Page 1735 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1204 PART 11: Special Problems in Critical Care

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The use of activated charcoal (AC) in acute overdose has become a WHOLE-BOWEL IRRIGATION
source of heated debate in the last few years. The largest prospective ran- The routine use of whole-bowel irrigation (WBI) is not recommended,
domized clinical trial to date, published by Eddleston et al in 2008, failed as efficacy has not been established in controlled clinical trials. Based
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to show difference between poisoned patients given AC, multidose AC, on case reports, its use can be considered in a few cases: (1) potentially
and supportive care only ; although the study has been criticized for fatal or otherwise highly toxic ingestion of sustained-release or enteric-
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its mean length from time of ingestion to hospital presentation and AC coated drugs, (2) ingestion of a large amount of iron, and (3) ingestion
administration (greater than 4 hours) and the frequent use of forced of large number of packets of illicit drugs (in the case of body packers).
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emesis prior to presentation. Other prospective trials, large retrospective WBI is performed with a polyethylene glycol electrolyte solution
studies, and meta-analyses, however, show effective absorption of drug (eg, GoLYTELY) 1 to 2 L/h by mouth or nasogastric tube. Irrigation is
and improvement in clinical outcome measures. 57-59 generally continued until the rectal effluent is clear or there is radio-
In light of these conflicting studies, the routine use of single-dose acti- graphic evidence of clearance. Contraindications to WBI include ileus,
vated charcoal in every poisoned patient is not recommended. Those gastrointestinal hemorrhage, and bowel perforation.
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patients who should receive single-dose activated charcoal include those
that have no contraindications for AC use and have a potentially toxic/ ■ FORCED DIURESIS AND URINARY pH MANIPULATIONS
fatal ingestion of drugs that can bind to AC. 61
If AC is administered, it should be done in a timely fashion after We do not recommend forced diuresis by volume loading and diuretic
ingestion, as efficacy has been shown to decrease over time. While clas- administration, which is intended to augment elimination of renally
sically taught that AC should be given within 1 hour of ingestion, there is excreted toxins through inhibition of tubular reabsorption. This regi-
evidence that it continues to significantly reduce drug absorption for up men is of unproven benefit and has the potential to compromise fluid
to 4 hours. Activated charcoal should be avoided in stuporous, coma- and electrolyte homeostasis and lead to fluid overload (pulmonary or
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tose, or convulsing patients unless an endotracheal tube protects the cerebral edema). 74
airway and a gastric tube is in place to administer the charcoal. Aspiration Therapeutic manipulation of urinary pH can enhance elimination of
of this particulate has been associated with pneumonia, bronchiolitis some intoxicants (Table 124-20). Most drugs are weak acids or bases
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obliterans, acute respiratory distress syndrome, and death. 65 and are present in both ionized and nonionized fractions in serum and
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Activated charcoal is generally given as a single dose. The dose is glomerular filtrate. Normally, passive renal tubular reabsorption of the
based on patient weight (1 g/kg added to four parts water to form an nonionized lipid-soluble fraction of such drugs occurs by nonionic
aqueous slurry). Mixing AC with juice, soda, or chocolate milk may diffusion; this process is accentuated by the progressive tubular reab-
improve patient acceptance of this unpleasant adsorbent. sorption of water and solutes as the glomerular filtrate traverses the
Multiple-dose AC (MDAC) can enhance the elimination of selected nephron, resulting in an increasing filtrate/serum concentration gradi-
toxins that have been absorbed. This may occur through interruption ent which favors drug reabsorption. Back-diffusion of some acidic and
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of the enterohepatic/enterogastric circulation of drugs or through the basic drugs from renal tubular lumen to the peritubular fluid and capil-
binding of drugs that diffuse from the circulation into the gut lumen. laries can be decreased by manipulation of urinary pH to create more of
However, multiple-dose AC is of limited use because the toxin must have the ionized (less lipid-soluble) salt of the drug.
a low volume of distribution, low protein binding, prolonged elimination Currently, urinary alkalinization is most frequently recommended
half-life, and low pK (negative logarithm of the acid ionization constant), in moderate salicylate toxicity not yet meeting criteria for hemo-
a
which maximizes transport across mucosal membranes into the gastroin- dialysis, although it may also be useful in enhanced elimination of
testinal tract. Based on experimental and clinical studies, the American chlorpropamide, 2,4-dichlorophenoxyacetic acid, diflunisal, fluoride,
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Academy of Clinical Toxicology and the European Association of Poisons mecoprop, methotrexate, and phenobarbital. 75
Centres and Clinical Toxicologists recommend it should be considered Urinary alkalinization (pH >7) is usually achieved by administration
only in life-threatening ingestions of selected drugs: carbamazepine, of intravenous sodium bicarbonate (1-2 mEq/kg every 3-4 hours); this
dapsone, phenobarbital, quinine, or theophylline. 68 may be administered as two 50-mL ampules of 8.4% sodium bicarbonate
In their position statement, the AACT/EAPCCT reported that MDAC (each containing 50 mEq of NaHCO ) per liter of 5% dextrose in water
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increases drug elimination, but has not been shown to reduce morbidity infused at 250 mL/h. 76
and mortality in controlled trials. The optimal dose and frequency of Complications of urinary alkalinization include alkalemia (particu-
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administration of AC following the initial dose has not been established. larly in the presence of concurrent respiratory alkalosis), volume over-
Most experts recommend a dose not less than 12.5 g/h. After the initial load, hypernatremia, and hypokalemia. It is particularly important to
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dose of 1 g/kg, AC may be administered at 0.5 g/kg every 2 to 4 hours avoid hypokalemia, which prevents excretion of alkaline urine by pro-
for at least three doses. Multiple doses should be used with caution in moting distal tubular potassium reabsorption in exchange for hydrogen
patients with decreased bowel sounds, abdominal distension, and emesis.
Contraindications for MDAC use are the same as those for single-dose AC.
Combining AC with a cathartic may facilitate evacuation of the toxin TABLE 124-20 Toxins Eliminated by Manipulation of Urinary pH
and avoid constipation. Preparations for coadministration with AC Alkaline Urine Acid Urine
include 1 to 2 mL/kg of a 70% solution of sorbitol titrated to several loose
stools over the first day of treatment. An alternative is to use 2 to 3 mL/kg 2,4 Dichlorophenoxyacetic acid Amphetamines
of a 10% solution of magnesium sulfate PO, but magnesium-based Fluoride Bismuth
cathartics may lead to magnesium accumulation in the setting of renal Isoniazid Ephedrine
failure, and sodium-based products carry the risk of exacerbating hyper-
tension or congestive heart failure. If aspirated, oil-based cathartics may Mephobarbital Flecainide
produce lipoid pneumonia. Methotrexate Nicotine
The efficacy of adding a cathartic to AC is unclear. Keller and col-
leagues demonstrated that AC with sorbitol decreased absorption of Phenobarbital Phencyclidine
salicylates compared to AC alone. McNamara and colleagues found Primidone Quinine
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no benefit to adding sorbitol to a simulated acetaminophen overdose. Quinolone antibiotics
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Catharsis has not been shown to decrease morbidity, mortality, or hospi- Salicylic acid
tal length of stay, and it is not recommended for routine use in combina-
tion with AC by the American Academy of Clinical Toxicology. 72 Uranium

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