923

production, but did not inhibit cyclo-oxygenation. After boiling for10 min the extract lost all inhibitory activity. A second extraction offresh feverfew leaves without flowers or stem was made and tested inthe same way. This solution gave a biphasic dose/response line forinhibition ofPG production, with a peak of activity (58%&plusmn;5’ 5 SEMinhibition) at 5 1/ml (P<0 - 02). Like the extract of the whole plant,the leaf extract did not inhibit cyclo-oxygenation of arachidonicacid.These experiments suggest that feverfew contains a factor that

inhibits PG biosynthesis, but differs from salicylates, in that it doesnot inhibit cyclo-oxygenation by PG synthase. The ability offeverfew to inhibit PG production may account for its effectivenessas a herbal remedy in conditions responding to acetylsalicylate andlike-acting drugs.We thank Mrs Pamela Freeman for specimens of feverfew.

Research Department,Miles Laboratories Ltd,Stoke Poges, Slough SL2 4LY

H. O. J. COLLIERN. M. BUTTW. J. MCDONALD-GIBSONS. A. SAEED

EOSINOPHILIA DURING CAPTOPRIL TREATMENT

SIR,-Among the adverse effects observed in twenty patients withchronic congestive heart failure treated for one year with captoprilwe noted eosinophilia in seven. Orthostatic hypotension, nephroticsyndrome, and taste loss have been described 1-4 but we have foundonly one published case of eosinophilia associated with captopril.The mean captopril dosage was 200 mg daily. None of our pa-

tients had a history of atopy (a history of allergy or asthma was con-sidered as a contraindication for this therapy).Eosinophilia was the most frequent adverse effect: we noted seven

cases of eosinophil counts above 400/1. The mean count rose from

EOSINOPHOL COUNTS (IElg) BEFORE AND AFTER ONE MONTH OFCAPTOPRIL TREATMENT

270 to 767/1 after the first month of treatment (p<0 001), and thischange was still present after 6 months.Only one of the twenty patients had an itching rash with desqua-

mation, leading us to stop treatment. This patient (no. 4) had themost striking eosinophilia and had received the highest dosage ofcaptopril (350 mg/day). Patient 3 showed itching without rash, andhad the second highest eosinophil count. Renal function in thepatients with eosinophilia was not significantly different from thatin the other patients on captopril.All the patients were on digoxin and frusemide before and after

captopril treatment, and no other drug was added during the study.Eosinophol counts may help to prevent clinical skin reactions in

patients on captopril. With an important eosinophilia, dosagesshould be decreased; in this way we were able to continue treatmentin patient 3 without any cutaneous problem.

Cardiology Department,C.H.U Rangueil,31054 Toulouse, France

J G. KAYANAKISP. GIRAUD

J. M. FAUVELJ. P. BOUNHOURE

1. McNeil JJ Taste associated with oral captopril treatment Br Med J 1979; ii: 1555.2. Rollin H. Drug related gustatory disorders. Ann Otol Rhinol Laryngol 1978; 87: 37.3. Vlasses PH, Ferguson RK. Temporary agueusia related to captopril. Lancer 1979; ii:

526.4 Prins EJL, Boorntje SJ, Weening JJ, Donker AJM Nephrotic syndrome in patients on

captopril. Lancet 1979; ii: 306.5. Boorneje SJ. Serum-sickness-like syndrome with membranous glomerulopathy in

patients on captopril. Lancer 1979; ii: 1297.

HEROIN AND HYPERKAL&AElig;MIA

SIR,-Morbidity and mortality from opiate abuse is usuallyassociated with respiratory depression and sepsis; electrolytedisturbance has received little attention. We have seen a case ofheroin overdosage with dangerously high plasma potassium levelsand corresponding ECG abnormalities.A 25-year-old male was admitted to hospital in deep coma. His

relatives said that he had intermittently experimented withnarcotics, and we learned later that, some 8 h before admission, hehad injected himself intravenously with an unknown quantity of"street" heroin. He had lost consciousness almost immediately andhad been found 7 h later. He was well-nourished with no signs ofchronic intravenous drug abuse on his skin. He was cyanosed,hypotensive (blood pressure 80/60 mm Hg) and the pulse 110/minregular. The pupils were small and equal with no reaction to light.There was a generalised increase in muscle tone with symmetricallybrisk reflexes; both plantar responses were extensor.He was given naloxone 0-4 4 mg intravenously with prompt

improvement in his conscious level. Emergency plasma electrolyteswere requested (table). The ECG showed sinus rhythm was

LABORATORY DATA

CPK = Creatine phosphokinase.

abnormal with tall tented T waves and widening of the QRScomplex with a bizarre ST configuration. Intravenous calciumgluconate 10 ml 10% was given and an infusion of 10% dextrosewith 20 units of soluble insulin per 500 ml was started. The plasmapotassium fell to normal over 6 h and by the following morning thepatient was fully conscious and symptom-free. There was noevidence of injury. The ECG reverted to normal.We believe that the hyperkalaemia in this patient was the result of

ischxmic injury to muscle during the period of unconsciousnessand prolonged immobility following the overdose, with leakage ofpotassium ions from the muscles into the extracellular fluid.

Athough there were no physical signs of muscle damage, the CPKactivities indicate muscle necrosis. This situation is analogous to,though less severe than, the crush syndrome classically described byBywaters and Beall in 1942,1 though the muscle necrosis was notsevere enough to release myoglobin and compromise renal function.CPK activity fell to normal over the next 3 days.Schreiber et a1.2 describe the full-blown crush syndrome

following heroin overdosage. Their patients had increased warmthand tenderness of the affected muscles. One patient requiredperitoneal dialysis but plasma electolytes were not reported.In view of the dangerously high plasma potassium found in our

case in the absence of any signs of tissue injury, it seems prudent toask for urgent electrolyte estimations in all cases of drug overdosage,particularly if there has been prolonged immobility. It may be thatsome at least of the patients who die following drug overdosage do sofrom hyperkalasmic cardiac arrest. Many hospitals have a separateroom in the accident and emergency department for drug addictsadmitted following overdosage: pulse, temperature, and consciouslevel are monitored but electrolytes are seldom measured. Thispolicy mav require review.

Northwick Park Hospital,Harrow, Middlesex HA1 3UJ

C. J. PEARCEJ. G. C. COX

1. Bywaters EGL, Beall D. Crush injuries with impairment of renal function Br Med J1941; i: 427-32.

2. Schreiber SN, Liebowitz MR, Bernstein LH, et al. Limb compression and renalimpairment (crush syndrome) complicating narcotic overdose. N Engl Med1971; 284: 368-69.