Michael J. Connor

Successful Delivery of RRT in Ebola Virus Disease

AKI has been observed in cases of Ebola virus disease. We describe the protocol for the first known successful delivery of RRT with subsequent renal recovery in a patient with Ebola virus disease treated at Emory University Hospital, in Atlanta, Georgia. Providing RRT in Ebola virus disease is complex and requires meticulous attention to safety for the patient, healthcare workers, and the community. We specifically describe measures to decrease the risk of transmission of Ebola virus disease and report pilot data demonstrating no detectable Ebola virus genetic material in the spent RRT effluent waste. This article also proposes clinical practice guidelines for acute RRT in Ebola virus disease.

Pharmacokinetics and Pharmacodynamics of Piperacillin-Tazobactam in 42 Patients Treated with Concomitant CRRT

BACKGROUND AND OBJECTIVES Current recommendations for piperacillin-tazobactam dosing in patients receiving continuous renal replacement therapy originate from studies with relatively few patients and lower continuous renal replacement therapy doses than commonly used today. This study measured the pharmacokinetic and pharmacodynamic characteristics of piperacillin-tazobactam in patients treated with continuous renal replacement therapy using contemporary equipment and prescriptions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A multicenter prospective observational study in the intensive care units of two academic medical centers was performed, enrolling patients with AKI or ESRD receiving piperacillin-tazobactam while being treated with continuous renal replacement therapy. Pregnant women, children, and patients with end stage liver disease were excluded from enrollment. Plasma and continuous renal replacement therapy effluent samples were analyzed for piperacillin and tazobactam levels using HPLC. Pharmacokinetic and pharmacodynamic parameters were calculated using standard equations. Multivariate analyses were used to examine the association of patient and continuous renal replacement therapy characteristics with piperacillin pharmacokinetic parameters. RESULTS Forty-two of fifty-five subjects enrolled had complete sampling. Volume of distribution (median=0.38 L/kg, intraquartile range=0.20 L/kg) and elimination rate constants (median=0.104 h(-1), intraquartile range=0.052 h(-1)) were highly variable, and clinical parameters could explain only a small fraction of the large variability in pharmacokinetic parameters. Probability of target attainment for piperacillin was 83% for total drug but only 77% when the unbound fraction was considered. CONCLUSIONS There is significant patient to patient variability in pharmacokinetic/pharmacodynamic parameters in patients receiving continuous renal replacement therapy. Many patients did not achieve pharmacodynamic targets, suggesting that therapeutic drug monitoring might optimize therapy.

Critical Care for Multiple Organ Failure Secondary to Ebola Virus Disease in the United States.

Objective:This report describes three patients with Ebola virus disease who were treated in the United States and developed for severe critical illness and multiple organ failure secondary to Ebola virus infection. The patients received mechanical ventilation, renal replacement therapy, invasive monitoring, vasopressor support, and investigational therapies for Ebola virus disease. Data Sources:Patient medical records from three tertiary care centers (Emory University Hospital, University of Nebraska Medical Center, and Texas Health Presbyterian Dallas Hospital). Study Selection:Not applicable. Data Extraction:Not applicable. Data Synthesis:Not applicable. Conclusion:In the severe form, patients with Ebola virus disease may require life-sustaining therapy, including mechanical ventilation and renal replacement therapy. In conjunction with other reported cases, this series suggests that respiratory and renal failure may occur in severe Ebola virus disease, especially in patients burdened with high viral loads. Ebola virus disease complicated by multiple organ failure can be survivable with the application of advanced life support measures. This collective, multicenter experience is presented with the hope that it may inform future treatment of patients with Ebola virus disease requiring critical care treatment.

Therapeutic Drug Monitoring of Piperacillin-Tazobactam Using Spent Dialysate Effluent in Patients Receiving Continuous Venovenous Hemodialysis

ABSTRACT Sepsis and multisystem organ failure are common diagnoses affecting nearly three-quarters of a million Americans annually. Infection is the leading cause of death in acute kidney injury, and the majority of critically ill patients who receive continuous dialysis also receive antibiotics. Dialysis equipment and prescriptions have gradually changed over time, raising concern that current drug dosing recommendations in the literature may result in underdosing of antibiotics. Our research group directed its attention toward antibiotic dosing strategies in patients with acute renal failure (ARF), and we sought data confirming that patients receiving continuous dialysis and antibiotics actually were achieving therapeutic plasma drug levels during treatment. In the course of those investigations, we explored “fast-track” strategies to estimate plasma drug concentrations. As most antimicrobial antibiotics are small molecules and should pass freely through modern high-flux hemodialyzer filters, we hypothesized that continuous renal replacement therapy (CRRT) effluent could be used as the medium for drug concentration measurement by reverse-phase high-pressure liquid chromatography (HPLC). Here we present the first data demonstrating this approach for piperacillin-tazobactam. Paired blood and dialysate trough-peak-trough samples were drawn from 19 patients receiving piperacillin-tazobactam and continuous venovenous hemodialysis (CVVHD). Total, free, and dialysate drug concentrations were measured by HPLC. Dialysate drug levels predicted plasma free drug levels well (r 2 = 0.91 and 0.92 for piperacillin and tazobactam, respectively) in all patients. These data suggest a strategy for therapeutic drug monitoring that minimizes blood loss from phlebotomy and simplifies analytic procedures.

Rapid Development and Implementation of an ECMO Program

Extracorporeal membrane oxygenation (ECMO) is an established therapy in the management of patients with refractory cardiogenic shock or acute respiratory failure. In this report, we describe the rapid development and implementation of an organized ECMO program at a facility that previously provided ad hoc support. The program provides care for patients within the Emory Healthcare system and throughout the Southeastern United States. From September 2014 to February 2015, 16 patients were treated with either venovenous or venoarterial ECMO with a survival to decannulation of 53.3% and survival to intensive care unit discharge of 40%. Of the 16 patients, 10 were transfers from outside facilities of which 2 were remotely cannulated and initiated on ECMO support by our ECMO transport team. Complications included intracerebral hemorrhage, bleeding from other sites, and limb ischemia. The results suggest that a rapidly developed ECMO program can provide safe transport services and provide outcomes similar to those in the existing literature. Key components appear to be an institutional commitment, a physician champion, multidisciplinary leadership, and organized training. Further study is required to determine whether outcomes will continue to improve.

Vancomycin Clearance in High-Volume Venovenous Hemofiltration

OBJECTIVE To report the pharmacokinetic and pharmacodynamic properties of vancomycin in 4 patients undergoing high-volume continuous venovenous hemofiltration (CVVH). CASE SUMMARY Data from 4 patients prescribed high-volume CVVH for acute renal failure treated with vancomycin were analyzed. Vancomycin plasma concentrations were measured 4 and 24 hours after the end of a 1-hour vancomycin infusion. The mean therapy fluid rate on initiation of vancomycin was 56.2 mL/kg/h (range 48.0–65.5). The mean loading dose of vancomycin was 18.3 mg/kg (range 14.7–19.7). Median vancomycin concentration 4 hours after the dose was 18.1 mg/L (range 13.1–30.0). At 24 hours after the dose, only 1 patient had a detectable vancomycin concentration (5.2 mg/L). DISCUSSION There was a large variability in the clearance of vancomycin in this patient population. Current strategies for dosing vancomycin may lead to subtherapeutic trough concentrations. Vancomycin dosing in this patient population should be based on a detailed assessment of the CVVH prescription, vancomycin concentrations, and clinical needs and response. CONCLUSIONS An initial vancomycin dose of 20–25 mg/kg with frequent monitoring and adjustment is recommended for patients receiving high-volume CVVH.

Pharmacokinetics and Pharmacodynamics of Extended Infusion Versus Short Infusion Piperacillin-Tazobactam in Critically Ill Patients Undergoing CRRT.

BACKGROUND AND OBJECTIVES Infection is the most common cause of death in severe AKI, but many patients receiving continuous RRT do not reach target antibiotic concentrations in plasma. Extended infusion of β-lactams is associated with improved target attainment in critically ill patients; thus, we hypothesized that extended infusion piperacillin-tazobactam would improve piperacillin target attainment compared with short infusion in patients receiving continuous RRT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted an institutional review board-approved observational cohort study of piperacillin-tazobactam pharmacokinetics and pharmacodynamics in critically ill patients receiving continuous venovenous hemodialysis and hemodiafiltration at three tertiary care hospitals between 2007 and 2015. Antibiotic concentrations in blood and/or dialysate samples were measured by liquid chromatography, and one- and two-compartment pharmacokinetic models were fitted to the data using nonlinear mixed effects regression. Target attainment for piperacillin was defined as achieving four times the minimum inhibitory concentration of 16 μg/ml for >50% of the dosing cycle. The probabilities of target attainment for a range of doses, frequencies, and infusion durations were estimated using a Monte Carlo simulation method. Target attainment was also examined as a function of patient weight and continuous RRT effluent rate. RESULTS Sixty-eight participants had data for analysis. Regardless of infusion duration, 6 g/d piperacillin was associated with ≤45% target attainment, whereas 12 g/d was associated with ≥95% target attainment. For 8 and 9 g/d, target attainment ranged between 68% and 85%. The probability of target attainment was lower at higher effluent rates and patient weights. For all doses, frequencies, patient weights, and continuous RRT effluent rates, extended infusion was associated with higher probability of target attainment compared with short infusion. CONCLUSIONS Extended infusions of piperacillin-tazobactam are associated with greater probability of target attainment in patients receiving continuous RRT.

Optimal Role of the Nephrologist in the Intensive Care Unit

As advances in Critical Care Medicine continue, critically ill patients are surviving despite the severity of their illness. The incidence of acute kidney injury (AKI) has increased, and its impact on clinical outcomes as well as medical expenditures has been established. The role, indications and technological advancements of renal replacement therapy (RRT) have evolved, allowing more effective therapies with less complications. With these changes, Critical Care Nephrology has become an established specialty, and ongoing collaborations between critical care physicians and nephrologist have improved education of multi-disciplinary team members and patient care in the ICU. Multidisciplinary programs to support these changes have been stablished in some hospitals to maximize the delivery of care, while other programs have continue to struggle in their ability to acquire the necessary resources to maximize outcomes, educate their staff, and develop quality initiatives to evaluate and drive improvements. Clearly, the role of the nephrologist in the ICU has evolved, and varies widely among institutions. This special article will provide insights that will hopefully optimize the role of the nephrologist as the leader of the acute care nephrology program, as clinician for critically ill patients, and as teacher for all members of the health care team.

Micronutrient Alterations During Continuous Renal Replacement Therapy in Critically Ill Adults: A Retrospective Study:

BACKGROUND Continuous renal replacement therapy (CRRT) is commonly used to provide renal replacement therapy in the intensive care unit. Limited published data suggest that CRRT may lead to depletion of water-soluble vitamins and trace elements. The goal of this study was to identify the incidence of trace element and vitamin deficiencies in critically ill patients during CRRT. MATERIALS AND METHODS This study is based on a retrospective chart review of patients who were referred to Emory University Hospitals nutrition support services and had at least 1 serum micronutrient level measured during CRRT (thiamin, pyridoxine, ascorbic acid, folate, zinc, and copper) between April 1, 2009, and June 1, 2012. RESULTS Seventy-five patients were included in the study. Nine of 56 patients (16%) had below-normal whole blood thiamin concentrations, and 38 of 57 patients (67%) had below-normal serum pyridoxine levels. Serum ascorbic acid and folate deficiencies were identified among 87% (13 of 15) and 33% (3 of 9) of the study patients, respectively. Nine of 24 patients had zinc deficiency (38%), and 41 of 68 patients had copper deficiency (60%). Of the 75 total subjects, 60 patients (80%) had below-normal levels of at least 1 of the micronutrients measured. CONCLUSIONS The incidence of various micronutrient deficiencies in critically ill patients who required CRRT was higher than previously reported. Prospective studies are needed to determine the impact of CRRT on micronutrient status and the potential clinical and metabolic efficacy of supplementation in the intensive care unit setting.

Comparison of circuit patency and exchange rates between 2 different continuous renal replacement therapy machines.

BACKGROUND Continuous renal replacement therapy (CRRT) is an important tool in the care of critically ill patients. However, the impact of a specific CRRT machine type on the successful delivery of CRRT is unclear. The purpose of this study was to evaluate the effectiveness of CRRT delivery with an intensive care unit (ICU) bedside nurse delivery model for CRRT while comparing circuit patency and circuit exchange rates in 2 Food and Drug Administration-approved CRRT devices. This article presents the data comparing circuit exchange rates for 2 different CRRT machines. MATERIALS AND METHODS A group of ICU nurses were selected to undergo expanded training in CRRT operation and empowered to deliver all aspects of CRRT. The ICU nurses then provided all aspects of CRRT on 2 Food and Drug Administration-approved CRRT devices for 6 months. Each device was used exclusively in the designated ICU for a 2-week run-in period followed by 3-month data collection period. The primary end point for the study was the differences in average number of filter exchanges per day during each CRRT event. RESULTS A total of 45 unique patients who underwent 64 separate CRRT treatment periods were included. Four CRRT events were excluded (see text for details). Twenty-eight CRRT events occurred in the NxStage System One arm (NxStage Medical, Lawrence, Mass) and 32 events in the Gambro Prismaflex arm (Gambro Renal Products, Boulder, Colo). Average (SD) filter exchanges per day was 0.443 (0.60) for the NxStage System One machine and 0.553 (0.65) for Gambro Prismaflex machine (P = .09). CONCLUSIONS There was no demonstrable difference in circuit patency as defined by the rate of filter exchanges per day of CRRT therapy.