adult toxicology in critical care: part i: general ......miosis-adrenergic tachycardia albuterol...

DOI 10.1378/chest.123.2.577 2003;123;577-592 Chest

Corbridge Babak Mokhlesi, Jerrold B. Leiken, Patrick Murray and Thomas C.

General Approach to the Intoxicated PatientAdult Toxicology in Critical Care: Part I:

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Adult Toxicology in Critical Care*Part I: General Approach to the Intoxicated Patient

Babak Mokhlesi, MD; Jerrold B. Leiken, MD; Patrick Murray, MD; andThomas C. Corbridge, MD, FCCP

Intensivists are confronted with poisoned patients on a routine basis, with clinical scenariosranging from known drug overdose or toxic exposure, illicit drug use, suicide attempt, oraccidental exposure. In addition, drug toxicity can also manifest in hospitalized patients frominappropriate dosing and drug interactions. In this review article, we describe the epidemiologyof poisoning in the United States, review physical examination findings and laboratory data thatmay aid the intensivist in recognizing a toxidrome (symptom complex of specific poisoning) orspecific poisoning, and describe a rational and systematic approach to the poisoned patient. It isimportant to recognize that there is a paucity of evidence-based information on the managementof poisoned patient. However, the most current recommendations by the American Academy ofClinical Toxicology and European Association of Poisons Centers and Clinical Toxicologists willbe reviewed. Specific poisonings will be reviewed in the second section of these review articles.

(CHEST 2003; 123:577–592)

Key words: critical care; ICU; poisoning; toxicology; toxidromes

Abbreviations: GL � gastric lavage; pKa � negative logarithm of the acid ionization equilibrium constant

A high index of suspicion for intoxication is war-ranted in the practice of critical care medicine.

The protean manifestations of intoxication challengeeven the most astute clinicians, particularly whenpatients present with altered mental status or whenthere is no history of intoxication. Recognition of aspecific toxic syndrome (or toxidrome) helps (Table1), but symptoms are often nonspecific (as in earlyacetaminophen poisoning) or masked by other con-ditions (eg, myocardial ischemia in the setting ofcarbon monoxide poisoning).

In the first of this two-part series, we will reviewthe epidemiology of poisonings, both intentional and

unintentional, provide an approach to the diagnosisof the poisoned patient, and discuss strategies forgeneral supportive care. In part II, we will review theassessment and management of specific intoxications.

Epidemiology

Since 1983, the American Association of PoisonControl Centers has compiled data from the ToxicExposure Surveillance System. In their 2000 annualreport, 63 poison centers reported a total of 2,168,248human toxic exposure cases. Adults accounted forapproximately one third of exposures. Most exposureswere unintentional (71% of cases) and involved a singletoxic substance (92%). Fewer than 5% of cases involvedan adverse reaction to a medication or food. Oralingestion was the commonest route of exposure (Fig 1).Most exposures occurred at the patient’s own resi-dence, and most patients (75%) were managed on-sitewith assistance from a poison information center anddid not require an emergency department visit. Only3% of patients required critical care.

The categories of substances/toxins with the larg-

*From the Division of Pulmonary and Critical Care Medicine(Dr. Mokhlesi), Cook County Hospital/Rush Medical College,Chicago; Evanston Northwestern Healthcare-OMEGA (Dr.Leiken), Chicago; Section of Nephrology (Dr. Murray), Univer-sity of Chicago, Chicago; and Medical Intensive Care Unit(Dr. Corbridge), Northwestern University Medical School,Chicago, IL.Manuscript received March 19, 2002; revision accepted July 12,2002.Correspondence to: Babak Mokhlesi, MD, Division of Pulmonaryand Critical Care Medicine, Cook County Hospital/RushMedical College, 1900 West Polk St, Chicago, IL 60612; e-mail:[email protected]

critical care review

www.chestjournal.org CHEST / 123 / 2 / FEBRUARY, 2003 577



Table 1—Common Toxidromes

Toxidrome Features Drugs/Toxins Drug Treatment

Anticholinergic“Hot as a hare, dry as a

bone, red as a beet, madas a hatter”

MydriasisBlurred visionFeverDry skin

AntihistaminesAtropineBaclofenBenztropine

Physostigmine (for life-threateningevents, do not use in cyclicantidepressant overdose because ofpotential worsening of conductiondisturbances)Flushing Tricyclic antidepressants

Ileus PhenothiazinesUrinary retention PropanthelineTachycardia ScopolamineHypertensionPsychosisComaSeizuresMyoclonus

Cholinergic “SLUDGE” Salivation Carbamate AtropineLacrimation Organophosphates Pralidoxime for organophosphatesUrination PhysostigmineDiarrhea PilocarpineGI crampsEmesisWheezingDiaphoresisBronchorrheaBradycardiaMiosis

�-Adrenergic Tachycardia Albuterol �-Blockade (caution in asthmatics)Hypotension Caffeine Potassium replacementTremor Terbutaline

Theophylline

�-Adrenergic HypertensionBradycardiaMydriasis

PhenylephrinePhenylpropanolamine

Treat hypertension with phentolamineor nitroprusside, not with �-blockers alone

�- and �-Adrenergic Hypertension Amphetamines BenzodiazepinesTachycardia CocaineMydriasis EphedrineDiaphoresis PhencyclidineDry mucus membranes Pseudoephedrine

Sedative/hypnotic Stupor and coma Anticonvulsants NaloxoneConfusion Antipsychotics FlumazenilSlurred speechApnea

BarbituratesBenzodiazepinesEthanolMeprobamateOpiates

Urinary alkalinization forphenobarbital

Hallucinogenic Hallucinations Amphetamines BenzodiazepinesPsychosis CannabinoidsPanic CocaineFever Lysergic acid diethylamideMydriasisHyperthermiaSynesthesia

Phencyclidine (maypresent with miosis)

Extrapyramidal Rigidity/tremor Haloperidol DiphenhydramineOpisthotonos Phenothiazines BenztropineTrismus RisperidoneHyperreflexia OlanzapineChoreoathetosis

Narcotic Altered mental status Dextromethorphan NaloxoneSlow shallow breaths OpiatesMiosis PentazocineBradycardia PropoxypheneHypotensionHypothermiaDecreased bowel sounds

578 Critical Care Review



est number of deaths were analgesics, antidepres-sants, sedative/hypnotics/antipsychotics, stimulants,“street” drugs, cardiovascular drugs, and alcohols(Table 2). Of all deaths, 920 fatalities, a 5% increasecompared to 1999, 88% occurred in 20- to 99-year-old individuals. The mortality rate was higher inintentional rather than unintentional exposures (79%vs 10.5%, respectively).1

Diagnosis of Toxic Ingestion

History and Physical Examination

Table 3 includes clinical features mandating con-sideration of toxic ingestion. Although the history isimportant, it may be unreliable or incomplete.2 Con-sider that family members, friends, and pharmacistsmay have additional information. In the absence of aclassic presentation or toxidrome, separating patientswith suspected poisoning into broad categories based

on vital signs, ocular findings, mental status, and muscletone can help determine drug or toxin class.3

Vital Signs

Anticholinergic and sympathomimetic substancesincrease heart rate, BP, and temperature. In contrast,organophosphates, opiates, barbiturates, �-blockers,benzodiazepines, alcohol, and clonidine cause hypo-thermia, bradycardia, and respiratory depression. Table4 lists various toxins altering temperature. Drugs/toxinscausing tachycardia or bradycardia are listed in Table 5.

Ocular Findings

Anticholinergics and sympathomimetics cause my-driasis. In contrast to anticholingeric overdose, thepupils remain somewhat light responsive in cocaineintoxication. Table 6 lists drugs that affect pupil size.Horizontal nystagmus is common in alcohol intoxi-

Table 1—Continued

Toxidrome Features Drugs/Toxins Drug Treatment

Serotonin Irritability Fluoxetine BenzodiazepineHyperreflexia Meperidine Withdrawal of drugFlushing Paroxetine CyproheptadineDiarrhea SertralineDiaphoresis TrazodoneFever ClomipramineTrismusTremorMyoclonus

Epileptogenic Hyperthermia Strychnine Antiseizure medicationsHyperreflexia Nicotine Pyridoxine for isoniazidTremorsMay mimic stimulant

LindaneLidocaine

Extracorporeal removal of drug (lindane,camphor, xanthines)

patterns Cocaine Physostigmine for anticholinergic agentsXanthines Avoid phenytoin for theophyllineIsoniazid induced seizuresChlorinated hydrocarbonsAnticholinergicsCamphorPhencyclidine

Solvent Lethargy Hydrocarbons Avoid catecholaminesConfusion Acetone Withdrawal of toxinHeadache TolueneRestlessness NaphthaleneIncoordination TrichloroethaneDerealization Chlorinated hydrocarbonsDepersonalization

Uncoupling of oxidativephosphorylation

HyperthermiaTachycardiaMetabolic acidosis

Aluminum phosphideSalicylates2,4-DichlorophenolDinitrophenolGlyphosatePhosphorusPentachlorophenolZinc phosphide

Sodium bicarbonate for metabolic acidosisPatient coolingAvoid atropine and salicylatesHemodialysis in refractory acidosis




cation. Other drugs causing nystagmus are lithium,carbamazepine, solvents, meprobamate, quinine,and primidone. Phencyclidine and phenytoin causehorizontal, vertical, and rotary nystagmus.

Mental Status, Behavior, and Muscle Tone

It is important to determine whether the patient iscomatose, stuporous, lethargic, delirious, confused,or alert (Table 7). Some toxins cause seizures (Table8); others alter muscle tone (Table 9).

Laboratory Evaluation

Three gaps are important in toxicology: the aniongap, osmolal gap, and oxygen saturation gap. Toxi-

cology screening confirms (or not) toxin exposure butrarely alters management (see below).

Anion Gap

The normal range of anion gap may vary from 3to 12 mEq/L in some laboratories.4 An increase inanion gap (� 20 mEq/L) suggests lactic acidemia,uremia, ketoacidemia, or selected intoxications

Figure 1. Route of exposure for human poisoning. Data from the 2000 Toxic Exposure SurveillanceSystem of the American Association of Poison Control Centers.1

Table 2—Most Lethal Human Toxin ExposuresReported to Poison Control Centers in 2000*

Substance/ToxinCategory

Adult Exposures,No. (% of All

Adult Exposures)

Total Deathsper Category

IncludingChildren andAdults, No.†

Analgesics 92,245 (13.3) 405Alcohols (ethanol

and nonethanol)37,451 (5.4) 103

Antidepressants 55,429 (8) 242Cardiovascular

drugs28,941 (4.2) 108

Sedatives/hypnotics/antipsychotics

67,946 (9.8) 225

Stimulants andstreet drugs

17,423 (2.5) 187

*Data obtained from cases reported by 63 poison control centersduring 2000. Not all poisonings and intoxications are reported topoison control centers.1

†No. of deaths are based on an unlimited number of substancescoded per exposure.

Table 3—Clinical Features Mandating Considerationof Toxic Ingestion*

History of drug overdose or substance abuseSuicidal ideation or prior suicide attemptHistory of other psychiatric illnessAgitation and hallucinationsStupor or comaRotary nystagmusDelirium or confusionSeizuresMuscle rigidityDystoniaCardiopulmonary arrestUnexplained cardiac arrhythmiaHyper/hypotensionVentilatory failureAspirationBronchospasmLiver failureRenal failureHyper/hypothermiaRhabdomyolysisOsmolal gapAnion gap acidosisHyper/hypoglycemiaHyper/hyponatremiaHyper/hypokalemiaPolypharmacy

*Modified with permission from Corbridge and Murray.68




(Tables 10, 11). A normal anion gap does notpreclude intoxication because most toxins do notelevate the anion gap or there may be a coexistingcondition that lowers the gap (Table 10). Commonamong these conditions is hypoalbuminemia: forevery 1 g/L decrease in the plasma albumin, theanion gap falls by 2.5 mEq/L.5 Intensivists shouldpay special attention to this correction factor toavoid missing a clinically significant anion gap.Also, in methanol or polyethylene glycol poison-ing, concurrent ethanol use delays the develop-ment of an elevated anion gap metabolic acidosis.In this case, an elevated osmolal gap may be theonly early clue to the diagnosis.6

Osmolal Gap

Low-molecular-weight drugs and toxins increasethe discrepancy between measured and calculatedplasma osmolality (Table 12). Normal plasma osmo-lality is 285 to 295 mOsm. The calculated value isdetermined as follows:

Table 4—Drugs Affecting Temperature

Hypothermia Hyperthermia

Alcohols AmphetaminesBarbiturates AnticholinergicsCyclic antidepressants AntihistaminesHypoglycemic agents CocaineOpioids Cyclic antidepressantsPhenothiazines Drug withdrawalColchicine Lysergic acid diethylamideAkee fruit poisoning Monoamine oxidase inhibitorsLithium Malignant hyperthermia

Neuroleptic malignant syndromePhencyclidinePhenothiazinesSalicylatesSerotonin syndrome

Table 5—Selected Drugs/Toxins Causing Tachycardiaand Bradycardia*

Tachycardia Bradycardia

Amphetamines Antiarrhythmics (types 1a and 1c)Anticholinergics �-BlockersAntihistamines Calcium-channel blockersCaffeine CarbamatesCarbon monoxide ClonidineClonidine Cyclic antidepressantsCocaine DigoxinCyanide LithiumCyclic antidepressants MetoclopramideDrug withdrawal OpioidsEphedrine OrganophosphatesHydralazine PhenylpropanolamineHydrogen sulfide PhysostigmineMethemoglobinemia PropoxyphenePhencyclidine QuinidinePhenothiazinesPseudoephedrineTheophyllineThyroid hormone overdose


Table 6—Selected Drugs Affecting Pupil Size*

Miosis Mydriasis

Barbiturates AmphetaminesCarbamates AnticholinergicsClonidine AntihistaminesEthanol CocaineIsopropyl alcohol Cyclic antidepressantsOrganophosphates DopamineOpioids (meperidine may

cause mydriasis)Drug withdrawalGlutethimide

Phencyclidine Lysergic acid diethylamidePhenothiazines Monamine oxidase inhibitorsPhysostigmine PhencylidinePilocarpine


Table 7—Selected Drugs Altering Mental Status

Depressed PhysiologicState

Agitated PhysiologicState

Delirium andConfusion

Sympatholytics Sympathomimetics Alcohol/drugAdrenergic blockers Adrenergic agonists withdrawalAntiarrhythmics Amphetamines AnticholinergicsAntihypertensives Caffeine AntihistaminesAntipsychotics Cocaine Carbon monoxideCyclic antidepressants

CholinergicsBethanecholCarbamatesNicotineOrganophosphatesPhysostigminePilocarpine

Sedative/hypnoticsAlcoholsBarbituratesBenzodiazepinesGamma

hydroxybutyrateEthchlorvynol

NarcoticsAnalgesicsAntidiarrheal agents

OtherCyanideHydrogen sulfideHypoglycemic agentsLithiumSalicylates

Ergot alkaloidsMonoamine oxidase

inhibitorsTheophylline

AnticholinergicsAntihistaminesAntiparkinsonian

drugsAntipsychoticsAntispasmoticsCyclic antidepressantsCyclobenzaprine

Drug withdrawal�-blockersClonidineEthanolOpioidsSedative/hypnotics

HallucinogensLysergic acid

diethylamideMarijuanaMescalinePhencyclidine

OtherThyroid hormones

CimetidineHeavy metalsLithiumSalicylates




calculated osmolality � 1.86[Na�] � BUN/2.8

� glucose/18 � ethanol/4.6

in which Na� (in millimoles per liter) is multipliedby nearly two to account for accompanying anions(chloride and bicarbonate), and measured BUN,glucose, and ethanol are converted from milligramsper deciliter to mmol/L by the appropriate denomi-nator.

The osmolal gap must be interpreted with caution.Measurement of osmolality by vapor pressure os-mometry does not detect volatile alcohols such asethanol and methanol; however, it does detect eth-ylene glycol. Freezing point depression osmometry,the most frequently used method, measures all ofthese solutes.7,8 Therefore, it is important for clini-cians to know the method used by their institution toavoid missing methanol poisoning. By using thestandard formula, the normal osmolal gap may rangefrom � 9 mOsm to � 5 mOsm; 10 mOsm is consid-

ered the upper limit of normal.9 However, an osmo-lal gap of 10 mOsm in a patient who started at � 9mOsm may be significantly elevated.10–12

Oxygen Saturation Gap

An oxygen saturation gap is present when there ismore than a 5% difference between the saturationcalculated from an arterial blood gas and the satura-tion measured by co-oximetry. Co-oximetry deter-mines oxygen saturation by detecting the absorptionof four different wavelengths, enabling it to directlymeasure levels of four types of hemoglobin species:oxyhemoglobin, reduced hemoglobin, carboxyhemo-globin, and methemoglobin. However, arterial bloodgas analysis calculates oxygen saturation from themeasured oxygen tension using an assumed standard

Table 8—Common Drugs and Toxins CausingGeneralized Seizures*

AmphetaminesAntihistamines/anticholinergic agentsAntipsychoticsCaffeine/theophyllineCarbamatesCarbon monoxideCocaineCyclic antidepressantsEthylene glycolIsoniazidLeadLidocaineLithiumMethanolOrganophosphatesPhencyclidineHypoglycemic agent (focal)Chlorambucil (focal)PropranololSalicylatesWithdrawal from alcohol or sedative/hypnotics


Table 9—Selected Drugs Affecting Muscle Tone*

Dystonic Reactions Dyskinesias Rigidity

Haloperidol Anticholinergics Black widow spider biteMetoclopramide Cocaine Malignant hyperthermiaOlanzapine Phenylcyclidine Neuroleptic malignant

syndromePhenothiazines Risperidone PhenylcyclidineRisperidone Strychnine

Fentanyl


Table 10—Common Causes of Abnormal Anion Gap

Elevated Anion Gap Decreased Anion Gap

Lactic acidosis (type A) Increased unmeasured cationUremia HyperkalemiaSepsis HypercalcemiaRhabdomyolysis HypermagnesemiaKetoacidosis

DiabeticAlcoholicStarvation

Toxic ingestions*Ethylene glycolMethanolParaldehydeSalicylate

Metabolic alkalosis withvolume depletion

Acute lithium intoxicationElevated IgG (myeloma;

cationic paraprotein)Decreased unmeasured anion

HypoalbuminemiaDrugs

BromideIodideLithiumPolymyxin BTromethamine

Analytical artifactHypernatremia (� 170 mEq/L)Hyperlipidemia

*See Table 11.

Table 11—Selected Drugs Associated With an ElevatedAnion Gap Metabolic Acidosis

Acetaminophen (� 75 g)AmilorideAscorbic acidCarbon monoxideChloramphenicolColchicineNitroprussideDapsoneEpinephrineEthanolEthylene glycolFormaldehydeHydrogen sulfideIronIsoniazid

KetamineMetforminMethanolNiacinNitroprussideNonsteroidal anti-inflammatory drugsPapaverineParaldehyde (hippuric acid)PhenforminPropofolSalicylatesTerbutalineTetracycline (outdated)Toluene (hippuric acid)Verapamil




oxygen-hemoglobin dissociation curve. Toxins thatare associated with an elevated oxygen saturation gapinclude carbon monoxide, methemoglobinemia, cy-anide, and hydrogen sulfide (sulfhemoglobin is notroutinely measured by co-oximetry). Pulse oximetryestimates oxygen saturation by emitting a red light(wavelength of 660 nm) absorbed mainly by reducedhemoglobin and a near-infrared light (wavelength of940 nm) absorbed by oxyhemoglobin.13 Methemo-globin absorbs almost equally at both these wave-lengths. At high methemoglobin levels (35%), theoxygen saturation by pulse oximetry tends to regresstoward 85% and plateaus at that level despite furtherincrements in methemoglobin levels. Thus, if theactual oxygen saturation by co-oximetry is � 85%,the pulse oximetry would be underestimating it; if itis � 85% by co-oximetry, it would be overestimatingoxygen saturation.14 Therefore, pulse oximetry maybecome unreliable in the setting of methemoglobin-emia registering falsely high in patients with severemethemoglobinemia and falsely low with mild met-hemoglobinemia. Since many laboratories do notroutinely use co-oximetry, a more commonly seengap may be the disparity between measured oxygensaturation by blood gas and that measured by pulseoximetry.15 Oxygen saturation measured by pulseoximetry may be falsely elevated in methemoglobin-emia and should be utilized with caution in deter-mining the oxygen saturation gap.16,17 Carbon mon-oxide has a wavelength absorption coefficient similarto that of oxyhemoglobin; therefore, it is registeredas oxyhemoglobin by pulse oximetry leading to over-estimation of oxygen saturation when compared toco-oximetry. An abnormally high venous oxygencontent (arteriolization of venous blood) is charac-teristic of cyanide and hydrogen sulfide poisoning.

Toxicology Screening

In spite of providing direct evidence of intoxica-tion, screening tests alter management in � 5% of

cases.18,19 Toxicology screening can identify a spe-cific toxin for which an antidote is available and insome instances quantify a toxin allowing for titratedtherapy.

Most institutions offer urine testing for six orseven of the most commonly abused drugs (Table13). Results are generally available in 30 min. Morecomprehensive urine screening (usually performedoff-site) may take up to 2 to 3 h. Testing of blood orgastric contents is rarely indicated.20 However, bloodquantification of certain toxins is useful, particularlyin cases of alcohol (ethanol and nonethanol), acet-aminophen, salicylate, phenobarbital, theophylline,digoxin, iron, and lithium intoxication. A strongargument can be made for checking acetaminophenlevels in all cases of suspected intoxication given thesubtle manifestations of early acetaminophen poi-soning and importance of targeted therapy.

Poison Control Center Consultation

Regional poison control center consultation ishighly recommended in cases of suspected poisoningand to help guide management in confirmed cases.21

These centers provide 24-h emergency and up-to-date technical information. They are staffed bynurses, pharmacists, pharmacologists, and physicianstrained and certified in toxicology. The nationaltoll-free number for poison control centers is 800-222-1222.

Initial Supportive Measures

Airway, Breathing, Circulation

Supportive measures including the “ABCs” (air-way, breathing, circulation) are often required be-fore confirmation of intoxication. With cervical spineprecautions in place (unless trauma has been exclud-ed), airway patency must be ensured in all cases.Endotracheal intubation is not always necessarywhen cough and gag reflexes are present and there isadequate spontaneous ventilation, but when there isconcern regarding airway protection and clinical

Table 12—Drugs/Toxins Associated With an ElevatedOsmolal Gap*

Ethanol (if not included in the formula)Ethylene glycol/glycolaldehydeGlycerolGlycineIV immunoglobulin (maltose)Isopropanol/acetoneMannitolMethanol/formaldehydePropylene glycolRadiocontrast mediaHypermagnesemia (� 9.5 mEq/L)Sorbitol


Table 13—Drugs Commonly Included in UrineSubstances-of-Abuse Screens (Available in 30 min)*

AmphetaminesBarbituratesBenzodiazepinesCannabinoidsCocaineOpioidsPhencyclidine

*Immunoassay technique; modified with permission from Corbridgeand Murray.68




deterioration it is better to secure the airway. Intu-bation is indicated in acute respiratory failure (Table14 for causes of hypoxemia in intoxicated patients).Other specific indications include the need for highlevels of supplemental oxygen in carbon monoxidepoisoning and the need to protect the airway forgastric emptying. Endotracheal intubation decreases(but does not eliminate) the risk of aspiration (whichis approximately 11% in the comatose patient withdrug overdose).22–24

Depending on the intoxication, patients maypresent with hypotension or hypertension, brady-arrhythmias or tachyarrhythmias. The pathogenesisof hypotension varies and may include hypovolemia,myocardial depression, cardiac arrhythmias, and sys-temic vasodilation. Treatment should be individual-ized, but an initial strategy of rapid IV normal salinesolution infusion is indicated in most instances.Vasopressors may be required for refractory hypo-tension. The vasopressor of choice depends on thetype of intoxication (see below). Hypertension occursin the setting of sympathomimetic drugs, anticholin-ergics, ergot derivatives, phenylpropanolamine over-dose, and withdrawal from nicotine, alcohol, andsedatives. Treatment of the hypertension depends onits chronicity and severity and the inciting agent (seebelow). Hypertension-induced (reflex) bradycardiagenerally should not be treated.

Coma Cocktail

Immediately after establishing IV access, a “cock-tail” of thiamine, dextrose, and naloxone should beadministered to patients with depressed mental sta-tus. This cocktail can be both therapeutic and diag-nostic.25 Thiamine (100 mg by vein) is administeredto treat and/or avoid Wernicke-Korsakoff syndromein comatose patients. This strategy is not well sup-ported by the literature, and few patients regainconsciousness following thiamine infusion. Still, rou-tine use of thiamine is safe, inexpensive, andprevents the possibility of delayed deterioration sec-ondary to nutritional deficiency.25 Thiamine is par-ticularly important in the nutritionally deplete alco-holic. There is no evidence that dextrose should bewithheld until thiamine is administered.26 Comatosepatients should receive dextrose, 50 g IV. A normalvalue by blood dipstick does not necessarily excludelow serum glucose. A high value on dipstick testingshould lead to rapid confirmation by blood draw,thus avoiding unnecessary dextrose (although admin-istration of dextrose to hyperglycemic patients isunlikely to cause harm).25 Naloxone rapidly reversescoma, respiratory depression, and hypotension in-duced by opioids. An initial dose of 0.2 to 0.4 mg isadministered IV (or endotracheally). If there is no

Table 14—Selected Causes of Hypoxemia in DrugOverdose and Toxic Ingestion*

Cause Drugs/Toxins

Hypoventilation AlcoholsBarbituratesBenzodiazepinesBotulinum toxinCyclic antidepressantsNeuromuscular blockadeOpioidsSedative/hypnoticsSnake biteStrychnineTetanus

Aspiration Drugs/toxins depressing mental status

Pneumonia Drugs resulting in aspiration; IV drugabuse with pulmonary seeding ofinfectious agents; inhalation injuryinterfering with lung protectivemechanisms

Cardiogenicpulmonary edema

Antiarrhythmics�-BlockersCyclic antidepressantsVerapamil

Inert gases Carbon dioxideMethaneNitrogenPropane

Noncardiogenicpulmonary edema

CocaineEthylene glycolHydrocarbonsInhalation injuryOpioidsPhosgeneParaquatSalicylates

Bronchospasm �-BlockersCocaineHeroinOrganophosphatesDrugs resulting in aspirationDrugs associated with myocardial

depression (cardiac asthma)Alveolar hemorrhage Cocaine

AnticoagulantsThrombolyticsAmiodaroneParaldehydeNitrofurantoinPenicillamineToluene

Pneumothorax CocaineIV drug abuse with aberrant

venipuncture or bullous lungdisease

KeroseneCellular hypoxia Carbon monoxide

CyanideHydrogen sulfideMethemoglobinemiaSulfhemoglobinemia





response after 2 to 3 min, an additional 1 to 2 mg canbe administered and repeated up to 10 mg asrequired. Using a higher dose up front may pre-cipitate large cardiovascular changes in opioiddependent patients. Several opioids such as me-peridine, propoxyphene, diphenoxylate, metha-done, and pentazocine require large doses ofnaloxone,27 but lack of response to 10 mg ofnaloxone generally excludes opioid toxicity. Opioidantagonism with naloxone lasts 1 to 4 h requiringrepeat doses or continuous infusion in significantintoxication.28 Acute pulmonary edema,29,30 opioidwithdrawal,31 and seizures32 have been reportedwith naloxone administration.

Flumazenil should be considered in cases werebenzodiazepine overdose is suspected or reversal oftherapeutic conscious sedation is desired.25,33 Casereports have cautioned clinicians of the risk ofprecipitating seizures with flumazenil when there is asuspicion of benzodiazepine plus cyclic antidepres-sant overdose.34,35 Nonetheless, data suggest thatflumazenil is safe as part of the coma cocktail evenwith coma induced by the combination of benzodi-azepines and cyclic antidepressants.36 In a largeprospective trial of unconscious patients suspected ofbenzodiazepine overdose, Weinbroum et al36 ran-domized patients to receive either placebo or fluma-zenil in addition to usual care. Seventy-one percentof the patients had concomitant cyclic antidepressantingestion. These investigators did not observe anysignificant side effects with flumazenil, even in pa-tients with coma caused by a mixed overdose ofbenzodiazepine and cyclic antidepressants. We typ-ically administer an initial 0.2 mg of IV flumazenilover 30 s followed by another 0.3-mg dose if neces-sary. Doses beyond 3 mg generally do not provideadditional benefit. Repeat sedation may occur in thesetting of high-dose or long-term use of benzodiaz-epines. Although flumazenil is successful in improv-ing the Glasgow coma scale score, it does not appearto alter cost or major diagnostic/therapeutic inter-ventions in patients presenting with decreased levelof consciousness due to an intentional unknown drugoverdose.37 Therefore, the cost-effectiveness of rou-tine use of flumazenil as part of the coma cocktailremains controversial,38 except in cases of acutebenzodiazepine overdose.36

Prevention of Absorption

The route of entry for toxic substances can bedermal, ocular, GI, inhalational, or parenteral (Fig1). Skin decontamination requires removal of thetoxin with nonabrasive soap and water. Contami-nated clothing may serve as a reservoir for continued

exposure and must be removed with caution andplaced in plastic bags or other containers that areimpervious to the toxin. This will limit exposure tomedical personnel and patient. Ocular decontamina-tion may require prolonged periods of irrigation withnormal saline solution using a Morgan lens (MorTan;Missoula, MT). Inhalational exposure presents agreater challenge since the toxin cannot be accessedand removed. Inhalational lung injury is beyond thescope of this review. The majority of toxin exposuresand poisonings managed by intensivists occurthrough the GI tract. There are four methods of GIdecontamination including three mechanical ap-proaches (emesis, gastric emptying or gastric lavage[GL], and whole-bowel irrigation) and the use ofactivated charcoal combined with a cathartic.

Emesis

Ipecac-induced emesis should be considered onlyin fully alert patients, and is virtually never indicatedafter hospital admission. Ipecac is generally lesstraumatic than GL, and is therefore the preferredmethod of gastric emptying in pediatric patients.Ipecac may be helpful at home if administeredimmediately after ingestion. In the best of circum-stances, a 30 to 40% removal rate can be achievedwithin 1 h after ingestion.39 Because of questionableefficacy hours after ingestion, in-hospital use is de-creasing.40,41 Contraindications to its use includepoisoning with corrosives, petroleum products, orantiemetics. The potential for aspiration precludesits use in situations where there is a high risk ofseizures (ingestion of a rapidly acting convulsantsuch as strychnine) or altered consciousness.42 Theusual dose of ipecac syrup in adults is 30 mLfollowed by 16 oz of water. This dose usuallyinduces vomiting within 20 to 30 min. The dosecan be repeated once after 30 min if vomiting doesnot occur. There is little evidence that ipecacprevents drug absorption or systemic toxicity,43

and there are no convincing data that it signifi-cantly alters the clinical outcome of patients whoare awake and alert on presentation to the emer-gency department. Ipecac is rarely used (approxi-mately 1% of all overdoses reported to the poisoncenters),1 and its use may soon be confined to themedical history books.

Gastric Emptying

GL through a 28F to 40F Ewald tube is similarlyaimed at physically removing a toxin. Prior to insert-ing the Ewald tube, the mouth should be inspectedfor foreign material and equipment should be readyfor suctioning. Large gastric tubes (37F to 40F) areless likely to enter the trachea than smaller nasogas-




tric tubes, and are necessary to facilitate removal ofgastric debris. After insertion, proper position needsto be confirmed by aspirating acidic stomach con-tents and auscultating the left upper abdominalquadrant during insufflation of air. Experiencedpersonnel should perform GL in a facility whereresources are available to manage complications.Nonintubated patients must be alert (and be ex-pected to remain alert) and have adequate pharyn-geal and laryngeal protective reflexes. In semicoma-tose patients, GL should be performed only after acuffed endotracheal tube has been inserted. Intuba-tion for the sole purpose of gastric emptying isreasonable only if there is a high likelihood that ahighly lethal agent remains in the stomach.

GL is performed by instilling 200-mL aliquots ofwarmed tap water until there is clearing of aspiratedfluid. Stomach contents should be retained for anal-ysis. Tap water may avoid unnecessary salt loadingcompared to normal saline solution. Neither irriganthas been shown to significantly alter blood cell orelectrolyte concentrations.44 After clearing, theEwald tube may be replaced by a nasogastric tubefor subsequent intermittent suctioning and/or ad-ministration of activated charcoal.

GL has been advocated in the initial managementof many orally ingested agents. The risks associatedwith this procedure include aspiration, arrhythmias,and stomach perforation.45 Because of these risks,GL should not be performed in patients who haveingested a nontoxic substance, a nontoxic amount ofa toxic substance, or when the toxin is no longerexpected to be present in the stomach. Examplesinclude patients who have vomited extensively priorto hospital admission, patients who present severalhours after ingesting an agent that does not decreasegut motility, and patients who have received agentsthat are readily absorbed from the GI tract. AlthoughGL has been common in the management of patientswith toxic ingestion, its use remains controversial.46

In obtunded patients, GL results in a more satisfac-tory clinical outcome only if performed within 1 h47

or 2 h of ingestion.48 Kulig et al47 compared theutility of GL plus activated charcoal in 72 obtundedpatients with 44 obtunded patients who receivedonly activated charcoal by nasogastric tube andsupportive care. They reported an improved clinicalcourse if lavage was performed within 1 h of inges-tion. In contrast, Pond et al49 performed a prospec-tive, randomized, controlled trial of 347 obtundedpatients receiving GL plus activated charcoal oractivated charcoal alone. There was no significantdifference in outcome even when patients presentedwithin 60 min of ingestion. Because of limited data,the American Academy of Clinical Toxicology doesnot recommend routine use of GL in the manage-

ment of poisoning unless a patient has ingested apotentially life-threatening amount of a poison andthe procedure can be undertaken within 60 min ofingestion.50 Although controversial, some expertssuggest that the time limit may be extended to 12 hin cases of poisoning with agents that delay gastricemptying such as tricyclic antidepressants, opioids,or salicylates. In addition, gastric emptying may bebeneficial if the ingested drug is not adsorbed byactivated charcoal (eg, ferrous sulfate, lithium). Incases of ingestion of a caustic liquid such as keroseneor its derivatives, GL should be avoided because ofthe risk of aspiration-induced lung injury. Clinicalstudies evaluating the efficacy of GL are limited bysmall study size, heterogeneity of toxins studied, anddifferent methodologies. There is also a concern thatGL may propel material into the duodenum increas-ing the chance of drug absorption.51

Activated Charcoal

Charcoal is a by-product of the combustion ofvarious organic compounds such as wood, coconutparts, bone, sucrose, rice, and starch. Its adsorptivecapacity is increased or activated by removing mate-rials previously adsorbed by a process that involvessteam heating and chemical treatment, thereby in-creasing the surface area available for adsorption tobetween 1,000 m2/g and 3,000 m2/g. This results in apowerful, inert, nontoxic, and nonspecific adsorbentthat irreversibly binds intraluminal drugs and inter-feres with their absorption. It is particularly effectivein binding high-molecular-weight compounds. Acti-vated charcoal decreases serum drug levels in somecases by creating a favorable diffusion gradient be-tween blood and gut, referred to as GI dialysis (seebelow).52 The efficacy of activated charcoal has leadto a resurgence of its use over the past few years.

Charcoal can be administered after both GL oripecac-induced emesis, but it is usually administeredas the sole GI decontaminating agent. Airway pro-tection is imperative in stuporous, comatose, orconvulsing patients. Prior gastric stapling is an addi-tional risk factor for emesis and aspiration with singleor repeated doses.53 Charcoal aspiration has beenassociated with pneumonia54 (including fungal pneu-monia55), bronchiolitis obliterans,56 ARDS,57 anddeath.58

Despite the mentioned complications, activatedcharcoal is generally effective and well tolerated.Complications are infrequent. The ideal dose shouldgive a charcoal-to-drug ratio of 10:1. However, sincethe quantity of poison ingested is usually unknown tothe clinician, the dose is based on actual patientweight (1 g/kg). It is commonly co-administered witha cathartic (see below) to facilitate evacuation of the




toxic substance and avoid constipation. Commonlyused agents include magnesium sulfate, magnesiumcitrate, or sorbitol. Mixing the solution with juicemay increase acceptance of this black and grittyadsorbent in children and adults. Single-dose acti-vated charcoal is effective against most toxins anddrugs. Table 15 lists selected toxins for which char-coal is not particularly effective. Based on volunteerstudies, the effectiveness of activated charcoal de-creases with time; the greatest benefit is within 1 h ofingestion.59

Catharsis

The use of cathartics with activated charcoal mayreduce the transit time of drugs and toxins in the GItract and decrease the constipating effects of char-coal. Sorbitol is the cathartic of choice. It is generallyadministered only with the first dose of activatedcharcoal. The usual dosage is 1 to 2 mL/kg of a 70%solution of sorbitol titrated to several loose stoolsover the first day of treatment (total dose, 1 g/kg).Magnesium-based cathartics (2 to 3 mL/kg po of a10% solution of magnesium sulfate) may lead tomagnesium accumulation in the setting of renalfailure, and sodium-based products carry the risk ofexacerbating hypertension or congestive heart fail-ure. Oil-based cathartics, if aspirated, may producelipoid pneumonia.

Cathartics have never been shown to decreasemorbidity and mortality or to decrease hospitalstay.60 In a cross-over study, Keller et al61 demon-strated that activated charcoal with sorbitol led to a28% decrease in the absorption of salicylates whencompared to activated charcoal alone. However,McNamara and colleagues62 were unable to demon-strate enhanced efficacy of activated charcoal withsorbitol catharsis in a simulated acetaminophen over-dose. Based on available data, the routine use of acathartic in combination with activated charcoal isnot endorsed by the American Academy of ClinicalToxicology and the European Association of PoisonsCenters and Clinical Toxicologists. If a cathartic is

administered, it should be limited to a single dose inorder to minimize adverse effects.63

Whole-Bowel Irrigation

Whole-bowel irrigation with a polyethylene glycol,electrolyte solution (Colyte; Schwarz Pharma; Mil-waukee, WI) or potassium chloride (Golytely; Brain-tree Laboratories; Braintree, MA), 1 to 2 L/h, inadults is used to push tablets or packages through theGI track. The optimal regimen in regards to volumeinfused per hour, duration of use, and dosage ofactivated charcoal prior to whole-bowel irrigation hasnot been well established.46 It may take 3 to 5 h forcomplete bowel irrigation to clear the rectal effluent.These isotonic solutions are not absorbed and do notcause major electrolyte shift or imbalance.64 Thetechnique is time consuming and requires a cooper-ative patient. Most studies supporting this approachare limited to case reports, and there are no estab-lished indications for its use. However, whole-bowelirrigation may have a role in intoxications whereactivated charcoal is not effective, such as ingestionof iron and sustained-release tablets, lithium, or incases of “body packing” with packages of illicitdrugs.65 Contraindications to whole-bowel irrigationinclude ileus, GI hemorrhage, and bowel perforation.

Enhancement of Elimination

Forced Diuresis and Urinary pH Manipulation

Routine use of volume-loading to promote diuresishas not been well studied or supported in theliterature and cannot be recommended. Its goal is toaugment elimination of renally excreted toxinsthrough inhibition of tubular reabsorption. Thus, inorder to be effective, the toxin needs to undergoextensive tubular reabsorption that can be inhibitedby forced diuresis. However, forced diuresis has thepotential to cause electrolyte imbalance, pulmonaryedema, and raised intracranial pressure.66 The tech-nique consists of achieving a urine flow rate from 3to 6 mL/kg/h with a combination of isotonic fluidsand/or diuretics.67 When tubular reabsorption of atoxin is pH sensitive, then increased urine flow doesnot significantly increase urinary drug eliminationwhen added to alkaline or acid diuresis.

Manipulation of urinary pH can be used therapeu-tically to enhance elimination of some intoxicants(Table 16). The limits of urinary pH are 4.5 to 7.5under conditions of enhanced acidification and alka-linization. Thus, elimination of very strong (negativelogarithm of the acid ionization equilibrium constant[pKa] � 3) or very weak (pKa � 8) acids is unalteredby urinary pH manipulation. Other acidic or basic

Table 15—Toxins and Drugs Not Adsorbed byActivated Charcoal

AlcoholsHydrocarbonsOrganophosphatesCarbamatesAcidsPotassiumDichloro diphenyl trichloroethane (DDT)AlkaliIronLithium




drugs do not undergo renal tubular absorption,irrespective of urinary pH, since they are polar intheir nonionized form.

Urinary alkalinization (pH � 7) is most often usedto eliminate salicylates and phenobarbital. It can beachieved by administration of IV sodium bicarbonate(1 to 2 mEq/kg every 3 to 4 h); this may beadministered as two 50-mL ampules of 8.4% sodiumbicarbonate (each containing 50 mEq of NaHCO3)per liter of 5% dextrose in water infused at250 mL/h. Complications of this therapy includealkalemia (particularly in the presence of concurrentrespiratory alkalosis), volume overload, hypernatre-mia, and hypokalemia. It is particularly important toavoid hypokalemia, which prevents excretion of al-kaline urine by promoting distal tubular potassiumreabsorption in exchange for hydrogen ion. Accord-ingly, bicarbonate administration in the presence ofsignificant hypokalemia will not alkalinize the urine,yet will increase the risk of alkalemia. Since urinaryalkalinization therapy can cause hypokalemia (due toalkalemia-induced intracellular potassium shift andincreased urinary potassium loss with alkaline diure-sis), addition of potassium chloride to the bicarbon-ate infusion is commonly required. Acetazolamideshould not be used to alkalinize urine. Resultantmetabolic acidosis can increase toxicity of certainpoisonings (particularly in the case of salicylatepoisoning).68

Urinary acidification (pH � 5.5) increases renalclearance of some nonpolar weak bases with pKavalues between 6 and 12. Arginine or lysine hydro-chloride or ammonium chloride have been used forurinary acidification. However, due to the potentialof urinary acidification to exacerbate myoglobinuricrenal tubular injury, this therapy is virtually neverused. Also, systemic acidosis must be avoided inorder to avoid potential additive effects with toxin-induced metabolic or respiratory acidosis.68

Multiple-Dose Activated Charcoal

Multiple-dose activated charcoal can be an effec-tive way to enhance the elimination of toxins that

have been absorbed.69 The mechanism by which thismodality accomplishes enhancement of eliminationis either by interrupting the enterohepatic/entero-gastric circulation of drugs or through the binding ofany drug that diffuses from the circulation into thegut lumen (called GI dialysis). However, it haslimited application because the toxin must have a lowvolume of distribution, low protein binding, pro-longed elimination half-life, and low pKa, whichmaximizes transport across mucosal membranes intothe GI tract.67 Although optimal dosage and fre-quency of administration following the initial dose ofactivated charcoal is not well established, most ex-perts recommend a dose not � 12.5 g/h.70 After theinitial dose of 1 g/kg, activated charcoal may beadministered at 0.5 g/kg every 2 to 4 h for at leastthree doses. Cathartics are generally not adminis-tered to avoid hypernatremia, hypokalemia, andhypermagnesemia. Multiple dosing should be usedwith caution in patients with decreased bowelsounds, abdominal distension, and persistent emesis.Unless a patient has an intact or protected airway,the administration of multidose charcoal is contrain-dicated. In a review of all the relevant scientificliterature, the American Academy of Clinical Toxi-cologists reported that although multidose charcoalenhances drug elimination significantly, it has not yetbeen evaluated in a controlled trial of poisonedpatients with the objective of demonstrating a reduc-tion in morbidity and mortality.71 Table 17 providesa list of drugs and toxins where there may be a rolefor multiple dosing of activated charcoal.67 However,based on experimental and clinical studies, it shouldbe considered only in patients with a life-threateningingestion of carbamazepine, dapsone, phenobarbital,quinine, or theophylline.71

Table 16—Toxins Eliminated by UrinaryAlkalinization

2,4 Dichlorophenoxy-acetic acidFluorideIsoniazidMephobarbitalMethotrexatePhenobarbitalPrimidoneQuinolone antibioticsSalicylic acidUranium

Table 17—Toxins and Drugs Eliminated by MultipleDosing of Activated Charcoal*

Amitriptyline MeprobamateAmoxapine MethyprylonBaclofen (?) NadololBenzodiazepines (?) NortriptylineBupropion (?) PhencyclidineCarbamazepine PhenobarbitalChlordecone PhenylbutazoneDapsone Phenytoin (?)Diazepam PiroxicamDigitoxin PropoxypheneDigoxin QuinineDisopyramide Salicylates (?)Glutethimide SotalolMaprotiline Theophylline

*? Represents equivocal data.




Extracorporeal Removal of Toxins

In situations where previously mentioned support-ive measures fail to improve a patient’s condition,extracorporeal removal of toxins can be lifesav-ing.72,73 Although clear proof that extracorporealtoxin removal favorably alters the course of anyintoxication is generally lacking,74 it should be con-sidered when the intoxication is projected to un-dergo delayed or insufficient clearance because ofother organ dysfunction, the intoxicating agent pro-duces toxic metabolites, or delayed toxicity is char-acteristic of the intoxication. In addition to physico-chemical properties of the intoxicant, serum toxinlevels or certain clinical features may mandate extra-corporeal removal techniques. Three methods forextracorporeal removal of toxins are generally avail-able: (1) dialysis (usually hemodialysis rather thanperitoneal dialysis), (2) hemoperfusion; and (3) he-mofiltration. Plasmapheresis and exchange transfu-sion are rarely used and will not be further discussedin this review. A complete list of drugs and toxinsthat may be removed by different extracorporealremoval techniques is beyond the scope of thisreview.67,68

Hemodialysis

Hemodialysis is the primary extracorporealmethod to remove toxins or drugs. Toxins for which

hemodialysis may be useful should have a low mo-lecular weight (� 500 d), be water soluble, have lowprotein binding (� 70 to 80%), and have a smallvolume of distribution (� 1 L/kg). It can especiallybe effective in correcting concomitant electrolyteabnormality and metabolic acidosis. Toxins in whichhemodialysis may be required in an early stage ofintoxication include methanol, ethylene glycol, boricacid, salicylates, and lithium. Hemodialysis can alsobe used for heavy metal chelation in patients withrenal failure.

Hemoperfusion

Hemoperfusion is defined as direct contact ofblood with an adsorbent system.75 Charcoal he-moperfusion involves pumping blood through acharcoal canister. Unlike hemodialysis, drug clear-ance is not limited by low water solubility, highmolecular weight, or increased protein binding, buton the ability of the adsorbent to bind to thedrug/toxin. However, the toxin needs to be presentin the central compartment for hemoperfusion to beeffective. Hemoperfusion is essentially the paren-teral analog of oral activated charcoal. Complicationsof hemoperfusion include the following: (1) cartridgesaturation; (2) thrombocytopenia that commonly oc-curs due to platelet adsorption, inducing up to 30%decrement in platelet count; (3) hypoglycemia andhypocalcemia; (4) access complications; (5) hypo-

Table 18—Antidotes*

Drug/poison Antidotes

Acetaminophen N-acetylcysteineAnticholinergics PhysostigmineAnticholinesterases AtropineBenzodiazepines FlumazenilBlack widow spider bite Equine-derived antiveninCarbon monoxide OxygenCoral snake (Eastern and

Texas) biteEquine-derived antivenin

Cyanide Amyl nitrite, sodium nitrite, sodiumthiosulfate, hydroxycobalamin

Digoxin Digoxin-specific antibodiesEthylene glycol Ethanol/fomepizole, thiamine, and

pyridoxineHeavy metals (arsenic,

copper, gold, lead,mercury)

Dimercaprol (BAL), EDTA,penicillamine

Hypoglycemic agents Dextrose, glucagon, octreotideIron Deferoxamine mesylateIsoniazid PyridoxineMethanol Ethanol or fomepizole, folic acidMethemoglobinemia Methylene blueOpioids NaloxoneOrganophosphate Atropine, pralidoxamineRattlesnake bite Equine-derived antivenin

*EDTA � ethylenediamine tetra-acetic acid.

Table 19—Criteria for Admission of the PoisonedPatient to the ICU*

Respiratory depression (Paco2 � 45 mm Hg)Emergency intubationSeizuresCardiac arrhythmia (second- or third-degree atrioventricular block)Systolic BP � 80 mm HgUnresponsiveness to verbal stimuliGlasgow coma scale score � 12Need for emergency dialysis, hemoperfusion, or ECMOIncreasing metabolic acidosisPulmonary edema induced by toxins (including inhalation) or drugsHypothermia or hyperthermia including neuroleptic malignant

syndromeTricyclic or phenothiazine overdose manifesting anticholinergic

signs, neurologic abnormalities, QRS duration � 0.12 s, or QT� 0.5 s

Body packers and stuffersConcretions caused by drugsEmergency surgical interventionAdministration of pralidoxime in organophosphate toxicityAntivenom administration in Crotalidae, coral snake, or arthropod

envenomationNeed for continuous infusion of naloxoneHypokalemia secondary to digitalis overdose (or need for digoxin-

immune antibody Fab fragments)

*ECMO � extracorporeal membrane oxygenation.




thermia, since hemoperfusion pumps do not warmblood as hemodialysis does; and (6) charcoal embo-lization (prevented by a filter in the line returningeffluent blood to the patient).

Most drugs are extractable by hemoperfusion,which is particularly suitable for extracorporeal re-moval of toxins that are of high molecular weight,highly protein bound, or lipid soluble. It has beeneffectively used to enhance elimination of theophyl-line, phenobarbital, phenytoin, carbamazepine, para-quat, and glutethimide. Drugs poorly extracted byhemoperfusion include the following: heavy metals(lithium, bromide), some alcohols (ethanol, metha-nol), carbon monoxide, and some illicit drugs (co-caine, phencyclidine, and others). Efficacy of intox-icant removal is diminished for substances with alarge volume of distribution that are highly lipidsoluble and/or extensively tissue bound. These intox-icants may be more effectively removed by hemofil-tration.

Hemofiltration

Hemofiltration achieves drug and toxin removal byconvection. It transports solutes through a highlyporous membrane that is permeable to substanceswith weights of up to 6,000 d, including virtually alldrugs. In some cases, hemofiltration membranes arepermeable to substances weighing up to 20,000d.76,77 Although the application of this technique hasnot been vigorously studied in poisoned patients,there are increasing numbers of case reports ofextracorporeal intoxicant removal by either the con-tinuous arteriovenous or venovenous hemofiltrationmethods.78–80 Hemofiltration is potentially useful forremoval of substances with a large volume of distri-bution, slow intercompartmental transfer, or exten-sive tissue binding. Specific highly porous hemofil-tration cartridges are also particularly useful forremoval of large-molecular-weight solutes or com-plexes, such as combined digoxin-Fab fragment com-plexes, or desferoxamine complexes with iron or withaluminum.

Antidotes

An antidote is a substance that increases the meanlethal dose of a toxin, or that can favorably affect thetoxic effects of a poison. Some are toxic themselvesand therefore should be used only when indicated.Table 18 lists antidotes for specific drugs/poisons.These will be discussed further next month in part IIof this article.

Indications for ICU Admission

In the current health-care climate, the practice ofroutinely admitting the poisoned patient to the ICUis being questioned. Brett et al81 identified eightclinical risk factors that can predict ICU interven-tions: (1) Paco2 � 45 mm Hg, (2) need for endotra-cheal intubation, (3) toxin-induced seizures, (4) car-diac arrhythmias, (5) QRS duration � 0.12 s,(6) systolic BP � 80 mm Hg, (7) second- or third-degree atrioventricular block, and (8) unresponsive-ness to verbal stimuli. In this retrospective study, if apoisoned patient did not exhibit any of the eightcharacteristics, no ICU interventions (intubation,vasopressors or antiarrhythmics, and dialysis or he-moperfusion) were required. Other indications forICU admission include a Glasgow coma scale score� 12,82 need for emergency dialysis or hemoperfu-sion, progressive metabolic acidosis, and a cyclicantidepressant or phenothiazine overdose with signsof anticholinergic cardiac toxicity.83,84 Severe hyper-kalemia, wide alterations in body temperature, andneed for continuous infusion of naloxone are alsoreasons to admit a patient to an ICU. In addition,staffing issues such as the availability of a “sitter” incases of attempted suicide may impact patient dis-position. Table 19 provides a list of criteria for ICUadmission.67

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DOI 10.1378/chest.123.2.577 2003;123;577-592 Chest

Babak Mokhlesi, Jerrold B. Leiken, Patrick Murray and Thomas C. Corbridge Intoxicated Patient

Adult Toxicology in Critical Care: Part I: General Approach to the

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