Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) - short version.

In 2010, under the guidance of the DGAI (German Society of Anaesthesiology and Intensive Care Medicine) and DIVI (German Interdisciplinary Association for Intensive Care and Emergency Medicine), twelve German medical societies published the "Evidence- and Consensus-based Guidelines on the Management of Analgesia, Sedation and Delirium in Intensive Care". Since then, several new studies and publications have considerably increased the body of evidence, including the new recommendations from the American College of Critical Care Medicine (ACCM) in conjunction with Society of Critical Care Medicine (SCCM) and American Society of Health-System Pharmacists (ASHP) from 2013. For this update, a major restructuring and extension of the guidelines were needed in order to cover new aspects of treatment, such as sleep and anxiety management. The literature was systematically searched and evaluated using the criteria of the Oxford Center of Evidence Based Medicine. The body of evidence used to formulate these recommendations was reviewed and approved by representatives of 17 national societies. Three grades of recommendation were used as follows: Grade "A" (strong recommendation), Grade "B" (recommendation) and Grade "0" (open recommendation). The result is a comprehensive, interdisciplinary, evidence and consensus-based set of level 3 guidelines. This publication was designed for all ICU professionals, and takes into account all critically ill patient populations. It represents a guide to symptom-oriented prevention, diagnosis, and treatment of delirium, anxiety, stress, and protocol-based analgesia, sedation, and sleep-management in intensive care medicine.

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.

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.

[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.

Intervention at the level of the neuroendocrine-immune axis and postoperative pneumonia rate in long-term alcoholics.

RATIONALE: Postoperative pneumonia is three to four times more frequent in patients with alcohol use disorders followed by prolonged intensive care unit (ICU) stay. Long-term alcohol use leads to an altered perioperative hypothalamus-pituitary-adrenal (HPA) axis and immunity. OBJECTIVES: The aim of this study was to evaluate HPA intervention with low-dose ethanol, morphine, or ketoconazole on the neuroendocrine-immune axis and development of postoperative pneumonia in long-term alcoholic patients. METHODS: In this randomized, double-blind controlled study, 122 consecutive patients undergoing elective surgery for aerodigestive tract cancer were included. Long-term alcohol use was defined as consuming at least 60 g of ethanol daily and fulfilling the Diagnostic and Statistical Manual of Mental Disorders IV criteria for either alcohol abuse or dependence. Nonalcoholic patients were included but only as a descriptive control. Perioperative intervention with low-dose ethanol (0.5 g/kg body weight per day), morphine (15 mug/kg body weight per hour), ketoconazole (200 mg four times daily), and placebo was started on the morning before surgery and continued for 3 d after surgery. Blood samples to analyze the neuroendocrine-immune axis were obtained on the morning before intervention and on Days 1, 3, and 7 after surgery. MEASUREMENTS AND MAIN RESULTS: In long-term alcoholic patients, all interventions decreased postoperative hypercortisolism and prevented impairment of the cytotoxic T-lymphocyte type 1:type 2 ratio. All interventions decreased the pneumonia rate from 39% to a median of 5.7% and shortened intensive care unit stay by 9 d (median) compared with the placebo-treated long-term alcoholic patients. CONCLUSIONS: Intervention at the level of the HPA axis altered the immune response to surgical stress. This resulted in decreased postoperative pneumonia rates and shortened intensive care unit stay in long-term alcoholic patients.

Immune reactivity is more suppressed in patients with alcoholic liver disease than in patients with virus-induced cirrhosis after CRH stimulation.

BACKGROUND: The most frequent diagnoses for liver transplantation are virus-induced cirrhosis (VIC) and alcoholic liver disease (ALD), after an abstinence period of at least 6 months. Chronic ethanol consumption has been linked to an abnormal neuroendocrine-immune axis and to an altered surgical stress response inducing an increased infection rate. Preoperative stress testing might be relevant to detect stress-induced immune alteration. The aim of this study was to investigate the preoperative stress-like response to corticotrophin-releasing-hormone challenge (CRH) of patients with ALD compared with patients with VIC and their immune sequelae. METHODS: Nine patients with ALD and 8 patients with VIC were included in this clinical study prior to transplantation. All patients received CRH in the morning. Blood samples were drawn before and after stress testing. RESULTS: In response to CRH, the ALD patients showed a significant decrease in the plasma interleukin (IL)-6/IL-10 ratio. After lipopolysaccharide stimulation of whole blood from CRH-challenged ALD patients, IL-10 increased significantly. The cytotoxic T1-(Tc1) to cytotoxic T2 (Tc2) ratio was significantly decreased in ALD patients after the stress test. Infections occurred significantly more often in ALD patients within the past year before study inclusion. CONCLUSIONS: ALD patients showed a stronger anti-inflammatory immune status and response than VIC patients. This difference was associated with a higher infection rate despite a median alcohol abstinence time of 3.5 years. Although an altered immune response is well known among patients with actual alcohol-use disorders, to the best of our knowledge, it is not described in patients after such a long abstinence time.

Antibiotic-mediated release of tumour necrosis factor alpha and norharman in patients with hospital-acquired pneumonia and septic encephalopathy.

OBJECTIVE: To investigate antibiotic-mediated release of tumour necrosis factor (TNF)-alpha and norharman in patients with hospital-acquired pneumonia with and without additional septic encephalopathy. DESIGN: Prospective observational study with a retrospective post hoc analysis. SETTING: Surgical intensive care unit (ICU) at a university hospital. PATIENTS: Thirty-seven patients were consecutively included (9 patients with hospital-acquired pneumonia, 11 patients with hospital-acquired pneumonia and septic encephalopathy, 17 control patients) in the study. Pneumonia was defined according to the criteria of the American Thoracic Society. INTERVENTIONS: Patients received cephalosporins for antibiotic treatment of hospital-acquired pneumonia. Blood samples were taken before, immediately after and 4 h after application of cephalosporins. MEASUREMENTS AND RESULTS: Of the pneumonia patients, 55% developed septic encephalopathy. ICU stay, complications and mortality were significantly increased. An increased release of TNF-alpha was immediately seen in all pneumonia patients after antibiotics compared to controls, whereas the level did not differ between patients with and without septic encephalopathy. Norharman was significantly increased in pneumonia patients 4 h after antibiotic treatment, in tendency more enhanced in the pneumonia patients without encephalopathy. CONCLUSIONS: Patients with hospital-acquired pneumonia and septic encephalopathy had a significantly longer ICU stay with higher mortality rate compared to patients with hospital-acquired pneumonia alone. Antibiotic-mediated TNF-alpha release may induce the kynurenine pathway. TNF-alpha activates indolamine-2,3-dioxygenase with neurotoxic quinolinic acid as the end product. Norharman seems to counteract this mechanism and seems to play a role in neuroprotection. The worse outcome of patients with encephalopathy expresses the need to investigate protective factors and mechanisms.

Altered cell-mediated immunity and increased postoperative infection rate in long-term alcoholic patients.

BACKGROUND: Preoperative alteration of T cell-mediated immunity as well as an altered immune response to surgical stress were found in long-term alcoholic patients. The aim of this study was to evaluate perioperative T cell-mediated immune parameters as well as cytokine release from whole blood cells after lipopolysaccharide stimulation and its association with postoperative infections. METHODS: Fifty-four patients undergoing elective surgery of the aerodigestive tract were included in this prospective observational study. Long-term alcoholic patients (n = 31) were defined as having a daily ethanol consumption of at least 60 g and fulfilling the Diagnostic and Statistical Manual of Mental Disorders for either alcohol abuse or alcohol dependence. The nonalcoholic patients (n = 23) were defined as drinking less than 60 g ethanol/day. Blood samples to analyze the immune status were obtained on morning before surgery and on the morning of days 1, 3, and 5 after surgery. RESULTS: Basic patient characteristics did not differ between groups. Before surgery, the T helper 1:T helper 2 ratio (Th1: Th2) was significantly lower (P < 0.01), whereas plasma interleukin 1beta and lipopolysaccharide-stimulated interleukin 1ra from whole blood cells were increased in long-term alcoholic patients. After surgery, a significant suppression of the cytotoxic lymphocyte ratio (Tc1:Tc2), the interferon gamma:interleukin 10 ratio from lipopolysaccharide-stimulated whole blood cells, and a significant increase of plasma interleukin 10 was observed. Long-term alcoholics had more frequent postoperative infections compared with nonalcoholic patients (54%vs. 26%; P = 0.03). CONCLUSIONS: T helper cell-mediated immunity was significantly suppressed before surgery and possibly led to inadequate cytotoxic lymphocyte and whole blood cell response in long-term alcoholic patients after surgery. This altered cell-mediated immunity might have accounted for the increased infection rate in long-term alcoholic patients after surgery.

Blood alcohol concentration for monitoring ethanol treatment to prevent alcohol withdrawal in the intensive care unit.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a serious complication during postoperative treatment in chronic alcoholics. Despite prophylactic treatment, AWS occurs in at least 25% of these patients after elective surgery. An established protocol for the prevention of AWS is ethanol administration. The aim of this study was to evaluate possible differences in ethanol dose and levels between successfully treated patients and those who developed AWS. DESIGN: Prospective, observational study with retrospective post hoc analysis. SETTING: Intensive care unit (ICU). PATIENTS: Thirty-two alcohol-dependent patients undergoing elective or emergency surgery after trauma with postoperative admission to ICU. INTERVENTIONS: Continuous postoperative i.v. ethanol substitution. MEASUREMENTS AND RESULTS: Despite treatment, 13 patients developed AWS (failure group) and therapy was successful in the other 19 patients (success group). Major complications occurred more frequently in the failure group. The total dose of ethanol treatment and ethanol levels did not differ between the groups. Ethanol levels were determined in whole arterial blood (aBAC) and simultaneously taken in venous blood (vBAC), urine (UAC) and exhaled air (EAC). The following bias and precision, compared with aBAC, were found: vBAC less than UAC less than EAC. CONCLUSIONS: There is a high failure rate for i.v. ethanol prophylaxis. None of the methods to determine alcohol concentration were sufficient to monitor suitable ethanol treatment. It therefore seems to be more useful to titrate the individual dose for each patient by closer monitoring of the clinical status, adding additional therapy to counteract AWS if higher ethanol doses are required.