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Biomedical subjects

Ramesh Venkataraman

Publications and source records attributed to Ramesh Venkataraman.

At least 19 recordsLinked to original sources
PubMed2007

Prevention of acute renal failure.

Acute renal failure (ARF) comprises a family of syndromes that is characterized by an abrupt and sustained decrease in the glomerular filtration rate. In the ICU, ARF is most often due to sepsis and other systemic inflammatory states. ARF is common among the critically ill and injured and significantly adds to morbidity and mortality of these patients. Despite many advances in medical technology, the mortality and morbidity of ARF in the ICU continue to remain high and have not improved significantly over the past 2 decades. Primary strategies to prevent ARF still include adequate hydration, maintenance of mean arterial pressure, and minimizing nephrotoxin exposure. Diuretics and dopamine have been shown to be ineffective in the prevention of ARF or improving outcomes once ARF occurs. Increasing insight into mechanisms leading to ARF and the importance of facilitating renal recovery has prompted investigators to evaluate the role of newer therapeutic agents in the prevention of ARF.

Acetylcysteine↗
PubMed2006

RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis.

INTRODUCTION: The lack of a standard definition for acute kidney injury has resulted in a large variation in the reported incidence and associated mortality. RIFLE, a newly developed international consensus classification for acute kidney injury, defines three grades of severity--risk (class R), injury (class I) and failure (class F)--but has not yet been evaluated in a clinical series. METHODS: We performed a retrospective cohort study, in seven intensive care units in a single tertiary care academic center, on 5,383 patients admitted during a one year period (1 July 2000-30 June 2001). RESULTS: Acute kidney injury occurred in 67% of intensive care unit admissions, with maximum RIFLE class R, class I and class F in 12%, 27% and 28%, respectively. Of the 1,510 patients (28%) that reached a level of risk, 840 (56%) progressed. Patients with maximum RIFLE class R, class I and class F had hospital mortality rates of 8.8%, 11.4% and 26.3%, respectively, compared with 5.5% for patients without acute kidney injury. Additionally, acute kidney injury (hazard ratio, 1.7; 95% confidence interval, 1.28-2.13; P < 0.001) and maximum RIFLE class I (hazard ratio, 1.4; 95% confidence interval, 1.02-1.88; P = 0.037) and class F (hazard ratio, 2.7; 95% confidence interval, 2.03-3.55; P < 0.001) were associated with hospital mortality after adjusting for multiple covariates. CONCLUSION: In this general intensive care unit population, acute kidney 'risk, injury, failure', as defined by the newly developed RIFLE classification, is associated with increased hospital mortality and resource use. Patients with RIFLE class R are indeed at high risk of progression to class I or class F. Patients with RIFLE class I or class F incur a significantly increased length of stay and an increased risk of inhospital mortality compared with those who do not progress past class R or those who never develop acute kidney injury, even after adjusting for baseline severity of illness, case mix, race, gender and age.

Acute Kidney Injury↗
PubMed2006

Vascular surgery critical care: perioperative cardiac optimization to improve survival.

OBJECTIVE: To review the literature on perioperative cardiac management of patients who are scheduled to undergo vascular surgery. DATA SOURCE: MEDLINE- and PubMed-based review of literature published from 1965 to 2005. CONCLUSIONS: Perioperative cardiac events (myocardial infarction, heart failure) remain the leading cause of morbidity and mortality in vascular surgery patients. Existing guidelines allow physicians to cost-effectively streamline preoperative cardiac risk assessment and stratification. Perioperative optimization of volume status and cardiac function and the routine use of perioperative beta-blockers can significantly improve outcomes after major vascular surgery. Perioperative addition of statins to beta-blockers in high-risk patients undergoing vascular surgery merits further evaluation. Preoperative coronary revascularization should be restricted to patients with unstable cardiac symptoms.

Adrenergic beta-Antagonists↗
PubMed2005

Prevention of acute renal failure.

Acute renal failure (ARF) complicates the clinical course of many critically ill patients and significantly adds to their morbidity and mortality. Efforts to develop techniques to prevent ARF or to facilitate its resolution largely have been unsuccessful. Aggressive hydration, minimizing nephrotoxins, and maintenance of "adequate" mean arterial pressure remain the main nonpharmacologic strategies to prevent ARF in the ICU. Increasing insight into mechanisms that lead to ARF prompted investigators to evaluate the role of novel therapeutic agents in the prevention of ARF. Recent data suggest that N-acetylcysteine may reduce the incidence of ARF secondary to radio-contrast agents.

Acetylcysteine↗
PubMed2005

Adequacy of dialysis in acute renal failure.

Renal replacement therapy (RRT) is currently the mainstay of management for patients with acute renal failure (ARF). Adequacy of dialysis in the setting of renal failure is defined poorly and encompasses multiple domains of clinical and biochemical outcomes. Multiple operational factors influence the delivery of adequate dialysis. No current standards exist for RRT for ARF; current RRT practices for ARF generally have been extrapolated from end-stage renal disease (ESRD) literature. The heterogeneity of patient population, variation in RRT practices, and differences in outcomes studied have made it difficult to define or study adequate dialysis in ARF or its impact on clinical outcomes.

Acute Kidney Injury↗
PubMed2005

Acute renal failure in the critically ill.

PURPOSE OF REVIEW: Acute renal failure occurs frequently in hospitalized patients and is associated with significant morbidity and mortality. An effort to better understand the epidemiology and pathophysiology of this disease will hopefully lead to improvement in patient outcomes. Considerable effort has been expended to develop techniques to prevent acute renal failure or to facilitate its resolution. In this review we attempt to summarize some of these recent advances. RECENT FINDINGS: Attempts have been made to clearly define acute renal failure. Among the available pharmacologic agents, current evidence suggests that with the possible exception of radio-contrast-induced acute renal failure, no drugs are capable of preventing the condition or hastening its recovery. Advances in techniques and understanding of how to best provide renal replacement therapy appear to have improved patient outcomes and several newer treatments are under preclinical evaluation and may hold promise for the future. SUMMARY: Preventing acute renal failure, improving clinical outcomes of the condition and attempts to hasten renal recovery have all been very attractive but difficult propositions. Recent efforts to explore the underlying pathophysiology and insight into mechanisms leading to acute renal failure have triggered investigators to evaluate novel therapeutic agents and enhance existing dialytic techniques. These hold great promise for improving patient outcomes in the near future.

Journal Article↗
PubMed2004

Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-kappaB DNA binding, and improves short-term survival in lethal endotoxemia.

OBJECTIVES: Previous studies have shown that inflammatory mediators can be removed from the circulation with hemofiltration and that adsorption plays an important role. Because adsorptive capacity of hollow-fiber dialyzers is limited, we sought to determine whether hemoadsorption using high surface area beads would result in greater mediator removal and improved survival in experimental sepsis. DESIGN: Randomized controlled laboratory experiment. SETTING: University laboratory. SUBJECTS: Sixty-six adult Sprague-Dawley rats. INTERVENTIONS: We conducted two ex vivo and two in vivo experiments. For in vivo experiments, we administered Escherichia coli endotoxin (20 mg/kg) by intravenous infusion and then randomized each animal to receive either hemoadsorption or a sham circuit for 4 hrs. Hemoadsorption was performed for 4 hrs using an arterial-venous circuit and a CytoSorb cartridge containing 10 g of polystyrene divinyl benzene copolymer beads with a biocompatible polyvinylpyrrolidone coating. Survival time was measured to a maximum of 12 hrs. In a separate set of experiments, we studied 12 animals using the same protocol except that we killed all animals at 4 hrs and removed standardized sections of liver for analysis of nuclear factor-kappaB DNA binding. MEASUREMENTS AND MAIN RESULTS: Mean survival time among hemoadsorption-treated animals was 629+/-114 vs. 518+/-120 mins for sham-treated animals (p <.01). Overall survival (defined at 12 hrs) was also significantly better in the hemoadsorption group, seven of 20 vs. one of 20 (p <.05). Plasma interleukin-6 and interleukin-10 concentrations and liver nuclear factor-kappaB DNA binding were significantly reduced by hemoadsorption. Ex vivo experiments showed no endotoxin adsorption but strengthened our in vivo observations by showing rapid adsorption of tumor necrosis factor, interleukin-6, and interleukin-10. CONCLUSIONS: Hemoadsorption was associated with reduced inflammation and improved survival in this murine model of septic shock.

Analysis of Variance↗
PubMed2004

Hemoadsorption to improve organ recovery from brain-dead organ donors: a novel therapy for a novel indication?

While brain-dead organ donors represent the majority of the organ donor pool, it appears that graft survival is adversely affected by brain death itself. Brain death has been shown to cause severe disturbances in the hormonal, hemodynamic and immunological homeostasis, which could in part be responsible for the inferior outcome of organs originating from brain-dead donors compared to living donors. Hemodynamic effects of brain death lead to a wide fluctuation in mean perfusion pressures, blood flow to the organs and systemic oxygen consumption, altering regional perfusion. In addition, a wide array of immunological changes has been shown to occur after brain death contributing to organ injury and hemodynamic instability. Recent studies have shown that brain death upregulates multiple lymphocyte- and macrophage-derived cytokines and the injured brain itself may be the source of proinflammatory factors such as S100B. This increased inflammatory response seen during and immediately after brain death has also been associated with poor allograft function. Furthermore, there is evidence to suggest that the massive inflammatory response seen in brain-dead donors could also lead to increased immunogenicity and accelerated allograft rejection after transplantation. Hence, we hypothesize that nonspecific downregulation of this inflammatory response by hemoadsorption could potentially lead to improved donor organ and allograft function. As a 'proof of concept' we tested the ability of a novel hemoadsorbent to remove S100B in vitro using two human glioblastoma cell lines. Our results indicate a >80% reduction in S100B after 2 h of circulation with the sorbent.

Brain↗
PubMed2004

Effects of hyperchloremic acidosis on arterial pressure and circulating inflammatory molecules in experimental sepsis.

STUDY OBJECTIVE: To determine the effects of hyperchloremic acidosis, induced by dilute HCl infusion, on BP and circulating inflammatory mediators in an experimental model of severe sepsis in the rat. DESIGN: Randomized, open-label, controlled experiment. SETTING: University research laboratory. PARTICIPANTS: Twenty-four adult, male, Sprague-Dawley rats. INTERVENTION: Eighteen hours after inducing lethal sepsis by cecal ligation and puncture, animals were randomized and classified into three groups. In groups 2 and 3, we began an IV infusion of 0.1 N HCl to reduce the standard base excess (SBE) by 5 to 10 mEq/L and 10 to 15 mEq/L, respectively. In group 1, we infused a similar volume of lactated Ringer solution. In all groups, infusions were continued for 8 h or until the animals died. MEASUREMENTS: We measured mean arterial pressure (MAP), arterial blood gases, electrolytes, plasma nitrate/nitrite, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 levels at 0 h, 3 h, 6 h, and 8 h. RESULTS: MAP remained stable in group 1 but decreased in groups 2 and 3 (p < 0.001), such that at 8 h MAP was much higher in group 1 (94 +/- 9.2 mm Hg) [+/- SD] compared to either group 2 (71.6 +/- 20.1 mm Hg) or group 3 (49.4 +/- 33.2 mm Hg) [p = 0.01]. This change in MAP correlated with the increase in plasma Cl(-) (R(2) = 0.50, p < 0.0001) and less well with the decrease in pH (R(2) = 0.24, p < 0.001). After 6 h of acidosis, plasma nitrite levels were significantly higher in group 2 animals compared to either group 1 or group 3 animals (p < 0.05). Plasma TNF-alpha, IL-6, or IL-10 levels were not significantly different from control animals. CONCLUSION: Moderate acidosis (SBE of 5 to 10 mEq/L), induced by HCl infusion, worsened BP and increased plasma nitrate/nitrite levels but had no effect on circulating cytokines in septic rats. However, severe acidosis (SBE of 10 to 15 mEq/L), while still causing hypotension, did not affect plasma nitrate/nitrite levels.

Acid-Base Equilibrium↗
PubMed2003

Clinical review: extracorporeal blood purification in severe sepsis.

Sepsis and septic shock are the leading causes of acute renal failure, multiple organ system dysfunction, and death in the intensive care unit. The pathogenesis of sepsis is complex and comprises a mosaic of interconnected pathways. Several attempts to improve patient outcomes by targeting specific components of this network have been unsuccessful. For these reasons, the ideal immunomodulating strategy would be one that restores immunologic stability rather than blindly inhibiting or stimulating one or another component of this complex network. Hence, the recent focus of immunomodulatory therapy in sepsis has shifted to nonspecific methods of influencing the entire inflammatory response without suppressing it. Here, we discuss the various modalities of extracorporeal blood purification, the existing evidence, and future prospects.

Hemofiltration↗
PubMed2003

Novel approaches to the treatment of acute renal failure.

Acute renal failure (ARF) occurs frequently in hospitalised patients and is associated with significant morbidity and mortality. Many therapeutic strategies have been undertaken both to prevent acute renal injury and, once ARF occurs, to improve renal function and reduce mortality. Among the available pharmacological options, no specific therapy has been shown to alter the course of ARF. This article reviews the efficacy of several strategies in experimental renal disease and raises the possibility that similar interventions might be available to the clinician in the near future for the prevention and management of ARF. The prospect of these novel strategies, together with the ever-increasing understanding of the complex pathophysiology of ARF, offers the promise of effective and more physiological therapeutic interventions in this new millennium.

Acetylcysteine↗
PubMed2002

Influence of dialysis membranes on outcomes in acute renal failure: a meta-analysis.

BACKGROUND: Considerable controversy exists as to whether synthetic (more biocompatible) dialysis membranes improve outcome in patients with acute renal failure (ARF) compared to cellulose-based membranes. Numerous trials conducted have yielded inconsistent results. Although the discordant results of existing studies could be explained by the varying degrees of biocompatibility among the different membranes used, these studies also had low statistical power. Thus, we sought to determine whether combining results from all published trials would provide a better estimate of the effect of membrane composition on survival in ARF. METHODS: We performed a meta-analysis of all previously published prospective trials comparing the use of synthetic membranes with cellulose-based membranes for hemodialysis in patients with ARF. RESULTS: Of the 10 prospective trials identified, eight trials (867 patients) provided survival data and six trials (641 patients) provided data on recovery of renal function. We used the Mantel-Haenszel test based on a fixed effects model to analyze the data. The cumulative odds ratio (OR) for survival in favor of synthetic membranes was 1.37 (95% CI: 1.02 to 1.83), P = 0.03 and that for renal recovery was 1.23 (95% CI: 0.90 to 1.68), P = 0.18. We performed a sensitivity analysis by stratifying studies on the basis of control group membrane type (unsubstituted or substituted cellulose) and found that the survival advantage for synthetic membranes was mainly limited to comparison with the unsubstituted cellulose group [OR 1.64 (95% CI: 1.10 to 2.45) vs. OR 1.20 (95% CI: 0.73 to 1.97)]. CONCLUSIONS: Synthetic membranes appear to confer a significant survival advantage over cellulose-based membranes. We could not demonstrate a similar benefit with use of synthetic membranes over cellulose-based membranes for recovery of renal function but sample size was limited. Finally, our results suggest that the survival disadvantage for cellulose-based membranes may be limited to unsubstituted cellulose (cuprophane) membranes.

Acute Kidney Injury↗
PubMed2002

Dosing patterns for continuous renal replacement therapy at a large academic medical center in the United States.

PURPOSE: We sought to retrospectively review the dosing patterns of continuous renal replacement therapy (CRRT) in patients with acute renal failure (ARF) and determine their actual delivered dosage of CRRT. MATERIALS AND METHODS: Computerized records of patients (n = 115) who received CRRT for ARF at a single, large, academic, tertiary care hospital from September 1, 1999 through August 31, 2000 were reviewed. The delivered dose of CRRT for each patient/day was calculated from the hourly effluent flow rate, the patient's weight, and the duration (in hours) of CRRT for that day. A mean effluent flow rate (in L/h) for each patient was then calculated. RESULTS: The average number of hours/day on CRRT was 16.1 +/- 3.53 (mean +/- SD), with a mean flow rate (averaged over 24 h) of 1.36 +/- 0.31 L/h. The mean CRRT dose prescribed for these patients was 24.46 +/- 6.73 mL/Kg/h, but the mean dose delivered was only 16.55 +/- 5.41 mL/Kg/h (68% of the prescribed dose, P <.000001). CONCLUSIONS: Many patients are prescribed low doses of CRRT. Furthermore, the dose delivered is considerably lower than that prescribed. Methods and procedures to extend CRRT system life may improve the dose delivery.

Academic Medical Centers↗