Traumatic brain injury (TBI) represents a major health care problem and a significant socioeconomic challenge worldwide. In the United States alone, approximately 1.5 million patients are affected each year, and the mortality of severe TBI remains as high as 35%-40%. These statistics underline the urgent need for efficient treatment modalities to improve posttraumatic morbidity and mortality. Despite advances in basic and clinical research as well as improved neurological intensive care in recent years, no specific pharmacological therapy for TBI is available that would improve the outcome of these patients. Understanding of the cellular and molecular mechanisms underlying the pathophysiological events after TBI has resulted in the identification of new potential therapeutic targets. Nevertheless, the extrapolation from basic research data to clinical application in TBI patients has invariably failed, and results from prospective clinical trials are disappointing. We review the published prospective clinical trials on pharmacological treatment modalities for TBI patients and outline future promising therapeutic avenues in the field.

BackgroundRemote ischemic preconditioning (RIPC) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham‐RIPC.Methods and ResultsIn this follow‐up paper, we present 1‐year follow‐up of the composite primary end point and its individual components (all‐cause mortality, myocardial infarction, stroke and acute renal failure), in a sub‐group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidence of postoperative neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither showed any beneficial effect on the 1‐year composite primary end point (RIPC versus sham‐RIPC 16.4% versus 16.9%) and its individual components (all‐cause mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved intraoperative myocardial dysfunction or incidence of postoperative neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients) and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively.ConclusionsSimilar to our main study, RIPC had no effect on intraoperative myocardial dysfunction, neurocognitive function and long‐term outcome in cardiac surgery patients undergoing propofol anesthesia.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703.

BackgroundLung-protective strategies are the cornerstone of mechanical ventilation in critically ill patients with both ARDS and other disorders. Extracorporeal CO2 removal (ECCO2R) may enhance lung protection by allowing even further reductions in tidal volumes and is effective in low-flow settings commonly used for renal replacement therapy. In this study, we describe for the first time the effects of a labeled and certified system combining ECCO2R and renal replacement therapy on pulmonary stress and strain in hypercapnic patients with renal failure.MethodsTwenty patients were treated with the combined system which incorporates a membrane lung (0.32 m2) in a conventional renal replacement circuit. After changes in blood gases under ECCO2R were recorded, baseline hypercapnia was reestablished and the impact on ventilation parameters such as tidal volume and driving pressure was recorded.ResultsThe system delivered ECCO2R at rate of 43.4 ± 14.1 ml/min, PaCO2 decreased from 68.3 ± 11.8 to 61.8 ± 11.5 mmHg (p < 0.05) and pH increased from 7.18 ± 0.09 to 7.22 ± 0.08 (p < 0.05). There was a significant reduction in ventilation requirements with a decrease in tidal volume from 6.2 ± 0.9 to 5.4 ± 1.1 ml/kg PBW (p < 0.05) corresponding to a decrease in plateau pressure from 30.6 ± 4.6 to 27.7 ± 4.1 cmH2O (p < 0.05) and a decrease in driving pressure from 18.3 ± 4.3 to 15.6 ± 3.9 cmH2O (p < 0.05), indicating reduced pulmonary stress and strain. No complications related to the procedure were observed.ConclusionsThe investigated low-flow ECCO2R and renal replacement system can ameliorate respiratory acidosis and decrease ventilation requirements in hypercapnic patients with concomitant renal failure.Trial registration NCT02590575, registered 10/23/2015.

Background Extracorporeal life support (ECLS) has become an integral part of modern intensive therapy. The choice of support mode depends largely on the indication. Patients with respiratory failure are predominantly treated with a venovenous (VV) approach. We hypothesized that mortality in Germany in ECLS therapy did not differ from previously reported literature Methods Inpatient data from Germany from 2007 to 2018 provided by the Federal Statistical Office of Germany were analysed. The international statistical classification of diseases and related health problems codes (ICD) and process keys (OPS) for extracorporeal membrane oxygenation (ECMO) types, acute respiratory distress syndrome (ARDS) and hospital mortality were used. Results In total, 45,647 hospitalized patients treated with ECLS were analysed. In Germany, 231 hospitals provided ECLS therapy, with a median of 4 VV-ECMO and 9 VA-ECMO in 2018. Overall hospital mortality remained higher than predicted in comparison to the values reported in the literature. The number of VV-ECMO cases increased by 236% from 825 in 2007 to 2768 in 2018. ARDS was the main indication for VV-ECMO in only 33% of the patients in the past, but that proportion increased to 60% in 2018. VA-ECMO support is of minor importance in the treatment of ARDS in Germany. The age distribution of patients undergoing ECLS has shifted towards an older population. In 2018, the hospital mortality decreased in VV-ECMO patients and VV-ECMO patients with ARDS to 53.9% (n = 1493) and 54.4% (n = 926), respectively. Conclusions ARDS is a severe disease with a high mortality rate despite ECLS therapy. Although endpoints and timing of the evaluations differed from those of the CESAR and EOLIA studies and the Extracorporeal Life Support Organization (ELSO) Registry, the reported mortality in these studies was lower than in the present analysis. Further prospective analyses are necessary to evaluate outcomes in ECMO therapy at the centre volume level.