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Toxicological Emergencies. Dr. Shahid Aziz MBBS, MRCP (UK), MCEM (London) Assistant professor and consultant emergency medicine, DEM King Khalid University Hospital. Objectives. History and Physical Examination Toxicology Screening Three gaps are important in toxicology Treatment

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Toxicological emergencies

Toxicological Emergencies

Dr. Shahid Aziz MBBS, MRCP (UK), MCEM (London)

Assistant professor and consultant emergency medicine, DEM

King Khalid University Hospital


Objectives
Objectives

  • History and Physical Examination

  • Toxicology Screening

  • Three gaps are important in toxicology

  • Treatment

  • ICU Admission


History and Physical Examination

Difficulties

  • No reliable history in patients with profoundly altered metal status

  • Focused treatment decisions quite difficult.

  • Multiple substances


History and Physical Examination

  • Separating patients who have suspected poisoning into broad categories that are based on vital signs, eye findings, mental status, and muscle tone, that helps to determine drug or toxin class i.e.“toxidromes.”


Diagnosing toxicity from vital signs

Bradycardia (PACED)

Propranolol (beta-blockers), poppies (opiates), propoxyphene, physostigmine

Anticholinesterase drugs, antiarrhythmics

Clonidine, calcium channel blockers

Ethanol or other alcohols

Digoxin, digitalis


Tachycardia (FAST)

Free base or other forms of cocaine, freon

Anticholinergics, antihistamines, antipsychotics, amphetamines, alcohol withdrawal

Sympathomimetics (cocaine, caffeine, amphetamines, PCP), solvent abuse, strychnine

Theophylline, TCAs, thyroid hormones


Hypothermia (COOLS)

Carbon monoxide

Opioids

Oral hypoglycemics, insulin

Liquor (alcohols)

Sedative-hypnotics


Hyperthermia (NASA)

Neuroleptic malignant syndrome, nicotine

Antihistamines, alcohol withdrawal

Salicylates, sympathomimetics, serotonin syndrome

Anticholinergics, antidepressants, antipsychotics


Hypotension (CRASH)

Clonidine, calcium channel blockers

Rodenticides (containing arsenic, cyanide)

Antidepressants, aminophylline, antihypertensives

Sedative-hypnotics

Heroin or other opiates


Hypertension (CT SCAN)

Cocaine

Thyroid supplements

Sympathomimetics

Caffeine

Anticholinergics, amphetamines

Nicotine


Rapid respiration (PANT)

PCP(phencyclidine), paraquat, pneumonitis (chemical), phosgene

ASA and other salicylates

Noncardiogenic pulmonary edema, nerve agents

Toxin-induced metabolic acidosis


Slow respiration (SLOW)

Sedative-hypnotics (barbiturates, benzodiazepines)

Liquor (alcohols)

Opioids

Weed (marijuana)


COMA

L: Lead, lithiumE: Ethanol, ethylene glycol, ethchlorvynolT: Tricyclic antidepressants, thallium, tolueneH: Heroin, hemlock, hepatic encephalopathy, heavy metals, hydrogen sulfide, hypoglycemicsA: Arsenic, antidepressants, anticonvulsants, antipsychotics, antihistaminesR: Rohypnol (sedative hypnotics), risperidoneG: GHB

I: Isoniazid, insulinC: Carbon monoxide, cyanide, clonidine


Agents that cause seizures (OTIS CAMPBELL)

Organophosphates, oral hypoglycemicsTricyclic antidepressants

Isoniazid, insulinSympathomimetics, strychnine, salicylatesCamphor, cocaine, carbon monoxide, cyanide, Amphetamines, anticholinergicsMethylxanthines (theophylline, caffeine), methanolPhencyclidine (PCP), propranololBenzodiazepine withdrawal,bupropion, GHBEthanol withdrawal, ethylene glycol

Lithium, lidocaine Lead, lindane


Agents that affect pupil size

Miosis (COPS)

Cholinergics, clonidine, carbamates

Opiates, organophosphates

Phenothiazines (antipsychotics), pilocarpine)

Sedative-hypnotics

Mydriasis (SAW)

Sympathomimetics

Anticholinergics

Withdrawal


Agents that cause skin signs

Diaphoretic skin (SOAP)

SympathomimeticsOrganophosphatesAcetylsalicylic acid or other salicylatesPhencyclidine

Dry Skin

Antihistamines, anticholinergics

Bullae

Barbiturates and other sedative-hypnotics,Bites: Snakes and spiders

Acneiform rash

BromidesChlorinated aromatic hydrocarbons (dioxin)


Flushed or red appearance

Anticholinergics, niacinBoric acidCarbon monoxide (rare)Cyanide (rare)

Cyanosis

ErgotamineNitratesNitritesAniline dyesPhenazopyridineDapsoneAny agent causing hypoxemia, hypotension, or methemoglobinemia.


Common toxidromes

Cholinergic (Examples: organophosphates, carbamates, pilocarpine)

(DUMBELLS)

Diarrhea, diaphoresisUrinationMiosisBradycardia, bronchosecretionsEmesisLacrimationLethargicSalivation


Nicotinic (recalled by the days of the week)

Monday: Miosis

Tuesday: Tachycardia

Wednesday: Weakness

Thursday: Tremors

Friday: Fasciculations

Saturday: Seizures

Sunday: Somnolent


Anticholinergic (Examples: antihistamines, cyclic antidepressants, atropine, benztropine, phenothiazines, scopolamine)

Hyperthermia (HOT as a hare)

Flushed (RED as a beet)

Dry skin (DRY as a bone)

Dilated pupils (BLIND as a bat)

Delirium, hallucinations (MAD as a hatter)

Tachycardia

Urinary urgency and retention


Sympathomimetic (Examples: cocaine, amphetamines, ephedrine, phencyclidine, pseudoephedrine)

Mydriasis

Tachycardia

Hypertension

Hyperthermia

Seizures


Opioid (Examples: heroin, morphine, codeine, methadone, fentanyl, oxycodone, hydrocodone)

Miosis

Bradycardia

Hypotension

Hypoventilation

Coma


Table fentanyl, oxycodone, hydrocodone) --  Antidotes and their indications


Enhanced elimination by charcoal hemoperfusion fentanyl, oxycodone, hydrocodone)


History and Physical Examination fentanyl, oxycodone, hydrocodone)

Treat

Toxidrome

Yes

No

  • vital signs

  • ocular findings

  • mental status

  • muscle tone

determine drug

or toxin class


History and Physical Examination fentanyl, oxycodone, hydrocodone)

  • Initially, a rapid survey for ABCs & life-threatening nature

  • Then, a more focused examination for

Physical examination

A rapid but careful physical examination of the patient is performed in stages.

  • Signs of trauma

  • Neurologic findings

  • Skin changes

  • Odors

  • Eyes


History and Physical Examination fentanyl, oxycodone, hydrocodone)

Physical examination

Patients may present with

  • hypotension or hypertension

  • bradyarrhythmias or tachyarrhythmias.

  • The pathogenesis of hypotension varies and may include

  • Hypovolemia

  • Myocardial depression

  • Cardiac arrhythmias

  • Systemic vasodilation.


Urine drug screens
Urine Drug Screens fentanyl, oxycodone, hydrocodone)

  • Detect only natural opiates

  • Do not detect synthetic or semisynthetic products

  • morphine

  • codeine

  • heroin

  • Oxycodone

  • Hydrocodone

  • Fenanyl

  • Propoxyphene

  • Meperidine

  • methadone.


Laboratories investigation
Laboratories Investigation fentanyl, oxycodone, hydrocodone)

  • Most hospital laboratories have the capability to rapidly identify and quantify only a small fraction of the substances commonly encountered in clinical practice.


Toxicology screening
Toxicology Screening fentanyl, oxycodone, hydrocodone)

Check acetaminophen levels in all cases of suspected intoxication


Supportive serum toxicology assays fentanyl, oxycodone, hydrocodone)

AcetaminophenLithiumSalicylateValproic acidCarbamazepineCo-oximetry (carboxyhemoglobin, methemoglobin)

DigoxinPhenobarbitalIronEthanolMethanolEthylene glycol

Theophylline

  • Data from Wu AH, McKay C, Broussard LA, et al. National Academy of Clinical Biochemistry Laboratory Medicine practice guidelines: recommendations for the use of laboratory tests to support poisoned patients who present to the emergency department. Clin Chem 2003;49:357–79.

  • SkeltonH.,DannL.M.,et al. Drug screening of patients who deliberately harm themselves admitted to the emergency department. Ther Drug Monit (1998) 20 : pp 98-103.


General treatment
GENERAL TREATMENT fentanyl, oxycodone, hydrocodone)

  • ABCs.

  • Protection of the cervical spine (unless trauma has been excluded).

  • A rapid assessment of the need of endotracheal intubation

  • Attention to any abnormalities of the vital signs.

  • Discontinuing the offending

  • Any life-threatening abnormalities

  • A 12-lead EKG is obtained along with continuous cardiac monitoring.

  • ABG


Initial supportive measures
Initial supportive measures fentanyl, oxycodone, hydrocodone)

Endotracheal intubation is indicated

  • when there is concern regarding airway protection and clinical deterioration

  • acute respiratory failure.

  • the need for high levels of supplemental oxygen

It decreases (but does not eliminate) the risk of aspiration

(which is approximately 11% in the comatose patient with drug overdose).


Initial supportive measures1
Initial supportive measures fentanyl, oxycodone, hydrocodone)

  • Rapid IV normal saline solution infusion is indicated in most instances.

  • Vasopressors may be required for refractory hypotension.

  • The vasopressor of choice depends on the type of intoxication

  • Hypertension-induced (reflex) bradycardia generally should not be treated.


Initial supportive measures2

Coma Cocktail fentanyl, oxycodone, hydrocodone)

Initial supportive measures

  • Dexrtrose, flumazenil, naloxone, thiamine.

.


Coma Cocktail fentanyl, oxycodone, hydrocodone)

Initial supportive measures

There is no evidence that dextrose should be withheld until thiamine is administered.

  • Reuler JB, Girard DE, Cooney TG. Wernicke's encephalopathy. N Engl J Med 1985; 312:1035–1039


Coma Cocktail fentanyl, oxycodone, hydrocodone)

Initial supportive measures

Naloxone

  • rapidly reverses coma, respiratory depression, and hypotension induced by opioids.

  • An initial dose of 0.2 to 0.4 mg is administered IV (or endotracheally).

  • If there is no response after 2 to 3 min, repeated up to 10 mg as required.

  • lack of response to 10 mg of naloxone generally excludes opioid toxicity.


Coma Cocktail fentanyl, oxycodone, hydrocodone)

Initial supportive measures

Naloxone

  • a higher dose may precipitate large cardiovascular changes in opioid dependent patients.

  • Observe for

  • acute pulmonary edema

  • opioid withdrawal

  • seizures


Coma Cocktail fentanyl, oxycodone, hydrocodone)

Initial supportive measures

Flumazenil

  • Its use in undifferentiated ED patients is not recommended

  • Withdrawal seizures in mixed overdoses or in patients with long-term use of benzodiazepines.

    HoffmanR.S.,GoldfrankL.R., The poisoned patient with altered consciousness: controversies in the use of a coma cocktail. JAMA (1995) 274 : pp 562

    SpiveyW.H., Flumazenil and seizures: analysis of 43 cases. Clin Ther (1991) 14 : pp 292-305.


Coma Cocktail fentanyl, oxycodone, hydrocodone)

Initial supportive measures

Flumazenil

  • Case reports have cautioned clinicians of the risk of precipitating seizures with flumazenil when there is a suspicion of benzodiazepine plus TCA overdose

  • 0.2 mg of IV flumazenil over 30 s followed by another 0.3-mg dose if necessary.

  • Doses beyond 3 mg generally do not provide additional benefit.


GASTRIC LAVAGE fentanyl, oxycodone, hydrocodone)

Decontamination

  • Patients must be able to maintain their airways or be intubated.

  • Should not be performed on patients who have ingested medications that may cause seizures or abrupt central nervous system deterioration.


GASTRIC LAVAGE fentanyl, oxycodone, hydrocodone)

Decontamination

  • There is no clear definition of when to end the procedure.


GASTRIC LAVAGE fentanyl, oxycodone, hydrocodone)

Decontamination

  • One study using radiographic markers suggested that GL may actually propel gastric contents past the pylorus, moving the poison into the small intestine, where most of the drug will be absorbed

    SaettaJ.P.,MarchS.,GauntM.E.,et al. Gastric emptying procedures in the self-poisoned patient: are we forcing contents beyond the pylorus?. J R Soc Med (1991) 84 : pp 274-276.


GASTRIC LAVAGE fentanyl, oxycodone, hydrocodone)

Decontamination

  • three clinical trials have failed to demonstrate improved outcomes when GL is added to AC for the management of undifferentiated symptomatic poisoning patients.

KuligK.,Bar-OrD.,CantrillS.V.,et al. Management of acutely poisoned patients without gastric emptying. Ann Emerg Med (1985) 14 : pp 562-567. PondS.M.,Lewis-DriverD.J.,WilliamsG.M.,et al. Gastric emptying in acute overdose: a prospective randomised trial. Med J Aust (1995) 163 : pp 345-349.

SaettaJ.P.,MarchS.,GauntM.E.,et al. Gastric emptying procedures in the self-poisoned patient: are we forcing contents beyond the pylorus?. J R Soc Med (1991) 84 : pp 274-276


GASTRIC LAVAGE fentanyl, oxycodone, hydrocodone)

Decontamination

  • GI tract perforation

  • hypoxia

  • aspiration.

  • esophageal perforation

  • Arterial oxygen tension dropped 17% during GL

  • pneumothorax

Complications associated with GL include


GASTRIC LAVAGE fentanyl, oxycodone, hydrocodone)

Decontamination

  • Based on the available data, the American Academy of Clinical Toxicology does not recommend gastric lavage unless a patient has ingested a potentially life-threatening amount of a poison and the procedure can be undertaken within 60 minutes of ingestion


ACTIVATED fentanyl, oxycodone, hydrocodone)

CHARCOAL

Decontamination

  • Current consensus recommendations are that adult overdose patients receive 25 to 100 g

  • The efficacy of charcoal is time dependent.

  • A recent consensus statement suggests that charcoal should be administered within 60 minutes of ingestion

LaineK.,KivistoK.T.,NeuvonenP.J., Effect of delayed administration of activated charcoal on the absorption of conventional and slow-release verapamil. J Toxicol Clin Toxicol (1997) 35: pp 263-268


ACTIVATED fentanyl, oxycodone, hydrocodone)

CHARCOAL

Decontamination

CLINICAL EFFICACY OF ACTIVATED CHARCOAL

  • A study evaluated AC versus supportive care alone in asymptomatic pt.

  • 231 patients were assigned to observation and 220 were assigned to AC.

  • No patient in either group deteriorated, suggesting that AC provided no benefit in the management of asymptomatic poisoning patients.

  • MerigianK.S.,WoodardM.,HedgesJ.R.,et al. Prospective evaluation of gastric emptying in the self-poisoned patient.

  • Am J Emerg Med (1990) 8 : pp 479-483.


ACTIVATED fentanyl, oxycodone, hydrocodone)

CHARCOAL

Decontamination

  • a large study was published comparing AC with supportive care for symptomatic and asymptomatic overdose patients.

  • This study is described as a randomized controlled trial (RCT) where 1479 patients were assigned on an alternating-day basis to either AC or supportive care.

  • MerigianK.S.,BlahoK.E., Single-dose oral activated charcoal in the treatment of the self- poisoned patient: a prospective, randomized, controlled trial. Am J Ther (2002) 9 : pp 301-308.


ACTIVATED fentanyl, oxycodone, hydrocodone)

CHARCOAL

Decontamination

  • One additional RCT with Preliminary results suggest that the patients who were given AC had a trend toward longer ED stay and no change in mortality

  • CooperG.M.,Le CouteurD.G.,RichardsonD.,et al.A randomised controlled trial of activated charcoal for the routine management of oral drug overdose. J Toxicol Clin Toxicol (2002) 40 : pp 313-.


ACTIVATED fentanyl, oxycodone, hydrocodone)

CHARCOAL

Decontamination

The major complications of AC are

  • Vomiting

  • intestinal obstruction

  • aspiration.


ACTIVATED fentanyl, oxycodone, hydrocodone)

CHARCOAL

Decontamination

  • Clinical benefits remain unproved

    American Academy of Clinical Toxicology and European Association of Poison Centers and Toxicologist. Position paper: single-dose activated charcoal. J Toxicol Clin Toxicol (2005) 43 : pp 61-87


ACTIVATED fentanyl, oxycodone, hydrocodone)

CHARCOAL

Decontamination

Complication

  • pneumonia

  • bronchiolitis obliterans

  • ARDS

  • death.


ACTIVATED fentanyl, oxycodone, hydrocodone)

CHARCOAL

Decontamination

Toxins and Drugs Not Adsorbed by Activated Charcoal


Extracorporeal fentanyl, oxycodone, hydrocodone)

Removal of Toxins

Three methods

  • (1) dialysis (usually hemodialysis rather than peritoneal dialysis)

  • (2) hemoperfusion

  • (3) hemofiltration.


Hemodialysis fentanyl, oxycodone, hydrocodone)

Toxins Characteristics

  • low molecular weight (< 500 d)

  • water soluble

  • low protein binding (< 70 to 80%)

  • small volume of distribution (< 1 L/kg).

    It can especially be effective in correcting concomitant electrolyte abnormality and metabolic acidosis.

    I,e:

  • methanol,

  • ethylene glycol,

  • boric acid,

  • Salicylates

  • lithium.


Hemoperfusion fentanyl, oxycodone, hydrocodone)

  • Hemoperfusion is defined as direct contact of blood with an adsorbent system

  • drug clearance is not limited by low water solubility, high molecular weight, or increased protein binding, but on the ability of the adsorbent to bind to the drug/toxin.

  • toxin needs to be present in the central compartment for hemoperfusion to be effective.

  • used to enhance elimination of theophylline, phenobarbital, phenytoin, carbamazepine, paraquat.


Hemofiltration fentanyl, oxycodone, hydrocodone)

  • application of this technique has not been vigorously studied in poisoned patients

  • there are increasing numbers of case reports of extracorporeal intoxicant removal by either the continuous arteriovenous or venovenous hemofiltration methods

  • Hemofiltration is potentially useful for removal of substances with a large volume of distribution, slow intercompartmental transfer, or extensive tissue binding.

  • combined digoxin-Fab fragment complexes, or desferoxamine complexes with iron or with aluminum.


ICU Admission fentanyl, oxycodone, hydrocodone)

Initial supportive measures


ICU Admission fentanyl, oxycodone, hydrocodone)

Initial supportive measures

Criteria for Admission of the Poisoned Patient to the ICU

  • Hypothermia or hyperthermia including neuroleptic malignant syndrome

  • Tricyclic or phenothiazine overdose manifesting anticholinergic signs, neurologic abnormalities, QRS duration > 0.12 s, or QT > 0.5 s

  • Body packers and stuffers

  • Emergency surgical intervention

  • Administration of pralidoxime in organophosphate toxicity

  • Antivenom administration

  • continuous infusion of naloxone

  • Hypokalemia secondary to digitalis overdose (or need for digoxin-immune antibody Fab fragments)


ICU Admission fentanyl, oxycodone, hydrocodone)

Initial supportive measures

  • In this retrospective study, if a poisoned patient did not exhibit any of the eight characteristics, no ICU interventions (intubation, vasopressors or antiarrhythmics, and dialysis or hemoperfusion) were required.

    (1) PaCO2 > 45 mm Hg,

    (2) need for intubation,

    (3) toxin-induced seizures,

    (4) cardiac arrhythmias,

    (5) QRS ≥ 0.12 s,

    (6) sBP < 80 mm Hg,

    (7) 2nd or 3rd degree AV block,

    (8) unresponsiveness to verbal stimuli.

  • Brett AS, Rothschild N, Gray R, et al. Predicting the clinical course in intentional drug overdose: implications for the use of the intensive care unit. Arch Intern Med 1987; 147:133–137

  • Mokhlesi B, Leikin JB, Murray P, et al. Adult toxicology in critical care: part I: general approach to the intoxicated patient. Chest 2003;123(2):577-92.


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