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Common poisonings

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  • 1. Common PoisoningsCommon Poisonings www.freelivedoctor.com
  • 2. General Points about Poisoning Per annum in the UK there are: • some 300,000 cases of poisoning • 100,000 hospital admissions for poisoning (in-patient mortality <1 %) • 3,500-4000 deaths from poisoning (1000 of these are due to CO) Remember: • drug history may be unreliable • 65% of drugs used are prescribed to the patient, a relative or friend • 30% of self-poisonings involve multiple drugs • 50% of drug-overdose also involve alcohol …. Question witnesses or family about ANY access to drugs or ANY bottles found. …. There may be clues from the clinical signs (eg pin-point pupils with opiates), signs of solvent/ethanol abuse or signs of IV drug use (venepuncture sites). www.freelivedoctor.com
  • 3. … and their Management The role of antidotes is restricted to a minority of drugs. In most cases of overdose, survival is crucially dependent on supportive care ….  Monitor the airway (recovery position +/- intubation)  Maintain normoxia (+/- IPPV)  Maintain body temperature  Correct any hypotension (+/- volume expansion) or hypertension  Correct acid-base or electrolyte disturbance  Treat any fits (DZP +/- IPPV)  Monitor for dysrrhythmias (2ary role of antiarrhythmics)  Beware of skin blistering and rhabdomyolysis. Remember to take account of concurrent medical problems eg an IV drug user may be septicaemic or have hepatitis, SBE or HIV-related disease. www.freelivedoctor.com
  • 4. • One of the commonest drugs taken in OD • Across all age-groups, 20% men and 30% women take OTC analgesics regularly • Reduction in paracetamol pack size in 1998 has led to shift in UK consumption in favour of NSAIDs … ASPIRIN Occasionally poisoning follows topical application of salicylic acid in keratolytics or ingestion of methyl salicylate ('oil of wintergreen‘). 1ary toxic effect is to uncouple oxidative phosphorylation. Presentation • SalicylismSalicylism=sweating, vomiting, epigastric pain, tinnitus and blurring of vision. • Early respiratory alkalosis (not seen in children) precedes the later metabolic acidosis. • In severe overdose, acidosis reduces the ionization of salicylic acid enhances CNS penetration => agitation, tremor and fits … eventually to coma and respiratory depression. www.freelivedoctor.com
  • 5. ASPIRIN Complications • Electrolyte Disturbance universal hypokalaemia and deranged Na+ (high > low) glucose (hyper > hypo) • Pulmonary oedema (often non-cardiogenic) & acute renal failure. • Hypoprothrombinaemia is very rare. • Significant GI bleeds are surprisingly infrequent. Management - therapeutic [salicylate] is <300mg/l (2.2 mmol/l)  Mild/moderate salicylism requires only rehydration + KCl supplements.  Marked salicylism or levels > 750mg/l need specific elimination therapy: (1) Oral activated charcoal (50g 4 hourly) (2) Forced alkaline diuresis NO LONGER RECOMMENDED - it is no more effective than simple alkalinisation (eg 1 L 1.26% NaHCO3 over 2 hrs and repeated to keep the urinary pH > 7.5). (3) Haemodialysis is required for any of the following: level >1000mg/1 (7.25 mmol/l); persistent/progressive acidosis; deteriorating level of consciousness. www.freelivedoctor.com
  • 6. HN C CH3 OH O Paracetamol (Acetaminophen, Tylenol ® ) NB component of compound analgesics such as co- codamol, co-dydramol & co-proxamol and amongst OTCs some Alka-Seltzer ® , Anadin ® and Beechams-Powders ® preparations. • 15 – 20 tablets (7.5-10g) = overdose • Causes severe centrilobular necrosis of the liver • 10% have renal toxicity (acute tubular necrosis) • Accounts for ~ 200 deaths/year in UK PARACETAMOL www.freelivedoctor.com
  • 7. OH HN C CH3 O O HN C CH3 O Sulphate O HN C CH3 O glucuronide OH HON C CH3 O 60% 40% CYP2E - minor pathwayCYP2E - minor pathway exceptexcept in overdose!in overdose! Paracetamol MetabolismParacetamol Metabolism O N C CH3 O NABQINABQI www.freelivedoctor.com
  • 8. (Glutathione-S-transferase) O N C CH3 O δ +ve OH HN C CH3 O S G GSH SH Detoxifcation of NABQIDetoxifcation of NABQI consumes GSHconsumes GSH www.freelivedoctor.com
  • 9. Protection by glutathione (GSH) and its substitution with exogenous N-acetyl-cysteine - OOC – CH2 – N – C – CH – N – C – CH2 – CH2 - CH O CH2 SH H H O COO- NH3+ Tripeptide (γ-ECG). Present in all cells – high in hepatocytes ~ 5mM • Exogenous GSH cannot enter hepatocyte • NAC is SH donor to scavenge NABQI • Also protects intracellular levels of GSH in hepatocytes • Depletion of GSH by >80% causes toxicity www.freelivedoctor.com
  • 10. PARACETAMOL Presentation • Apart from mild nausea, vomiting and anorexia, patients presenting within 24 hrs of ingestion are generally asymptomatic. • Hepatic necrosis becomes apparent at 24-36 hrs with: – right subchondral pain/tenderness – reappearance of vomiting and neuroglycopenia – Deepening Encephalopathy over the next 72 hrs. Complications • The predictable consequences of liver failure i.e. metabolic acidosis, hypoglycaemia, cerebral oedema, cardiac arrhythmias and GI bleeding. • 10% of patients develop renal impairment from acute tubular necrosis - occasionally in the absence of hepatic failure. • Very rarely patients with G6PD deficiency develop methaemoglobinaemia and haemolysis. Prognostic features • Untreated, the fatal dose in adults is usually >10g - lower in chronic alcoholics or subjects with underlying liver disease or treated epileptics. • A PT of 20s at 24 hrs indicates significant hepatocellular damage; the more rapid the rise in PT thereafter the poorer the prognosis. • In patients developing hepatic failure, a poor prognosis is suggested by: (1) arterial pH <7.3; (2) prothrombin time >100s; (3) creatinine of >300 mol/l. They should be considered for early liver transplantation.www.freelivedoctor.com
  • 11. PARACETAMOL Management • Within 4 hrs of ingestion lavage (?) or activated charcoal • Paracetamol levels checked at 4hrs & compared to treatment curve (200mg/1 or 1.32mmol/l at 4h joined to with 6mg/1 or 0.04mmol/l at 24h). Some 60% of patients above the line develop severe liver damage defined as AST >1000. • Patients on or above the line should be given IV N-acetylcysteine* * up to 10% have a rash, bronchospasm or hypotension during the IVI (acts as a mast cell releaser). Stopping and giving chlorpheniramine IV usually allows the IVI to be safely restarted. www.freelivedoctor.com
  • 12. CARBON MONOXIDE HSE limit 200ppm (0.02%) causes headaches in 2-3 hours cf >10,000ppm (1%) that can cause death in a few minutes. The commonest sources are: – smoke inhalation – poorly maintained domestic gas/oil appliances – deliberate inhalation of car exhaust fumes Causes intense tissue hypoxia by two mechanisms: – interrupts electron transport in mitochondria – blocks tissue O2 delivery • competes with O2 for binding to Hb (Ka CO 220-fold > 02) • alters shape of the HbO2 dissociation curve (less sigmoidal) www.freelivedoctor.com
  • 13. CARBON MONOXIDE Signs of hypoxia without cyanosis - 'cherry-red' colouration most obvious post mortem! Symptoms & signs correlate with % COHb*: <30% causes only headache and dizzyness 50-60% produces syncope, tachypnoea, tachycardia and fits >60% increasing risk of cardiorespiratory failure and death. NB Pulse-oximetry unhelpful – it measures functional saturation … * Non-smoker 1%; Smoker 5-8%; Jogger in London 12% … www.freelivedoctor.com
  • 14. CARBON MONOXIDE Management • Check ABG - PaO2 may be normal but metabolic acidosis indicates severe poisoning. • Give O2 by mask unless comatose then IPPV with FiO2 =1 (t1/2 COHb 320 mins on room air vs 80 mins at 100%)*. [Also consider if severely acidotic or evidence of myocardial ischaemia.] • Control fits with IV diazepam. Hyperbaric 02 will shorten the washout of COHb further (half-life of 25 mins at 2 atmospheres), but access and transfer times to a hyperbaric chamber may make this impractical. Recent trial suggest may be worthwhile (cognitive sequelae at 6/52 were reduced from 35/76 to 19/76 by this Rx …. NEJM 2002;347:1057 www.freelivedoctor.com
  • 15. Complications   Sites at particular risk are: • CNS - cerebral, cerebellar or midbrain (Parkinsonism and akinetic- mutism)  • Myocardium - ischaemia/infarction  • Skeletal muscle - rhabdomyolysis/myoglobinuria  • Skin - erythyema to severe blistering.  NB (1) Anaemia, increased metabolic rate (e.g. children) and underlying  ischaemic heart disease all increase susceptibility to CO. (2) Neurological recovery depends on the duration of hypoxic coma:  complete recovery has been reported in young subjects (under 50)  after up to 21 hrs versus 11 hrs in older ones. CARBON MONOXIDE www.freelivedoctor.com
  • 16. COCAINE •  Coca leaves chewed by Pre-Columbian Indians for several millenniaCoca leaves chewed by Pre-Columbian Indians for several millennia •  1884, Koller discovers efficacy as ophthalmic local anaesthetic1884, Koller discovers efficacy as ophthalmic local anaesthetic •  Freud adds his endorsement the same year, Freud adds his endorsement the same year, ‘Uber Coca’‘Uber Coca’ •  Merck and Parke Davis compete for commercial productionMerck and Parke Davis compete for commercial production •  Widespread addition to wines (Vin Mariani) and ‘tonics’ (Pemberton’s) …Widespread addition to wines (Vin Mariani) and ‘tonics’ (Pemberton’s) … Erythroxylon CocaErythroxylon Coca Leaves contain up to 10mg/g of cocaineLeaves contain up to 10mg/g of cocaine ‘‘According to forensic experts, around 80 According to forensic experts, around 80  per cent of all banknotes in circulation per cent of all banknotes in circulation  are contaminated with drugs, a figure are contaminated with drugs, a figure  that rises to 99 per cent in the London that rises to 99 per cent in the London  area. Research by Mass Spec Analytical, area. Research by Mass Spec Analytical,  the Bristol-based forensics company the Bristol-based forensics company  which analyses banknotes seized by which analyses banknotes seized by  police and customs, shows that cocaine police and customs, shows that cocaine  is the most common substance’ is the most common substance’ TheThe Observer from Nov 10, 2002.Observer from Nov 10, 2002. www.freelivedoctor.com
  • 17. Traub, S. J. et. al. N Engl J Med 2003;349:2519-2526 COCAINE Users, Carriers & Routes ofUsers, Carriers & Routes of AdministrationAdministration •  In 1999, an estimated 1.5m Americans In 1999, an estimated 1.5m Americans  were current users and 3.7m had taken it were current users and 3.7m had taken it  in the past 12 months. Hair analysis for in the past 12 months. Hair analysis for  metabolites suggests a 4-5 fold larger metabolites suggests a 4-5 fold larger  problem.problem. •  Its subjective and sympathomimetic Its subjective and sympathomimetic  actions are often indistinguishable from actions are often indistinguishable from  amphetamine even for experienced users.amphetamine even for experienced users. •  Onset can be very rapid when snorted or Onset can be very rapid when snorted or  smoked (freebasing 'crack').smoked (freebasing 'crack'). •  Occasionally massive overdose in drug Occasionally massive overdose in drug  smugglers presents after smugglers presents after  swallowed/secreted packets rupture. swallowed/secreted packets rupture.     www.freelivedoctor.com
  • 18. Presentation • Indirect sympathomimetic effects c.f. amphetamines  • Seizures common as well as ventricular arrythmias.  • Very high doses cause CNS depression particularly in the medullary centres  with cardiorespiratory failure. Complications • Vasoconstrictor effects on the coronary circulation - even with  angiographically normal vessels. • Hypertensive strokes.  • Psychotic reactions (c.f. amphetamine psychosis).  • Cocaine can cause seizures in epileptics in 'recreational' doses but for non- epileptics presentation in status epilepticus generally implies massive  overdose which is often resistant to treatment and carries a poor prognosis.  • A syndrome of acute rhabdomyolysis, hyperpyrexia, renal failure, severe liver  dysfunction and DIC has been reported and also carries a high mortality cf  ecstasy.  • Patients with deficiency of serum pseudocholinesterase appear to be at  particular risk of life threatening cocaine toxicity.  COCAINE www.freelivedoctor.com
  • 19. Management • Monitor ECG continuously. Ensure the airway is clear and if the  patient is comatose intubate and mechanically ventilate early. Watch  for evidence of hyperpyrexia.  • Seizures: IV diazepam (10-20mg IV stat and if necessary an IVI of  up to 200mg/24hrs). If new focal seizures CT indicated.  • Hypertension: IV GTN or phentolamine first-choice; labetalol IV  second-choice (inadequate α-blockade?) NEVER pure beta- blockers!  • Ventricular arrythmias may be treated with lignocaine (100mg stat  then an IVI of 4mg/min) provided the patient is paralysed and  ventilated otherwise seizures may be precipitated. In concious  patients, IV labetalol may be useful. Phenytoin 3rd Iine but especially  useful in the presence of seizures.  • Hyperpyrexia prompt cooling (aim for rectal temp <38.5).  Chlorpromazine ? (25-50mg IM) beware sedation and hypotension.  Dantrolene? COCAINE www.freelivedoctor.com
  • 20. Papaver SomniferumPapaver Somniferum OPIATES Presentation • Pin-point pupils & Coma • Severe respiratory depression/cyanosis  • BP may be low but often well maintained - NB pentazocine overdose actually ↑ BP • Hypotonia often marked - dextropropoxyphene and pethidine ↑ muscle tone and cause fits Complications •All opiates can cause non-cardiogenic pulmonary oedema - but most frequent with IV heroin.  • Rhabdomyolysis is common in opiate-induced coma - it should be looked for in all cases.  • Substances used to dilute ('cut') illicit opiates may be toxic e.g. talc and quinine.  www.freelivedoctor.com
  • 21. OPIATES Prognostic features • Non-cardiogenic pulmonary oedema carries a poor prognosis (it is not  naloxone reversible) • Patients ingesting paracetamol+opiate combinations (i.e. co-proxamol and  co-dydramol) obviously run the additional risk of paracetamol toxicity • Patients with underlying ischaemic heart disease seem more susceptible  to haemodynamic disturbance after naloxone is given to reverse opiate  intoxication (see below) NB Renal impairment reduces the elimination of many opiates (or their glucuronidated metabolites), so prolonging their duration of action.  www.freelivedoctor.com
  • 22. OPIATES Management • If paracetamol+opiate combinations ingested measure a paracetamol level and treat accordingly. • Specific antidote is naloxone given as IV in boluses of 0.4mg at 2-3 minute intervals until rousable and respiratory depression corrected. •Convulsions (usually pethidine or dextropropoxyphene) usually respond to IV naloxone without additional anti-convulsant therapy. • Pulmonary oedema present on admission generally requires IPPV. Important points re use of Naloxone …. If >2mg given with no response, revisit the diagnosis of opiate overdose! Naloxone has a short half-life compared to most opiates. With long-acting opiates such as methadone a naloxone IVI may be necessary for 48- 72hrs. www.freelivedoctor.com
  • 23. OPIATES Beware Cold Turkey! …. Giving sufficient naloxone to completely reverse the effect of opiates in an opiate-dependent subject is likely to precipitate an acute withdrawal reaction. …. Marked hypertension, acute pulmonary oedema and VT/VF have been observed in non-adducts given naloxone to reverse the effects of high therapeutic doses of opiates for pain. Further points 1. Dextropropoxyphene + alcohol can cause marked CNS depression. Respiratory arrest can evolve within <30 mins of ingestion. Give naloxone even if the patient is only mildly drowsy. It also causes an acute cardiotoxicity with arrhythmias due to a membrane-stabilising effect (naloxone ineffective). 2. The respiratory depressant effects of buprenorphine are not fully reversed by naloxone. Doxapram has been used in milder cases of buprenorphine overdose as a respiratory depressant (1-4mg/min) although severe cases may require IPPV. www.freelivedoctor.com
  • 24. • MDMA synthesized by chemists at Merck in 1912 and patent granted in 1914 – later resurfaced in Gottlieb’s CIA campaign, MKULTRA • Used legally by psychotherapists until 1985 when it was first made a schedule I drug in USA • Recreational use now exceeds 750,000 tabs/week in NY – probably similar number in UK. • Single tablet doses typically 50- 100mg. Occasionally unexpected adulterants e.g. strychnine. Jacob Merck’s ‘Engel-Apotheke’,Jacob Merck’s ‘Engel-Apotheke’, Darmstadt circa 1668Darmstadt circa 1668 3,4-methylenedioxy-methamphetamine (MDMA, Ecstasy) www.freelivedoctor.com
  • 25. Presentation – following typical of amphetamines but not features of usual recreational doses of E • Sympathomimetic effects - mydriasis, ↑BP, ↑HR, skin pallor. • Central effects - hyperexcitability, talkativeness and agitation. • [Paranoid features may be obvious especially in chronic users – not applicable to E]. Complications • A 'heat-stroke' like syndrome: rhabdomyolysis, hyperpyrexia (>42 C), DIC and acute renal failure. It carries a poor prognosis (see cocaine). ? PK problem ?? CYP2D6 metaboliser status important • [Intracranial (and subarachnoid) haemorrhage (? 2ary to hypertensive effect but can occur after single therapeutic doses and vasospasm reported at angiography 'string-of- beads' sign) – not applicable to E]. 3,4-methylenedioxy-methamphetamine (MDMA, Ecstasy) www.freelivedoctor.com
  • 26. Management • Agitation - diazepam IV or lorazepam IM. Haloperidol if psychotic. • Seizures - diazepam IV (if new focal signs urgent CT). • Hypertension – First choice, GTN IV or α-blockade (phentolamine IV); Second choice, labetalol IV NEVER pure β-blockers. • Hyperpyrexia - prompt cooling (aim for rectal temp <38.5). Chlorpromazine? (25-50mg IM) beware sedation and hypotension. Dantrolene? • Acidification of the urine? - can substantially increase elimination but must be weighed against the electrolyte and pH disturbance caused. 3,4-methylenedioxy-methamphetamine (MDMA, Ecstasy) www.freelivedoctor.com