379 effect was not consistent. In-vitro experiments on vascular smooth muscle preparations have shown that droperidol has a cell-membrane stabilising effect like that of quinidine and may block the sodium-carrying system of the surface membrane.7 This may explain the transient arterial hypotension, heartblock, and cardiac arrests which may occur when the drug is used clinically by the intravenous or intra-aortic route.8.9 Fentanyl and morphine have some effects on the central nervous system similar to those of dopamine. 10. 11 They reverse drug-induced parkinsonism, they stimulate the chemoreceptors of the medulla oblongata to cause nausea and vomiting and they inhibit indirectly the release of growth and other hormones from the pituitary gland. Droperidol has opposite effects on the central nervous system. It causes parkinsonism, it prevents opiate-induced nausea and vomiting and, like other dopamine antagonists, it may be expected to release pituitary hormones when given without a dopamine agonist such as
morphine or fentanyl. It would seem that neurolepsy is a complex interaction between dopamine agonists and antagonists. Whatever its clinical significance may be it does not justify the assumption that droperidol is an alpha-adrenoceptor blocker. The confusion that surrounds droperidol and its cardiovascular effects in man emphasises the need for volume-pulse plethysmography in the clinical assessment of drugs that are supposed to protect patients from the vasoconstrictor reaction to the adrenergic stress of surgery. Each drug should be examined separately because it is unwise to comment on the action of one drug when others are given simultaneously. The only anaesthetic that is known consistently to prevent the vasoconstrictor reaction to surgery is halothane. I should like to remind you, Sir, that hepatitis has followed morphine, pethidine, thiopentone, acupuncture, and neuroleptanxsthesia and the cause has been correctly diagnosed in all cases. I can assure you that most anaesthetists know that all anxsthetic drugs and techniques are as ineffective as halothane in conferring immunity to viral hepatitis transmitted or otherwise. Department of Anæsthetics, Royal Infirmary, MICHAEL
Manchester M13 9WL
JOHNSTONE
we considered that there was sufficient evidence of ; cause-and-effect relationship in some of these cases to justif; an addition to the adverse-reactions section of the data shee for cimetidine: "Reversible confusional states have als( occurred, usually in elderly or already very ill patients (e.g those with renal failure)." This has been agreed with the U.K licencing authority and is now "in press". Schentag et al. also suggest that the dosage of cimetidine should be reduced in patients with hepatic failure but norma renal function. This suggestion is based on a single patien who had significant changes in mental state from a total of five in this subgroup. Cimetidine has been used in many patient with severe hepatic failure at the full dosage currently recom mended in the data sheet.2 We do not therefore consider tha sufficient evidence is available to recommend a reduction o: dosage in patients with isolated hepatic failure. The advice t( reduce dosage in patients with renal failure has been given ir the data sheet since cimetidine became generally available ir November, 1976. We agree that these patients should be close ly monitored.
theless,
’
Medical Department, Smith Kline & French Laboratories Ltd, Welwyn Garden City, Hertfordshire AL7 1EY
A. C. FLIND D. ROWLEY-JONE
ALUMINIUM IN HÆMODIALYSIS
interested in the letter by Dr Masselot and aluminium (Al) and haemodialysis and would report our experience with Al in patients on long-term
SIR,-We
colleagues’ like
to
were
on
hsemodialysis. Pre-dialysis
serum-Al levels were screened routinely, and in Al kinetics were studied. For preparation of dialysate untreated tap water with a very low Al content (0-3 µmol/1) was used. All patients received AI(OH)3’ with an average daily intake of 4.65 g. Al was measured by flameless atomic-absorption spectrophotometry in serum before dialysis, in plasma of the afferent arterial limb and efferent venous access limb, and in plasma ultrafiltrate 20 min after the start of dialysis and after 6 h of dialysis. The mean Al values before dialysis were 3.40 µmol/1 (range 1 - 81-5-92) and were significantly correlated with daily AI(OH)3 ingestion (p
morphine or fentanyl. It would seem that neurolepsy is a complex interaction between dopamine agonists and antagonists. Whatever its clinical significance may be it does not justify the assumption that droperidol is an alpha-adrenoceptor blocker. The confusion that surrounds droperidol and its cardiovascular effects in man emphasises the need for volume-pulse plethysmography in the clinical assessment of drugs that are supposed to protect patients from the vasoconstrictor reaction to the adrenergic stress of surgery. Each drug should be examined separately because it is unwise to comment on the action of one drug when others are given simultaneously. The only anaesthetic that is known consistently to prevent the vasoconstrictor reaction to surgery is halothane. I should like to remind you, Sir, that hepatitis has followed morphine, pethidine, thiopentone, acupuncture, and neuroleptanxsthesia and the cause has been correctly diagnosed in all cases. I can assure you that most anaesthetists know that all anxsthetic drugs and techniques are as ineffective as halothane in conferring immunity to viral hepatitis transmitted or otherwise. Department of Anæsthetics, Royal Infirmary, MICHAEL
Manchester M13 9WL
JOHNSTONE
we considered that there was sufficient evidence of ; cause-and-effect relationship in some of these cases to justif; an addition to the adverse-reactions section of the data shee for cimetidine: "Reversible confusional states have als( occurred, usually in elderly or already very ill patients (e.g those with renal failure)." This has been agreed with the U.K licencing authority and is now "in press". Schentag et al. also suggest that the dosage of cimetidine should be reduced in patients with hepatic failure but norma renal function. This suggestion is based on a single patien who had significant changes in mental state from a total of five in this subgroup. Cimetidine has been used in many patient with severe hepatic failure at the full dosage currently recom mended in the data sheet.2 We do not therefore consider tha sufficient evidence is available to recommend a reduction o: dosage in patients with isolated hepatic failure. The advice t( reduce dosage in patients with renal failure has been given ir the data sheet since cimetidine became generally available ir November, 1976. We agree that these patients should be close ly monitored.
theless,
’
Medical Department, Smith Kline & French Laboratories Ltd, Welwyn Garden City, Hertfordshire AL7 1EY
A. C. FLIND D. ROWLEY-JONE
ALUMINIUM IN HÆMODIALYSIS
interested in the letter by Dr Masselot and aluminium (Al) and haemodialysis and would report our experience with Al in patients on long-term
SIR,-We
colleagues’ like
to
were
on
hsemodialysis. Pre-dialysis
serum-Al levels were screened routinely, and in Al kinetics were studied. For preparation of dialysate untreated tap water with a very low Al content (0-3 µmol/1) was used. All patients received AI(OH)3’ with an average daily intake of 4.65 g. Al was measured by flameless atomic-absorption spectrophotometry in serum before dialysis, in plasma of the afferent arterial limb and efferent venous access limb, and in plasma ultrafiltrate 20 min after the start of dialysis and after 6 h of dialysis. The mean Al values before dialysis were 3.40 µmol/1 (range 1 - 81-5-92) and were significantly correlated with daily AI(OH)3 ingestion (p
