[Healthcare in Germany: Including Physician Assistants into the Team of Physicians]. / Gesundheitsversorgung in Deutschland durch Mitarbeit von Physician Assistants im ärztlichen Team.

BACKGROUND: Physicians in Germany are overburdened. Delegation of tasks to Physician Assistants (PA) is one way of providing relief. Although PA work in Germany since 2012, few data are available. We studied advantages and disadvantages from those physicians point of view, who cooperate with PA since years, as well as working conditions, satisfaction and duration of work processes of PA. METHOD: Semi-quantitative cross-sectional survey on a course of PA graduates and the physicians they work with since three years. Retrospective analysis of patients´ waiting time and duration of stay in an emergency department. RESULTS: Physicians were very satisfied with PA and reported a high degree of relief from workload. PA were highly satisfied with their job. Processing time in the emergency department was not longer when a PA was involved in patient care. CONCLUSION: Physicians are satisfied with PA as they are relieved from a heavy workload. More data on effectiveness and efficiency of PA in Germany are needed.

A brief introduction to PAs in Germany.

ABSTRACT: The first German physician assistant (PA) program began in 2005 at Steinbeis University in Berlin. Since 2005, there has been a rapid expansion of PA education, and 22 German universities have opened or are planning to develop PA programs. In fall 2021, about 1,100 PAs worked in Germany, mostly in the inpatient setting, with a scope of practice focused on delegation and the performance of medical and administrative activities. After completing a PA program, students are awarded a bachelor of science; programs also offer options for specialization. With no formal PA program-specific accreditation processes, the universities are responsible for ensuring the quality and content of PA courses. The profession is not regulated in Germany, and laws to guide PA education and scope of practice are necessary for the further development of the profession.

A cross-sectional survey of German PA employment and workforce entry.

OBJECTIVE: The contribution of physician assistants (PAs) to the German healthcare workforce has increased significantly since their introduction in 2005. From five training programs, the number has increased to the current 18, with 560 PAs awarded the PA bachelor of science degree as of 2020. Despite the growth, researchers lack systemic and reliable empirical data that provide insight into the German PA educational and professional profile. The German University Association Physician Assistant (DHPA) undertook the first nationwide cross-sectional survey on PAs in Germany to understand the German PA movement. This survey aimed to describe German PAs' entry into the profession and PA educational and job satisfaction. METHODS: PA alumni of all universities affiliated with the DHPA and all subscribers of the Facebook online social media platform PA Blog were invited to complete an online questionnaire. RESULTS: Of the 282 PAs who completed the survey, 77% were female and under age 25 years. Almost all (94%) were employed, predominantly as PAs (91%, 241 of 265), although some held other positions. Most worked full time (87%), with some citing child-care needs as reasons for part-time employment (n = 21). Few reported unemployment (1.4%, 4 of 282). Eighty-two percent said they would probably or very likely choose the same course of study again. Most employed participants found the inclusion of frequent rotations between didactic and clinical training in PA programs beneficial. However, a small number of participants (26.8%) agreed that German PA programs' didactic and clinical teaching objectives were well aligned. CONCLUSIONS: German PAs have a high level of satisfaction with their profession and report low unemployment. Improvement in the alignment of didactic and clinical educational objectives to improve academic qualifications and satisfaction emerged as an area of research.

Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial.

BACKGROUND: Three perioperative factors impair host defence against recurrence during cancer surgery: the surgical stress response, use of volatile anaesthetic, and opioids for analgesia. All factors are ameliorated by regional anaesthesia-analgesia. We tested the primary hypothesis that breast cancer recurrence after potentially curative surgery is lower with regional anaesthesia-analgesia using paravertebral blocks and the anaesthetic propofol than with general anaesthesia with the volatile anaesthetic sevoflurane and opioid analgesia. A second hypothesis was that regional anaesthesia-analgesia reduces persistent incisional pain. METHODS: We did a randomised controlled trial at 13 hospitals in Argentina, Austria, China, Germany, Ireland, New Zealand, Singapore, and the USA. Women (age <85 years) having potentially curative primary breast cancer resections were randomised by computer to either regional anaesthesia-analgesia (paravertebral blocks and propofol) or general anaesthesia (sevoflurane) and opioid analgesia. The primary outcome was local or metastatic breast cancer recurrence. The secondary outcome was incisional pain at 6 months and 12 months. Primary analyses were done under intention-to-treat principles. This trial is registered with ClinicalTrials.gov, NCT00418457. The study was stopped after a preplanned futility boundary was crossed. FINDINGS: Between Jan 30, 2007, and Jan 18, 2018, 2132 women were enrolled to the study, of whom 24 were excluded before surgery. 1043 were assigned to regional anaesthesia-analgesia and 1065 were allocated to general anaesthesia. Baseline characteristics were well balanced between study groups. Median follow-up was 36 (IQR 24-49) months. Among women assigned regional anaesthesia-analgesia, 102 (10%) recurrences were reported, compared with 111 (10%) recurrences among those allocated general anaesthesia (hazard ratio 0·97, 95% CI 0·74-1·28; p=0·84). Incisional pain was reported by 442 (52%) of 856 patients assigned to regional anaesthesia-analgesia and 456 (52%) of 872 patients allocated to general anaesthesia at 6 months, and by 239 (28%) of 854 patients and 232 (27%) of 852 patients, respectively, at 12 months (overall interim-adjusted odds ratio 1·00, 95% CI 0·85-1·17; p=0·99). Neuropathic breast pain did not differ by anaesthetic technique and was reported by 87 (10%) of 859 patients assigned to regional anaesthesia-analgesia and 89 (10%) of 870 patients allocated to general anaesthesia at 6 months, and by 57 (7%) of 857 patients and 57 (7%) of 854 patients, respectively, at 12 months. INTERPRETATION: In our study population, regional anaesthesia-analgesia (paravertebral block and propofol) did not reduce breast cancer recurrence after potentially curative surgery compared with volatile anaesthesia (sevoflurane) and opioids. The frequency and severity of persistent incisional breast pain was unaffected by anaesthetic technique. Clinicians can use regional or general anaesthesia with respect to breast cancer recurrence and persistent incisional pain. FUNDING: Sisk Healthcare Foundation (Ireland), Eccles Breast Cancer Research Fund, British Journal of Anaesthesia International, College of Anaesthetists of Ireland, Peking Union Medical College Hospital, Science Fund for Junior Faculty 2016, Central Bank of Austria, and National Healthcare Group.

Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery - a sub-analysis of the RIPHeart-Study.

BACKGROUND: The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. METHODS: We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. RESULTS: A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10- 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10- 5 from the GWAS. CONCLUSIONS: We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.

Temporal Changes in Ventilator Settings in Patients With Uninjured Lungs: A Systematic Review.

In patients with uninjured lungs, increasing evidence indicates that tidal volume (VT) reduction improves outcomes in the intensive care unit (ICU) and in the operating room (OR). However, the degree to which this evidence has translated to clinical changes in ventilator settings for patients with uninjured lungs is unknown. To clarify whether ventilator settings have changed, we searched MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science for publications on invasive ventilation in ICUs or ORs, excluding those on patients <18 years of age or those with >25% of patients with acute respiratory distress syndrome (ARDS). Our primary end point was temporal change in VT over time. Secondary end points were changes in maximum airway pressure, mean airway pressure, positive end-expiratory pressure, inspiratory oxygen fraction, development of ARDS (ICU studies only), and postoperative pulmonary complications (OR studies only) determined using correlation analysis and linear regression. We identified 96 ICU and 96 OR studies comprising 130,316 patients from 1975 to 2014 and observed that in the ICU, VT size decreased annually by 0.16 mL/kg (-0.19 to -0.12 mL/kg) (P < .001), while positive end-expiratory pressure increased by an average of 0.1 mbar/y (0.02-0.17 mbar/y) (P = .017). In the OR, VT size decreased by 0.09 mL/kg per year (-0.14 to -0.04 mL/kg per year) (P < .001). The change in VTs leveled off in 1995. Other intraoperative ventilator settings did not change in the study period. Incidences of ARDS (ICU studies) and postoperative pulmonary complications (OR studies) also did not change over time. We found that, during a 39-year period, from 1975 to 2014, VTs in clinical studies on mechanical ventilation have decreased significantly in the ICU and in the OR.

A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery.

BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. METHODS: We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. RESULTS: A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed. CONCLUSIONS: Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.).

The release of cardioprotective humoral factors after remote ischemic preconditioning in humans is age- and sex-dependent.

BACKGROUND: Preclinical and proof-of-concept studies suggest a cardioprotective effect of remote ischemic preconditioning (RIPC). However, two major clinical trials (ERICCA and RIPHeart) failed to show cardioprotection by RIPC. Aging and gender might be confounding factors of RIPC affecting the inter-organ signalling. Theoretically, confounding factors might prevent the protective potency of RIPC by interfering with cardiac signalling pathways, i.e. at the heart, and/or by affecting the release of humoral factor(s) from the remote organ, e.g. from the upper limb. This study investigated the effect of age and sex on the release of cardioprotective humoral factor(s) after RIPC in humans. METHODS: Blood samples were taken from young and aged, male and female volunteers before (control) and after RIPC (RIPC). To investigate the protective potency of the different plasma groups obtained from the human volunteers, isolated perfused hearts of young rats were used as bioassay. For this, hearts were perfused with the volunteer plasma (0.5% of coronary flow) before hearts underwent global ischemia and reperfusion. In addition, to characterize the protective potency of humoral factor(s) after RIPC to initiate protection not only in young but also aged hearts, plasma from young male volunteers were transferred to isolated hearts of aged rats. At the end of the experimental protocol, infarct sizes were determined by TTC-staining (expressed as % of left ventricle). RESULTS: RIPC plasma of young male volunteers reduced infarct size in young rat hearts from 47 ± 5 to 31 ± 10% (p = 0.02). In contrast, RIPC plasma of aged male volunteers had no protective effect. Infarct size after application of control plasma of young female volunteers was 33 ± 10%, and female RIPC plasma did not lead to an infarct size reduction. RIPC plasma of old female initiated no cardioprotection. RIPC plasma of young male volunteers reduced infarct size in isolated hearts from aged rats (41 ± 5% vs. 51 ± 5%; p < 0.001). CONCLUSIONS: The release of humoral factor(s) into the blood after RIPC in humans is affected by both age and sex. In addition, these blood borne factor(s) are capable to initiate cardioprotection within the aged heart.

Monitoring of argatroban and lepirudin anticoagulation in critically ill patients by conventional laboratory parameters and rotational thromboelastometry - a prospectively controlled randomized double-blind clinical trial.

BACKGROUND: Argatroban or lepirudin anticoagulation therapy in patients with heparin induced thrombocytopenia (HIT) or HIT suspect is typically monitored using the activated partial thromboplastin time (aPTT). Although aPTT correlates well with plasma levels of argatroban and lepirudin in healthy volunteers, it might not be the method of choice in critically ill patients. However, in-vivo data is lacking for this patient population. Therefore, we studied in vivo whether ROTEM or global clotting times would provide an alternative for monitoring the anticoagulant intensity effects in critically ill patients. METHODS: This study was part of the double-blind randomized trial "Argatroban versus Lepirudin in critically ill patients (ALicia)", which compared critically ill patients treated with argatroban or lepirudin. Following institutional review board approval and written informed consent, for this sub-study blood of 35 critically ill patients was analysed. Before as well as 12, 24, 48 and 72 h after initiation of argatroban or lepirudin infusion, blood was analysed for aPTT, aPTT ratios, thrombin time (TT), INTEM CT,INTEM CT ratios, EXTEM CT, EXTEM CT ratios and maximum clot firmness (MCF) and correlated with the corresponding plasma concentrations of the direct thrombin inhibitor. RESULTS: To reach a target aPTT of 1.5 to 2 times baseline, median [IQR] plasma concentrations of 0.35 [0.01-1.2] µg/ml argatroban and 0.17 [0.1-0.32] µg/ml lepirudin were required. For both drugs, there was no significant correlation between aPTT and aPTT ratios and plasma concentrations. INTEM CT, INTEM CT ratios, EXTEM CT, EXTEM CT ratios, TT and TT ratios correlated significantly with plasma concentrations of both drugs. Additionally, agreement between argatroban plasma levels and EXTEM CT and EXTEM CT ratios were superior to agreement between argatroban plasma levels and aPTT in the Bland Altman analysis. MCF remained unchanged during therapy with both drugs. CONCLUSION: In critically ill patients, TT and ROTEM parameters may provide better correlation to argatroban and lepirudin plasma concentrations than aPTT. TRIAL REGISTRATION: ClinicalTrials.gov , NCT00798525 , registered on 25 Nov 2008.

Ventilation with high versus low peep levels during general anaesthesia for open abdominal surgery does not affect postoperative spirometry: A randomised clinical trial.

BACKGROUND: Invasive mechanical ventilation during general anaesthesia for surgery typically causes atelectasis and impairs postoperative lung function. OBJECTIVE: We investigated the effect of intraoperative ventilation with high positive end-expiratory pressure (PEEP) and recruitment manoeuvres (RMs) on postoperative spirometry. DESIGN: This was a preplanned, single-centre substudy of an international multicentre randomised controlled trial, the PROVHILO trial. SETTING: University hospital from November 2011 to January 2013. PATIENTS: Nonobese patients scheduled for major abdominal surgery at a high risk of postoperative pulmonary complications (PPCs). INTERVENTION: Intraoperative low tidal volume ventilation with PEEP levels of 12 cmH2O and RM (the high PEEP group) or with PEEP levels of 2 cmH2O or less without RM (the low PEEP group). MAIN OUTCOME MEASURES: Time-weighted averages (TWAs) of the forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) up to postoperative day five. RESULTS: Thirty-one patients were allocated to the high PEEP group and 32 to the low PEEP group. No postoperative spirometry test results were available for 6 patients. In both groups, TWA of FEV1 and FVC until postoperative day five were lower than preoperative values. Postoperative spirometry test results were not different between the high and low PEEP group; Data are median [interquartile range], TWA FVC 1.8 [1.6 to 2.4] versus 1.7 [1.2 to 2.4] l (P = NS) and TWA FEV1 1.2 [1.1 to 2.5] versus 1.2 [0.9 to 1.9] l (P = NS). Patients who developed PPCs had lower FEV1 and FVC on postoperative day five; 1.1 [0.9 to 1.6] versus 1.6 [1.4 to 1.9] l (P = 0.001) and 1.6 [1.2 to 2.6] versus 2.3 [1.7 to 2.6] l (P = 0.036), respectively. CONCLUSION: Postoperative spirometry is not affected by PEEP and RM during intraoperative ventilation for open abdominal surgery in nonobese patients at a high risk of PPCs, but rather is associated with the development of PPCs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01441791.

Argatroban for anticoagulation of a blood salvage system - an ex-vivo study.

BACKGROUND: Blood salvage systems help to minimize intraoperative transfusion of allogenic blood. So far no data is available on the use of argatroban for anticoagulation of such systems. We conducted an ex-vivo trial to evaluate the effectiveness of three different argatroban doses as compared to heparin and to assess potential residual anticoagulant in the red cell concentrates. METHODS: With ethical approval and individual informed consent, blood of 23 patients with contraindications for use of blood salvage systems during surgery was processed by the Continuous-Auto-Transfusion-System (C.A.T.S. ® Cell Saver System, Fresenius Kabi, Bad Homburg, Germany) using 5,50 or 250 mg of argatroban or 25.000 U of heparin in 1000 ml saline for anticoagulation of the system. Emergency and high-quality washing modes were applied in random order. Patency of the system and residual amount of anticoagulants in the re-transfusion bag were measured. The collected blood was not re-infused, but only used for analysis of hematocrit, heparin and argatroban concentrations. RESULTS: Patency of the system was provided by all anticoagulants except for 3/8 cases with 5 mg of argatroban. Residual anticoagulant was found in 2/10 (20 %) heparin samples in two different patients (1 emergency and 1 high-quality washing) and in all argatroban samples. High quality washing eliminated 89-95 % and emergency washing 60-90 % of the initial argatroban concentration. Residual argatroban concentrations ranged from 55 ng ml(-1) to 6810 ng ml(-1), with initial argatroban concentrations of 5 and 250 mg, respectively. CONCLUSION: The C.A.T.S. does not reliably remove heparin and should therefore not be used in HIT patients. Anticoagulation with 50 and 250 mg argatroban, maintains the systems patency and is significantly removed during washing. In this ex-vivo study a concentration of 50 µg ml(-1) argatroban provided the best ratio of system patency and residual argatroban concentration. Additional dose-finding studies with different blood salvage systems are needed to evaluate the optimal argatroban concentration.

Protective versus Conventional Ventilation for Surgery: A Systematic Review and Individual Patient Data Meta-analysis.

BACKGROUND: Recent studies show that intraoperative mechanical ventilation using low tidal volumes (VT) can prevent postoperative pulmonary complications (PPCs). The aim of this individual patient data meta-analysis is to evaluate the individual associations between VT size and positive end-expiratory pressure (PEEP) level and occurrence of PPC. METHODS: Randomized controlled trials comparing protective ventilation (low VT with or without high levels of PEEP) and conventional ventilation (high VT with low PEEP) in patients undergoing general surgery. The primary outcome was development of PPC. Predefined prognostic factors were tested using multivariate logistic regression. RESULTS: Fifteen randomized controlled trials were included (2,127 patients). There were 97 cases of PPC in 1,118 patients (8.7%) assigned to protective ventilation and 148 cases in 1,009 patients (14.7%) assigned to conventional ventilation (adjusted relative risk, 0.64; 95% CI, 0.46 to 0.88; P < 0.01). There were 85 cases of PPC in 957 patients (8.9%) assigned to ventilation with low VT and high PEEP levels and 63 cases in 525 patients (12%) assigned to ventilation with low VT and low PEEP levels (adjusted relative risk, 0.93; 95% CI, 0.64 to 1.37; P = 0.72). A dose-response relationship was found between the appearance of PPC and VT size (R2 = 0.39) but not between the appearance of PPC and PEEP level (R2 = 0.08). CONCLUSIONS: These data support the beneficial effects of ventilation with use of low VT in patients undergoing surgery. Further trials are necessary to define the role of intraoperative higher PEEP to prevent PPC during nonopen abdominal surgery.

Thoracic paravertebral regional anesthesia improves analgesia after breast cancer surgery: a randomized controlled multicentre clinical trial.

BACKGROUND: The contribution of regional anesthesia with thoracic paravertebral blockade to postoperative analgesia remains unclear. We compared the effect of a combination of paravertebral blockade and propofol general anesthesia (GA) with sevoflurane GA and opioid analgesia on postoperative pain and opioid use for patients undergoing breast cancer surgery. METHODS: Patients having breast cancer surgery were randomly assigned to paravertebral analgesia with propofol GA (PPA, n = 187) or sevoflurane GA with perioperative opioid analgesia (SOA, n = 199). The PPA and SOA groups were compared for opioid consumption and pain outcomes (on a 0-10 visual analogue scale [VAS]) at two hours postoperatively using superiority and inferiority statistics. We compared our results with previous publications in a meta-analysis. RESULTS: Compared with the SOA group, the PPA group experienced reduced median [interquartile range] pain VAS scores (1 [1,3] vs 2.5 [1,4], respectively; median difference -1.0; 99% confidence intervals [CI]: -1.5 to -0.5) and required less intraoperative fentanyl (50 [0, 125] µg vs 200 [100, 300] µg, respectively; median difference -100; 99% CI: -150 to -100) and less long-acting opioid (0 [0, 0] mg vs 3.0 [0, 12] mg, respectively, morphine equivalents; median difference -3; 99% CI: -4 to -2). Thus, non-inferiority was detected for all the above outcomes, and superiority tests for each outcome were highly significant in the expected directions (P < 0.001). Meta-analysis, including the current study, estimated a reduction in worst pain of 2.3 points (95% CI: 1.8 to 2.8) on a 0-10 scale and a 72% reduction (95% CI: 42 to 87) in mean opioid consumption in the immediate two postoperative hours for PPA vs SOA. CONCLUSION: Our results were largely consistent with previous much smaller studies. Compared with sevoflurane GA with opioid analgesia, the combination of paravertebral analgesia with propofol GA provides an early clinical analgesic benefit in females having breast cancer surgery. This analysis is a substudy of an ongoing multicentre double-blinded randomized trial ( www.clinicaltrials.gov , NCT00418457) of cancer recurrence.

Argatroban versus Lepirudin in critically ill patients (ALicia): a randomized controlled trial.

INTRODUCTION: Critically ill patients often require renal replacement therapy accompanied by thrombocytopenia. Thrombocytopenia during heparin anticoagulation may be due to heparin-induced thrombocytopenia with need for alternative anticoagulation. Therefore, we compared argatroban and lepirudin in critically ill surgical patients. METHODS: Following institutional review board approval and written informed consent, critically ill surgical patients more than or equal to 18 years with suspected heparin-induced thrombocytopenia, were randomly assigned to receive double-blind argatroban or lepirudin anticoagulation targeting an activated Partial Thromboplastin Time (aPTT) of 1.5 to 2 times baseline. In patients requiring continuous renal replacement therapy we compared the life-time of hemodialysis filters. We evaluated in all patients the incidence of bleeding and thrombembolic events. RESULTS: We identified 66 patients with suspected heparin-induced thrombocytopenia, including 28 requiring renal replacement therapy. Mean filter lifetimes did not differ between groups (argatroban 32 ± 25 hours (n = 12) versus lepirudin 27 ± 21 hours (n = 16), mean difference 5 hours, 95% CI -13 to 23, P = 0.227). Among all 66 patients, relevant bleeding occurred in four argatroban- versus eleven lepirudin-patients (OR 3.9, 95% CI 1.1 to 14.0, P = 0.040). In the argatroban-group, three thromboembolic events occurred compared to two in the lepirudin group (OR 0.7, 95% CI 0.1 to 4.4, P = 0.639). The incidence of confirmed heparin-induced thrombocytopenia was 23% (n = 15) in our study population. CONCLUSIONS: This first randomized controlled double-blind trial comparing two direct thrombin inhibitors showed comparable effectiveness for renal replacement therapy, but suggests fewer bleeds in surgical patients with argatroban anticoagulation. TRIAL REGISTRATION: Clinical Trials.gov NCT00798525. Registered 25 November 2008.

Electrical impedance tomography during major open upper abdominal surgery: a pilot-study.

BACKGROUND: Electrical impedance tomography (EIT) of the lungs facilitates visualization of ventilation distribution during mechanical ventilation. Its intraoperative use could provide the basis for individual optimization of ventilator settings, especially in patients at risk for ventilation-perfusion mismatch and impaired gas exchange, such as patients undergoing major open upper abdominal surgery. EIT throughout major open upper abdominal surgery could encounter difficulties in belt positioning and signal quality. Thus, we conducted a pilot-study and tested whether EIT is feasible in patients undergoing major open upper abdominal surgery. METHODS: Following institutional review board's approval and written informed consent, we included patients scheduled for major open upper abdominal surgery of at least 3 hours duration. EIT measurements were conducted prior to intubation, at the time of skin incision, then hourly during surgery until shortly prior to extubation and after extubation. Number of successful intraoperative EIT measurements and reasons for failures were documented. From the valid measurements, a functional EIT image of changes in tidal impedance was generated for every time point. Regions of interest were defined as horizontal halves of the picture. Monitoring of ventilation distribution was assessed using the center of ventilation index, and also using the total and dorsal ventilated lung area. All parameter values prior to and post intubation as well as extubation were compared. A p < 0.05 was considered statistically significant. RESULTS: A total of 120 intraoperative EIT measurements during major abdominal surgery lasting 4-13 hours were planned in 14 patients. The electrode belt was attached between the 2(nd) and 4(th) intercostal space. Consecutive valid measurements could be acquired in 13 patients (93%). 111 intraoperative measurements could be retrieved as planned (93%). Main obstacle was the contact of skin electrodes. Despite the high belt position, distribution of tidal volume showed a significant shift of ventilation towards ventral lung regions after intubation. This was reversed after weaning from mechanical ventilation. CONCLUSIONS: Despite a high belt position, monitoring of ventilation distribution is feasible in patients undergoing major open upper abdominal surgery lasting from 4 to 13 hours. Therefore, further interventional trials in order to optimize ventilatory management should be initiated.

Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial--the RIPHeart-Study.

AIMS: Transient ischaemia of non-vital tissue has been shown to enhance the tolerance of remote organs to cope with a subsequent prolonged ischaemic event in a number of clinical conditions, a phenomenon known as remote ischaemic preconditioning (RIPC). However, there remains uncertainty about the efficacy of RIPC in patients undergoing cardiac surgery. The purpose of this report is to describe the design and methods used in the "Remote Ischaemic Preconditioning for Heart Surgery (RIPHeart)-Study". METHODS: We are conducting a prospective, randomized, double-blind, multicentre, controlled trial including 2070 adult cardiac surgical patients. All types of surgery in which cardiopulmonary bypass is used will be included. Patients will be randomized either to the RIPC group receiving four 5 min cycles of transient upper limb ischaemia/reperfusion or to the control group receiving four cycles of blood pressure cuff inflation/deflation at a dummy arm. The primary endpoint is a composite outcome (all-cause mortality, non-fatal myocardial infarction, any new stroke, and/or acute renal failure) until hospital discharge. CONCLUSION: The RIPHeart-Study is a multicentre trial to determine whether RIPC may improve clinical outcome in cardiac surgical patients.

Effect of remote ischemic conditioning on atrial fibrillation and outcome after coronary artery bypass grafting (RICO-trial).

BACKGROUND: Pre- and postconditioning describe mechanisms whereby short ischemic periods protect an organ against a longer period of ischemia. Interestingly, short ischemic periods of a limb, in itself harmless, may increase the ischemia tolerance of remote organs, e.g. the heart (remote conditioning, RC). Although several studies have shown reduced biomarker release by RC, a reduction of complications and improvement of patient outcome still has to be demonstrated. Atrial fibrillation (AF) is one of the most common complications after coronary artery bypass graft surgery (CABG), affecting 27-46% of patients. It is associated with increased mortality, adverse cardiovascular events, and prolonged in-hospital stay. We hypothesize that remote ischemic pre- and/or post-conditioning reduce the incidence of AF following CABG, and improve patient outcome. METHODS/DESIGN: This study is a randomized, controlled, patient and investigator blinded multicenter trial. Elective CABG patients are randomized to one of the following four groups: 1) control, 2) remote ischemic preconditioning, 3) remote ischemic postconditioning, or 4) remote ischemic pre- and postconditioning. Remote conditioning is applied at the arm by 3 cycles of 5 minutes of ischemia and reperfusion. Primary endpoint is the incidence AF in the first 72 hours after surgery, detected using a Holter-monitor. Secondary endpoints include length-of-stay on the intensive care unit and in-hospital, and the occurrence of major adverse cardiovascular events at 30 days, 3 months and 1 year.Based on an expected incidence in the control group of 27%, 195 patients per group are needed to detect with 80% power a reduction by 45% following either pre- or postconditioning, while allowing for a 10% dropout and at an alpha of 0.05. With the combined intervention expected to be stronger, we need 75 patients in this group to detect a reduction in incidence of AF of 60%. DISCUSSION: The RICO-trial (the effect of Remote Ischemic Conditioning on atrial fibrillation and Outcome) is a randomized controlled multicenter trial, designed to investigate whether remote ischemic pre- and/or post-conditioning of the arm reduce the incidence of AF following CABG surgery. TRIAL REGISTRATION: ClinicalTrials.gov under NCT01107184.

[What is the contribution of physician assistants to health care in Germany? A differentiation between physician assistants and physicians in training]. / Welchen Beitrag können Physician Assistants zur Gesundheitsversorgung leisten? Eine Abgrenzung zu Ärztinnen und Ärzten in Weiterbildung.

BACKGROUND: Physicians in training are major contributors to the German health care system. After graduation from medical school, physicians in training qualify for a certain specialty. The workload of physicians in training in Germany is so high that they have expressed their need for support. One opportunity to support physicians in training is by delegating tasks to physician assistants (medical assistants qualified by a specific course of study, graduated from universities of applied sciences). However, there is a lack of knowledge about the qualification of physician assistants and the conditions which allow support of physicians in training by physician assistants in Germany. METHODS: Based on a focused internet search, this paper describes the development of the profession physician assistance in Germany and the currently offered graduation courses including their duration and qualification requirements. Furthermore, we present available recommendations for the content of physician assistants' education and characterize conditions for the support of physicians in training by physician assistants. RESULTS: In Germany, physician assistance has been an academic discipline since 2005, the profession is, however, still quite seldom. Qualification requirements and the duration of education are determined by the universities. The aim is to qualify students for several competencies, which enable physician assistants to perform tasks of physicians under delegation. The conditions for delegation to physicians in training and to physician assistants are quite similar, resulting in partly comparable practice. Major differences relate to the so called "physician reservation" or physicians' core area, both of which define tasks that may only be carried out by physicians. DISCUSSION: Integrating physician assistants into a medical team means supporting the specialists by delegating tasks, thus reducing the workload of all physicians in the team, including physicians in training. Currently, there are no data on and no outcomes of the performance of physician assistants in Germany. CONCLUSION: In everyday practice, health care delivered by physician assistants and by physicians in training is similar, at least as regards activities and tasks that do not need physician supervision.