Critical Care Vol 4 No 4 CarrascoThe clinical utility of each available tool must be evaluated In order to assist the reader in determining the relativerigorously before deciding on whether they have applica- methodological authority of the evidence presentedtions in routine practice, because assessment of sedation herein, a rating system is employed that facilitates objec-is a primary objective in intensive care management. tive analysis (Table 1) .From both practical and evidence-based points of view, Considerations regarding clinical and experimentalthe present review assesses the available instruments evidencefor monitoring and controlling sedation in ICU patients The technical assessment of each instrument should notwho are undergoing mechanical ventilation. It is struc- only be subjected to a critical analysis of its methodology,tured in two parts. The first part introduces some but also to a review of the quality of the studies on which itmethodological concepts to facilitate a critical review of has been based. This is essential in order to make a cri-each instrument. The second part provides practical tique of the advantages and limitations of such instru-recommendations, on the basis of evidence and experi- ments. The quality of these studies can be classifiedence, for a clinical approach to the application of each according to three categories:tool in ICU settings. (1) class I evidence – the instrument has been validated by one or more double-blinded, or randomized con-Methodological concepts regarding the trolled clinical trials carried out in an adequate sampleassessment of sedation of critically ill patients;Considerations concerning validity and reliability of (2) class II evidence – the instrument has been validatedinstruments according to data provided by one or more adequatelyThe clinical utility of each new instrument should be designed and controlled clinical studies, but not in crit-assessed according to a rational evaluation of its validity, ically ill patients; andreliability and applicability. (3) class III evidence – the instrument has not been vali- dated or has only been validated on the basis of‘Validity’ is the ability of a tool to actually measure the experts’ opinions, studies with historical controls, orparameter that it is designed for. In monitoring of sedation case reports.this concept implies the ability to document agitation anddistress symptoms (anxiety, delirium and pain), as well as The references have been qualified according to the clas-to identify the end-points of each level of sedation that sification described above.each sedative agent can achieve. It is indispensable alsothat it measures the reality from an interpretation scheme Rational scheme for adjusting doses of sedativeswith validity on both content and construct in order to Sedation level should be assessed on a continuous basisensure that the same clinical situations will always be for each instrument. Three levels of sedation can be con-interpreted in the same way. sidered: adequate – sedation is measured accurately within the desired range; insufficient – the measured levelIf a standard criterion exits, then the new test should of sedation is lower than the actual level of sedation,compare favourably with it. The ‘gold standard’ is easy to within the desired range; and excessive – the measureddefine for some conditions, but is more much elusive when level of sedation is higher than the actual level of sedation,testing diagnosis of subjective experiences such as within the desired range. It is critical that the level of seda-anxiety or agitation. For this reason, the validation of these tion is measured accurately, because if the measured levelinstruments is more much difficult and complex. Accord- is insufficient or excessive, then the intravenous infusioningly, validity tends to be confirmed on the basis of opinion will be increased or decreased (Fig. 1).of recognized practitioners (face validity) searching forsigns and symptoms as logical consequences (or con- Adequacy of sedation in ICU settings: individualized levelstructs) of the target disorders. of sedation The vast majority of experts agree that the adequate level‘Reliability’ is the capacity of a new test to obtain similar of sedation level is different for each patient, according tomeasures with different observers (inter-rater) or with the their different clinical circumstances (severity of the respi-same observer at different times (intrarater). In clinical ratory insufficiency, haemodynamic state, etc) [4,5]. Inresearch, interobserver agreement (calculated as addition, the different definitions of the ideal levels ofweighted κ index) is the best indicator of the reliability of sedation are only the opinions of investigators, and are notthese instruments. necessarily based on experimental evidence. For this reason, these subjective concepts are not applicable to‘Applicability’ in this context implies that an instrument is the general population of critical care patients. Neverthe-easy to learn to operate, and that it is suitable for routine less, the concept that must be emphasized is the need foruse by physicians and nurses. sedation to be applied on an individualized basis, under
http://ccforum.com/content/4/4/217Table 1Rating system to determine the clinical utility of instruments for monitoring ICU sedationCondition Description PointsValidity Capacity to document agitation- and distress-related symptoms (pain, anxiety, delirium) 0–5 Content and construct validity 0–10 Exact definition of level of sedation end-points 0–10Reliability Inter-rater and intra-rater agreement 0–20Applicability Easy learning and routine recording by physicians and nurses 0–5Total points 0–50the clinical criteria of intensivists, because any definition is Figure 1valid for all the sedation needs that our patients require indaily practise. ADEQUATE LEVEL OFThere are recent contributions to this topic. The most SEDATIONremarkable is the study of Kress et al . Those investiga-tors suggested that the interruption of sedation can in Increase 10–20% infusion doses of sedatives ±some patients reduce the necessary time of mechanical supplementaryventilation. Also, in the methodology of this work is that itis the intensivist who must decide which patients can be Decrease 10–20% INSUFFICIENTawakened. Each physician also decides the adequate infusion doses of sedativelevel of sedation for each patient included in the study. Iagree with the author in considering that sedation must be EXCESSIVEadjusted in an individualized way. This approach is cur-rently the best way to administer sedation.Quality of sedationUndersedation and oversedation cause several problems.Undersedation usually produces sudden changes in the Rational scheme for adjusting doses of sedativeslevel of consciousness as a consequence of stress. Thischanges results in inadequate ventilation, hypertension,tachycardia and discomfort, all of which have adverse con-sequences for the outcome of ICU patients . Overseda- Practical recommendationstion often occurs as a result of accumulation of sedative Assessments systems for sedationand analgesic agents, and it can be associated with pro- The methods that are suitable for assessing the depth oflongation of mechanical ventilation and weaning . sedation can be considered under two headings – objec- tive or subjective assessment – depending on whether theTo avoid these problems a reliable definition of quality of techniques require the application of an index that issedation is necessary. This concept should be defined as derived from a quantifiable physiological variable (mea-the percentage of hours in which a patient maintains an surement system) or of a scoring system, respectively .adequate or desired level of sedation according to theassessment method used : Objective methods: sedation measuring systems The development of methods for objective measurement adequate sedation hours of sedation has paralleled the development of methods forQuality of sedation = × 100 assessment of the depth of surgical anaesthesia. In addi- total hours of sedation tion, the available equipment has been developed from technology used in anaesthesia. Unfortunately, none ofThus, quality of sedation is expressed as a percentage. A these measures has been validated for clinical use in thereasonable goal is to achieve a quality of sedation greater ICU . Most of them are in the process of developmentthan 85% . To have a method to measure the quality of and validation. However, they may be used as alternativessedation is as important as choosing the best instrument. in sedated patients for whom sedation scores cannot be
Critical Care Vol 4 No 4 CarrascoTable 2Characteristics of measurement systems Clinical utilityMeasuring system Advantages and limitations (rating points 0–50) ReferencePlasma drug concentration Lack of agreement with level of sedation 5 Frontalis electromyography Interindividual variation 10 Lower oesophageal contractility Low sensitivity 10 Continuous electroencephalography Difficult interpretation 15  Interagent variationCerebral function monitor Complex and difficult to interpret 20 Cerebral function analyzing monitor Complex and difficult to interpret 25 Power spectral analysis Not available for clinical use 5 AEPs Limited reliability in light sedation 35  Adequate for researchapplied. Table 2 illustrates the characteristics and rating Continuous electroencephalographyclassifications of these methods. This method was proposed by Peter  50 years ago for monitoring of opiate intravenous anaesthesia. It provides aPlasma drug concentration record of cortical activity, measured from a series of scalpAlthough monitoring of therapeutic drug concentrations is electrodes, against time. Decreases in the level of con-useful for antibiotics, anticonvulsants and antiarrythmics, sciousness result in changes in electroencephalographythere is no correlation between plasma concentration and readings. However, different sedatives alter the readingsthe effect of a drug at its site of action. In contrast to post- in different ways, making interpretation very difficult. Inoperative patients, critically ill patients often have continu- addition, electroencephalography does not correlate withously varying degrees of organic dysfunction that lead to sedation score or plasma drug concentration .alterations in their responses to drugs (pharmacodynam-ics) and in their ability to eliminate drugs by biotransforma- In centres that have experience in collecting electroen-tion and excretion (pharmacokinetics). Sample processing cephalography records, this information can be useful indelays before results are available result in an inadequate interpreting neurological function in patients after headreference on which to base adjustment of sedation. A injury or in evaluating coma versus brain death. However,further limitation pertains to interindividual variation in the continuous electroencephalography cannot be recom-sedative effects of some agents, such as benzodi- mended for routine monitoring of ICU sedation.azepines. High plasma concentrations of midazolam havebeen associated with an increase in agitation . Conse- Cerebral function monitorquently, this method cannot be recommended for monitor- The cerebral function monitor was described by Dubois eting sedation in daily practice. al  for the purpose of monitoring the level of general anaesthesia. It is a device that processes electroen-Frontalis electromyogram cephalography readings, but remains in time domain. TheThe frontalis muscle contracts in response to stress, and electroencephalography is filtered to minimize the impactthis contraction can be recorded even in the presence of of low frequency activity and is rectified to eliminate itsneuromuscular blocking agents. This method was used by biphasic value. The electrical activity is recorded from oneEdmonds et al  to monitor anaesthesia. Unfortunately, channel, and is displayed as a low-speed paper trace.this technique is not sufficiently sensitive for the purposeof monitoring the level of sedation in ICU patients. The adequacy of the cerebral function monitor has not been confirmed in critically ill patients because it is drugLower oesophageal contractility dependent . For this reason, the cerebral functionEvans et al  observed a correlation of peristaltic con- monitor cannot be recommended for clinical use.tractility with depth of anaesthesia. Spontaneous loweroesophageal contractility represents a response to stress. Cerebral function analyzing monitorHowever, this response is subject to considerable interpa- This system uses two electroencephalography channels. Ittient variation, and it may also be influenced by atropine. was used by Sebel et al  to monitor the depth of
http://ccforum.com/content/4/4/217anaesthesia. It produces information that is easy to inter- Figure 2pret and that varies with depth of sedation. It is not as yetavailable for daily practice. Further studies are necessary Nb (ms)to validate the use of this device in ICU settings. 80 r 2 = 0.72Power spectral analysis 70This technique employs an alternative analysis of the elec-troencephalography signal. The signal is digitized at fixed 60time, analyzed and subjected to power-spectrum calcula- 50tion. Vesalis et al  described a correlation betweenspectral edge frequency and sedation with midazolam in 40ICU patients. Recently, the median frequency has beenused to regulate a closed loop of total intravenous anaes- 30thesia. This finding has not been confirmed in patients 20with more severe organic dysfunction . The utility ofthis technique in critically ill patients remain unknown. 10Sensory evoked potentials 0Evoked potentials (EPs) are electrophysiologic responses 15 10 5 Glasgow Coma Score modified by Cook (points)of the nervous system to sensory stimulation. A computeris used to average individual time-locked responses torepeated stimuli. EPs are divided into three classes on the Correlation between AEPs (low latency Nb) and scoring system (morebasis of latency. Long-latency EPs (hundreds of millisec- than 10 points corresponds to deep sedation).onds) are suppressed under surgical anaesthesia, and arenot useful for monitoring of sedation. Medium-latency EPs(tens of milliseconds) are often recordable under anaes- Interobserver agreement (calculated as weighted κ index) isthesia, and can be affected by anaesthetic state. Short- the most important feature in assessing scales of sedation.latency EPs (milliseconds), which are predominantly It is also desirable that other characteristics are included ingenerated at subcortical levels, are sufficiently strong to the assessment, such as simplicity, reliability, accuracy andbe recorded under sedation. minimal additional discomfort to the patient .The auditory evoked potentials (AEPs) are the simplest There is no ideal scoring system. More than 30 clinicalEPs to produce. Auditory stimulation is accomplished with scales have been described in the medical literature.filtered clicks delivered by headphones. EPs are recorded However, only two of these instruments have been ade-from scalp electrodes in response to a standard noise. quately validated for use in the ICU: the Ramsay scale and the GCSC. Because there is no goal standard againstThere is clinical evidence regarding the clinical utility of which to validate the sedation scales, researchers have tar-AEPs for monitoring of sedation. A recent study  corre- getted their investigations at determining the ‘clinimetric’lated this method with the results from five different scoring properties of these scales. De Jonghe et al , in a recentsystems. Further studies are required to validate the use of systematic review, observed the high reliability and satis-AEPs in monitoring of sedation. AEPs can only be recom- factory correlation with other scales achieved by themended for research in patients with deep levels of seda- Ramsay scale and Comfort scale. The only limitationtion, because light levels of sedation resulted in AEPs that observed was the lack of studies that validated these scaleare poorly correlated with scoring system results (Fig. 2). in detecting changes in the sedation status over time.The clinical utilities of other types of evoked response Ramsay scale(motor or visual) have not been demonstrated. This scoring system was described by Ramsay et al  in 1974 for the purpose of monitoring sedation withSubjective methods: scoring systems alphaxolone/alphadolone. It continues to be the mostThe only instruments that have demonstrated usefulness widely used scale for monitoring sedation in daily practice,in the critical care setting are the scoring systems that are as well as in clinical research.widely known as scales of sedation . These instru-ments are based on clinical observation. The scores are This instrument identifies situations of agitation or sleeprecorded according to direct evaluation by an observer. visually (Table 3). Some experts consider that it is more aEach scale should be validated according to the training scale of consciousness than a tool for measurement ofand characteristics of the professionals that use it. sedation . Those authors have also suggested that the
Critical Care Vol 4 No 4 CarrascoTable 3 Table 4Ramsay scale Glasgow Coma Scale modified by Cook and PalmaLevel Characteristics Characteristic Score1 Patient awake, anxious, agitated, or restless Eyes open Spontaneously 42 Patient awake, cooperative, orientated and tranquil In response to speech 33 Patient drowsy, with response to commands In response to pain 2 None 14 Patient asleep, brisk response to glabella tap or loud auditory Response to nursing procedures stimulus Obeys commands 55 Patient asleep, sluggish response to stimulus Purposeful movements 4 Nonpurposeful flexion 36 Patient has no response to firm nail-bed pressure or other Nonpurposeful extension 2 noxious stimuli None 1 Cough Spontaneous strong 4 Spontaneous weak 3 On suction only 2sedation levels identified using this scale are not clearly None 1defined or fully conclusive. Consequently, they considerthat this scale is excessively subjective and that it has Respiration Obeys commands 5poor validity. Spontaneous intubated 4 Spontaneous intermittent mandatory ventilator triggering 3Contrary to these opinions, in our experience this method Respiration against ventilator 2has good reliability, with good interobserver agreement No respiratory efforts 1(Cohen κ index 0.79; P < 0.0001) . This qualifies thisscale as sufficiently reproducible for clinical practice.Glasgow Coma Scale modified by Cook and Palma Figure 3Described by Cook in 1987 , this instrument providesa score of the reactivity of the patient under mechanical GCSC 0.98ventilation according to response to external stimuli 0.96(Table 4). Opening of the eyes is considered to be indica- 0.94 κ index: 0.94tive of higher functioning, and motor response is evaluated 0.92 (P < 0.00001)on the basis of somatic stimulation. It causes minimal addi- 0.90tional discomfort to the patient. Ramsay 0.88 scale 0.86The above cited study  confirmed the reproducibility 0.84of this scale, with good agreement between observers 0.82(Cohen κ index 0.94; P < 0.0001) which validated it for 0.80 κ index: 0.79practice as well as for clinical research . Fig. 3 illus- 0.78 (P < 0.0001)trates these findings. 0.76Bion scaleIn 1988, Bion  designed a three-dimensional linear Interobserver agreement in two sedation scales with two observers.analogue scale that combines evaluation of depth of seda-tion and degree of distress (a level of comprehension ofconsciousness). Although this system provides usefulinformation, it is too complex for use in daily practice.Comfort scale Sedation–agitation scale1994, Max et al  reported experience with a new desig- This scoring system was described by Riker et al  fornated scale in 85 mechanically ventilated children. Those the purpose of controlling treatment with haloperidol inauthors consider this scale to be sufficiently reliable, despite agitated ICU patients. It achieved good inter-rater correla-the fact that discrepancies between observers were tion (Cohen κ index 0.92), but it does not evaluate theobserved in 38% of the measurements. The characteristics relation between patient and ventilator. However, it is suffi-of this method mean that it has little application in adults. ciently reproducible for use in clinical practice.
http://ccforum.com/content/4/4/217Table 5Characteristics of scoring systemsScoring system Interoberver agreement Clinical utility (rating points 0–50) ReferenceRamsay scale 0.79 40 GCSC 0.94 45 Bion scale 0.45 30 Comfort scale Unavailable – Sedation–agitation scale 0.92 35 Motor activity assessment scale 0.83 35 Motor activity assessment scale Table 6This scale was described by Clemmer, and has recently Recommendations to guide sedative therapy according tobeen evaluated in surgical ICU patients by Devlin et al ventilatory mode. The reliability observed in this study was good(Cohen κ index 0.83), but this agreement should be con- Ventilatory mode Therapeutic goal Therapeutic goalfirmed in critically ill patients. (Ramsay scale level) (GCSC points) Assisted CMV (< 24 h) 3 8–12Rational selection of sedation scalesAll validated scales can be used in clinical practice. Assisted CMV (24–72 h) 3 8–12However, for research purposes the GCSC  is prefer- Assisted CMV (> 72 h) 3 8–12able. Table 5 summarizes the characteristics and rating Pressure controlled ventilation 4–5 15–18classification of sedation scales. Synchronous intermittent 2 13–15 mandatory ventilationPractical recommendations to guide sedative therapyaccording to ventilatory mode Pressure support ventilation 2 13–15The following recommendations are guidelines for special- Continuous positive airway 2 13–15ists. There is, to my knowledge, only one published article pressureregarding this topic . For this reason, the followingrecommendations are based on my experience. Obviously,the selection of treatment must be made according to clin-ical judgement, adapting it to the clinical circumstances of resistance must be evaluated. At present, we think that theeach patient. Table 6 summarize these recommendations. best approach is to maintain a light and comfortable level of sedation, if it is reasonably possible, in order toAssisted-controlled mechanical ventilation decrease the incidence of adverse effects of high dosesThe traditional controlled mechanical ventilation (CMV) of sedatives. The ideal sedation depth for most of thesemode does not permit synchronization between sponta- patients is mean sedation (level 3 of the Ramsay scale orneous breaths of the patient and the cycle of the respira- between 8 and 12 points of the GCSC).tor. For this reason, modern ventilators have substitutedCMV with assisted CMV. The assisted CMV mode is more The second factor is the anticipated duration of mechanicalflexible and permits spontaneous patient breathing at ventilation. If it is anticipated that sedation of less than 24 hsome points in the cycle. This means that it is not neces- (short-term sedation) will be required, then both propofol orsary for sedation to suppress totally the spontaneous midazolam should be selected. The initial dose of propofolbreathing of patient. Assisted CMV is the recommended should be 1 mg/kg, preceded by 1 mg/kg as a bolus.mode for initiating mechanical ventilation, because it Adjustments to the dose should be made in 10–20% incre-assures a specific minute volume even in the absence or ments or decrements. Midazolam should be administered atweakness of respiratory stimuli. Generally, this mode an initial dose of 0.1 mg/kg, preceded by 0.05 mg/kg as aachieves good synchronization between the ventilator bolus. Adjustments to the dose should also be made incycle and the effort of the patient. 10–20% increments or decrements. If the anticipated dura- tion of sedation is between 24 and 72 h (medium-termIn order to formulate the sedation regimen, two fundamen- sedation) then propofol is preferable to midazolam becausetal factors must be considered. First, the degree of patient of the unnecessary accumulation and extended sedation
Critical Care Vol 4 No 4 Carrascothat can occur with this drug. Nevertheless, if midazolam is For patients who experience disturbance in nocturnal sleep,used, then the dose should be titrated 12–24 h before overnight sedation under controlled ventilation is recom-sedation is due to be discontinued. If it is expected that mended, according to the plan described above .sedation will need to be sustained for longer than 3 days(long-term sedation), then midazolam is preferable. Two The preferred analgesic regimen is a combination of adays before discontinuation of sedation, midazolam should nonsteroideal anti-inflammatory drug with morphine orbe substituted with propofol to facilitate elimination of the pethidine, administered parenterally. The recommendedbenzodiazepines before the patient awakes. plan is a fixed regimen combined with an ‘on-demand’ regimen if the patient is able to cooperate. In patients withComplementary analgesia will also be necessary in most refractory pain, morphine administration at bolus doses ofcases, because none of the available sedatives have anal- 1–2.5 mg, subcutaneously or intravenously, via a patient-gesic properties. In my opinion, analgesics should be controlled analgesia pump can achieve excellent results.administered always if communication with the patient isnot possible. The initial plan should be to administer mor- Pressure support ventilationphine as a continuous infusion (0.5–1.5 mg/kg per h), with This form of ventilation is also considered partial support.a supplementary bolus of 3–5 mg if indicated. Alterna- It was designed for use during weaning from mechanicaltively, fentanyl may be used at equivalent doses. ventilation. Pressure support ventilation requires that the patient is able to initiate breathing. If the patient is ade-Pressure controlled ventilation quately ventilated, with an appropriate degree of analge-Some authors have postulated that this ventilatory mode sia, then sedation is not generally required. In exceptionalcan reduce the incidence of barotrauma, decreasing cases, in which the patient presents with agitation result-airway pressure and alveolar overdistension. This mode ing from a nonrespiratory cause, propofol or midazolamhas been used in refractory hypoxaemia, and it has been may be administered at anxyolitic doses as was describedassociated with other ventilatory techniques as the inver- for synchronized intermittent mandatory ventilation (lightsion of the inspiration–expiration relationship or high fre- sedation; level 2 of the Ramsay scale or 13–15 points onquency ventilation. There are practical limitations to the the GCSC) under close respiratory monitoring.use of this mode because it can cause a degree ofpatient–ventilator asynchrony, so most of the patients Continuous positive airway pressureneed deep sedation (level 4–5 of the Ramsay scale or This mode of partial respiratory support is widely used8–12 points on the GCSC). The recommended sedation because of technical considerations, and in order to avoidregimen is the same as that for assisted CMV (see above). total respiratory substitution with controlled ventilation. It also requires that the patient is able to initiate breathing.Synchronized intermittent mandatory ventilation Therefore, the recommendations are similar to those forThis mode is a partial support system that requires preser- pressure support ventilation, described above.vation of spontaneous breathing. It requires a degree ofcooperation from the patient. It is commonly used without Future strategies for selected patientscontinuous sedation in patients who are being weaned New evidence suggests that daily interruption of sedation infrom mechanical ventilation. selected patients may improve their situation by allowing clin- icians to optimize the administration of sedatives while ensur-Some patients ventilated in this manner require sedation ing optimal comfort for the patient . A word of caution isbecause of agitation as a result of nonrespiratory cause. If necessary regarding these findings, because this approachit is necessary to administer sedatives, the patient should is appropriate only for certain, stable patients. Furtherbe carefully monitored; if there is confusional symptoma- research is necessary to confirm these findings in thetology, then a combined regimen of a sedative at a low general population of ICU patients. However, these promis-dose and a neuroleptic should be administered. The thera- ing strategies might be an exciting prospect for the future.peutic goal is light sedation (level 2 of the Ramsay scaleor 13–15 points on the GCSC). For this purpose, propo- Instruments to monitor neuromuscular blockadefol is indicated at anxiolytic doses (0.5 mg/kg per h, ini- The above-described scoring systems are not useful fortially). Alternatively, midazolam can be used at a low dose monitoring sedation in patients treated with muscular(0.05 mg/kg per h), provided that the treatment is not blocking agents. Because these agents have a very lowextended beyond than 24 h. This combination achieves margin of safety, they should be reserved for extreme situ-excellent results in patients under assisted ventilation, and ations in which the potential benefit to the patient justifiesit has little effect on respiratory stimuli . If the patient is their use. In such circumstances, we recommend discon-in a confused state, then haloperidol may be administered tinuing their administration every 24 or 48 h in order toin a continuous infusion at a dose of 1–2 mg/h, with an perform an accurate assessment of neuromuscular func-initial bolus of 5 mg. tion. If this is not possible, an alternative can be to monitor
http://ccforum.com/content/4/4/217neuromuscular function using a nerve stimulator . The 11. Bion JF, Ledingham IMcA. Sedation in intensive care-a postalpurpose of this device is to provide sufficient stimuli to survey. Intensive Care Med 1987, 13:215–216. 12. Shelly MP, Mendel L, Park GR: Failure of critically ill patients toproduce action potentials in all fibres of a nerve. The sim- metabolise midazolam. Anaesthesia 1987, 42:619–626.plest way to stimulate nerves is to apply single stimuli at 13. Edmonds HL, Paloheimo M: Computerised monitoring of the EMG and EEG during anaesthesia: an evaluation of the anaesthesiaintervals no shorter than 10 s. Neuromuscular monitoring and brain function motor. Intensive Clin Monit Comput 1985, 1:offers the advantage of rapid response and objective data. 201–210. 14. Evans JM, Bithell JF, Vlachonikolic IG: Relationship between lower oesophageal contractility, clinical signs and surgery in man. Br JConclusion Anesth 1987, 59:1346–1355.The present review describes and compares the available 15. Peter S: Effects of high dose fentanyl anaesthesia on the elec-instruments for monitoring ICU sedation, from a practical troencephalogram. Anesthesiology 1959, 20:359–376. 16. Dubois M, Savege TM, O’Carroll TM, Frank M: General anaesthesiaand evidence-based point of view. Although many promis- and changes on the cerebral function monitor. Anaesthesia 1978,ing objective methods (measuring systems) are available, 33:157–164. 17. Sebel PS, Maynard DE, Major E, Frank M: The cerebral functionthere are no truly validated instruments for use in clinical analysing monitor (CFAM). Br J Anaesth 1983, 55:1265–1270.practice. AEPs can be used only for research in patients 18. Vesalis RA, carlon GC, Bedford SF: Spectral edge frequency corre-with deep levels of sedation. Other measuring systems lates with sedation level in ICU patients receiving i.v. midazolam [abstract]. Anesthesiology 1989, 71:A156.require further development and validation before they can 19. Schulte-Tamburen AM, Scheier J, Briegel J, Scwender D, Peter K:be considered useful in ICU. Continuing research will Comparison of five sedation scoring systems by means of audi- tory evoked potentials. Intensive Care Med 1999, 25:377–382.provide an objective system for improving the monitoring 20. Carrasco G, Molina R, Costa J, Soler JM, Paniagua J, Cobra Ll: Use-and controlling of this essential treatment for ICU patients. fulness of sedation scales in ICU. A comparative-randomised study in patients sedated with propofol, midazolam or opiates plus benzodiazepines [abstract]. Intensive Care Med 1992, 18Subjective methods (scoring systems) that are based on (Suppl 2):57.clinical observations have proven utility in guiding sedative 21. De Jonghe B, Cook D, Appere-De-Vecchi C, Meade M, Outin H:therapy. The GCSC achieves good face validity and relia- Using and understanding sedation scoring systems: a systematic review. Intensive Care Med 2000, 26:275–285.bility, which assures its clinical utility for routine practice 22. Ramsay MAE, Savege TM, Simpson BRJ, Goodwin R: Controlledand research. Other scales, in particular the Ramsay sedation with alphaxolone/alphadolone. Br Med J 1974, ii:656–659. 23. Hansen-Flaschen J, Cowen J, Polomano RC: Beyond the Ramsayscale, can be recommended for clinical use. scale: need for a validated measure of sedating drug efficacy in the intensive care unit. Crit Care Med 1994, 22:732–733.A conclusion that arises from the present review is that the 24. Carrasco G, Cabré L, Serra J: What can you associate with opiates for sedation and resuscitation [in French]. Rean Urg 1995; 4appropriate use of instruments to monitor sedation can (Suppl):33–38.improve the sedative treatment that we deliver to our 25. Cook S, Palma O: Propofol as a sole agent for prolonged infusion in intensive care. J Drug Dev 1989, (Suppl 2):65–67.patients. It is anticipated that future contributions to this 26. Bion JF: Sedation and analgesia in the intensive care unit. Hospitalforgotten field will result in improvements in the quality of Update 1988, 14:1272–1286.care that our patients need and deserve. 27. Max CM, Smith PG, Lowie LH, et al: Optimal sedation of mechani- cally ventilated pediatrical patients. Crit Care Med 1994, 22:163– 170. 28. Riker RR, Picard JT, Fraser GL: Prospective evaluation of the seda-References tion-agitation scale for adult critically ill patients. Crit Care Med1. Carrasco G, Cabré Ll. Sedation in intensive medicine [in Spanish]. 1999, 27:1325–1329. Farmacia Hospitalaria 1994, 19:59–64. 29. Devlin JW, Boleski G, Mlinarek M, et al: Motor activity assessment2. Shapiro BA, Warren J, Egol AB, et al: Practice parameters for intra- scale: a valid and reliable sedation scale for use with mechani- venous analgesia and sedation for adult patients in the intensive cally ventilated patients in adult surgical intensive care unit. Crit care unit: an executive summary. Crit Care Med 1995, 23:1596– Care Med 1997, 27:1271–1275. 1600. 30. Carrasco G, Cabré L: Control of sedation in patients with acute3. Carrasco G, Cabré L, Sobrepere G, et al: Synergistic sedation with respiratory distress syndrome. In: Acute Respiratory Distress Syn- propofol and midazolam in intensive care patients after coronary drome [in French]. Edited by Mancebo J, Blanch L. Paris: Elsevier; artery bypass grafting. Crit Care Med 1998, 26:844–851. 1999:68–81.4. O’Sullivan GF, Park GR: The assessment of sedation in critically ill 31. Wheeler A: Sedation, analgesia, and paralyisis in the intensive patients. Clin Intensive Care 1991, 1:116–122. care unit. Chest 1993, 104:566–577.5. Hole A: Monitoring sedation in the ICU patient. Clin Intensive Care 1993, (Suppl 2):27–29.6. Kress JP, Pohlman RN, O’Connor MF, Hall JB: Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000, 342:1471–1477.7. Fowler SB, Hertzog J, Wagner BK: Pharmacological interventions for agitation in head injured patients in the acute care setting. J Neurosci Nursing 1995, 27:119–123.8. Kollef MH, Levy NT, Ahrens TS, et al: The use of continuous i.v. sedation is associated with prolongation of mechanical ventila- tion. Chest 1998, 114:541–548. Author’s affiliation: Intensive Care Service, SCIAS – Hospital de9. Costa J, Cabré L, Molina R, Carrasco G: Cost of ICU sedation: com- Barcelona, Barcelona, Spain parison of empirical and controlled sedation methods. Clin Inten- sive Care 1994; 5:17–21.10. Cruspinera A, Gimeno G, Figueras MJ, et al: Nurses control of Correspondence: Genís Carrasco, MD PhD, Intensive Care Service, patients in critically ill patients [abstract; in Spanish]. Med Inten- SCIAS – Hospital de Barcelona, Barcelona, Spain. siva 1993; 17:N7. Tel: +933 230 699; fax: +932 800 710