Modification in ICU Design May Affect Delirium and Circadian Melatonin: A Proof of Concept Pilot Study.

OBJECTIVES: Nonpharmacologic delirium management is recommended by current guidelines, but studies on the impact of ICU design are still limited. The study's primary purpose was to determine if a multicomponent change in room design prevents ICU delirium. Second, the influence of lighting conditions on serum melatonin was assessed. DESIGN: Prospective observational cohort pilot study. SETTING: The new design concept was established in two two-bed ICU rooms of a university hospital. Besides modifications aimed at stress relief, it includes a new dynamic lighting system. PATIENTS: Seventy-four adult critically ill patients on mechanical ventilation with an expected ICU length of stay of at least 48 hours, treated in modified or standard rooms. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The clinical examination included a prospective assessment for depth of sedation, delirium, and pain every 8 hours using validated scores. Blood samples for serum melatonin profiles were collected every 4 hours for a maximum of three 24-hour periods. Seventy-four patients were included in the analysis. Seventy-six percent ( n = 28) of patients in the standard rooms developed delirium compared with 46% of patients ( n = 17) in the modified rooms ( p = 0.017). Patients in standard rooms (vs. modified rooms) had a 2.3-fold higher delirium severity (odds ratio = 2.292; 95% CI, 1.582-3.321; p < 0.0001). Light intensity, calculated using the measure of circadian effective irradiance, significantly influenced the course of serum melatonin ( p < 0.0001). Significant interactions ( p < 0.001) revealed that differences in serum melatonin between patients in standard and modified rooms were not the same over time but varied in specific periods of time. CONCLUSIONS: Modifications in ICU room design may influence the incidence and severity of delirium. Dedicated light therapy could potentially influence delirium outcomes by modulating circadian melatonin levels.

[Chronobiological interventions for prevention and treatment of delirium in critically ill patients]. / Chronobiologische Interventionen zur Prävention und Therapie von Delirien bei Intensivpatienten.

Circadian body and behavior rhythms serve to coordinate and maintain the physiological processes in the human body. A disruption of these rhythms frequently occurs in intensive care patients and can be the cause for the development of delirium. This review article discusses the underlying pathophysiological mechanisms and develops a chronobiologically oriented prevention and treatment approach for delirium in the context of intensive care medicine.

[Light Therapy for Prevention of Delirium in Critically Ill Patients: What's the Evidence?] / Lichttherapie zur Delirprävention bei Intensivpatienten: Was sagt die Evidenz?

Circadian dysrhythmia affects the majority of ICU patients and has far-reaching effects on organ functioning. At the level of the central nervous system, circadian misalignment facilitates executive cognitive dysfunction and the development of ICU delirium. The pathophysiological mechanisms, especially in the cohort of critically ill patients, appear to be complex, multilayered and far from understood. Results from preliminary research indicate that multidimensional, patient-specific chronotherapeutic concepts developed specifically for the ICU setting may help improve the healing process of patients. Circadian lighting therapy might be a promising intervention in this context.

Influence of Patient-Specific Covariates on Test Validity of Two Delirium Screening Instruments in Neurocritical Care Patients (DEMON-ICU).

BACKGROUND: Delirium screening instruments (DSIs) should be used to detect delirium, but they only show moderate sensitivity in patients with neurocritical illness. We explored whether, for these patients, DSI validity is impacted by patient-specific covariates. METHODS: Data were prospectively collected in a single-center quality improvement project. Patients were screened for delirium once daily using the Intensive Care Delirium Screening Checklist (ICDSC) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Reference was the daily assessment using criteria from the Diagnostic and Statistical Manual, 4th Edition, Text Revision (DSM-IV-TR). In a two-step receiver operating characteristics regression analysis adjusting for repeated measurements, the impact of acute diagnosis of stroke or transient ischemic attack (TIA), neurosurgical intervention, Richmond Agitation Sedation Scale, and ventilation status on test validity was determined. RESULTS: Of 181 patients screened, 101 went into final analysis. Delirium incidence according to DSM-IV-TR was 29.7%. For the first complete assessment series (CAM-ICU, ICDSC, and DSM-IV-TR), sensitivity for the CAM-ICU and the ICDSC was 73.3% and 66.7%, and specificity was 91.8% and 94.1%, respectively. Consideration of daily repeated measurements increased sensitivity for the CAM-ICU and ICDSC to 75.7% and 73.4%, and specificity to 97.3% and 98.9%, respectively. Receiver operating characteristics regression revealed that lower Richmond Agitation Sedation Scale levels significantly impaired validity of the ICDSC (p = 0.029) and the CAM-ICU in its severity scale version (p = 0.004). Neither acute diagnosis of stroke or TIA nor neurosurgical intervention or mechanical ventilation significantly influenced DSI validity. CONCLUSIONS: The CAM-ICU and ICDSC perform well in patients requiring neurocritical care, regardless of the presence of acute stroke, TIA, or neurosurgical interventions. Yet, even very light or moderate sedation can significantly impair DSI performance.

Influence of Sedation Level and Ventilation Status on the Diagnostic Validity of Delirium Screening Tools in the ICU-An International, Prospective, Bi-Center Observational Study (IDeAS).

Background and objectives: The use of delirium screening instruments (DSIs) is recommended in critical care practice for a timely detection of delirium. We hypothesize that the patient-related factors "level of sedation" and "mechanical ventilation" impact test validity of DSIs. Materials and Methods: This is a prospective, bi-center observational study (clinicaltrials.gov: NCT01720914). Critically ill patients were screened for delirium daily for up to seven days after enrollment using the Nursing Delirium Screening Scale (Nu-DESC), Intensive Care Delirium Screening Checklist (ICDSC), and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Reference standard for delirium diagnosis was the neuropsychiatric examination using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Immediately before delirium assessment, ventilation status and sedation levels were documented. Results: 160 patients were enrolled and 151 patients went into final analysis. Delirium incidence was 23.2%. Nu-DESC showed a sensitivity and specificity of 88.5%, a positive predictive value (PPV) of 71.9%, and a negative predictive value (NPV) of 95.8%. ICDSC had a sensitivity of 62.5%, a specificity of 92.4%, a PPV of 71.4%, and a NPV of 89.0%. CAM-ICU showed a sensitivity of 75.0%, a specificity of 94.7%, a PPV of 85.7%, and a NPV of 90.0%. For Nu-DESC and ICDSC, test validity was significantly better for non-sedated patients (Richmond Agitation Sedation Scale (RASS) 0/-1), whereas test validity for CAM-ICU in a severity scale version showed no significant differences for different sedation levels. No DSI showed a significant difference in test validity between noninvasively and invasively ventilated patients. Conclusions: Test validities of DSIs were comparable to previous studies. The observational scores ICDSC and Nu-DESC showed a significantly better performance in awake and drowsy patients (RASS 0/-1) when compared with other sedation levels. Physicians should refrain from sedation whenever possible to avoid suboptimal performance of DSIs.

Critical care guidelines on pain, agitation and delirium management: Which one to use? A systematic literature search and quality appraisal with AGREE II.

BACKGROUND: Clinical practice guidelines (CPGs) facilitate the provision of standardized, high-quality intensive care medicine. For the management of pain, agitation and delirium, several coexisting CPGs have been published. This study aims at the appraisal of CPGs on pain, agitation and delirium management in the intensive care unit to (a) identify high quality guidelines appropriate for clinical use and (b) identify potential areas for future improvement. METHODS: We performed a systematic literature search of Medline, three guideline registers and two grey-literature databases. The scope covered guidelines from 2007 to 2020 available in English or German. Identified CPGs were appraised by three independent reviewers using the appraisal of Guidelines Research and Evaluation (AGREE II) instrument. RESULTS: Eight CPGs were included in the final analysis. Three of the included guidelines exceeded the quality threshold of 60% in all six domains. The highest median [IQR] scores were achieved in the domain "Scope and Purpose" (84.3% [78.7-88.9]), whereas "Applicability" (45.8% [19.4-79.9]) received the lowest median score. CONCLUSION: Three of the eight reviewed guidelines exceeded the quality threshold in all domains, while the overall guideline quality was also very high. Focusing on guideline applicability and identifying strategies to facilitate implementation can improve future CPGs.

Innovative ICU Solutions to Prevent and Reduce Delirium and Post-Intensive Care Unit Syndrome.

Delirium, the most common form of acute brain dysfunction affecting up to 80% of intensive care unit (ICU) patients, has been shown to predict long-term cognitive impairment, one of the domains in "Post-ICU Syndrome" (PICS). The ICU environment affects several potentially modifiable risk factors for delirium, such as disorientation and disruption, of the sleep-wake cycle. Innovative solutions aim to transform standard concepts of ICU room design to limit potential stressors, and utilizing the patient care space as a treatment tool, exerting positive, therapeutic effects. The main areas affected by most architectural and interior design modifications are sound environment, light control, floor planning, and room arrangement. Implementation of corresponding solutions is challenging considering the significant medical and technical demands of ICUs. This article discusses innovative concepts and promising approaches in ICU design that may be used to prevent stress and to support the healing process of patients, potentially limiting the impact of delirium and PICS.

Routine delirium monitoring is independently associated with a reduction of hospital mortality in critically ill surgical patients: A prospective, observational cohort study.

PURPOSE: Although delirium monitoring is recommended in international guidelines, there is lacking evidence for improved outcome due to it. We hypothesized that adherence to routine delirium monitoring would improve clinical outcome in adult critically ill patients. MATERIAL AND METHODS: We present the results of a prospective, noninterventional, observational cohort study that was conducted on 2 intensive care units (ICUs) of a tertiary care medical center between July and October 2007 (International Standard Registered Clinical Trial Record identifier: 76100795). We assessed delirium-monitoring and outcome parameters on a daily basis. Besides multivariate logistic and robust linear regression to analyze the relationship between delirium monitoring and outcome, we used the doubly robust augmented inverse probability weighting method for observational data to estimate effect sizes. RESULTS: Of 355 screened patients, we included 185 surgical ICU patients into our final analysis, of which 87 were mechanically ventilated. We found an independent association between delirium-monitoring adherence and in-hospital mortality for ventilated patients (odds ratio, 0.973; P= .041). Estimating the effect size, delirium monitoring indicated a reduction of 22% of in-hospital mortality if conducted 50% or more of ICU days per patient. The average ICU length of stay of 46 days was estimated to be reduced by 19 days (P= .031) if patients were sufficiently monitored. CONCLUSION: Our data suggest an improved outcome for mechanically ventilated patients being screened for delirium in clinical routine.

Validity of Different Delirium Assessment Tools for Critically Ill Children: Covariates Matter.

OBJECTIVES: To evaluate test validity of the Pediatric Confusion Assessment Method for the ICU, the Pediatric Anesthesia Emergence Delirium scale, and the newly developed severity scale for the Pediatric Confusion Assessment Method for the ICU; to prospectively assess covariates and their influence on test validity of the scores. DESIGN: Prospective observational cohort study. SETTING: PICU of a tertiary care medical center. PATIENTS: Critically ill patients 5 years old or older ventilated or nonventilated with an ICU length of stay of at least 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were scored with the Pediatric Confusion Assessment Method for the ICU and the Pediatric Anesthesia Emergence Delirium scale once daily for a maximum of 21 days. Validity was determined by comparing scoring results with the evaluations of the delirium experts who used the criteria of the Diagnostic and Statistical Manual, 4th Edition, Text Revision, for delirium diagnosis. Sixty-four patients were enrolled and 214 assessments were conducted and included in data analysis. The first assessments within each patient revealed sensitivities of 69.2% for the Pediatric Anesthesia Emergence Delirium scale, 76.9% for the Pediatric Confusion Assessment Method for the ICU, and 84.9% for the severity scale for the Pediatric Confusion Assessment Method for the ICU. Specificities were 98% for all scores. Considering repeated measurements, sensitivities decreased to 35.9% for the Pediatric Anesthesia Emergence Delirium scale and to 52.3% for the Pediatric Confusion Assessment Method for the ICU. The sensitivity of the severity scale for the Pediatric Confusion Assessment Method for the ICU dropped to 71.8%, which was significantly higher compared to the Pediatric Anesthesia Emergence Delirium scale (p = 0.0008). Receiver operator characteristic regression unveiled that sedation and mechanical ventilation had a significant negative effect on the validity of the Pediatric Anesthesia Emergence Delirium scale and the severity scale for the Pediatric Confusion Assessment Method for the ICU. Age and gender had a significant impact on the receiver operator characteristic curve of the severity scale for the Pediatric Confusion Assessment Method for the ICU. CONCLUSIONS: The severity scale for the Pediatric Confusion Assessment Method for the ICU showed the best test validity when used in critically ill children of 5 years old or older. Nevertheless, validity of delirium screening itself depends on patient specific factors. These factors should be taken into consideration when choosing a delirium screening instrument.

Influence of Granulocyte-Macrophage Colony-Stimulating Factor or Influenza Vaccination on HLA-DR, Infection and Delirium Days in Immunosuppressed Surgical Patients: Double Blind, Randomised Controlled Trial.

PURPOSE: Surgical patients are at high risk for developing infectious complications and postoperative delirium. Prolonged infections and delirium result in worse outcome. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and influenza vaccination are known to increase HLA-DR on monocytes and improve immune reactivity. This study aimed to investigate whether GM-CSF or vaccination reverses monocyte deactivation. Secondary aims were whether it decreases infection and delirium days after esophageal or pancreatic resection over time. METHODS: In this prospective, randomized, placebo-controlled, double-blind, double dummy trial setting on an interdisciplinary ICU of a university hospital 61 patients with immunosuppression (monocytic HLA-DR [mHLA-DR] <10,000 monoclonal antibodies [mAb] per cell) on the first day after esophageal or pancreatic resection were treated with either GM-CSF (250 µg/m2/d), influenza vaccination (Mutagrip 0.5 ml/d) or placebo for a maximum of 3 consecutive days if mHLA-DR remained below 10,000 mAb per cell. HLA-DR on monocytes was measured daily until day 5 after surgery. Infections and delirium were followed up for 9 days after surgery. Primary outcome was HLA-DR on monocytes, and secondary outcomes were duration of infection and delirium. RESULTS: mHLA-DR was significantly increased compared to placebo (p < 0.001) and influenza vaccination (p < 0.001) on the second postoperative day. Compared with placebo, GM-CSF-treated patients revealed shorter duration of infection (p < 0.001); the duration of delirium was increased after vaccination (p = 0.003). CONCLUSION: Treatment with GM-CSF in patients with postoperative immune suppression was safe and effective in restoring monocytic immune competence. Furthermore, therapy with GM-CSF reduced duration of infection in immune compromised patients. However, influenza vaccination increased duration of delirium after major surgery. TRIAL REGISTRATION: www.controlled-trials.com ISRCTN27114642.

Delirium, sedation and analgesia in the intensive care unit: a multinational, two-part survey among intensivists.

Analgesia, sedation and delirium management are important parts of intensive care treatment as they are relevant for patients' clinical and functional long-term outcome. Previous surveys showed that despite this fact implementation rates are still low. The primary aim of the prospective, observational multicenter study was to investigate the implementation rate of delirium monitoring among intensivists. Secondly, current practice concerning analgesia and sedation monitoring as well as treatment strategies for patients with delirium were assesed. In addition, this study compares perceived and actual practice regarding delirium, sedation and analgesia management. Data were obtained with a two-part, anonymous survey, containing general data from intensive care units in a first part and data referring to individual patients in a second part. Questionnaires from 101 hospitals (part 1) and 868 patients (part 2) were included in data analysis. Fifty-six percent of the intensive care units reported to monitor for delirium in clinical routine. Fourty-four percent reported the use of a validated delirium score. In this respect, the survey suggests an increasing use of delirium assessment tools compared to previous surveys. Nevertheless, part two of the survey revealed that in actual practice 73% of included patients were not monitored with a validated score. Furthermore, we observed a trend towards moderate or deep sedation which is contradicting to guideline-recommendations. Every fifth patient was suffering from pain. The implementation rate of adequate pain-assessment tools for mechanically ventilated and sedated patients was low (30%). In conclusion, further efforts are necessary to implement guideline recommendations into clinical practice. The study was registered (ClinicalTrials.gov identifier: NCT01278524) and approved by the ethical committee.

Intravenous Lormetazepam during Sedation Weaning in a 26-Year-Old Critically Ill Woman.

Recent evidence revealed that sedation is related to adverse outcomes including a higher mortality. Despite this fact, patients sometimes require deep sedation for a limited period of time to control, for example, intracranial hypertension. In particular in these cases, weaning from sedation is often challenging due to emerging agitation, stress, and delirium. The submitted research letter reports a rare case of severe and persisting agitation that was unresponsive to all available treatments. Ultimately, lormetazepam which has recently become available for intravenous use in Germany resolved the problem by stress-reduction and anxiolysis without leading to measurable sedation.

How to implement monitoring tools for sedation, pain and delirium in the intensive care unit: an experimental cohort study.

PURPOSE: Systematic monitoring of sedation, pain and delirium in the ICU is of paramount importance in delivering adequate patient care. While the use of systematic monitoring instruments is widely agreed upon, these tools are infrequently implemented into daily ICU care. The aim of this study is to compare the effectiveness of two different training strategies (training according to the local standard vs. modified extended method) on the implementation rate of scoring instruments on the ICU. METHODS: In this experimental cohort study we analyzed the frequency of scoring on three surgical ICUs before and after training, and in a 1 year follow-up. A modified extended training included establishing a local support team helping to resolve immediate problems. In addition we evaluated the impact on patients' outcome. RESULTS: ICUs trained by the modified extended method showed increased documentation rates of all scores per patient and day. In a 1 year follow-up, increased scoring rates for all scores were maintained. Scoring rates with training according to the local standard training protocol did not increase significantly. Implementation of delirium and pain monitoring were associated with a decrease in mortality [odds ratio (OR) 0.451; 95 % confidence interval (CI): 0.22-0.924, and, respectively, OR 0.348; 95 % CI: 0.140-0.863]. Monitoring had no significant influence on ventilation time or ICU length of stay. CONCLUSIONS: A modified extended training strategy for ICU monitoring tools (sedation, pain, delirium) leads to higher intermediate and long-term implementation rates and is associated with improved patient outcome. However, these findings may have been biased by unmeasured confounders.

The paediatric Confusion Assessment Method for the Intensive Care Unit (pCAM-ICU): translation and cognitive debriefing for the German-speaking area.

PURPOSE: To date there are only a few studies published, dealing with delirium in critically ill patients. The problem with these studies is that prevalence rates of delirium could only be estimated because of the lack of validated delirium assessment tools for the paediatric intensive care unit (PICU). The paediatric Confusion Assessment Method for the Intensive Care Unit (pCAM-ICU) was specifically developed and validated for the detection of delirium in PICU patients. The purpose of this study was the translation of the English pCAM-ICU into German according to international validated guidelines. METHODS: The translation process was performed according to the principles of good practice for the translation and cultural adaptation process for patient reported outcomes measures: From three independently created German forward-translation versions one preliminary German version was developed, which was then retranslated to English by a certified, state-approved translator. The back-translated version was submitted to the original author for evaluation. The German translation was evaluated by clinicians and specialists anonymously (German grades) in regards to language and content of the translation. RESULTS: The results of the cognitive debriefing revealed good to very good results. After that the translation process was successfully completed and the final version of the German pCAM-ICU was adopted by the expert committee. CONCLUSION: The German version of the pCAM-ICU is a result of a translation process in accordance with internationally acknowledged guidelines. Particularly, with respect to the excellent results of the cognitive debriefing, we could finalise the translation and cultural adaptation process for the German pCAM-ICU.

Weaning from mechanical ventilation and sedation.

PURPOSE OF REVIEW: Guidelines for weaning from sedation and weaning from ventilator gained increasing interest in recent years. This includes patients with acute respiratory distress syndrome, as well as other mechanically ventilated patients. This review will give an overview of the current literature and practice guidelines in ventilator and sedation weaning. RECENT FINDINGS: Sedation and ventilator weaning are closely linked. Weaning protocols for both sedation and ventilator weaning should be implemented in daily routine. The essential element of such algorithm should be a daily spontaneous awakening trial and spontaneous breathing trial. Furthermore, regularly monitoring for deepness of sedation and delirium should be implemented. Too deep sedation, as well as prolonged delirium is associated with higher mortality. SUMMARY: The most important conclusion we come to from recent randomized controlled trials is that only using an integrative algorithm for sedation and ventilator weaning can improve survival of ICU patients.

A comparison of three scores to screen for delirium on the surgical ward.

BACKGROUND: Postoperative delirium is associated with adverse outcome. The aim of this study was to find a valid and easy-to-use tool to screen for postoperative delirium on the surgical ward. METHODS: Data were collected from 88 patients who underwent elective surgery. Delirium screening was performed daily until the sixth postoperative day using the Confusion Assessment Method (CAM), the Nursing Delirium Screening Scale (Nu-DESC), and the Delirium Detection Score (DDS), and the DSM-IV criteria as the gold standard. RESULTS: Seventeen of 88 patients (19%) developed delirium on at least one of the postoperative days according to the gold standard. The DDS scored positive for 40 (45%) patients, the CAM for 15 (17%), and the Nu-DESC for 28 (32%) patients. Sensitivity and specificity were 0.71 and 0.87 for the DDS, 0.75 and 1.00 for the CAM, and 0.98 and 0.92 for the Nu-DESC. The interrater reliability was 0.83 for the Nu-DESC, 0.77 for the DDS, and 1.00 for the CAM. CONCLUSIONS: All scores showed high specificity but differed in their sensitivity. The Nu-DESC proved to be the most sensitive test for screening for a postoperative delirium on the surgical ward followed by the CAM and DDS when compared to the gold standard.

Different assessment tools for intensive care unit delirium: which score to use?

OBJECTIVE: To compare validity and reliability of three instruments for detection and assessment of delirium in intensive care unit (ICU) patients. Delirium in critically ill patients is associated with higher mortality, prolonged duration of ICU stay, and greater healthcare costs. Currently, there are several assessment tools available for detection of delirium, but only a few of these assessment systems are developed specifically to screen for delirium in ICU patients. DESIGN: Prospective cohort study. SETTING: ICU at a university hospital. PATIENTS: A total of 156 surgical patients aged > or = 60 yrs consecutively admitted to the ICU, with a length of stay of at least 24 hrs. MEASUREMENTS AND MAIN RESULTS: This study was approved by the institutional ethics committee. Trained staff members performed daily and independently the Confusion Assessment Method for the ICU (CAM-ICU), the Nursing Delirium Screening Scale (Nu-DESC), and the Delirium Detection Score (DDS). These evaluations were compared against the reference standard conducted by a delirium expert (blinded to the study), who used delirium criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Of 156 patients, 63 (40%) were identified as delirious by the reference standard during the study. Using the CAM-ICU and the Nu-DESC, we measured comparable sensitivities (CAM-ICU, 81%; Nu-DESC, 83%). The specificity of the CAM-ICU was significantly higher than that of the Nu-DESC (96% vs. 81%, p < .01). In contrast, the DDS showed poor sensitivity (30%), whereas the specificity was significantly higher compared with the Nu-DESC (DDS, 91%; Nu-DESC, 81%, p < .05). The interrater reliability was "almost perfect" for the CAM-ICU (kappa = 0.89) and "substantial" for DDS and Nu-DESC (kappa = 0.79, 0.68). CONCLUSION: The CAM-ICU showed the best validity of the evaluated scales to identify delirium in ICU patients. The Nu-DESC might be an alternative tool for detection of ICU delirium. The DDS should not be used as a screening tool.