Page 1752 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 124: Toxicology in Adults 1221

TABLE 124-27 Clinical Features of Salicylate Intoxication TABLE 124-28 Indications for Hemodialysis in Salicylate Intoxication
Mild to Moderate Severe Serum level: >120 mg/dL acutely, or >100 mg/dL 6 h after ingestion
Headache Lethargy Volume overload
Dizziness Hallucinations Noncardiogenic pulmonary edema
Tinnitus Delirium Renal failure precluding bicarbonate therapy
Deafness Seizures CNS toxicity: coma or seizures
Hyperventilation Coma Refractory acidosis
Nausea Respiratory alkalosis Deteriorating course
Vomiting Metabolic acidosis Chronic ingestion
Vasodilation Gastrointestinal bleeding
Tachycardia Hypotension
Special attention should be paid to patients with severe salicylate
Pulmonary edema
toxicity and altered mental status that require mechanical ventilation.
Cerebral edema Inappropriate ventilator settings that produce respiratory acidosis
Hypoglycemia can increase salicylate concentration in the CNS, and thereby worsen
outcome. The patient’s acid-base status should be followed closely
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Hyperpyrexia
after intubation aiming for an arterial pH of 7.5 to 7.6. 363
Renal and liver failure ■
SELECTIVE SEROTONIN REUPTAKE INHIBITORS
The lethal adult dose is approximately 10 to 30 g (35 tablets or more). The selective serotonin reuptake inhibitors (SSRIs) are noncyclic anti-
Lethality correlates poorly with serum levels, although levels are useful to depressant agents that selectively inhibit the presynaptic neural uptake
establish the diagnosis. Levels are even less useful in chronic salicylism, of serotonin. Most SSRIs are relatively nontoxic when taken alone, but
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which may occur unintentionally in elderly patients receiving long-term when taken in high dose, or combination with a number of other drugs
analgesic therapy. These patients are more likely to present with CNS (listed in Table 124-29), there can be excessive stimulation of 5-HT1A
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toxicity or noncardiogenic pulmonary edema ; isolated mild eleva- and 5-HT2 receptors that leads to the serotonin syndrome. Because of
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tion of the prothrombin time is another telltale sign. Urine tests with
Phenistix or ferric chloride can be used to detect salicylate poisoning. 359
Optimal management of a salicylate-intoxicated patient requires
appreciation of the toxicokinetics of ingestion and the importance of TABLE 124-29 Selected Drugs That Increase Risk of Serotonin Syndrome
serum pH in determining drug disposition. At therapeutic levels, sali- in Patients Taking Selective Serotonin Reuptake Inhibitors
cylic acid is 90% protein bound. Most (75%) is partially glycinated in Almotriptan
the liver to form salicyluric acid, a less toxic and more water soluble,
renally excreted metabolite. Proximal organic anion secretion, rather Buspirone
than glomerular filtration, is normally responsible for the bulk of Caffeine
salicylate excretion, since salicylate is a highly protein-bound drug, and Cocaine
pH-dependent nonionic back-diffusion from the tubular lumen occurs
at alkaline urine pH. At toxic levels, however, only 50% of salicylic acid Dextromethorphan
is protein bound, so that (with increased tissue distribution) the cus- “Ecstasy” (3,4-methylenedioxymethamphetamine; MDMA)
tomary metabolic pathway via salicyluric acid becomes saturated, and Eletriptan
elimination half-life increases from 3 to 12 hours to 15 to 30 hours. Ergotamine
The extent of tissue distribution of absorbed salicylate is influ-
enced by plasma pH. For instance, CNS toxicity may be ameliorated Frovatriptan
by administration of bicarbonate and raising plasma pH. Systemic l-tryptophan
alkalinization has the additional salutary effect of augmenting renal Linezolid
salicylate excretion. Raising urinary pH from 6.1 to 8.1 results in an over
18-fold increase in renal clearance by preventing nonionic tubular back- Lithium
diffusion. This decreases the half-life of salicylates from 20 to 24 hours Monoamine oxidase inhibitors
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to <8 hours. To accomplish urinary alkalinization, it is vital to avoid Meperidine
hypokalemia that prevents excretion of alkaline urine by promoting dis-
tal tubular potassium reabsorption in exchange for hydrogen ion. One Methylphenidate hydrochloride
recommended alkalization regimen includes combining three ampules Mirtazapine
of sodium bicarbonate (44 mEq Na per ampule) in D5W and infuse at Naratriptan
+
a rate of 2 to 3 mL/kg/h to maintain urine output at 1 to 2 mL/kg/h and Nefazodone
aiming for urinary pH of 7.5 to 8.5. As mentioned above, 40 mEq of KCl
is added to the bicarbonate infusion to prevent hypokalemia. 361 Rizatriptan
Additional supportive care includes empiric administration of dex- Sumatriptan
trose even in euglycemic patients to theoretically treat low CSF glucose Tramadol
levels. Treatment of an acute ingestion starts with gastric lavage and
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AC in the appropriate clinical setting. These strategies are not helpful in Trazodone
chronic salicylism. Tricyclic antidepressants
Indications for hemodialysis are listed in Table 124-28. In chronic Venlafaxine
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overdose, HD may be necessary for symptomatic patients with serum
levels over 60 mg/dL. 78 Zolmitriptan

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