Toxicology: General management principles

Supportive measures should supersede all other considerations in the management of the poisoned patient. The ABC's always come first. Subsequently, the focus may switch to confirmation of a toxic ingestion and specific management issues.

The majority of poisoned patients only require supportive therapy alone in order to recover. Supportive measures alone (Scandinavian method) including mechanical ventilation and circulatory support will permit survival of most patients who are alive upon arrival at the hospital.

In general, the use of antidotes or specific measures should be limited to those patients with clear indications.

Immediately after establishing iv access, a"coma cocktail"of dextrose, thiamine, naloxone and oxygen should be given to all patients with altered mental status. Hypoglycemia must always be a consideration in the unconscious or poisoned patient. Thiamine should be given routinely to all alcoholics or malnourished patients with altered mental status. Naloxone should be considered in all with respiratory depression. Flumazenil rarely, if ever, has to be given emergently, and more careful consideration of its use should be made.

It is important to seek history from sources other than the patient who is often an unreliable historian. These sources include family, friends, the prescribing physician, pharmacists, pre-hospital care personnel, police, and pill bottles or drug paraphernalia at the scene

Attempt to establish the time and size of the ingestion and thus the likelihood that a potentially lethal quantity was ingested. Also try to determine if the patient has vomited spontaneously as this will decrease the need for gastric emptying procedures.

The vital signs are the most important clues to the diagnosis of poisoning and should be measured often and accurately.

The physical exam should focus on identifying a"toxidrome"or toxic syndrome. This is a pattern of signs and symptoms that suggests a specific class of poisoning and allows one to narrow the differential diagnosis. This provides a starting point for management and may suggest the laboratory tests that follow. However, it should be kept in mind that there are many exceptions to the toxidromes and that polydrug ingestions can present with a confusing variety of mixed and overlapping syndromes.

The physical exam should also include evaluation for head trauma, focal neurologic findings, needle track marks, chest auscultation for signs of aspiration or non-cardiogenic pulmonary edema, and unusual odors on the patients breath.

Toxicology screening provides direct evidence of ingestion (although false positives and false negatives do occur), but rarely impacts upon initial management. Initial management should never await results of such analysis.

Toxidromes

"A pattern of signs or symptoms that suggests a specific class of poisoning"

Opioids

triad of respiratory depression, pinpoint pupils, decreased LOC

bradycardia, hypotension, hypothermia

needle tracks

Sedative / Hypnotics

- benzodiazepines, alcohol, barbituates

altered mental status, stupor, coma, slurred speech

respiratory depression

variable pupil changes

hypotension

hypothermia

barbiturate blisters

Sympathemimetics / Withdrawal

- Cocaine, amphetamines, PCP, pseudoephedrine

HTN, tachycardia,

Mydriasis

Anxiety, delirium, paranoid delusions

Diaphoresis

Increased temperature

Seizures

Anticholinergics

TCA, antihistamines, antipsychotics, Gravol

Hot as a hare, Red as a beet, Dry as a bone, Blind as a bat, Mad as a hatter

Hyperpyrexia, cutaneous vasodilation, decreased saliva, mydriasis, hallucinations

tachycardia

Urinary retention

Decreased bowel sounds

Seizures, dysrhythmias

Important to recognize because there is life-saving treatment and because failure to recognize immediately places health care workers at risk.

Cholinergics

insecticides,carbamate, organophosphates, nerve gas, physostigmine

Salivation, Lacrimation, Urination, Defecation, Gastric cramping, Emesis SLUDGE

Drowning in secretions, profuse sweating

AMS, seizures, coma

Muscle fasciculations

Miotic pupils

Salicylates

fever

tachypnea

tinnitus, lethargy, altered mental status

respiratory alkalosis

metabolic acidosis, ketosis

vomiting

Serotonin Syndrome

fluoxetine, trazadone, meperidine

irritability, agitation, AMS

hyperreflexia, tremor, myoclonus, trismus

ataxia, incoordination

flushing,diaphoresis

diarrhea

fever

Difficult to distinguish from NMS, MH, cocaine intoxication, thyroid storm

Extrapyramidal

haloperidol, phenothiazines

rigidity, tremor

opisthotonus, trismus

choreoathetosis

hyperreflexia

Hallucinogenic

amphetamines, cannabinoids, cocaine, LSD, PCP

hallucinations, psychosis, panic

fever

mydriasis

Bradycardia

Beta- blockers, calcium-channel blockers, Digoxin

Clonidine

Phenylpropanolamine

Carbamates, organophosphates, physostigmine

TCA's

Antidysrhythmics ( Types 1A AND 1C)

Opioids

Hypoxemia, MI, hyperkalemia, hypothermia, hypothyroidism, ICP

Agitation/ Seizures

Temperature alterations


Toxicology laboratory

Toxicology screening provides direct evidence of ingestion (although false positives and false negatives do occur), but rarely impacts upon initial management. Initial supportive management should never await results of such analysis

The notion that ordering a"tox screen"on every patient with a suspected overdose will result in a definitive answer as to what the ingested agents were, is incorrect.

The toxicology laboratory does not even attempt to screen for a large number of substances including most antihypertensives and cardiac medications, hallucinogens, MAOI's, the newer antidepressants, plants, mushrooms, fentanyl, cyanide, metals, and household products.

If the initial urine screen is done too soon after ingestion, the concentration in the urine may be too low for detection.

Furthermore, the drugs found on the screen may not be responsible for the symptoms seen, especially if the drugs are not quantitated. Cocaine metabolites may be detected for days and marijuana metabolites for weeks post-exposure. In addition, the tox results usually do not come back until several hours after most important treatment decisions are made.

Numerous studies have demonstrated that tox screens rarely change initial management and have questioned whether their high cost is justified for routine use.

The following readily obtainable laboratory tests should also be obtained in specific circumstances:

Arterial Blood Gas with Co-oximetry

CO, MetHgb, CN-

Oxygen saturation gap

Respiratory or metabolic acidosis

Urinalysis

FeCl3 test for salicylates

Ketones ( salicylates, ketoacidosis )

Calcium oxalate crystals ( ethylene glycol )

Woods lamp ( ethylene glycol )

Rule out rhabdomyolysis

Electrolytes, BUN, Cr, CPK

Lactate

Serum ketones

Serum osmolarity

 

Anion gap metabolic acidosis AG = [Na+] - [Cl-] - [HCO3-] Methanol Uremia Diabetic Ketoacidosiss ( AKA, SKA ) Phenformin, Paraldehyde Iron, INH Lactic acidosis Ethylene Glycol Salicylates

 

Osmol Gap

Calculated osmolality = 2[Na+] + [BUN] + [glucose] + [ ethanol]

 

Abdominal X-Ray

Choral hydrate, heavy metals, iron, phenothiazines, enteric coated are all radio-opaque

ECG - important to search for signs of TCA's or other cardiotoxic drugs

Beta-HCG in all women of child-bearing age

Toxicology Screening - Knowledge of the quantitative serum levels of the following drugs may impact on therapy:

Acetaminophen

ASA

Digoxin

Theophylline

Phenobarb

Iron

Lithium

Methanol, Ethylene glycol

Antidotes

- As many antidotes have the potential for causing harm, they should not be given as a reflex

Antidote

Toxin used for

 

Comments

Naloxone

Opiates

 

Less to avoid withdrawal

Flumazenil

Benzodiazepines

 

Avoid if TCA's, epilepsy, addiction

Bicarbonate

TCA, ASA

 

 

Calcium

CCB

   

Glucagon

Beta-blockers, CCB

 

Follow with infusion of same dose/hr

Physostigmine

Anticholinergics

 

Avoid in TCA's

Atropine

Organophosphates, Carbamates

 

Titrate to drying of pulmonary secretions

Protopam

Organophosphates

   

Ethanol

Methanol, ethylene glycol

   

Pyridoxine

INH

   

Digibind

Digoxin

   

N-acetylcysteine

Acetaminophen

   

EDTA

Lead

   

DMSA

Lead

   

BAL

Arsenic, mercury,lead

   

D-penicillamine

Ar,lead,Mercury

Cyproheptadine

Serotonin syndrome

   

Sodium nitrite, sodium thiosulfate

cyanide

   

Desferoxamine

iron

   

Methylene blue

Met-hemogloninemia

   

Gastric emptying/ decontaimination

Major change in the approach to GI decontamination in the past 10 years. The older recommendations were that the stomach should be emptied using either Ipecac or gastric lavage on all patients suspected of an oral drug overdose.

Several outcome studies have demonstrated superior (due to fewer complications) or equivalent outcomes in patients managed with Activated Charcoal alone as compared to charcoal plus a gastric emptying procedure.

Activated Charcoal used alone as a measure of GI decontamination, when the agents are well adsorbed to charcoal, is the recommended decontamination procedure of choice.

If there is a role for gastric emptying procedures at all, their use should be highly selective and not routine

Risk/ Benefit ratio of gastric emptying is unfavorable for the majority of poisonings, it should not be used for non-toxic doses or non-toxic substances, or when the toxin is no longer likely to be in the stomach ( already vomited, several hours since ingestion, agent rapidly absorbed from stomach)

Gastric lavage

Risks

Aspiration (Charcoal lung)

Upper airway, esophageal, gastric trauma (perforations)

Pneumothorax

Dysrhythmias

Benefits

33% (13 - 70 %) recovery of ingested toxin

? Improved clinical outcomes if performed within 1 hour

Indications ( selective use )

Toxic substance and toxic amount (not for benign ingestions)

Less than one hour from presentation and symptomatic

Airway protected

Agent which doesn't bind to charcoal (iron, lithium, hydrocarbons, alcohols)

Considerations

How well charcoal will bind to toxin

Likelihood the toxin is still in the stomach (time since ingestion)

Limitations of lavage (large pills)

Contraindications

Nontoxic substance or amount

Vomiting (stomach already emptied)

Greater than 1 hour since ingestion

Toxin readily absorbed

Caustics, sharps, petroleum

Large pills or packets (won't fit up tube)

Loss of gag reflex without ETT

- Problems with lavage

Requires patient cooperation unless comatose

Most pills too large to fit through holes in even a 40Fr lavage tube

May"push"stomach contents distally beyond charcoal

Time consuming

Evidence

1)Kulig ( 1985) - Gastric emptying + charcoal vs charcoal alone

No benefit to Ipecac vs AC alone

No benefit to lavage if done > 1 hour after ingestion

2) Albertson ( 1989) - Ipecac + AC vs AC alone

Fewer complications without Ipecac

No difference in outcomes

3) Merrigan ( 1990) - Observation vs AC vs Gastric empty+AC

No benefit to gastric emptying vs AC alone

Gastric emptying increases aspiration pneumonia

4) Pond ( 1995) - 495 Gastric empty + AC vs 417 Ac only

No benefit including < 1 hour and those with severe toxicity

"Gastric emptying procedures can be omitted from the treatment regimen for adults after acute overdose, including those that present within one hour of overdose and those that manifest severe toxicity."

Activated Charcoal

- The most important agent for GI decontamination

Prevents absorption by binding to the drug. May also increase elimination of drug already absorbed by pulling drug from the bloodstream into the gut by creating a favorable diffusion gradient between blood and gut ("GI dialysis"). It can also prevent reabsorption of drugs that have an enterohepatic circulation.

Limitations of charcoal include:

Need 10:1 ratio for 100% absorption, it is difficult to give 10 times as much charcoal as toxin in some intoxications where many grams of drug may be ingested ( i.e., 60 gm of theophylline requires 600 gm of charcoal)

Does not bind small, charged molecules like iron, lithium, arsenic, lead, cyanide

Does not bind alcohols, hydrocarbons, and pesticides

Does not bind caustics ( strong acids and bases)

Aspiration of charcoal has been associated with aspiration pneumonia, ARDS, bronchiolitis obliterans, and death. It should not be given to stuporous, comatose, or convulsing patients unless the airway is protected by an endotracheal tube and a ng tube is in place to administer the charcoal

Multiple- Dose Activated Charcoal (MDAC) - giving repetitive doses of charcoal without sorbitol every 1 to 2 hours may be beneficial in selected overdoses such as theophylline, phenobarbitol, ASA, digoxin, tegretol, nadolol, and dilantin

Whole Bowel Irrigation

WBI with a polyethylene glycol/ electrolyte solution given at 1 to 2 L/hr is used to push tablets or capsules through the GI system. It causes diarrhea by mass action

Indications include drugs not well absorbed by charcoal ( iron, lithium, heavy metals), sustained release pills, or"body-packing"with illicit drugs

Contraindications include obstruction, perforation, or GI hemorrhage

Complications include vomiting, bloating, and rectal irritation

Hemodialysis

Useful for small, water soluable, poorly protein bound drugs, with small volumes of distribution, that are usually eliminated by the kidney

Indications include intoxications with severe end-organ compromise, renal failure, metabolic acidosis or electrolyte disturbances not easily correctable by medical methods, or pulmonary edema

The five most commonly dialyzed drugs are methanol, ethylene glycol, ASA, lithium, and theophylline

Indications for ICU admission

  • TCA overdose with signs of cardiac toxicity ( QRS > 0.10 secs )
  • Wide alterations in body temperature
  • Need for intubation/ ventilation
  • Hemodynamic instability, dysrhythmias
  • Decreased level of consciousness
  • Need for continuous naloxone infusions
  • Progressive metabolic acidosis, electrolyte abnormalities
  • Need for emergency dialysis
  • Staffing issues including the availability of a sitter for suicidal patients
  • Rare or poorly understood poisoning (where clinical course and
  • potential complications not well understood)
  • Rising drug levels requiring close observation / monitoring (e.g. Lithium / ASA / theophylline). Even if dialysis criteria not yet met.
  • Potential for delayed toxicity requiring prolonged monitoring (e.g. SR CCBs or BBs)
  • Patient with significant underlying medical conditions which may exacerbate toxicity (heart disease / etc)

References

General

1) Kulig K: Initial management of ingestions of toxic substances.

N Engl J Med 326: 1677-1681,1992

2) Brett AS: Implications of discordance between clinical impressions and toxicology analysis in drug overdose. Arch Intern Med 148:437, 1988

3) Kellerman AL, Fihn SD, LoGerfo JP, et al: Impact of drug screening in suspected overdose. Ann Emerg Med 16:1206,1987.

4)Mahoney JD, Gross PL, Stern TA, et al: Quantitative serum toxic screening in the management of suspected drug overdose. Am J Emerg Med 8:16, 1990

5) Kulling P, Persson H : The role of the intensive care unit in the management of the poisoned patient. Med Toxicol 1:375-386,1986

Gastric Emptying

Kulig K, Barr-Or D, Cantril SV, et al: Management of acutely poisoned patients without gastric emptying. Ann Emerg Med 14:562-567,1985

Merigan KS, Woodward M, Hedges et al: Prospective evaluation of gastric emptying in the self-poisoned patient. Am J Emerg Med 8;479-483,1990

Pond SM, Lewis-Driver DJ, Williams GM, et al: Gastric emptying in the acute overdose: A prospective randomized controlled trial. Med J of Aust 163:345-349,1995

Albertson TE, Derlet RW, Foulke GE, et al: Superiority of activated charcoal alone compared with ipecac and activated charcoal in the treatment of acute toxic ingestions. Ann Emerg Med 18:56-59,1989

Kornberg AE, Dolgin J: Pediatric ingestions: Charcoal alone versus ipecac and charcoal. Ann Emerg Med 20:648-651, 1991.