A2: Antidotes in Depth

To alter xenobiotic pharmacokinetics, the approach to a poisoned patient may include administration of gastrointestinal (GI) evacuants. Selected patients may benefit from minimizing systemic exposure by decreasing GI transit time and increasing rectal expulsion. The most effective process of evacuating the GI tract in poisoned patients is referred to as whole-bowel irrigation (WBI). WBI is typically accomplished using polyethylene glycol with a balanced electrolyte lavage solution (PEG-ELS). A detailed discussion of the merits of WBI in the context of various decontamination strategies is provided in Chap. 8.

In 1625 while endeavoring to recover from febrile “Hungarian disease,” Johann Glauber drank from a well from which he later isolated sal mirabile, now known as sodium sulfate, Na₂SO₄.⁴⁷ He advocated its use as a purgative and determined a synthetic production method.⁴⁷ In 1675, Nehemiah Grew first observed the presence of a purgative salt in the springs at Epsom, later determined to be magnesium sulfate.¹¹³ Phosphate of soda, called “tasteless purging salt,” was found in the urine by Hellot in 1737 and introduced into clinical practice as a purgative by George Pearson some 50 years later.¹⁰⁷ In 1882 to 1883, Hay reported on a series of experiments that provided the basis for the understanding of the mechanism of action of the saline cathartics. He identified the viscus as the main source of bowel fluid, which was secretory in nature, and established a dose–response principle of decreased time to stool as salt concentrations were increased.^43,44 PEG was introduced in 1957 as a nonabsorbable marker for the study of human fat, carbohydrate, and protein absorption.¹⁵ Experimental studies of intestinal lavage in normal human subjects appeared in 1968.⁷⁸ In 1973, Hewitt and colleagues reported on WBI in clinical practice, their method of “whole-gut irrigation” with a solution of sodium chloride, potassium chloride, and sodium bicarbonate in distilled water to prepare the large bowel for surgery.⁴⁶ WBI was used therapeutically for poisoning in 1976 in a patient ingesting 300 lead airgun pellets who was unresponsive to oral magnesium sulfate purgation.¹⁴⁷

Nomenclature

Xenobiotics that promote intestinal evacuation are referred to as laxatives, cathartics, purgatives, promotility agents, and evacuants. Depending upon dose, the same xenobiotic may accomplish some or all of these tasks, with differing side effect profiles. Laxatives promote a soft-formed or semifluid stool within 6 hours to 3 days. Cathartics promote a rapid, watery evacuation within 1 to 3 hours.¹¹⁹ The term purgatives relates the force associated with bowel evacuation. Evacuants are commonly used for pre-procedural bowel cleansing, with an onset of action of as little as 30 to 60 minutes, but typically require 4 hours for a more complete effect. Promotility agents stimulate GI motor function via the enteric nervous system via acetylcholine, serotonin, motilin, or intestinal chloride channels.

Laxatives are further classified into categories of bulk forming, softener or emollient, lubricant, stimulant or irritant, saline, hyperosmotic, and evacuant. Bulk-forming agents include high-fiber products such as methylcellulose, polycarbophil, and psyllium; softeners or emollients include docusate calcium. Mineral oil is the sole lubricant. None of these cathartics is used therapeutically in medical toxicology because their onset of action is delayed. Stimulant or irritant laxatives include anthraquinones (sennosides, aloe, and casanthranol), diphenylmethane (bisacodyl), and castor oil. Saline (meaning salt) cathartics, which include magnesium citrate, magnesium hydroxide, magnesium sulfate, sodium phosphate, and sodium sulfate, are used infrequently. Hyperosmotic agents, generally nonabsorbable sugars and alcohols including sorbitol and lactulose, are occasionally considered in poisoned patients. The most common process of evacuating the intestinal tract in poisoned patients is WBI.

Chemistry and Preparation

Magnesium citrate (C₆H₆MgO₇) and magnesium sulfate (MgSO₄, “Epsom salt”) are water-soluble salts of magnesium; magnesium hydroxide (Mg{OH}₂, “milk of magnesia”) is insoluble.⁵⁶ Sodium sulfate can be prepared through purification of naturally occurring brine deposits or other manufacturing processes. Sodium phosphate is supplied as a combination of the monobasic monohydrate (NaH₂PO₄·H₂O) and dibasic anhydrous (Na₂HPO₄) forms. d-Sorbitol (C₆H₁₄O₆), an isomer of mannitol, is a hexitol naturally occurring in many fruits and is produced commercially by the reduction of glucose. Lactulose is a water-soluble, synthetic disaccharide, 4-O-β-d-galactopyranosyl-d-fructofuranose.

The addition reaction of ethylene oxide (C₂H₄O) to an ethylene glycol equivalent creates ethylene oxide polymerization into polyethylene glycol (PEG). The “n” in the molecular structure of PEG, H-(OCH₂CH₂)_n-OH refers to the average number of repeating oxyethylene groups.⁶⁰ The number after PEG represents its average molecular weight (MW). PEG, also known as macrogol, has numerous medicinal applications. It can be conjugated to pharmaceuticals to delay vascular clearance (“PEGylation”), serve as a solvent in oral liquids and soft capsules, function as a nonalcohol solubilizer and diluent for liquid oral-dose medications, provide a base for medical ointment and cosmetics, and act as a base liquid for producing vapor in electronic cigarettes.¹⁰³ Low-molecular-weight PEG (eg, 300 or 400 Da), because of its advantageous solvent properties, is used to decontaminate phenol burns, although animal studies demonstrated the equal efficacy of copious (deluge) quantities of water.⁵¹ Higher-molecular-weight variants are used to promote laxation. Although PEG’s physical properties (eg, water solubility, hygroscopicity, vapor pressure, melting or freezing range, and viscosity) vary with MW and blending because of chain-length effects, the chemical properties are similar.¹³¹ PEG 3350 used in pharmaceutical, personal care, and food applications is water soluble. It has a MW range of 3015 to 3685 Da, an average number of 75.7 repeating oxyethylene units, a pH of a 5% aqueous solution of 4.5 to 7.5 at 25°C, a density of 1.09 g/cm³ at 60°C, a melting or freezing range between 53° and 57°C, a water solubility of 67% by weight at 20°C, and a viscosity of 90.8 centistokes at 100°C.^130,132 PEG 3350 without electrolytes is sold for nonprescription use for short-term constipation treatment. WBI used in poison management is typically accomplished using PEG 3350 added to a balanced electrolyte lavage solution (PEG-ELS), which contains an isotonic mixture of sodium sulfate, sodium bicarbonate, sodium chloride, and potassium chloride.¹¹⁹

Mechanisms of Action

The effects of saline cathartics are largely attributed to their relatively nonabsorbable ions that establish an osmotic gradient and draw water into the gut.¹⁰⁴ The increased water leads to increased intestinal pressure and a subsequent increase in intestinal motility. Magnesium ions also lead to the release of cholecystokinin from the duodenal mucosa, which stimulates intestinal motor activity and alters fluid movement, contributing to catharsis.^14,119,126 A lack of endogenous hydrolytic enzymes allows sorbitol and lactulose to reach the colon unchanged. Colonic bacteria metabolize sorbitol into acetic and other short chain fatty acids and lactulose into lactic acid and small amounts of formic and acetic acids. This results in a slight acidification of colonic contents, an increase in osmotic pressure that draws water into the lumen, and stimulation of colonic propulsive motility.¹¹⁹

Long-chain PEGs (eg, MW ~3350 Da) are nonabsorbable, isoosmotic, indigestible molecules that remain in the colon together with the water diluent, resulting in WBI primarily by the mechanical effect of large-volume lavage. The added balanced electrolyte solution practically eliminates electrolyte abnormalities and helps preclude fluid shifts across the GI mucosa. Sodium sulfate in many preparations reduces sodium absorption in the small intestine because of the absence of chloride, the accompanying anion necessary for active absorption against the electrochemical gradient.⁸³

Promotility agents such as metoclopramide and erythromycin stimulate gut motor function. Metoclopramide mediates GI 5-HT₄ receptor agonist and D₂ receptor antagonist activity, which both result in increased acetylcholine release and GI motility. Erythromycin also stimulates gut motor function but via direct stimulation of GI motilin receptors.¹³⁹ Lubiprostone is a promotility drug that stimulates chloride secretion and enhances the contraction of gastric and colonic musculature.⁶¹ Although lubiprostone has been used with WBI for the treatment of constipation, their combined use has not yet been reported in poisoned patients.

Pharmacokinetics

Absorption of magnesium, phosphate, and other electrolytes contained in hypertonic products is well described and may risk morbidity.^27,98,104 In one prospective, nonrandomized study, nine of 14 patients developed elevated magnesium concentrations (2.2–5.0 mEq/L) after multiple doses of magnesium-containing cathartics for suspected drug overdose despite normal blood urea nitrogen and creatinine values.¹²³ During the 24 hours after administration of oral sodium phosphate solution in seven healthy volunteers, serum phosphorus reached a mean peak of 7.6 mg/dL (range, 3.6–12.4 mg/dL), and ionized calcium reached a mean nadir 4.6 mg/dL (range,4.4–5.2 mg/dL).²⁷

By virtue of its high osmotic nature long-chain PEG is poorly absorbed, is retained in the lumen, and does not distribute. PEG is therefore eliminated unmetabolized in rectal effluent.

Pharmacodynamics

Patients ingesting 45 mL of an aqueous sodium phosphate preparation taken the evening before and the morning of a procedure initiated bowel activity within 1.7 hours of the first dose and within 0.7 hours of the second dose, with a mean duration of activity of 4.6 and 2.9 hours, respectively, and an end of bowel activity within 4 to 5 hours.⁷⁴ In six volunteers, saline cathartics decreased activated charcoal (AC) mean GI transit time from 29.3±1.2 hours to 24.4±1.2 hours, 15.4±3.0 hours, 17.3±1.9 hours, and 17.5±2.3 hours with sodium chloride, sodium sulfate, magnesium sulfate, and a proprietary cathartic “salt” (36.7% anhydrous citric acid, 17.65% magnesium sulfate, and 45.6% sodium bicarbonate), respectively.¹⁰⁵ When different cathartics were compared with respect to time to first stool and number of stools,^{54,68,96,97,127} sorbitol produced 10 to 15 watery stools and the most abdominal cramping before catharsis. Sorbitol produced stools in the shortest amount of time, which also was associated with the highest incidence of nausea, vomiting, generated gas, and flatus.^62,64,99 In one systematic review, mean transit times after administration of sorbitol, magnesium citrate, magnesium sulfate, and sodium sulfate were 0.9 to 8.5 hours, 3 to 14 hours, 9.3 hours, and 4.2 to 15.4 hours, respectively.⁵ In comparison, the first bowel movement typically occurs relatively quickly after the initiation of WBI with PEG-ELS. Patients ingesting GoLYTELY (1.2–1.8 L/h until the rectal effluent was clear) completed their colonic preparation within 1.5 to 3 hours after averaging a total of 5.5 L per patient (range, 3–8 L).³⁹

Although recommended for basic poison management for many years, cathartics should not be used routinely in the management of overdosed patients.⁵ Intuitively, the advantages of cathartics appear to result from their ability to decrease the potential for constipation or obstruction from AC and hasten the delivery of AC to the small intestine. However, these theoretical advantages have never been demonstrated clinically.

Studies demonstrate that when administered alone, cathartics such as sorbitol or sodium sulfate may decrease peak or total absorption of some xenobiotics, but no study of cathartics alone has achieved results comparable to that of AC alone.^{2,24,88,108,141} When comparing the efficacy of a single dose of AC alone with that of AC plus a single dose of cathartic, studies suggest the combination to be equal to,^2,93,102,122 slightly better than,^24,62 or even slightly worse than AC alone.^88,141 WBI with PEG-ELS is currently advocated to hasten the elimination of poorly absorbed xenobiotics or sustained-release medications before they can be absorbed. This approach is theoretically sound and does not produce the fluid and electrolyte complications associated with cathartics. Unfortunately, evidence of efficacy is limited to anecdotal case reports and volunteer studies.

Many studies of WBI using PEG-ELS demonstrate patient acceptance, effectiveness, and safety when used for bowel preparation, its labeledindication.^{4,12,16,17,28,31,32,109,133,136} Animal models suggest that WBI may enhance systemic clearance via GI dialysis, similar to multiple-dose activated charcoal (MDAC).⁷³ In actuality, low flow rates, the typical delay in administering WBI in actual clinical situations, and the inconvenience of this procedure make it highly unlikely that enhanced systemic clearance can be achieved in humans. In human volunteer studies, WBI was more effective than AC with sorbitol for enteric-coated acetylsalicylic acid (ASA) when administered 4 hours after ingestion,⁶⁴ decreased peak lithium concentrations, and lithium AUC (area under the plasma drug concentration vs. time curve) compared with control participants;¹²⁴ decreased the bioavailability of two sustained-release medications;^21,71 and propelled radiopaque markers through the gut more efficiently than control participants.⁸⁰ In a retrospective analysis of 59 acute-on-chronic lithium overdoses, those decontaminated at an early stage with sodium polystyrene sulfonate, WBI, or both achieved statistically significant and clinically relevant decreases in peak serum lithium concentrations compared with those with delayed (>12 hours) or no decontamination (2.39 vs. 4.08 mEq/L).¹⁸ A retrospective chart review of 176 pediatric cases in a state electronic database from 2000 and 2010 documented WBI use in 72 cases involving sustained- and delayed-release medications, such as nifedipine, bupropion, verapamil, diltiazem, and felodipine.⁷⁵ Abdominal radiographs were performed in 36 cases, of whom 16 had demonstrable radiopaque pills. Four of these had repeat abdominal radiographs, all of which demonstrated a decrease in opacities.

Not unexpectedly, WBI was inferior to AC with regard to prevention of absorption when administered after 650 mg of immediate-release aspirin.¹¹² Additionally, after the aspirin was absorbed, WBI was unable to enhance systemic clearance.⁸⁷ Likewise, only a small, statistically insignificant effect of WBI could be demonstrated on the absorption of extended-release acetaminophen in a human volunteer study.⁸⁰ These findings highlight the limited utility of WBI to assist in the prevention of absorption of relatively rapidly absorbed xenobiotics. Reports have shown successful WBI use in themanagement of overdoses of iron,^{33,59,85,128,129} sustained-release theophylline,⁵⁵ sustained-release verapamil,¹⁹ modified-release fenfluramine,⁹⁵ zinc sulfate,²⁰ lead,^{92,94,116,147} arsenic trioxide,⁵³ arsenic-containing herbicide,⁷² mercuric oxide powder,⁸¹ strontium,⁶³ potassium chloride capsules,^42,50 and clonidine and fentanyl transdermal patches^36,52 and in body packers.^49,134,138 Although some clinicians express enthusiasm for the use of WBI for a variety of ingestions, others question its efficacy.^20,114 WBI for 5 hours after ingestion of 10 fluorescent coffee beans by each of seven volunteers removed an average of only four beans (range, 1–8).¹¹⁴ Similar failures are reported with jequirity beans,²⁰ iron,^23,142 and button batteries.¹²⁸ It can be argued that because of physical characteristics (eg, density, solubility, size, or pharmacobezoar formation), these cases might not be representative of xenobiotics amenable to WBI.

Internal Drug Concealment

The approach to patients with internal concealment and enteral transport of illicit substances (eg, cocaine, heroin, amphetamines, and hashish) is comprehensively reviewed in Special Considerations: SC5. Close coordination with surgical services is advised because of the risks of obstruction, intestinal retention, or rupture. Mineral oil rapidly degrades latex condoms.¹⁴⁴ Use of mineral oil in evacuating drug packets, which may be constructed in this fashion, risks fatal rupture.¹⁴³ In a retrospective descriptive case series of 16 body packers, conservative management with WBI was successful in 14; a ruptured cocaine packet produced mild toxicity in one patient, and packets were retained in one of the heroin body packers.³⁵ In another retrospective analysis of 34 cocaine body stuffers who were asymptomatic on presentation, one received WBI alone, and 19 received WBI plus AC and remained asymptomatic and were discharged after 24 hours.⁵⁸ A review of 1250 confirmed body packers found the success rate of a conservative management strategy of WBI to be 98%.⁸⁴ All conservatively managed patients passed all of their packets within 5 days. WBI may not always evacuate all of the drug packets because of inadequate dosing, partial obstruction, or the nature of the procedure. In one case, prolonged WBI failed to clear a methamphetamine body stuffer who engaged in “parachuting.”⁴⁵ As a result of these failures, promotility agents were added to WBI and presumably successfully enhanced bowel evacuation in two body packers suspected of having ingested well-constructed drug packets.¹³⁵

Potential adverse effects associated with various cathartics and promotility agents include dehydration, hypokalemia and metabolic alkalosis from dehydration, absorption of magnesium or other absorbable electrolytes, activation of the renin–angiotensin–aldosterone system, phosphate-induced nephropathy, and colonic fermentation of digestible sugars.^22,37,121 Cathartic-induced rectal prolapse is reported in geriatric patients.⁶⁶ The use of repetitive doses of cathartics, either by design or unintentionally, has led to hypermagnesemia, altered mental status, and death.^{57,98,123,146} Hypocalcemia, hyperphosphatemia, and hypokalemia have accompanied the use of hypertonic phosphate enemas and oral sodium phosphate despite adherence to recommended dosing.^{29,37,41,77,86,110,125} Frail elderly patients, children, and those with decreased kidney function may be most susceptible to adverse effects.^11,13

Softeners may increase intestinal permeability and therefore increase the absorption of some xenobiotics.^9,119 Mineral oil risks enhanced absorption of lipid-soluble xenobiotics, lipoid pneumonia in the event of aspiration, and rupture of concealed drug packets packaged in latex.¹⁴³ Stimulant and irritant laxatives are rarely used today in medical toxicology because of their significant GI side effects, including abdominal discomfort, cramping, and tenesmus and with chronic administration, bowel habituation and intestinal tissue damage.

Contraindications to WBI include prior, current, or anticipated diarrhea; volume depletion; significant GI anatomical or functional compromise such as colitis, hemorrhage, ileus, obstruction, perforation, or toxic megacolon; an unprotected or compromised airway; and hemodynamic instability.^6,128

MDAC regimens containing 70% sorbitol used to enhance elimination resulted in severe cathartic-related adverse effects in several case reports.^3,34,76,89 The potential for sorbitol-related adverse events from the unintentional use of repetitive AC dosing was emphasized by a survey revealing that 16% of hospitals surveyed only stocked AC premixed with sorbitol.¹⁴⁵ The retention of sorbitol after repetitive doses in an aperistaltic gut may lead to significant morbidity from gas formation and abdominal distention as a result of the digestive action of gut bacteria.⁷⁶

Adverse effects resulting from the use of WBI with PEG-ELS include vomiting, particularly after rapid administration, abdominal bloating, fullness, cramping, flatulence, and pruritus ani. Of the 176 pediatric cases detailed in the California Poison Control System electronic database, 16 vomited, and one experienced abdominal pain.⁷⁵ In an alternative administration strategy in which 46 children were provided 238 g of PEG-3350 mixed with 1.9 L of Gatorade, complaint rates of nausea and vomiting, abdominal pain and cramping, and fatigue and weakness were 60%, 44%, and 40%, respectively.¹ Typically, patients need to remain near a commode for 4 to 6 hours to complete WBI therapy. Slow or low-volume administration of PEG-ELS results in sodium absorption. If a total of 500 mL of PEG-ELS was used instead of multiple liters, potentially 1.5 g of sodium may be absorbed.³⁰ This adverse effect might have resulted in the exacerbation of congestive heart failure in an unstable patient with cardiac and renal dysfunction.⁴⁰ An unusual complication of WBI is colonic perforation, which occurred in a patient with active diverticulitis.⁷⁰ Other adverse effects noted by the manufacturer include isolated reports of upper GI bleeding from a Mallory-Weiss tear, esophageal perforation, aspiration pneumonitis after vomiting, and ARDS. Rare cases of both hypo- and hypernatremia, leading to altered consciousness, seizures, cerebral edema, and death, are reported with PEG, alone or in combination with ELS.^10,100,115

Unintentional administration of PEG-ELS by other than the enteral route has occurred. A 4 year-old child inadvertently received 390 mL of PEG-ELS intravenously with no obvious adverse result.¹¹¹ In contrast, acute respiratory distress syndrome (ARDS) developed in an 11 year-old child administered PEG-ELS through a nasogastric tube inadvertently inserted in the trachea.¹⁰¹ In a similar case, a poorly placed nasogastric tube was responsible for PEG-ELS aspiration in a 3 year-old boy, with resultant hypoxia and hemodynamic instability requiring endotracheal intubation.³⁸ An 8 year-old girl with emesis during nasogastric infusion of 1 L of PEG-ELS experienced gagging, coughing, and emesis, and respiratory distress 2 hours after infusion, resulted in ARDS and requiring intubation and ventilatory support for 2 days.¹⁰⁶ A report of two cases suggests that vomiting and aspiration may be more frequent than previously recognized in hemodynamically unstable patients.²⁶ Presumably, a patient’s hypotension results in GI hypoperfusion and ileus, which, with the continued administration of WBI in the presence of decreased GI motility, produces abdominal distention and vomiting.

For MiraLax to be useful in WBI, it would need to be administered at a dose of 2 L/h (8 heaping teaspoons in 2 L of water/h) in adults. This is not recommended for WBI because it does not contain any added electrolytes and could result in an electrolyte imbalance and shifts.

Activated Charcoal and Whole-BowelIrrigation Interactions

Several in vitro studies (with cocaine, chlorpromazine, fluoxetine, salicylate, and theophylline) demonstrate that the addition of PEG-ELS to AC significantly decreases the adsorptive capacity of AC.^7,8,48,65,82 Some interactions were affected by pH and magnified by high ratios of PEG-ELS to AC.^8,65,82 The most likely explanation is competition with the AC surface for solute adsorption. Additionally, in an animal model, WBI appeared to have an adverse effect by washing the AC away from the sustained-release theophylline.²¹ One controlled study evaluated the effect of WBI added to 25 g of AC in nine healthy human volunteers simultaneously ingesting 200 mg of carbamazepine, 200 mg of theophylline, and 120 mg of verapamil.⁷¹ Compared with AC alone, WBI provided with AC significantly decreased verapamil peak concentration (C_max) and AUC but significantly increased carbamazepine C_max and AUC and nonsignificantly increased theophylline C_max and AUC. One case report documents rapid increases in carbamazepine concentrations temporally related to the initiation of WBI.⁷⁹ Although the patient had received MDAC and hemoperfusion, xenobiotic concentrations were increasing 58 hours after ingestion. It is possible that PEG-ELS competed for carbamazepine binding to AC, displacing some drug and making it available for absorption. A similar rapidly increasing drug concentration was noted after the initiation of WBI in a patient with a reported 10-g phenytoin overdose.²⁵ In this case, AC had not been given before the initiation of WBI. One possible explanation is that the massive dose of phenytoin prevented its own absorption by exceeding its solubility, but the administration of WBI provided sufficient diluent to allow phenytoin dissolution before GI emptying with subsequent absorption. One human study evaluated the influence of various decontamination strategies on the probability of seizures in 319 patients who overdosed on venlafaxine on 436 occasions.⁶⁹ WBI added to AC alone in a mean ingestion of 2100 mg further reduced the odds ratio (OR) of a seizure to 0.25 (0.08–0.62) compared with an OR of 0.48 (0.25–0.89) with AC alone. Most of these patients ingested extended-release venlafaxine. Their results demonstrated that combining AC and WBI provided a greater benefit than the sum of the independent effects of single-dose activated charcoal (SDAC) and WBI and argued against adverse clinical effects caused by desorption in venlafaxine ingestion.⁶⁹

Commercial preparations of PEG-ELS are pregnancy category C.^{16,17,117,118} Animal reproduction studies have not been conducted with Colyte, GoLYTELY, NuLYTELY, or TriLyte.^{16,17,117,118} The underlying elevated prevalence of nausea and vomiting in pregnancy⁶⁷ might predispose pregnant patients to vomit more frequently, although this is speculative. WBI with large volumes of fluid has been used successfully in pregnant women at 26 and 38 weeks of gestation.^137,140 The lack of absorption PEG-ELS would not predispose it to excretion in breast milk, although definitive safety in lactation is not established.

The usual nonprescription daily dose for the short-term treatment (2 weeks) of occasional constipation is 17 g of powder in 8 oz (240 mL) of water. The recommended dose of WBI with PEG-ELS solution is considerably larger: 0.5 L/h or 25 mL/kg/h for small children and 1.5 to 2.0 L/h or 20 to 30 mL/min for adolescents and adults. WBI solution may be administered orally or through a nasogastric tube for 4 to 6 hours or until the rectal effluent becomes clear. An antiemetic such as metoclopramide or a 5-HT₃ serotonin antagonist may be required for the treatment of nausea or vomiting. In select patients, promotility agents may serve as useful adjuncts.¹³⁵ If the xenobiotic being removed is radiopaque, a diagnostic imaging technique demonstrating the absence of the xenobiotic may serve as an initial clinical endpoint (Special Considerations: SC5).

The original WBI solution was GoLYTELY manufactured by Braintree. This solution contained PEG with electrolytes and sodium sulfate as an added laxative. Colyte is manufactured by Schwartz Pharma and is similar to GoLYTELY. Braintree later introduced NuLYTELY, a PEG formulation with 52% less total salt than GoLYTELY without added sodium sulfate. These changes decreased the salty taste and the risk of fluid- or electrolyte-related complications.⁹⁰ Many products are available with flavors. The available PEG-ELS products are prepared by filling the container to the 4-L (or 1-gal) mark with water and shaking vigorously several times to ensure dissolution. Lukewarm water facilitates dissolution, but subsequent chilling improves palatability. Chilled solutions are not recommended for infants because of hypothermia risk. Products are stable with refrigeration for48 hours after reconstitution. Available PEG-ELS products (eg, GoLYTELY, Colyte, NuLYTELY, TriLyte) differ slightly in their composition. All contain PEG 3350 with varying amounts of sodium chloride, potassium chloride, sodium sulfate, and sodium bicarbonate, which upon reconstitution yieldsodium, 65 to 125 mEq/L; potassium, 5 to 10 mEq/L; chloride, 35 to 53 mEq/L; bicarbonate, 17 to 20 mEq/L; and sulfate, 0 to 80 mEq/L.^{16,17,117,118}

MiraLax contains electrolyte-free PEG 3350 powder meant for oral administration after dissolution in water, juice, or soda. It is indicated for occasional constipation and not for poisoning management, with a recommended dose of 1 heaping teaspoon (17 g) in 8 oz (240 mL) of liquid per day. However, alternative WBI formulations using electrolyte-free PEG 3350 with Gatorade have been used clinically. One study of 139 patients comparing 4 L of PEG-ELS with electrolyte-free PEG combined with 1.9 L of Gatorade and found no differences in colonoscopy preparation scores, higher overall patient satisfaction scores with the Gatorade mixture, and fewer adverse effects (bloating and nausea).⁹¹ In 46 children provided PEG 3350 mixed with 1.9 L of Gatorade over a few hours, 93.5% completed the regimen, and 77% achieved effective colonic visualization.¹ In a retrospective evaluation of an endoscopic database analysis, patients undergoing bowel preparation using PEG 3350 without electrolytes (238 g of MiraLax in 64 oz of Gatorade) and four 5-mg bisacodyl tablets were more likely to achieve an excellent or good bowel cleansing compared with patients receiving a GoLytely preparation (93.3% vs. 89.3%), without any adverse events.¹²⁰

• Cathartics are not considered part of routine management of poisoning and overdose in children or adults and should not be used as an AC substitute when xenobiotics known to be adsorbed to AC are involved.

• When MDAC is administered, if a cathartic is used at all, it should be provided only with the first dose. Sufficient oral fluids should always accompany cathartic administration to avoid dehydration and inspissation.

• AC should be given to patients for whom it is indicated, and if WBI is being performed in conjunction, a comparable dose of AC should be given after WBI to prevent or overcome the potential desorption and possible further systemic absorption of the xenobiotic.

• Unless contraindicated, WBI is preferable to repetitive dose cathartics for evacuation of sustained-release or poorly soluble xenobiotics not adsorbed to AC.

• WBI’s precise role and the interactions between PEG-ELS and AC in overdosed patients remain ill defined. Absent controlled clinical studies to assess outcome, WBI may be considered in ingestions of sustained-release xenobiotics, xenobiotic ingestions with a slow absorptive phase and a high expectation of morbidity; xenobiotics not adsorbed by activated charcoal (eg, iron, lead, lithium); and foreign body ingestions, specifically drug packets in body packers.

References