Medication Dosing and Renal Insufficiency in a Pediatric Cardiac Intensive Unit

Abstract

Appropriate drug dosing in renal insufficiency is an important consideration to optimize therapeutic outcomes and to minimize toxicity. In this issue of the journal, Moffett and colleagues [4] remind health care providers of the clinical benefits of pharmacist involvement on drug dosing for patients with renal insufficiency in a pediatric cardiac intensive care unit. The authors adapted a wellknown list of drugs primarily excreted by the kidneys for patients with renal impairment. They noted that patients who required medication adjustments were significantly younger compared to those who did not require medication adjustment. Moffett et al. also report that clinical pharmacist consultation for prescribing drugs in the pediatric intensive care setting would be associated with shorter length of stay, lower costs, and lower rate of medication errors. Clinical pharmacist services in the hospital setting are proven to be beneficial. Such services are labor-intensive and require collecting patient data, calculating a creatinine clearance (CrCl) level, and contacting a physician to change the order to increase the likelihood of accurate medication selection and dosing based on an estimated CrCl. A rational approach to drug dosing in patients with renal impairment begins with a thorough history and physical examination. Particularly important is the history of previous drug allergy or toxicity and the use of concurrently prescribed or nonprescription drugs. Physical assessment should include estimating the extracellular fluid volume (ECFV); the presence of edema or dehydration alters drug dose. Body weight and height need to be measured, and the ideal body weight should be calculated and drug doses estimated accordingly. The renal excretion of drugs depends on glomerular filtration and renal tubular secretion and reabsorption. The glomerular elimination of drugs also depends on the molecular size and protein binding of the agent. Although protein binding decreases the filtration of drugs, it may increase the amount that the renal tubule secretes. When glomerular filtration is impaired by renal disease, the clearance of drugs that are eliminated primarily by this mechanism will be decreased and the plasma half-life of the drugs prolonged. The secretion of drugs eliminated by active transport systems in the renal tubule also will be affected in patients with renal disease. As the rate of CrCl decreases, drugs dependent on renal tubular excretion for elimination will be excreted more slowly. Furthermore, because the proximal tubular secretion of some agents is carrier mediated and capacity limited, concurrent use of multiple drugs eliminated by renal tubular secretion may saturate the transport system. Renal insufficiency alters both the disposition of drugs in the body (pharmacokinetics) and tissue responses to drugs (pharmacodynamics). If drugs or their metabolites are excreted by the kidneys, they can accumulate in patients with renal insufficiency and cause adverse effects. When the necessity for drug therapy has been established, renal function should be measured. Because the rate of elimination of drug excreted by the kidneys is proportional to the glomerular filtration rate (GFR), the serum creatinine or CrCl should be used to estimate renal function. The Schwartz equation can be used to estimate CrCl in children and adolescents [5]. However, estimating GFR from the serum creatinine assumes that renal function is stable and that the serum creatinine measurement is constant. With changing renal function, the serum creatinine level will no F. Assadi (&) Rush University Medical Center, Chicago, IL, USA e-mail: Ra-Id_Abdulla@rush.edu