An Evidence Based Flowchart to Guide the Management of Acute Salicylate (Aspirin) Overdose P I Dargan, C I Wallace, a L Jones

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ORIGINAL ARTICLE Emerg Med J: first published as 10.1136/emj.19.3.206 on 1 May 2002. Downloaded from An evidence based flowchart to guide the management of acute salicylate (aspirin) overdose P I Dargan, C I Wallace, A L Jones ......

See end of article for Emerg Med J 2002;19:206–209 authors’ affiliations ......

Correspondence to: Dr P Dargan, National Poisons Information Objective: To develop a flowchart to be used as a tool to guide clinicians step by step through the Service, Guy’s and St management of salicylate poisoning. Thomas’ NHS Trust, Methods: A comprehensive literature search was carried out. Avonley Road, London, SE14 5ER, UK; Results: The evidence base was used to develop a management flowchart that guides the clinician paul.dargan@ through the three main steps in caring for the patient with salicylate poisoning: preventing further gstt.sthames.nhs.uk absorption, assessing the severity of poisoning and, where appropriate, increasing elimination. Accepted for publication Conclusions: Salicylate poisoning can result in severe morbidity and mortality and this flowchart pro- 29 October 2001 vides an evidence based guideline that will guide clinicians through the management of patients pre- ...... senting to the emergency department with salicylate poisoning.

lthough the overall mortality in salicylate poisoning is DISCUSSION low, such figures can be very deceptive as severe poison- There is no antidote to salicylate poisoning and management ing may cause metabolic acidosis, convulsions, coma, is directed towards preventing further absorption and A 1 hyperpyrexia, pulmonary oedema, and renal failure. Death increasing elimination of the drug in patients with features of can occur in 5% of patients who have such features of severe moderate or severe intoxication. poisoning and is attributable to cardiac arrest or multiple complications after severe brain damage.1–3 Critically, in severe Prevention of further absorption salicylate poisoning, delay in diagnosis was associated with a A study on volunteers taking 1.5 g aspirin comparing activated mortality of 15% compared with a much lower rate in those charcoal, emesis, and gastric lavage had several limitations; patients in whom early diagnosis and initiation of treatment salicylate elimination was followed up for only 24 hours, the http://emj.bmj.com/ was made.4 The current problem is that because salicylate poi- analytical method used underestimated some salicylate soning is not seen so commonly, through lack of familiarity, metabolites, and plasma salicylate concentrations were not 5 medical and nursing staff may underestimate the severity of measured. Like similar volunteer studies in other drugs it poisoning or fail to administer sufficiently vigorous treat- does not accurately reflect the effect of treatment regimens in ments early enough to prevent morbidity and mortality (NPIS poisoned patients, but none the less taken with the other evi- data, not shown). dence shown in figure 1, it provides some rationale to support 6 Once the severity of poisoning is recognised, management the use of activated charcoal within one hour of an overdose. Repeated doses of activated charcoal may have the added is a success story for clinical toxicology as over the past 40 on September 24, 2021 by guest. Protected copyright. years techniques to reduce the absorption of salicylate and advantage of shortening the elimination half life of 7 increase its elimination have been developed. This evidence salicylates. This study is controversial in clinical toxicology based flowchart has been developed to help guide decision because the charcoal administered in this study contained making in salicylate poisoning. It is a guide however, not a bicarbonate (Medicoal) but in our view its implications have 89 protocol and individual decisions will still need to be made for been too readily dismissed. A study in adult volunteers given each patient. Further advice on the management of salicylate 1.9 g of aspirin showed that three, four hourly 50 g doses of poisoning is also always available from a poisons centre (in the charcoal resulted in a significant decrease in salicylate absorp- 10 UK the single national number, 0870 600 6266, will connect tion when compared with one or two doses of charcoal. 11 12 you to your local poisons centre) Aspirin forms concretions within the stomach and it may be important to recoat surfaces of such concretions with charcoal to reduce ongoing absorption. The administration of a METHODS second dose of activated charcoal is of particular value in A literature search was carried out using Medline (1966–4/ adults who have ingested substantial quantities of an enteric 2000), Toxline (1966–4/2000) and EMBASE (1988–4/2000). coated or sustained release preparation. Gastric decontamina- The following terms were used: (*aspirin OR exp sali- tion in salicylate poisoning remains controversial even among cylate$.mp) AND (exp poisoning OR *overdose$.mp). No lim- toxicologists.13 However, we would advocate that patients with its were placed. Using this evidence base, an algorithmic flow- salicylate poisoning are given repeat doses of activated chart was constructed to guide the clinician through the charcoal (four hourly doses of 50 g in adults, 1 g/kg body management of salicylate poisoning in a stepwise fashion. weight in children) until the salicylate level peaks to minimise delayed absorption of salicylates.

RESULTS Assessing the severity of salicylate poisoning The results are shown in ﬁgure 1, which is a ﬂowchart for The serum salicylate should be determined on admission pro- management guidance in salicylate poisoning and supporting vided that more than four hours have elapsed from the time of references from the literature. ingestion of the overdose. Measurements made before this

www.emjonline.com Management of acute salicylate (aspirin) overdose 207

PRESENTATION

Note: some salicylate preparations contain other agents Emerg Med J: first published as 10.1136/emj.19.3.206 on 1 May 2002. Downloaded from such as opiates, paracetamol and caffeine. This flowchart deals only with the management of the salicylate component; the other agents need separate consideration

< 125 mg/kg Gastric lavage24 25 < 1 hour > 500 mg/kg26 27 and asymptomatic26 27 Discharge patient if sure of dose if sure of dose and When Dose Advise to return if develops any time of ingestion. taken? taken? symptoms, particularly vomiting, Ensure that the tinnitus, sweating airway is protected ≥ 26 27 125 mg/kg or unknown Before the patient is discharged an assessment of > 1 hour their mental state and risk of repeated episodes of deliberate self harm should be carried out, ideally 50 g Oral activated charcoal5 6 28–30 by a psychiatrist or psychiatric liaison nurse (children 1 g/kg bodyweight) Ensure that the airway is protected

Severe clincial features1: Coma, convulsions Acute renal failure Pulmonary oedema Haemodialysis Does the If these develop at any stage: + Yes patient have 1 Resuscitate i.e airway, Give sodium bicarbonate any of the breathing, circulation (cautious with volume if severe clinical 2 Check ABGs anuric)1 11 22 features? 3 Discuss with local poisons unit and ITU 4 Consider haemodialysis Conversion factors for plasma No salicylate concentration: - to convert mmol/l to mg/l divided by 0.0072 Rehydrate the patient and take blood for salicylate level, U&E, FBC, INR (at least 4 - to convert mg/l to mmol/l Metabolic acidosis? hours after ingestion) multiply by 0.0072 i) If arterial pH < 7.3, treat with 1 ml/kg 8.4% ABG should be checked in symptomatic cases sodium bicarbonate iv to increase pH to 7.4 ii) If arterial pH < 7.2, consider haemodialysis Check blood results

Before the patient is discharged an assessment of Yes No their mental state and risk of repeated episodes of Is this the first deliberate self harm should be carried out, ideally salicylate level? by a psychiatrist or psychiatric liaison nurse.

Discharge patient Advise to return if develops NOTE: Has the salicylate • Children (< 12 y and the elderly (> 65 y) level peaked? any symptoms, particularly are more susceptible to the effects of salicylate (ie. is the current vomiting, tinnitis, sweating poisoning and tend to get more severe clinical No level less than the Yes effects at lower blood salicylate concentrations • Not all of the features described need to be previous level) present for each of the classifications of mild, Oral activated moderate or severe poisoning. The plasma charcoal:7 8 10 31 32 http://emj.bmj.com/ salicylate concentration needs to be interpreted Is the peak level Yes - Adults 50 g in the context of the patient's clinical features < 300 mg/l (adults) - Children 1 g/kg and degree of metabolic acidosis. Clinical or < 200 mg/l No features are more important in grading the (children/elderly)? severity of salicylate poisoning

Salicylate level: Mild poisoning: Moderate poisoning2 16: Severe poisoning1 22: - Adults < 300 mg/l Salicylate level: Salicylate level: Salicylate level: - Children/elderly < 200 mg/l - Adults 300–600 mg/l - Adults 600–800 mg/l - Adults > 800 mg/l Clinical features: - Children/elderly 200–450 mg/l - Children/elderly 450–700 mg/l - Children/elderly > 700 mg/l Patient asymptomatic Clinical features: Clinical features: Clinical features: on September 24, 2021 by guest. Protected copyright. Lethargy, nausea, vomiting, Mild features + tachypnoea, Hypotension, significant metabolic tinnitus, dizziness hyperpyrexia, sweating, dehydration, acidosis after rehydration, renal loss of coordination, restlessness failure (oliguria), CNS features e.g. hallucinations, stupor, fits, coma

Rehydrate with Rehydrate with oral Urinary Haemodialysis1 11 22 oral fluids or intravenous fluids alkalinisation11 16 22 + (see box for details) Give sodium bicarbonate (cautious with volume if anuric)

Monitor urine output and Urinary alkalinisation fluid balance carefully Adults: Give 1 of 1.26% sodium bicarbonate with 20 to 40 mmol potassium as an iv infusion over 3 hours. Children: Dilute 1 ml/kg 8.4% sodium bicarbonate in 10 ml/kg sodium chloride solution and add 1 mmol/kg potassium. This should be given at a rate of Repeat salicylate level every 3 hours until a 2 ml/kg/h as an iv infusion. peak concentration is reached Check urinary pH hourly, aiming for a pH of 7.5–8.5; the rate of sodium bicarbonate administration given above will need to be increased if the urine pH remains < 7.5. (this can be as late as 12 hours after ingestion, Check U&E every 3 hours, the serum potassium should be kept in the range 4.0 to 4.5 particularly with enteric coated aspirin)17 18 19

Figure 1 Flowchart for management guidance in salicylate poisoning (numbers in superscripts relate to the supporting references). time are difﬁcult to interpret. It is important to repeat the 500–700 mg/l (moderate toxicity) measurement to make sure the salicylate concentration is not >750 mg/l (severe toxicity) 14 continuing to rise because of continued absorption. In adults The presence of symptoms and signs and the degree of aci- or children, plasma concentrations six hours after an overdose dosis should be considered when interpreting the plasma sali- 215 very roughly correlate with toxicity as follows : cylate concentration and deciding upon management.24 The 300–500 mg/l (mild toxicity) reason that the arterial pH needs to be taken into account

www.emjonline.com 208 Dargan, Wallace, Jones when interpreting a plasma salicylate concentration is that in diuresis has been performed. Nevertheless its use has the the presence of acidaemia, more salicylic acid crosses the advantage of normalising acid base balance and electrolyte Emerg Med J: first published as 10.1136/emj.19.3.206 on 1 May 2002. Downloaded from blood brain barrier resulting in greater CNS toxicity. abnormalities while removing salicylate, without the In mild or early poisoning burning in the mouth, lethargy, thrombocytopenia that frequently accompanies charcoal nausea, vomiting, tinnitus, or dizziness can occur. In moderate haemoperfusion.23 The role of haemofiltration remains un- poisoning all of the above plus tachypnoea, hyperpyrexia, proven in salicylate poisoning. sweating, dehydration, loss of coordination, and restlessness, can occur.216 In severe poisoning hallucinations, stupor, CONCLUSIONS convulsions, cerebral oedema, oliguria, renal failure, cardio- Salicylate poisoning can result in severe morbidity and vascular failure, and coma may be seen together with mortality. It is important that clinicians caring for patients 124 metabolic acidosis. with salicylate poisoning are able to identify patients that are After ingestion of enteric coated tablets, plasma salicylate severely poisoned on the basis of clinical features, metabolic concentrations on admission are unreliable guides to the acidosis and their plasma salicylate concentrations so that 17 severity of poisoning. Salicylate levels may not peak until appropriate treatment can be started. This evidence based 17–19 more than 12 hours after such an overdose. The use of gas- flowchart will guide the clinician step by step through the troscopic and other measures to remove enteric coated tablets management of salicylate poisoning. requires further evaluation in the future. As well as aspirin tablets, other sources of salicylate poisoning include excessive Contributors topical application or ingestion of salicylate containing Paul Dargan was responsible for the literature review and ointments, keratolytic agents or agents containing methylsali- together with Craig Wallace designed the management cylate (for example, oil of wintergreen).20 21 These agents con- flowchart. Alison Jones reviewed the literature review and the tain liquid preparations and many of them are concentrated management flowchart. All these authors were involved in the and lipid soluble and so there is the potential for severe, rapid writing of the paper and all three authors will act as onset salicylate poisoning.21 We would advise that doctors guarantors looking after a patient poisoned with one of these agents con- tact their local poisons centre for advice on treatment...... Authors’ affiliations Methods used to increase the elimination of salicylates P I Dargan, C I Wallace, A L Jones, National Poisons Information The elimination of salicylate may be increased by alkalinisa- Service, Guy’s and St Thomas’ NHS Trust, London, UK tion of the urine (see fig 1 for details).16 There is a 10-fold to Funding: none. 20-fold increase in renal salicylate clearance associated with an increase in urine pH from 5 to 8 and renal excretion of sali- Conflicts of interest: none. cylate depends much more on urine pH than flow rate.16 A urine pH of 7.5 or higher is indicated and careful monitoring REFERENCES of the urine pH is necessary. The pH of blood should not 1 Chapman BJ, Proudfoot AT. Adult salicylate poisoning: deaths and exceed pH 7.55 however. The most common recommendation outcome in patients with high salicylate concentrations. QJMed 1989;72:699–707. is to continue treatment until the plasma salicylate concentra- 2 Proudfoot AT. Toxicity of salicylates. Am J Med 1983;75:99–103. tion decreases to the therapeutic range but cessation of the 3 McGuigan MA. A two-year review of salicylate deaths in Ontario. Arch http://emj.bmj.com/ patient’s symptoms are also a crucial factor in the decision to Intern Med 1987;147:510–12. 4 Thisted B,KrantzT,StroomJ,et al. Acute salicylate self-poisoning in discontinue alkalinisation. Although it is prudent to adminis- 177 consecutive patients treated in ICU. Acta Anaesthesiol Scand ter supplemental potassium to hypokalaemic patients, it is 1987;31:312–16. inappropriate to delay the administration of sodium bicarbo- 5 Danel V, Henry JA, Glucksman E. Activated charcoal, emesis, and gastric lavage in aspirin overdose. BMJ (Clin Res Ed) 1988;296:1507. nate solution until normokalaemia is achieved. Forced diure- 6 American Academy of Clinical Toxicology; European Association of sis alone has little effect and is potentially harmful because of Poison Control Centres and Clinical Toxicologists. Position statement: the potential for pulmonary oedema, hypernatraemia, and single dose activated charcoal. J Toxicol Clin Toxicol 1997;35:721–41.

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