Jan Adriaan Graw

Managing End-Of-Life Decision Making in Intensive Care Medicine – A Perspective from Charité Hospital, Germany

Introduction End-of-life-decisions (EOLD) have become an important part of modern intensive care medicine. With increasing therapeutic possibilities on the one hand and many ICU-patients lacking decision making capacity or an advance directive on the other the decision making process is a major challenge on the intensive care unit (ICU). Currently, data are poor on factors associated with EOLD in Germany. In 2009, a new law on advance directives binding physicians and the patient´s surrogate decision makers was enacted in Germany. So far it is unknown if this law influenced proceedings of EOLD making on the ICU. Methods A retrospective analysis was conducted on all deceased patients (n = 224) in a 22-bed surgical ICU of a German university medical center from 08/2008 to 09/2010. Patient characteristics were compared between patients with an EOLD and those without an EOLD. Patients with an EOLD admitted before and after change of legislation were compared with respect to frequencies of EOLD performance as well as advance directive rates. Results In total, 166 (74.1%) of deaths occurred after an EOLD. Compared to patients without an EOLD, comorbidities, ICU severity scores, and organ replacement technology did not differ significantly. EOLDs were shared within the caregiverteam and with the patient´s surrogate decision makers. After law enacting, no differences in EOLD performance or frequency of advance directives (8.9% vs. 9.9%; p = 0.807) were observed except an increase of documentation efforts associated with EOLDs (18.7% vs. 43.6%; p<0.001). Conclusions In our ICU EOLD proceedings were performed patient-individually. But EOLDs follow a standard of shared decision making within the caregiverteam and the patient´s surrogate decision makers. Enacting a law on advance directives has not affected the decision making-process in EOLDs nor has it affected population´s advance care planning habits. However, it has led to increased EOLD-associated documentation on the ICU. Trail Registration ClinicalTrials.gov NCT01294189.

Stimulation of the Angiotensin II AT2 Receptor is Anti-inflammatory in Human Lipopolysaccharide-Activated Monocytic Cells

Recently, AT2 receptors have been discovered on the surface of human immunocompetent cells such as monocytes. Data on regulative properties of this receptor on the cellular immune response are poor. We hypothesized that direct stimulation of the AT2 receptor mediates anti-inflammatory responses in these cells. Human monocytic THP-1 and U937 cells were stimulated with lipopolysaccharide (LPS) and the selective AT2 receptor agonist Compound 21 (C21). Expression of pro- and anti-inflammatory cytokines IL-6, IL-10, tumor necrosis factor-α (TNFα), and IL-1β were analyzed on both the transcriptional and the translational level over course of time. Treatment with C21 attenuated the expression of TNFα, IL-6, and IL-10 after LPS challenge in both cell lines in a time- and dose-dependent manner. We conclude that selective AT2 receptor stimulation acts anti-inflammatory in human monocytes. Modulation of cytokine response by AT2 receptor activation might be a beneficial and novel treatment concept in inflammatory conditions.

Hydrothorax After Retraction of a Subclavian Central Venous Catheter

Central venous catheters (CVCs) are frequently used in intensive care patients. However, their use is associated with mechanical and infectious complications. Most mechanical complications arise during insertion, rarely while the catheter is in situ or upon its removal.[1][1] The most frequent

End-of-life decisions in surgical intensive care medicine – the relevance of blood transfusions

BACKGROUND End-of-life decisions (EOLDs) are common in the intensive care unit (ICU). EOLDs underlie a dynamic process and limitation of ICU-therapies is often done sequentially. Questionnaire-based and observational studies on medical ICUs and in palliative care reveal blood transfusions as the first therapy physicians withhold as an EOLD. METHODS To test whether this practice also applies to surgical ICU-patients, in an observational study, all deceased patients (n = 303) admitted to an academic surgical ICU in a three-year period were analyzed for the process of limiting ICU-therapies. RESULTS Restriction of further surgery (85.4%) and limiting doses of vasopressors (75.8%) were the most frequent forms of limitations in surgical ICU therapies. Surgical patients, who had blood transfusions withheld (44.6%), had more ICU-therapies withheld or withdrawn simultaneously than patients who had transfusions maintained (5 ± 2 vs. 2 ± 1, p < 0.001). Secondary EOLDs and subsequent limitations occurred less frequently in patients who had transfusions withheld with their first EOLD (17.1% vs. 35.6%, p < 0.05). CONCLUSION Limitation orders for blood transfusions are not a prioritized decision in EOLDs of surgical ICU patients. Withholding blood transfusions correlates with discontinuation of further significant life-support therapies. This suggests that EOLDs to withhold blood transfusions are part of the most advanced limitations of therapy on the surgical ICU.

Der Einfluss des OP-Zeitpunktes bei Sprunggelenkfrakturen auf das Komplikationsrisiko und die Verweildauer – eine multivariate Analyse

BACKGROUND With an incidence of 9/1000 per year, ankle fracture is one of the most common skeletal injuries. It is currently unclear whether time to surgery affects the complication rate or the hospital length of stay and whether there are confounders in patient characteristics or comorbidities. MATERIAL AND METHODS In a retrospective cohort study (n = 421), the risk of perioperative complications in patients with a primary operative fracture treatment within 6 hours of trauma was compared to a secondary surgical treatment. Furthermore, the influence of patient characteristics and comorbidities was examined in a multivariate regression analysis. RESULTS In comparison to secondary therapy, there was no benefit of a surgical fracture treatment within 6 hours after trauma was detected with regard to the perioperative complication rate or the hospital length of stay. Advanced patient age and severe soft tissue damage were associated with prolonged hospital length of stay but not with an increased rate of local perioperative complications. CONCLUSION The occurrence of severe local perioperative complications after surgical treatment of an ankle fracture is not associated with the time to surgery or covariates such as patient age or comorbidities. Current German guidelines for ankle fractures recommend surgical treatment within 6 - 8 hours, but these should be re-evaluated in further prospective randomised studies.

Biomechanics of common fixation devices for first tarsometatarsal joint fusion—a comparative study with synthetic bones

BackgroundHallux valgus disease is a common deformity of the forefoot. There are currently more than 100 surgical approaches for operative treatment. Because hypermobility of the first tarsometatarsal joint is considered to be causal for hallux valgus disease, fusion of the tarsometatarsal joint is an upcoming surgical procedure. Despite the development of new and increasingly stable fixation devices like different locking plates, malunion rates have been reported in 5 to 15% of cases.MethodsBiomechanical comparison of three commonly used fixation devices (a dorsal locking plate, a plantar locking plate, and an intramedullary fixation device) was performed by weight-bearing simulation tests on synthetic bones. Initial compression force and stiffness during simulation of postoperative weight-bearing were analysed.ResultsFixation of the first tarsometatarsal joint with the plantar plate combination demonstrated a higher stiffness compared to fixation with the intramedullary implant or the medial locking plate. The intramedullary device provided the highest initial compression force. Failure was detected in the following ranking: (1) the angle-stable intramedullary fixation device, (2) the medial located plate, and (3) the plantar locking plate.ConclusionThe intramedullary device demonstrated the highest initial compression force of the three tested implants. The plantar locking plate showed the best overall stability during weight-bearing simulation. Further clinical research is necessary to analyse if the intramedullary fixation device needs a longer period of non-weight-bearing to reach a better non-union rate compared to the plantar locking plate.

Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury

Purpose Although the role of the angiotensin II type 2 (AT2) receptor in acute lung injury is not yet completely understood, a protective role of this receptor subtype has been suggested. We hypothesized that, in a rodent model of acute lung injury, stimulation of the AT2 receptor with the direct agonist Compound 21 (C21) might have a beneficial effect on pulmonary inflammation and might improve pulmonary gas exchange. Materials and methods Male adult rats were divided into a treatment group that received pulmonary lavage followed by mechanical ventilation (LAV, n=9), a group receiving pulmonary lavage, mechanical ventilation, and direct stimulation of the AT2 receptor with C21 (LAV+C21, n=9), and a control group that received mechanical ventilation only (control, n=9). Arterial blood gas analysis was performed every 30 min throughout the 240-min observation period. Lung tissue and plasma samples were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid were assessed and the wet/dry-weight ratio of lungs was determined. Transcriptional and translational regulation of pro- and antiinflammatory cytokines IL-1β, tumor necrosis factor-alpha, IL-6, IL-10, and IL-4 was determined in lungs and in plasma. Results Pulmonary lavage led to a significant impairment of gas exchange, the formation of lung edema, and the induction of pulmonary inflammation. Protein content of lavage fluid was increased and contained washed-out surfactant. Direct AT2 receptor stimulation with C21 led to a significant inhibition of tumor necrosis factor-alpha and IL-6 expressions in the lungs, whereas the expressions of IL-1, IL-10, and IL-4 remained unchanged. During the 240-min observation period, AT2 receptor stimulation did not improve pulmonary gas exchange or lung edema. Conclusion In this rodent model of acute lung injury after repeated pulmonary lavage, AT2 receptor stimulation attenuates pulmonary inflammation but does not improve gas exchange.

Characterization of inflammation in a rat model of acute lung injury after repeated pulmonary lavage

ABSTRACT Aim of the study: Repeated pulmonary lavage allows to reliably reproduce failure of gas exchange and major histological findings of acute lung injury (ALI). However, because the capacity of pulmonary lavage to induce pulmonary inflammation is not well established in rodents, this study aims to characterize the induction of pulmonary inflammation in a rat model of ALI. Materials and Methods: Male adult rats were divided into a treatment group (n = 9) that received pulmonary lavage with consecutive mechanical ventilation, and a control group that received mechanical ventilation only (n = 9). Arterial blood gas analyses were performed every 30 min throughout the study. Pressure-volume curves, and lung tissue and plasma samples, were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid was assessed. Transcriptional and translational regulation of pro- and anti-inflammatory cytokines IL-1β, TNF-α, IL-6, and IL-10 was determined in lungs and plasma. Markers of cellular stress were measured in lung tissue. Results: Pulmonary lavage significantly decreased lung compliance, induced hypoxia and hypercapnia, and mediated respiratory acidosis. Protein content of lavage fluid was significantly increased and contained washed out surfactant. Expression of IL-1β, TNF-α, and IL-6 mRNA and protein expression of IL-1β and TNF-α was significantly induced in lavaged lungs, without spillover into the systemic circulation. Markers of cellular stress were significantly upregulated in lavaged lungs. Conclusions: This model of ALI applied in rats can induce pulmonary inflammation. The model might be used to develop therapeutic strategies that target pulmonary inflammation in ALI.