WCC \200\201, platelets \200\201 Hypoglycaemia Mental retardation Failure to thrive PKU (phenylalanine ketonuria) \200\224Cause: Mutation of phenylalanine hy- droxylase (PAH) gene (chromosome 1 \200\224autosomal recessive) leading to ab- sent or reduced activity of phenylalanine hydroxylase. Classic PKU leads to gradual mental impairment. The defect leads to \200\201CNS dopamine, reduced protein synthesis, and demyelination.567 Milder forms of hyperphenylala- naemia can occur with diff erent mutations to the same gene, or mutations to co-factor tetrahydrobiopetrin (BH4). Clinical features: Fair hair, \201 ts, ec- zema, musty urine. The chief manifestations is \200\201IQ (eg dyscalculia poor spelling \200\201cognition).568 Tests: Hyperphenylalaninaemia (reference interval: 50 \200\223120 m ol/L). Treatment instigated in infants with levels >360 mol/L \200\224to avoid \200\201IQ which may start with levels of >394 mol/L.569 Treatment: Get ex- pert help. Diet: protein substitute that lacks pheny lalanine but is enriched in tyrosine. Aim to keep phenylalanin e levels to <360 mol/L570 by prescribing arti \201 cial food substitutes (amino acid drin ks) to give <300mg \200\2238g of natural protein/day (depending on age and severity of phen ylalanine hydroxylase de \201 ciency).571 Hypomyelination may be proportional to degree of phenylke- tonaemia, but some studies fail to show stricter diets are associated with highe r IQs. Despite treatment, children are more prone to depression, anxi- ety, phobic tendenci es, isolation, and a less \200\230masculine \200\231 self-image.572 Adher- ence to the die t may be poor (it \200\231s unpalatable).573 Also, the diet may cause changes of questionab le signi \201 cance in levels of selenium, zinc, iron, retinol, and polyunsaturated fatty acids.574 Prevention of manifestations: Screen blood at 1 week (using a heel-prick and \201 lter paper impregnation \200\224the Guthrie test). Maternal phenylketonuria \200\207P reconception counseling is vital. Eff ects on the baby: facial dysmorphism, microcephaly, g rowth retardation, IQ \200\201. 1 Anderson \200\223Fabry disease may present with torturing , lancinating pains in the extremities ( abdomen) made worse by cold, heat, or exercise. It is a neuritis (vasculitis of the vasa nervorum). By adolescence, angiokeratomata appear (clusters of dark, non-blanching, petechiae) in the \200\230bathing trunk \200\231 area (e sp. um- bilicus & scrotum). Also: paraesthesiae, corneal opacities, hypohidrosis, proteinur ia and renal failure. It may respond to enzyme \200\224 ( \200 -galacotosidase is \200 \201). Carbamazepine may help the pain. 2 MCAD de \201 ciency is screened for in neonates on the same sample as for PKU & hypothyroidism. It \200\231s an au- tosomal recessive (muta tion of the medium-chain acyl-CoA dehydrogenase gene; ACADM; 1p31). Signs: hypo- ketotic hy poglycaemic coma; metabolic acidosis; LFT \200\200; medium chain dicarboxylic aciduria; \200\230SIDS \200\231. \200 : \200 \211\210 1 : 1. \200\224: avoid fasting; diet to giv e more calories from carbohydrates & proteins, while minimizing lipids. It is the chief inh erited disorder of mitochondrial fatty acid oxidation in N. Europe. Carrier rate: 1 : 65. Precocious puberty Puberty may start as early as 8yrs in girls and 9yrs in boys. Refer to a pae- diatric endocrinologist if onset before this. \200 : \200 \211\21010 : 1. 575 Ca uses may be central (gonadotrophin dependent, eg craniopharyngioma or pituitary tumor) or p e- ripheral (eg testis or adrenal problem, or HCG \200\200 from rare tumors \200\230anywhe re \200\231). Biology Think of each physical signs of puberty as a bioassay for a separate en- docrine event. Enlargement of the testes is the 1st sign of puberty in boys, and is due to pulses of pituitary gonadotrophin. Breast enlargement in girls and penis enlargement in boys is due to gonadal sex steroid secretion. Pubic hair is a mani- festation of adrenal a ndrogen production. Growth in boys accelerates when testis volume reaches 10 \200\22312mL ( if measured by comparison with orchidometer beads rather than ultrasound, expect overestima tes by up to 60%). 576 Girls start to grow more quickly once their breasts have started to develop. Stage 4 breast development is a prerequisite for menarche (in most girls). The bes t sign that precosity is pathological is when this consonance of puberty goes awry: in Cush - ing \200\231s syndrome, pubic hair is \200\230too much \200\231 for the testicular volum e; in hypothyroid- ism, the testes are large (FSH \200\200 as TSH \200\200 \200\200) while growth velocity is low. 577 184 Sexual signs may be obvious or subtle.1 Gynae- comastia may worry boys.2 One consequence is short stature caused by early fusion of epiphyses. Premature adrenal maturity (adrenarche) may presage insulin resistance. Ask about general hypothalamic dysfunction? Polyuria, poly dipsia, obesity, sleep, and temperature regulation. There may also be signs of ICP \200\200 visual disturbance. Rare causes \200 Stress (eg adoption) \200 CNS tumors/empty sella \200 Craniopharyngi oma \200 Thyroid disorders \200 Choriocarcinoma \200 Meningoencephalitis \200 McCun e \200\223Albright syn. \200 21-hydroxylase lack \200 Rare genetic defects s c i r t a d e a P i If onset is before 2yrs, suspect a hypothalamic hamartoma. LH receptor gene mutations cause sporadic or familial male gonadotrophin-independent precocious puberty. Tests Growth chart s; puberty staging (Tanner charts); CNS CT/MRI; bone age (skeletal X-ray); urinary 17-ketos teroids; karyotype; adrenal, testis & pelvic \200 ultrasound, T4; TSH; LH; FSH; HCG; AFP; GH; pituitary tests (OHCM p224); oestro- gen/testosterone (if no adrenal source of \200 \200testosterone is found, left vs right spermatic vein sampling may suggest one testis has a tiny Leydig cell tumor or hyperplasia). 578 Virilizing 21-hydroxylase de \201 ciency is con \201 rmed by \200\20017- hydroxyprogesterone on ACTH stimulation. 579 Management: a physiological approach Initiation of puberty depends on release from inhibition of neurons in the medial basal hypothalamus that secrete gonadotrophin-releasing hormone (GnRH), and o n decreasing hypo- thalamic-pituitary sensitivity to \200\223ve feedback from gonadal ster oids. These changes are accompanied by \200\200frequency and magnitude of \200\230pulses \200\231 of LH. GnRH pulses are needed for normal gonadal function. Continuous high levels of GnRH paradoxically suppress secretion of pituitary gonadotrophins; this forms the basis for treating precocious puberty with synthetic GnRH analogs (nasal or SC). There is a rever sal of gonadal maturation and all the clinical correlates of puberty (not for pubic hair, a s there is no change in the secretion of androgens by the adrenal cortex). There is deceler ation in skeletal maturation. Treatment is continued eg up to 11yrs. Families need reassura nce that the child will de- velop normally. Endogenous estrogen accelerates growth ( \200 & \200 ), as well as mediating \200 sexual characteristics: testolactone can help by \200\201its biosynthesis. Anti-androgens (eg \202 utamide) and spironolactone also have a role. 580 1 Eg in boys: rapid growth of penis and testes; \200\200frequency of erections; masturbati on; appearance of pubic hair; body odor; acne \200\224maybe a tendency to high IQ; \200 \200energy expenditure tantrums/impulsive anger; early occurrence of capacity for frank sexual imagery in dreams and daydreams; early capacity for erotic and sexual arousal in rel ation to visual imagery, visual perception, and tactile sensation. 2 There is often transie nt estrogen/testosterone imbalance early in \200 puberty. Try to avoid tests (test- oster one, oestradiol; gonadotropins; karyotype if testes <6mL). Reassure, and delay requests for mam- moplasty. This page intentionally left blank Diabetes mellitus (DM): patient-centered care in action Type 1 DM is the third most common chronic disease in UK children (after asth- ma and cerebral palsy). Don \200\231t medicaliz e the young person, but do personal- ize the medicine. Paternalistic care almost never achi eves good results. Good care of the child with diabetes requires involving the family unit and carers at school \200\224over 50% of American children report being prevented from self - management of diabetes or using a bathroom at school. 581 Typical presentation: Several w eeks of polyuria, lethargy, polydipsia, and weight loss infection, poor growth; ketosis. 1 Typical age: 4 \200\22312yrs.2 Diagnos- tic criteria: Based on WHO criteria: 582 signs of hyperglycaemia with \200\200venous blood glucose, ie \211 11.1 mmol/L (random) or \211 7mmol/L (fasting) , or raised ven- ous blood glucose on 2 occasions without symptoms. Oral glucose tolerance tests are rarely required in children, but they are based on glucose leve ls at 0h and 2h post a 1.75g/kg glucose load, \201\227: Should be delivered by a multi- di sciplinary pediatric diabetes care team \200\224which provides 24h access to ad- vise. \200 583 For diabetic ketoacidosis see p188. If non-ketotic, IV \202 uids are rarely need ed. Inform children and parents that they may experience a partial remis- sion phase ( \200 \230honeymoon period \200\231) with the start of insulin. Starting insulin: Discuss with pe diatric endocrinologist and use local protocols. One regimen would be to estimate total dai ly requirement of insulin (0.8 \200\2231 units/kg/24h for prepubertal children; 1.5units/kg /24h if pubertal) \200\224this daily dose should be \205\223 rapid acting (eg Novorapid ) and \205\224 long-acting (eg protaphane). \205\224 of the daily dose should be given pre -breakfast, and \205\223 should be given pre dinner. 584 Tailor insulin regimen to your pa tient and their family. They may bene \201 t from a con- tinuous subcutaneous insulin infu sion. Diet: Ask a pediatric dietician. Energy needs \211\2101500kcal/m2 or 1000kcal +100 t o 200kcal for each year of age. Aiming for 30% of this with each major meal, and 10% as a b edtime snack suits some children. Giving 20% of calories as protein, 50% as unre \201 ne d carbohydrate, and \211 30% as fat is a rule of thumb. If the child is mildly to moderate ly sympto- matic and clinically well, subcutaneous insulin and oral diet and \202 uids ma y be begun at diagnosis, avoiding hospital admission. 585 Type 2 DM is rare in children (0. 2 : 100,000; 586 \200\200 \211\210 13 if of Asian extraction); but insulin resistance/pre -syndrome X is burgeoning: \200\207see p156 for prevention. Have a detailed written care p lan What other things should a newly diag- nosed child and his or her family know? \200 I nsulin: doses (eg during illness); practice self-injecting skills on oranges. \200 Diet: What? When? Why important? What do you do if the child is hungry? \200 Can blood glucose be monitored accurately? Watch the carer \200\231s technique. \200 What does the carer do if the blood sugar is not well controlled? \200 Does the parent or carer know what \200 \230well controlled \200\231 means? \200 Too much insulin? Signs: weakness \200\203hunger \200\203bolshy \200\203faintness \200\203sweating \200\203 abdo pain \200\203vomiting \200 \203 \201 ts \200\203coma. Some units practice hypoglycaemia (glu- cose <2mmol/L) on the w ard (ie no breakfast after morning insulin). Explain symptoms as they happen, and reversal with drinks (or Glucogel oral gel). 186 \200 s c i r t a d e a P i What should happen if the child misses a meal, or is sick afterwards? \200 What happens t o insulin requirements during \200\231 \202 u and other illnesses? \200 Who does mother or father contact in emergency? Give written advice. \200 Is the GP told of discharge/fo llow-up plans? His role is vital in encouraging optimism, and in keeping in touch with thos e who skip appointments. 587 \200 Encourage membership of a Diabetic Association (UK tel: 0207 323 1531). 1 Mean duration of symptoms pre-diagnosis is 30 days. Feeding with cows \200\231 milk, and infant exposure to enteroviruses, may \200\200incidence. 10% have mild coeliac disease, so screening these patients is wise. 2 Genes & environment: DM was a disease of the over-5s, but in the UK, incidence is rising in infancy from 1 : 10,000 in 1985 \200\22390 to >1.6 : 10,000. Islet cell antibodies are found in HLA-DR3/4 DQ8588 (but not HLA-B15) chil- dren. \200\2064 genes are important (6q partly determines islet sensitivity to damage), but most susceptibility to is environmentally acquired. Most with type 1 DM have antibodies to cows \200\231 milk albumin which react with \200 -cell surface proteins. Also, mumps, rubella, coxsackie & CMV have the potential to injure \200 -cells (exact role unclear). If one chi ld in a family has DM, risk to siblings is >5%. 187 MODY: maturity onset diabetes of the young589 MODY is a autosomal dominant kind of non-keto tic diabetes, in childhood or young adults. The defect is one of pancreatic beta cell dysfu nction \200\224lead- ing to impaired insulin secretion. 590 \211 6 causal genes exist. MOD Y is caused by single gene defects, as opposed to type 1 & type 2 diabetes which are have p olygenic and environmental causes. Classic MODY accounts for <5% of all childhood diabetes in Caucasians. 591 MODY2 (GCK subtype) is caused by mutations in the glucokinase gene on ch ro- mosome 7. Glucokinase converts glucose to glucose-6-phosphate, which is needed to stimu late insulin secretion by the beta-cells. There is mild, asympto- matic, stable hyperglycae mia from birth. Microvascular disease is rare. Drugs are rarely needed. MODY3 (HNF1A subtyp e) is the most common type. It is caused by a defect on chromosome 12 leading to a progress ive decrease in insulin production. It features severe hyperglycaemia after puberty, which often leads to a di- agnosis of type 1 DM. Despite progressive hyperglycaemia, sensitivity to sul- fonylureas is retained for years. Diabetic retinopathy and nephropathy often occur in MODY3. Frequency of cardiovascular disease is not increased. Owing to the pleiotropic ch aracter of transcription factors, most MODY subtypes are diseases with multi-organ involvem ent in addition to diabetes. MODY5 (HNF-1B)is more frequent than originally thought. It is associated with pancreatic atrophy, renal abnormalities, and genital tract malformations. M ODY 1 , 4 & 6 These subtypes of MODY are all rare. Molecular diagnosis matters because it h as important consequences for prognosis, family screening, and management. Although MODY is dominantly inherited, expression varies, so a family history of DM is not always present. s c i r t a i d e a P Hypoglycaemic coma \200 Get IV access. Get help. Intra-oral GlucoGel has a role if IV ac cess fails. \200 Give glucose 5mL/kg of 10% IVI, or by rectal tube if no IV access, with g luca- gon 0.5 \200\2231mg IM or slowly IV (0.5mg if <25kg). Expect quick return to con- sci ousness. If not, recheck glucose; if low, give IV dexamethasone (p200); if normal, ask your self is this is a post-ictal state after a hypoglycaemic \201 t? Here, giving more glucos e worsens cerebral oedema. \200\230What are the aims of routine follow-up in the diabetes clinic? \200\231 \200 To approach normoglycaemia via motivational education. Group learning is better than didactic doctor-sermons. To prevent complications (esp. renal & retinal). Check growth & fundi (dilate pupils; retin opathy takes 10yrs to develop). Blood: glucose, HbA1c, micro- albuminuria \200\224present in 25% after 10yrs (50% after 20yrs): \200\207reducible to 15% if glucose well-controlled; microalbuminuria may spontaneously reverse. If normoglycaemia is unachievable, choose the best compromise with the child \200\231s way of life and strict glucose control. Insulin-storing pen-shaped injectors allow \202 exibility in the timing and dose of insul in, delivering a variable dose (2u/push) without inconvenient drawing up of insulin (eg dur ing a party). Introduce to a friendly diabetic nurse-teacher; ask \200\234Is real-time continuous glucose monitoring indicated? \200\235. Feedback helps motivation and safety. Childhood diabetic ketoacidosis (DKA)1 Just 100 years ago, DKA was universally fatal. The \201 rst patient to receive insu- lin (on January 11th 1922), was Leonard Thompson \200 \224a 14-yr-old boy, who went on to live a further 13 years. DKA results from a de \201 ci ency of insulin, often in combination with increased levels of counter-regulatory hormones (catecho- lamines, glucagon, cortisol and growth hormone \200\224eg due to sepsis). The big concern with childhood DKA, (as opposed to adult DKA), is the increased fre- quency of cer ebral oedema (see BOX), which occurs in 1% of childhood DKA and has a mortality of 25%. Ot her fatal events in DKA include hypokalaemia and aspiration pneumonia (use NGT if semi-cons cious and protect airway). The patient Listlessness; confusion, vomiting; polyuria; polydip sia; weight loss; abdominal pain. Look for: Dehydration; deep and rapid (Kussmaul) respi- r ations; ketotic (fruity-smelling) breath; shock; drowsiness; coma. Diagnosis Requires the c ombination of hyperglycaemia ( \211 11mmol/L), acido- sis (venous pH <7.3) and ketones in u rine and blood. Severity is categorized by degree of acidosis: mild \200\224pH <7.3; modera te \200\224pH <7.2; or severe \200\224pH <7. 1 Management Do GCS (p720; p201 if <4yrs). Tru e coma is rare (<10%) in DKA: exclude other causes of coma; remember DKA may be precipitate d secondarily. Take the following action if shocked, consciousness \200\201, coma, or vomit ing.1 \200 Resuscitate: ABC: Oropharyngeal airway 100% O2 NGT. Consider intubation. Gi ve 10mL/kg IV boluses of 0.9% saline only if shocked, to a max. of 30mL/kg: over-enthusiast ic \202 uid resuscitation may cause cerebral oedema. Consider ITU if BP \200\201, or <2yr s, or ward staff busy (all children with DKA initially require high level of nursing care \200\224usually 1 : 1). 188 \200 s c i r t a d e a P i Rapidly con \201 rm diagnosis: with history, \201 nger-prick glucose + ketones; ve- nous blood gas; urine dip for ketones/glucose. 3 \200\223; blood gas; ECG Formal investigations: Weigh; FBC; U&E; glucose; Ca2+; PO4 monitoring (look for peaked T-wa ves of hyperkalaemia), lab urine. Use clinical signs to assess dehydration (BOX 2) Now calculate the volume of \202 uid to be replaced ( \202 uid requirement): ie maintenance \202 uid plus the dehy- dration de \201 cit minus any \202 uid already given as resuscitation \202 uid. It should be given at a constant steady rate over the 1st 48h. (see worked example). Start IV \202 uids: Start with 0.9% saline + 20mmol KCl/500mL. When blood glucose falls t o 14mmol/L use 0.9% saline + 5% glucose + 20mmol KCl /500mL. After 12h, if plasma sodium is stable, change to 0.45% saline + 5% glucose + 20mmol KCl/500mL. Start IV insulin only after 1h of IV \202 uids: Cerebral oedema may be more likely if ins ulin is started early. There is no need for an initial bolus of in- sulin. Use a 1 unit/mL solution of fast acting insulin (eg Actrapid ). Run at 0.1 units/kg/h. Ensure there is glu cose in the IV \202 uids when venous glucose is <14mmol/L. DO NOT stop insulin at this st age it is still required to switch off ketogenesis. Once pH >7.3 and glucose is <14mmol/L c onsider reducing insulin to 0.05units/kg/h. Stop IV insulin: When blood ketone levels are <1.0mmol/L, and patient is able to tolerate f ood, give a dose of subcutaneous insulin; feed the patient. Stop infusion 10 \200\22360mins after subcutaneous insulin injection Avoid bicarbonate in DKA: it can increase the risk of cerebral oedema. If acido- sis persis ts, consider \200\200dose of insulin (more glucose may be needed in the IV \202 uids). A sk yourself: is this child septic? Ongoing monitoring \200 Hourly blood glucose \200 CN S status \211 half-hourly. \200 Nurses must tell you of headache or behavior change prom ptly as these may indicate cerebral oedema (BOX) \200 Hourly \202 uid balance \200 U& E + blood gasses 2h after start- ing IVI, then 4-hourly. Have a dedicated line for drawing blood. \200 If a central venous catheter (CVC) is used to aid monitoring, consider DVT pr ophylaxis.2, 592 \200 Weigh twice daily \200 Monitor ECG for T-wave changes \200 Infe ction screen. 189 Pitfalls in diabetic ketoacidosis Cerebral oedema (MINIBOX) is a big threat, and is almost exclusively a condition of childhood. Pathophysiology is poorly understood: it usu- ally oc curs 4 \200\22312h from the start of treatment, but it may be present at onset of DKA or up to 24h afterwards, presenting as a sudden CNS de- terioration after an initial improvement . It is the major cause of death in diabetic children, not the much-feared hypoglycaemia Le ukocy- tosis (even a leukaemoid reaction) may occur without any infection. Infection: (ther e may be no fever). Do MSU, blood cultures, and CXR. Start broad-spectrum antibiotics (p202 ) if in- fection suspected. Creatinine: some assays for creatinine crossreact with ketone b odies, so plasma creatinine may not re \202 ect true renal function. Hyponatraemia (from o smotic eff ects of glucose): if <120mmol/L, search for other causes, eg triglycerides \200 \200 \200\200. Hypernatraemia >150mmol/L may be treated with of 0.45% saline to start with (0.9% saline thereafter). Ketonuria does not equate with ketoacidosis. Normal individuals m ay have ketonuria after an overnight fast. Not all ketones are due to diabetes \200\224con- sider alcohol, if glucose normal. Test plasma with Ketostix or Acetest to demonstrate ketonaemia. Acidosis without gross elevation of glucose may occur, but consider poisoning, eg with aspirin. Serum amylase is often raised (up to 10 \200\223fold), and nonspeci \201 c abdominal pain is common even in the absence of pancreatitis. Degree of dehydration1 \200 Mild \200\224is hard to detect; it approximates to 3% weight loss. \200 Moderate \200\224dry mucous membranes and \200\201skin turgor: 5%. \200 Severe \200\224sunken ey es and \200\201capillary re \201 ll time: 8% Overestimation of dehydration is dangerous \200\224 \200\207don t use an estimation of greater than 8%. NB: 8% dehydrated = water de \201 cit of 80mL/kg CNS deterioration If warning signs: headache, \200\201pulse, \200\200BP, restlessness, ir - ritability, focal neuorology (CN palsies), posturing, \200\200ICP, or falling consciousn ess: \200 Call your senior \200 Exclude hypoglycaemia \200 Mannitol 0.25 \200\2231.5g/kg IVI or NaCl 2.7% 5mL/kg \200 Restrict IV maintenance \202 uids by and replace de \201 cit over 72h s c i r t a i d e a P \200 Move to PICU and do CT \200 Treat sepsis vigorously Calculating \202 uid requirement in DKA1 Hourly rate = (48h maintenance + de \201 cit \200\223 \202 uid already given) 48 The BPSED1 suggests the following maintenance requ irements based on weight (diff erent from standard APLS rates): 80mL/kg/24h <12.9kg 65mL/kg/24h 13 \200\22319.9kg 20 \200\22334.9kg 55mL/kg/24h 35 \200\22359.9kg >60kg 45mL/kg/24h 35mL/kg/24h A 20kg 6-year-old boy who is 8% dehydrated, and who has already had 20mL/ kg of saline will require: (48h maintenance + de \201 cit \200\223 \202 uid already given) 48 \211\210 55mL \211\210 20kg \211\210 2 (as 48h) + (80mL/kg \211\210 20kg) \200\223 (20mL \211\210 20k g) 48 \211\210 (2200mL + 1600mL \200\223 400mL) 48 \211\210 3400mL 48 = 71mL/h 1 Guidelines for the management of DKA in children, British Society for Pediatric Endocrino logy and Diabetes (BSPED) 2009 \200\224available at: http://www.bsped.org.uk/clinical/docs/ DKAGuideline.pdf. These have been endorsed by NICE. 2 Because thrombotic complications are rare, heparin isn \200\231t usually needed and is not recommended as part of standard thera py, but see brighton-healthcare.nhs.uk/diabetes/newpage17.htm593 SE: thrombotic thrombocyto poenia.594 3 Note that pooling of KCl and insulin may cause uneven delivery in some IVI con tainers, so repeated mixing may be needed.595 \200 Poisoning: general points Determine what, how much and when poison was ingested; the number of tablets dispensed is often given on the pack \200\224count how many are left and consider the maximum dose that could have been taken. Ask if other medi- cines/chemicals ar e kept in the same place and could the child have taken more than one poison? Was this chil d playing with any others? If so, they too may have shared some of the poison. If the table ts are from an unlabelled box, the dispenser may have records and be able to name the table ts; to help identify medication from loose tablets brought in by parents use sites such as www. drugs.com/pill_identi \201 cation.html \200\224this is USA based \200\224your hospit al may subscribe to a equivalent local system. Once the poison has been identi \201 ed con sult TOX- BASE (www.toxbase.org) or local equivalent. \200\207Contact a National Poisons I nformation Service (NPIS, eg 0844 892 0111 in UK). Examination: Look for signs of toxidrome s. (see BOX). Ensure complete set of vital signs are obtained. Note GCS and pupils. Princip les of management \200 As always: ABC is your priority. Also check blood glucose. \200 Consider intubation if GCS <8, or respiratory failure; if GCS 8 \200\22314 consider oral/ n asopharyngeal airway (caution if vomiting) and put in recovery position. 190 \200 s c i r t a d e a P Maintain BP; correct hypoglycaemia; monitor urine output. \200 Baseline studies may inclu de: FBC, U&E; glucose; ECG \200 Do a blood gas: a metabolic acidosis with an increased an ion gap can be due to drugs such as metformin; alcohol; ethylene; toluene; cyanide; isoniaz id; iron; aspirin; paraldehyde or other causes (DKA; lactic acidosis) i Certain drugs can be measured in serum \200\224so test for paracetamol; ethanol; methanol; ethylene glycol; salicylates; iron; anti-convulsants; lithium; digox- in; theophylline; car boxyhaemaglobin if these are suspected. The mainstay of care is supportive management. \200 Consider gastric decontamination \200 \224discuss with a toxicologist. \200 Ipecac syrup, or any form of forced vomiting, is no longer recommended. 596 Activated charcoal is controversial as there is no evidence it imp roves clinical outcome. 597 It is most eff ective (in volunteer studies) if given within 1h of ingestion. Concerns exist about the risk of aspiration of charcoal if the patient vomit s (increased in hydrocarbon poisonings) or becomes drowsy. Avoid with lithium, alcohol, cya nide, iron ingestions or rapid acting ingestions. 597 Cathartics and Gastric lavage are vir tually never indicated. 598 \200\223 \200 600 Whole bowel irrigation should not be routinel y used, but it may be of bene \201 t in sustained released ingestions. 601 Only use after consulting NPIS or if speci \201 cally recommended in TOXBASE. \200 600 \200 Determine if a speci \201 c antidote is available (see below and p192 \200\2233). Speci \201 c anti dotes \200 Beta-blockers: cause hypotension, bradycardia, heart block and heart failure. Monitor ECG; atropine 40 g/kg IV for bradycardia, then glucagon (50 \200\223150 g/ kg IV + infusion of 50 g/kg/h in 5% glucose). Consider adrenaline or dopa- mine infusions. Carbon monoxide: High \202 ow oxygen and mannitol for cerebral oedeme. Se- vere cases may bene \201 t from hyperbaric oxygen therapy. Digoxin: Atropine is used if bradycardic. Digoxin speci \201 c antibody (Digib- ind \210 \217) is used in those with severe dysrhythmias/hyperkalaemia. Historically use of calcium in digoxin-induced hyperkalaemia has been avoided due to fears about cardiac tetany: this h as recently been considered less likely. 601 \200 Opioids: use IV naloxone 10 g/kg; if n o response try 100 g/kg (max 2mg). An infusion may be required. \200 Methanol/ethylene g lycol: Fomepizole. 602 Contact poisons unit promptly. \200 Sulfonylureas: ?Try octreotide . 603 Other antidotes: OHCM p852. 191 Toxidromes \200 Opioid \200\224eg morphine, codeine, methadone, oxycodone, heroin \200 \224bradycar- dia, hypotension, decreased respiratory rate, and pin-point pupils. Cholinergic \200\224eg organophosphates; pilocarpine \200\224(DUMBELLS): Diarrhea; Urinatio n; Miosis; Bradycardia; Emesis; Lacrimation; Lethary; Salivation. \200 Anticholinergic \200\224eg antihistamines, tricyclic antidepressants, deadly nightshade, atropine \200\224t hese patients are Hot as a hare, Red as a beet, Dry as a bone, Blind as a bat and, Mad as a hatter \200\224with hyperthermia, facial \202 ushing, dry skin, dilated pupils, and deli rium. They also have tachycardia and urinary retention. Sympathomimetic \200\224eg cocaine, amphetamines, pseudoephedrine \200\224patient is tachyc ardic, hypertensive, hyperthermic and has dilated pupils. Risk of seizures. s c i r t a i d e a P Iron poisoning Iron is a common childhood poison. It is absorbed as Fe2+, oxidized to Fe3+ and bound to transferrin. Toxicity occurs when transferrin binding capacity is reached. Ide ntify the exact preparation, as formulations contain diff erent amounts of elemental iron. A 200mg FeSO4 tablet contains 65mg elemental iron. 125mg/ mL FeSO4 drops contain 25mg iron /mL. A 300mg ferrous fumarate tablet may contain 100mg of iron (depends on brand), whereas a 300mg ferrous gluconate tablet may only contain 35mg iron. Expect mild toxicity at doses of >20mg/ kg of elemental iron. Mod-severe toxicity occurs with doses of >60mg/kg. 604,605 Presentation: Patients may have ingested tablets, liquid or multi-vitamins containing iron. He may present with nausea, vomiting, haematemesis, diar- rhoea, altered mental status or hypotension. Between 6 \200\22312 hours there may be a phase of apparent improvement. Betwe en 12 \200\22324 hours cardiovascular collapse and massive GI bleeding can occur. Severe me tabolic acidosis may develop as each Fe3+ ion combines with water to produce 3H+ and FeOH3. Renal and hepatic failure may ensue. Hepatotoxicity is a marker of severity and is a commo n cause of death. Survivors may develop pyloric strictures after 4 \200\2236 weeks secondar y to scarring. Tests: Baseline blood gas, serum iron concen- tration, U&E, FBC, glucose. Ir on levels at 4 \200\2236h help determine level of severity. Levels of <350 g/dL ( 60 mol/ L) are associated with minimal symptoms. Lev- els >500 g/dL ( 90 mol/L) are associated wi th serious toxicity. An abdominal radiograph may show tablets within the gut and reveal a b ezoar. \200\207In servere toxicity do not wait for tests: start desferrioxamine. Managemen t: \200 Obtain expert help as this is one of the few instances when gastric lavage/ endoscopy to remove tablets in the stomach may be recommended. \200 Activated charcoal is not given as it has no eff ect on iron absorption. \200 Whole bowel irrigation may help (esp. in slow-release preparations). 606 \200 Supportive care \200\224IV \202 uids and sodium bicarbonate to correct acidosis \200 Chelation with IV desferrioxamine (5 \200\223 15mg/kg/h \200\224start at higher dose then reduce after 4 \200\2236h \200\224max 80mg/kg/2 4h). Therapy should be stopped when the acidosis improves. It is rarely required for >24h. Use of desferrioxamine leads to orangey-red urine which demonstrates that free iron has bee n bound to the desferrioxamine. It is also associated with hypotension, rashes, pulmo- nary oedema and acute respiratory distress syndrome. Haemo \201 ltration has been used in children, in combination with desferriox- amine to ra pidly reduce iron levels. 607 Salicylate poisoning The most common salicylate is acetylsalicylic acid, ie aspirin, which is not rec- ommended in children <16y due to its association with Reye s syndrome (p652). C holine salicylate is found in Bonjela \210\217 for adults. Since 2009, Bonjela teeth- ing g el \210\217 in the UK has used lidocaine as its active ingredient, however Bonjela teething gel \210\217 in other countries (eg Australasia) continues to contain choline salicylate ( 8.7%) and there are reports of toxicity in children. 608 Methyl salicy- late is found in oi l of wintergreen (98%). As little as 3mL can be fatal in chil- dren. 609 Methyl salicylate is also found in muscle rubs such as Bengay \210\217, Deep Heat \210\217, and Tiger Balm \210\217 ( 15 \200\22340%). Presentation: Toxicity occurs at 100mg/kg aspirin. Early signs include tinnitus and hearing loss. Stimulation of respiratory centers leads to tachypnoea and a respiratory alkalosis. Interference with aer- obic metabolism leads to the metabolic (lactic) acidosis which is character- istic of salicylate poisoning. GI irritation (nausea, vomiting, abdominal pain is common). Central eff ects lead to agitation, delirium and seiz ures. Rhabdomy- olysis, pulmonary oedema and electrolyte disturbances may also occur. Tests : Blood gas; FBC; U&E, glucose. Salicylate levels are best obtained at 6 hours (re- \202 ects a peak level) however, do an initial level to con \201 rm diagnosis, and then levels every 2h to con \201 rm levels are decreasing \200\224enteric coated (EC) prepara- tions c an lead to delayed absorption. Large bezoars of EC aspirin may be seen on radiograph. Manag ement: Resuscitate with boluses of 10 \200\22320mL/kg of 0.9% saline. Correct hypoglycaemia . Potassium may be needed as hypokalaemia is common. Serious poisoning is indicated by leve ls >2.5 \200\2233.6mmol/L \200\224consider urinary alkalinization with IV sodium bicarbonat e to enhance elimination (un- der expert guidance in ITU). Activated charcoal is eff ective in adsorbing aspi- rin, but as patients are liable to vomit or experience \200\201GCS con sider intubating \201 rst and using a NGT. Repeat doses can be given. Haemodialysis is th e de \201 nitive treatment: use when evidence of end organ injury 610 (seizures, severe ac idosis, rhabdomyolysis, renal failure, pulmonary oedema). Seek expert help. 192 s c i r t a d e a P i Paracetamol (acetaminophen) poisoning The therapeutic dose is 15mg/kg. Hepatotoxicity can o ccur if \211 150mg/kg/24h ingested. The initial features are nausea and pallor. Hepatic en zymes rise after 24h. Jaundice and an enlarged, tender liver occur after 48h. Hypoglycaemi a, hypotension, encephalopathy, coagulopathy, coma may also occur. Management of single ora l paracetamol overdoses: \200 If you are certain the ingested paracetamol is <150mg/kg in a child with no hepatic risk factors (below), then management may be safely done at home. 611 \200 Admit those presenting within 8h of ingesting >150mg/kg (or an unknown amount or with high risk factors) and do a serum paracetamol concentration at \211 4h post ingestio n. If presenting <1h, and >150mg/kg of tablets ingested, and no contra-indication (eg vomit ing; \200\201GCS), give activated charcoal \200\224not bene \201 cial if elixir has been ingested which is absorbed in 15 mins. 612 \200 Decide if the child has any high-risk fa ctors, eg patients who are on enzyme- inducers (p300) or who are malnourished (eg anorexia, alcoholism, HIV +ve), or have febrile illness \200\224in whom toxicity may occur at doses of >75mg/kg. 613 \200 Consult the nomogram on the opposite page. If the child is high ris k, use the lower treatment line, if not \200\224use the upper line. If plasma paracetamol l evel is above the appropriate line, treat with acetylcysteine (NAC). The initial dose is 15 0mg/kg in up to 200mL (depending weight; see BNF) of 5% dextrose infused over 15min, follow ed by 50mg/kg IVI over the next 4h, and 100mg/kg IVI over next 16h. It is very eff ective i n preventing liver damage if given in <8h. Patients with a delayed presentation (>8h) or in whom a level cannot be ob- tained within 8 h, should have acetylcysteine started immediately if ingested dose is >150mg/kg, or dose is unknown. Check often for hypoglycaemia. Consider the cause: typically teenage girls seeking attention. All need psy- chiatric evalu ation. Causes may be extremely complex and deep-seated: although the patient may claim a se emingly super \201 cial cause this may be hiding deep social or psychiatric pathology. 193 Staggered overdose: Seek expert help: these patients are at potentially great- er risk than those with single point overdoses, and may present with greater delays. 614 Paracetamol le vels alone may not be reliable in staggered overdoses, so LFT and INR are also done. If >8h from 1st dose, treat with NAC; don \200\231t wait for levels as effi cacy is waning fast. If <8h, do levels (see graph). s c i r t a i d e a P Fig 1. Graph for use in deciding who should receive acetylcysteine. Dr Alun Hutchings (University of Wales). \200\207This graph DOES NOT apply to IV paracet amol. If 4h level following IV par- acetamol overdose is >50mg/L (below high-risk treatment line) or if a single IV overdose of >60mg/kg has been given, then treatment should be star ted. 615,616 This is because IV paracetamol plasma concentration peaks at the end of ad- mi nistration. By 4h levels may have dropped considerably. Consult with NPIS. Other countries use diff erent nomograms. Australasian guidelines have a sin- gle treatment line which star ts at 150mg/L \200\224that is midway between the UK high risk and normal treatment lines. 6 17