transfusion. If there is ANY discrepancy, DO NOT transfuse. Con \201 rm the details on the traceability label on the blood component match the patient \200\231s full name, date of birth, and hospital number (wrist band if unconscious). Check that the traceability label is attached to the blood bag. \200 Ensure the donation number, the patient \200\231s blood group/RhD type all match and that any special requirements are covered. Check every component before starting transfusion for signs of discol- ouration, leaks, clots etc. and the expiry date. If all checks are satisfactory, the 2 practitioners should ensure that the component has be en prescribed (prescription form and/or \202 uid balance chart) and sign the front of the traceability label before commencing the transfusion. Infuse all components through a giving set with integral \201 lter to trap large aggregat es. Microaggregate \201 lters are not routinely required. Never add any drug to a blood component infusion. \200 Do not use giving-sets which previ ously contained glucose or gelatin. \200 Red cell concentrates may be diluted with 0.9 % saline using a Y giving- set to improve \202 ow rates. Never add any other solution. Use a blood warmer, especially for large and/or rapid transfusions. \200 Once the transfu sion has started, peel off the portion of the signed label and attach to the appropriate place in the \202 uid balance sheet. \200 Sign the prescr iption form to con \201 rm the patient identity checks. \200 Complete and sign the label and return it to the laboratory. See: www.transfusionguidelines.org.uk 174 CHAPTER 3 Medicine Blood transfusion 2 Massive transfusion Loss of 50 % of circulating blood volume within 3hr is perhaps the most relevant ED de \201 nition. Resuscitation requires an interdisciplina ry team and clear organization. In the event of massive blood loss \200 Protect the airway and give high \202 ow O 2 . \200 Get help \200\224 two nurses and a senior doctor. \200 Insert two large bore cann ulae and start IV warm saline 1000mL stat. \200 Take FBC, U&E, LFTs, coagulation, and cro ss-match. Label the blood tubes and ensure they are sent directly to the laboratory. Do not leave them unlabelled or lying around in the resusitation room. Telephone the hematology laboratory to warn of potential massive transfusion. Request ABO g roup-speci \201 c red cells if the patient is peri- arrest. This will take only 10min in t he laboratory. Otherwise, request full cross-match and give number of units required. Accurate patient ID is essential, even if the patient is unknown. \200 Call appropriate s enior surgeon \200\224 to stop bleeding as soon as possible. \200 Start blood transfusio n if the patient remains tachycardic and/or hypo- tensive despite crystalloid resuscitation. Repeat all bloods, including FBC, clotting, U&Es, calcium, and magne- sium levels, every hour. Start platelet transfusion if platelet count falls below 75 \227 10 9 /L. \200 Anticipat e the requirement for FFP and consider giving early during the resuscitation. FFP will repl ace clotting factors and \201 brinogen. Aim to maintain \201 brinogen > 1.0g/L and the INR and APTT <1.5 normal. Cryoprecipitate may also be used. Recombinant Factor VIIa might be used as a \200\230last ditch attempt \200\231 to control bleeding in young patients where surgical control of bleeding is not possible, and the abov e has already been corrected. If the drug is available it is usually ordered by a hematolog ist. Massive transfusion complications Rapid infusion of blood products may lead to: Hypothermia Blood products are normally stored at 2 \200\2236 C. Rapid infusion can caus e signi \201 cant hypothermia. Use blood warmers routinely for rapid transfusions (eg > 50 mL/kg/hr or 15mL/kg/hr in children). Never warm a blood product by putting a pack into hot water, on a radiator or any other heat source. Electrolyte disturbances With massive transfusion, the citrate anticoagulant may cause sign i \201 cant toxicity, d plasma Ca 2 + (impairing cardiac function) and acid \200\223base b alance disturbance. This is aggravated in patients with underlying liver disease, hypotensi on or hypothermia. Citrate may also bind Mg 2 + , causing arrhythmias. Prophylactic or rout ine administration of IV calcium salts is not recommended. Monitor ECG and measure ionized plasma Ca 2 + levels during massive transfusion. K + levels i in stored blood and hyperkala emia may follow massive infusion. Routinely monitor the ECG and check plasma K + levels. Tr ansient hypokalaemia may follow 24hr after large volume transfusion 175 BLOOD TRANSFUSION 2 Blood product administration Blood transfusion is not a panacea. An improvement in O 2 deli very cannot be assumed. RBC function deteriorates during storage and changes in O 2 af \201 nity occur withe d 2,3-DPG levels, while d ATP levels alter RBC mem- brane deformabili ty causing i cell stiffness and micro-circulatory problems. UK donations are routinely scre ened for hepatitis B, HIV, HTLV, syphilis, and where necessary, CMV. However, blood cannot be sterilized: small but de \201 nite risks of infection transmission exist. Transfusion reactions Monitor the patient closely for the \201 rst 5 \200\22310min of the infusion of each unit of blood to detect early clinical evidence of acute reactions. If th e patient develops a temperature, shortness of breath, chest or abdom- inal pain or hypoten sion, suspect a transfusion reaction. Treat allergic reactions including itching, urticaria , bronchospasm and fever convention- ally (see b Anaphylaxis treatment, p.43). Mismatched t ransfusion By far the commonest cause is a clerical error when labeling, ordering or admini stering blood. Transfusion of ABO incompatible blood causes acute severe haemolysis and cir culatory collapse. In a hypovolaemic, shocked, or anesthetized patient these features may b e obscured and missed. If a transfusion reaction is suspected: ABO incompatability, haemolytic reaction, bacterial infection, severe allergic reaction, or transfusion-related acute lung injury: \200 Stop the transfusion. \200 Keep the IV lin e open with 0.9 % saline. \200 Record all observations, give supplemental oxygen. \200 Double-check the blood unit label with the patient \200\231s wrist identity band and other identi \201 ers. Send the unit of blood product and the giving set to the blood bank. \200 Take 40mL of bl ood. Send it as follows: 5mL anticoagulated and 5mL clotted blood to blood bank; \200 10mL for U&E; \200 10mL fo r coagulation screening; \200 10mL for blood cultures. Contact the blood bank directly by phone. \200 Contact hematologist directly. \200 Give broad spectrum antibiotic if infection suspected . \200 Monitor \202 uid balance and u rinary output. 176 CHAPTER 3 Medicine Sickle cell disease Sickle cell disease occurs in African, Indian, Middle Eastern, Caribbea n, USA, and Mediterranean populations. It is caused by a genetic mutation in one of the cha ins of the Hb molecule. The normal adult Hb genotype AA produces HbA. In heterozygotes (sic kle cell trait) one gene is abnormal (HbAS) and about 40 % of the patient \200\231s Hb will be HbS. In homozygotes (sickle cell anemia), both genes are abnormal (SS) and > 80 % of th e Hb will be HbS. HbS molecules polymerize in deoxygenated or acidotic con- ditions, causin g RBC sickling. Sickle cells are rigid and fragile. They may haemolyse, or block small vess els leading to tissue ischaemia, infarction and further sickling (see Fig. 3.26 ). Sickling also occurs with genes coding other analogous amino acid substitutions (eg HbSC and SD dis eases). Clinical features Sickle cell trait causes no disability except during conditions of severe hypoxia (eg sudden depressurization in aircraft, or cardiac arrest). Patients with sickle cell anemia have chronic anemia (Hb 8 \200\22310g/dL) with alternating good health and acute crises. Later, chronic ill health supervenes with renal failure, bon e necrosis (evident in 50 % of patients by age 35 years), osteomyelitis, leg ulcers and iro n overload as a consequence of transfusions. There is predisposition to infection, especial ly Staphylococcus, Pneumococcus , and Haemophilus. Sickle cell crises can occur de novo or follow infection, cold, dehydration, or any situation where tissue hypoxia/ischaemia occurs . The crisis may involve thrombosis, haemolysis, marrow aplasia, or acute splenic/liver seq uestration (especially in children aged <5 years). Any acute medical or surgical emergency may be mimicked (eg acute abdomen, PE, stroke). Severe aching bony pain and low-grade fever (even in the absence of infection) is common. Cerebral sickling may present with bizarre b ehavior, psychosis, \201 ts, TIAs, stroke, or other focal neurological signs. Priapism, j aundice, and painful swelling of hands and feet may occur. Acute chest syndrome The leading cause of death in sickle cell anemia. It presents as chest pain, hypoxia and pulmonary in \201 ltrates. There may be cough, tachypnoea, and wheezing . Poorly understood, but infection may be a precipitant. Acute splenic sequestration Sudden trapping of large numbers of RBCs in the spleen results in severe anemia, an enlarging spleen, hypovolaemia, and thrombocytopenia. It occurs most c ommonly in young children \200\224 those with sickle cell disease have a 30 % chance of ha ving acute splenic sequestration by the age of 5 years. It may present with shock and splen omegaly, with a mortality of > 15 % . Osteomyelitis and septic arthritis Osteomyelitis and septic arthritis occur more commonly i n sickle cell disease. Be suspicious if a patient presents with high fever, soft tissue swe lling, or pain in a different pattern to normal. Salmonella is frequently implicated. 177 SICKLE CELL DISEASE Investigations No speci \201 c tests can detect a sickle cell crisis: \200 All patients in the at-risk groups require a sickle test before any anesthetic procedure (including regional anesthesia, Bier \200\231s block). Sickle testing (using an oxidizing agent) will detect sickling in homo- and heterozygote fo rms. Hb electrophoresis can then distinguish between HbSS, HbAS and other Hb variants. FBC typically shows anemia (Hb 6 \200\2238g/dL, but Hb may be much lower if acute haemolysi s, sequestration or aplasia is present). Post-splenectomy features may be seen on blood \201 lm. WCC may be i (20 \200\22360 \227 10 9 /L) in the absence of infection and platele t count is also usually i . Infection screen, including blood cultures, midstream specimen of urine (MSU) and CXR. Joint aspiration for culture if septic arthritis is suspected. \200 U&E, ABG, ECG. \200 Arrange CT brain scan if there are neurological symptoms or signs. Management of crises Provide supportive therapy, directed to the patient \200\231s symptoms : \200 Get expert help! \200 Keep the patient warm, rested and give O 2 if any obvious symptoms or SpO 2 <94 % . Opioids (given IV and titrated to the response) are often required for pain. Consider morphine IVI or patient analgesia pump. Commence rehydration with oral or IV \202 uids, but take care not to pre- cipitate heart failure. Transfusion may be required if severe anemia from acute haemolysis, sequestration or aplasi a occurs, or if there are central nervous system (CNS) or lung complications. Empirical antibiotic therapy may be required if infection is thought to be the trigger for the sickling crisis. Sickling Blood viscosity Deoxygenation and acidosis Sludging Stasis Fig. 3.26 Sickling cycle. This page intentionally left blank 179 Chapter 4 Toxicology Poisons: general principles Diagnosis of poisoning Poisons: supportive care Reducing absorp tion of poison Antidotes for poisons Opioid poisoning Salicylate poisoning Paracetamol pois oning Tricyclic antidepressant poisoning Benzodiazepine poisoning Clomethiazole poisoning P henothiazine poisoning Barbiturate poisoning Lithium poisoning Sulphonylurea poisoning Beta blocker poisoning Calcium antagonist poisoning Digoxin poisoning ACE inhibitor poisoning T heophylline poisoning Salbutamol poisoning Iron poisoning Ethanol poisoning Methanol poison ing Ethylene glycol poisoning Paraquat poisoning Gasoline and paraf \201 n poisoning Organ ophosphate poisoning Cyanide poisoning Carbon monoxide poisoning Chlorine poisoning CS gas (tear gas) Chemical incidents Decontamination of patients Plants, berries and mushrooms But ton batteries Illicit drugs Serotonin syndrome Body packers 180 182 183 184 186 188 189 190 194 196 196 196 197 197 197 198 198 199 199 200 200 201 202 202 203 204 205 206 207 208 209 209 210 211 212 213 214 216 217 180 CHAPTER 4 Toxicology Poisons: general principles Emergency treatment Clear and maintain the Airway . If Breathin g appears inadequate ventilate with oxygen using a bag and mask or ET tube (not mouth-to-mo uth in poisoned patients). Give naloxone for respiratory depression due to opioids ( b p. 1 88). Circulation Check pulse. If unconscious and pulseless, start CPR. Types of poisoning Unintentional or \200\230accidental \200\231 poisoning is most common i n inquisitive small children (1 \200\2234 years) who eat tablets, household chemicals, and plants. Older children and adults may be poisoned by chemicals at school or work, or by dri nking toxic \202 uids decanted into drinks bottles. Poisoning by drugs may result from mi scalculation or confusion of doses or by taking the same drug under different names. Drug s mugglers who swallow drugs wrapped in condoms or polythene, or stuff them in the rectum or vagina, may suffer poisoning if the packages leak ( b p.217). Deliberate self-poisoning is the commonest form of poisoning in adults and may occur in children as young as 6yrs (usual ly with a family history of self- poisoning). Drugs or poisons are often taken impulsively, sometimes to manipulate relatives or friends. Suicidal intent is relatively uncommon, but assess all patients for this ( b p.612). A few patients leave suicide notes, and conceal th e drugs or poison to evade detection. Non-accidental poisoning of children is a form of fabricated or induced illness (previously known as Munchausen \200\231s syndrome by proxy \200\224 b p.733), in which a parent deli berately poisons a child. Homicidal poisoning is rare and may involve acute or chronic pois oning with chemicals such as arsenic or thallium. Chemical plant incidents and terrorism are potential threats to large numbers of people. Information about poisons Tablets may be identi \201 ed from MIMS Color Index and descript ions in the BNF . Drug Information Centers and Poisons Information Services (see opposite) have access to TICTAC , a computer-aided tablet and capsule identi \201 cation system ( ww w.tictac.org.uk ). Martindale 1 gives information on many drugs and poisons, and detailed c onstituents of non-prescription drugs. Identi \201 cation of plants and fungi from reference books may be dif \201 cult, especia lly if only vague descriptions or chewed fragments are available. The CD-ROM computer softw are Poisonous Plants and Fungi in Britain and Ireland 2 helps with identi \201 cation and details of toxicity. Local botanic gardens may provide additional help. See also b p.212. 1 Sweetman SC ( ed ). ( 2009 ) Martindale: The Complete Drug Reference , 36 th edn . Pharma ceutical Press , London . 2 Dauncey EA et al . ( 2002 ) Poisonous Plants and Fungi in Britain and Ireland ( interacti ve identi \201 cation system on CD-ROM ), 2 nd edn. Kew Publishing , Kew , www.kewbooks.com. 181 POISONS: GENERAL PRINCIPLES Poisons Information Centers in the UK TOXBASE, the UK National Poisons Information Service \200\231s database on clinical toxicology, is on the internet ( www.toxbase.org ) with a ba ckup site at www.toxbasebackup.org . It includes information about poisoning with drugs, ho usehold products, plants and fungi, as well as industrial and agricultural chemicals and ag ents which might be deliberately released by terrorists. Access to TOXBASE is password prot ected and is restricted to NHS professional staff in the UK and also hospitals in Ireland. TOXBASE or reference books provide suf \201 cient information for most cases of poisoning. More detailed information and specialist advice is available from Poisons Information Cent ers and is especially useful for complex cases or severe poisoning. The UK National Poisons Information Service has four centers, with a single telephone numbe r 0844 892 0111 which directs the call to the nearest center, or to the on-call center out of hours. In Ireland advice is available from the National Poisons Information Center, Dubl in, telephone (01) 809 2566. Enquiries to Poisons Information Centers are usually answered initially by an information o f \201 cer using TOXBASE and other reference sources. Medical staff with specialist toxico logy experience are available for advice about seriously poisoned patients. Poisons Informa tion Centers can also advise about sources of supply of antidotes that are needed only occa sionally, and about laboratory analyzes that may be helpful in managing some patients. Admission and psychiatric assessment after poisoning Adults Patients who are seriously pois oned need admission to a medical ward, or if appropriate, to ICU. However, most patients wh o take overdoses suffer no serious ill effects and may be treated satisfactorily on an ED o bservation ward or a Clinical Decisions Unit. Even if there is no risk of toxicity, admissi on overnight provides a \200\230cooling off \200\231 period for the patient to get away fr om the situation that precipitated the overdose. This should allow a more rational appraisa l of the problems and may reduce the risk of further self-poisoning. Look for the causes of every episode of deliberate self-harm. A patient who seems suicidal (see b p.612) must be observed carefully in the ED and on the ward, because of the risk of further self-harm. Children with poisoning Serious poisoning is uncommon in children. Many children appear wel l but have been exposed to an unknown amount of a compound which could be toxic. Admit such children to a pediatric ward for observation: they can be discharged after a few hours if no toxic effects occur. A child may be discharged home directly from the ED if the substanc e taken is known to be non-toxic. The health visitor may usefully visit the home to advise about poisoning prevention. In children > 6 years, consider the possibility of deliberate s elf-harm and the need for assessment by a child psychiatrist. 182 CHAPTER 4 Toxicology Diagnosis of poisoning The patient or relatives/friends may state what drugs or poison have been taken, but this information is not always accurate. Self-poisoning is often an impuls ive act whilst under the in \202 uence of alcohol: the patient may not know which tablets he/she took. The amount involved is often unclear. Check any bottles or packets for the nam es and quantities of drugs or poisons that were available. If a patient is unconscious or s everely poi- soned, look in hospital notes for details of previous overdoses, and \201 nd out from the GP what drugs had been prescribed. Record the time of ingestion of the drug o r poison. Examine the patient all over for signs of poisoning, injection marks or self-inju ry. Exclude other diverse processes mimicking poisoning (eg head injury, meningitis). In th e Far East, and in EDs where Asian people present with non-speci \201 c symptoms, hepatiti s, or suspected poisoning, remember that traditional Chinese medicines or herbs can cause s igni \201 cant toxicity. Toxidromes: features suggesting a particular poison \200 Coma with dilated pupils, diverg ent squint, tachycardia, i muscle tone, i re \202 exes and extensor plantars suggests tric yclic antidepressant or orphenadrine poisoning ( b p.194). Coma with hypotension, respiratory depression and d muscle tone suggests barbiturates, clom ethiazole (b p.196), benzodiazepines with alcohol, or severe tricyclic antidepressant poiso ning ( b p.194). Coma with slow respiration and pinpoint pupils is typical of opioid poisoning (give naloxone, b p.188). Tinnitus, deafness, hyperventilation, sweating, nausea and tachycardia are typical of salicylate poisoning ( b p.189). Agitation, tremor, dilated pupils, tachycardia, suggest amphetamines, ecstasy, cocaine, sym pathomimetics ( b p.214), tricyclic antidepressants ( b p.194), or selective serotonin re-u ptake inhibitors (b p.216). Assessment and monitoring \200 Assess and record conscious level ( b p.361). Observe freq uently. \200 Check blood glucose in patients with confusion, coma or \201 ts. \200 Mo nitor breathing and record respiratory rate. Use a pulse oximeter, but note that SpO 2 may be misleadingly high in carbon monoxide (CO) poisoning \200\224 see b p.208). Check ABG if patient is deeply unconscious or breathing abnormally. \200 Record and monit or the ECG if a patient is unconscious, has tachy- or bradycardia or has taken drugs or poi sons with risk of arrhythmias. Record BP and temperature. Investigations in poisoned patients The most useful investigations are paracetamol and sali cylate levels, blood glucose, ABG, and urea & electrolytes (U&E). Measure paracetamol if th ere is any possibility of paracetamol poisoning (this includes all uncon- scious patients). Record the time of the sample on the bottle, and in the notes. Many labs can measure salic ylate, iron and lithium and also check for paraquat if necessary. Comprehensive drug screen ing is rarely needed and is only available in specialist centers (ask Poisons Information S ervice, b p.181). 183 POISONS: SUPPORTIVE CARE Poisons: supportive care Protect the airway In an unconscious patient use a cuffed ET tube if there is no gag re \202 ex. If an oral or nasal airway is used, nurse in the recovery p osition to minimize risk of aspiration should vomiting or regurgitation occur. Monitor breathing and ventilate if necessary Hypoxia and CO 2 retention are common in deep coma. Hypotension This may result from relative hypovolaemia, arrhythmias and cardio- depre ssive effects of drugs. Treat according to the cause. Elevate the foot of the trolley. If B P <90mmHg, consider giving saline or a plasma expander such as gelatin 500mL IV. Monitor CV P in patients who are elderly or have cardiac disease. Inotropes such as dopamine (2 \200 \2235micrograms/kg/min), dob- utamine (2.5 \200\22310micrograms/kg/min), glucagon ( b p.198 ) or insulin therapy ( b p.187) are occasionally needed, under expert guidance. Cardiac arr hythmias Generally rare in poisoned patients. The most likely drugs responsible are tricycl ic antidepressants, beta-blockers, chloral hydrate, digoxin, potassium, bronchodilators, ve rapamil, and amphetamines. Look for and correct hypoxia, respiratory depression, metabolic acidosis and electrolyte abnormalities. Anti-arrhythmic drugs are very rarely needed: consu lt a poisons expert \201 rst. Convulsions Dangerous because they cause hypoxia and acidosis, and may precipi- tate cardia c arrest. Drugs responsible include tricyclic antidepressants, mefenamic acid, and theophyl line. Check for and correct hypoxia and hypoglycaemia. Do not give anticonvulsants if \201 ts are single and brief, but if \201 ts are repeated or prolonged give IV lorazepam 4mg (or PR diazepam or buccal midazolam if venous access is not available). Hypothermia May occur with any drug causing coma, especially barbiturates, clomethiazole, a nd phenothiazines. Check rectal T with a low-reading thermometer. Insulation and passive rewarming are usually adequate. Hyperthermia ( b p.264) May occur with amphetamines, cocai ne, ecstasy, monoamine oxidase inhibitors, sympathomimetics, and theophylline. Convulsions and rhab- domyolysis are common. Active cooling, chlorpromazine and possibly dantrolene are needed. Get expert help. Complications of immobility Prolonged immobility (eg due to tricyclics and barbiturates) ri sks pressure areas. Treat blisters like minor burns. Immobility may cause rhabdomyolysis (l eading to renal failure), nerve palsies, and compartment syndrome: if this is suspected che ck CK, test urine for myoglobinuria, and get urgent ortho- paedic advice about measuring co mpartment pressures. Urinary retention Common in coma, especially after tricyclic poisoning. Suprapubic pressure often stimulates re \202 ex bladder emptying. Catheterization may be needed to empty the bladder or to measure urine output. 184 CHAPTER 4 Toxicology Reducing absorption of poison Background information If a poison has been swallowed it is l ogical to try to remove it and reduce absorption from the gut. Possible measures include ga stric lavage, induced emesis (eg with ipecacuanha), oral adsorbents (especially activated c harcoal) and whole-bowel irrigation. None of these can be recom- mended routinely. They may cause signi \201 cant morbidity and there is very little evidence that they improve outco mes. Gastric lavage This does not empty the stomach of solids and may force gastric contents thr ough the pylorus into the small bowel. It may cause hypoxia, aspiration pneumonia and occas ionally oesophageal perforation. Gastric lavage > 1hr after overdose is ineffective in d ab sorption of poisons. Gastric lavage does not reduce mortality from poisoning, and it does n ot deter patients from taking repeated overdoses. Practical advice on use of gastric lavage Only consider this if the patient has taken a lif e-threatening amount of poison within the previous 1 hour or is deeply unconscious because of poisoning. Only consider performing it if there is a strong cough re \202 ex or the air way is protected by a cuffed ET tube. Do not use lavage for poisoning with corrosives (risk of perforation) or with gasoline/paraf \201 n compounds (risk of pneumonitis), except rar ely in severe poisoning on specialist advice. \200 Before starting gastric lavage, check that powerful suction is immedi- ately available. Elevate the foot of the trolley and place the patient in the left lateral position. Give O 2 via nasal cannulae. Monitor ECG. \200 Lubricate large disposable stomach tube (3 6 or 40 French Gauge-FG) and pass it through the mouth into the stomach. Con \201 rm posit ion by aspirating gastric contents or blowing air down the tube while listening over the st omach. Aspirate gastric contents and keep labeled sample for later analysis if necessary. Perform lavage by pouring 300mL aliquots of tepid tap water down the tube and siphoning it back, while massaging over stomach to help dislodge tablet debris. Continue until the ef \202 uent is clear. \200 Consider leaving activated charcoal (50g) in the stomach. \200 While withdrawing the tube, occlude it between the \201 ngers to prevent aspiration of \202 uid from the tube. 185 REDUCING ABSORPTION OF POISON Induced emesis Never use emetics. Ipecacuanha was once used frequently, but it may cause pr olonged vomiting, drowsiness and aspiration pneumonia, and it does not reduce drug absorpti on. There is no indication for using ipecac. Salt solutions may cause fatal hypernatraemia and must never be used as an emetic. Activated charcoal Given within 1hr, this d absorption of therapeutic doses of many drugs, but there is little evidence of clinical bene \201 t after overdose. Charcoal d the half-l ife of some drugs (eg digoxin), which undergo entero-hepatic recycling. However, charcoal i s messy, unpleasant to take and often causes vomiting. Aspiration into the lungs can result in fatal pneumonitis. Various formulations of activated charcoal are available. Actidose A qua Advance is less unpalatable than some of the other formulations. Carbomix may cau se severe constipation, especially if given in repeated doses. Do not give activated charcoal for substances which do not bind to it. These include: iron, lithium, boric acid, cyanide, ethanol, ethylene glycol, methanol, organophosphates, petrol eum distillates and strong acids and alkalis. Charcoal is most likely to be useful for pois ons which are toxic in small quantities (eg tricyclic antidepressants and theophylline deri vatives). If a dangerous overdose has been taken in the previous 1hr, give charcoal (PO or via an orogastric tube: adult 50g; child 1g/kg, max 50g). Charcoal may be effective for > 1 hr for sustained release formulations or drugs that delay gastric emptying (eg tricyclic an tidepressants and opioids). Obtain expert advice before giving charcoal in repeated doses, which are only helpful in life-threatening poisoning with a few drugs (eg carbamazepine, da psone, digoxin, phenobarbital, quinine, theophylline, and salicylate, and a few other drugs rarely taken in overdose). Whole-bowel irrigation Whole-bowel irrigation is rarely needed and should only be used on e xpert advice. The aim of whole-bowel irrigation is to empty the bowel rapidly of solid cont ents by giving \202 uid down a nasogastric (NG) tube until the rectal ef \202 uent becom es clear. The value of this is uncertain. It may be useful for poisoning with sustained-rel ease drug formulations or for poisons such as iron or lithium, which are not absorbed by ac tivated charcoal. It has also been used to remove packets of cocaine from body packers and button batteries from children. Bowel cleansing solutions of polyethylene glycol and electrolytes (eg Klean-Prep ) shoul d be used for whole-bowel irrigation: 2L/hr in adults (500mL/hr in small children) for 2hr, or occasionally longer. Do not use normal saline since it may cause \202 uid overload an d hypokalaemia. Activated charcoal may be given by NG tube, if appropriate, before whole- bowel irrigation is started. Continue the irrigation until the rectal ef \202 uent is clear. Nausea, vomiti ng, abdominal pain and electrolyte disturbances may occur. Monitor ECG, U&E and urine outpu t. 186 CHAPTER 4 Toxicology Antidotes for poisons The provision of supportive care is essential in all patients. Antido tes are available for only a few drugs and poisons (Table 4.1 ), and are not always necessa ry. More information is available from reference books, TOXBASE and Poisons Information Cen ters ( b p.181). Table 4.1 Poison Antidote Notes b p.198 b p.208 b p.207 Beta-blockers Glucagon, atropine Carbon monoxide Oxygen Cyanide Sodium nitrite, sodium thiosulphate, dicobalt edetate, hydroxocobalamin b p.199 b p.203 b p.201 b p.187, b p.284 b p.202 b p.188 b p.206 b p.190 b p.197 Digoxin antibodies (Digibind) \200 Digoxin Ethanol, fomepizole \200 Ethylene glycol Iron salts Desferrioxamine Lipid emulsion (Intralipid ) Local anesthetics Ethanol, fomepizole \200 Methanol Opioids Naloxone Atropine, pralidoxime \200 Organophosphates Paracetamol Acetylcysteine, methionine Sulphonylureas Glucose, octreotide Sodium bicarbonate, Intralipid b p.187, b p.194 Vitamin K, clotting factors, FFP b p.170 b p.417 Expert advice b p.181 Tricyclic antidepressants Warfarin Adder bites Zagreb antivenom Antivenoms \200 Foreign snakes Antidotes are also available for arsenic, lead, mercury, thallium, and other metals. Specia list advice is essential. Some antidotes (marked \200 ) are very rarely needed: get exper t advice (b p.181) about when and how to use these antidotes and where to obtain them. Increasing elimination of poisons The vast majority of poisoned patients recover with suppo rtive care, plus appropriate antidotes if necessary. Active removal of absorbed poison is o nly needed in special circumstances. Alkalinization of the urine is useful in salicylate po isoning ( b p.189), but forced alkaline diuresis is no longer recommended. Haemodialysis is occasionally helpful for severe poisoning with salicylates, ethylene glycol, methanol, lit hium, phenobarbital, and chlorates. Haemoperfusion is rarely needed, but might be helpful i n severe poisoning with barbiturates, chloral hydrate or theophylline: specialist advice is essential. 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.