Human cytomegalovirus seropositivity is associated with reduced patient survival during sepsis.

BACKGROUND: Sepsis is one of the leading causes of death. Treatment attempts targeting the immune response regularly fail in clinical trials. As HCMV latency can modulate the immune response and changes the immune cell composition, we hypothesized that HCMV serostatus affects mortality in sepsis patients. METHODS: We determined the HCMV serostatus (i.e., latency) of 410 prospectively enrolled patients of the multicenter SepsisDataNet.NRW study. Patients were recruited according to the SEPSIS-3 criteria and clinical data were recorded in an observational approach. We quantified 13 cytokines at Days 1, 4, and 8 after enrollment. Proteomics data were analyzed from the plasma samples of 171 patients. RESULTS: The 30-day mortality was higher in HCMV-seropositive patients than in seronegative sepsis patients (38% vs. 25%, respectively; p = 0.008; HR, 1.656; 95% CI 1.135-2.417). This effect was observed independent of age (p = 0.010; HR, 1.673; 95% CI 1.131-2.477). The predictive value on the outcome of the increased concentrations of IL-6 was present only in the seropositive cohort (30-day mortality, 63% vs. 24%; HR 3.250; 95% CI 2.075-5.090; p < 0.001) with no significant differences in serum concentrations of IL-6 between the two groups. Procalcitonin and IL-10 exhibited the same behavior and were predictive of the outcome only in HCMV-seropositive patients. CONCLUSION: We suggest that the predictive value of inflammation-associated biomarkers should be re-evaluated with regard to the HCMV serostatus. Targeting HCMV latency might open a new approach to selecting suitable patients for individualized treatment in sepsis.

[Surgery in the balance between humanity, ethics and economics]. / Chirurgie im Spannungsfeld "Humanität-Ethik-Ökonomie".

BACKGROUND: The economic pressure in the healthcare system has noticeably increased in the past few years. The manifestation of an "economization in medicine" development raises questions about the compatibility of physicians' duties and economic incentives in the healthcare system. OBJECTIVE: Against this background the article analyzes areas of conflict in the German healthcare system and surgery in particular. The main questions focus on: what lines of conflict can arise between ethical duties and economic requirements and what possibilities for conflict resolution can provide orientation on the macrolevel and microlevel? MATERIAL AND METHODS: The article is based on the analysis of normative regulations, guidelines and statements from the self-administrative institutions and multidisciplinary literature from medicine, medical ethics and health economics. Core issues in the conflict area between "humanity-ethics-economics" are structured and recommendations for action are derived. RESULTS AND DISCUSSION: Superordinate regulatory framework conditions and their subsequent incentives must not conflict with the ethical principles of medical care, especially the primary orientation to patient welfare. Institutional and individual healthcare providers have a responsibility towards patients first and only secondarily for an economically appropriate spending of public resources. The provision of medical care for people must enable an adequate livelihood. Institutional maximization of profits is to be avoided, especially concerning financial investors. In the corona pandemic, economic disincentives are becoming apparent and necessitate readjustments. Possible recommendations for action are the empowerment of the medical profession and management to engage in a qualified exchange.

Implementation of anesthesia quality indicators in Germany : A prospective, national, multicenter quality improvement study.

BACKGROUND: In 2016 the German Society of Anesthesiology and Intensive Care Medicine (DGAI) and the Association of German Anesthetists (BDA) published 10 quality indicators (QI) to compare and improve the quality of anesthesia care in Germany. So far, there is no evidence for the feasibility of implementation of these QI in hospitals. OBJECTIVE: This study tested the hypothesis that the implementation of the 10 QI is feasible in German hospitals. MATERIAL AND METHODS: This prospective three-phase national multicenter quality improvement study was conducted in 15 German hospitals and 1 outpatient anesthesia center from March 2017 to February 2018. The trial consisted of an initial evaluation of pre-existing structures and processes by the heads of the participating anesthesia departments, followed by a 6-month implementation phase of the QI as well as a final re-evaluation phase. The implementation procedure was supported by web-based implementation aids ( www.qi-an.org ) and internal quality management programs. The primary endpoint was the difference in the number of implemented QI per center before and after implementation. Secondary endpoints were the number of newly implemented QI per center, the overall number of successful implementations of each QI, the identification of problems during the implementation as well as the kind of impediments preventing the QI implementation. RESULTS: The average number of implemented QI increased from 5.8 to 6.8 (mean of the differences 1.1 ± 1.3; P < 0.01). Most frequently the QI perioperative morbidity and mortality report (5 centers) and the QI temperature management (4 centers) could be implemented. After the implementation phase, the QI incidence management and patient blood management were implemented in all 16 centers. Implementation of other quality indicators failed mainly due to a lack of time and lack of structural resources. CONCLUSION: In this study the implementation of QI was proven to be mostly feasible in the participating German hospitals. Although several QI could be implemented with minor effort, more time, financial and structural resources would be required for some QI, such as the QI postoperative visit.

[Implementation of anesthesia quality indicators in Germany : A prospective, national, multicenter quality improvement study]. / Implementierung anästhesiologischer Qualitätsindikatoren in Deutschland : Eine prospektive, nationale, multizentrische Qualitätssteigerungsstudie German version.

BACKGROUND: In 2016 the German Society of Anesthesiology and Intensive Care Medicine (DGAI) and the Association of German Anesthetists (BDA) published 10 quality indicators (QI) to compare and improve the quality of anesthesia care in Germany. So far, there is no evidence for the feasibility of implementation of these QI in hospitals. OBJECTIVE: This study tested the hypothesis that the implementation of the 10 QI is feasible in German hospitals. MATERIAL AND METHODS: This prospective three-phase national multicenter quality improvement study was conducted in 15 German hospitals and 1 outpatient anesthesia center from March 2017 to February 2018. The trial consisted of an initial evaluation of pre-existing structures and processes by the heads of the participating anesthesia departments, followed by a 6-month implementation phase of the QI as well as a final re-evaluation phase. The implementation procedure was supported by web-based implementation aids ( www.qi-an.org ) and internal quality management programs. The primary endpoint was the difference in the number of implemented QI per center before and after implementation. Secondary endpoints were the number of newly implemented QI per center, the overall number of successful implementations of each QI, the identification of problems during the implementation as well as the kind of impediments preventing the QI implementation. RESULTS: The average number of implemented QI increased from 5.8 to 6.8 (mean of the differences 1.1 ± 1.3; P < 0.01). Most frequently the QI perioperative morbidity and mortality report (5 centers) and the QI temperature management (4 centers) could be implemented. After the implementation phase, the QI incidence management and patient blood management were implemented in all 16 centers. Implementation of other quality indicators failed mainly due to a lack of time and lack of structural resources. CONCLUSION: In this study the implementation of QI was proven to be mostly feasible in the participating German hospitals. Although several QI could be implemented with minor effort, more time, financial and structural resources would be required for some QI, such as the QI postoperative visit.

[Positioning therapy and early mobilization in intensive care units : Findings from the current 2015 guidelines]. / Lagerungstherapie und Frühmobilisation auf der Intensivstation : Erkenntnisse aus der aktuellen Leitlinie 2015.

The 2007 guidelines "Positioning for prophylaxis and therapy of pulmonary disorders" were completely revised in 2015 on behalf of the German Society of Anaesthesiology and Intensive Care Medicine. With regard to practical and scientific relevance, early mobilization of patients in critical care has been included in the guidelines for the first time. Furthermore, the recommendations for prone positioning have been updated, based on current evidence in medicine and nursing. In addition, recommendations regarding unsuitable positions that may actually harm patients were made. As such, the flat supine position should only be used in cases of urgent medical or nursing needs. This underlines the importance of a moderately elevated head of bed position (20(o)-45(o)) in mechanically ventilated patients.

S2e guideline: positioning and early mobilisation in prophylaxis or therapy of pulmonary disorders : Revision 2015: S2e guideline of the German Society of Anaesthesiology and Intensive Care Medicine (DGAI).

The German Society of Anesthesiology and Intensive Care Medicine (DGAI) commissioneda revision of the S2 guidelines on "positioning therapy for prophylaxis or therapy of pulmonary function disorders" from 2008. Because of the increasing clinical and scientificrelevance the guidelines were extended to include the issue of "early mobilization"and the following main topics are therefore included: use of positioning therapy and earlymobilization for prophylaxis and therapy of pulmonary function disorders, undesired effects and complications of positioning therapy and early mobilization as well as practical aspects of the use of positioning therapy and early mobilization. These guidelines are the result of a systematic literature search and the subsequent critical evaluation of the evidence with scientific methods. The methodological approach for the process of development of the guidelines followed the requirements of evidence-based medicine, as defined as the standard by the Association of the Scientific Medical Societies in Germany. Recently published articles after 2005 were examined with respect to positioning therapy and the recently accepted aspect of early mobilization incorporates all literature published up to June 2014.

[Short version S2e guidelines: "Positioning therapy and early mobilization for prophylaxis or therapy of pulmonary function disorders"]. / Kurzversion S2e-Leitlinie - "Lagerungstherapie und Frühmobilisation zur Prophylaxe oder Therapie von pulmonalen Funktionsstörungen".

The German Society of Anesthesiology and Intensive Care Medicine (DGAI) commissioned a revision of the S2 guidelines on "positioning therapy for prophylaxis or therapy of pulmonary function disorders" from 2008. Because of the increasing clinical and scientific relevance the guidelines were extended to include the issue of "early mobilization" and the following main topics are therefore included: use of positioning therapy and early mobilization for prophylaxis and therapy of pulmonary function disorders, undesired effects and complications of positioning therapy and early mobilization as well as practical aspects of the use of positioning therapy and early mobilization. These guidelines are the result of a systematic literature search and the subsequent critical evaluation of the evidence with scientific methods. The methodological approach for the process of development of the guidelines followed the requirements of evidence-based medicine, as defined as the standard by the Association of the Scientific Medical Societies in Germany. Recently published articles after 2005 were examined with respect to positioning therapy and the recently accepted aspect of early mobilization incorporates all literature published up to June 2014.

Determination of 'recruited volume' following a PEEP step is not a measure of lung recruitability.

BACKGROUND: It has been proposed that the analysis of positive end-expiratory pressure (PEEP)-induced volume changes can quantify alveolar recruitment. The potential of a lung to be recruited is expected to be high in acute respiratory distress syndrome (ARDS), where collapsed lung tissue is very common. The volume change that is beyond the delta volume because of the patient's compliance has been termed 'recruited volume' (RecV). However, data of patients with low and high RecV showed less severe lung disease in high 'recruiters', indicating that RecV may not equal the 'potentially recruitable lung tissue' seen in computed tomography scans. We hypothesized that RecV is higher in lung-healthy (LH) patients with little collapsed lung compared with ARDS patients. METHODS: RecV and inspiratory capacity (IC) were determined in 12 LH and in 25 ARDS patients during incremental PEEP (steps of 2 cmH2 O). RecV was determined as the time-dependent increase in end-expiratory volume following the first expiration to the new PEEP level (ΔTDV). Gas distribution in LH patients was analyzed by electric impedance tomography. RESULTS: Cumulative RecV(ΔTDV) and IC were higher (P < 0.01) in LH compared with ARDS patients, 1739 ml vs. 832 ml and 4432 ml vs. 2020 ml, respectively. In both groups, RecV correlated excellently with IC (R(2) = 0.86). In LH, RecV emanated mainly from nondependent lung regions at PEEP below 15 cmH2O. Maximum plateau pressure was reached with fewer PEEP steps in ARDS compared with LH patients (11 vs. 14, P < 0.01). CONCLUSION: Our findings suggest that RecV predominately measures a slow fraction of inflation of already aerated lung tissue and not recruitment of collapsed alveoli.

Pumpless arterio-venous extracorporeal lung assist compared with veno-venous extracorporeal membrane oxygenation during experimental lung injury.

BACKGROUND: Extracorporeal lung support is effective to prevent hypoxaemia and excessive hypercapnia with respiratory acidosis in acute respiratory distress syndrome. Miniaturized veno-venous extracorporeal membrane oxygenation (mECMO) and arterio-venous pumpless extracorporeal lung assist (pECLA) were compared for respiratory and haemodynamic response and extracorporeal gas exchange and device characteristics. METHODS: After induction of acute lung injury by repeated lung lavage, 16 anaesthetized and mechanically ventilated pigs were randomized to mECMO (Medos Hilite/Deltastream) or pECLA (iLA Novalung) for 24 h. RESULTS: Improved gas exchange allowed reduced ventilation and plateau pressure in both groups. An arterio-venous shunt flow of up to 30% of cardiac output resulted in a left cardiac work of 6.8 (2.0) kg m for pECLA compared with 5.0 (1.4) kg m for mECMO after 24 h (P<0.05). Both devices provided adequate oxygen delivery to organs. The oxygen transfer of pECLA was lower than mECMO due to inflow of arterial oxygenated blood [16 (5) compared with 64 (28) ml min(-1) after 24 h, P<0.05]. Unexpectedly, the carbon dioxide transfer rate was also lower [58 (28) compared with 111 (42) ml min(-1) after 24 h, P<0.05], probably caused by a Haldane effect preventing higher transfer rates in combination with lower extracorporeal blood flow. CONCLUSIONS: Both devices have the potential to unload the lungs from gas transfer sufficiently to facilitate lung-protective ventilation. Although technically less complex, oxygen uptake and carbon dioxide removal are limited in pECLA, and cardiac work was increased. mECMO overcomes these limitations and might provide better cardiopulmonary protection.

Effects of hypercapnia and hypercapnic acidosis on attenuation of ventilator-associated lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with impaired gas exchange, severe inflammation and alveolar damage including cell death. Patients with ALI or ARDS typically experience respiratory failure and thus require mechanical ventilation for support, which itself can aggravate lung injury. Recent developments in this field have revealed several therapeutic strategies that improve gas exchange, increase survival and minimize the deleterious effects of mechanical ventilation. Among those strategies is the reduction in tidal volume and allowing hypercapnia to develop during ventilation, or actively inducing hypercapnia. Here, we provide an overview of hypercapnia and the hypercapnic acidosis that typically follows, as well as the therapeutic effects of hypercapnia and acidosis in clinical studies and experimental models of ALI. Specifically, we review the effects of hypercapnia and acidosis on the attenuation of pulmonary inflammation, reduction of apoptosis in alveolar epithelial cells, improvement in sepsis-induced ALI and the therapeutic effects on other organ systems, as well as the potentially harmful effects of these strategies. The clinical implications of hypercapnia and hypercapnic acidosis are still not entirely clear. However, future research should focus on the intracellular signaling pathways that mediate ALI development, potentially focusing on the role of reactive biological species in ALI pathogenesis. Future research can also elucidate how such pathways may be targeted by hypercapnia and hypercapnic acidosis to attenuate lung injury.

[Airway management]. / Atemwegsmanagement.

Managing the difficult airway poses an enormous challenge for anaesthesiologists, intensivists and A&E physicians, particularly because of the high probability of a potentially fatal outcome. Development and (pre-) clinical distribution of supraglottic airway devices (e.g. LMA, LT) and their enhancements, as well as the broad acceptance of awake fibre-optic intubation, led to a profound change in the strategy for managing the difficult airway. This is reflected in the revised ASA guidelines, implementing the use of the laryngeal mask airway and fibre-optic intubation. In view of the utmost importance of this topic the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) framed an independent German guideline, considering German national terms and conditions. In analogy algorithms and guidelines of the ILCOR, ERC and ATLS were revised as well as those of many other national anaesthesiological boards. Nevertheless, massive national and international deficits exist in implementing these guidelines into practice and the implicated structural requirements with respect to education, reflection, team building and equipment concerning the individual institution.

[Coagulopathy in multiple trauma: new aspects of therapy]. / Koagulopathie. Bedeutung beim polytraumatisierten Patienten und aktuelle Aspekte der Gerinnungstherapie.

Coagulopathy after trauma is a major cause for uncontrolled hemorrhage in trauma victims. Approximately 40% of trauma related deaths are attributed to or caused by exsanguination. Therefore the prevention of coagulopathy is regarded as the leading cause of avoidable death in these patients. Massive hemorrhage after trauma is usually caused by a combination of surgical and coagulopathic bleeding. Coagulopathic bleeding is multifactorial, including dilution and consumption of both platelets and coagulation factors, as well as dysfunction of the coagulation system. Because of the high mortality associated with hypothermia, acidosis and progressive coagulopathy, this vicious circle is often referred to as the lethal triad, potentially leading to exsanguination. To overcome this coagulopahty-related bleeding an empiric therapy is often instituted by replacing blood components. However, the use of transfusion of red blood cells has been shown to be associated with post-injury infection and multiple organ failure. In the management of mass bleeding it is therefore crucial to have a clear strategy to prevent coagulopathy and to minimize the need for blood transfusion.

Cardiopulmonary effects of intravenous prostaglandin E1 during experimental one-lung ventilation.

BACKGROUND: One-lung ventilation greatly improves operating conditions during thoracic surgery. Serious disadvantages of one-lung ventilation are hypoxaemia and increased pulmonary vascular resistance. Prostaglandins, like prostaglandin I2 (PGI2), are potent pulmonary vasodilators but may also influence venous admixture and systemic circulation. Since the lung is capable of extensive degradation of prostaglandin E1 (PGE1) but not of PGI2, PGE1 might affect systemic circulation to a lesser degree. Hence, we studied the effects of intravenous PGE1 on systemic and pulmonary circulation and on oxygenation during one-lung ventilation. METHODS: Lateral thoracotomy and cross-clamping of the left main stem bronchus was performed in twelve anaesthetised and ventilated pigs. Animals were cannulated with arterial, central venous and fast response thermodilution pulmonary artery catheters for haemodynamic measurements. PGE1 was administered with infusion rates of 25, 50, and 100 ng x kg (-1) x min (-1) during one-lung ventilation. RESULTS: All doses of PGE1 significantly decreased pulmonary vascular resistance and mean pulmonary artery pressure. However, a comparable significant reduction in systemic vascular resistance and mean arterial pressure was found. Arterial oxygen tension and venous admixture showed a slight but significant deterioration. Oxygen delivery remained unchanged or increased since the cardiac index increased. CONCLUSION: During one-lung ventilation in the pig, infusion of PGE1 significantly decreased pulmonary vascular resistance and pulmonary artery pressure but failed to achieve selective pulmonary vasodilation.

Influence of a 30-min break on divided attention and working memory in resident anaesthetists on daily routine.

BACKGROUND: The aim of this study is to test the hypothesis that a standard 30-min break in a routine 7.5 h period of work makes a difference in cognitive function. METHODS: In a double-blinded, cross-over trial 30 residents in anaesthesia were randomized to receive or not to receive a 30-min break between the assessment times of 07:30 and 14:00. in a normal working day. After at least 28 days the test was repeated with each resident in the opposite group. Primary outcome measure was the Test for Attentional Performance with the subtest of working memory and divided attention. Secondary outcomes are the Stanford Sleepiness Scale and the State-Trait Anxiety Inventory test. RESULTS: The sleep, caffeine and nicotine habits in both groups were comparable. There was no difference between the two groups in the Test for Attentional Performance, Stanford Sleepiness Scale and the State-Trait Anxiety Inventory. The correlation between recovery through sleep and sleep disturbance in the night before investigation to the Stanford Sleepiness Scale (P<0.001 and P=0.003) and State-Trait Anxiety Inventory (P<0.001 and P=0.001) at the 07:30 assessment is significant. For the 14:00 assessment the only significant correlation is between the recovery through sleep with the Stanford Sleepiness Scale (P=0.04) and the State-Trait Anxiety Inventory (P=0.05). CONCLUSION: A 30-min break during a 7.5 h daily routine did not influence cognitive function tests.

Cardiopulmonary effects of iloprost in experimental acute lung injury.

Iloprost, a prostacyclin analogue with a prolonged plasma half-life has beneficial effects in chronic pulmonary hypertension, whereas the effects in acute lung injury (ALI) are unknown. The present study was performed to evaluate the cardiopulmonary effects of iloprost in experimental ALI. ALI was induced in 18 pigs by repeated lung lavage. Animals were randomised to controls, i.v. or inhaled iloprost for 15 min. Haemodynamics, gas exchange and ventilation-perfusion distribution were measured at the end of iloprost application and after 1 and 2 h. As a short-term effect, both i.v. and inhaled iloprost significantly decreased pulmonary artery pressure without major effects on gas exchange or systemic haemodynamics. After 1 and 2 h, a reduction of pulmonary hypertension was no longer present. As a long-term effect, inhaled, but not i.v., iloprost decreased pulmonary shunt and significantly improved gas exchange after 1 and 2 h. In conclusion, the single application of iloprost revealed short-term pulmonary vasodilation without other major cardiopulmonary effects. However, inhaled iloprost improved gas exchange due to a decrease of pulmonary shunt as a long-term effect, possibly as a result of a reduction of lung oedema formation.

[Pulmonary gas exchange: classical and modern findings]. / Pulmonaler Gasaustausch: Klassische und neuere Erkenntnisse.

The functional anatomy of the pulmonary gas exchanger enables an adequate oxygenation even in extreme situations, e. g. high altitude. An important mechanism is the distribution of ventilation and pulmonary perfusion. With induction of anaesthesia a relevant ventilation-perfusion mismatch results in oxygenation impairment, which can be prevented by specific anaesthetic techniques.

[Neuromonitoring with S-100 protein in the intensive care unit]. / Neuromonitoring in der Intensivmedizin mit S-100 Protein.

During the last years biochemical neuromonitoring with various molecules such as S-100 protein has become popular. A huge number of investigations both experimental and clinical have been undertaken to determine diagnosis and prognosis of patients with acute neurologic diseases. This article gives a review on the current knowledge, indications and limitations on the use of S-100 protein with regard to most of the acute neurological diseases an intensivist is confronted with in everyday practice.

Modulating the pulmonary circulation: an update.

Pulmonary hypertension is a common finding in pulmonary circulatory disorders of different origin. Chronic pulmonary hypertension may develop due to either cardiopulmonary or systemic diseases whereas acute and acute-on-chronic pulmonary hypertension often occur in the course of cardiothoracic surgery. Right heart failure is the major risk particularly in the course of acute pulmonary hypertension. Thus, besides basic treatment of the underlying disease the use of vasodilators is a valuable therapeutic option to decrease right ventricular afterload, but intravenous vasodilators may provoke systemic arterial hypotension and impair gas exchange due to vasodilation of pulmonary shunt areas. Therefore, inhaled vasodilators such as nitric oxide and prostacyclin have been suggested for the treatment of pulmonary hypertension especially when concomitant hypoxemia is present due to a ventilation-perfusion mismatch. However, randomised controlled trials performed to evaluate long-term effects revealed different results: thus, in chronic pulmonary hypertension inhaled vasodilators improved outcome whereas the results for the treatment of the acute respiratory distress syndrome revealed beneficial effects only when used as a rescue and/or bridging therapy in severe hypoxemia. In cardiothoracic surgery, inhaled vasodilators have been shown to improve pulmonary circulation when severe pulmonary hypertension is present. Although effective in experimental studies no clear recommendation can be made in view to the use of other vasodilators such as phosphodiesterase inhibitors or endothelin antagonists. Likewise, the combination of different vasodilators merit further investigations to prove efficacy in randomised controlled trials.

Anesthetic considerations in patients with chronic pulmonary diseases.

AIM: Increasing age and co-morbidities of patients admitted for surgery impose new challenges on the anesthesiologist. METHODS: Review of current literature regarding the perioperative management of patients with chronic pulmonary disease. RESULTS: If patients are treated adequately, surgery can be safely performed under regional and general anaesthesia. Major risk factors include type of surgery, type and duration of anesthesia, general health status and smoking history, but not certain lung function parameters. Regional anesthesia remains the first choice for intra- and postoperative care, and if general anesthesia is necessary, early extubation should be achieved. Non-invasive ventilation could be a possible alternative in weaning failure. CONCLUSION: Assessing the functional status of patients admitted to surgery remains a difficult task, and in patients identified at risk by clinical examination additional spirometry and blood gases may be helpful. If there are signs of respiratory failure, the anaesthetist should monitor the patient closely and invasively, yet there is no reason to deny any patient a substantially beneficial operation.