William L. Macias

Vancomycin pharmacokinetics in acute renal failure: Preservation of nonrenal clearance

The normal nonrenal clearance of vancomycin is reduced in patients with chronic renal failure (40 versus 6 ml/min). The nonrenal clearance of vancomycin in patients with acute renal failure has not been characterized extensively.

Effects of Dialysis Membrane on Intradialytic Vancomycin Administration

Study Objective. To quantify the influence of hemodialyzers on vancomycin removal when the drug was infused during hemodialysis.

Acid‐Base Balance in Continuous Renal Replacement Therapy

The use of continuous hemofiltration and hemodiafltration to manage the volume overload and azotemia of critically ill patients with acute renal failure (ARF) has been discussed extensively in the medical literature and is reviewed elsewhere in this volume (1-3). However, the ability of these therapies to provide normal or near normal acid-base balance, which is implicit in the concept of adequate metabolic and azotemic control, has not been extensively analyzed. The objective of this manuscript is, therefore, to provide a review of the available literature which has focused on acid-base balance in critically ill patients treated with continuous renal replacement therapies. However, the inhomogeneity of the patient population, the use of multiple therapeutic modalities (i.e., CAVH, CVVH, CAVHD, CVVHD), the availability of multiple replacement solutions and dialysates (i.e., lactatebased, bicarbonate-based and citrate-based solutions), and the absence of any well controlled trials comparing each of these makes this type of analysis extremely difficult. Consequently, only general conclusions and recommendations can be amved at based upon the available information. The impact of continuous renal replacement therapies on acid-base homeostasis in critically ill patients is dependent on: l) the metabolic characteristics of the patient (e.g., presence and type of organ failure, simultaneous presence of multiple acid-base disorders, degree of protein catabolism); 2) the amount of administered renal replacement therapy; 3) the clearance of endogenous bicarbonate by that therapy; and 4) the amount of bicarbonate or bicarbonate equivalent administered in the replacement fluid or dialysate. In this review, each of these points will be discussed in the general context of the patient and the type of anion used in the continuous renal replacement therapy. A discussion of the alkali load necessary to manage adequately the acidemia of renal failure and the acidemia of severe lactatemia is included in the review.

Solute Control in Acute Renal Failure: Prescription and Delivery of Adequate Extracorporeal Therapy

The cause of death in critically ill patients with acute renal failure (ARF) is frequently attributed to an underlying condition, particularly sepsis (1). However, recent information suggests that characteristics of the renal replacement therapy (RRT) regimen with which a patient is treated may also influence outcome in ARF. The three major considerations for the clinician prescribing a RRT in ARF are therapy mode (intermittent vs continuous), type of membrane, and intensity (dose) of treatment. Although an increasing volume of literature has focused on the appropriate RRT in ARF, the majority of this effort has addressed only the first two of these considerations, each of which is discussed elsewhere in this volume. Although quantification of the dose of dialysis prescribed and delivered to patients with end-stage renal disease (ESRD) has become routine (2-4), similar assessment of RRT regimens used in ARF has only rarely been reported (5-8). One possible explanation for this dichotomy is the failure of prior investigations to demonstrate a convincing correlation between degree of azotemic control and outcome in ARF (9). Another potential explanation is the lack of agreement on the manner in which solute control by intermittent hemodialysis (IHD) and a continuous RRT (CRRT) should be compared (10, 11). This review will attempt to provide a rational approach to quantifying the dose of extracorporeal RRT delivered to patients with ARF. The discussion will emphasize the difficulties in extrapolating to the ARF setting the urea kinetic modeling (UKM) methods employed in ESRD patients. The determinants of small solute clearance and their impact on the degree of delivered therapy are reviewed. A methodology to compare solute removal by IHD and CRRT also is included. Finally, data pertaining to azotemia control by each of these therapies are presented. It is hoped that the ability to

Comment: Vancomycin and Tobramycin Continuous Hemofiltration Clearance Methodologies:

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