Analgesics and Antidepressants

Chapter 79 Analgesics and Antidepressants

Aaron B. Skolnik, MD , Susan R. Wilcox, MD

1 What are the signs and symptoms of salicylate poisoning?

Supratherapeutic levels of salicylate produce characteristic tinnitus. Salicylate poisoning induces a central nervous system (CNS)–mediated respiratory alkalosis, while producing a metabolic acidosis. Aspirin in particular is highly irritating to the gastrointestinal tract, and patients may present with nausea, vomiting, abdominal pain, or hematemesis. Severe poisoning can induce hypoglycemia and hyperthermia due to uncoupling of oxidative phosphorylation and may also cause acute respiratory distress syndrome. Aspirin significantly inhibits platelet function, and any salicylate-containing product can inhibit vitamin K–dependent clotting factors when taken in overdose. The most serious poisonings involve the CNS and may present with confusion, agitation, delirium, hallucinosis, seizures, coma, or death.

2 When patients die of salicylate poisoning, of what do they usually die?

Usually, they die of cerebral edema or refractory shock with terminal arrhythmias. Their shock, in turn, is often related to severe and refractory acidemia.

3 What constitutes a toxic dose of aspirin?

Acute ingestion of greater than 150 mg/kg of aspirin or equivalent is sufficient to produce toxicity that may include gastrointestinal symptoms, metabolic disturbances, tinnitus, and tachypnea and/or hyperpnea. Acute ingestion of greater than 300 mg/kg of aspirin may be lethal. Be aware that chronic salicylate toxicity may also develop in elderly patients, dehydrated patients, or those taking carbonic anhydrase inhibitors. This can happen even at stable therapeutic dosing depending on the patient’s underlying health status and salicylate clearance.

4 What are the initial steps in treating salicylate poisoning?

First, delay and prevent absorption of salicylate. Early initial management of an acute ingestion should include administration of activated charcoal, when possible. Multiple dose activated charcoal may also be considered.

Patients should also be resuscitated.

Patients with moderate or severe poisoning are typically volume depleted, and intravenous fluids should be administered via bolus.

It is important to remember that salicylate-poisoned patients have a very high minute ventilation, both from primary respiratory alkalosis and to compensate for metabolic acidosis. Physicians must be especially cautious in administering sedation or initiating mechanical ventilation so as not to worsen acidosis.

5 What is the role of bicarbonate in the treatment of salicylate poisoning?

Alkalinization of serum is important in limiting the distribution of salicylate into tissues, especially the CNS. The ensuing urinary alkalinization traps salicylate in its ionized form in the urine and enhances renal clearance. Sodium bicarbonate solutions (typically dextrose 5% with 150 mEq/L sodium bicarbonate) should be infused to a goal serum pH of 7.5 to 7.55. Administration of intravenous bicarbonate will also help to alkalinize the urine, with a goal urinary pH of 8. To maintain alkaluria, potassium must also be replaced. Often, 40-50 mEq/L of potassium chloride is added to sodium bicarbonate infusions to maintain normokalemia.

6 What laboratory values are important in salicylate toxicity?

To guide therapy, arterial pH, serum electrolytes, and urinary pH must be measured frequently and high urine output maintained. As salicylate’s absorption from the gastrointestinal tract can be erratic, salicylate levels must also be checked serially, as often as every 1 to 2 hours in the most severely poisoned patients.

7 What are the indications for hemodialysis in salicylate poisoning?

Patients with renal failure, hemodynamic instability, any sign of CNS toxicity, or rising serum salicylate levels despite maximal medical therapy should undergo hemodialysis. Most patients with any salicylate level more than 100 mg/dL will require hemodialysis at some point in their treatment. Hemodialysis should be also considered for those with salicylate levels greater than 80 mg/dL on the basis of their clinical status. Failure to initiate hemodialysis promptly for neurotoxic patients is a common error in management, and salicylate-poisoned patients can very rapidly decompensate.

8 What are the signs and symptoms of acetaminophen poisoning?

The challenge of recognizing and treating acetaminophen toxicity is that patients are often asymptomatic after acute acetaminophen ingestion. Nausea, vomiting, anorexia, and/or lethargy may occur within hours of ingestion. Very rarely, massive overdose can cause altered mental status and metabolic acidosis within 6 hours of an overdose. Twenty-four to 48 hours after overdose, hepatic injury with transaminitis may develop or even acute or hyperacute liver failure with accompanying hyperbilirubinemia, jaundice, coagulopathy, and encephalopathy. Acute renal failure, which is probably multifactorial in origin, may also occur. Acetaminophen toxicity should be considered in any patient with unexplained liver failure.

9 What is the mechanism of acetaminophen-induced hepatotoxicity?

Acetaminophen’s hepatotoxicity is due to a reactive metabolite called N-acetyl-p-benzoquinone imine (NAPQI). Under therapeutic dosing conditions, most acetaminophen is metabolized in the liver by glucuronidation and sulfation. A tiny amount is excreted unchanged in the urine, and about 4% is metabolized by the cytochrome system (mostly cytochrome P 2E1) into NAPQI. NAPQI is then safely detoxified by the antioxidant effects of hepatic glutathione. However, under overdose conditions, hepatic glutathione stores become depleted, allowing NAPQI to bind to and cause death of hepatocytes.

< div class='tao-gold-member'>

Only gold members can continue reading. Log In or Register to continue

Related

Tags: Critical Care Secrets

Jul 6, 2016 | Posted by admin in CRITICAL CARE | Comments Off

Full access? Get Clinical Tree

Get Clinical Tree app for offline access

Get Clinical Tree app for offline access