College of American Pathologists
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  Q and A




April 2008

Question Q. We recently had an 84-year-old female patient with a BUN result of 110 mg/dL. Our phy­sician wanted to know why we did not have a critical value for BUN. I have never worked at a place that lists one. Is there a true need for this and why?

A. The definition of a critical value has not changed significantly since originally described by George Lundberg, MD, in his classic 1972 Medical Laboratory Observer article. A critical value represents a pathophysiologic state at such variance with normal that it is life-threatening unless something is done promptly and for which some corrective action could be taken.

Not every analyte will or should have a critical value. As a collaborative effort between the lab, physicians, and nursing, each institution should define the critical analytes and ranges. It is important to periodically review and prune the list to maintain the clinical pertinence of a critical value call. There are many references on critical values. It is helpful to benchmark and compare your critical value list with other local, state, and national institutions. For example, the critical value list of Massachusetts General Hospital can be found at

BUN is not frequently included on critical value lists. BUN is useful in evaluating renal disease and nutritional status. It is increased in renal and prerenal azotemia. BUN elevations can be seen in a variety of disorders, including congestive heart failure, dehydration, acute and chronic renal failure, and others. An elevated BUN is unlikely to be the sole indicator of a life-threatening condition and should not be interpreted separately from other lab values like creatinine. BUN should be monitored over time to better assess the patient’s condition.

For this patient, a BUN of 110 mg/dL may indeed have been an indicator of serious illness. However, critical value calls cannot be the only red flags in the system. Most labs are processing thousands of tests a day, and any one of those results could be critical for a given patient. Your hospital should establish a critical value list based on benchmarking data, the literature, and the needs of your patient population. Results should be truly critical for almost any patient. The lab’s critical value system cannot substitute for a physician’s constant vigilance over the results of lab tests he or she orders for the patient.

  1. Dighe AS, Rao A, Coakley AB, et al. Analysis of laboratory critical value reporting at a large academic medical center. Am J Clin Pathol. 2006;125:758–764.
  2. Howanitz PJ, Steindel SJ, Heard NV. Laboratory critical values policies and procedures: a College of American Pathologists Q-Probes study in 623 institutions. Arch Pathol Lab Med. 2002; 126:663–669.
  3. Lundberg GD. When to panic over an abnormal value. Medical Laboratory Observer. 1972; 4:47–54.

Sherry Woodhouse, MD
Chief of Pathology
Memorial Hospital Miramar
Miramar, Fla.

Question Q. If serum is tested negative for Helicobacter pylori antibody, is it necessary to confirm the results by breath test or biopsy? If so, how many serum-negative results are false-negative?

A. Serologic testing is the primary screening meth­od for patients not requir­ing EGD endoscopic studies. Serum IgG and IgA levels persist for months to years and correlate with active infection in untreated individuals. Serum IgG immunoassays are more sensitive than IgA immunoassays, since IgG levels are more consistently elevated. The mean performance of the different IgG serologic assays is 92 percent sensitivity and 83 percent specificity, but performance can vary significantly depending on the assay. One study found that seven percent of samples with a negative IgG result were IgA positive. The positive predictive values (95 percent to 100 percent) and negative predictive values (84 percent to 89 percent) for serology were comparable to histopathologic exam, rapid urease testing, and urea breath testing, or UBT. Whole-blood serologies have reduced sensitivities as compared with serum enzyme immunoassays.

Fecal antigen detection has been used as a diagnostic tool for pretreated patients and as a followup for treated patients. The sensitivities of the assays vary from 89 percent to 94 percent, and specificities vary from 93 percent to 97 percent. Factors that can affect the sensitivity of the antigen assay include time from sample collection to testing, constipation, and frequency of bowel movements. Fecal antigen testing and UBT are recommended noninvasive methods to confirm infection in pediatric patients, since serology in this population is less than reliable.

Rapid urease testing of gastric biopsy material depends on the organism load and on the number and location of biopsy samples. Sensitivities range from 89 percent to 98 percent and specificities from 93 percent to 100 percent.

Urea breath testing has excellent sensitivity and specificity (both >95 percent). This noninvasive procedure is recommended for followup of patients who remain symptomatic after treatment. UBT may be negative as early as six weeks after successful therapy, whereas serology can remain positive six to 12 months after eradication.

Recommended testing strategies include:
  • Uncomplicated dyspeptic disease (especially in people <50 years old)—serologic testing IgG or combination.
  • If serology negative but suspicion high for disease—UBT or fecal antigen test, serum IgA.
  • If older age, gastrointestinal bleeding, weight loss—upper intestinal endoscopy, gastric mucosal biopsy (antral and corpus) for rapid urease testing, and histopathologic exam.


Versalovic J. Helicobacter pylori: pathology and diagnostic strategies. Am J Clin Pathol. 2003;119:403–412.

Christine C. Ginocchio, PhD
Director of Microbiology, Virology, and Molecular Diagnostics
North Shore-LIJ Health System Laboratories
Lake Success, NY

Consultant, CAP Microbiology Resource Committee