Toxicology Flashcards
Calcium Channel Blockers
2016
Slow release verapamil overdose
Interpret ECG and give management plan
Tips:
- CCB toxicity causes hyperglycaemia, BB toxicity does not
- BB cause reduced LOC. GCS is maintained in CCB tox
- high dose insulin takes 30-45min to work so it needs to be started ASAP
Need early arterial line
Need early central line for 50% dextrose, calcium chloride and vasopressors
Bedside echo to see if problem is vasodilation or pump failure
Adrenaline for non-dihydropyridines (verapamil, diltiazem)
Noradrenaline for dihydropyridines (amlodipine, nifedipine)
Adrenaline infusion
Draw up 6 mL of adrenaline 1:1000 solution. This contains 6 mg of adrenaline. Add to 94 mL of 5% dextrose.
The resulting solution contains adrenaline 60 micrograms/mL, so that an infusion of 1 mL/hour delivers 1 microgram/minute
Reference: Toxicology handbook
FEATURES:
bradycardia, heart block, hypotension, refractory shock
- hyperglycemia and metabolic acidosis
seizure and coma are rare (coma suggests co-ingestant)
MANAGEMENT:
ATROPINE 1.2mg IV (probably won’t work)
CALCIUM:
calcium gluconate 10% 30 mL IV over 2-3min, followed by calcium gluconate 10% infusion 30ml/hr
calcium chloride 10% 10 mL IV over 2-3min, followed by calcium chloride 10% infusion 10ml/hr through a central line
HIGH DOSE INSULIN EUGLYCEMIC THERAPY:
- 1u/kg slow IV push, followed by infusion 1u/kg/hr
uptitrate insulin every 15min (max dose 10u/kg/hr) - 50ml 50% dextrose IV push followed by infusion 20ml/hr
Glucagon 1mg IV
DECONTAMINATION:
Activated charcoal 1g/kg with 1hr or 4hrs for XR preparations
WHOLE BOWEL IRRIGATION
NGT and confirm position with CXR
- Polyethylene glycol 2L/hr (25ml/kg/hr in child) until watery diarrhoea runs clear
High flow oxygen
GCS and airway reflexes are usually maintained (reduced LOC indicates beta blocker overdose or co-ingestion)
Invasive BP monitoring with arterial line activated
Fluid resuscitation 20ml/kg IV
Adrenaline (not usually effective) 10-20mcg IV followed by infusion 1mcg/kg/min
Potassium replacement (hypokalemia with insulin) 10mmol/hr
Consider:
Transcutaneous pacing (often can’t get capture)
20% intralipid 1.5ml/kg IV bolus
ECMO
Acute digoxin toxicity
2021.2 CBD station
Discuss with the examiner, the assessment and management of a patient with acute digoxin toxicity.
Medical Expertise: Assessment and Diagnosis (30%)
* Correctly interprets the ECG
* Formulates a provisional diagnosis to match the immediate issues
* Identifies the elements that must be sought on initial assessment to formulate an initial management plan
Medical Expertise: Management – (40%)
* Outlines an overall plan for resuscitating a patient
* Initiates treatments specific to identified severe abnormalities in circulation
* Creates a safe and clear disposition plan for a patient
Prioritisation and Decision Making (30%)
* Highlights high-risk features identified during patient assessment
* Summarises and prioritises the key issues that must be addressed during and following the
emergency encounter
* Involves toxicology for additional expertise
Candidates were required to interact with the examiner and to:
* interpret the ECG
* provide their risk assessment for this patient
* answer further questions from the examiner as the case unfolds.
DIFFERENTIAL DIAGNOSIS for bradycardia & hypotension:
Toxicological causes:
- calcium blocker toxicity
- beta blocker toxicity
- digoxin toxicity
Non-toxicological causes:
- hypothyroid myxoedema
- severe hypothermia
- severe hyperkalemia
- inferior MI with AV block or cardiogenic shock
- raised intracranial pressure (imminent brain herniation)
- spinal cord injury
Digoxin has a narrow therapeutic index
Chronic digoxin toxicity has higher mortality. Classic triggers include volume depletion/renal failure (digoxin is renally excreted) and medication changes/interactions.
- pre-existing hypokalemia and hypomagnesia can also trigger toxicity
CLINICAL FEATURES:
CVS - bradycardias with AV block, hypotension, syncope, arrythmias, cardiac arrest
GI - nausea and vomiting
CNS - delirium, confusion, lethargy
Eyes - chromatopsia - abnormal colour vision, xanthopsia - yellow colour vision, reduced VA
ECG:
Digitalis effect:
- salvador dali scooped ST segments
Digoxin toxicity:
- premature ventricular contractions/PVC’s (most common)
- slow AF
- AV block
- Junctional escape rhythm
- bidirectional tachycardia
- hyperkalemia ECG
ASSESSMENT:
HISTORY:
How much?
When?
Co-ingestion?
Intentional?
Self decontamination - vomiting
Body weight?
Co-morbidities?
Symptoms? GI upset, weakness, confusion
EXAMINATION:
Level of alertness
GCS
BP, HR,
Signs of dehydration - dry mm’s, poor skin tugor
POCUS assessment of IVC, cardiac, lungs
INVESTIGATIONS:
ECG and cardiac monitoring - dysrhythmias
Digoxin level:
- digoxin levels do not correlate with toxicity
- digoxin levels cannot be interpreted if given digoxin immune fab
Acute ingestion - baseline digoxin level, then 6hrs post ingestion (takes 6hrs to distribute to tissues)
Chronic ingestion - single level 6hrs post last dose
UEC - hyperkalemia (important marker of mortality - high mortality with K+ >5.5
UEC - renal failure as cause for toxicity
VBG - acidosis, K+ (high or low), lactate (hypoperfusion), BSL if altered mentation
MANAGEMENT:
Resuscitation
Call for help, extra staff
Cardiac monitoring - dysrhythmias
Pulse oximetry
Oxygen - 2L NP, target Sa)2 100%
2x large bore IV canulae
DECONTAMINATION with activated charcoal if alert, protecting own airway and within 2hrs of acute ingestion
ANTIDOTE:
digoxin specific antibody fragments ‘digibind’
DOSE:
cardiac arrest:
- 5 vials = 200mg
not in cardiac arrest:
- 2 vials = 80mg (can repeat dose in 30min)
INDICATIONS FOR DIGIBIND:
- haemodynamic instability
- hyperkalemia >5
- Acute ingestion >10mg in adults, >4mg in children
- 6h digoxin level >10nanomol/L
- End organ dysfunction (Renal failure, Altered mentation)
DIGIBIND COMPLICATIONS:
- Hypokalemia
- Exacerbation of heart failure
- Serum sickness
- Anaphylaxis
Seek urgent toxicologist advice if serum digoxin >20nanomol/L
FLUID RESUSCITATION:
- may exacerbated CHF
- resuscitation should be guided by frequent POCUS IVC, heart and lung assessment
BRADYCARDIA:
- treated with digibind
- may temporise with atropine
Not for TRANSCUTANEOUS PACING or TRANSVENOUS PACING as the myocardium is irritable and can precipitate ventricular arrythmias
HYPERKALEMIA:
- Digibind is the preferred treatment
- Calcium is NOT contraindicated
- Can temporise with insulin, sodium bicarbonate, salbutamol until digibind is given
HYPOKALEMIA:
- Hypokalemia will exacerbate digoxin toxicity, so it must be treated
- digibind will drop K+ further so this needs to be corrected before giving digibind
HYPOMAGNESIA:
- low Mg+ will exacerbate dig tox
- treat with IV magnesium 2g over 20min
DISPOSITION:
Admit for 72hr cardiac monitoring if digi fab given
Tricyclic Antidepressants
PHYSIOLOGY:
- Sodium channel blockade - prolong QRS
- Anticholinergic
- Alpha 1 blockade - vasodilation
- Antihistamine - somnolence
ANTICHOLINERGIC EFFECTS
- mydriasis
- dry, flushed skin
- urinary retention
- fever
- delirium
OTHER Na+ CHANNEL blockers:
- propanolol
- fleicanide
- carbamazipine
- quinidine
- quinine
TOXIC DOSE:
<5mg/kg = usually non-toxic
5-20mg/kg = sedation and anticholinergic effects
>20mg/kg = severe toxicity
ECG:
Sinus tachycardia due to anticholinergic effects (Muscarinic)
Wide QRS
>100ms seizures likely
>160ms ventricular arrythmias likely
Terminal R wave >3mm in aVR
or R/S ratio >0.7 in aVR
Acidosis enhances drug binding to Na+ channels. This increases Na+ blockade effects.
MANAGEMENT:
Treat seizures aggressively with benzodiazepine to prevent acidosis
Treat arrythmias, QRS widening, acidosis with sodium bicarbonate 8.4% 2ml/kg up to 100ml IV bolus, repeat every 3-5min to maintain pH 7.45-7.55
Monitor serum Na+ <155
TREAT HYPOTENSION:
- fluid resuscitation 500ml hartmann’s IV bolus (target MAP 65)
- noreadrenaline infusion 0.2-1mcg/kg/min (target MAP 65)
TREATMENT GOALS:
QRS <100ms
pH 7.5-7.55
avoid excessive hypernatremia
Monitor K+ & Ca+ (bicarbonate causes drop)
SECOND LINE:
Lignocaine for refractory ventricular arrythmias
- 1.5mg/kg (100mg) IV over 2-3min
THIRD LINE:
Intralipid 20%
1.5ml/kg (100ml) over 2-3 min
repeat bolus 0.75ml/kg (50ml) over 2-3min
start infusion 1.5ml/kg/hr
INTUBATION:
Early intubation indicated in severe toxicity
Avoid acidosis at induction
Give sodium bicarb before induction allow patient to blow off CO2 from the infused bicarbonate
Noradrenaline infusion 0.2-1mcg/kg/min (target MAP >65)
Fluid resuscitation 500ml crystalloid IV
Induction agent - ketamine 1-2mg/kg
Paralytic - suxamethonium 1-2mg/kg
Most experience operator
Bag mask ventilation during apnoeic period
POST INTUBATION:
- Hyperventilate post intubation
aim for PCO2 20
- post intubation sedation with propofol infusion 4-12mg/kg/hr (antiepileptic properties)
-
GIT decontamination
- Activated charcoal down NGT if intubated 1g/kg up to 50g
- Anticholinergic effects slow gastric motility so still effective 4hrs post ingestion
Paediatric Poisoning
2023.2 CBD station
Essential oil poisoning in paediatric
Outline assessment and management
Tips:
- suspet NAI/intentional poisoning in age <6 months or >5yrs
- meticulous documentation and mandatory reporting
- in unclear situations, admit the child for observation to allow time for social work to evaluate circumstances fully
Red flags for NAI:
- presentation inconsistent with history
- caregive recount of events changes
- non-ambulant child <6months
- carefully review how the child gained access to poison
- long time between ingestion and presentation
- signs of physical abuse (bruises, burns, dirty and unkempt)
- documented history of abuse
- maunchausen syndrome by proxy
- poison is alcohol or recreational drugs
Concerning paediatric toxins:
- fleicanide
- TCA’s
- beta blockers (propanolol, sotalol)
- non-dihydropyridine calcium channel blockers (verapamil, diltiazem)
- opioids (hydromorphone, methadone)
- sulphonyurea (glipizide)
- salicylates (oil of wintergreen)
Essential oils poisoning
Clove & Pennyoral - need urgent discussion with toxicologist as they cause same sequela as paracetamol poisoining - hepatotoxicity, renal failure, DIC and coma
Oil of wintergreen - salicylates poisoing
Eucalyptus oil
Children can have toxicity to the essential oil itself, or the HYDROCARBON used to prepare it
Hydrocarbons:
- rapid CNS depression, coma and seizures within 2hrs
- aspiration –> chemical pneumonitis
(cough, gagging, wheeze = aspiration)
(haemoptysis, hypoxia, pulmonary oedema - late sign)
ASSESSMET:
History:
- what oil ingested, concentration
- when
- co-ingestion
- self decontamination
- syptoms of toxicity and progression
- any indication of NAI, intentional overdose, neglect
- child weight
- medical co-morbidities
- regular medications
BSL
ECG
VBG - respiratory failure in aspiration
Paracetamol level
FBC, UEC, LFT’s - pennyroyal and clove oil can cause significant hepatotoxicity
CXR - pneumonitis
MANAGEMENT:
High flow 100% oxygen 15L NRBM
Bronchodilators for wheeze in aspiration pneumonitis
- nebulised salbutamol 2.5-5mg
Discuss with toxicologist for consideration of NAC in pennyoral or clove poisoning
Decontmination:
- essential oils are well absorbed through mucous membranes and the skin
- wash skin with soapy water
- irrigate eyes
- Activated charcoal don’t bind to hydrocarbons
- Aspiration is managed with oxygen and bronchodilators
- Antibiotics aren’t indicated in chemical pneumonitis
Polypharmacy Overdose
2023.2 RMO interaction
Paediatric Iron Overdose
- the amount of elemental iron ingested determines the risk, not the amount of iron salt
ASSESSMENT:
- dose of elemental iron (mg/kg)
- preparation (immediate release vs extended release)
- when
- co-ingestion
- self decontamination (vomiting)
- syptoms of toxicity and progression
- any indication of NAI, intentional overdose, neglect
- child weight
- medical co-morbidities
- regular medications
Tips:
- charcoal does not bind iron
- discuss with toxicologist in severe toxicity
DOSE RESPONSE:
<20mg/kg - asymptomatic
20-60mg/kg - GI upset
60-120mg/kg - metabolic acidosis, altered mental state
>120mg/kg - coma, seizure, arrythmias, end organ failure
CLINICAL FEATURES:
Gstrointestinal phase 0-6hrs:
- corrosive effect on GI tract
- haemorrhagic gastroenteritis
- massive fluid losses
Latent phase 6-24hrs:
- resolution of GI symptoms
- ongoing iron absorption
- evolving metabolic acidosis
Cardiogenic shock & multiorgan failure 24-48hrs:
- refractory hypotension
- pulmonary oedema
- coma & seizures
- liver failure + loss of synthetic function
- DIC
3-4days
Hepatic necrosis phase
2-8 weeks:
GI scarring and strictures leading bowel obstructions
c)
BSL - hypoglycemia
VBG - HAGMA
Iron level at 4-6hrs post ingestion (levels >90micromol/L will require Desferroxamine)
AXR - iron is radio-opaque, can help quantify ingestion and assess effective whole bowel irrigation
AXR is not indicated in liquid iron ingestion
UEC - renal failure, significant electrolyte imbalances with diarrhoea and vomiting
LFT’s - transaminitis, liver failure
BSL - hypoglycemia with liver failure
Coags - high INR with liver failure
G&H - encase of massive GI haemorrhage requiring blood transfusion
DECONTAMINATION:
Whole bowel irrigation
Polyethylene glycol 2 L/h in adults, children 25 mL/kg per hour (maximum 2 L/h)
- place nasogastric tube
- 25ml/kg/hr
- contraindicated in GI bleeding and bowel obstruction
Endoscopic retrieval of iron tablets
Charcoal does not bind iron
ANTIDOTE:
Discuss with toxicologist
Desferroxamine 15/kg/hr IV infusion
Desferrioxamine is a chelating agent that forms a water soluble desferrioxamine-iron complex so that it is excreted in urine
- if oligouric renal failure will need consideration of haemodialysis
For Serum iron >90micromol/L or obvious severe systemic toxicity
Desferrioxamine infusions usually for 12-16hrs OR
- The child is asymptomatic
- Decontamination complete
- Anion-gap acidosis resolved
- Serum iron concentration <60 micromol/L
List four (4) criteria that must be met for safe discharge home from ED:
- Clinically well 6 hours after ingestion for IR or 12 hours after ingestion for XR iron preparation.
- Peak serum iron concentration <90 micromol/L
- No iron on AXR
- No evidence of metabolic acidosis
- No suspicion of intentional poisoning, NAI, neglect
Adult Polypharmacy Overdose
2023.2 RMO interaction
Assessment and management
Consider different toxidromes
ECG findings
Toxidromes
Anticholinergic - atropine, amitriptyline, antihistamines
Features:
- Altered mental status - mad as a hatter
- Mydriasis
- Dry flushed skin - red as a beet
- Urinary retention
- Decreased bowel sounds
- Fever
- Dry mucous membranes
- Seizures, arrhythmias, rhabdomyolysis
Cholinergic - organophosphates
Features:
- Miosis
- Salivation
- Lacrimation
- Diaphoresis
- Vomiting
- Urination
- Defecation
- Bronchorrhoea
- Muscle fasciculations
- Weakness
- Bradycardia, seizures
Opioid - heroin, morphine, hydromorphone, methadone
Features:
- Miosis
- Respiratory depression
- CNS depression
- Hypothermia
- Bradycardia
Sympathomimetic - cocainne, amphetamines
Clinical features:
- Agitation
- Tachycardia
- Hypertension
- Hyperpyrexia
- Diaphoresis
- Fever
- Seizures, acute coronary syndrome
Thyrotoxicosis
Heat stroke
Salicylates - aspirin, oil of wintergreen
Features:
- Altered mental status
- Respiratory alkalosis
- Metabolic acidosis
- Tinnitus
- Tachypnea, tachycardia, diaphoresis, nausea, vomiting
- Hyperpyrexia (low grade)
Extrapyramidal - haloperidol, risperidone
Features:
- Dystonia
- Torticollis
- Muscle rigidity
- Choreoathetoid movements
- Hyperreflexia
- Seizures
Hypoglycemia - insulin, sulphonyureas
Features:
- Altered mental status
- diaphoresis
- tachycardia
- hypertension
- Dysarthria, behavioral change, seizures
Neuroleptic malignant syndrome - antipsychotics
Features
- Lead-pipe muscle rigidity
- Bradyreflexia
- Hyperpyrexia
- Altered mental status
- Autonomic instability
- Diaphoresis
- Mutism
- Incontinence
Serotonin syndrome -
fluoxetine
Features:
- Altered mental status
- Hyperreflexia and hypertonia (>lower limbs)
- Clonus
- Tachycardia
- Diaphoresis
- Hypertension, flushing, tremor
Paediatric Poisoning
2023.1 CBD station
paediatric with poisoning
perform a risk assessment
patient deteriorates and requires intubation
Concerning poisons in paediatrics:
- calcium channel blockers
- sulphonyureas
- TCA
- iron
- propanolol
- fleicanide
- opioids (methadone, hydromorphone)
- essential oils, hydrocarbons, camphor, pennyroyal, clove
- paraquat
- organophosphates
- moth balls
Organophosphate / Carbamate Toxicity
2022.1 discussion with registrar station
Medical Expertise: Assessment – 40%
* Elicits a focused, relevant history of organophosphate exposure
* Performs a focused, structured and relevant physical examination of the patient with
organophosphate poisoning
* Identifies risks of deterioration/need for intervention in the patient with organophosphate
toxicity.
Medical Expertise: Management – 40%
* Outlines an appropriate plan regarding decontamination of a patient with organophosphate
poisoning
* Outlines an overall plan for the management of the patient with established organophosphate
toxicity.
Prioritisation and Decision Making – 20%
* Lists specific triggers for intubation in a patient with organophosphate toxicity.
Candidates were required to interact with a junior registrar (role player) and to:
* answer the registrar’s questions regarding this patient’s presentation.
Pesticides & insecticides used in agriculture
- carbamates are less toxic than organophosphates and have shorter duration of action
- any ingestion in children can be lethal
- deliberate ingestion in adults will cause life threatening toxicity
- accidental dermal or inhalational exposure causes toxicity but is rarely life threatening
***Large amounts of atropine, hundreds of milligrams, may be necessary in massive ingestions. Proactive contact with the hospital pharmacy (or even other centres) may be necessary to ensure access to adequate amounts of atropine.
MECHANISM:
- inhibits acetylcholinesterase
- accumulation of acetylcholine at muscurinic and nicotinic receptors
HISTORY:
Which agent ingested?
When?
How much?
Co-ingestion?
Self decontamination with emesis?
Symptoms since ingestion?
“Cholinergic crisis”
Muscurinic effects ‘DUMBBELS’
- diarrhoea & diaphoresis
- urinarion
- miosis
- bronchorrhoea & bronchospasm
- bradycardia & hypotension
- emesis
- lacrimation
- salivation
Nicotinic effects:
- fasciculations
- tremor
- weakness
- respiratory muscle paralysis
- tachycardia/hypertension
CNS effects- agitation, coma, seizures
Respiratory effects:
- progressive neuromuscular junction dysfunction and respiratory failure over 1 to 4 days
- Chemical pneumonitis (if contains hydrocarbons)
Intentional - Will need psychiatric assessment
EXAMINATION:
Bradycardia or tachycardia
hypotension or hypertension
Respiratory distress - dyspnoeic, hypoxic, wheeze
GCS - coma, confused, delirius
seizures
diaphoresis
miosis
lacrimation
salivation
vomiting
incontinent - urine, diarrhoea
INVESTIGATIONS:
ECG - arrythmia
CXR - chemical pneumonitis
*plasma cholinesterase activity - if the diagnosis is unclear
*red cell cholinesterase activity - better correlation with severity of poisoning
MANAGEMENT:
PPE - impervious gown, gloves, mask, eye protection for resus team
DECONTAMINATION:
- no role for activated charcoal with oral ingestion as rapidly absorbed and distributed
- remove and dispose of clothing, wash skin with water and detergent for dermal exposures
ENHANCED ELIMINATION:
- none
ANTIDOTE:
atropine 1.2mg (0.05mg/kg) IV
double dose every 5min until adequate atropinisation - chest clear, no wheeze
- HR 80
- SBP >80
then use 10-20% of the loading dose per hour infusion
reduce infusion if over atropinisation
- confusion
- pyrexia
- mydriasis
- absent bowel sounds
*Atropine has no effects on the neuromuscular junction
PRALIDOXIME:
- controversial
- causes reactivation of acetylcholinesterase with SOME organophosphate poisonings (not carbamate poisonings)
- studies have shown that although it does increase red cell cholinesterase activations, it does not improve survival or intubation rates
- if poisoning is refractory to atropine, discuss use of pralidoxime with toxicologist
CHEMICAL PNEUMONITIS
- oxygen
- ventilatory support
- steroids
SEIZURES:
- midazolam 5mg IV
AGITATION:
- midazolam
RESPIRATORY FAILURE:
- Intubation and mechanical ventilation
EARLY INTUBATION:
*atropine improves wheeze and clears secretions but DOES NOT reverse respiratory muscle paralysis
*also many have an aspiration pneumonitis
OPTIMISE PRE-INTUBATION:
- Preoxygenate
- Fluid resuscitation
- Noreadrenaline infusion
- using ketamine 1mg/kg and rocuronium 1.2mg/kg
***A non-depolarizing agent should be used when neuromuscular blockade is needed.
Succinylcholine is metabolized by plasma butyrylcholinesterase; therefore, prolonged paralysis may result.
- using video laryngoscope and experienced operator to increase likelihood of first pass success.
DISPOSITION:
ICU
Toxic Alcohol Poisoning
- methanol
- ethylene glycol
2021.1 CBD station
Assessment and management of an adult female who has been brought to the ED in a highly agitated state.
Interpret VBG
Differential diagnosis for HAGMA
“MUD PILES”
Metformin, Methanol
Uremia
DKA
Paracetamol toxicity
Iron toxicity, Isoniazid
Lactic acidosis (sepsis)
Ethanol, ethylene glycol
Salicylates
Anion gap = Na+ - Cl - HCO3-
normal anion gap =12
Osmolar gap = measured osmolarity - calculated osmolarity
calculated osmolarity = (2x Na+) + glucose + urea
normal osmolar gap = <10
Outline your care for the obtunded patient
Signs of hypocalcemia “CATs go numb”
Convulsions
Arrythmias (prolonged QTc)
Tetany
numbness (perioral, hands, feet parasthesias)
Trousseau sign
Chvostek sign
Ethylene glycol + Methanol
Methanol - poorly distilled alcohol
Ethylene glycol - antifreeze, break fluid and some solvents
Metabolised by alcohol dehydrogenase and aldehyde dehydrogenase to form toxic metabolites
ethylene glycol –> oxalic acid –> calcium oxalate precipitation in kidneys and brain
methanol –> formic acid –> affects retina + basal ganglia
Fomepizole inhibits alcohol dehydrogenase
haemodialysis removes toxic metabolites
- formic acid
- glycolic acid
- oxalic acid
PRESENTATION:
- drunk
- hyperventilation (due to metabolic acidosis)
- reduced visual acuity with methanol - “snow storm vision”
- become more obtunded
- seizure (due to hypocalcemia)
ECG - prolonged QTc with hypocalcemia
*HAGMA
*raised osmolar gap
*lactic acidosis
*hypocalcemia
*hypoglycemia
*hyperkalemia
*calcium oxalate crystals in urine
*raised serum methanol or ethylene glycol levels
- gas chromatography is not widely available
*methanol level >15mmol/L
*ethylene glycol level >8mmol/L
are associated with severe toxicity in adults and children
measure serum ethanol levels
DECONTAMINATION:
- charcoal doesn’t bind alcohols
ANTIDOTE:
- fomepizole (inhibit alcohol dehydrogenase)
- 15mg/kg Q12hr
- very expensive and not readily available
- toxic alcohols have long half lives so prolonged treatment required
Second line:
- Ethanol 10% 6 mL/kg IV or NGT loading dose, followed by 50-100ml/hr infusion
If ethanol 10% is not available, then white spirits (eg vodka), can be administered orally or via a nasogastric tube. Use serial serum ethanol concentrations to guide the rate of administration.
ethanol 0.6 g/kg orally or via nasogastric tube, as a loading dose
ethanol 5 -10 g/hour (child: 0.1 to 0.2 g/kg/hour up to 10 g/hour) via nasogastric tube. Measure the serum ethanol concentration regularly and aim to maintain a serum ethanol concentration 22-44 mmol/L
Need to double the dose of ethanol if having dialysis. Aim for serum ethanol 22-44mmol/L
ENHANCED ELIMINATION:
- haemodialysis removes toxic metabolites
- shorten hospital length of stay
Indications for haemodialysis:
- pH <7.15
- end organ damage (renal failure, coma, seizures, blindness)
- high serum levels
continue fomepizole during dialysis
don’t treat hypocalcium unless tetany, seizures, QT prolongation - giving calcium will precipitate calcium oxylate in the tissues
Patient is obtunded and has a seizure. Outline your management.
- Intubate and hyperventilate
- Sodium bicarbonate 50-100ml IV bolus for acidemia
Ethanol 10% 6 mL/kg IV or NGT loading dose, followed by 50-100ml/hr infusion
Fomepizole 15 mg/kg IV loading, then 10mg/kg IV BD, dosing increases to Q4h during dialysis
Folic acid 50mg IV QID - for methanol poisoning. metabolises formic acid to non-toxic metabolite.
Thiamine 300mg IV daily OR Pyridoxime 50mg IV QID for ethylene glycol poisoning. metabolises oxalic acid to non-toxic metabolite.
Dialysis
Snake Bite
2023.1 Teaching Station
Discuss with a junior doctor (role player) the approach to
the assessment and management of a patient with snakebite.
INVESTIGATIONS:
Coags:
“complete VICC” is defined as:
INR >3
undetectable fibrinogen
D-dimer >100x normal limit
~~~
“partial VICC” is defined as:
INR<3
low but detectable fibrinogen
FBC
- Hb drop (bleeding)
- Neutrophilia
- Thrombocytopenia
Group and Hold /Cross match
- Bleeding risk
UEC
- Hyperkalaemia in rhabdomyolysis
- Renal impairment in rhabdomyolysis
Urine analysis
- Haematuria
- Myoglobinuria (rhabdomyolysis)
CK
- raised in rhabdomyolysis
VBG to assess ventilation and oxygenation in respiratory failure
Swab for SVDK
- Cut window in pressure bandage to access bite
- Urine sample for SVDK
Repeat bloods 1hr after removal of pressure bandage
Repeat bloods at 6hrs and 12hrs post bite
Neuroleptic Malignant Syndrome
- Caused by dopamine antagonists (any antipsychotics) or stopping dopaminergic drugs Ievodopa, carbidopa, bromocryptine
Ref: Tintinalli’s Table
Diagnostic Criteria for Neuroleptic Malignant Syndrome
Major features
- Fever >38°C
- Lead-pipe muscle rigidity
- Psychomotor slowing and altered mental status
- Sympathetic nervous system lability (2 or more)
- Hypertension
- Diaphoresis
- Urinary incontinence - Recent dopamine antagonist or cessation of dopamine agonist
Minor features
- Raised CK (> 4 × upper limit) or Myoglobinuria
- Tachycardia
- Tachypnoea
- Hypersalivation
- Tremor
- Muscle cramps
Exclusion criteria
- no other infectious, toxic, metabolic or neurological cause identified
Differentiation from Serotonin syndrome
*slower onset
- No ocular myoclonus
- limb rigidity is common in NMS but a late sign in serotonin syndrome
hyperreflexia and clonus in serotonin syndrome
decreased or absent deep tendon reflexes in NMS
*bowel sounds increased in serotonin syndrome
(normal or decreased in NMS)
- severe rhabdomyolysis in NMS (rhabdo is rare in serotonin syndrome)
- hyperthermia is more prominent in NMS (mild in serotonin syndrome)
- seizures uncommon in serotonin syndrome
- pupils dilated in serotonin syndrome (usually normal in NMS)
“SPROD RHHOB”
S - seizure (more common in SS) P - pupils (mydriasis in SS) R - rigidity (NMS) O - onset (rapid in SS) D - Delirium (in NMS)
R - rhabdomyolysis (more pronounced in NMS)
H - hyperthermia (more pronounced in NMS)
H - hyperreflexia (in SS)
O - ocular clonus (in SS)
B - bowels (diarhhoea in SS)
MANAGEMENT:
Withdraw antipsychotics
Fluid resuscitation
Treat hyperthermia
- cooling
Sedation with benzodiazepines
Airway protection - especially if hypersalivation
- Non-depolarizing neuromuscular blocking agents
Consider agents to reduce severe muscle rigidity
Dantrolene, 2.5 mg/kg IV load, followed by 1mg/kg IV QID
OR
Bromocriptine 2.5mg PO TDS
or
Amantadine, 100mg PO TDS
The Agitated Patient
Excited delirium
MANAGEMENT:
Danger to patient and staff
Apply high flow oxygen with a non-rebreather mask - provides oxygen but also stops spit
Give IM droperidol 10mg IM through the clothes to lateral thigh, repeat 10mg IM
Alternative ketamine 400mg IM (4-6mg/kg)
Methaemoglobinaemia
A 12 year old boy has had a Biers Block performed for manipulation of a distal radius/ulnar fracture.
During the procedure he develops Methaemoglobinaemia.
METHAEMGLOBINAEMIA:
- The ferrous (HbFe2+) form of iron is needed to bind oxygen.
- in MetHb red blood cells are oxidised to the ferric state and can no longer bind or transport oxygen.
- G6PD deficiency
- paediatrics > adults
- not dose related
TRIGGERS:
Local anesthetics:
“PBL”
- Prilocaine
- Benzocaine
- Lignocaine
Nitrates:
- GTN
- Inhaled nitric oxide.
- Nitroprusside
- Amyl nitrate.
Antibiotics:
- Dapsone.
- Rifampin.
Antimalarials (chloroquine, primaquine).
Methaemoglobin level:
<2% is normal.
3-15%: Asymptomatic.
Cyanosis can occur at levels above 5-10%.
20-30%: Moderate symptoms.
- Fatigue, tachypnea, dyspnea, tachycardia.
- Anxiety, dizziness, confusion.
Nausea, vomiting.
> 40%: Severe symptoms can occur:
- Seizure, coma.
- Arrhythmia.
- High lactate.
- Death
CLINICAL FINDINGS:
- central cyanosis
- refractory hypoxaemia (low sats despite high flow oxygen)
- chocolate brown blood
DIAGNOSIS:
ABG - PaO2 will be high >100
ABG or VBG - methaemoglobin level %
MANAGEMENT:
methylene blue 1% 0.1 - 0.2mL/kg (1-2mg/kg IV, over 3 to 5 minutes.
Contraindications:
- G6PD deficiency - may cause haemolysis (need to consult with toxicologist)
- patients prone to serotonin syndrome. Methylene blue is a MAO inhibitor
Additional treatments:
*high dose IV vitamin C and ribolavin (vitamin B12)
*cimetidine for dapsone induce methaemoglobinaemia
*exchange transfusion
G6PD deficiency methaemoglobinaemia:
- need to consult toxicologist
- IV vitamin c and riboflavin vitamin b12
- exchange transfusion
- or trial of methylene blue
Local Anaesthetic Toxicity
A 12 year old boy has had a Biers Block performed for manipulation of a distal radius/ulnar fracture.
During the procedure he develops local anaesthetic toxicity.
Nerve blocks:
- High-volume blocks, with doses approaching the maximal safe dose range
- Placement of catheter for prolonged anesthetic infusion.
- Failure to use ultrasound guidance.
- Bupivacaine has greater risks than ropivacaine or lidocaine.
LOCAL ANAESTHETICS MAX DOSING:
- Bupivacaine 2mg/kg
- Ropivacaine 2mg/kg
- Lignocaine 4mg/kg (7mg/kg with adrenaline)
- Prilocaine 5mg/kg
EARLY SYMPTOMS:
tinnitus, metallic taste, circumoral numbness, blurred vision
- Delirium, dysarthria,
CARDIAC SYMPTOMS 2nd:
- Bradycardia and AV block, widened QRS complexes.
- Hypotension (reduced cardiac contractility)
- Cardiac arrest (VT, VF, PEA, asytole)
ECG - prolonged QRS, terminal R wave in aVR
Respiratory depression and apnoea
Seizures
MANAGEMENT:
Resus
Cardiac monitoring and pulse oximetry
High flow oxygen 15L NRBM
IV access
Treat seizures - midazolam 0.2mg/kg
Treat QRS widening and ventricular dysrythmias:
- Sodium bicarbonate 8.4% 2 mL/kg up to 100 mL
IV every 5 minutes, titrated to a narrowing of the QRS complex <100ms
Lipid emulsion 20% 1.5 mL/kg IV, over 1 minute. Repeat every 5 minutes.
Fluid bolus 20/kg 0.9% SN IV - fluid resuscitation will be guided by POCUS assessment of IVC and LV
Vasopressors with adrenaline infusion starting at 0.05mcg/kg/min titrating up to target a systolic blood pressure of 100-120mmHg
RSI, intubation and hyperventilation to target PCO2 30, pH >7.4
ICU admission
Consider ECMO
Discuss with toxicologist
Snake Bite
2021.2 case based discussion
discuss with an examiner the assessment and management of an adult male patient who suspects he has been bitten by a snake.
CLINICAL FEATURES:
COAGULOPATHY:
Venom Induced Consumptive Coagulopathy (VICC)
INR very high or unrecordable
APTT very high or unrecordable
Fibrinogen very low or undetectable
D-dimer very high or unrecordable
fragmented red cells on blood film
Partial VICC
- detectable fibrinogen, INR <3
THROMBOTIC MICROANGIPATHY:
- always associated with VICC
- haemolysis (fragmented red blood cells) on blood film
- thrombocytopenia
- acute renal failure
NEUROTOXICITY:
- descending flaccid paralysis
- 1st eye involvement (ptosis, ophthalmoplegia with diplopia and blurred vision)
- 2nd bulbar palsy (dysarthria, dysphagia)
- 3rd respiratory muscle involvement with respiratory failure
- 4th limb paralysis
MYOTOXICITY:
- Myalgias with rhabdomyolysis
- CK normal on admission, rapidly rises day 2
CARDIOVASCULAR COLLAPSE:
- hypotension and collapse
- cardiac arrest or seizure
ANTICOAGULANT COAGULOPATHY:
- APTT mildly raised, INR and D-dimer normal
- Black snake envenomation
- not clinically important
SYSTEMIC SYMPTOMS:
- nausea and vomiting
- abdominal pain
- diarrhoea
- diaphoresis
- headache
Brown Snakes:
- most common cause of severe envenoming
- geographically everywhere
- minimal pain, redness, swelling with brown snakes
- early collapse, seizure or cardiac arrest in 30%
- VICC in 80%
*brown snake anti-venom available
Tiger Snakes:
- SA and Tasmania
- cause marked pain, redness and swelling at the bite site
- Systemic symptoms common
- Neurotoxicity & myotoxicity 20%
- VICC is rare
*Tiger snake venom available
Black Snakes:
- east coast
- cause pain, redness, swelling at bite site
- anticoagulant coagulopathy (not significant)
- myotoxicity
Taipan:
- northern territory
- cause neurotoxicity
EPIDEMIOLOGY:
- majority in rural areas in warmer months
Can manage in a rural setting if:
- laboratory facilities
- antivenom
FIRST AID:
Pressure bandage
- tight, cover the entire limb
Immobilisation
PBI can be removed if no signs of envenomation and normal lab tests.
HISTORY:
Bite pain, redness, swelling, bleeding
Collapse, seizure
Coagulopathy - any bleeding
Neurological toxicity:
- diplopia, blurred vision
- dysphagia, dysarthria, dysphonia
- breathing difficulties
- limb weakness
Myotoxicity - Muscle aches
Systemic toxicity:
- diaphoresis
- headaches
- nausea and vomiting
- diarrhoea
- abdominal pain
EXAMINATION:
Bleeding from snake bite, IV cannulae, haematuria, hemetemesis, intracranial haemorrhage
Neurologica:
- ptosis, ophthalmoplegia, diplopia
- bulbar weakness
- respiratory failure
- limb weakness
Muscle tenderness
INVESTIGATIONS:
Bloods taken on arrival, Repeat 1hr after removal of pressure bandage
Repeat bloods at 6hrs and 12hrs post bite
DO NOT use point of care testing
Coags:
- INR
- APTT
Fibrinogen
D-dimer
FBC:
- Hb drop (haemolysis)
- thrombocytopenia (thrombotic microangiopathy)
- leukocytosis or lymphopenia (non-specific sign of systemic envenoming)
BLOOD FILM is important to look for fragmented RBC’s in thrombotic microangiopathy which would indicate VICC
LDH - haemolysis
Group and Screen - if blood transfusion required
UEC:
- renal failure (thrombotic microangiopathy)
- hyperkalemia
CK:
- myotoxicity and rhabdomyolysis
- may be normal initially
Urine:
- haematuria
- myoglobinuria (rhabdomyolysis)
Choice of antivenom is guided by
- Geography
- Clinical and laboratory findings
- Expert toxicologist consultation
Snake Venom Detection Kits (SVDK)
- swab of bite, can be performed on urine
- can be stored if needed for processing LATER
- can help guide choice of anti-venom (avoid use of polyvalent antivenom) if clinical picture unclear
- complex and operator dependent
- false positives, false negatives and inconclusive results
MANAGEMENT:
ABSOLUTE INDICATIONS FOR ANTI-VENOM:
- Sudden collapse, cardiac arrest or seizure
- High INR
- Paralysis with ptosis and ophthalmoplegia
RELATIVE INDICATIONS:
- Systemic symptoms (vomiting, headache, diarrhoea etc)
- Raised aPTT
- CK >1000
- Leucocytosis/lymphopenia
One (1) vial of snake antivenom is required to treat both children and adults for all terrestrial
snake envenomings.
Administered in resus with cardiac monitoring due to the risk of anaphylaxis in 5%.
- Premedication with adrenaline or antihistamines is not indicated.
- Diluted in NS given IV over 30min
SERUM SICKNESS:
- warn patients of developing serum sickness
- flu-like symptoms: fever, myalgia, arthralgia, rash develops day 4-14.
- serum sickness can be treated with prednisone 25mg bd (0.5mg/kg)for 5-7 days.
- prophylactive prednisone is not indicated
ANTIVENOM EFFECTS:
VICC - Stops progression
Neurotoxicity - Will reverse if post-synaptic (Death
adder) however will prevent progression
if pre-synaptic (brown or tiger)
Myotoxicity - Stops progression, early administration likely to prevent
Anticoagulant coagulopathy - Rapidly reversed
SAFE DISCHARGE:
- daylight hours - do not discharge overnight
- no physical signs or symptoms of envenomation at 12hrs post bite (VICC, neurotoxicity etc)
- normal bloods at 12hrs post bite
Amanita Phalloides
EM Board Bombs ep 219
Key points:
- urgent toxicologist consultation
- mycologist
- decontamination and enhanced elimination with multidose activated charcoal - patient has to be alert and protecting own airway
- haemodialysis for renal failure and metabolic acidosis
- Antidotes (limit the uptake of amatoxin by hepatocytes) - silibinin, benzylpenicillin, rifampicin
- N acetylcystein
- liver transplant
CLINICAL FEATURES:
*delayed onset of GI symptoms >6hrs
other non-lethal mushrooms cause GI symptoms soon after eating them
mushroom characteristic - olive brown cap, white stem, white gills, cup like structure at base of stem - *send photos to MYCOLOGIST to confirm mushroom species
amanita phalloides is only in NZ, Victoria, ACT and Adelaide - if ingested mushroom not from these regions, unlikely to be lethal
DISEASE PROGRESSION:
up to 6-12hrs - may be asymptomatic
1-2days:
- severe gastroenetritis (abdominal pain, nausea, vomting, profuse watery diarrhoea)
- dehydration and hypotension
- electrolyte derrangements,
- acute renal failure
- metabolic acidosis
- transaminitis
2-7days:
- gastroenteritis subsides,
- progressive liver failure
- coagulopathy,
- encephalopathy,
- hepatorenal syndrome
> 7 days
- either died 10-30%,
- fully recovered,
- or recovered with chronic hepatitis
INVESTIGATIONS:
VBG - metabolic acidosis
high lactate second to hypoperfusion
UEC - electrolyte disturbances and renal impairment with severe gastroenteritis
LFT - particularly ALT raised in poisoning
MANAGEMENT:
**urgent toxicologist consultation
*management is mainly supportive and aims to limit liver injury and fulminant liver failure
*GI decontamination and enhanced elimination with activated charcoal is critical (reduces mortality)
Patients are alert - no need for airway management
Fluid resuscitation and inotropic support
Correction of electrolyte disturbances
DECONTAMINATION AND ENHANCED ELIMINATION
Place NG tube
Check placement with CXR
(multi-dose activated charcoal)
activated charcoal - 50g Q4hr or place NGT 12.5g/hr continuous feed via enteric pump
Amatoxin undergoes significant enterohepatic recycling, remaining in the portal circulation for a long time after mushroom ingestion. Even if the patient presents 2 days after ingestion, giving activated charcoal is likely to be beneficial.
Dialysis does not remove amanita toxins but may be needed in severe acidosis or renal failure with electrolyte disturbance
PREVENTION OF LIVER INJURY:
- limit uptake of amanita toxic by the liver
*silibinin - 5mg/kg IV over 1hr, then infusion 20mg/kg/24hrs
OR
*benzylpenicillin - 60mg/kg up to 3g IV Q4h
OR rifampicin 600mg IV daily
PLUS
*N-acetylcysteine infusion 200mg/kg IV over 4hrs, then 100mg/kg IV over 16hrs
PLUS
*Thioctic acid 25mg/kg IV Q6h on day 1, 75mg/kg IV Q6h on day 2,
LIVER TRANSPLANTATION
Indications for transfer to liver transplant facility
* INR >6 4 days after ingestion
* Oligouria or Cr >200
* Acidosis pH < 7.3 after resuscitation
*Hypotension SBP < 80
* Hypoglycemia
* Severe thrombocytopenia
* Encephalopathy
Amatoxin can be detected in blood for up to 2 days and in urine for up to 4 days. To reduce the risk of residual amatoxin poisoning in the transplanted liver, wait at least 4 days after ingestion before undertaking a liver transplant.
Salicylates (aspirin, oil of wintergreen)
Drugs amenable to haemodialysis
Low volume of distribution
Low protein binding
“PLASMA TV”
Phenobarbital
Lithium
Alcohols (methanol/ethylene glycol)
Salicylates
Metformin-induced lactic acidosis
Theophylline
Valproate
Toxic dose >150mg/kg
CLINICAL FEATURES:
**Tachypnoea
Hyperthermia
Gastritis - vomiting, haematemesis
Tinnitus, vertigo, ataxia, deafness.
Delirium, agitation, seizure, coma
Non-cardiogenic pulmonary oedema
INVESTIGATIONS:
VBG - HAGMA, respiratory alkalosis
hypo or hyperglycemia
hypokalemia
Serial salicylate level
MANAGEMENT:
DECNTAMINATION:
prolonged absorption
decontamination with activated charcoal 50g (1g/kg) only if alert with no protracted vomiting
Optimise prior to intubation
Bipap - increase pressure support to increase minute ventilation to blow off CO2
Given 100ml sodium bicarbonate IV (5-10min before intubation so has time to blow off CO2)
most experienced operator
apnoeic BVM ventilation
post intubation hyperventilation to achieve high minute ventilation
TV 8-10ml/kg
RR 25
Avoid acidosis
- Optimise prior to intubation
- BIPAP to blow off CO2, assess minute ventilation for post intubation ventilation settings
- Give 1-2 vials of Sodium Bicarbonate prior to intubation
- Apnoeic BVM ventilation
- Most experienced intubator to get ETT in ASAP
- Hyperventilate once intubated - aim to match pre-intubation minute ventilation as seen on BIPAP
FLUID RESUSCITATION:
fluid resuscitation 20ml/kg 0.9% NS IV
URINE ALKALINIZATION:
sodium bicarbonate 100ml (1 mL/kg ) IV
FOLLOWED BY
sodium bicarbonate 25ml/hr by IV infusion
add 150ml sodium bicarb to 850ml 5% dextrose run at 166ml/hr
MONITOR URINE OUTPUT:
place IDC
aim 1-2ml/kg/hr, urinary pH 7.5
REPLACE K+
30mmol K+ in 1L NS IV over 3hrs targeting K+ 3.5-4.5
TREAT HYPOGLYCAEMIA:
5% dextrose infusion 125ml/hr target bsl 4-11mmol/L
INDICATIONS FOR DIALYSIS:
Renal failure - anuria
Unable to maintain urinary alkalinization
Rising salicylate levels >7.2mmol/L
Severe metabolic acidosis pH <7.1
Renal failure with pulmonary oedema
Organophosphate Poisoning
2022.1 Registrar Interaction
advise a junior registrar on the management of a patient presenting after an organophosphate ingestion.
Pesticides and insecticides in agriculture
inhibit anticholinesterase leading to increased acetylcholine activity
dermal absorption and inhalation
Toxicity with 1 mouthful of concentrated solutions
Cholinergic crisis:
“DUMBBELS” - muscurinic effects of cholineesterase inhibition
Diarrhoea
Urination
Miosis
Bradycardia
Bronchorrhoea, bronchospasm
Emesis
Lacrimation
Salivation
Nicotinic effects of cholineesterase inhibition
- Muscle fasciculations
- Tremor
- Weakness
- Respiratory muscle paralysis
- Tachycardia
- Hypertension
- Mydriasis
CNS
- agitation
- confusion
- coma
- seizures
Respiratory:
- chemical pneumonitis if aspirated
PPE for staff to prevent secondary poisoning
***Large amounts of atropine, hundreds of milligrams, may be necessary in massive ingestions. Proactive contact with the hospital pharmacy (or even other centres) may be necessary to ensure access to adequate amounts of atropine.
DECONTAMINATION:
Removal of clothes and cleaning patient with soap and water.
ANTIDOTE:
Atropine
Initial bolus of 1.2-2.4mg IV (children 20mcg/kg IV).
Double the dose of IV atropine every 5 min to achieve adequate atropinization:
- Drying of secretions - clear chest
- Resolution of bradycardia - HR >60
Follow with continuous infusion of 10%–20% per hour of the initial dose of atropine that was required to achieve adequate atropinization (typical infusion rates vary from 0.4 to 4 milligrams/h IV in adults).
Adjust infusion rate to maintain adequate atropinization and avoid atropine toxicity (absent bowel sounds, hyperthermia, delirium).
Pralidoxime 30mg/kg IV, followed by infusion 8mg/kg/hr
(Pralidoxime - reverses muscle paralysis by reactivation of acetylholinesterase)
Treat seizures with benzodiazepines
Consult Toxicologist
Admit to ICU
Paracetamol Overdose
HISTORY:
Time ingestion
Dose ingested - >200mg/kg (or 10g), massive overdose >30mg/kg (0r 30g)
Formulation – immediate vs sustained release
Staggered vs one-off ingestion
Co-ingestants
Self-decontamination ie vomiting
Co-morbidities - pre-existing liver/renal disease
chronic alcoholism, prolonged fasting, on medications that induce cytochrome p450
DECONTAMINATION:
- Within 2 hrs for immediate release ingestion >200mg/kg
- Within 4 hrs for sustained release >200mg/kg
- Massive (>30g) ingestion – within 4 hours immediate release and all SR
Must be alert, no intractable vomiting, maintain own airway
STANDARD NAC REGIMEN:
Bag 1:
200 mg/kg (max 22 g) in 500 mL (glucose 5% or sodium chloride 0.9%) over 4 hours
For paediatrics use a dilution volume of 7mL/kg up to a max of 500 mL
Bag 2:
100 mg/kg (max 11 g) in 1000 mL (glucose 5% or sodium chloride 0.9%) over 16 hours
For paediatrics use a dilution volume of 14 mL/kg up to a max of 1000 mL
DOUBLE DOSE NAC is just 200mg/kg in second bag
INDICATIONS FOR TRANSFER TO TRANSPLANT CENTRE:
- INR >3 at 48hrs
- Oligouria or Cr >200
- Acidosis pH < 7.3 after resuscitation
- Hypotension SBP < 80
- Hypoglycemia
- Severe thrombocytopenia
- Encephalopathy
