187 ANTIDOTES FOR POISONS Lipid emulsion (Intralipid ) therapy for drug toxicity IV lipid emulsion is rarely neede d but can be lifesaving in overdoses of local anesthetics such as lidocaine or bupivacaine ( b p.284). 1 , 2 , 3 It may be useful in cardiac arrest caused by some other drugs: the in di- cations are unclear but case reports record dramatic recovery from cardiac arrests due to haloperidol, verapamil, and a mixed overdose of bupropion and lamotrigine. 1 , 2 In anim als, 2 lipid emulsion was effective in poisoning from verapamil (but not nifedipine) and cl omipramine (but not amitriptyline). Consider lipid emulsion in drug-induced cardiac arrest unresponsive to standard treatment ( b p.50). EDs, theaters, and ICU should stock lipid emu lsion for this emergency. Lipid emulsion acts as a \200\230lipid sink \200\231, binding li pophilic drugs and reducing the amount of active free drug. It may also affect myocardial m etabolism. Lipid emulsion is not licensed for use in drug overdose and the safety of rapid infusion is unknown. Lipid interferes with analysis of blood samples, so if possible take t hese before starting lipid emulsion, including blood for later measurement of drug concentr ations. Give Intralipid 20 % 1.5mL/kg IV over 1min, then 15mL/kg/hr by intrave- nous inf usion (IVI) (for a 70kg patient give 100mL over 1min, then 500mL over 30min). Continue CPR. If the circulation is still inadequate after 5min repeat IV bolus of Intralipid 1.5mL/k g twice at 5min intervals and increase IVI to 30mL/kg/hr (500mL in 15min for 70kg). The max imum recommended total dose of Intralipid 20 % is 12mL/kg (840mL for a 70kg patient). 3 Report cases in which lipid emulsion is used to the Poisons Information Service ( b p.181) or the Lipid Registry ( http://www.lipidregistry.org ). Insulin therapy in poisoning Poison ing with cardiac drugs such as calcium channel blockers (b p.198) and B -blockers (b p.198) may cause severe hypotension. If standard treat- ments are ineffective, get expert advice (b p.181) and consider using insulin therapy, which may improve myocardial carbohydrate met abolism and i BP and cardiac output. Some case reports and animal studies of severe calcium channel blocker and B -blocker poisoning have shown bene \201 ts from high dose insulin, but the optimum dosage is unclear. 4 , 5 Continuous monitoring is needed, with invasive BP monitoring. Check blood glucose and potassium at least hourly and give glucose 10 % and pot assium (max 20mmol/hr) as needed. Give an IV bolus of short-acting insulin 1 unit/ kg, then 0.5 \200\2232units/kg/hr IVI, titrated to keep systolic BP > 90mmHg and heart rate > 60/mi n. In extreme cases, consider increasing insulin dosage to 5 \200\22310units/kg/hr, titrate d according to response. 1 http://lipidrescue.squarespace.com 2 Jamaty C et al . ( 2010 ) Lipid emulsions in the tre atment of acute poisoning: a systematic review of human and animal studies . Clin Toxicol 48 : 1 \200\223 27 . 3 Association of Anesthetists of Great Britain and Ireland ( 2010 ) Management of Severe Lo cal Anesthetic Toxicity . Available at: http://www.aagbi.org/publications/guidelines.htm 4 Lheureux PER et al . ( 2006 ) Bench-to-bedside review: Hyperinsulinaemia/euglycaemia ther apy in the management of overdose of calcium-channel blockers . Critical Care 10 : 212 . Availa ble at: http://ccforum.com/content/10/3/212 5 Nickson CP , Little M ( 2009 ) Early use of high-dose insulin euglycaemic therapy for ver apamil toxicity . Med J Aust 191 ( 6 ) : 350 \200\223 2 . 188 CHAPTER 4 Toxicology Opioid poisoning The opioids include morphine, diamorphine (heroin), pethidine, codeine, bu prenorphine, nalbuphine, methadone, diphenoxylate, and related drugs. These are used as ana lgesics (sometimes combined with paracetamol, as in co-codamol and co-proxamol), cough supp ressants and anti-diarrhoeal agents. Acute opioid poisoning often occurs in addicts (who ma y have needle marks and thrombosed veins and a high risk of HIV and hepatitis). Clinical features Opioid poisoning causes coma, d respiratory rate, pinpoint pupils, and so metimes cyanosis, apnoea, convulsions and hypotension. Hypertension may occur in pentazocin e poisoning. Non-cardiogenic pulmonary oedema may result from \200\230main-lining \200\231 heroin or other opioids. Respiratory depression may cause death within 1hr of an opioid overdose. However, delayed r espiratory depression can occur in poisoning with co-phenotrope (diphenoxylate and atropine ), in which the opioid effects usually predominate over atropine toxicity. Delayed toxicity may occur with slow-release formulations of drugs, and also with methadone, which has a ve ry long duration of action (half-life 25 \200\22350hr). Treatment Clear and maintain the airway. If breathing appears inadequate, ventilate on O 2 with a bag and mask or ET tube. Naloxone is a speci \201 c antago- nist for opioids and re verses coma and respiratory depression if given in suf \201 cient dosage. Naloxone may be used as a therapeutic trial in sus- pected opioid poisoning: record coma level, pupil size and respiratory rate and check for any response. The usual initial dose of naloxone for adu lts is 0.8mg IV, repeated at 2 \200\2233min intervals if necessary. However, in known or su spected drug addicts it is best to avoid reversing the opioid completely, so start with 0.1 mg IV (or intranasal, if there is no venous access) and repeat this at 2 \200\2233min inter vals until the patient is breathing adequately, but still drowsy. For children, give 10 mic rograms/kg (IV, IM or IN), repeated as necessary. Intranasal naloxone is given by dripping or spraying the IV solution into the nose, where it is absorbed rapidly. Naloxone has a much shorter duration of action than most opioids and so coma and respirator y depression often recur when naloxone wears off. The mean half-life of naloxone is 62min, but in some patients the half-life is > 5hr. Careful observation is essential. More naloxon e is often needed, given IV, by IVI or IM, the dose adjusted depending on the response (occ asionally as much as 75mg in 24hr in methadone poisoning). Observation is needed for 6hr af ter the last dose of naloxone. Patients at risk of respiratory depression should not be all owed to leave hospital: rather than reversing an opioid fully it is better to keep a patien t sedated but safe by constant observation and titration of naloxone. A patient who insists on leaving could be given naloxone IM, but will still be at risk of fatal respiratory depr ession. In opioid addicts, naloxone may precipitate a withdrawal syndrome with abdominal cr amps, nausea and diarrhea, but these usually settle within 2hr. Ventricular tachyarrhythmia s occur occasionally. 189 SALICYLATE POISONING Salicylate poisoning Standard aspirin tablets contain 300mg acetylsalicylic acid. Ingestion of 150mg/kg body weight usually produces mild toxicity; 500mg/kg will cause severe and pos sibly fatal poisoning. Poisoning can result from absorption of salicylate ointment through the skin. Clinical features Commonly vomiting, tinnitus, deafness, sweating, vasodilatation, hyperven - tilation, and dehydration. Hypokalaemia may occur. Severe poisoning may produce confusion, coma, and convulsions. Children are prone to develop hyperpyrexia and hypoglycaemia. Rare features include non-cardiogenic pulmonary oedema, cerebral oedema, and renal failure. Metabolic and acid-base disturbances These may be complex: adults usually have a mixed meta bolic acidosis and respiratory alkalosis, but the respiratory effects predominate. In small children and a few adults, acidosis predominates, and is often associated with confusion o r coma. Management Consider gastric lavage if a patient has ingested > 500mg/kg body weight in the previous 1hr. After ingestion of > 4.5g (or 2g in a child) give 50g activated charcoal (25g in a child) to d absorption and i elimination of salicylate. Measure plasma salicylate con centration (and repeat after a few hours if further symptoms occur, since salicylate level may i due to continuing absorption). Check U&E, glucose, and ABG if there are CNS features or signs of severe poisoning. A second dose of charcoal may be useful if the plasma salicyl ate increases, suggesting delayed gastric emptying, or if enteric-coated tablets have been taken. Mild poisoning Children with plasma salicylate <350mg/L (2.5mmol/L) and adults with <450mg/ L (3.3mmol/L) usually need only i oral \202 uids. Moderate poisoning Children with salicy late > 350mg/L and adults with > 450mg/L need IV \202 uids to correct dehydration and i e limination of salicylate: sodium bicarbonate 1.26 % (adults 500mL hourly for 3hr) alkaliniz es the urine (which is much more effective than a massive diuresis in i salicylate excretio n). Urine pH should be > 7.5, ideally 8.0 \200\2238.5. Repeat salicylate level, check U&E a nd add K + as necessary. Severe poisoning CNS features, acidosis or salicylate > 700mg/L (5.1mmol/L) are associated with signi \201 cant mortality. Get expert advice ( b p.181) and consider urgent referral for haemodialysis. Correct acidosis and give repeated activated charcoal via a NG tube. In life-threatening poisoning with coma and extreme hyperventilation, paralysis and IPPV may h elp, while haemodialysis removes salicylate and corrects the electrolyte disturbances. Give glucose IV, since brain glucose levels may be low despite normal blood glucose concentrati ons. Do not use forced diuresis, which is ineffective and may cause pulmonary oedema. 190 CHAPTER 4 Toxicology Paracetamol poisoning Paracetamol ( \200\230acetaminophen \200\231 in USA) may cause severe liver damage if 12g (24 tablets) or > 150mg paracetamol/kg body weight are taken. Some pat ients have risk factors for enhanced toxicity (see below) and may be at risk if > 75mg/kg h as been taken. In obese patients ( > 110kg) calculate the toxic dose in mg/kg, and the dose of acetylcyste ine, using a weight of 110kg, rather than the patient \200\231s actual weight. A metabolite of paracetamol (N-acetyl-p-benzoquinoneimine, NAPQI) binds glutathione in the liver and causes hepatic necrosis when stores of glutathione are exhausted. Renal failure f rom acute tubular necrosis occurs occasionally, but renal failure without liver failure is rare. Risk factors for paracetamol toxicity Alcoholics and patients on drugs that induce hepatic enzymes are at greater risk of toxicity, because of i production of the toxic metabolite of paracetamol. The relevant drugs are anticonvulsants, rifampicin, and St John \200\231s wor t. Patients with malnutrition, anorexia, cachexia, HIV infection or cystic \201 brosis may h ave d glutathione stores and be at i risk of liver damage. Clinical features Nausea, vomiting and abdominal discomfort are common within a few hours. In untreated patients developing liver damage, vomiting continues beyond 12hr and there is pain and tenderness over the liver (from 24hr), jaundice (at 2 \200\2234 days), and sometim es coma from hypoglycaemia (at 1 \200\2233 days) and hepatic encephalopathy (onset at 3 \200\2235 days). Loin pain, haematuria and proteinuria suggest incipient renal failure. Hep atic failure causes bleeding from coagulation abnormalities and hyperventilation from metab olic acidosis. In fatal cases cerebral oedema, septicaemia and DIC are common. However, man y patients survive severe liver damage and recover completely. LFTs are normal until > 18hr after the overdose. The most sensitive lab evidence of liver d amage is often a prolonged INR (from 24hr after overdose). Liver enzymes (ALT and AST) may reach > 10,000units/L at 3 \200\2234 days. Bilirubin rises more slowly (max at about 5 days ). Paracetamol antidotes Acetylcysteine (Parvolex ; previously called N-acetylcysteine) is given by IV infusion in 5 % glucose. Initial dose is 150mg/kg body weight in 200mL glucose over 15min, 50mg/kg in 500mL over 4hr, then 100mg/kg in 1L over 16hr. Acetylcysteine can ca use side effects (which are more likely if the plasma paracetamol level is low) \200\224 e rythema and urticaria around the infusion site or more generalized rashes, itching, nausea, angioedema, bronchospasm, and rarely hypotension or hypertension. Side effects are dose re lated and usually start in the \201 rst hour of treatment. If they occur, stop the infusi on and give an antihistamine (eg chlorphenamine 10mg IV over 1min). When symptoms have sett led, acetylcysteine can usually be resumed at the lowest infusion rate (100mg/kg body weigh t over 16hr). 191 PARACETAMOL POISONING Methionine is rarely needed but may be useful in patients who refuse IV treatment or if ace tylcsteine is not available. Methionine is given orally as capsules or tablets, 2.5g every 4hr to a total of 10g. Methionine has no signi \201 cant adverse effects. It is less effec tive than acetylcysteine in patients who are vomiting or who present > 8hr after ingestion. Methionine may be ineffective in patients treated with activated charcoal. Children Serious paracetamol poisoning is rare in children. Young children rarely take larg e amounts of paracetamol, and they metabolize it differently from adults and may have less risk of hepatotoxicity. However, there is no data for assessing the risk in children, so us e the same treatment guidelines as for adults. If it is certain that <150mg/kg has been tak en (or <75mg/kg if there are risk factors for toxicity: see b p.190, then no investigation or treatment is needed and the child may be discharged. Treatment with acetylcysteine is ra rely needed in children. Doses are as for adults (opposite), but with smaller volumes of \202 uid for IV infusion. Pregnancy Assess the risk of toxicity and treat as for non-pregnant patients. Acetylcystein e and methionine do not seem to carry any risk to the fetus, and may protect the fetal live r from damage. Paracetamol overdose does not appear to cause teratogenic effects. Staggered overdoses If the patient took two or more paracetamol overdoses in a day assess t he risk by plotting on the treatment graph the time interval since the \201 rst dose. For overdoses taken over several days the graph cannot be used. If the patient has symptoms of toxicity or the amount taken was > 150mg/kg (75mg/kg in high risk groups) take blood for I NR, LFTs, U&E and paracetamol (which may con \201 rm that some was taken, even if the trea tment graph cannot be used), and treat with acetylcysteine. If in doubt start treatment and get expert advice. Outcome of treatment Treatment with acetylcysteine or methionine within 8hr of an overdose is very effective in preventing liver and renal damage. Later treatment is less effective, but still worthwhile. Late presentation after paracetamol poisoning Patients who present late are more likely to be severely poisoned than those who present soon after ingestion. Late presenters often hav e con- tinuing vomiting and abdominal pain, which are symptoms of liver damage. The treatme nt graph ( b p.193) may be unreliable at > 15hr, because of insuf \201 cient data on untre ated patients. Liver transplantation Liver transplantation is occasionally needed for hepatic failure due to para- cetamol overdose in patients who presented or were treated late. Appropriate patie nts must be identi \201 ed and referred to a liver transplant unit as soon as possible. Tr ansplant criteria include arterial pH <7.30 (H + > 50nmol/L) after resuscitation, or PT > 1 00 seconds (INR > 6.7) and creatinine > 300micromol/L in patients with grade 3 or 4 hepatic encephalopathy. 192 CHAPTER 4 Toxicology Management of paracetamol poisoning The time since ingestion is crucial in interpreting par acetamol concentra- tions and assessing the need for speci \201 c treatment. Record the ti me of ingestion as accurately as possible. When taking blood for paracetamol levels record the precise time in the notes and on blood bottles and forms. Start treatment immediately i f the time of ingestion is unknown. Management within 4 hours of ingestion Consider activat ed charcoal ( b p.185) if > 12g or 150mg/kg paracetamol has been taken in the previous 1hr. Take blood at 4 hr from ingestion and use graph (Fig. 4.1 ) to assess risk of liver damage : use line A for most patients; line B for high risk patients. If the result is above the r elevant line, give IV acetylcysteine or oral methionine (see b p.190). Management at 4 \200 \2238 hours from ingestion Measure paracetamol and use the graph to assess risk of liver da mage: for most patients use line A, for high risk patients use line B. If above the relevan t line, or only just below it, give IV acetylcysteine or oral methio- nine (for doses see b p.190). Treatment is most effective if started before 8 hours: start it at once if paracet amol level is not available by this time and > 150mg/kg has been taken. Patients treated wi th acetylcysteine or methionine within 8 hours of an overdose should be medically \201 t for dis- charge at the end of the treatment course. Management at 8 \200\22315 hours from i ngestion Urgent action is needed: start treatment with IV acetylcysteine immedi- ately if > 150mg/kg or 12g paracetamol have been taken. Measure plasma paracetamol and use the graph to assess the risk of liver damage: for most patients use line A; for high risk patients us e line B. If the paracetamol level is well below the line and patient is asymptomatic, stop acetylcysteine treat- ment. Continue acetylcysteine if level is above the relevant line, i f there is doubt about the time of ingestion or if the patient has nausea or vomiting. At t he end of acetylcysteine treatment check INR and plasma creatinine: if these are normal and the patient asymptomatic he/she is medically \201 t for discharge. Management at 15 \200 \22324 hours from ingestion Urgent action is needed: give IV acetylcysteine immediately if > 150mg/kg or > 12g paracetamol have been taken. Measure plasma paracetamol, cre- atinine a nd INR. If at 24hr after ingestion a patient is asymptomatic, with normal INR, normal creat inine, and plasma paracetamol <10mg/L he/she may be discharged. Other patients need continu ing monitoring and possibly further treatment with acetylcysteine. Management at > 24 hours from ingestion Measure paracetamol, LFTs, U&E, creatinine, INR, and ABG. Start treat- ment with IV acetylcysteine if > 150mg/kg or 12g paracetamol have been taken, investigations ar e abnormal or patient is symptomatic. Seek expert advice from Poisons Information Service ( b p.181) or liver unit. 193 PARACETAMOL POISONING Plasma paracetamol (mg/L) Plasma paracetamol (mmol/L) 200 1.3 190 1.2 180 170 1.1 160 1.0 150 A Normal treatment line 140 0.9 130 0.8 120 110 0.7 100 0.6 90 80 0.5 70 0.4 60 50 0.3 40 0.2 30 20 B High risk treatment line 0.1 10 0 0 0 1 2 3 4 5 6 87 12 16 Hours after ingestion 9 10 14 18 20 22 24 Fig. 4.1 Paracetamol treatment graph. Normal treatment line A for most patients. High risk treatment line B for patients with chronic alcoholism, malnutrition, anorexia, ca chexia, HIV infection, or cystic \201 brosis, or taking anticonvulsants, rifampicin or St John \200\231s wort. Note Check whether the laboratory reports paracetamol in mg/L or mmol/L. Start treatment at once if in doubt about the time of the overdose, or if the plasma paracetamol is only just below the relevant treatment line. 194 CHAPTER 4 Toxicology Tricyclic antidepressant poisoning Anticholinergic poisoning is usually caused by an overdo se of tricyclic anti- depressants, but may result from other drugs, eg procyclidine or atro pine (present in Atropa belladonna , \200\230deadly nightshade \200\231). Clinical features Common features are tachycardia, dry skin, dry mouth, dilated pupils, uri nary retention, ataxia, jerky limb movements, and drowsiness leading to coma. Unconscious p atients often have a divergent squint, i muscle tone and re \202 exes, myoclonus and exten sor plantar responses. The pupils may be dilated and unreactive. In deep coma there may be muscle \202 accidity with no detectable re \202 exes and respiratory depression requirin g IPPV. Convulsions occur in 810 % of unconscious patients and may precipitate cardiac arre st. Patients recovering from coma often suffer delirium and hallucinations and have jerky l imb movements and severe dysarthria. ECG changes Sinus tachycardia is usual, but as poisoning worsens PR interval and QRS durati on i . These changes help to con \201 rm a clinical diagnosis of tricyclic poisoning in an unconscious patient. The P wave may be superimposed on the preceding T wave, so the rhythm can look like VT when it is actually sinus tachycardia with prolonged conduction. In very severe poisoning, ventricular arrhythmias and bradycardia may occur, especially in hypoxic patients. Death may follow cardio-respiratory depression and acidosis. Management \200 Clear airway, intubate and ventilate if necessary, and give nursing care. \200 Observe continuously, in view of the potential for rapid deterioration. \200 Moni tor ECG and check ABG in unconscious or post-ictal patients. \200 Give activated charcoal by mouth or gastric tube if more than 4mg/kg has been taken within 1hr and the airway is s afe or can be protected. \200 Do not give anticonvulsants for single brief \201 ts, but give lorazepam or diazepam IV if \201 ts are frequent or prolonged. Most arrhythmias occur in unconscious patients within a few hours of overdose. Treat arrhyt hmias by correcting hypoxia and acidosis. Sodium bicarbonate (8.4 % , adult: 50 \200\223100 mL IV; child: 1mL/kg) may dramatically improve cardiac rhythm and output (by altering prote in binding and d active free tricyclic drug). Consider further bicarbonate, depending on th e clinical response, ECG and arterial pH. Aim for pH 7.5 \200\2237.55, avoiding excessive a lkalosis (pH > 7.65), which may be fatal. Avoid anti-arrhythmic drugs. If arrhythmias do not respond to bicarbo- nate, discuss with a poisons specialist ( b p.181). Correct hypotension by elevating the foot of the trolley and giving IV \202 uids. Glucago n may help in severe hypotension ( b p.198). Dopamine (2 \200\22310micrograms/kg/min) is oc casionally indicated for unresponsive hypotension on specialist advice. Consider Intralipid ( b p.187) for severe arrhythmias or cardiac arrest. \200 Do not u se physostigmine or \202 umazenil (risk of precipitating \201 ts). \200 Unconscious p atients usually improve over about 12hr and regain con- sciousness within 36hr. Delirium an d hallucinations may persist for 2 \200\2233 days and require sedation with oral diazepam i n large doses (sometimes 20 \200\22330mg PO every 2hr initially). 195 TRICYCLIC ANTIDEPRESSANT POISONING ECG changes in tricyclic antidepressant poisoning I V1 aVR V4 II V2 aVL V5 aVF III V3 V6 Fig. 4.2 ECG in tricyclic antidepressant poisoning, showing sinus tachycardia with prolonge d conduction, which may be mistaken for VT. 1 am 4 am 9.30 am 1 second Fig. 4.3 Serial ECG rhythm strips in amitriptyline poisoning, showing spontaneous recovery with supportive care. 1 second Fig. 4.4 ECG trace in very severe tricyclic antidepressant poisoning. The patient was uncon scious, GCS 3, and was intubated and ventilated, with BP 70/50. 196 CHAPTER 4 Toxicology Benzodiazepine poisoning Benzodiazepine drugs (eg diazepam, nitrazepam, and temazepam) rare ly cause serious poisoning when taken alone in overdose. However, they potentiate the effec ts of other CNS depressants, such as alcohol, tricyclic antidepressants and barbiturates. C linical features Drowsiness, dizziness, ataxia, dysarthria. Rarely, coma, respiratory depre s- sion, mild hypotension. Fatal poisoning is unusual, but may occur from respiratory depre ssion in elderly patients and those with chronic COPD. Management Clear the airway and main tain ventilation if necessary. Provide supportive care. Gastric lavage and activated charco al are not indicated if only a benzodiazepine has been taken. Many benzodiazepines have lon g-acting metabolites, which may affect driving and other motor skills for several days or e ven weeks after an overdose. Give appropriate warnings about this. Flumazenil is a speci \201 c benzodiazepine antagonist, but is not licensed in the UK for treating overdosage. It reverses the effects of benzodiazepines within 1min, but has a short duration of action (< 1hr) \200\224 as a result, toxic effects often recur. Flumazenil can cause convulsions and cardiac arrhythmias and may precipitate a withdrawal syndrome in patients who are dependen t on benzodiazepines. It is particularly dangerous in patients with combined benzodiazepine and tricyclic antidepressant poisoning, in whom it may cause convulsions and cardiac arres t. Flumazenil may occasionally be used by experts managing very severe benzodiazepine poiso ning, but there is no place for its use by the non-specialist. Clomethiazole poisoning Clomethiazole overdosage may cause coma, respiratory depression, d muscle tone, hypotension and hypothermia. Excessive salivation and a characteristic smell o f clomethiazole on the breath are often noticeable. Treat supportively. IPPV may be necessa ry. Phenothiazine poisoning The phenothiazines (eg chlorpromazine), butyrophenones (eg haloperi dol), and related drugs are used as antipsychotics and anti-emetics. In over- dosage they m ay cause drowsiness, coma, hypotension, and hypothermia. Deep coma and respiratory depressi on are uncommon. Some conscious patients suffer dystonic reactions with oculogyric crises a nd muscle spasms causing torticollis or opisthotonus. Convulsions may occur. ECG changes of prolonged PR, QRS, and ST intervals, and arrhythmias are seen particularly with thioridazi ne poisoning. Treat supportively. Activated charcoal may help. If cardiac arrhythmias occur , correct hypoxia, acidosis and electrolyte abnormalities before giving any anti-arrhythmic drug. Treat dystonic reactions with procyclidine (5mg IV or 5 \200\22310mg IM), repeated i f symptoms recur. 197 SULPHONYLUREA POISONING Barbiturate poisoning Now uncommon, except in drug addicts. Overdosage with phenobarbitone is seen occasionally. Barbiturate poisoning may cause coma, respiratory depression, hypoten sion and hypothermia. There are no speci \201 c neuro- logical signs. Skin blisters and rh abdomyolysis may result from prolonged immobility. Treat supportively, with IPPV if necessa ry. Repeated doses of activated charcoal may help to remove barbiturates. Very rarely, char coal haemoperfusion is indicated in some patients with deep and prolonged coma and respirat ory complications. Lithium poisoning Clinical features Often due to therapeutic overdosage or drug interac- ti ons (eg with diuretics or NSAIDs), rather than deliberate self-harm. Symptoms may start up to 24hr after an overdose, especially with slow- release tablets. Nausea, vomiting and diar rhea are followed by tremor, ataxia, confusion, increased muscle tone and clonus. In severe cases there may be convulsions, coma and renal failure. Lithium-induced nephrogenic diabet es insipidus may complicate treatment. Investigations Measure U&E and lithium (plain tube, not lithium heparin). Therapeutic lithium levels are <1.2mmol/L. Toxic effects are often se en at > 1.5mmol/L. Soon after a large overdose, higher levels may occur with little clinica l effects, before lithium is distributed to tissues. Management Activated charcoal does not absorb lithium. Gastric lavage is indicated within 1hr of a single large overdose, except for slow- release tablets, which are too large to pass up a gastric tube. Whole- bowel irri gation ( b p.185) may be considered for slow-release tablets: discuss this with a poisons s pecialist ( b p.181). Use standard supportive measures and control convulsions with diazepa m. Observe all patients for > 24 hours. Give oral \202 uids in conscious patients. Forced diuresis is contraindicated. Haemodialysis is the best treatment in severe poisoning, but often has to be repeated because of rebound release of lithium from tissue stores. Sulphonylurea poisoning Sulphonylurea drugs are used to treat non-insulin-dependent diabete s. Accidental or deliberate overdosage causes hypoglycaemia, which may recur over several d ays after long-acting drugs, such as chlorpropamide or glibenclamide. In the Far East, sulp honylurea contamination of illicit drugs used for erectile dysfunction has caused several c ases of hypoglycaemia. Check blood glucose and U&E. Correct hypoglycaemia with oral or IV g lucose ( b p.150). Observe for at least 24hr (72hr for long-acting drugs) and check BMG hou rly. To prevent recurrent hypoglycaemia give 10 % glucose IV infusion; in severe cases 20 % glucose may be needed, via central line because of venous irritation. Hypokalaemia may occ ur. Check U&E and add potassium as needed. In severe poisoning, get expert advice ( b p.181 ) and consider octreotide (unlicensed indication) which blocks pancreatic insulin release: initial dose for adults 50micrograms subcutaneous (SC) or IV. 198 CHAPTER 4 Toxicology Beta-blocker poisoning Clinical features Overdosage with B -blockers (propranolol, oxprenol ol, atenolol, labetolol, sotalol) may cause rapid and severe toxicity with hypotension and cardio- genic shock. There is usually a sinus bradycardia, but sometimes the heart rate rem ains normal. Coma, convulsions, and cardiac arrest may occur. ECG changes include marked QR S prolongation, and ST and T wave abnormalities. Propranolol may cause bronchospasm in asth matics and hypoglycaemia in children. Sotalol can cause prolonged QTc and VT, with torsades de pointes. Management Monitor ECG, heart rate, and BP. Obtain reliable venous access. Check U&E and bl ood glucose. Consider activated charcoal ( b p.185). Bradycardia and hypotension may respon d to atropine (1 \200\2232mg for adult; 0.02mg/kg for child), but this is often ineffective . Glucagon is the best treatment for severe cardiotoxicity and seems to work by activating myocardial adenylcyclase in a way not blocked by B -blockade. Glucagon 5 \200\22310mg IV (5 0 \200\223150micrograms/kg for a child) usually produces a dramatic improvement in pulse an d BP, with return of cardiac output and consciousness. Glucagon often causes sudden vomitin g \200\224 anticipate this and position the patient appropriately. In severe poisoning glu cagon has a transient effect on cardiac output and further doses or an infusion are needed (4mg/hr, sometimes up to 15mg/hr, reducing gradually). Some patients need a total of 50 \200\22375mg of glucagon, which is reconstituted from 1mg vials of dry powder. If glucagon is unavailable or ineffective, give adrenaline (5 \200\22310micrograms/min) or dobutamine ( 2.5 \200\22310micrograms/kg/min), increasing the dose if necessary. Get expert advice ( b p .181) in severe poisoning. Cardiac pacing may be tried for bradycardia, but is often ineffective. Occasionally, circul atory support has to be provided by prolonged chest compressions or extracorporeal cardiac bypass while more glucagon is obtained or the B -blocker is metabolized. Consider insulin t herapy ( b p.187) for severe hypotension, and Intralipid ( b p.187) in cardiac arrest. Calcium antagonist poisoning Poisoning with verapamil, nifedipine, diltiazem or other calci um-channel blockers is rare, but may be fatal. Nausea, vomiting, dizziness and confusion ma y occur. Bradycardia and AV block may lead to AV dissociation, with hypotension and cardiac arrest (especially in patients taking B -adrenergic blockers). Metabolic acidosis, hyperka laemia and hyperglycaemia may occur. Provide supportive treatment. Monitor ECG and BP. Obta in venous access. Consider activated charcoal. Check U&E, glucose, calcium. Give atropine ( 1 \200\2232mg, child 0.02mg/kg) for symptomatic bradycardia. Get expert help. Pacing may be needed. Calcium gluconate (10 \200\22320mL of 10 % slowly IV, observing ECG) may d prolong ed intra-cardiac conduction. Glucagon may help, as in B -blocker poisoning (see above). Ino tropic support with dobutamine, adrenaline or high dose insulin therapy (b p.187) may be ne eded to maintain cardiac output. In severe poisoning or cardiac arrest consider Intralipid ( b p.187). 199 ACE INHIBITOR POISONING Digoxin poisoning Toxicity from the therapeutic use of digoxin is relatively common. Acute poisoning is rare, but may be fatal. Similar effects occur with digitoxin and very rarely w ith plants containing cardiac glycosides (foxglove, oleander and yew). Clinical features Nausea, vomiting, malaise, delirium, xanthopsia (yellow \202 ashes or d iscolouration of vision). Acute poisoning usually causes bradycardia with PR and QRS prolon gation. There may be AV block, AV disso- ciation and escape rhythms, sometimes with ventric ular ectopics or VT. Hyperkalaemia occurs, and in severe cases metabolic acidosis due to hy potension and d tissue perfusion. Management Provide supportive treatment. Monitor ECG and BP. Obtain venous access. Give act ivated charcoal to d absorption and prevent entero-hepatic recycling of digoxin ( b p.185). Measure U&E, plasma digoxin, and ABG in severe poisoning. Get expert help for patients who are severely poisoned. Correct severe metabolic acidosis with sodium bicarbonate. Treat hy per- kalaemia > 6mmol/L ( b p.162). Bradycardia and AV block often respond to atropine IV t otal 1 \200\2232mg (child 0.02mg/kg). Cardiac pacing is not always effective and a high vol tage is often needed for capture. VT may respond to lidocaine or a B -blocker. Treat severe poisoning with digoxin anti- bodies (Digibind ), which rapidly correct arrhythmias and hyperkalaemia. Digibind is expensive and rarely needed, so is not stocked in many hospi- tals: Poisons Information Services (b p.181) can advise about emergency supplies and the d ose required for the patient \200\231s body weight and plasma digoxin concentration or the quantity taken. ACE inhibitor poisoning Overdosage with angiotensin converting enzyme (ACE) inhibitors (eg captopril, enalapril, lisinopril) may cause drowsiness, hypotension, hyperkalaemia and rare ly, renal failure. Monitor BP and ECG. Give IV 0.9 % saline if BP is low. Check U&E. Consid er activated charcoal ( b p.185). 200 CHAPTER 4 Toxicology Theophylline poisoning Theophylline and aminophylline can cause fatal poisoning. Many prepa rations are slow-release and may not produce serious toxicity until 12 \200\22324 hours aft er ingestion, so careful observation is essential. Features Nausea, vomiting (often severe and not helped by anti-emetics), abdominal pain, haematemesis, restlessness, i muscle tone, i re \202 exes, headache, convulsions. Coma, hyperventilation, hyperpyrexia and rhabdomyo lysis may occur. Sinus tachycardia may be followed by supraventricular and ventricular arrh ythmias and VF. BP may initially i , but later d in severe poisoning. Complex metabolic dis turbances include a respiratory alkalosis followed by metabolic acidosis, hyperglycaemia, a nd severe hypokalaemia. Management \200 Treat supportively. \200 Monitor ECG, heart rat e and BP. \200 Obtain venous access and measure U&E, glucose, ABG, plasma theo- phylline (repeated after a few hours). Repeat K + hourly if patient is symptomatic, since early corr ection of hypokalaemia may prevent dan- gerous arrhythmias. Correct hypokalaemia with K + ( large amounts may be needed, but no faster than 20mmol/hr). Perform gastric lavage if <1hr since ingestion. Give repeated activated charcoal ( b p.185), by NG tube if necessary. Intractable vomiting may respond to ondansetron (8mg slowly IV in adult). \200 GI bleedin g may require transfusion and ranitidine (but not cimetidine, which slows metabolism of theophylline). Tachycardia with an adequate cardiac output should be observed, but not treated. Non-select ive B -blockers (eg propranolol) may help severe tachyarrhythmias and hypokalaemia, but cau se bronchospasm in asth- matics. Lidocaine and mexiletine may precipitate \201 ts, so dis opyramide is preferable for ventricular arrhythmias. Control convulsions with diazepam or lorazepam. Paralyze, intubate, and provide IPPV if the airway is at risk from coma, \201 ts and vomiting. \200 Charcoal haemoperfusion may be needed in severe poisoning, especially if oral or NG activated charcoal is impracticable b ecause of vomiting. Serious hyperkalaemia may occur during recovery from theophylline poiso ning if large amounts of K + were given earlier. Salbutamol poisoning B 2 -agonists (eg salbutamol, terbutaline) may cause Poisoning with vo miting, agitation, tremor, tachycardia, palpitations, hypokalaemia and hypertension. Rarely , there may be hallucinations, hyperglycaemia, ventricular tachyarrhythmias, myocardial isc haemia, and convulsions. Treat supportively: \200 Correct hypokalaemia by infusion of K + (max 20 mmol/hour). \200 Monitor ECG and BP. \200 Activated charcoal may d drug absorp tion. \200 Do not treat tachycardia if there is an adequate cardiac output. Propranolol m ay help severe tachyarrhythmias and hypokalaemia, but can precipitate bronchospasm in asthm atics. 201 IRON POISONING Iron poisoning Small children often eat iron tablets, many of which resemble sweets. Seriou s poisoning is uncommon, but fatalities can occur. Note that iron is present in some weed/s eed preparations. Different preparations contain the equivalent of 35 \200\223110mg of elemental iron per tab let, sometimes in slow-release form. Serious toxicity is unlikely unless > 60mg elemental iron/kg body weight has been taken. Th e estimated lethal dose is about 150 \200\223300mg/kg. Features In the \201 rst few hours after ingestion nausea, vomiting, diarrhea and abdomin al pain are common. Vomit and stools are often gray or black and may contain blood. Hypergl ycaemia and i WCC may occur. Most patients do not develop further features. In severe poisoning, early effects include haematemesis, drowsiness, convulsions, coma, met abolic acidosis and shock. Early symptoms settle after 6 \200\22312hr, but a few patients then deteriorate 24 \200\223 48hr after ingestion, with shock, hypoglycaemia, jaundice, metabolic acidosis, hepatic ence phalopathy, renal failure, and occasionally bowel infarction. Survivors may develop gastric strictures or pyloric obstruction 2 \200\2235 weeks after the overdose. Management \200 Check serum iron, FBC, glucose, and also ABG in severe poisoning. \200 Perform gastric lavage if > 20mg elemental iron/kg body weight has been taken in the previo us 1hr. Do not give charcoal, which does not absorb iron. Iron tablets are radio-opaque and can be counted on a plain abdominal X-ray \201 lm. Whole-bowel irrigation ( b p.185) may be useful if many tablets remain in the gut, especially with slow-release formulations. Use supportive measures if required. \200 Obtain expert advice in serious poisoning. Coma and shock indicate severe poisoning needing immediate treatment with desferrioxamine by IV infusion (15mg/kg/hr, max 80mg/kg in 24hr). Desferrioxamine should also be given if the se rum iron exceeds the expected total iron binding capacity (about 54 \200\22375mmol/L): meas urement of total iron binding capacity may give misleading results after iron poisoning. De sferrioxamine causes hypotension if infused too rapidly and can produce rashes and rarely, anaphylaxis, pulmonary oedema or ARDS. The iron-desferrioxamine complex makes the urine ora nge or red, which con \201 rms that free iron has been bound and that desferrioxamine was required. Reduce desferrioxamine dosage when there is clinical improvement and serum iron i s less than the expected total iron binding capacity.