Letters to the Editor

Acetylcysteine to Prevent Acute Contrast-Induced Nephropathy

to the editor: I read with interest the article by Dr. Maddox on adverse reactions to contrast material1 in American Family Physician. Patients often report an allergy to intravenous contrast material that sometimes is not a true allergy. Physicians should ask their patients to describe the specific reaction to the contrast material. Systemic side effects, such as nausea, flushing, or metallic taste, do not preclude the use of intravenous contrast in the future. Renal failure is a common, and often neglected, consequence of contrast media. The monitoring strategy proposed by Dr. Maddox seems reasonable for inpatients who may be monitored closely with laboratory testing,1 but the procedures often occur in an outpatient setting. It has been my practice to monitor serum creatinine levels in the office for three to five days after an outpatient procedure for patients with chronic renal insufficiency. Hydration remains the easiest and most effective means of prevention, although this can be problematic in patients with congestive heart failure or chronic renal insufficiency who are already at high risk for complications from contrast material and fluid overload.

It has become common in our practice to use n-acetylcysteine (Mucomyst) to help prevent acute contrast-induced nephropathy in patients with chronic renal insufficiency. Acetylcysteine is an antioxidant that attenuates ischemic renal failure in animal studies. We use a dosage of 600 mg every 12 hours for 48 to 72 hours, beginning the day before the procedure. Several small trials2-4 support this strategy. However, another trial5 was less favorable, demonstrating benefit only when small amounts of contrast were used. A meta-analysis6 looked at seven studies comparing hydration and acetylcysteine with hydration alone in the prevention of contrast-induced nephropathy in 805 patients with chronic renal insufficiency. The authors6 not only cite a significant reduction in the risk of contrast nephropathy with the use of acetylcysteine but also note that it remains unclear whether the changes observed in serum creatinine levels will correspond to a clinical benefit. Given these findings, the low cost of acetylcysteine and its limited risk, its use as a preventive agent in contrast-induced nephropathy should receive further investigation.

James M. Mears, M.D.
West Virginia University, Charleston Division
Kanawha Valley Family Practice Center
401 Division St., Ste. 205
South Charleston, WV 25039

REFERENCES

in reply: I agree with Dr. Mears' comments on the use of N-acetylcysteine in the prevention of contrast media-induced nephropathy. As mentioned in Dr. Mears' letter, the use of Mucomyst has been demonstrated in some studies to have protective effects. I also agree that further studies should be encouraged to demonstrate this on a larger scale.

Thomas G. Maddox, M.D.
Department of Family Practice
Saint Luke's Hospital
4620 J.C. Nichols Pkwy., Ste. 405
Kansas City, MO 64112

Correction

The article "Insulin Therapy for Type 2 Diabetes: Rescue, Augmentation, and Replacement of Beta-Cell Function" (August 1, 2004, page 489) incorrectly gave the unit of measurement for insulin as milligrams rather than as units. In the abstract on page 489, the ninth sentence should state, "The starting dose of 0.15 units per kg per day for augmentation or 0.5 units per kg per day for replacement can be increased several times as needed." In Figure 3 on page 493, the box for augmentation should state 0.15 units per kg per day. Finally, on page 496, the fourth sentence under the heading "Dosing" should state, "The starting dose for replacement therapy is 0.5 units per kg per day."

On page 496, the first sentence under the heading "Dosing" incorrectly gave the starting insulin dose for augmentation as 0.2 units per kg per day. The correct dose is 0.15 units per kg per day. This correction affects Question 1 of the "Clinical Quiz" on page 438. The correct answer to Question 1 is now D, rather than E.

On page 497, the fourth and fifth sentences under the heading "Oral Medications Plus Insulin" contained errors in the characteristics of thiazolidinedione drugs. The two sentences should have stated, "Thiazolidinedione drugs (i.e., rosiglitazone [Avandia] and pioglitazone [Actos]) administered with insulin can decrease the total insulin dose up to 50 percent, but this may cause edema and is contraindicated in patients with congestive heart failure. Rosiglitazone is restricted to a 4-mg dose if co-administered with insulin."

The online version of the article and quiz answer block have been corrected, and the corrected question and figure are reprinted below.

Q1. The starting insulin dosage for augmentation therapy should contain how many units per kg per day?

Management of Type 2 Diabetes *-Fasting plasma glucose goal is 90 to 130 mg per dL (5 to 7.2 mmol per L), preprandial goal is less than 140 mg per dL (7.8 mmol per L), and postprandial goal is less than 180 mg per dL to achieve an A1C of 7 percent. A1C goals should be individualized.

Figure 3. Algorithm for the management of type 2 diabetes. (FPG = fasting plasma glucose)

Insulin Therapy Components

TO THE EDITOR: The following errors appear in Table 1 of the article "Insulin Therapy for Type 2 Diabetes: Rescue, Augmentation, and Replacement of Beta-Cell Function."1

NovoLog Mix 70/30 is incorrectly identified as "NovoLog 70/30" and is incorrectly described as 70 percent neutral protamine Hagedorn (NPH) insulin and 30 percent aspart. NovoLog Mix 70/30 does not contain NPH insulin, but rather 70 percent insulin aspart (rDNA origin) protamine suspension and 30 percent insulin aspart (rDNA origin) injection. NovoLog Mix 70/30 is a single solution containing a premixed formulation of 70 percent insulin aspart in the crystalline protamine form and 30 percent insulin aspart in the soluble form.

The table states that NovoLog Mix 70/30 has a dual peak. The glucose-lowering effects for this insulin begin as early as 10 to 20 minutes after subcutaneous injection and are maximal at 2.4 ± 0.80 hours; the duration of action may be as long as 24 hours because of the protaminated insulin aspart. However, examination of the pharmacokinetic profile of NovoLog Mix 70/30 reveals only one peak.

TABLE 1 Description of Onset, Peak, and Duration of Insulins Insulin Onset Peak (hours) Usual effective duration (hours) Usual maximum duration (hours) Cost* Bolus or mealtime insulin   Aspart (NovoLog) 5 to 10 minutes 1 to 3 3 to 5 4 to 6 $59   Lispro (Humalog) < 15 minutes 0.5 to 1.5 2 to 4 4 to 6 59   Regular (Humulin R, Novolin R) 30 to 60 minutes 2 to 3 3 to 6 6 to 10 28 Basal insulin   NPH (Humulin N, Novolin N) 2 to 4 hours 4 to 10 10 to 16 14 to 18 28   Lente (insulin zinc suspension) 3 to 4 hours 4 to 12 12 to 18 16 to 20   Ultralente (extended insulin zinc suspension) 6 to 10 hours Peakless 18 to 20 20 to 24 28   Glargine (Lantus) 1 hour, 6 minutes Peakless 24 24 51 Combinations   50% NPH/50% regular 30 to 60 minutes Dual 10 to 16 14 to 18   70% NPH/30% regular (Humulin R 70/30, Novolin R 70/30) 30 to 60 minutes Dual 10 to 16 14 to 18 28   75% NPL/25% lispro (Humalog 75/25) < 15 minutes Dual 10 to 16 14 to 18 59†   70% APS/30% aspart (NovoLog Mix 70/30) 10 to 20 minutes 2.4 + 0.80 24 24 59 NPH = neutral protamine Hagedorn; NPL = neutral protamine lispro; APS = aspart protamine suspension. *-Estimated cost to the pharmacist for one 10-ml vial based on average wholesale prices in Red book. Montvale, N.J.: Medical Economics Data, 2004. Cost to the patient will be higher, depending on prescription filling fee. †-20-mL volume only-cost shown is one half of the cost of a 20-mL vial. Adapted with permission from Resource guide 2004. Insulin. Diabetes Forecast 2004;57:RG16.

ALAN MOSES, M.D.
Associate Vice President, Medical Affairs
Novo Nordisk Pharmaceuticals, Inc.

REFERENCE

EDITOR'S NOTE: The online version of this article has been corrected, and the corrected table is reprinted above.