Extracorporeal blood purification in patients with liver failure: Considerations for the low-and-middle income countries of Latin America.

Severe liver failure is common in Low-and-Medium Income Countries (LMIC) and is associated with a high morbidity, mortality and represents an important burden to the healthcare system. In its most severe state, liver failure is a medical emergency, that requires supportive care until either the liver recovers or a liver transplant is performed. Frequently the patient requires intensive support until their liver recovers or they receive a liver transplant. Extracorporeal blood purification techniques can be employed as a strategy for bridging to transplantation or recovery. The most common type of extracorporeal support provided to these patients is kidney replacement therapy (KRT), as acute kidney injury is very common in these patients and KRT devices more readily available. However, because most of the substances that the liver clears are lipophilic and albumin-bound, they are not cleared effectively by KRT. Hence, there has been much effort in developing devices that more closely resemble the clearance function of the liver. This article provides a review of various non-biologic extracorporeal liver support devices that can be used to support these patients, and our perspective keeping in mind the needs and unique challenges present in the LMIC of Latin America.

Continuous Renal Replacement Therapy Dosing in the Severely Underweight: A Case Report.

Guidelines recommend that patients treated with continuous renal replacement therapy be delivered an effluent dose of 20 to 25 mL/kg/h. There is debate, especially at the extremes of body mass index, as to whether actual or ideal body weight (IBW) should be used in these dose calculations. A middle-aged woman with severe anorexia presented with 48 hours of altered mental status. Laboratory tests showed severe metabolic acidosis necessitating intubation, which was ultimately found to be due to nonprescribed use of metformin for weight loss. The patient became anuric and was initiated on continuous venovenous hemodialysis. Due to refractory acidosis, the modality was converted to continuous venovenous hemodiafiltration by adding postfilter hypertonic bicarbonate solution. Based on changes in sodium and bicarbonate levels over 4 hours with hypertonic bicarbonate solution, we were able to calculate an "effective" volume of distribution for this severely underweight patient. Our calculations suggest that IBW gives a better approximation of effective volume of distribution than actual body weight in a severely underweight woman. Inadequate effluent flow rate calculated based on actual rather than IBW may lead to insufficient correction of metabolic derangements in extremely underweight patients.

A 2-year-old boy with circulatory failure owing to streptococcal toxic shock syndrome: case report.

A 2-year-old boy presented with severe hypotension and acute kidney injury after a prodrome of non-bloody diarrhoea and fever in the preceding 3 days. He had a mild Ebstein cardiac anomaly but otherwise a normal past history and growth. On examination, he looked ill, his temperature was 37.5 °C, circulation was poor, and there were several purpuric lesions on the face, hands and scrotum. Haemoglobin was 7.8 g/dL (11-14), total white cell count 27 × 109/L, platelets 62 × 109/L, blood urea nitrogen 20.7 mmol/L (4.2-17.1), serum creatinine 95.4 µmol/L (21.2-36.2), CRP 154 mg/L (<5), AST 296 U/L (11-50), ALT 909 U/L (7-40) and C3 component of complement 0.8 g/L (0.9-1.8). Activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged and fibrinogen level was 1.0 g/L (2-4). He received immediate fluid resuscitation (IV 0.9% saline solution, 2 × 10 ml/kg boluses, followed by glucose 5/0.45% sodium chloride solution, 2 × 10 ml/kg) and antibiotics (ciprofloxacin and amikacin) but circulation continued to deteriorate with development of decreased consciousness. He was placed on mechanical ventilation and vasopressor agents were added. Despite improved circulation over the next 2 days, he developed oliguria, progressive fluid overload, generalised oedema and a right-sided pleural effusion. Dialysis was commenced on day 3 of admission. Differential diagnosis included sepsis, atypical haemolytic uraemic syndrome and lupus nephritis. Blood and urine cultures remained negative but an anti-streptolysin O titre of 1318 (<200) IU/mL led to the diagnosis of streptococcal toxic shock syndrome which is rare in early childhood and associated with high mortality. Haemodialysis was commenced and continued for 10 days with successful treatment of fluid overload and subsequent extubation. Renal function was completely restored over the following 6 weeks and he was discharged in good clinical condition about 2 months after intial admission. The clinical course and outcome are discussed, and the importance of timely initiation of dialysis when there is fluid overload is emphasised.

Análise de custo-efetividade da terapia renal substitutiva contínua versus intermitente para pacientes graves com lesão renal aguda, na perspectiva do Sistema Suplementar de Saúde brasileiro / Cost-effectiveness analysis of continuous versus intermittent renal replacement therapy for critically ill acute kidney injury patients under the perspective of the Brazilian Private Healthcare System

Objetivo: O objetivo deste estudo é comparar custos e desfechos da Terapia de Substituição Renal Contínua (CRRT) versus Hemodiálise Intermitente (IRRT) em pacientes com lesão renal aguda sob a perspectiva do sistema suplementar de saúde no Brasil. Métodos: Um modelo analítico de decisão foi desenvolvido baseado nos resultados clínicos encontrados no estudo de Ethgen et al., 2015. Este estudo seguiu o padrão CHEERS (Consolidated Health Economic Evaluation Reporting Standards) para reportar a avaliação econômica. Quando a lesão renal aguda ocorre na UTI, inicia-se a CRRT ou IRRT. Definiu-se que o tempo de internação hospitalar e o tempo em UTI foram os mesmos para as duas modalidades. O modelo também assumiu que, se os pacientes ficassem dependentes de diálise, eles não recuperavam sua função renal e permaneciam em diálise ou evoluíam a óbito. O horizonte do estudo foi de 1 ano, 5 anos (caso-base) e 20 anos. Apenas custos diretos para o sistema privado foram considerados. Para desfechos clínicos (utilities), a referência foi o estudo de Klarenbach & Manns, 2009. Conforme diretrizes brasileiras de avaliação de tecnologias em saúde, tanto custos como desfechos foram descontados à taxa de 5% ao ano com análise de sensibilidade na faixa de 0% a 10% ao ano. Além disso, foram realizadas duas análises de sensibilidade: uma univariada e outra determinística bivariada considerando os dois parâmetros-chave que diferenciam CRRT de IRRT: a diferença de custo de implementação por dia e o risco cumulativo de dependência de diálise. Ambas as análises foram rodadas com o horizonte de tempo de 1 ano, 5 anos e de tempo total de vida. Para determinar se o tratamento era custo-efetivo, conforme práticas locais, utilizou-se o limiar de três vezes o Produto Interno Bruto (PIB) per capita, qual seja R$ 84.741 (3 x R$ 28.247). Resultados: Quando se compara CRRT à IRRT para o tratamento inicial da lesão renal aguda, CRRT é dominante versus IRRT a partir de 17 meses de tratamento. Com base nas premissas deste estudo, a coorte de pacientes inicialmente tratada com CRRT tem melhores desfechos clínicos (QALYs ­ Anos de Vida Ajustados pela Qualidade) e custos totais de tratamento mais baixos. Pacientes tratados com CRRT têm maior probabilidade de recuperar a função renal. Conclusão: Os resultados sugerem que CRRT, quando comparada à IRRT, pode ser considerada uma terapia preferencial, ou seja, apresenta melhores desfechos com menor custo total de tratamento, sob a perspectiva do sistema suplementar de saúde no Brasil.

Objective: The objective of this study is to compare the costs and outcomes of Continuous Renal Replacement Therapy (CRRT) versus Intermittent Hemodialysis (IRRT) in patients with acute kidney injury from the perspective of the private healthcare system in Brazil. Methods: An analytical decision model was developed based on the clinical results found in the Ethgen et al., 2015 study. Our study followed the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) to report economic valuation. When acute kidney injury occurs in the ICU, patients are initiated in CRRT or IRRT. It was assumed that the length of hospital stay and ICU are the same for both modalities. The model assumes that once patients become dialysis dependent they do not recover their kidney function and remain on dialysis or die. The study horizon was 1 year, 5 years (base-case) and 20 years. Only direct costs to the private system were considered. The clinical outcomes (utilities) are from the Klarenbach & Manns, 2009 study. According to the Brazilian guidelines for health technology assessment, costs and outcomes were discounted at a rate of 5% per year with a sensitivity analysis in the range of 0% to 10% per year. In addition, two sensitivity analyzes were performed: a one-way, which generated a tornado diagram, and a two-way deterministic one considering the two key parameters that differentiate CRRT from IRRT: the daily implementation cost difference and the cumulative risk of dialysis dependence. We ran both analyzes with the time horizon of 1 year, 5 years and lifetime. According to local practices, we used the threshold of 3 times per capita GDP, that is, R $ 84,741 (3 x R$ 28,247) as the threshold for cost-effectiveness. Results: When we compare CRRT to IRRT for the initial treatment of acute kidney injury, CRRT is dominant vs. IRRT from 18 months of treatment. Based our assumptions, the cohort of patients initially treated with CRRT had better clinical outcomes (QALYs ­ Quality Adjusted Life Year) and lower total costs of treatment. Patients treated with CRRT are more likely to recover renal function. Conclusion: The results suggest that CRRT when compared to IRRT can be considered a dominant therapy, that is, it offers better outcomes and lower total treatment costs, under the perspective of the private healthcare system in Brazil.

The impact of continuous renal replacement therapy on renal outcomes in dialysis-requiring acute kidney injury may be related to the baseline kidney function.

BACKGROUND: Many controversies exist regarding the management of dialysis-requiring acute kidney injury (D-AKI). No clear evidence has shown that the choice of dialysis modality can change the survival rate or kidney function recovery of critically ill patients with D-AKI. METHODS: We conducted a retrospective study investigating patients (≥16 years old) admitted to an intensive care unit with D-AKI from 1999 to 2012. We analyzed D-AKI incidence, and outcomes, as well as the most commonly used dialysis modality over time. Outcomes were based on hospital mortality, renal function recovery (estimated glomerular filtration rate-eGFR), and the need for dialysis treatment at hospital discharge. RESULTS: In 1,493 patients with D-AKI, sepsis was the main cause of kidney injury (56.2%). The comparison between the three study periods, (1999-2003, 2004-2008, and 2009-2012) showed an increased in incidence of D-AKI (from 2.56 to 5.17%; p = 0.001), in the APACHE II score (from 20 to 26; p < 0.001), and in the use of continuous renal replacement therapy (CRRT) as initial dialysis modality choice (from 64.2 to 72.2%; p < 0.001). The mortality rate (53.9%) and dialysis dependence at hospital discharge (12.3%) remained unchanged over time. Individuals who recovered renal function (33.8%) showed that those who had initially undergone CRRT had a higher eGFR than those in the intermittent hemodialysis group (54.0 × 46.0 ml/min/1.73 m2, respectively; p = 0.014). In multivariate analysis, type of patient, sepsis-associated AKI and APACHE II score were associated to death. For each additional unit of the APACHE II score, the odds of death increased by 52%. The odds ratio of death for medical patients with sepsis-associated AKI was estimated to be 2.93 (1.81-4.75; p < 0.001). CONCLUSION: Our study showed that the incidence of D-AKI increased with illness severity, and the use of CRRT also increased over time. The improvement in renal outcomes observed in the CRRT group may be related to the better baseline kidney function, especially in the dialysis dependence patients at hospital discharge.