ECMO for drug-refractory electrical storm without a reversible trigger: a retrospective multicentric observational study.

AIMS: Drug-refractory electrical storm (ES) is a life-threatening medical emergency. We describe the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in drug-refractory ES without a reversible trigger, for which specific guideline recommendations are still lacking. METHODS AND RESULTS: Retrospective observational study in four Iberian centres on the indications, treatment, complications, and outcome of drug-refractory ES not associated with acute coronary syndromes, decompensated heart failure, drug toxicity, electrolyte disturbances, endocrine emergencies, concomitant acute illness with fever, or poor compliance with anti-arrhythmic drugs, requiring VA-ECMO for circulatory support. Thirty-four (6%) out of 552 patients with VA-ECMO for cardiogenic shock were included [71% men; 57 (44-62) years], 65% underwent cardiopulmonary resuscitation before VA-ECMO implantation, and 26% during cannulation. Left ventricular unloading during VA-ECMO was used in 8 (24%) patients: 3 (9%) with intraaortic balloon pump, 3 (9%) with LV vent, and 2 (6%) with Impella. Thirty (88%) had structural heart disease and 8 (24%) had an implantable cardioverter-defibrillator. The drug-refractory ES was mostly due to monomorphic ventricular tachycardia (VT) and ventricular fibrillation (VF) (59%), isolated monomorphic VT (26%), polymorphic VT (9%), or VF (6%). Thirty-one (91%) required deep sedation, 44% overdrive pacing, 36% catheter ablation, and 26% acute autonomic modulation. The main complications were nosocomial infection (47%), bleeding (24%), and limb ischaemia (21%). Eighteen (53%) were weaned from VA-ECMO, and 29% had heart transplantation. Twenty-seven (79%) survived to hospital discharge (48 (33-82) days). Non-survivors were older [62 (58-67) vs. 54 (43-58); P < 0.01] and had a higher first rhythm disorder-to-ECMO interval [0 (0-2) vs. 2 (1-11) days; P = 0.02]. Seven (20%) had rehospitalization during follow-up [29 (12-48) months], with ES recurrence in 6%. CONCLUSIONS: VA-ECMO bridged drug-refractory ES without a reversible trigger with a high success rate. This required prolonged hospital stays and coordination between the ECMO centre, the electrophysiology laboratory, and the heart transplant programme.

Standardized approach for extubation during extracorporeal membrane oxygenation in severe acute respiratory distress syndrome: a prospective observational study.

BACKGROUND: Extubation during extracorporeal oxygenation (ECMO) in severe acute respiratory distress syndrome (ARDS) has not been well studied. Despite the potential benefits of this strategy, weaning from ECMO before liberation from invasive mechanical ventilation remains the most frequent approach. Our aim was to evaluate the safety and feasibility of a standardized approach for extubation during ECMO in patients with severe ARDS. RESULTS: We conducted a prospective observational study to assess the safety and feasibility of a standardized approach for extubation during ECMO in severe ARDS among 254 adult patients across 4 intensive care units (ICU) from 2 tertiary ECMO centers over 6 years. This consisted of a daily assessment of clinical and gas exchange criteria based on an Extracorporeal Life Support Organization guideline, with extubation during ECMO after validation by a dedicated intensive care medicine specialist. Fifty-four (21%) patients were extubated during ECMO, 167 (66%) did not reach the clinical criteria, and in 33 (13%) patients, gas exchange precluded extubation during ECMO. At ECMO initiation, there were fewer extrapulmonary organ dysfunctions (lower SOFA score [OR, 0.88; 95% CI, 0.79-0.98; P = .02] with similar PaO2/FiO2) when compared with patients not extubated during ECMO. Extubation during ECMO associated with shorter duration of invasive mechanical ventilation (7 (4-18) vs. 32 (18-54) days; P < .01) and of ECMO (12 (7-25) vs. 19 (10-41) days; P = .01). This was accompanied by a lower incidence of hemorrhagic shock (2 vs. 11%; P = .05), but more cannula-associated deep vein thrombosis (49 vs. 31%; P = .02) and failed extubation (20 vs. 6%; P < .01). There were no increased major adverse events. Extubation during ECMO is associated with a lower risk of all-cause death, independently of measured confounding (adjusted logistic regression OR 0.23; 95% confidence interval 0.08-0.69, P = .008). CONCLUSIONS: A standardized approach was safe and feasible allowing extubation during ECMO in 21% of patients with severe ARDS, selecting patients who will have a shorter duration of invasive mechanical ventilation, ECMO course, and ICU stay, as well as fewer infectious complications, and high hospital survival.

An integrated program of extracorporeal membrane oxygenation (ECMO) assisted cardiopulmonary resuscitation and uncontrolled donation after circulatory determination of death in refractory cardiac arrest.

AIM: To assess the feasibility of an integrated program of extracorporeal cardiopulmonary resuscitation (ECPR) and uncontrolled donation after circulatory determination of death (uDCDD) in refractory cardiac arrest (rCA). METHODS: Single center, prospective, observational study of selected patients with in-hospital (IHCA) and out-of-hospital (OHCA) rCA occurring in an urban area of ∼1.5 million inhabitants, between October-2016 and May-2018. 65 year old or younger patients without significant bleeding or comorbidities with witnessed nonasystolic cardiac arrests were triaged to ECPR if they had a reversible cause and high quality CPR lasting < 60 min. Otherwise they were considered for uDCDD after a ten minute no touch period using normothermic regional perfusion. RESULTS: 58 patients were included, of which 41 (71%) were OHCA and 18 (31%) had ECPR initiated. Median age was 52 (IQR 45-56) years. Cannulation was successful in 49/58 (84%) cases. Compared to ECPR, patients referred for uDCDD were more frequently OHCA (90 vs. 28%), had bystander CPR (28 vs. 83%) and prolonged low-flow period (40 (35-50) vs. 60 (49-78) min). Survival to hospital discharge with full neurological recovery (cerebral performance category 1) occurred in 6/18 (33%) ECPR patients. uDCDD resulted in transplantation of 44 kidneys. CONCLUSIONS: An integrated program for rCA consisting of a formal pathway to uDCDD referral in ECPR ineligible patients is feasible. ECPR-referred patients had a reasonable survival with full neurologic recovery. Successful kidney transplantation was achieved with uDCDD.

Biomarkers of renal recovery after acute kidney injury. / Biomarcadores de recuperação renal após lesão renal aguda.

Novel biomarkers can be suitable for early acute kidney injury diagnosis and the prediction of the need for dialysis. It remains unclear whether such biomarkers may also play a role in the prediction of recovery after established acute kidney injury or in aiding the decision of when to stop renal support therapy. PubMed, Web of Science and Google Scholar were searched for studies that reported on the epidemiology of renal recovery after acute kidney injury, the risk factors of recovery versus non-recovery after acute kidney injury, and potential biomarkers of acute kidney injury recovery. The reference lists of these articles and relevant review articles were also reviewed. Final references were selected for inclusion in the review based on their relevance. New biomarkers exhibited a potential role in the early diagnosis of acute kidney injury recovery. Urine HGF, IGFBP-7, TIMP-2 and NGAL may improve our ability to predict the odds and timing of recovery and eventually renal support withdrawal. Acute kidney injury recovery requires more study, and its definition needs to be standardized to allow for better and more powerful research on biomarkers because some of them show potential for the prediction of acute kidney injury recovery.

Novos biomarcadores podem ser apropriados para o diagnóstico precoce da lesão renal aguda e predição da necessidade de diálise. Não é claro se tais biomarcadores podem também desempenhar um papel na predição da recuperação após se ter estabelecido o diagnóstico de lesão renal aguda, ou se podem ajudar na tomada de decisão a respeito do momento de interromper a terapia de suporte renal. Realizamos uma busca nas plataformas PubMed, Web of Science e Google Scholar por estudos que relatassem a epidemiologia da recuperação renal após lesão renal aguda, sobre fatores de risco para recuperação em comparação a não recuperação após lesão renal aguda, e potenciais biomarcadores de recuperação da lesão renal aguda. A lista de referências destes artigos e os artigos de revisão relevantes foram revisados. As referências finais foram selecionadas para inclusão nesta revisão, com base em sua relevância. Novos biomarcadores revelaram ter um potencial papel no diagnóstico precoce de recuperação da lesão renal aguda. Os níveis urinários do fator de crescimento de hepatócitos, do fator de crescimento semelhante à insulina 7, do inibidor de metalopeptidase 7 e da lipocalina associada com gelatinase de neutrófilos podem aprimorar nossa capacidade de predizer as tendências e a ocasião da recuperação, e eventual remoção do suporte renal. A recuperação da lesão renal aguda demanda mais estudo, e sua definição precisa ser padronizada para permitir melhor e mais potente pesquisa de biomarcadores, pois alguns deles revelam potencial para predição da recuperação de lesão renal aguda.

Biomarcadores de recuperação renal após lesão renal aguda / Biomarkers of renal recovery after acute kidney injury

RESUMO Novos biomarcadores podem ser apropriados para o diagnóstico precoce da lesão renal aguda e predição da necessidade de diálise. Não é claro se tais biomarcadores podem também desempenhar um papel na predição da recuperação após se ter estabelecido o diagnóstico de lesão renal aguda, ou se podem ajudar na tomada de decisão a respeito do momento de interromper a terapia de suporte renal. Realizamos uma busca nas plataformas PubMed, Web of Science e Google Scholar por estudos que relatassem a epidemiologia da recuperação renal após lesão renal aguda, sobre fatores de risco para recuperação em comparação a não recuperação após lesão renal aguda, e potenciais biomarcadores de recuperação da lesão renal aguda. A lista de referências destes artigos e os artigos de revisão relevantes foram revisados. As referências finais foram selecionadas para inclusão nesta revisão, com base em sua relevância. Novos biomarcadores revelaram ter um potencial papel no diagnóstico precoce de recuperação da lesão renal aguda. Os níveis urinários do fator de crescimento de hepatócitos, do fator de crescimento semelhante à insulina 7, do inibidor de metalopeptidase 7 e da lipocalina associada com gelatinase de neutrófilos podem aprimorar nossa capacidade de predizer as tendências e a ocasião da recuperação, e eventual remoção do suporte renal. A recuperação da lesão renal aguda demanda mais estudo, e sua definição precisa ser padronizada para permitir melhor e mais potente pesquisa de biomarcadores, pois alguns deles revelam potencial para predição da recuperação de lesão renal aguda.

ABSTRACT Novel biomarkers can be suitable for early acute kidney injury diagnosis and the prediction of the need for dialysis. It remains unclear whether such biomarkers may also play a role in the prediction of recovery after established acute kidney injury or in aiding the decision of when to stop renal support therapy. PubMed, Web of Science and Google Scholar were searched for studies that reported on the epidemiology of renal recovery after acute kidney injury, the risk factors of recovery versus non-recovery after acute kidney injury, and potential biomarkers of acute kidney injury recovery. The reference lists of these articles and relevant review articles were also reviewed. Final references were selected for inclusion in the review based on their relevance. New biomarkers exhibited a potential role in the early diagnosis of acute kidney injury recovery. Urine HGF, IGFBP-7, TIMP-2 and NGAL may improve our ability to predict the odds and timing of recovery and eventually renal support withdrawal. Acute kidney injury recovery requires more study, and its definition needs to be standardized to allow for better and more powerful research on biomarkers because some of them show potential for the prediction of acute kidney injury recovery.

Prognostics factors for mortality and renal recovery in critically ill patients with acute kidney injury and renal replacement therapy.

OBJECTIVE: Identify prognostic factors related to mortality and non-recovery of renal function. METHODS: A prospective single-center study was conducted at the intensive care medicine department of a university hospital between 2012 and 2015. Patients with acute kidney injury receiving continuous renal replacement therapy were included in the study. Clinical and analytical parameters were collected, and the reasons for initiation and discontinuation of renal replacement therapy were examined. RESULTS: A total of 41 patients were included in the study, of whom 43.9% had sepsis. The median Simplified Acute Physiology Score II (SAPSII) was 56 and the mortality was 53.7%, with a predicted mortality of 59.8%. The etiology of acute kidney injury was often multifactorial (56.1%). Survivors had lower cumulative fluid balance (median = 3,600mL, interquartile range [IQR] = 1,175 - 8,025) than non-survivors (median = 12,000mL, IQR = 6,625 - 17,875; p = 0.004). Patients who recovered renal function (median = 51.0, IQR = 45.8 - 56.2) had lower SAPS II than those who do not recover renal function (median = 73, IQR = 54 - 85; p = 0.005) as well as lower fluid balance (median = 3,850, IQR = 1,425 - 8,025 versus median = 11,500, IQR = 6,625 - 16,275; p = 0.004). CONCLUSIONS: SAPS II at admission and cumulative fluid balance during renal support therapy were risk factors for mortality and non-recovery of renal function among critically ill patients with acute kidney injury needing renal replacement therapy.

Fatores prognósticos para mortalidade e recuperação da função renal em doentes com lesão renal aguda e necessidade de suporte renal em cuidados intensivos / Prognostics factors for mortality and renal recovery in critically ill patients with acute kidney injury and renal replacement therapy

RESUMO Objetivo: Identificar fatores prognósticos relacionados com a mortalidade ou com a não recuperação da função renal. Métodos: Estudo monocêntrico, prospectivo, realizado em um serviço de medicina intensiva de um hospital universitário, entre 2012 e 2015. Incluíram-se doentes com lesão renal aguda em suporte renal contínuo. Foram coletados parâmetros clínicos e analíticos, assim como foi investigado o motivo para o início e o término do suporte renal. Resultados: Foram incluídos 41 doentes, 43,9% deles com sepse. O Simplified Acute Physiology Score II (SAPS-II) foi de 56, com mortalidade prevista de 59,8% e verificada de 53,7%. A etiologia da lesão renal aguda foi principalmente multifatorial (56,1%). Os sobreviventes apresentaram menor balanço hídrico acumulado (mediana de 3.600mL com intervalo interquartil de 1.175 - 8.025 versus 12.000mL [6.625 - 17.875] e p = 0,004. Os doentes que recuperaram função renal apresentaram SAPS II mais baixo do que os que não recuperaram (51,0 [45,8 - 56,2] versus 73 [54 - 85]; p = 0,005), assim como menor balanço hídrico (3850 [1.425 - 8.025] versus 11.500 [6.625 - 16.275]; p = 0,004). Conclusão: SAPS II na admissão e balanço hídrico acumulado durante o suporte renal foram fatores de risco para mortalidade e para a não recuperação da função renal em doentes graves com lesão renal aguda e necessidade de suporte renal.

ABSTRACT Objective: Identify prognostic factors related to mortality and non-recovery of renal function. Methods: A prospective single-center study was conducted at the intensive care medicine department of a university hospital between 2012 and 2015. Patients with acute kidney injury receiving continuous renal replacement therapy were included in the study. Clinical and analytical parameters were collected, and the reasons for initiation and discontinuation of renal replacement therapy were examined. Results: A total of 41 patients were included in the study, of whom 43.9% had sepsis. The median Simplified Acute Physiology Score II (SAPSII) was 56 and the mortality was 53.7%, with a predicted mortality of 59.8%. The etiology of acute kidney injury was often multifactorial (56.1%). Survivors had lower cumulative fluid balance (median = 3,600mL, interquartile range [IQR] = 1,175 - 8,025) than non-survivors (median = 12,000mL, IQR = 6,625 - 17,875; p = 0.004). Patients who recovered renal function (median = 51.0, IQR = 45.8 - 56.2) had lower SAPS II than those who do not recover renal function (median = 73, IQR = 54 - 85; p = 0.005) as well as lower fluid balance (median = 3,850, IQR = 1,425 - 8,025 versus median = 11,500, IQR = 6,625 - 16,275; p = 0.004). Conclusions: SAPS II at admission and cumulative fluid balance during renal support therapy were risk factors for mortality and non-recovery of renal function among critically ill patients with acute kidney injury needing renal replacement therapy.

Flow cytometry assessment of graft-infiltrating lymphocytes can accurately identify acute rejection in kidney transplants.

BACKGROUND: Previously, we have reported that flow cytometry analysis of fine-needle aspirates can accurately predict rejection in kidney transplants treated with cyclosporine-azathioprine-prednisolone. In this study, we examined this technique's accuracy using current immunosuppression. METHODS: Kidney transplant recipients were treated with calcineurin inhibitors, mycophenolate mofetil, and prednisolone: 92 remained rejection-free - Group I - and 37 developed acute rejection - Group II. An allograft aspiration specimen and peripheral blood were collected from Group I on post-transplant day 7 and from Group II on the day of clinical rejection. RESULTS: Significant changes were seen in both aspiration and peripheral blood samples in several T cell subsets when comparing Groups I and II. A sensitivity of 94.6%, specificity of 85%, and AUC = 0.966 were observed through combining CD8DR with CD3CD69 values from aspiration specimen; the corresponding AUC in peripheral blood was 0.847. Irreversible rejections displayed a significantly higher activation score (p = 0.024). CONCLUSIONS: Flow cytometry analysis of aspiration specimen achieved high diagnostic performance in renal transplants through studying CD8DR and CD3CD69 under current immunosuppressive therapy. Peripheral blood analysis, although not significant, showed the same trend. The activation score anticipated the irreversibility of rejection. The data suggest this test, through an easily tolerated technique, merits further diagnostic use.

Extracorporeal therapies in sepsis.

The treatment of sepsis is an ongoing challenge for clinicians; despite the wide choice of effective antibiotics to treat infection, sepsis remains the leading cause of morbidity and mortality for patients admitted to an intensive care unit. Dysregulation of the immune response is now recognized to be a key factor in multiple organ dysfunction, yet our therapy for inflammation remains ineffective. It has been advocated for more than a decade that cytokine reduction in blood compartment could lead to a reduction in mortality in sepsis. Over the years, multiple extracorporeal techniques have evolved, with the intent of influencing the circulating levels of inflammatory mediators like cytokines and chemokines, the complement system, as well as factors of the coagulation system. These include high-volume hemofiltration, use of high cutoff membranes, and systems based on adsorption, such as coupled plasma filtration adsorption and the polymyxin-B column. In addition, new experimental systems that utilize human phagocytic cells and immobilized antibodies for targeted immunomodulation have emerged. In the context of limited resources and growing expansion in the availability of technologies, a better understanding of these therapies is required before they can be properly integrated into standard clinical practice in the hope of influencing major clinical outcomes. In this article, we will provide a concise overview of selected extracorporeal modalities currently in clinical use and briefly introduce some new promising techniques for sepsis.

Neutrophil gelatinase-associated lipocalin as a biomarker of cardiovascular disease: a systematic review.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury (AKI). Recently, elevated NGAL levels have also been reported in heart failure, coronary heart disease, and stroke. Other studies demonstrate that NGAL is upregulated in failing myocardium and in atherosclerotic plaque. Our aim was to synthesize the current evidence on NGAL and cardiovascular disease (CVD), and to clarify the prognostic significance of systemic NGAL levels in CVD. METHODS: We performed a systematic review to identify experimental and human studies on NGAL and CVD. We excluded articles which specifically dealt with AKI or renal endpoints. RESULTS: We identified 22 studies, including both animal and human data. NGAL is highly expressed in the heart, both in failing myocardium and myocarditis, and is also expressed in atherosclerotic plaques. Areas of co-localization of NGAL and matrix metalloproteinase (MMP)-9 exhibited increased MMP-9 proteolytic activity. Systemic NGAL levels correlated with renal function and severity of CVD in several, but not all, studies. An association between elevated systemic NGAL levels and clinical outcomes (e.g., death, hospital readmissions) were reported in six CVD studies, but these had limited adjustment for potential confounders. CONCLUSIONS: There is ample literature to support a putative role of NGAL in the pathophysiology of CVD, but at present there is insufficient data regarding the clinical utility of systemic NGAL levels in the management of CVD. Available evidence regarding NGAL as a predictor of outcomes in CVD is very limited.