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Biomedical subjects

J A Kellum

Publications and source records attributed to J A Kellum.

At least 19 recordsLinked to original sources
PubMed2006

Acute kidney dysfunction and the critically ill.

Given the devastating effect that acute kidney dysfunction (AKD) has on the clinical course and outcome of critically ill patients, it is incumbent on every intensive care provider to understand the causes and effects of AKD. AKD is common and costly and even mild forms warrant attention. Promising new therapies are being explored. But even after they arrive, attention to first principles of avoiding further injury from volume depletion, hypotension and nephrotoxins will be of the primary concern of Intensive Care Unit (ICU) team. For established AKD, more and possibly sooner renal replacement therapy is likely to be better than less and later.

Acute Kidney Injury↗
PubMed2005

Application of blood purification to non-renal organ failure.

The application of artificial organs to the task of blood purification in the setting of non-renal organ failure simultaneously presents important challenges and opportunities. Failures of cardiovascular, hepatic, coagulation and immune systems are all characterized by dysregulation leading to multi-organ failure. When sustained, these conditions result in multiple organ system dysfunction and death and are far too common in modern intensive care units (ICUs). While the pathogenesis of each of these organ failures is complex and variable, brought about by a variety of underlying conditions, the potential to improve patient outcomes by simultaneously targeting multiple pathways can perhaps best be realized by blood purification. Unlike drug strategies, which are usually limited to one component of these complex networks, blood purification is, by its very nature, broad spectrum and self regulating. For example, as the concentration of mediators or toxins increases, so does removal. Furthermore, given the many failed trials of specific therapy, the recent focus of immunomodulatory therapy in sepsis has shifted to non-specific methods of influencing the entire inflammatory response without suppressing it. In this issue of the journal, members of the Acute Dialysis Quality Initiative (ADQI) present systematic reviews on the application of hemofiltration, ultrafiltration, plasma therapies and liver-assist therapy for the treatment of non-renal organ failure. The focus of these reviews is on clinical evidence as well as recommendations for future research.

Animals↗
PubMed2004

Incidence and definition of sepsis and associated organ dysfunction.

AIMS: To discuss the incidence, outcome and predisposing factors to systemic inflammatory response syndrome (SIRS), sepsis, and multiple organ failure. METHODS: A qualitative review of the literature. RESULTS: Case definitions of sepsis and severe sepsis, though clarified recently, are still arbitrary. It seems, however, that SIRS is not useful in identifying severe sepsis while organ failure has become a cornerstone for this definition. Incidence of severe sepsis appears to be approximately 10% of all ICU admissions, totaling nearly one million cases annually in the U.S. alone, and rising. Mortality associated with these events is still high, especially among ICU patients. Recent studies have been demonstrating an association between a variety of genetic polymorphisms and progression to and dying from sepsis. CONCLUSION: Recently there has been an increasing amount of information enabling characterization of the epidemiology of sepsis, which may help to direct appropriate care in the coming years.

Biomarkers↗
PubMed2004

What can be done about acute renal failure?

Acute renal failure (ARF) complicates the clinical course of as many as 5% of all hospitalized patients with the critically ill and injured disproportionably at risk. Considerable effort has been expended to develop techniques to prevent ARF or to facilitate its resolution. However, to date, studies have failed to demonstrate that drugs can prevent onset or deterioration of renal function in the critically ill, and some studies have even suggested harm. Recent data suggest that NAC can reduce the incidence of ARF secondary to radio-contrast agents and improved techniques for RRT and, perhaps, new drugs aimed at improving cellular repair, will improve outcome from ARF in the future.

Acute Kidney Injury↗
PubMed2004

Metabolic acidosis in patients with sepsis: epiphenomenon or part of the pathophysiology?

OBJECTIVE: To review the mechanisms of metabolic acidosis in sepsis. DATA SOURCES: Articles and published reviews on metabolic acidosis in sepsis. SUMMARY OF REVIEW: Sepsis affects millions of patients each year and efforts to limit mortality have been limited. It is associated with many features one of which is acidosis which may be a result of the underlying pathophysiology (e.g. respiratory failure, shock, renal failure) or may also result from the way in which we manage critically ill patients. Lactic acidosis identifies septic patients at risk and aggressive fluid resuscitation (along with inotropes and blood in some patients) to reverse acidosis and improve venous oxygen saturation will improve mortality. However, most patients with severe sepsis or septic shock receive 0.9% saline and therefore may develop hyperchloraemic acidosis as a consequence of their resuscitation. Therefore alterations in acid-base balance are almost always in the background in the management of patients with sepsis. What is unknown is whether acidosis is in the causal pathway for organ dysfunction or whether it is simply an epiphenomenon. Changes in acid-base balance, of the type and magnitude commonly encountered in patients with sepsis, significantly alter the release of inflammatory mediators. Less significant changes in the immune response have already been implicated in influencing outcome for patients with sepsis and a reduction in acidosis in septic patients may have the same effect. CONCLUSIONS: Understanding the effects of acid-base on the inflammatory response is relevant as all forms of metabolic acidosis appear to be associated with prolonged hospital and ICU length of stay. Since metabolic acidosis is both commonly caused and treated by clinicians, understanding of the physiologic consequences of altered blood pH is imperative.

Journal Article↗
PubMed2003

Genetic variation and risk of sepsis.

Sepsis is the leading cause of death in non-coronary intensive care unit patients. Sepsis is caused by the immune response to infection and is manifest by pain, fever and edema as the result of the activation of coagulation and inflammatory responses. In severe cases, sepsis leads to organ dysfunction and failure. Sepsis affects more than 750,000 people each year in the US alone, with a mortality rate of over 35 percent making it one of the leading causes of death in developed countries. In addition many patients that die of other diseases have their hospital courses complicated by sepsis. Most patients with infection do not develop severe sepsis and septic shock and yet those that do have a significantly increased risk of death. Genetic and environmental variables may influence why one patient with infection gets sicker than the next. For example, people may be programmed to respond to infection in different ways; some with aggressive immune responses that may be able to wipe out infection before it manifests itself in physical symptoms, while others may have less aggressive immune systems that allow them to get sick more often. The discovery of various common genetic polymorphisms in genes that control the inflammatory response (e.g. tumor necrosis factor) has lent credence to this hypothesis. Yet discovery of the actual relationship between risks of infection / severe sepsis and individual genotypes will require larger, more rigorously designed studies.

Animals↗
PubMed2002

Nitric oxide contamination of hospital compressed air improves gas exchange in patients with acute lung injury.

OBJECTIVE: We tested the hypothesis that NO contamination of hospital compressed air also improves PaO(2) in patients with acute lung injury (ALI) and following lung transplant (LTx). DESIGN: Prospective clinical study. SETTING: Cardiothoracic intensive care unit. PATIENTS: Subjects following cardiac surgery (CABG, n=7); with ALI (n=7), and following LTx (n=5). INTERVENTIONS: Four sequential 15-min steps at a constant FiO(2) were used: hospital compressed air-O(2) (H1), N(2)-O(2) (A1), repeat compressed air-O(2) (H2), and repeat N(2)-O(2) (A2). MEASUREMENTS AND RESULTS: NO levels were measured from the endotracheal tube. Cardiorespiratory values included PaO(2) were measured at the end of each step. FiO(2) was 0.46+/-0.05, 0.53+/-0.15, and 0.47+/-0.06 (mean+/-SD) for three groups, respectively. Inhaled NO levels during H1 varied among subjects (30-550 ppb, 27-300 ppb, and 5-220 ppb, respectively). Exhaled NO levels were not detected in 4/7 of CABG (0-300 ppb), 3/6 of ALI (0-140 ppb), and 3/5 of LTx (0-59 ppb) patients during H1, whereas during A1 all but one patient in ALI and three CABG patients had measurable exhaled NO levels (P<0.05). Small but significant decreases in PaO(2) occurred for all groups from H1 to A1 and H2 to A2 (132-99 Torr and 128-120 Torr, P <0.01, respectively). There was no correlation between inhaled NO during H1 and exhaled NO during A1 or the change in PaO(2) from H1 to A1. CONCLUSIONS: Low-level NO contamination improves PaO(2) in patients with ALI and following LTx.

Air↗
PubMed2001

Declining critical care research publications by authors from U.S. Institutions, 1990-1999.

PURPOSE: To determine whether the proportion of authors from U.S. institutions to those from non-U.S. institutions has changed for published critical care research in three critical care journals over the past ten years. METHOD: The authors of designated critical care clinical or laboratory investigations published from 1990 to 1999 in the three leading U.S. critical care journals, American Journal of Respiratory and Critical Medicine, Chest, and Critical Care Medicine, were evaluated according to the locations of their institutions (U.S. versus non-U.S.) through a review of these publications. RESULTS: The proportion of authorship by investigators from U.S. institutions has declined for critical care research publications from 61% of all authors in 1990 to 41% in 1999 (p < .00001). Statistically significant declines in the proportions of authors from U.S. institutions to those from non-U.S. institutions occurred in the American Journal of Respiratory and Critical Care Medicine (p < .05) and Critical Care Medicine (p < .00001), but not in Chest (p = .69). CONCLUSIONS: The reasons for the decline in authorship by investigators from U.S. institutions are speculative and likely multifactorial. They are, however, consistent with other published data showing limited non-clinical time allocated for education activities for critical care faculty. Anecdotal concerns expressed by many faculty that rising clinical commitments necessitated by current health care and reimbursement pressures preclude research and educational academic activities are supported by these data.

Academies and Institutes↗
PubMed2001

Use of dopamine in acute renal failure: a meta-analysis.

OBJECTIVE: To determine whether low-dose dopamine administration reduces the incidence or severity of acute renal failure, need for dialysis, or mortality in patients with critical illness. DATA SOURCES AND STUDY SELECTION: We performed a MEDLINE search of literature published from 1966 to 2000 for studies addressing the use of dopamine in the prevention and/or treatment of renal dysfunction. DATA EXTRACTION: Data were abstracted regarding design characteristics, population, intervention, and outcomes. Results of individual randomized clinical trials were pooled using a fixed effects model and a Mantel-Haenszel weighted chi-square analysis. DATA SYNTHESIS: We identified a total of 58 studies (n = 2149). Of these, outcome data were reported in 24 studies (n = 1019) and 17 of these were randomized clinical trials (n = 854). Dopamine did not prevent mortality, (relative risk, 0.90 [0.44-1.83]; p =.92), onset of acute renal failure (relative risk, 0.81 [0.55-1.19]; p =.34), or need for dialysis, (relative risk, 0.83 [0.55-1.24]; p =.42). There was sufficient statistical power to exclude any large (>50%) effect of dopamine on the risk of acute renal failure or need for dialysis. CONCLUSIONS: The use of low-dose dopamine for the treatment or prevention of acute renal failure cannot be justified on the basis of available evidence and should be eliminated from routine clinical use.

Acute Kidney Injury↗
PubMed2000

Hemofiltration in sepsis: where do we go from here?

Hemofiltration as an adjunct to therapy for sepsis is now 10 years old. Despite early successes and significant theoretical advantages, the treatment remains experimental. Although feasibility has been established, efficacy has proved to be much more difficult. Clinical as well as technical difficulties remain important considerations to future studies. These issues are discussed and the brief history of hemofiltration in sepsis is reviewed.

Critical Care↗
PubMed2000

Determinants of blood pH in health and disease.

An advanced understanding of acid-base physiology is as central to the practice of critical care medicine, as are an understanding of cardiac and pulmonary physiology. Intensivists spend much of their time managing problems related to fluids, electrolytes, and blood pH. Recent advances in the understanding of acid-base physiology have occurred as the result of the application of basic physical-chemical principles of aqueous solutions to blood plasma. This analysis has revealed three independent variables that regulate pH in blood plasma. These variables are carbon dioxide, relative electrolyte concentrations, and total weak acid concentrations. All changes in blood pH, in health and in disease, occur through changes in these three variables. Clinical implications for these findings are also discussed.

Acid-Base Equilibrium↗
PubMed2000

Accuracy of mucosal pH and mucosal-arterial carbon dioxide tension for detecting mesenteric hypoperfusion in acute canine endotoxemia.

OBJECTIVE: To determine the level of mucosal-arterial Pco2 (Pco2 gap) that is both sensitive and specific for the detection of mesenteric hypoperfusion as defined by either a >50% reduction in portal blood flow or release of lactate by the gut. DESIGN: Animal experiment. SUBJECTS: Seven anesthetized, intubated, mechanically ventilated, and surgically instrumented mongrel dogs. INTERVENTION: Escherichia coli endotoxin (1 mg/kg) given intravenously for 5 mins. MEASUREMENTS AND MAIN RESULTS: Tonometric Pco2, arterial blood gases, arterial and portal venous lactates, and portal and systemic hemodynamic variables were measured. Mucosal pH (pHi) was calculated according to the manufacturers' instructions. From these data, receiver operating characteristics were calculated. Although animals were resuscitated to maintain a constant cardiac output, portal flow decreased from 350+/-101 to 152+/-75 mL/min (p<.01) and the gut released lactate into the portal circulation in all animals. Pco2 gap increased from 13.1+/-3.9 to 40.2+/-39.2 torr (p<.01) and was inversely correlated with portal blood flow (r2 = .20; p<.05). For detection of a >50% reduction in portal blood flow, a Pco2 gap of 20 torr yielded a maximum accuracy of 67% (sensitivity, 55%; specificity, 73%) and was less accurate than a pHi of 7.20, which yielded a maximum accuracy of 76% (sensitivity, 90%; specificity, 70%), although this difference was not significant (p = .24). There was also a correlation between pHi and portal blood flow (r2 = .31; p<.01). For detection of lactate release by the gut, a Pco2 gap of 20 torr was also 67% accurate (sensitivity, 53%; specificity, 78%), whereas a pHi of 7.10 achieved an accuracy of 64% (sensitivity, 40%; specificity, 83%), which was not significantly different. CONCLUSION: Pco2 gap measurements are neither sensitive nor specific for mesenteric hypoperfusion with regard to total gut blood flow reductions of >50% or the release of lactate into the portal circulation.

Animals↗