 (mean, 42.3 ± 14).
Overall, 387 BIS readings (15%) showed a 30% change from the previously documented BIS number. These changes were in agreement with HR changes, MAP changes, and both HR and MAP changes 10.6%, 23.8%, and 5.7% of the time, respectively. Patients who were 1 year old showed similar results to older patients, as well as to the entire group of patients (Fig 1
).
One thousand seventy BIS recording were documented in 21 patients who were not receiving vasoactive medications during the study period. Among these, 157 BIS recordings (15%) showed a 30% change from the previously documented BIS number. The percentages of agreement with HR, MAP, and HR and MAP for these patients were 14.6%, 17.2%, and 7.6%, respectively (Fig 2
). In 26 patients receiving vasoactive medications, 1,504 BIS recordings were documented. Among these, 230 BIS recordings (15%) showed a 30% change from the previously documented BIS number. For these patients, the percentages of agreement were 7.8%, 28.3%, and 4.3%, respectively (Fig 2). The relative poor percentage of agreement with HR and the better agreement with MAP in patients receiving vasoactive medications was statistically significant (p < 0.05; Fisher exact test).
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Discussion
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Assessment of depth of sedation in critically ill pediatric patients receiving mechanical ventilation presents a challenge to the critical care practitioner. While several scales for determining depth of sedation that are based on patients’ responsiveness to stimuli have been established,234 none are applicable to patients receiving NMBAs. Traditionally, the evaluation of adequacy of sedation in the paralyzed critically ill patient has been predicated on nonspecific clinical observations. Changes in autonomic variables have most commonly been utilized for this purpose.51415 A faster HR or a higher BP may indeed indicate inadequate light sedation, and vice versa. However, vital signs in critically ill patients may be affected by numerous other physiologic factors.2351617 Yet, the question whether or not changes in vital signs can serve as reliable markers for depth of sedation during critical illness has never been fully answered.
The development of the BIS has introduced an objective method for evaluating depth of sedation in patients receiving NMBAs. This technology is based on the observation that changes in EEG correspond to changes in the level of sedation.18 The BIS monitor has been evaluated in numerous studies that have validated its efficacy in the assessment of sedation in adults79 and children.810111213 Our study sought to determine whether or not significant changes in BIS, thought to correspond to significant changes in level of sedation, are in clinical agreement with changes in autonomic variables as well. We found that changes in BIS correlated poorly with changes in HR and MAP. Had we found a high order of agreement between changes in BIS readings and changes in autonomic variables, it would have indicated that changes in HR and MAP are indeed valid markers for the determination of level of sedation. It should be emphasized that the poor agreement between changes in BIS and changes in autonomic variables found in our study may only apply to chemically paralyzed critically ill pediatric patients and not necessarily to other patients in different clinical circumstances or of different age ranges.
Various physiologic parameters, such as hydration status, body temperature, vasoactive drug treatment, cardiac function, and respiratory function, can all contribute to instability of vital signs and thereby to their unreliable value as markers of sedation.3 It was impossible, in our retrospective study, to eliminate or take into account all of those possible physiologic factors. However, we did examine the effect that vasoactive drug management had on the agreement between changes in BIS readings and changes in vital signs. It was found that patients receiving vasoactive drugs demonstrated a better agreement between changes in BIS and changes in MAP than with HR. We postulate that patients under chronotropic effect secondary to exogenous catecholamines might not respond with a significant increase in HR in the face of light sedation or a significant decrease in HR when oversedated. Yet, different levels of sedation can still affect cardiac contractility and/or systemic vascular resistance despite high levels of catecholamines.
Overall, the rate of agreement in our study between changes in BIS and changes in MAP was approximately 25%, changes in HR were approximately 10%, and changes in both HR and MAP were approximately 5%. While these results indicate that MAP was a better marker for sedation than HR, the 25% agreement it had with BIS is far from being clinically satisfactory. In the absence of BIS, using changes in MAP for assessment of depth of sedation may lead to 75% incidence of inaccurate assessment causing a higher risk of patient complications,1 while the actual etiology for the observed changes in vital signs may be unaccounted for. The ideal level of sedation for pediatric patients requiring NMB has never been established. One report19 suggests that for patients who are not chemically paralyzed, sedation should result in their being asleep but easily aroused. This would coincide with a BIS value between 60 and 70. We feel that paralyzed patients should be in a deeper level of sedation to avoid untoward anxiety and discomfort when being unable to physically express these feelings. Therefore, we aimed at BIS numbers between 40 and 50 for our patients. Using previously published correlation between BIS and depth of sedation,78 it is reasonable to say that any 30% change in these numbers would indicate a change in the level of sedation. Yet, our study failed to demonstrate that when changes of this magnitude in BIS occur, they can be corroborated by changes in vital signs.
In summary, our study was based on the assumption that BIS meets the goals of a reliable monitor: it is accurate, reproducible, and pertinent to patient care, and thus should be considered as an objective method for sedation assessment. Therefore, the clinical assessment of sedation by changes in vital signs was found to be an unreliable method for paralyzed critically ill pediatric patients in our study. Significant changes in BIS have a very low rate of agreement with changes in vital signs. In the absence of BIS, sedation might be better guided by changes in MAP than in HR, yet with very limited rate of accuracy.
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Footnotes
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Abbreviations: BIS = bispectral index; HR = heart rate; MAP = mean arterial pressure; NMB = neuromuscular blockade; NMBA = neuromuscular blockade agent
Presented as an abstract at the Fourth World Congress on Pediatric Intensive Care, Boston, MA, June 8 to 12, 2003.
Received for publication October 16, 2004.
Accepted for publication December 23, 2004.
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References
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Abstract
Introduction
