Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload

Background Icodextrin is a high molecular weight, starch-derived glucose polymer, which is capable of inducing sustained ultrafiltration over prolonged (12–16 hour) peritoneal dialysis (PD) dwells. The aim of this study was to evaluate the ability of icodextrin to alleviate refractory, symptomatic fluid overload and prolong technique survival in PD patients. Methods A prospective, open-label, pre-test/post-test study was conducted in 17 PD patients (8 females/9 males, mean age 56.8 ± 2.9 years) who were on the verge of being transferred to haemodialysis because of symptomatic fluid retention that was refractory to fluid restriction, loop diuretic therapy, hypertonic glucose exchanges and dwell time optimisation. One icodextrin exchange (2.5 L 7.5%, 12-hour dwell) was substituted for a long-dwell glucose exchange each day. Results Icodextrin significantly increased peritoneal ultrafiltration (885 ± 210 ml to 1454 ± 215 ml, p < 0.05) and reduced mean arterial pressure (106 ± 4 to 96 ± 4 mmHg, p < 0.05), but did not affect weight, plasma albumin concentration, haemoglobin levels or dialysate:plasma creatinine ratio. Diabetic patients (n = 12) also experienced improved glycaemic control (haemoglobin Alc decreased from 8.9 ± 0.7% to 7.9 ± 0.7%, p < 0.05). Overall PD technique survival was prolonged by a mean of 11.6 months (95% CI 6.0–17.3 months). On multivariate Cox proportional hazards analysis, extension of technique survival by icodextrin was only significantly predicted by baseline net daily peritoneal ultrafiltration (adjusted HR 2.52, 95% CI 1.13–5.62, p < 0.05). Conclusions Icodextrin significantly improved peritoneal ultrafiltration and extended technique survival in PD patients with symptomatic fluid overload, especially those who had substantially impaired peritoneal ultrafiltration.

Intrathecal analgesia and restrictive perioperative fluid management within enhanced recovery pathway: hemodynamic implications.

BACKGROUND: Intrathecal analgesia and avoidance of perioperative fluid overload are key items within enhanced recovery pathways. Potential side effects include hypotension and renal dysfunction. STUDY DESIGN: From January 2010 until May 2010, all patients undergoing colorectal surgery within enhanced recovery pathways were included in this retrospective cohort study and were analyzed by intrathecal analgesia (IT) vs none (noIT). Primary outcomes measures were systolic and diastolic blood pressure, mean arterial pressure, and heart rate for 48 hours after surgery. Renal function was assessed by urine output and creatinine values. RESULTS: One hundred and sixty-three consecutive colorectal patients (127 IT and 36 noIT) were included in the analysis. Both patient groups showed low blood pressure values within the first 4 to 12 hours and a steady increase thereafter before return to baseline values after about 24 hours. Systolic and diastolic blood pressure and mean arterial pressure were significantly lower until 16 hours after surgery in patients having IT compared with the noIT group. Low urine output (<0.5 mL/kg/h) was reported in 11% vs 29% (IT vs noIT; p = 0.010) intraoperatively, 20% vs 11% (p = 0.387), 33% vs 22% (p = 0.304), and 31% vs 21% (p = 0.478) for postanesthesia care unit and postoperative days 1 and 2, respectively. Only 3 of 127 (2.4%) IT and 1 of 36 (2.8%) noIT patients had a transitory creatinine increase >50%; no patients required dialysis. CONCLUSIONS: Postoperative hypotension affects approximately 10% of patients within an enhanced recovery pathway and is slightly more pronounced in patients with IT. Hemodynamic depression persists for <20 hours after surgery; it has no measurable negative impact and therefore cannot justify detrimental postoperative fluid overload.

Obstructive Sleep Apnea Severity and Overnight Body Fluid Shift before and after Hemodialysis.

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea is associated with significantly increased cardiovascular morbidity and mortality. Fluid overload may promote obstructive sleep apnea in patients with ESRD through an overnight fluid shift from the legs to the neck soft tissues. Body fluid shift and severity of obstructive sleep apnea before and after hemodialysis were compared in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seventeen patients with hemodialysis and moderate to severe obstructive sleep apnea were included. Polysomnographies were performed the night before and after hemodialysis to assess obstructive sleep apnea, and bioimpedance was used to measure fluid overload and leg fluid volume. RESULTS: The mean overnight rostral fluid shift was 1.27±0.41 L prehemodialysis; it correlated positively with fluid overload volume (r=0.39; P=0.02) and was significantly lower posthemodialysis (0.78±0.38 L; P<0.001). There was no significant difference in the mean obstructive apnea-hypopnea index before and after hemodialysis (46.8±22.0 versus 42.1±18.6 per hour; P=0.21), but obstructive apnea-hypopnea index was significantly lower posthemodialysis (-10.1±10.8 per hour) in the group of 12 patients, with a concomitant reduction of fluid overload compared with participants without change in fluid overload (obstructive apnea-hypopnea index +8.2±16.1 per hour; P<0.01). A lower fluid overload after hemodialysis was significantly correlated (r=0.49; P=0.04) with a lower obstructive apnea-hypopnea index. Fluid overload-assessed by bioimpedance-was the best predictor of the change in obstructive apnea-hypopnea index observed after hemodialysis (standardized r=-0.68; P=0.01) in multivariate regression analysis. CONCLUSIONS: Fluid overload influences overnight rostral fluid shift and obstructive sleep apnea severity in patients with ESRD undergoing intermittent hemodialysis. Although no benefit of hemodialysis on obstructive sleep apnea severity was observed in the whole group, the change in obstructive apnea-hypopnea index was significantly correlated with the change in fluid overload after hemodialysis. Moreover, the subgroup with lower fluid overload posthemodialysis showed a significantly lower obstructive sleep apnea severity, which provides a strong incentive to further study whether optimizing fluid status in patients with obstructive sleep apnea and ESRD will improve the obstructive apnea-hypopnea index.

Fluid management and goal-directed therapy as an adjunct to Enhanced Recovery After Surgery (ERAS)

© 2014, Canadian Anesthesiologists' Society.Optimal perioperative fluid management is an important component of Enhanced Recovery After Surgery (ERAS) pathways. Fluid management within ERAS should be viewed as a continuum through the preoperative, intraoperative, and postoperative phases. Each phase is important for improving patient outcomes, and suboptimal care in one phase can undermine best practice within the rest of the ERAS pathway. The goal of preoperative fluid management is for the patient to arrive in the operating room in a hydrated and euvolemic state. To achieve this, prolonged fasting is not recommended, and routine mechanical bowel preparation should be avoided. Patients should be encouraged to ingest a clear carbohydrate drink two to three hours before surgery. The goals of intraoperative fluid management are to maintain central euvolemia and to avoid excess salt and water. To achieve this, patients undergoing surgery within an enhanced recovery protocol should have an individualized fluid management plan. As part of this plan, excess crystalloid should be avoided in all patients. For low-risk patients undergoing low-risk surgery, a “zero-balance” approach might be sufficient. In addition, for most patients undergoing major surgery, individualized goal-directed fluid therapy (GDFT) is recommended. Ultimately, however, the additional benefit of GDFT should be determined based on surgical and patient risk factors. Postoperatively, once fluid intake is established, intravenous fluid administration can be discontinued and restarted only if clinically indicated. In the absence of other concerns, detrimental postoperative fluid overload is not justified and “permissive oliguria” could be tolerated.

Systemic and Local Inflammation in Peritoneal Dialysis: Mechanisms, Biomarkers and Effects on Outcome

Thanks to the technological development in peritoneal dialysis (PD) during the last three decades, the most important problem nowadays for the nephrologists is the maintenance of the long-term function of the peritoneal membrane. Although PD may exert an early survival benefit as compared with hemodialysis (HD), long-term PD is often associated with histopathological alterations in the peritoneal membrane that are linked to peritoneal ultrafiltration deficit and increased mortality risk. These alterations are closely related to the presence of a chronic activated (local and systemic) inflammatory response. PD itself may have other factors associated that could further modulate the inflammatory response, such as the bioincompatibility of dialysis solutions, fluid overload and changes in the body composition. Understanding the pathophysiology of inflammation in PD is essential for the adoption of adequate strategies to improve both membrane and patient survival. Copyright (C) 2009 S. Karger AG, Basel

Dose-dependent acute and sustained renal effects of the endothelin receptor antagonist avosentan in healthy subjects.

The endothelin receptor antagonist avosentan may cause fluid overload at doses of 25 and 50 mg, but the actual mechanisms of this effect are unclear. We conducted a placebo-controlled study in 23 healthy subjects to assess the renal effects of avosentan and the dose dependency of these effects. Oral avosentan was administered once daily for 8 days at doses of 0.5, 1.5, 5, and 50 mg. The drug induced a dose-dependent median increase in body weight, most pronounced at 50 mg (0.8 kg on day 8). Avosentan did not affect renal hemodynamics or plasma electrolytes. A dose-dependent median reduction in the fractional renal excretion of sodium was found (up to 8.7% at avosentan 50 mg); this reduction was paralleled by a dose-related increase in proximal sodium reabsorption. It is suggested that avosentan dose-dependently induces sodium retention by the kidney, mainly through proximal tubular effects. The potential clinical benefits of avosentan should therefore be investigated at doses of <or= 5 mg.

Dose-dependent acute and sustained renal effects of the endothelin receptor antagonist avosentan in healthy subjects

Enjeu : L'incidence d'insuffisance rénale terminale augmente d'environ 5-6% par année dans nos régions. L'une des causes majeures d'insuffisance rénale est la néphropathie diabétique qui représente selon les pays entre 25 et 40% des néphropathies terminales. La progression de la néphropathie diabétique peut être ralentie de manière efficace par un bon contrôle du diabète et de l'hypertension artérielle et par le blocage du système rénine-angiotensine. Néanmoins, malgré l'application stricte de ces thérapies préventives, la néphropathie de bons nombres de patients diabétiques continue de progresser. Il est donc important de développer de nouvelles stratégies permettant de préserver la fonction rénale des patients diabétiques soit en améliorant le contrôle de la pression artérielle soit en diminuant la protéinurie. Contexte : Il existe un certain nombre d'évidences expérimentales que le blocage des récepteurs de l'endothéline pourrait avoir un effet positif sur le devenir de la néphropathie diabétique en diminuant de manière efficace la protéinurie même chez des animaux déjà traités efficacement avec un bloqueur du système rénine-angiotensine. Dans des études de phase 2 impliquant l'avosentan, un antagoniste des récepteurs de l'endothéline actuellement en cours de développement pour le traitement de la néphropathie diabétique, on a pu démontrer que cet antagoniste, prescrit à des doses oscillant entre 5 et 50 mg par jour per os, diminue la protéinurie d'environ 20-40% chez des patients déjà traités avec un IEC ou un antagoniste de l'angiotensine. Toutefois, une grande étude de phase III conduite avec ce médicament chez des patients diabétiques a du être interrompue précocement en raison de l'apparition d'oedèmes et d'une surcharge hydrosodée conduisant dans certains cas à une décompensation cardiaque aiguë. La rétention hydrosodée est un effet secondaire connu des antagonistes de l'endothéline déjà sur le marché. Toutefois, pour l'avosentan, on ne savait pas si des doses plus faibles du médicament avaient aussi un effet négative sur la balance hydrosodée. En outre, les mécanismes rénaux responsables de la rétention hydrosodée sont encore mal connus chez l'homme. C'est pourquoi, nous avons organisé et réalisé cette étude de pharmacologie clinique chez le volontaire sain posant 2 questions : 1) des doses faibles d'avosentan produisent-elles aussi une rétention hydrosodée chez l'homme ? et 2) quels sont les mécanismes rénaux pouvant expliquer la rétention hydrosodée ? Cette thèse est donc une étude clinique de phase I testant chez 23 volontaires sains les effets rénaux de différentes doses d'avosentan ou d'un placebo pour établir la courbe dose-réponse des effets rénaux de ce médicament. L'idée était également de définir quelle dose est sure et bien tolérée pour être utilisée dans une nouvelle étude de phase II. L'avosentan a été administré par voie orale une fois par jour pendant 8 jours à des doses de 0.5, 1.5, 5 et 50 mg. Les effets rénaux hémodynamiques et tubulaires ont été étudiés chez chaque sujet lors de la première administration (jour 1) et après une semaine de traitement (jour 8). Le médicament a induit une prise de poids dose-dépendante déjà présente à 5 mg et maximale à 50 mg (+ 0.8 kg au jour 8). Nous n'avons pas mesuré d'impact de l'avosentan sur l'hémodynamique rénale ni sur les électrolytes plasmatiques. En revanche, nous avons constaté une diminution dose-dépendante de la fraction d'excrétion de sodium (jusqu'à -8.7% avec avosentan 50 mg). Cette diminution était en rapport avec une augmentation dose-dépendante de la réabsorption proximale de sodium. Nous avons également constaté une baisse de la pression artérielle aux doses élevées et une hémodilution marquée par une baisse de l'hématocrite suggérant une rétention hydrique à la plus haute dose. Nos résultats suggèrent donc que l'avosentan induit une rétention sodée rénale dose-dépendante expliquée avant tout par une rétention du sodium au niveau du tubule proximal. Cet effet n'est pas observé à des doses plus basses que 5 mg chez le volontaire sain, suggérant que ce médicament devrait être évalué pour son activité réno-protectrice à des doses inférieures ou égales à 5 mg par jour. La raison pour laquelle les hautes doses produisent plus de rétention sodée est peut être liée à une perte de sélectivité pour les sous-types (A et B) de récepteurs à l'endothéline lorsque l'on administre des doses plus élevées que 5 mg. Perspectives : Les résultats de ce travail de thèse ont donc permis de caractériser les propriétés rénales d'un nouvel antagoniste des récepteurs de l'endothéline chez l'homme. Ces résultats ont aussi permis de guider le développement futur de ce médicament vers des doses plus faibles avec l'espoir de garder les effets bénéfiques sur la protéinurie tout en améliorant le profil de tolérance du médicament par l'utilisation de doses plus faibles. ANGLAIS The endothelin receptor antagonist avosentan may cause fluid overload at doses of 25 and 50 mg, but the actual mechanisms of this effect are unclear. We conducted a placebo-controlled study in 23 healthy subjects to assess the renal effects of avosentan and the dose dependency of these effects. Oral avosentan was administered once daily for 8 days at doses of 0.5, 1.5, 5, and 50 mg. The drug induced a dose-dependent median increase in body weight, most pronounced at 50 mg (0.8 kg on day 8). Avosentan did not affect renal hemodynamics or plasma electrolytes. A dose-dependent median reduction in the fractional renal excretion of sodium was found (up to 8.7% at avosentan 50 mg); this reduction was paralleled by a dose-related increase in proximal sodium reabsorption. It is suggested that avosentan dose-dependently induces sodium retention by the kidney, mainly through proximal tubular effects. The potential clinical benefits of avosentan should therefore be investigated at doses of ≤ 5 mg.

L'insuffisance rénale chronique: quelle est la diète optimale

The optimal diet for chronic kidney disease (CKD) is an issue frequently brought up by patients and/or their relatives during outpatient visits. For patients without malnutrition who are motivated and supported by an experienced multidisciplinary team, the optimal protein intake of 0,6 g/kg of ideal body weight/day is recommended to halt the progression of CKD. A calorie intake of 30 to 35 kcal/kg of ideal body weight/day is necessary to reduce the risk of malnutrition from a low protein diet and to maintain a neutral nitrogen balance. A low-salt diet, namely 5 to 6 g/d, is useful to optimize the treatment of hypertension associated with CKD and to limit fluid overload. At the advanced stage of CKD, it is also necessary to restrict the intake of phosphorus and sometimes potassium. Given the complexity of optimal renal diet, coordination between general practitioners, nephrologists and dietitians is essential to foster optimal care.

Inverse association between serum creatinine and mortality in acute kidney injury

Introduction: Sepsis is a leading precipitant of Acute Kidney Injury (AKI) in intensive care unit (ICU) patients, and is associated with a high mortality rate. Objective: We aimed to evaluate the risk factors for dialysis and mortality in a cohort of AKI patients of predominantly septic etiology. Methods: Adult patients from an ICU for whom nephrology consultation was requested were included. End-stage chronic renal failure and kidney transplant patients were excluded. Results: 114 patients were followed. Most had sepsis (84%), AKIN stage 3 (69%) and oliguria (62%) at first consultation. Dialysis was performed in 66% and overall mortality was 70%. Median serum creatinine in survivors and non-survivors was 3.95 mg/dl (2.63 - 5.28) and 2.75 mg/dl (1.81 - 3.69), respectively. In the multivariable models, oliguria and serum urea were positively associated with dialysis; otherwise, a lower serum creatinine at first consultation was independently associated with higher mortality. Conclusion: In a cohort of septic AKI, oliguria and serum urea were the main indications for dialysis. We also described an inverse association between serum creatinine and mortality. Potential explanations for this finding include: delay in diagnosis, fluid overload with hemodilution of serum creatinine or poor nutritional status. This finding may also help to explain the low discriminative power of general severity scores - that assign higher risks to higher creatinine levels - in septic AKI patients.

Incidência de parada cardíaca durante anestesia, em hospital universitário de atendimento terciário: estudo prospectivo entre 1996 e 2002

JUSTIFICATIVA E OBJETIVOS: A incidência e causas de parada cardíaca (PC) durante a anestesia variam e são difíceis de comparar diante dos diversos métodos usados nos estudos. A pesquisa teve como objetivo estudar todas as PC ocorridas no intra e pós-operatório, durante um período de sete anos, de 1996 a 2002, em hospital de ensino de atendimento terciário para determinar incidência e causas da PC. MÉTODO: A incidência prospectiva de PC ocorrida durante a anestesia em 40.941 pacientes consecutivos foi identificada, utilizando-se um Banco de Dados. Todos os casos de PC e óbito foram revisados por uma Comissão, para determinar o fator desencadeante da PC ou óbito. A incidência de PC foi calculada em relação à idade, sexo, estado físico, segundo a classificação da ASA, tipo de atendimento, fatores desencadeantes, como alteração do estado físico do paciente e complicações cirúrgicas e anestésicas, tipo de anestesia e evolução para óbito. RESULTADOS: Ocorreram 138 PC (33,7:10.000), sendo a maioria em recém-nascidos, crianças até um ano e idosos, no sexo masculino (65,2%), em pacientes com estado físico ASA III ou superior, em atendimento de emergência e durante anestesia geral. Alterações do estado físico foram o principal fator de PC (23,9:10.000), seguidas de complicações cirúrgicas isoladamente (4,64:10.000) ou associadas a alterações do estado físico (2,44:10.000) e da anestesia isoladamente (1,71:10.000) ou associadas a alterações do estado físico (0,98:10.000). O risco de óbito relacionado à anestesia como fator principal ou contributivo foi igual para ambos (0,49:10.000). As principais causas da mortalidade associada à anestesia foram os problemas ventilatórios (45,4%), eventos relacionados à medicação empregada (27,3%), aspiração pulmonar (18,2%) e hidratação excessiva (9,1%). CONCLUSÕES: A incidência de PC durante a anestesia ainda continua elevada. A maioria das PC e óbitos associados à anestesia foi relacionada ao manuseio das vias aéreas e à administração de medicamentos e anestésicos.

Advances in Peritoneal Dialysis in Acute Kidney Injury

Peritoneal dialysis (PD) is a simple, safe, cheap, and efficient renal replacement therapy method. It can correct metabolic disorders and fluid overload in acute kidney injury (AKI) patients both in and out of the intensive care unit. Use of PD in AKI is enhanced by placement of a Tenckhoff catheter, which can be safely accomplished at the bedside. Some PD modalities, such as high-volume PD and continuous-flow PD, can provide dialysis doses and efficiency comparable to extracorporeal blood purification methods. PD is particularly suitable for neonates, children, and patients with refractory heart failure or who are otherwise hemodynamically unstable. PD should be considered in situations where systemic anticoagulation and/or vascular access are problematic. PD is limited by a lower efficiency that may produce inadequate renal replacement in larger and/or severely hypercatabolic patients. Fluid removal can be unpredictable, there is a risk of infection, and possible issues with mechanical ventilation. In this article, we discuss the use of PD in AKI, with emphasis on recent advances. Copyright (c) 2012 S. Karger AG, Basel

Relevância do estado de hidratação na interpretação de parâmetros nutricionais em diálise peritoneal

OBJETIVO: Identificar determinantes do estado de hidratação de pacientes em diálise peritoneal crônica, bem como investigar os efeitos da sobrecarga líquida sobre o estado nutricional. MÉTODOS: Foi feito estudo transversal, realizado em 2006, avaliando 27 pacientes em diálise peritoneal crônica, acompanhados no Hospital das Clínicas da Faculdade de Medicina de Botucatu (SP), quanto a parâmetros clínicos, dialíticos, laboratoriais, antropométricos e de bioimpedância elétrica. Para avaliar a influência de parâmetros sobre o estado de hidratação empregou-se modelo de regressão linear múltipla. A amostra foi estratificada quanto ao estado de hidratação pela relação entre água extracelular e água corporal total (0,47 para homens e 0,52 para mulheres), parâmetros obtidos por meio de bioimpedância elétrica. Comparações foram realizadas por análise de covariância, Mann-Whitney, Qui-quadrado ou teste exato de Fisher. Considerou-se significância estatística quando p≤0,05. RESULTADOS: Pacientes com maior volume urinário e em modalidade dialítica automatizada apresentaram melhor estado de hidratação. Pacientes com maior sobrecarga líquida, comparados àqueles com menor sobrecarga, apresentaram menor ângulo de fase (M=4,2, DP=0,9 vs M=5,7, DP=0,7º; p=0,006), menor albumina (M=3,06, DP=0,46 vs M=3,55, DP=0,52g/dL; p=0,05) e maior % prega cutânea tricipital (M=75,3, DP=36,9 vs M=92,1, DP=56,9%; p=0,058), sem outras evidências antropométricas. CONCLUSÃO: Pode-se sugerir que os níveis reduzidos de albumina e ângulo de fase nos pacientes com maior sobrecarga líquida não estiveram relacionados a pior estado nutricional. Para o diagnóstico nutricional em vigência de sobrecarga líquida, deve-se considerar o conjunto de variáveis obtidas por diversos métodos, buscando relacioná-las e interpretá-las de maneira abrangente, possibilitando um diagnóstico nutricional fidedigno.

Associations between bioelectrical impedance parameters and cardiovascular events in chronic dialysis patients

Purpose: Malnutrition and fluid overload contribute to the poor cardiovascular prognosis of dialysis patients. Since bioelectrical impedance analysis is an option for the evaluation of body composition and for the monitoring of hydration state, it may assist in the identification of subjects at high cardiovascular risk. The objective of this study was to evaluate the association between bioelectrical impedance parameters and cardiovascular events. Methods: The association between bioelectrical impedance parameters and fatal and non-fatal cardiovascular outcome was evaluated in 145 dialysis patients. Results: The mean age of the population studied was 54.9 ± 15.4 years, 49.7 % were males, and 35.9 % had diabetes. Forty (27.6 %) patients developed cardiovascular events during the 16 months (8; 32) of follow-up. Comparison of patients with and without cardiovascular events revealed higher extracellular mass/body cell mass (ECM/BCM) and extracellular water/total body water ratios and higher C-reactive protein levels in the former. Survival analysis showed that an ECM/BCM ratio >1.2 and a phase angle <6° were associated with poor cardiovascular prognosis. Among nondiabetic patients, these parameters and capacitance were independently associated with cardiovascular events, suggesting that poor nutritional status and fluid overload are associated with the occurrence of these events. Conclusions: Phase angle, capacitance and ECM/BCM ratio are valuable parameters for the evaluation of cardiovascular prognosis, supporting the use of bioelectrical impedance for the clinical assessment of dialysis patients. © 2012 Springer Science+Business Media Dordrecht.

Associações entre estado de hidratação, inflamtório e marcadores nutricionais em pacientes em diálise peritoneal crônica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)