[Treatment of severe COVID-19 courses in intensive care medicine]. / Therapie schwerer COVID-19-Verläufe in der Intensivmedizin.

The pandemic triggered by coronavirus disease 2019 (COVID-19) has put intensive care medicine into the focus of public attention. The mortality of patients with the disease escalates, particularly at the moment when the treatment possibilities of intensive medical care end. In the routine intensive medical care practice, the challenges due to the special features of infections with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its treatment become obvious. These occur in the development and treatment of respiratory and multiorgan failure as well as the severe inflammatory syndrome. For these severe courses there is still only little evidence available as to which interventions are the most effective. In addition to the knowledge that can be gained from the rapid performance of clinical trials, the treatment is therefore based on analogies to other syndromes, such as sepsis and macrophage activation syndrome.

Prolonged Mechanical Ventilation After Lung Transplantation-A Single-Center Study.

This single-center study examines the incidence, etiology, and outcomes associated with prolonged mechanical ventilation (PMV), defined as time to definite spontaneous ventilation >21 days after double lung transplantation (LTx). A total of 690 LTx recipients between January 2005 and December 2012 were analyzed. PMV was necessary in 95 (13.8%) patients with decreasing incidence during the observation period (p < 0.001). Independent predictors of PMV were renal replacement therapy (odds ratio [OR] 11.13 [95% CI, 5.82-21.29], p < 0.001), anastomotic dehiscence (OR 8.74 [95% CI 2.42-31.58], p = 0.001), autoimmune comorbidity (OR 5.52 [95% CI 1.86-16.41], p = 0.002), and postoperative neurologic complications (OR 5.03 [95% CI 1.98-12.81], p = 0.001), among others. Overall 1-year survival was 86.0% (90.4% for LTx between 2010 and 2012); it was 60.7% after PMV and 90.0% in controls (p < 0.001). Conditional long-term outcome among hospital survivors, however, did not differ between the groups (p = 0.78). Multivariate analysis identified renal replacement therapy (hazard ratio [HR] 3.55 [95% CI 2.40-5.25], p < 0.001), post-LTx extracorporeal membrane oxygenation (HR 3.47 [95% CI 2.06-5.83], p < 0.001), and prolonged inotropic support (HR 1.95 [95% CI 1.39-2.75], p < 0.001), among others, as independent predictors of mortality. In conclusion, PMV complicated 14% of LTx procedures and, although associated with increased in-hospital mortality, outcomes among patients surviving to hospital discharge were unaffected.

[Fomepizole, ethanol or dialysis in the case of life-threatening ethylenglycol intoxication?] / Fomepizol, Ethanol oder Dialyse bei lebensbedrohlicher Ethylenglykolvergiftung?

The EXTRIP (EXtracorporeal Treatments In Poisoning) workgroup is a collaborative international effort of pharmacologists, toxicologists, critical care physicians and nephrologists reviewing all available evidence in extracorporeal procedures for the treatment of intoxications in a standardized way to distill treatment recommendations for the physician at the bedside. The second round of guidelines will include recommendations for ethylenglycol intoxication. The case reported here is of a 60-year old man with a body weight of 65 kg who ingested approximately half a bottle (500 mL) of Aral Antifreeze in a suicidal attempt and presented around 12 h later with severe metabolic acidosis (venous blood gas analysis: pH 7.13; lactate 30 mmol/l, anion gap 23.3 mmol/l). As fomepizole, the inhibitor of the alcohol dehydrogenase, was not readily available, therapy with intermittent hemodialysis was started, as well as ethanol infusion. The first available ethylenglycol concentration before prolonged intermittent hemodialysis was 1230 mg/L. The total removed amount of ethylenglycol during intermittent hemodialysis, as well as following prolonged intermittent renal replacement therapy, was quantified (102 and 65 g). Based on this case report, the new EXRIP recommendations for the role of extracorporeal treatment in the case of ethylenglycol intoxication are discussed.

Extracorporeal membrane oxygenation in nonintubated patients as bridge to lung transplantation.

We report on the use of veno-arterial extracorporeal membrane oxygenation (ECMO) as a bridging strategy to lung transplantation in awake and spontaneously breathing patients. All five patients described in this series presented with cardiopulmonary failure due to pulmonary hypertension with or without concomitant lung disease. ECMO insertion was performed under local anesthesia without sedation and resulted in immediate stabilization of hemodynamics and gas exchange as well as recovery from secondary organ dysfunction. Two patients later required endotracheal intubation because of bleeding complications and both of them eventually died. The other three patients remained awake on ECMO support for 18-35 days until the time of transplantation. These patients were able to breathe spontaneously, to eat and drink, and they received passive and active physiotherapy as well as psychological support. All of them made a full recovery after transplantation, which demonstrates the feasibility of using ECMO support in nonintubated patients with cardiopulmonary failure as a bridging strategy to lung transplantation.

[Treatment of severe COVID-19 courses in intensive care medicine]. / Therapie schwerer COVID-19-Verläufe in der Intensivmedizin.

The pandemic triggered by coronavirus disease 2019 (COVID-19) has put intensive care medicine into the focus of public attention. The mortality of patients with the disease escalates, particularly at the moment when the treatment possibilities of intensive medical care end. In the routine intensive medical care practice, the challenges due to the special features of infections with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its treatment become obvious. These occur in the development and treatment of respiratory and multiorgan failure as well as the severe inflammatory syndrome. For these severe courses there is still only little evidence available as to which interventions are the most effective. In addition to the knowledge that can be gained from the rapid performance of clinical trials, the treatment is therefore based on analogies to other syndromes, such as sepsis and macrophage activation syndrome.

Are metallic stents really safe? A long-term analysis in lung transplant recipients.

Airway complications affect 20% of all lung transplant recipients. Self-expandable metallic stents (SEMS) are one treatment option but their use in benign airway disorders is controversial. We studies the long-term safety of SEMS in lung transplant recipients. Between January 1998 and February 2008, all lung transplant recipients with SEMS were analysed retrospectively at a single centre. Complications were recorded until September 2008. In 65 (9.2%) out of 706 recipients, 111 (91% noncovered) bronchial SEMS were implanted a median (range) 133 (55-903) days after lung transplantation; follow-up was 777 (7-3.655) days. Clinical improvement was noted in 80% of recipients. The forced expiratory volume in 1 s increased by (mean+/-SD) 21+/-33%. Most frequent early complications were migration (3%) and mucus plugging (11%). No procedure-related deaths were noted. Re-stenosis occurred in 34 (52%) out of 65 recipients 85 (7-629) days after insertion. In multivariate analysis, stent insertion before post-operative day 90 was independently associated with an increased risk of re-stenosis (HR 3.29, 95% CI 1.50-7.18; p = 0.003). In 40% of recipients, new bacterial airway colonisation occurred after SEMS insertion. In SEMS patients, 5-yr survival was significantly lower than in the total cohort (60% versus 76%; p = 0.02). Late complications in lung transplant recipients treated with SEMS are frequent. The major problems are re-stenosis and airway colonisation.

[Hypoxic lung failure]. / Das hypoxämische Lungenversagen.

Hypoxic lung failure is among the major indications for patients' referral to intensive care units either for surveillance or if necessary therapy. There are a vast number of pathophysiological causes of lung failure and the optimal treatment highly depends on the underlying pathology; therefore, no standard algorithm exists. So-called acute respiratory distress syndrome (ARDS) represents a very severe manifestation of hypoxemic lung failure that is of particular relevance for intensivists and is therefore the focus of this review. In addition to fundamental pathophysiology of lung injury, the article also focuses on established and modern treatment strategies. Moreover, we will briefly highlight innovative concepts of ARDS treatment that might become relevant in the future.

Self-expanding metallic stent placement with laryngeal mask in lung transplant recipients.

BACKGROUND: Bronchial stent insertion is a suitable method to treat airway complications. We present our experience with laryngeal mask airway (LMA) for stent insertion in lung transplant (LT) recipients. METHODS: From April 2007 to March 2009, 27 LT recipients underwent insertion of self-expanding nitinol stents to manage airway complications after LT, using LMA for general anesthesia. All procedures were performed with flexible fiberoptic bronchoscopy without fluoroscopy; stent release was visualized with ultrathin bronchoscopes. We followed technical success, safety, improvement of lung function, and clinical symptoms. RESULTS: Forty-one stents were inserted in 27 patients in 32 sessions. The indications for stent insertion were necrotic lesions (7%) and obstructive lesions (90%). Technical success and safety were 94%. Twice, the stent dislocated, requiring replacements. In 91% of patients, postinterventional improvement in graft function (1 minute forced expiratory volume) was >10% after the intervention. Improvement of clinical symptoms was achieved in 94%. The median procedure time was 38 minutes (range, 30-85 minutes). CONCLUSIONS: LMA offered an excellent condition for stent insertion in LT recipients with airway complications. It provided adequate ventilation and safe airway control during the procedure. This technique may serve as alternative to established techniques using fluoroscopy and rigid bronchoscopy.

Expression of cathepsins B, H, K, L, and S during human fetal lung development.

Cathepsins are involved in lysosomal protein degradation, proenzyme activation, antigen processing, and hormone maturation. They are secreted by tumor cells and macrophages and catalyze the remodeling of extracellular matrix proteins. To gain insight into the expression pattern of cathepsins during fetal lung development, the expression of cathepsins B, H, K, L, and S at protein and mRNA levels were evaluated by using immunohistochemistry and in situ hybridization. Early expression of cathepsins B, H, and K was found in epithelial cells of the branching presumptive bronchi (<12th week of gestation). The most intense cathepsin K-specific immunoreactivity was found in developing airways with a lumen. Cathepsin K was found in epithelial cells only, whereas in contrast, cathepsins B and H were detected both in epithelial and interstitial cells. During fetal maturation, interstitial cells displayed cathepsin L immunoreactivity and, in the saccular phase (>26th week of gestation), both cathepsin L and S immunoreactivities. A continuous decline in the proportion of cathepsin H-positive interstitial CD68-positive cells was observed. These discrete temporal and spatial variations in cathepsin expression during organogenesis of the human lung indicate different physiological roles for the individual enzymes in different cell types and developmental stages.