Updates in Clinical ToxicologyEmerging Trends in Emergency Medicine 2012-13

Introduction• Welcome

• CGD – Toxicology 20-40 mins

• My Background• Emergency Medicine• 6 months as Toxicology Registrar in 2010

• Disclosures• None to declare

Learning Objectives

•Aims and Learning Objectives Topics

Emerging Therapies in Toxicology Emerging Illicit Drugs Updates in Toxinology

Approach Case based approach Interactive session Discussion of emerging topics in Toxicology

* There is emerging evidence in the areas discussed but an absence of Randomised Control Trials (RCTs)

Risk Assessment Based Approach to Poisonings

Risk Assessment

• (1)  Drug* taken, form, route and dose ▫Defined Daily Dose▫Threshold for Toxicity                

• (2)  Time  since  the Ingestion        • (3)  Progress  and  Clinical  Features• (4)  Patient  Specific  Factors  

▫Age▫Weight▫Past Medical History

•Resources – CIAP, Toxinz, Handbooks, Poisons

Toxicology in Retrieval

•Common Secondary Transfer•3/50 for me•Data from recent months….

- High Dose Insulin- Intralipid Emulsion (ILE)- Methylene Blue

Case 1

•Cassie •17 years old, no medical history•From Parkes (rural NSW)•Living with her parents and grandma•After a fight with her mother at dinner she

stormed out stating ‘I hate you all’ – 1 hour later she tells her mother she has taken ‘Gran’s pills’

•Mum tearfully calls an Ambulance and she is brought to the local rural Emergency Department with single weekend coverage

Parkes

Case 1 - Cassie

•On arrival in Emergency she states regret at taking the tablets and wants to go home

•Risk assessment▫2 hours ago she took 2 full blisters (24) of

Verapamil▫The tablets were Slow release (240mg)▫She also took 7 Panadol (5oomg)

• Is this a concerning overdose?•What do we expect to happen?

Progress

•Cassie initially has normal observations (BP 121/70)

•Activated Charcoal (50g) is given •Routine bloods are taken from the patient•On advice from poisons information IV fluids are

started and she is monitored. •A discussion in regards to W.B.I. is undertaken

and it is decided against

Progress 2•The patient is persuaded to stay in hospital•After 4 hours of observation she feels light headed

and nauseous. She has had 20ml/kg of fluid •Her blood pressure quickly drops to 70/40

(confirmed by manual readings)•Her heart rate is now 45/min and despite further

fluids, IV calcium, atropine and glucagon she develops evidence of cardiac failure…

•Now Retrieval Rescue 23 is tasked to get patient

High Dose Insulin Therapy•High-dose insulin euglycemic therapy (HIET)•High-dose insulin therapy with IV glucose

▫Emerging as an effective treatment for severe beta-blocker & calcium channel-blocker poisoning

•Animal data and case reports demonstrate that high-dose insulin (1-10 U/kg/hour) is a superior to standard treatment* in terms of safety and survival in both beta-blocker and calcium-channel blocker poisoning**.

▫S

Kearns et al – Free at http://emcrit.org/wp-content/uploads/ccb.pdf

Local Case Reports

Case 2

•John•79 year old •Presenting to hospital following a fall on

the front porch of his house•He was unable to get up afterwards and

has an obvious deformity of his right leg

Analgesia

•John receives Morphine and Paracetamol IV but still has persistent pain

•The local locum places a femoral block using Marcaine® (Bupivicaine) 20mls with a landmark technique with aspiration every 5mls infiltrated

•A few moments later the patient becomes unresponsive and CPR is started

•The patient’s rhythm is Asystole

Intralipid Emulsion (ILE)•Intralipid is emerging as a first line

therapy for treating the cardiotoxic effects of Local Anaesthetic toxicity and other refractory emergencies

•First described in the 1990s •Data emerging for LA and TCA from

▫Human Case Series▫Animal Data

Intralipid

•Oil and Water Micro Emulsion•Derived from Soya Bean•pH 8.0

•How does it work?▫(1) Lipid Sink

Redistribution**▫(2) Effects on channels

Sodium Channels Calcium Channels

▫(3) Metabolotropic

How to give…

Intralipid Emulsion (ILE)

Intralipid Emulsion (ILE)

Methylene Blue – EAPCCT Abstract

Summary

•Risk assessment is the mainstay of good management of toxicological emergencies

•New therapies are emerging and awareness of these is useful

•These new therapies should be used in the context of advice from a toxicologist and reserved in the main for refractory cases

- Quetiapine - The Synthetic Cannabinoids

Case 3

•Richard is a 41 year old man•History of Schizophrenia managed with

“Seroquel®”•Treated in the community

Case 3

•Richard presents to his GP in Warren (NSW) stating he has taken extra tablets ‘to help him sleep’ but is now worried he has taken too many!

•An ambulance is called after he reveals he has taken 40 x 200mg tablets (a total of 8g) today

•On route he is tachycardic (120) and drowsy but opens his eyes to speech and obeys commands

•Where is Warren?•What is your risk assessment?

Warren

Risk Assessment•(1)  Drug* taken, form, route and dose 

▫Defined Daily Dose▫Threshold for Toxicity                

•(2)  Time  since  the Ingestion        • (3)  Progress  and  Clinical  Features•(4)  Patient  Specific  Factors  

▫Age▫Weight▫Past Medical History

On arrival at Warren Hospital

Quetiapine (Seroquel®)

Emerging as the number 1 toxicological cause of ICU admission in Australia

Adverse Effects

•Tachycardia (common)•Reduced Level of Consciousness (variable) •Delirium (masked)•Coma (dose dependent)

▫Common in overdoses > 3 grams•Respiratory Depression•Hypotension•ECG changes include prolonged QT

▫Arrhythmias are described but are unusual

The ECG of Quetiapine overdose

ECG QT interval

Case 4

•Raymond is a 39 year old•He doesn’t normally take drugs•However he accepted the offer of trying a

‘new’ drug at a party•After a short time Raymond became

agitated and appeared to be disorientated•An ambulance was called and he arrives

at your ED being held down by police and paramedics

K2 Spice – Synthetic Drug

•Potent Cannabinoid▫Multiple Formulations

•Reports of Seizures and Psychosis at increased rates compared to organic Marijuana

•Risk of seizures•Risk assessment should predict a higher

likelihood of adverse outcomes and a longer duration of observation in the ED

•Treatment is primarily supportive

K2 Spice

‘New’ Drugs

‘New’ Drugs

Summary

- Snake antivenom use - what has changed in recent years? - Trends in Red-back spider antivenom use

Case 5

Jason - 13 years old•Playing cricket•While retrieving the ball stood on a ‘twig’ •He ran back to the field complaining of pain•A few minutes later he collapsed and is taken

to hospital by ambulance•On the way to hospital he develops epistaxis

and bleeding from the gums

•What is the most likely diagnosis?

Australian Snakes *Brown Snake (pictured) – A common snake,

can be aggressive Causes the most fatalities due to Coagulopathy

*Death Adder *Tiger Snake *(Red Bellied) Black Snake Mulga & Collett’s Snake *Taipan - reclusive hunter and therefore has

minimal contact with humans. Bites are therefore uncommon. This snake having the most potent venom (LD50) of all snakes

*Sea Snake

Envenomation Summary COAGULOPATHY (VICC, AC) and MAHA LOCAL EFFECTS MYOTOXICITY RENAL FAILURE NEUROTOXICITY

Snake Bite - Updates

•Recent years have seen changes in recommendations:▫Antivenom

Cross over Quantity Indications for antivenom Effectiveness of antivenom Use of the Snake VDK

▫Snake Coagulopathy FFP and antivenom

▫When to Discharge?

Antivenom Dosing

Antivenom – early 2000s

Antivenom Effectiveness

Discharge

Summary

•PIB•PIB removal in a monitored setting•VDK•Antivenom use•FFP

Case 5

•A young mother presents in distress after being bitten by a spider in a shoe

•She has severe leg pain, nausea and has noticed sweating on both legs as well as ‘goose-bumps’ at the site of the bite

•Her confident husband identifies the spider as a Redback and has brought the ‘specimen’ into hospital (alive) in a glass jar

Spider Bite – Redback

•Common presentation•Clinical Syndrome

▫Pain +▫Sweating▫Piloerection

Redback Spider Bite

Clinical Effects

Local andRegional

NB – ThereMay be no ‘History’ ofSpider Bite

SystemicEffects

Local PainRadiating Pain

PiloerectionLocal Sweating

NauseaVomiting

HeadachesLethargy

Remote PainAgitation

HypertensionNeurological

Spider Bite – Redback

Redback Antivenom

•Historically there has been a low threshold for use

•Now Controversial

Redback Antivenom

IM Antivenom

Summary and Future Directions•Provisional results of the FFP and RAVE II

study are imminently pending

•A single vial of antivenom is sufficient for the treatment of snake envenomation

•Analgesia is the mainstay of treatment for redback spider bite.

Other Emerging Topics (Brief Discussion if Time)

•New Anticoagulants•Decontamination and WBI•Naloxone•Sulphonyureas

Questions and Discussion