Maurizio Dan

Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial

BACKGROUND Continuous veno-venous haemofiltration is increasingly used to treat acute renal failure in critically ill patients, but a clear definition of an adequate treatment dose has not been established. We undertook a prospective randomised study of the impact different ultrafiltration doses in continuous renal replacement therapy on survival. METHODS We enrolled 425 patients, with a mean age of 61 years, in intensive care who had acute renal failure. Patients were randomly assigned ultrafiltration at 20 mL h(-1) kg(-1) (group 1, n=146), 35 mL h(-1) kg(-1) (group 2, n=139), or 45 mL h(-1) kg(-1) (group 3, n=140). The primary endpoint was survival at 15 days after stopping haemofiltration. We also assessed recovery of renal function and frequency of complications during treatment. Analysis was by intention to treat. RESULTS Survival in group 1 was significantly lower than in groups 2 (p=0.0007) and 3 (p=0.0013). Survival in groups 2 and 3 did not differ significantly (p=0.87). Adjustment for possible confounding factors did not change the pattern of differences among the groups. Survivors in all groups had lower concentrations of blood urea nitrogen before continuous haemofiltration was started than non-survivors. 95%, 92%, and 90% of survivors in groups 1, 2, and 3, respectively, had full recovery of renal function. The frequency of complications was similarly low in all groups. INTERPRETATION Mortality among these critically ill patients was high, but increase in the rate of ultrafiltration improved survival significantly. We recommend that ultrafiltration should be prescribed according to patients bodyweight and should reach at least 35 mL h(-1) kg(-1).

A pilot study of coupled plasma filtration with adsorption in septic shock

ObjectiveTo test the hypothesis that nonselective plasma adsorption by a hydrophobic resin (coupled plasmafiltration and adsorption) could improve hemodynamics and restore leukocyte responsiveness in patients with septic shock. DesignProspective, pilot, crossover clinical trial. SettingGeneral intensive care unit in a teaching hospital. SubjectsTen patients with hyperdynamic septic shock. InterventionsPatients were randomly allocated to 10 hrs of either coupled plasma filtration adsorption plus hemodialysis (treatment A) or continuous venovenous hemodiafiltration (treatment B) in random order. We measured the change in mean arterial pressure, norepinephrine requirements, and leukocyte tumor necrosis factor-&agr; (TNF-&agr;) production (both spontaneous and lipopolysaccharide-stimulated) after 10 hrs of each treatment. We also tested TNF-&agr; production from normal human adherent monocytes incubated with patients’ plasma obtained before and after the resin, both with or without incubation with an anti-interleukin-10 monoclonal antibody. ResultsMean arterial pressure increased after 10 hr by 11.8 mm Hg with treatment A and by 5.5 mm Hg with treatment B (p = .001). There was an average decrease of norepinephrine requirement of 0.08 &mgr;g/kg/min with treatment A and 0.0049 &mgr;g/kg/min with treatment B (p = .003). All patients but one survived. Spontaneous and lipopolysaccharide-induced TNF-&agr; production from patients’ whole blood increased over time with treatment A. This increase was more marked in blood drawn after the device (plasmafiltrate-sorbent plus hemodialyzer) (p = .009). Preresin plasma suppressed lipopolysaccharide-stimulated production of TNF-&agr; by 1 × 106 cultured adherent monocytes from healthy donors. This suppressive effect was significantly reduced after passage of plasma through the resin (p = .019) and after incubation with anti-interleukin-10 monoclonal antibodies (p = .028). ConclusionsIn patients with septic shock, coupled plasmafiltration-adsorption combined with hemodialysis was associated with improved hemodynamics compared with continuous venovenous hemodiafiltration. This result might be related to its ability to restore leukocyte responsiveness to lipopolysaccharide. These findings suggest a potential role for blood purification in the treatment of septic shock.

Pulse high-volume haemofiltration for treatment of severe sepsis: effects on hemodynamics and survival

IntroductionSevere sepsis is the leading cause of mortality in critically ill patients. Abnormal concentrations of inflammatory mediators appear to be involved in the pathogenesis of sepsis. Based on the humoral theory of sepsis, a potential therapeutic approach involves high-volume haemofiltration (HVHF), which has exhibited beneficial effects in severe sepsis, improving haemodynamics and unselectively removing proinflammatory and anti-inflammatory mediators. However, concerns have been expressed about the feasibility and costs of continuous HVHF. Here we evaluate a new modality, namely pulse HVHF (PHVHF; 24-hour schedule: HVHF 85 ml/kg per hour for 6–8 hours followed by continuous venovenous haemofiltration 35 ml/kg per hour for 16–18 hours).MethodFifteen critically ill patients (seven male; mean Acute Physiology and Chronic Health Evaluation [APACHE] II score 31.2, mean Simplified Acute Physiology Score [SAPS] II 62, and mean Sequential Organ Failure Assessment 14.2) with severe sepsis underwent daily PHVHF. We measured changes in haemodynamic variables and evaluated the dose of noradrenaline required to maintain mean arterial pressure above 70 mmHg during and after pulse therapy at 6 and 12 hours. PHVHF was performed with 250 ml/min blood flow rate. The bicarbonate-based replacement fluid was used at a 1:1 ratio in simultaneous pre-dilution and post-dilution.ResultsNo treatment was prematurely discontinued. Haemodynamics were improved by PHVHF, allowing a significant reduction in noradrenaline dose during and at the end of the PHVHF session; this reduction was maintained at 6 and 12 hours after pulse treatment (P = 0.001). There was also an improvement in systolic blood pressure (P = 0.04). There were no changes in temperature, cardiac index, oxygenation, arterial pH or urine output during the period of observation. The mean daily Kt/V was 1.92. Predicted mortality rates were 72% (based on APACHE II score) and 68% (based on SAPS II score), and the observed 28-day mortality was 47%.ConclusionPHVHF is a feasible modality and improves haemodynamics both during and after therapy. It may be a beneficial adjuvant treatment for severe sepsis/septic shock in terms of patient survival, and it represents a compromise between continuous renal replacement therapy and HVHF.

Continuous Renal Replacement Technology: From Adaptive Technology and Early Dedicated Machines towards Flexible Multipurpose Machine Platforms

Since the initial description of continuous arteriovenous hemofiltration (CAVH) in 1977 by Peter Kramer [1], continuous renal replacement therapies (CRRT) have progressively evolved from a last-chance therapy for acute renal failure (ARF) to a standardized, widely used, fully independent form of artificial kidney support. This happened since the shortcomings of intermittent hemodialysis are becoming more evident, especially when treating critically ill septic patients with multiple organ failure [2]. Moreover, the technology supporting the application of CRRT has greatly improved both as far as the hardware and the software are concerned. The trend of this evolution and the potential of CRRT is today growing to a point in which multiple organ support therapy (MOST) is envisaged as a possible therapeutic approach in the critical care setting [3].

Heart rate variability and severe brain damage: preliminary data

Severe brain damage may cause alterations of cardiovascular function: heart rate, particularly, require the integrity of the vagal, sympathetic and central nervous systems. We studied brain-heart functional relation and neurovegetative modulation by spectral analysis of heart rate variability (HRV). This technique allows separate evaluation of the sympathetic and vagal components of heart rate modulation.In order to correlate changes in HRV with brain damage, we performed 45 recordings in 6 patients (5/1 M/F) by means of autoregressive analysis (AAR). All patients were admitted to the ICU for severe brain damage (anoxic, traumatic or vascular). In 4 patients clinical outcome was brain death, in 2 permanent vegetative status.Two different patterns were found: one in patients with brain death, the other in patients with vegetative status.The small number of patients does not allow definitive conclusions from collected data, but that application of spectral analysis of HRV seems to be a useful monitoring of brain damage subjects.

A new machine for continuous renal replacement therapy: from development to clinical testing

A new continuous renal replacement therapy machine has been designed to fulfill the expectations of nephrologists and intensivists operating in the common ground of critical care nephrology. The new equipment is called Prismaflex® and it is the natural evolution of the PRISMA® machine that has been utilized worldwide for continuous renal replacement therapy in the last 10 yeas. The authors performed a preliminary a-trial to establish the usability, flexibility and reliability of the new device. Accuracy was also tested by recording various operational parameters during different intermittent and continuous renal replacement modalities during 62 treatments. This article will describe our first experience with this new device and touch upon the historic and technologic background leading to its development.

Machines for Continuous Renal Replacement Therapy

Evolution in the field of hemodialysis has led to a parallel development of new systems for acute renal replacement therapy in the intensive-care patients (1). The use of new devices and machines, together with a better understanding of the underlying mechanisms of solute and water removal in continuous renal replacement therapies (CRRT), have made it possible to achieve higher levels of efficiency and clinical tolerance. The first objective has been reached by increasing the automation of the extracorporeal circuits and the setting of operational levels at higher levels; the second has been reached by means of a new generation of monitoring techniques and new machines equipped with specific interfaces and alarms (2–4). A brief review of the evolution and the most recent technology available in the field of CRRT is presented in this chapter.

Bioethical issues related to continuous renal replacement therapy in intensive care patients

Objective: To examine the ethical approach of intensivists and nephrologists to continuous renal replacement therapy (CRRT).¶Design: A questionnaire.¶Setting: The First International Course on Critical Care Nephrology.¶Participants: The participants in the course (around 500).¶Results: Most participants think that establishing ethical criteria for managing CRRT is a medical task, as clinicians have adequate criteria for defining futility. However, many responders would grant the request of starting futile CRRT or would maintain it if requested by the family. Only 55 % believe that informed consent is necessary for initiating CRRT; one out of four would start or maintain unwanted life-saving CRRT. In case of lack of equipment, the majority would select the patients, excluding the worst one or on a “first-come, first-served” basis. Withholding and withdrawing are regarded differently by most responders. Again, most think that every vital support should be withdrawn when futile, but practical and psychological aspects still influence the final decision. Responders think that ethics critical care committees can help in the management of ethical problems in ICU.¶Conclusions: Our results show that several ethical questions are still unsolved and that practical and psychological aspects of the treatment process can be stronger than bioethical principles.

Continuous renal replacement therapy in patients with HELLP syndrome

&NA; The HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count) is a well‐recognized complication of severe preeclampsia and eclampsia, associated with poor maternal and fetal outcomes. There is still some controversy concerning the relationship between the HELLP syndrome and preeclampsia and eclampsia, and despite numerous publications the pathophysiology of the syndrome is not fully understood. In about 20% of patients, the classic signs of gestosis are absent; also, about 30% of the cases occur in the postpartum period, and these patients are at greater risk of pulmonary edema, adult respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), and acute renal failure. The HELLP syndrome is mainly a systemic endothelial disease with associated activation of platelets and diffuse ischemic disorders. Similar to many other conditions (eg, sepsis, multiple trauma), it results in the generalized intravascular activation in inflammatory cells mediated by cytokines and leading to distinct organ injury. From this point of view, continuous renal replacement therapy (CRRT) can be used with success in these patients. Also, our observations, although limited, have shown that CRRT is able not only to heal the acute renal failure, but also to restore normal respiratory and liver function and heart contractility, making it difficult to separate the renal and nonrenal effects of continuous hemofiltration in this setting. Although more controlled trials are needed, we believe that CRRT should become a specific treatment for severe HELLP syndrome.

Evaluation of a portable prototype to analyze heart rate variability

Power spectrum analysis of heart rate fluctuations provide a quanitative noninvasive means of assessing the functioning of the cardiovascular control system.Until now the equipment used to study heart rate variability (HRV) have been complicated systems utilized mostly in research centers. Simpler systemsare needed for routine clinical application. We have evaluated, through clinical practice, the usefulness of prototype equipment which allows acquisition and analysis of ECG signals by a portable electrocardiograph and a personal computer in which sophisticated software is installed.We performed one hundred forty-five recordings in twenty-two patients admitted to ICU. With this technique two different predictive patterns were detected: one concerning survivors, the other concerning nonsurvivors.Reliability, portability, simplicity and quality results are the main advantages of the system. The disadvantage is that it is difficult to perform HRV analysis in patients with ECG arrhythmia. This is because the program does not allow the choice of an arrhythmia-free section of the tachoram to analyze.