UPDATES IN TOXICOLOGY: Critical Appraisal and updates of Interventions in the ED

Cherie Grace G. Quingking,MD

Objectives

Briefly discuss a rational ED approach to poisoning patients

Assess level of evidence of toxicologic interventions to provide rational ED management

Updates on management of specific xenobiotics requiring critical care at ED

Alteration of function of a cellular receptor, ion channel, organelle, or chemical pathway to the extent that critical organ systems can no longer support life.

Poisoning has been likened to trauma on the cellular level, destroying the natural workings of a victim’s physiology

Vanden Hoek et al (2010) Circulation: http://circ.ahajournals.org

GENERAL ED Management

Emergency Department Intervention of acute poisoning: 90% of cases in a nutshell Gastrointestinal

decontamination techniques

Investigations Antidotes Increasing Elimination Disposition10% Immediate care: BLS and Acute cardiac life support

Level of evidence (CEBM) & Clinical Toxicology

The evidence for recommendations :

I: Definitely recommended.Definitive, excellent evidence provides support. II: Acceptable and useful. Good evidence provides support. III: May be acceptable,possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research.

Level of evidence & Clinical Toxicology

Clinical Pathway: Basic Toxicologic Interventions

Determine the need for lavage or charcoal Serious overdose

presenting to the ED within one hour?

Potentially serious overdose presenting to ED after one hour?

Determine whether toxin is adsorbed to charcoal

Routine administration in nontoxic ingestion is not indicated

Determine the need for whole bowel irrigation:• Large ingestion of iron, heavy

metals, lithium and other drugs poorly adsorbed by activated charcoal

• Drug packets (body packers)

• Gather lavage if life-threatening overdose within one hour of ED arrival (carries risk of aspiration , esophageal perforation) Class Interderminate

• Activated Charcoal 1 g/kg or 10:1 ratio of charcoal to toxin (Class II)

• MDAC: Antimalarials, Aminophylline, Barbiturates, Beta Blockers (Class II-III)• Polyethelene glycol (1-2L in adults, 25 cc/kg in children orally by NG Tube (Class III)

Determine suicide risk (Class I-II)Restrain as needed (Class II)Drug levelsSuicide attempt

• Cardiotoxin ingestion (known or potential

• Chest pain or shortness of breath

• Abnormal heart rate or hypotension

• Any unstable patient (Class II)

ECG?Yes, if

Xray ?

Chest x-ray (Class I-II)• Dyspnea , tachynea, coma, or

obtundation• Cyanosis• Symptomatic patients who

ingest: opiods, phenobarbital, phenothiazines and salicylates

KUB – suspected metals or drug packets (Class II)Enteric coated preparationsCocaine /opiate packetsArsenic other heavy metals

Yes, if

Toxicology ScreenQualitative/Quantitative: plasma drug concentrations of :

o Paracetamolo Salicylateso Irono Lithium o Ethylene glycol

o MEDICOLEGAL PURPOSES

Diagnostics/Labs• Abnormal vital signs• Altered mental status• Symptomatic patients and

unknown toxin• Ingestion of substance that

can produce metabolic acidosis

• Toxic alcohol?• Cyanosis or respiratory

distress• Suspected rhabdomyolysis• Female of childbearing age

CBGElectrolytesSerum osmolality, anion gapABGCPKPregnancy test, urinalysis

TOXICOLOGY SCREEN?

Need for antidote?

Dialysis?

Yes, if

Yes, if

Specific Agents

:Symptomatic patient with ingestion of (Class II)IsopropanolSalicylatesTheophyllineUremiaMethanolBarbiturates, beta blockersLithium Ethylene Glycol

Yes, if

Yes, if

Antidotes

AGENT ANTIDOTES AGENT ANTIDOTESparacetamol N-Acetylcysteine iron DeferoxamineAnticholinergics Physostigmine Isoniazid Pyridoxinebenzodiazepines Flumazenil metals BAL, EDTA, DMSABeta blockers Glucagon Nitrates/nitrites Methylene bluecarbamates Atropint opiates Naloxone,

nalmefernedigoxin Fab Fragments organophosphates Atropine,

pralidoximeEthylene glycol Ethanol, fomefizole snales Antivenin,crofab

Disposition

Initial approach to Critically poisoned patient

TOXICOLOGY UPDATES:

Approach to critically ill patients

Caveats: Patients may not be able to provide

acute history of exposure to a toxic substance

In cases of suicide attempts, multiple substance exposure

Comprehensive toxicology laboratory testing is never available on time

Worst case scenario: cardiac arrest associated with toxic ingestion

Basic life support and ACLS current standards should be followed, except for toxin-specific interventions recommended once with ROSC Hypotension Arrhythmia seizures

toxidromes

A clinical syndrome – a constellation of signs , symptoms, and laboratory findings – suggestive of the effects of a specific toxin.

Toxidrome Approach:

•Amphetamines* anticholinergic drugs*antihistamines*cocaine*theophylline/caffeine

Tachycardia/hypertention

•Beta blockers/calcium channel blockers; clonidine, digoxin, and related glycosides, organophosphates and carbamates

Bradycardia/hypotention

•Cocaine/ tricyclic antidepressants, local anethetics, antiarrythmics (quinidine, flecanide)

Cardiac conduction

delays (wide QRS)

THINK! Toxidrome Approach:

Toxidromes: cardiovascular and Central Nervous System

•Cyclic antidepressants;isoniazid; selective and nonselective norepinephrine reuptake inhibitors; withdrawal states

seizures

•Antidepressants, benzodiazepines, carbon monoxide, ethanol, methanol, opiods, oral hypoglycemics

CNS or respiratory depression

•Cyanide, ethylene glycol, metformin, methanol and salicylates

Metabolic acidosis

hypotension

Intravenous fluids NOREPINEPHRINE

Peripheral vasodilation

Epinephrine for myocardial depressants

OpioidsBeta blockersdigoxin

NaloxoneGlucagonDigoxin specific antibodies

Greene et al (2005) Postgrad Med J; 81:204-216

Arrythmias

Anti arrythmics : not first line agents Proarrythmics

Electrical Cardioversion May produce asystole in a

poisoned myocardium

Watch out for : conduction delays (widened

QRS) Torsade de pointes

Correction of:AcidosisHypokalemiaHypomagnesemiaHypoxia

Immediate antidotal therapy

Greene et al (2005) Postgrad Med J; 81:204-216

Seizures and agitations

Benzodiazepines as first line agents

Agitation: avoid phenothiazines or butyrophenones

Resistant seizures: General anesthetics: IV

barbiturates Supportive care

(intubation and mechanical ventilation)

Caveats:NO PHENYTOIN for: TCAs and cocaine

•has sodium channel blocking properties

Benzodiazepines

Benzodiazepines (BZD) exert their action by potentiating the activity of Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS

Flumazenil as an antidote Evidence: administration of flumazenil to

patients with undifferentiated coma confers risk and is not recommended (Class III, LOE B) : seizures, hypotension and arrhythmia with TCAs

Indication: reversal of excessive sedation during procedural sedation

Lheureux P, Vranckx M, Leduc D, Askenasi R. Flumazenil in mixed benzodiazepine/tricyclic antidepressant overdose: a placebo-controlled study in the dog. Am J Emerg Med. 1992;10:184 –188.Pitetti RD, Singh S, Pierce MC. Safe and efficacious use of procedural sedation and analgesia by nonanesthesiologists in a pediatric emergencydepartment. Arch Pediatr Adolesc Med. 2003;157:1090 –109

Antihypertensives :β-Blockers β-Blockers: myocardial membrane-

stabilizing activity >>> QRS widening and decreased myocardial contractility

Cardiovascular complications of B-blocker toxicity: include hypotension, bradycardia, AV blocks of different degrees, and CHF with or without pulmonary edema.

Most common: propranolol seizure is highest with propranolol,

particularly when the QRS complex is > 100 ms

Beta Blockers

Glucagon

-blocker

• Secreted by pancreas secondary to hypoglycemia• Glucagon Receptors found in heart muscle• Acts by stimulating adenylate cyclase.

independent of -receptorglucagon+

Glucagonreceptor

Drug of choice for -blocker (& CCB) O.D.

Beta Blockers: Glucagon

The final outcome:

positive chronotropic and inotropic effects despite -adrenergic blockade.

Onset within minutes, peak levels in 5-7 minutes, duration of action of 10-15 minutes.

Beta Blockers

Glucagon - precautions

2. Side effects from glucagon include:i. dose-dependent nausea and vomiting

aspirationii. hyperglycemia, hypokalemia (not

clinically important)iii. Some Reports of treatment failure

1. Diluent contains 2 mg/ml phenol as preservativei. Max 10-h dose of phenol = 50 mg = 5mg glucagonii. Use sterile water instead of diluent

Insulin??Shown to have positive inotropic effects on animal and human myocardium

Beta Blockers: Insulin

24 dogs, anesthetized and infused with propanol.Hemodynamics before & after treatment with: i. Normal Saline (n=6)ii. Insulin (4IU/min) + glucose PRN (n=6)iii. Glucagon (50 ug/kg) + infusion (n=6)iv. Epinephrine (1ug/kg/min) + titrated (n=6)

Kerns, et al. Ann Em Medicine. 1997. 29:748-757

Results:

6/6 Controls died within 150 min5/6 Epinephrine animals died after 240 min2/6 Glucagon animals died “ “ “0/6 Insulin animals died “ “ “

Kaplan-Meier Survival CurveInsulin vs. Glucagon (p<0.05)Insulin vs. Epinephrine (p<0.02)

Beta Blockers

1. May enhance catecholamine release2. May enhance myocardial substrate use In normal myocardium, FFA are preferred substrate. In poisoned myocardium, glucose becomes 1o

substrate3. May increase cytosolic calcium

Pathophysiology ?:

Beta Blockers

Insulin in Acute Beta Blocker OD.

:β-Blockers: Management Supportive therapy : activated charcoal for

decontamination; combinations of fluid resuscitation, vasopressor agents, atropine, transvenous pacing

Specific antidotes: glucagon bolus of 3 to 10 mgadministered slowly over

3 to 5 minutes, followed by an infusionof 3 to 5 mg/h (0.05 to 0.15 mg/kg followed by an infusion of 0.05 to 0.10 mg/kg per hour) (Class IIb, LOE C)

high-dose IV insulin, accompanied by IV dextrose supplementation (Class IIb,LOE C)

Other: Calcium, 0.3 mEq/kg of calcium (0.6 mL/kg of 10% calcium gluconate solution or 0.2 mL/kg of 10% calcium chloride solution) IV over 5 to 10 minutes,followed by an infusion of 0.3 mEq/kg per hour.

Calcium Channel Blockers hypotension and bradycardia extended-release (ER) formulations can

result in delayed onset of arrhythmias, shock, sudden cardiac collapse, and bowel ischemia.

Treatment: IV insulin/Dextrose Calcium (Calcium chloride (1-4 g IV; preferably via

central line; (30 mL) of 10% calcium gluconate can be administered IV over 10-15 minutes in adults. Boluses may be repeated every 15-20 minutes for a total of 3 doses)

Haddad LM. Resuscitation after nifedipine overdose exclusively with intravenous calcium chloride. Am J Emerg Med. Oct 1996;14(6):602-3Hung YM, Olson KR. Acute amlodipine overdose treated by high dose intravenous calcium in a patient with severe renal insufficiency. Clin Toxicol (Phila). 2007;45(3):301-3

Cocaine and methamphetamine and derivaties

Arrhythmia, hypertension, acute coronary syndrome HX: Onset and duration of symptoms depend on

route of administration, dose, and patient tolerance Clinical Presentation

Central Nervous System: agitation, psychosis, AMS etc Cardiovascular: ACS (6% ), hypertension, hyperthermia Acute Pulmonary Syndrome: y dyspnea, diffuse infiltrates,

and hemoptysisCan act as a Vaughan-Williams class Ic antiarrhythmic, producing wide-complex tachycardia through several mechanisms, including blockade of cardiac sodium channels >>> Wide complex tachycardia

Treatment and Caveats

Methamphetamine – MDAC Ascorbic acid no longer recommended

Cocaine related ACS Diagnosis of cocaine related MI is difficult as 84% of

patients with cocaine related chest pain have abnormal ECGs Half of all cocaine users have increased creatinine

kinase concentrations in the absence of myocardial infarction

Troponin concentrations are more sensitive and specific Pathophysiology: sympathomimetic action of cocaine

produces an increase in myocardial oxygen demand and direct cocaine induced coronary artery vasospasm

Treatment and Caveats

Benzodiazepines (lorazepam, diazepam), calcium channel blockers (verapamil), morphine, and sublingual nitroglycerin

(Class IIb, LOE B) Aspirin for Cocaine ACS ; Lidocaine? Supportive: rapid cooling measures Caveats: phentolamine can be used but

not propranolol, labetalol ineffective ( Class IIb, LOE C)

Cocaine induced Arrhythmia

(+) Wide complex tachycardia

Sodium bicarbonate 1 mL/ kg (cocaine) IV as a

bolus, repeated as needed until hemodynamic stability is

restored and QRS duration is < 120 ms

Cyanide

cyanide can be found in jewelry cleaners,

electroplating solutions; fire smoke Joint DOH-DENR Advisory: Series of

2010-001 on reporting of cases to DOH-FDA

Clinical Manifestations: causes rapid cardiovascular collapse,

which manifests as hypotension, lactic acidosis, central apnea, and seizures

management

Enhancement of body’s natural mechanisms for dealing with cyanide:i. oxygen

  ii. Sodium thiosulphate

Cyanide will also bind to methaemoglobin formed after administration of:i. Amyl nitrite;ii. Sodium nitrite, or;iii. 4-dimethylaminophenol

(4-DMAP)

Cobalt containing drugs:

i. Hydroxocobalamin, orii. Dicobalt edetate.

In summary

Approach using evidenced based toxicologic interventions and supportive care guided by expert referrals on intervention and disposition from poison control centers

Consider the toxidromes In critical care situations utilize

standard AHA/ECC guidelines for BLS and ACLS Consider exceptions among severely

poisoned individuals with exposure to specific toxic agents

Hotlines: Information Services

UP PGH NPMCC:       02-5218451  loc 2311

Department of Health:East Avenue Medical Center:  (02)

4342511      Rizal Medical Center: (02) 5241078Batangas Regional Medical Center:

(043) 7233578    

“Give a man a fish, and he can eat for a day. But teach a man how to fish, and he’ll be dead of mercury poisoning inside of three years.”

—Charlie Haas (1889-1964)