ACUsmart Continuous Renal Replacement Therapy Platform: Multicenter Pilot Study for Technical and Clinical Assessment (A.M.P. Study).

BACKGROUND: ACUsmart (Medica S.P.A., Italy) is a new-generation, continuous renal replacement therapy (CRRT) machine for critically ill patients with acute kidney injury. We designed a multicenter international pilot study to provide a description of outlines of the ACUsmart system, evaluation aspects of functionality, usability, and feasibility, discriminating reasons of possible treatment's withdrawals or discontinuations and highlighting strong and weak points of the machine. METHODS: Data of 23 CRRT (and 11 plasma exchange) treatments were collected from 4 intensive care units. Parameters such as treatment duration, downtime, delivered dose, and number and type of alarms were recorded. The general perception of the machine was quantified through the administration of a survey to each component of the evaluating staff. RESULTS: A total treatment time of 447 h was carried with ACUsmart. Eleven continuous veno-venous hemofiltration, 4 continuous veno-venous hemodialysis , and 8 continuous veno-venous hemodiafiltration were performed. The average percentage of net treatment duration with respect to total treatment duration was 92.37%. The mean prescribed dose and delivered dose were 26.33 and 24.10 mL/kg/h, respectively. In general, the machine was rated by users involved as practical and easy to use, although few components need to be slightly improved. CONCLUSION: ACUsmart is a new multifunctional machine that meets most of the features required in a fourth-generation CRRT equipment.

A multicentre randomized controlled trial of moderate hypothermia to prevent intracranial hypertension in acute liver failure.

BACKGROUND & AIMS: Animal models and human case series of acute liver failure (ALF) suggest moderate hypothermia (MH) to have protective effects against cerebral oedema (CO) development and intracranial hypertension (ICH). However, the optimum temperature for patient management is unknown. In a prospective randomized controlled trial we investigated if maintenance of MH prevented development of ICH in ALF patients at high risk of the complication. METHODS: Patients with ALF, high-grade encephalopathy and intracranial pressure (ICP) monitoring in specialist intensive care units were randomized by sealed envelope to targeted temperature management (TTM) groups of 34°C (MH) or 36°C (control) for a period of 72h. Investigators were not blinded to group assignment. The primary outcome was a sustained elevation in ICP >25mmHg, with secondary outcomes the occurrence of predefined serious adverse effects, magnitude of ICP elevations and cerebral and all-cause hospital mortality (with or without transplantation). RESULTS: Forty-six patients were randomized, of whom forty-three were studied. There was no significant difference between the TTM groups in the primary outcome during the study period (35% vs. 27%, p=0.56), for the MH (n=17) or control (n=26) groups respectively, relative risk 1.31 (95% CI 0.53-3.2). Groups had similar incidence of adverse events and overall mortality (41% vs. 46%, p=0.75). CONCLUSIONS: In patients with ALF at high risk of ICH, MH at 33-34°C did not confer a benefit above management at 36°C in prevention of ICH or in overall survival. This study did not confirm advantage of its prophylactic use. (ISRCTN registration number 74268282; no funding.) LAY SUMMARY: Studies in animals with acute liver failure (ALF) have suggested that cooling (hypothermia) could prevent or limit the development of brain swelling, a dangerous complication of the condition. There is limited data on its effects in humans. In a randomized controlled trial in severely ill patients with ALF we compared the effects of different temperatures and found no benefit on improving survival or preventing brain swelling by controlling temperature at 33-34°C against 36°C.

Cost-effectiveness analysis of anidulafungin for the treatment of candidaemia and other forms of invasive candidiasis.

BACKGROUND: Candidaemia and other forms of invasive candidiasis (C/IC) in the intensive care unit are challenging conditions that are associated with high rates of mortality. New guidelines from the European Society for Clinical Microbiology and Infectious Diseases strongly recommend echinocandins for the first-line treatment of C/IC. Here, a cost-effectiveness model was developed from the United Kingdom perspective to examine the costs and outcomes of antifungal treatment for C/IC based on the European Society for Clinical Microbiology and Infectious Diseases guidelines. METHODS: Costs and treatment outcomes with the echinocandin anidulafungin were compared with those for caspofungin, micafungin and fluconazole. The model included non-neutropenic patients aged ≥16 years with confirmed C/IC who were receiving intravenous first-line treatment. Patients were categorised as either a clinical success or failure (patients with persistent/breakthrough infection); successfully treated patients switched to oral therapy, while patients categorised as clinical failures switched to a different antifungal class. Other inputs were all-cause mortality at 6 weeks, costs of treatment-related adverse events and other medical resource utilisation costs. Resource use was derived from the published literature and from discussion with clinical experts. Drug-acquisition/administration costs were taken from standard United Kingdom costing sources. RESULTS: The model indicated that first-line anidulafungin could be considered cost-effective versus fluconazole (incremental cost-effectiveness ratio £813 per life-year gained) for the treatment of C/IC. Anidulafungin was cost-saving versus caspofungin and micafungin due to lower total costs and a higher rate of survival combined with a higher probability of clinical success. DISCUSSION: European Society for Clinical Microbiology and Infectious Diseases guidelines recommend echinocandins for the first-line treatment of C/IC; our model indicated that anidulafungin marries clinical effectiveness and cost-effectiveness. CONCLUSIONS: From the United Kingdom perspective, anidulafungin was cost-effective compared with fluconazole for the treatment of C/IC and was cost-saving versus the other echinocandins.

The impact of organ dysfunction in cirrhosis: survival at a cost?

BACKGROUND & AIMS: The incidence of cirrhosis and subsequent development of organ dysfunction (OD) requiring intensive care unit (ICU) support is rising. Historically, critically ill cirrhotics are perceived as having poor prognosis and substantial cost of care. METHODS: The aim was to prospectively analyse resource utilisation and cost of a large cohort of patients (n=660) admitted to a Liver ICU from 2000 to 2007 with cirrhosis and OD. Child Pugh, MELD, SOFA, APACHE II, and organ support requirements were collected. The Therapeutic Intervention Scoring System (TISS) score, a validated tool for estimating cost in ICU, was calculated daily. Logistic regression was used to determine independent predictors of increased cost. RESULTS: Alcohol was the most common etiology (47%) and variceal bleeding (VB) the most common reason for admission (35%). Invasive ventilatory support was required in 74% of cases, vasopressors in 49%, and 50% required renal replacement therapy. Forty-nine per cent of non-transplanted patients survived to ICU discharge. Median TISS score and ICU cost per patient were 261 and €14,139, respectively. VB patients had the highest survival rates (53% vs. 24%; p<0.001) and lower associated cost. A combination of VB (OR 0.48), need for ventilation (OR 2.81), low PO(2)/FiO(2) on admission (OR 0.97), and lactate (OR 0.93) improved cost prediction on multivariate analysis (AUROC 0.7; p<0.001) but organ failure scores per se were poor predictors of cost. CONCLUSIONS: Patients with cirrhosis and OD result in considerable resource expenditure but have acceptable hospital survival. Further health economic assessment and outcome prediction tools are required to appropriately target resource utilisation.

Increased model for end-stage liver disease score at the time of liver transplant results in prolonged hospitalization and overall intensive care unit costs.

Organ allocation based on Model for End-Stage Liver Disease (MELD) resulted in decreased waiting list mortality in the United States. However, reports suggest an increase in resource utilization as a consequence of this. The aim of this study is to assess the correlation of MELD at transplant with post-liver transplant (LT) intensive care unit (ICU) costs. We assessed clinical and demographic variables of 402 adult patients who underwent LT at King's College Hospital, London, UK, between January 2000 and December 2003. ICU cost calculations were based on the therapeutic intervention scoring system (TISS). Graft quality was assessed using the donor risk index (DRI). Patients with a MELD score > 24 had significantly longer post-LT ICU stay (P < 0.0001) and total post-LT hospital stay (P = 0.008). In addition, they had significantly increased TISS scores, ICU cost, and need for renal replacement therapy (RRT) (P < 0.001). MELD score (by point) and MELD > 24 was associated with prolonged ICU stay (P = 0.004 and P = 0.005, respectively). On univariate analysis, etiology of alcohol-related liver disease (ALD), repeat LT, Budd-Chiari syndrome, and refractory ascites were associated with prolonged ICU stay. Using multivariate analysis, MELD > 24, refractory ascites, ALD and Budd-Chiari syndrome were associated with prolonged ICU stay. There was no association between using grafts with higher DRI and longer ICU stay, need for RRT, increased cost, or hospital survival on univariate analyses (P = not significant). Use of MELD as a method of organ allocation results in significant increase in ICU cost after LT. Using TISS as surrogate marker for ICU costs reveals that the cost implications are related to the need for RRT and prolonged ICU stay.

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis.

BACKGROUND: Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting, particularly in the intensive care unit (ICU). OBJECTIVES AND METHODS: To review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review of the literature and a European expert panel discussion. RESULTS AND CONCLUSIONS: Candida albicans remains the most frequently isolated fungal species followed by C. glabrata. The diagnosis of invasive candidiasis involves both clinical and laboratory parameters, but neither of these are specific. One of the main features in diagnosis is the evaluation of risk factor for infection which will identify patients in need of pre-emptive or empiric treatment. Clinical scores were built from those risk factors. Among laboratory diagnosis, a positive blood culture from a normally sterile site provides positive evidence. Surrogate markers have also been proposed like 1,3 beta-D: glucan level, mannans, or PCR testing. Invasive candidiasis and candidemia is a growing concern in the ICU, apart from cases with positive blood cultures or fluid/tissue biopsy, diagnosis is neither sensitive nor specific. The diagnosis remains difficult and is usually based on the evaluation of risk factors.