Serum sodium valproate testing: is it appropriate?

Sodium valproate (SVP) is widely used for treating epilepsy, pain syndromes and psychiatric disturbance. Following its introduction in 1960,1 many studies found that there was a poor correlation between serum SVP concentration and dose. As a result, measurement of serum SVP concentration has been in routine clinical use for over 25 years, with a suggested therapeutic range of 300–700 μmol/L.2

Measurement of a trough level is required, so the blood sample has to be taken at least 8 hours after the most recent dose. This requirement is often not met in busy clinical settings and, even when it is, studies have still found a poor correlation between SVP dose and serum concentration.3-7

Several studies have further suggested that serum SVP concentration bears little relation to clinical effectiveness (eg, seizure control) or to the magnitude of side effects.8,9 In fact, a patient’s dose of SVP can be adjusted on the basis of clinical parameters (ie, effectiveness in controlling symptoms set against magnitude of side effects). Thus, for day-to-day use, measuring serum SVP concentration is unnecessary.2,4,10-13 Current evidence suggests that measuring SVP is not clinically useful except in certain situations such as the assessment of toxicity or compliance7,14,15 or, possibly, in the alteration of dosage for individual patients on polypharmacy.2 In spite of this, the practice of routine measurement of serum SVP concentration is widespread, particularly in emergency departments (EDs), outpatient departments and general practice settings, and many clinicians are unaware of the significance of measuring trough levels. Audits elsewhere16-20 have repeatedly indicated inappropriate use of the test.

The cost of SVP testing is considerable. In 2003, 969 SVP tests were performed at The Canberra Hospital (TCH), costing the health service a total of $19 816.05. (The Medicare Benefits Schedule reimbursement amount was $20.45 in 2003 and $18.45 at the time of our study.) Clearly, if tests are being requested inappropriately, there are significant potential savings to be made by tightening the criteria for ordering tests.

We undertook a retrospective audit of requests for serum SVP concentration estimation on inpatients and ED patients at TCH. Our main aim was to assess the magnitude of inappropriate serum SVP concentration testing.

Using the ACT Pathology database, we retrospectively examined all requests for serum SVP concentration measurement for inpatients and ED patients over the 3-month period May–July 2005. If multiple tests were performed on an individual patient, the initial test in the list was retained but the remainder were discarded after counting the total number of repeats. All non-duplicated tests were then entered into a database for further analysis. Information about why and when each test was performed was extracted from case notes. All data collected were de-identified. Our study was approved by the TCH Deputy General Manager and the Medical Records Committee.

A total of 211 index tests were retrieved. Of these, 116 (55%) were duplicate tests and were therefore not investigated further. For the remaining 95 tests, 89 sets of notes (94%) could be retrieved and analysed.

Our study demonstrated that only 6%–15% of requests for serum SVP level estimation were appropriate when assessed against evidence-based guidelines, and only 29% of samples met the stated criteria for validity. Using the simple criterion of documentation of the result in the patient’s notes, 57% of tests had an effect on patient management, but most of these tests would have been either inappropriate or invalid.

The high proportion of inappropriate requests almost certainly reflects a lack of awareness among clinicians of the evidence-based indications for requesting serum SVP level testing. Our results also suggest that many clinicians are unaware of the need for precise timing of the blood sample to obtain a valid measurement. Such errors are a source of substantial unnecessary cost to the health care system.

At a rate of $18.45 per test, the cost of performing all 211 tests requested over the 3-month period was $3893, translating to an estimated annual cost of $15 572. If only 15% of those tests were appropriate, the unnecessary expenditure for this test on the population sampled at TCH amounts to about $13 236 a year.

There is no reason to suggest that the practices followed in Canberra differ significantly from those in any other part of Australia. Extrapolating to all tests performed in Australia, a potential saving to the health service of many tens of thousands of dollars would result if inappropriate SVP tests could be avoided.

One way to overcome the inappropriate or invalid use of the SVP test would be to have laboratory staff “police” the test and only perform it if the request form indicated that the reason for the test was appropriate and that the sample had been collected in a valid manner. In this context, it is noteworthy that only 44% of forms analysed in our study would have permitted this.

In conclusion, our study shows that most requests for serum SVP concentration measurement are inappropriate when judged against evidence-based criteria. Our suspicion is that similar results would be found if laboratory tests for serum concentrations of many other drugs were examined. Better education of the clinicians who request these tests as to how to manage patients without the need for such measurements, and what the evidence-based appropriate indications actually are, would undoubtedly result in major savings to the health service. Such an education program is currently being set up at TCH, and the effects of this program will be audited in due course.

3 Serum sodium valproate (SVP) concentration as a function of daily dose in 89 separate patients*

* The “therapeutic range” for SVP measurements at The Canberra Hospital (350–700 μmol/L) is represented by horizontal lines on the graph.