Comparative Study of Acute Kidney Injury in Liver Transplantation: Donation after Circulatory Death versus Brain Death

BACKGROUND Acute kidney injury (AKI) after orthotopic liver transplantation (OLT) contributes to morbidity and mortality. Donation after circulatory death (DCD) has been established to increase the pool of organs. While surgical complications are reported to be comparable in DCD and donation after brain death (DBD) OLT, there is a knowledge gap concerning adverse kidney events in these 2 groups. MATERIAL AND METHODS In this retrospective cohort study, 154 patients received a DBD and 68 received a DCD organ (2016-2020). The primary outcome was a major adverse kidney event within 30 days (MAKE-30). The secondary outcome was dynamics of AKI and kidney replacement therapy (KRT) during the first postoperative week and on postoperative day 30. Incidence and resolution from AKI and KRT and patient survival (PS) 30 days after OLT were compared between the DCD and DBD recipients. RESULTS MAKE-30 incidence after OLT was comparable in DCD (n=27, 40%) vs DBD (n=41, 27%) recipients (risk ratio 1.49 [95% CI 1.01, 2.21], p=0.073). AKI incidence was comparable in DCD (n=58, 94%) vs DBD (n=95, 82%) recipients (risk ratio 1.14 [95% CI: 1.03, 1.27], P=0.057). Overall, 40% (n=88) of patients required KRT, with no difference between DCD (n=27, 40%) vs DBD (n=61, 40%) recipients (risk ratio 1.00 [95% CI 0.71, 1.43], P>0.999). Resolution of AKI by day 30 was lower in DCD (n=29, 50%) than in DBD (n=66, 69%) recipients (risk ratio 0.71 [95% CI: 0.53, 0.95], P=0.032). Survival after 30 days (DCD: n=64, 94% vs DBD: n=146, 95%, risk ratio 0.99 [95% CI 0.93, 1.06], P>0.999) was also comparable. CONCLUSIONS MAKE-30, short-term renal outcome, and survival did not significantly differ between DBD and DCD-OLT. Resolution of AKI by day 30 was lower in DCD than in DBD recipients

Renal Tubular Acidosis in Pregnant Critically Ill COVID-19 Patients: A Secondary Analysis of a Prospective Cohort

Background: Renal tubular acidosis (RTA) is an extremely rare cause of metabolic acidosis (10 in 100,000). RTA has been linked neither to pregnancy nor to severe coronavirus disease 2019 (COVID-19). The purpose of this study was to analyze the prevalence and clinical course of normal anion gap metabolic acidosis in critically ill pregnant COVID-19 patients and to compare them to an age-matched nonpregnant female patient cohort. Methods: Secondary analysis was conducted on a prospective observational cohort of critically ill patients suffering from COVID-19 consecutively admitted to a tertiary intensive care unit (ICU) between February 2020 and April 2021. Results: A total of 321 COVID-19 patients required admission to the ICU; 95 (30%) were female, and 18 (19%) were of childbearing age. Seven of eight (88%) pregnant women (all in the last trimester) required advanced respiratory support due to COVID-19. The estimated glomerular filtration rate was 135 (123–158) mL/min/m$^{2}$ body surface area, and six pregnant women (86%) were diagnosed with a normal, respiratory compensated, anion gap metabolic acidosis (pH$_{min}$ 7.3 (7.18–7.31), HCO3−$_{min}$ 14.8 (12.8–18.6) mmol/L, and paCO2 3.4 (3.3–4.5) kPa). Three (43%) acidotic pregnant women fulfilled diagnostic criteria for RTA. All women recovered spontaneously within less 7 days. Conclusions: Metabolic acidosis seems to be very common (85%) in pregnant critically ill COVID-19 patients, and the prevalence of RTA might be higher than normal. It remains to be demonstrated if this observation is an indirect epiphenomenon or due to a direct viral effect on the tubular epithelium

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

OBJECTIVES 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 × e$^{11}$ HSV-2 copies and 2.11 × e$^{6}$ 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

EXCHANGE-2: investigating the efficacy of add-on plasma exchange as an adjunctive strategy against septic shock—a study protocol for a randomized, prospective, multicenter, open-label, controlled, parallel-group trial

Background Sepsis is as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. The mortality of sepsis and particular of septic shock is very high. Treatment mostly focuses on infection control but a specific intervention that targets the underlying pathological host response is lacking to the present time. The investigators hypothesize that early therapeutic plasma exchange (TPE) will dampen the maladaptive host response by removing injurious mediators thereby limiting organ dysfunction and improving survival in patients with septic shock. Although small prospective studies demonstrated rapid hemodynamic stabilization under TPE, no adequately powered randomized clinical trial has investigated hard outcomes. Methods This is a randomized, prospective, multicenter, open-label, controlled, parallel-group interventional trial to test the adjunctive effect of TPE in patients with early septic shock. Patients with a refractory (defined as norepinephrine (NE) ≥ 0.4 μg/kg/min ≥ 30 min OR NE 0.3 μg/kg/min + vasopressin) and early (shock onset < 24 h) septic shock will be included. The intervention is a standard TPE with donor fresh frozen plasma (1.2 × individual plasma volume) performed within 6 h after randomization and will be compared to a standard of care (SOC) control arm. The primary endpoint is 28 days mortality for which the power analysis revealed a group size of 137 / arm (n = 274) to demonstrate a benefit of 15%. The key secondary objective will be to compare the extent of organ failure indicated by mean SOFA over the first 7 days as well as organ support-free days until day 28 following randomization. Besides numerous biological secondary, safety endpoints such as incidence of bleeding, allergic reactions, transfusion associated lung injury, severe thrombocytopenia, and other severe adverse events will be assessed during the first 7 days. For exploratory scientific analyses, biomaterial will be acquired longitudinally and multiple predefined scientific subprojects are planned. This study is an investigator-initiated trial supported by the German Research Foundation (DFG, DA 1209/7–1), in which 26 different centers in Germany, Switzerland, and Austria will participate over a duration of 33 months. Discussion This trial has substantial clinical relevance as it evaluates a promising adjunctive treatment option in refractory septic shock patients suffering from an extraordinary high mortality. A positive trial result could change the current standard of care for this septic subgroup. The results of this study will be disseminated through presentations at international congresses, workshops, and peer-reviewed publications. Trial registration ClinicalTrials.gov NCT05726825, Registered on 14 February 2023

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

Die Hyperammonämie ist ein lebensbedrohliches Krankheitsbild, dessen Prognose von einer raschen Senkung des Ammoniaks abhängt. Ist eine hepatische Ursache ausgeschlossen, ist die Differenzialdiagnose breit und umfasst auch im Erwachsenenalter hereditäre Stoffwechselerkrankungen. Hier beschreiben wir den Fall einer 25-jährigen Patientin mit einer schweren, therapierefraktären Hyperammonämie und betonen die Relevanz der extrakorporalen Elimination des Ammoniaks

Donor-derived fulminant herpes simplex virus hepatitis after liver transplantation: Two cases and review of literature

BACKGROUND Fulminant herpetic hepatitis due to herpes simplex virus (HSV), serotype 1 or 2, is a rare but often fatal complication after solid organ transplantation (SOT). HSV hepatitis in SOT recipients can occur either due to primary infection acquired post transplantation, viral reactivation in a seropositive patient, or as donor-derived infection. Cases of fatal hepatitis have been reported in the liver as well as in other SOT recipients. The fatal outcome is mostly due to delayed diagnosis and treatment, which is explained by the lack of clinical specificity of HSV hepatitis. METHODS We report two cases of fatal donor-derived HSV hepatitis in liver-transplanted recipients. We reviewed all published cases of donor-derived HSV infections after SOT with an evaluation of the presence of prophylaxis and outcome. RESULTS In both liver recipients, the retrospective determination of HSV serostatus was negative, and both cases occurred in the absence of cytomegalovirus or HSV prophylaxis. A review of the literature showed a significant series of cases of severe hepatitis, mostly fatal, as well as the absence of specific preventive therapy guidelines in cases of HSV serology mismatch. CONCLUSIONS The occurrence of two fatal donor-derived hepatitis made the Swiss Transplant Infectious Diseases working group modify its national recommendations regarding pretransplant serostatus determination and HSV prophylaxis after liver transplantation. Further studies are needed to assess this approach

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

ObjectiveVeno-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.DesignMulticenter, retrospective analysis between January 2008 and September 2021.SettingThree tertiary care ECMO centers in Germany (Hannover, Bonn) and Switzerland (Zurich).PatientsSeventy-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 resultsFifty-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 &gt; 14 and higher lactate concentrations at the day of V-VA upgrade were independent predictors of mortality in the multivariate regression analysis.ConclusionIn 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 &gt; 14 and elevated lactate levels at the day of V-VA upgrade predict unfavorable outcome

Carboxyhemoglobin predicts oxygenator performance and imminent oxygenator change in extracorporeal membrane oxygenation

Background The continuous exposure of blood to a non-biological surface during extracorporeal membrane oxygenation (ECMO) may lead to progressive thrombus formation in the oxygenator, hemolysis and consequently impaired gas exchange. In most centers oxygenator performance is monitored only on a once daily basis. Carboxyhemoglobin (COHb) is generated upon red cell lysis and is routinely measured with any co-oximetry performed to surveille gas exchange and acid–base homeostasis every couple of hours. This retrospective cohort study aims to evaluate COHb in the arterial blood gas as a novel marker of oxygenator dysfunction and its predictive value for imminent oxygenator change. Results Out of the 484 screened patients on ECMO 89, cumulatively requiring 116 oxygenator changes within 1833 patient days, including 19,692 arterial COHb measurements were analyzed. Higher COHb levels were associated with lower post-oxygenator pO$_{2}$ (estimate for log(COHb): − 2.176 [95% CI − 2.927, − 1.427], p < 0.0001) and with a shorter time to oxygenator change (estimate for log(COHb): − 67.895 [95% CI − 74.209, − 61.542] hours, p < 0.0001). COHb was predictive of oxygenator change within 6 h (estimate for log(COHb): 5.027 [95% CI 1.670, 15.126], p = 0.004). Conclusion COHb correlates with oxygenator performance and can be predictive of imminent oxygenator change. Therefore, longitudinal measurements of COHb in clinical routine might be a cheap and more granular candidate for ECMO surveillance that should be further analyzed in a controlled prospective trial design