Ulcerating Ileocolitis in Severe Amatoxin Poisoning

Amatoxin poisoning is still associated with a great potential for complications and a high mortality. While the occurrence of acute gastroenteritis within the first 24 hours after amatoxin ingestion is well described, only very few descriptions of late gastrointestinal complications of amatoxin poisoning exist worldwide. We present the case of a 57-year-old female patient with severe amatoxin poisoning causing fulminant but reversible hepatic failure that on day 8 after mushroom ingestion developed severe abdominal pain and watery diarrhea. Ulcerating ileocolitis was identified by computed tomography identifying a thickening of the bowel wall of the entire ileum and biopsies taken from the ileum and large bowel revealing distinct ileitis and proximally accentuated colitis. The absence of discernible alternative etiologies such as infectious agents makes a causal relationship between the ulcerating ileocolitis and the amatoxin poisoning likely. Diarrhea and varying abdominal pain persisted over several weeks and clinical follow-up after six months showed a completely symptom-free patient. The case presented highlights the importance to consider the possibility of rare complications of Amanita intoxication in order to be able to respond to them early and adequately

Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema

Introduction. Acute exposure to high altitude induces inflammation. However, the relationship between inflammation and high altitude related illness such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) is poorly understood. We tested if soluble urokinase-type plasminogen activator receptor (suPAR) plasma concentration, a prognostic factor for cardiovascular disease and marker for low grade activation of leukocytes, will predict susceptibility to HAPE and AMS. Methods. 41 healthy mountaineers were examined at sea level (SL, 446 m) and 24 h after rapid ascent to 4559 m (HA). 24/41 subjects had a history of HAPE and were thus considered HAPE-susceptible (HAPE-s). Out of the latter, 10/24 HAPE-s subjects were randomly chosen to suppress the inflammatory cascade with dexamethasone 8 mg bid 24 h prior to ascent. Results. Acute hypoxic exposure led to an acute inflammatory reaction represented by an increase in suPAR (1.9 ± 0.4 at SL versus 2.3 ± 0.5 at HA, p < 0.01), CRP (0.7 ± 0.5 at SL versus 3.6 ± 4.6 at HA, p < 0.01), and IL-6 (0.8 ± 0.4 at SL versus 3.3 ± 4.9 at HA, p < 0.01) in all subjects except those receiving dexamethasone. The ascent associated decrease in PaO2 correlated with the increase in IL-6 (r = 0.46, p < 0.001), but not suPAR (r = 0.27, p = 0.08); the increase in IL-6 was not correlated with suPAR (r = 0.16, p = 0.24). Baseline suPAR plasma concentration was higher in the HAPE-s group (2.0 ± 0.4 versus 1.8 ± 0.4, p = 0.04); no difference was found for CRP and IL-6 and for subjects developing AMS. Conclusion. High altitude exposure leads to an increase in suPAR plasma concentration, with the missing correlation between suPAR and IL-6 suggesting a cytokine independent, leukocyte mediated mechanism of low grade inflammation. The correlation between IL-6 and PaO2 suggests a direct effect of hypoxia, which is not the case for suPAR. However, suPAR plasma concentration measured before hypoxic exposure may predict HAPE susceptibility

Increased Longevity of a Novel Gas Exchanger System for Low-Flow Veno-Venous Extracorporeal CO2 Removal in Acute Hypercapnic Respiratory Failure

Introduction: Low-flow veno-venous extracorporeal CO2 removal (ECCO2R) is an adjunctive therapy to support lung protective ventilation or maintain spontaneous breathing in hypercapnic respiratory failure. Low-flow ECCO2R is less invasive compared to higher flow systems, while potentially compromising efficiency and membrane lifetime. To counteract this shortcoming, a high-longevity system has recently been developed. Our hypotheses were that the novel membrane system provides runtimes up to 120 h, and CO2 removal remains constant throughout membrane system lifetime. Methods: Seventy patients with pH ≤ 7.25 and/or PaCO2 ≥9 kPa exceeding lung protective ventilation limits, or experiencing respiratory exhaustion during spontaneous breathing, were treated with the high-longevity ProLUNG system or in a control group using the original gas exchanger. Treatment parameters, gas exchanger runtime, and sweep-gas VCO2 were recorded across 9,806 treatment-hours and retrospectively analyzed. Results: 25/33 and 23/37 patients were mechanically ventilated as opposed to awake spontaneously breathing in both groups. The high-longevity system increased gas exchanger runtime from 29 ± 16 to 48 ± 36 h in ventilated and from 22 ± 14 to 31 ± 31 h in awake patients (p < 0.0001), with longer runtime in the former (p < 0.01). VCO2 remained constant at 86 ± 34 mL/min (p = 0.11). Overall, PaCO2 decreased from 9.1 ± 2.0 to 7.9 ± 1.9 kPa within 1 h (p < 0.001). Tidal volume could be maintained at 5.4 ± 1.8 versus 5.7 ± 2.2 mL/kg at 120 h (p = 0.60), and peak airway pressure could be reduced from 31.1 ± 5.1 to 27.5 ± 6.8 mbar (p < 0.01). Conclusion: Using a high-longevity gas exchanger system, membrane lifetime in low-flow ECCO2R could be extended in comparison to previous systems but remained below 120 h, especially in spontaneously breathing patients. Extracorporeal VCO2 remained constant throughout gas exchanger system runtime and was consistent with removal of approximately 50% of expected CO2 production, enabling lung protective ventilation despite hypercapnic respiratory failure

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry

Background: It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. Methods: Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. Results: Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. Conclusion: Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic. Keywords: ARDS; COVID-19; Disease dynamics; Intensive care unit; Pandemic

Ulcerating Ileocolitis in Severe Amatoxin Poisoning

Amatoxin poisoning is still associated with a great potential for complications and a high mortality. While the occurrence of acute gastroenteritis within the first 24 hours after amatoxin ingestion is well described, only very few descriptions of late gastrointestinal complications of amatoxin poisoning exist worldwide. We present the case of a 57-year-old female patient with severe amatoxin poisoning causing fulminant but reversible hepatic failure that on day 8 after mushroom ingestion developed severe abdominal pain and watery diarrhea. Ulcerating ileocolitis was identified by computed tomography identifying a thickening of the bowel wall of the entire ileum and biopsies taken from the ileum and large bowel revealing distinct ileitis and proximally accentuated colitis. The absence of discernible alternative etiologies such as infectious agents makes a causal relationship between the ulcerating ileocolitis and the amatoxin poisoning likely. Diarrhea and varying abdominal pain persisted over several weeks and clinical follow-up after six months showed a completely symptom-free patient. The case presented highlights the importance to consider the possibility of rare complications of Amanita intoxication in order to be able to respond to them early and adequately

Effects of enhanced adsorption haemofiltration versus haemoadsorption in severe, refractory septic shock with high levels of endotoxemia: the ENDoX bicentric, randomized, controlled trial

Background Endotoxin adsorption is a promising but controversial therapy in severe, refractory septic shock and conflicting results exist on the effective capacity of available devices to reduce circulating endotoxin and inflammatory cytokine levels. Methods Multiarm, randomized, controlled trial in two Swiss intensive care units, with a 1:1:1 randomization of patients suffering severe, refractory septic shock with high levels of endotoxemia, defined as an endotoxin activity ≥ 0.6, a vasopressor dependency index ≥ 3, volume resuscitation of at least 30 ml/kg/24 h and at least single organ failure, to a haemoadsorption (Toraymyxin), an enhanced adsorption haemofiltration (oXiris) or a control intervention. Primary endpoint was the difference in endotoxin activity at 72-h post-intervention to baseline. In addition, inflammatory cytokine, vasopressor dependency index and SOFA-Score dynamics over the initial 72 h were assessed inter alia. Results In the 30, out of 437 screened, randomized patients (10 Standard of care, 10 oXiris, 10 Toraymyxin), endotoxin reduction at 72-h post-intervention-start did not differ among interventions (Standard of Care: 12 [1–42]%, oXiris: 21 [10–51]%, Toraymyxin: 23 [10–36]%, p = 0.82). Furthermore, no difference between groups could be observed neither for reduction of inflammatory cytokine levels (p = 0.58), nor for vasopressor weaning (p = 0.95) or reversal of organ injury (p = 0.22). Conclusions In a highly endotoxemic, severe, refractory septic shock population neither the Toraymyxin adsorber nor the oXiris membrane could show a reduction in circulating endotoxin or cytokine levels over standard of care