biochemistry and clinical toxicology
TRANSCRIPT
![Page 1: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/1.jpg)
Biochemistry andClinical Toxicology
Mike HallworthRoyal Shrewsbury Hospital
ACB North West RegionAutumn Meeting – 18 October 2005
![Page 2: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/2.jpg)
Poisoning - epidemiology
• Incidence approx. 3 per thousand pa
• Approx. 100 000 hospital admissions pa
• <5% unconscious• <0.5% die
![Page 3: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/3.jpg)
Most frequent enquiries to Toxbase [relative to paracetamol]
1. Paracetamol 1.002. Diazepam 0.303. Aspirin 0.284. Ibuprofen 0.265. Zopiclone 0.256. Ecstasy 0.237. Amitriptyline 0.208. Dothiepin 0.209. Temazepam 0.1810. Coproxamol 0.17
(Camidge et al, 2003)
![Page 4: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/4.jpg)
Commonest poisons on admission to hospital
(Watson and Proudfoot, 2002)
• Paracetamol 60%• Ethanol 35%• Salicylate 30%• Carbon monoxide 25%• Tricyclics & phenothiazines 12%• Others 30%
![Page 5: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/5.jpg)
Laboratory support for drug-related emergencies:
• standard laboratory tests
• specific drug concentrations
• drug screens
![Page 6: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/6.jpg)
Standard laboratory tests
• Arterial blood gases– Ventilation problems– Acid-base disturbances
• Urea & electrolytes (incl Cl, HCO3, creat)– Hyper/hypo kalaemia– Anion gap
• Osmolality– Alcohols
• Calcium, albumin, Mg– Oxalate/fluorides
![Page 7: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/7.jpg)
Standard laboratory tests ii
• Glucose– Differential diagnosis of coma– Hypoglycaemic
agents/EtOH/salicylates
• LFTs– Paracetamol– Iron salts– Halogenated hydrocarbons
![Page 8: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/8.jpg)
Standard laboratory tests iii
• Creatine kinase– Rhabdomyolysis
• FBC/INR– Paracetamol
• Urine tests– Colour– Hb, (myoglobin)– Crystals
![Page 9: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/9.jpg)
Emergency measurement of plasma drug concentrations
• assessing severity of poisoning – if this is not possible clinically
• determining need for specific treatment
• monitoring efficacy of treatment
• guiding therapy in severely ill patients
in rapidly changing circumstances
![Page 10: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/10.jpg)
Toxicological testing in overdose
1. Toxicity predictable based on serum levels. Drug-specific therapy can be instituted when levels dictate:
Salicylate Theophylline LithiumDigoxin ParacetamolMethanol Ethylene glycol
2. Toxicity correlates with serum level, but supportive care only required:
Ethanol Barbiturates Phenytoin
![Page 11: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/11.jpg)
Toxicological testing in overdose
3. Toxicity and requirement for specific treatment depend on clinical parameters - testing only confirms:
Tricyclics Narcotics (naloxone)Cyanide OrganophosphatesBenzodiazepines (flumazenil)
4. Toxicity poor correlation with serum level - supportive care only required:
Neuroleptics CocaineHallucinogens PhenylpropanolamineAmphetamine Phencyclidine
(Mahoney, 1990)
![Page 12: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/12.jpg)
Reducing absorption
• ((emesis))• (lavage)• ORAL CHARCOAL
![Page 13: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/13.jpg)
Increasing elimination
• (forced diuresis)• Urine alkalinization• Dialysis• Charcoal/resin haemoperfusion• Multiple-dose oral charcoal
![Page 14: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/14.jpg)
Specific antidotes
• Paracetamol:N-acetylcysteine Methionine
• Methanol/ ethylene glycol: Ethanol, fomepizole
• Opiates : Naloxone• Metals: Chelators
(DFO, EDTA, etc)
![Page 15: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/15.jpg)
Laboratory analyses for poisoned patients:joint position paper
National Poisons Information Service and the Association of Clinical Biochemists
Ann Clin Biochem 2002; 39: 328-339
![Page 16: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/16.jpg)
Concentration measurements required at
any time:(NPIS/ACB, 2002)
• Salicylate• Paracetamol• Iron• Lithium• Theophylline
• Ethanol• CoHb, MetHb• Digoxin• Paraquat (qual)
within 2h
![Page 17: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/17.jpg)
Specialist assays that may be required urgently
(ACB/NPIS, 2002)
• Methanol• Ethylene glycol• Phenytoin• Carbamazepine • Phenobarbital• Methotrexate• Paraquat (quant.
plasma)
• AChE• As• Hg• Pb• Thyroxine
• Unknown screen
![Page 18: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/18.jpg)
Drug screens
• Usually of very limited value
![Page 19: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/19.jpg)
Mahoney et al., 1990 - Boston, USA
Impact of qualitative toxic screening in management of suspected OD
176 cases of drug OD164 screened by:
GC, HPLC x3, acid GCMS, basic GCMS
![Page 20: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/20.jpg)
Mahoney et al., 1990 - Boston, USA
81% screens POSITIVE
19% screens NEGATIVE
![Page 21: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/21.jpg)
Mahoney et al., 1990 - Boston, USA
Impact of screens on management:
Treatment: n %No impact 146 90 Initiated 2 1 theophylline, salicylate
Continued 12 7 salicylate x2, lithium x2
paracetamol x2,
digoxin x1, Hg x1
Discontinued 4 2 paracetamol x4
![Page 22: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/22.jpg)
Mahoney et al., 1990 - Boston, USA
Impact of screens on disposition:
35/176 admitted to hospital:
20 because of clinical findings7 because of clinical findings + drug screen
(6 salicylate, 1 imipramine)8 because of drug screen alone
(3 paracetamol, 2 lithium, 1 salicylate, 1 carbamazepine,
1 diphenhydramine)
![Page 23: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/23.jpg)
Utility of toxicology screening in paediatric ER
(Sugarman; Pediatr Emerg Care 1997; 15: 194-7)
• Full toxicological screens on 338 children
• Unexpected results in 7% of screens• Management altered as a result of
screening results in 3 patients (<1%)– All three had abnormal symptoms
![Page 24: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/24.jpg)
Urgent drug screens
• Poisoned patient very ill – ? Nature of poison
• Deteriorating unconscious patient without
![Page 25: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/25.jpg)
“Routine” toxicology
• Diagnosis of brain death• Suitability of organs for Tx• Medico-legal (e.g. “date rape”)• Forensic
![Page 26: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/26.jpg)
Exposure to poisons
Toxin Age <5 Age >15
Drugs 50.9% 74.8%Household prods. 20.4% 7.3%Toiletries 7.4% 1.4%Petroleum distill. 5.7% 1.4%Chemicals 6.2% 10.1%
(SPIB, 1994)
![Page 27: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/27.jpg)
Poisonings other than drugs
• “Detection of poisonings by substances other than drugs: a neglected art”
Badcock NR Ann Clin Biochem 2000; 37:
146-57
![Page 28: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/28.jpg)
S.B., 40 years, F
• On admission (1600, 18.1.97):– Na 147, K 4.4, Cl 103, urea 1.5, creat
91
– pH 6.73, pO2 51.2 , pCO2 6.2, bicarb 6, glucose 16.9
– Anion Gap = 42 mmol/L (12-20)– Osmolality: calc: 320, meas: 470– Osmolar Gap = 150 mmol/L
![Page 29: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/29.jpg)
Gaps
• ANION GAP:Raised in:
– lactic acidosis– ketoacidosis– salicylate
poisoning– methanol/ethylene
glycol poisoning– CRF
• OSMOLAR GAPRaised with:
– Unmeasured osmoles:
• ethanol/methanol• (ethylene glycol)• mannitol/glycine
– severe shock– high
lipid/protein
![Page 30: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/30.jpg)
Methanol / ethylene glycol
• Usually latent period before symptoms (12-72h)
• Headache• Pale, restless• Sweating• Convulsions• Nausea/vomiting
• Visual symptoms• Severe metabolic
acidosis• Cardiorespirator
y failure• Crystalluria &
renal tubular necrosis (glycol)
![Page 31: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/31.jpg)
Ethanol(intoxication)
Methanol(intoxication)
Ethylene glycol(intoxication)
Acetaldehyde(hangover, flushing)
Formaldehyde(blindness,
cerebral oedema)
Glycoaldehyde(CNS effects)
Acetic acid Formic acid(metabolic acidosis)
Glycolic acid(metabolic acidosis)
CO2 + H2O Glyoxylate(lactic acidosis)
Oxalate(cerebral and renal
damage, hypocalcaemia)
Alcoholdehydrogenase
Aldehydedehydrogenase
LDH or glycolic acid oxidase
LDH or aldehyde oxidase
![Page 32: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/32.jpg)
Diagnosis of methanol poisoning
• Metabolic acidosis• High anion gap• High osmole gap• Eye signs
presumptive
![Page 33: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/33.jpg)
Estimation of alcohol concentration
• Ethanol (mg/dL) / 4.6 = osmolalityi.e. 80 mg/dL = 17 mmol/kg
• Methanol (mg/dL) / 3.2 = osmolality
• Ethylene glycol (mg/dL) / 6.2 = osmolality
![Page 34: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/34.jpg)
M.McG, age 28, female
• OD 20 tabs Theo-Dur (husband’s) + 7 cans strong lager
• Anxious ++, pulse 130-160/reg• SWO 1h after ingestion• at 11h, Fits ++, pH = 6.9 : xfer to ITU• K+ 2.3 mmol/L• Theophylline @ 16h = 138 mg/L (760
mol/L)• Start HD & CHP• CK 113,300 U/L, ARF developed (creat =
1355)
![Page 35: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/35.jpg)
Key points (i)
• Laboratory support for drug-related emergencies consists of standard biochemical/haematological tests, measurement of specific substances and drug screens for unknown poisons.
• Standard laboratory tests are most important for determining immediate management in most patients.
• Emergency measurement of specific substances is indicated in a small number of cases where specific therapy may be instituted depending on the nature and quantity of the poison ingested.
![Page 36: Biochemistry and Clinical Toxicology](https://reader033.vdocuments.mx/reader033/viewer/2022061518/5561a776d8b42afd708b4ecb/html5/thumbnails/36.jpg)
Key points (ii)
• Laboratories in hospitals dealing with acute admissions need key toxicological analyses available 24/7
• Repeated measurement of specific substances may be used to guide therapy.
• Drug screens rarely of immediate value but may be necessary when the patient is critically ill, or when the patient is ill and not improving, and the diagnosis is uncertain.