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Biomedical subjects

W Silvester

Publications and source records attributed to W Silvester.

At least 19 recordsLinked to original sources

A before and after trial of the effect of a high-dependency unit on post-operative morbidity and mortality.

OBJECTIVE: It has been suggested that the availability of a high-dependency unit (HDU), to facilitate graded admission to, and discharge from, an intensive care unit (ICU), might decrease post-operative morbidity. We wished to determine whether the addition of a 4-bed HDU to a tertiary 17-bed ICU facility at a University-affiliated hospital would decrease post-operative morbidity and mortality. PATIENTS AND METHODS: A prospective controlled before-and-after trial was performed with the opening of a 4-bed HDU. Consecutive patients admitted to hospital for major surgery during a 4-month control (pre-HDU) phase and during a 4-month intervention (HDU) phase were studied for the incidence of serious adverse events (SAEs), mortality after major surgery and mean duration of hospital stay. RESULTS: There were 1319 operations performed in 1125 patients during the pre-HDU period and 1369 operations performed in 1127 patients during the HDU period. During the HDU period there was an excess in unscheduled surgery cases (674 during HDU vs. 531 during the pre-HDU period; p < 0.0001). In the pre-HDU period, there were 414 SAEs in 190 patients compared with 456 SAEs in 209 patients during the HDU period (NS). There were no significant changes in any of the individual SAEs measured except for the incidence of post-operative acute pulmonary edema, which increased from 19 cases to 46 during the HDU period (p = 0.028). This increase was associated with a greater number of patients requiring re-intubation (52 vs. 75 cases; p = 0.044). The introduction of an HDU had no effect on mortality (80 deaths vs. 76; NS) and failed to reduce mean hospital length of stay (21.8 vs. 24 days; NS). CONCLUSIONS: The introduction of a 4-bed HDU in a teaching hospital was associated with a marked increase in unscheduled surgery and failed to reduce the incidence of post-operative SAEs, post-operative mortality, and mean duration of hospital stay.

Journal Article↗

Platelet loss across the hemofilter during continuous hemofiltration.

BACKGROUND: Thrombocytopenia is a common finding in patients in the intensive care unit receiving continuous renal replacement therapy (CRRT). It is unknown if the hemofilter itself contributes to the platelet loss. OBJECTIVE: To measure the direct effect of the hemofilter on platelet counts during CRRT. DESIGN: Prospective, observational study. SETTING: Intensive care unit of a University hospital. PATIENTS: Critically ill patients with acute renal failure receiving CRRT. METHODS: Two samples of blood were drawn simultaneously, pre-filter and post-filter, and analyzed for platelet count. A correction factor was applied to the post-filter platelet count to adjust for the hemoconcentrating effect of net ultrafiltration. RESULTS: Forty-eight sets of paired data from 22 patients were studied. There was a small but significant decrease in mean platelet count across the hemofilter. The mean platelet count drop was 2.32 x 10(9)/L (s.e. 1.06, p = 0.0487, 95% CI (0.01, 4.62)). Blood flow was strongly related to degree of platelet loss, with a decreased loss of 0.07 x 10(9)/L for every ml/min increase in blood flow (p = 0.015). There was no overall decrease in concurrently measured red cell counts across the hemofilter. However, there was a machine-specific affect on red cell loss (p < 0.0001). The total calculated daily platelet loss across the filter was 625 x 10(9) cells. CONCLUSION: The hemofilter may contribute to the thrombocytopenia seen during CRRT, by means of either destruction or retention of platelets during passage. This affect appears attenuated by higher blood flows. This information is useful in the assessment of a low platelet count in patients receiving CRRT.

Acute Kidney Injury↗

Early and intensive continuous hemofiltration for severe renal failure after cardiac surgery.

BACKGROUND: The aim of this study was to test whether early and intensive use of continuous venovenous hemofiltration (CVVH) achieved a better than predicted outcome in patients with severe acute renal failure undergoing cardiac operations, and whether a simple and yet accurate model could be developed to predict their outcome before starting CVVH. METHODS: Medical record analysis with collection of demographic, clinical, and outcome information was used. RESULTS: Sixty-five consecutive patients were treated with early and intensive CVVH (mean operation to CVVH time, 2.38 days; pump-controlled ultrafiltration rate, 2 L/h) after coronary artery bypass grafting (56.9%), single valve procedure (16.9%), or combined operations (26.2%). In 32.3% of patients, intraaortic balloon counterpulsation was required and 20% of patients were emergencies. Sustained hypotension despite inotropic and vasopressor support occurred in 40% of patients and prolonged mechanical ventilation in 58.5%. Using an outcome prediction score specific for acute renal failure, the predicted risk of death was 66%. Actual mortality was 40% (p = 0.003). Using multivariate logistic regression analysis and neural network analysis, patient outcome could be predicted with good levels of accuracy (receiver operating characteristic 0.89 and 0.9, respectively). CONCLUSIONS: Early and aggressive CVVH is associated with better than predicted survival in severe acute renal failure after cardiac operations. Using readily available clinical data, the outcome of such patients can be predicted before the implementation of CVVH.

Acute Kidney Injury↗

An extracorporeal membrane oxygenation-based approach to cardiogenic shock in an older population.

BACKGROUND: We investigated the efficacy of an integrated system of advanced supportive care based on extracorporeal membrane oxygenation (ECMO) in older patients with an estimated mortality of more than 90% to establish whether its use is justifiable. METHODS: Treatment was provided by cardiac surgeons and critical care physicians and included the following key elements: (1) ECMO, (2) early application of continuous venovenous hemofiltration, (3) inhaled nitric oxide, (4) maintenance of perfusion pressure with norepinephrine, (5) maintenance of pulmonary blood flow by ventricular filling with intravenous colloids, (6) avoidance of early postoperative anticoagulation, (7) frequent use of transesophageal echocardiography, and (8) low tidal volume ventilation. Demographic features, intraoperative details, postoperative course, ECMO weaning rate, morbidity, survival to hospital discharge, and the quality of life of survivors were recorded. RESULTS: Seventeen consecutive patients (median age, 69 years) with refractory cardiogenic shock were studied. The median duration of ECMO was 86 hours (20 to 201 hours). Eleven patients (65%) were successfully weaned from ECMO. Seven patients (41%) survived to discharge. The major causes of morbidity were bleeding and leg ischemia. All patients who survived to discharge were alive and well at follow-up (median, 21 months) and reported a satisfactory quality of life. CONCLUSIONS: An ECMO-based approach can be used with acceptable results in the treatment of refractory cardiogenic shock, even in older patients.

Aged↗

Epidemiology, management, and outcome of severe acute renal failure of critical illness in Australia.

OBJECTIVE: To study the epidemiology, style of management, and outcome of intensive care patients with acute renal failure requiring replacement therapy in Australia. DESIGN: Prospective epidemiologic study. SETTING: Australian adult intensive care units providing acute renal replacement therapy. PATIENTS: Adult intensive care patients with acute renal failure treated with renal replacement therapy. INTERVENTIONS: Demographic and clinical data collection for 3 months. MEASUREMENTS AND MAIN RESULTS: A standardized data collection form for each case of severe acute renal failure was used to collect demographic, biochemical, clinical, and outcome data. Severe acute renal failure affected 299 patients (approximately eight cases per 100,000 adults per year). Among these patients, 99 (33.1%) had impaired baseline renal function, 238 (79.6%) needed mechanical ventilation, and 232 (77.6%) needed continuous vasoactive drug administration. Critical care physicians controlled patient care and renal replacement therapy in 289 cases (96.7%). Critical care nurses performed such therapy alone in 288 (96.3%) cases. Continuous renal replacement therapy was used in 292 (97.7%) patients. There was no nephrological input in 173 (57.8%) cases. Predicted mortality rates were 52.1% by Simplified Acute Physiology Score II, 49.5% by Acute Physiology and Chronic Health Evaluation II score, and 51.9% by an acute renal failure-specific score. Actual mortality rate was 46.8%. Only 25 (15.7%) patients were dialysis-dependent at hospital discharge. Of these patients, 20 (80%) had premorbid chronic impairment of renal function. CONCLUSION: In Australia, critical care physicians and nurses manage severe acute renal failure with limited consultative nephrological input. Renal replacement therapy is continuous and outcomes are satisfactory. Our findings support the view that this approach to management of severe acute renal failure is safe.

Acute Kidney Injury↗

A prospective, multicenter study of the epidemiology, management, and outcome of severe acute renal failure in a "closed" ICU system.

The safety and effectiveness of "closed" intensive care units (ICUs) are highly controversial. The epidemiology and outcome of acute renal failure (ARF) requiring replacement therapy (severe ARF) within a "closed" ICU system are unknown. Accordingly, we performed a prospective 3-mo multicenter observational study of all Nephrology Units and ICUs in the State of Victoria (all "closed" ICUs), Australia, and focused on the epidemiology, treatment, and outcome of patients with severe ARF. We collected demographic, clinical, and outcome data using standardized case report forms. Nineteen ward patients and 116 adult ICU patients had severe ARF (13.4 cases/100, 000 adults/yr). Among the ICU patients with severe ARF, 37 had impaired baseline renal function, 91 needed ventilation, and 95 needed vasoactive drugs. Intensivists controlled patient care in all cases. Continuous renal replacement therapy (CRRT) was used in 111 of the ICU patients. Nephrological opinion was sought in only 30 cases. Predicted mortality was 59.6%. Actual mortality was 49.2%. Only 11 ICU survivors were dialysis dependent at hospital discharge. In the state of Victoria, Australia, intensivists manage severe ARF within a "closed" ICU system. Renal replacement is typically continuous and outcomes compare favorably with those predicted by illness severity scores. Our findings support the safety and efficacy of a "closed" ICU model of care.

Acute Kidney Injury↗

Mediator removal with CRRT: complement and cytokines.

The evidence from animal sepsis models that hemofiltration may ameliorate the hemodynamic changes that occur in septic shock has led to speculation that continuous renal replacement therapy may have nonrenal benefits in septic patients. Much of the subsequent work has been done to elucidate the mechanisms of this benefit, in particular the role of removal of inflammatory mediators including cytokines and complement. The significance of extracorporeal removal of such products is dependent on the relative importance of endogenous production and clearance in the setting of sepsis and multiple organ failure and on the method of blood purification. This article reviews the evidence thus far, consisting of in vitro, animal, and human studies; a range of mediators (TNFalpha, IL-1beta, IL-6, IL-8, complement factors C3a, C5a, and D); various membranes (polyacrylonitrile, polysulfone, and polyamide); and clearance by diffusion, convection, and adsorption. The most consistent results suggest that the plasma levels of some mediators are lowered by a combination of membrane adsorption and convection, the clinical significance of which is still uncertain. The review shows the need for further work to unravel the role of CRRT in treating septic patients.

Animals↗

Renal replacement therapy in the ICU: the Australian experience.

The structure of health care drives medical practice in a powerful way, shaping choices of therapy and approaches, and influencing scientific evidence. The Australian experience with continuous renal replacement therapy (CRRT) confirms the importance of structure. A public health system like that of Australia's contains the following variables: well-developed intensive care tradition and expertise, a dominant "closed" intensive care unit (ICU) model, well-developed training of intensive care nurses with established one-to-one nurse-patient ratios, salaried medical practitioners, overworked general dialysis units with inadequate nursing resources, and lack of fee-for-service incentive for nephrologists to see ICU patients with acute renal failure. The likely outcome of such a system is for CRRT to be run by intensive care staff. As shown by a recent regional survey, this approach, although somewhat unique, is dominant and appears to work well with excellent clinical results and constant clinical research output.

Australia↗

Who should manage CRRT in the ICU? The intensivist's viewpoint.

The arrival of continuous renal replacement therapy (CRRT) has given the intensivist and the intensive care nurse the opportunity to treat acute renal failure (ARF) independently by giving them the necessary technology and taking CRRT away from absolute nephrological control. This structural shift has created a controversy between those countries where control of CRRT has completely shifted to the intensivist and those countries where nephrological input is still dominant. The argument in favor of intensivist-driven CRRT rests upon several observations, including the fact that therapy is continuous, as is the presence of the intensivist in the intensive care unit (ICU). Critically ill patients require rapid changes in treatment that are best directed by physicians who are at the bedside all the time. CRRT must be seen within the totality of patient care, and the intensivist can see the larger picture more accurately. Intensivists are successfully performing more and more procedures that were previously seen as part of other specialties and, last but not least, "closed" models of ICU care appear to work best. Australian intensivists have taken up CRRT from the start and now control it. Patient outcomes under such a system, as reported here, are above average, and confirm the effectiveness of such an approach.

Acute Kidney Injury↗

Impaired endothelium-dependent and independent dilatation of forearm resistance arteries in men with diet-treated non-insulin-dependent diabetes: role of dyslipidaemia.

1. We measured endothelium-dependent and independent dilatation of forearm resistance arteries in 29 men with diet-treated non-insulin-dependent diabetes mellitus and 18 age- and sex-matched control subjects. None of the diabetic patients had hypercholesterolaemia, overt hypertension or microproteinuria. 2. We examined endogenous and exogenous nitric oxide-mediated vasodilatation by measuring forearm blood flow with venous occlusive plethysmography after administration of acetylcholine (7.5 and 15 micrograms/min) and sodium nitroprusside (3 and 10 micrograms/min), respectively, into the brachial artery. NG-monomethyl-L-arginine was also infused to study the inhibition of basal and stimulated release of nitric oxide. 3. The vasodilatory response to acetylcholine, expressed as area under curve, was significantly decreased in the diabetic patients compared with the control subjects (P = 0.019). NG-monomethyl-L-arginine significantly reduced basal (P < 0.001) and acetylcholine-stimulated blood flow (P < 0.02) in both groups. The vasodilatory response (also expressed as area under curve) to sodium nitroprusside was significantly less (P = 0.044) in the diabetic patients than in the control subjects. 4. In the diabetic patients, impaired vasodilatory responses to acetylcholine were significantly correlated with higher serum triacylglycerols (P = 0.048) and lower high-density lipoprotein-cholesterol concentrations (P = 0.007); the association with high-density lipoprotein was independent of age, glycated haemoglobin and blood pressure. Sodium nitroprusside responses were not correlated with lipid and lipoprotein concentrations. 5. We conclude that there is impaired endothelial and smooth muscle cell function in men with diet-treated non-insulin-dependent diabetes mellitus uncomplicated by overt hypertension or microproteinuria. Endothelial dysfunction may be related to diabetic dyslipidaemia and associated metabolic disturbances.

Acetylcholine↗

High-volume, zero-balanced hemofiltration to reduce delayed inflammatory response to cardiopulmonary bypass in children.

BACKGROUND: In previous studies, researchers suggested a beneficial role of hemofiltration performed during cardiopulmonary bypass in children. This study was performed to assess both clinical effects and inflammatory mediator removal by high-volume, zero-fluid balance ultrafiltration during rewarming (Z-BUF). METHODS: Twenty children undergoing cardiac surgery were assigned randomly to Z-BUF or a control group. Plasma C3a, interleukin (IL)-1, IL-6, IL-8, IL-10, tumor necrosis factor, myeloperoxidase, and leukocyte count were measured before (T1) and after (T2) hemofiltration and 24 h later (T3). The intensive care unit staff was blinded to the patient's group. Postoperative alveolar-arterial oxygen gradient, time to extubation, body temperature, and postoperative blood loss were monitored. RESULTS: Ultrafiltration rate was 4,972 (3,183-6,218) mL/m2 (median [minimum-maximum]) in the Z-BUF group, where significant reductions were observed in postoperative blood loss, time to extubation (10.8[9-18] vs. 28.2 [15-58] h) and postoperative alveolar-arterial oxygen gradient (320 [180-418] vs. 551 [485-611] mmHg at T3). In the Z-BUF group, significant removal of tumor necrosis factor, IL-10, myeloperoxidase, and C3a were observed at T2. Interleukin 1, IL-6, IL-8, and myeloperoxidase were decreased at T3, suggesting earlier removal of factor(s) that may trigger their release. CONCLUSIONS: These results suggest that hemofiltration exerts some beneficial clinical effects that are not due to water removal. The role of the early removal of factors triggering the inflammatory response, rather than a direct removal of cytokines, deserves further investigation.

Anesthetics↗

Plasma degradation of platelet-activating factor in severely ill patients with clinical sepsis.

OBJECTIVE: To study the plasma degradation of platelet-activating factor in severely ill patients with clinical sepsis. DESIGN: A prospective, nonrandomized control study. SETTING: Intensive care unit in a university hospital. PATIENTS: Thirteen critically ill male patients with clinical sepsis, due to medical or surgical illness, and ten normal male volunteers were studied. Measurements were repeated in seven patients who survived. MEASUREMENTS AND MAIN RESULTS: The plasma activity of acetylhydrolase, the lipoprotein-associated enzyme that hydrolyses platelet-activating factor to its biologically inactive lyso-derivative was determined using an optimized enzyme assay. The plasma half-life of platelet-activating factor was also measured, along with phospholipase A2 activity, lyso-platelet-activating factor, and serum lipid concentrations. Patients results were compared with those results of normal controls and followed once in survivors. Acetylhydrolase activity in the patient group was significantly lower than in normal subjects (median 34, interquartile range 17 to 54 nmol/min/mL vs. median 60, interquartile range 56 to 80 nmol/min/mL; p < .002), while overall, the plasma half-life of platelet-activating factor did not differ significantly between the groups. However, the half-life of platelet-activating factor in six patients who died (median 3.3, range 3.3 to 4.3 mins) was significantly greater than in either survivors (median 2.1, range 1.4 to 2.9 mins; p < .001) or the normal group (median 2.5, range 2.2 to 2.8 mins; p < .001). Consistent with theoretical prediction, a significant linear relationship existed between platelet-activating factor half-life and the reciprocal of acetylhydrolase activity in the patient group (p < .05). Plasma phospholipase A2 activity was markedly increased in the patient group, while plasma lyso-platelet-activating factor and serum lipid concentrations were severely decreased. CONCLUSIONS: Depression of acetylhydrolase activity was consistent with the concentration of lipids with which it is associated. Platelet-activating factor half-life was relatively well preserved because of the nature of its relationship with enzyme activity. The half-life was prolonged in those patients with the worst outcome and the breakdown in plasma degradation of platelet-activating factor could have contributed to pathophysiology in these subjects.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Nitrogenase activity and growth of Frankia in batch and continuous culture.

Frankia grown in batch culture was unable to maintain a high rate of nitrogenase activity and, once a peak level was reached, activity rapidly declined. Addition of 5 mM carbon source of cultures or transfer to fresh medium was followed by brief recovery of nitrogenase activity. The extent of recovery decreased as additions or transfers were made to progressively older cultures. Daily addition of fresh medium (dilution rate = 0.125 day-1) allowed Frankia to be maintained in continuous, derepressed culture with stable rates of growth and nitrogenase activity for more than 30 days. The proportion of active, mature vesicles also remained constant in continuous culture but decreased with time in batch culture.

Bacteria↗