Relevance of peripheral cholinesterase activity on postoperative delirium in adult surgical patients (CESARO): A prospective observational cohort study.

BACKGROUND: The cholinergic system is considered to play a key role in the development of postoperative delirium (POD), which is a common complication after surgery. OBJECTIVES: To determine whether peri-operative acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities are associated with the development of POD in in-hospital surgical patients, and raise hypotheses on cholinergic regulatory mechanisms in POD. DESIGN: A prospective multicentre observational study by the Peripheral Cholinesterase-activity on Neurocognitive Dysfunctions in Surgical Patients (CESARO) study group. SETTING: Nine German hospitals. PATIENTS: Patients of at least 18 years of age scheduled for inpatient elective surgery for a variety of surgical procedures. A total of 650 patients (mean age 61.5 years, 52.8% male) were included. METHODS: Clinical variables, and peripheral AChE and BuChE activities, were assessed throughout the peri-operative period using bedside point-of-care measurements (one pre-operative and two postoperative measurements). POD screening was conducted postoperatively for at least 24 h and up to the third postoperative day using a validated screening tool (nursing delirium screening scale). RESULTS: In all, 179 patients (27.5%) developed POD within the early postoperative phase. There was a lower BuChE activity in patients with delirium compared with patients without delirium pre-operatively (Cohen's r = 0.07, P = 0.091), on postoperative day 1 (Cohen's r = 0.12, P = 0.003) and on postoperative day 2 (Cohen's r = 0.12, P = 0.002). In contrast, there was a significantly higher AChE activity in patients with delirium compared with patients without delirium pre-operatively (Cohen's r = 0.10, P = 0.012), on postoperative day 1 (Cohen's r = 0.11, P = 0.004) and on postoperative day 2 (Cohen's r = 0.13, P = 0.002). After adjusting for covariates in multiple logistic regression, a significant association between both BuChE and AChE activities and POD was not found. However, in the multivariable analysis using the Generalized Estimating Equation, cholinesterase activities showed that a decrease of BuChE activity by 100 U L increased the risk of a delirium by approximately 2.1% (95% CI 1.6 to 2.8%) and for each 1 U g of haemoglobin increase in AChE activity, there was a 1.4% (95% CI 0.6 to 2.2%) increased risk of POD. CONCLUSION: Peri-operative peripheral cholinesterase activities may be related to the development of POD, but the clinical implications remain unclear. Further studies, in homogeneous patient groups with a strict protocol for measurement time points, are needed to investigate the relationship between cholinesterase activities and POD. TRIAL REGISTRATION: www.clinicaltrials.gov. Identifier NCT01964274.

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.

A prospective, randomized, double-blind, multicenter study comparing remifentanil with fentanyl in mechanically ventilated patients.

PURPOSE: To compare the quality of analgesia provided by a remifentanil-based analgesia regime with that provided by a fentanyl-based regime in critically ill patients. METHODS: This was a registered, prospective, two-center, randomized, triple-blind study involving adult medical and surgical patients requiring mechanical ventilation (MV) for more than 24 h. Patients were randomized to either remifentanil infusion or a fentanyl infusion for a maximum of 30 days. Sedation was provided using propofol (and/or midazolam if required). RESULTS: Primary outcome was the proportion of patients in each group maintaining a target analgesia score at all time points. Secondary outcomes included duration of MV, discharge times, and morbidity. At planned interim analysis (n = 60), 50% of remifentanil patients (n = 28) and 63% of fentanyl patients (n = 32) had maintained target analgesia scores at all time points (p = 0.44). There were no significant differences between the groups with respect to mean duration of ventilation (135 vs. 165 h, p = 0.80), duration of hospital stay, morbidity, or weaning. Interim analysis strongly suggested futility and the trial was stopped. CONCLUSIONS: The use of remifentanil-based analgesia in critically ill patients was not superior regarding the achievement and maintenance of sufficient analgesia compared with fentanyl-based analgesia.

Evidence and consensus-based German guidelines for the management of analgesia, sedation and delirium in intensive care--short version.

Targeted monitoring of analgesia, sedation and delirium, as well as their appropriate management in critically ill patients is a standard of care in intensive care medicine. With the undisputed advantages of goal-oriented therapy established, there was a need to develop our own guidelines on analgesia and sedation in intensive care in Germany and these were published as 2(nd) Generation Guidelines in 2005. Through the dissemination of these guidelines in 2006, use of monitoring was shown to have improved from 8 to 51% and the use of protocol-based approaches increased to 46% (from 21%). Between 2006-2009, the existing guidelines from the DGAI (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin) and DIVI (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin) were developed into 3(rd) Generation Guidelines for the securing and optimization of quality of analgesia, sedation and delirium management in the intensive care unit (ICU). In collaboration with another 10 professional societies, the literature has been reviewed using the criteria of the Oxford Center of Evidence Based Medicine. Using data from 671 reference works, text, diagrams and recommendations were drawn up. In the recommendations, Grade "A" (very strong recommendation), Grade "B" (strong recommendation) and Grade "0" (open recommendation) were agreed. As a result of this process we now have an interdisciplinary and consensus-based set of 3(rd) Generation Guidelines that take into account all critically illness patient populations. The use of protocols for analgesia, sedation and treatment of delirium are repeatedly demonstrated. These guidelines offer treatment recommendations for the ICU team. The implementation of scores and protocols into routine ICU practice is necessary for their success.

[If delirium is not monitored it will often be not detected]. / Was wir nicht messen, detektieren wir meist auch nicht.

The reported incidence of delirium in critically ill patients ranges widely - from 11% to 87%. Both in the recovery room as well as in the intensive care unit postoperative delirium is the most common psychiatric disease. Patients with ICU delirium have a significant higher 6-month mortality rate. Recent studies could show that the use of a validated delirium assessment tool significantly improves the ability of physicians and nurses to detect delirium in ICU patients. The following article gives a review about different assessment tools of ICU delirium and focuses on the differences between validated delirium scores.

[Postoperative delirium and cognitive deficit. Prevention and therapy]. / Postoperatives Delir und kognitives Defizit. Prävention und Therapie.

To date, there are few studies available focusing on prevention and therapy of delirium in ICU patients. Monitoring during routine care is important because without using validated tools only one third of the delirious patients will be detected. A lot of non-pharmacological interventions like re-orientation and helping the patient to get back his autonomy, but also goal-orientated sedation support prevention and therapy of delirium. Furthermore, there are hints that pharmacological intervention can reduce incidence and severity of delirium. For delirium prevention there are drugs available acting on different receptor systems (acetylcholine, dopamine, opioid, glutamate). For the use of this drugs, a strict risk-benefit-consideration is necessary due to the low level of evidence of the existing studies. Therapeutically causative and symptom-orientated approaches should be preferred.

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.

[The Intensive Care Delirium Screening Checklist (ICDSC)--translation and validation of intensive care delirium checklist in accordance with guidelines]. / Die Intensive Care Delirium Screening Checklist (ICDSC)--Richtlinienkonforme Ubersetzung und Validierung einer intensivmedizinischen Delirium-Checkliste.

BACKGROUND: Although Delirium is the most common psychiatric disease in ICU settings, it is recognized late or not at all in up to 84 % of all cases. METHODS: Translation of the ICDSC, in accordance with ISPOR guidelines and validation by conducting a screening of 68 ICU patients. RESULTS: The translation process was authorized by the original author. The final German translation of the ICDSC showed a sensitivity and specificity of 89 % and 57 % respectively. CONCLUSION: The ICDSC is suitable for delirium screening by nurses even on ventilated patients. Besides a high sensitivity another advantage is the possibility to screen for a subsyndromal delirium.

[The Nursing Delirium Screening Scale (NU-DESC)]. / Die Nursing Delirium Screening Scale (Nu-DESC) - Richtlinienkonforme Ubersetzung für den deutschsprachigen Raum.

BACKGROUND: Both in the recovery room as well as in the intensive care unit post-operative delirium is the most common psychiatric disease. The post-operative delirium is stated in literature to occur in 15 % to 50 % of patients, whereby up to 80 % of patients requiring intensive care with artificial respiration develop a delirium. The delirium correlates with the length of hospital stay and leads to a tripple rate of the six-month-mortality. Nu-DESC, developed by Gaudreau et al. is a measuring instrument for the clinical diagnostics of deliriums which is quickly operable, care-based and which can thus be easily integrated in everyday routine. The aim of this study was the translation of Nu-DESC from English as basis for the use in clinical research and routine. MATERIALS AND METHODS: The translation process was conducted in accordance with the internationally acknowledged guidelines of Translation and Cultural Adaptation of Patient Reported Outcomes Measures - Principles of Good Practice (PGP). An interim German version was developed from 3 independently devised translations, a back-translation of which was then conducted by a registered state-approved translator. The back-translation was then presented to the author of the original for evaluation. RESULTS: The back-translation of the German translation was authorised by the author of the original. On the basis of the cognitive debriefing results which were consistently very good to good, the translation process could be finalised and the final German version of Nu-DESC could be passed by the expert team. An evaluation of the German Nu-DESC regarding its practicability showed significant differences between doctors and nursing staff. CONCLUSION: The German version of Nu-DESC provides an instrument for evaluating the delirium in the area of clinical routine and research.

[Implementation of standard operating procedures for the initial empirical antimicrobial therapy for adults--a new computer program at the University Hospital Charité]. / Einführung von SOPs zur initialen kalkulierten Antibiotikatherapie bei Erwachsenen--Ein neues Computerprogramm an der Charité.

Nowadays 40-50 % of the patients receive inappropriate antibiotic treatment. Evidence based recommendations are not considered and there is an increasing burden of resistant pathogens. Therefore, standard operating procedures (SOPs) should be implemented considering guidelines and resistant species in the specific ICU. The authors developed algorithms and generated a user friendly computer program available for all ICU physicians all the time.