[Legal considerations in the care of patients with "terminal dehydration" in Germany]. / Rechtliche Rahmenbedingungen in der Versorgung von Patienten mit "terminaler Dehydration" in Deutschland.

BACKGROUND: The legal framework for fluid management in the palliative care setting varies between continents and even between countries. OBJECTIVES: What legal implications must be taken into account in Germany in dealing with "terminal" dehydration? MATERIALS AND METHODS: Relevant publications in English and German have been identified. Notably, German recommendations and guidelines were reviewed, whereas national mindsets were contrasted with those of other countries like the United Kingdom and Canada. RESULTS: Our legal considerations are in line with the recommendations of the German Federal Medical Association. Key components are "patient autonomy", "best possible symptom control" and a "steady therapeutic risk-benefit assessment". Dehydration should then continue to be regarded as a "symptom" that must be "controlled" as long as it can be improved by therapeutic means and as long as the patient is not opposed to this approach. However, if dehydration remains therapeutically refractory, it is justified either not to initiate clinically assisted hydration (CAH) or to stop the ongoing therapy. The "shared decision-making model" practiced in Canada is diametrically opposed to this approach, where paternalistic decision-making is possible, provided that patients or relatives appear to be ill-informed and unprepared to decide "correct" according to expert opinion. CONCLUSIONS: A "non-refractory" state of dehydration at the end of life must not be left untreated under German law and must not be used as an option to hasten the death process if the development of dehydration does not correspond to the patient's will or if this will cannot be determined.

[Ethical implications in the therapeutic management of dehydrated patients at the end of life]. / Ethische Implikationen bei der Therapie von dehydrierten Patienten am Lebensende.

BACKGROUND: The ethical framework for fluid management in the palliative care setting can vary. OBJECTIVES: What are the relevant ethical implications related to dehydration during end-of-life care and what are the special requirements we need to consider as far as "terminal dehydration" is concerned? MATERIALS AND METHODS: A comprehensive literature search was conducted to identify relevant articles published in English and German. RESULTS: Our inferences represent an attitude rather than an evidence-based position-a fact that is due to the underlying normative and ethical references which are hardly amenable to statistical evaluation. As far as ethical considerations are concerned, evidence is lacking to support clear decision-making and, thus, does not justify moving away from established concepts of clinically assisted hydration (CAH) at the end of life as long as measures can be effectually implemented. CONCLUSIONS: Dehydration must not be considered a measure to hasten death. Hence, dehydration in the palliative care setting must be regarded a "symptom" that should be "controlled" if it can be corrected by therapeutic means and if the patient's will does not contradict that approach. However, if CAH is futile, it is justified to refuse or stop it.

[Requirements for outpatient care after implantation of a ventricular assist device : Views of patients and their relatives]. / Anforderungen an die ambulante Versorgung nach Implantation eines ventrikulären Herzunterstützungssystems : Sichtweise von Patienten und Angehörigen.

Ventricular assist device (VAD) implantation has developed into a well-established option when conservative treatment of terminal heart failure has been exhausted. Figures from 2015 make this clear: only 283 heart transplantations were performed nationwide but 959 VAD systems were implanted. It is noteworthy that the survival times with a VAD are approaching the survival times after heart transplantation. Patients with VADs have a life-long dependency on their proximity to specialists. So far, the requirements for outpatient care have not been systematically recorded from the perspective of VAD patients and their relatives. In September 2016, VAD patients (n = 30) and their relatives (n = 25) were anonymously questioned about their views on postoperative outpatient care. For this purpose, the VAD Patient Satisfaction Survey was adapted to the needs of this study. Patients with VADs and their relatives were found to experience their daily life with a VAD in a positive manner. Information, training, accessibility and regular contacts with the implantation clinic and the VAD coordinator are important pillars of outpatient care after VAD implantation. Almost 95% of surveyed patients regarded good home support as an important factor that makes life with a VAD easier. These aspects should be taken into account in the care of patients living with a VAD.

Reversal of dabigatran by intraosseous or intravenous idarucizumab in a porcine polytrauma model.

BACKGROUND: Idarucizumab is licensed to reverse dabigatran in life-threatening haemorrhage. Establishment of venous access can be challenging, and the intraosseous (IO) route is a potentially life-saving alternative. In this study, we compared the efficacy and safety of IO or intravenous (i.v.) idarucizumab for dabigatran reversal in a porcine polytrauma model. METHODS: Male pigs (n=21) received oral dabigatran etexilate (30 mg kg-1 bid) for 3 days. On the 4th day, animals received dabigatran infusion and were randomised 1:1:1 to receive IO saline (control), i.v. idarucizumab (60 mg kg-1), or IO idarucizumab (60 mg kg-1), or animals were included in a sham group (n=7). Study treatment was administered after polytrauma and the animals were monitored for 240 min, or until death. Coagulation status was monitored by thromboelastometry, thromboelastography, and thrombin measurements. RESULTS: Total blood loss was lowest in sham animals [521 (52) ml, P<0.01 vs all other groups], and comparable in the two idarucizumab groups [IO: 1085 (102) ml vs i.v.: 1142 (125) ml], and highest in the control group [4065 (557) ml, P<0.001 vs all other groups]. Survival to 240 min was 100% in the sham group and both idarucizumab groups, and 14% in the control group. IO and i.v. idarucizumab promptly normalised global coagulation assays and thrombin generation. Thromboelastography showed a strong correlation between dabigatran concentrations and R-time (R2=0.90 and 0.89) in idarucizumab-treated animals. CONCLUSIONS: Intravenous and intraosseous idarucizumab were comparable for reversing dabigatran in a porcine trauma model. Dabigatran reversal could be monitored using fully automated thromboelastography.

9th Hatter Biannual Meeting: position document on ischaemia/reperfusion injury, conditioning and the ten commandments of cardioprotection.

In the 30 years since the original description of ischaemic preconditioning, understanding of the pathophysiology of ischaemia/reperfusion injury and concepts of cardioprotection have been revolutionised. In the same period of time, management of patients with coronary artery disease has also been transformed: coronary artery and valve surgery are now deemed routine with generally excellent outcomes, and the management of acute coronary syndromes has seen decade on decade reductions in cardiovascular mortality. Nonetheless, despite these improvements, cardiovascular disease and ischaemic heart disease in particular, remain the leading cause of death and a significant cause of long-term morbidity (with a concomitant increase in the incidence of heart failure) worldwide. The need for effective cardioprotective strategies has never been so pressing. However, despite unequivocal evidence of the existence of ischaemia/reperfusion in animal models providing a robust rationale for study in man, recent phase 3 clinical trials studying a variety of cardioprotective strategies in cardiac surgery and acute ST-elevation myocardial infarction have provided mixed results. The investigators meeting at the Hatter Cardiovascular Institute workshop describe the challenge of translating strong pre-clinical data into effective clinical intervention strategies in patients in whom effective medical therapy is already altering the pathophysiology of ischaemia/reperfusion injury-and lay out a clearly defined framework for future basic and clinical research to improve the chances of successful translation of strong pre-clinical interventions in man.

Intubation performance using different laryngoscopes while wearing chemical protective equipment: a manikin study.

OBJECTIVES: This study aimed to compare visualisation of the vocal cords and performance of intubation by anaesthetists using four different laryngoscopes while wearing full chemical protective equipment. SETTING: Medical simulation center of a university hospital, department of anaesthesiology. PARTICIPANTS: 42 anaesthetists (15 females and 27 males) completed the trial. The participants were grouped according to their professional education as anaesthesiology residents with experience of <2 years or <5 years, or as anaesthesiology specialists with experience of >5 years. INTERVENTIONS: In a manikin scenario, participants performed endotracheal intubations with four different direct and indirect laryngoscopes (Macintosh (MAC), Airtraq (ATQ), Glidescope (GLS) and AP Advance (APA)), while wearing chemical protective gear, including a body suit, rubber gloves, a fire helmet and breathing apparatus. PRIMARY AND SECONDARY OUTCOME MEASURES: With respect to the manikin, setting time to complete 'endotracheal intubation' was defined as primary end point. Glottis visualisation (according to the Cormack-Lehane score (CLS) and impairments caused by the protective equipment, were defined as secondary outcome measures. RESULTS: The times to tracheal intubation were calculated using the MAC (31.4 s; 95% CI 26.6 to 36.8), ATQ (37.1 s; 95% CI 28.3 to 45.9), GLS (35.4 s; 95% CI 28.7 to 42.1) and APA (23.6 s; 95% CI 19.1 to 28.1), respectively. Intubation with the APA was significantly faster than with all the other devices examined among the total study population (p<0.05). A significant improvement in visualisation of the vocal cords was reported for the APA compared with the GLS. CONCLUSIONS: Despite the restrictions caused by the equipment, the anaesthetists intubated the manikin successfully within adequate time. The APA outperformed the other devices in the time to intubation, and it has been evaluated as an easily manageable device for anaesthetists with varying degrees of experience (low to high), providing good visualisation in scenarios that require the use of chemical protective equipment.

[Cardioprotection in cardiac surgical patients : Everything good comes from the heart]. / Kardioprotektion beim herzchirurgischen Patienten : Alles Gute kommt von Herzen.

BACKGROUND: Despite substantial success in the anesthetic and surgical management of cardiac surgery, patients frequently show postoperative complications and organ dysfunctions. This is highly relevant for mid- to long-term outcomes. OBJECTIVES: To evaluate cardioprotective strategies that may offer effective protection in vulnerable cardiac surgery patients. METHODS: To demonstrate recent cardioprotective approaches for cardiac surgery patients, aiming to modulate the body's own protective mechanisms in cardiac surgery patients. RESULTS: Both cardioplegia and hypothermia belong to the well-established protective strategies during myocardial ischemia. Volatile anesthetics have been repeatedly shown to improve the left ventricular function and reduce the extent of myocardial injury compared to a control group with intravenous anesthesia. Furthermore, patients receiving volatile anesthetics showed a significantly shortened stay in the ICU and in hospital after cardiac surgery. In contrast, numerous other protective strategies failed translation into the clinical practice. Despite the published reduction of troponin release after remote ischemic preconditioning, two recent large-scale randomized multicenter trials were unable to demonstrate a clinical benefit. CONCLUSIONS: Beside the use of cardioplegia and hypothermia, the use of volatile anesthetics is well-established during cardiac surgery because of its conditioning and protective properties. Regardless of the promising results derived from experimental studies and small clinical trials, the majority of other approaches failed to translate their findings into the clinic. Therefore, systematic experimental studies are needed to identify potential confounding factors that may affect the protective effects.

[Anesthesiological management of elderly trauma patients]. / Anästhesiologisches Management in der Alterstraumatologie.

BACKGROUND: The demographic change is accompanied by an increasing number of elderly trauma patients. Geriatric patients with trauma often show several comorbidities and as a result have a high perioperative risk to develop postoperative morbidity and mortality. The 30-day mortality is high. AIM: This article presents an overview of the perioperative management of elderly trauma patients in order to improve the perioperative outcome of these high risk patients. MATERIAL AND METHODS: A literature search was carried out focusing on the latest developments in the field of elderly trauma patients in order to present guidance on preoperative, intraoperative and postoperative anesthesiological management. RESULTS: Elderly trauma patients should undergo operative interventions as soon as possible. Many of these patients have a high risk profile. This can be estimated using risk scores in order to allow a prognosis for the outcome of patients. The informed consent needs to be discussed accordingly. The perioperative management is ideally addressed in a multidisciplinary approach. An array of questions in perioperative management, such as the mode of anesthesia, the ideal individual transfusion trigger and fluid management have not yet been adequately addressed in studies. CONCLUSION: The level of evidence in the perioperative management of elderly trauma patients is poor; therefore, there is an urgent need for large prospective studies in order to define uniform standards and guidelines.

A core outcome set for all types of cardiac surgery effectiveness trials: a study protocol for an international eDelphi survey to achieve consensus on what to measure and the subsequent selection of measurement instruments.

BACKGROUND: Cardiovascular disease (CVD) is a major contributor to the burden of disease and the number one cause of death worldwide. From 1990 until today, more people died from coronary heart disease than from any other cause. CVD is regularly treated with minimally or non-minimally invasive off- or on-pump cardiothoracic surgery and several interventions related to the outcome of the surgical procedures have been evaluated in clinical trials, but heterogeneity in outcome reporting hinders comparison of interventions across trials and limits the ability of research synthesis. This problem is encountered with the introduction of core outcome sets (COSs), which should be measured and reported, as a minimum, in all clinical trials for a specific clinical field. METHODS/DESIGN: This study protocol describes the methods used to develop a COS for all types of cardiac surgery effectiveness trials. We aim to reach consensus on what to measure in an international three-round eDelphi exercise involving adult patients in need or after cardiothoracic surgery, cardiothoracic surgeons, cardiologists, anaesthesiologists, nursing staff and researchers with expertise in this particular field of medical research. Subsequently, outcome measurement instruments (how to measure) will be determined. Recommendations on COS development given by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative and the Outcome Measures in Rheumatology (OMERACT) Initiative were followed. DISCUSSION: The proposed COS aims to provide methodological guidance for future cardiothoracic surgical trials to ensure the comparability of effects of interventions across studies and enable research synthesis. This does not imply that primary outcomes should always and exclusively be those of the COS. However, to ensure the comparability of results across trials, the outcomes included in this COS should be considered for inclusion besides measuring trial-specific clinical endpoints.

Comparison of the effects of xenon and sevoflurane anaesthesia on leucocyte function in surgical patients: a randomized trial.

BACKGROUND: While most anaesthetics are known to suppress immune reactions, data from experimental studies indicate the enhancement of reactivity to inflammatory stimulators under xenon treatment. We investigated the effect of xenon anaesthesia on leucocyte function in surgical patients. METHODS: We performed a subgroup analysis of subjects undergoing xenon or sevoflurane anaesthesia in a randomized clinical trial. After oral premedication with midazolam, two separate blood samples were obtained from subjects undergoing elective abdominal surgery, directly before and 1 h after induction of anaesthesia. General anaesthesia was maintained with either 60% xenon or 2.0% sevoflurane in 30% O2. Leucocyte count, phagocytotic function, and pro-inflammatory cytokine release after ex vivo lipopolysaccharide (LPS) stimulation were determined. RESULTS: Except for lymphocyte numbers, leucocyte subpopulations did not differ between the groups. Phagocytosis and oxidative burst of granulocytes were reduced in both groups after 1 h of anaesthesia, whereas monocytes were not affected. Pro-inflammatory cytokine release in response to LPS was not affected. CONCLUSIONS: In vivo, xenon and sevoflurane anaesthesia did not have a pro-inflammatory effect, at least in combination with the types of surgery performed in this study. Notably, the impact of xenon anaesthesia did not differ significantly from sevoflurane anaesthesia with regard to leucocyte function. However, an underestimation of treatment effects due to limited sample sizes cannot be fully excluded.

A laboratory comparison of the performance of the buddy lite™ and enFlow™ fluid warmers.

Maintenance of normothermia is crucial to avoid patient morbidity. Newly released fluid warming devices have become smaller in size, but this change might impair efficacy. We performed an evaluation of the buddy lite™ and enFlow™ fluid warmers. We measured inflow and outlet temperatures of the devices at flow rates between 25 and 100 ml.min(-1) using saline at room temperature or cooled to 10 °C. At a flow rate of 25 ml.min(-1) , the outlet temperature of the buddy lite was significantly higher than that of the enFlow (p < 0.0001), but at flow rates of 75 and 100 ml.min(-1) , it was significantly lower (p < 0.0001). This pattern was the same for both room temperature and cooled saline. There was a significant drop in the temperature of saline along the length of a 1-m outflow tube. We conclude that both devices provide effective fluid warming at a low flow rate, although the heating capability of the buddy lite is limited at high flow rates.

Feasibility and safety of xenon compared with sevoflurane anaesthesia in coronary surgical patients: a randomized controlled pilot study.

BACKGROUND: To date, only limited data exist about the use of xenon as an anaesthetic agent in patients undergoing cardiac surgery. The favourable cardio- and neuroprotective properties of xenon might attenuate postoperative complications, improve outcome, and reduce the incidence of delirium. Thus, the aims of this study were to investigate the feasibility and safety of balanced xenon anaesthesia in patients undergoing cardiac surgery and to gather pilot data for a future randomized multicentre study. METHODS: Thirty patients undergoing elective coronary artery bypass grafting were enrolled in this randomized, single-blind controlled trial. They were randomized to receive balanced general anaesthesia with either xenon (45-50 vol%) or sevoflurane (1-1.4 vol%). The primary outcome was the occurrence of adverse events (AEs). Secondary outcome parameters were feasibility criteria (bispectral index, perioperative haemodynamic, and respiratory profile) and safety parameters (dosage of study treatments, renal function, intraoperative blood loss, need for inotropic support, regional cerebral tissue oxygenation). Furthermore, at predefined time points, systemic and pulmonary haemodynamics were assessed by the use of a pulmonary artery catheter. RESULTS: There were no patient characteristic differences between the groups. Patients undergoing xenon anaesthesia did not differ with respect to the incidence of AE (6 vs 8, P=0.464) compared with the sevoflurane group. No differences were detected regarding secondary feasibility and safety criteria. The haemodynamic and respiratory profile was comparable between the treatment groups. CONCLUSIONS: Balanced xenon anaesthesia is feasible and safe compared with sevoflurane anaesthesia in patients undergoing coronary artery bypass surgery. Acronym CARDIAX: A pre- and post-coronary artery bypass graft implantation disposed application of xenon. Clinical trial registration ClinicalTrials.gov: NCT01285271; EudraCT-number: 2010-023942-63. Approved by the ethics committee 'Ethik-Kommission an der Medizinischen Fakultät der Rheinisch-Westfälischen Technischen Hochschule Aachen (RWTH Aachen)': EK-218/10.

[EzPAP® therapy of postoperative hypoxemia in the recovery room : experiences with the new compact system of end-expiratory positive airway pressure]. / EzPAP® zur therapie der postoperativen hypoxämie im aufwachraum : erfahrungen mit dem neuen kompaktsystem zum "endexpiratory positive airway pressure"

BACKGROUND: Postoperative hypoxemia is a common complication in the anesthesia recovery room (ARR), which is predominantly based on the development of atelectasis, excessive intraoperative fluid shift and insufficient ventilation. The goal of this prospective observational study was to compare the effect of standard oxygen administration via a face mask with oxygen administration using the EzPAP® system, a device which additionally provides a positive end-expiratory pressure (PEEP). METHODS: This study included 210 patients with postoperative hypoxemia (S(p)O(2) < 93%) subdivided into the control group (105 patients) and the EzPAP group (105 patients). Postoperative residual paralysis was excluded using relaxometry and a train of four (TOF) ratio of 0.9 was assumed to ensure sufficient recovery of respiratory function from neuromuscular blockade. Patients who received a reversal of neuromuscular blockade were excluded. In cases of hypoxemia (S(p)O(2) < 93%) control patients were treated with oxygen (6 l/min) using a face mask, whereas the EzPAP group received oxygen using the EzPAP® system. In order to adjust the PEEP in the EzPAP group, the O(2) flow was verified and measured by a manometer. After 1 h of oxygen therapy, the oxygen supply was stopped. In cases of reoccurring hypoxemia (S(p)O(2) < 93%, persistence > 5 min), the oxygen therapy was restarted in both groups via a facemask. Both groups were compared using repeat measurement analysis of variance (ANOVA), the unpaired t-test, the Mann-Whitney U-test, Fisher's exact test and the χ(2)-test. The correlation of O(2) flow and PEEP was evaluated by regression analysis and p < 0.05 was considered to be statistically significant. Apart from this a subgroup analysis was performed depending on body-mass index (BMI), American Society of Anesthesiologists (ASA) classification, intraoperative airway management, the use of neuromuscular blocking agents and co-existing disorders, e.g. chronic obstructive lung disease (COLD), obesity and chronic heart failure. RESULTS: All patients were equally distributed between both groups with respect to demographic data, ASA classification, BMI, co-existing disorders and surgical procedures. The S(p)O(2) values did not differ between the EzPAP patients and the control group, except for 0.5 min after initiation of oxygen therapy: EzPAP group 96 ± 3.7% (mean ± standard deviation) versus the control group 93.8 ± 4.4% (p < 0.001). However, restarting oxygen therapy was less common in the EzPAP group (EzPAP group 25 versus control group 41, p = 0.03), as well as the occurrence of postoperative complications (EzPAP group 13 versus control group 25, p = 0.02), e.g. nosocomial pneumonia (0 versus 4) and wound infections (2 versus 3). Furthermore, patients with obesity and pulmonary disorders, such as COLD had a benefit from oxygen administration using the EzPAP device and showed higher postoperative than preoperative S(p)O(2) values. In contrast, the subgroup analysis of patients with heart failure did not reveal any differences between both groups and both groups did not differ in terms of time spent in the recovery room (EzPAP group 113 min versus control group 174.8 min, p = 0.2). CONCLUSIONS: In this observational study oxygen supply using the EzPAP® system appeared to be at least equally as effective in the therapy of postoperative hypoxemia compared to standard oxygen supply using a face mask. In patients with a high risk of postoperative hypoxemia, such as patients with obesity and/or pulmonary disorders, oxygen administration using the EzPAP® system possibly improves pulmonary oxygenation more effectively and is longer lasting compared to standard oxygen supply via a face mask. Hence, the EzPAP® system represents a well-tolerated, effective, cost-effective and easily operated tool to improve postoperative oxygenation. In order to investigate the possibilities of this promising tool more intensively, randomized clinical trials are warranted.

aepEX monitor for the measurement of hypnotic depth in patients undergoing balanced xenon anaesthesia.

BACKGROUND: Previously, we showed a significant difference in the measurements of hypnotic depth by the bispectral index (BIS) and auditory-evoked potentials (AEPs) using the A-line autoregressive index during xenon anaesthesia. In the present study, we evaluate the alternative AEP-based auditory-evoked potential index (aepEX) for the measurement of hypnotic depth in patients undergoing general anaesthesia with xenon. METHODS: Forty-two patients undergoing elective abdominal surgery were enrolled in this controlled, double-blinded, randomized, clinical study. Patients were randomized to receive either xenon (n=21) or sevoflurane anaesthesia (n=21). During anaesthesia, BIS values were recorded simultaneously with the aepEX monitoring. The anaesthetist performing the anaesthesia was blinded to the hypnotic depth monitors. After surgery, the incidence of recalls and awareness was evaluated. RESULTS: Patients' characteristics such as gender, age, and weight did not differ between the groups. The aepEX and BIS values behaved similarly during anaesthesia. The comparison of aepEX values during xenon and sevoflurane anaesthesia revealed significantly lower aepEX values in the xenon group after 25 min [xenon: 32.9 (4.8) vs sevoflurane: 39.3 (9.0); P=0.008] and after 35 min [xenon: 31.4 (6.6) vs sevoflurane: 37.0 (6.8); P=0.012]. During anaesthesia, aepEX values correlated with the clinical evaluation of depth of anaesthesia (e.g. >20% changes of the baseline arterial pressure or heart rate, spontaneous breathing and/or intolerance of mechanical ventilation, coughing, abdominal pressing, sweating, eye tearing). CONCLUSIONS: We found the aepEX monitor to provide index in the range of adequate depth of xenon anaesthesia, when combined with remifentanil infusion in intubated patients undergoing elective abdominal surgery.