The Association Between Intradialytic Symptom Clusters and Recovery Time in Patients Undergoing Maintenance Hemodialysis: An Exploratory Analysis.

Background: Individuals receiving hemodialysis often experience concurrent symptoms during treatment and frequently report feeling unwell after dialysis. The degree to which intradialytic symptoms are related, and which specific symptoms may impair health-related quality of life (HRQoL) is uncertain. Objectives: To explore intradialytic symptoms clusters, and the relationship between intradialytic symptom clusters with dialysis treatment recovery time and HRQoL. Design/setting: We conducted a post hoc analysis of a prospective cohort study of 118 prevalent patients receiving hemodialysis in two centers in Calgary, Alberta and Hamilton, Ontario, Canada. Participants: Adults receiving hemodialysis treatment for at least 3 months, not scheduled for a modality change within 6 weeks of study commencement, who could provide informed consent and were able to complete English questionnaires independently or with assistance. Methods: Participants self-reported the presence (1 = none to 5 = very much) of 10 symptoms during each dialysis treatment, the time it took to recover from each treatment, and weekly Kidney Disease Quality of Life 36-Item-Short Form (KDQoL-36) assessments. Principal component analysis identified clusters of intradialytic symptoms. Mixed-effects, ordinal and linear regression examined the association between symptom clusters and recovery time (categorized as 0, >0 to 2, >2 to 6, or >6 hours), and the physical component and mental component scores (PCS and MCS) of the KDQoL-36. Results: One hundred sixteen participants completed 901 intradialytic symptom questionnaires. The most common symptom was lack of energy (56% of treatments). Two intradialytic symptom clusters explained 39% of the total variance of available symptom data. The first cluster included bone or joint pain, muscle cramps, muscle soreness, feeling nervous, and lack of energy. The second cluster included nausea/vomiting, diarrhea and chest pain, and headache. The first cluster (median score: -0.56, 25th to 75th percentile: -1.18 to 0.55) was independently associated with longer recovery time (odds ratio [OR] 1.62 per unit difference in score, 95% confidence interval [CI]: 1.23-2.12) and decreased PCS (-0.72 per unit difference in score, 95% CI: -1.29 to -0.15) and MCS scores (-0.82 per unit difference in score, 95% CI: -1.48 to -0.16), whereas the second cluster was not (OR 1.24, 95% CI: 0.97-1.58; PCS 0.19, 95% CI -0.46 to 0.83; MCS -0.72, 95% CI: -1.50 to 0.06). Limitations: This was an exploratory analysis of a small data set from 2 centers. Further work is needed to externally validate these findings to confirm intradialytic symptom clusters and the generalizability of our findings. Conclusions: Intradialytic symptoms are correlated. The presence of select intradialytic symptoms may prolong the time it takes for a patient to recover from a dialysis treatment and impair HRQoL.

Contexte: Il arrive fréquemment que les personnes qui reçoivent des traitements d'hémodialyse éprouvent des symptômes concomitants pendant la dialyze et signalent un malaise après le traitement. On en sait toutefois peu sur le degré de corrélation de ce malaise avec les symptômes intradialytiques et sur les symptômes précis qui peuvent altérer la qualité de vie liée à la santé (QVLS). Objectifs: Explorer différents groupes de symptômes intradialytiques et la relation de ceux-ci avec le temps de récupération post-dialyze et la QVLS. Cadre et conception de l'étude: Nous avons procédé à une analyze post-hoc d'une étude de cohorte prospective portant sur 118 patients prévalents recevant une hémodialyse dans deux centers, soit à Calgary (Alberta) et à Hamilton (Ontario) au Canada. Sujets: Des adultes qui recevaient des traitements d'hémodialyse depuis au moins trois mois ­ sans changement de modalité prévu dans les six semaines suivant le début de l'étude ­ qui pouvaient donner leur consentement éclairé et qui étaient en mesure de remplir des questionnaires en anglais de façon autonome ou avec de l'aide. Méthodologie: Pour chaque traitement de dialyze, les participants devaient autoévaluer le degré de présence (de 1 [non présent] à 5 [très présent]) de dix symptômes et le temps nécessaire pour récupérer de chaque traitement, puis remplir des évaluations hebdomadaires à l'aide du questionnaire KDQoL-36. Une analyze des composantes principales a permis de définir des groupes de symptômes intradialytiques. Une régression à effets mixtes, ordinale et linéaire, a servi à examiner l'association entre les groupes de symptômes et le temps de récupération (0 heure; de 0 à 2 heures; de 2 à 6 hures; plus de 6 heures), et les scores des composantes physiques et psychologiques du KDQoL-36. Résultats: Cent seize patients ont rempli un total de 901 questionnaires sur les symptômes intradialytiques. Le symptôme le plus fréquemment déclaré était le manque d'énergie (56 % des traitements). Deux groupes de symptômes intradialytiques ont expliqué 39 % de la variance totale des données disponibles sur les symptômes. Le premier groupe comprenait des douleurs osseuses ou articulaires, des crampes musculaires, des douleurs musculaires, une sensation de nervosité et un manque d'énergie. Le deuxième groupe comprenait des nausées/vomissements, de la diarrhée, des douleurs thoraciques et des maux de tête. Le premier groupe (score médian : ­0,56; du 25e au 75e percentile : ­1, 18 à 0,55) a été indépendamment associé à un temps de récupération plus long (rapport de cotes : 1,62 par unité de différence de score; IC 95 % : 1,23 à 2,12) et à une diminution des scores des composantes physiques (RC : ­0,72; IC 95 % : ­1, 29 à ­0,15) et des scores des composantes psychologiques (RC : ­0,82; IC 95 % : ­1, 48 à ­0,16). Le deuxième groupe n'a pas été associé avec le temps de récupération (RC : 1,24; IC 95 % : 0,97 à 1,58) ni avec le score des composantes physiques (RC : 0,19; IC 95 % : ­0,46 à 0,83) et les scores des composantes psychologiques (RC : ­0,72; IC 95 % : ­1, 50 à 0,06). Limites: Il s'agissait d'une analyze exploratoire d'un petit ensemble de données provenant de deux centers. D'autres études externes sont nécessaires pour valider ces résultats et, ainsi, confirmer nos groupes de symptômes intradialytiques et la généralisabilité de nos résultats. Conclusion: Les symptômes intradialytiques sont corrélés. La présence de certains symptômes intradialytiques peut prolonger le temps de récupération post-dialyze et altérer la qualité de vie des patients.

Pyoderma Gangrenosum After Insertion of a Hemodialysis Catheter: Koebner Phenomenon, Systemic Inflammatory Response Syndrome, and a Delay in Diagnosis.

Rationale: Pyoderma gangrenosum is a rare neutrophilic dermatosis. Misdiagnosis of pyoderma gangrenosum as an infection is not uncommon. Pyoderma gangrenosum can be associated with Koebner phenomenon and rarely results in systemic inflammatory response syndrome and shock. Presenting concerns of the patient: A 61-year-old woman had recently started maintenance hemodialysis, using a tunneled catheter. She was admitted with fever and signs of inflammation at the catheter exit site and along the tunnel. Diagnoses: The initial diagnosis was catheter-related tunnel infection. The exit site broke down into a 5 cm × 5 cm lesion typical of pyoderma, and a new similar lesion developed at a subcutaneous injection site in her abdomen. Clinical diagnosis of pyoderma gangrenosum was made. She remained febrile despite broad antibiotic coverage and catheter removal and developed systemic inflammatory response syndrome (SIRS) that necessitated transfer to intensive care unit. Interventions: She responded well to fluids and intravenous steroids. Viral and bacterial cultures were negative throughout; echocardiography and computed tomography were unrevealing. Insertion of a new hemodialysis catheter was deferred as long as clinically possible, was undertaken while the patient was taking steroids, and was uncomplicated. Outcomes: She remained hemodynamically stable and was discharged after rehabilitation. Her wounds slowly granulated and healed. Steroids were tapered. Teaching points: To our knowledge, this is the first case report of a patient with pyoderma gangrenosum developing at the site of tunneled hemodialysis catheter. Our patient developed SIRS with no evidence of infection. We summarize 11 previous case reports of pyoderma leading to SIRS and responsive to steroids.

Justification: Le pyoderma gangrenosum est une dermatose neutrophile rare que l'on méprend souvent d'abord pour une infection. Cette affection qui peut être associée au phénomène de Koebner entraîne rarement un syndrome de réponse inflammatoire systémique (SRIS) et un choc. Présentation du cas: Une femme de 61 ans qui avait récemment amorcé un traitement d'hémodialyse d'entretien par cathéter tunnelisé. À l'admission, la patiente présentait de la fièvre et des signes d'inflammation au point d'émergence du cathéter et le long du tunnel. Diagnostic: On a d'abord diagnostiqué une infection du tunnel liée au cathéter. Le point d'émergence s'est étendu en une lésion de 5 cm x 5 cm typique du pyoderma et une nouvelle lésion similaire s'est développée sur l'abdomen à un point d'injection sous-cutanée. Un diagnostic clinique de pyoderma gangrenosum a été établi. La fièvre a persisté malgré une antibiothérapie étendue et le retrait du cathéter; la patiente a développé un SRIS qui a nécessité son transfert à l'unité des soins intensifs. Intervention: La patiente a bien répondu à l'administration de liquides et de stéroïdes par voie intraveineuse. Les cultures virales et bactériennes sont demeurées négatives tout au long; l'échocardiographie et la tomodensitométrie étaient non révélatrices. L'insertion d'un nouveau cathéter d'hémodialyse a été reportée aussi longtemps que le permettait l'état clinique de la patiente. La réinsertion a été entreprise alors que la patiente était sous stéroïdes et elle n'a pas entraîné de complications. Résultats: La patiente est restée hémodynamiquement stable et a obtenu son congé après la réinsertion. Les plaies ont granulé et guéri lentement. Les stéroïdes ont été réduits progressivement. Enseignements tirés: À notre connaissance, il s'agit du premier cas rapporté d'une patiente atteinte de pyoderma gangrenosum développé au point d'émergence d'un cathéter d'hémodialyse tunnelisé. Notre patiente a développé un SRIS sans signe d'infection. Nous résumons 11 cas précédents de pyoderma ayant entraîné un SRIS et ayant répondu aux stéroïdes.

Two phosphAte taRGets in End-stage renal disease Trial (TARGET): A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Hyperphosphatemia is common among recipients of maintenance dialysis and is associated with a higher risk of mortality and cardiovascular events. A large randomized trial is needed to determine whether lowering phosphate concentrations with binders improves patient-important outcomes. To inform such an effort we conducted a pilot randomized controlled trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a randomized controlled trial of prevalent hemodialysis recipients already receiving calcium carbonate as a phosphate binder at five Canadian centers between March 31, 2014 and October 2, 2014. Participants were randomly allocated to 26 weeks of an intensive phosphate goal of 2.33-4.66 mg/dl (0.75-1.50 mmol/L) or a liberalized target of 6.20-7.75 mg/dl (2.00-2.50 mmol/L) by titrating calcium carbonate using a dosing nomogram. The primary outcome was the difference in the change in serum phosphate from randomization to 26 weeks. RESULTS: Fifty-three participants were randomized to the intensive group and 51 to the liberalized group. The median (interquartile range) daily dose of elemental calcium at 26 weeks was 1800 (1275-3000) mg in the intensive group, and 0 (0-500) mg in the liberalized group. The mean (SD) serum phosphate at 26 weeks was 4.53 (1.12) mg/dl (1.46 [0.36] mmol/L) in the intensive group and 6.05 (1.40) mg/dl (1.95 [0.45] mmol/L) in the liberalized group. Phosphate concentration in the intensive group declined by 1.24 (95% confidence interval, 0.75 to 1.74) mg/dl (0.40 [95% confidence interval, 0.24 to 0.56] mmol/L) compared with the liberalized group. There were no statistically significant differences between the two groups in the risk of hypercalcemia, hypocalcemia, parathyroidectomy, or major vascular events. CONCLUSIONS: It is feasible to achieve and maintain a difference in serum phosphate concentrations in hemodialysis recipients by titrating calcium carbonate. A large trial is needed to determine if targeting a lower serum phosphate concentration improves patient-important outcomes.

The Safety and Efficacy of Mineralocorticoid Receptor Antagonists in Patients Who Require Dialysis: A Systematic Review and Meta-analysis.

BACKGROUND: Patients who require dialysis are at high risk for cardiovascular mortality, which may be improved by mineralocorticoid receptor antagonists (MRAs). STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING & POPULATION: Adults undergoing long-term hemodialysis or peritoneal dialysis with or without heart failure. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials evaluating an MRA in dialysis and reported at least one outcome of interest. INTERVENTION: Spironolactone (8 trials) or eplerenone (1 trial) compared to placebo (7 trials) or standard of care (2 trials). OUTCOMES: Cardiovascular and all-cause mortality, hyperkalemia, serum potassium level, hypotension, change in blood pressure, and gynecomastia. RESULTS: We identified 9 trials including 829 patients. The overall quality of evidence was low due to methodologic limitations in most of the included trials. The relative risk (RR) for cardiovascular mortality was 0.34 (95% CI, 0.15-0.75) for MRA-treated compared with control patients. The RR for all-cause mortality was 0.40 (95% CI, 0.23-0.69). The RR for hyperkalemia for MRA treatment was 3.05 (95% CI, 1.21-7.70). Sensitivity analyses demonstrated wide variability in RRs for cardiovascular mortality, all-cause mortality, and hyperkalemia, suggesting further uncertainty in the confidence of the primary results. LIMITATIONS: Trial quality and size insufficient to robustly and precisely identify a treatment effect. CONCLUSIONS: Given the uncertainty of both the benefits and harms of MRAs in dialysis, large high-quality trials are required.

Coronary artery calcification, cardiovascular events, and death: a prospective cohort study of incident patients on hemodialysis.

BACKGROUND: Coronary calcification in patients with end-stage renal disease (ESRD) is associated with an increased risk of cardiovascular outcomes and death from all causes. Previous evidence has been limited by short follow-up periods and inclusion of a heterogeneous cluster of events in the primary analyses. OBJECTIVE: To describe coronary calcification in patients incident to ESRD, and to identify whether calcification predicts vascular events or death. DESIGN: Prospective substudy of an inception cohort. SETTING: Tertiary care haemodialysis centre in Ontario (St Joseph's Healthcare Hamilton). PARTICIPANTS: Patients starting haemodialysis who were new to ESRD. MEASUREMENTS: At baseline, clinical characterization and spiral computed tomography (CT) to score coronary calcification by the Agatston-Janowitz 130 scoring method. A primary outcome composite of adjudicated stroke, myocardial infarction, or death. METHODS: We followed patients prospectively to identify the relationship between cardiac calcification and subsequent stroke, myocardial infarction, or death, using Cox regression. RESULTS: We recruited 248 patients in 3 centres to our main study, which required only biochemical markers. Of these 164 were at St Joseph's healthcare, and eligible to participate in the substudy; of these, 51 completed CT scanning (31 %). Median follow up was 26 months (Q1, Q3: 14, 34). The primary outcome occurred in 16 patients; 11 in the group above the median and 5 in the group below (p = 0.086). There were 26 primary outcomes in 16 patients; 20 (77 %) events in the group above the coronary calcification median and 6 (23 %) in the group below (p = 0.006). There were 10 deaths; 8 in the group above the median compared with 2 in the group below (p = 0.04). The hazard ratios for coronary calcification above, compared with below the median, for the primary outcome composite were 2.5 (95 % CI 0.87, 7.3; p = 0.09) and 1.7 (95 % CI 0.55, 5.4; p = 0.4), unadjusted and adjusted for age, respectively. For death, the hazard ratios were 4.6 (95 % CI 0.98, 21.96; p = 0.054) and 2.4 (95 % CI 0.45, 12.97; p = 0.3) respectively. LIMITATIONS: We were limited by a small sample size and a small number of events. CONCLUSIONS: Respondent burden is high for additional testing around the initiation of dialysis. High coronary calcification in patients new to ESRD has a tendency to predict cardiovascular outcomes and death, though effects are attenuated when adjusted for age.

CONTEXTE: La calcification de l'artère coronaire chez les patients atteints d'insuffisance rénale terminale (IRT) est associée à un risque accru de troubles cardiovasculaires et de mortalité, toutes causes confondues. Les données précédemment recueillies se limitaient à un suivi de courte durée, de même qu'à l'inclusion de séries d'accidents non liés lors de l'analyse préliminaire. OBJECTIFS: Décrire la calcification de l'artère coronaire chez les patients atteints d'IRT et déterminer si la calcification de l'artère coronaire peut prédire des accidents vasculaires et la mort. TYPE D'ÉTUDE: Sous-étude prospective de cohorte selon le mode d'installation. CADRE: Une unité de soins tertiaires en dialyse, en Ontario (St Joseph's Healthcare Hamilton). PARTICIPANTS: Des patients qui sont nouvellement atteints d'IRT et qui entament une hémodialyse. MESURES: En début de traitement, une caractérisation clinique et une tomodensitométrie (TDM) hélicoïdale qui permettent de mesurer la calcification de l'artère coronaire sur 130, selon l'échelle d'Agatston-Janowitz. L'indicateur principal des résultats comprend l'AVC, l'infarctus du myocarde ou la mort. MÉTHODES: Nous avons suivi les patients de manière prospective, afin de cibler la relation entre la calcification de l'artère coronaire et l'AVC, l'infarctus du myocarde ou la mort subséquente, en utilisant la régression de Cox. RÉSULTATS: Nous avons recruté 248 patients dans trois unités, dans le cadre de l'étude principale, qui ne requérait que des biomarqueurs chimiques. De ces patients, 164 étaient de St Joseph's Healthcare, et étaient admissibles à la sous-étude; 51 avaient effectué une tomographie par ordinateur (31 %). Le suivi médian s'étendait sur 26 mois (Q1, Q3: 14, 34). L'indicateur principal a été observé chez 16 patients; 11 dans le groupe se trouvant au-dessus de la médiane, et 5 dans le groupe inférieur (p?=?0,086). On a observé 26 indicateurs principaux chez 16 patients; 20 (77 %) accidents dans le groupe se trouvant au-dessus de la médiane en ce qui a trait à la calcification et 6 (23 %) dans le groupe inférieur (p?=?0,006). Il y a eu 10 décès; 8 dans le groupe se trouvant au-dessus de la médiane et 2 dans le groupe inférieur (p?=?0,04). Les taux de risque de calcification de l'artère coronaire se trouvant au-dessus et sous la médiane, pour les indicateurs principaux, étaient respectivement de 2,5 (95 % IC 0,98; 21,96; p?=?0,054) et 2,4 (95 % IC 0,45, 12,97; p?=?0,3). LIMITES DE L'ÉTUDE: Nous avons été limités par la taille restreinte de l'échantillon, de même que par le petit nombre d'accidents. CONCLUSION: Le fardeau du répondant repose sur des examens supplémentaires au moment de commencer la dialyse. Un fort taux de calcification de l'artère coronaire chez les patients nouvellement atteints d'IRT tend à prédire des accidents cardiovasculaires et la mort, bien que les effets soient atténués après révision en fonction de l'âge.

Impact of haemoglobin and erythropoietin dose changes on mortality: a secondary analysis of results from a randomized anaemia management trial.

BACKGROUND: Anaemia is a common complication of chronic kidney disease. A number of studies have identified an adverse association between haemoglobin (Hgb) variability and mortality. To date, no study has evaluated the impact of Hgb variability on mortality in the setting of a uniform Hgb target and erythropoiesis-stimulating agents (ESA) dosing strategy. METHODS: One hundred and fifty-four haemodialysis (HD) patients from a previous randomized anaemia management study were followed up for up to 6 years. The impact of Hgb variability and ESA dosing parameters on subsequent mortality risk were evaluated. RESULTS: More rapid rises in Hgb (Hgb deflect(pos)) and ESA dose increases were independently associated with mortality in multivariate analysis, whereas more rapid Hgb declines (Hgb deflect(neg)) and ESA dose decreases were not. Each gram per litre per week increase in Hgb deflect(pos) was associated with an adjusted hazard ratio (HR) of 1.23 (1.03-1.48), while for every 1000-unit increase in ESA dose, the adjusted HR was 1.12 (1.01-1.24). Factors associated with positive Hgb deflections included frequency and magnitude of ESA dose changes, baseline Hgb, patient weight and presence of an HD catheter. CONCLUSIONS: Rapid Hgb rises and greater average Eprex dose increases were independently associated with a higher mortality risk in HD patients after adjustment for baseline Hgb and Eprex dose. A randomized controlled trial evaluating different ESA dosing strategies in response to individual patient ESA responsiveness is needed.

Meta-analysis: peritoneal membrane transport, mortality, and technique failure in peritoneal dialysis.

Peritoneal membrane solute transport in peritoneal dialysis (PD) patients is assessed by the peritoneal equilibration test, which measures the ratio of creatinine in the dialysate to plasma after a standardized 4-h dwell (D/Pc). Patients then are classified as high, high-average, low-average, or low transporters on the basis of this result. A meta-analysis of observational studies was carried out to characterize the relationship between D/Pc and mortality and technique failure in patients who are on PD. Citations were identified in Medline by using a combination of Medical Subject Heading search terms and key words related to PD, peritoneal membrane permeability/transport, and mortality and technique failure. The table of contents of relevant journals and bibliographies of relevant citations were reviewed in duplicate. Twenty studies that met study criteria were identified. Nineteen studies were pooled to generate a summary mortality relative risk of 1.15 for every 0.1 increase in the D/Pc (95% confidence interval 1.07 to 1.23; P < 001). This result equated to an increased mortality risk of 21.9, 45.7, and 77.3% in low-average, high-average, and high transporters, respectively, as compared with patients with low transport status. Meta-regression analysis showed that the proportion of patients who were on continuous cycler PD within a study was inversely proportional to the mortality risk (P = 0.05). The pooled summary relative risk for death-censored technique failure was 1.18 (95% confidence interval 0.96 to 1.46; P = 0.12) for every 0.1 increase in the D/Pc. This meta-analysis demonstrates that a higher peritoneal membrane solute transport rate is associated with a higher mortality risk and a trend to higher technique failure.

Thromboembolism and anticoagulant management in hemodialysis patients: a practical guide to clinical management.

The need for anticoagulation in dialysis patients is common and the incidence of venous thromboembolism (VTE) and atrial fibrillation in this population is high. While direct data are lacking on the management of anticoagulation in dialysis patients, careful weighing of risks and benefits on the basis of evidence from other populations is crucial. VTE should be managed with adjusted dose warfarin for most patients. Placement of an inferior vena cava filter is a reasonable option for those patients with unacceptable bleeding risks. Studies are ongoing to assess the safety of some low-molecular-weight heparins (LMWH), which may potentially be useful for long-term anticoagulation in hemodialysis patients. In atrial fibrillation the available data on risk of bleeding, risk of stroke, and patient preferences should all be taken into account when considering long-term anticoagulation. We have constructed an evidence model to help quantitate the risks and benefits for an individual patient. The impact of dialysis on risk of bleeding is such that the risk of bleeding will outweigh the benefit in many patients, and anticoagulation will not be used: in some of these patients aspirin therapy may be an alternative. Finally, in the area of prevention of graft and access thrombosis, some randomized controlled trials are available, but none have to date shown benefit from anticoagulation for primary or secondary prevention of thrombosis, and the risk of bleeding in these studies was high.

Thrombocytopenia in medical-surgical critically ill patients: prevalence, incidence, and risk factors.

OBJECTIVE: The purpose of this study is to describe the prevalence, to analyze the incidence and independent risk factors for thrombocytopenia, and to examine the impact of thrombocytopenia developing in the intensive care unit (ICU) on patient outcome in a well-defined cohort of critically ill patients in a medical-surgical ICU. MATERIALS AND METHODS: As part of a prospective cohort study examining the frequency and clinical importance of venous thromboembolism in the ICU, we enrolled consecutive patients older than 18 years expected to be in the ICU for more than 72 hours. Exclusion criteria were an admitting diagnosis of trauma, orthopedic surgery or cardiac surgery, pregnancy, and life support withdrawal. Patients had platelet counts performed as directed by clinical need. We defined thrombocytopenia as a platelet count of less than 150 x 10(9)/L and severe thrombocytopenia as a platelet count of less than 50 x 10(9)/L. Protocol-directed care included routine thromboprophylaxis and twice weekly screening ultrasonography of the legs. Patients were followed to hospital discharge. RESULTS: Of the 261 enrolled patients, 121 (46%, 95% confidence interval [CI], 40%-53%) had thrombocytopenia (62 on ICU admission and 59 acquired during their ICU stay). Patients who developed a platelet count less than 150 x 10(9)/L during their ICU stay had higher ICU and hospital mortality (P = .03 and .005, respectively), required longer mechanical ventilation (P = .05), and were more likely to receive platelets (P < .001), fresh frozen plasma (P = .005), and red blood cell transfusions (P = .004) than patients who did not develop thrombocytopenia. The only independent risk factors for thrombocytopenia developing during the ICU stay were administration of nonsteroidal anti-inflammatory drugs before ICU admission (hazard ratio, 2.8; 95% CI, 1.3-6.0) and dialysis during the ICU stay (hazard ratio, 3.1; 95% CI, 1.2-7.8). Of the 33 patients who underwent 36 tests for heparin-induced thrombocytopenia, none tested positive. CONCLUSIONS: We found that about 50% of the patients admitted to the ICU had at least one platelet count of less than 150 x 10(9)/L during their ICU stay. Patients who developed thrombocytopenia were more likely to die, required longer duration of mechanical ventilation, and were more likely to require blood product transfusion. Heparin-induced thrombocytopenia was frequently suspected but did not develop in these critically ill patients.

Dalteparin thromboprophylaxis for critically ill medical-surgical patients with renal insufficiency.

PURPOSE: Thromboprophylaxis with low-molecular-weight heparin (LMWH) may be more effective than unfractionated heparin but also more likely to bioaccumulate and potentially cause bleeding in patients with renal insufficiency. The objectives of this study were to assess, among medical-surgical patients in the intensive care unit receiving dalteparin 5,000 IU daily for thromboprophylaxis, (1) the relationship between renal dysfunction and LMWH bioaccumulation as measured by trough anti-Xa levels, (2) the relationship between renal dysfunction and risk of bleeding as measured by a surrogate marker (peak anti-Xa levels), and (3) the relationship between anti-Xa levels, bleeding events, and thrombotic events. MATERIALS AND METHODS: In this prospective single-center cohort study, we enrolled patients 18 years or older, expected to stay 72 hours or longer, and with a creatinine clearance 30 mL/min or higher at intensive care unit admission. We administered 5,000 IU dalteparin subcutaneously each day. The main phase 1 objective was to detect bioaccumulation of dalteparin by measuring trough anti-Xa levels (22-23 hours post dalteparin). The main phase 2 objective was to examine the relationship between renal dysfunction and peak anti-Xa levels (4 hours post dalteparin). We recorded creatinine clearance daily and bleeding and thrombotic events, blinded to anti-Xa levels. RESULTS: We enrolled 19 patients aged 62.7 (13.2) years with an APACHE II score of 23.5 (9.4). We measured trough anti-Xa levels on 185 occasions in 19 patients; we measured peak anti-Xa levels on 113 occasions in 11 patients. We identified no bioaccumulation of LMWH in this study, as detected by trough anti-Xa levels. Most peak anti-Xa levels were in the conventional prophylactic range. CONCLUSIONS: When administered in prophylactic doses to critically ill patients with a wide range of calculated creatinine clearances, we found no evidence of bioaccumulation of dalteparin. If dalteparin does not bioaccumulate, it may be an attractive alternative agent for thromboprophylaxis.

Protocolized anemia management with erythropoietin in hemodialysis patients: a randomized controlled trial.

Treatment of the anemia of chronic renal failure with exogenous recombinant human erythropoietin (rHuEpo) is well established. The objective of this randomized clinical trial was to evaluate an anemia management team protocol in hemodialysis patients, using subcutaneous rHuEpo and intravenous iron. A total of 215 patients were randomized to either usual care or the protocol. The primary outcome was the proportion of patient hemoglobin (Hgb) values between 11.0 and 12.5 g/dl over the final 8 wk. The study was halted after 240 d because of an institutional change to intravenous rHuEpo. The proportion of Hgb values in the target range increased from 47.4% to 62.8% overall (P = 0.001); there was no difference between treatment groups. The proportion of baseline Hgb values between 11.0 and 12.5 g/dl increased from 44.6% in patients who had enrolled within the first 3 mo of study inception to 75.0% in those who started later (P = 0.017), suggesting a Hawthorne effect. A nonsignificant decrease in rHuEpo dose was observed in the protocol group; subgroup analysis in patients who were enrolled for at least 5 mo demonstrated a reduction in the rHuEpo dose of 2788 units/wk in the protocol group (P < 0.05), independent of intravenous iron dose. Multivariate analysis demonstrated that a higher transferrin saturation and albumin and protocol group assignment were associated with a lower final rHuEpo dose. This study demonstrated that a protocolized approach to anemia management in hemodialysis patients results in comparable Hgb levels and may reduce rHuEpo requirements, independent of iron use.

Prognostic value of myocardial perfusion studies in patients with end-stage renal disease assessed for kidney or kidney-pancreas transplantation: a meta-analysis.

The prognostic utility of myocardial perfusion studies (MPS) such as thallium scintigraphy and dobutamine stress echocardiography (DSE) for stratifying cardiac risk among candidates for kidney or kidney-pancreas transplantation is uncertain. This study is a meta-analysis to determine the prognostic significance of MPS results on future myocardial infarction (MI) and cardiac death (CD) in patients with end-stage renal disease (ESRD) assessed for kidney or kidney-pancreas transplantation. MEDLINE was searched using combinations of MeSH headings and text words for transplantation, coronary artery disease, prognosis, end-stage renal disease, and noninvasive cardiac testing (nuclear scintigraphy and DSE) for primary studies. Studies were included if they reported MPS results and cardiac events in patients assessed for kidney or kidney-pancreas transplantation. Methodologic study quality and outcome data were independently abstracted in duplicate by two researchers. The relative risks (RR) of MI and CD were calculated using a random effects model. Twelve articles met all inclusion criteria; 12 studies reported CD, and 9 reported MI. In eight studies, thallium scintigraphy was used (four with pharmacologic stress, four with exercise stress), whereas four used DSE. When compared with negative tests, positive tests had a significantly increased RR of MI (2.73 [95% CI, 1.25 to 5.97]; P = 0.01) and CD (2.92 [95% CI, 1.66 to 5.12]; P < 0.001). Subgroup analyses of studies of diabetic patients indicated that positive tests were associated with a RR of CD 3.95 (95% CI, 1.48 to 10.5; P = 0.006) and a RR of MI 2.68 (95% CI, 0.95 to 7.57; P = 0.06) when compared with negative tests. In studies evaluating mixed populations of diabetic and nondiabetic patients, positive tests were associated with a RR of CD 2.52 (95% CI, 1.25 to 5.08; P = 0.01) and with a RR of MI 2.79 (95% CI, 0.85 to 9.21; P = 0.09) when compared with a negative test. The presence of reversible defects was associated with an increased risk of MI in diabetic patients and of CD in both subgroups; fixed defects were associated with an increased risk of CD but not MI. It is concluded that positive MPS are useful in identifying patients with significantly increased risk of future MI and CD in both diabetic and nondiabetic ESRD patients.

Comparison of mortality risk for dialysis patients and cadaveric first renal transplant recipients in Ontario, Canada.

In population-based studies, renal transplantation has been shown to improve survival compared to dialysis patients awaiting transplantation in the United States. However, dialysis mortality in the United States is higher than in Canada. Whether transplantation offers a survival advantage in regions where dialysis survival is superior to that in the United States is uncertain. This study examines a cohort of 1156 patients who started end-stage renal disease (ESRD) therapy and were wait-listed for cadaveric renal transplantation in the province of Ontario, Canada between January 1, 1990 and December 31, 1994. Patients were followed from wait-listing for renal transplant (n = 1156), to cadaveric first renal transplant (n = 722), to death, or to study end (December 31, 1995). The annual crude mortality rates for wait-listed dialysis patients and transplanted patients were 5.0 and 3.4%, respectively. In Cox proportional hazards models, mortality in wait-listed patients was associated with increased age and diabetes, but not time from onset of ESRD to wait-listing. Factors associated with death following transplantation include older age, diabetes, and longer time spent on the waiting list before transplantation. In a time-dependent Cox regression model, the relative risk of death after transplantation compared to dialysis varied in a time-dependent manner. Covariates associated with increased risk included older age, diabetes, and time from onset of ESRD to wait-listing. The average relative risk (RR) of dying was 2.91 (95% confidence interval [CI], 1.34 to 6.32) in the first 30 d after transplantation, but was significantly lower 1 yr after transplantation (RR 0.25; 95% CI, 0.14 to 0.42), indicating a beneficial long-term effect when compared to wait-listed dialysis patients. This long-term benefit was most evident in subgroups of patients with diabetes (RR 0.38; 95% CI, 0.17 to 0.87) and glomerulonephritis (RR 0.13; 95% CI, 0.04 to 0.39) as the cause of ESRD. The survival advantage associated with renal transplantation is evident in this cohort of patients with a lower wait-listed dialysis mortality than that reported previously in the United States. The magnitude of the treatment effect is consistent across studies.