High index of suspicion: diagnosing a carotid-cavernous fistula.

A woman in her 70s presented with acute bilateral retro-orbital headache, diplopia, chemosis and eye swelling. Ophthalmology and neurology were consulted after detailed physical examination and diagnostic workup including laboratory analysis, imaging and lumbar puncture. The patient was diagnosed with non-specific orbital inflammation and was started on methylprednisolone and dorzolamide-timolol for intraocular hypertension. The patient's condition improved slightly, but a week later, she developed subconjunctival haemorrhage in the right eye, which prompted investigation for a low-flow carotid-cavernous fistula. Digital subtraction angiography showed bilateral indirect carotid-cavernous fistula (Barrow type D). The patient underwent bilateral carotid-cavernous fistula embolisation. Her swelling improved considerably on day 1 after the procedure and her diplopia improved over the following weeks.

The German Quality Network Sepsis: Evaluation of a Quality Collaborative on Decreasing Sepsis-Related Mortality in a Controlled Interrupted Time Series Analysis.

Background: Sepsis is one of the leading causes of preventable deaths in hospitals. This study presents the evaluation of a quality collaborative, which aimed to decrease sepsis-related hospital mortality. Methods: The German Quality Network Sepsis (GQNS) offers quality reporting based on claims data, peer reviews, and support for establishing continuous quality management and staff education. This study evaluates the effects of participating in the GQNS during the intervention period (April 2016-June 2018) in comparison to a retrospective baseline (January 2014-March 2016). The primary outcome was all-cause risk-adjusted hospital mortality among cases with sepsis. Sepsis was identified by International Classification of Diseases (ICD) codes in claims data. A controlled time series analysis was conducted to analyze changes from the baseline to the intervention period comparing GQNS hospitals with the population of all German hospitals assessed via the national diagnosis-related groups (DRGs)-statistics. Tests were conducted using piecewise hierarchical models. Implementation processes and barriers were assessed by surveys of local leaders of quality improvement teams. Results: Seventy-four hospitals participated, of which 17 were university hospitals and 18 were tertiary care facilities. Observed mortality was 43.5% during baseline period and 42.7% during intervention period. Interrupted time-series analyses did not show effects on course or level of risk-adjusted mortality of cases with sepsis compared to the national DRG-statistics after the beginning of the intervention period (p = 0.632 and p = 0.512, respectively). There was no significant mortality decrease in the subgroups of patients with septic shock or ventilation >24 h or predefined subgroups of hospitals. A standardized survey among 49 local quality improvement leaders in autumn of 2018 revealed that most hospitals did not succeed in implementing a continuous quality management program or relevant measures to improve early recognition and treatment of sepsis. Barriers perceived most commonly were lack of time (77.6%), staff shortage (59.2%), and lack of participation of relevant departments (38.8%). Conclusion: As long as hospital-wide sepsis quality improvement efforts will not become a high priority for the hospital leadership by assuring adequate resources and involvement of all pertinent stakeholders, voluntary initiatives to improve the quality of sepsis care will remain prone to failure.

Mid-German Sepsis Cohort (MSC): a prospective observational study of sepsis survivorship.

PURPOSE: The Mid-German Sepsis Cohort (MSC) aims to investigate mid-term and long-term functional disabilities in sepsis survivors from intensive care unit (ICU) discharge until 1 year after. Secondary, post-acute mortality and morbidity, health-related quality of life and healthcare utilisation will be investigated. PARTICIPANTS: The MSC comprises adult (aged ≥18 years) patients who were treated for (severe) sepsis or septic shock on ICU. The participants were recruited between 15 April 2016 and 30 November 2018 from five German centres. Three thousand two hundred and ten patients with sepsis were identified, of which 1968 survived their ICU stay and were eligible for enrolment in the follow-up cohort. Informed consent for follow-up assessment was provided by 907 patients (46.1% of eligible patients). FINDINGS TO DATE: The recruitment of the participants for follow-up assessments and the baseline data collection is completed. Incidence of sepsis was 116.7 patients per 1000 ICU patients. In this cohort profile, we provide an overview of the demographics and the clinical characteristics of both the overall sepsis cohort and the ICU survivors who provided informed consent for follow-up assessment (907 out of 1968 ICU survivors (46.1%)). FUTURE PLANS: The follow-ups are conducted 3, 6 and 12 months after ICU discharge. Another yearly follow-up up to 5 years after ICU discharge is pursued. Several cooperation and satellite projects were initiated. This prospective cohort offers a unique resource for research on long-term sequelae of sepsis survivors. TRIAL REGISTRATION NUMBER: German Clinical Trials Registry (DRKS00010050).

Functional impairment assessed by the Barthel Index influenced outcomes after transcatheter aortic valve implantation.

Objective. We investigated the influence of functional impairment assessed by the Barthel index (BI) on the three-month outcomes after transfemoral-transcatheter aortic valve intervention (TF-TAVI) under general anesthesia. Design. We included retrospectively analyzed 336 patients undergoing TAVI between January 2017 and January 2018 in central hospital, Bad Berka, Germany. All patients were followed up at three-month in our center's outpatient clinic. We stratified the patients according to the BI. Results. At baseline, 76 patients had a BI <80. Patients with a BI <80 were characterized by advanced age (80.6 ± 5.6 vs. 83 ± 4.1 years. p = .027), diabetes mellitus on insulin and higher surgical risk scores. A prior cerebral ischemic event was recorded more in patients with a BI ≥80. Regarding intermediate outcomes, three-month mortality was significantly higher in patients with a BI <80. Patients with a BI <80 developed significantly more postoperative cardiac decompensation, delirium and strokes. Patients with BI <80 had lower hemoglobin level preoperative and needed more blood transfusion postoperative. Other valve academic research consortiums (VARCs) complications were equally distributed in both groups. A BI <80 was associated with prolonged postoperative hospital stay and was an independent predictor of FT protocol failure (OR 4; CI 95% 1.3-11. p .02). Conclusions. A BI <80 is associated with increased mortality and risk of neurological events and cardiac decompensations after TF TAVI. A BI <80 is an independent predictor of failure in fast track TAVI.

Caloric consumption during early mobilisation of mechanically ventilated patients in Intensive Care Units.

OBJECTIVE: To evaluate a) the magnitude of the increase in caloric consumption due to early mobilisation of patients with mechanical ventilation (MV) in Intensive Care Units (ICU) as part of routine care, b) whether there are differences in caloric consumption due to active or passive mobilisation, and c) whether early mobilisation in routine care would lead to additional nutritional requirements. DESIGN: Prospective, observational, multi-centre study. SETTING: Medical, surgical and neurological ICUs from three centres. PATIENTS: Patients on MV in ICU who were mobilised out of bed as part of routine care. MEASUREMENTS AND MAIN RESULTS: Caloric consumption was assessed in 66 patients by indirect calorimetry at six time points: (1) lying in bed 5-10 min prior to mobilisation, (2) sitting on the edge of the bed, (3) standing beside the bed, (4) sitting in a chair, (5) lying in bed 5-10 min after mobilisation, and (6) 2 h after mobilisation. Differences in caloric consumption in every mobilisation level vs. the baseline of lying in bed were measured for 5 min and found to have increased significantly by: +0.4 (Standard Deviation (SD) 0.59) kcal while sitting on the edge of the bed, +1.5 (SD 1.26) kcal while standing in front of the bed, +0.7 (SD 0.63) kcal while sitting in a chair (all p < 0.001). Active vs. passive transfers showed a higher, but non-significant consumption. A typical sequence of mobilisation including sitting on edge of the bed, standing beside the bed, sitting in a chair (20 min) and transfer back into bed, would require an additional 4.56 kcal compared to caloric consumption without mobilisation. CONCLUSIONS: Based on this data, routine mobilisation of MV patients in ICU increases caloric consumption, especially in active mobilisation. Nevertheless, an additional caloric intake because of routine mobilisation does not seem to be necessary.

Characterization of the seven-day course of pulmonary response following unilateral lung acid injury in rats.

BACKGROUND: Aspiration of gastric acid is an important cause of acute lung injury. The time course of the pulmonary response to such an insult beyond the initial 48 hours is incompletely characterized. The purpose of this study was to comprehensively describe the pulmonary effects of focal lung acid injury over a seven day period in both directly injured and not directly injured lung tissue. METHODS: Male Wistar rats underwent left-endobronchial instillation with hydrochloric acid and were sacrificed at 4, 24, 48, 96 or 168 h after the insult. Healthy non-injured animals served as controls. We assessed inflammatory cell counts and cytokine levels in right and left lung lavage fluid and blood, arterial oxygen tension, alterations in lung histology, lung wet-to-dry weight ratio and differential lung perfusion. RESULTS: Lung acid instillation induced an early strong inflammatory response in the directly affected lung, peaking at 4-24 hours, with only partial resolution after 7 days. A less severe response with complete resolution after 4 days was seen in the opposite lung. Alveolar cytokine levels, with exception of IL-6, only partially reflected the localization of lung injury and the time course of the functional and histologic alterations. Alveolar leucocyte subpopulations exhibited different time courses in the acid injured lung with persistent elevation of alveolar lymphocytes and macrophages. After acid instillation there was an early transient decrease in arterial oxygen tension and lung perfusion was preferentially distributed to the non-injured lung. CONCLUSION: These findings provide a basis for further research in the field of lung acid injury and for studies exploring effects of mechanical ventilation on injured lungs. Incomplete recovery in the directly injured lung 7 days after acid instillation suggests that increased vulnerability and susceptibility to further noxious stimuli are still present at that time.

Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial.

PURPOSE: Guidelines recommend administering antibiotics within 1 h of sepsis recognition but this recommendation remains untested by randomized trials. This trial was set up to investigate whether survival is improved by reducing the time before initiation of antimicrobial therapy by means of a multifaceted intervention in compliance with guideline recommendations. METHODS: The MEDUSA study, a prospective multicenter cluster-randomized trial, was conducted from July 2011 to July 2013 in 40 German hospitals. Hospitals were randomly allocated to receive conventional continuous medical education (CME) measures (control group) or multifaceted interventions including local quality improvement teams, educational outreach, audit, feedback, and reminders. We included 4183 patients with severe sepsis or septic shock in an intention-to-treat analysis comparing the multifaceted intervention (n = 2596) with conventional CME (n = 1587). The primary outcome was 28-day mortality. RESULTS: The 28-day mortality was 35.1% (883 of 2596 patients) in the intervention group and 26.7% (403 of 1587 patients; p = 0.01) in the control group. The intervention was not a risk factor for mortality, since this difference was present from the beginning of the study and remained unaffected by the intervention. Median time to antimicrobial therapy was 1.5 h (interquartile range 0.1-4.9 h) in the intervention group and 2.0 h (0.4-5.9 h; p = 0.41) in the control group. The risk of death increased by 2% per hour delay of antimicrobial therapy and 1% per hour delay of source control, independent of group assignment. CONCLUSIONS: Delay in antimicrobial therapy and source control was associated with increased mortality but the multifaceted approach was unable to change time to antimicrobial therapy in this setting and did not affect survival.

Hyperlactatemia is an independent predictor of mortality and denotes distinct subtypes of severe sepsis and septic shock.

PURPOSE: Current guidelines and most trials do not consider elevated lactate (Lac) serum concentrations when grading sepsis severity. We therefore assessed the association of different types of circulatory dysfunction regarding presence of hyperlactatemia and need for vasopressor support with clinical presentation and outcome of sepsis. METHODS: In a secondary analysis of a prospective observational multicenter cohort study, 988 patients with severe sepsis were investigated regarding vasopressor support, Lac levels, and outcome. RESULTS: Twenty-eight-day mortality regarding shock or hyperlactatemia was as follows: hyperlactatemia more than 2.5 mmol/L and septic shock (tissue dysoxic shock): 451 patients with a mortality of 44.8%; hyperlactatemia without vasopressor need (cryptic shock): 72 patients, mortality 35.3%; no hyperlactatemia with vasopressor need (vasoplegic shock): 331 patients, mortality 27.7%; and absence of hyperlactemia or overt shock (severe sepsis): 134 patients, mortality 14.2% (P < .001). These groups showed differences in source and origin of infection. The influence of hyperlactatemia on 28-day mortality (P < .001) (odds ratio 3.0, 95% confidence interval 2.1-4.1 for Lac >4 mmol/L) was independent of vasopressor support (P < .001) (odds ratio 2.0, 95% confidence interval 1.3-3.0 for norepinephrine >0.1 µg/kg per minute) in logistic regression. CONCLUSIONS: Hyperlactatemia increases risk of death independent of vasopressor need resulting in different phenotypes within the classic categories of severe sepsis and septic shock.

Pilot study for compact microbeam radiation therapy using a carbon nanotube field emission micro-CT scanner.

PURPOSE: Microbeam radiation therapy (MRT) is defined as the use of parallel, microplanar x-ray beams with an energy spectrum between 50 and 300 keV for cancer treatment and brain radiosurgery. Up until now, the possibilities of MRT have mainly been studied using synchrotron sources due to their high flux (100s Gy/s) and approximately parallel x-ray paths. The authors have proposed a compact x-ray based MRT system capable of delivering MRT dose distributions at a high dose rate. This system would employ carbon nanotube (CNT) field emission technology to create an x-ray source array that surrounds the target of irradiation. Using such a geometry, multiple collimators would shape the irradiation from this array into multiple microbeams that would then overlap or interlace in the target region. This pilot study demonstrates the feasibility of attaining a high dose rate and parallel microbeam beams using such a system. METHODS: The microbeam dose distribution was generated by our CNT micro-CT scanner (100 µm focal spot) and a custom-made microbeam collimator. An alignment assembly was fabricated and attached to the scanner in order to collimate and superimpose beams coming from different gantry positions. The MRT dose distribution was measured using two orthogonal radiochromic films embedded inside a cylindrical phantom. This target was irradiated with microbeams incident from 44 different gantry angles to simulate an array of x-ray sources as in the proposed compact CNT-based MRT system. Finally, phantom translation in a direction perpendicular to the microplanar beams was used to simulate the use of multiple parallel microbeams. RESULTS: Microbeams delivered from 44 gantry angles were superimposed to form a single microbeam dose distribution in the phantom with a FWHM of 300 µm (calculated value was 290 µm). Also, during the multiple beam simulation, a peak to valley dose ratio of ~10 was found when the phantom translation distance was roughly 4x the beam width. The first prototype CNT-based x-ray tube dedicated to the development of compact MRT technology development was proposed and planned based on the preliminary experimental results presented here and the previous corresponding Monte Carlo simulations. CONCLUSIONS: The authors have demonstrated the feasibility of creating microbeam dose distributions at a high dose rate using a proposed compact MRT system. The flexibility of CNT field emission x-ray sources could possibly bring compact and low cost MRT devices to the larger research community and assist in the translational research of this promising new approach to radiation therapy.

Susceptibility to ventilator induced lung injury is increased in senescent rats.

INTRODUCTION: The principal mechanisms of ventilator induced lung injury (VILI) have been investigated in numerous animal studies. However, prospective data on the effect of old age on VILI are limited. Under the hypothesis that susceptibility to VILI is increased in old age, we investigated the pulmonary and extrapulmonary effects of mechanical ventilation with high tidal volume (VT) in old compared to young adult animals. INTERVENTIONS: Old (19.1±3.0 months) and young adult (4.4±1.3 months) male Wistar rats were anesthetized and mechanically ventilated (positive end-expiratory pressure 5 cmH2O, fraction of inspired oxygen 0.4, respiratory rate 40/minute) with a tidal volume (VT) of either 8, 16 or 24 ml/kg for four hours. RESULTS: Compared to young adult animals, high VT (24 ml/kg body weight) caused more lung injury in old animals as indicated by decreased oxygenation (arterial oxygen tension (PaO2): 208±3 vs. 131±20 mmHg; P<0.05), increased lung wet-to-dry-weight ratio (5.61±0.29 vs. 7.52±0.27; P<0.05), lung lavage protein (206±52 mg/l vs. 1,432±101; P<0.05) and cytokine (IL-6: 856±448 vs. 3,283±943 pg/ml; P<0.05) concentration. In addition, old animals ventilated with high VT had more systemic inflammation than young animals (IL-1ß: 149±44 vs. 272±36 pg/ml; P<0.05--young vs. old, respectively). CONCLUSIONS: Ventilation with unphysiologically large tidal volumes is associated with more lung injury in old compared to young rats. Aggravated pulmonary and systemic inflammation is a key finding in old animals developing VILI.

Oxygenation during one-lung ventilation with propofol or sevoflurane.

60 patients, ASA I-III, underwent one-lung ventilation for open or video-assisted thoracic surgery randomized either with intravenous anesthesia with propofol or with inhalational anesthesia with 1 MAC sevoflurane. Propofol was titrated during one-lung ventilation to achieve a mean arterial pressure of 75-80 mmHg. Blood gas analyses, hemodynamic and respiratory parameters were measured during two-lung ventilation at the beginning of the surgical procedure and 10 min, 20 min and 30 min after start of one-lung ventilation. At all time points, hemodynamic and respiratory parameters were comparable in both groups. Oxygenation did not differ between groups at comparable mean arterial blood pressures.

Students insert the laryngeal tube quicker and more often successful than the esophageal-tracheal combitube in a manikin.

BACKGROUND: Endotracheal intubation remains the standard of airway management. Because intubation skills are difficult to acquire, for medical students teaching of easier to learn techniques should be considered. METHODS: We retrospectively analyzed data that were collected in a University teaching facility. 264 medical students were taught how to use laryngeal tube (LT) and Esophageal Tracheal Combitube((R)) (ETC) in a manikin. The students underwent one of two different types of extraglottic airway management training consisting of either long lecture (30min) and intensive training (2h) (group IT, n=48), or brief (10min) lecture and 20min of training (group BT, n=216). Both groups underwent a test 6 weeks after training, group IT had an additional test 24h after training. RESULTS: After 24h students in group IT were faster using the LT than the ETC (31.7s+/-2.1 vs. 51.9s+/-5.8, p<0.001). Up to 6 weeks after training students were able to place the LT significantly faster than the ETC in both groups (26.5s+/-2.1 vs. 53.9s+/-5.8 group IT and 43.4s+/-1.6 vs. 103.8s+/-4.4 group BT, p<0.001). At 24h and 6 weeks following intensive training, there was no statistical difference in the time required for insertion of either device. CONCLUSION: Following different training scenarios in a manikin, students were able to place the LT much faster than the ETC. Even brief training was sufficient to generate short insertion times for the LT.

Present-day prehospital airway management in the former Eastern German state of Thuringia: equipment and education of emergency physicians.

We describe the condition of education and equipment regarding prehospital airway management in the German federal state of Thuringia, representing a part of former Eastern Germany. In 2006 a postal survey of the 39 emergency medical stations (EMS) in Thuringia was carried out. The response rate was 100%. In 72% of the EMS, a device for extraglottic airway management and in all EMS a device for cricothyrotomy was available. A device to monitor end-tidal CO2 was available in 41%. Difficulties in airway management in the past two years were reported from 74% of the EMS. Ongoing training and education in airway management is provided in 82% of the emergency districts. This survey reveals wide variations in the equipment for airway management available to prehospital emergency physicians in Thuringia. Given the reported difficulties in airway management, availability of a more standardized set of airway management devices in Thuringia may be helpful.

The level of cardiac output affects the relationship and agreement between pulmonary artery and transpulmonary aortic thermodilution measurements in an animal model.

OBJECTIVE: The authors investigated the relationship between pulmonary artery and transpulmonary aortic thermodilution cardiac output measurements under conditions of increasing cardiac output (CO). DESIGN: Animal study with repeated simultaneous measurements comparing 2 cardiac output measurement techniques. SETTING: Experimental animal facility of a university hospital. PARTICIPANTS: Ten female pigs. INTERVENTIONS: In anesthetized pigs, an aortic thermistor catheter and a pulmonary artery catheter (PAC) were inserted. Then dobutamine was infused under continuous cardiac output (CCO) monitoring to target different levels of CO. After each L/min increase of CCO simultaneous aortic and PAC thermodilution, CO measurements were performed by using a bolus injection of cooled normal saline and the amount of thermal indicator loss (TL) was calculated. MEASUREMENTS AND MAIN RESULTS: Pooled analysis of CO data with the method of Bland and Altman showed that aortic thermodilution CO was higher than PAC thermodilution CO with a bias of 3.8% +/- 11.1%. The range of TL was 30.4% to -10.1%. Differential analysis according to the range of CO revealed that, in each animal under conditions of low CO, aortic thermodilution CO was higher than PAC thermodilution CO, whereas results were inverse under conditions of high CO. CONCLUSIONS: The authors concluded that the amount of CO differentially affects the relationship between aortic and PAC thermodilution CO. TL and recirculation may be the explanation for this finding.

Low-dose intravenous midazolam reduces etomidate-induced myoclonus: a prospective, randomized study in patients undergoing elective cardioversion.

BACKGROUND: Myoclonic movements are a common problem in unpremedicated patients during induction of anesthesia with etomidate. METHODS: In a double-blind fashion, 40 patients (ASA physical status III-IV) scheduled for elective cardioversion were randomly assigned to receive either 0.015 mg/kg midazolam or placebo 90 s before the injection of 0.3 mg/kg etomidate. Myoclonic movements and sedation were recorded on a scale between 0 and 3. Pulse oximetry, noninvasive arterial blood pressure, and heart rate were recorded during the study period. RESULTS: Two patients (10%) in the midazolam group had myoclonic movements after the administration of etomidate, whereas 10 of the 20 patients (50%) receiving placebo experienced such movements (P = 0.006). No other differences were found between the groups; in particular, there was no difference in recovery 5 min after the administration of etomidate. CONCLUSIONS: IV midazolam 0.015 mg/kg administered 90 s before induction of anesthesia with etomidate is effective in reducing myoclonic movements and does not prolong recovery in unpremedicated patients after short procedures.

Percutaneous transtracheal emergency ventilation with a self-made device in an animal model.

BACKGROUND: Special equipment for emergency percutaneous transtracheal ventilation is often not immediately available. We used a self-made device consisting of a three-way stopcock connected between a G-15 transtracheal airway catheter and an oxygen supply in a simulated 'cannot intubate, cannot ventilate' scenario and tested the hypothesis that the effectiveness of the device depends on the body weight of the experimental animals. METHODS: With approval of the local animal protection committee, two groups of six pigs each with a body weight of 21 +/- 2 and 36 +/- 6 kg, respectively, were tracheally intubated and mechanically ventilated after induction of anesthesia. Hemodynamic monitoring included cardiac output and arterial, central venous and pulmonary artery pressures. An emergency transtracheal airway catheter was inserted into the trachea and a situation of partial expiratory airway obstruction was created. Each animal was ventilated for 15 min via the transtracheal airway catheter with the self-made device (FiO(2) 1.0 at an oxygen flow of 15 l x min(-1); respiratory rate of 60 min(-1); I/E ratio approximately 1:1). RESULTS: Whereas satisfactory oxygenation was achieved in all animals, sufficient ventilation was obtained only in the lightweight animals. CONCLUSIONS: Adequate oxygenation could be provided by jet-like transtracheal ventilation with a simple self-made device using easily available materials. Sufficient ventilation depends on the body weight of the animals.

Effects of a catecholamine-induced increase in cardiac output on lung injury after experimental unilateral pulmonary acid instillation.

OBJECTIVES: Increasing pulmonary blood flow aggravated ventilation-associated lung injury in ex vivo animal experiments, but data were less consistent in an in vivo animal model and do not reflect redistributed lung perfusion seen in clinical acute lung injury. We sought to determine the effects of increased cardiac output on markers of lung injury in an in vivo model of inhomogeneous lung perfusion and injury. DESIGN: Prospective, controlled animal study. SETTING: Experimental research laboratory of a university hospital. SUBJECTS: A total of 50 anesthetized, mechanically ventilated, male Wistar rats. INTERVENTIONS: Unilateral lung injury was induced in rats by left lung acid instillation. After 24 hrs, animals were anesthetized and subjected to mechanical ventilation (tidal volume, 8 mL/kg; positive end-expiratory pressure, 7 cm H2O; FIO2, 0.4) and continuous infusion of either 10 microg x kg x min dobutamine or isotonic saline (control) for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Cardiac output and differential lung perfusion were recorded throughout the ventilation period. Right and left lung wet-to-dry weight ratio, cytokines and inflammatory cells in lung lavage, and histologic lung injury were measured postmortem. After acid injury, lung perfusion was preferentially distributed to the noninjured lung. Dobutamine increased baseline cardiac output (>70%) and perfusion of both lungs (left, acid-instilled lung: from 16 +/- 2 to 29 +/- 6 mL/min; right, non-acid-instilled lung: from 54 +/- 3 to 98 +/- 7 mL/min). There was no difference in left lung injury between dobutamine- and saline-infused animals, but right lung injury was aggravated in dobutamine-infused animals, as indicated by increased lung edema, histologic lung injury, and cell counts in lavage. CONCLUSIONS: In the setting of unilateral lung injury and uneven lung perfusion, a dobutamine-induced increase in cardiac output has potentially detrimental effects on the opposite lung.

Both gram-negative and gram-positive experimental pneumonia induce profound lymphocyte but not respiratory epithelial cell apoptosis.

To determine whether and by which pathway (via the death receptor or mitochondrial mediated pathway) lymphocyte apoptosis occurs in pneumonia and to determine if increased bronchial epithelial cell apoptosis occurs in pneumonia. Prospective randomized study in a university research laboratory. Male C57BL/6 mice (n = 30). Animals received an intratracheal injection of Streptococcus pneumoniae or Pseudomonas aeruginosa to induce gram-positive or gram-negative pneumonia, respectively and were killed 24, 30, or 48 h later. Presence of pneumonia was confirmed via gross visual examination of lungs and by histology. Lymphocyte apoptosis in spleen and thymus was analyzed by flow cytometry for active caspases 3, 8, and 9 and by immunohistochemical (IHC) staining for active caspase 3 and DNA strand breaks. Respiratory epithelial cell apoptosis was assessed by IHC. Histologically, pneumonia was present in all bacteria-treated animals but none in sham-treated mice. Extensive lymphocyte apoptosis in spleen and thymus was documented by characteristic morphological changes on hematoxylin and eosin staining and by IHC staining in both S. pneumonia and P. aeruginosa infection. Flow cytometry confirmed IHC and showed apoptotic lymphocytes positive for active caspases 3, 8, and 9 in both thymi and spleens in both infections. In contrast to the extensive lymphocyte apoptosis, only rare scattered apoptotic changes were seen in respiratory epithelial or endothelial cells in pneumonia due to either organism. Increased lymphocyte but not bronchial cell apoptosis occurs in both gram-positive and gram-negative pneumonia and probably involves both the extrinsic and intrinsic pathway.

A novel model of selective lung ventilation to investigate the long-term effects of ventilation-induced lung injury.

Mechanical ventilation (MV) with large tidal volumes (V(T)) causes ventilator induced lung injury. Whereas immediate effects of short-term injurious ventilation are well studied, little is known about its long-term effects. We aimed to establish an animal model of selective injurious MV, permitting assessment of the long-term course of ventilation-induced lung injury. In anesthetized and instrumented rats (n = 26), laryngoscopy was performed, and one cannula for MV was placed in the left main bronchus and a second one in the trachea. Two ventilators were used to ventilate the left lung with high (20 mL/kg) and the right lung with low (4 mL/kg) V(T). In control animals, both lungs received low V(T). After 2 h of MV, animals were extubated and observed for 24 h and then killed. Left and right lungs were excised and sampled for further investigations. Survival in animals ventilated with the high V(T) was 90%. Twenty-four hours after MV, alveolar levels of humoral (tumor necrosis factor alpha, interleukin 6) and cellular (polymorphonuclear leukocytes) inflammatory markers were increased, and histological alterations were present in lungs ventilated with high V(T). A delayed decrease in PaO2 was noted 24 h after MV, with high V(T) delivered to one lung as compared with low V(T) delivered to both lungs. This animal model permits assessment of the long-term course of ventilation-induced lung injury and shows that pulmonary inflammation and histological alterations are present 24 h after unilateral injurious ventilation.

Percutaneous transtracheal emergency ventilation during respiratory arrest: comparison of the oxygen flow modulator with a hand-triggered emergency jet injector in an animal model.

The oxygen flow modulator is a device for percutaneous transtracheal emergency ventilation. Simulating a respiratory arrest situation, we studied the effects of this device in comparison with a hand-triggered emergency jet injector during pulmonary resuscitation. Nine pigs were anesthetized and mechanically ventilated. After surgical exposure, an emergency transtracheal airway catheter was inserted into the trachea. Ventilation was stopped until SpO2 was below 70%. Each animal was subsequently randomly ventilated via the transtracheal airway catheter with either the hand-triggered emergency jet injector or the oxygen flow modulator. After 10 minutes, respiratory and hemodynamic parameters were recorded. Ventilation was stopped again until SpO2 reached 70%, and the animal was ventilated with the second device. With both devices, pulmonary resuscitation was successful. Whereas PaO2 differed not significantly between the two devices, PaCO2 was lower during percutaneous transtracheal ventilation with the hand-triggered emergency jet injector.