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A General Approach to acute drug overdoses and intoxications
Patrick Melanson, MD FRCPC
When faced with a patient, who has potentially overdosed on a drug or toxic substance, the clinician can rely on several basic management principles, which are applicable to the majority of potentially poisoned patients. The first priority is always assessment and stabilization of Airway, Breathing, Circulation, and neurologic Deficits. Following patient stabilization, the focus will shift to identification of the potential toxins using history, a directed physical examination for 'toxidromes', and judicious and focussed laboratory testing. Once a specific toxin is identified as the agent responsible for the patient's signs and symptoms, then the clinician must decide whether the administration of an antidote may favorably alter the patient's course. The clinician must also decide whether specific measures to hasten elimination of the drug from the patient's GI tract or bloodstream would be indicated. Finally, once the patient is felt to be no longer at risk from the toxin and is "medically cleared", then steps must be taken to try to prevent a similar occurrence in the future. These steps may include parental education or psychiatric consultation.
Supportive measures should supersede all other considerations in the management of the poisoned patient. The ABC's always come first. Many toxic agents and drugs taken in overdoses can lead to significant impairment in airway patency or protection, hypoventilation, hyperventilation, non-cardiogenic pulmonary edema, aspiration pneumonitis, bradycardias, tachycardias, hypotension, hypertension, alterations in thermoregulation, or altered mental status. These potentially life-threatening derangements should be identified and treated promptly. Subsequently, the focus may switch to confirmation of a specific toxic ingestion and more specific management issues.
In fact, the majority of poisoned patients only require supportive therapy alone in order to recover. Supportive measures alone, without specific antidotes or means of enhanced elimination(the "Scandinavian method"), will permit survival of most patients who are alive upon arrival at the hospital. These supportive measures would include mechanical ventilation and circulatory support with ionotropes or vasopressors. Since, supportive measures are usually all that are required, one should be fairly conservative in ones use of aggressive measures such as GI decontamination and antidotes. These measures do carry the risk of significant iatrogenic complications. For many of the patients who present with an overdose, the risk-benefit ratio does not favor their use. 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 should never be given as a reflex part of the 'coma cocktail"as it can be detremental in patients who have a TCA overdose, a seizure disorder, or are chronically habituated to benzodiazepines.
Once the initial stabilization is completed, the focus can shift to identifying the causative drug or toxin. 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 the 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.
A careful, focussed physical exam, based on a knowledge of pharmacology and the effects of drugs on the autonomic nervous system, will often allow the astute clinician to establish the most likely class or classes of agents involved. 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 drug involved in the poisoning and allows one to narrow the differential diagnosis. This provides a starting point for subsequent 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 the presence of unusual odors on the patients breath.
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 (the first 6 to 8 hours). 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:
1.Arterial Blood Gas with Co-oximetry
- CO, MetHgb, CN-
- Oxygen saturation gap
- Respiratory or metabolic acidosis
2.Urinalysis
- FeCl3 test for salicylates
- Ketones ( salicylates, ketoacidosis )
- Calcium oxalate crystals ( ethylene glycol )
- Woods lamp ( ethylene glycol )
- Rule out rhabdomyolysis
3.Electrolytes, BUN, Cr, CPK
4.Lactate
5.Serum ketones
6.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]
7.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
8.Beta-HCG in all women of child-bearing age
9.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
Gastric emptying/ decontaimination
There has been a 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.
Ipecac
In five randomized studies of over 2000 patients, no advantage has been seen in using Ipecac in addition to activated charcoal (AC) compared with AC alone. In hospiatalized patients increases in pulmonary infiltrates were noted in those receiving the Ipecac. It is now felt that Ipecac should not be used in the hospital setting. There may still be a limited role for the use of Ipecac in a situation where a child has ingested a potentially lethal quantity of a drug and he is more than 45 to 60 minutes away from a hospital.
Gastric lavage
Likewise, there is no compelling evidence that gastric lavage should be used routinely in treating the poisoned patient. Although studies with volunteers have demonstrated recovery of 13% to 70% of the ingested toxin, its rate of recovery deteriorates rapidly with time. For the most part, there is negligible recovery of ingested toxin beyond one hour. To date no clinincal study has been able to demonstrate a benefit for gastric lavage. Significant complications including aspiration pneumonia, laryngospasm, mechanical injury to the pharynx, esophagus, and stomach, hypoxia, and hypercapnia, have been reported with lavage.
For the most part, the risk/benefit ratio of gastric lavage does not favor its use in the vast majority of overdoses. If it is to be used at all, it should only be used for selected limited indications. These would include ingestion of a known toxic substance in a quantity known to be life-threatening. Furhermore, the ingestion should have occurred within the last hour so that a significant quantity of toxin could be presumed to be still present in the stomach. If the patient is to be lavaged, there should be strong consideration to intubate the patient prioir to lavage in order to protect his airway.
Activated Charcoal
The most important agent for GI decontamination is activated charcoal. 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
The first randomized prospective study on gastric emptying. Found no benefit for Ipecac compared with AC alone. No benefit to lavage if done > 1 hour after ingestion.
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
Compared observation vs AC vs Gastric empty+AC
Found no benefit to gastric emptying vs AC alone
However, gastric emptying increased aspiration pneumonia.
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
The largest and latest of a total of 5 clinical trials that have failed to show any advantages to gastric emptying procedures before activated charcoal compared to activated charcoal alone with poisoned patients.
Concluded that "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."
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
Compared Ipecac + AC vs AC alone
Fewer complications without Ipecac. No difference in outcomes.
Kornberg AE, Dolgin J: Pediatric ingestions: Charcoal alone versus ipecac and charcoal. Ann Emerg Med 20:648-651,1991
American Academy of Clinical Toxicology; European Association of Poison Centres and Clinical Toxicologists. Position Statement: Ipecac syrup. J Toxicol Clin Toxicol 1997; 35: 699-709.
Strong statement limiting the use of Ipecac to possibly within 60 minutes of ingestion.
American Academy of Clinical Toxicology; European Association of Poison Centres and Clinical Toxicologists. Position Statement: Gastric lavage. J Toxicol Clin Toxicol 1997;35: 711-719.
Recent strong statement suggesting limiting the use of gastric lavage.
American Academy of Clinical Toxicology; European Association of Poison Centres and Clinical Toxicologists. Position Statement:Single-dose activated charcoal.. J Toxicol Clin Toxicol 1997; 35: 721-741
Questions the data that support the routine use of activated charcoal in the management of poisoned patients
.
American Academy of Clinical Toxicology; European Association of Poison Centres and Clinical Toxicologists. Position Statement: Cathartics. J Toxicol Clin Toxicol 1997; 35:743-752
Strong statement suggesting there is no role for the use of cathartics alone in the treatment of poisoned patients. Based on limited clinincal and experimental data, routine use of cathartics with activated charcoal is not endorsed
.
American Academy of Clinical Toxicology; European Association of Poison Centres and Clinical Toxicologists. Position Statement: Whole bowel irrigation. J Toxicol Clin Toxicol 1997; 35:753-762
The recommendation states that WBI should not be used routinely. It is a theorectical option for treating toxic ingestions of iron, lead, zinc or packets of illicit drugs
.
Manoguerra AS: Gastrointestinal decontaimination after poisoning. Where is the science? Crit Care Clinics 1997; 13: 709-725.
Review article examines the literature on GI decontaimination.