The COMFORT scale contains behavioral and physiologic factors (eight items, each scored from 1 to 5) to evaluate pain and was originally designed to assess distress in pediatric ICU patients 25. The scale measures alertness, calmness, facial tension, physical movement, muscle tone, ventilator respiratory response, blood pressure and heart rate, and it exhibits good inter-rater reliability 26.

The FLACC was developed to provide a simple and consistent method for nurses to identify, document, and evaluate pain in children 2728. The FLACC scale assesses pain by using behavioral indicators and assessment of body movements (face, legs, activity), verbal responses (cry), and consolability. It has been validated for assessing pain in children with cognitive impairment, in young children 29 and in children with postoperative pain 27, and in comparison with children's self report of pain 30. However, there are few data to support its use in adult critically ill patients. Specific components such as cry and consolability are not appropriate for the critically ill, intubated adult.

The Behavior Pain Scale (BPS) 15 is based on a sum score of three items: facial expression, movements of upper limbs, and compliance with mechanical ventilation. Based upon the assumption that a relationship exists between each score and pain intensity, each pain indicator is scored from 1 (no response) to 4 (full response), with a maximum score of 12. Initial validity and reliability was established using 269 assessments in 30 sedated mechanically ventilated patients during painful procedures (endotracheal suctioning and mobilization) as well as nonpainful procedures (compression stocking application, central venous catheter dressing change). Nociceptive stimulation resulted in higher BPS values than did non-nociceptive stimuli (4.9 versus 3.5; P < 0.01), whereas the groups had comparable scores prior to stimulation. Excellent inter-rater reliability was also found during multiple testing (r² = 0.50 to 0.71). Young and coworkers 30 conducted additional validity and reliability testing of the BPS in critically ill patients during routine painful and nonpainful procedures. A significant (P < 0.003) increase in BPS scores was found after painful procedures, and no significant increase was found after the nonpainful procedure. The odds of an increase in BPS between pre-procedure and post-procedure assessments were more than 25 times higher for repositioning (painful) compared with eye care (nonpainful; P < 0.0001), after controlling for analgesics and sedatives. A limitation of BPS is that responsiveness (increase in score in response to noxious stimuli) decreases substantially with deepening levels of sedation 15. In addition, because compliance with mechanical ventilation may be considered to be a separate domain from the other behaviors, some intensivists only score facial expression and movements of upper limbs in order to assess the individual pain state.

Chanques and coworkers 31 evaluated pain in 230 ICU patients using the combination of BPS (for noncommunicative patients) and NPS (for communicative patients). The periods considered were a 21-week control phase with usual care as regards pain evaluation, and a subsequent 29-week intervention phase, during which nurses assessed pain levels using the two tools and notified physicians of high pain levels. The incidence of pain as well as the rate of severe pain events decreased significantly during the intervention phase. A significant decrease in the duration of mechanical ventilation was also noted 18.

The Adult Nonverbal Pain Scale is a modification of the FLACC scale and was developed for use in adult, non-communicative patients. It evaluates five parameters: face, activity, guarding, physiologic I (vital signs), and physiologic II (skin and pupils). It has been pilot tested in a burn-trauma unit during all three patient care shifts in 200 paired assessments with the FLACC scale 32. It exhibited good correlation with the FLACC scale (r = 0.86, P < 0.001). Although it shows promise as a tool for use in the nonverbal adult population, it has not been evaluated against any other measures of pain in the adult population.

A recently developed behavior pain tool, the Critical Care Pain Observation Tool (CPOT), has four components: facial expression, body movements, muscle tension, and compliance with the ventilator for intubated patients or vocalization for extubated patients. Each of these behaviors is assigned a rating of 0 to 2. The CPOT was adapted from three different pain assessment tools 152533 and three different descriptive/qualitative studies 131734. Gelinas and coworkers 34 conducted a validation study in 105 cardiac surgery patients, using periods of rest, nociception, and 20 minutes after the nociceptive procedure (positioning) during three separate testing periods while patients were conscious and unconscious. The tool exhibited criterion validity because significant associations were found between the patients' self-reports of pain and CPOT, whereas discriminant validity was supported by higher scores during the nociceptive procedure compared with the score at rest. Inter-rater reliability was also good. Of note, changes in scores with nociceptive stimulation were similar whether the patient was conscious or unconscious.

Current practice for adult ICU patients commonly includes a combination of NPS or similar self-reported pain quantification tool, plus an instrument designed to identify pain using behavior and physiologic parameters in the noncommunicative patient. This sequential approach is supported in the form of grade B recommendations from the SCCM 1. More work is needed to provide convincing evidence of the validity of these tools as well as to address limitations in application, such as how to assess for pain in the presence of heavy sedation. Although new scales and additional validation studies are frequently reported in this evolving field, we support use of either the BPS or CPOT for noncommunicative scales (Tables 1 and 2). Combining pain testing with a standardized approach to management can lead to better pain control without prolonging the duration of mechanical ventilation 31.

The routine use of a sedation scale in ICU patients who are receiving sedative medications is endorsed in SCCM's Clinical Practice Guidelines for Sustained Use of Sedatives and Analgesics in the Critically Ill Adult 1 and is supported by other expert reviews 234. The SCCM guidelines specifically recommend that a sedation goal or end-point should be established and regularly redefined for each patient, and that regular assessment and response to therapy should be systematically documented (grade C recommendation) 1. The use of a validated sedation assessment scale was also specifically recommended (grade B recommendation). Additionally, the treatment algorithm depicted in the guidelines indicate that clinicians should use a sedation scale to assess for agitation/anxiety 1. Historically, the use of a sedation scale has been disappointingly low, with sedation assessment performed in fewer than one-half of ICU patients, ICUs, and days of observation in multiple studies from throughout the world 44454647484950.

Although all of the aforementioned studies were performed before publication of the SCCM guidelines in 2002, a recently reported prospective surveillance study conducted in 44 ICUs during 2004 revealed that sedation assessment is still not performed in many patients who are receiving sedative drugs 18. For example, on the second ICU day, 72% of patients were receiving sedative medications but only 43% received sedation assessment. The missed opportunity to titrate medications effectively by using a sedation scale is apparent, because 57% of assessed patients were under deep sedation 18.

Each sedation scale is constructed somewhat differently (Table 3), although there are several common themes regarding domains to be evaluated and the structure of the instrument. The key domain of most scales is consciousness, typically ranging from alert to comatose, with a subdomain of arousal or awakeness, often in response to stimuli of increasing intensity (as with RSS, RASS, ATICE, and MSAT). In addition, higher states of consciousness may be further defined by testing cognition or comprehension (as with RASS and ATICE), or sustainability (as with RASS). These instruments (RSS, RASS, ATICE, and MSAT) rely upon noting a simple response (movement, eye opening, or following a command such as 'look at me') spontaneously or responses to simple cues (speaking to the patient or physically stimulating the patient) that proceed in a logical progression reflecting progressively deeper sedation 42. This structure produces little overlap in levels of consciousness because of the step-wise approach, but the assessment can be quickly performed and the results easily recalled. In contrast, the structure of some instruments is to sum multiple subscales 3840 or to test multiple criteria for each sedation level 3637, thus adding complexity and potentially impairing ease of recall.

Assessment of agitation, or conversely of calmness, is another important domain that is measured using many sedation instruments, either as a distinct subscale (VICS and ATICE) or incorporated into a single scale (SAS, MAAS, and RASS). With RASS various levels of agitation are assigned positive numbers, whereas sedation levels receive negative numbers, providing distinction despite the single scale design. Research suggests that the majority of ICU patients exhibit agitation at some time during their ICU stay 51. This is an important patient safety concern because behaviors such as aggressive behavior against care givers or self-removal of an important tube or catheter can have serious consequences 52535455. Use of a sedation-agitation scale can enhance identification of agitation or anxiety, thus prompting therapeutic intervention 1 and reducing the subsequent incidence of agitation 31, as well as leading to identification and better management of pain, delirium, or other conditions that might produce agitation 251545657. It is worth emphasizing that agitated behavior may be a manifestation of inadequate pain control or it could be due to distress from a problem that requires immediate attention, such as a malpositioned endotracheal tube or myocardial ischemia.

ICU sedation instruments that have been tested for inter-rater reliability and validity in multiple patient populations are summarized in Table 3, listed in order of year of publication. Inter-rater reliability has been formally tested in research investigators, as well as in clinical ICU nurses, for most of these instruments, as noted in Table 3 363738394041585960. It is noteworthy that some scales such as SAS and RASS have been tested extensively, including as many as five raters representing nurses, physicians, and pharmacists, in research and clinical settings, at multiple hospitals, and in different patient populations (with or without mechanical ventilation). Excellent reliability has been demonstrated for the majority of scales. Face, construct, or criterion validity has been demonstrated for many of the domains of these instruments using a variety of comparators. These comparators include expert opinion 404159, quantity of sedative drug administered 404158, visual-analog scales 395961, other sedation instruments 3639415862, processed electroencephalography (EEG) such as Bispectral Index (BIS) and Patient State Index (PSI) 6163646566676869, and limb acceleration and movement using actigraphy 62 or digital imaging 70 (Table 3). In most cases good to excellent validity is demonstrated. Far less work has been conducted to validate the agitation domain of sedation-agitation scales. Additionally, some scales incorporate domains that are more difficult to validate. For example, the motor activity domain of the MSAT exhibited only weak correlations with the comparator (the VICS calmness scale).

Implementation of a sedation assessment instrument can have a positive impact on precision of sedative administration 7172, with greater frequency of appropriate sedation level and lower incidence of over-sedation, reduction in sedative and analgesic drug doses, shorter duration of mechanical ventilation, and even reduced use of vasopressor medications. Implementation of strategies that incorporate scheduled assessment for agitation, within the context of additional monitoring and targeted management, has been associated with a reduction in agitation, shorter duration of mechanical ventilation, and even fewer nosocomial infections 3157. Use of a sedation scale is an integral component of most patient-focused management algorithms.

The regular performance and documentation of level of sedation and agitation using a logical, easy to use, validated instrument is strongly recommended because it promotes optimal patient-focused sedation management. The authors endorse RSS and RASS (Tables 4 and 5, respectively) as sedation scales, which have excellent inter-rater reliability and validity, and were the most frequently used sedation scales in the latest survey 18.

The available cortical activity monitors record the cortical EEG signals and use the frequency, power, or disorder of these signals to determine the patient's status. These monitors process data through various proprietary algorithms to a dimensionless number that reflects the depth of sedation of the brain. The effect of sedative drugs on the electrical activity of the human brain was first reported in 1937 73. The very sensitive 20-channel devices were not conducive to routine clinical monitoring, so in 1969 a simpler two-channel device was developed that recorded cortical activity as a continuous power strip. The width of the power band was dependent on the amount and frequency of the cortical electrical signal 74. Since then many different methodologies have been developed to process and simplify the EEG signal. The overall goal was to quantify the EEG signal in a display that can be easily interpreted by the practitioner. The Cooley and Tukey algorithm applied to the Fourier theorem – the Fast Fourier Transform – allows a power versus frequency histogram to be developed that may be displayed as a spectral array. This concept has led to application of these monitors as tools for the objective measurement of the depth of sedation. However, this approach relies on the concept that consciousness lies at a cortical level, which perhaps is an over-simplification of a very complex process. Cortical electrical activity may only be an expression of consciousness.

The BIS (Aspect Medical Systems, Norwood, MA, USA) is composed of time domain, frequency domain, and high-order spectral subparameters. This integrates several disparate descriptors using a proprietary algorithm into a dimensionless index. The BIS algorithm has been compared with a growing database of clinical data and continues to be updated. The resulting BIS number has been correlated with a minimal value that should be attained to prevent patient awareness under anesthesia or sedation 75. The BIS displays a raw EEG trace obtained from a two-channel sensor but only from a unilateral prefrontal lobe site, and a power trend is displayed with a number from 0 to 100 (0 indicating no cortical activity and 100 a patient who is wide awake). There are no units of measurement and one patient's response to a sedation agent may be dependent on many factors, so whether a BIS number can correlate uniformly with depth of sedation remains controversial. The effect of the electromyogram (EMG) signal may artificially increase the BIS number. This can be detected by viewing the raw signal and seeing the high frequency of the EMG signal within the low voltage signal from EEG. Filters designed to remove the EMG signal have limited efficiency with any of the cortical monitors. However, the EMG signal may be used as a guide to the elimination of muscle relaxant drugs and the return of muscle activity – another type of twitch monitor.

The PSI, displayed on the Sedline Monitor (Hospira, Lake Forest, IL, USA), is another approach to quantifying cerebral cortical activity. This monitor has four channels and monitors both hemispheres of the brain. Similar to the BIS, the PSI converts the raw EEG signal using the Fast Fourier Theorem and a proprietary algorithm to display a dimensionless scale from 0 to 100 that reflects the depth of sedation of the patient. The scale is updated every 1.2 seconds, which makes this monitor quick to respond to changes in cerebral cortical activity. The PSI algorithm was constructed following an analysis of the quantitative EEG changes that accompanied the loss and return of consciousness after administration of sedative drugs. It was validated in a large database of patients and volunteers 76.

The Cerebral State Monitor (Danmeter A/S, Odense, Denmark) is a handheld wireless device that also uses a proprietary algorithm and a 0 to 100 scale, with 40 to 60 indicating an adequate depth of hypnosis. The Cerebral State Index (CSI) that is calculated by the device is derived from the time and frequency domain analysis, which inputs into a fuzzy logic inference system that calculates the index. In a comparative study, both the BIS and the CSI had a predictive probability statistic for depth of anesthesia of 0.87, which demonstrates good performance 77. The CSI performed better for deeper levels of anesthesia than the BIS, which was better at lighter levels.

The Narcotrend monitor (MonitorTechnik, Bad Bramstedt, Germany) is another monitor that processes raw EEG signals using one-channel or two-channel recordings from different electrode positions. Early models graded the depth of hypnosis into five stages from A (awake) to F (very deep level of anesthesia). The latest Narcotrend software (version 4.0) now calculates the Narcotrend Index, another dimensionless 0 to 100 scale that is similar to those calculated by the monitors described above. When compared with BIS, the performance of the Narcotrend Index in terms of prediction probability of depth of sedation was slightly better than BIS (predictive probability statistic 0.88, as compared with 0.85) 78.

Additional approaches to brain monitoring in the ICU include response entropy and state entropy 79. The irregularity of the EEG signal can be quantified, and by using an algorithm that is in the public domain, quantified to reflect depth of sedation. This Entropy Monitor (GE Healthcare, Fairfield, CT, USA) utilizes the EMG signal, which may provide information useful for assessing whether a patient is responding to an external stimulus, for instance a painful stimulus. The combination of EEG and EMG is presented as the response entropy, and the lower frequency EEG signals alone are presented as the state entropy. The prediction probability values of the entropy indices for differentiating between consciousness and unconsciousness are high and comparable with those for BIS 80. Noxious stimulation does increase the difference between response entropy and state entropy, but an increase in the difference does not always indicate inadequate analgesia 81.

Auditory evoked responses have extensively been studied with increasing depths of sedation 82. Auditory stimuli stimulate the auditory axis, and the middle-latency auditory evoked responses are reduced in amplitude and elevated in terms of latency with increases in sedation. This Auditory Evoked Potential monitor (Danmeter A/S) studies more than just cortical electrical activity. The monitor uses an algorithm that calculates a numerical index, the Alaris Auditory Response Index (AAI™), from the latency and amplitude of the evoked potential. AAI™ transforms the AEP (auditory evoked potential) and the EEG signal into a value on a 0 to 100 scale that is used to measure depth of sedation. This index correlates well with the BIS index 83.

The use of these cerebral function monitors as objective monitors of depth of sedation in the ICU has not yet been universally embraced. This is because many factors may alter the signal in the critically ill patient, particularly EMG signals, which can cause erroneously high BIS and PSI scores. These artifacts can be identified by observing the raw EEG signal and seeing a very high frequency low voltage 'noise' within the EEG signal. Thus, an understanding of the basic EEG signal is important to interpreting the data presented by these cerebral function monitors. A variety of confounders, including EMG interference, sleep, drugs such as catecholamines, and temperature changes, may influence the BIS value 84. In a comprehensive review, LeBlanc and colleagues 84 demonstrated mixed results when BIS was correlated with clinical sedation scales, with r² ranging from 0.21 to 0.93. Much of the variability is probably related to EMG interference, because BIS values decline significantly when muscle relaxants are administered to ICU patients 8586.

Where does cerebral function monitoring fit into current ICU practice? The recommendations found in SCCM's Clinical Practice Guidelines, published in 2002, do not endorse routine use 1. They state that 'objective measures of sedation such as BIS have not yet been evaluated and are not yet proven in the ICU', based upon grade C evidence. Although there is evidence for better operating room outcomes, such as early recognition of unintended awareness 75 or better anesthetic management 87, such evidence is scant in the ICU setting. The incidence of unintended awareness in the ICU is unknown and is mainly observed in those patients who are paralyzed either as a result of their disease process or the use of muscle relaxants. This patient group may be well served by monitoring, because the sequelae of inadequate sedation are severe. Accordingly, use of cerebral function monitoring is likely to be of greatest benefit in patients who are deeply sedated or who are receiving muscle relaxant medications 188. The most compelling reason to promote further research and clinical experience in cerebral function monitoring in the ICU is patient safety. Examples of changes in PSI in response to clinical events are noted in Figures 1 and 289. Cerebral insults may be detected at a stage when they are still reversible. The brain is the most complex and most important organ in the human body and deserves more attention than it currently receives. Cerebral function monitors may provide another level of safety for our patients and, as this area of technology advances, improved care of the mental and cognitive functions of the critical care patient is likely to follow.