prevention measures vary according to the type of contrast media used (i.e., low-osmolar contrast media vs. iso-osmolar contrast media)? c. How does the comparative effectiveness of prevention measures vary by characteristics of the interventions (e.g., dose, duration, and timing)? 4 Figure 1. Analytic framework comparing the benefits and harms of different methods used to prevent contrast-induced nephropathy in patients receiving low-osmolar or iso-osmolar contrast media . Patients needing imaging with contrast media intravenously, or intraarterially CIN risk factor status: § None § CKD § Diabetes § Hypertension § Cardiovascular disease § Nephrotoxic drugs Intermediate outcomes § CIN Short and long-term final outcomes of CIN § AKI § Hospitalization § RRT § CKD § ESRD § Mortality Preventive measures (see Table 1) (KQ) Immediate harms § Delayed imaging § Extra imaging § Fluid overload § Heart failure Short and long-term final outcomes of harms § Hospitalization § Mortality AKI=acute kidney injury; CIN=contrast induces nephropathy; CKD=chronic kidney disease; ESRD=end stage renal disease; IOCM=iso-osmolar contrast media; KQ=Key Question; LOCM=low-osmolar contrast media; RRT=renal replacement therapy 5 Table 1. PICOTS (populations, interventions, comparisons, outcomes, timing, and setting) criteria for defining the scope of the review Populations • All adults and children undergoing procedures requiring low-osmolar or iso-osmolar contrast media • All patients regardless of their risk of developing CIN (as defined by risk factors such as age, cardiovascular and other comorbidity, creatinine level, etc.) • Patients using contrast media for any type of imaging study Interventions • IV volume expansion with saline • IV volume expansion with sodium bicarbonate • IV volume expansion with saline and sodium bicarbonate • IV or oral N-acetylcysteine, high-dose • IV fluids without pharmacologic agents • IV fluids with pharmacologic agents* • Oral fluids • Oral statins • IV dopamine • IV fluids matched to urine output • Discontinuation of metformin because of concern about inducing lactic acidosis • Discontinuation of medications that could have adverse effects on kidney function (e.g., angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, diuretics, and nonsteroidal anti-inflammatory drugs) • Renal replacement therapy (e.g., hemodialysis or hemofiltration) Comparators (see Table 2) • Usual care vs. any of the interventions listed above • Volume expansion with saline vs. volume expansion with sodium bicarbonate • Volume expansion with saline vs. volume expansion with saline and sodium bicarbonate • Volume expansion with sodium bicarbonate vs. volume expansion with saline and sodium bicarbonate • High-dose vs. low-dose N-acetylcysteine • Timing and duration of above Outcomes • Short-term (≤7 days): a) Harms of prevention interventions – Imaging delay – Need for additional imaging – Fluid overload or heart failure b) Renal function measures – CIN as defined by change in serum creatinine or glomerular filtration rate c) Renal disease-specific outcomes – Need for renal replacement therapy (dialysis or hemofiltration) d) Other clinical outcomes – Mortality (in-hospital or within 7 days) – Cardiac outcomes e) Prolonged hospital stay • Long-term (>7 days): a) Renal function measures – Development of chronic kidney disease, including end stage renal disease – Rate of conversion to chronic kidney disease at 3 and 6 months – Chronic change in kidney function b) Renal disease-specific outcomes – Need for renal replacement therapy (dialysis, hemofiltration, or kidney transplant) c) Other clinical outcomes – Cardiac outcomes – Mortality in-hospital or at 3 or 6 months Timing • For short-term outcomes, any followup during hospitalization or within 7 days of procedure • For long-term outcomes, followup for more than 7 days • For observational studies, followup for at least 2 years. Setting • Inpatient and outpatient CIN=contrast-induced nephropathy; IV=intravenous * Pharmacological agents include: angiotensin converting enzyme inhibitors, angiotensin receptor blockers, ascorbic acid, calcium antagonists, theophylline, aminophylline, dopamine, fenoldopam mesylate, atrial natriuretic peptide, statins, mannitol, MENSA fluid, allopurinol, furosemide, trimetazidine, anisodamine, probucol, and pentoxifylline. 6 Table 2. Major interventions for preventing contrast-induced nephropathy and main comparisons of interest (number of studies/total number of study participants)* IV Saline IV NaHCO3 IV or Oral NAC, High-Dose IV or Oral NAC, low or High-Dose, Plus IV NaHCO3 Adenosine Antagonists RRT-HD or HF Statins Statins + NAC IV Dopamine Ascorbic Acid IV Fluids With Other Drugs† IV sali7 ACE= angiotensin-converting enzyme; HD=hemodialysis; HF=hemofiltration; IV=IV; NAC=N-acetylcysteine; NaHCO3=sodium bicarbonate; RRT=renal replacement therapy *These are the comparisons that had sufficient evidence to merit inclusion in this systematic review. † Pharmacological agents include: ACE inhibitors, angiotensin receptor blockers, calcium antagonists, theophylline, aminophylline, dopamine,