Effects of Drugs on Clinical Laboratory Tests

Abstract

In 1962, Caraway I highlighted the potential for therapeutic drugs and endogenous compounds to modify the concentrations of various analytes in body fluids. A few years later, others, including Elking and Kabat! and Sunderman;' amplified Caraway's earlier report. These early papers prompted many clinical chemists to begin to question their test results, something that clinicians often did when the results did not appear to fit the clinical picture of their patients. At the time these papers were written there was legitimate concern about the analytical specificity of many laboratory methods, and clinicians did not have confidence in the test results. The clinician's view was that any test result that did not conform to his or her clinical impression was erroneous. My personal interest in the effects of drugs on clinical laboratory tests was triggered by physicians criticizing certain test results that my laboratory produced. They felt that the results were not in keeping with their clinical impressions. They concluded the test results were wrong. Yet I knew that quality assurance data were within acceptable limits. Obtaining drug histories often identified likely causes of abnormal results. Sometimes, the clinicians were not aware of all the in vivo effects of the drugs they were using. It was possible to show that the abnormal test result was related to a side-effect. Sometimes we were able to demonstrate an interference of a drug with an analytical method. It seemed worth capturing the effort put into tracking the causes of spurious results so that other laboratory staff might find it easier to explain unanticipated test results. The information I accumulated was first published in a regular issue of Clinical Chemistry.' updated in a special issue of the journal, and then, periodically, in books published by the American Association for Clinical Chemistry (AACC), the most recent in 1995.5 The amount of information related to the effect of drugs on clinical laboratory tests is growing. One continuing concern is the point at which data should be considered obsolete and not reported. Generally, data on analytical interferences of drugs have been deleted from the master file when references are more than 15 years old. However, for procedures that continue to be widely used, e.g. urine dipsticks, the reported effects have been republished. In the early editions of the publication there was considerable emphasis on the effects of drugs on the analytical methods. In the later editions there has been less emphasis on analytical interferences as analytical specificity has improved. In all the editions I have adopted the philosophy that it is as important to document that a drug has been demonstrated not to have an effect on a particular method as it is to describe the effects that it does have. The clinician is often faced with an unexpected abnormal result. He or she needs to know all the possible causes. Invariably, clinicians are unaware of the analytical methods used to measure the analytes that they require to be measured. They are also often unaware of some of the side-effects of drugs that they use relatively infrequently. Thus, to provide all the information that clinicians and laboratory staff need to properly interpret the test results, the database of the effects of drugs must be fully comprehensive. A repeatedly asked question is whether the availability of databases of effects of drugs on clinical laboratory tests can influence medical practice. Most users of the database can provide anecdotal accounts of instances when it was able to provide an explanation for unexpected abnormal results. Shortly after the publication of the second compilation of the database.P we embarked on a study at the University of Wisconsin Hospitals? to determine whether automatic reporting to physicians of potential drug-induced causes of abnormal test results could modify medical practice. More than 13 000 patient-days in patients in general surgical, minimal or moderate medical care, or intensive care units, were followed.