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Clinical review: Agitation and delirium in the critically ill – significance and management

Jean-Claude Chevrolet* and Philippe Jolliet

Author Affiliations

Hôpital Cantonal Universitaire, rue Micheli-du-Crest, CH 1211 Geneva 4, Switzerland

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Critical Care 2007, 11:214  doi:10.1186/cc5787


The electronic version of this article is the complete one and can be found online at: http://ccforum.com/content/11/3/214


Published:17 May 2007

© 2007 BioMed Central Ltd

Abstract

Agitation is a psychomotor disturbance characterized by a marked increase in motor and psychological activity in a patient. It occurs very frequently in the intensive care setting. It may be isolated, or accompanied by other mental disorders, such as severe anxiety and delirium. Frequently, agitation is a sign of brain dysfunction and, as such, may have adverse consequences, for at least two reasons. First, agitation can interfere with the patient's care and second, there is evidence demonstrating that the prognosis of agitated (and delirious) patients is worse than that of non-agitated (non-delirious) patients. These conditions are often under-diagnosed in the intensive care unit (ICU). Consequently, a systematic evaluation of this problem in ICU patients should be conducted. Excellent tools are presently available for this purpose. Treatment, including prevention, must be undertaken without delay, and the ICU physician should follow logical, strict and systematic rules when applying therapy.

Introduction

Agitation is a psychomotor disturbance characterized by a marked increase in both motor and psychological activities, often accompanied by a loss of control of action and a disorganization of thought. This problem is driven by frequently occurring situations in the intensive care unit (ICU), such as anxiety and delirium. Therefore, it is fairly common in the ICU setting, particularly in older patients, and it may be caused by numerous factors, linked both to the disease itself (metabolic disorders, medications, sepsis-associated encephalopathy, and so on) and to external factors (noise, discomfort, pain, and so on) [1]. Agitation per se may be dangerous in the ICU: its occurrence may compromise care, raise metabolic requirements and, finally, increase morbidity and mortality [2]. Length of stay in the ICU as well as in the hospital may also be increased, in turn leading to an increase in costs. In addition, compared to that of similar but non-delirious patients, the post-hospital mortality rate may be higher in patients having presented with agitation and delirium. For all these reasons, these mental disorders should be a source of serious concern and, therefore, vigorously managed through a systematic approach [3]. It is generally accepted that these symptoms represent a marker of acute cerebral insufficiency.

Significance of agitation and delirium in the ICU

Besides agitation, several mental disturbances may be observed in the ICU, in particular anxiety and delirium. It is not presently known if these mental states express different types of brain dysfunction, or if they represent some sort of spectrum in the severity of the cerebral insult [1]. Anxiety is a diffuse sensation of fear, which is not related to a real and actual external danger. This sensation is expected to occur in the ICU due to the numerous stressful situations occurring in this setting (pain, noise, and loss of body control, among others) [4]. If a certain degree of anxiety seems to be 'normal' in the ICU environment, some authors have described a 'pathological' anxiety when this sensation appears to be disproportionately high considering its cause, and when it is associated with other severe signs, such as severe dysautonomia, loss of self-control, and cannot be appropriately treated due to a complete lack of patient cooperation [5].

Delirium is defined as an acute change in mental status, or a fluctuation of mood, associated with impaired attention, disorganized thinking, confusion and an altered level of consciousness [5]. It is often referred to as a state of acute confusion. Most cases of delirium have an acute onset, particularly in the ICU. Typically, this cognitive alteration varies throughout the day, and achieves peak intensity during the night. This symptom is usually reversible within a period of days or weeks, whereas some patients can progress to permanent brain failure. Illusions and hallucinations may also occur. Florid delirium with intense agitation in a combative patient (active delirium) is easy to detect, but delirium can also be present in a calm and quiet patient (hypoactive delirium), the succession of both types being possible [6]. Despite the fact that this disturbance is frequent in the ICU (occurring in 15% to 40% of patients) [7,8], it seems that critical care physicians' performance in detecting it remains poor; around two-thirds of these patients are not identified [1,9]. Fortunately, simple tools that can be used by non-psychiatrists at the bedside have been developed to detect delirium in the ICU [10,11].

Many difficult but interesting questions regarding agitation and delirium in the ICU remain unanswered. First, it is not known precisely if the prevention [12] or the timely detection and treatment of this condition can favorably influence a patient's outcome [13]. Second, the exact relationships between agitation and delirium, on the one hand, and mortality and cerebral dysfunction, on the other, are poorly understood. In particular, it would be of great interest to understand if the brain is just a passive victim, one of many organs to dysfunction in critical illness, expressing its injury through agitation and delirium, or if it is an active player, participating and contributing to the extracerebral organ dysfunction [14,15]. The indication and type of treatment for agitation and delirium are clearly related to the answers to these questions.

The exact mechanisms causing the mental problems described above in ICU patients have not been fully characterized, except when a metabolic cause is obvious, such as hypoglycemia, or hypoxemia. Nevertheless, these disturbances are believed to have an organic basis [16]. The generalized electroencephalographic abnormalities observed during this condition represent an argument in favor of such a diffuse neurological dysfunction [17].

Several hypotheses are actively discussed today. First, the role of abnormalities at the level of the central neurotransmission process is debated; these abnormalities are characterized by an excess in dopaminergic activity consecutive with a depletion in cholinergic stores [18,19]. Importantly, many drugs prescribed in the ICU have an anticholinergic activity and some of them have been clearly associated with delirium, such as antiarrhythmic medications, antibiotics (penicillin, rifampin), and so on. These drugs should be avoided in delirious patients when possible. Interestingly, an 'inflammatory reflex' has recently been observed, leading to a real cooperation between the central nervous system and the inflammatory pathways [20]. More precisely, an anti-inflammatory action exerted by vagus nerve endings located at the vicinity of macrophages in inflammatory foci, through nicotinic receptors at the surface of these cells, has been demonstrated [21]. These observations could provide some explanation as to the origin of delirium caused by a neuronal dysfunction, as well as a substrate for the causal role of the brain in immunomodulation [15]. Other central neurotransmitters have been thought to play a role in delirium, such as dopamine [22], serotonin [23], or gamma-aminobutyric acid (GABA) [16]. This probably represents the substrate for the delirium occasionally associated with benzodiazepines or propofol (so-called 'paradoxical reactions'). Note also that benzodiazepines [24] and opioids [25] have been clearly shown to be independent factors for the occurrence of delirium.

The second group of hypotheses to explain the mental dysfunction observed in the ICU relates to the presence of potential organic cerebral lesions not detectable by currently available technology (computed tomography (CT) scan, magnetic resonance imaging, and so on) [26]. There are clinical and epidemiological arguments in favor of these hypotheses. Thus, some patients who suffer a mental dysfunction during their ICU stay never fully recover, whereas a rapid decline in the cognitive function of others has been described after an ICU stay during which delirium occurred [27,28]. It is known that in severe sepsis, for instance, many organs are affected by structural damage, particularly in the microcirculation (microthromboses, endothelial swelling, and so on). There is no a priori reason for the brain to be spared by such damage.

Even if the causes of mental disturbance observed in the ICU are poorly known, their consequences have been largely described. Severe psychological sequellae have been documented [29]. A dangerous increase in the metabolic demand due to agitation may compromise already limited myocardial or cerebral functions, and intracranial hypertension may be worsened [3]. Finally, mortality and overall morbidity may be increased by, for example, accidental tracheal extubation, asynchrony with the ventilator, removal of catheters in which vital medications are administered, and so on [3,30], and hospital length of stay is also increased [31].

Management

Evaluation of mental disturbance in the ICU

Clinical evaluation

Before treating agitation, anxiety or delirium in the ICU, these symptoms have to be closely scrutinized, and their diagnosis firmly established. Firstly, the clinician needs to know about the patient's pre-existing mental state in order to establish whether a link exists between the presently observed condition and the disease that resulted in ICU admission. Indeed, it is important to recall that around 30% to 40% of ICU patients present with some degree of cognitive impairment prior to their admission [32]. The second step is to perform an objective assessment of the patient's present mental state. A non-standardized evaluation by a non-psychiatrist is not recommended, especially as several evaluation methods that have been validated in the ICU are presently available; these methods can be used by ICU physicians and nurses at the bedside, without being too time-consuming [33]. The 'reliability' (consistency of the evaluation when repeated over time) and the 'validity' (accuracy when evaluating the patient's mental state) of these measurements, as well their 'reactivity' (ability to detect small changes in the variable being studied) [34], are excellent [33]. Many scores for evaluating agitation, sedation and confusion in the ICU are presently available [10,11,34-37].

However, all these scores suffer from the same conceptual difficulty: each is constructed in a similar manner, that is, they combine several clinical parameters and psychological measurements into a continuous scale score. This approach, while providing a reproducible and easy to use tool, also carries the risk of lack of specificity regarding specific aspects of mental alterations. Nonetheless, we are convinced that, despite their weaknesses, it is important to measure sedation, agitation and confusion in ICU patients with these tools. This position finds support from recent data showing that not only is caregiver compliance with their use excellent in the ICU [38], but also that their use can improve the management of agitated patients [39]. In addition, for research purposes, an algorithm aimed at detecting delirium has been recently developed [40].

Non-clinical investigations

EEGs (electroencephalograms) generally confirm the results of clinical examinations, that is, that mental disorders occurring in ICU patients are associated with a global brain dysfunction. In addition, in some patients, particularly when these disorders are associated with sepsis (sepsis associated encephalopathy) [41], coma [17,42] or brain damage [42], continuously recorded EEGs can detect subclinical seizures or predict the occurrence of ischemic brain lesions. However, no specific EEG recording in mental disorders associated with the ICU has been performed, and several technical concerns remain, particularly for continuous EEG monitoring [43]. In addition, several issues remain unanswered regarding continuous EEG recording in the ICU, namely its exact indication, the required duration of monitoring, and the clinical significance of certain tracing patterns, such as periodic lateralized epileptiform discharges (PLEDs) [44]. Therefore, the consequences of EEG recording on treatment options and patient outcome remain to be investigated in the ICU [45].

Simplified analysis of EEGs, such as bispectral analysis, has been extensively studied in the operating room to assess the depth of anesthesia. However, this technique seems difficult to use in the ICU, even for assessing the degree of patient arousal [46], and it is quite inappropriate for the evaluation of mental disorders such as delirium, either because the patient is agitated, or because of a lack of specificity in a non-agitated delirious patient [47]. Other techniques, among which evoked potentials, are not presently employed in the routine monitoring of ICU patients suffering mental disorders [48,49].

Treatment of ICU-associated mental disorders

As stated above, agitation, anxiety and delirium are frequent in the ICU, but they are under-diagnosed, which in turn can have adverse consequences on patient outcome [9].

Therefore, every effort should be undertaken to prevent and treat these problems, even if there is to date no formal proof of an improvement in mortality with treatment [1]. An algorithm may help the clinician to conduct a systematic approach to the management of agitation and delirium in the ICU (Figure 1).

thumbnailFigure 1. Assessment and management of delirium. BZD, benzodiazepine; CAM-ICU, confusion assessment method for the intensive care unit [32]; CT, computed tomography; DSM, Diagnostic and Statistical Manual of Mental Disorders [5]; EEG, electroencephalogram; ICU, intensive care unit; MRI, magnetic resonance imaging.

Non-pharmacological treatment must be considered first, common sense and good clinical practice being the rule to avoid light anxiety in ICU patients, for example, reassurance, a comfortable position in the bed, voiding of a full and painful bladder, and so on. Physical restraint can also be considered, keeping in mind the ethical concerns regarding its use [50]. Physically restraining a patient should, therefore, never be considered a trivial measure. It should in our view be the result of a rational, systematic and documented (written) approach, following an accepted algorithm. The patient's family should be given clear, complete and objective explanations regarding treatment choices. Follow-up and monitoring should follow a clear procedure to avoid complications (the lethal strangulation of an ICU patient has even been observed!), and the rationale for pursuing its application in a given patient regularly discussed.

When simple measures are not sufficient to treat agitation, a pharmacological approach must be undertaken. Beforehand, a few simple principles should be remembered. First, before undertaking a symptomatic treatment with drugs, every potential cause of the mental disorder (hypoglycaemia, hyponatremia, and so on) must have been corrected. Second, it should be remembered that several drugs commonly prescribed for agitation (such as benzodiazepines) may, by themselves, cause or increase psychological or cognitive disturbances. Third, the objectives of treatment (for example, reducing pain, diminishing anxiety, inducing a better sleep rhythmicity, treating delirium, and so on) must be clearly defined in order to choose the appropriate drug. Fourth, the level of sedation and the therapeutic goal when a delirious patient is treated must be strictly adjusted and periodically assessed by objective means (scores and scales) in order to avoid the dangers of both under- and over-sedation.

An abundant literature is available on the treatment of agitation and behavioral disturbances [51], but only a small amount of information is specifically related to the ICU setting [52,53]. Only a few classes of drugs have been sufficiently evaluated in the ICU to be mentioned here, that is, benzodiazepines, propofol and ketamine, as well as classic and atypical neuroleptics. Myorelaxation must remain a rare exception for treatment of behavioral disturbances. Only patients with severe neurotrauma who require a strict control of their movements as a result of intracranial hypertension or vertebral instability, patients with unstable myocardial ischemia before a coronary intervention, or some patients with severe ARDS in whom mechanical ventilation proves very difficult can be considered for a brief course of myorelaxants. A simple approach is to first ensure adequate pain control with opioids, and then treat anxiety with a benzodiazepine, adding a neuroleptic drug if delirium is present. It should be kept in mind that no controlled study is presently available confirming the usefulness of administering neuroleptics in the ICU setting [54]. However, haloperidol remains largely used today in ICU patients, given its various benefits: a rapid onset of action, a lowering of the epileptic threshold (subclinical epileptic seizures are not rare in such patients) and a possible favorable effect on the outcome of patients with delirium, albeit this effect was suggested only in a retrospective analysis [55]. However, many side-effects have been reported with this medication, such as cardiac arrhythmias, extrapyramidal symptoms, anticholinergic action, and so on. To date, there has been no formal study on the new atypical antipsychotic drugs in ICU patients, except for olanzapine [56]. This drug may be useful in case of contraindication or side-effects with haloperidol. Studies should now focus on these drugs in the ICU setting, and one study (MIND) is ongoing, comparing placebo, haloperidol and ziprazidone [57].

Abbreviations

EEG = electroencephalogram; ICU = intensive care unit.

Competing interests

The authors declare that they have no competing interests.

References

  1. Pandharipande P, Jackson J, Ely E: Delirium: acute cognitive dysfunction in the critically ill.

    Curr Opin Crit Care 2005, 11:360-368. PubMed Abstract | Publisher Full Text OpenURL

  2. Ely E, Shintani A, Truman B, Speroff T, Gordon S, Harrell F, Inouye S, Bernard G, Dittus R: Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit.

    JAMA 2004, 291:1753-1762. PubMed Abstract | Publisher Full Text OpenURL

  3. Siegel M: Management of agitation in the intensive care unit.

    Clin Chest Med 2003, 24:713-725. PubMed Abstract | Publisher Full Text OpenURL

  4. Novaes M, Knobel B, Bork A, Pavao O, Nogueira-Martins L, Ferraz M: Stressors in ICU: perception of the patient, relatives and health care team.

    Intensive Care Med 1999, 25:1421-1426. PubMed Abstract | Publisher Full Text OpenURL

  5. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 4th edition (DSM IV). Washington, DC: American Psychiatric Publishing; 1994. OpenURL

  6. Meagher D, Hanlon D, Mahony E: Relationship between symptoms and motoric subtypes of delirium.

    J Neuropsychiatry Clin Neurosci 2000, 12:51-58. PubMed Abstract | Publisher Full Text OpenURL

  7. Cohen IL, Gallagher TJ, Pohlman AS, Dasta JF, Abraham E, Papadokos PJ: Management of the agitated intensive care unit patient.

    Crit Care Med 2002, 30(1):S97-S124. Publisher Full Text OpenURL

  8. Inouye S: The dilemma of delirium: clinical and research controversies regarding diagnosis and evaluation of delirium of hospitalized elderly medical patients.

    Am J Med 1994, 97:278-288. PubMed Abstract | Publisher Full Text OpenURL

  9. Francis J, Martin D, Kapoor W: A prospective study of delirium in hospitalized elderly.

    JAMA 1990, 263:1097-1101. PubMed Abstract | Publisher Full Text OpenURL

  10. Bergeron N, Dubois M, Dumont M, Dial S, Skrobic Y: Intensive care delirium screening checklist: evaluation of a new screening tool.

    Intensive Care Med 2001, 27:1432-1438. PubMed Abstract | Publisher Full Text OpenURL

  11. Ely E, Margolin R, May L, Francis J, May L, Truman B, Dittus R, Speroff T, Gautam S, Bernard G, Inouye S: Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).

    Crit Care Med 2001, 29:1370-1379. PubMed Abstract | Publisher Full Text OpenURL

  12. Inouye S, Bogardus S, Charpentier P, Leo-Summers L, Acampora D, Holford T, Cooney LJ: A multicomponent intervention to prevent delirium in hospitalized older patients.

    N Engl J Med 1999, 340:669-676. PubMed Abstract | Publisher Full Text OpenURL

  13. Riker R, Fraser G: Einstein, quantum mechanics and delirium.

    Crit Care Med 2005, 33:1421-1422. PubMed Abstract | Publisher Full Text OpenURL

  14. Crippen D: Life-threatening brain failure and agitation in the intensive care unit.

    Crit Care 2000, 4:81-90. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL

  15. Sharshar T, Hopkinson N, Orlikowski D, Annane D: Science review: The brain in sepsis – culprit and victim.

    Crit Care 2005, 9:37-44. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL

  16. Milbrandt E, Angus D: Potential mechanisms and markers of critical illness-associated cognitive dysfunction.

    Curr Opin Crit Care 2005, 11:355-359. PubMed Abstract | Publisher Full Text OpenURL

  17. Hirsch L: Continuous EEG monitoring in the intensive care unit: an overview.

    J Clin Neurophysiol 2004, 21:332-340. PubMed Abstract | Publisher Full Text OpenURL

  18. Flacker J, Wei J: Endogenous anticholinergic substances may exist during acute illness in elderly medical patients.

    J Gerontol A Biol Sci Med Sci 2001, 56:M353-M355. PubMed Abstract | Publisher Full Text OpenURL

  19. Mussi C, Ferrari R, Ascari S, Salvioli G: Importance of serum anticholinergic activity in the assessment of elderly patients with delirium.

    J Geriatr Psychiatry Neurol 1999, 12:82-86. PubMed Abstract | Publisher Full Text OpenURL

  20. Czura C, Tracey K: Autonomic neural regulation of immunity.

    J Intern Med 2005, 257:156-166. PubMed Abstract | Publisher Full Text OpenURL

  21. Borovikova L, Ivanova S, Zhang M, Yang H, Botchkina G, Watkins L, Wang H, Abumrad N, Eaton J, Tracey K: Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin.

    Nature 2000, 405:458-462. PubMed Abstract | Publisher Full Text OpenURL

  22. Sommer B, Wise L, Kraemer H: Is dopamine administration possibly a risk factor for delirium?

    Crit Care Med 2002, 30:1508-1511. PubMed Abstract | Publisher Full Text OpenURL

  23. Boyer E, Shannon M: The serotonin syndrome.

    N Engl J Med 2005, 352:1112-1120. PubMed Abstract | Publisher Full Text OpenURL

  24. Pandharipande P: Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients.

    Anesthesiology 2006, 104:21-26. PubMed Abstract | Publisher Full Text OpenURL

  25. Marcantonio E, Juarez G, Goldman L, Mangione C, Ludwig L, Lind L, Katz N, Cook F, Orav J, Lee T: The relationship of postoperative delirium with psychoactive medications.

    JAMA 1994, 272:1518-1522. PubMed Abstract | Publisher Full Text OpenURL

  26. Orlikowski D, Sharshar T, Annane D: The brain in sepsis.

    Adv Sepsis 2003, 3:4-8. OpenURL

  27. Jackson J: The association between delirium and cognitive decline: a review of the empirical litterature.

    Neuropsychol Rev 2004, 14:87-98. PubMed Abstract | Publisher Full Text OpenURL

  28. Jackson J, Hart R, Gordon S, Shintani A, Truman B, May L, Ely E: Six-month neuropsychological outcome of medical intensive care unit patients.

    Crit Care Med 2003, 31:1226-1234. PubMed Abstract | Publisher Full Text OpenURL

  29. Jones C, Griffith R, Humpris G: Memory, delusions, and the development of of acute posttraumatic stress disorder-related symptoms after intensive care.

    Crit Care Med 2001, 29:573-580. PubMed Abstract | Publisher Full Text OpenURL

  30. Lorente L, Huidoboro M, Martin M, Jimenez A, Mora M: Accidental catheter removal in critically ill patients: a prospective and observational study.

    Crit Care 2004, 8:R229-R233. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL

  31. Thomason J, Shintani A, Peterson E, Pun B, Jackson J, Ely E: Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients.

    Crit Care 2005, 9:R375-R381. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL

  32. Pisani M, Inouye S, McNicoll L, Redlich C: Screening for pre-existing cognitive impairment in older intensive care patients.

    J Am Geriatr Soc 2003, 51:591-598. PubMed Abstract | Publisher Full Text OpenURL

  33. De Jonghe B, Cook D, Appere-De-Vecchi C, Guyatt GH, Mead M, Outin H: Using and understanding sedation scoring systems: a systematic review.

    Intensive Care Med 2000, 26:275-285. PubMed Abstract | Publisher Full Text OpenURL

  34. De Jonghe B, Cook D, Griffith R, Appere-de-Vecchi C, Guyatt GH, Théron V, Vagnerre V, Outin H: Adaptation to the intensive care environment (ATICE): development and validation of a new sedation assessment instrument.

    Crit Care Med 2003, 31:2344-2354. PubMed Abstract | Publisher Full Text OpenURL

  35. Ely E, Inouye S, Bernard G, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, et al.: Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU).

    JAMA 2001, 286:2703-2710. PubMed Abstract | Publisher Full Text OpenURL

  36. Devlin J, Boleski G, Mlynarek M, Mark R, Nerenz D, Peterson E, Jankowski M, Horst H, Zarowitz B: Motor activity assessment scale: a valid and reliable sedation scale for use with mechanical ventilated patients in an adult surgical intensive care unit.

    Crit Care Med 1999, 27:1271-1275. PubMed Abstract | Publisher Full Text OpenURL

  37. Riker R, Picard J, Fraser G: Prospective evaluation of the Sedation-Agitation Scale (SAS) for adult critically ill patients.

    Crit Care Med 1999, 27:1325-1329. PubMed Abstract | Publisher Full Text OpenURL

  38. Truman B, Gordon S, Peterson J, Shintani A, Jackson J, Foss J, Harding S, Bernard G, Dittus R, Ely E: Large-scale implementation of sedation and delirium monitoring in the intensive care unit: a report from two medical centers.

    Crit Care Med 2005, 33:1199-1205. PubMed Abstract | Publisher Full Text OpenURL

  39. Micek S, Anand N, Laible B, Shannon W, Kollef M: Delirium as detected by the CAM-ICU predicts restraint use among mechanically ventilated patients.

    Crit Care Med 2005, 33:1260-1265. PubMed Abstract | Publisher Full Text OpenURL

  40. Pisani M, Araujo K, Van Ness P, Zhang Y, Ely E, Inouye S: A research algorithm to improve detection of delirium in the intensive care unit.

    Crit Care 2006, 10:R121-R129. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL

  41. Consales G, de Gaudio A: Sepsis assopciated encephalopathy.

    Minerva Anestesiol 2005, 71:39-52. PubMed Abstract | Publisher Full Text OpenURL

  42. Claassen J, Mayer S, Hirsch L: Continuous EEG monitoring in patients with subarachnoid hemorrhage.

    J Clin Neurophysiol 2005, 22:92-98. PubMed Abstract | Publisher Full Text OpenURL

  43. Jordan K: Continuous EEG monitoring in the neuroscience intensive care unit and emergency department.

    J Clin Neurophysiol 1999, 16:14-39. PubMed Abstract | Publisher Full Text OpenURL

  44. Chong D, Hirsch L: Which EEG patterns warrant treatment in the critically ill ? Reviewing the evidence for treatment of periodic epileptiform discharges and related patterns.

    J Clin Neurophysiol 2005, 22:79-91. PubMed Abstract | Publisher Full Text OpenURL

  45. Hirsch L, Brenner R, Drislane F, So E, Kaplan P, Jordan K, Herman S, LaRoche S, Young B, Bleck T, et al.: The ACNS subcommittee on research terminology for continuous EEG monitoring: proposed standardized terminology for rythmic and periodic EEG patterns encountered in critically ill patients.

    J Clin Neurophysiol 2005, 22:128-135. PubMed Abstract | Publisher Full Text OpenURL

  46. Nasraway S, Wu E, Kelleher R, Yasuda C, Donnelly A: How reliable is the bispectral index in critically ill patients ? A prospective, comparative, single-blinded observer study.

    Crit Care Med 2002, 30:1483-1487. PubMed Abstract | Publisher Full Text OpenURL

  47. Ely E, Truman B, Manzi D, Sigl J, Shintani A, Bernard G: Consciousness monitoring in ventilated patients: bispectral EEG monitors arousal, not delirium.

    Intensive Care Med 2004, 30:1537-1543. PubMed Abstract | Publisher Full Text OpenURL

  48. Schulte-Tamburen A, Scheier J, Briegel J, Schwender D, Peter K: Comparison of five sedation scoring systems by means of auditory evoked potentials.

    Intensive Care Med 1999, 25:350-352. PubMed Abstract | Publisher Full Text OpenURL

  49. Zauner C, Gendo A, Kramer L, Funk G, Bauer E, Schenk P, Raatheiser K, Madl C: Impaired subcortical and cortical sensory evoked potential pathways in septic patients.

    Crit Care Med 2002, 30:1136-1139. PubMed Abstract | Publisher Full Text OpenURL

  50. Maccioli G, Dorman T, Brown B, Mazuski J, McLean B, Kuszaij J, Rosenbaum S, Frankel L, Devlin J, Govert J, et al.: Clinical practice guidelines for the maintenance of patient physical safety in intensive care unit: use of retraining therapies – American College of Critical Care Medicine Task Force 2001–2002.

    Crit Care Med 2003, 31:2665-2676. PubMed Abstract | Publisher Full Text OpenURL

  51. Battaglia J: Pharmacological management of acute agitation.

    Drugs 2005, 65:1207-1222. PubMed Abstract | Publisher Full Text OpenURL

  52. Walder B, Tramèr M: Analgesia and sedation in critically ill patients.

    Swiss Med Wkly 2004, 134:333-336. PubMed Abstract | Publisher Full Text OpenURL

  53. Jacobi J, Fraser G, Coursin D, Riker R, Fontaine D, Wittbrodt E, Chalfin D, Masica M, Bjerke H, Coplin W, et al.: Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult, developed through the Task Froce of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM) in collaboration with the American Society of Health-System Pharmacists (ASHP), and in alliance with the American College of Chest Physicians, and approved by the Board of Regents of ACCM, and the Council of SCCM and the ASHP Board of Directors.

    Crit Care Med 2002, 30:119-141. PubMed Abstract | Publisher Full Text OpenURL

  54. Battaglia J, Moss S, Rush J, Leedom L, Dubin W, McGlynn C, Goodman L: Haloperidol, lorazepam, or both for psychotic agitation ? A multicenter, prospective, double-blind, emergency department study.

    Am J Emerg Med 1997, 15:335-340. PubMed Abstract | Publisher Full Text OpenURL

  55. Milbrandt E, Kersten A, Kong L, Weissfeld L, Clermont G, Fink M, Angus DC: Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients.

    Crit Care Med 2005, 33:226-229. PubMed Abstract | Publisher Full Text OpenURL

  56. Skrobic Y, Bergeron N, Dumont M, Gottfried S: Olanzapine vs. haloperidol: treating delirium in a critical care setting.

    Intensive Care Med 2004, 30:444-449. PubMed Abstract | Publisher Full Text OpenURL

  57. Ely E: The MIND Study. [http:/ / www.clinicaltrials.gov/ ct/ gui/ show/ NCT00096863;jessionid=D25B155CB67EE A3F8C98F5D6B67C9F1B?order=2] webcite