Multiplex polymerase chain reaction to diagnose bloodstream infections in patients after cardiothoracic surgery.

BACKGROUND: Sepsis and other infectious complications are major causes of mortality and morbidity in patients after cardiac surgery. Whereas conventional blood culture (BC) suffers from low sensitivity as well as a reporting delay of approximately 48-72 h, real-time multiplex polymerase chain reaction (PCR) based technologies like "SeptiFast" (SF) might offer a fast and reliable alternative for detection of bloodstream infections (BSI). The aim of this study was to compare the performance of SF with BC testing in patients suspected of having BSI after cardiac surgery. METHODS: Two hundred seventy-nine blood samples from 169 individuals with suspected BSI were analyzed by SF and BC. After excluding results attributable to contaminants, a comparison between the two groups were carried out. Receiver operating characteristic (ROC) curves were generated to determine the accuracy of clinical and laboratory values for the prediction of positive SF results. RESULTS: 14.7% (n = 41) of blood samples were positive using SF and 17.2% (n = 49) using BC (n.s. [p > 0.05]). In six samples SF detected more than one pathogen. Among the 47 microorganisms identified by SF, only 11 (23.4%) could be confirmed by BC. SF identified a higher number of Gram-negative bacteria than BC did (28 vs. 12, χ2 = 7.97, p = 0.005). The combination of BC and SF increased the number of detected microorganisms, including fungi, compared to BC alone (86 vs. 49, χ2 = 13.51, p < 0.001). C-reactive protein (CRP) (21.7 ± 11.41 vs. 16.0 ± 16.9 mg/dl, p = 0.009), procalcitonin (28.7 ± 70.9 vs. 11.5 ± 30.4 ng/dl, p = 0.015), and interleukin 6 (IL 6) (932.3 ± 1306.7 vs. 313.3 ± 686.6 pg/ml, p = 0.010) plasma concentrations were higher in patients with a positive SF result. Using ROC analysis, IL-6 (AUC 0.836) and CRP (AUC 0.804) showed the best predictive values for positive SF results. CONCLUSION: The SF test represent a valuable method for rapid etiologic diagnosis of BSI in patients after cardiothoracic surgery. In particular this method applies for individuals with suspected Gram-negative blood stream. Due to the low performance in detecting Gram-positive pathogens and the inability to determine antibiotic susceptibility, it should be used in addition to BC only (Pilarczyk K, et al., Intensive Care Med Exp ,3(Suppl. 1):A884, 2015).

Esophageal Heat Exchanger Versus Water-Circulating Cooling Blanket for Targeted Temperature Management.

To date, the optimal cooling device for targeted temperature management (TTM) remains unclear. Water-circulating cooling blankets are broadly available and quickly applied but reveal inaccuracy during maintenance and rewarming period. Recently, esophageal heat exchangers (EHEs) have been shown to be easily inserted, revealed effective cooling rates (0.26-1.12°C/h), acceptable deviations from target core temperature (<0.5°C), and rewarming rates between 0.2 and 0.4°C/h. The aim of this study was to compare cooling rates, accuracy during maintenance, and rewarming period as well as side effects of EHEs with water-circulating cooling blankets in a porcine TTM model. Mean core temperature of domestic pigs (n = 16) weighing 83.2 ± 3.6 kg was decreased to a target core temperature of 33°C by either using EHEs or water-circulating cooling blankets. After 8 hours of maintenance, rewarming was started at a goal rate of 0.25°C/h. Mean cooling rates were 1.3 ± 0.1°C/h (EHE) and 3.2 ± 0.5°C/h (blanket, p < 0.0002). Mean difference to target core temperature during maintenance ranged between ±1°C. Mean rewarming rates were 0.21 ± 0.01°C/h (EHE) and 0.22 ± 0.02°C/h (blanket, n.s.). There were no differences with regard to side effects such as brady- or tachycardia, hypo- or hyperkalemia, hypo- or hyperglycemia, hypotension, shivering, or esophageal tissue damage. Target temperature can be achieved faster by water-circulating cooling blankets. EHEs and water-circulating cooling blankets were demonstrated to be reliable and safe cooling devices in a prolonged porcine TTM model with more variability in EHE group.

Intravascular Cooling Device Versus Esophageal Heat Exchanger for Mild Therapeutic Hypothermia in an Experimental Setting.

BACKGROUND: Targeted temperature management is a standard therapy for unconscious survivors of cardiac arrest. To date, multiple cooling methods are available including invasive intravascular cooling devices (IVDs), which are widely used in the clinical setting. Recently, esophageal heat exchangers (EHEs) have been developed providing cooling via the esophagus that is located close to the aorta and inferior vena cava. The objective was to compare mean cooling rates, as well as differences, to target temperature during maintenance and the rewarming period of IVD and EHE. METHODS: The study was conducted in 16 female domestic pigs. After randomization to either IVD or EHE (n = 8/group), core body temperature was reduced to 33°C. After 24 hours of maintenance (33°C), animals were rewarmed using a target rate of 0.25°C/h for 10 hours. All cooling phases were steered by a closed-loop feedback system between the internal jugular vein and the chiller. After euthanasia, laryngeal and esophageal tissue was harvested for histopathological examination. RESULTS: Mean cooling rates (4.0°C/h ± 0.4°C/h for IVD and 2.4°C/h ± 0.3°C/h for EHE; P < .0008) and time to target temperature (85.1 ± 9.2 minutes for IVD and 142.0 ± 21.2 minutes for EHE; P = .0008) were different. Mean difference to target temperature during maintenance (0.07°C ± 0.05°C for IVD and 0.08°C ± 0.10°C for EHE; P = .496) and mean rewarming rates (0.2°C/h ± 0.1°C/h for IVD and 0.3°C/h ± 0.2°C/h for EHE; P = .226) were similar. Relevant laryngeal or esophageal tissue damage could not be detected. There were no significant differences in undesired side effects (eg, bradycardia or tachycardia, hypokalemia or hyperkalemia, hypoglycemia or hyperglycemia, hypotension, overcooling, or shivering). CONCLUSIONS: After insertion, target temperatures could be reached faster by IVD compared to EHE. Cooling performance of IVD and EHE did not significantly differ in maintaining target temperature during a targeted temperature management process and in active rewarming protocols according to intensive care unit guidelines in this experimental setting.

Incidence of peri-operative paediatric cardiac arrest and the influence of a specialised paediatric anaesthesia team: Retrospective cohort study.

BACKGROUND: Peri-operative critical events are still a major problem in paediatric anaesthesia care. Access to more experienced healthcare teams might reduce the adverse event rate and improve outcomes. OBJECTIVE: The current study analysed incidences of peri-operative paediatric cardiac arrest before and after implementation of a specialised paediatric anaesthesia team and training programme. DESIGN: Retrospective cohort study with before-and-after analysis. SETTING: Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Germany. PATIENTS: A total of 36 243 paediatric anaesthetics (0 to 18 years) were administered between 2008 and 2016. INTERVENTION: Implementation of a specialised paediatric anaesthesia team and training programme occurred in 2014 This included hands-on supervised training in all fields of paediatric anaesthesia, double staffing for critical paediatric cases and a 24/7 emergency team. A logistic regression analysis with risk factors (age, ASA physical status, emergency) was used to evaluate the impact of implementation of the specialised paediatric anaesthesia team. MAIN OUTCOME MEASURES: Incidences of peri-operative paediatric cardiac arrest and anaesthesia-attributable cardiac arrest before and after the intervention. RESULTS: Twelve of 25 paediatric cardiac arrests were classified as anaesthesia-attributable. The incidence of overall peri-operative paediatric cardiac arrest was 8.1/10 000 (95% CI 5.2 to 12.7) in the period 2008 to 2013 and decreased to 4.6/10 000 (95% CI 2.1 to 10.2) in 2014 to 2016. Likewise, the incidence of anaesthesia-attributable cardiac arrest was lower after 2013 [1.6/10 000 (95% CI 0.3 to 5.7) vs. 4.3/10 000 (95% CI 2.3 to 7.9)]. Using logistic regression, children anaesthetised after 2013 had nearly a 70% lower probability of anaesthesia-attributable cardiac arrest (odds ratio 0.306, 95% CI 0.067 to 1.397; P = 0.1263). For anaesthesia-attributable cardiac arrest, young age was the most contributory risk factor, whereas in overall paediatric cardiac arrest, ASA physical statuses 3 to 5 played a more important role. CONCLUSION: In this study on incidences of peri-operative paediatric cardiac arrest from a European tertiary care university hospital, implementation of a specialised paediatric anaesthesia team and training programme was associated with lower incidences of peri-operative paediatric cardiac arrest and a reduced probability of anaesthesia-attributable cardiac arrest.

Evaluation of small intestinal damage in a rat model of 6 Minutes cardiac arrest.

BACKGROUND: Contribution of the small intestine to systemic inflammation after cardiac arrest (CA) is poorly understood. The objective was to evaluate whether an in vivo rat model of 6 min CA is suitable to initiate intestinal ischaemia-reperfusion-injury and to evaluate histomorphological changes and inflammatory processes in the small intestinal mucosa resp. in sera. METHODS: Adult male Wistar rats were subjected to CA followed by cardio-pulmonary resuscitation. Proximal jejunum and serum was collected at 6 h, 24 h, 72 h and 7 d post return of spontaneous circulation (ROSC) and from a control group. The small intestine was evaluated histomorphologically. Cytokine concentrations were measured in jejunum lysates and sera. RESULTS: Histomorphological evaluation revealed a significant increase in mucosal damage in the jejunum at all timepoints compared to controls (p < 0.0001). In jejunal tissues, concentrations of IL-1α, IL-1ß, IL-10, and TNF-α showed significant peaks at 24 h and were 1.5- to 5.7-fold higher than concentrations at 6 h and in the controls (p < 0.05). In serum, a significant higher amount of cytokine was detected only for IL-1ß at 24 h post-ROSC compared to controls (15.78 vs. 9.76 pg/ml). CONCLUSION: CA resulted in mild small intestinal tissue damage but not in systemic inflammation. A rat model of 6 min CA is not capable to comprehensively mimic a post cardiac arrest syndrome (PCAS). Whether there is a vital influence of the intestine on the PCAS still remains unclear.

Incidence and risk factors of anaesthesia-related perioperative cardiac arrest: A 6-year observational study from a tertiary care university hospital.

BACKGROUND: In recent decades, the incidences of anaesthesia-related perioperative mortality and adverse outcomes have decreased drastically. However, to date, data on perioperative cardiac arrest and risk factors of perioperative cardiac arrest from European countries are scarce. OBJECTIVES: To determine the incidences of perioperative cardiac arrest and rates of anaesthesia-related and anaesthesia-contributory cardiac arrest. Identification of pre-existing risk factors leading to perioperative cardiac arrest. DESIGN: Retrospective cohort study. SETTING: Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Germany. INTERVENTIONS: Perioperative critical incident reports between 2007 and 2012 were screened, and reports on cardiac arrest within 24 h postoperatively were identified. Cardiac arrests were classified as 'anaesthesia-related', 'anaesthesia-contributory' or 'anaesthesia-unrelated' by two reviewers independently. Univariate and multi-variate logistic regression analysis was used to identify risk factors associated with perioperative cardiac arrest. RESULTS: Analysis of 318 critical incidents from 169 500 anaesthetics revealed 99 perioperative cardiac arrests. This is an overall incidence of perioperative cardiac arrest of 5.8/10 000 anaesthetics [95% confidence interval (CI), 4.7 to 7.0]. The rate of anaesthesia-related cardiac arrest was 0.7/10 000 (95% CI, 0.3 to 1.1), and the rate of anaesthesia-contributory cardiac arrest was 1.7/10 000 (95% CI, 1.1 to 2.3). Most cardiac arrests related to anaesthesia were due to respiratory events. From the multi-variate analysis, American Society of Anesthesiologists physical status grade at least 3 [P = 0.007, odds ratio (OR) 2.59 (95% CI, 1.29 to 5.19)], emergency surgery [P < 0.001, OR 4.00 (95% CI, 2.15 to 7.54)] and pre-existing cardiomyopathy [P < 0.001, OR 17.48 (95% CI, 6.18 to 51.51)] emerged as predictors of cardiac arrest. CONCLUSION: These first available European data on perioperative cardiac arrest from a large unselected cohort indicate that the overall perioperative incidence of cardiac arrest at our institution was slightly lower than published in the literature, whereas rates of anaesthesia-related and anaesthesia-contributory cardiac arrest were comparable. Most cardiac arrests related to anaesthesia were due to respiratory events. American Society of Anesthesiologists physical status grade at least 3, emergency surgery and pre-existing cardiomyopathy appear to be relevant risk factors for cardiac arrest.

Oesophageal heat exchangers with a diameter of 11mm or 14.7mm are equally effective and safe for targeted temperature management.

BACKGROUND: Targeted temperature management (TTM) is widely used in critical care settings for conditions including hepatic encephalopathy, hypoxic ischemic encephalopathy, meningitis, myocardial infarction, paediatric cardiac arrest, spinal cord injury, traumatic brain injury, ischemic stroke and sepsis. Furthermore, TTM is a key treatment for patients after out-of-hospital cardiac-arrest (OHCA). However, the optimal cooling method, which is quick, safe and cost-effective still remains controversial. Since the oesophagus is adjacent to heart and aorta, fast heat-convection to the central blood-stream could be achieved with a minimally invasive oesophageal heat exchanger (OHE). To date, the optimal diameter of an OHE is still unknown. While larger diameters may cause thermal- or pressure-related tissue damage after long-term exposure to the oesophageal wall, smaller diameter (e.g., gastric tubes, up to 11mm) may not provide effective cooling rates. Thus, the objective of the study was to compare OHE-diameters of 11mm (OHE11) and 14.7mm (OHE14.7) and their effects on tissue and cooling capability. METHODS: Pigs were randomized to OHE11 (N = 8) or OHE14.7 (N = 8). After cooling, pigs were maintained at 33°C for 1 hour. After 10h rewarming, oesophagi were analyzed by means of histopathology. The oesophagus of four animals from a separate study that underwent exactly the identical preparation and cooling protocol described above but received a maintenance period of 24h were used as histopathological controls. RESULTS: Mean cooling rates were 2.8±0.4°C°C/h (OHE11) and 3.0±0.3°C °C/h (OHE14.7; p = 0.20). Occasional mild acute inflammatory transepithelial infiltrates were found in the cranial segment of the oesophagus in all groups including controls. Deviations from target temperature were 0.1±0.4°C (OHE11) and 0±0.1°C (OHE14.7; p = 0.91). Rewarming rates were 0.19±0.07°C °C/h (OHE11) and 0.20±0.05°C °C/h (OHE14.7; p = 0.75). CONCLUSIONS: OHE with diameters of 11 mm and 14.7 mm achieve effective cooling rates for TTM and did not cause any relevant oesophageal tissue damage. Both OHE demonstrated acceptable deviations from target temperature and allowed for an intended rewarming rate (0.25°C/h).

Novel Navigated Ultrasound Compared With Conventional Ultrasound for Vascular Access­a Prospective Study in a Gel Phantom Model.

OBJECTIVES: The authors hypothesized that, compared with conventional ultrasound (CUS), the use of a novel navigated ultrasound (NUS) technology would increase success rates and decrease performance times of vascular access procedures in a gel phantom model. DESIGN: A prospective, randomized, crossover study. SETTING: A university Hospital. PARTICIPANTS: Participants were 44 anesthesiologists with varying clinical experience. INTERVENTIONS: Anesthesiologists performed in-plane and out-of-plane vascular access procedures using both NUS and CUS for needle visualization in a gel phantom model. MEASUREMENTS AND MAIN RESULTS: Procedure time was measured from needle insertion to verbalization of final needle positioning by the participants, and successful needle placement into the simulated vessel was verified by aspiration of simulated blood. By employing ultrasound navigation capabilities in addition to real-time ultrasound imaging during in-plane/long-axis vascular access procedures, median procedure time showed a nonsignificant decrease (7.5 seconds v 13.0 seconds; p = 0.028), and the observed increase in procedure success rate (90.9% v 100%; p = 0.125) did not reach statistical significance. For out-of-plane/short-axis vascular access procedures, a significant reduction in median procedure time (5.0 seconds v 11.5 seconds; p<0.001) and a significant increase in procedure success rate (75% v 100%; p<0.001) were achieved by using navigation technology combined with real-time ultrasound. CONCLUSIONS: NUS technology improved the performance times and success rates of vascular access procedures conducted by anesthesiologists in a gel phantom model.

Comparison of different video laryngoscopes for emergency intubation in a standardized airway manikin with immobilized cervical spine by experienced anaesthetists. A randomized, controlled crossover trial.

BACKGROUND: The aim of the present study was to evaluate whether different video laryngoscopes (VLs) facilitate endotracheal intubation (ETI) faster or more secure than conventional laryngoscopy in a manikin with immobilized cervical spine. METHODS: After local ethics board approval, a standard airway manikin with cervical spine immobilization by means of a standard stiff collar was placed on a trauma stretcher. We compared times until glottic view, ETI, cuff block and first ventilation were achieved, and verified the endotracheal tube position, when using Macintosh laryngoscope, Glidescope Ranger, Storz C-MAC, Ambu Pentax AWS, Airtraq, and McGrath Series5 VLs in randomized order. Wilcoxon signed-rank test and McNemar's test were used for statistical analysis; p<0.05 was considered as significant. RESULTS: Twenty-three anaesthetists (mean age 32.1±4.9 years, mean experience in anaesthesia of 6.9±4.8 years) routinely involved in the management of multitrauma patients participated. The primary study end point, time to first effective ventilation, was achieved fastest when using Macintosh laryngoscope (21.0±7.6s) and was significantly slower with all other devices (Airtraq 33.2±23.9 s, p=0.002; Pentax AirwayScope 32.4±14.9 s, p=0.001; Storz C-MAC 34.1±23.9 s, p<0.001; McGrath Series5 101.7±108.3 s, p<0.001; Glidescope Ranger 46.3±59.1 s, p=0.001). Overall success rates were highest when using Macintosh, Airtraq and Storz C-MAC devices (100%), and were lower in Ambu Pentax AWS and Glidescope Ranger (87%, p=0.5) and in McGrath Series5 device (72.2%, p=0.063). CONCLUSION: When used by experienced anaesthesiologists, video laryngoscopes did not facilitate endotracheal intubation in this model with an immobilized cervical spine in a faster or more secure way than conventional laryngoscopy. However, data was gathered in a standardized model and further studies in real trauma patients are desirable to verify our findings.

[Cardiac insufficiency: acute right heart failure]. / Herzinsuffizienz - Das akute Rechtsherzversagen.

Acute right heart failure (RHF) is a frequent and severe complication during perioperative and intensive care treatment in intensive care units (ICUs). The most common causes are pulmonary hypertension, left heart failure, pulmonary embolism, sepsis, acute lung injury (ALI) and thoracosurgical procedures. Acute RHF is not only a major contributor to morbidity and mortality; it also influences efficacy and outcome of routinely performed procedures, such as vasopressors, in critically ill patients. In contrast to the left ventricle, the right ventricle's physiology and pathophysiology are understudied, and the diagnosis of acute RHF is frequently challenging. Although many drugs are available for the treatment of RHF, randomized trials for this setting are still missing. This article gives an overview of aetiology and pathogenesis of RHF and reviews the diagnostic and therapeutic interventions currently available for providers in anaesthesiology and critical care.

Hypothermia and neuroprotection by sulfide after cardiac arrest and cardiopulmonary resuscitation.

BACKGROUND: Poor neurological outcome remains a major problem in patients suffering cardiac arrest. Recent data have demonstrated potent neuroprotective effects of the administration of sulfide donor compounds after ischaemia/reperfusion injury following cardiac arrest and resuscitation. Therefore, we sought to evaluate the impact of sodium sulfide (Na(2)S), a liquid hydrogen sulfide donor on core body temperature and neurological outcome after cardiac arrest in rats. METHODS: Fifty male Wistar rats were randomized into two groups (sulfide vs. placebo, n=25 per group). Cardiac arrest was induced by transoesophageal ventricular fibrillation during general anaesthesia. After 6 min of global cerebral ischaemia, animals were resuscitated by external chest compressions combined with defibrillation. An investigator blinded bolus of either Na(2)S (0.5 mg/kg body weight) or placebo 1 min before the beginning of CPR, followed by a continuous infusion of Na(2)S (1 mg/kg body weight/h) or placebo for 6 h, was administered intravenously. 1 day, 3 days, and 7 days after restoration of spontaneous circulation, neurological outcome was evaluated by a tape removal test. After 7 days of reperfusion, coronal brain sections were analyzed by TUNEL- and Nissl-staining. A caspase activity assay was used to determine antiapoptotic properties of Na(2)S. RESULTS: Temperature course was similar in both groups (mean minimal temperature in the sulfide group 31.3±1.2°C vs. 30.8±1.9°C in the placebo group; p=0.29). Despite significant neuroprotection demonstrated by the tape removal test after 3 days of reperfusion in the sulfide treated group, there was no significant difference in neuronal survival at day 7. Likewise results from TUNEL-staining revealed no differences in the amount of apoptotic cell death between the groups after 7 days of reperfusion. CONCLUSION: In our rat model of cardiac arrest, sulfide therapy was associated with only a short term beneficial effect on neurological outcome.

[Retention management by means of applied human resource development: lessons from cardiovascular anaesthesiology]. / Mitarbeiterbindung durch Personalentwicklung - Am Beispiel Kardioanästhesie.

At present, besides well-known financial problems, German hospitals are facing a serious lack of qualified medical staff. Given these facts, it is of great importance, especially in work load burdened disciplines, such as cardiovascular anaesthesiology, to retain highly qualified medical staff. Here, human resource development measures offer valuable tools for efficient retention management. Moreover, most of these are applicable to almost any clinical specialty. Surprisingly, financial aspects play a minor role in such concepts, in contrast to human resource development tools, such as mentoring, interviews, training and motivational activities. Especially, with regard to "Generation Y", an efficient retention management will play a key role to keep these physicians as hospital employees of long duration in the future.

[Human resource management - Motivation of medical staff in intensive care medicine]. / Moderne Personalführung - Motivation von ärztlichen Mitarbeitern in der Intensivmedizin.

Recently, human resource development concepts have become more important in intensive care medicine. Motivationally oriented leadership is an essential part of this strategy. Of particular significance, leadership first of all means not to demotivate the personnel. Furthermore, a motivationally oriented leadership concept creates a framework in which the physicians' own motivation may thrive. Intensive care supervisory staff today should be familiar with mechanisms and potential of established motivational concepts and should be able to transfer them consequently into clinical practice.

Effects of abciximab on postresuscitation microcirculatory dysfunction after experimental cardiac arrest in rats.

BACKGROUND: The term "postresuscitation syndrome" includes among other pathophysiology impaired microcirculation and endothelial leakage. GPIIb/IIIa receptor antagonists like abciximab have been shown to reduce endothelial leakage and to improve microcirculatory disturbances during experimental endotoxaemia where comparably similar endothelial dysfunction has been observed. Previous investigations on postresuscitation endothelial leakage have indicated a possible role of platelets. Therefore, we investigated effects of abciximab on postresuscitation microcirculation applying in vivo microscopy of postcapillary mesenteric venules after experimentally induced cardiac arrest and cardiopulmonary resuscitation in rats. METHODS: After 6 min of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR), male Wistar rats were randomised into two groups (n=10) to receive abciximab (1mg/kg i.v.) or placebo (0.9% NaCl). Sham operated animals (n=10) served as non-ischaemic controls. At 360, 420 and 480 min after return of spontaneous circulation (ROSC) in vivo microscopy was performed to assess venular wall shear rate (WSR) and plasma extravasation (PE). RESULTS: Besides typical signs of severe endothelial leakage in both CA groups, no significant differences between the treatment groups were observed with regard to WSR and PE. CONCLUSION: In our study, a distinct postresuscitation microcirculatory splanchnic impairment after CA and successful CPR was observed. However, abciximab had no effects on WSR and PE. Our data does not support a valid resemblance between postresuscitation microcirculatory dysfunction observed in connection with experimental endotoxaemia. Furthermore, our data indicate that mechanisms other than GPIIb/IIIa mediated platelet activation play a role in postresuscitation syndrome. A better understanding of "postresuscitation disease" should enable the development of future therapeutic strategies for cardiac arrest survivors.

Effects of activated protein C on post cardiac arrest microcirculation: an in vivo microscopy study.

BACKGROUND: The clinical symptoms and pathophysiologic mechanisms during and after ischaemia-reperfusion following cardiac arrest (CA) and successful cardiopulmonary resuscitation (CPR) closely resemble those observed in patients with severe sepsis. Impairment of microcirculation and endothelial leakage seem to play key roles in the underlying pathophysiology. Recombinant human activated protein C (rhAPC) is the first drug being licensed for the treatment of severe sepsis in patients. Therefore, for the first time, we investigated effects of rhAPC on microhaemodynamic changes and endothelial leakage applying in vivo microscopy of postcapillary mesenteric venules after CA and CPR in rats. METHODS: After 6 min of CA, male Wistar rats were randomised into two groups (n=10) to receive rhAPC or placebo (0.9% NaCl). Sham-operated animals (n=10) served as non-ischaemic controls. At 360, 420, and 480 min after CA in vivo microscopy was performed to assess wall shear rate (WSR) and plasma extravasation (PE). RESULTS: Both treatment groups showed typical signs of impaired microcirculation and a severe endothelial leakage after CA at all time points studied when compared to the sham group. However, no significant differences between the treatment groups were observed with regard to WSR and PE. CONCLUSION: Our results show that CA with consecutive successful CPR leads to a microcirculatory impairment closely resembling experimentally induced sepsis. Intriguingly, despite these similarities, rhAPC had no significant effects on WSR and PE. Our results strongly suggest that further mechanisms such as mast cell activation might play an important role and have therefore to be studied to elucidate the pathophysiology of "postresuscitation disease".

Time course of caspase activation in selectively vulnerable brain areas following global cerebral ischemia due to cardiac arrest in rats.

This study evaluated the time course of caspase activation in selectively vulnerable brain areas (hippocampus, nucleus reticularis thalami (NRT), cortex and striatum) following cardiopulmonary resuscitation (CPR) after global cerebral ischemia due to cardiac arrest (CA) in rats. Caspases are well known to play a crucial role in the apoptotic cascade and inflammatory syndromes and, therefore, represent potential therapeutic postischemic targets. Given the delayed neurodegeneration following CA, it is highly important to study the time course of caspase activation in regard to therapeutic interventions after CA. To assess caspase activity, in situ staining was applied to detect general caspase activity at 6h, 3d and 7d and caspase-3 activity at 3d after return of spontaneous circulation (ROSC). For detection of neuronal apoptosis, TUNEL staining was applied at 7d after ROSC. Distinct patterns of early caspase activation were observed at 6h and 3d in the NRT and striatum and of late activation at 7d in the hippocampal CA-1 sector. General caspase and caspase-3 activity correlated strongly at 3d after ROSC in all areas studied. At 7d, the TUNEL-positive neuron counts in the hippocampal CA-1 sector correlated strongly with caspase activation. In conclusion, general caspase and caspase-3 activity after 6 min of CA and the delayed occurrence of TUNEL-positive neurons strongly indicate that neuronal degeneration after CA is at least strongly associated with apoptosis. Therefore, postischemic antiapoptotic interventions might offer potential future therapeutic opportunities global cerebral ischemia due to CA.

Neurological outcome and inflammation after cardiac arrest--effects of protein C in rats.

BACKGROUND: The response of the human body to cardiac arrest (CA) and cardiopulmonary resuscitation is characterised by excessive coagulation, inadequate endogenous anti-coagulation and fibrinolysis as well as an inflammatory syndrome that closely resembles the immunological profile observed in patients with sepsis. Recombinant human activated protein C (rhAPC) has been found to be protective in severe sepsis and in animal models of stroke and spinal cord injury. In the present study, we evaluated the effects of rhAPC on neurological outcome after CA in rats. METHODS: After 6 min of CA and subsequent cardiopulmonary resuscitation, male Wistar rats were randomized into 3 treatment groups: high dose rhAPC (2 mg/kg bolus and 0.1 mg/(kg h) for 6 h), low dose rhAPC (0.5 mg/kg and 0.025 mg/(kg h) for 6 h), and placebo (n=12 per treatment and reperfusion time). Neurological outcome was determined using a tape removal test and a composite neurological deficit score (NDS). As secondary measurements, we evaluated overall and neuronal survival, hippocampal caspase activity and inflammatory markers. RESULTS: No difference between groups was found with the NDS. The tape removal test showed only a transitory improvement in the low dose group at 3 d after CA (P=0.041). No significant differences were observed for secondary measurements. CONCLUSION: A clear and lasting effect of rhAPC on neurological outcome or inflammation after CA could not be shown in this study but the detailed analysis of the postresuscitation syndrome given here builds a firm basis for further research.

Absinthe--a review.

The alcoholic beverage absinthe is recently experiencing a revival after a yearlong prohibition. This review article provides information on all aspects of this bitter spirit and its major components, especially wormwood (Artemisia absinthium L.), which contains the toxic monoterpene thujone. Over 100 references on historic and current literature are provided. The topics comprise the history of the alcoholic drink starting from its invention in the eighteenth century. Historical and modern recipes are discussed in the context of different quality categories and possibilities to reduce the content of thujone are given. The analytical techniques used to verify compliance with the maximum limit of thujone as well as further possibilities for quality control of absinthe are discussed. The toxicology of absinthe is reviewed with regard to the cause of a syndrome called "absinthism," which was described after chronic abuse of the spirit in the nineteenth century. Finally, a food regulatory and food chemical evaluation is provided and minimum requirements for absinthe are suggested. Absinthe should have a recognizable wormwood flavor and after dilution with water the characteristic clouding should arise (louche-effect). Products, which are advertized as being of premium grade should be made by distillation, should have an alcoholic strength of at least 45%vol, and should not contain artificial dye.

Accidental autoerotic death by volatile substance abuse or nonsexually motivated accidents?

In contrast to typical autoerotic fatalities, when death is due to asphyxia mostly by mechanical compression of the neck, atypical autoerotic accidental deaths (AADs) involve sexual self-stimulation by other means such as electrocution or inhalation of chemical agents. Especially in lethal cases of volatile substance abuse (VSA), a differentiation between suicide or sexually or nonsexually motivated accident is often complicated in practical casework. Considering the small number of AADs involving chemical substance abuse reported in the literature, the number of unreported cases seems to be very high. We report about 5 lethal cases of VSA; analysis was performed using headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC/MS). When headspace sampling is not performed at autopsy, the analysis of volatile substances can be very complicated. In 2 cases, an AAD was diagnosed considering findings at the scene, reconstruction of the event, and discussion of the circumstances of the death. These findings demonstrate the importance of VSA in atypical autoerotic asphyxia. Therefore, in cases of suspected lethal inhalational intoxications, as a matter of principle, headspace asservation should be performed at autopsy and an autoerotic motivational background should be taken into consideration for differential diagnosis.