Letters to the Editor

(Aust Prescr 2006;29:91-3)

Letters, which may not necessarily be published in full, should be restricted to not more than 250 words. When relevant, comment on the letter is sought from the author. Due to production schedules, it is normally not possible to publish letters received in response to material appearing in a particular issue earlier than the second or third subsequent issue.

Pre-eclampsia

Editor, - I read with interest the article on biochemical tests in pregnancy (Aust Prescr 2006;29:48-52) and wish to comment on the discussion of pre-eclampsia. The author maintains that the diagnosis is based on a triad of hypertension, proteinuria and oedema, yet the Australasian Society for the Study of Hypertension in Pregnancy has issued a consensus statement which asserts otherwise.1 While hypertension is a requirement, proteinuria (as one of a range of possible end organ effects) is not mandatory to make the diagnosis. Oedema is specifically excluded unless its onset is rapid and generalised. This is important to appreciate as severe forms of pre-eclampsia (and indeed eclampsia) can occur in the absence of the 'triad'. Furthermore, 'routine' urinalysis at each visit in low-risk pregnancies has been discontinued in many centres due to its limited value.

Colin Weatherill
Obstetrician
Mount Gambier, SA

Reference

1. Brown MA, Hague WM, Higgins J, Lowe S, Mc Cowan L, Oats J, et al. Australasian Society for the Study of Hypertension in Pregnancy. The detection, investigation and management of hypertension in pregnancy: full consensus statement. Aust N Z J Obstet Gynaecol 2000;40:139-55.

Associate Professor HA Tran, author of the article, comments:

In pre-eclampsia the detection of hypertension is of utmost importance and blood pressure needs to be rigorously controlled. The presence of proteinuria and oedema is less critical but will further assist in arriving at the correct diagnosis. Although eclampsia can occur in the absence of the 'triad', alternative differential neurological diagnoses need to be considered.

While the clinical utility of 'routine' urinalysis may not be as important in the diagnosis of pre-eclampsia, it is sometimes useful in detecting asymptomatic bacteriuria and glycosuria. Bacteriuria confers an increased risk of pyelonephritis and prematurity1, and glycosuria may identify unsuspected diabetes other than gestational diabetes. Interventions for both of these conditions can result in better outcomes.1,2 It is of additional interest that the current British guideline for antenatal care recommends that 'whenever blood pressure is measured in pregnancy a urine sample should be tested at the same time for proteinuria'.3The decision to discontinue this practice in low-risk patients is then probably a function of cost versus benefit.

References

1. Raz R. Asymptomatic bacteriuria - clinical significance and management. Nephrol Dial Transplant 2001;16 (Suppl 6):135-6.

2. Crowther CA, Hiller JE, Moss JR, Mc Phee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005;352:2477-86.

3. Antenatal care: Routine care for the healthy pregnant woman. London: National Collaborating Centre for Women's and Children's Health; 2003. http://www.rcog.org.uk/resources/Public/pdf/Antenatal_Care.pdf [cited 2006 Jul 4]

Deleterious cognitive effects of antimuscarinic drugs

Editor, - I suggest that the article 'Anticholinergic drugs for overactive bladder' (Aust Prescr 2006;29:22-4) gives insufficient prominence to the inevitable occurrence of cognitive impairment from antimuscarinic drugs. There is overwhelming evidence that all antimuscarinic drugs cause cognitive impairment even in healthy people1, and this is frequently clinically significant in older people.2,3,4 Any possibility that a treatment will worsen patients' mental function has profound implications and must be regarded with the utmost seriousness.

The therapeutic margin is narrow, or non-existent, and individual variations in blood concentrations and response mean that in practice it will be difficult to achieve a consistently favourable therapeutic effect. Many other commonly used drugs also have antimuscarinic effects so interactions are likely to be frequent. I suggest the average practitioner has insufficient knowledge of these interactions to successfully avoid them.5

Ken Gillman
Consultant psychiatrist
Pioneer Valley Private Hospital
North Mackay, Qld

References

1. Robbins TW, Semple J, Kumar R, Truman MI, Shorter J, Ferraro A, et al. Effects of scopolamine on delayed-matching-to-sample and paired associates tests of visual memory and learning in human subjects: comparison with diazepam and implications for dementia. Psychopharmacology (Berl) 1997;134:95-106.

2. Ancelin ML, Artero S, Portet F, Dupuy AM, Touchon J, Ritchie K. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ 2006;332:455-9.

3. Lu CJ, Tune LE. Chronic exposure to anticholinergic medications adversely affects the course of Alzheimer disease. Am J Geriatr Psychiatry 2003;11:458-61.

4. Tune LE, Egeli S. Acetylcholine and delirium. Dement Geriatr Cogn Disord 1999;10:342-4.

5. Guay DR. Clinical pharmacokinetics of drugs used to treat urge incontinence. Clin Pharmacokinet 2003;42:1243-85.

Associate Professor KH Moore, one of the authors of the article, comments:

Dr Gillman makes an important point regarding the potential for anticholinergic drugs to induce or exacerbate cognitive impairment, especially in the elderly. However, he paints a rather black picture with very broad strokes so an examination of the evidence is needed.

Reference 1 describes a very precise psychometric analysis of scopolamine administration in 24 people, that showed significant decline in performance on spatial and pattern memory tests. This is hardly 'overwhelming evidence that all antimuscarinic drugs cause cognitive impairment'.

Similarly, references 2 and 3 describe studies with 30 and 16 users of a wide range of anticholinergic drugs. The first study showed a 19% attributable risk of mild cognitive impairment for these drugs. In the second paper, all patients were receiving the cholinesterase inhibitor donepezil for Alzheimer's disease. Not surprisingly, donepezil was less effective for preventing cognitive decline in those on anticholinergic drugs (at two years, but not at one year). Reference 4 is an interesting review article about the role of anticholinergic drugs in delirium but also discusses studies that included small numbers of patients (n = 15-34).

Reference 5 is a detailed review of the pharmacokinetics of a range of bladder-active anticholinergics. It is very informative but does not appear to support the suggestion that they should be avoided.

Nevertheless, our article could have made greater mention of the risks of anticholinergic therapy in exacerbating or precipitating cognitive impairment, especially in the elderly. These drugs should only be given in conjunction with bladder training at the lowest dose possible to achieve reduced frequency, urgency or urge incontinence, and for the shortest duration possible.

Confessions of a biased reader

Editor, - I wonder how many other people share my obsession about checking declarations of conflicts of interest before they read any letter or article?

I note many well-credentialled academics seem very committed to evidence-based medicine when presenting their arguments. For me, all this effort becomes completely neutralised when I realise that they have received sponsorship associated with the very products they are arguing for. Unfortunately, my bias is so compelling that I cannot take their well presented discussion seriously. How many other people suffer from this problem?

Chris Commens
Dermatologist
Pennant Hills, NSW