Kv7 channel inhibition increases hypoxic pulmonary vasoconstriction in endotoxemic mouse lungs.

PURPOSE: Hypoxic pulmonary vasoconstriction (HPV) regulates regional pulmonary blood flow in order to match regional ventilation to preserve arterial oxygenation. HPV is impaired in patients with sepsis or acute respiratory distress syndrome (ARDS). Endotoxemic mice show reduced HPV and recent evidence suggests a central role of voltage gated potassium channel 7 (Kv7) in regulating HPV. Therefore, we tested the hypothesis if Kv7 is induced and inhibition of Kv7 increases HPV in endotoxemia. MATERIALS AND METHODS: Isolated lungs of LPS-pretreated and untreated animals were perfused with and without specific inhibitors of Kv7 (linopirdine (LI) 0, 0.1, 1 and 10 µM) or Kv7.1 (HMR1556 100 nM). Pulmonary artery pressure (PAP) during normoxic (FiO2 0.21) as well as hypoxic (FiO2 0.01) ventilation were obtained. Expressions of Kv7 composing (KCNQ1-5) as well as auxiliary subunits (KCNE1-5) were measured in mouse lungs with and without endotoxemia. RESULTS: HPV was impaired in lungs from LPS mice (16 ± 7% vs 105 ± 13% control, p < 0.05). Perfusion of control lungs with 10 µM LI or 100 nM HMR1556 did not affect HPV (LI 105 ± 12% vs 105 ± 13% vehicle, HMR1556 100 ± 6% vs 98 ± 26%, P = NS). In LPS mice perfusion with 10 µM LI (74.2 ± 7% vs. 16 ± 7% vehicle, P < 0.05) or HMR1556 100 nM augmented HPV (74 ± 28% vs. 15 ± 17% vehicle, P < 0.05). KCNQ1, 4 and 5 gene- and protein expressions as well as KCNE1, 2 and 4 gene expressions were unaltered in endotoxemic lungs. KCNE3 gene and protein expressions were increased in lungs of LPS treated mice (3.1 ± 1.3-fold and 1.8 ± 0.3-fold, respectively, P < 0.05 for both). CONCLUSIONS: Endotoxemia does not alter KCNQ1, 4 and 5 gene and protein expressions but increases pulmonary KCNE3 gene and protein expression. In isolated perfused endotoxemic mouse lungs, perfusion with 10 µM LI or 100 nM HMR1556 augments HPV.

The effects of antibiotic cycling and mixing on acquisition of antibiotic resistant bacteria in the ICU: A post-hoc individual patient analysis of a prospective cluster-randomized crossover study.

BACKGROUND: Repeated rotation of empiric antibiotic treatment strategies is hypothesized to reduce antibiotic resistance. Clinical rotation studies failed to change unit-wide prevalence of antibiotic resistant bacteria (ARB) carriage, including an international cluster-randomized crossover study. Unit-wide effects may differ from individual effects due to "ecological fallacy". This post-hoc analysis of a cluster-randomized crossover study assesses differences between cycling and mixing rotation strategies in acquisition of carriage with Gram-negative ARB in individual patients. METHODS: This was a controlled cluster-randomized crossover study in 7 ICUs in 5 European countries. Clinical cultures taken as routine care were used for endpoint assessment. Patients with a first negative culture and at least one culture collected in total were included. Community acquisitions (2 days of admission or less) were excluded. Primary outcome was ICU-acquisition of Enterobacterales species with reduced susceptibility to: third- or fourth generation cephalosporins or piperacillin-tazobactam, and Acinetobacter species and Pseudomonas aeruginosa with reduced susceptibility for piperacillin-tazobactam or carbapenems. Cycling (altering first-line empiric therapy for Gram-negative bacteria, every other 6-weeks), to mixing (changing antibiotic type every empiric antibiotic course). Rotated antibiotics were third- or fourth generation cephalosporins, piperacillin-tazobactam and carbapenems. RESULTS: For this analysis 1,613 admissions were eligible (855 and 758 during cycling and mixing, respectively), with 16,437 microbiological cultures obtained. Incidences of acquisition with ARB during ICU-stay were 7.3% (n = 62) and 5.1% (n = 39) during cycling and mixing, respectively (p-value 0.13), after a mean of 17.7 (median 15) and 20.8 (median 13) days. Adjusted odds ratio for acquisition of ARB carriage during mixing was 0.62 (95% CI 0.38 to 1.00). Acquired carriage with ARB were Enterobacterales species (n = 61), Pseudomonas aeruginosa (n = 38) and Acinetobacter species (n = 20), with no statistically significant differences between interventions. CONCLUSIONS: There was no statistically significant difference in individual patients' risk of acquiring carriage with Gram-negative ARB during cycling and mixing. These findings substantiate the absence of difference between cycling and mixing on the epidemiology of Gram-negative ARB in ICU. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, registered 10 January 2011, NCT01293071.

[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.

[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.

Effects of ketamine on hypoxic pulmonary vasoconstriction in the isolated perfused lungs of endotoxaemic mice.

BACKGROUND AND OBJECTIVE: During sepsis and endotoxaemia, hypoxic pulmonary vasoconstriction (HPV) is impaired. Sedation of septic patients in ICUs is performed with various anaesthetics, most of which have pulmonary dilatory properties. Ketamine is a sympathetic nervous system-activating anaesthetic that preserves cardiovascular stability. The effects of ketamine on the pulmonary vasculature and HPV during sepsis have not been characterized yet. METHODS: Therefore, isolated lungs of mice were perfused with ketamine (0, 0.1, 1.0, and 10 mg kg(-1) body weight min) 18 h following intraperitoneal injection of lipopolysaccharide (LPS); untreated mouse groups served as controls (n = 7 per group, respectively). Pulmonary artery pressure (PAP) and pressure-flow curves during normoxic (FiO(2) = 0.21) and hypoxic (FiO(2) = 0.01) ventilation were obtained. RESULTS: HPV was reduced in endotoxaemic animals when compared with controls (means +/- SD; DeltaPAP control 103 +/- 28% vs. LPS 23 +/- 25%, P < 0.05). Ketamine caused a dose-dependent reduction of HPV in the lungs of control (DeltaPAP 0 mg kg(-1) min(-1) ketamine 103 +/- 28% vs. 10 mg kg(-1) min(-1) ketamine 28 +/- 21%, P < 0.05) and septic animals (DeltaPAP 0 mg kg(-1) min(-1) ketamine 23 +/- 25% vs. 10 mg kg(-1) min(-1) ketamine 0 +/- 4%, P < 0.05). Analysis of pressure-flow curves revealed that ketamine partly reversed the endotoxin-induced changes in basal pulmonary vascular wall properties rather than interfering with the HPV response itself. CONCLUSION: Ketamine modified baseline pulmonary vascular properties, resulting in a reduced HPV responsiveness in untreated mice. Further, ketamine counteracted the LPS-induced changes in pulmonary vascular pressure-flow relationships, but did not affect impaired HPV in this murine endotoxaemia model.

Intracerebroventricular application of granulocyte colony-stimulating factor after cardiac arrest does not promote beneficial effects on cerebral recovery after cardiac arrest in rats.

SUBJECT: Recent data demonstrated potent neuroprotective effects of growth hormones such as granulocyte colony-stimulating factor (G-CSF) after focal cerebral ischaemia. In order to assess possible effects of intracerebroventricular application of G-CSF on cerebral recovery after cardiac arrest (CA) in rats, neurological testing and histological analyses were performed. INTERVENTIONS: After 6 min of electrically induced CA, rats were resuscitated (CPR) and divided into two groups (G-CSF vs. placebo) with two different reperfusion times (7 and 14 days). G-CSF (3.84 microg) or placebo was applied 30 min after restoration of spontaneous circulation (ROSC). At 24h, 3, 7, 10 and 14 days, behavioural neurological testing was done (tape removal test, TRT). Neuronal degeneration of the hippocampal CA-1 sector was analyzed by TUNEL- and Nissl-staining. RESULTS: Before CA all animals passed the TRT (G-CSF 7 [4-12] s, placebo 9 [6-10] s). After ROSC both groups showed a clear neurological deficit (24h: G-CSF and placebo 180 [180-180] s), that improved with ongoing reperfusion times, without reaching baseline values (14 days: G-CSF 25 [21-59] s, placebo 34 [14-175] s). Survival rates did not differ between the groups. All animals showed massive neurodegeneration histologically without any differences between the groups 7 days after CA (TUNEL-positive: G-CSF 63.2 [53.8-72.1], placebo 72.6 [66.6-82.7]; Nissl-positive: G-CSF 2.5 [1.8-3.4], placebo 2.8 [2.0-5.1]). At 14 days, TUNEL-staining revealed no differences (G-CSF 45.2 [35.0-60.0], placebo 56.0 [37.6-63.4]), while G-CSF treatment led to fewer Nissl-positive neurons (G-CSF 1.5 [1.2-2.2], placebo 3.1 [2.1-4.2]; p=0.011). CONCLUSIONS: Despite promising experimental data concerning focal cerebral ischaemia, in this model of 6 min of normothermic CA no beneficial effects of G-CSF application could be demonstrated by behavioural testing and histological analyses of the hippocampal CA-1 sector.

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.

Time-limited hyporesponsiveness to inhaled nitric oxide and pulmonary phosphodiesterase activity in endotoxemic rats.

In acute lung injury (ALI) pulmonary hyporesponsiveness to inhaled nitric oxide (iNO) still represents an unresolved clinical challenge. In septic ALI-patients the incidence of hyporesponsiveness to iNO is increased; therefore, endotoxemia appears to play a major role. Experimental data suggest that endotoxemia, e.g., induced by lipopolysaccharides (LPS), contribute to the hyporesponsiveness to iNO. Guanosine 3',5'-cyclic monophosphate (cGMP) is metabolized by phosphodiesterases (PDE). The role of PDE in reduced pulmonary vascular response in experimental endotoxemia is still not known. Here, we hypothesized that PDE activity modulates initial pulmonary responsiveness to iNO in ALI following systemic endotoxin exposure. Rats were treated with LPS or used as controls. Lungs were isolated-perfused 0-36 h after LPS injection and the synthetic thromboxane analogue U46619 was added to increase pulmonary artery pressure by 6-8 mmHg (n = 47). Then, the pulmonary vasodilatory response to 3 doses of iNO (0.4, 4 and 40 ppm) was measured. Furthermore, lungs were prepared as described previously, and 2, 10, and 18 h after LPS the change in pulmonary artery pressure in response to two different inhibitors of PDE, one of which is PDE sensitive (8-Br-cGMP) and one is PDE stable (8-pCPT-cGMP), was determined (n = 43). Serum nitrite/nitrate levels started to increase 4 h after LPS, with a maximum at 18 h. In contrast, decreased pulmonary vasoreactivity in response to iNO developed as early as 2 h later and remained depressed up to 18 h. The pulmonary vasoreactivity to the PDE-sensitive 8-Br-cGMP after LPS-stimulation was lower than that in lungs treated with the PDE-stable 8-pCPT-cGMP. In rats pretreated with LPS, hyporesponsiveness of pulmonary vessels to iNO is time-limited and associated with increased serum nitrite/nitrate levels, and appears to be attributed in part to increased pulmonary PDE activity.

Thrombolysis and other drugs during cardiopulmonary resuscitation.

PURPOSE OF REVIEW: No specific drug therapy has been shown to improve long-term survival after cardiac arrest, and only few drugs have a proven benefit for short-term survival. This study reviews recent studies on drugs during cardiopulmonary resuscitation. RECENT FINDINGS: Epinephrine is the first-line vasopressor during cardiopulmonary resuscitation. Arginine vasopressin may be more effective than epinephrine in patients presenting with asystole or as a second vasopressor in refractory cardiac arrest. Sodium bicarbonate should not be 'blindly' administered during cardiopulmonary resuscitation unless an arterial blood gas analysis can be obtained or after prolonged unsuccessful cardiopulmonary resuscitation. Amiodarone may improve short-term survival. Thrombolytic therapy during cardiopulmonary resuscitation may be beneficial if a pulmonary embolism or acute myocardial infarction is suggested to be the cause of cardiac arrest. SUMMARY: Epinephrine is the vasopressor of first choice for routine use during cardiopulmonary resuscitation. Arginine vasopressin may be considered in patients presenting with asystole or who are unresponsive to initial treatment with epinephrine. Amiodarone should be used in shock-refractory ventricular fibrillation. Although not recommended for routine use, thrombolytic therapy during cardiopulmonary resuscitation may be considered in patients with suspected pulmonary embolism or after unsuccessful conventional cardiopulmonary resuscitation in patients with a presumably thrombotic cause of cardiac arrest.

The effect of intracerebroventricular application of the caspase-3 inhibitor zDEVD-FMK on neurological outcome and neuronal cell death after global cerebral ischaemia due to cardiac arrest in rats.

BACKGROUND: Global cerebral ischaemia after cardiac arrest (CA) leads to programmed cell death (PCD) with characteristic signs of apoptosis in selectively vulnerable areas of the brain. The activation of caspase-3, an executioner caspase, plays a key role in the apoptotic cascade. We, therefore, studied the effects of the application of the specific caspase-3 inhibitor zDEVD-FMK on neurological outcome and neuronal cell death after experimental CA in rats. METHODS: A 6-min CA was induced in anaesthetised and mechanically ventilated male Wistar rats. After cardiopulmonary resuscitation (CPR) and restoration of spontaneous circulation (ROSC) the animals were randomised to two groups to receive a continuous intracerebroventricular (i.c.v.) infusion for 7 days of zDEVD-FMK or placebo (artificial cerebrospinal fluid, CSF). At 24h, 3 and 7 days after ROSC, animals were tested according to a neurological deficit score (NDS). Seven days after ROSC, coronal sections of the brain were taken at the dorsal hippocampal level and analysed with cresyl-violet staining, the TUNEL technique and a caspase activity assay. Viable and TUNEL-positive neurons were counted in the hippocampal CA-1 sector. RESULTS: The NDS demonstrated severe deficits 1 and 3 days after ROSC, which resolved by 7 days with no difference between the two groups. At 7 days after ROSC neuronal death could be detected using cresyl-violet and TUNEL staining with no difference between the groups. CONCLUSION: We conclude that zDEVD-FMK administration has no effect on neurological outcome and PCD after global cerebral ischaemia following CA in rats. Other mechanisms or pathways must be identified in the pathophysiology of PCD after 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.

[Emergency medicine and myocardial ischaemia - thrombolysis during cardiopulmonary resuscitation - available data and recommendations]. / Thrombolyse während Reanimation - Aktuelle Datenlage und Empfehlungen.

Patients suffering cardiac arrest still have a poor prognosis. Up to the present, no drug therapy has shown to improve longterm survival after cardiac arrest. Acute myocardial infarction (AMI) or massive pulmonary embolism (PE) are the underlying causes for sudden cardiac arrest in 50-70 % of patients. Thrombolysis is an effective and causal therapy in patients with AMI or PE. Therefore, combining cardiopulmonary resuscitation (CPR) with thrombolysis may be a promising therapeutic approach. Experimental studies have demonstrated that thrombolytic therapy during CPR is not only a causal treatment for coronary or pulmonary arterial thrombi, but may also improve microcirculatory reperfusion after cardiac arrest. Although numerous case series and small clinical studies showed evidence for the success of thrombolytic therapy during CPR, a large randomised study did not confirm these results. Thrombolysis during CPR today can not be recommended as a standard therapy in patients suffering cardiac arrest. However, it should be considered if a massive PE is supposed to be the cause of cardiac arrest or if conventional CPR has not been successful in a patient with presumed thrombotic cause of cardiac arrest. The expected bleeding risk is outweighed by the potential benefit of this therapy in selected patients.

Fluid therapy and outcome: a prospective observational study in 65 German intensive care units between 2010 and 2011.

BACKGROUND: Outcome data on fluid therapy in critically ill patients from randomised controlled trials may be different from data obtained by observational studies under "real-life" conditions. We conducted this prospective, observational study to investigate current practice of fluid therapy (crystalloids and colloids) and associated outcomes in 65 German intensive care units (ICUs). In total, 4545 adult patients who underwent intravenous fluid therapy were included. The main outcome measures were 90-day mortality, ICU mortality and acute kidney injury (AKI). Data were analysed using logistic and Cox regression models, as appropriate. RESULTS: In the predominantly post-operative overall cohort, unadjusted 90-day mortality was 20.1%. Patients who also received colloids (54.6%) had a higher median Simplified Acute Physiology Score II [25 (interquartile range 11; 41) vs. 17 (7; 31)] and incidence of severe sepsis (10.2 vs. 7.4%) on admission compared to patients who received exclusively crystalloids (45.4%). 6% hydroxyethyl starch (HES 130/0.4) was the most common colloid (57.0%). Crude rates of 90-day mortality were higher for patients who received colloids (OR 1.845 [1.560; 2.181]). After adjustment for baseline variables, the HR was 1.666 [1.405; 1.976] and further decreased to indicate no associated risk (HR 1.003 [0.980; 1.027]) when it was adjusted for vasopressor use, severity of disease and transfusions. Similarly, the crude risk of AKI was higher in the colloid group (crude OR 3.056 [2.528; 3.694]), after adjustment for baseline variables OR 1.941 [1.573; 2.397], and after full adjustment OR 0.696 [0.629; 0.770]), the risk of AKI turned out to be reduced. The same was true for the subgroup of patients treated with 6% HES 130/0.4 (crude OR 1.931 [1.541; 2.419], adjusted for baseline variables OR 2.260 [1.730; 2.953] and fully adjusted OR 0.800 [0.704; 0.910]) as compared to crystalloids only. CONCLUSIONS: The present analysis of mostly post-operative patients in routine clinical care did not reveal an independent negative effect of colloids (mostly 6% HES 130/0.4) on renal function or survival after multivariable adjustment. Signals towards a reduced risk in subgroup analyses deserve further study. Trial registration ClinicalTrials.gov Identifier: NCT01122277, registered May 11th, 2010.

The effects of antibiotic cycling and mixing on antibiotic resistance in intensive care units: a cluster-randomised crossover trial.

BACKGROUND: Whether antibiotic rotation strategies reduce prevalence of antibiotic-resistant, Gram-negative bacteria in intensive care units (ICUs) has not been accurately established. We aimed to assess whether cycling of antibiotics compared with a mixing strategy (changing antibiotic to an alternative class for each consecutive patient) would reduce the prevalence of antibiotic-resistant, Gram-negative bacteria in European intensive care units (ICUs). METHODS: In a cluster-randomised crossover study, we randomly assigned ICUs to use one of three antibiotic groups (third-generation or fourth-generation cephalosporins, piperacillin-tazobactam, and carbapenems) as preferred empirical treatment during 6-week periods (cycling) or to change preference after every consecutively treated patient (mixing). Computer-based randomisation of intervention and rotated antibiotic sequence was done centrally. Cycling or mixing was applied for 9 months; then, following a washout period, the alternative strategy was implemented. We defined antibiotic-resistant, Gram-negative bacteria as Enterobacteriaceae with extended-spectrum ß-lactamase production or piperacillin-tazobactam resistance, and Acinetobacter spp and Pseudomonas aeruginosa with piperacillin-tazobactam or carbapenem resistance. Data were collected for all admissions during the study. The primary endpoint was average, unit-wide, monthly point prevalence of antibiotic-resistant, Gram-negative bacteria in respiratory and perineal swabs with adjustment for potential confounders. This trial is registered with ClinicalTrials.gov, number NCT01293071. FINDINGS: Eight ICUs (from Belgium, France, Germany, Portugal, and Slovenia) were randomly assigned and patients enrolled from June 27, 2011, to Feb 16, 2014. 4069 patients were admitted during the cycling periods in total and 4707 were admitted during the mixing periods. Of these, 745 patients during cycling and 853 patients during mixing were present during the monthly point-prevalence surveys, and were included in the main analysis. Mean prevalence of the composite primary endpoint was 23% (168/745) during cycling and 22% (184/853) during mixing (p=0·64), yielding an adjusted incidence rate ratio during mixing of 1·039 (95% CI 0·837-1·291; p=0·73). There was no difference in all-cause in-ICU mortality between intervention periods. INTERPRETATION: Antibiotic cycling does not reduce the prevalence of carriage of antibiotic-resistant, Gram-negative bacteria in patients admitted to the ICU. FUNDING: European Union Seventh Framework Programme.

[Out-of-hospital and early clinical management of polytrauma in a patient after severe car accident]. / Kasuistik interaktiv: Polytrauma nach Verkehrsunfall--Präklinische und frühe klinische Versorgung.

We report the case of a 30 year old driver of a car who was jammed after a severe traffic accident. In a step-by-step description of the out-of-hospital and early clinical management of the patient, the case report focuses on diagnostic, therapeutic, and strategic issues. Current controversies in the management of patients with combined thoracic and abdominal trauma are discussed in the light of recent literature.

Safety of thrombolysis during cardiopulmonary resuscitation.

The prognosis is generally poor for patients who experience a cardiac arrest. The most common causes of sudden cardiac arrest are massive pulmonary embolism (PE) and acute myocardial infarction (MI). While thrombolysis is a first-line treatment option in massive PE and acute MI, cardiopulmonary resuscitation (CPR) has been regarded as a relative contraindication for thrombolysis because of the anticipated bleeding risk caused by traumatic cardiocompressions. However, an increasing number of case reports and clinical studies on thrombolysis during and after CPR highlight an increased frequency of the return of spontaneous circulation and a better neurological outcome of surviving patients. These effects are mainly due to the thrombolysis of macroscopic blood clots and the amelioration of microcirculatory reperfusion. This article reviews case reports and clinical studies of thrombolysis during and shortly after CPR in order to estimate the risk of severe bleeding events caused by CPR in association with thrombolysis compared with CPR without thrombolysis. Although thrombolysis per se can cause severe and potentially fatal haemorrhage, there is no evidence that severe bleeding events occur more often when thrombolysis is combined with cardiocompressions. In addition, by far the majority of bleeding complications can be treated effectively. Thus, in many cases, the possible benefit of thrombolysis during CPR seems to outweigh the potential risks. However, there may be a publication bias in some case reports and studies towards reporting successful rather than unsuccessful CPRs. In addition, not enough controlled clinical trials have yet been conducted. Therefore, data from large randomised, multicentre studies are needed to definitely answer the question of the relationship between safety and efficacy of this promising treatment option. We conclude that the currently available data do not indicate that thrombolysis contributes to a significant increase in bleeding complications when administered during CPR.

Successful thrombolysis after pulmonary embolectomy for persistent massive postoperative pulmonary embolism.

Massive postoperative pulmonary embolism (PE) is associated with a poor prognosis in patients presenting with haemodynamic instability. Since recent surgery is a commonly accepted contraindication for thrombolytic therapy, pulmonary embolectomy is an appropriate therapeutic approach in these patients. If life-threatening symptoms of PE persist after pulmonary embolectomy, however, very few other therapeutic options are available. We report the successful use of locally administered low-dose thrombolysis 2 days after pulmonary embolectomy in a patient with postoperative PE and persistent severe hypoxaemia and pulmonary hypertension. During and after thrombolysis, no bleeding complications occurred. We conclude that low-dose thrombolysis for PE may be considered even in patients who have recently undergone major thoracic and abdominal surgery if embolectomy and continued intravenous heparin have failed to be successful and life-threatening symptoms of PE persist.

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".