[OCT, Triple H or anything else?] / OCT, Triple H oder doch etwas anderes?

Hyperammonemia is a life-threatening condition, the prognosis of which depends on a rapid reduction of ammonia. If a hepatic cause is excluded, the differential diagnosis is broad and even in adulthood includes hereditary metabolic diseases. Here, the case of a 25-year-old female patient with severe hyperammonemia refractory to standard therapy is described and the relevance of extracorporeal elimination of ammonia emphasized.

Metabolic disturbances potentially attributable to clogging during continuous renal replacement therapy.

BACKGROUND: Clogging is characterized by a progressive impairment of transmembrane patency in renal replacement devices and occurs due to obstruction of pores by unknown molecules. If citrate-based anti-coagulation is used, clogging can manifest as a metabolic alkalosis accompanied by hypernatremia and hypercalcemia, primarily a consequence of Na3Citrate infusion. An increased incidence of clogging has been observed during the COVID-19 pandemic. However, precise factors contributing to the formation remain uncertain. This investigation aimed to analyze its incidence and assessed time-varying trajectories of associated factors in critically ill patients on continuous renal replacement therapy (CRRT). METHODS: In this retrospective, single-center data analysis, we evaluated COVID-19 patients undergoing CRRT and admitted to critical care between March 2020 and December 2021. We assessed the proportional incidence of clogging surrogates in the overall population and subgroups based on the specific CRRT devices employed at our institution, including multiFiltrate (Fresenius Medical Care) and Prismaflex System (Baxter). Moderate and severe clogging were defined as Na > 145 or ≥ 150 mmol/l and HCO3- > 28.0 or ≥ 30 mmol/l, respectively, with a total albumin-corrected calcium > 2.54 mmol/l. A mixed effect model was introduced to investigate factors associated with development of clogging. RESULTS: Fifty-three patients with 240 CRRT runs were analyzed. Moderate and severe clogging occurred in 15% (8/53) and 19% (10/53) of patients, respectively. Twenty-seven percent (37/136) of CRRTs conducted with a multiFiltrate device met the criteria for clogging, whereas no clogging could be observed in patients dialyzed with the Prismaflex System. Occurrence of clogging was associated with elevated triglyceride plasma levels at filter start (p = 0.013), amount of enteral nutrition (p = 0.002) and an increasing white blood cell count over time (p = 0.002). CONCLUSIONS: Clogging seems to be a frequently observed phenomenon in critically ill COVID-19 patients. The presence of hypertriglyceridemia, combined with systemic inflammation, may facilitate the development of an impermeable secondary membrane within filters, thereby contributing to compromised membrane patency.

Outcomes of patients with acute respiratory failure on veno-venous extracorporeal membrane oxygenation requiring additional circulatory support by veno-venoarterial extracorporeal membrane oxygenation.

Objective: Veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) is increasingly used to support patients with severe acute respiratory distress syndrome (ARDS). In case of additional cardio-circulatory failure, some experienced centers upgrade the V-V ECMO with an additional arterial return cannula (termed V-VA ECMO). Here we analyzed short- and long-term outcome together with potential predictors of mortality. Design: Multicenter, retrospective analysis between January 2008 and September 2021. Setting: Three tertiary care ECMO centers in Germany (Hannover, Bonn) and Switzerland (Zurich). Patients: Seventy-three V-V ECMO patients with ARDS and additional acute cardio-circulatory deterioration required an upgrade to V-VA ECMO were included in this study. Measurements and main results: Fifty-three patients required an upgrade from V-V to V-VA and 20 patients were directly triple cannulated. Median (Interquartile Range) age was 49 (28-57) years and SOFA score was 14 (12-17) at V-VA ECMO upgrade. Vasoactive-inotropic score decreased from 53 (12-123) at V-VA ECMO upgrade to 9 (3-37) after 24 h of V-VA ECMO support. Weaning from V-VA and V-V ECMO was successful in 47 (64%) and 40 (55%) patients, respectively. Duration of ECMO support was 12 (6-22) days and ICU length of stay was 32 (16-46) days. Overall ICU mortality was 48% and hospital mortality 51%. Two additional patients died after hospital discharge while the remaining patients survived up to two years (with six patients being lost to follow-up). The vast majority of patients was free from higher degree persistent organ dysfunction at follow-up. A SOFA score > 14 and higher lactate concentrations at the day of V-VA upgrade were independent predictors of mortality in the multivariate regression analysis. Conclusion: In this analysis, the use of V-VA ECMO in patients with ARDS and concomitant cardiocirculatory failure was associated with a hospital survival of about 50%, and most of these patients survived up to 2 years. A SOFA score > 14 and elevated lactate levels at the day of V-VA upgrade predict unfavorable outcome.

Elimination of Herpes Simplex Virus-2 and Epstein-Barr Virus With Seraph 100 Microbind Affinity Blood Filter and Therapeutic Plasma Exchange: An Explorative Study in a Patient With Acute Liver Failure.

Herpes simplex virus (HSV)-2 is a rare cause of hepatitis that can lead to acute liver failure (ALF) and often death. The earlier the initiation of acyclovir treatment the better the survival. With regard to ALF, controlled randomized data support the use of therapeutic plasma exchange (TPE) both as bridge to recovery or transplantation-possibly by modulating the systemic inflammatory response and by replacing coagulation factors. Seraph 100 Microbind Affinity Blood Filter (Seraph; Ex Thera Medical, Martinez, CA), a novel extracorporeal adsorption device, removes living pathogens by binding to a heparin-coated surface was shown to efficiently clear HSV-2 particles in vitro. Here, we tested the combination of Seraph with TPE to reduce a massive HSV-2 viral load to reach a situation in that liver transplantation would be feasible. DESIGN: Explorative study. SETTING: Academic tertiary care transplant center. PATIENT: Single patient with HSV-2-induced ALF. INTERVENTIONS: TPE + Seraph 100 Microbind Affinity Blood Filter. MEASUREMENTS AND MAIN RESULTS: We report Seraph clearance data of HSV-2 and of Epstein-Barr virus (EBV) in vivo as well as total viral elimination by TPE. Genome copies/mL of HSV-2 and EBV in EDTA plasma were measured by polymerase chain reaction every 60 minutes over 6 hours after starting Seraph both systemically and post adsorber. Also, HSV-2 and EBV were quantified before and after TPE and in the removed apheresis plasma. We found a total elimination of 1.81 × e11 HSV-2 copies and 2.11 × e6 EBV copies with a single TPE (exchange volume of 5L; 1.5× calculated plasma volume). Whole blood clearance of HSV-2 in the first 6 hours of treatment was 6.64 mL/min (4.98-12.92 mL/min). Despite much lower baseline viremia, clearance of EBV was higher 36.62 mL/min (22.67-53.48 mL/min). CONCLUSIONS: TPE was able to remove circulating HSV-2 copies by 25% and EBV copies by 40% from the blood. On the other hand, clearance of HSV-2 by Seraph was clinically irrelevant, but Seraph seemed to be far more effective of removing EBV, implicating a possible use in EBV-associated pathologies, but this requires further study.

How to Synchronize Longitudinal Patient Data With the Underlying Disease Progression: A Pilot Study Using the Biomarker CRP for Timing COVID-19.

The continued digitalization of medicine has led to an increased availability of longitudinal patient data that allows the investigation of novel and known diseases in unprecedented detail. However, to accurately describe any underlying pathophysiology and allow inter-patient comparisons, individual patient trajectories have to be synchronized based on temporal markers. In this pilot study, we use longitudinal data from critically ill ICU COVID-19 patients to compare the commonly used alignment markers "onset of symptoms," "hospital admission," and "ICU admission" with a novel objective method based on the peak value of the inflammatory marker C-reactive protein (CRP). By applying our CRP-based method to align the progression of neutrophils and lymphocytes, we were able to define a pathophysiological window that improved mortality risk stratification in our COVID-19 patient cohort. Our data highlights that proper synchronization of longitudinal patient data is crucial for accurate interpatient comparisons and the definition of relevant subgroups. The use of objective temporal disease markers will facilitate both translational research efforts and multicenter trials.

Liver Transplantation because of Acute Liver Failure due to Heme Arginate Overdose in a Patient with Acute Intermittent Porphyria.

In acute attacks of acute intermittent porphyria, the mainstay of treatment is glucose and heme arginate administration. We present the case of a 58-year-old patient with acute liver failure requiring urgent liver transplantation after erroneous 6-fold overdose of heme arginate during an acute attack. As recommended in the product information, albumin and charcoal were administered and hemodiafiltration was started, which could not prevent acute liver failure, requiring super-urgent liver transplantation after 6 days. The explanted liver showed no preexisting liver cirrhosis, but signs of subacute liver injury and starting regeneration. The patient recovered within a short time. A literature review revealed four poorly documented cases of potential hepatic and/or renal toxicity of hematin or heme arginate. This is the first published case report of acute liver failure requiring super-urgent liver transplantation after accidental heme arginate overdose. The literature and recommendations in case of heme arginate overdose are summarized. Knowledge of a potentially fatal course is important for the management of future cases. If acute liver failure in case of heme arginate overdose is progressive, super-urgent liver transplantation has to be evaluated.

Pulse-pressure variation and hemodynamic response in patients with elevated pulmonary artery pressure: a clinical study.

INTRODUCTION: Pulse-pressure variation (PPV) due to increased right ventricular afterload and dysfunction may misleadingly suggest volume responsiveness. We aimed to assess prediction of volume responsiveness with PPV in patients with increased pulmonary artery pressure. METHODS: Fifteen cardiac surgery patients with a history of increased pulmonary artery pressure (mean pressure, 27 +/- 5 mm Hg (mean +/- SD) before fluid challenges) and seven septic shock patients (mean pulmonary artery pressure, 33 +/- 10 mm Hg) were challenged with 200 ml hydroxyethyl starch boli ordered on clinical indication. PPV, right ventricular ejection fraction (EF) and end-diastolic volume (EDV), stroke volume (SV), and intravascular pressures were measured before and after volume challenges. RESULTS: Of 69 fluid challenges, 19 (28%) increased SV > 10%. PPV did not predict volume responsiveness (area under the receiver operating characteristic curve, 0.555; P = 0.485). PPV was >or=13% before 46 (67%) fluid challenges, and SV increased in 13 (28%). Right ventricular EF decreased in none of the fluid challenges, resulting in increased SV, and in 44% of those in which SV did not increase (P = 0.0003). EDV increased in 28% of fluid challenges, resulting in increased SV, and in 44% of those in which SV did not increase (P = 0.272). CONCLUSIONS: Both early after cardiac surgery and in septic shock, patients with increased pulmonary artery pressure respond poorly to fluid administration. Under these conditions, PPV cannot be used to predict fluid responsiveness. The frequent reduction in right ventricular EF when SV did not increase suggests that right ventricular dysfunction contributed to the poor response to fluids.

When drugs disappear from the patient: elimination of intravenous medication by hemodiafiltration.

Twenty-three hours after heart transplantation, life-threatening acute right heart failure was diagnosed in a patient requiring continuous venovenous hemodiafiltration (CVVHDF). Increasing doses of catecholamines, sedatives, and muscle relaxants administered through a central venous catheter were ineffective. However, a bolus of epinephrine injected through an alternative catheter provoked a hypertensive crisis. Thus, interference with the central venous infusion by the dialysis catheter was suspected. The catheters were changed, and hemodynamics stabilized at lower catecholamine doses. When the effects of IV drugs are inadequate in patients receiving CVVHDF, interference with adjacent catheters resulting in elimination of the drug by CVVHDF should be suspected.

Inverse thermodilution with conventional pulmonary artery catheters for the assessment of cerebral, hepatic, renal, and femoral blood flow.

Assessment of regional blood flow changes is difficult in the clinical setting. We tested whether conventional pulmonary artery catheters (PACs) can be used to measure regional venous blood flows by inverse thermodilution (ITD). Inverse thermodilution was tested in vitro and in vivo using perivascular ultrasound Doppler (USD) flow probes as a reference. In anesthetized pigs, PACs were inserted in jugular, hepatic, renal, and femoral veins, and their measurements were compared with simultaneous USD flow measurements from carotid, hepatic, renal, and femoral arteries and from portal vein. Fluid boluses were injected through the PAC's distal port, and temperature changes were recorded from the proximally located thermistor. Injectates of 2 and 5 mL at 22 degrees C and 4 degrees C were used. Flows were altered by using a roller pump (in vitro), and infusion of dobutamine and induction of cardiac tamponade, respectively. In vitro: At blood flows between 400 mL . min-1 and 700 mL . min-1 (n = 50), ITD and USD correlated well (r = 0.86, P < 0.0001), with bias and limits of agreement of 3 +/- 101 mL . min-1. In vivo: 514 pairs of measurements had to be excluded from analysis for technical reasons, and 976 were analyzed. Best correlations were r = 0.87 (P < 0.0001) for renal flow and r = 0.46 (P < 0.0001) for hepatic flow. No significant correlation was found for cerebral and femoral flows. Inverse thermodilution using conventional PAC compared moderately well with USD for renal but not for other flows despite good in vitro correlation in various conditions. In addition, this method has significant technical limitations.