Toxicology Flashcards
Charcoal - give for the Killer Cs
Indications
Agents bound
Improve clinical outcome
Benefits»_space; risks
Good outcome not expected with supportive care alone
< 2hrs post ingestion, 4hrs if XR
Dose 1g/kg up to 50g
Agents effective for
Cyanide
Colchicine
CCB
TCAs
Cardiac-glycosides
Cyclopeptide mushrooms
Cocaine
Cicutoxin (water hemlock)
Salicylates
Complications
Vomiting / mess
GI - bowel obstruction and perforation
Aspiration
Corneal abrasions
Distraction from resus and supportive care
Charcoal CI
Initial resus incomplete
Non-toxic or sub-toxic dose
Good outcome with supportive care alone
Unprotected airway
Risk Ax - imminent risk of seizures or decreased GCS
Corrosive ingestion
Uncooperative patient
Agent not bound - Corrosives/ Hydrocarbon / Metals ingestion
Charcoal - substances do not bind
Pesticides
Heavy metals / Hydrocarbons
Acids / Alkalis / Alcohols
Li
Solvents
Also can use Against Medical Advice
Acids/Alkalis
Metals
Alcohols
Whole Bowel Irrigation Indications
Indications:
* Metals: Iron > 60mg/kg, SR KCl > 2.5 mmol/kg Lead, Li,
* Life threatening SR Verapamil or diltiazem
* Body Packers (wrapped drug ingestion)
Endpoint - clear effluent
Procedure:
PEG solution 1-2L/hr via NGT (25ml/kg/hr in kids)
Prokinetic e.g. metoclopramide 10-20mg IV q6h
CI
Good outcome with supportive care
Uncoopertive pt
Unalbe to pass NGT
Vomiting
BO or ileus
I+V (relative CI)
Complications
Vomiting
Aspiration
NAGMA
Distraction from resus and supportive care
Delay retrieval to hospital offering definitve care
Charcoal MDAC
Interrupts enterohepatic circulation
- prevents reabsorption in SB
GI dialysis
- small, lipid solublem small Vd, low protein binding
Prevent Drugs Crossing Too Quickly
**Phenobarbitone
Dapsone
Carbamazepine
Theophylline
Quinine
**
Initial dose: 1g/kg up to 50g
Subsequent: 0.5g/kg q4hr
Drugs amenable to HD
Isoniazid
Salicylates / Sodium Valproate
Toxic alcohols and Theopylline
Uraemia
Metformin, Methanol
Barbiturates
Lithium
Ethylene glycol
Dabigatran, Diethylene and triethylene glycols
Massive carbamazapine / valproate overdose
Potassium salt w/ life-threatening hyperkalaemia
Low MW
Low protein binding
Low Vd
Low plasma clearance
Urinary alkalinisation
Indications: salicylate toxicity, phenobarbitone (2nd Line)
Complications:
Alkalaemia
Inc Na, Dec K+, Dec Ca2+
Fluid overload /pulmonary oedema
Method
Correct hypokalaemia - hypoK inhibits UA
1ml 8.4% NaHCO3 = 1mmol NAHCO3
1-2mmol/kg over 5-10 mins
Then infusion 150mls into 850mls 5% Dextrose at 200ml/hr
Monitoring:
Monitor serum Na, HCO3 and K+ 4 hourly
Urine pH aim for 7.5-8.0, do not inc serum pH >7.5
VBGs
Salicylate levels
Endpoints
Resolving clinical symptoms
Resolving biochemical abN i.e. met acidosis
Decreasing salicylate elvels
Ricin communis (castor beans)
Abrin precatorius (jequirity bean)
Poisonus seeds - cytotoxic agents inhibit protein synthesis
Risk
- Greater risk if chewed or crushed c.f. whole ingestion
- 1000 x more potent if inhaled (ricin)
- Oil from castor bean readily extracted making it potential biological weapon if aersolised
- Abrin may present late - 3-14 days post ingestion
- Beware - kids - like “pretty” beads
Supportive treatment only
Presentation
- GI upset
- N/V/D
- Haematemsis or melaena
- Multiorgan failure
- CNS - Drowsy, confused, convulsion, coma
- Pulmonary - ARDS if inhaled
- Cardiac
- DIC
- Electrolyte disturbances - GI losses
- Renal
- Hepatic
Rx
- Supportive
- Decontanimate
- ABC
- NIV for ARDS
- IVF +/- inotopres
- Charocal / WBI
- ICU / Tox
Sulfonylureas
Profound prolonged hypoglycaemia, onsets within 8 hrs, can be more for SR or XR preparations
Can dvp at therapeutic doses in context of renal failure
Children - 1 tablet can kill
Pharm
- Stimulate endogenous insulin secretion - OD leads to hyperinsulinaemia
- Rapid and complete absorption, peak 4-6hrs, hepatic metabolism and renal excretion
Sx
- CNS Sx
- Autonomic Sx (NB Beta blockers)
Mx
- Charcoal - within 1 hr or 4hrs for MR/XR preparation
- Supportive
- Check BSL hrly
- Aim to Mx with PO complex carb intake
- Rx hypoglycaemia with dextrose 50%
- Start octreotide (decreases insulin secretion)
- 50mcg bolus then 25mcg/hr
- Disposition
- Children 18hrs
- At least 8hrs or 12hrs if MR preparation
- Must be euglycaemic, ASx and well can be DC home
Insulin
Profound prolonged hypoglycaemia, may result in life threatening seizures, coma and permanent neurlogical injury
Pharm
- DoA extended - days
- Slow and erretic release from SC injection site
- Prolonged clearance
Sx - can persist > 3 days
- CNS Sx
- Autonomic Sx (NB Beta blockers)
Mx
- No role for charcoal / WBI / dialysis
- Resus
- Rx hypoglycaemia
- Adult - 50mls 50% dextrose
- Then 10% at 100mls/hr
- May need 25% or 50% dextrose
- Child - 2mls/kg 10% dextrose
- Adult - 50mls 50% dextrose
- Monitor and replace electrolytes - K/Mg/PO4
- Disposition
- ICU/HDU
- Can be D/C home or Psych review if well at 6 hours, not recieved any medical Rx
Metformin
Life-threatening lactic acidosis
Therapeutic doses + renal failure (context of sepsis => 50% mortality)
Toxic Mechanism
Metformin inhibits gluconeogenesis, reduces hepatic glucose output and increases peripheral uptake
Type B lactic acidosis ? by inhibiting hepatic reuptake of lactate
Clinical Features
Hypoglycaemia not a feature
Early GI upset
Lactic acidosis
CVS - Tachycardia, hypotension - may progress to shock
CNS - sedation, coma seiziures
Mx
* Decon - AC if >10g + < 2hrs for IR, < 4 hrs for SR preps
* Supportive
- Maintain UO, discontinue nephrotoxic meds
* Lactic acidosis
- NaHCO3 to control severe acidosis
* Correct hyperkaelamia
* Heamodialysis
- Lactate > 20mmol/l
- Refractory hyper K+
- Worsening acidosis
B-Blockers
Propanolol (1g) / Sotalol potentially life-threatening
Risk
* Co-ingestion with Brady Bunch
* Age
Pharm
* met / chrono / inotropic effects
* Rapid absorption, peak at 1-3 hrs,
Clinical Effects
* Propanolol - Na+ channel block - Rx like TCA
* Cardiac - bradycardia, hypotension, QRS prolongation, AV block, vent dysrrhythmias
* CNS - delirium / seizures / coma
* Sotalol - K+ channel block
* QT prolongation
* Bronchospasm, Pulm oedema
* Hypoglycaemia
Mx
* Decon - AC if <2hrs IR or 4 hrs MR/SR
* IVF bolus for hypotension
* Bradycardia and refractory hypotension
* Atropine
* Isoprenaline or adrenaline/NA/Vasopressin
* HIET
* Wide QRS >120ms
* NaHCO3 1-2mEQ/kg over 1-2mins
* Torsades
* Isoprenaline
* Mg
* Overdrive pacing
* Seizures
* As per normal
* Consider IV Dextrose dosing as may be neuroglycopaenia
* Consider intra-lipid - not enough data
Calcium Channel Blockers
Verapamil/Diltiazem commonly lead to CVS collapse
- Cardiogenic +/- vasoplegic shock
Risk
* 2-3 x normal dose or >10 tabs can cause severe toxicity
* Co-ingestion with Brady Bunch
* Onset 2hrs or 16hrs for SR preps
Pharm
* block L-type Ca-channels
* SM relaxation -> peripheral + coronary vasodilation
* Negative ino/chronotropy
* Inhibit insulin release -> hyperglycaemia
* peak 1-2 hrs or 16hrs for SR preps
* Both have active metabolites with vasodilator activity
Clinical Effects
* Cardiac - bradycardia, refractory hypotension, QRS prolongation, AV block, vent dysrrhythmias
* MI / CVA / mesenteric ischaemia potential complications
* CNS - depression if co-ingestant
* Met - hyperglycaemia + lactic acidosis - severe
Early life threats
* Hypotension
* Cardiac dysrrhythmia
* Cardiac arrest
Mx
* Cardiogenic shock
* Atropine for bradycardia - 3 doses
* Inotropes - adrenaline for bradycardia, NA for vaspoplegia
* * HIET - takes 30 mins to work
* Antidote Calcium 30mls 10% Ca gluconate (0.2mmol/kg for child)
* Refractory shock
* Methylene blue
* Ventricular pacing - TC/TV
* Cardiac bypass/ ECMO / IABP
* (Others - intralipid / albumin dialysis)
- Decontamination - AC if <2hrs IR, < 4hrs SR
- Elimination
- WBI - >10tabs SR
HIET
Inotrope in context of CCB and BB overdose with haemodynamic compromise
Mx
- Initiate
- Dextrose 25g (50mls 50%)
- CHILD: 2.5mls/kg 10% IV for children
- Insulin 1u/kg IV bolus
- Maintenance
- Glucose 25g/hr through CVC
- Insulin 0.5u/kg/hr (increase to 1-2u/kg/hr)
- BSL check q10min then 30-60min when insulin dose stable - Aim BSL 4-8 mmol/l
- Electrolytes - K / Mg / PO4
- Glucose supplementation may be required up to 24 hours after stopping insulin therapy
NOACs
Warfarin
INR > 5.0 => increased bleeding risk
>2mg/kg => sig increase in INR in 72hrs, <0.5mg/kg unlikely adverse events
Mech
- inhibits vit K metabolism, a cofactor for factors II, VII, IX, X, protein C and S synthesis,
- > 12hrs before anticoagulant effect, peak at 72hrs
- T1/2 6, 24, 40. 60h for factors VII, IX, X, II resp
Mx
- INR > 5.0 + no bleeding - withold warfarin
- INR 5-9 + no bleeding - withold 1-2 doses, PO vit K
- INR >9 + no bleeding - withold until therapeutic, PO vit K
- Bleeding - , withold,IV vit K, FFP / aPTC
- Life-threatening bleeding - withold, IV vit K, aPTC, FVII
Dispo
- Kids >0.5mg/kg - 10mg PO vit K, DC
- No anticoagulation requirement - 5mg vit K BD for 48hrs, INR 48hrs
- Anticoagulant requirement - admit and INR monitoring, titrate vit K 0.5-2mg if INR >5
NB large doses of vit K for pts requiring anticoagulation - will need heparin until INR therapeurtic again
Tick Paralysis
Species most likely Ixodes holocyclus
Significant illness more common in small children, some cases in adults
Holocyclotixin => inhibition of ACh release at presynaptic region NMJ
Signs/Sx
- Drowsiness or unsteady gait
- Ascending paralyis over days
- Frequent cranial nerve involvement
- Paralysis may progress up to 48 hrs post removal
- Death secondary to respiratory failure
DDx
- GBS - no ocular signs with GBS
- Infant botulism - tick paralysis more mobile kids
- Snake bite - faster onset
- Blue-ringed octopus - faster onset
Mx
- Supportive - resp support
- Likely to require I+V for days to weeks
- Removal of tick
- Pyrethrin-based insecticide
- Remove intact
- Admit for neuro obs
Complications
- Local
- Tick paralysis
- Anaphylaxis
- Mammalian meat allergy
- Typhus - Rickettsia
Redback Spider
Latrodectus - member of black widow family
Bites from mature females more severe
Tox - alpha-latrotoxin opens pre-synaptic cation channels releasing many motor endplate neurotransmitters => 4 main actions
- Motor NMJ paralysis
- Catecholamine release
- Stimulation of cholinergic nerve endings - sweating
- Local pain - may be severe
Signs/Sx
- Local
- Intense pain builds over 5-10 minutes
- Piloerection
- Sweating
- Erythema
- Distal
- LN swelling
- Systemic
- Fever, headache, malaise
- N/V
- HTN + tachycardia
- Myalgia
- Sweating
- Priapism
- Neuro
- Paraesthesia
- Paralysis - patchy
Mx
- Ice
- Analgesia
- Antivenom
- Not used in NSW secondary to RAVE II study
- ONLY used if pain control an issue
- Complicatiosn include serum sickness
- DC when Sx resolve
*
Paracetamol - General
Toxic mechanism
- Build up of NAPQI => depletion of glutathione stores
- NAPQI binds other proteins leading to hepatocyte injury
- Hallmark is centrilobular necrosis
Toxicokinetics
* Good PO absorption
* Peaks 1-2 hours tabs and 30 mins liquid
* 90% hepatic glucuronidation or sulfation
* 10% oxidsed by CYP-450 to form NAPQI - normally bound by GSH and excreted in urine
Clinical Phases
**Phase 1 (24hrs)
ASx or N/V
Phase 2 (1-3 days)
* RUQ pain
* Hepatotoxicity = ALT or AST > 1000 IU/L
* ALT/AST peak at 48-72 hrs (can reach 15-20,000)
Phase 3 (3-4 days)
* Severe cases hepatoxicity may progress to fulminant liver failure - coagulopathy, jaundice, encehpalopathy., MOD
* Poor prognosis - metabolic acidosis with high lactate, ARF, worsening coagulopathy and encephalopathy
Phase 4 (4 days to 2 weeks)
* Hepatic structure and function return to normal**
Paracetamol - ACUTE
Acute - toxic dose is >200mg/kg (Lifethreatening >30g or >500mg/kg)
Chronic >3g/day
High Risk
* Chronic ETOH
* Anticonvulsants
* Phenobarbitol, carbamazepine
* phenytoin
* Starvation - poor glutathione stores
Complications
* GI
* Mild - N/V, RUQ pain
* Fulminant liver failure
* Renal failure
* Pancreatitis
* Metabolic (lactic) acidosis
Call Toxicologist if:
* Massive ingestions >50g or >1g/kg
* Serum paracetamol concentration versus the time more than 3 x level on nomogram
* Hepatotoxicity (AST/ALT > 1000U/L)
* Coma
* Lactic acidosis
* IV paracetamol dose errors
* Neonatal paracetamol poisoning
Management
* Supportive/ABCDEs
* AC - tablet only
* 2 hrs if >10g or 200mg/kg
* 4 hrs if >30g or 500mg/kg
*NAC
Dosing over 20 hours
4hrs : 200mg/kg in 5% dextrose 500ml (kids 7ml/kg)
16hrs : 100mg/kg in 5% dextrose 1L (kids 14ml/kg)
High dose if > 2 x treatment line on nomogram or massive ingestion
Discuss / Transfer to liver trasnplant facility
* INR >3.0 at 48 hours or >4.5 at any time
* Oliguria or creatinine >200micromol/L
* Acidosis with pH < 7.3 or lactate > 3 after resus
* SBP <80mmHg
* Hypoglycaemia
* Severe thrombocytopaenia
* Encephalopathy of any degree
* Altered level of consciousness with nil sedation / co-ingestion
Snake Bite - Toxinology
4 main types of toxin
- Neurotoxins
- Pre-synaptic
- Tiger and taipan
- Inhibit release of NT → progressive neuromuscular paralysis
- Not as amenable to antivenom
- Post-synaptic
- Death adder
- Rapid onset
- Non-depolarising block
- More readily reversible with anti-venom
- Usual pattern of both neurotoxins → cranial nerve involvement THEN limb muscle paralysis THEN resp muscle paralysis
- Myotoxins
- Rhabdo and its effects
- Haemotoxins
- Direct acting
Snake bite - clinical features
- Local + regional
- Pain, wound site, swelling
- Systemic
- Diaphoresis, headache, GIT Sx
- Sudden collapse / cardiac arrest
- Spont recovery in minutes
- Toxin syndromes
- Coagulopathy
- VICC
- Anti-coagulant coagulopathy
- Thrombotic microangiogrpahy
- Myotoxicity
- Myalgia, tenderness, weakness
- Elevated CK, K+, renal impairment
- Neurotoxicity
- Descending flaccid paralysis
- Eyes - ptosis, diplopia, blurred vision
- Bulbar palsy
- Limb
- Resp
- Renal Impairment
- Part of thrombotic microangiopathy, rarley secondary to rhabdomyolysis
- Coagulopathy
Snake bite - VICC vs Anticoagulant coagulopathy
VICC (like DIC)
Partial - Low fibrinogen, INR <3.0
Complete - undetectable fibrinogen, INR >3.0, +++ D-dimer
ACC
Moderate increase in aPTT and INR
Normal Fibrinogen, PLT and D-dimer
Response to antivenom - ACC easier to reverse
Thrombotic microangiopathy
Fragmented RBCs on blood film(MAHA)
Thrombocytpopaenia
Inc creatinine <120mmol/l
May lead to renal failure and HD
Snakes and envenomation syndromes
Snake Bite Mx
First Aid
Pressure bandage + Immobilisation
Take to facility with antivenom + 24h lab service
Initial Ix
- Clinical exam
- Iv access x 2
- Consider VDK
- Bloods - G+S, FBC, EUC, LFTS, coags inc Fibrinogen, CK
Ongoing Monitoring
- Features of envenomation or multiple bites or severe envenomation - give one vial of polyvalent or monovalent anti-venom
- If no features of envenomation clinically or on labs:
- Rpt clinical assessment
- Rpt bloods 1hr after removal of PIB
- 6 and 12 hours post bite, before considering discharge
-vast majority of cases of severe envenoming are likely to be detected with repeat assessment over 12 hours
Snake Bite Complications
Children - 1 tablet can kill
Early onset toxicity
- Calcium channel blockers / clonidine
- Amphetamines/ Ecstacy / ICE / Cocaine
- Na channel blockers - propanolol,
KILL
- TCA - amitriptyline, dothiepin
- Opioids / methadone
- Theophylline
- Sulphonlyureas
Others include:
* Benzodiazepines
* Olanzapine/clozapine
* Hydroxychloroquine
Delayed onset
- SR CCBs
- SR opioids/methadone
- Sulfonylureas
Children - 1 sip can kill
Toxic alcohols - EG, Methanol
Hydrocarbons
* Petrol, turpentine, kerosene
Essential oils - Eucalyptus, tea tree oils
Organophosphates
Carbamate insectcides
Paraquaat
Caustic - NaOH
Camphor - mothballs
Napthalene - mothballs
Strychnine - rat pesticide
Oil of wintergreen (1ml = 1.4g aspirin)
Hydrocarbons
Aliphatic - eucalyptus, essential oils
Aromatic - benzene, toluene
Halogenated - carbon tetrachloride, mehtylene chloride, chloroform
Alkane - propane, butane
Toxicity
Oral - GI irritation, high risk aspiration
Inhalation -
Dermal - dermatitis, chemical burns
Clinical features:
Resp - cough, inc RR, SOB, wheeze, low sats
Prolonged inhalation → asphyxia
CNS - euphoria, CNS depression, seizures
Renal - acute - HAGMA, chronic - RTA (NAGMA) and low K+
Hepatic - halogenated hydrocarbons
CVS - palpitations, Porlonged QT, arrhythmia, sudden sniffing death sydrome (rare)
Metabolic - toluene causes NAGMA (RTA), HAGMA, hypoK
Mx
Supportive
Decontaminate - remove clothing
Seizures - BZ
Aspiration pneumonitis - O2, bronchodilators, NIV or I+V
- No role for ABx or steroids
Cardiotoxicity - more likely with inhalation
- Prolonged QT - correct electrolyte disturbances
- Consider short active BB (esmolol or metoprolol) for refractory VT
- Cardiac arrest - adrenaline may worsen myocardial sensitisation
Hepatotoxicity
- NAC may be hepatoprotective - clove oil, halogentated hydrocarbons
Disposition
Normal CXR + Asx D/C after 6 hours
Consider MH assessment
Aspirin
Toxic dose
MILD 150-300mg/kg
Severe >300mg/kg
Death >500mg/kg
Clinical presentation:
* GI - N/V/dyspepsia (GI distress)
* Metabolic - resp alkalosis then met acidosis, hypoglycaemia, Hypokalaemia
* CNS - tinnitus, agiation, seizures, cerebral oedema
* Other - APO, renal failure, hepatic failure
Mx
1. Start urinary alkalinization
2. Correct hypovolemia
o Urine output 2-3 mL/kg/hr
3. Keep [K] >4.5 mM, correct any hypomagnesemia
- Correct electrolytes before bicarb or intubation
4. Give glucose for any CNS changes
5. Haemodialysis
Endpoints
Resolution of clinical features, acid base status, BSL and K+
Decreasing ASA levels - serial
Salicylate Sources
Topical
Oil of wintergreen
Willow Bark
Bismuth salicylate
Pathophysiology of salicylate toxicity
Uncoupling of mitochondrial oxidative phosphorylation
- Metabolic rate increase → metabolic acidosis
- Tissue glycolysis → hypoglycemia and ketosis
- NB Only un-ionized particles can cross the BBB and accumulate in the CNS and other tissues.
- Because salicylic acid has a pKa of 3.5, the majority of salicylate is ionized and unable to enter tissue at the physiologic pH of 7.4.
- However, as serum pH decreases, more particles become un-ionized and cross the BBB / enter tissues
Clinical manifestations
* Seizures, coma, death
* Cerebral oedema
* Neuroglycopaenia
* Direct nephrotoxicity
* Salicylate induced pulmonary oedema
* Tinnitus
Dialysis in Salicylate toxicity
- Serum salicylate levels:
o >7.2 mmol/L) in acute
o > 6.5 mmol/L + ARF
- Serum salicylate levels:
Severe toxicity:
* Altered mental status, including coma, seizure(s)
* Renal or hepatic failure
* Pulmonary oedema
* Severe acid-base imbalance (pH <7.2)
* Rapidly rising serum salicylate level
* Failure to respond to decontamination or urinary alkalinisation
Acid - Base Disturbance Salicylate Toxicity
- Respiratory alkalosis - direct stimulation of the medullary respiratory centre
- Metabolic acidosis - multifactorial
o Loss of bicarb - renal
o ASA itself that is a weak acid
o Impaired Kreb cycle -> increasing lactate and ketones
o Impaired ability to excrete acids in urine - Respiratory acidosis - from cerebral toxicity, neuroglycopenia, salicylate induced pulmonary oedema
- Metabolic alkalosis from GI losses
Iron
Total vs ELEMENTAL
- Ingesting <20mg/kg no symptoms
- Mild/moderate toxicity: 20-60 mg/kg
- Severe: > 60mg/kg
- Potentially lethal > 120mg/kg
- LD50 (50% mortality) = 200-250 mg/kg
* Children - 130mg can cause sig effects
Toxic mechanism
- Direct GI caustic injury
- Uncoupling oxidative phosphorylation in heart/ CNS / liver
STAGES - see flashcard
Ix
AXR - confirm or quantify ingestion
Iron level 4-6hrs
Mx
Supportive - replace fluid losses, anti-emetic
Specific:
- Polyethylene glycol - whole bowel irrigation
- AC - does not bind iron
- Antidote - desferrioxamine
- Systemic toxicity
- Iron level >90 umol/L (500 mcg/dL)
Disposition
* Children < 40mg/kg + Asx can be managed from home
* Adults < 60mg/kg + Asx at 6hrs, d/c
* Sx - WBI
* Systemic toxicity - IV chelation + ICU
* Consider endoscopic removal for large ingestions
Stages Iron Toxicity
Iron Tablets - Elemental content
Desferrioxamine
Indications:
- Systemic toxicity
- Fe levels > 90 umol/L or 500mcg/dL
Mech - binding of iron to make ferrioxamine, excreted in urine.
Turns urine vin-rose colour
Infusion - 15-35mg/kg/hr for 24hrs
Adverse effects:
- Rash at infusion site
- Hypotension
- Anaphylactoid rxn
- ARDS
- Yersinia sepsis
Cholinergic toxicity
Killer B’s = bronchorrhoea, bronchospasm, bradycardia
MUSCARINIC
Diarrhoea
Urination
Miosis
Bronchhorrhoea
Bronchospasm
Emesis
Lacrimation
Salivation
NICOTINIC
Mydriasis
Tachycardia
Weakness
Tremors
Fasciculations
Seizures
Somnolence
Organophosphates
OP exposure results in MOD, Resp muscle weakness and bronchorrhoea -> death
Organophosphates: Chlorpyrifos, Fenthion, Malathion, Parathion
Carbamates: Aldicarb, Carbofurna, Carbosulfan
Clinical features
Time of onset of toxicity - variable
Early death due to excessive resp secretions and T2RF from muscle paralysis
Sx
Muscarinic - killer B’s, DUMBELLS
Nicotinic - MTWTFS
Mx
DO NOT delay resus with decontamination
PPE - contact precautions
Resus
- HF O2
- IVF for Hypotension + bradycardia
- Seizures
- Resp failure - bronchorrhoea / bronchospasm
Antidotes
- Atropine
- 1.2mg for adults, double dose q5min
- Infusion at 10-20% total dose per hour
- kids = 50mcg/kg
- End point = drying of secretions, resolution of hypotension or dvpt of ACh toxicity
- Pralidoxime
- D/W tox as not effective for all OPs - works better for chlorpyrifos, diazinon)
- 2g for adults over 15 mins
- infusion at 500mg/hr
- kids = 25-50mg/kg, then infusion 10-20mg/kg/hr
- End point = unlikely effective > 24hrs
Complications
Anticholinergic delirium
Organophosphate Clinical Presentations
ACUTE
- Muscarinic - killer B’s, DUMBBELS
- Nicotinic - fasciculation, tremor, weakenss, resp muscle paralysis, tachycardia, hypertension
- CNS - agitation, coma, seizures
- Resp - cholinergic syndrome, chemical pneumonitis if hydrocarbon solvent aspiration
INTERMEDIATE
D2-4 - delayed onset paralysis
DELAYED NEUROTOXICITY
1-5 weeks - delayed neuropathy
CHRONIC ORGANOPHOSPHATE NEUROPSYCH DISORDER
Follows acute intoxication or chronic low level exposure
Sodium bicarbonate
INDICATIONS
- Hyperkalaemia
- Treatment of sodium channel blocker overdose (e.g. tricyclic overdose)
- Urinary alkalinisation (salicylate poisoning)
- Metabolic acidosis (NAGMA) due to HCO3 loss (RTA, fistula losses)
Controversial
- Cardiac arrest (in prolonged resuscitation + documented severe metabolic acidosis)
- Diabetic ketoacidosis (very rarely, perhaps if shocked and pH < 6.8)
- Severe pulmonary hypertension with RVF to optimize RV function
- Severe ischemic heart disease where lactic acidosis is thought to be an arrhythmogenic risk
ADVERSE EFFECTS
- hypernatraemia (1mmol of Na+ for every 1mmol of HCO3-)
- hyperosmolality (cause arterial vasodilation and hypotension)
- volume overload
- rebound or ‘overshoot’ alkalosis
- hypokalaemia
- ionised hypocalcaemia
- CSF acidosis
- hypercapnia (CO2 readily passes intracellularly and worsens intracellular acidosis)
- severe tissue necrosis if extravasation takes place
- bicarbonate increases lactate production by: — increasing the activity of the rate limiting enzyme phosphofructokinase and removal of acidotic inhibition of glycolysis — shifts Hb-O2 dissociation curve, increased oxygen affinity of haemoglobin and thereby decreases oxygen delivery to tissues
Seizure- Causing Toxins
Organosphosphates, Oral hypoglycaemics
TCAs
Insulin, isoniazid
Sympathomimetics, salicylates
Cyanide, CO, cocaine, camphor, chlorinated hydrocarbons
Amphetamines, anticholinergics
Methanol, methylxanthines
Propanolo, PCPs
Benzo withdrawal, botanicals, bupropion
ETOH withdrawal, EG
Lithium, lignocaine
Lead
Kings College Criteria for Transfer to Liver Transplant Centre
- pH < 7.3
- Lactate > 3.0 mmol/L after resus
- INR > 6.5
- Creat > 300 umol/L or oliguria
- Grade III or IV encephalopathy
- PO4 > 1.2 mmol/L at 48-96 hrs
Other considerations (Not part of criteria)
* Oliguria
* Hypotension despite IVF resus
* Hypoglycaemia
* Severe thrombocytopaenia
* Altered mental state with no other sedative co-ingestions
Caustic ingestion
Acids = coagulative necrosis
Alkalis = liquefactive necrosis
>60ml HCl can be fatal = > metabolic acidosis, multiorgan failure and perforation
Hx
Timing, concentration, volume, viscosity, pH, duration contact, ingested w/ food
Ax
Oral pain, AP, vomiting, drooling common
CP, wheezing, cough, resp distress, horseness, odynophagia, dysphagia, stridor and dysphonia
Decontamination
Not useful
Dispo
Asx = obs for 6 hrs and then psych
Sx - below
Ix
VBG
IV ABx for perforation
CXR - erect
CT
Endoscopy betw/ 12-24hrs
NO NGT until after OGD
Caustic ingestion - complications
Early
- Metabolic acidosis
- Electrolyte disturbances
- Dysrrhythmias
- Airway compromise
- GI perforation
Subacute
- Strictures
Late
- Oesophageal cancer
Met Hb
Hb containing Ferric (Fe3+), not ferrous iron (Fe2+)
Drugs/Toxins cause MetHb
- Congenital - Hb M, NADH depedent Met Hb reductase deficiency
- Acquired
- Nitrites, (nitrates)
- Aniline dyes - inks, paints, varnish
- LA agents - prilocaine, procaine
- Abx - sulfonamides, dapsone
- Phenytoin
- Quinones - chloroquine, primaquine
- Toxins - propanil (herbicide)
Presentation
Cyanosis (Sats ~85%) not responding to O2 therapy
Signs and symptoms of hypoxia
Chocolate brown blood
Diagnosis with VBG - MetHb
- <15% - nil Sx
- 15% - Cyanosis
- 30% - Resp distress, SOB, tachycardia
- >60% - Resp distress, seizures, confusion, arrhytmias, hypotension
- >70% - lethal
Mx
- Supportive / resuscitative care
- Consider charcoal if recent ingestion
-
Methylene blue 1mg/kg over 5min
- Up to 2mg/kg, rpt q30-60 mins
- CI in G6PD def
- Hyperbaric oxygen therpay
- Exchange transfusion
Cyanide
CN binds to Fe3+ ion → anaerobic metabolism → severe lactic acidosis
1mg/kg of cyanide salt = potentiall lethal
Sources
- House fires +/- CO poisoning
- Industry - mining, plastics
- Plants - amygdalin
- Medical - Nitroprusside
- Chemical warefare
Clinical Features
- Mild tox
- Headache, vomiting, tachycardia, dizzy, SOB
- Mod-severe tox
- Collapse, seizures, resp distress, confusion, severe met acidosis, CVS collapse, arrhythmias, death
Bloods levels
- Consider if VBG - sats > 90% - unable to use O2 at tissue level
- Correlation between lactate levels and toxicity
- > 10mmol/l indicates severe poisoning
- CN levels
- >20 - symptomatic
- >40 - potentially toxic
- >100 - lethal
Mx
- Supportive/resus care
- Airway - HF O2, I+V
- Hypotension - IVF bolus
- Decon
- HCN = gas = no role
- 50g AC for CN salts < 2hrs
- Antidotes
- Mod - Severe tox = Hydroxycobalamin + Na thiosulfate
- Hydroxycobalamin
- 5mg IV in 200mls Saline over 15 mins
- Up to 15mg
- Sodium thiosulfate
- 12.5 IV over 10 mins
- Dicobalt edetate
- 300mg IV over 1 min + 50% dextrose
- End points
- Improved LOC
- Haemodynamic stability
- Resolution metabolic acidosis
- Dispo
- ASx - monitor 6 hours
- Severe poisoning - ICU
Carbon monoxide
Sources
- Fires, exhaust fumes, machinery closed spaces
- Smoking - hookah (30%), smoking 10-15%)
Vulnerable tissues - CNS, CVS, foetus
Clinical Features
- General - weak, N+V, headcahe, cherry red
- CNS - dizzy, ataxia, confusion, coma
- CVS - ST, AF, PVCs, ventricular arrythmias, MI
- Severe - ARF, rhabdomyolysis, hepatic injury
- Delayed neurologic sequelae
- Impaire judgement, memory, concentration, dementia
Mx
- Supportive / resus
- NRB O2 or I+V with 100% O2 for 6 hrs
- Hypotension Rx
- HBO
- COHb > 25% or 15% pregnancy
- End point - COHb < 5%
Digoxin ACUTE
Acute toxicity presents with GI symptoms progressing to life-threatening arrhythmias and CV collapse
Lethal ingestion:
>10mg ingested
Serum digoxin level > 15nmol/L
K > 5.5mmol/l
KIDS > 75mcg/kg
Progression
2-4h - GI symptoms
6h - peak serum
8-12hrs - CV collapse
Clinical features:
GI
CVS - increased automaticity (VEBs, bigeminy, VT), bradydysrrhythmias (Slow AF, AV block), hypotension
CNS - lethargy, delirium, confusion
Mx
* Decontamination
* AC if < 2hrs OR < 4hrs massive ingestion
* Arrhythmias
* Brady - atropine, adrenaline, pacing
* Tachy - MgSO4 or lignocaine 100mg slow IV push
* Hyperkalaemia
* Consider calcium only with ECG changes + severe hyperK+
* Antidote
* Digibind (see flashcard)
Digoxin CHRONIC
At risk
Elderly with multiple co-morbidties
Meds affecting K+ homeostasis
CVS drugs - BB, CCB
Poor cardiac and renal function
Clinical features
Those of acute toxicity
Visual - dec VA, yellow halos
Digoxin - Digibind
INDICATIONS
* Cardiac arrest
* Ventricular arrhythmias
* High degree AV block
* Acute : [Digoxin] >15nmol/L
* Chronic: [Digoxin] > 3ng/mL
* K+ > 5.0mmol/l
* Acute K+ > 5.5 assoc 100% mortality
Cardiac arrest
ACUTE: 5 vials IV push, rpt q5-10min
CHRONIC: 2 vials IV push, rpt q5-10min
Non-arrested pt
1-2 vials in 100ml 0.9% saline over 30mins
ENDPOINT
Resolution of cardiotoxicity + GI symptoms
Digoxin ECG - effect vs toxicity
Effect
- Downsloping ST depression with a characteristic “reverse tick”
- Flattened, inverted, or biphasic T waves
- Shortened QT interval
Toxicity
- SVT (inc automaticity)
- Slow ventricular response (vagal tone)
- Frequent PVCs (the most common abnormality), including ventricular bigeminy and trigeminy
- Sinus bradycardia
- Slow Atrial Fibrillation
- Any AV block
- Regularised AF = AF with complete heart block and a junctional or ventricular escape rhythm
- Ventricular tachycardia, including polymorphic and bidirectional VT
Digoxin Pharmacology
Reversible inhibition of Na-K-ATPase pump, inhibiting Na-Ca exchange →** increased intracellular Ca → inc myocardial inotropy / extracellular K+**
Toxic doses → after depolarisations → inc risk of arrhythmias and shortened refractory period → increased automaticity
Inc parasymp tone → SA/AV nodal block
TCAs
Significant OD produces rapid onset CVS and CNS toxicity
Clinical toxicitiy worse with acidosis
> 5-10mg/kg - Tachycardia, mild CNS depression, agitation, mydriasis
10mg/kg - Anticholinergic features
20mg/kg - Seizures, coma, hypotension, arrhythmias and death
ECG
R wave in aVR >3mm - most specific
Sinus tachycardia, increased QRS and QT intervals
QRS > 120ms inc risk seizures, > 160 inc risk ven arrhythmias
Mx
Mainstay is supportive care with intubation and hyperventilation, IV NaHCO3, BZ for seizures and ALS for ventricular arrhythmias
Resus
- Seizures - BZs and NaHCO3 if not responding ot benzos
- Hypotension - IVF + inotropes
- Na Channel blockade - NAHCO3
- Recurrent ventricular arrhymthmias - adrenaline and lignocaine 100mg when pH > 7.5 and then ECMO referral
Decontamination
- AC if < 1hr post ingestion or after I+V
Local anaesthetics
MAx Doses
Hydrofluoric Acid
Found: wheel cleaner, glass etching, cement/brick cleaner
Any concentration + > 5% TBSA = risk systemic fluorosis
>50% concentration + 1% TBSA = risk of systemic fluorosis
INH - irritation -> pneumonitis -> ARDS
PO - GI corrosion, hypo Mg, hypo Ca, hyper K, inc QTc -> arrhytmias / cardiac arrest, seizures
Ocular - pain, erosion, tissue damage
Mx
* Decontamination - remove clothes, wash skin, irrigate eyes 20 mins
* Ingestion / systemic features
* Correct electrolytes
* Ca gluconate 10% 30mls
* MgSO4
* Aggressive K+ Mx
* Cardiac arrest - Ca + Mg every 5mins
* Dermal
* Ca gluconate gel
* SC or regional infiltration
* Intra-arterial infusion for limb exposure
* Inhalational
* 1ml Ca gluconate in 3ml saline nebulised
Colchicine
> 0.1mg/kg potential toxicity and death
0.8mg/kg -> MOF + death
Clinical
* 0-24h - GI Sx, dehydration, ARF + leucocytosis
* 24-72h - CV collapse, BM failure, ARF, Liver failure, cerebral oedema, rhabdomyolysis, Low K, Ca, Mg
* >1week - leucocytosis, alopecia, neuropathy, myopathy
Mx
1. Offer AC to all and may need ETT to facilitate this
2. Replace IV fluid losses
3. Electrolyte replacement
4. Enhanced elimination
a. MDAC
b. HD for acid-base (does not eliminate colchicine)
Box Jellyfish
Chironex fleckeri
Most lethal envenoming creature in the world
Death within 20-30 mins if severe envenomation
Toxinology
Envenomnation caused by microscopic stinging capsules called nematocysts
Major stings > 50% limb involvement
Children more likely to incur severe envenomation given smaller BSA
Clinical
Local - pain, dermal lesions (whip like whelts), lymphadenopathy
Systemic
- CNS - HA, confusion, seizures, coma
- CVS - hyper/hypotension, arrhythmias, cardiac arrest
- Resp - Resp arrest
- MSK / skin rxns
Ix
Bloods - inc CK and troponin
ECG
CXR for resp symptoms
Mx
Cardiac arrest Mx
First aid
- Vinegar prevents further discharge from nematocysts
- Washwound with salt water (fresh water causes discharge from nematocysts)
- Ice packs
- Removal of tentacles
- Analgesia
- opioids
- MgSO4
Antivenom inidcated for collapse, hypotension, arrhythmias, cardiac arrest
- 6 vials for cardiac arrest
- 3 vials for cardiac arrhythmias
Dispo
Asx and no local pain for 2 hrs can be D/C
ICU for others
NB Portuguese Man O War - Physalia physalis - Severe local pain but no fatal enveonmations. NO Vinegar as it increases nematocyst discharge, otherwise Mx same.
Irukandji Syndrome
Carukia Barnesi
Inhabits northern Autralia from WA (Geraldton) to QLD (Mackay)
Deaths occur from catecholamine surge rather then venom itself
Clinical feature
Local - initial sting not felt, pain dvps at 20-30 mins, resolves 6-12 hours
Local - rsah
Irukandji Syndrome
- N/V/MSK pain
- Hyperadrenergic response - Anxiety, dysphoria, HTN, tachycardia,
- Rare: ICH, Cariogenic shock, APO
Ix
ECG
Bloods - CK, trop
Echo for trop rise
Mx
Vinegar - not great evidence
Analgesia - opioids, MgSO4
HTN Mx - BZ, Clonidine
Dispo
6hr obs - if well and Asx D/C
Any cardiac involvement HDU/ICU
Blue Ringed Octopus
Shallow coastal waters of Australia
Lethal antivenom -> rapid paralysis
Toxinology
Tetrodotoxin in saliva of BRO bite - venom introduced from beak, not tentacles
Clincal Features
Collapse and paralysis after seemingly monior bite = CLASSIC
Local - bite site painless
Neurotoxicity = RAPID, PROGRESSIVE, SYMMETRICAL, DESCENDING
- Early = numbness, paraesthesia tonuge/lips
- Progressing = Bulbar Sx = Ptosis, diplopia, swallowing difficulty
- UnRx = paralysis, T2RF -> hypoxic arrest
Mx
Paralysis resolves spontaneously within 24 hours
ABC - I+V
PBI
IVF/inotropes for hypotension
ADT
NO antivenom
UDS Limitations
Tox related ECG changes
Tox Anion Osmolar Gap Causes
Effects of ETOH on Salts
Na Channel Blockers -> QRS widening
CVS Drug Ingestion Algorithm
Lithium (Acute)
Lithium toxicity comes in a three flavors: acute, chronic and acute on chronic. Each form will have a different presentation as well as management.
Lithium levels are often unreliable in terms of guiding management and must be taken in context with symptoms and time of ingestion (in acute overdose).
IV fluids are a cornerstone of management as increasing intravascular volume and increasing renal elimination are critical.
Hemodialysis is indicated for a lithium level > 5 mEq/L or a level > 4 mEq/L in a patient with renal failure. However, dialysis decisions should be made in conjunction with a toxicologist.
Two forms of lithium
Standard release peak 1-2 hours
Extended release peak 4 hours
Toxicokinetics
95% renal excretion
Increased lithium levels often result outside of overdose when the patient takes a kidney hit (infection/medications) and GFR goes down.
Toxidrome:
Mild toxicity - N/V/D, AP, hyperreflexia, tremor, agitation, muscle weakness
Mod toxicity - stupor, rigidity, hypertonia, hypotension
Severe toxicity - ataxia, confusion, somnolence, myoclonus, coma, convulsions
Chronic Li toxicity – can develop nephrogenic DI
Pearl: make sure you don’t send a lithium level in a lithium salt tube – typically a green top in the US
Management
Decon: no role for AC, but conisider WBI ingestions > 50g SR and < 4hrs
IV fluids aiming for 2-3ml/kg
Cease nephrotoxic meds - NSAIDs, ARBs, ACEi, diuretics
Monitor electrolytes and fluid balance
Dialysis - D/w toxicologist:
- Neuro Sx or Dysrrhytmias regardless of [Li]
- Lithium >4 mmol/l + renal impairment
- Lithium >5 mmol/l and rising
- End point = [Li] < 1 mmol/l
Lithium (chronic)
Snake Bite PIB principles
Snake bites < 4hrs presentation
Broad 15cm bandage over bite site covering entire limb using smae pressure as for sprained ankle
Immobilise limb and then patient for banddage to be effective
The pressure bandage should only be removed if either:
1. Antivenom therapy has started
2. Clinical and Bloods confirm no systemic envenoming
Snake bite Mx
Key Ix
Coags - INR, PT, aPTT, D-dimer, fibronigen
FBC - RBC feagmentation
UEC, LFTs
LDH
CK
Urinalyis - detect myoglobinuria
Antivenom:
Rpt above Ix at 6 and 12 hours post
Rpt every 24 hrs until resoled
NO Antivenom:
1 hour after removal of PIB, then 6 and 12 hrs post bite
Coags - INR, APTT
CK
Mushroom
Amanita phylloides
One mushroom can kill
Heat stable - not inactivated by cooking
Clinical Presantation
0-5 h - ASx
5-24h - N/V/D/AP, mild LFT inc, ARF
1-7d - Fulminant Hepatic Failure, ARF, Encephalopathy and death
Mx
Discuss all cases w/ TOx
Support - IVF gor GI losses
Decon - charcoal may benefit up to 72 hrs
Antidotes - NAC, SIlibinin (some benefit from rifampicin or benpen)
Liver transplant - D/W Tx if ALT > 250
Dispo - if ASx 24 hrs post w/ normal bloods then D/C
Fulminant Hepatic Failure
Rapid onset of hepatic synthetic failure + encepaholopathy
Causes
Drugs - Paracetamol, NSAIDS, amanita, ABx, dapsone, halothane
Alcohol
Viruses - EBV, CMV< HIV, Hep B/C, HSV
Extras
- Obstetric - HELLP, acute fattyl iver of pregnancy
- Autoimmune - a1-antitrypsin
- Vascular - Budd-Chiari
Sepsis
Ix
FBC, UEC. LFTs, CMP
Hepatitis, HIV, EBV, CMV screen
Bloods cultures
Urine Drug screen
ANA, SMA
Serum protein electrophoresis
Serum copper, caeruloplasmin
Mx
Supportive
- A - intubate if encephalopathic
- B - ventilation, may have pleural effusions
- C - IVF and Na+ restriction + diuretics
- D - BGL monitoring
- E - nutrition, correct electrolyte imbalances
Antidotes
Liver Transplant
Paracetamol - pH < 7.3 / INR > 6.5 OR Cr > 200 OR > gd III encephalopathy
Complications
Cerebreal oedema
Coagulopathy
GIH
Renal failure
Hypoglycaemia
Electrolyte abN
Resp failure: impaired ventilation, coma, pl effusions, ARDS, aspiration, sepsis
Venlafaxine
Potent SNRI
OD can be fatal - seizures / CVS toxicity in large OD
Risk
<3g ~ 10% seizure risk
>3g ~ 30% risk of seizures
>4.5g = 100% risk seizures
>7g - Hypotension and LV dysfunction
Clinical
Features of serotonin toxicity, usually prominent if other serotinergic drug
Seizures - may be delayed up to 16hrs, preceded by agitation, tachycardia and tremor
NO Coma
Hypotension and LV dysnfunction after large OD
Resolves in 24hrs
Mx
Benzo for agitation / tachycardia / tremor and seizures
Temp Mx
IVF for hypotension +/- inotropes
Decon: AC 50g for >4.5g ingestions within 2 hrs presentation
Elim: WBI if > 8g ingestion
Dispo:
< 2g D/C after 8 hours
> 2g 16-24 hrs observation
Strychnine
Funnel Web Spider Bite
Mx
PIB
Antivenom
TIG
Venlafaxine / Desvenlafaxine
Toxicity dose dependent and can be delayed
NB Coma not a feature so consider other causes
Risk
Seizures all ingestions> 5g
Serotonin toxicity > 5g or other serotoniergic agents
CVS - rare unless > 8g
- LV dysfunction => hypotension and tachyarrhythmias
Other - mydriasis, sweating, agitation, clonus
Mx
Early intubation > 8g ingestion
Decon - >2g and alert <2 hrs of presentation
Seizure Mx
Serotonin toxicity Mx
Cardiotoxicity Mx
- IVF +/- inotropic support
Dispo
< 2g - 8 hrs obs
2-5g - 16 hours obs
>5g - 24hrs cardiac monitoring
>8g - Early ETT and ICU
Toxidrome comparison
Body Packer vs Stuffer vs Drug pushing
Body** packing** well-planned ingestion of wrapped drugs for the purpose of trafficking.
Body stuffing hurried swallowing of either poorly packaged or unpackaged drugs to avoid prosecution.
Drug pushing is the hurried placement of poorly packaged or unpackaged drugs into the rectum, vagina, or other orifices to avoid arrest or for resale at a later time.
Amanita phylloides
One mishroom can kill
Symptoms > 6hours associated with more serious toxicity
Presentation
0-5 hrs - Asx
6-24 hrs - N/V/AP/mild elevation liver and renal dysfunction
1-7 d - Fulminant heptic failure, renal failure, encephalopathy and death
Mx
Supportive - IVF, correct GI losses
Early decontamination - AC
BZ for seizures
ACh Sx - atropine
Antidote - NAC, Silibilin, penicillin G or rifampicin (if penicillin not avilaiable)
Adjuncts - cimetidine, pyridoxine,
Murray toxidrome table
Rumack Matthew Nomogram
CI
Unknown time of ingestion
< 4hrs since ingestion
>24hrs since ingestion
Chronic ingestions
Co-ingestions that affect gut motility
Na Channel Blockade
Sinus tachycardia
Terminal RAD - R wave > 3mm in aVR
Wide QRS > 120ms - 50% risk seizures, >160ms seizures imminent
Drugs causing Na Channel Blockade
TCAs
Type Ia AR - procainamide, quinidine
Type Ic AR - flecainide
LAs - lignocaine, bupivicaine, ropivicaine
BB - propanolol
Anti-epileptics - carbamazepine, phenytoin
Antihistamines - chlorpheniramine
Anti-malarials - chloroquine, quinine, hydroxychloroquine
Antipsych - thioidazine
Muscle relaxants - orphenadrine
Misc - cocaine, tramadol
