Hyperuricaemia, and Myoglobinuria
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BRITISH MEDICAL JOURNAL 12 MAY 1979 1233 theatre, but errors would be reduced. In 1978 the Medical The wrong drug Defence Union2 described six errors of injection; two were related to anaesthesia, and both led to the death ofthe patients. Br Med J: first published as 10.1136/bmj.1.6173.1233-a on 12 May 1979. Downloaded from Patients are sometimes given either the wrong drug or an 1 Medico-Pharmaceutical Forum, Dangerous Mistakes in Drug Administra- excessive amount of the right one. Anaesthetists are at especial tion. London, Royal Society of Medicine, 1979. risk of such errors, since not only do they prescribe drugs but 2 Medical Defence Union, Annual Report 1978. London, MDU, 1978. they also administer them; many of their drugs are potent; and the polypharmacy of modern anaesthesia increases the possibilities of drug interactions. Should an emergency arise during anaesthesia (or resuscitation, when anaesthetists are Acute renal failure; often present) there may not be the normal check on what drugs the patient is having. Finally, some drugs used by hyperuricaemia, and anaesthetists may be prepared for them by non-nursing ancil- - lary staff. In these circumstances errors can be dangerous and myoglobinuria they sometimes cost patients their lives. The Medico-Phar- maceutical Forum has just published' some recommendations Patients with severe renal failure, whatever the cause, may intended to reduce these risks, and anaesthetists should look at have a raised serum uric acid concentration and in chronic their routine practice in the light of these warnings. renal failure this may result occasionally in secondary gout. How do mistakes occur ? Verbal prescriptions are notorious In an increasing number of illnesses, however, there are as sources of error. Doctors' writing, too, is often illegible; and reports of serum uric acid concentrations that are out of even prescription sheets on the London Hospital pattern do proportion to the degree of renal failure and are thought to not remove all hazards, especially with the "once only" or "as be its cause. They fall into two broad categories, characterised needed" sections. on the one hand by massive destruction of leukaemic or More serious are the errors in administration. Nowadays lymphoma cells and on the other by damage or necrosis of drugs reach patients through a complex process. A bulk supply skeletal muscle-in both of which uric acid is a metabolic to the pharmacy is broken into smaller packs and sent to the breakdown product, though its role in the second group is theatre. The ampoules may then be used individually, trans- more controversial. ferred to a second pack on an anaesthetic machine, or-worst Hyperuricaemic acute renal failure is a well-recognised of all-taken out, not used, and returned to one of the packs. occurrence with leukaemias and lymphomas-either as a rare Each handling carries a risk of error and the more the handling spontaneous complication or, more usually, as a complication the more the probabilities multiply. Finding adrenaline am- of intensive chemotherapy. The pathogenesis, however, has poules in atropine packs is not unknown and may cause deaths. changed over the years.1 The first cases reported2 were due to Next is the problem of different drugs with similar names, a obstruction of the ureters by uric acid crystals, and in these problem that may be compounded by using proprietary names. patients a brisk diuresis followed retrograde ureteric When a pharmacy changes its supplier there may be catheterisation and lavage. At this time the acute leukaemias further complications-suxamethonium may change from and lymphomas had a high death rate and chemotherapy was http://www.bmj.com/ Scoline to Anectine, producing confusion-and possibly lead- in its infancy. Thus only those with more chronic disease ing to its use instead of atropine. Similarly, changes ofneostig- survived long enough to develop ureteric obstruction due to mine from amber-coloured to clear ampoules has caused prolonged hyperuricaemia and hyperuricosuria. In a review confusion and irritation if nothing worse. going up to 19663 about one-third ofthe patients had symptoms What can be done to minimise the risks? Only the most suggestive of urinary tract obstruction. But by the time extreme emergency should allow verbal prescriptions to be Kjellstrand et al4 reviewed the condition in 1974 the picture accepted. The hazard of prescribing a neuromuscular blocking had changed. Chemotherapy for the leukaemias and drug such as pancuronium to "settle" patients on ventilators lymphomas had improved considerably, and the more on 30 September 2021 by guest. Protected copyright. without cancelling the prescription once the patient is breath- aggressive chemotherapy resulted in massive cell destruction, ing spontaneously derives from the anaesthetist alone. Ifsuch a with release of large amounts of nucleic acid and dramatic patient is given pancuronium subsequently he has only himself rises in serum uric acid concentrations. Thus in the 16 patients to blame. they reviewed the mean plasma uric acid concentration was The problems of incorrect administration can be minimised 1-19 mmol/l (20 mg/100 ml)-range 071-2-14 mmol/l (12- by thought and some action from the pharmaceutical industry. 36 mg/100 ml)-at the time of acute renal failure, which The labelling ofampoules could be improved, and the Medico- was considered to be due to precipitation of uric acid crystals Pharmaceutical Forum suggests a format with the approved in the distal tubules and collecting ducts. In only one of the name, the proprietary name, and the amount of drug in the 16 cases was there any suggestion of obstruction of the ureter. volume of content of the ampoule (for example, "Gallamine, Besides the changing pathogenesis there has also been a B P, Flaxedil, 80 mg in 2 ml"). Concentrations should not notable improvement in the management and treatment of be given, and paper labels should be replaced by ceramic labels acute renal failure, with a greatly improved prognosis. Fourteen as far as possible. Pharmacies and anaesthetists should decide of 30 patients reported by Lilje3 died during the acute renal how to keep drug transfers to a minimum. Despite the cost the failure, but all 16 patients reviewed by Kjellstrand et a14 practice of returning ampoules to pharmaceutical packs must survived it. Kjellstrand et al have summarised the principles be forbidden. Finally, the person administering the drug of management. Clearly the doctor should anticipate acute (the anaesthetist) should have the responsibility of drawing up hyperuricaemia during chemotherapy in patients with the drug from the ampoule-the label of which he has read. leukaemias and lymphomas, and start treatment with allo- Delegation to nursing or operating department staff should not purinol well before chemotherapy to minimise the rise in uric be allowed, except in emergencies such as cardiac arrest. acid concentration. Patients must not become dehydrated, This may mean that the anaesthetist spends more time in and alkalinisation of the urine during intense chemotherapy 1234 BRITISH MEDICAL JOURNAL 12 MAY 1979 is advisable to reduce the proportion of insoluble uric acid in phosphokinase, and lactic dehydrogenase concentrations. the urine. The dosage of allopurinol may need to be increased Myoglobinuria should be suspected when the urine is at such times. The risk of xanthine nephropathy from dark and positive to orthotolidine but contains no red blood Br Med J: first published as 10.1136/bmj.1.6173.1233-a on 12 May 1979. Downloaded from allopurinol treatment is remote.5 Hyperphosphataemia- cells. It has not always been found in these types of acute again presumably due to massive cell necrosis-is also renal failure; but myoglobin is rapidly excreted and must be important in some of these patients,4 and they may need oral looked for during the first 24-48 hours. It is reliably identified aluminium hydroxide gel during intensive chemotherapy to by acrylamide gel electrophoresis or immunodiffusion minimise the possibility of metastatic calcification. techniques. Spectrophotometry is less reliable, particularly in Urgent rehydration and alkalinisation of the urine are the an acid urine.8 first lines of treatment for hyperuricaemic acute renal failure, The role of hyperuricaemia in causing the acute renal failure provided the diagnosis is made at an early stage and before in these circumstances is not clear, but recent reports suggest acute renal failure and oliguria are established. Once oliguric that it may be important in those cases that occasionally acute renal failure is established, however, the most effective follow unaccustomed strenuous muscular exercise or heat treatment is haemodialysis. This was shown by Kjellstrand exhaustion and repeated grand mal fits.'6-'9 Evidence of et al to be 10-20 times more effective than peritoneal dialysis non-traumatic rhabdomyolysis and myoglobinuria after at removing uric acid and lowering the serum uric acid repeated fits was found in four patients reported by Grossman concentration. The patients they reviewed all survived the et al,8 but they did not study serum uric acid concentrations. acute renal failure and recovered good renal function in Warren et al'8 considered that severe hyperuricaemia was three weeks or less. The possibility of bilateral ureteric chiefly responsible for the acute renal failure in their cases obstruction should always be borne in mind, and excluded if that followed epileptic fits, and they found no evidence of there is anything to suggest it. Cystoscopy, retrograde ureteric myoglobinuria (as judged by Haematest results). Luhdorf catheterisation, and retrograde pyelography should not often et al19 documented significant increases in serum uric acid be necessary these days, because in many cases urinary tract concentrations after repeated grand mal fits and observed obstruction can be excluded by high-dose intravenous renal impairment in two cases, but they did not report on the urography or gamma-camera renography, or both.