Page 1748 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 124: Toxicology in Adults 1217

digoxin toxicity in patients with renal insufficiency, including chronic overdose. Lithium is a low-molecular-weight monovalent cation, has a
hemodialysis patients; the potential late complication of rebound small volume of distribution, and is eliminated by glomerular filtration.
intoxication because of impaired Fab-digoxin complex excretion is not It has a prolonged elimination half-life that is increased by advancing
commonly seen even in such circumstances. Nevertheless, monitoring age, renal insufficiency, and duration of therapy. Lithium is predomi-
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of free (rather than total) plasma digoxin levels, and consideration of nantly (80%) reabsorbed in the proximal renal tubule; the other 20% of
follow-up plasmapheresis to remove Fab-digoxin complexes, has been filtered load is excreted. Any stimulus that augments proximal tubular
advocated to prevent late rebound toxicity in renal failure patients. 286 sodium reabsorption tends to cause increased Li reabsorption in paral-
Supportive therapy of overdose includes rapid correction of elec- lel and may precipitate Li intoxication; volume depletion, congestive
trolytes, particularly hypokalemia. As noted above, hyperkalemia may heart failure, cirrhosis, and other salt-avid states all reduce Li clearance
also require treatment unless Fab therapy is immediately available. in this manner, independently of effects on glomerular filtration rate.
Historically, medical management of hyperkalemia in the setting of Lithium toxicity can be divided into three categories: acute (in patients
digoxin overdose has avoided calcium use because of case reports in not on lithium), acute-on-chronic (acute ingestion in patients who are
1936 of a condition dubbed “stone heart.” Although numerous studies on lithium therapy), and chronic toxicity (toxic effects without acute
have not shown adverse effects of giving calcium in patients and animal overdose). Acute or acute-on-chronic lithium overdose with suicidal
287
models with severe hyperkalemia and elevated digoxin levels, recom- intent or by medication error occurs in only 10% to 20% of cases of
288
mendations remain to try to avoid its use or to use it in only refractory lithium toxicity. 304
cases where Fab fragments are not immediately available. Severe brady- Serum levels following acute Li ingestion correlate poorly with
arrhythmias that are unresponsive to atropine may require electrical intracellular Li levels and clinical symptoms. A closer correlation exists
pacing. Ventricular tachycardia should be treated with lidocaine. Electrical between serum levels and clinical symptoms in chronic and acute-on-
cardioversion of any digitalis toxicity–induced arrhythmia should be chronic intoxications. Thus severe toxicity may occur at lower serum
reserved as a last resort, using the minimum effective energy level. levels in the setting of chronic Li ingestion than following acute inges-
■ γ-HYDROXYBUTYRATE tion without previous use. 305
Clinical manifestations of overdose are primarily neurologic. Clinical
γ-hydroxybutyrate (GHB), also known as “liquid ecstasy,” “liquid G,” features of mild (1.5-2.5 mEq/L) and moderate (2.5-3.5 mEq/L) intoxi-
“date-rape drug,” or “fantasy,” has been popular among young cation include nausea, vomiting, diarrhea, weakness, and neurologic
individuals. In the 1980s, the drug was promoted to bodybuilders as a dysfunction (confusion, tremor, nystagmus, dysarthria, ataxia, and
growth hormone stimulator and muscle-bulking agent. Recreationally, it other signs of cerebellar dysfunction), and choreiform and Parkinsonian
was claimed to cause euphoria without a hangover and to increase sen- movements reflecting basal ganglia involvement. Severe toxicity
suality and disinhibition. In 1990, GHB was banned outside of clinical (>3.5 mEq/L) is characterized by worsening neurologic dysfunction
trials approved by the FDA, although the sodium salt of GHB (sodium (seizures and coma) and cardiovascular instability (sinus bradycardia
oxybate or Xyrem) remains available for the treatment of cataplexy and and hypotension). Decreased serum anion gap (<6 mEq/L, because
narcolepsy. of excess cation) is an interesting consequence of severely elevated
GHB is derived from γ-aminobutyric acid (GABA) and is thought (>3.5 mEq/L) Li levels. Both hypothermia and hyperthermia have been
to function as an inhibitory transmitter through specific brain recep- reported to occur in Li-intoxicated patients. Acute overdose has a 25%
tors for GHB and through GABA receptors. 289,290 GHB increases stage mortality, and 10% of survivors have permanent neurologic deficits.
IV of non–rapid eye movement sleep (slow-wave deep sleep). In Chronic use is associated with development of nephrogenic diabetes
291
narcoleptics it decreases cataplexy, sleep paralysis, hallucinations, and insipidus, renal insufficiency, hypothyroidism, and leukocytosis.
daytime sleep attacks. Clinical manifestations of GHB depend on the Treatment of Li intoxication is guided by a combination of clinical
292
dose ingested. Regular use causes tolerance and dependence, and abrupt features and serum levels. Supportive care includes seizure control and
discontinuation can result in delirium and psychosis. Low doses of use of vasopressors for hypotension refractory to fluids. Gastrointestinal
293
GHB can induce a state of euphoria. Higher doses can cause coma and decontamination following excessive lithium ingestion is the subject
death. Emesis, bradycardia, hypotension, and respiratory acidosis of a number of in vitro and animal studies and is particularly impor-
294
have all been described. 295 tant because sustained-release preparations are usually involved. Oral
Treatment of GHB poisoning is mainly supportive. It is important activated charcoal is ineffective in preventing Li absorption, because it
to keep in mind that coingestions are common, especially with ethanol adsorbs Li poorly. 306-308 In the setting of overdose with multiple medica-
and amphetamines. While mechanical ventilation may be initially tions, its use can be considered (if there are no other contraindications)
295
required, it is typical for most patients to regain consciousness within 1 to limit absorption of the other poisons. Animal studies and retrospec-
to 5 hours, allowing for extubation. 295,296 tive analyses have suggested that oral sodium polystyrene sulfonate
307,309
In 2000, Yates and Viera described two patients with GHB overdose (Kayexalate) impairs absorption of ingested Li, although its use
who awoke in less than 5 minutes after a single dose of physostigmine. requires close monitoring of serum potassium. Polyethylene glycol
297
Although the efficacy of physostigmine in reversing GHB-induced coma whole-bowel irrigation has also been used to limit absorption of an
310
is still debatable ; furthermore, numerous concerns have been raised acute overdose of sustained-release lithium in normal volunteers.
298
about its safety. In another case series, physostigmine was associated Elimination of Li is enhanced by volume loading (with normal saline)
299
with atrial fibrillation, bradycardia, and hypotension. 300 of hypovolemic patients, as dehydrated patients will continue to reab-
Usual toxicologic screens do not include GHB. However, when docu- sorb lithium. This therapy has limited efficacy after normovolemia has
mentation is important in cases of sexual assault, GHB can be detected been restored and risks precipitating hypernatremia in the presence of
in urine and blood by special laboratories using gas chromatography- excessive ongoing water loss because of underlying diabetes insipidus.
mass spectroscopy. 301,302 Lithium is the prototypical dialyzable intoxicant, owing to its hydrophi-
licity, low molecular weight, complete absence of protein binding, small
■ LITHIUM apparent volume of distribution, and prolonged half-life.
The decision to proceed to HD should be based on clinical char-
Despite its low therapeutic index (target range = 0.5-1.25 mEq/L), lith- acteristics. There are three absolute indications for HD: (1) severe
ium (Li) is used for treatment of bipolar disorder. Most cases of intoxica- neurologic symptoms, (2) symptoms of toxicity in the setting of renal
tion, associated with levels above 1.5 mEq/L, are caused by unintentional failure, and (3) the inability to safely rehydrate with IV fluids (eg, those
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overdose during chronic therapy. Volume depletion (aggravated by with pulmonary edema). These clinical indications should be used
underlying diabetes insipidus) and renal insufficiency can precipitate in conjunction with measured serum Li levels. As general guidelines,

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