Numerous factors contribute to the medication errors that kill up to 98,000 patients each year. Unnecessarily high dosages can result in increased side effects with only a small therapeutic benefit, especially in elderly patients. Lack of patient information-such as a history of allergies or adverse drug reactions-is another cause of error and injury. Communication failures include the use of ambiguous abbreviations, misinterpretation of verbal orders, and lack of timely response to a patient's medication-related symptoms. Dosing errors are common in children because of variability in dosage expressions in drug references. Remedies for prescribing errors are described in detail here.
Medication errors are a significant cause of injury and expense. An Institute of Medicine report estimated that between 44,000 and 98,000 persons die in US hospitals annually as a result of these errors.1 This report fueled dramatic interest in health care reform, including measures to reduce medication errors.2
A medication error is a preventable event that could result in inappropriate therapy or harm to a patient.3 Although errors occur frequently during various steps in the drug treatment process (ie, prescribing, interpreting, dispensing, and administering), they infrequently lead to harm.4 As a result, investigation has focused on errors that result in harm.
An adverse drug event (ADE) is an injury from a drug-related intervention.3,5 ADEs include nonpreventable side effects of medications, such as bradycardia associated with β-blocker use. Ameliorable effects are those in which severity or duration can be significantly reduced with prompt recognition and appropriate management.6 Preventable ADEs are those that can be avoided entirely-for example, by awareness that a patient is allergic to a specific antibiotic. Ameliorable and preventable ADEs are examples of medication errors associated with harm.
A recent ambulatory care studyfound that 25% of 661 respondents reported an ADE.6 Thirty-nine percent of these events were ameliorable or preventable; of this number, 6% were serious.6 A study of inpatients found that ADEs occurred at a rate of 6.5 per 100 admissions. Forty-two percent were either life-threatening or serious; nearly half of these events were judged preventable.5 In both of these studies, most preventable events occurred in the prescribing stage of the drug treatment process.
Numerous factors contribute to medication errors. Here we focus on preventable ADEs that occur in the drug-prescribing stage, and we describe strategies that may avert miscalculation, miscommunication-and mismanagement.
LACK OF DRUG KNOWLEDGE
Errors often arise from a lack of knowledge about drugs, including indications and contraindications, appropriate doses, maximum dosages, routes, and drug-drug interactions.
Indication errors. These include underuse, overuse, and misuse.7,8Underuse is the failure to provide a medical intervention when it is likely to produce a favorable outcome.8 An example is the failure to prescribe an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker to prevent progression of diabetic nephropathy in a patient with diabetes and microalbuminuria.
Overuse occurs with unnecessary treatment: for example, when a broad-spectrum antibiotic (such as levofloxacin) is prescribed for uncomplicated bronchitis or pharyngitis of probably viral origin in a patient with no history of smoking, recurrent infection, or immunosuppression. The main bacterial cause of pharyngitis is group A β-hemolytic streptococci, which remain susceptible to penicillin or erythromycin.9 Prescriptions for more than half of diagnosed cases of pharyngitis are likely unnecessary; however, the overprescribing of fluoroquinolones, which increases resistance to this class of antibiotics, continues unabated.9
A more subtle form of overuse occurs when unnecessary treatment is initiated for an unrecognized side effect resulting from current drug therapy. For example:
•Antihypertensive agents are frequently prescribed for patients whose high blood pressure is a result of NSAID use.
•Gout medications are initiated to treat mild hyperuricemia from thiazide diuretics.
•Parkinsonian symptoms resulting from metoclopramide are overtreated with levodopa.10
Misuse refers to actions that result in preventable complications. An example is prescribing amoxicillin for a patient with a history of anaphylaxis to penicillin.8 Misuse can occur when a contraindication is unrecognized, as when metformin is prescribed for women whose serum creatinine level exceeds 1.4 mg/dL (1.5 mg/dL for men). The risk of lactic acidosis increases dramatically, and death occasionally ensues.11
Dosing errors. These can occur in elderly patients at the initiation of therapy. For example, hydrochlorothiazide is sometimes started at a dosage of 25 or 50 mg/d, even though 6.25 mg/d is often effective.10,11 When therapy is not gradually titrated upward and monitored, ADEs-such as orthostatic hypotension-are more likely to occur.7,11 Unnecessarily high dosages can result in increased side effects with only a small therapeutic benefit. When amlodipine is prescribed at 20 mg/d instead of the maximum of 10 mg/d, a small benefit in blood pressure control is offset by a substantially increased risk of peripheral edema.11
Drug-drug interactions. These can have serious consequences. During the winter, patients frequently self-treat influenza and cold symptoms. They may use several over-the-counter (OTC) agents that contain the same compounds: symptoms may worsen or toxicity may develop as a result.
Antibiotics are sometimes prescribed for patients with influenza or cold symptoms without a careful review of the patient's other medications. For example, quinolones such as ciprofloxacin and levofloxacin can inhibit warfarin metabolism and increase the anticoagulation effect and the risk of bleeding.11 The same effect can occur with metronidazole, azithromycin, and especially trimethoprim-sulfamethoxazole.11 Cautious monitoring is always prudent when prescribing medications for patients taking warfarin.
Drug-drug interactions can be reduced by periodically updating your patients' records and reviewing them for self-care therapies.
LACK OF PATIENT INFORMATION
Inadequate records and incorrect reporting of allergies and drug reactions are significant sources of prescribing errors.
Inadequate records. In one study, lack of information about hospitalized patients was the second leading cause of prescribing errors that resulted in ADEs.12 Such errors frequently occur in the ambulatory care setting as well. In another report, discrepancies between medications indicated in outpatient medical records and those actually taken by patients occurred in 76% of cases.13 Another study discovered the potential for ADEs in 50% of the discrepancies.14
Preventable errors and ADEs are particularly evident during transitions of care, as when patients are hospitalized and clinicians base treatment decisions on incomplete outpatient records. In patients hospitalized for cardiovascular disorders, most prescribing errors have been attributed to this discontinuity.15 Likewise, increased rates of rehospitalization have been associated with incomplete inpatient records.16
Special care is warranted with documentation of cardiovascular medications. A study examining the medical records of elderly outpatients found that this class of agents was most frequently associated with ADEs.17 Although these are the most commonly prescribed medications, they are potentially dangerous, and their use must be documented.
Maintain and update a list of drugs for each of your patients. Periodically ask patients to bring their medications (including vitamins, supplements, and alternative medicines) with them to office visits.13 Although this chore may be cumbersome, it ultimately saves time, reduces confusion, and builds trust. This is especially important for patients at greatest risk for medication errors-those who have chronic and comorbid conditions.13
Another option is to call the pharmacy where the patient has prescriptions filled. Research has shown that-questions of adherence aside-the outpatient prescription profile almost identically reflects what medications a patient is taking.18
Outpatient medical records also frequently lack documentation of ADEs. An ambulatory care study found that patients reported about 3 times as many ADEs as trained chart reviewers.6
Diagnosing an ADE is often difficult, because every drug has a plethora of possible side effects. Formulating associations between ADEs and drugs in a patient's regimen can take time. Common side effects to watch for are faintness, fatigue, nausea, vomiting, changes in bowel habits, headache, mood changes, sleep disturbances, and maculopapular rashes.
Undocumented allergies. The risk of an undocumented ADE is that it can be repeated and then become an error. Antibiotics were associated with nearly 40% of the prescribing errors in one study, in part because of undocumented drug allergies.19 About 10% to 13% of prescribing errors involve ordering drugs for patients with known allergies to those drugs (including potentially cross-reactive agents).19 Penicillin, ampicillin, amoxicillin, and piperacillin commonly cross-react.11
Conversely, adverse reactions to antibiotics and opioid analgesics, such as nausea or constipation, are often labeled in medical records as allergies.20,21 A study of records at a university hospital and clinic found that drug allergies reported as "rashes" attributed to -lactam and sulfa antibiotics were "true allergies" in about 80% of the cases; for opioid analgesics the rate was 30%.21 A substantial number of inaccurate allergy reports were also observed for psychotropics, cardiovascular agents, and NSAIDs. Because a known allergy is a contraindication to prescribing the allergenic drug and cross-reactive drugs in the same class, this potential error unnecessarily limits therapeutic options and can result in the use of medications that are more toxic, less effective, and more costly.22
Allergy information in a chart signals the need for further investigation. Always confirm the allergy history yourself with a patient before prescribing. Ask patients to describe their reactions-including the circumstances surrounding the ADE and the symptoms of the reaction-before excluding therapeutic options.
Failed communication--associated with poor handwriting, misinterpreted verbal orders, and the use of abbreviations or misplaced decimals--is an important source of prescribing errors.
The Joint Commission for the Accreditation of Healthcare Organizations requires hospitals to develop a list of abbreviations that are unacceptable for use on medication orders.23Tables 1, 2, and 3 list abbreviations and punctuation that have resulted in medication errors. Death or serious injury has resulted from misinterpretations of each of the abbreviations found in these tables. This includes the recent death of a child from a prescribing error that involved a trailing decimal point.23
Office-based clinicians frequently call orders in to pharmacies, and errors in transcribing verbal instructions are common. Always require the person taking your order to read it back to you and to spell out the names of the drugs you have ordered.
Pharmacies can misinterpret appropriately written prescriptions in ways prescribers might never anticipate. Recently, confusion between opium tincture (10 mg/mL of morphine) and camphorated tincture of opium (0.4 mg/mL of morphine) (paregoric) resulted in 2 deaths from morphine overdoses.24 Although pharmacists were responsible for both of these errors, you can minimize the risk of this occurrence by writing "paregoric" instead of "camphorated tincture of opium," and writing doses in weight units (eg, 2 mg) instead of volume units (eg, 1 tsp).
Clinician-patient communication. In an ambulatory care study, 63% of ameliorable ADEs occurred when physicians failed to respond to patients' medication-related symptoms.6 Strategies to improve patient-physician communication are essential; they include discussing the potential side effects of newly prescribed medications, using open-ended questions about ADEs during office visits, and providing patients with educational materials. Some physicians use e-mail to communicate with their patients.
An independent risk factor for ADEs in outpatients is the failure of the clinician to explain potential adverse effects before treatment is initiated.25 In one study, 18% of preventable ADEs in ambulatory older persons were attributed to inadequate patient education.17 Some clinicians are reluctant to discuss potential ADEs because of concern that such discussions may compromise adherence; however, evidence suggests that such concerns are unwarranted.26 Pretreatment counseling helps patients recognize and appropriately attribute ADEs to the drug they are taking and to discuss them with you. Patients often interpret side effects as poor care; effective communication will help neutralize this response.25
Often patients do not know how to articulate their concerns. Open-ended questions--such as "How are you feeling about your medicines?"--prompt patients to relate any problems they might be having. Follow-up contact soon after a new therapy is initiated helps identify potential problems early.
ERRORS IN SPECIAL POPULATIONS
Children. Drugs are commonly dosed for children based on body weight. Variability in dosage expressions-such as "100 mg/kg/d in 4 divided doses" versus "100 mg/kg per day divided every 6 hours" or "25 mg/kg qid"-can cause confusion or error.27
Remedies include prescriber education, standardization of drug reference reporting (including tables), and computerized order entry.27
Elderly persons. Increasingly, clinicians care for older patients with comorbid conditions, each of which might require several medications.7 Therapy-whether prescribed by a physician or self-prescribed by a patient-often includes combinations of prescription, OTC, and alternative products. Approximately two thirds of persons aged 65 years or older use prescription and nonprescription drugs. On average, these patients take 4 or 5 prescription medications and 2 OTC products concurrently.7 Make a point to ask older patients about the OTC and alternative products they are taking; patients often do not consider these to be medications.
Communicating with older patients poses special difficulties. Visual or hearing impairments, which patients sometimes deny, can result in misunderstandings. In a study of older outpatients, errors in patient adherence accounted for 21% of preventable errors, such as taking the wrong dose.17 Give legible written instructions and specify times when medications are to be taken. You may wish to recommend pillboxes.
Patients may feel uncomfortable if a clinician speaks loudly or slowly to them. Ask your hearing and visually impaired patients how best to communicate with them, or use pictograms to emphasize important points. Ask them to repeat back important instructions. A higher frequency of clinic visits results in improved adherence and decreased misunderstanding.26
Monitoring errors. In one study, 61% of preventable prescribing errors in older outpatients occurred in the monitoring stage.17 These include failure to respond to signs and symptoms of drug toxicity and inadequate laboratory monitoring of drug therapies. A frequent ameliorable ADE is sexual dysfunction associated with selective serotonin reuptake inhibitors (SSRIs). Patients did not tell providers of the side effects; or, when they did, a different SSRI was prescribed.6 However, all of the SSRIs are associated with decreased libido in 1% to 11% of patients.11 Cardiovascular medications can also cause side effects involving sexual dysfunction. Ask patients specifically about these effects. If they occur, switch to a different class of medications. However, if the therapy is successful, a joint decision can be made not to interrupt the therapy. In many cases, temporary sexual dysfunction can be reversed with a medication such as sildenafil.
In an ambulatory care study, the rates of ADEs largely reflected the drugs' prevalence of use-with the exception of anticoagulants, which were associated with a disproportionately high rate of events.6 Continuous, careful warfarin monitoring is often difficult for individual clinicians. A study that compared bleeding and thromboembolic events in anticoagulation clinics with those that occurred during standard care found significantly fewer events in the clinics, which were also more cost-effective.28
Declining renal function is an important consideration in prescribing for elderly patients. For example, digoxin toxicity can occur with even small decreases in renal function.11 One study described the failure to respond to signs and symptoms of digoxin toxicity-nausea, vomiting, and anorexia-as a common preventable error.17 Regular evaluation of the renal function of patients taking digoxinis essential.
A number of organizations have developed recommendations to reduce prescribing errors (Box).2 Computerized physician order entry with clinical decision support systems has helped improve drug selection, screening for drug interactions, dosing calculations and scheduling, and integration of laboratory results.29
Many organizations recommend that clinicians have point-of-care drug information available. Personal digital assistants are light, hold copious amounts of information, and are updated more frequently than print references. Programs such as ePocrates Pro, Lexicomp, and electronic versions of Tarascon's Pharmacopeia are readily available and easy to use.
Another frequent recommendation is that the role of pharmacists be expanded from passive order entry to active contact with clinicians. Pharmacists can bring additional knowledge and expertise to bear in ambiguous situations. Clinical pharmacists in outpatient clinics can provide evidence-based information about new drugs, perform medication use studies, evaluate the overall performance of the clinic, monitor patients at risk for ADEs, and provide point-of-care support to help clinicians treat their patients most effectively.
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