Pubblicazioni - Bottiroli Dott. Maurizio
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Early intra-aortic balloon pump in acute decompensated heart failure complicated by cardiogenic shock: Rationale and design of the randomized Altshock-2 trial.
Am Heart J2020 Dec;233():39-47. doi: S0002-8703(20)30399-9.
Morici Nuccia, Marini Claudia, Sacco Alice, Tavazzi Guido, Cipriani Manlio, Oliva Fabrizio, Rota Matteo, De Ferrari Gaetano Maria, Campolo Jonica, Frigerio Gianfranco, Valente Serafina, Leonardi Sergio, Corrada Elena, Bottiroli Maurizio, Grosseto Daniele, Cacciavillani Luisa, Frigerio Maria, Pappalardo Federico,
Abstract
BACKGROUND:
Cardiogenic shock (CS) is a systemic disorder associated with dismal short-term prognosis. Given its time-dependent nature, mechanical circulatory support may improve survival. Intra-aortic balloon pump (IABP) had gained widespread use because of the easiness to implant and the low rate of complications; however, a randomized trial failed to demonstrate benefit on mortality in the setting of acute myocardial infarction. Acute decompensated heart failure with cardiogenic shock (ADHF-CS) represents a growing resource-intensive scenario with scant data and indications on the best management. However, a few data suggest a potential benefit of IABP in this setting. We present the design of a study aimed at addressing this research gap.
METHODS AND DESIGN:
The Altshock-2 trial is a prospective, randomized, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients with ADHF-CS will be randomized to early IABP implantation or to vasoactive treatments. The primary end point will be 60 days patients' survival or successful bridge to heart replacement therapy. The key secondary end point will be 60-day overall survival; 60-day need for renal replacement therapy; in-hospital maximum inotropic score, maximum duration of inotropic/vasopressor therapy, and maximum sequential organ failure assessment score. Safety end points will be in-hospital occurrence of bleeding events (Bleeding Academic Research Consortium >3), vascular access complications and systemic (noncerebral) embolism. The sample size for the study is 200 patients.
IMPLICATIONS:
The Altshock-2 trial will provide evidence on whether IABP should be implanted early in ADHF-CS patients to improve their clinical outcomes.
Copyright © 2020 Elsevier Inc. All rights reserved.
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Takotsubo syndrome as a complication in a critically ill COVID-19 patient.
ESC Heart Fail2020 Sep;():. doi: 10.1002/ehf2.12912.
Bottiroli Maurizio, De Caria Daniele, Belli Oriana, Calini Angelo, Andreoni Patrizia, Siragusa Antonio, Moreo Antonella, Ammirati Enrico, Mondino Michele, Fumagalli Roberto
Abstract
Coronavirus disease 2019 (COVID-19) patients with cardiac injury have an increased risk of mortality. It remains to be determined the mechanism of cardiac injury and the identification of specific conditions that affect the heart during COVID-19. We present the case of a 76-year-old woman with COVID-19 pneumonia that developed a takotsubo syndrome (TTS). Although the patient presented normal left ventricular ejection fraction and normal levels of troponin on admission, after 16 days in intensive care unit due to respiratory distress, she suddenly developed cardiogenic shock. Shock occurred few hours after a spontaneous breathing trial through her tracheostomy. Bed-side echocardiographic revealed apical ballooning promptly supporting the diagnosis of TTS. She was successfully treated with deep sedation and low dosage of epinephrine. The relevance of this case is that TTS can occur in the late phase of COVID-19. Awareness of late TTS and bed-side echocardiographic evaluation can lead to prompt identification and treatment.
© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
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High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in ARDS with Class III Obesity.
Am J Respir Crit Care Med2020 Sep;():. doi: 10.1164/rccm.201909-1687OC.
De Santis Santiago Roberta, Teggia Droghi Maddalena, Fumagalli Jacopo, Marrazzo Francesco, Florio Gaetano, Grassi Luigi G, Gomes Susimeire, Morais Caio C A, Ramos Ozires P S, Bottiroli Maurizio, Pinciroli Riccardo, Imber David A, Bagchi Aranya, Shelton Kenneth, Sonny Abraham, Bittner Edward A, Amato Marcelo B P, Kacmarek Robert M, Berra Lorenzo,
Abstract
Obesity is characterized by elevated pleural pressure (P) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). To determine the effects of lung recruitment maneuver (LRM) in the presence of elevated P on hemodynamics, left and right ventricular pressures and pulmonary vascular resistance. We hypothesized that elevated P protects the cardiovascular system against high airway pressures and prevents lung overdistension. First, an interventional crossover trial in adult subjects with ARDS and BMI ?35 kg/m (n=21) was performed to explore the hemodynamic consequences of LRM. Second, cardiovascular function was studied during low/high PEEPs in a model of swine with ARDS and high P (n=9) versus healthy swine with normal P (n=6). Subjects with ARDS and obesity (BMI=57±12 kg/m), following LRM, required an increase in PEEP of 8[7, 10] cmHO above traditional ARDSnet settings to improve lung function, oxygenation and ventilation/perfusion matching, without impairment of hemodynamics or right heart function. ARDS swine with high P demonstrated unchanged transmural left ventricle pressure and systemic blood pressure after LRM protocol. Pulmonary artery hypertension decreased 8[13, 4] mmHg, as did vascular resistance 1.5[2.2, 0.9] WU, and transmural right ventricle pressure 10[15, 6] mmHg during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized ventilation/perfusion ratio. High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. Additionally, patients with ARDS and class III obesity tolerate hemodynamically LRM with high airway pressure.
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Safety and efficacy of anti-il6-receptor tocilizumab use in severe and critical patients affected by coronavirus disease 2019: A comparative analysis.
J Infect2020 10;81(4):e11-e17. doi: S0163-4453(20)30467-9.
Rossotti Roberto, Travi Giovanna, Ughi Nicola, Corradin Matteo, Baiguera Chiara, Fumagalli Roberto, Bottiroli Maurizio, Mondino Michele, Merli Marco, Bellone Andrea, Basile Andriano, Ruggeri Ruggero, Colombo Fabrizio, Moreno Mauro, Pastori Stefano, Perno Carlo Federico, Tarsia Paolo, Epis Oscar Massimiliano, Puoti Massimo,
Abstract
BACKGROUND:
As the novel SARS-CoV-2 pandemic occurred, no specific treatment was yet available. Inflammatory response secondary to viral infection might be the driver of severe diseases. We report the safety and efficacy (in terms of overall survival and hospital discharge) of the anti-IL6 tocilizumab (TCZ) in subjects with COVID-19.
METHODS:
This retrospective, single-center analysis included all the patients consecutively admitted to our Hospital with severe or critical COVID-19 who started TCZ treatment from March 13th to April 03rd, 2020. A 1:2 matching to patients not treated with TCZ was performed according to age, sex, severity of disease, P/F, Charlson Comorbidity Index and length of time between symptoms onset and hospital admittance. Descriptive statistics and non-parametric tests to compare the groups were applied. Kaplan Meier probability curves and Cox regression models for survival, hospital discharge and orotracheal intubation were used.
RESULTS:
Seventy-four patients treated with TCZ were matched with 148 matched controls. They were mainly males (81.5%), Caucasian (82.0%) and with a median age of 59 years. The majority (69.8%) showed critical stage COVID-19 disease. TCZ use was associated with a better overall survival (HR 0.499 [95% CI 0.262-0.952], p?=?0.035) compared to controls but with a longer hospital stay (HR 1.658 [95% CI 1.088-2.524], p?=?0.019) mainly due to biochemical, respiratory and infectious adverse events.
DISCUSSION:
TCZ use resulted potentially effective on COVID-19 in terms of overall survival. Caution is warranted given the potential occurrence of adverse events.
FINANCIAL SUPPORT:
Some of the tocilizumab doses used in the subjects included in this analysis were provided by the "Multicenter study on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia" (EudraCT Number: 2020-001110-38) supported by the Italian National Agency for Drugs (AIFA). No specific funding support was planned for study design, data collection and analysis and manuscript writing of this paper.
Copyright © 2020. Published by Elsevier Ltd.
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Role of von Willebrand Factor and ADAMTS-13 in the Pathogenesis of Thrombi in SARS-CoV-2 Infection: Time to Rethink.
Thromb Haemost2020 09;120(9):1339-1342. doi: 10.1055/s-0040-1713400.
Morici Nuccia, Bottiroli Maurizio, Fumagalli Roberto, Marini Claudia, Cattaneo Marco
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[Platypnea-orthodeoxia syndrome associated with patent foramen ovale and aortic root aneurysm].
G Ital Cardiol (Rome)2020 Jul;21(7):562-563. doi: 10.1714/3386.33646.
Bottiroli Maurizio, Vignati Gabriele, Cannata Aldo, Colombo Jacopo, Pinciroli Riccardo, Mondino Michele
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Update on acute myocarditis.
Trends Cardiovasc Med2020 Jun;():. doi: S1050-1738(20)30079-7.
Ammirati Enrico, Veronese Giacomo, Bottiroli Maurizio, Wang Dao Wen, Cipriani Manlio, Garascia Andrea, Pedrotti Patrizia, Adler Eric D, Frigerio Maria
Abstract
Acute myocarditis (AM), a recent-onset inflammation of the heart, has heterogeneous clinical presentations, varying from minor symptoms to high-risk cardiac conditions with severe heart failure, refractory arrhythmias, and cardiogenic shock. AM is moving from being a definitive diagnosis based on histological evidence of inflammatory infiltrates on cardiac tissue to a working diagnosis supported by high sensitivity troponin increase in association with specific cardiac magnetic resonance imaging (CMRI) findings. Though experts still diverge between those advocating for histological definition versus those supporting a mainly clinical definition of myocarditis, in the real-world practice the diagnosis of AM has undoubtedly shifted from being mainly biopsy-based to solely CMRI-based in most of clinical scenarios. It is thus important to clearly define selected settings where EMB is a must, as information derived from histology is essential for an optimal management. As in other medical conditions, a risk-based approach should be promoted in order to identify the most severe AM cases requiring appropriate bundles of care, including early recognition, transfer to tertiary centers, aggressive circulatory supports with inotropes and mechanical devices, histologic confirmation and eventual immunosuppressive therapy. Despite improvements in recognition and treatment of AM, including a broader use of promising mechanical circulatory supports, severe forms of AM are still burdened by dismal outcomes. This review is focused on recent clinical studies and registries that shed new insights on AM. Attention will be paid to contemporary outcomes and predictors of prognosis, the emerging entity of immune checkpoint inhibitors-associated myocarditis, updated CMRI diagnostic criteria, new data on the use of temporary mechanical circulatory supports in fulminant myocarditis. The role of viruses as etiologic agents will be reviewed and a brief update on pediatric AM is also provided. Finally, we summarize a risk-based approach to AM, based on available evidence and clinical experience.
Copyright © 2020. Published by Elsevier Inc.
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Fulminant myocarditis triggered by OC43 subtype coronavirus: a disease deserving evidence-based care bundles.
J Cardiovasc Med (Hagerstown)2020 07;21(7):529-531. doi: 10.2459/JCM.0000000000000989.
Veronese Giacomo, Cipriani Manlio, Bottiroli Maurizio, Garascia Andrea, Mondino Michele, Pedrotti Patrizia, Pini Daniela, Cozzi Ottavia, Messina Antonio, Droandi Ginevra, Petrella Duccio, Frigerio Maria, Ammirati Enrico
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Successful recovery from severe COVID-19 pneumonia after kidney transplantation: The interplay between immunosuppression and novel therapy including tocilizumab.
Transpl Infect Dis2020 Oct;22(5):e13334. doi: 10.1111/tid.13334.
Lauterio Andrea, Valsecchi Mila, Santambrogio Sara, De Carlis Riccardo, Merli Marco, Calini Angelo, Centonze Leonardo, Buscemi Vincenzo, Bottiroli Maurizio, Puoti Massimo, Fumagalli Roberto, De Carlis Luciano
Abstract
Although immunosuppressed patients may be more prone to SARS-CoV-2 infection with atypical presentation, long-term immunosuppression therapy may provide some sort of protection for severe clinical complications of COVID-19. The interaction between immunosuppression and new antiviral drugs in the treatment of transplanted patients contracting COVID-19 has not yet been fully investigated. Moreover, data regarding the optimal management of these patients are still very limited. We report a case of the successful recovery from severe COVID-19 of a kidney-transplanted patient treated with hydroxychloroquine, lopinavir/ritonavir, steroid, and tocilizumab.
© 2020 Wiley Periodicals LLC.
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Endotoxin Activity Assay for the Detection of Whole Blood Endotoxemia in Critically Ill Patients.
J Vis Exp2019 06;(148):. doi: 10.3791/58507.
Pinciroli Riccardo, Checchi Simone, Bottiroli Maurizio, Monti Gianpaola, Casella Giampaolo, Fumagalli Roberto
Abstract
Lipopolysaccharide, also known as endotoxin, is a fundamental component of gram-negative bacteria and plays a crucial role in the development of sepsis and septic shock. The early identification of an infectious process that is rapidly evolving to a critical illness might prompt a quicker and more intensive treatment, thereby potentially leading to better patient outcomes. The Endotoxin Activity (EA) assay can be used at the bedside as a reliable biomarker of systemic endotoxemia. The detection of elevated endotoxin activity levels has been repeatedly shown to be associated with an increased disease severity in patients with sepsis and septic shock. The assay is quick and easy to perform. Briefly, after sampling, an aliquot of whole blood is mixed with an anti-endotoxin antibody and with added LPS. Endotoxin activity is measured as the relative oxidative burst of primed neutrophils as detected by chemioluminescence. The assay's output is expressed on a scale from 0 (absent) to 1 (maximal) and categorized as "low" (<0.4 units), "intermediate" (0.4-0.59 units), or "high" (?0.6 units). The detailed methodology and rationale for the implementation of the EA assay are reported in this manuscript.
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Cardiogenic shock: old and new circulatory assist devices: the role of counter-pulsation.
Eur Heart J Suppl2019 Mar;21(Suppl B):B59-B60. doi: 10.1093/eurheartj/suz020.
Viola Giovanna, Morici Nuccia, Sacco Alice, Stucchi Miriam, Brunelli Dario, Cipriani Manlio, Garascia Andrea, Bottiroli Maurizio, Frigerio Maria, Oliva Fabrizio
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Major contraindication to the endotoxemia activity assay in septic shock patients - Authors' reply.
J Crit Care2018 02;43():382-383. doi: S0883-9441(17)31371-0.
Bottiroli Maurizio, Pinciroli Riccardo, Monti Gianpaola, Casella Giampaolo, Fumagalli Roberto
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Survival and Left Ventricular Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis.
Circulation2017 Aug;136(6):529-545. doi: 10.1161/CIRCULATIONAHA.117.026386.
Ammirati Enrico, Cipriani Manlio, Lilliu Marzia, Sormani Paola, Varrenti Marisa, Raineri Claudia, Petrella Duccio, Garascia Andrea, Pedrotti Patrizia, Roghi Alberto, Bonacina Edgardo, Moreo Antonella, Bottiroli Maurizio, Gagliardone Maria P, Mondino Michele, Ghio Stefano, Totaro Rossana, Turazza Fabio M, Russo Claudio F, Oliva Fabrizio, Camici Paolo G, Frigerio Maria
Abstract
BACKGROUND:
Previous reports have suggested that despite their dramatic presentation, patients with fulminant myocarditis (FM) might have better outcome than those with acute nonfulminant myocarditis (NFM). In this retrospective study, we report outcome and changes in left ventricular ejection fraction (LVEF) in a large cohort of patients with FM compared with patients with NFM.
METHODS:
The study population consists of 187 consecutive patients admitted between May 2001 and November 2016 with a diagnosis of acute myocarditis (onset of symptoms <1 month) of whom 55 required inotropes and/or mechanical circulatory support (FM) and the remaining 132 were hemodynamically stable (NFM). We also performed a subanalysis in 130 adult patients with acute viral myocarditis and viral prodrome within 2 weeks from the onset, which includes 34 with FM and 96 with NFM. Patients with giant-cell myocarditis, eosinophilic myocarditis, or cardiac sarcoidosis and those <15 years of age were excluded from the subanalysis.
RESULTS:
In the whole population (n=187), the rate of in-hospital death or heart transplantation was 25.5% versus 0% in FM versus NFM, respectively (<0.0001). Long-term heart transplantation-free survival at 9 years was lower in FM than NFM (64.5% versus 100%, log-rank <0.0001). Despite greater improvement in LVEF during hospitalization in FM versus NFM forms (median, 32% [interquartile range, 20%-40%] versus 3% [0%-10%], respectively; <0.0001), the proportion of patients with LVEF <55% at last follow-up was higher in FM versus NFM (29% versus 9%; relative risk, 3.32; 95% confidence interval, 1.45-7.64, =0.003). Similar results for survival and changes in LVEF in FM versus NFM were observed in the subgroup (n=130) with viral myocarditis. None of the patients with NFM and LVEF ?55% at discharge had a significant decrease in LVEF at follow-up.
CONCLUSIONS:
Patients with FM have an increased mortality and need for heart transplantation compared with those with NFM. From a functional viewpoint, patients with FM have a more severely impaired LVEF at admission that, despite steep improvement during hospitalization, remains lower than that in patients with NFM at long-term follow-up. These findings also hold true when only the viral forms are considered and are different from previous studies showing better prognosis in FM.
© 2017 American Heart Association, Inc.
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Prevalence and clinical significance of early high Endotoxin Activity in septic shock: An observational study.
J Crit Care2017 10;41():124-129. doi: S0883-9441(17)30218-6.
Bottiroli Maurizio, Monti Gianpaola, Pinciroli Riccardo, Vecchi Irene, Terzi Valeria, Ortisi Giuseppe, Casella Giampaolo, Fumagalli Roberto
Abstract
PURPOSE:
To measure the prevalence of elevated Endotoxin Activity (EA) in a large cohort of patients with Septic Shock (SS), and to assess its value as an early indicator of Gram-Negative (GN) infection, disease severity, and patient risk.
MATERIALS AND METHODS:
Adult patients were enrolled in this observational study if an EA determination was obtained within 24-h from SS onset. Demographic, clinical, and microbiological data were collected. In-hospital follow-up was also conducted.
RESULTS:
A high prevalence of endotoxemia was observed in the 107 subjects included, with 82% of patients showing either intermediate (?0.4 units), or high (?0.6) EA. Patients with positive cultures for GNs showed a higher mean EA (0.63±0.18 vs. 0.53±0.22; p<0.05). However, the test showed poor accuracy in the identification of GN bacteria as SS causative agents. Significantly higher lactate concentration (p=0.006), SOFA (p=0.04) and inotropic score (p=0.006) were observed in patients with endotoxemia. However, higher EA levels neither influenced mortality, nor length of stay.
CONCLUSIONS:
Early after SS onset, patients showed a high prevalence of endotoxemia, particularly those infected with GN bacteria. The EA assay might be a useful marker of disease severity. The complexity of such patients, however, limits EA accuracy in identifying GN sepsis and predicting outcome.
Copyright © 2017 Elsevier Inc. All rights reserved.
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Vasopressors and inotropes in cardiogenic shock: is there room for "adrenaline resuscitation"?
Crit Care2016 Sep;20(1):302.
Morici Nuccia, Stucchi Miriam, Sacco Alice, Bottiroli Maurizio A, Oliva Fabrizio,
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End-inspiratory pause prolongation in acute respiratory distress syndrome patients: effects on gas exchange and mechanics.
Ann Intensive Care2016 Dec;6(1):81. doi: 10.1186/s13613-016-0183-z.
Aguirre-Bermeo Hernan, Morán Indalecio, Bottiroli Maurizio, Italiano Stefano, Parrilla Francisco José, Plazolles Eugenia, Roche-Campo Ferran, Mancebo Jordi
Abstract
BACKGROUND:
End-inspiratory pause (EIP) prolongation decreases dead space-to-tidal volume ratio (Vd/Vt) and PaCO2. We do not know the physiological benefits of this approach to improve respiratory system mechanics in acute respiratory distress syndrome (ARDS) patients when mild hypercapnia is of no concern.
METHODS:
The investigation was conducted in an intensive care unit of a university hospital, and 13 ARDS patients were included. The study was designed in three phases. First phase, baseline measurements were taken. Second phase, the EIP was prolonged until one of the following was achieved: (1) EIP of 0.7 s; (2) intrinsic positive end-expiratory pressure ?1 cmH2O; or (3) inspiratory-expiratory ratio 1:1. Third phase, the Vt was decreased (30 mL every 30 min) until PaCO2 equal to baseline was reached. FiO2, PEEP, airflow and respiratory rate were kept constant.
RESULTS:
EIP was prolonged from 0.12 ± 0.04 to 0.7 s in all patients. This decreased the Vd/Vt and PaCO2 (0.70 ± 0.07 to 0.64 ± 0.08, p < 0.001 and 54 ± 9 to 50 ± 8 mmHg, p = 0.001, respectively). In the third phase, the decrease in Vt (from 6.3 ± 0.8 to 5.6 ± 0.8 mL/Kg PBW, p < 0.001) allowed to decrease plateau pressure and driving pressure (24 ± 3 to 22 ± 3 cmH2O, p < 0.001 and 13.4 ± 3.6 to 10.9 ± 3.1 cmH2O, p < 0.001, respectively) and increased respiratory system compliance from 29 ± 9 to 32 ± 11 mL/cmH2O (p = 0.001). PaO2 did not significantly change.
CONCLUSIONS:
Prolonging EIP allowed a significant decrease in Vt without changes in PaCO2 in passively ventilated ARDS patients. This produced a significant decrease in plateau pressure and driving pressure and significantly increased respiratory system compliance, which suggests less overdistension and less dynamic strain.
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Cardiogenic shock: How to overcome a clinical dilemma. Unmet needs in Emergency medicine.
Int J Cardiol2015 ;186():19-21. doi: 10.1016/j.ijcard.2015.02.111.
Morici Nuccia, Sacco Alice, Paino Roberto, Oreglia Jacopo Andrea, Bottiroli Maurizio, Senni Michele, Nichelatti Michele, Canova Paolo, Russo Claudio, Garascia Andrea, Kulgmann Silvio, Frigerio Maria, Oliva Fabrizio
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First case of trans-axillary direct flow implantation.
Int J Cardiol2014 Dec;177(3):e176-8. doi: 10.1016/j.ijcard.2014.08.097.
Bruschi Giuseppe, Botta Luca, Cannata Aldo, Colombo Paola, Barosi Alberto, Soriano Francesco, Bottiroli Maurizio, Nava Stefano, Klugmann Silvio, De Marco Federico
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Endotoxin activity level and septic shock: a possible role for specific anti-endotoxin therapy?
Contrib Nephrol2010 ;167():102-110. doi: 10.1159/000315924.
Monti Gianpaola, Bottiroli Maurizio, Pizzilli Giacinto, Minnini Maria, Terzi Valeria, Vecchi Irene, Gesu Giovanni, Brioschi Paolo, Vesconi Sergio, Casella Giampaolo
Abstract
Endotoxin activity (EA) plays an essential role in sepsis syndrome pathogenesis. There has been considerable interest in measuring and removing EA to predict and improve the morbidity and mortality of patients with sepsis. We performed a prospective study to assess the prevalence of EA in critically ill patients and its association with organ dysfunction and outcome, as well as in septic shock. EA (EAA(TM)) was measured within 24 h from onset of refractory septic shock in an intensive care unit. Our study demonstrated that EA level is independent from the type or the source of infection, but reflects the severity of illness in critically ill septic shock patients. Extracorporeal EA removal (PMX-HP) was assessed following our ICU clinical practice. PMX-HP seems to have better outcome, but further studies are required to verify this hypothesis.
Copyright 2010 S. Karger AG, Basel.
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