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Br Med J (Clin Res Ed): first published as 10.1136/bmj.289.6454.1291 on 10 November 1984. Downloaded from BRITISH MEDICAL JOURNAL VOLUME 289 10 NOVEMBER 1984 1291

0 ~~~~~~~~JOHNHENRY ABC ofPoisoning GLYN VOLANS

PSYCHOACTIVE

Tricyclic

ofthe drugs used to treat psychiatric disorders are relatively toxic, and Amitriptyhgne &3O AmXrijyD IMostsince suicidal behaviour is often a feature ofthese conditions the risk of CHCH2CH2N ICH3)2 overdose, often with potentially serious consequences, is real. Those Related antidepressants: prescribing psychoactive drugs should ensure not only that the diagnosis is correct and the treatment but that use Butriptylie X appropriate the proper and possible Bothiepiline side effects of the are carefully explained to the patient. If suicide IS thought to be a risk th leat toxic ofthe available drugs should be ucchosen. Protriptylire

Ilmipramine CH2CH2CH2N (CH3 )2 Related tricyclic antidepressants: Desipbamine Tricyclic antidepressants have a three ring structure, Dibeozepin hence their name. iL- http://www.bmj.com/ Clinical features

Selfpoisoning with tricyclic antidepressants accounts for about 300 SymTptoms of tricyclic deaths a year in adults in England and Wales. Patients prescribed tricyclic poisoning antidepressants should be told that the will not fully reverse their

Anticholinergic: depression for some weeks and that they should persevere with their on 24 September 2021 by guest. Protected copyright. Sinus tachycardia treatment. These drugs are also the major cause offatal accidental poisoning Mydriasis in children in the United Kingdom, causing about 5 deaths a year. Urinary retention Although the antidepressant activity ofthese drugs probably relates to Central nervous effects. their effects on the neurotransmitter systems in the brain, their toxic effects Hallucinations are largely due to anticholinergic and cardiodepressant effects. Symptoms Co=a include dilated pupils, sinus tachycardia, hallucinations, urinary retention, Brisk tendon reflexes and ileus. Cerebral toxicity may result in deepening coma, convulsions, Extensor plantr reflexes Respiratory depression brisk tendon reflexes, and extensor plantar responses. In severe poisoning Convulsions tendon reflexes and muscle tone may be lost, and brain stem reflexes may be absent. or cardiac lead to CardiQc g Respiratory depression may hypoxaemia. Metabolic acidosis iS common, and can also occur. Death iis Eleatrdicardiogmphic chans ElectrocardioMtaolcgciossrsaom onpadhypkaaeiacahasoocureDathypokalaemia Ventriculardorrhythmias usually due to cardiotoxicity or respiratory depression. The most frequent Hypotensiona cardiac effect is sinus tachycardia without impairment ofcardiac output. Metebolic X Further electrocardiographic abnormalities may, however, occur, with Hypothermia wide bizarre QRS complexes, heart block, and sometimes ventricular Hvyrmin ectopic beats or ventricular tachycardia. A cardiac depressant effect can produce hypotension, which may accentuate the hypoxaemia and metabolic Metabolic aacidosis MetHypokalaeiia acidosis. Sudden death has been reported up to six days after overdose but is ______I______very rare. Br Med J (Clin Res Ed): first published as 10.1136/bmj.289.6454.1291 on 10 November 1984. Downloaded from 1292 BRITISH MEDICAL JOURNAL VOLUME 289 10 NOVEMBER 1984

I II III poisoning can often be diagnosed confidently when the typical signs are present. A QRS complex of over 100 ms on the electrocardiogram is the rule in severe poisoning. When a I II III patient has a combination ofbilateral extensor plantar reflexes, brisk tendon jerks, and absent brain stem reflexes, differentiation from a cerebrovascular accident may be difficult, but the signs are always symmetrical. The diagnosis is helped by knowing that the patient has a history ofdepression and was prescribed tricyclic antidepressants. Nevertheless, the help ofa 20ms Sinus tachycardia and intraventricular conduction defect in patients with toxicology laboratory may be needed in difficult or complicated cases. tricyclic antidepressant poisoning Tricyclic antidepressants can be detected in the urine, but measurement of blood values is not usually helpful in managing acute overdoses.

Management (1) Cardiopulmonary status must be assessed immediately. If themselves help to correct hypotension, cardiac arrhythmias, necessary resuscitation should be started at once. Recovery or convulsions. may still occur after prolonged cardiac massage. (5) Hypotension usually responds to fluid replacement and (2) Since the anticholinergic effects ofthese drugs include or . Cardiac arrhythmias may respond delayed gastric emptying, gastric lavage should be performed to phenytoin or , but lignocaine, disopyramide, up to 12 hours after ingestion in a seriously poisoned patient. , and procainamide should be avoided. Direct Oral activated charcoal should then be given, since as little as current shock will be required for ventricular tachycardia or 10 g can adsorb potentially fatal amounts ofthe fibrillation, and cardiac pacing may be necessary for antidepressant. bradyarrhythmias causing hypotension. (3) Arterial blood gases and plasma electrolytes should be (6) Convulsions should first be treated by ensuring adequate or measured in all patients in grade III or IV coma and oxygenation, after which intravenous diazepam phenytoin electrocardiography and chest radiography should be may be used. performed. When possible the patient should be managed in (7) Haemoperfusion or haemodialysis does not remove an intensive therapy unit with continuous significant amounts ofthese drugs and has no place in electrocardiographic monitoring for at least 24 hours. management. (4) The hypoxaemic patient should be mechanically (8) The use ofphysostigmine is controversial, and it should ventilated and any other metabolic disturbances (metabolic never be given routinely. Nevertheless, intractable cardiac acidosis or hypokalaemia) corrected. A bicarbonate infusion arrhythmias, hypotension, or convulsions may respond to an (0X5-2X0 mmol/kg given rapidly) is often helpful, even if intravenous infusion ofphysostigmine salicylate 4-6 mg/h there is no metabolic acidosis. These measures may in (double this rate for the first 10 minutes).

Monoamine oxidase inhibitors http://www.bmj.com/

Several drugs and foods are prohibited for patients taking monoamine Monoamine oxidase inhibitors oxidase inhibitors to prevent the well known "cheese" reaction, which Trade name consists of a sudden and severe rise in blood pressure. An overdose of a Tranylcypromine Parnate monoamine oxidase inhibitors does not, however, usually produce hypertensive crisis unless the patient deliberately provokes the interaction. on 24 September 2021 by guest. Protected copyright. Phenelzine Nardil Initially the patient is not particularly unwell; symptoms usually build up Iproniazid Marsi lid over 12-24 hours, with muscle twitching progressing to widespread muscle Isocarboxazid Marplan spasms, trismus, and opisthotonus. The blood pressure may vary between Tranylcypromine plus Parstelin hypotension and moderate hypertension; there is usually a sinus tachycardia; and the patient is warm to the touch, sweats profusely, and has fixed dilated pupils. The core temperature may rise steeply and the patient can die ofhyperthermia. The muscle spasms may lead to rhabdomyolysis, 41 t Axillary and rectal temperatures in a patient with hyperpyrexia following an which can cause renal failure. overdose of trany Icypromine. Treatment Z3 40 with pancuronium resulted in afll in Management- Sedation with diazepam is oflittle use. The rectal to \ temperature. PI temperature should be monitored closely and ifit rises above 39°C the B9 o Axillary| patient should be electively paralysed with pancuronium and mechanically ventilated for 12-24 hours to prevent hyperthermia and rhabdomyolysis. E > *~~~~Rectal | External cooling is oflittle help as the body is generating more heat than it can lose due to profound muscle contraction. Hypotension is usually due to :37. hypovolaemia, but a low dose ofdopamine can be tried iffluid replacement A AA" A AAAAA A fails to restore blood pressure.

6 222 2 224 24 36 - 4mgpancuronium 0 2 4 6 8 10 12 14 16 18 20 2222628 Time after intubation (hours) Br Med J (Clin Res Ed): first published as 10.1136/bmj.289.6454.1291 on 10 November 1984. Downloaded from BRITISH MEDICAL JOURNAL VOLUME 289 10 NOVEMBER 1984 1293 Other antidepressants

Maprotiline is a bridged tricyclic antidepressant. It has anticholinergic Other antidepressants effects and the toxic symptoms are similar to those ofthe tricyclic antidepressants. Convulsions should be expected in overdose and have been reported during therapeutic use. Lofepromine does not have anticholinergic effects and is less cardiotoxic than the tricyclic antidepressants. Drowsiness is the main clinical feature. Tryptophan Deaths from overdose are rare and are usually clearly attributable to a Maproti line number ofproblems including mixed overdose and underlying disease. Nomifensine-Toxicity is generally mild. Drowsiness and tremor M ianserin sometimes occur, and coma is rare. . Toxicity is usually mild. Trazodone can cause drowsiness, Nomifensine X dizziness, and occasionally coma. is metabolised to the tricyclic antidepressant Trozodone and might be expected to show the same effects in overdose. Claims have been made for increased safety, but there is not yet enough information to Viloxazine support this.

Lithium

Lithium salts are widely and effectively used to treat bipolar or Lithium toxicity manic-depressive disorders. This metal is eliminated by the kidneys, and Nausea, vomiting, diarrhoea X reduced renal function can lead to accumulation. The therapeutic range is narrow (plasma concentrations between 1 0 and 1-4 mmol/l (6-9-9-7 g/l)), Tremor, weakness, ataxia, rigidity and toxicity in therapeutic use can be caused by changes in fluid or Stupor, convulsions, como electrolyte balance (particularly due to reduction in fluid intake or increased fluid loss from diarrhoea or vomiting or diuretic therapy). Deaths from lithium poisoning are rare, but the fact that lithium toxicity usually resolves completely should not lead to complacency. http://www.bmj.com/ o(\,% Serum lithium concentrations before, during 3-0 o*and after hoemodialysis in a severely Q intoxicated 66 year old patent. Note how lithium Clinicalfeatures is removed by hoemodialysis but that the serum E lithium values 'rebound" after hoemodialysis Chronic lithium toxicity usually presents with nausea, vomiting, apC '. ob o Arterial site diarrhoea, and tremor. Nephrotoxicity also occurs during chronic ti - Venous site treatment. In acute overdose neurological features are the rule, with 0 .4C %% Haemodialysis tremor, rigidity, nystagmus, and convulsions starting within hours of % -. c ingestion as the lithium enters brain tissue. Plasma concentrations correlate on 24 September 2021 by guest. Protected copyright. ya L- 0 b, poorly with toxic effects, and patients are often asymptomatic with plasma u *IS O, p lithium concentrations as high as 4 mmol/l (28 g/l). Lithium preparations are usually formulated for sustained release, so that toxic features may be

n A.. . . delayed even in acute overdose. 18 24 06 12 1'8 A42 0'6 19 April 20 April 21 April

Management oflithiumpoisoning (1) Gastric lavage should be carried out up to six hours after increase excretion oflithium, however, and should not be ingestion to remove any lithium remaining in the stomach. used. Likewise, peritoneal dialysis is not recommended. (2) A plasma or serum sample should be obtained for measuring lithium concentration. Remember that blood (4) In a symptomatic patient with high plasma lithium concentrations after an acute overdose haemodialysis should should not be collected into a lithium heparin tube. be considered. Although well removed by haemodialysis, (3) Lithium is excreted by the kidneys, and a good urine lithium has a large volume ofdistribution and repeated output should be ensured. Forced diuresis does not greatly dialyses may be necessary. Br Med J (Clin Res Ed): first published as 10.1136/bmj.289.6454.1291 on 10 November 1984. Downloaded from 1294 BRITISH MEDICAL JOURNAL VOLUME 289 10 NOVEMBER 1984 agents

Chlorpromazine has been used to treat psychotic disorders for over 30 years, and many other and related drug groups are now also Antipsychotic agents used. In therapeutic use parkinsonian rigidity and tremor are common and Phenothiazines often require treatment with anticholinergic drugs such as , Clopenthixol which can themselves be toxic in overdose. Excessive doses in therapeutic Flupenthixol use may cause drowsiness, tremor, or convulsions. Patients may die Methotrimeprazine suddenly while under treatment: the reason for this is not clear OxypertineOxprtn (" sudden death"). The neuroleptic malignant syndrome is Pericyozine Deoperidol another complication which may occur at any time in patients under Pipothiazine.. ~~~~ treatment, hours or months after initial exposure to the drug. It consists of ProchlorperazinePro.hiorperozin muscular rigidity, hyperthermia, rapid pulse and respiration, lethargy, and jPromazine coma. Mortality is 30%. In overdose the antipsychotic agents can cause drowsiness, hypotension, Trifluoperazine Fluspiriline tachycardia, supraventricular and ventricular tachyarrhythmias, and convulsions. Acute dystonic reactions sometimes occur after overdosage.

Management ofpoisoning with antipsychotic drugs (1) Gastric lavage should be performed up to six hours after 1 Dantrolene + cooling ingestion. 0 39I Use of dantrolene in treatment (2) Activated charcoal should be given. 1 of neuroleptic malignant syndrome (3) Supportive care is the mainstay oftreatment. c)38j (4) Dystonic reactions normally respond rapidly to E 5-10mg or orphenadrine 20-40 mg given 9 37 . * intramuscularly or intravenously. 14 16 18'20 22 .Q 2 4 6 8 10 12 C (5) Dantrolene is the drug ofchoice in the neuroleptic Time (h) x malignant syndrome.

Dr John Henry, MRCP, is consultant physician and Dr Glyn Volans, MD, FRCP, director, National Poisons Information Service, Guy's Poisons Unit, New Cross Hospital, London SE14 5ER. http://www.bmj.com/

What are the merits ofthe implant operationfor cataract? What are the contrain- positions in which a lens may be supported within the eye: the anterior dications for this procedure, and what are the complications over and above other chamber lens that spans the anterior chamber from drainage angle to drain- cataract operations? age angle, the iris clip lens that is supported by the tissues of the iris, and the posterior chamber lens that lies behind the iris. Anterior chamber lenses Most patients undergoing cataract extraction are elderly, and many find have caused recurrent haemorrhages from the iris, damage to the drainage on 24 September 2021 by guest. Protected copyright. their thick glasses or contact lenses difficult to see through and to handle. angle (sometimes with the formation of adhesions), uveitis, and glaucoma; But patients receiving an intraocular lens at the time of their cataract during implantation of anterior chamber lenses it is possible to damage the operation enjoy almost immediate improved sight. Intraocular lens implant- comeal endothelium with the development of chronic corneal oedema. ation is therefore becoming an increasingly popular surgical option, and Nevertheless, anterior chamber lenses are widely and safely used and are world wide over one million intraocular lenses have now been implanted. An particularly useful for secondary lens implantations. Lenses that clip on to intraocular lens offers patients permanent correction of their aphakia, and the iris enjoyed a vogue in the 1970s and early 1980s but are less popular now with newer techniques the surgeon can now decide which power of lens a because they are relatively unstable, moving continuously and causing particular patient needs, although spectacles are usually necessary to focus chronic irritation of the iris, and releasing prostaglandins that are thought to the vision exactly for distant and near objects. As to whether the lenses are lead to chronic macular oedema. Lenses placed in the posterior chamber of safe, the early problems of design were that they were too heavy and the the eye, behind the iris, are occasionally unstable but on the whole their use materials and methods used were of poor quality or toxic.' These problems seems to be the safest of the three lens types, though an extracapsular have been virtually solved and with microsurgical techniques an intraocular technique ofcataract extraction is required. The arguments about technique lens implantation is tolerated by almost every eye. Large clinical studies in and lens design will continue, but it is increasingly clear that intraocular lens the United States and smaller studies in the United Kingdom underline the implantation is a safe adjunct to good cataract surgery, and the improve- safety of intraocular lenses when inserted by orthodox techniques and with ments in the quality of vision enjoyed by patients receiving such an implant approved materials.2 As experience with lenses has expanded so too have the is much better than that offered by any of the other methods for correcting number ofcases when the use ofan intraocular lens is considered acceptable. aphakia.-B A NOBLE, consultant ophthalmic surgeon, Leeds. In particular niany younger patients with cataracts now receive intraocular lens implantations routinely. Their use is controversial and probably I Drews RC. Quality control, and changing indications for lens implantation. Ophthalmology contraindicated in children, adolescents, patients with glaucoma or active 1983;90:301-10. uveitis, and diabetic patients with retinopathy.3 2 Stark WJ, Worthen DM, Holladay JT, et al. The FDA report on intraocular lenses. Ophthalmology 1983;90:31 1-20. Many complications are directly related to the style oflens as well as to the 3 Straatsma BR, Petitt TH, Wheeler N, et al. Diabetes mellittLs ollki intraocular lens implantation. anatomical site chosen for the fixation of the lens. There are three basic Ophthalmology 1983;90: 336-43.