Validation of core competencies during residency training in anaesthesiology.

BACKGROUND AND GOAL: Curriculum development for residency training is increasingly challenging in times of financial restrictions and time limitations. Several countries have adopted the CanMEDS framework for medical education as a model into their curricula of specialty training. The purpose of the present study was to validate the competency goals, as derived from CanMEDS, of the Department of Anaesthesiology and Intensive Care Medicine of the Berlin Charité University Medical Centre, by conducting a staff survey. These goals for the qualification of specialists stipulate demonstrable competencies in seven areas: expert medical action, efficient collaboration in a team, communications with patients and family, management and organisation, lifelong learning, professional behaviour, and advocacy of good health. We had previously developed a catalogue of curriculum items based on these seven core competencies. In order to evaluate the validity of this catalogue, we surveyed anaesthetists at our department in regard to their perception of the importance of each of these items. In addition to the descriptive acquisition of data, it was intended to assess the results of the survey to ascertain whether there were differences in the evaluation of these objectives by specialists and registrars. METHODS: The questionnaire with the seven adapted CanMEDS Roles included items describing each of their underlying competencies. Each anaesthetist (registrars and specialists) working at our institution in May of 2007 was asked to participate in the survey. Individual perception of relevance was rated for each item on a scale similar to the Likert system, ranging from 1 (highly relevant) to 5 (not at all relevant), from which ratings means were calculated. For determination of reliability, we calculated Cronbach's alpha. To assess differences between subgroups, we performed analysis of variance. RESULTS: All seven roles were rated as relevant. Three of the seven competency goals (expert medical action, efficient collaboration in a team, and communication with patients and family) achieved especially high ratings. Only a few items differed significantly in their average rating between specialists and registrars. CONCLUSIONS: We succeeded in validating the relevance of the adapted seven CanMEDS competencies for residency training within our institution. So far, many countries have adopted the Canadian Model, which indicates the great practicability of this competency-based model in curriculum planning. Roles with higher acceptance should be prioritised in existing curricula. It would be desirable to develop and validate a competency-based curriculum for specialty training in anaesthesiology throughout Germany by conducting a national survey to include specialists as well as registrars in curriculum development.

The combinations C1 esterase inhibitor with coagulation factor XIII and N-acetylcysteine with tirilazad mesylate reduce the leukocyte adherence in an experimental endotoxemia in rats.

The study's objective was to determine the effects of the administration of combinations of C1 esterase inhibitor (C1-INH) with coagulation factor XIII (F XIII) and N-acetylcysteine (NAC) with tirilazad mesylate (TM) on leukocyte adherence and on intestinal functional capillary density during experimental endotoxemia in rats. In a prospective, randomized, controlled animal study, 40 male Wistar rats were divided into 4 groups. Group 1 (CON group) served as control group. Group 2 (LPS group), group 3 (C1-INH+F XIII group) and group 4 (NAC+TM group) received endotoxin infusions (10 mg/kg/h for 2 h). In C1-INH+F XIII group, 100 U/kg b.w. C1-INH and 50 U/kg b.w. F XIII were administered after the first 30 min of endotoxemia. In the NAC+TM group, 150 mg/kg b.w. N-acetylcysteine and 10 mg/kg b.w. Tirilazad mesylate were administered after 30 min of endotoxemia. Leukocyte adherence at venules of the intestinal submucosal layer and functional capillary density in the villi intestinales and in the longitudinal and circular muscle layers were estimated by intravital fluorescence microscopy (IVM). C1-INH+F XIII reduced the count of firmly adherent leukocytes that was increased after LPS administration in the V3 venules (CON group 69 (17-160)/mm2; LPS group 635 (556-814)/mm2; C1-INH+F XIII group 503 (337-646)/mm2). NAC+TM reduced the firmly adherent leukocytes in the V3 venules (NAC+TM group 403 (309-572)/mm2) and in the V1 venules (CON group 55 (16-131)/mm2; LPS group 368 (306-475)/mm2; NAC+TM group 270 (216-308)/mm2) as well. FCD was not impaired after LPS challenge and there was no influence of both combinations on the FCD. We conclude that both drug combinations can reduce the leukocyte adherence in a sepsis model in rats.

[Acute renal failure - anticoagulation in continuous renal replacement therapy]. / Antikoagulation bei der kontinuierlichen Nierenersatztherapie.

Anticoagulation plays a pivotal role for the efficacy of continuous renal replacement therapy. The equilibrium between avoiding bleeding complications and keeping the system open considering patients} multiple diseases demands an individual and dynamic reasoned anticoagulation regime. For patients at risk of bleeding citrate anticoagulation has shown high efficacy and lesser bleeding complications than the standard heparin or other alternative anticoagulants such as regional protamin-heparin-, prostaglandin-heparin-anticoagulation or no anticoagulation.

The effect of stimulating versus nonstimulating catheters for continuous interscalene plexus blocks in short-term pain management.

STUDY OBJECTIVE: To investigate whether placement, and use of stimulating catheters for interscalene brachial plexus blocks improves short-term postoperative analgesia. DESIGN: Controlled, prospective, randomized, pilot study. SETTING: University hospital. PATIENTS: 60 patients undergoing shoulder surgery. INTERVENTIONS AND MAIN MEASUREMENTS: The brachial plexus was identified using a stimulating needle. In conventional catheter group 1 (CC 1), local anesthetic (LA) was injected through the needle and catheters were advanced blindly thereafter. In catheter group 2 (CC 2), catheters were blindly inserted and LA was injected through the catheter. In the stimulating catheter group (SC), LA was injected only after catheter tip location was confirmed by nerve stimulation. Time required to perform the block, pain intensity at rest, and dynamic pain (defined movement: lifting of arm; numeric rating scale, 0-10), patient satisfaction (verbal rating scale, Likert scale), and plasma concentrations of ropivacaine were measured. MAIN RESULTS: Patients in the SC group had significantly decreased pain scores. The median block performance time was 6 minutes in CC 1 (CI 25%-75%: 4-8 min), 11 minutes in CC 2 (CI 25%-75%: 7-13 min), and 12 minutes in SC (CI 25%-75%: 10-24 min). Patient satisfaction and plasma concentrations of ropivacaine did not differ among the groups. CONCLUSIONS: Stimulating catheters for interscalene plexus blocks improve postoperative analgesia at rest in patients undergoing shoulder surgery.

Iloprost for additional anticoagulation in continuous renal replacement therapy--a pilot study.

PURPOSE: The aim of this pilot study was to compare the effect of heparin anticoagulation with and without iloprost administration during continuous renal replacement therapy (CRRT) in critically ill patients. MATERIAL AND METHODS: In a prospective, randomized, controlled pilot study at an intensive care unit at a university hospital, 20 patients requiring CRRT were investigated. Patients were allocated into two groups: group 1, the heparin group; and group 2, the heparin plus 1 ng/kg/min iloprost. In both groups, activated partial thromboplastin time (aPTT) was adjusted to 40-50 sec. Observation time was a maximum of 7 days. RESULTS: Median filter run time was significantly prolonged by iloprost administration to a median of 14 h (13-26 h) compared to 10 h (4-12 h) in the heparin group (p = 0.004). A decrease in platelet count was attenuated by iloprost administration (p = 0.012). There were no bleeding complications in either group. Hemofiltration efficiency did not differ significantly between the groups. CONCLUSION: Additional administration of iloprost prolonged the filter run time of continuous veno-venous hemofiltration (CVVH) in this setting and attenuated the fall in platelet count during CRRT.

Three-year survival after four major post-cardiac operative complications.

OBJECTIVE: After cardiac surgery, major morbidities known to be primary contributors to perioperative mortality are cardiac failure, respiratory failure, renal failure, and the need for mediastinal exploration. The first aim of this study was to ascertain long-term survival in cardiac surgery patients with and without the occurrence of major morbidities to investigate if long-term survival was comparable. The second aim of this study was to evaluate the prevalences and risk factors related to the four major morbidities in this patient population. DESIGN: Retrospective observational outcome study. SETTING: Cardiothoracic intensive care unit at a university hospital. PATIENTS: We included 2,683 of 3,253 consecutive cardiac surgery patients cared for in a uniform fashion. METHODS AND MAIN RESULTS: Perioperative mortality was significantly increased by the occurrence of major morbidity. In-hospital mortality was 0.7% in the absence of major morbidity compared with 72% when all major morbidities occurred. Three-year mortality for the entire study population was 15%, whereas the 3-yr long-term survival was significantly less for patients with morbidities compared with those without. Various independent perioperative risk factors were found for perioperative major morbidity and mortality. CONCLUSIONS: Successful acute treatment and measures to identify and reduce the risk of major morbidities are necessary to improve outcome. In addition, long-term follow-up and management of morbidities are necessary to possibly improve long-term survival.

Effects of dopexamine on the intestinal microvascular blood flow and leukocyte activation in a sepsis model in rats.

INTRODUCTION: The administration of dopexamine may constitute a therapeutical option to improve hepatosplanchnic perfusion in sepsis. In order to verify this hypothesis, we administered dopexamine in an experimental sepsis model in rats. METHODS: This prospective, randomized, controlled laboratory study was conducted in 42 Wistar rats. The animals were divided into 3 groups. Group 1 (CON group) served as control group. The Animals of groups 2 (LPS Group) and 3 received an endotoxin infusion (20 mg/kgfor 15 min). In addition, in group 3 (DPX group) dopexamine was administered 0.5 microg/kg/minover 4 hours. One half of the animals of each group underwent studies of intestinal microvascular blood flow (IMBF) using laser Doppler fluxmetry. In the other half an intravital microscopic evaluation of the leukocyte endothelium cell interaction in the intestinal microcirculation was performed. Functional capillary denstity (FCD) in the intestinal mucosaand the circular as well as the longitudinal muscle layer was estimated. RESULTS: One hour after endotoxin challenge IMBF decreased significantly in the untreated LPS group to 51% compared to baseline (p<0.05). In DPX treated endotoxin animals we found significantly higher values at the level of CON group. The after endotoxin challenge impaired FCD was improved by dopexamine in the longitudinal (DPX + 33% vs. LPS; p <0.05) and in the circular muscle layer (DPX + 48% vs. LPS; p < 0.05) as a result of dopexamine administration. The administration of dopexamine reduced the count of firmly adherent leukocytes when compared to the untreated LPS group (-31%, p<0.05). TNF-alpha plasma levels were reduced by dopexamine infusion (LPS group 3637 +/- 553 pg/mL; DPXgroup 1933 +/- 201 pg/mL) one hour after endotoxin challenge. CONCLUSIONS: The administration of dopexamine improved IMBF and FCD as parameters of intestinal microcirculation and reduced leukocyte activation as a parameter of inflammation in experimental sepsis.

Effects of coagulation factor XIII on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation in experimental endotoxemia.

INTRODUCTION: The objective of this study was to determine the effects of the administration of the coagulation factor XIII (F XIII) on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation during experimental endotoxemia. METHODS: In a prospective, randomized, controlled animal study 42 male Wistar rats were divided into three groups. Group 1 served as the control group. Groups 2 (lipopolysaccharide (LPS) group) and 3 (F XIII group) received endotoxin infusions (2.5 mg/kg/h for 2 hours). In group 3, 50 U/kg body weight F XIII was continuously administered during the first 30 minutes of endotoxemia. F XIII levels were measured in all animals. One half of the animals of each group were studied for intestinal functional capillary density (FCD) and leukocyte adherence on venular endothelium by intravital fluorescence microscopy (IVM). In the other half of each group, mesenteric plasma extravasation (FITC-albumin) was determined by IVM. RESULTS: The F XIII level was significantly increased in the F XIII treatment group. In the LPS group, endotoxemia led to a significant reduction of mucosal FCD (-18.5%; p < 0.01 versus control group). F XIII administration in the F XIII group attenuated the decrease in mucosal FCD (-3.7% compared to control; p < 0.05 versus LPS group). During endotoxemia, a significant increase of leukocyte adherence at the endothelium could be noted in the LPS group compared to the control group. Leukocyte adherence at the endothelium and plasma extravasation in the F XIII group did not differ significantly from the LPS group. CONCLUSION: Factor XIII protected mucosal capillary perfusion against endotoxin-induced impairment in an experimental sepsis model in rats, whereas leukocyte adherence and plasma extravasation remained unchanged.

WITHDRAWN: Protracted intensive care unit-stay >14 days in cardiac surgery: risk factors and long-term survival.

Ahead of Print article withdrawn by publisher.

Prolonged intensive care unit stay in cardiac surgery: risk factors and long-term-survival.

BACKGROUND: Risk factors have been found for prolonged intensive care unit (ICU) stay in cardiac surgery patients in only a few studies; conflicting results have been described. The focus of this study was twofold: first, to evaluate preoperative, intraoperative, and postoperative risk factors for ICU stay greater than 3 days in a cardiac surgery patient population; second, to evaluate long-term survival in cardiac surgery patients with prolonged ICU stay. METHODS: Records from 2,683 cardiac surgery patients were retrospectively evaluated. Univariate and multivariate analyses for risk factors were performed for an ICU stay greater than 3 days. Thereafter, 2,563 patients were enrolled in a follow-up study for an observational time of 3 years after surgery. RESULTS: Mortality was dependent on renal, respiratory, and heart failure, as well as age, elevated APACHE II scores, and reexploration. Long-term survival analyses demonstrated a significantly lower survival in patients with longer ICU stay. However, the 6-month to 3-year long-term survival was comparable with survival in patients without prolonged ICU stay. CONCLUSIONS: Because of the increasing acuity of patients needing cardiac surgery, it is important to identify those at risk for a prolonged ICU course. It is therefore of paramount interest to implement measures throughout their entire hospital stay that would maximize organ function to improve survival and resource utilization.

Circulating immune parameters predicting the progression from hospital-acquired pneumonia to septic shock in surgical patients.

INTRODUCTION: Hospital-acquired pneumonia after surgery is one of the major causes of septic shock. The excessive inflammatory response appears to be responsible for the increased susceptibility to infections and subsequent sepsis. The primary aim of this study was to investigate immune parameters at the onset of pneumonia, before the development of subsequent septic shock. The secondary aim was to investigate the usefulness of these immune parameters in predicting progression from hospital-acquired pneumonia to septic shock. METHODS: This prospective clinical study included 76 patients with the diagnosis of hospital-acquired pneumonia. Approval was obtained from the local institutional ethics committee and relatives of the patients gave informed consent. Of the 76 patients, 29 subsequently developed septic shock. All patients were included within 4 h of establishing the diagnosis of hospital-acquired pneumonia (first collection of blood samples and the analysis of immune mediators). In addition, we defined early (within 12 h of onset of septic shock) and late (within 72 to 96 h of onset) stages of septic shock for the collection of blood samples and the analysis of immune mediators. The immune parameters tumor necrosis factor-alpha, IL-1beta, IL-6, IL-8 and IL-10 as well as the endothelial leucocyte adhesion molecule were analyzed. RESULTS: In the pneumonia group with subsequent septic shock, levels of IL-1beta, IL-6, IL-8 and IL-10 were significantly increased before the onset of septic shock compared to patients without subsequent septic shock. This progression was best predicted by IL-1beta, IL-6, IL-8 and IL-10 (area under the curve > or = 0.8). CONCLUSION: At the onset of hospital-acquired pneumonia, a significant relevant systemic cytokine mediated response had already been initiated. It might, therefore, be possible to identify patients at risk for septic shock with these predictive markers during early pneumonia. In addition, immune modulating therapy might be considered as adjuvant therapy.

Time course of endothelial damage in septic shock: prediction of outcome.

INTRODUCTION: Endothelial damage accounts greatly for the high mortality in septic shock. Higher expression of mediators (IL-6, IL-8, soluble intercellular adhesion molecule 1 [sICAM-1], soluble endothelial-linked adhesion molecule 1 [sELAM-1]) have been described for non-survivors in comparison with survivors. We investigated the predictive value of the mediators IL-6, IL-8, sELAM-1 and sICAM-1 and their time course in intensive care unit patients who developed septic shock with respect to outcome. MATERIALS AND METHODS: We measured serum levels of IL-6, IL-8, sELAM-1 and sICAM-1 in 40 intensive care unit patients who developed septic shock. Measurements were performed until death or until resolution of septic shock. Clinical and laboratory data were also recorded. RESULTS: After 48 hours the levels of sELAM-1 and sICAM-1 increased in non-survivors and decreased in survivors. sELAM-1 was predictive for outcome on the third day (P = 0.02) and the fourth day (P = 0.02) after diagnosis of septic shock. This difference in the time course between survivors and non-survivors occurred 7 days before death of the patients (median, 10 days). sICAM-1 levels increased significantly in non-survivors over the study period (P < 0.001). sELAM-1 (P = 0.04), IL-6 (P = 0.04) and IL-8 (P = 0.008) were significantly higher in non-survivors over the whole study period. The age and norepinephrine dose >0.5 mug/kg/min were significantly different between the groups. CONCLUSION: sELAM-1 showed a markedly opposing course after 48 hours of septic shock. This adhesion molecule may be a useful early predictor of disease severity in the course of septic shock after early initial treatment of the patients, and might suggest considering endothelial-restoring therapy.

Validity and reliability of the DDS for severity of delirium in the ICU.

INTRODUCTION: Until now, there has been no gold standard for monitoring delirium in intensive care unit (ICU) patients. In this prospective cohort study, a new score, the Delirium Detection Score (DDS), for severity of delirium in the ICU was evaluated. METHODS: After ethical approval and written informed consent, intensive care doctors and nurses assessed 1073 consecutive patients in surgical ICUs using the DDS together with the Ramsay Sedation Scale (RSS). The DDS is composed of eight criteria (orientation, hallucination, agitation, anxiety, seizures, tremor, paroxysmal sweating, and altered sleep- wake rhythm). Additionally, intensive care doctors had to document the Sedation-Agitation Scale (SAS) combined with a defined clinical assessment. For interrater reliability, pair of evaluators assessed patients in a blinded fashion at the same time. RESULTS: RSS1 (9%) was associated with a significantly (p < 0.001) higher DDS than RSS levels 2-6. The DDS increased with the severity of delirium (p < 0.001). The receiver operating characteristics (ROC) for the differentiation between no delirium (SAS < 4) and symptoms of delirium at all (SAS 5-7) showed an area under the curve (AUC) of 0.802 (95% confidential interval (CI): 0.719-0.898; p < 0.001) and 69% sensitivity and 75% specificity was determined. For reliability, a Cronbach's alpha of 0.667 was calculated. The paired comparisons revealed an intraclass correlation between 0.642 and 0.758. CONCLUSION: The DDS demonstrated good validity with excellent sensitivity and specificity for delirium. The severity of delirium can be more accurately estimated by the DDS. By its composition of several items, the DDS might help to start a symptom-guided therapy immediately.

Protracted bleeding after hirudin anticoagulation for cardiac surgery in a patient with HIT II and chronic renal failure.

Heparin-induced thrombocytopenia type II (HIT II) requires alternative anticoagulation. Hirudin has been effectively used in patients with HIT II scheduled for cardiac surgery. However, bleeding complications were observed in patients with renal impairment. In vitro hemodialysis (HD) has been questioned over its efficacy in eliminating hirudin. Another approach to stop bleeding is the application of recombinant factor VIIa (rFVIIa). We report on a patient with HIT II and chronic renal failure who suffered from severe hirudin-induced bleeding after cardiac surgery who was safely treated with a combined approach of surgical hemostasis, substitution of blood products, HD, and rFVIIa to stop finally bleeding.

Altered immune parameters in chronic alcoholic patients at the onset of infection and of septic shock.

INTRODUCTION: Chronic alcoholic patients have a threefold to fourfold increased risk for developing a severe infection or septic shock after surgery, which might be due to altered immune response. The aim of this outcome matched study was to investigate proinflammatory and anti-inflammatory immune parameters during the course of infection and subsequent septic shock in chronic alcoholic patients, and to compare these parameters with those in nonalcoholic patients. METHODS: Twenty-eight patients from a cohort of fifty-six with either pneumonia or peritonitis and subsequent septic shock were selected. Fourteen patients were chronic alcoholics whereas fourteen were nonalcoholic patients. Chronic alcoholic patients met criteria (Diagnostic and Statistical Manual of Mental Disorders IV, of the American Psychiatric Association) for alcohol abuse or dependence. Measurements were performed during the onset of infection (within 24 hours after the onset of infection), in early septic shock (within 12 hours after onset of septic shock) and in late septic shock (72 hours after the onset). Blood measurements included proinflammatory and anti-inflammatory cytokines. RESULTS: Chronic alcoholic patients exhibited significantly lower plasma levels of IL-8 (P < 0.010) during the onset of infection than did matched nonalcoholic patients. In early septic shock, chronic alcoholic patients had significantly decreased levels of IL-1beta (P < 0.015), IL-6 (P < 0.016) and IL-8 (P < 0.010). The anti-inflammatory parameters IL-10 and tumour necrosis factor receptors I and II did not differ between alcoholic and nonalcoholic patients. CONCLUSION: At the onset of infection and during early septic shock, chronic alcoholic patients had lower levels of proinflammatory immune parameters than did nonalcoholic patients. Therefore, immunomodulatory therapy administered early may be considered in chronic alcoholic patients at the onset of an infection because of their altered proinflammatory immune response.

Mild hypothermia after near drowning in twin toddlers.

INTRODUCTION: We report a case of twin toddlers who both suffered near drowning but with different post-trauma treatment and course, and different neurological outcomes. METHODS AND RESULTS: Two twin toddlers (a boy and girl, aged 2 years and 3 months) suffered hypothermic near drowning with protracted cardiac arrest and aspiration. The girl was treated with mild hypothermia for 72 hours and developed acute respiratory dysfunction syndrome and sepsis. She recovered without neurological deficit. The boy's treatment was conducted under normothermia without further complications. He developed an apallic syndrome. CONCLUSION: Although the twin toddlers experienced the same near drowning accident together, the outcomes with respect to neurological status and postinjury complications were completely different. One of the factors that possibly influenced the different postinjury course might have been prolonged mild hypothermia.

Intermittent hirudin versus continuous heparin for anticoagulation in continuous renal replacement therapy.

BACKGROUND: Besides possible bleeding complications a further problem in anticoagulation during continuous renal replacement therapy (CRRT) is the development of heparin-induced thrombocytopenia type II (HIT II) where further anticoagulation with heparin is contraindicated. The application of continuous hirudin as alternative for heparin caused bleeding complications by comparable filter efficacy. Aim of this prospective-controlled pilot study was to compare the efficacy and safety of intermittent hirudin and continuous heparin for anticoagulation during CRRT in critically ill patients. METHODS: 26 patients receiving CRRT were randomly allocated to two groups: Heparin group (14 patients): continuous administration of 250 IU/h heparin, dose was adjusted in 125 IU/h steps with a targeted activated clotting time (ACT) of 180-210 s. Hirudin group (12 patients): initial bolus application of 2-2-5 microg/kg hirudin, dose was adjusted in 2 microg/kg bolus steps with a targeted ecarin clotting time (ECT) >80 s. Observation time was 96 hours. RESULTS: Measured filter run time was virtually longer for heparin. No bleeding complications were observed in the hirudin group, two bleeding complications in the heparin group. CONCLUSIONS: Intermittent hirudin can be used safely for anticoagulation in CRRT. However, the in tendency better filter survival for heparin elucidates the need for further investigations to find the right dosage equilibrium between filter clotting and bleeding complications.

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.