Determining the optimal time for liberation from renal replacement therapy in critically ill patients: a systematic review and meta-analysis (DOnE RRT).

INTRODUCTION: Renal replacement therapy (RRT) is associated with high mortality and costs; however, no clinical guidelines currently provide specific recommendations for clinicians on when and how to stop RRT in recovering patients. Our objective was to systematically review the current evidence for clinical and biochemical parameters that can be used to predict successful discontinuation of RRT. METHODS: A systematic review and meta-analysis were performed with a peer-reviewed search strategy combining the themes of renal replacement therapy (IHD, CRRT, SLED), predictors of successful discontinuation or weaning (defined as an extended period of time free from further RRT), and patient outcomes. Major databases were searched and citations were screened using predefined criteria. Studied parameters were reported and, where possible, data was analyzed in the pooled analysis. RESULTS: Our search yielded 23 studies describing 16 variables for predicting the successful discontinuation of RRT. All studies were observational in nature. None were externally validated. Fourteen studies described conventional biochemical criteria used as surrogates of glomerular filtration rate (serum urea, serum creatinine, creatinine clearance, urine urea excretion, urine creatinine excretion). Thirteen studies described physiologic parameters such as urine output before and after cessation of RRT, and 13 studies reported on newer kidney biomarkers, such as serum cystatin C and serum neutrophil gelatinase-associated lipocalin (NGAL). Six studies reported sensitivity and specificity characteristics of multivariate models. Urine output prior to discontinuation of RRT was the most-studied variable, with nine studies reporting. Pooled analysis found a sensitivity of 66.2% (95% CI, 53.6-76.9%) and specificity of 73.6% (95% CI, 67.5-79.0%) for urine output to predict successful RRT discontinuation. Due to heterogeneity in the thresholds of urine output used across the studies, an optimal threshold value could not be determined. CONCLUSIONS: Numerous variables have been described to predict successful discontinuation of RRT; however, available studies are limited by study design, variable heterogeneity, and lack of prospective validation. Urine output prior to discontinuation of RRT was the most commonly described and robust predictor. Further research should focus on the determination and validation of urine output thresholds, and the evaluation of additional clinical and biochemical parameters in multivariate models to enhance predictive accuracy.

Routine use of post-bronchodilator testing in pulmonary function testing labs.

PURPOSE: Pulmonary function tests (PFTs), including spirometry with and without post-bronchodilator (post-BD) testing, are frequently performed in the assessment of asthma, along with other obstructive airway disorders. Multiple publications over the past 15 years have noted that one in three physician-diagnosed asthma cases are not in fact asthma. In this quality assurance project, we assess whether PFT labs in Alberta have policies on post-BD testing, as extraneous and unnecessary use of post-BD testing can lead to wasted staff and patient time and unnecessary expenses to the health care system. METHODS: We reviewed, in collaboration with the College of Physicians and Surgeons of Alberta and Alberta Medical Association, all PFT labs in the province of Alberta (hospital-based private not-for-profit [NFP] and private for-profit [FP] labs). This health policy study of PFT labs involved identifying the proportions and regional distribution of NFP and private FP labs in the province of Alberta while assessing post-BD policies. Each PFT lab was asked for their policy regarding spirometry and asthma diagnosis from May 1 to August 31, 2017. RESULTS: A total of 92 PFT labs were identified in Alberta, 74 of which were private FP (independent) labs, while 18 were private NFP (public) hospital-based labs. Policies were as follows: (i) post-BD policy existed (and if so routinely performed / not routinely done); (ii) no post-BD policy; and (iii) lab chose not to participate. All 18 hospital labs responded: 10 had no policy; six had a policy or algorithm; one did not perform post-BD testing (exercise testing) and one had multiple testing sites. Of the private FP labs, three had relevant policies and/or algorithm and 10 had none. No information was provided from 61 labs. Access to PFT labs in Northern Alberta was limited. CONCLUSIONS: Lab policies surrounding post-BD testing were found to be heterogeneous in Alberta. Low response rates, despite the use of a systems approach and requests in writing and in person from FP labs, were notable. Development of a standardized policy across the province would be beneficial. Further higher-level review of the appropriateness of post-BD use in both FP and NFP PFT labs is needed.

Intraoperative continuous renal replacement therapy during liver transplantation: a pilot randomized-controlled trial (INCEPTION).

PURPOSE: To evaluate the feasibility of intraoperative continuous renal replacement therapy (IoCRRT) during liver transplantation (LT), in terms of recruitment, protocol adherence, and ascertainment of follow-up. METHODS: In this pilot randomized open-label controlled trial in adults receiving LT with a Model for End-Stage Liver Disease (MELD) score ≥ 25 and preoperative acute kidney injury (RIFLE - RISK or higher) and/or estimated glomerular filtration rate < 60 mL·min-1·1.73 m-2, patients were randomized to receive IoCRRT or standard of care (SOC). Primary endpoints were feasibility and adverse events. Primary analysis was intention-to-treat (n = 32) and secondary analysis was per-protocol (n = 28). RESULTS: The trial was stopped early because of slow patient accrual and inadequate funding. Sixty patients were enrolled and 32 (53%) were randomized (n = 15 IoCRRT; n = 17 SOC). Mean (standard deviation) MELD was 36 (8), 81% (n = 26) had cirrhosis; 69% (n = 22) received preoperative RRT; 66% (n = 21) received LT from the intensive care unit. Four patients (n = 2 IoCRRT, n = 2 SOC) did not receive LT post-randomization. Seven patients (41%) allocated to SOC crossed over intraoperatively to IoCRRT. Three patients were lost to follow-up at one year. No adverse events occurred related to IoCRRT. There were no differences in survival at one year (IoCRRT, 71% [n = 10/14] vs SOC, 93% [n = 14/15]; risk ratio, 0.77; 95% confidence interval, 0.54 to 1.1). In the per-protocol analysis (n = 28 received IoCRRT after randomization - n = 20 IoCRRT, n = 8 SOC), one-year survival was 92% and perioperative complications were similar between groups. Only one patient was receiving dialysis one year after LT. CONCLUSION: In this pilot randomized trial, IoCRRT was feasible and safe with no difference in complications. Crossover rates were high. Despite high preoperative severity of illness, one-year survival was excellent. These data can inform the design of a larger multicentre trial. TRIAL REGISTRATION: www.clinicalTrials.gov (NCT01575015); registered 12 April, 2012.

RéSUMé: OBJECTIF: Notre but était d'évaluer la faisabilité d'un traitement substitutif peropératoire continu de l'insuffisance rénale pendant une greffe hépatique, notamment en matière de recrutement, d'adhésion au protocole, et de suivi. MéTHODE: Dans cette étude randomisée contrôlée non aveugle pilote réalisée auprès d'adultes recevant une greffe hépatique avec un score MELD (Model for End-Stage Liver Disease) ≥ 25 et une insuffisance rénale aiguë préopératoire (RIFLE - RISQUÉ ou plus élevé) et/ou un taux de filtration glomérulaire estimé < 60 mL·min−1·1,73 m−2, les patients ont été randomisés à recevoir un traitement substitutif peropératoire continu de l'insuffisance rénale (le traitement) ou les soins habituels (la norme). Les critères d'évaluation principaux étaient la faisabilité et les événements indésirables. L'analyse principale était l'analyse du projet thérapeutique (intention-to-treat; n = 32) et l'analyse secondaire était l'analyse selon le protocole (n = 28). RéSULTATS: L'étude a été précocement interrompue en raison du recrutement lent de patients et du manque de fonds. Soixante patients ont été recrutés et 32 (53 %) ont été randomisés (n = 15 traitement; n = 17 norme). Le score MELD moyen (écart type) était de 36 (8), 81 % (n = 26) des patients souffraient de cirrhose; 69 % (n = 22) ont reçu un traitement substitutif de l'insuffisance rénale préopératoire; 66 % (n = 21) ont reçu une greffe hépatique à partir de l'unité de soins intensifs. Quatre patients (n = 2 traitement, n = 2 norme) n'ont pas reçu de greffe hépatique après la randomisation. Sept patients (41 %) alloués au groupe norme sont passés dans le groupe traitement en période peropératoire. Trois patients ont été perdus au suivi au cours de la première année. Aucun événement indésirable n'est survenu en association au traitement substitutif peropératoire continu de l'insuffisance rénale. Aucune différence en matière de survie à un an n'a été observée (traitement, 71 % [n = 10/14] vs norme, 93 % [n = 14/15]; risque relatif, 0,77; intervalle de confiance 95 %, 0,54 à 1,1). Dans l'analyse selon le protocole (n = 28 ont reçu un traitement après la randomisation - n = 20 traitement, n = 8 norme), la survie à un an était de 92 % et les complications périopératoires étaient semblables dans les deux groupes. Un seul patient recevait de la dialyse un an après la greffe hépatique. CONCLUSION: Dans cette étude randomisée pilote, le traitement substitutif peropératoire continu de l'insuffisance rénale s'est avéré faisable et sécuritaire, et aucune différence en matière de complications n'a été observée. Les taux de transfert d'un groupe à l'autre étaient élevés. Malgré une sévérité préopératoire élevée de la maladie, la survie à un an était excellente. Ces données peuvent être utiles pour concevoir une étude multicentrique plus importante. ENREGISTREMENT DE L'éTUDE: www.clinicalTrials.gov (NCT01575015); enregistrée le 12 avril 2012.

Healthcare Provider Perceptions of Causes and Consequences of ICU Capacity Strain in a Large Publicly Funded Integrated Health Region: A Qualitative Study.

OBJECTIVES: Discrepancy in the supply-demand relationship for critical care services precipitates a strain on ICU capacity. Strain can lead to suboptimal quality of care and burnout among providers and contribute to inefficient health resource utilization. We engaged interprofessional healthcare providers to explore their perceptions of the sources, impact, and strategies to manage capacity strain. DESIGN: Qualitative study using a conventional thematic analysis. SETTING: Nine ICUs across Alberta, Canada. SUBJECTS: Nineteen focus groups (n = 122 participants). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Participants' perspectives on strain on ICU capacity and its perceived impact on providers, families, and patient care were explored. Participants defined "capacity strain" as a discrepancy between the availability of ICU beds, providers, and ICU resources (supply) and the need to admit and provide care for critically ill patients (demand). Four interrelated themes of contributors to strain were characterized (each with subthemes): patient/family related, provider related, resource related, and health system related. Patient/family-related subthemes were "increasing patient complexity/acuity," along with patient-provider communication issues ("paucity of advance care planning and goals-of-care designation," "mismatches between patient/family and provider expectations," and "timeliness of end-of-life care planning"). Provider-related factor subthemes were nursing workforce related ("nurse attrition," "inexperienced workforce," "limited mentoring opportunities," and "high patient-to-nurse ratios") and physician related ("frequent turnover/handover" and "variations in care plan"). Resource-related subthemes were "reduced service capability after hours" and "physical bed shortages." Health system-related subthemes were "variable ICU utilization," "preferential "bed" priority for other services," and "high ward bed occupancy." Participants perceived that strain had negative implications for patients ("reduced quality and safety of care" and "disrupted opportunities for patient- and family-centered care"), providers ("increased workload," "moral distress," and "burnout"), and the health system ("unnecessary, excessive, and inefficient resource utilization"). CONCLUSIONS: Engagement with frontline critical care providers is essential for understanding their experiences and perspectives regarding strained capacity and for the development of sustainable strategies for improvement.

The Evolution of Critical Care Nephrology in Edmonton.

The University of Alberta (UofA) in Edmonton, Canada has a rich and productive history supporting the development of critical care medicine, nephrology and the evolving subspecialty of critical care nephrology. The first hemodialysis program for patients with chronic renal failure in Canada was developed at the University of Alberta Hospital. The UofA is also recognized for its early pioneering work on the diagnosis, etiology and outcomes associated with acute kidney injury (AKI), the development of a diagnostic scheme renal allograft rejection (Banff classification), and contributions to the Renal Disaster Relief Task Force. Edmonton was one of the first centers in Canada to provide continuous renal replacement therapy. This has grown into a comprehensive clinical, educational and research center for critical care nephrology. Critical care medicine in Edmonton now leads and participates in numerous critical care nephrology initiatives dedicated to AKI, renal replacement therapy, renal support in solid organ transplantation, and extracorporeal blood purification. Critical care medicine in Edmonton is recognized across Canada and across the globe as a leading center of excellence in critical care nephrology, as an epicenter for research innovation and for training a new generation of clinicians with critical care nephrology expertise.

Disaster nephrology: crush injury and beyond.

Disasters result in a substantial number of renal challenges, either by the creation of crush injury in victims trapped in collapsed buildings or by the destruction of existing dialysis facilities, leaving chronic dialysis patients without access to their dialysis units, medications, or medical care. Over the past two decades, lessons have been learned from the response to a number of major natural disasters that have impacted significantly on crush-related acute kidney injury and chronic dialysis patients. In this paper we review the pathophysiology and treatment of the crush syndrome, as summarized in recent clinical recommendations for the management of crush syndrome. The importance of early fluid resuscitation in preventing acute kidney injury is stressed, logistic difficulties in disaster conditions are described, and the need for an implementation of a renal disaster relief preparedness program is underlined. The role of the Renal Disaster Relief Task Force in providing emergency disaster relief and the logistical support required is outlined. In addition, the importance of detailed education of chronic dialysis patients and renal unit staff in the advance planning for such disasters and the impact of displacement by disasters of chronic dialysis patients are discussed.

Impact of intensive care unit admission during morning bedside rounds and mortality: a multi-center retrospective cohort study.

INTRODUCTION: Recent data have suggested that patient admission during intensive care unit (ICU) morning bedside rounds is associated with less favorable outcome. We undertook the present study to explore the association between morning round-time ICU admissions and hospital mortality in a large Canadian health region. METHODS: A multi-center retrospective cohort study was performed at five hospitals in Edmonton, Canada, between July 2002 and December 2009. Round-time ICU admission was defined as occurring between 8 and 11:59 a.m. Multivariable logistic regression analysis was used to explore the association between round-time admission and outcome. RESULTS: Of 18,857 unique ICU admissions, 2,055 (10.9%) occurred during round time. Round-time admissions were more frequent in community hospitals compared with tertiary hospitals (12.0% vs. 10.5%; odds ratio [OR] 1.16; 95% CI, 1.05-1.29, P < 0.004) and from the ward compared with the emergency department (ED) or operating theater (17.5% vs. 9.2%; OR 2.1; 95% CI, 1.9-2.3, P < 0.0001). Round-time admissions were more often medical than surgical (12.6% vs. 6.6%; OR 2.06; 95% CI, 1.83-2.31, P < 0.0001), had more comorbid illness (11.9% vs. 10.5%; OR 1.15; 95% CI, 1.04-1.27, P < 0.008) and higher APACHE II score (22.2 vs. 21.3, P < 0.001), and were more likely to have a primary diagnosis of respiratory failure (37.0% vs. 31.3%, P < 0.001) or sepsis (11.1% vs. 9.0%, P = 0.002). Crude ICU mortality (15.3% vs. 11.6%; OR 1.38; 95% CI, 1.21-1.57, P < 0.0001) and hospital mortality (23.9% vs. 20.6%; OR 1.21; 95% CI, 1.09-1.35, P < 0.001) were higher for round-time compared with non-round-time admissions. In multi-variable analysis, round-time admission was associated with increased ICU mortality (OR 1.19, 95% CI, 1.03-1.38, P = 0.017) but was not significantly associated with hospital mortality (OR 1.02; 95% CI, 0.90-1.16, P = 0.700). In the subgroup admitted from the ED, round-time admission showed significantly higher ICU mortality (OR 1.54; 95% CI, 1.21-1.95; P < 0.001) and a trend for higher hospital mortality (OR 1.22; 95% CI, 0.99-1.51, P = 0.057). CONCLUSIONS: Approximately 1 in 10 patients is admitted during morning rounds. These patients are more commonly admitted from the ward and are burdened by comorbidities, are non-operative, and have higher illness severity. These patients admitted during morning rounds have higher observed ICU mortality but no difference in hospital mortality.

An evaluation of intraoperative renal support during liver transplantation: a matched cohort study.

BACKGROUND: Intraoperative continuous renal replacement therapy (CRRT) has been utilized during liver transplantation (LT). Our objective was to assess intraoperative CRRT for metabolic control, postoperative complications and outcomes. METHODS: Retrospective matched cohort study. Cases were LT patients receiving intraoperative CRRT. Controls were matched for demographics and Model for End-Stage Liver Disease (MELD) score. Data were extracted on physiology, course and outcomes. RESULTS: 72 patients were included. Despite effort to match by MELD, cases had higher scores (35.4 vs. 29.9, p = 0.01) compared to controls. Preoperatively, cases received more vasopressors (p = 0.006), and more RRT (94.4 vs. 25.7%, p < 0.0001). There was no difference in complications (p = 0.35) or ICU re-admission rate (p = 0.29). Cases were more likely to require postoperative RRT (p < 0.0001). There was no difference in hospital mortality (p = 0.61). CONCLUSIONS: LT patients selected for intraoperative CRRT more commonly have hemodynamic instability and preoperative acute kidney injury requiring RRT. Despite higher illness severity for cases, there were no differences in complications or mortality.

Validation of the Work Observation Method By Activity Timing (WOMBAT) method of conducting time-motion observations in critical care settings: an observational study.

BACKGROUND: Electronic documentation handling may facilitate information flows in health care settings to support better coordination of care among Health Care Providers (HCPs), but evidence is limited. Methods that accurately depict changes to the workflows of HCPs are needed to assess whether the introduction of a Critical Care clinical Information System (CCIS) to two Intensive Care Units (ICUs) represents a positive step for patient care. To evaluate a previously described method of quantifying amounts of time spent and interruptions encountered by HCPs working in two ICUs. METHODS: Observers used PDAs running the Work Observation Method By Activity Timing (WOMBAT) software to record the tasks performed by HCPs in advance of the introduction of a Critical Care clinical Information System (CCIS) to quantify amounts of time spent on tasks and interruptions encountered by HCPs in ICUs. RESULTS: We report the percentages of time spent on each task category, and the rates of interruptions observed for physicians, nurses, respiratory therapists, and unit clerks. Compared with previously published data from Australian hospital wards, interdisciplinary information sharing and communication in ICUs explain higher proportions of time spent on professional communication and documentation by nurses and physicians, as well as more frequent interruptions which are often followed by professional communication tasks. CONCLUSIONS: Critical care workloads include requirements for timely information sharing and communication and explain the differences we observed between the two datasets. The data presented here further validate the WOMBAT method, and support plans to compare workflows before and after the introduction of electronic documentation methods in ICUs.

Critical care providers refer to information tools less during communication tasks after a critical care clinical information system introduction.

Electronic documentation methods may assist critical care providers with information management tasks in Intensive Care Units (ICUs). We conducted a quasi-experimental observational study to investigate patterns of information tool use by ICU physicians, nurses, and respiratory therapists during verbal communication tasks. Critical care providers used tools less at 3 months after the CCIS introduction. At 12 months, care providers referred to paper and permanent records, especially during shift changes. The results suggest potential areas of improvement for clinical information systems in assisting critical care providers in ensuring informational continuity around their patients.

Review article: Renal support in critical illness.

PURPOSE: This review provides a focused and comprehensive update on established and emerging evidence in acute renal replacement therapy (RRT) for critically ill patients with acute kidney injury (AKI). PRINCIPAL FINDINGS: There have been considerable technological innovations in the methods and techniques for provision of extracorporeal RRT in critical illness. These have greatly expanded our capability to provide both renal and non-renal life-sustaining organ support for critically ill patients. Recent data suggest earlier initiation of RRT in AKI may confer an advantage for survival and renal recovery. Two large trials have recently shown no added benefit to augmented RRT dose delivery in AKI. Observational data have also suggested that fluid accumulation in critically ill patients with AKI is associated with worse clinical outcome. However, several fundamental clinical questions remain to be answered, including issues regarding the time to ideally initiate/discontinue RRT, the role of high-volume hemofiltration or other blood purification techniques in sepsis, and extracorporeal support for combined liver-kidney failure. Extracorporeal support with RRT in sepsis, rhabdomyolysis, and liver failure are discussed, along with strategies for drug dosing and management of RRT in sodium disorders. CONCLUSIONS: We anticipate that this field will continue to expand to promote research and innovation, hopefully for the benefit of sick critically ill patients.

[Review article: Acute kidney injury in critical illness].

PURPOSE: This review provides a focused and comprehensive update on emerging evidence related to acute kidney injury (AKI). PRINCIPAL FINDINGS: Acute kidney injury is a significant clinical problem that increasingly complicates the course of hospitalization and portends worse clinical outcome for sick hospitalized patients. The recent introduction of consensus criteria for the diagnosis of AKI (i.e., RIFLE/AKIN classification) have greatly improved our capacity not only to standardize the diagnosis and classification of severity of AKI, but also to facilitate conducting comparative epidemiologic studies in an effort to better understand the burden of adult and pediatric AKI and its syndromes (i.e., septic, cardio-renal, hepato-renal). The characterization of several novel AKI-specific biomarkers (i.e., neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and interleukin-18) is extending our understanding of the pathophysiology of AKI. Moreover, these biomarkers appear to have clinical relevance for early detection and they provide prognostic value. These innovations are aiding in the design of epidemiologic surveys and randomized trials of therapeutic interventions. Strategies for prevention and conservative management of AKI across a range of clinical settings are discussed, including sepsis, hepato-renal syndrome, cardio-renal syndrome, rhabdomyolysis and in the perioperative setting. CONCLUSIONS: Acute kidney injury is an escalating clinical problem in hospitalized patients. Recent advances in AKI have improved knowledge of its pathogenesis, diagnosis, and prognosis; however, considerable research effort is needed. There are still relatively few interventions proven to alter the natural history of established AKI in hospitalized settings, and its development foretells less favourable outcomes.

Impact of a critical care clinical information system on interruption rates during intensive care nurse and physician documentation tasks.

Computerized documentation methods in Intensive Care Units (ICUs) may assist Health Care Providers (HCP) with their documentation workload, but evaluating impacts remains problematic. A Critical Care clinical Information System (CCIS) is an electronic charting tool designed for ICUs that may fit seamlessly into HCP work. Observers followed ICU nurses and physicians in two ICUs in Edmonton, Canada, in which a CCIS had recently been introduced. Observers recorded amounts of time HCPs spent on documentation related tasks, interruptions encountered by HCPs, and contextual information in field notes. Interruption rates varied depending on the charting medium used, with physicians being interrupted less frequently when performing documentation tasks using the CCIS, than when performing documentation tasks using other methods. In contrast, nurses were interrupted more frequently when charting using the CCIS than when using other methods. Interruption rates coupled with qualitative observations suggest that physicians utilize strategies to avoid interruptions if interfaces for entering textual notes are not well adapted to interruption-rich environments such as ICUs. Potential improvements are discussed such that systems like the CCIS may better integrate into ICU work.

Intraoperative renal support during liver transplantation.

Acute kidney injury (AKI) is common in liver failure prior to orthotopic liver transplantation (OLT) and may complicate the intraoperative course. We describe the logistics of intraoperative continuous renal replacement therapy (CRRT) during OLT and the associated clinical outcomes. We performed a retrospective review of adult patients (age > 18 years) receiving intraoperative CRRT during OLT at the University of Alberta Hospital between January 1, 1996 and December 31, 2005. Demographic, detailed clinical, and perioperative data, physiologic and laboratory measures, details of renal replacement therapy (RRT) provided, and data on renal recovery and survival were ascertained. Of 636 OLTs, 41 (6.4%) received intraoperative CRRT. The most common indications for OLT in these patients were hepatitis C (34.2%) and alcoholic (29.3%) cirrhosis. The median [interquartile range (IQR)] Model for End-Stage Liver Disease score was 38 (31-43), and 90.2% were classified as Child-Pugh class C. Preoperatively, 70% were in the intensive care unit, 58.5% were mechanically ventilated, and 48.7% required vasopressor support. The median (IQR) duration of intraoperative CRRT was 258 (189-390) minutes, representing 57% of the total operative time. Filter circuit clotting occurred in 40% but was not associated with a shorter CRRT duration (P = 0.41). No other complications were described. CRRT allowed an even or negative intraoperative fluid balance in 92.7%. CRRT was continued in 78% after OLT for a median (IQR) of 5 (3-11) days. Of these, 24 (75%) were transitioned to intermittent hemodialysis for a median (IQR) of 15 (4-39) days. Survival was 97.6% at 1 month and 75.6% at 1 year. Renal recovery to RRT independence occurred in 100% of survivors by 1 year; however, the mean (standard deviation) estimated glomerular filtration rate (eGFR) was 54.7 (19.1) mL/minute/m(2), with 62.1% having an eGFR < 60 mL/minute/m(2). In conclusion, our data suggest that intraoperative CRRT during OLT is achievable and safe. Intraoperative CRRT may be a valuable adjuvant therapy for those with preoperative AKI. Additional investigations are warranted.

A proposed algorithm for initiation of renal replacement therapy in adult critically ill patients.

Critically ill patients whose course is complicated by acute kidney injury often receive renal replacement therapy (RRT). For these patients, initiation of RRT results in a considerable escalation in both the complexity and associated cost of care. While RRT is extensively used in clinical practice, there remains uncertainty about the ideal circumstances of when to initiate RRT and for what indications. The process of deciding when to initiate RRT in critically ill patients is complex and is influenced by numerous factors, including patient-specific and clinician-specific factors and those related to local organizational/logistical issues. Studies have shown marked variation between clinicians, and across institutions and countries. As a consequence, analysis of ideal circumstances under which to initiate RRT is challenging. Recognizing this limitation, we review the available data and propose a clinical algorithm to aid in the decision for RRT initiation in critically ill adult patients. The algorithm incorporates several patient-specific factors, based on evidence when available, that may decisively influence when to initiate RRT. The objective of this algorithm is to provide a starting point to guide clinicians on when to initiate RRT in critically ill adult patients. In addition, the proposed algorithm is intended to provide a foundation for prospective evaluation and the development of a broad consensus on when to initiate RRT in critically ill patients.

A case-control study of single-pass albumin dialysis for acetaminophen-induced acute liver failure.

BACKGROUND: Extracorporeal support with single-pass albumin dialysis (SPAD) may remove protein-bound toxins in acute liver failure. We evaluated the clinical, physiological and laboratory parameters of SPAD in acetaminophen-induced acute liver failure (AALF). METHODS: Retrospective case-control studies of AALF patients were used. RESULTS: We identified 13 AALF patients (6 SPAD-treated, 7 controls). The average age was 38 years, 92% were female, none had cirrhosis and the Model for End-Stage Liver Disease (MELD) scores were 43. Eleven patients (85%) fulfilled the King's College criteria for a liver transplant. SPAD-treated patients received 21 sessions (total: 147 h, mean 3.5 runs or 24.5 h/patient). There were no complications. No significant changes in clinical, physiological or biochemical parameters occurred during SPAD. Compared with the controls, there were no significant differences in ICU or 1-year survival, liver recovery or referral for a liver transplant. CONCLUSION: SPAD was well-tolerated in AALF; however, it was not associated with differences in clinical outcomes. While SPAD may be an adjuvant supportive therapy in AALF, prospective trials are needed.

Conventional markers of kidney function.

Acute kidney injury remains a serious clinical problem for intensive care unit patients, and its incidence is rising. The detection and diagnosis of acute kidney injury in the intensive care unit currently require use of conventional markers of kidney function, specifically, serum creatinine and urea levels and, less frequently, other urinary tests. These conventional markers are familiar to clinicians and have long been used at the bedside. However, these markers are clearly not ideal, each has limitations, and none reflect real-time changes in glomerular filtration rate or a genuine acute injurious process to the kidney. More importantly, these conventional markers can contribute to delays in recognition of acute kidney injury and, hence, delays to appropriate supportive and therapeutic interventions. The early detection and diagnosis of acute kidney injury should be a clinical priority. A diagnostic test or panel of tests that are capable of evaluating aspects both of kidney function and acute injury are desperately needed in critical care nephrology. Cystatin C has been shown superior to conventional markers and may assume a greater role in intensive care unit patients for detecting both early changes in glomerular filtration rate and evidence of acute injury. Other newly characterized markers of kidney function or acute injury have the potential to revolutionized the field of critical care nephrology and greatly improve the supportive and therapeutic management of intensive care unit patients with acute kidney injury.

When should renal replacement therapy for acute kidney injury be initiated and discontinued?

BACKGROUND: Critically ill patients with acute kidney injury (AKI) are at high risk for death and frequently require initiation of renal replacement therapy (RRT). There is wide variation in clinical practice on the indications for and timing of initiation and discontinuation of RRT. Numerous clinical and biochemical factors (i.e. uremic, metabolic, fluid balance) have been used; however, at present there is no consensus to guide clinicians on the most favorable time to initiate and/or discontinue RRT to optimize patient outcomes. METHODS: In this review, we appraise the available clinical studies that have assessed timing of initiation and/or discontinuation of RRT for critically ill patients with AKI. 'Timing' of initiation has been variably defined including use of conventional biomarkers (i.e. serum urea and creatinine), urine output, fluid balance, and time relative to intensive care unit admission. CONCLUSIONS: Numerous studies consistently point toward a survival benefit to early initiation of RRT; however, there is a paucity of high-quality randomized trials. If early RRT is associated with clinical benefit, it remains uncertain whether this is attributable to more rapid metabolic/uremic control, management of fluid balance or a combination of clinical factors. In addition, timing of RRT initiation is likely context-specific and varies by clinical factors and/or etiology of AKI. There is also little data to accurately distinguish in advance between the injured kidney that will need extracorporeal renal support and one that retains capacity for early recovery. Fewer studies have evaluated the process of weaning of RRT or ideal methods to predict sufficient recovery to avoid re-initiation. Longer duration of RRT support, higher illness severity and lower urine output (independent of diuretic therapy) have all predicted need for re-initiation. Additional investigations on these issues are clearly warranted and urgently needed.

Outcome comparisons of intermittent and continuous therapies in acute kidney injury: what do they mean?

Despite the fact that no new clinical outcome studies comparing intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) have been published in the past year, two meta-analyses addressing the topic (Bagshaw et al, Crit Care Med 2008; 36: 610-7, and Pannu et al, JAMA 2008; 299: 793-805) have been published recently. With respect to randomized controlled trials (RCTs), there was a substantial overlap between the studies considered in the analysis by Bagshaw et al and those considered in the analysis by Pannu et al. Although neither metaanalysis showed a benefit for either modality with respect to mortality or renal recovery, the two publications offered vastly different conclusions. Bagshaw et al concluded it is impossible to make any definitive recommendations about dialysis modality choice in AKI because previous studies were not adequately powered and failed to standardize for treatment dose. On the other hand, because the metaanalysis of Pannu et al demonstrated equivalent patient outcomes, and in light of the lower costs of IHD, they suggested that alternate-day hemodialysis should become the preferred therapy in many critically ill patients. As the clinical practice recommendations made by Pannu and colleagues have very important implications, we believe their analysis should be critically assessed. In this review, the weaknesses of the RCTs considered in the meta-analysis by Pannu et al are presented. Furthermore, the assumption by Pannu et al that IHD is associated with lower costs than CRRT is challenged, as they did not consider adequately both the short-term and long-term costs associated with the dialytic management of AKI patients. Based on our critical analysis, we believe the AKI dialytic treatment approach recommended by the JAMA investigators (Pannu et al) is not supported by the aggregate of the available clinical outcome data and, therefore, remains highly controversial. We would like to join with others in the AKI field by strongly recommending that investigators and other clinicians stop trying to make conclusive determinations about dialysis modalities when robust supportive data simply are not available. Instead of additional intermodality comparisons, the focus of future clinical research should be toward generating high-quality data on intramodality interventions, such as treatment dose and timing of treatment initiation. In this regard, at least for CRRT, we anxiously await the results of the ongoing RCTs evaluating the effect of CRRT dose on patient outcome.

Acetaminophen-induced acute liver failure treated with single-pass albumin dialysis: report of a case.

BACKGROUND: Acetaminophen (paracetamol) overdose is a leading cause of acute liver failure (ALF). When patients fulfill the King's College criteria for acetaminophen-induced ALF (AALF), they have a poor prognosis for survival without liver transplantation. Recent advances in artificial liver support have used albumin as a binding and scavenging molecule in ALF. One method, single-pass albumin dialysis (SPAD), involves dialyzing blood against an albumin-containing solution across a high-flux membrane to remove albumin-bound toxins. Herein, we describe our protocol for SPAD and report its use in a case of AALF as a bridge to native liver recovery. CASE: A 41-year-old female with no documented history of liver disease presented with acute acetaminophen toxicity and developed hepatic encephalopathy, coagulopathy and lactic acidosis. The patient met King's College criteria for liver transplantation, based on pH and INR, but was deemed not suitable as a candidate due to psychosocial comorbidities. On day 3 of her ICU admission, she received the first of five consecutive daily runs (total ~77 hours) of SPAD. The patient's course was complicated by cerebral edema requiring mannitol. She was extubated on day 11 and transferred to the ward by day 13. At ICU discharge, her liver function (INR 1.9, bilirubin 435 mmol/L) and kidney function were recovering. She did not have any long-term neurological sequelae. By hospital discharge (day 46) her native liver function had recovered with a bilirubin <100mmol/L. CONCLUSION: We describe a case of a patient with acetaminophen-induced acute liver failure who was successfully bridged to spontaneous native liver recovery as a result of SPAD treatment. In patients with ALF, SPAD may be an additional intervention for temporary extracorporeal support. Further investigation in larger prospective studies is warranted.