Sigrun Friesecke

Treatment of severe neurological deficits with IgG depletion through immunoadsorption in patients with Escherichia coli O104:H4-associated haemolytic uraemic syndrome: a prospective trial

BACKGROUND In May 2011, an outbreak of Shiga toxin-producing enterohaemorrhagic E coli O104:H4 in northern Germany led to a high proportion of patients developing post-enteritis haemolytic uraemic syndrome and thrombotic microangiopathy that were unresponsive to therapeutic plasma exchange or complement-blocking antibody (eculizumab). Some patients needed ventilatory support due to severe neurological complications, which arose 1 week after onset of enteritis, suggesting an antibody-mediated mechanism. Therefore, we aimed to assess immunoadsorption as rescue therapy. METHODS In our prospective non-controlled trial, we enrolled patients with severe neurological symptoms and confirmed recent E coli O104:H4 infection without other acute bacterial infection or raised procalcitonin concentrations. We did IgG immunoadsorption processing of 12 L plasma volumes on 2 consecutive days, followed by IgG replacement (0·5 g/kg intravenous IgG). We calculated a composite neurological symptom score (lowest score was best) every day and assessed changes before and after immunoadsorption. FINDINGS We enrolled 12 patients who initially presented with enteritis and subsequent renal failure; 10 (83%) of 12 patients needed renal replacement therapy by a median of 8·0 days (range 5-12). Neurological complications (delirium, stimulus sensitive myoclonus, aphasia, and epileptic seizures in 50% of patients) occurred at a median of 8·0 days (range 5-15) and mandated mechanical ventilation in nine patients. Composite neurological symptom scores increased in the 3 days before immunoadsorption to 3·0 (SD 1·1, p=0·038), and improved to 1·0 (1·2, p=0·0006) 3 days after immunoadsorption. In non-intubated patients, improvement was apparent during immunoadsorption (eg, disappearance of aphasia). Five patients who were intubated were weaned within 48 h, two within 4 days, and two patients needed continued ventilation for respiratory problems. All 12 patients survived and ten had complete neurological and renal function recovery. INTERPRETATION Antibodies are probably involved in the pathogenesis of severe neurological symptoms in patients with E coli O104:H4-induced haemolytic uraemic syndrome. Immunoadsorption can safely be used to rapidly ameliorate these severe neurological complications. FUNDING Greifswald University and Hannover Medical School.

Outcome of severe lactic acidosis associated with metformin accumulation

IntroductionMetformin associated lactic acidosis (MALA) may complicate metformin therapy, particularly if metformin accumulates due to renal dysfunction. Profound lactic acidosis (LA) generally predicts poor outcome. We aimed to determine if MALA differs in outcome from LA of other origin (LAOO).MethodsWe conducted a retrospective analysis of all patients admitted with LA to our medical ICU of a tertiary referral center during a 5-year period. MALA patients and LAOO patients were compared with respect to parameters of acid-base balance, serum creatinine, hospital outcome, Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) score, using Pearsons Chi-square or the Mann-Whitney U-test.ResultsOf 197 patients admitted with LA, 10 had been diagnosed with MALA. With MALA, median arterial blood pH was significantly lower (6.78 [range 6.5 to 6.94]) and serum lactate significantly higher (18.7 ± 5.3 mmol/L) than with LAOO (pH 7.20 [range 6.46 to 7.35], mean serum lactate 11.2 ± 6.1 mmol/L). Overall mortality, however, was comparable (MALA 50%, LAOO 74%). Furthermore, survival of patients with arterial blood pH < 7.00 (N = 41) was significantly better (50% vs. 0%) if MALA (N = 10) was the underlying condition compared to LAOO (N = 31).ConclusionsCompared to similarly severe lactic acidosis of other origin, the prognosis of MALA is significantly better. MALA should be considered in metformin-treated patients presenting with lactic acidosis.

Comparison of pulmonary artery and aortic transpulmonary thermodilution for monitoring of cardiac output in patients with severe heart failure: validation of a novel method.

Objective:Hemodynamic monitoring with the pulmonary artery catheter is frequently used in the management of severe heart failure. For measurement of cardiac output (CO), transpulmonary thermodilution (TPTD) has recently been adopted into clinical practice as an alternative to pulmonary artery thermodilution. However, no data have been published on the comparability of the two methods for patients with severely reduced left ventricular function. Our objective was to evaluate the correlation between these two methods of CO determination in patients with severe left ventricular dysfunction. Design:Prospective observational clinical study. Setting:Cardiological intermediate care unit and medical intensive care unit of a university hospital. Patients:Twenty-nine patients with left ventricular ejection fraction <35% and symptoms of heart failure (New York Heart Association class III–IV). Intervention:None. Measurements and Main Results:The two methods of intermittent CO measurement were compared by simultaneously recording the results of pulmonary artery thermodilution and TPTD after injection of a cold saline bolus. Measurements were performed when clinically necessary. A total of 325 data pairs were analyzed. Mean CO of both methods was 4.4 L/min with a bias of 0.45 L/min (2 sd 1.20 L/min), resulting in a percentage error of 27.3%. Conclusion:In patients with severely impaired left ventricular function, measurement of CO by TPTD provides valid results.

Improvement of enteral nutrition in intensive care unit patients by a nurse-driven feeding protocol

AIMS AND OBJECTIVES To examine whether early enteral nutrition (EN) of critically ill patients could be improved by a nurse-driven implementation of an existing feeding protocol. DESIGN Before and after design. METHODS Responsibility for starting and timely escalating EN - subject to physicians ordering before - was assigned to the intensive care unit (ICU) nursing staff. A short written instruction was extracted from the comprehensive standard operating procedure (SOP) for nutrition. The nursing team was trained to use this instruction; after completing the training they managed early EN autonomously. Time to start of enteral feeding and applied quantity in the first 5 ICU days were recorded prospectively for the patients treated during the following 6 months. The data were compared to a retrospectively analysed cohort from 6 months before, which was fed according to the SOP-based prescription of the physician on duty. RESULTS A total of 101 and 97 patients were included, respectively, before and after the intervention. Following intervention, enteral feeding started significantly earlier (28 ± 20 h versus 47 ± 34 h, p<0.001), within 24 h in 64% versus 25% (p<0.0001); and for each of the first 5 days, the proportion of patients meeting their nutritional goal was significantly higher. CONCLUSIONS Assigning the responsibility for implementation of an existing SOP to the nursing team led to earlier start of enteral feeding and more frequent achievement of caloric targets in ICU patients. RELEVANCE TO CLINICAL PRACTICE Adherence to guidelines regarding early start and timely escalation of EN can be improved if ICU nursing staff is responsible for translating it into action with the help of a written algorithm.

CytoSorb, a novel therapeutic approach for patients with septic shock: a case report

Introduction Hemoadsorption using CytoSorb has gained attention as a potential immunotherapy to control systemic inflammation and sepsis. We report on a patient with septic shock, successfully treated with CytoSorb therapy. Methods A 72-year-old male with periodically recurring infectious episodes was admitted with the suspicion of urosepsis. In the following hours his hemodynamic situation deteriorated markedly, exhibiting respiratory-metabolic acidosis, elevated inflammatory marker plasma levels, a severely disturbed coagulation, increased retention parameters, liver dysfunction, and confirmation of bacteria and leucocytes in urine. After admission to the ICU in a state of septic shock the patient received renal support with additional hemoadsorption using CytoSorb. Three CytoSorb sessions were run during the following days. Results The first and consecutive second session resulted in a reduction of procalcitonin, C-reactive protein and bilirubin and a markedly reduced need for vasopressors while hemodynamics improved significantly (i.e., cardiac index, extravascular lung water). Due to a recurring inflammatory “second hit” episode, another session with CytoSorb was run, resulting in a marked decrease in leukocytosis and liver (dys)function parameters. Conclusions The rapid hemodynamic stabilization with reduction of vasopressor needs within hours and reduction of the capillary leakage as well as a quick reduction in infection markers were the main conclusions drawn from the use of CytoSorb in this patient. Additionally, treatment appeared to be safe and was well tolerated. Despite the promising results of CytoSorb application in this patient, further studies are necessary to elucidate to what extent these favorable consequences are attributable to the adsorber itself.

Alternative diagnosis to heparin-induced thrombocytopenia in two critically ill patients despite a positive PF4/heparin-antibody test

Abstract Thrombocytopenia can cause diagnostic challenges in patients who have received heparin. Heparin-induced thrombocytopenia (HIT) is often considered in the differential diagnosis, and a positive screening can be mistaken as confirmation of the disorder. We present two patients who both received low-molecular-weight heparin for several days. In the first patient, clinical judgment rejected the suspicion of HIT despite a positive screening assay, and treatment for the alternative diagnosis of post-transfusion purpura was correctly initiated. In the second patient, the inaccurate diagnosis HIT was pursued due to a positive screening assay, while the alternative diagnosis of drug-dependent thrombocytopenia caused by piperacillin/tazobactam was rejected. This resulted in re-exposure to piperacillin/tazobactam which caused a second episode of severe thrombocytopenia. A positive screening assay for platelet factor 4/heparin-antibody should be verified by a functional assay, especially in patients with low pretest probability for HIT.

Non‐thrombotic fatal pulmonary embolism with a ‘rule‐out’ CT scan

We report on a 36‐year‐old woman suffering from metastasized breast cancer and severe dyspnoea owing to right heart failure. Symptoms and findings were highly suggestive of pulmonary embolism. In rare cases, pulmonary embolism is caused not by migration of venous thrombi but by emboli of other origin. Patients with cancer can suffer from non‐thrombotic pulmonary embolism, either by (macroscopic) embolization of tumour mass or by microembolism also known as microscopic tumour microangiopathy. In patients with cancer with clinical presentation highly suggestive of pulmonary embolism, with echocardiographic findings confirming right ventricular dysfunction, and with negative CT angiography, pulmonary tumour microembolism should be considered as possible diagnosis.

Nodular hemangiomatosis of pleura and peritoneum

Multiple, simultaneously occurring hemangiomas in one or more organs are known as hemangiomatosis syndromes in the context of phacomatosis manifesting in childhood. Nevertheless, hemangiomas of the serous membranes are extremely rare and often present as solitary lesions. We report the case of an elderly patient who suffered from diffuse hemangiomatosis of the visceral peritoneum and pleura and deceased due to acute respiratory distress syndrome following persistent and unmanageable pulmonary hemorrhage. We present an unusual case of a disseminated but histologically benign appearing hemangiomatosis of the serous membranes.

No Relapse of Calcineurin Inhibitor-Associated Thrombotic Microangiopathy after Discontinuation of Eculizumab

common practice and most patients undergo plasma exchange despite the activity of ADAMTS-13 being commonly normal. In consequence, this approach has an unsatisfying response rate between 20 and 50%. Eculizumab is a humanized monoclonal antibody blocking complement activation. It is directed against C5 [6]. The major indication for eculizumab is paroxysmal nocturnal hemoglobinuria (PNH). However, it has been used with success in atypical hemolytic uremic syndrome (HUS), even after alloSCT [7, 8]. Eculizumab has been recommended as a lifelong therapy since PNH clones will not be eliminated and genetic alterations leading to atypical HUS persist. Since eculizumab inhibits the complement pathway, this therapy can be associated with severe infections as side effects [6, 9]. The approach to withdraw eculizumab after successful therapy of atypical HUS is under discussion [10–12]. Therefore, it would be desirable and could be possible to limit the administration of eculizumab in nongenetically determined TMA, especially in highly immunosuppressed patients after alloSCT with or without GvHD. Calcineurin inhibitor (CNI)-associated thrombotic microangiopathy (TMA) is a severe and often fatal complication after allogeneic stem cell transplantation (alloSCT) [1–3]. Administration of the CNIs cyclosporine-A and tacrolimus as well as sirolimus has been described as a risk factor [4]. Thrombocytopenia, the occurrence of schistocytes, and progredient anemia in conjunction with an increase in lactate dehydrogenase in the absence of antierythrocyte antibodies leads to diagnosis. Progredient renal failure and involvement of the CNS as described for TTP may occur. Diagnosis may be difficult since a variety of other problems may cause the addressed symptoms (except the occurrence of schistocytes): cytopenia may be caused by infections or related to graft-versushost disease (GvHD), and drugs like cyclosporine-A can induce an increase in creatinine. Treatment of TMA is difficult and a therapeutic standard for therapy of CNIassociated TMA has not been established so far [5]. The discontinuation of CNIs is Received: September 20, 2017 Accepted: September 22, 2017 Published online: November 15, 2017

Transesophageal echocardiography-guided, bed-side bail-out aortic valvuloplasty.

A 73-year-old man developed hemodynamic deterioration in the context of bilateral pneumonia, despite treatment of septic shock according to guidelines. Transthoracic echocardiography was of poor quality, due to obesity, but revealed severely reduced left ventricular (LV) function. Significant