Adverse Drug Reactions: A Review.
Gharaibeh MN, Greenberg, HE, Waldman SA. Drug Information Journal. 1998;32:323-38. [ see abstract below ]
Given the recent emphasis in the medical and lay press regarding the seriousness and extent of adverse drug reactions within health-care systems, it is useful for practitioners in anesthesiology to review some of the current thinking expressed in the literature about this subject. The Drug Information Journal (click here to visit their web site)is an ongoing source of new information regarding drug design and development, and the authors of the present article from that journal provide a nice update on the definitions, epidemiology, demographics, and economics of adverse drug reactions.
The World Health Organization (WHO) describes an adverse drug reaction (ADR) as "the noxious and unintended drug effect which occurs at doses employed in man for prophylaxis, diagnosis or therapy". However, most preventable drug-related injuries suffered by patients do not result from an inherent problem with the drug itself but from errors in proper use. The FDA defines an ADR as "an undesirable effect, reasonably associated with the use of the drug, that may occur as a part of the pharmacologic action of a drug or may be unpredictable in its occurrence." For reporting purposes, the FDA includes incidents of overdose and incidents due to drug dependence or withdrawal after cessation of drug administration. The utilization of a more liberal definition for reporting a suspected ADR, and a more restrictive one for its review, will more accurately reflect the reality of reported ADRs. Adverse drug events (ADEs), defined as "an injury resulting from medical intervention related to drug," appears to be a more comprehensive and clinically relevant description of the problem than does the term ADR. These terms are frequently interchangeable, but nevertheless have important distinctions.
For perspective, the authors provide a discussion on the epidemiology, demography and economics of ADRs. It is estimated that the average adult in United States takes at least two drugs on a regular basis. In hospitalized patients, the number increases to nine. In a prospective case-controlled study in hospitalized patients, ADRs complicated 2.3 percent of the cases, caused 3.5 percent mortality, increased hospital stays by 174 percent, and resulted in a doubling of mean costs of hospitalization from $5,335 to $10,010. About 12,000 deaths and 15,000 hospitalization's due to ADRs were reported to the FDA in 1987. Importantly, it was suggested that 50 percent of ADEs were potentially preventable.
Regarding the financial impact of ADRs, the National Association of Insurance Commissioners reported that drug-related injuries accounted for the highest total expenditure for any type of procedure-related malpractice claims. The annual cost of screening, diagnosing, and treating ADRs in the United States was estimated to be $76.6 billion a year, which translates to a per capita cost of over $300. In addition, indirect costs to study ADRs and associated legal expenses further increase the prices of new drugs.
According to the Harvard Medical Practice Study, conducted in New York State in 1984, 3.7 percent of 30,000 hospitalized patients suffered an adverse event, defined as an injury due to medical treatment. In this study, the leading cause of medical injury was the use of drugs, which accounted for 19.4 percent of injuries. In a more recent study, it was estimated that for a 700-bed teaching hospital, the annual costs attributable to ADRs is $ 5.6 million, of which $2.8 million is attributable to preventable ADRs.
ADRs occur more frequently in the presence of one or more of the following factors: extremes of age; female gender; multiple medications; diseases of the liver, kidney and heart; past history of ADRs or drug allergy; certain predisposing genetic factors; and, high drug dosage. Further, ADRs may be classified into two general types: Type I and Type II. Type I ADRs can be predicted from the known pharmacology of the drug and frequently may be dose-dependent. Type II ADRs are idiosyncratic and characteristically not dose-dependent.
The authors of this article emphasize the obvious importance of diagnosing and preventing ADRs, yet acknowledge the complexities associated with doing so. They summarize the details of the current status of ADR diagnosis and prevention in their concluding paragraph: "Several positive steps may be initiated by health-care professionals to improve outcomes with respect to ADRs. Publicizing the extensive potential harmful effects of drugs in patients might reduce the tendency to over-dispense and discourage misuse of drugs. Enhancing patient-physician communication and relationships could obviate many preventable errors experienced in pharmacotherapy. The utilization of modern technology in diagnosis, molecular biology, databases, and national and international communication will also be useful. Finally, the implementation and encouragement of programs of continuing health profession education and proper reporting and discovery of ADRs should have a significant impact on this substantial medical problem."
Anesthesia practitioners can and should play a central role in minimizing adverse drug reactions in patients.
ABSTRACT
The focus of this review is to increase the knowledge and raise the awareness of health care professional with respect to adverse drug reactions (ADRs) and to integrate the various elements of this subject in a comprehensive fashion. The review addresses the definitions of ADRs, and their epidemiology, demographics, and economics.
Risk factors for the development of ADRs are defined, their general pathophysiological mechanisms are presented (type 1 or �predictable� and type 2 or �unpredictable�), and their causes and subclassifications are described. A paradigm for diagnosing ADRs is suggested and criteria are presented that assess the causal relationship between drug administration and clinical observations. Laboratory and clinical diagnostic and investigative methods that aid in ADR reporting mechanisms are reviewed. Methods to prevent ADRs and increase compliance in reporting are also discussed.
