1113 SODIUM CONTENT OF SOME
SODIUM CONTENT OF INJECTABLE &bgr;-LACTAM ANTIBIOTICS D. N. BARON
J. M. T. HAMILTON-MILLER W. BRUMFITT
Departments of Chemical Pathology and Medical Microbiology, Royal Free Hospital and School of Medicine, London
Many users of antibiotics are unaware of their ionic content. The ionic content is a particularly important factor for injectable &bgr;-lactam compounds in patients on a restricted sodium intake. A table of the sodium content of commonly prescribed &bgr;-lactam compounds is provided.
INJECTABLE antibiotics, unlike most drugs, are usually administered in gram amounts; hence the accompanying ionic load may be considerable. There is a tendency for very large amounts of these drugs to be used in immunocompromised patients, whose renal function may be unstable. Difficulties can arise when there are pre-existing disorders of electrolyte balance. Furthermore, in the many other patients whose sodium intake should be restricted, the sodium content of the antibiotic should not be ignored. Restriction and regulation of all sodium intake is of great importance when treating patients with liver disease, especially if they have ascites, and in some patients with cardiac or renal failure. Therefore it is important that those who prescribe antibiotics remain fully aware of the fact that most injectable antibiotics contain substantial amounts of sodium, although the actual amount varies from one to another. In the process of compiling a list of the ionic content of antimicrobial agents we have been surprised and somewhat alarmed to discover that the sodium content of antibiotics is not mentioned at all in MIMS,1 and the British National Formulary2 merely discusses the problem in general terms and gives no details. When information is available, it is scattered widely among various sources,3-6 and details on the same preparation may vary from reference to reference. To collect and compare all the information on the subject is time-consuming and frustrating. We thought it helpful to present a summary of our findings in respect of injectable 3-lactam antibiotics, for
1 Ingram TTS. Intermittent hearing
loss in young children. Devel Med Child Neurol
1976, 18: 239-41. 2 Brooks DN The use of the electro-acoustic impedance bridge in the assessment of middle ear function Int Audiol 1969, 8: 563-69 3 Malcomson KG Section of otology Proc R Soc Med 1969; 62: 463-64. 4 Paradise JL Pediatrician’s view of middle ear effusions: more questions than answers.
Ann Otol Rhinol Laryngol 1976; 25 5
Pediatr 1974; 13: 919-21 6 Eagles EL, Wishik SM, Doerfler LG. Hearing sensitivity and ear disease
prospective study. Laryngoscope suppl 1967, 1-274 7 Renvall U, Liden G, Jungert S, Nilsson E. Impedance audiometry as screening method in school children. Scand Audiol 1973; 2: 133-37. 8 Paradise JL. Testing for otitis media: diagnosis ex-machina. N Engl J Med 1977; 296: 445-48
PA, Pelton SI, Finkelstein J. Tympanometry in the diagnosis of middle ear effusion. N Engl JMed 1977; 296: 412-17. 10 Holborow CA Deafness associated with cleft palate J Laryngol Otol 1962; 76: 762-73. 11 Fulton R, Lloyd L Hearing impairment in a population of children with Down’s syndrome. Am J Ment Defic 1968; 73: 298-302. 12 Jarvis JF. Audiologic status of children with cleft palate: a review of 350 cases.
facilitate solution. Old formulation.
which the difficulties due to the are greatest since they may be 40 g/day.
accompanying sodium load given in amounts of up to
We have taken the basic information (February, 1984) from several sources of reference,3-6 as well as from individual product handbooks and data sheets. It has been augmented when necessary: for instance, some manufacturers give sodium content in millimoles, while others give it only in milligrams. In addition, we have calculated the approximate daily load of sodium when the maximum recommended dose is given to a patient. The sodium content of each antibiotic was calculated from the molecular mass and the stated formulation, and the sodium load calculated assuming that each vial contains the exact amount of antibiotic preparation stated. RESULTS AND DISCUSSION
The table shows the advantage of prescribing drugs in substance units (moles) rather than mass units (grams). With
Audiology 1976, 15: 242-48 13. Task Force- Recommendations for the Task
formal presentations and discussions at a symposium on impedance screening for children held at Vanderbilt University School of Medicine Tennessee June 20-22, 14.
Howie VM, Ploussard JH. Treatment of serous otitis media with ventilatory tubes
*Monosodium derivatives except for carbenicillin, ceftnaxone, latamoxef, and ticarcillin, which are disodium derivatives. tWith added sodium compound as
1977). Beery J, Bluestone CD, Cantekin EI Otologic history, audiometry and tympanometry as a case finding procedure for school screening. Laryngoscope 1975; 85: 1976-85. Renvall U, Liden G, Jungert S, Nilsson E Impedance audiometry in the detection of
secretory otitis media. Scan Audiol 1975; 4: 119-24. 16. Ferrer HP Use of impedance audiometry in school children Publ Hlth 1974; 88: 153-63 17. Harker L, Van-Wagoner R. Application of impedance audiometry as a screening instrument Acta Otolaryngol 1974, 77: 198-210 18. Kessner DM, Snow CK, Singer J. Assessment of medical care for children, vol. 3. Washington DC, Institute of Medicine, National Academy of Science, 1974 19. Pelton SI, Shurin PA, Klein JO Persistence of middle ear effusion after acute otitis media. Pediatr Res 1977; 11: 504-08 20. Doyle WJ A functional-anatomic description of eustachian tube function in four ethnic populations: an osteologic study. University of Pittsburgh, thesis, 1977 21 Shurin PA, Pelton SI, Donner A, Klein JO. Persistence of middle ear effusion after acute otitis media in children. N Engl J Med 1979; 300: 1121-23.
monosodium salts the daily load of sodium is numerically the same as the daily dose of antibiotic when both are expressed in millimoles, unless extra sodium salts are added. Some cephalosporins for injection contain no sodium ions; cephaloridine and ceftazidime are betaines, and cephradine in its latest formulation is in the form of the free acid buffered with L-arginine. However, it should be noted that sodium carbonate is added to some cephalosporins (ceftazidime, cephamandole, and the old formulation of cephradine) to prepare the injection. Thus, the only injectable forms of cephalosporins which contain no sodium ions are cephaloridine and the new formulation of cephradine. The figures we have derived by calculating the sodium content of antibiotics from first principles do not always agree with the manufacturers’ figures; this is a matter for concern. We do not know whether these discrepancies are due to deliberate overfilling of vials, to the presence of compounds other than antibiotic, or to other factors. Ions other than sodium may be present in antimicrobial compounds. The potassium salt of benzylpenicillin is also available for injection, with a possible daily potassium load of 56 mmol, though this is not at present used in the UK. Antibiotics taken by mouth are not likely to lead to ionic overload, because generally dosages are much smaller than for antibiotics given parenterally. However, two compounds are taken orally in sufficient amounts to be of importance in this context. Sodium para-aminosalicylate dihydrate (also no
Medical Education WHAT PRICE THE MASTERSHIP OF SURGERY? K. G. BURNAND St
A. E. YOUNG
London SE1 7EH
APPLICANTS for consultant posts in general surgery are expected to possess a higher degree and even aspiring senior registrars may find they need a mastership of surgery to lift them clear of the fierce competition. The mastership should, ideally, be taken after 12-18 months of reflection and critical appraisal. The present form of the examination expects this reflective period to be combined with original and constructive scientific work designed to test a surgical hypothesis. The habits of a research post are alien to the practical young surgeon, used to a fixed timetable of clinical work, and the post should therefore be stimulating and refreshing. Sadly, this is not always so; we explore here why the time spent on mastership may be both unhappy and
unproductive. We strongly suspect that most surgeons in training entering research are driven by a wish to advance their career prospects rather than the frontiers of knowledge. This is not a reason for not pursuing a mastership, but it must colour the candidate’s attitude
the time in research. THE
Few, if any, would-be researchers have the ability to select a topic and provide facilities and funding to achieve a degree an approach would not, in any case, be supported by the universities, which recommend close supervision by established’ academic staff to prevent submission of substandard work. Pragmatism demands the latter approach, but it does little to stimulate individual thought when it is most necessary-at the beginning of the project. Too often it leads to the plaintive request from a
marketed in the UK) contains 10.9% by weight of sodium and is given in doses of 12 g (63 mmol) per day, making a sodium load of 63 mmol per day. Neomycin (sulphate) is given orally in such conditions as hepatic coma in amounts of up to 6 g (about 8’ 5 mmol) per day: as it contains about 30% by weight of sulphate, the daily sulphate load is about 18 mmol. The purpose of this article is to draw attention to the risk of causing sodium overload when giving certain intravenous antimicrobial agents. This danger has increased with the practice of giving very large doses of antibiotic to certain groups of patients, and smaller doses may be critical where renal function is diminished.
We thank Dr C. W. H. Havard for constructive and Miss J. Lytle for typing the manuscript.
of the manuscript,
Correspondence should be addressed to J. M. T. H-M., Department of Medical Microbiology, Royal Free Hospital, Pond Street, London NW3 2QG. REFERENCES 1. MIMS:
Monthly index of medical specialities. London: Medical Publications (published monthly). 2. British National Formulary, no 6. London: British Medical Association and Pharmaceutical Society of Great Britain, 1983. 3. ABPI Data Sheet Compendium, 1983-84. London: Datapharm Publications 4. British Pharmacopoeia, 1980 (and Addenda 1982 and 1983). London HM Stationery Office 5
ed. Martindale the Extra Pharmacopoeia, 28th ed. London: Pharmaceutical Press, 1982. 6. Windholz M, ed. Merck Index, 10th ed. Rahway Merck & Co, 1983.
registrar, "Have you got a research project for me?". In practice, most surgeons embarking on research for a higher degree join academic departments, where they work under close supervision on preordained projects designed to provide suitable work for a thesis. Obtaining finance for salary, equipment, and running expenses has become increasingly difficult. Very little research money is available from the National Health Service, and university lecturer positions are few and highly sought after. The large national research bodies, such as the Medical Research Council and the Imperial Cancer Research Fund, tend to favour large pre-existing research programmes within established academic departments. A draft protocol of the proposed research must be submitted for expert appraisal and the candidate must then attend an interview for detailed questioning on the aims and proposed methods of study. Many questions asked at these interviews cannot be adequately answered if the research is truly original. For example, one of us was asked whether a particular investigative technique was going to work; he had to reply that he did not know, since testing the technique was an integral part of the research. Success may depend more on the composition of the grant committee and the research record of the supervisor than on the value and originality of the proposed research or the quality of the applicant. Smaller projects must now be supported by hospital research funds, where they exist, and increasingly by drug or equipment manufacturers; the latter source has seveal drawbacks. The sponsored research must be designed to show the efficacy of the sponsoring company’s products, since commercial sources are rarely philanthropic and demand return for outlay. Although money from rich companies is sometimes used to pay for personnel only partly involved in the relevant research, commercial organisations are now demanding more for their money, so more time will have to be spent on commercial rather than pure research. "Negative" results may be considered undesirable, and their publication may be discouraged or