Andrew D Shaw

Vanderbilt University, Нашвилл, Michigan, United States

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Publications (133)599.57 Total impact

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    ABSTRACT: Clinicians have access to limited tools that predict which patients with early AKI will progress to more severe stages. In early AKI, urine output after a furosemide stress test (FST), which involves intravenous administration of furosemide (1.0 or 1.5 mg/kg), can predict the development of stage 3 AKI. We measured several AKI biomarkers in our previously published cohort of 77 patients with early AKI who received an FST and evaluated the ability of FST urine output and biomarkers to predict the development of stage 3 AKI (n=25 [32.5%]), receipt of RRT (n=11 [14.2%]), or inpatient mortality (n=16 [20.7%]). With an area under the curve (AUC)±SEM of 0.87±0.09 (P<0.0001), 2-hour urine output after FST was significantly better than each urinary biomarker tested in predicting progression to stage 3 (P<0.05). FST urine output was the only biomarker to significantly predict RRT (0.86±0.08; P=0.001). Regardless of the end point, combining FST urine output with individual biomarkers using logistic regression did not significantly improve risk stratification (ΔAUC, P>0.10 for all). When FST urine output was assessed in patients with increased biomarker levels, the AUC for progression to stage 3 improved to 0.90±0.06 and the AUC for receipt of RRT improved to 0.91±0.08. Overall, in the setting of early AKI, FST urine output outperformed biochemical biomarkers for prediction of progressive AKI, need for RRT, and inpatient mortality. Using a FST in patients with increased biomarker levels improves risk stratification, although further research is needed. Copyright © 2015 by the American Society of Nephrology.
    Journal of the American Society of Nephrology 02/2015; · 9.47 Impact Factor
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    ABSTRACT: Severity of AKI is determined by the magnitude of increase in serum creatinine level or decrease in urine output. However, patients manifesting both oliguria and azotemia and those in which these impairments are persistent are more likely to have worse disease. Thus, we investigated the relationship of AKI severity and duration across creatinine and urine output domains with the risk for RRT and likelihood of renal recovery and survival using a large, academic medical center database of critically ill patients. We analyzed electronic records from 32,045 patients treated between 2000 and 2008, of which 23,866 (74.5%) developed AKI. We classified patients by levels of serum creatinine and/or urine output according to Kidney Disease Improving Global Outcomes staging criteria for AKI. In-hospital mortality and RRT rates increased from 4.3% and 0%, respectively, for no AKI to 51.1% and 55.3%, respectively, when serum creatinine level and urine output both indicated stage 3 AKI. Both short- and long-term outcomes were worse when patients had any stage of AKI defined by both criteria. Duration of AKI was also a significant predictor of long-term outcomes irrespective of severity. We conclude that short- and long-term risk of death or RRT is greatest when patients meet both the serum creatinine level and urine output criteria for AKI and when these abnormalities persist. Copyright © 2015 by the American Society of Nephrology.
    Journal of the American Society of Nephrology 01/2015; · 9.47 Impact Factor
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    ABSTRACT: Tissue inhibitor metalloproteinase-2 (TIMP-2) and IGF-binding protein-7 (IGFBP7) have been validated for risk stratification in AKI. However, the association of urinary TIMP-1 and IGFBP7 with long-term outcomes is unknown. We evaluated the 9-month incidence of a composite end point of all-cause mortality or the need for RRT in a secondary analysis of a prospective observational international study of critically ill adults. Two predefined [TIMP-2]⋅[IGFBP7] cutoffs (0.3 for high sensitivity and 2.0 for high specificity) for the development of AKI were evaluated. Cox proportional hazards models were used to determine risk for the composite end point. Baseline [TIMP-2]⋅[IGFBP7] values were available for 692 subjects, of whom 382 (55.2%) subjects developed stage 1 AKI (defined by Kidney Disease Improving Global Outcomes guidelines) within 72 hours of enrollment and 217 (31.4%) subjects met the composite end point. Univariate analysis showed that [TIMP-2]⋅[IGFBP7]>2.0 was associated with increased risk of the composite end point (hazard ratio [HR], 2.11; 95% confidence interval [95% CI], 1.37 to 3.23; P<0.001). In a multivariate analysis adjusted for the clinical model, [TIMP-2]⋅[IGFBP7] levels>0.3 were associated with death or RRT only in subjects who developed AKI (compared with levels≤0.3: HR, 1.44; 95% CI, 1.00 to 2.06 for levels>0.3 to ≤2.0; P=0.05 and HR, 2.16; 95% CI, 1.32 to 3.53 for levels>2.0; P=0.002). In conclusion, [TIMP-2]⋅[IGFBP7] measured early in the setting of critical illness may identify patients with AKI at increased risk for mortality or receipt of RRT over the next 9 months. Copyright © 2014 by the American Society of Nephrology.
    Journal of the American Society of Nephrology 12/2014; · 9.47 Impact Factor
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    ABSTRACT: Fluid management during critical illness is a dynamic process that may be conceptualized as occurring in four phases: rescue, optimization, stabilization, and de-escalation (mobilization). The selection and administration of resuscitation fluids is one component of this complex physiological sequence directed at restoring depleted intravascular volume. Presently, the selection of i.v. fluid is usually dictated more by local practice patterns than by evidence. The debate on fluid choice has primarily focused on evaluating outcome differences between 'crystalloids vs colloids'. More recently, however, there is interest in examining outcome differences based on the chloride content of crystalloid solutions. New insights into the conventional Starling model of microvascular fluid exchange may explain that the efficacy of colloids in restoring and maintaining depleted intravascular volume is only moderately better than crystalloids. A number of investigator-initiated, high-quality, randomized controlled trials have demonstrated that modest improvements in short-term physiological endpoints with colloids have not translated into better patient-centred outcomes. In addition, there is substantial evidence that certain types of fluids may independently worsen patient-centred outcomes. These include hydroxyethyl starch and albumin solutions in selected patient populations. There is no evidence to support the use of other colloids. The use of balanced salt solutions in preference to 0.9% saline is supported by the absence of harm in large observational studies. However, there is no compelling randomized trial-based evidence demonstrating improved clinical outcomes with the use of balanced salt solutions compared with 0.9% saline at this time.
    BJA British Journal of Anaesthesia 11/2014; 113(5):772-83. · 4.35 Impact Factor
  • J A Kellum, M G Mythen, A D Shaw
    BJA British Journal of Anaesthesia 11/2014; 113(5):729-31. · 4.35 Impact Factor
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    ABSTRACT: Recent data suggest that both elevated serum chloride levels and volume overload may be harmful during fluid resuscitation. The purpose of this study was to examine the relationship between the intravenous chloride load and in-hospital mortality among patients with systemic inflammatory response syndrome (SIRS), with and without adjustment for the crystalloid volume administered.
    Intensive Care Medicine 10/2014; · 5.54 Impact Factor
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    ABSTRACT: Background The objective of this systematic review and meta-analysis was to assess the relationship between the chloride content of intravenous resuscitation fluids and patient outcomes in the perioperative or intensive care setting.Methods Systematic searches were performed of PubMed/MEDLINE, Embase and Cochrane Library (CENTRAL) databases in accordance with PRISMA guidelines. Randomized clinical trials, controlled clinical trials and observational studies were included if they compared outcomes in acutely ill or surgical patients receiving either high-chloride (ion concentration greater than 111 mmol/l up to and including 154 mmol/l) or lower-chloride (concentration 111 mmol/l or less) crystalloids for resuscitation. Endpoints examined were mortality, measures of kidney function, serum chloride, hyperchloraemia/metabolic acidosis, blood transfusion volume, mechanical ventilation time, and length of hospital and intensive care unit stay. Risk ratios (RRs), mean differences (MDs) or standardized mean differences (SMDs) and confidence intervals were calculated using fixed-effect modelling.ResultsThe search identified 21 studies involving 6253 patients. High-chloride fluids did not affect mortality but were associated with a significantly higher risk of acute kidney injury (RR 1·64, 95 per cent c.i. 1·27 to 2·13; P < 0·001) and hyperchloraemia/metabolic acidosis (RR 2·87, 1·95 to 4·21; P < 0·001). High-chloride fluids were also associated with greater serum chloride (MD 3·70 (95 per cent c.i. 3·36 to 4·04) mmol/l; P < 0·001), blood transfusion volume (SMD 0·35, 0·07 to 0·63; P = 0·014) and mechanical ventilation time (SMD 0·15, 0·08 to 0·23; P < 0·001). Sensitivity analyses excluding heavily weighted studies resulted in non-statistically significant effects for acute kidney injury and mechanical ventilation time.ConclusionA weak but significant association between higher chloride content fluids and unfavourable outcomes was found, but mortality was unaffected by chloride content.
    British Journal of Surgery 10/2014; · 4.84 Impact Factor
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    ABSTRACT: Acute kidney injury (AKI) remains a deadly condition. Tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein (IGFBP)7 are two recently discovered urinary biomarkers for AKI. We now report on the development, and diagnostic accuracy of two clinical cutoffs for a test using these markers.
    Nephrology Dialysis Transplantation 09/2014; 29(11). · 3.49 Impact Factor
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    ABSTRACT: Despite many clinical trials and investigative efforts to determine appropriate therapeutic intervention(s) for shock, this topic remains controversial. The use of i.v. fluid has represented the cornerstone for the treatment of hypoperfusion for two centuries.
    BJA British Journal of Anaesthesia 09/2014; · 4.35 Impact Factor
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    ABSTRACT: Standard treatment practice for the hypotensive patient with poor tissue perfusion is rapid volume resuscitation; in some scenarios, such as septic shock, this is performed with targeted goal-directed endpoints within 6 h of presentation. As a result, patients often develop significant positive fluid accumulation, which has been associated with poor outcomes above certain thresholds.
    BJA British Journal of Anaesthesia 09/2014; · 4.35 Impact Factor
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    ABSTRACT: I.V. fluid therapy plays a fundamental role in the management of hospitalized patients. While the correct use of i.v. fluids can be lifesaving, recent literature demonstrates that fluid therapy is not without risks. Indeed, the use of certain types and volumes of fluid can increase the risk of harm, and even death, in some patient groups. Data from a recent audit show us that the inappropriate use of fluids may occur in up to 20% of patients receiving fluid therapy. The delegates of the 12th Acute Dialysis Quality Initiative (ADQI) Conference sought to obtain consensus on the use of i.v. fluids with the aim of producing guidance for their use. In this article, we review a recently proposed model for fluid therapy in severe sepsis and propose a framework by which it could be adopted for use in most situations where fluid management is required. Considering the dose-effect relationship and side-effects of fluids, fluid therapy should be regarded similar to other drug therapy with specific indications and tailored recommendations for the type and dose of fluid. By emphasizing the necessity to individualize fluid therapy, we hope to reduce the risk to our patients and improve their outcome.
    BJA British Journal of Anaesthesia 09/2014; · 4.35 Impact Factor
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    ABSTRACT: The Acute Dialysis Quality Initiative (ADQI) dedicated its Twelfth Consensus Conference (2013) to all aspects of fluid therapy, including the management of fluid overload (FO). The aim of the working subgroup 'Mechanical fluid removal' was to review the indications, prescription, and management of mechanical fluid removal within the broad context of fluid management of critically ill patients.
    BJA British Journal of Anaesthesia 09/2014; · 4.35 Impact Factor
  • Anesthesia and analgesia. 09/2014; 119(3):731-736.
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    ABSTRACT: Isotonic saline is the most commonly used crystalloid in the ICU, but recent evidence suggests that balanced fluids like Lactated Ringer's solution may be preferable. We examined the association between choice of crystalloids and in-hospital mortality during the resuscitation of critically ill adults with sepsis. A retrospective cohort study of patients admitted with sepsis, not undergoing any surgical procedures, and treated in an ICU by hospital day 2. We used propensity score matching to control for confounding and compared the following outcomes after resuscitation with balanced versus with no-balanced fluids: in-hospital mortality, acute renal failure with and without dialysis, and hospital and ICU lengths of stay. We also estimated the dose-response relationship between receipt of increasing proportions of balanced fluids and in-hospital mortality. Three hundred sixty U.S. hospitals that were members of the Premier Healthcare alliance between November 2005 and December 2010. A total of 53,448 patients with sepsis, treated with vasopressors and crystalloids in an ICU by hospital day 2 including 3,396 (6.4%) that received balanced fluids. None. Patients treated with balanced fluids were younger and less likely to have heart or chronic renal failure, but they were more likely to receive mechanical ventilation, invasive monitoring, colloids, steroids, and larger crystalloid volumes (median 7 vs 5 L). Among 6,730 patients in a propensity-matched cohort, receipt of balanced fluids was associated with lower in-hospital mortality (19.6% vs 22.8%; relative risk, 0.86; 95% CI, 0.78, 0.94). Mortality was progressively lower among patients receiving larger proportions of balanced fluids. There were no significant differences in the prevalence of acute renal failure (with and without dialysis) or in-hospital and ICU lengths of stay. Among critically ill adults with sepsis, resuscitation with balanced fluids was associated with a lower risk of in-hospital mortality. If confirmed in randomized trials, this finding could have significant public health implications, as crystalloid resuscitation is nearly universal in sepsis.
    Critical care medicine 03/2014; · 6.15 Impact Factor
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    ABSTRACT: Functional mitral regurgitation (FMR) occurs as a consequence of left ventricular remodeling and is an independent predictor of adverse outcome. FMR is assessed qualitatively with two-dimensional echocardiography, but accurate quantitation of the actual degree of mitral valve (MV) coaptation is not possible with this method. We evaluated a novel three-dimensional (3D) approach to quantify the MV coaptation zone in patients with FMR. We hypothesized that measuring the 3D MV coaptation zone is feasible and would correlate with FMR severity when indexed to MV area. Data were gathered on 25 patients with FMR undergoing cardiac operations, and included a comprehensive two-dimensional and 3D examination with intraoperative transesophageal echocardiography. Using available 3D MV quantification software, offline analysis of end-systolic MV coaptation zone and MV area was performed. A novel MV coaptation index was calculated by the following formula: [3D end-systolic MV coaptation zone/3D MV area]. FMR severity was described as trace, mild, moderate, and severe using the integrative approach recommended by official guidelines. Analysis of variance demonstrated that the coaptation index was associated with the severity of FMR (F = 20.5, r(2) = 0.75, p < 0.0001). There was also a correlation between 2D vena contracta and the coaptation index (r = -0.74, p < 0.0003). We describe a novel 3D approach to direct assessment of the MV coaptation zone. When indexed to the MV area, the 3D MV coaptation zone is closely associated with FMR severity. Assessment of the mitral coaptation may be a potentially powerful tool in the perioperative evaluation of the competency of the MV.
    The Annals of thoracic surgery 03/2014; · 3.45 Impact Factor
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    ABSTRACT: Rationale. We recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest. Objectives. We now validate a clinical test for urinary [TIMP-2]•[IGFBP7] at a high-sensitivity cutoff > 0.3 for AKI risk stratification in a diverse population of critically ill patients. Methods. We conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary [TIMP-2]•[IGFBP7] to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were blinded to the results of the test. Measurements. Urinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. Main Results. The primary endpoint was reached in 17% of patients. For a single urinary [TIMP-2]•[IGFBP7] test, sensitivity at the pre-specified high-sensitivity cutoff of 0.3 (ng/ml)2/1000 was 92% (95% CI 85%-98%) with a negative likelihood ratio of 0.18 (95% CI 0.06-0.33). Critically ill patients with urinary [TIMP-2]•[IGFBP7] > 0.3 had seven times the risk for AKI (95% CI 4-22) compared to critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary [TIMP-2]•[IGFBP7] remained statistically significant and a strong predictor of AKI (AUC 0.70, 95% CI 0.63-0.76 for clinical variables alone, versus AUC 0.86, 95% CI 0.80-0.90 for clinical variables plus [TIMP-2]•[IGFBP7]). Conclusions. Urinary [TIMP-2]•[IGFBP7] > 0.3 (ng/ml)2/1000 identifies patients at risk for imminent AKI. Funding. Funded by Astute Medical. (ClinicalTrials.gov NCT01573962).
    American Journal of Respiratory and Critical Care Medicine 02/2014; · 11.04 Impact Factor
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    ABSTRACT: Fluid therapy is perhaps the most common intervention received by acutely ill hospitalized patients; however, a number of critical questions on the efficacy and safety of the type and dose remain. In this review, recent insights derived from randomized trials in terms of fluid type, dose and toxicity are discussed. We contend that the prescription of fluid therapy is context-specific and that any fluid can be harmful if administered inappropriately. When contrasting ''crystalloid vs colloid'', differences in efficacy are modest but differences in safety are significant. Differences in chloride load and strong ion difference across solutions appear to be clinically important. Phases of fluid therapy in acutely ill patients are recognized, including acute resuscitation, maintaining homeostasis, and recovery phases. Quantitative toxicity (fluid overload) is associated with adverse outcomes and can be mitigated when fluid therapy based on functional hemodynamic parameters that predict volume responsiveness and minimization of non-essential fluid. Qualitative toxicity (fluid type), in particular for iatrogenic acute kidney injury and metabolic acidosis, remain a concern for synthetic colloids and isotonic saline, respectively. Physiologically balanced crystalloids may be the ''default'' fluid for acutely ill patients and the role for colloids, in particular hydroxyethyl starch, is increasingly unclear. We contend the prescription of fluid therapy is analogous to the prescription of any drug used in critically ill patients.
    World journal of critical care medicine. 02/2014; 3(1):24-33.
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    ABSTRACT: Cardiorenal syndromes (CRS) have been recently classified into five distinct entities, each with different major pathophysiologic mechanisms. CRS type 1 most commonly occurs in the setting of acutely decompensated heart failure where approximately 25% of patients develop a rise in serum creatinine and a reduction of urine output after the first several doses of intravenous diuretics. Altered cardiac and renal hemodynamics are believed to be the most important determinants of CRS type 1. CRS type 2 is the hastened progression of chronic kidney disease (CKD) in the setting of chronic heart failure. Accelerated renal cell apoptosis and replacement fibrosis is considered to be the dominant mechanism. CRS type 3 is acutely decompensated heart failure after acute kidney injury from inflammatory, toxic, or ischemic insults. This syndrome is precipitated by salt and water overload, acute uremic myocyte dysfunction, and neurohormonal dysregulation. CRS type 4 is manifested by the acceleration of the progression of chronic heart failure in the setting of CKD. Cardiac myocyte dysfunction and fibrosis, so-called 'CKD cardiomyopathy', is believed to be the predominant pathophysiologic mechanism. Type 5 CRS is simultaneous acute cardiac and renal injury in the setting of an overwhelming systemic insult such as sepsis. In this scenario, the predominant pathophysiological disturbance is microcirculatory dysfunction as a result of acutely abnormal immune cell signaling, catecholamine cellular toxicity, and enzymatic activation which result in simultaneous organ injury often extending beyond both the heart and the kidneys. This paper will summarize these and other key findings from an international consensus conference on the spectrum of pathophysiologic mechanisms at work in the CRS. © 2013 S. Karger AG, Basel.
    Blood Purification 01/2014; 37 Suppl 2:2-13. · 1.92 Impact Factor
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    ABSTRACT: AKI is associated with major adverse kidney events (MAKE): death, new dialysis, and worsened renal function. CKD (arising from worsened renal function) is associated with a higher risk of major adverse cardiac events (MACE): myocardial infarction (MI), stroke, and heart failure. Therefore, the study hypothesis was that veterans who develop AKI during hospitalization for an MI would be at higher risk of subsequent MACE and MAKE. Patients in the Veterans Affairs (VA) database who had a discharge diagnosis with International Classification of Diseases, Ninth Revision, code of 584.xx (AKI) or 410.xx (MI) and were admitted to a VA facility from October 1999 through December 2005 were selected for analysis. Three groups of patients were created on the basis of the index admission diagnosis and serum creatinine values: AKI, MI, or MI with AKI. Patients with mean baseline estimated GFR<45 ml/min per 1.73 m(2) were excluded. The primary outcomes assessed were mortality, MAKE, and MACE during the study period (maximum of 6 years). The combination of MAKE and MACE-major adverse renocardiovascular events (MARCE)-was also assessed. A total of 36,980 patients were available for analysis. Mean age±SD was 66.8±11.4 years. The most deaths occurred in the MI+AKI group (57.5%), and the fewest (32.3%) occurred in patients with an uncomplicated MI admission. In both the unadjusted and adjusted time-to-event analyses, patients with AKI and AKI+MI had worse MARCE outcomes than those who had MI alone (adjusted hazard ratios, 1.37 [95% confidence interval, 1.32 to 1.42] and 1.92 [1.86 to 1.99], respectively). Veterans who develop AKI in the setting of MI have worse long-term outcomes than those with AKI or MI alone. Veterans with AKI alone have worse outcomes than those diagnosed with an MI in the absence of AKI.
    Clinical Journal of the American Society of Nephrology 12/2013; · 5.07 Impact Factor

Publication Stats

2k Citations
599.57 Total Impact Points

Institutions

  • 2014–2015
    • Vanderbilt University
      • Department of Anesthesiology
      Нашвилл, Michigan, United States
  • 2006–2014
    • Duke University
      • Department of Anesthesiology
      Durham, North Carolina, United States
    • Duke University Medical Center
      • Department of Anesthesiology
      Durham, North Carolina, United States
  • 2013
    • St. John Providence Health System
      Detroit, Michigan, United States
    • St. John's Medical Center
      Jackson, Wyoming, United States
    • University of California, San Diego
      • Department of Medicine
      San Diego, CA, United States
  • 2012
    • Indiana University-Purdue University Indianapolis
      • Department of Medicine
      Indianapolis, IN, United States
  • 2010
    • London Health Sciences Centre
      • Division of Nephrology
      London, Ontario, Canada
    • University of Alberta
      • Division of Critical Care Medicine
      Edmonton, Alberta, Canada
    • National University (California)
      San Diego, California, United States
    • William Beaumont Army Medical Center
      El Paso, Texas, United States
  • 2002–2010
    • University of Texas MD Anderson Cancer Center
      • • Department of Critical Care
      • • Division of Radiation Oncology
      Houston, Texas, United States
  • 2007
    • University of Oklahoma Health Sciences Center
      • Department of Radiation Oncology
      Oklahoma City, OK, United States
  • 2005
    • Emory University
      Atlanta, Georgia, United States
    • University of Texas Medical School
      Houston, Texas, United States
  • 2004
    • University of Texas Health Science Center at Houston
      • Division of Critical Care Medicine (Internal Medicine)
      Houston, Texas, United States