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Toxicology

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Elizabeth Hall

on 1 April 2015

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Transcript of Toxicology


By Douglas Stanglin, USA TODAY
CAPTIONBy Ashtabula Division of Fire/AP

One man died and six people were hurt, including two suspects, when a homemade methamphetamine lab exploded inside a nursing home in Ashtabula, Ohio, authorities say.

Update at 3:41 p.m. ET: WKYC-TV
reports that dead man has been i
dentified as Shaun Warrens, 31, of Ashtabula.
Police said he was neither a resident no
r employee of the Park Haven Nursing Home.

Two other suspects who
were burned are expected t
o be charged.

The Associated Press reports that police believe two visitors and one Park Haven resident knew about the meth lab, Police Chief Robert Stell told the Star Beacon of Ashtabula.

Organophosphates

OP poisoning is a relatively common and major cause of death from poisoning in low-income countries. pesticide poisoning kills upwards of 300,000 patients a year. - It has been also used in chemical warfare.
SLUDGE BBB/ dumbbels
Quick Tox Update
KROKODIL
Desomorphine
COMMON & BRAND NAMES
Krokodil, Crocodile, Permonid
EFFECTS CLASSIFICATION
Opioid; Sedative; Stimulant
CHEMICAL NAME
4,5-alpha-epoxy-17-methylmorphinan-3-ol
DESCRIPTION
Desomorphine is an opioid that has gained attention because of low-quality black market synthesis in Russia, where it began being sold as "krokodil" in 2010. Synthesized from codeine (using iodine and red phosphorous, in a process similar to that used for street methamphetamine) the final street product is often contaminated with corrrosive, toxic chemicals. Heavy opioid users who inject street desomorphine can experience serious medical problems. News reports sometimes refer to desomorphine as "flesh eating" because of these problems.
Toxicology
“The surest poison is time.” —Ralph Waldo Emerson (1803-1882)
or Adam Berman or soon-to-be tox fellow
Meruba Anwar
27 year old male called in as a notification for unresponsiveness. Mother found empty pill bottles by his side.
ELIZABETH HALL
Essential Cases in Toxicology
You are working in a rural clinic in Burundi and family members carry in a 27 y/o male with no PMH. You examine the patient who is somnolent.

A drowsy 27 y/o M presents to the ED after taking a handfull of his grandmother's BP pills. On exam, you note a weak, thready radial pulse.
Consider Glucagon....(in refractory hypotension).. 2-5 mg IVP

Insulin (increases inotropy/chronotropy) 0.1 U /kg up to 1U/kg and Dextrose
-20-30 minutes before taking effect
-check electrolytes?

Pressors? Norepinephrine
Atropine?
Lipid Emuslion Therapy?
What antedote is most effective?

A- pralidoxime 1mg IV
B- atropine 2mg IV
C Diazepam 5 mg IV
D- Albuterol 0.5 mg neb
Vitals:
BP 74/34
HR 134
RR 28
O2 98% on RA
Fingerstick: 72
The Case of the Sleeping Beauty
Anticholinergic effects:

— Delirium/confusion/agitation, sedation, seizures, coma (often precedes cardiovascular signs)

— Restlessness, delirium, mydriasis (big pupil), dry, warm skin, tachycardia, ileus, urinary retention
Metabolic acidosis

Cardiovascular effects
— Sinus tachycardia, hypertension,
hypotension (due to alpha1-adrenoreceptor
blockade), broad complex tachycardia
(can develop bradycardia pre-arrest)




The ECG is one of the
most vital investigations
in this scenario

— Diagnostic features include prolongation of QRS, PR intervals, dominant R wave in aVR, and QT prolongation

— QRS widening reflects the degree of fast sodium channel blockade

Boehnert and Lovejoy (N Engl J Med): examined QRS duration and found that:
QRS <100ms no significant toxicity
QRS > 100ms is predictive of seizures,
QRS > 160ms is predictive of ventricular tachycardia

Niemann and Bessen study: RAD, QRS prolong., QTc prolong., and sinus tachy in setting of OD had a PPV of 66% and NPV of 100%

Liebelt (1995): large R wave (>3mm) in aVR had a PPV of 81%
Sodium bicarbonate

If QRS >100ms:
sodium bicarbonate 100 mmol bolus every few minutes while monitoring the effect on ECG until HD stable (1-2mEq/kg)
the optimal total dose is “enough” (to reverse cardiotoxicity)


Once stable after resuscitation:

consider further sodium bicarbonate to maintain pH 7.5- 7.55/
QRS width (aim for <100 ms)
if there is ongoing arrhythmia, QRS >140 ms, or hypotension then options include:

sodium bicarbonate infusion(3 amps NaHCO3 in 1L D5W at 2x maintenance)

Consider hyperventiliation and/or hypertonic saline for pH 7.5-7.55

BREAK DOWN THE CASE
It is often prudent to consider a bolus of sodium bicarbonate prior to intubation to counter the effects of increased acidosis while ventilation is ceased.
Blackman K, Brown SG, Wilkes GJ. Emerg Med (Fremantle). Plasma alkalinization for tricyclic antidepressant toxicity: a systematic review. 2001 Jun;13(2):204-10. PMID: 11482860
Harvey M, Cave G. Intralipid outperforms sodium bicarbonate in a rabbit model of clomipramine toxicity. Ann Emerg Med. 2007 Feb;49(2):178-85, 185.e1-4. PMID: 17098328
Liebelt EL, et al. Serial electrocardiogram changes in acute tricyclic antidepressant overdoses. Crit Care Med. 1997 Oct;25(10):1721-6. PMID: 9377889
Liebelt EL, et al. ECG lead aVR versus QRS interval in predicting seizures and arrhythmias in acute tricyclic antidepressant toxicity. Ann Emerg Med. 1995 Aug;26(2):195-201. PMID: 7618783
McCabe JL, et al. Experimental tricyclic antidepressant toxicity: a randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation. Ann Emerg Med. 1998 Sep;32(3 Pt 1):329-33. PMID: 9737495
Murray L, Daly FFS, Little M, and Cadogan M. Chapter 3.65 TCAs: Tricyclic Antidepressants; in Toxicology Handbook, Elsevier Australia, 2007. [Google Books Preview]
Murray L, Daly FFS, Little M, and Cadogan M. Chapter 4.24 Sodium bicarbonate; in Toxicology Handbook, Elsevier Australia, 2007. [Google Books Preview]
Eddleston et al Early management after self-poisoning with an organophosphorus or carbamate pesticide – a treatment protocol Critical Care 2004, 8:R391-R397 (DOI 10.1186/cc2953) Open Access
Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning.Lancet. 2007 Aug 14
Roberts DM, Aaron CK.Management of acute organophosphorus pesticide poisoning.BMJ. 2007 Mar 24;334(7594):629-34.
Eddleston M. Buckley NA. Eyer P. Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607.
Eddleston M, Singh S, Buckley N. Acute organophosphorus poisoning. ClinEvid 2003;9:1542–1553.
Eddleston M, Szinicz L, Eyer P, Buckley N. Oximes in acute organophosphorus pesticide poisoning: a systematic review of clinical trials. QJM. 2002;95:275-283.
References
Leading cause of poisoning deaths (50d/1mill pres)

TCAs are weak bases and fx as NE, dopamine, serotonin reuptake inhibitors and GABA-A receptor blockers.
The CASE of the Sloppy Winemaker and the boy who thought he could
Vitals: HR 55, BP 107/62 , RR 12, O2 91%
On exam you note, pupils are equal/reactive, rales on auscultation, secretions at his mouth, and muscle faciculations.
The CASE of the SAD Resident:
BUN/Cr 23/12, Na is 140. K is 3.8, Cl is 104 and bicarb is 19.
The Brady Bunch
Risk factors

insecticides/fertilisers
surface and room sprays
baits for cockroaches
shampoos against head lice
pet preparations
crop protection and livestock dipping
fumigation
nerve agents (sarin)
DUMBBELS: diarrhoea, urination, miosis, bronchorhea, bradycardia, emesis, lacrimation, salivation
SLUDGE: salivation, lacrimation, urination, defaecation, emesis
Resuscitation

aspiration/bronchospasm/seizures
may necessitate
airway protection
and mechanical ventilation
hemodynamic monitoring and management
remove contaminated clothes
-> wash
Standard Therapy in the US
And the Bolus Approach

Atropine: 0.02mg/kg
boluses
-> recurrent boluses q5min, treats bradycardia, hypotension and excess secretion production

pralidoxime chloride 30mg/kg IV -> 8mg/kg/hr: muscle weakness

benzodiazepines: midazolam 0.2mg/kg, seizures or agitation

activated charcoal if presents with 1-2 hours
Clinical Syndrome

Respiratory Issues secondary to Acute Cholinergic:

-Central Muscarinic
-Peripheral Muscarinic
Intermediate Syndrome
• A cause of delayed Respiratory Failure
– Proximal muscle weakness and cranial nerve lesions
– Typically 1-4 days after cholinergic crisis has resolved
• Prolonged effects on Nicotinic receptors – Pre synaptic post synaptic failure
-fasciculations/muscle weakness/
paralysis
-confusion, lethargy, coma, central
hypoventilation, seizures

Dimethoate or fenthion had higher proportion of death and morbidity requiring ET.

Dimethoate-poisoned patients died sooner than those ingesting other pesticides and often from hypotensive shock.
Fenthion poisoning initially caused few symptoms but many patients subsequently required intubation.

Acetylcholinesterase inhibited by fenthion or dimethoate responded poorly to pralidoxime treatment compared with chlorpyrifos-inhibited acetylcholinesterase.
Not all OPs are created equal
Eddleston M et al Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet. 2005
Glasgow Coma Score & Mortality

Normal GCS 5%
GCS <14 30%
GCS <10 60%


OP Type & Mortality
N Chlorpyrifos 7%
N Fenthion 14%
N Dimethoate 21%
Load quickly until atropinsed
– Doubling protocol
– If you are needing more than 60 mgs consider other additional diagnosis and complications
Role of 2-PAM??
Vitals : HR of 44, BP 71/45, RR 22, pulse ox of 97%.
312
Dihydropyridine and
non-dihydrophyridines
Cardiovascular:
SA node: bradycardia
AV node: 1/2/3rd degree block
QRS and Qtc prolongation
Hypotension (decreased CO or vasodilation)
Pulmonary edema

CNS: in severe OD, lethargy, coma, ischemia/seizures

Hyperglycemia
Acute lung injury
Clinical Manifestiations
Management
Activated Charcol (if not aspiration risk)
Calcium: (first line)
1g of calcium chloride (1-2 amps)
1g of calcium gluconate (3-6 amps)
then start infusion
Infusion doses:
20-40mg/kg/h CaCl2
or
60-120 mg/kg/hr Ca gluconate
What to try next?
Tricyclic Antidepressants
Anticholinergic (antimuscarinic effects)
Sodium Channel Blockage
Cardiotoxic effects primarily result from blockade of inactivated fast sodium channels in a use-dependent manner (blockade is higher at faster heart rates).
Alpha-1 adrenergic receptor blockade
Antihistamine effects
GABA antagonism

additional therapy
-Activated Charcoal 1gm/kg
Benzos for seizures
Vasopressors (NE)
Fat Emulsion Therapy (20% Intralipid of 1.5 mL/kg and infusion of .25 mL/kg/min for 30-60min
SARIN
-Nerve Gas developed in 1938-1944 in Germany as a war-fare agent.
-Death may follow in 1 to 10 minutes after direct inhalation of a lethal dose. Sarin is 26 times more deadly than cyanide.
-1995: Aum Shinrikyo sect released an impure form of sarin in the Tokyo Metro. Thirteen people died.

-21 August 2013: Sarin was used
in an attack in the Ghouta region
of the Rif Dimashq Governorate
of Syria during the Syrian civil
war. Varying sources gave a
death toll of 322 to 1,729.

Killer Bs: Bradycardia/Bronchorrhea/Bronchocontriction
Mar 06, 2012
One dead after meth lab explodes at Ohio nursing home
Ashtabula, Ohio
Starring Steven Bunch, MD
Narrated by
The process of AGING
Calcium
Indications for sodium bicarbonate in tricyclic antidepressant overdose:

Severe cardiotoxicity

cardiac arrest
ventricular dysrhythmias
hypotension resistant to fluid challenge


OR
Consider for prevention of severe cardiotoxicity resulting from:

seizure – leads to metabolic acidosis
prolonged intubation attempts – leads to respiratory acidosis
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