SIDE-EFFECTS OF EPIDURAL MORPHINE

203 in combination with the administration of natriuretic drugs, reduces blood pressure. Thiazides, which effect renal sodium loss, also relax the peripheral arteriolar smooth muscle, and, though the reason for this action is not known, the suggestion that changes in the fluid and ionic content of the blood vessel wall may be the mode of action is reasonable. Severe sodium restriction is not practical but the combination of an effective oral diuretic and mild salt limitation (80-150 mmol) is a practical approach to volume contraction and lowered blood pressure. In addition, the antihypertensive effect of the thiazides may be augmented by moderate salt restriction. Thus, current evidence supports the suggestion that patients with hypertension will benefit from the sparse use of salt. This objective would be achieved more easily if the approximate salt content of commercially available food was given on the label. Widespread reduction in the salt content of food is not envisaged, but the amount of salt in each food should be stated

plainly. Provident

Hospital,

Baltimore, Maryland 21215, U.S.A.

JOSEPH

M. MILLER

HYPERTENSION IN THE OVER-60s

SIR,-I liked the general approach of your June 28 editorial but wonder about your comment which implies that the diuretics and beta blockers are without postural effects. I certainly see a significant number of people with profound hypotension who are taking diuretics. Williamson and his colleagues, in their study of about 2000 consecutive admissions to geriatric departments, found that diuretics were the greatest single cause of adverse reactions and that 8% of people taking diuretics at the time of their admission demonstrated adverse reactions to them.l I accept that the diuretics were probably often used for heart-failure or conditions that look like it, but are you prepared to stick to your statement that diuretics when used in the treatment of hypertension are without postural effects? London Hospital, London E1 4DG

C. REISNER

SIR Your editorial asks for a further trial, using betaadrenergic antagonists, in addition to that mounted by the European Working Party on High Blood Pressure in the Elderly. Such a trial is in progress, and is a multicentre study in British general practices, in patients of the age-range 60-79, using atenolol and bendrofluazide. Patients with blood pressures over 170 mm Hg systolic or 105 mm Hg diastolic (phase 5) on three readings are randomised into treatment and control groups. The patients are selected on the basis of a total screening of the elderly in the practices and the incidence of cardiovascular end points and total mortality is being recorded in both the treatment and control groups and in patients with "normal" blood pressures. The trial aims to include 600 patients in the hypertensive group. So far, 350 have been recruited, with an adherence rate to the protocol of 85%, good tolerance of the drug regimen, and a mean reduction in blood pressure of 27 mm Hg systolic and 13 mm Hg diastolic in the treatment group compared with the controls. Any general practices interested in joining this study should write to me. The W aterhouse,

Bollington, near Macclesfield, Cheshire SK10 5JL

1. W illiamson J, Chopin elderly A multicentre

JOHN R. COOPE, Coordinator, General Practice Study of Hypertension in the Elderly

JM. Adverse reactions to prescribed drugs investigation. Age Aging 1980; 9: 73.

in the

SIDE-EFFECTS OF EPIDURAL MORPHINE

SIR,-Since the first reports by Yaksh’ and Wang,2 the

use

epidural and intrathecal opiates for pain relief has spread rapidly.3-= We would like to report on our experience in 1200 patients of the side-effects of epidural morphine chloride (2 mg in 10 ml of normal saline) for postoperative pain relief. In the first 242 patients a commercial preparation containing sodiumpyrosulphite 0-1mg and sodium-EDTA 0.1mg per 10 mg morphine chloride was used. The remaining 958 patients were treated with a preservative-free, filtered solution. The side-effects regarded as related to epidural morphine of

were:

No. 204

Side-effect Nausea or vomiting Blood pressure drop

(20

Hg) Itching (first 242 patients) Itching (next 958 patients) Urinary retention Respiratory depression

(17’1c)

mm

24 36 9 181 1

(2%) (15%) (1%) 15%)

The frequency of nausea and vomiting was considerably lower after epidural morphine (17%) than in a control group given 2 mg morphine chloride in 10 ml normal saline intravenously (57%). Also a fall in blood pressure of 20 mm Hg or more was considerably less common in the epidural group (2%) than in the controls (14%). The mechanism behind the blood pressure drop after epidural morphine seemed to be a direct intravenous injection of morphine through the vertebral venous plexus, because blood could be aspirated through the epidural catheter directly after the infusion in most of these patients. In the remaining patients rapid systemic absorption through the venous plexus is the likely explanation. An embarrassing side-effect was sustained itching. It was usually segmental, within the limit of the spread of the solution, but in some patients itching was widespread and diffuse, frequently located to the neck and head. When morphine chloride with preservatives was discontinued, the frequency of itching dropped (see table). Itching was not affected by antihistamines, and was probably caused by the preservatives rather than by histamine release. Urinary retention was recorded in 15% of the patients, 70% of whom were men. This might be a local anxsthetic effect. The frequency did not decrease with preservative-free solution. 1 patient was found in the recovery room with a respiratory depression after her second epidural infusion of 2 mg morphine in 10 ml of normal saline in 15 h. Severe respiratory depression has previously been reported in close association with epidural infusion of high doses of pethidine.6 This patient had undergone a laparotomy the day before and had good pain relief for 10 h without side-effects after her first epidural morphine injection. 4 h after the second infusion of morphine she was found almost unresponsive with a respiratory rate of 9/min and pin-

point pupils. She was given 0.2 mg naloxone i.v. and responded immediately. The respiratory rate increased to 20/min and her pupils became normal in size. The pain relief was, however, still effective. 20 min later her respiratory rate was down to 10/min and she was somnolent. Another 0-2 mg naloxone induced a rise in respiratory rate to 18/min and mental alertness. The patient was then stable and pain free for another 6 h. She then requested analgesics and was given another infusion of 2 mg morphine epidurally. No side effects were observed during the next 24 h at which time the patient was discharged from the unit. Rostral flow of cerebrospinal fluid containing TL, Rudy TA. Analgesia mediated by a direct spinal action of narScience 1976; 192: 1357. 2. Wang JK. Analgesic effect of intrathecally administered morphine. Regional Anesth 1977; 2: 8. 3. Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology 1979; 50: 149. 4. Behar M, Olshwang D, Magora F, Davidson JT. Epidural morphine in the treatment of pain. Lancet 1979; i: 527. 5. Cousins MJ, Mather LE, Glynn CJ, Wilson PR, Graham JR. Selective spinal analgesia. Lancer 1979; i: 1141. 6. Scott DB, McClure J. Selective epidural analgesia. Lancet 1979; i: 1410. 1. Yaksh

cotics.

,

204 unbound morphine has been suggested this unexpected, but rare, complication.’

as a

probable mechanism for

We suggest the use of preservative-free solutions of epidural to avoid itching. Furthermore, some commercially available solutions contain substances which may be neurotoxic.7,8 Even though the incidence of respiratory depression is very low patients must be closely monitored because respiratory depression may occur long after the epidural infusion.

morphine

Department of Anæsthesia and Critical Care Medicine, University of Umeå, Regionsjukhuset, 901 85 Umeå, Sweden

SEBASTIAN REIZ MATS WESTBERG

PRURITUS AFTER EPIDURAL MORPHINE use of narcotics in the epidural space is increasis generally without complication. McQuay et al.’ the problem of severe pruritus which usually began 30 min after the onset of analgesia. They did not say which analgesics were involved. I would like to report details of severe pruritus after epidural morphine. A 40-year-old man who smoked 30 cigarettes a day was admitted following a fall in which he sustained fractures of the left 9th, 10th, and llth ribs. Sputum retention developed due to inadequate cough and severe pain. A catheter was introduced into the epidural space at the interspace of the llth and 12th thoracic vertebrx and 12 ml saline containing 5 mg morphine sulphate (bacteriostat-free but containing 1 mg/ml sodium metabisulphite) was given. This provided good pain relief. However, 3 h after the injection the patient complained of a very itchy faint red rash from his nipples to his knees. Although pain was relieved the patient was distressed by the itch and was unable to sleep at all that night. The next morning the itch disappeared as the pain from the fractured ribs returned; the patient was most reluctant to have a repeat dose of morphine and the pain was managed by intermittent intramuscular pethidine. The frequency of this complication has not yet been determined but when it does occur it is a disabling complication and one which deserves further study.

SIR The

ing and reported

Department of Anæsthetics, Westmead Centre, Westmead, Sydney, N.S.W., Australia

P. HALES

mg/l;1 however, 600 mg daily produces a fsecal concentration of 351±172 mg/1, well above the minimum inhibitory concentration for C. difficile (16 mg/1). The costs of 5 days courses of 2 g and 600 mg vancomycin

daily are &110

and [33, respec-

tively. Relapses after discontinuation of vancomycin have been recordedeven with courses up to 17 days long at 2 g vancomycin per day. These relapses all responded to a further course of vancomycin. There is no evidence to suggest that an initial course of more than 5 days’ length would significantly decrease the relapse rate. Although C. difficile is sensitive to metronidazole, this antibiotic, when given orally, is rapidly absorbed in the small intestine and does not reach therapeutic concentrations in the colon.4 Metronidazole is thus unlikely to be of any help in the treatment of PMC. We suggest that, PMC is most efficiently and economically treated by a 5 day course of 125 mg vancomycin 6-hourly. Careful follow-up must be maintained for a limited period as a small number of patients may relapse; relapses respond to a further course of vancomycin.

Department of Surgery, Westminster Hospital,

A. H. V. SCHAPIRA P. H. P. DYSON

London SW1

PRIMARY HYPERPARATHYROIDISM

SIR The report from Birmingham in your issue of June 21 confirms all features of primary hyperparathyroidism found in our study.5 The striking similarity of our nominal annual incidence rates (25 vs. 27-7 cases per 100 000 population) should greatly increase confidence in the validity of these results. Dr Mundy and his colleagues comment that our data do not indicate whether or not primary hyperparathyroidism increases in frequency past the age of 60. We did not report incidence rates by decade because the numbers were too small. However, when all cases are pooled, the incidence rates for both sexes appear to rise linearly until at least age 80. We agree that where one looks for primary hyperparathyroidism in the elderly (particularly in women), it will be found. Whether we do good in finding it is very much in dispute. I tend to prefer knowledge to ignorance. Decisions about treatment once hyperparathyroidism is found may require careful

judgment. VANCOMYCIN DOSE FOR PSEUDOMEMBRANOUS COLITIS

SIR,-A 74-year-old woman was readmitted 6 weeks after large bowel surgery, complaining of profound diarrhoea. She had received preoperative bowel preparation with neomycin and metronidazole followed by parenteral metronidazole postoperatively plus ampicillin and cephradine for a mixed urinarytract infection. Sigmoidoscopy and biopsy revealed changes characteristic of pseudomembranous colitis (PMC). Clostriisolated from the stool. After fluid and electrolyte replacement and oral vancomycin 125 mg 6-hourly the patient became well and was free of diarrhoea and fit to be discharged home after 5 days. In the outpatient clinic 4 weeks later there was no sign of recurrence. The treatment of PMC has been radically altered by the recognition of C. difficile as the offending organism and with the finding that this toxin-producing gram positive rod is sensitive to vancomycin. The manufacturer recommends 2 g daily, which produces a faecal vancomycin concentration of 714±341 dium

difficile

was

7. Boas RA. Morpheus without dreams. Regional Anesth 1980; 5: 2. 8. Mathews E. Epidural morphine. Lancet 1979; i: 673. 1. McQuay HJ, Bullingham RES, Evans PJD, Lloyd JW, Moore RA. Demand analgesia to assess pain relief from epidural opiates. Lancet 1980; i: 768-69.

Your editorial misconstrues our cost figures on diagnosis and treatment of primary hyperparathyroidism: the figures cited are not "median cost ... ion the United States". The numbers given are derived from a small sample in our own practice only. In fact, the nationwide average charge for initial diagnosis and treatment is almost certainly higher than ours, while the costs for medical follow-up could be lower, depending upon the assiduousness of search for complications. Endocrine Research Unit, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55901, U.S.A.

1.

2.

HUNTER HEATH III

Keighley MRB, Burdon DW, Arabi Y, Alexander-Williams J, Thompson H, Youngs D, Johnson M, Bentley S, George RH, Mogg GAG. Randomised controlled trial of vancomycin for pseudomembranous colitis and postoperative diarrhoea. Br Med J 1978; ii: 1667-69. Finch RG, McKim Thomas HJ, Lewis MJ, Slack RCB, George RH. Relapse of pseudomembranous colitis after vancomycin therapy. Lancet 1979; ii: 1076.

George WL, Volpicelli NA, Stiner DB, Richman DD, Liechty EJ, Mok HY, Rolfe RD, Finegold SM. Relapse of pseudomembranous colitis after vancomycin therapy. N Engl J Med 1979; 301: 414-23. 4. Arabi Y, Dimock F, Burdon DW, Alexander-Williams J, Keighley MR. In-

3.

fluence of

neomycin

and metronidazole

on

colonic microflora of volun-

teers. J Antimicrob Chemother 1979; 5: 531-37. 5.Heath H, Hodgson SF, Kennedy MA. Primary hyperparathyroidism: Incidence, morbidity, and potential economic impact in a community. N Engl J Med 1980; 302: 189-93.