[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.

[Extracorporeal Membrane Oxygenation in Thoracic Surgery: the Anesthesiologist's Perspective]. / Extrakorporale Membranoxygenierung in der Thoraxchirurgie: die Sicht des Anästhesisten.

"Enhanced Recovery after Surgery" programs have been developed for thoracic surgery over the last couple of years. Besides minimally invasive surgical techniques, there are a number of anaesthesiological aspects like the choice of short acting anaesthetics, the use of regional analgesia, a balanced intraoperative fluid therapy, the avoidance of postoperative nausea and vomiting and, most importantly, protective ventilation, that need to be considered. In patients undergoing thoracic surgery procedures with preexisting severe limitations in pulmonary function, protective ventilation under the conditions of one lung ventilation often leads to severe dysfunction of pulmonary gas exchange. In this situation, establishing veno-venous membrane oxygenation (vvECMO) is a sufficient and safe method to facilitate perioperative treatment of these patients. Postoperatively, patients benefit from the continuation of the conscious vvECMO by augmentation of necessary therapeutic procedures such as physical and respiratory therapy or early mobilisation as well as healing of air leakage of the operated lung. To avoid bleeding complications, ECMO can be operated without anticoagulation intraoperatively with heparin-coating of the tube system. Postoperatively, heparin, argatroban or bivalirudin are options for anticoagulation. New techniques like minimally-invasive thoracic surgery under regional anaesthesia and sedation can potentially be developed further using vvECMO support in the future.

Interaction between peri-operative blood transfusion, tidal volume, airway pressure and postoperative ARDS: an individual patient data meta-analysis.

BACKGROUND: Transfusion of blood products and mechanical ventilation with injurious settings are considered risk factors for postoperative lung injury in surgical Patients. METHODS: A systematic review and individual patient data meta-analysis was done to determine the independent effects of peri-operative transfusion of blood products, intra-operative tidal volume and airway pressure in adult patients undergoing mechanical ventilation for general surgery, as well as their interactions on the occurrence of postoperative acute respiratory distress syndrome (ARDS). Observational studies and randomized trials were identified by a systematic search of MEDLINE, CINAHL, Web of Science, and CENTRAL and screened for inclusion into a meta-analysis. Individual patient data were obtained from the corresponding authors. Patients were stratified according to whether they received transfusion in the peri-operative period [red blood cell concentrates (RBC) and/or fresh frozen plasma (FFP)], tidal volume size [≤7 mL/kg predicted body weight (PBW), 7-10 and >10 mL/kg PBW] and airway pressure level used during surgery (≤15, 15-20 and >20 cmH2O). The primary outcome was development of postoperative ARDS. RESULTS: Seventeen investigations were included (3,659 patients). Postoperative ARDS occurred in 40 (7.2%) patients who received at least one blood product compared to 40 patients (2.5%) who did not [adjusted hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.25-4.33; P=0.008]. Incidence of postoperative ARDS was highest in patients ventilated with tidal volumes of >10 mL/kg PBW and having airway pressures of >20 cmH2O receiving both RBC and FFP, and lowest in patients ventilated with tidal volume of ≤7 mL/kg PBW and having airway pressures of ≤15 cmH2O with no transfusion. There was a significant interaction between transfusion and airway pressure level (P=0.002) on the risk of postoperative ARDS. CONCLUSIONS: Peri-operative transfusion of blood products is associated with an increased risk of postoperative ARDS, which seems more dependent on airway pressure than tidal volume size.

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.

Comparison of mortality prediction models in acute respiratory distress syndrome undergoing extracorporeal membrane oxygenation and development of a novel prediction score: the PREdiction of Survival on ECMO Therapy-Score (PRESET-Score).

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy in acute respiratory distress syndrome (ARDS) patients but is associated with complications and costs. Here, we validate various scores supposed to predict mortality and develop an optimized categorical model. METHODS: In a derivation cohort, 108 ARDS patients (2010-2015) on veno-venous ECMO were retrospectively analysed to assess four established risk scores (ECMOnet-Score, RESP-Score, PRESERVE-Score, Roch-Score) for mortality prediction (receiver operating characteristic analysis) and to identify by multivariable logistic regression analysis independent variables for mortality to yield the new PRESET-Score (PREdiction of Survival on ECMO Therapy-Score). This new score was then validated both in independent internal (n = 82) and external (n = 59) cohorts. RESULTS: The median (25%; 75% quartile) Sequential Organ Failure Assessment score was 14 (12; 16), Simplified Acute Physiology Score II was 62.5 (57; 72.8), median intensive care unit stay was 17 days (range 1-124), and mortality was 62%. Only the ECMOnet-Score (area under curve (AUC) 0.69) and the RESP-Score (AUC 0.64) discriminated survivors and non-survivors. Admission pHa, mean arterial pressure, lactate, platelet concentrations, and pre-ECMO hospital stay were independent predictors of death and were used to build the PRESET-Score. The score's internal (AUC 0.845; 95% CI 0.76-0.93; p < 0.001) and external (AUC 0.70; 95% CI 0.56-0.84; p = 0.008) validation revealed excellent discrimination. CONCLUSIONS: While our data confirm that both the ECMOnet-Score and the RESP-Score predict mortality in ECMO-treated ARDS patients, we propose a novel model also incorporating extrapulmonary variables, the PRESET-Score. This score predicts mortality much better than previous scores and therefore is a more precise choice for decision support in ARDS patients to be placed on ECMO.

Outcome of acute respiratory distress syndrome in university and non-university hospitals in Germany.

BACKGROUND: This study investigates differences in treatment and outcome of ventilated patients with acute respiratory distress syndrome (ARDS) between university and non-university hospitals in Germany. METHODS: This subanalysis of a prospective, observational cohort study was performed to identify independent risk factors for mortality by examining: baseline factors, ventilator settings (e.g., driving pressure), complications, and care settings-for example, case volume of ventilated patients, size/type of intensive care unit (ICU), and type of hospital (university/non-university hospital). To control for potentially confounding factors at ARDS onset and to verify differences in mortality, ARDS patients in university vs non-university hospitals were compared using additional multivariable analysis. RESULTS: Of the 7540 patients admitted to 95 ICUs from 18 university and 62 non-university hospitals in May 2004, 1028 received mechanical ventilation and 198 developed ARDS. Although the characteristics of ARDS patients were very similar, hospital mortality was considerably lower in university compared with non-university hospitals (39.3% vs 57.5%; p = 0.012). Treatment in non-university hospitals was independently associated with increased mortality (OR (95% CI): 2.89 (1.31-6.38); p = 0.008). This was confirmed by additional independent comparisons between the two patient groups when controlling for confounding factors at ARDS onset. Higher driving pressures (OR 1.10; 1 cmH2O increments) were also independently associated with higher mortality. Compared with non-university hospitals, higher positive end-expiratory pressure (PEEP) (mean ± SD: 11.7 ± 4.7 vs 9.7 ± 3.7 cmH2O; p = 0.005) and lower driving pressures (15.1 ± 4.4 vs 17.0 ± 5.0 cmH2O; p = 0.02) were applied during therapeutic ventilation in university hospitals, and ventilation lasted twice as long (median (IQR): 16 (9-29) vs 8 (3-16) days; p < 0.001). CONCLUSIONS: Mortality risk of ARDS patients was considerably higher in non-university compared with university hospitals. Differences in ventilatory care between hospitals might explain this finding and may at least partially imply regionalization of care and the export of ventilatory strategies to non-university hospitals.

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.

Association between driving pressure and development of postoperative pulmonary complications in patients undergoing mechanical ventilation for general anaesthesia: a meta-analysis of individual patient data.

BACKGROUND: Protective mechanical ventilation strategies using low tidal volume or high levels of positive end-expiratory pressure (PEEP) improve outcomes for patients who have had surgery. The role of the driving pressure, which is the difference between the plateau pressure and the level of positive end-expiratory pressure is not known. We investigated the association of tidal volume, the level of PEEP, and driving pressure during intraoperative ventilation with the development of postoperative pulmonary complications. METHODS: We did a meta-analysis of individual patient data from randomised controlled trials of protective ventilation during general anesthaesia for surgery published up to July 30, 2015. The main outcome was development of postoperative pulmonary complications (postoperative lung injury, pulmonary infection, or barotrauma). FINDINGS: We included data from 17 randomised controlled trials, including 2250 patients. Multivariate analysis suggested that driving pressure was associated with the development of postoperative pulmonary complications (odds ratio [OR] for one unit increase of driving pressure 1·16, 95% CI 1·13-1·19; p<0·0001), whereas we detected no association for tidal volume (1·05, 0·98-1·13; p=0·179). PEEP did not have a large enough effect in univariate analysis to warrant inclusion in the multivariate analysis. In a mediator analysis, driving pressure was the only significant mediator of the effects of protective ventilation on development of pulmonary complications (p=0·027). In two studies that compared low with high PEEP during low tidal volume ventilation, an increase in the level of PEEP that resulted in an increase in driving pressure was associated with more postoperative pulmonary complications (OR 3·11, 95% CI 1·39-6·96; p=0·006). INTERPRETATION: In patients having surgery, intraoperative high driving pressure and changes in the level of PEEP that result in an increase of driving pressure are associated with more postoperative pulmonary complications. However, a randomised controlled trial comparing ventilation based on driving pressure with usual care is needed to confirm these findings. FUNDING: None.

Intraoperative mechanical ventilation strategies to prevent postoperative pulmonary complications in patients with pulmonary and extrapulmonary comorbidities.

A variety of patient characteristics and comorbidities have been identified, which increase the risk of postoperative pulmonary complications (PPCs), including smoking, age, chronic obstructive pulmonary disease, pulmonary hypertension, obstructive sleep apnea, cardiac and neurologic diseases as well as critical illness. In contrast to the variety of conditions, evidence for specific intraoperative ventilation strategies to reduce PPC is very limited for most comorbidities. Here, we provide an overview of and discuss possible implications for the intraoperative ventilatory management of patients with comorbidities.

[Protective ventilation reduces postoperative pulmonary complications - Contra]. / Protektive Beatmung reduziert postoperative pulmonale Komplikationen - Contra.

Protective ventilation is a treatment strategy for patients with ARDS. The main goals are the prevention of de-recruitment and overinflation and hence development of VILI. Therefore, protective ventilation is an individualised therapy by adjusting PEEP and Vt in respect to patient' own volume-pressure-curve. Nowadays the term "protective ventilation" is reduced to ventilation with Vt 6 ml/kg only. Although protective ventilatory strategies are used in patients with severe pulmonary impairment there is a trend to transfer this strategy to healthy humans undergoing surgery. In ventilated patients with healthy lungs a ventilation with Vt higher than 17 ml/kg seems to increase the risk for development of VILI. Nevertheless, many studies show a association between application of protective intraoperative ventilatory strategies and a reduced rate of postoperative pulmonary complications. However, "protective ventilation" has not been standardised yet, and the adequate Vt and PEEP in an individual patient undergoing surgery has still to be clarified. Therefore, due to inconsistent intraoperative ventilation and methodical flaws it remains questionable if a generalized Vt reduction copes this complex topic. One should be aware that reduction of Vt may increase the rate of atelectasis and has been shown to be associated with increased mortality.

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.

Incidence of mortality and morbidity related to postoperative lung injury in patients who have undergone abdominal or thoracic surgery: a systematic review and meta-analysis.

BACKGROUND: Lung injury is a serious complication of surgery. We did a systematic review and meta-analysis to assess whether incidence, morbidity, and in-hospital mortality associated with postoperative lung injury are affected by type of surgery and whether outcomes are dependent on type of ventilation. METHODS: We searched MEDLINE, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials for observational studies and randomised controlled trials published up to April, 2014, comparing lung-protective mechanical ventilation with conventional mechanical ventilation during abdominal or thoracic surgery in adults. Individual patients' data were assessed. Attributable mortality was calculated by subtracting the in-hospital mortality of patients without postoperative lung injury from that of patients with postoperative lung injury. FINDINGS: We identified 12 investigations involving 3365 patients. The total incidence of postoperative lung injury was similar for abdominal and thoracic surgery (3·4% vs 4·3%, p=0·198). Patients who developed postoperative lung injury were older, had higher American Society of Anesthesiology scores and prevalence of sepsis or pneumonia, more frequently had received blood transfusions during surgery, and received ventilation with higher tidal volumes, lower positive end-expiratory pressure levels, or both, than patients who did not. Patients with postoperative lung injury spent longer in intensive care (8·0 [SD 12·4] vs 1·1 [3·7] days, p<0·0001) and hospital (20·9 [18·1] vs 14·7 [14·3] days, p<0·0001) and had higher in-hospital mortality (20·3% vs 1·4% p<0·0001) than those without injury. Overall attributable mortality for postoperative lung injury was 19% (95% CI 18-19), and differed significantly between abdominal and thoracic surgery patients (12·2%, 95% CI 12·0-12·6 vs 26·5%, 26·2-27·0, p=0·0008). The risk of in-hospital mortality was independent of ventilation strategy (adjusted HR 0·71, 95% CI 0·41-1·22). INTERPRETATION: Postoperative lung injury is associated with increases in in-hospital mortality and durations of stay in intensive care and hospital. Attributable mortality due to postoperative lung injury is higher after thoracic surgery than after abdominal surgery. Lung-protective mechanical ventilation strategies reduce incidence of postoperative lung injury but does not improve mortality. FUNDING: None.

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.

Argatroban in extracorporeal membrane oxygenation.

The objective of this study was to assess the required dose and anticoagulatory effect of argatroban (Mitsubishi, Pharma Deutschland GmbH, Düsseldorf, Germany), a direct thrombin inhibitor approved for anticoagulation in patients with heparin-induced thrombocytopenia (HIT) undergoing extracorporeal membrane oxygenation (ECMO). Nine consecutive patients undergoing ECMO for severe acute respiratory distress syndrome (ARDS) and presenting with suspected HIT were treated with a continuous argatroban infusion. Coagulation variables were measured and dose adjustments of argatroban were performed to target for an activated partial thromboplastin time (aPTT) of 50 to 60 s. The first patient received argatroban 2 microg/kg/min as recommended by the manufacturer. This resulted in excessive anticoagulation and severe bleeding. The consecutive eight patients received a 10-fold lower dose (0.2 microg/kg/min). This dose sufficiently increased aPTT time from 46 +/- 6 s to 65 +/- 14 s (P < 0.001) and thrombin time from 18 +/- 8 s to 45 +/- 11 s (P = 0.001). The maintenance dose averaged 0.15 microg/kg/min. Duration of argatroban infusion for ECMO averaged 4 +/- 1 days and no oxygenator or extracorporeal system clotting was observed. In three of nine patients (33%), HIT was confirmed. Argatroban is a feasible and effective anticoagulant for patients with suspected HIT undergoing ECMO. However, a dose 10-fold lower than that recommended by the manufacturer is sufficient to achieve appropriate anticoagulation in critically ill patients undergoing ECMO.

Insertion/deletion polymorphism in the promoter of NFKB1 influences severity but not mortality of acute respiratory distress syndrome.

OBJECTIVE: This study investigated whether the insertion/deletion polymorphism in the promoter of NFKB1 is associated with severity and/or mortality in ARDS. DESIGN AND SETTING: Prospective study in a mixed anesthesiological ICU of the University Hospital Essen. PATIENTS AND PARTICIPANTS: 103 adult patients with ARDS (white Germans). MEASUREMENTS AND RESULTS: Patients with ARDS were genotyped for the insertion/deletion polymorphism in the promoter of NFKB1 (-94ins/delATTG). In ARDS patients genotypes differed significantly between those with severe ARDS [Lung Injury Score (LIS)>or=3; 23 homozygote deletion (DD), heterozygote (ID) 31, and homozygote insertion wildtype (II) 23], and those with LIS below 3 (1 DD, 9 ID, 16 II). Likewise, the frequency of the D allele was significantly less in patients with higher LIS (50% D) than lower LIS (21% D). Using these values produces a significantly higher OR of 16.0 (95% CI 1.96-130.9) for DD than for II, while the OR for ID vs. II was 2.4 (95% CI 0.9-6.4). Genotypes of the NFKB1 promoter polymorphism were associated neither with 30-day survival nor with duration of ICU stay. CONCLUSIONS: The insertion/deletion polymorphism in the promoter of NFKB1 influences the severity but not the mortality of ARDS.