Jerrold B. Leikin
The general treatment plan is support of the airway, breathing, and circulation before addressing the poisoning specific treatments with an organized approach essentially similar irrespective of the toxic exposure. This basic poison management encompasses the following intervention (Fig. 296.1):
FIGURE 296.1 The algorithm is a basic guide to the management of poisoned patients. A more detailed description of the steps in management may be found in the accompanying text. This algorithm is only a guide to actual management, which must, of course, consider the patient’s clinical status.
1. Prevention of absorption or decontamination
2. Antidote administration, if available
3. Removal of absorbed toxin or enhancing elimination
4. Support and monitoring for adverse effects
PREVENTION OF ABSORPTION
The route of entry for toxic substances can be dermal, ocular, GI, inhalational, or parenteral. Skin decontamination requires removal of the toxin with nonabrasive soap and copious irrigation with water. Contaminated clothing may serve as a reservoir for continued exposure and must be removed with caution and placed in plastic bags or other containers that are impervious to the toxin. This will limit exposure to medical personnel and patient. Ocular decontamination may require prolonged periods of irrigation with normal saline solution using a Morgan lens. Inhalational exposure presents a greater challenge since the toxin cannot be accessed and removed. Most irrigant solutions for ocular, dermal, or gastrointestinal lavage are water or saline based with a few exceptions. The vast majority of toxin exposures and poisonings occur through the gastrointestinal (GI) tract (1). There are three methods of GI decontamination including (1) gastric lavage (GL), (2) whole-bowel irrigation (WBI), and (3) activated charcoal (2,3). Syrup of ipecac, previously used, is relegated to medical history or veterinary toxic exposures (4–7).
Gastric Emptying
GL through a 28- to 40-French Ewald tube is aimed at physically removing an unabsorbed toxin (Table 296.1) (8–10). Before inserting the Ewald tube, the mouth should be inspected for foreign material and equipment should be ready for suctioning. Large gastric tubes are less likely to enter the trachea than smaller nasogastric tubes, and have large holes to facilitate removal of gastric debris. After insertion, proper position should be confirmed by aspirating stomach contents and auscultating the left upper abdominal quadrant during insufflation of air. Nonintubated patients should be alert (and be expected to remain alert) and have adequate gag reflexes. In unresponsive patients, GL should be performed after a cuffed endotracheal tube has been inserted. Intubation for the sole purpose of gastric emptying is reasonable only if there is a high likelihood that a highly lethal agent remains in the stomach. GL is performed by instilling 200-mL aliquots of warmed tap water until there is clearing of aspirated fluid. After clearing, the Ewald tube may be replaced by a nasogastric tube for subsequent intermittent suctioning and/or administration of activated charcoal.
TABLE 296.1
Toxins which Should be Lavaged with Solutions Other Than Water
Activated Charcoal
Charcoal is a by-product of the combustion of compounds such as wood, coconut parts, bone, sucrose, rice, and starch. Its adsorptive capacity is increased or “activated” by removing materials previously adsorbed with steam heating and chemical treatment, increasing the surface area for adsorption to between 1,000 and 3,000 m2/g. This results in an inert, nontoxic, and nonspecific adsorbent that binds intraluminal drugs soon after ingestion and thus interferes with their absorption. Single-dose activated charcoal is effective against most toxins and drugs but should be used for cases with a higher probability of injury or illness Table 296.2. It is particularly effective in binding high–molecular-weight compounds and is ineffective for small ions such as lithium or potassium, acids, alkali, hydrocarbons, alcohols, and heavy metals Table 296.3. Activated charcoal decreases serum drug levels in some cases by creating a favorable diffusion gradient between blood and gut, often referred to as Gastrointestinal dialysis(8,10,11).
TABLE 296.2
Examples of Substances Removed by Activated Charcoal
TABLE 296.3
Toxins and Drugs Not Absorbed by Activated Charcoal
Charcoal can be administered after gastric lavage, but it is usually the sole GI decontaminating method (10–12). Airway protection is imperative in stuporous, comatose, or convulsing patients.
Activated charcoal is contraindicated in patients with central nervous system depression with an unprotected airway due to the risk of aspiration. Similarly, hydrocarbon ingestions are also an increased aspiration risk. Individuals at risk for gastrointestinal bleeding or perforation due to previous pathology, recent surgery, or other pre-existing medical conditions may be at increased risk for complications. Activated charcoal should not be administered if endoscopy is being considered. Complications are infrequent; however, charcoal aspiration has been associated with pneumonia, bronchiolitis obliterans, ARDS, and bronchial obstruction, particularly in very young children. Emesis is usually related to use of sorbitol when combined with activated charcoal. Considering the frequency of use of activated charcoal, the complication rate is relatively low but considering the low fatality rate of most poisonings, the greatest benefit is for chemicals or drugs with a high fatality rate such as cyclic antidepressants or calcium channel blockers.
The ideal dose should give a charcoal-to-drug ratio of 10:1. However, since the quantity of poison ingested is usually unknown, the dose is often based on patient weight (0.5 to 1 g/kg). In adolescents and adults, the usual dose is 25 to 100 g. Table 296.2 lists toxins for which charcoal is not particularly effective (13). Based on volunteer studies, the effectiveness of activated charcoal decreases with time; the greatest benefit is within 3 hours of ingestion although its overall clinical benefit (over that of supportive care) has been challenged (14).
The use of cathartics with activated charcoal may reduce the transit time of drugs and toxins in the GI tract and decrease the constipating effects of charcoal. The two types of osmotic cathartics used are saccharide based (sorbitol) and saline based (magnesium citrate, magnesium sulfate, sodium sulfate. Cathartics may decrease drug absorption but have never been shown to decrease morbidity and mortality or to decrease hospital stay (15–17). Based on available data, the routine use of a cathartic in combination with activated charcoal is not generally recommended (17).
Whole-Bowel Irrigation
WBI with polyethylene glycol electrolyte solution has been used over the past 20 years to prevent toxin absorption by cleansing the gastrointestinal tract. Since no net absorption or secretion of ions occurs, no significant change in water or electrolyte balance would be expected. WBI may have a role in intoxications where activated charcoal is not effective and considered for potentially toxic ingestions of sustained release or enteric-coated tablets, substantial amounts of iron, lead or other metals or ions such as lithium or packets of illicit drugs. The solution is best administered through a small bore 12-French nasogastric tube at age-based dosing: children 9 months to 6 years: 500 mL/hr, children 6 to 12 years: 1,000 mL/hr, adolescents and adults: 1,500 to 2,000 mL/hr. The patient should be seated or the head of the bed elevated to at least 45 degrees to decrease the likelihood of emesis and establish a dependent relationship of the intestines to the stomach. If emesis occurs, the infusion rate can be decreased by 50% for 30 to 60 minutes and then return to the original rate. Metoclopramide (which exhibits both antiemetic and gastric emptying effects) can also be administered.
The solution is administered until the rectal effluent is clear which may take over 5 hours. The technique is time consuming and requires a cooperative patient. Most studies supporting this approach are limited to case reports, and there are no established specific indications for its use (2,18,19). Contraindications to WBI include ileus, GI hemorrhage, uncontrolled vomiting, bowel perforation, and an unprotected compromised airway.
Antidotes
An antidote is a substance that increases the mean lethal dose of a toxin, or that can favorably affect the toxic effects of a poison. Some are toxic themselves and should be used only when indicated. Only approximately 5% of overdose patients require antidotal administration (1).
Table 296.4 lists antidotes for specific drugs/poisons. These will be discussed in the individual toxin chapters.
TABLE 296.4
Examples of Antidotes
ENHANCEMENT OF ELIMINATION
Forced Diuresis and Urinary pH Manipulation
Routine use of volume loading to promote diuresis has not been supported in the literature and is not recommended. Manipulation of urinary pH can be used therapeutically to enhance elimination of some intoxicants (Table 296.5). The limits of urinary pH are 4.5 to 7.5 under conditions of enhanced acidification and alkalinization. Thus, elimination of very strong (negative logarithm of the acid ionization equilibrium constant [pKa] <3) or very weak (pKa >8) acids is unaltered by urinary pH manipulation. Other acidic or basic drugs do not undergo renal tubular absorption, irrespective of urinary pH, since they are polar in their nonionized form. Urinary alkalinization (pH >7.5) is most often used to eliminate salicylates and phenobarbital (20). It can be achieved by administration of IV sodium bicarbonate (1 to 2 mEq/kg every 3 to 4 hours); this may be administered as two 50-mL ampules of 8.4% sodium bicarbonate (each containing 50 mEq of NaHCO3) per liter of 5% dextrose in water infused at 250 mL/hr. Complications of this therapy include alkalemia (particularly in the presence of concurrent respiratory alkalosis), volume overload, hypernatremia, and hypokalemia. It is particularly important to avoid hypokalemia, which prevents excretion of alkaline urine by promoting distal tubular potassium reabsorption in exchange for hydrogen ion. Accordingly, bicarbonate administration in the presence of significant hypokalemia will not alkalinize the urine, yet will increase the risk of alkalemia. Since urinary alkalinization therapy can cause hypokalemia (due to alkalemia-induced intracellular potassium shift and increased urinary potassium loss with alkaline diuresis), addition of potassium chloride to the bicarbonate infusion is frequently required. Acetazolamide should not be used to alkalinize urine. Resultant metabolic acidosis can increase toxicity of certain poisonings (particularly with salicylate poisoning).
TABLE 296.5
Toxins Eliminated by Urinary Alkalinization
Multiple-Dose Activated Charcoal
Multiple-dose activated charcoal (MDAC) can be an effective way to enhance the elimination of toxins that have been absorbed (21). The mechanism by which this modality accomplishes enhancement of elimination is either by interrupting the enterohepatic/enterogastric circulation of drugs or through the binding of any drug that diffuses from the circulation into the gut lumen (called GI dialysis). However, it has limited application because the toxin must have a low volume of distribution, low protein binding, prolonged elimination half-life, and low pKa, which maximizes transport across mucosal membranes into the GI tract. Although optimal dosage and frequency of administration following the initial dose of activated charcoal is not well established, most experts recommend a dose of approximately 0.5 g/kg every 2 to 4 hours for at least three doses. Cathartics are generally not administered to avoid hypernatremia, hypokalemia, and hypermagnesemia. MDAC should be used with caution in patients with decreased bowel sounds, abdominal distension, and persistent emesis. Unless a patient has an intact or protected airway, the administration of multidose charcoal is contraindicated. A review of the literature reported that although MDAC enhances drug elimination significantly, it has not yet been evaluated in a controlled trial of poisoned patients with the objective of demonstrating a reduction in morbidity and mortality. Table 296.6 provides a list of drugs and toxins where there may be a role for MDAC. However, based on experimental and clinical studies, it should be considered in patients with a life-threatening ingestion of carbamazepine, dapsone, phenobarbital, quinine, or theophylline.
TABLE 296.6
Toxins and Drugs Eliminated by Multiple Dosing of Activated Charcoala
Extracorporeal Removal of Toxins
Although clear proof that extracorporeal toxin removal favorably alters the course of any intoxication is generally lacking, it should be considered when the intoxication is projected to undergo delayed or insufficient clearance because of either organ dysfunction, the intoxicating agent produces toxic metabolites, or delayed toxicity is characteristic of the intoxication. Three methods for extracorporeal removal of toxins are possible: (1) dialysis (usually hemodialysis rather than peritoneal dialysis), (2) hemoperfusion, and (3) hemofiltration (22,23). Plasmapheresis is rarely used although effective in reducing plasma levels of several drugs with high plasma protein binding (>80%) and a low volume of distribution (<0.2 L/kg) (Table 296.7) (24,25). Exchange transfusion has been used for neonatal/infant exposures (Table 296.8); therapeutic plasma exchange (TPE) with fresh frozen plasma has been used to remove toxins that are protein bound and not removed by dialysis (i.e., organophosphate insecticides, mushrooms) (26,27).
TABLE 296.7
Toxicants in which Plasmapheresis Has been Shown to Enhance Elimination
TABLE 296.8
Toxicants for which Exchange Transfusions May be Helpful
Hemodialysis
Hemodialysis is the primary extracorporeal method to remove toxins or drugs. Ideal toxins for hemodialysis have a low molecular weight (<500 d), water soluble, low protein binding (<70% to 80%), and a small volume of distribution (<1 L/kg). It is also effective in correcting concomitant electrolyte abnormality and metabolic acidosis. Toxins in which hemodialysis may be required in an early stage of intoxication include methanol, ethylene glycol, boric acid, salicylates, and lithium. Others are listed in Table 296.9. Hemodialysis can also be used for heavy metal chelation in patients with renal failure.
TABLE 296.9
Some Toxins and Drugs Removed by Hemodialysis
Hemoperfusion
Hemoperfusion is essentially the parenteral analog of oral activated charcoal. Most drugs are extractable by hemoperfusion, which is particularly suitable for extracorporeal removal of toxins that are of high molecular weight, highly protein bound, or lipid soluble. It has been effectively used to enhance elimination of theophylline, phenobarbital, phenytoin, carbamazepine, paraquat, and glutethimide. Due to the lack of availability of charcoal cartridges, this modality is rarely available.
Hemofiltration
Hemofiltration achieves drug and toxin removal by convection. It transports solutes through a highly porous membrane that is permeable to substances with weights of up to 6,000 d, including virtually all drugs. In some cases, hemofiltration membranes are permeable to substances weighing up to 20,000 d. Although the application of this technique has not been vigorously studied in poisoned patients, there are increasing numbers of case reports of extracorporeal intoxicant removal by 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. Specific highly porous hemofiltration cartridges are useful for removal of large–molecular-weight solutes or complexes, such as combined digoxin–Fab fragment complexes, or desferoxamine complexes with iron or with aluminum.
Lipid Rescue Resuscitation
Lipid emulsion infusion was first demonstrated in 1998 to improve resuscitation due to cardiovascular collapse from bupivacaine overdose (28). Since then, successful treatment of cardiovascular toxicity from a wide range of lipophilic drugs (such as calcium channel blocking agents, β-adrenergic blockers, tricyclic/SSRI antidepressants, and other local anesthetics) has been achieved by lipid or intralipid rescue. The therapeutic mechanisms of lipid emulsion infusion has been postulated to be (28): (1) lipid emulsion capture of drug (“lipid sink”), (2) mitochondrial uptake of fatty acid (metabolic effect), (3) Interference of cellular membrane sodium channel, (4) cytoprotection by inhibition of glycogen synthase kinase, and (5) calcium entry promotion through voltage-dependent calcium channels resulting in a cardiac inotropic effect.
The suggested dosage of a 20% lipid emulsion is a 1.5 mL/kg bolus over 2 to 3 minutes followed by an infusion of 20% lipid emulsion at a rate of 0.25 mL/kg/min (29,30). For asystolic patients, or those who do not respond to the bolus, the dose may be increased if hemodynamic instability remains. Whenever possible, lipid emulsion therapy should be terminated within 1 hour. Hyperamylasemia and hypertrilyceridemia have been reported following lipid emulsion therapy; however, this therapy has otherwise been shown to be relatively free of complications (27,30). Thus, the therapeutic profile of this intervention is quite promising and its use will likely increase to emergently reverse the cardiovascular effects of drug toxicity (30).
DISPOSITION
Indications for ICU Admission
In the current healthcare climate, the practice of routinely admitting the poisoned patient to the ICU is being questioned. Brett et al. (31) identified eight clinical risk factors that can predict ICU interventions: (1) PaCO2 >45 mm Hg, (2) need for endotracheal intubation, (3) toxin-induced seizures, (4) cardiac arrhythmias, (5) QRS duration ≤0.12 seconds, (6) systolic BP <80 mm Hg, (7) second- or third-degree atrioventricular block, and (8) unresponsiveness to verbal stimuli . 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 (31). Other indications for ICU admission include a Glasgow Coma Scale score <12, need for emergency dialysis or hemoperfusion, progressive metabolic acidosis, and a cyclic antidepressant or phenothiazine overdose with signs of anticholinergic cardiac toxicity (32). An important critical care intervention is extracorporeal membrane oxygenation (ECMO). Even though it has been used since 1972, recent advances in ECMO technology have rendered it more biocompatible. Thus it is increasingly being used as a salvage therapy for acute respiratory distress syndrome and circulatory shock, for up to 3 days, in certain exposures such as calcium channel antagonists, β-adrenergic blockers, tricyclic antidepressants, chloroquine, colchicine and hydrocarbons/inhalation toxic exposure (33). Severe hyperkalemia, wide alterations in body temperature, and the need for continuous infusion of naloxone are also reasons to admit a patient to an ICU. Hypotension on admission is the most significant predictor of fatality (34,35). In addition, staffing issues such as the availability of a “sitter” in cases of attempted suicide may impact patient disposition. Table 296.10 provides a list of criteria for ICU admission.
TABLE 296.10
Criteria for Admission of the Poisoned Patient to the ICU
In addition, the physician should be aware of certain ingestions, that in a single-dose form, can be potentially catastrophic to a toddler (Table 296.11) (36,37).
TABLE 296.11
Toxins/Medications that Could Cause Fatality in a Toddler (Under 20 kg Weight) if Ingested in a Single Dose Form
Common Pitfalls
• Failure to consider decontamination procedures upon presentation.
• Failure to consider delayed onset of the effects of certain toxins.
• Failure to institute extracorporeal removal techniques in a timely manner.
• Failure to consider seriously certain medications, which in a single-dose form, can be lethal to a toddler.
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