Toxicology Flashcards
Resus RSI DEAD
ABC, seizures, glucose, temp
Risk assessment - drug, dose, time, current clinical status (does picture fit), patient factors (comorbidities, weight)
Supportive care (fast hugs in bed please - fluids, analgesia/antiemetics, sedation, thromboprophylaxis, head up, ulcer prophylaxis, glucose control, skin/eye care, IDC, NGT, bowel care, environment, de-escalation, psychosocial support)
Investigations (ECG, paracetamol, others)
Decontamination - charcoal, whole bowel, endoscopy
Enhanced elimination - multi dose activated charcoal, urinary alkalinisation, dialysis
Antidotes
Disposition
Toxicology risk assessment
Pt details
- age
- weight
- sex
- medical and medication hx
Drug/toxin details
- intrinsic toxicity
- route of exposure
- toxic dose
- nature of exposure (acute vs chronic)
- cooingestions
Intent
Time since
Clinical effects
Investigation results (ECG, VBG, BSL)
When to NOT use charcoal
Later than 2-4 hours
Risk of aspiration
Alcohols
Hydrocarbons
Metals
Corrosives
Indications for whole bowel irrigation and how is it performed
Iron > 60mg/kg
Slow release potassium > 2.5mmol/kg
Lead
Arsenic
Life threatening slow release verapamil/diltiazem
Body packers
Dilute 8 sachets of movicol (or 2sachets of glycoprep C) in 2L of water and given 20-30ml/kg (1.5L) in the first hour (within 4hrs of ingestion) followed by 20-30ml/kg/hr (1L/hr) until diarrhea runs clear
Has risk of ileus, bowel obstruction and perforation
Indications for multi dose activated charcoal and how does it work
Carbamazapine
Colchicine
Phenytoin
Barbiturates (Phenobarbitone)
Theophylline
Quinine
Dapsone
Warfarin
Conisdered in Massive modified release paracetamol
Interrupts entero-hepatic circulation (requires biliary excretion leading to charcoal absorption in the small intestine)
GI dialysis - drug passing down concentration gradient across gut mucosa from intravascular to intraluminal space where it is absorbed by activated charcoal. Only for small molecules, lipid soluble with low protein binding and low VD
How is MDAC administered and what are the complications
1g/kg (50g) stat followed by 0.5g/kg (25g) every 2hrs
Need aspirate NG and to ensure bowel sounds prior to each dose
Rarely used past 6hrs
COMPLICATIONS
Vomiting +/- aspiration
Charcoal bezoar formation, BO and perforation is rare
Corneal abrasion
Constipation
Distraction from resus and other supportive care
Which toxins are able to be dialyzed (apart from AEIOU)
Toxic alcohols
Salicylate
Lithium
Metformin
Antiepileptics (Carbamazepine, Valproate, barbituates etc)
Potassium
Paraquat and herbicides
Theophylline
How do you perform urinary alkalinization
Alkaline urine pH promotes ionisation of highly acidic drugs preventing reabsorption in renal tubules and promotes excretion
Needs drug to be filtered at glomerulus, have small VD and be a weak acid
Salicylates and phenobarbitone
1-2mmol/kg (1 bottle =100mmol) sodium bicarb bolus and infusion of 150mmol NaHCO3 in 1L 5%glucose running at 166ml/hr
Will need 2hrly VBG and EUCs with strict K replacement to maintain K 3.5 - 4
Aim urinary pH>7.5 and UO 1-2ml/kg/hr
How and when to give sodium bicarbonate
- Cardiotoxicity due sodium channel blockade (propranolol, TCAs, chloroquine, quinine, bupropion)
- Urinary alkalisation (salicylates, phenobarbital)
- profound acidosis (cyanide, toxic alcohol, isoniazid)
CI - APO, hypoK, severe hyperNa, renal failure
Adverse effects - alkalosis (keep pH < 7.6), hyper Na, hyper osmolarity, hypoK, local tissue irritation, fluid overload
2mmol/kg bolus initially
In cardiotoxicity can repeat 5 mins until stable
Infusion 100mmol in 1000mls at 250ml/hr guided by ABG and ECG
What are the management steps for toxicological seizures
Always consider hypoglycemia as a cause, even with normal BSL with certain overdoses
- Glucose 10% 2.5ml/kg in children
- 50ml 50% in adults
Benzos are first line
Midaz 0.15mg/kg (5-10mg) IV/IM
Refractory seizures
- Phenobarbitone 20mg/kg (2g) over 30 minutes
- Levetiracetem 20mg/kg (2g) over 15minutes
Avoid phenytoin as ineffective for drug induced and withdrawal seizures as well as sodium channel blocking action increasing risk of arrhythmia
What are the management steps of toxicological hyperthermia
Cold IVF (4deg C) up to 20ml/kg (aim UO 1-2ml/kg/hr)
IV benzos to treat agitation and suppress shivering
- Diazepam 0.02mg/kg (2mg) q5min
- Midaz 0.01mg/kg (1mg) q5min
- Aim pt calm and relaxed
Ice to groin and axilla
Tepid sponging and fanning
Cooling mats and blankets
Antidotes if available
Severe hyperthermia (>41) or refractory consider
- Intubation and paralysis
- Immersion ice bath
Hemodialysis, ECMO, cooling catheter
Avoid restraints and antipyretics
1 pill can kill in toddler
Amphetamines
Beta bloackers - propanolol
CCB - Diltiazem/verapamil (15mg/kg fatal)
Chloroquine (20mg/kg)
Diabetics - Sulfonylureas (0.1mg/kg)
Depression - TCA (15mg/kg)
Opiates - Oxycodone, morphine, methadone
Theophylline
1 sip can kill in toddler
Organophosphates
Paraquat
Hydrocarbons
Toxic alcohols
Eucalyptus oil, camphor (50mg/kg fatal)
Naphthalene (1 mothball = methaehmoglobinaemia and haemolysis)
Caustic agents - ammonia, boric acid, hydrofluoric acid
Toxicological causes of delirium
Alcohol intoxication
Alcohol withdrawal
Serotonin syndrome - (SSRIs, SNRIs, TCAs, lithium, tramadol, fentanyl, MDMA)
Neuroleptic malignant syndrome - (haloperidol, metoclopramide, prochlorperazine)
Sympathamomietic syndrome - (amphetamine, cocaine, theophylline)
Anticholinergic syndrome - parkinson drugs, TCAs, antipsychotics, carbamazepine, oxybutynin
Cannabis
Hallucinogens
Salicylate OD
Theophylline OD
Atypical antipsychotic OD
Drugs that cause QT prolongation and its management
Delay cardiac repolarisation, most commonly potassium channel blockade but also in hypokalemia, hypocalcemia and hypomagnesemia.
Risk of Torsdes de points
Manage electrolytes
Torsades use Magnesium 0.2mmol/kg (8mmol) over 10 minutes then 0.12mmol/kg/hr (2-3mmol/hr) over 12-24hrs)
Keep HR >90, isoprenaline 0.1microg/kg (20microg) ever 2-3 minutes
What drugs cause sodium channel blockade
Wide QRS and tall R wave in aVR
Tricyclics with anticholinergic syndrome
Bupropion with seizures
Carbamazepine with antimuscarinic
Cocaine with high and fast toxidrome
Propanolol with low and slow toxidrome
Quinin with cinchonism (tinnitus hearing loss)
Hydroxychloroquine with antimalarial toxidrome (hyopK and altered LOC)
LA toxicity
Drugs that cause QRS widening and its management
Most commonly due to sodium channel blockade
1-2mmol/kg (100mmol) of NaHCO3 every 3-5 minutes aiming serum pH 7.45-7.55 (MAX 6mmol/kg)
+ Hyperventilation aim pCO2 30-35
Expect to need to replace potassium after
Defib unlikely to be successful
Lignocaine 1.5mg/kg (100mg) third line once pH>7.5
Differentials of the hot and confused patient
Meningoencephalitis
Systemic sepsis
Heat stroke
Thyrotoxicosis
Phaeochromocytoma
Anticholinergic syndrome
Serotonin syndrome
Neuroleptic malignant syndrome
Sympathomimetic syndrome
Alcohol withdrawal
Methylxanthine toxicity
Salicylate toxicity
Malignant hyperthermia
Neuroleptic malignant syndrome - causes, risk, diagnostic criteria, presentation and management
Caused by dopamine antagonist drug administration (antipsychotics but more common with high potency drugs like haloperidol or depots) or withdrawal from dopaminergic drugs (parkinson medications, bromocriptine)
Also prochlorperazine, metoclopramide etc
RISKS
Start, change, addition of drug increases risk
Young, male, dehydration, comorbid, organic brain disorder, genetic increases risk
DIAGNOSTIC CRITERIA
Slow onset over days, weeks to resolve
Major criteria (must have all 3)
- Exposure to dopamine antagonist drug
- Severe muscle rigidity
- hyperthermia
At least 2 minor criteria
- tachycardia, HTN, diaphoresis, labile BP
- Raised serum CK (>3xULN), leucocytosis
- Dysphagia, tremor
- Altered LOC, mutism, incontinence
Classic tetrad
- extrapyramidal : lead pipe rigidity, brady/akinesia, dystonia, dysphagia, tremor
- Temp dysregulation (>39)
- Autonomic effects: tachycardia, hypertension, labile BP, diaphoresis, tachypnea
- CNS effects: Drowsiness, confusion, coma, mutism, incontinence
Discontinue causative drugs
Supportive, cooling (cold IVF, ice packs, cooling blankets) , clonidine/GTN for HTN, ETT
Bromocriptine (dopamine agonist) - 2.5mg PO/NG Q8hr for severe or prolonged NMS (titrated to hyperthermia and rigiditiy)
Dantrolene 1mg IV to relax muscle rigidity and heat production can be considered
Serotonin syndrome - causes, risk, presentation, diagnostic criteria and management
SSRIs, SNRIs, TCAs, MAOIs, lithium, amphetamines, methadone, tramadol, St Johns Wort, methylene blue, hallucinogens
Venlafaxine asssociated with highest mortality
Start, change, addition, OD increases risk
More rapid onset over hours and resolve over 24hrs
CNS - apprehension, anxiety, seizure, coma
Autonomic - HTN, tachycardia, hyperthermia, sweating, mydriasis, flushing, diarrhoea
Neuromuscular excitation - clonus (sustained, ocular/ankle), hyperreflexia, increased tone, rigidity, tremor
Hunter diagnostic criteria help confirm diagnosis of moderate to severe serotonergic toxidrome (sensitivity 84% specificity 97%)
Taken serotonergic drug AND 1 of the following
- spontaneous clonus
- inducible clonus plus agitation or sweating
- ocular clonus plus agitation of sweating
- tremor plus hyperreflexia
- hypertonia plus temp >38 and inducible or ocular clonus
Supportive (self resolves within 12-24hrs)
Charcoal and hydration
Diazepam first line (0.2mg/kg, not more then 120mg in 24hrs)
Cyproheptadine 12mg second line, 8mg TDS for drugs with longer half life/modified release (fluoxetine and tramadol)
ETT if temp > 39.5
What are the differences between NMS and SS
NMS occurs within 1-2 weeks while SS more rapid (over hours)
NMS severe muscle rigidity, hyporeflexia and rhadbo while SS hyperreflexia, clonus, hyperactive bowel sounds/diarrhoea
NMS more frequently associated with multiorgan failure
NMS is idiosyncratic reaction after prolonged exposure to neuroleptics or after withdrawal of dopamine receptor agonist
NMS - mutism/confusion SS - apprehension/anxiety
NMS - lead pipe rigidity and hyporeflexia SS - cogwheel rigidity, hyperreflexia and clonus
NMS - hypoactive bowel sounds SS - hyperactive bowel sounds and diarrhea
Anticholinergic syndrome- causes, presentation, diagnostic criteria and management
Pure anticholinergic - atropine, benzatropine, oxybutynin, hyoscine (buscopan)
Mixed syndromes with anticholinergic -
Antiparkinson, antihistamine, TCAs, antipsychotics, carbamazepine,
Plants
Brugmansia (angels trumpet), Datura (Jimsonweed or thorn apple), Belladona/nightshade, Duboisia (corkwood)
Central - agitated delirium, repetitive gesturing like picking, visual hallucinations, mumbling/slurred/incoherent speech, fluctuating mental state, tremor, myoclonus, seizures, coma
Peripheral - tachycardia, dry mouth, dry skin, mydriasis, flushing, urinary retention, ileus(abdo distension and reduced bowel sounds), hyperthermia, hyperthermia
Supportive
Charcoal if possible
Benzo’s. Can use droperidol if not antipsychotic overdose
Adequate hydration, IDC
Antidote
Physostigmine if not responding to benzos and moderate to severe delirium - 0.5mg (0.01mg/kg) over 5 minutes every 15 minutes. Max 2mg over 60 minutes
Short acting and may need repeat dose
Contraindicated if bradycardia, bronchospasm, heart block as it is a cholinesterase inhibitor
Cholinergic syndrome- causes, presentation, diagnostic criteria and management
Acetylcholine agonists - acetylcholine, pilocarpine, nicotine, mushrooms (amanita, clitocybe and inocybe)
Acetylcholinesterase inhibitors - oraganophosphates, carbamates, chemical warfare, donepezil, neostigmine
CNS - agitation, seizures, coma
Muscarinic (DUMBBELLS) - diarrhea, diaphoresis, urination, miosis, bronchospasm, bronchorrhea, bradycardia, emesis, lacrimation, lethargy, salivation
Nicotinic - HTN, tachycardia, resp muscle weakness/paralysis, fasciculations, diaphoresis
Killer B’s - bronchospasm, bronchorrhea, bradycardia, breathing bad (resp muscle paralysis)
Early ETT (resp muscle weakness, secretions, coma)
Avoid succinylcholine
Hydration (lots of secretions)
Atropine 1.2g (50microg/kg) IV 2-3 mins doubling dose then infusion to stop bronchospasm/bronchorrhea and bradycardia (end points are HR>80, SBP>80 and clear chest)
Pralidoxime 2g (25mg/kg) or 8mg/kg/hr in organophosphate
Over atropinisation (Anticholinergic effects)
- Confusion
- Pyrexia
- Absent bowel sounds
Methaemoglobinaemia - causes, presentation and management
Consider when Sats 85-90% and cyanosis but normal paO2 on gas
Blood samples chocolate brown
Iron in oxidized form (ferrous to useless ferric) in Hb so not able to carry O2 (left shift of O2-Hb dissociation curve) causing functional anemia and impaired O2 delivery to tissues
CAUSES
Nitrites and nitrates (well water, preserved food, GTN, amyl nitrite)
LA - prilocaine, lidocaine
Herbicides (paraquat), pesticides, fertilizers
Chloroquine
Sulfonamides and dapsone can cause sulfhaemoglobinemia and require multiple doses of methylene blue
10-20% Slate grey cyanosis
20 - 30% Headache, tachycardia
30 - 50% Drowsiness, confusion, tachypnoea
50 - 70% Coma, seizures, arrhythmia, metabolic acidosis
>70% lethal
Methylene Blue if symptomatic with level>20% or asymptomatic but >25%
1-2mg/kg IV over 3-5 minutes. Can rpt after 30 minutes if still high or symptomatic
Alternatives include ascorbic acid, exchange transfusion or hyperbaric oxygen
Amanita Phalloides - signs, symptoms, prognosis, management
High source of cyclopeptides
1 mushroom cap can cause fulminant liver failure and death while other mushrooms need more then 10
Typically, asymptomatic for 6-18hrs. GI symptoms: Abdo pain, N/V, watery diarrhoea
Dehydration/AKI/electrolyte derangement/metabolic acidosis from above
Mildly elevated LFTs in first 24hrs
Over next 1-7 days: progressive liver failure, coagulopathy, multiorgan failure (mortality 10-30%)
> 7 days: complete resolution over weeks to months OR chronic hepatitis
POOR PROGNOSTIC FACTORS:
- Worse prognosis with earlier onset symptoms
- lactate >5 or progressive rise in context of hepatitis
- Rising ALT (may take up to 24hrs)
- AKI with acute liver injury
- Rising INR 3 days post ingestion or INR>6 on day 4
Onset of diarrhea 6-10hrs or INR>6 from day 4 indicate possible need for liver transplant
MANAGEMENT
Amatoxin has significant enterohepatic recycling, benefits from charcoal and MDAC even if presenting after 2days from ingestion
Antidote silibinin 5mg/kg over 1hr
then 20mg/kg/24hrs for 4 days
or benpen 3g (60mg/kg) q4hrly
or rifampacin
+
NAC 200mg/kg over 4hrs and 100mg/kg over 16hrs fro hepatoprotection
Methanol - toxic dose, symptoms and investigations.
Home brew, paints, varnishes, rocket and race car fuel, solvents/cleaners, embalming fluid, windshield wiper fluid
Metabolised to formaldehyde and then to formic acid (neurotoxic to retina and optic nerves) by ALDH
Ingestion > 0.1ml/kg signficiant toxicity in children
30g (30ml of 100%) will cause coma and blindness
Effects at 12-24 hours
CNS depression - Intoxicated, coma, seizure later due to acidosis
Retinal toxicity - blurred vision, scotomata, papilloedema, loss of light reflex, blindness
Cardio - hypotension secondary to acidosis
HAGMA (low pH best predictor of severe toxicity)
High osmolar gap (Serum osmo - 2xNa+Ur+Glucose+1.2xETOH>10)
NORMAL CALCIUM (low in ethylene glycol)
Normal renal function and no urinary calcium oxalate crystals (found in ethylene glycol
Brain imaging (CT/MRI): bilateral putamen necrosis, basal ganglia haemorrhages and necrosis of the caudate nucleus with atrophy of the optic chiasma and lesions in the occipital cortex and subcortical white matter.
Ethylene glycol
Antifreeze, radiator coolant, brake fluid, degreasing agents, foam stabilizers, metal cleaners
Metabolized to glycolaldehyde and then via ALDH glycolic acid. Then oxalic and glycoxylic acid. Oxalic acid combines with serum calcium and deposits in renal tubules leagding to ARF as well hypocalcemia (QT prolongation and ventricular arrhythmia)
Ingestion > 1ml/kg fatal
CNS depression
- intoxicatClincial
- Coma and seizures (secondary to acidosis)
GI - N/V and abdo pain
Cardio - hypotension secondary to acidosis (12-24hrs)
ARF, oligouria, flank pain (24-72hrs)
HAGMA (high anion gap best predictor of severe toxicity)
High osmolar gap (Serum osmo - 2xNa+Ur+Glucose+1.2xETOH>10)
HypoCa
Calcium oxalate crystals in urine
Lactate gap (glycolate interfering with POC lactate and artificially raising)
Treatment methanol/ethylene glycol
IVF and correct hyperK
No role for charcoal (too rapidly aborbed)
NaHCO3 for severe acidosis
Ethanol and fomepizole inhibit ADH and prevent toxic metabolites
Fomepizole has easier dosing regime and better side effect profile but costs more
Ethanol worsens sedation and agitation leading to higher rates of intubation and ICU admissions but more readily available
Should be commenced in any pt
- confirmed ingested toxic dose of methanol or ethylene glycol toxic dose
- unexplained metabolic acidosis
- High osmolar gap
ETHANOL
- Needs ETOH level prior
- IV or NG
- Aim ETOH level 22-44mmol/L and continue until methanol/ethylene glycol <20mg/dL (6.24 mmol/L for methanol, 3.23 mmol/L for ethylene glycol).
- Ethanol 10% 6ml/kg loading dose (if not already intoxicated)
Then Ethanol 10% 1-2ml/kg/hr (100ml/hr) thereafter.
- If dialysis then double
0.6g/kg followed by 0.1g/kg/hr (10g/hr) if using spirits
Alcohol volume= (required ethanol g)/(alcohol concentration %) x 100
FOMEPIZOLE
- 15mg/kg IV loading
then 10mg/kg q12hrly
- Give q4hrly if dialysis
continue until methanol/ethylene glycol <20mg/dL (6.24 mmol/L for methanol, 3.23 mmol/L for ethylene glycol)
DIALYSIS (intermittent hemodialysis preferred)
- Confirmed toxic dose ingestion
- Metabolic acidosis
- AKI
- Serum level > 50 mg/dL (15.6 mmol//L for methanol, 8.07 mmol/L for ethylene glycol)
EXTRA
Folate for methanol
- calcium folinate/folic acid 50mg IV QID
Vit B in Ethylene Glyco
- Pyridoxine (B6) 50mg IV QID or thiamine (B1) 100mg IV QID
Isopropanolol
Surgical spirits - disinfectant, solvents, window cleaners
4ml/kg can cause coma
Supportive as per ETOH intoxication
Only toxic alcohol that causes ketosis without acidosis
Beta blockers - risk assessment and clinical presentation
RISK FOR TOXICITY
- Propranolol (coma, seizures, Na channel blocker/QRS prolongation) and sotalol (cardiac K channel blocker/QT prolongation) most toxic
- Children 1 dose can be toxic
- >1g propanolol toxic
- Modified release (metoprolol only)
- Older Age
- Medical conditions (heart disease, cirrhosis)
- Co-ingestion with other cardiovascular drugs (CCB, diogxin, ACE etc)
CLINICAL - within 1-2 hrs
Cardiovascular
- Hypotension due to myocardial depression and bradycardia
- Sinus brady most common arrhythmia BUT PR prolongation earliest sign of toxicity
- 1st/2nd/3rd HB, junctional brady, ventricular brady and asystole in severe
- QRS widening in propranolol
- QT prolongation in sotalol
CNS
- Seizures, delirium and coma in lipophilic betablockers (propanolol)
Resp
- Bronchospasm and APO
Metabolic
- Hypo/hyperglycemia (interferes in gluconeogenesis and glycolysis but uncommon in adults)
- HyperK
Beta blocker toxicity management
Charcoal as soon as possible for severe overdose
Otherwise 2hrs in IR adn 4hrs in MR
Early intubation in refractory cardiovascular instability or decreased LOC with pretreatment of Atropine 600microg to prevent vagal mediated bradycardia during laryngoscopy
Hypotension with IVF first line
- TTE can be helpful in determining cardiogenic shock vs vasodilatory shock
Bradycardia with hypotension
- 1st line: Atropine 600microg q15min
- 2nd line: Adrenalin 10-20microg (0.1microg/kg) q3min followed by infusion 0.1microg/kg/min
- Isoprenaline 20microg (0.1microg/kg) q3min followed by infusion can also be used for bradycardia but may worsen hypotension
IN VASOPLEGIC SHOCK
Norad 0.05-0.5microg/kg/hr second line vasopressor
IN CARDIOGENIC REFRACTORY SHOCK
High dose insulin euglycemic therapy
1unit/kg actrapid with 50ml 50%glucose (2.5ml/kg of 10%)
Followed by
1unit/kg/hr (MAX 10unit/kg/hr) with 50% glucose 20ml/hr or 10% 100ml/hr (10g/hr)
- 2.5ml/kg/hr of 10% in children
Aim BSL 4-5 and check every 30min
K replacement and aim K 4-4.5. Check every 2-4hrs
Intralipid controversial but can be considered if still refractory
- 20% 1.5ml/kg bolus q5min for 2-3 doses if in asystole otherwise infusion 0.25ml/kg/min for 30-60minutes
Hemodialysis only effective in sotalol and atenolol
VA ECMO if available but not after intralipids as clots circuit. Evidence in cardiogenic shock but no vasoplegic shock
Sodium Bicab 1-2mmol/kg q3minutely (6mmol/kg) if refractory hypotension or cardiac arrest as acidosis decreases effectiveness of inotropes OR in Na channel blockade
QT prolongation management
Seizures
- Glucose first line (intracellularly deplete despite normal BSL)
- benzos second line
Glucagon no longer recommended as short half life and dose required quickly exhausts hospital supply
Calcium channel blocker OD features
Most concerning are diltiazem and verapamil
2-3x normal dose (10 tabs, > 15ml/kg) toxic
Can be immediate release - first 2-4 hours or delayed 4-16 up to 24 hours
Bradycardia, 1-3 HB, hypotension, ACS, CVA, ischaemic gut, hyperglycaemia, lactic acidosis, shock, seizures
Calcium channel OD treatment
- Charcoal (up to 4 hours slow release)
- Expect bradycardia and hypotension - IVF, pacing (rather than drugs), adrenaline, ECMO/bypass
- High dose insulin glucose therapy
Calcium glutinate 10-20mls 10% IV repeated with monitoring of Ca levels
Acute digoxin OD features
Drugs, toad toxin, oleanders
10 x daily dose toxic, lethal > 10mg (4mg children)
GI early - n+v, abdo pain
CVS later 8-12 hours - bradycardia, slow AF, HB, increased automaticity, bigeminy, SVT, VT, hypotension
CNS - leathery, confusion, seizure
Dig levels at 4 hours
< 1 therapeutic
2-3.2 potentially toxic
> 3.2 toxic
Often hyperkalaemia - poor sign if > 5.5 early
ECG - reverse tick ST depression lateral leads, shortened QTc
Acute digoxin OD treatment
- Cardiac arrest - 20 amps digibind
- Life threatening arrhythmia, refractory hypotension, refractory hyperK, significantly symptomatic then give digibind
- dose digibind vials = ingested dose in mgx0.8x2
- if unknown start 2-5
- atropine 0.6mg, pacing
- arrhythmia - magnesium, lignocaine
- hyperK - insulin/dextrose, bicarb NOT calcium
Chronic digoxin toxicity
Usually intercurrent illness (sepsis, NSAIDs etc) so renal impairment and delayed elimination
GI upset, bradycardia, syncope
Lower levels than acute cause problems
- bradycardia alone with level 2.5 50% toxic
- GI alone with level 2.5 60% toxic
- bradycardia and GI level 2.5 90%
- automaticity + others level 2.5 100%
- cardiac arrest 5 amps
- digibind 1-2 amps
What are some common salicylates in Australia and their toxic doses
Aspirin
Oil of Wintergreen (can be 98% methyl salicylate and 1 tsp=7000mg)
Topical gels for teething and skin peeling (choline salicylate and salicylic acid)
Alternative medicines (Willow bark)
Dose dependent toxicity and other salicylates should be converted to aspirin equivalents
Methyl salicylate conversion factor 1.4 (4mls of Wintergreen lethal in small child)
<150mg/kg mild toxicity (6hrs monitoring)
150-300mg/kg Mild to moderate but can evolve to severe (primary respiratory acidosis and salicylism) and so need admission and management
300-500mg/kg Severe (confusion, coma, seizures, mixed resp acidosis and metabolic acidosis)
>500mg/kg lethal
Chronic salicylate toxicity occurs with regular doses >100mg/kg/day
More likely in older pts and chronic liver or kidney disease
Explain the acid base disturbances in salicylate toxicity
First respiratory alkalosis though direct stimulation of medulla respiratory centers causing hyperopnoea
Second high anion gap metabolic acidosis through uncoupling of oxidative phosphorylation causing inhibition of electron transport chain in mitochondria causing lactic acidosis as well as the mild effects of the salicylic acid itself
Third is respiratory acidosis as preterminal event secondary to respiratory exhaustion, ARDS or severe CNS dysfunction
What are the effects of salicylate toxicity
6-12hrs to manifest but deterioration is rapid
Early
GI distress -N/V/epigastric pain
Tinnitus or altered hearing
Dizziness
Hyperventilation and respiratory alkalosis
Antiplatetlet effects
Late
Altered mental status/Coma
Seizures
Fevers
Hypoglycemia/hyperglycemia with intracellular hypoglycemia
Hypokalemia
ARDS
AKI
Chronic intoxication is nonspecific cause of delirium, confusion, fever with unexplained metabolic acidosis
Cerebral oedema and ARDS more common in acute
What is the specific management of Salicylate toxicity
Activated charcoal within 6hrs of ingestion of >150mg/kg and second dose 4hrs after if serum levels still rising
Correct hypoK 10-20mmol/hr, aim K 3.5-4 BEFORE Urinary Alkalization
- Check 2hrly on gas and formal EUC 2-4hrly
Urinary alkalinization to prevent penetration of salicylate into tissues and enhance urinary excretion by preventing tubular reabsorption
Sodium bicarb 1mmol/kg bolus followed by 25mmol/hr infusion (Add 15ml to 850ml of 5% glucose and run at 166ml/hr)
- Serum pH 2hrly aim 7.45-7.5
- Urine pH 2hrly aim pH7.5-8.0 and UO 1-2ml/kg/hr
Glucose 50ml of 50% or 2.5ml/kg of 10% with:
- hypoglycemia
- Altered LOC (likely cerebral hypoglycemia)
- Seizures (glucose first line then benzos)
- Check 2hrly and aim BSL 4-8
Avoid intubation but if needed pretreat with sodium bicarb, Ventilate through apneic period and set high MV (high TV and RR)
Hypotension often responds to fluids
Hemodialysis last line. Consider with:
- Altered LOC
- ARDS
- ARF
- Worsening acidosis (pH<7.2) or electrolyte disturbance
- Serum salicylate level >7.2 or rising despite medical management (check 4-6hrs to determine peak concentration and effectiveness of elimination/ongoing absorption)
What are the indications for dialysis in salicylate overdose
Altered LOC
ARDS
ARF
Worsening acidosis (pH<7.2) or electrolyte disturbance
Serum salicylate level >7.2 or rising despite medical management (check 4-6hrs to determine peak concentration and effectiveness of elimination/ongoing absorption)
Rarely needed as most pts respond to medical therapy
Intermittent hemodialysis preferred
When can Sodium bicarb/urinary alkalinsation be stopped in salicylate overdose
At least 6hrs AND
- Serum salicylate <2.2 and falling
- Acid base disturbances have resolved
- Pt asymptomatic
Opiods
Triad - miosis, resp depression, CNS depression
Aspiration, hypothermia, hypoxic brain injury, rhabdo
Pethidine - serotonin syndrome
Dextropropoxyphene - seizures
Naloxone 100-400mcg bolus
2 x boluses needed then start infusion at 2/3 initial dose required/hr and titrate
Iron
20-60mg/kg moderate, 60-90mg/kg requires decontamination, > 130 potentially fatal
Vomiting within 80 mins in 90%, direct GI irritation
Hypotension, acidosis, myocardial damage, inhibition coagulation, confusion, coma
0-3 hrs GI symptoms
12-48 hrs systemic symptoms
2 weeks strictures
Iron level at 4 hours
Hyperglycaemia, acute tubular necrosis, hepatoxicity, prolonged INR/APTT, elevated WCC, metabolic acidosis
CXR/AXR for FB
Resonium, gastric lavage, whole bowel irrigation, scope
Desferioxamine if coma, acidosis, peak level > 90. Can promote infection - stop if fever, give abs
Lithium
Narrow therapeutic index 0.8-1.2
Toxicity with intercurrent illness
Acute > 40mg/kg, symptoms over 3-5 days
< 1.5 Lethargy, fine tremor, memory deficits
< 2.5 confusion, visual disturbances, ataxia, coarse tremor, hyperactive reflexes
< 3.5 myoclonic twitches, nystagmus, stupor
> 3.5 seizure, flaccid paralysis, coma
T wave flattening or inversion, prolonged PR/QRS/QT
Hypokalaemia, abnormal TFTs
Gastric lavage
Diuresis with IVF
Dialysis
Supportive
Arsenic - causes, doses/concentrations, effects and management
CAUSES
Acute
- inhalation of arsine gas (metal refineries)
- Ingestion of INORGANIC arsenic compounds in older pesticides/insectiscides, wood treatment or metal refineries
- Arsenic trioxide in treatment in acute promyelocytic leukemia
Chronic
- Usually >10yrs to develop
- long term exposure to environmental arsenic (well water, industrialized areas, landfill/wastesites)
Organic arsenic in seafood, shellfish, organic rice relatively nontoxic
DOSES/CONCENTRATION
<0.05mg/kg mild Gi symptoms
Lethal dose of inorganic arsenic 1-3mg/kg
24hr urine concentrations >1000microg/L indicated acute poisoning
Raised urine levels on spot collection indicated recent exposure in symptomatic pts only. Nontoxic Organic arsenic raises urinary concentration for up to 2 weeks
EFFECTS
Binds to numerous cellular enzymes and interferes with cellular respiration. Also produces reactive oxygen intermediates causing lipid peroxidation
RAPID/IMMEDIATE EFFECTS
Classic - Hypersalivation and garlic odor
GI (rapid onset) - N/V, severe watery diarrhoea, abdo pain, GI hemorrhage
Metabolic acidosis
Within hours:
CVS - hypotension (peripheral vasodilation), QT prolongation, ventricular arrhythmias, acute heart failure (myocardial depressions), cardiovascular collapse
CNS - Encephalopathy, seizures
ARDS, ARF, hepatic injury
Acute severe hemolysis with arsine gas
DELAYED EFFECTS
Bone marrow suppression in 24-72hrs (lasts 2-3 weeks)
Ascending peripheral neuropathy 1-3weeks (predominately motor, mimic GBS but sensory component so can be painful)
Bone marrow suppression (leukopenia, anemia)
Hepatitis
Pigmented skin lesions
Chronic toxicity - constitutional symptoms, painful peripheral neuropathy (glove and stocking), hyperkeratosis of palms and soles, hyperpigmentation, hair loss, nail mees lines, malignancy of skin/ bladder/lung/liver/kidney, headache, confusion, haemolytic anemia
MANAGEMENT
ETT as needed
IVF and inotropes (dehydration + peripheral vasodilation and myocardial depression)
Optimize electrolytes and avoid bradycardia for QT prolongation
WBI if radioopaque material on Xray
NAC 200mg/kg over 4hrs then 100mg/kg over 16hrs for hepatoprotection, enhancing excretion of arsenic in acute poisoning and prevent arsenic binding to cellular proteins
Chelation (risk of micronutrient deficiency such as Fe, Zn, Cu. Need blood levels +arsenic checked weekly)
- PO Succimer 10mg/kg q8hr preferred but can cause abdo pain, neutropenia, elevated aminotransferase, neutropenia
- IV DMPS 5mg/kg QID OR dimercaprol and calcium EDTA
Lead
Fumes, FB retention, contaminated drinks, improper storage foods in pewter, leaded glass, paint, batteries
Myalgia, hypo chromic microcytic anaemia, painless wrist drop, encephalopathy, HTN, gout, nephritis, abdo pain, infertility
Lead levels represent last 3-5 weeks
Children > 0.5 act on, symptomatic > 2.9
Chelation BAL or CaEDTA
Mercury
Inorganic - batteries, vinyl, acetaldehyde, embalming, cosmetics
Ashen grey MM, metallic taste, stomatitis, abdo pain, poor muscle tone, red/oedmatous soles and palms, tachycardia, high/low BP
Organic - contaminated foods, paper/wood preservatives
Over days/weeks
Scotoma, ataxia, parasthesia, hearing loss, dysarthria, tremor, cognitive defects, paralysis
Mercury blood or urine levels
Xray
Decontamination
Can dialyse
Chelation - BAL, penicillamine
Chelating agents
CaEDTA - lead, zinc
Penicillamine - copper, second line lead, iron, zinc, mercury, arsenic.
CI in pregnancy, renal disease, penicillin allergy
BAL - acute inorganic mercury, lead
CI in peanut allergy
DMSA - mercury, lead
Paracetamol toxicity
Large ingestions mean P450 pathway needed to metabolise which produced NAPQI - hepatic, renal, cardiac, neuro toxic
Increased risk hepatoxicity:
- depletion glutathione - malnutrition, HIV, chronic hepatic
- induction P450 - ETOH, anticonvulsants etc
Toxic doses:
> 10g or > 200mg/kg
Very large > 50g or > 1000mg/kg or > 3 x above nomogram
Repeated:
> 12g or > 300mg/kg (>150mg/kg children) over single 48 hour period OR
> 4g or > 60mg/kg per 24 hour period for 48 hours with associated abdo pain/nausea/vomiting
Paracetamol levels and investigations
Level taken at 4 hours
Nomogram validated to 16 but extrapolated to 24
Check baseline ALT in all
If massive or features hepatoxicity then full LFTs, coats, electrolytes (hypokalaemia common), blood gas (for metabolic acidosis), glucose (hypogylcaemia common)
Acute single ingestion paracetamol within 8 hours
Charcoal if within 2 hours then NAC
200mg/kg IBW over 4 hours then
100mg/kg over 16 hours - if level is > 2 x nomogram then second bag is at double dose (so 200mg/kg over 16 hrs)
Check ALT 2 hours before stopping - if > 50 or rising then need to continue
Check paracetamol 2 hours before stopping only if initial level was > 2 x normogram - if > 66 then need to continue
If continuing then can only stop when:
ALT/AST decreasing
INR < 2
Patient clinically well
100% protection if started by 8 hours
Adverse effects - vomiting, fever, allergy - stop infusion, give antihistamine, restart at 1/2 rate for 30 mins then increase to normal rate
When to get advice with paracetamol toxicity
IV paracetamol overdose
Very large overdose - > 50g or > 1g/kg or > 3 x nomogram level
Initial hepatotoxicity ALT > 1000
Liver unit:
INR > 4.5 anytime or > 3 at 48 hours
Oliguria or creat > 200
Acidosis pH < 7.3 despite treatment
Persistent hypoglycaemia
SBP < 80 despite resus
Severe thrombocytopenia
Encephalopathy
Survival < 10% without transplant
Delayed single ingestion paracetamol
8-24 hours
Start NAC immediately
Check paracetamol and ALT levels
If under nomogram and ALT < 50 - no further treatment
If above line or > 50 then NAC as per protocol, recheck at 2 hours prior to stopping as per acute ingestion
> 24 hours
Start NAC and check levels
If paracetamol < 66 and ALT < 50 then stop
If either elevated continue as per acute ingestion
Repeated ingestion paracetamol
Measure paracetamol and ALT
Start NAC if paracetamol > 120 or ALT > 50
Repeat at 8 hours
If paracetamol < 66 and ALT < 50/static can stop
If elevated then continue NAC and recheck levels every 12 hours - stop when meets criteria above
Modified release paracetamol ingestion
If < 10g or 200mg/kg
- paracetamol level 4 hours post ingestion (start NAC if above line)
- further level 4 hours after this (start NAC if above line)
- if both below, d/c
If > 10g or 200mg/kg
- charcoal up to 4 hours and consider more than 1 dose
- start NAC and complete 20 hours regardless of initial paracetamol level
- check level and ALT 2 hours before stopping, stop if meets usual criteria
Amphetamines
Acute - sympathomimetic symptoms 4-6 hours
Supportive, benzos, labetolol to control BP, B blockers for arrhythmia, cooling
Chronic - weight loss, poor dentition, cardiomyopathy, insomnia, paranoia, psychosis, social effects
Withdrawal in 85% lasting 3-5 days or up to weeks
Cocaine
Acute - sympathomimetic symptoms
Myocardial ischaemia (50% thrombus, 50% vasospasm)
Prolonged QRS and QTc
HTN, ICH, seizures
Crack lung - fever and haemoptysis
Movement disorders
Chronic - Cardiomyopathy, myocarditis (IV), perforated nasal septum
Supportive with benzos
GTN or Phentolamine 1-2.5mg IV for HTN. Avoid betablockers
Sodium bicarb for QRS widening due to sodium channel blockade
May need ACS treatment
Opioids
Acute - triad CNS depression, resp depression, miosis
May be aspiration, hypothermia, rhabdo, compartment syndrome, hypoxic brain injury
Pethidine - serotonin syndrome
Dextropropxyphene - seizures
Naloxone 100-400mcg, repeat as needed, infusion if 2 x given (2/3 initial dose needed to reverse/hr and titrate)
Observe 4-12 hours depending on preparation
Withdrawal lasts 6hrs - 2 weeks - GI symptoms, lacrimation, salivation, anxiety, mydriasis, diaphoresis.
Admit if severe/complications/intercurrent illness. Give opiates or clonidine
Body packers/stuffers
Packing - concealing drugs in planned way, large amounts so can be severe toxicity if leaks, bowel obstruction
Stuffing - last minute concealment, smaller package but badly wrapped
Plain films useful, CT if concerns
Stuffers - observe 8 hours
Packers - observe until passed and repeat imaging OK
Carbon monoxide
Colourless and odourless
Cigarettes, car exhausts, heating malfunction
240 x affinity than O2 for Hb
Features correlate to end level CO exposure
Headache, vertigo, ataxia, visual disturbance, confusion, seizures, coma, n+v, arrhythmias, ischaemia, pulmonary oedema, cherry red skin
Long term neuropsychological symtoms (increased risk if pregnant, > 55, ischaemia, acidosis, significant LoC)
Ix - elevated CO level, metabolic acidosis, hyperglycaemia, rhabdo, renal injury
Rx - 100% O2 at least 8 hrs/until symptoms resolved (24hrs if pregnant)
Hyperbaric O2
Cyanide
Fires, photographic/tanning/plastic industries, sodium nitroprusside, pips/seeds (almonds, peaches, apples etc)
Death rapid
Burning MM, SOB, vomiting, tachycardia, confusion, seizures, coma, CVS collapse, bitter almond odour, cherry red macula, miosis
HAGMA with elevated lactate
Gastric aspirate - litmus blue/green if cyanide
Cyanide levels often delayed
Rx - remove clothing, do not wash, 100% O2, hyperbaric O2, supportive
Hydroxycobalamin 5g
Sodium thiosulphate 50mls 25%
Produce methaemoglobinaemia (not if CO poisoning also present) with sodium nitrite or amyl nitrite
What are the toxic effect of antiepileptic overdose and some potential toxic doses in pediatrics
CNS toxicity is main effect (if absent unlikely to develop significant toxicity)
- Horizontal and vertical nystagmus
- Ataxia
- Dysarthria
- Dose dependent decreased GCS (drowsiness to coma)
- Resp depression
- Seizures
GI - N/V
Cardio
- Hypotension
- Tachy/bradycardia
- Cardiotoxic effects (Na channel blockade and QRS prolongation particularly in carbamazepine and lamotrigine)
Consider serum drug concentration for carbamazepine, phenobarbitol, phenytoin and valproate
Management:
Intubation
IVF and management of QRS prolongation
Charcoal (even if delayed)
MDAC (carbamazepaine, phenytoin and barbiturate)
Dialysis (barbiturates, carbamazepine, lamotrigine and valproate)
Barbiturates - examples, doses, effects, management
EXAMPLES
Long acting - Phenobarbital, primidone
Medium - pentobarbital
Thiopental
DOSES
Narrow therapeutic index
Dose dependent sedation depends on tolerance
Normal range 60-240mg daily phenobarbital and 125mg-1.5g daily primidone
EFFECTS
Dose dependent CNS depression (drowsiness to coma)
Areflexia
Resp depression and apnoea
Hypotension (myocardial depression and reduced vascular resistance)
Hypothermia
Multiorgan failure due to hypoxica
MANAGEMENT
Phenobarbital level can confirm extent
Early intubation
IVF and inotropes (TTE can help determine which but start with adrenalin)
Charcoal, even if delayed due to potential for severe toxicity
Large primidone or phenobarbital overdose with coma, resp depression or hemodynamic instbailtiy can have MDAC +/- dialysis (if long acting phenobarbital, primidone)
High risk of withdrawal within 48hrs so regular dose should be restarted once toxicity resolved
When can flumazenil be considered in benzodiazepine overdose and what are the risks
Effects of benzo overdose usually results in mild to mod sedation
RISK for severe CNS depression
- Coingestions of other sedatives
- Extreme of age
- Naive to benzos
- alprazolam relatively more toxic
- newer designer benzos have higher potency
Flumazenil 5microg/kg (0.2mg) every minute up to 2mg (40microg/kg) can be considered
- to reverse procedural sedation
- avoid intubation in pts with resp disease or extreme of age
- intubation and ventilation not available on site
Half life <1hr, run infusion at half-2/3 bolus dose/hr
Can precipitate withdrawal and seizure if
- pt has hx of epilepsy
- Coingested proconvulsant (TCA)
- benzo dependence
Carbamazapine and oxcarbazepine - doses and concentrations, effects, management
DOSES
>20mg/kg - sedation
>50mg/kg - cardiovascular toxicity, GI effects and significant CNS depression
Oxcarbazepine poisoning is rare but managed the same with >30mg/kg dose needing monitoring
CONCENTRATIONS
5-12mg/L (21-51microg/L) - therapeutic
12-20mg/L (51-85microg/L) - nystagmus, sedation, ataxia
(occurs at slightly lower concentration 10mg/L or 40microg/L on RCH)
20-40mg/L (85-170microg/L) - horizontal and vertical nystagmus, progressive sedation
> 40mg/L (170microg/L) - respiratory depression, coma, seizures, cardiovascular toxicity
EFFECTS
Delayed onset of effects and peak (>48hrs)
Absorption cyclical and erratic due to intermittent ileus and bezoar formation
- fluctuating serum concentration and toxic effects
- serum concentrations do not indicate extent of toxicity but serial concentrations useful for progress and response to treatment
CNS
- horizontal and then vertical nystagmus
- ataxia with increasing severity, dysarthria
- agitation and fluctuating delirium
- drowsiness, altered LOC and coma
- Resp depression
- Seizures
CVS
- tachycardia
- hypotension (vasodilation and dehydration)
- heart block
- QRS prolongation +/- VF (>40mg/L serum concentration)
Anticholinergic effects
- Urinary retention
- Intermittent ileus +/-bezoar formation from MR preparation
- dry mouth
- sinus tachy
MANAGEMENT
Charcoal if >50mg/kg within 6hrs of ingestion or intubated
MDAC if bowel sounds present for >50mg/kg
IVF +/- inotropes (TTE for ?cardiogenic shock)
Serum alkalinization for QRS prolongation
- Sodium bicarb 1-2mmol/kg (100mmol) q5min (MAX 6mmol/kg), serum pH7.45-7.55 + hyperventilation pCO2 30-35
Early intubation with airway or breathing compromise
Benzos for seizures
Dialysis
- severe cardiovascular toxicity
- serum >5x UL theraputic range (>60mg/L or 255microg/L)
Consider ECMO for cardiovascular arrest or life threatening arrhythmia
Lamotrigine - doses, effects and management
DOSES
>4g assosciated with life threatening toxicity
Drug naive children provoked siezures with small doses (>10mg/kg)
EFFECTS
Peak effect within 4hrs
Generally resolves within 24hrs bit can be prolonged in severe
CNS
- Altered LOC
- Ataxia and involuntary movements (choreaathetosis, myoclonus, hemiballismus)
- Seizures including statis
CVS
- Sinus tachy and arrhythmia
- QRS prolongation, heart block, Brugada like pattern
- Refractory hypotension
Other
GI - N/V
MAOI effect - serotonergic toxidrome with coingestions (neuromuscular excitation, hyperthermia, altered LOC)
Eosinophilia and hepatitis in pts taking therapeutically
MANAGEMENT
Charcoal
Intubation if depressed LOC or status compromising airway
IVF +/- intropes for hypotension
- Dialysis and cardiac assist devices may be needed in refractory
Serum alkinisation for QRS prolongation
- Sodium bicarb 1-2mmol/kg (100mmol) q5min (MAX 6mmol/kg), serum pH7.45-7.55 + hyperventilation pCO2 30-35
Benzos for seizures
Management of serotonergic toxidrome as needed with cooling
Dialysis in severe cases possible due to low protein binding and moderate volume of distribution
Phenytoin - risks for overdoses, doses, concentration, effects, management
RISKS OF TOXICITY
- Saturable metabolism that can prolong half-life (resolution can take days to weeks)
- Undergoes metabolism via CP450/CYP2C9/CYP2C19 and there is increased risk of toxicity if there is concurrent use of drugs that inhibit these enzymes (amiodarone, fluoxetine, omeprazole, disulfrim etc)
- Escalation of doses or rpted doses of supratherapeutic doses in chronic therapy
- Acute large ingestions
DOSES
>20mg/kg - cerebellar toxicity (ataxia, dystharthria, nystagmus
>100mg/kg - sedation/coma
> 10mg/kg child’s usual daily dose also at risk
CONCENTRATION
Useful test to confirm acute ingestion and that cerebellar toxicity is related to chronic phenytoin therapy as well as guide management in se
40-80micormol/L (10-20mg/L) - therapeutic
80 - 120micromol/L (20-30mg/L) - horizontal nystagmus
120 -160micromol/L (30-40mg/L) - vertical nystagmus, diplopia, ataxia, tremor, hyperreflexia (significant cerebellar toxicity), N/V. drowsiness
160-200micromol/L (40-50mg/L) - Confusion, disorientation, lethargy, mania, respiratory depression >200micromol/L (50mg/L) - coma/seizures
EFFECTS
CNS effects
- Cerebellar toxicity (ataxia, dysarthria, nystagmus)
- confusion
-seizures
CVS effects
- bradycardia, hypotension and ventricular arrhythmias/conduction defects from rapid infusions secondary to propylene glycol diluent
GI
- Nausea/vomiting
- gingival hyperplasia (chronic)
MANAGEMENT
ETT and IVF as needed
Charcoal for >20mg/kg within 4hrs or after intubation
MDAC only for severe ingestions >100mg/kg as no evidence of improved outcomes
Dialysis can be considered in severe cases but low evidence of benefit
Can DC after 6hrs if asymptomatic, cognitive baseline and safely ambulant
- If moderate to severe or persisting symptoms after 6hrs, q6hrly concentration levels
Pregabalin and Gabapentin - effects and managemement
EFFECTS
Within 1-2hrs and resolve within 12hrs
Renally excreted, kidney injury prolongs toxicity
Minimal effects in single drug ingestion. Worse if coingestions with other sedatives
CNS depression
- Pregabalin >8g or >35mg/kg in drug naive children
- Gabapentin, saturable oral absorption so toxicity. >75mg/kg in drug naive children
Dizziness, ataxia, tremor, myoclonus and seizures
N/V with gabapentin
Sodium valproate - doses, concentration, effects, management
DOSES
<200mg/kg - minor effects
200mg-400mg/kg - moderate CNS depression
400-1000mg/kg - Multiorgan failure
>1000mg/kg - potentially life threatening, coma, multiorgan failure, cerebral oedema
CONCENTRATION
Check q6hrly in pts with altered LOC
50-100mg/L (350-700micromol/L) - therapeutic
>850mg/L (6000micromol/L) - coma respiratory depression and metabolic acidosis
EFFECTS
Within 4hrs of standard prep and up to 12hrs in enteric coated
GI - N/V, abdo pain, hepatotoxicity
CNS - dose dependent CNS depression, ataxia, cerebral oedema, seizures, respiratory depression
CVS - QT prolongation, hypotension, tachycardia
METABOLIC - hypoglycemia, hypernatremia (large ingestion from sodium load), hypocalcemia, metabolic acidosis/lactatemia/hyperammonemia in severe toxicity
HAEM - late onset (3-5 days) bone marrow suppression with mild-mod thrombocytopenia and neutropenia
MANAGEMENT
ETT as needed
IVF first line hypotension
Ca, Mg and K and avoid bradycardia for prolonged QT
Torsades rare but MgSO4 8mmol or 0.2mmol/kg over 10 minutes then 2-3mmol/hr or 0.12mmol/kg/hr for 12-24hrs)
Glucose
Charcoal for >200mg/kg or intubated
MDAC >500mg/kg or rising levels
Dialysis for ingestions >1g/kg, concentration >1000mg/L (7000micromol/L) or signs of severe toxicity (pH<7.1, cerebral oedema, shock)
Carnitine antidote: 100mg/kg bolus then 50mg/kg q8hrly until coma and acidosis resolved
- low evidence but reasonable biological basis, inexpensive and low risk of harm
- Consider with cerebral oedema, hepatotoxicity, hyperammonemia, severe acidosis
Organophosphatesha
Inhibit acetylcholinesterase increasing ACh at both muscrarinic and nicotinic cholinergic receptors
Can bind irreversibly in ageing (not carbamates)
Inhalation - usually within 5 mins
Transdermal/oral - several hours
Cholinergic signs (DUMBBELLS etc), pulmonary oedema in 40%, garlic smell
Delayed muscle weakness after resolution initial cholinergic signs 24-96hrs in 10-40% (resp muscles, cranial nerves, pros limb flexors)
Polyneuropathy at 2-3 weeks - rare
ST elevation, QTc prolongation, arrhythmias common
RBC acetylcholinesterase or plasma butyryl/pseudocholinesterase
(RBC correlates better with severity of exposure, take longer to recover ~120 days and improves post oxime therapy. Plasma levels sensitive biomarker for exposure but no relation to severity)
PPE - universal precautions, remove clothing, soap and water
Atropine 1.2mg (50microg/kg) IV Q5mins doubling dose until chest clear, secretions, dried, HR>80 SBP>80
Pralidoxime - must be given early especially for weakness/paralysis
Dimenthoate - early coma, CV collapse and death within 24hrs
Chlorpyrifos - early cholinergic symptoms
Fenthion - few early symptoms, late onset paralysis (up to 2days)
Organophosphate delayed effects
Paralysis 2-4 days after apparent recovery (fenthion, diazinon, malathion)
Organophosphate induced delayed neuropathy (OPIDN) rare and occurs 1-5 weeks post acute exposure (fenthion, parathion, chlorpyrifos)
Ascending sensorimotor polyneuropathy secondary to ageing
Chronic organophosphate induced neuropsychiatric disorder may occur following acute intoxication or chronic low level exposure
Organophosphate antidotes
Atropine in escalating doses indicated with
- diaphoresis
- Reduced breath sounds
- Wheeze
- Cough
- Bradycardia
- hypotension
1.2mg (50microg/kg) and double every 5 miuntes until HR>80, SBP>80 and drying of secretions with clear chest sounds. Infusion 10-20% total loading dose per hour
Pralidoxime can reverse neuromuscular blockade by reactivating inhibted AChE BEFORE AGEING OCCURS
1g IV then 250mg/hr for at least 24hrs
Not needed in carbamate intoxication
Has not shown to improve survival or reduce need for intubation but has been seen to reactivate RBC acetylcholinesterase
Controversy regarding serum alkalinsation and use of nondepolorising muscle relaxants. Early evidence suggests that it may reduce delayed neuromuscular effects by protecting the neuromuscular junction
Hydrocarbons/terpines/essential oils
Petrol, diesel, kerosene, turps, toluene, camphor
CNS - ataxia, euphoria, seizures, coma, myopathy, cerebellar dysfunction, encephalopathy
CVS - in severe - arrhythmias, hypotension
GIT - d+v, haematemesis
Pulmonary - aspiration, oedema
Bone marrow suppression
Metabolic acidosis
Supportive, dialysis
Paraquat
Most lethal poison, small sip can kill
Early - GI /corrosive injury
Multiorgan failure around 48 hours
If survive > 48 hours get pulmonary fibrosis
Serum level >5 fatal, >2.5 90% fatal
Extensive bloods to assess organ damage
PPE
Immediate decontamination, remove clothes, fullers earth/charcoal
Dialysis
O2 only is sats < 90 and aim no more than 92%
Consider palliation
SSRIs - examples, doses, signs and management
EXAMPLES
Citalopram, fluoxetine, sertraline, dapoxetine, fluvoxamine, paroxetine
DOSES
>600mg citalopram (>2mg/kg)
>300mg escitalopram (>1mg/kg) are associated with QT prolongation and torsades
otherwise >50x daily dose or >5-10mg/kg for serotonergic toxicity
EFFECTS
Onset 4 hours, offset 12 hours
Acute serotonergic toxidrome if with congestions or massive single agent ingestion (15% of SSRI poisoning)
Agitation, anxiety, confusion
Neuromuscular excitation (clonus, ocular clonus, tremor, hyperreflexia, hypertonia)
Autonomic (hyperthermia, sweating, flushing, mydriasis, tachycardia)
Seizure <2%
QT prolongation +/- torsades with citalopram and escitalopram.
Bradycardia citalopram, escitalopram and fluoxetine
MANAGEMENT
Supportive
Charcoal for large doses <4hrs
Adequate hydration
Diazepam 5-10mg q30min
Early ETT if temp >39.5
Cyproheptadine 8mg PO TDS if mild/mod
Mirtazapine - mechanism and toxic dose
Central alpha2 adrenoceptor blocker increasing noradrenalin and serotonin release.
Single ingestion of more 1000mg is associated with CNS depression but otherwise relatively safe.
Does not need decontamination
Does not cause serotonergic toxidrome
SNRIs - examples, doses, signs and management
EXAMPLES
Venlafaxine, desvenlafaxine, duloxetine, atomoxetine
Tramadol and tapentadol weak SNRIs
DOSES
Venlafaxine >2g or 12.5mg/kg in kids associated with seizures and serotonergic toxidrome
>5g 50% risk of seizures
>8g cardiotoxicity (tachyarrhythmia, Takotsubo, severe hypotension)
Desvenlafaxine <800mg or <8.75mg/kg in kids considered safe
EFFECTS
Within 4htrs but delayed up to 16hrs with SR preparations
1) Noradrenergic most prominent
- HTN, Tachycardia, diaphoresis, mydriasis
2) Serotonergic effects, especially if coingested with another serotonergic drug (MAOI)
- neuromuscular excitation, altered conscious state, hyperthermia
3) Seizures (50% if >5g venlafaxine)
4) Cardiotoxicity (>8g venlafaxine) - tachycardia ST or VT, takotsubo/acute and transient LV dysfunction, severe hypotension, QRS prolongation, QT prolongation with atomoxetine
MANAGEMENT
Charcoal (>2g)
Consider WBI for massive doses (>5g)
QT and QRS management as needed
Sedation and cooling (Serotonin syndrome, cold IVF and diazepam)
Inotropes as needed ?cardiogenic shock
Seizure control
Monitor for 6hrs IR, 16hrs ER, 24hrs >5g
TCAs - examples, doses, signs and management
EXAMPLES
Amitriptyline, clomipramine, dotheipine, doxepin, imipramine, nortryptiline
DOSES
<5mg/kg - non toxic
5-20mg/kg - sedation and anticholinergic
>20mg/kg - severe toxicity (coma, seizures, major cardiovascular toxicity
EFFECTS
- Rapid onset 1-2 hours, most serious effects within 6hrs
- Worse effects with acidosis (altered consciousness, respiratory depression and seizures exacerbate life risk)
CNS (noradrenalin and serotonin reuptake inhibition) - decreased LOC, resp depression, coma and seizures
CVS - hypotension/vasodilation and tachycardia (alpha adrenoreceptor blockade).
QRS prolongation +/- VT/VF myocardial depressions (fast sodium channel blockade)
QRS >100-120 predictive seizures, >160 predictive VT
Anticholinergic toxidrome
- Mydriasis/blurred vision, dry mouth, hyperthermia, urinary retention, reduced bowel sounds/ileus, delirium
MANAGEMENT
Charcoal for >5mg/kg if alert and cooperative within 2hrs or intubated
IVF for hypotension 20-30ml/kg
Norad 0.05-1microg/kg/minute (commence at 20microg/min for severe hypotension)
> 10mg/kg should be considered for intubation early especially developing signs of cardiotoxicity
Sodium bicarb 1-2mmol/kg bolus prior induction every 3-5 minutes (max 6mmol/kg) with continuous BVM ventilation to avoid apnoec respiratory acidosis and ongoing hyperventilation post, aim pH 7.45-7.55 and pCO2 30-35
Lidocaine (1mg/kg +/- 0.5mg/kg) IV is a third-line agent for arrhythmia (after bicarbonate and hyperventilation) once pH is > 7.5
Discharge
- 6hrs of observation
- Normal ECG
- Normal GCS (anticholinergic delirium that can persist beyond 24 to 48 hours)
- Low risk of further self-harm if deliberate ingestion
MAOIs - examples, toxic doses, effects and management
Irreversible nonselective MAOI (phenelzine and tranylcypromine) have narrow therapeutic window.
- days of unopposed serotonin, noradrenalin, dopamine, adrenalin, phenylethylamine (serotonin and sympathomimetic syndrome)
Reversible selective MAOI (moclobemide) and selective MAO - B (selegiline) have less serve effects and resolve faster.
Lamotrigine and isoniazid have weak MAOI effects
DOSES
>1mg/kg or coingested with serotonergic/adrenergic drug needs 24hrs admission. If less, then 12hrs monitoring
>2mg/kg serious toxicity
>4mg/kg lethal
Onset 6-12 hrs. Can be delayed up to 24 hours
Last 1-4 days
EFFECTS
Serotonin and sympathomimetic symptoms especially if coningestants for serotonergic reaction
Early - headache, agitation, tremor, sinus tachy, mydriasis, hyperreflexia and hyperventilation
Later - hypertension, muscle rigidity, hyperthermia, rhabdomyolysis, clonus, confusion
Severe - coma, seizures, hypotension, worsening hyperthermia, DIC, arrythmia and arrest
Death - multiorgan failure
MANAGEMENT
Supportive with IVF and benzos
Charcoal if within 2hrs
Benzos first line for agitation and HTN
Titratable antihypertensive (GTN, SNIP second line as large fluctuation from autonomic instability)
Hypotension and severe hyperthermia (>39.5) poor prognosis and need prompt management.
- eg norad and intubation
?SS need for cyroheptadine 12mg stat or 8mg TDS
What is tyramine and how does it react with Monoamine oxidase inhibitors
Dietary amine found in cheese, wine, preserved meats and yeast
Indirect sympathomimetic that normally is metabolized by intestinal and hepatic monoamine oxidase enzymes
MAOI cause excessive tyramine and leads to sympathomimetic toxidrome
Occurs within 90 minutes often with severe headache and hypertension
If having tyramine reaction, needs observation for at least 4hrs after symptom resolution and then 2-week period of tyramine free diet
Which snake bites are associated with Venom induced consumptive coagulopathy and describe its pathophysiology
Brown (pseudonaja), Taipan (Oxyuranus), Tiger (Notechis), Hoplocephalus species, and Rough scaled snakes (Tropidechis) always cause VICC in significant envenoming.
Not present in Death Adders, Sea Snakes or Black snakes but black snakes have anticoagulant in its venom and can cause mild to mod elevation in APPT and INR. Fibrinogen and D Dimer typically normal
In VICC, Prothrombin activators in venom lead to consumption of major coagulation factors including fibrinogen, factor V and factor VIII.
How is VICC diagnosed and managed
Complete VICC
- INR>3
- D Dimer 100 to 1000 times ULN
- Fibrinogen undetectably small
Partial VICC
- INR<3
- D DImer 10 times ULN
- Fibrinogen low but detectable
Presents with major bleeding
Thrombotic microangiopathy
Improves 12-36hrs after bite but faster when clotting factors are given
No reversal with snake antivenom. needs new clotting factors to be synthesized unlike anticoagulant coagulopathy with black snakes which is not clinically significant and reversed with antivenom
Which snake bites cause Neurotoxicity
Taipan (Oxyuranus) and Death Adders (Acanthophis) commonly cause neurotoxicity with death adders having slower onset over hours.
Tiger and Sea Snake can also cause it uncommonly with Tiger being slower onset over hours
Brown can rarely cause it
Not present in Black snakes
Which antidiabetic drug overdoses cause hypoglycemia
Insulin and sulfonylurea only
Metformin causes metabolic acidosis and lactatemia but no hypoglycemia
All others only cause GI effect
DPP4 inhibitors (gliptins)
GLP-1 agonists (glutides)
SGLTs inhibitors (flozins)
alph glucosidase inhibitors (acarbose)
Thiazolidinediones (glatizones)
Insulin overdose - risk assessment, clinical effects, management
RISK ASSESSMENT
Formulation (ulra, short, long etc)
Site and number of injections (single large injection can have depot effect)
Whether pt has diabetes (non diabetic will not have BSL rise post toxic effect have worn off due to endogenous insulin release and will need weaning of glucose therapy while T2DM have insulin resistance and lower risk of hypoglycemia)
Duration of symptoms dose and formulation dependent
EFFECTS
Symptoms of hypoglycemia may be blunted in long standing diabetics
- Within 1-2hrs, delayed in long acting
- CNS (dizziness, confusion, headaches, decreased GCS, seizures)
- Autonomic (tremor, tachycardia, sweating, nausea)
MANAGEMENT
Aim BSL 4-8 (q2hrly if asympomatic, q30min-1hr otherwise. q4hrly when >4hr for 4hrs)
Encourage oral intake of oral glucose and complex carbs if able
Bolus glucose 50% 50ml or 10% 5ml/kg
THEN
Glucose 50% 20ml/hr or 100ml/hr 10% (paeds 1-2ml/kg/hr 10%)
Glucose 10% vs 50%
- Glucose requirements
- Limitations in volume (50% preferred if >250ml/hr of 10% required)
- Venous access (CVC for 50% as phlebotoxic effects of concentrated glucose)
HypoK
Oral 14-16mmol (0.25mmol/kg) 2-4hrly
IV 10-20mmol (0.4mmol/kg) 2-4hrly
Aim K>3.5
Monitor
6hr short acting
18hr long acting (and dc in daylight)
8hrs post glucose therapy cessation
Metformin - toxic doses and risk, effects and management
Biguanide agent
- decreasing carbohydrate absorption from the gut
- increasing glucose uptake in peripheral tissues in the presence of insulin
- reducing hepatic gluconeogenesis
DOSES AND RISK
If healthy adult >20g can have severe toxicity
Lower doses needed in elderly, diabetics, kidney impairment or associated with antihypertensives (CCB/BB)
Even therapeutic doses can cause toxicity if acutely unwell
Chronic accumulation in renal impairment
<100mg/kg in children is likely safe
EFFECTS
NO HYPOGLYCEMIA
Effects mainly from profound acidosis
- Hyperlactatemia (predicts worse prognosis), metabolic acidosis, hyperK
- N/V abdo pain
- hypotension and tachycardia due to acidosis and dehydration +/- cardiogenic shock
- sedation, coma and seizure from acidosis
- Multiorgan failure (liver and renal failure)
MANAGEMENT
Early intubation in decreased LOC
Activated charcoal (2hr IR, 4hr MR or anytime post intubation)
Consider WBI if >50g of MR however high risk of ileus
IVF +/- norad
Sodium bicarb as bridging therapy to dialysis, aim serum pH>7.3
Dialysis (intermittent with lactate free dialysate preferred) when:
- pH<7 or lactate >20
- Refractory hypotension
- Rapid deterioration and AKI
DC criteria
Asymptomatic
Normal pH and lactate
Observation 6hr IR and 12hrs MR
Sulfonylurea - examples, doses, effects, management
EXAMPLES
Glibenclamide, gliclazide, glimepiride and glipizide
DOSES AND RISKS
Narrow therapeutic index
Single tablet 2mg can cause hypoglycemia in children
Risk of hypoglycemia even at therapeutic dose in elderly, AKI and pts taking CYP2C9 inhibitors (amiodarone, fluconazole, fluoxetine etc)
EFFECTS
Increase pancreatic insulin secretion causing prolonged and delayed hypoglycemia (6-12hrs however can be 18hrs in children)
Hypoglycemia symptoms can be blunted in long standing diabetics
- CNS: dizziness, altered LOC, headache, seizures, coma
- Autonomic: tremor, tachycardia, diaphoresis, nausea, anxiety
MANAGEMENT
Charcoal (2hrs of IR or 4hrs of MR)
Manage hypoglycemia first, aim BSL 4-8
- oral glucose/complex carbs if awake
- 50% 50ml or 10% 5ml/kg
- Glucose infusion (1-2ml/kg/hr 10% glucose may be needed)
Octreotide (long active somatostatin analogue. Blocks pancreatic insulin release). Commence for anyone with hypoglycemia following bolus glucose
- 50 microg (2microg/kg) subcut q8hrly for at least 24hrs
OR
- 50microg (2microg/kg) IV followed by 25microg/hr (1microg/kg/hr) IV for 24hrs
Can stop octreotide after 24hrs if
- daylight hours
- off glucose infusion >4hrs
- BSLs normal with no symptoms of hypoglycemia >4hrs
Needs hrly BSL for 12hrs post cessation of octreotide infusion
Superwarfarin or long-acting anticoagulant rodenticide poisoning (brodifacoum, bromadiolone, difethialone, diphacinone)
Rarely associated with accidental exposures to children due to deterrent taste
Can cause delayed onset anticoagulation which lasts months
Anticoagulant effects from >0.1mg/kg brodifacoum:
- 2g/kg of 0.005% bait (5mg/100g)
- 3x50g pellet packs (2.5mg brodifacoum each)
Unintentional ingestions of <1mg and children with single ingestion do not require investigations and can be discharged
Charcoal
Monitor INR 6hrly, peak effect after 48hrs. Normal INR without treatment excludes toxic ingestion
Superwarfarin levels confirms diagnosis
Phytomenadione (Vit K1) 20 - 100mg BD PO or IV for anyone with INR>2. Needs to continue for weeks to months until superwarfarin levels drop
Prothrombinex 50units/kg and FFP 15ml/kg if actively bleeding
Warfarin
Toxic dose >0.5mg/kg
Increased risk if on concurrent CYP2C9inhibitor (amiodarone, fluconazole, fluoxetine etc)
Charcoal
Consider MDAC or colestyramine for large overdoses
Phytomenadione (Vit K1) 0.25mg/kg (20mg) PO or IV if INR>2 every 6-12hrs if not taking warfarin therapeutically
If taking therapeutically then follow management of supratheraputic INR
NO BLEEDING
INR 4.5 - 10 = phytomenadione 1-2mg orally or 1mg IV
INR >10= phytomenadione 3-5mg PO/IV. Add on Prothrombinex 15-30units/kg IV if high bleeding risk
(Major bleed in last 4weeks, surgery in last 2 weeks, plt<50, liver disease, concurrent antiplatelet therapy)
If bleeding add on
Prothrombinex 50units/kg
FFP 15ml/kg
Methylxanthines (theophylline and caffeine) effects
Narrow therapeutic index and block adenosine receptors that cause smooth muscle relaxation and increased cardia output
Raise catecholamine concentration
Theophylline >10mg/kg can cause toxicity. >50mg/kg lethal
(200mg MR release tablet toxic in 10kg child)
Caffeine >15mg/kg mild to mod. >100mg/kg life threatening. Dose depends on tolerance with regular use. Caffeine tablets 100mg. Coffee is roughly 1-2 tablets
RISK FOR TOXICITY
Hypokalemia
Hyperglycemia
Age>60 (predictor of severity and poor outcome in chronic theophylline poisoning)
Effects of acute toxicity due to catecholamine excess (sympathomimetic)
Chronic theophylline has poorer outcomes and present with vomiting, tachycardia, seizures and dysrhythmia
GI
- N/V
CVS
- tachycardia, ectopics
- refractory hypotensoin due to beta2 adrenergic stimulation
- MI
- SVT, VT/VF rare and only with serum concentration >100mg/L (550microg/L)
CNS
-agitation, tremor, seizure
Metabolic (severity worse in acute)
- hyperglycemia
- hypercalcemia
- hypokalemia (can be refractory)
- hypophosphatemia
- hypomagnesemia
- metabolic acidosis
Methylxanthines (theophylline and caffeine) management
Measure serum concentration 2-4hrly
Chronic theophylline poisoning can have severe effects with lower concentrations
Charcoal if <2hr IR or <4hr MR) + antiemetic
MDAC if theophylline >30mg/kg and caffeine >50mg/kg
Consider WBI if >30mg/kg theophylline MR
Seizure control imperative
- Cerebral vasoconstriction and hypoxia from blocked adenosine receptors in CNS
- Cerebral hypoxia and brain injury worsened with increased metabolic demand in seizures
- Significant morbidity and mortality
- Can be refractory
- Treat with Benzos
Midazolam 0.15mg/kg (10mg) IV/IM q5minute. 0.3mg/kg buccal/intranasal
Phenobarbitone 20mg/kg (2g, 1g in kids) second line
(Phenytoin ineffective and increased sodium channel blockade)
Consider ETT
IVF +/- norad
Correct electrolytes
Hemodialysis increases clearance 1.5-2 fold but same as MDAC
Hemoperfusion 2-5 fold but more adverse effects (coagulopathy and eletrolyte disturbances)
Indicated if
- Serum theophylline >100mg/L (550microg/L) in acute
- Serum theophylline >60mg/L (330microg/L) in chronic
- Severe toxicity (dysrhythmia, hypotension, seizures)
Antihistamine - examples, doses, presentation, management
EXAMPLES
Sedating (H1 antagonists +central, alpha adrenergic, anticholinergic, serotinergic, Na channel blockade) - promethazine, diphenhydramine, dimenhydrinate, doxylamine, cyclizine, cyprohepatidine, dexchlorpheniramine
Nonsedating (peripheral H1 antagonists) - desloratadine, loratadine, fexofenadine, cetrizine
DOSES
>3x max daily doses of sedating antihistamines
Dimenhydrinate and diphenhydramine >300mg or 7.5mg/kg in kids (dimenhydrinate slower onset as needs to dissociate to diphenhydramine, 50mg=29mg)
Diphenhydramine >1g severe effects (cardiotoxicity)
Promethazine anticholinergic delirium dose dependent
31% 250mg
42% 500mg
55% 1g
Tolerances can develop if taking regularly
Non-sedating antihistamines normally benign
EFFECTS
Look out for coingestions (paracetamol, caffiene, etc)
CNS -
Dose dependent sedation
Sedation early, masking anticholinergic delirium
Sedation lasts 12-24hrs then delirium major effect
Anticholinergic delirium (particularly promethazine)
Seizures (pheniramine, dimenhydrinate, diphenhydramine) indicate severe toxicity, increased risk of cardiac events and worsen acidosis
Dystonia
CVS -
Tachycardia and postural hypotension most common
QRS/QT prolongation and torsades in diphenhydramine, dimenhydrinate and loratadine but rare
Rate dependent BBB with doxylamine
Other -
Urinary retention
Rhabdo with doxylamine and diphendramine
MANAGEMENT
Charcoal in 2hrs or after ETT (particularly promethazine to prevent delirium)
ETT as needed
IVF +/- norad
QRS management (serum alkalization)
QT management (electrolyte replacement and keeping rate >90)
Benzos for persistent or recurrent seizures
Anticholinergic Delirium - physostigmine 0.5mg (0.01mg/kg) IV q15min. Max 2mg in 60min. May need more after 1-2 hrs as short acting
Monitor for bradycardia and bronchospasm (cholinergic overdose)
Can then have oral diazepam 5-20mg q30min (0.2mg/kg) MAX 120mg in 24hrs for ongoing sedation
Droperidol 0.1mg/kg 2nd ling, then midaz 0.1mg/kg
Baclofen - doses, effects, management
GABA analogue used in muscle spascitiy, alcohol dependence and GHB withdrawal
DOSES
>200mg/kg in naive pts causes severe toxicity
EFFECTS
CNS effects
- Altered LOC/coma/resp depression
- Myoclonus and seizures (early due to reduced presynaptic GABA release and late due to baclofen withdrawal
- Delirium (lasts 1-3 days following resolution of coma)
- Hypotonia, hyporeflexia, mydriasis, hypothermia
- loss of brainstem reflexes in massive overdoses lasts 1-2 days
CVS effects
- Bradycardia, tachycardia, hypertension
- Hypotension less common
Skin
- Morbilliform rash rare
MANAGEMENT
ETT
IVF +/- inotropes
Charcoal within 2hrs or after ETT
Seizures generally self limiting. Benzos first line
Delirium: benzos or droperidol. Can try low dose baclofen for suspected withdrawal. Needs EED to rule out nonconvulsive status epilepticus
Buproprion - doses, effects, management
DOSES
Risk of seizures is dose dependent
~50% risk in >4.5g
>9g severe cardiovascular toxicity (hypotension, QRS prolongation and arrhythmia)
>10mg/kg in children needs assessment
EFFECTS
Can be delayed up to 24hrs (admit >4.5g or 10mg/kg for 24hrs with cardiac monitoring. Less needs at least 12hrs monitoring)
CNS - severe agitation and aggression (characteristic), hallucination, tremor, seizures
CVS - hypertension and tachycardia (most common), hypotension/QRS widening/arrhythmia with >9g
GI - N/V
MANAGEMENT
ETT as needed
Charcoal within 4hrs or if intubated
IVF +/- inotropes for hypotension
Serum alkanisartion for QRS prolongation (1-2mmol/kg sodiuum bicarb with hyperventilation aiming pH 7.45-7.55 and etCO2 30-35)
Benzos for agitation and seizures if not self limiting or recurrent
Spider bites - big black spider/funnel web presentation, first aid/ management
PRESENTATION
Severe envenoming more common in Eastern Australia
Commonly present with localized pain and bleeding from bite mark and hx of bite
Rapidly developing symptoms 10min-4hrs
Pathognomonic presentation is abrupt onset sweating, piloerection, coma and fasciculations
ANS - cholinergic and adrenergic excess (diaphoreiss, hypersalivation, lacrimation, piloerection, hypertension, brady/tachycardia, miosis/mydriasis
NMS - parasethesia (local, distal, perioral), fasciculations (tongue common), spasms
CVS - Adrenergic excess (hypertension and tachycardia followed by bradycardia and hypotension with myocardial injury)
CNS - agitation, anxiety, altered LOC/coma
Resp - APO
Nonspecific - abdo pain, N/V, headache
FIRST AID AND MANGEMENT
Pressure bandage with immobilisation of limb and pt within 4hrs
Broad (15cm) elastic bandage starting at bite site then distally to proximally to cover entire limb
Only removed once antivenom administered
Antivenom in all suspected funnel web bites with signs of severe envenoming
2 vials
4 vials in arrest
OTHER MEASURES
Tetanus booster
Analgesia - panadol/nurofen/oxycodone
NIV/ETT
Alpha blockers for hypertension/tachycardia
IVF, inotropes, atropine for hypotension
CPAP/ETT for APO
redback
Antipsychotics - examples, doses, effects, management
