Veno-venous extracorporeal membrane oxygenation as a bridge to and support for pulmonary thromboendarterectomy in misdiagnosed chronic thromboembolic pulmonary hypertension.

Diagnostic delay in patients suffering massive pulmonary embolism (PE) on chronic thromboembolic pulmonary hypertension (CTEPH) has inevitably fatal consequences. Indications to pulmonary thromboendarterectomy (PTE) and extracorporeal membrane oxygenation (ECMO) are limited by severe comorbid conditions, some of which, as neurologic disease, absolutely contraindicate these procedures. We reported the clinical course of a severely diseased patient with a history of meningitis, psychosis and epilepsy, experiencing acute massive pulmonary embolism complicated by acute respiratory failure, successfully treated by ECMO and PTE. A 51-year-old woman with massive PE complicating a misdiagnosed CTEPH needed mechanical ventilation because of acute respiratory insufficiency. Thoracic computed tomography (CT) scan demonstrated PE, and brain CT showed multiple cerebral and cerebellar ischemic lesions. Veno-venous ECMO assistance was instituted despite CT imaging. She recovered from acute respiratory insufficiency by means of veno-venous ECMO. Weaning from ECMO was however impossible until surgical exploration demonstrated an underlying chronic CTEPH, which was successfully addressed by PTE, switching the ECMO system to a standard cardiopulmonary bypass. Postoperative course was uneventful and the patient was discharged home in healthy condition. Despite the fact that the cost-effective ratio should always be considered in advanced life support, expanding the commonly accepted selection criteria for expensive procedures might be advisable in selected acute life-threatening cases, in view of the possibility to unexpectedly save lives.

Ethical, political, and social aspects of high-technology medicine: Eos and care.

OBJECTIVE: We discuss biosocial aspects of high-technology medicine (HTM) to provide a global view of the current model of medicine in the developed world and its consequences. METHODS: We analyze changes in the concept of death and in the use and cost of HTM. The consequences of HTM on the delivery of basic medical care within and among countries are discussed. Concepts derived from Greek mythology are used to illustrate the problems associated with HTM. RESULTS: HTM can be extremely effective in individual cases, but it poses important bioethical and biosocial problems. A major problem is related to the possibility of manipulating the process of dying and the consequent alteration in the social concept of death, which, if not carefully regulated, risks transforming medicine into an expensive way of pursuing pointless dreams of immortality (myth of Eos). Another problem is related to the extraordinary amount of resources necessary for HTM. This model of medicine (which is practiced daily) has limited sustainability, can work only in highly developed countries, may contribute to unequal access to health care, and has negligible positive impact on global health and survival. CONCLUSIONS: HTM poses very important biosocial questions that need to be addressed in a wider and transparent debate, in the best interest of society and HTM as well.

Practice patterns in the management of acute renal failure in the critically ill patient: an international survey.

BACKGROUND: Several controversies have developed over acute renal failure (ARF) definition and treatment: which approach to patient care is most desirable and which form of renal replacement therapy (RRT) should be applied is an everyday matter of debate. There is also disagreement on clinical practice for RRT including the best timing to start, vascular access, anti-coagulation, membranes, equipment and finally, if continuous or intermittent techniques should be preferred. In this lack of harmony, the epidemiology of ARF has recently displayed an outbreak of cases in the intensive care units and nephrologists and intensivists are now called to work together in the case of such a syndrome. SUBJECTS AND METHODS: We report on the responses of 560 contributors, mostly coming from Europe, to a questionnaire submitted during the third International Course on Critical Care Nephrology held in Vicenza, Italy in June 2004. The questionnaire was divided into several sections concerning demographic and medical information, definition of ARF, practice of RRT, current opinions about clinical advantages and problems related to different RRTs and modalities, and beliefs on alternative indications to extracorporeal treatments. RESULTS: More then 200 different definitions of ARF and about 90 RRT start criteria were reported. Oliguria and RIFLE (an acronym classifying ARF in different levels of severity: Risk of renal dysfunction; Injury to the kidney; Failure of kidney function; Loss of kidney function; End-stage kidney disease.) were the most frequent criteria used to define ARF. In 10% of centres all forms of renal replacement techniques are available, and in 70% of cases two or more different techniques are available: absolute analysis of different techniques showed that continuous renal replacement therapies are utilized by 511 specialists (91%), intermittent haemodialysis by 387 (69%) and sustained low efficiency dialysis by 136 (24%). Treatment prescription showed significant differences among specialists, 60% of intensivists being uncertain on RRT dose prescription compared to 40% of nephrologists (P = 0.002). The most frequently selected dosage was '35 ml/kg/h' for urea (25%) and creatinine targets (26%), and '2-3 l/h' for the septic dose (25%). Of the participants, 90% said that they used RRT for non-renal indications, 60% although responders admitted the lack of scientific evidence as a limiting factor to its use. CONCLUSIONS: New classifications such as RIFLE criteria might improve well-known uncertainty about ARF definition. Different RRT techniques are available in most centres, but a general lack of treatment dose standardization is noted by our survey. Non-renal indications to RRT still need to find a definitive role in routine practice.

Early isovolaemic haemofiltration in oliguric patients with septic shock.

OBJECTIVE: To evaluate the effects of early short-term, isovolaemic haemofiltration at 45 ml/kg/h on physiological and clinical outcomes in patients with septic shock. DESIGN: Retrospective study before and after a change of unit protocol (study period 8 years). SETTING: Intensive care unit of metropolitan hospital. PATIENTS: Eighty patients with septic shock. INTERVENTIONS: Introduction of a new septic shock protocol based on early isovolaemic haemofiltration (EIHF). In the pre-EIHF period (before), 40 patients received conventional supportive therapy. In the post-EIHF period (after), 40 patients received EIHF at 45 ml/kg/h of plasma-water exchange over 6 h followed by conventional continuous venovenous haemofiltration (CVVH). Anticoagulation policy remained unchanged. MEASUREMENTS AND MAIN RESULTS: The two groups were comparable for age, gender and baseline APACHE II score. Delivered haemofiltration dose was above 85% of prescription in all patients. PaO2/FiO2 ratio increased from 117+/-59 to 240+/-50 in EIHF, while it changed from 125+/-55 to 160+/-50 in the control group (p<0.05). In EIHF patients, mean arterial pressure increased (95+/-10 vs 60+/-12 mmHg; p<0.05), and norepinephrine dose decreased (0.20+/-2 vs 0.02+/-0.2 microg/kg/min; p<0.05). Among EIHF patients, 28 (70%) were successfully weaned from the ventilator compared with 15 (37%) in the control group (p<0.01). Similarly, 28-day survival was 55% compared with 27.5% (p<0.05). Length of stay in the ICU was 9+/-5 days compared with 16+/-4 days (p<0.002). CONCLUSIONS: In patients with septic shock, EIHF was associated with improved gas exchange, haemodynamics, greater likelihood of successful weaning and greater 28-day survival compared with conventional therapy.

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 years. The authors performed a preliminary alpha-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.

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

INTRODUCTION: Severe 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). METHOD: Fifteen 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. RESULTS: No 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%. CONCLUSION: PHVHF 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.

In vivo validation of the adequacy calculator for continuous renal replacement therapies.

INTRODUCTION: The study was conducted to validate in vivo the Adequacy Calculator, a Microsoft Excel-based program, designed to assess the prescription and delivery of renal replacement therapy in the critical care setting. METHODS: The design was a prospective cohort study, set in two intensive care units of teaching hospitals. The participants were 30 consecutive critically ill patients with acute renal failure treated with 106 continuous renal replacement therapies (CRRT). Urea clearance computation was performed with the Adequacy Calculator (KCALC). Simultaneous blood and effluent urea samples were collected to measure the effectively delivered urea clearance (KDEL) at the beginning of each treatment and, during 73 treatments, between the 18th and 24th treatment hour. The correlation between 179 computed and 179 measured clearances was assessed. Fractional clearances for urea were calculated as spKt/V (where sp represents single pool, K is clearance, t is time, and V is urea volume of distribution) obtained from software prescription and compared with the delivered spKt/V obtained from empirical data. RESULTS: We found that the value of clearance predicted by the calculator was strongly correlated with the value obtained from computation on blood and dialysate determination (r = 0.97) during the first 24 treatment hours, regardless of the renal replacement modality used. The delivered spKt/V (1.25) was less than prescribed (1.4) from the Adequacy Calculator by 10.7%, owing to therapy downtime. CONCLUSION: The Adequacy Calculator is a simple tool for prescribing CRRT and for predicting the delivered dose. The calculator might be a helpful tool for standardizing therapy and for comparing disparate treatments, making it possible to perform large multi-centre studies on CRRT.

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

OBJECTIVE: To 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. DESIGN: Prospective, pilot, crossover clinical trial. SETTING: General intensive care unit in a teaching hospital. SUBJECTS: Ten patients with hyperdynamic septic shock. INTERVENTIONS: Patients 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-alpha (TNF-alpha) production (both spontaneous and lipopolysaccharide-stimulated) after 10 hrs of each treatment. We also tested TNF-alpha 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. RESULTS: Mean 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 microg/kg/min with treatment A and 0.0049 microg/kg/min with treatment B (p =.003). All patients but one survived. Spontaneous and lipopolysaccharide-induced TNF-alpha 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-alpha by 1 x 10(6)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). CONCLUSIONS: In 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.