IODINATED CONTRAST MEDIA IN ESRD
607
The Use of Iodinated Contrast Media in Patients with End-Stage Renal Disease Sana F. Khan and Kambiz Kalantari Division of Nephrology, University of Virginia Health System, Charlottesville, Virginia
Characteristics of Iodinated Contrast Media Iodinated contrast media (ICM) are used in millions of patients undergoing imaging procedures. ICM were first used in the clinical setting with the development of sodium iodide in the 1920s. In the 1950s, sodium and meglumine salts of tri-iodinated benzoic acid came into clinical use as high-osmolar contrast agents, with osmolalities ranging from approximately 1500 to greater than 2000 mOsm/kg H2O. In the 1970s low osmolality, nonionic agents were introduced in the hope that toxicity would be improved (1). The ICM in current clinical use are characterized as either ionic or nonionic and structurally are either monomers or dimers. Osmolality of contrast agents is commonly used to categorize these agents into three broad categories; high-osmolar contrast media (HOCM), Low-osmolar (LOCM), and iso-osmolar (IOCM) (Table 1). HOCM were used widely until the mid-1980s and were ionic monomers. Subsequent structural changes led to the development of the LOCM and IOCM. Four classes of ICM are currently in use, high-osmolar ionic monomers, iso-osmolar nonionic dimers, low-osmolar ionic dimers, and low-osmolar nonionic monomers (Table 1). Pharmacokinetic Properties After intravascular administration, iodinated contrast media are distributed in the extracellular fluid compartment. There is no uptake into the intracellular compartment, and pharmacokinetics of ICM follows a two-compartment model involving blood and the interstitium. ICM are highly water soluble, minimally protein bound, and are eliminated unmetabolized in the urine (2,3). Within 2–5 minutes following intravenous administration, ICM diffuse from plasma into the extracellular space and the equilibrium between these two compartments is achieved after 2 hours of administration (3). ICM are excreted by glomerular filtration with no significant tubular secretion or reabsorption. Less than
Address correspondence to: Kambiz Kalantari, MD, MS, Associate Professor of Medicine, Division of Nephrology, University of Virginia Health System, Box 800133, Charlottesville, VA 22908, e-mail: [email protected]. Seminars in Dialysis—Vol 27, No 6 (November–December) 2014 pp. 607–610 DOI: 10.1111/sdi.12268 © 2014 Wiley Periodicals, Inc.
1% of the administered dose is excreted in sweat, tear, and saliva (4). In the presence of normal renal function, plasma half-life ranges from 40 minutes to 2 hours, depending on the type of the ICM administered, with near complete elimination in 24 hours (5). In patients with renal impairment, there is long lasting retention of contrast medium (up to several weeks) (6) with only slow biliary and intestinal excretion as compensatory alternative elimination routes. The major complications associated with these agents are due to their nephrotoxicity. Contrastinduced nephropathy remains an important cause of hospital-acquired acute kidney injury. Preexisting renal impairment, diabetic nephropathy, and dose (volume administered) of iodinated contrast are major risk factors in the development of contrastinduced nephropathy. Several studies have investigated the role of prophylactic hemodialysis for prevention of contrast-induced AKI (7–9), however, data in ESRD patients appear to be limited. Potential Concerns about ICM Exposure in ESRD Patients Excessive Solute Load The main concern regarding administration of ICM in ESRD patients has been the delivery of excessive solute load and acute volume overload. Three studies have addressed this concern and the need for urgent dialysis following intravascular injection of contrast media in chronic hemodialysis patients. Younathan et al. studied the effects of contrast administration in 10 patients on a stable three times weekly hemodialysis regimen (10). Volume of contrast medium injected ranged from 40 to 225 ml and average time prior to the regular scheduled hemodialysis session ranged from 16 to 47 hours. None of the patients developed signs of volume overload or other complications necessitating emergent dialysis prior to the scheduled treatment. Similarly, Hamani et al. reported no need of urgent hemodialysis in eight ESRD patients after receiving 50–300 ml of Iobitridol (11). Another group of investigators followed 1287 ESRD patients undergoing CT scans with Iohexol administration (12). One hundred milliliters of lowosmolar contrast was administered, an average of 27 hours (range 6–45 hours) prior to the next scheduled dialysis session. None of the patients had adverse reactions requiring urgent dialysis. Despite the limited number of studies, in the era of
608
Khan and Kalantari TABLE 1. Commonly used iodinated contrast media
Osmolarity High-osmolar contrast media (1500 mOsm/kgH2O— >2000 mOsm/kgH2O) Low-osmolar contrast media (600 mOsm/kgH2O— 1000 mOsm/kgH2O) Iso-osmolar contrast media (~ 290 mOsm/kgH2O)
Iodinated contrast media
Brand name
Diatrizoates Iothalamates Metrizoates Ioxithalamate Iohexol Iopromide Ioxaglate (ionic) Iopimadol Ioversol Iotrolan Iodixanol
Hypaque Conray Isopaque Telebrix Omnipaque Ultravist Hexabrix Isovue Optiray Iotrol Visipaque
low-osmolar ICM, there seems to be no evidence supporting the need for immediate postprocedure hemodialysis. However, in cases with larger doses of ICM, close monitoring for signs and symptoms of volume overload is recommended, especially in subjects with poor cardiac and pulmonary function. Besides overt volume overload, there are concerns regarding ICM-induced electrolyte and acid– base alterations in patients with impaired renal function. Sirken et al. reported a series of five patients with stages 4 (one patient) or 5 CKD who developed significant hyponatremia and hyperkalemia following exposure to ICM (13). The volume of contrast used (ioversol, 792 mOsm/kg water) ranged from 350 to 975 ml. All subjects received 5% dextrose in water intravenously with or without oral hydration (total volume range:
607
The Use of Iodinated Contrast Media in Patients with End-Stage Renal Disease Sana F. Khan and Kambiz Kalantari Division of Nephrology, University of Virginia Health System, Charlottesville, Virginia
Characteristics of Iodinated Contrast Media Iodinated contrast media (ICM) are used in millions of patients undergoing imaging procedures. ICM were first used in the clinical setting with the development of sodium iodide in the 1920s. In the 1950s, sodium and meglumine salts of tri-iodinated benzoic acid came into clinical use as high-osmolar contrast agents, with osmolalities ranging from approximately 1500 to greater than 2000 mOsm/kg H2O. In the 1970s low osmolality, nonionic agents were introduced in the hope that toxicity would be improved (1). The ICM in current clinical use are characterized as either ionic or nonionic and structurally are either monomers or dimers. Osmolality of contrast agents is commonly used to categorize these agents into three broad categories; high-osmolar contrast media (HOCM), Low-osmolar (LOCM), and iso-osmolar (IOCM) (Table 1). HOCM were used widely until the mid-1980s and were ionic monomers. Subsequent structural changes led to the development of the LOCM and IOCM. Four classes of ICM are currently in use, high-osmolar ionic monomers, iso-osmolar nonionic dimers, low-osmolar ionic dimers, and low-osmolar nonionic monomers (Table 1). Pharmacokinetic Properties After intravascular administration, iodinated contrast media are distributed in the extracellular fluid compartment. There is no uptake into the intracellular compartment, and pharmacokinetics of ICM follows a two-compartment model involving blood and the interstitium. ICM are highly water soluble, minimally protein bound, and are eliminated unmetabolized in the urine (2,3). Within 2–5 minutes following intravenous administration, ICM diffuse from plasma into the extracellular space and the equilibrium between these two compartments is achieved after 2 hours of administration (3). ICM are excreted by glomerular filtration with no significant tubular secretion or reabsorption. Less than
Address correspondence to: Kambiz Kalantari, MD, MS, Associate Professor of Medicine, Division of Nephrology, University of Virginia Health System, Box 800133, Charlottesville, VA 22908, e-mail: [email protected]. Seminars in Dialysis—Vol 27, No 6 (November–December) 2014 pp. 607–610 DOI: 10.1111/sdi.12268 © 2014 Wiley Periodicals, Inc.
1% of the administered dose is excreted in sweat, tear, and saliva (4). In the presence of normal renal function, plasma half-life ranges from 40 minutes to 2 hours, depending on the type of the ICM administered, with near complete elimination in 24 hours (5). In patients with renal impairment, there is long lasting retention of contrast medium (up to several weeks) (6) with only slow biliary and intestinal excretion as compensatory alternative elimination routes. The major complications associated with these agents are due to their nephrotoxicity. Contrastinduced nephropathy remains an important cause of hospital-acquired acute kidney injury. Preexisting renal impairment, diabetic nephropathy, and dose (volume administered) of iodinated contrast are major risk factors in the development of contrastinduced nephropathy. Several studies have investigated the role of prophylactic hemodialysis for prevention of contrast-induced AKI (7–9), however, data in ESRD patients appear to be limited. Potential Concerns about ICM Exposure in ESRD Patients Excessive Solute Load The main concern regarding administration of ICM in ESRD patients has been the delivery of excessive solute load and acute volume overload. Three studies have addressed this concern and the need for urgent dialysis following intravascular injection of contrast media in chronic hemodialysis patients. Younathan et al. studied the effects of contrast administration in 10 patients on a stable three times weekly hemodialysis regimen (10). Volume of contrast medium injected ranged from 40 to 225 ml and average time prior to the regular scheduled hemodialysis session ranged from 16 to 47 hours. None of the patients developed signs of volume overload or other complications necessitating emergent dialysis prior to the scheduled treatment. Similarly, Hamani et al. reported no need of urgent hemodialysis in eight ESRD patients after receiving 50–300 ml of Iobitridol (11). Another group of investigators followed 1287 ESRD patients undergoing CT scans with Iohexol administration (12). One hundred milliliters of lowosmolar contrast was administered, an average of 27 hours (range 6–45 hours) prior to the next scheduled dialysis session. None of the patients had adverse reactions requiring urgent dialysis. Despite the limited number of studies, in the era of
608
Khan and Kalantari TABLE 1. Commonly used iodinated contrast media
Osmolarity High-osmolar contrast media (1500 mOsm/kgH2O— >2000 mOsm/kgH2O) Low-osmolar contrast media (600 mOsm/kgH2O— 1000 mOsm/kgH2O) Iso-osmolar contrast media (~ 290 mOsm/kgH2O)
Iodinated contrast media
Brand name
Diatrizoates Iothalamates Metrizoates Ioxithalamate Iohexol Iopromide Ioxaglate (ionic) Iopimadol Ioversol Iotrolan Iodixanol
Hypaque Conray Isopaque Telebrix Omnipaque Ultravist Hexabrix Isovue Optiray Iotrol Visipaque
low-osmolar ICM, there seems to be no evidence supporting the need for immediate postprocedure hemodialysis. However, in cases with larger doses of ICM, close monitoring for signs and symptoms of volume overload is recommended, especially in subjects with poor cardiac and pulmonary function. Besides overt volume overload, there are concerns regarding ICM-induced electrolyte and acid– base alterations in patients with impaired renal function. Sirken et al. reported a series of five patients with stages 4 (one patient) or 5 CKD who developed significant hyponatremia and hyperkalemia following exposure to ICM (13). The volume of contrast used (ioversol, 792 mOsm/kg water) ranged from 350 to 975 ml. All subjects received 5% dextrose in water intravenously with or without oral hydration (total volume range:
