Hemoadsorption in the critically ill-Final results of the International CytoSorb Registry.

The aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score. The main secondary endpoints were SOFA scores, inflammatory biomarkers and overall evaluation of the general condition. 1434 patients were enrolled. Indications for hemoadsorption were sepsis/septic shock (N = 936); cardiac surgery perioperatively (N = 172); cardiac surgery postoperatively (N = 67) and "other" reasons (N = 259). APACHE-II-predicted mortality was 62.0±24.8%, whereas observed hospital mortality was 50.1%. Overall SOFA scores did not change but cardiovascular and pulmonary SOFA scores decreased by 0.4 [-0.5;-0.3] and -0.2 [-0.3;-0.2] points, respectively. Serum procalcitonin and C-reactive protein levels showed significant reduction: -15.4 [-19.6;-11.17] ng/mL; -17,52 [-70;44] mg/L, respectively. In the septic cohort PCT and IL-6 also showed significant reduction: -18.2 [-23.6;-12.8] ng/mL; -2.6 [-3.0;-2.2] pg/mL, respectively. Evaluation of the overall effect: minimal improvement (22%), much improvement (22%) and very much improvement (10%), no change observed (30%) and deterioration (4%). There was no significant difference in the primary outcome of mortality, but there were improvements in cardiovascular and pulmonary SOFA scores and a reduction in PCT, CRP and IL-6 levels. Trial registration: ClinicalTrials.gov Identifier: NCT02312024 (retrospectively registered).

Adjuvant treatment of severe/refractory bullous pemphigoid with protein A immunoadsorption.

BACKGROUND: While depletion of circulating autoantibodies using immunoadsorption (IA) is an established therapeutic approach in patients with pemphigus vulgaris, IA has only sporadically been used in other autoimmune bullous disorders. Although bullous pemphigoid (BP) usually responds well to topical and systemic corticosteroids, rapid depletion of serum autoantibodies may be an effective adjuvant treatment option in patients with severe and/or refractory disease. PATIENTS AND METHODS: Case series of 20 patients (13 women, 7 men; mean age 78.6 years; range 56-94 years) with severe or refractory BP. In addition to oral prednisolone (0.25-0.5 mg/kg/day), dapsone (1.0-1.5 mg/kg/day), and clobetasol propionate 0.05 % ointment (lesional application, twice daily), treatment consisted of protein A IA (three sessions on consecutive days). The mean follow-up period was 33.6 months (1-84 months). RESULTS: The majority of patients showed a rapid and sustained response. One month after treatment, eight patients (42 %; 19 patients were included in the follow-up) were in complete remission; at the last follow-up visit (after 1 to 84 months), that number was 13 (68 %). Not only was there an initial drop in anti-BP180 autoantibodies (by 92 %), the effect also continued after one and three months, with mean autoantibody levels at 26 % and 13 % of baseline, respectively (p < 0.001). Both previously treated and treatment-naive patients showed a significant reduction in anti-BP180NC16A antibody levels throughout the observation period. Adverse events occurred in 13 of the 20 patients (65 %). Three were severe of which two were likely or probably related to IA. CONCLUSION: Immunoadsorption is an effective adjuvant treatment option for (the usually elderly) patients with severe and/or refractory BP.

Adjuvante Behandlung des schweren/refraktären bullösen Pemphigoids mit Protein-A-Immunadsorption.

HINTERGRUND: Mittels Immunadsorption (IA) können Immunglobuline und Immunkomplexe aus dem Plasma entfernt werden. Während dieses therapeutische Verfahren beim Pemphigus vulgaris bereits etabliert ist, wird es bei anderen blasenbildenden Autoimmundermatosen bislang nur sporadisch eingesetzt. Das bullöse Pemphigoid (BP) spricht zwar meist gut auf eine Therapie mit topischen und systemischen Kortikosteroiden an, jedoch könnte bei Patienten mit ausgedehnten Läsionen oder bei einem Rezidiv die rasche Reduktion der pathogenen Autoantikörper eine effektive adjuvante Therapie darstellen. PATIENTEN UND METHODIK: Fallserie mit 20 Patienten (13 Frauen, 7 Männer; mittleres Alter 78,6 Jahre; 56-94 Jahre) mit schwerem oder refraktärem BP, die zusätzlich zur Basistherapie bestehend aus Prednisolon (0,25-0,5 mg/kg/d), Dapson (1,0-1,5 mg/kg/d) und Clobetasolpropionat 0,05 % Salbe (läsional 2 x/d) mit Protein-A-IA (3 IAs an aufeinander folgenden Tagen) behandelt wurden. Die durchschnittliche Nachbeobachtungszeit betrug 33,6 Monate (1-84 Monate). ERGEBNISSE: Bei der Mehrzahl der Patienten zeigte sich ein rascher und langandauernder Therapieeffekt. Nach einem Monat befanden sich acht Patienten (von 19 nachbeobachteten, 42 %) und zum Zeitpunkt des letzten Kontakts (nach 1-84 Monaten) 13 Patienten (68 %) in kompletter Remission. Die Anti-BP180-Autoantikörper wurden nicht nur initial (um 92 %) gesenkt, sondern lagen auch nach ein und drei Monaten im Mittel bei 26 % und 13 % des Wertes vor Therapiebeginn (p < 0,001). Bei Differenzierung in vortherapierte bzw. therapienaive Patienten zeigten sich in beiden Subgruppen signifikante Absenkungen der Anti-BP180NC16A-Antikörper-Spiegel zu allen Zeitpunkten. Unerwünschte Ereignisse traten bei dreizehn (65 %) der 20 Patienten auf, Drei der Ereignisse waren schwer und zwei davon wahrscheinlich oder möglicherweise in Zusammenhang mit der IA. SCHLUSSFOLGERUNGEN: Die IA ist eine effektive adjuvante Therapieoption bei den in aller Regel älteren Patienten mit einem schweren und/oder therapierefraktären BP.

IgE-Selective Immunoadsorption for Severe Atopic Dermatitis.

INTRODUCTION: Recent reports proposed the application of immunoadsorption (IA) for patients with recalcitrant atopic dermatitis (AD) and high-serum IgE levels. However, experience with this novel treatment approach, especially with the newly available IgE-specific adsorber, is limited and recommendation for its use in clinical practice awaits evidence from more studies. MATERIALS AND METHODS: Patients with severe AD (SCORAD ≥ 60) and total serum IgE levels ≥750 kU/L were included in this study. The treatment protocol consisted of two cycles of five consecutive treatments with IgE-selective IA 3 weeks apart. RESULTS: Ten patients were enrolled and four patients completed the study. The mean SCORAD was significantly improved by up to 43% within a few weeks and until the end of a 6-month follow-up period, with 50% of patients achieving an at least 50% individual reduction of the baseline SCORAD. Each IA cycle induced a temporal average decrement of total serum levels of IgE, IgM, IgA, and IgG by 92, 43, 38, and 35%, respectively. Except for one case of Staphylococcus aureus septicemia, no major adverse events occurred. CONCLUSION: Although limited by a considerable withdrawal rate, our observations strengthen our and other recent results further suggesting that IgE-selective IA is an effective treatment option for patients severely affected by AD with highly elevated IgE levels.

Renal tubular acidosis type IV in hyperkalaemic patients--a fairy tale or reality?

OBJECTIVE: Hyperkalaemia is a common feature in hospitalized patients and often attributed to drugs antagonizing the renin-angiotensin-aldosterone system (RAAS) and/or acute kidney injury (AKI), despite significantly preserved glomerular filtration rate (GFR). The objective of this study was to determine the prevalence and role of renal tubular acidosis type IV (RTA IV) in the development of significant hyperkalaemia. DESIGN: A single-centre retrospective study. PATIENTS: Patients admitted to a University Hospital over 12 months. MEASUREMENTS: Patients with a potassium value > 6·0 mm were identified. Clinical and laboratory data were revisited, and patients with a normal anion gap metabolic acidosis were evaluated for the existence of RTA IV. RESULTS: A total of 57 patients having significant hyperkalaemia (>6·0 mm) were identified. Twelve patients had end-stage renal disease, while 21 patients had solely AKI or progressive chronic renal failure. RTA IV was present in 24 patients (42%), of whom 71% had pre-existing renal insufficiency because of diabetic nephropathy or tubulointerstitial nephritis. All hyperkalaemic patients with urinary/serum electrolytes suggestive of RTA IV had evidence of AKI, but creatinine levels were significantly lower (P < 0·05), while the number of drugs antagonizing the RAAS was comparable. CONCLUSION: We demonstrated that RTA IV (i) is very common in patients with hyperkalaemia; (ii) should always be suspected in hyperkalaemic patients with only moderately impaired GFR; and (iii) may result in significant hyperkalaemia in the presence of both AKI and drugs antagonizing the RAAS.

Beating the odds--surviving extreme hyperkalemia.

Severe hyperkalemia (>7 mmol/L) is a medical emergency because of possible fatal arrhythmias. We here report the case of a 58-year-old woman surviving extreme hyperkalemia (>10 mmol/L). The patient with a history of congestive heart failure, a DDD pacemaker and mild chronic renal insufficiency was admitted with progressive weakness and sudden onset of hypotension and bradycardia in the absence of any pacemaker action. Laboratory tests revealed an extreme serum potassium level of 10.1 mmol/L, with a slightly elevated serum creatinine of 149 µmol/L. Treatment with norepinephrine, sodium bicarbonate, and insulin improved both the hemodynamic situation and the serum potassium with subsequent regaining pacemaker actions even before additional hemodialysis normalized the potassium level. A thorough investigation demonstrated that several mechanisms contributed to the extreme potassium level: urinalysis and a low transtubular potassium gradient in the presence of metabolic acidosis with normal anion gap pointed to preexisting interstitial nephritis, with renal tubular acidosis type IV as the predisposing factor, whereas several drugs and acute impairment of renal function contributed to the dangerous situation. Despite the odds for fatal outcome, the patient recovered completely, and long-term management was initiated to prevent recurrent hyperkalemia.

[Resistant hypertension despite nine different antihypertensive drugs?]. / Therapierefraktärer Hypertonus unter 9-facher antihypertensiver Medikation?

BACKGROUND: Treatment-resistant hypertension is a common problem in an outpatient setting and often results in hospital admission. Non-identified secondary hypertension, hypertensive nephrosclerosis and non-compliance are major reasons for treatment resistance. CASE REPORT: A 75-year old woman was admitted to the emergency room because of a hypertensive crisis with alleged treatment-resistant hypertension and progressive headache. Two months ago, renal artery stenosis had been ruled out and a diagnosis of hypertensive cardiomyopathy was established. On admission, the patient had a blood pressure of 210/100 mmHg despite an antihypertensive treatment with nine different drugs. Further investigations ruled out secondary hypertension due to an endocrine cause but were consistent with hypertensive nephrosclerosis. With a supervised drug intake the blood pressure was rather normal to hypotensive, resulting in the need for significant reduction of the antihypertensive medication. The apparent discrepancies were discussed in detail with the patient who finally admitted a previous inconsistent intake of the antihypertensive drugs. Following thorough training and education on the purpose of continued antihypertensive therapy, the patient could be discharged with a normotensive blood pressure profile. CONCLUSIONS: Therapy of treatment-resistant hypertension should always consider non-compliance and secondary hypertension as possible reason.

Effects of selective angiotensin II receptor blockade on sympathetic nerve activity in primary hypertensive subjects.

OBJECTIVE: The role of the renin-angiotensin system in the regulation of sympathetic nervous activity in human hypertension was evaluated in patients with moderate primary hypertension. For that purpose, the effects of selective angiotensin II (ANG II) receptor blockade by valsartan on sympathetic outflow to the muscle vascular bed and hemodynamic parameters were examined. Results were compared with the effects of the peripherally acting calcium antagonist amlodipine. DESIGN: Eighteen hypertensive but otherwise healthy subjects were examined in a double-blind, placebo-controlled, cross-over protocol receiving either valsartan or amlodipine or placebo for 7 days in a randomized sequence. Treatment periods were separated by washout periods of 2 weeks. METHODS: At the seventh day of treatment, blood pressure, heart rate, muscle sympathetic nerve activity (MSNA), norepinephrine, renin and angiotensin were measured during resting conditions. Additionally, parameters were measured after administration of negative pressure of -15 mmHg to the lower part of the body and after a cold pressor test. RESULTS: Both antihypertensive drugs significantly decreased oscillometrically measured systolic blood pressure and diastolic blood pressure without any difference in effect. While valsartan did not affect the heart rate at rest, amlodipine increased it significantly. Likewise, MSNA was significantly enhanced by amlodipine but not by valsartan. Only ANG II receptor blockade increased renin and angiotensin levels. CONCLUSIONS: Selective ANG II receptor blockade not only decreases blood pressure, but also shifts the baroreflex set-point for the initiation of counter-regulatory reflex responses of heart rate and blood pressure towards normal blood pressure levels. Thus, data suggest that ANG II plays a pathogenetic role in the elevation of the baroreflex set point in primary hypertensive subjects.