The Can delirium Assessments BeAccurately Labelled (CABAL)Investigators groupJohn W. DevlinGilles L. FraserAaron M. JoffeRichard R. RikerYoanna Skrobik

The accurate recognition of delirium in the ICU:the emperor’s new clothes?

Received: 3 September 2013Accepted: 6 September 2013Published online: 11 October 2013� Springer-Verlag Berlin Heidelberg and ESICM 2013

J. W. DevlinDepartment of Pharmacy Practice, Northeastern University,Boston, USA

G. L. FraserDepartments of Pharmacy and Critical Care, Tufts UniversitySchool of Medicine, Maine Medical Center, Portland, USA

A. M. JoffeDepartment of Anesthesiology and Pain Medicine, University ofWashington/Harborview Medical Center, Seattle, WA, USA

R. R. RikerNeuroscience Institute and Department of Critical Care Medicine,Tufts University School of Medicine, Maine Medical Center,22 Bramhall Street, Portland, ME, USA

Y. Skrobik ())Faculty of Medicine, Critical Care Chair, Universite de Montreal,Montreal, QC, Canadae-mail: yoanna.skrobik@umontreal.ca

Delirium among critically ill patients has been vigorouslyinvestigated over the last decade. Publications haveaddressed its diagnostic criteria, risk factors, preventionand treatment strategies and outcomes. Screening for adiagnosis of delirium in mechanically ventilated patientshas been reported using the Intensive Care DeliriumScreening Checklist (ICDSC) and the Confusion Assess-ment Method for the Intensive Care Unit (CAM-ICU),with both now being recommended for routine use in theICU [1]. These tools are important and are thought to aidclinicians in identifying delirium in patients in whom it

might otherwise go unrecognized [2]. However, a numberof recent reports should temper the unequivocalendorsement of delirium diagnosis in the ICU using atool-based approach.

Several reports now suggest that level of conscious-ness, an important component of delirium assessment inthe CAM-ICU (2 of 4 features) and ICDSC (1 of 8 fea-tures) screening tools, may also be a critical confounderduring delirium recognition efforts. The ICDSC specifiesthat ‘‘psychomotor slowing’’ should not be considered ifthis slowing is attributable to sedative administration [3],since consciousness is recognized to be the least validICDSC component, particularly when the ICDSC is per-formed by nurses [4, 5]. Whether this approach has beenused in studies using the ICDSC is usually not reported.This feature has not been tested with the CAM-ICU todate.

Patients too sedated to be vigilant or responsive canalter delirium assessment rates. In one report, CAM-ICUand Richmond Agitation and Sedation Score (RASS) datacomparison revealed that 69 % of CAM-ICU positiveassessments occurred in patients with a RASS B 0 [6];over half of the patients with a RASS of -2 and 25 % ofthose with a RASS -1 were not considered assessable.Among patients whose RASS scores changed more thantwo levels from the previous day, the presence of deliriumdetected with the CAM-ICU was five times more likely[6]. Analyzing data from the SEDCOM study revealedthat delirium (evaluated with the CAM-ICU) was leastfrequent with a RASS = 0 and increased significantlywith RASS assessments of -1, and even more so at -2and -3 [7]. Another study highlighted that the frequencyof delirium-positive CAM-ICU assessments rose by 20 %if the RASS was -2 to -3 [8]. Once persistently coma-tose patients were excluded from this study, these authorsfound 57/71 (80 %) were CAM-ICU positive at leastonce, but nearly a fifth (19.3 %, 95 % CI 11–31 %) wereCAM-ICU positive only when RASS levels were -2 or

Intensive Care Med (2013) 39:2196–2199DOI 10.1007/s00134-013-3105-7 WHAT’S NEW IN INTENSIVE CARE

-3. In another publication, the proportion of mechani-cally ventilated days spent delirium- and coma-freeimproved significantly from 28 to 56 % (p \ 0.001) if theCAM-ICU assessment followed, rather than preceded,sedation interruption [9]. The variability in deliriumincidence in studies using the CAM-ICU and ICDSC isdepicted in Fig. 1.

It has been argued [10] that raising the level of theconsciousness threshold at which delirium should beassessed is arbitrary and that patient outcomes, regardlessof sedation and in the context of delirium, are similar anduniformly poor. A recent report makes a compelling argu-ment to the contrary. Among 102 ICU patients receivingcontinuous sedation, coma or a positive CAM-ICU resultwere 10 times more likely to occur prior to sedation inter-ruption [11]. More importantly, patients with ‘‘delirium’’that cleared as sedation was lightened (termed ‘‘drug-rela-ted delirium’’) had outcomes virtually identical to patientswho never had delirium; the outcomes in these patientswere strikingly better in comparison to those in patientswith delirium not related to sedation. This dramatic dif-ference was consistent for ventilator-, ICU- and hospital-free days and for 1-year mortality; it argues strongly that theconfounding effect of sedation on delirium assessments isreal and that patients labeled as having delirium, when it isconfounded by sedation, behave rather like patients withoutdelirium. These data have only been presented in abstractform, and we eagerly await their formal publication.

If sedation does indeed confound accurate detection ofdelirium, the impact on recently published papers is sig-nificant. Among 23 patients diagnosed as delirious usingthe CAM-ICU and a RASS threshold of -3, doctors and

nurses diagnosed only 28 and 34 % of their delirium days,respectively. This suggests that residual sedation mayhave inflated the reported incidence of delirium using theCAM-ICU ‘‘gold standard,’’ falsely increasing the rate of‘‘under-recognition’’ [2]. As was pointed out in anotherstudy, caregivers in fact may be more accurate in theirrecognition of delirium’s clinical presentation withoutscreening scales [12]. In one group of post-cardiac sur-gery patients, the 28 % of patients diagnosed as deliriouswith the CAM-ICU had a lower bispectral index (BIS)score, and had many more RASS assessments of -2 (12vs. 1) and many fewer between 0 and -1 (18 vs. 80) [13].The BIS is known to correlate with sedation or arousallevel [14], and it is likely that these findings reflectresidual sedation among the patients scored as havingdelirium. Notably, and in agreement with the findings ofPatel and colleagues [11], Plaschke in this BIS studyreported distinguishing ‘‘drug-related’’ CAM-ICU posi-tive delirium, mortality and hospital length of stay wereidentical among delirious and non-delirious groups [13].

Additional questions surrounding the diagnosis ofdelirium in ICU patients remain. The frequent occurrenceand morbidity of prolonged sedation in ICU patients arewell understood [15]. Although the hypoactive motoricsubtype has been reported to account for the majority ofICU delirium, this concept must be re-evaluated in lightof the aforementioned data when a residual sedative effectmay have been a significant confounder. Systematicassessments of 600 ICU patients [5] showed nearly alldelirious patients developed agitation (85 %), while 52 %also experienced slowing, suggesting ‘pure’ hypoactivedelirium is, at best, uncommon. Delirium, depression and

Fig. 1 The rate of positivedelirium screening results for14 studies using the CAM-ICU(violet) and 5 studies using theICDSC (green). A column(blue) represents the average forthe CAM-ICU and for theICDSC

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post-traumatic stress disorder have all been described inICU patients, with overlapping symptoms. These ele-ments require further study before stating that‘‘hypoactive delirium’’ is frequent.

Finally, whether any delirium scale derived from theDiagnostic and Statistical Manual of Mental Disorders(DSM) IV (based on two phenomenological studies ofhospitalized geriatric patients) can reliably be applied toICU patients receiving sedation [16] can be questioned.The DSM V’s new recommendations include consideringthat ‘‘many non-comatose patients are incapable ofengaging with attempts to perform standard cognitivetesting.’’ We note with some concern that residual seda-tion is not retained as a possible cause for this finding.While this may be a reasonable assumption in non-ICUpatients, it should not be applied to ICU patients, partic-ularly in light of the concerns listed above. Instead,scoring recommendations suggest considering such non-engagement as inattention, leading to a more inclusivedefinition of delirium. The claim that these patients havesimilarly poor outcomes and require the same investiga-tion and treatment as patients with more traditionallydiagnosed delirium [10].should be questioned in light ofrecent ICU studies. Recently, the National Institute ofMental Health distanced itself from the new DSM V,citing its lack of validity and stating ‘‘…we cannot suc-ceed if we use DSM categories as the gold standard’’(

http://www.nimh.nih.gov/about/director/2013/transforming-diagnosis.shtml). We believe the critical care communityshould take a similar stance.

Lastly, our inability to accurately identify delirium inthe ICU might account, in part, for the fact that nopharmacologic intervention has been shown to alter thecourse of delirium. A recently published randomized,placebo-controlled trial (HOPE-ICU) found that intrave-nous haloperidol, the most commonly prescribedantipsychotic in critical care, had no impact on theduration of delirium or coma or other relevant outcomes[17]. In this study, delirium and/or coma, considered as asingle entity, were tracked longitudinally throughout ICUstay and resolved within 5 days in 65 and 67 % of halo-peridol and placebo patients, respectively. Whetherdelirium treatment was truly tested can be debated. Earlymobilization (which may, in addition to its non-pharma-cological intervention component, lighten sedation)appears to be the only beneficial strategy in preventingdelirium in the ICU [18]. Screening and diagnostic chal-lenges will, we hope, be the subject of some deliberation,as we struggle to refine and improve identification ofoutcome determinants that are meaningful to patients,stakeholders and caregivers.

Conflicts of interest The authors declare they have no conflict ofinterest.

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