A 48-year-old male is well known to your hospital for his severe alcohol use disorder. In the emergency department a breathalyzer showed an ethanol level of 250 mg/dL, and he was noted to be more somnolent than usual. He then had an episode of emesis streaked with bright red blood. He was intubated for airway protection and admitted to the ICU. In the ICU, an elevated osmolal gap is noted and he is started empirically on fomepizole. The next day, an arterial blood gas is drawn with a pH of 7.38, but the patient does not awaken to participate in a spontaneous awakening trial/spontaneous breathing trial (SAT/SBT).
What is the likely substance responsible for his continued altered mental status?
Correct Answer: A
Isopropyl alcohol is a common ingredient in some rubbing alcohols and nail polish removers. When ingested, it is a potent central nervous system (CNS) depressant, approximately two to four times more potent than the same dose of ethanol. In addition to its increased potency, the duration of action is approximately two to four times as long as ethanol.
Unlike the other toxic alcohols, where various metabolites are responsible for the toxic effects, isopropyl alcohol itself is responsible for the CNS depression. Therefore, inhibition of its metabolism via ethanol or fomepizole serves only to prolong the duration of action and is not indicated.
In this case, both the co-ingestion of ethanol and the iatrogenic administration of fomepizole have combined to maintain the toxic concentration of isopropyl alcohol in the blood and consequently the CNS depression and resultant altered mental status.
Isopropyl alcohol may be ingested in place of ethanol in an attempt to become inebriated and transdermal toxicity has been reported by “sponge bathing” in children. It is a potent gastrointestinal irritant when ingested enterically and may produce hemorrhagic gastritis. It is metabolized into acetone and can produce a characteristic “fruity” odor to the breath. Because acetone is a ketone, not an organic acid, metabolism of isopropyl alcohol does not produce the characteristic metabolic acidosis seen with other toxic alcohols.
Although ethanol may be contributing to the patient’s altered mental status, isopropyl alcohol is a more potent CNS depressant and is likely the substance responsible for his altered mental status. Methanol, ethylene glycol, and propylene glycol can all produce an elevated anion gap but do not produce the same hemorrhagic gastritis or altered mental status as isopropyl alcohol.
References:
A 53-year-old female is well known to your hospital for her neardaily visits for acute alcohol intoxication. After a curious 3-day absence from the emergency department, she is brought in by local paramedics after being found, confused, in a local park. Her heart rate on arrival is 163 bpm and her blood pressure is 210/105. She is noted to be tremulous and diaphoretic and tells the ED that she quit alcohol “cold turkey” 3 days prior. Despite repeated doses of parenteral lorazepam, she continues to be in moderate-to-severe alcohol withdrawal and a continuous infusion of lorazepam is initiated. Assuming that the infusion is titrated to avoid oversedation, what acid-base disturbance would you expect to see with a prolonged infusion of lorazepam?
Correct Answer: C
Intravenous lorazepam is most commonly mixed in a solution of propylene glycol. Propylene glycol is metabolized by alcohol dehydrogenase (ADH) to lactaldehyde and then by aldehyde dehydrogenase (ALDH) into lactic acid. As an organic acid, lactic acid produces a metabolic acidosis.
Commonly used ICU medications that are mixed in propylene glycol include lorazepam (Ativan), diazepam (Valium), phenytoin (Dilantin), and phenobarbital. Prolonged or high-dose infusions of this medication can produce a lactic (metabolic) acidosis and resulting organ dysfunction including hypotension and dysrhythmias. Most propylene glycol overdoses are therefore iatrogenic and should be in the differential of any new lactic acidosis seen in the ICU. The treatment is supportive and involves discontinuing the offending medication.
A 19-year-old male was brought to the emergency department of your hospital by his fraternity brothers after he “chugged” two full bottles of whiskey as part of a pledging ritual. EMS transported the patient to the emergency department where he was intubated for unresponsiveness. Point-of-care glucose was normal, as were serum electrolytes. An ethanol level is measured at 450 mg/dL. He is admitted to the ICU for further management.
What is the appropriate next step in management?
Correct Answer: D
Ethanol is one of the most commonly used and abused intoxicants in the world. Most of the morbidity and mortality in the acute phase of ethanol ingestion is from accidental injury such as trauma. Ingestion of large volumes of alcohol or co-ingestion with other medications such as benzodiazepines or opioids can cause respiratory suppression and death. For most ethanol intoxication, clinical observation and ruling out other causes of altered mental status such as hypoglycemia is the mainstay of treatment. However, some patients may require tracheal intubation for airway protection and admission to the ICU.
Ethanol is absorbed quickly from the gastrointestinal tract into the bloodstream, typically within the first hour after ingestion. Therefore, gastric lavage is rarely indicated, even for acute intoxication, as it requires intubation and serves only to increase the risk of aspiration. Although activated charcoal can be used for certain poisonings immediately after ingestion, its use is contraindicated in patients with altered mental status. Furthermore, activated charcoal does not bind ethanol.
Many patients with alcohol intoxication will present with some aspect of hypovolemia due to increased diuresis from ethanol. However, administration of intravenous fluids does not aid in the metabolism of ethanol and large-volume crystalloid administration is not indicated in the management of acute alcohol ingestions. Additionally, large-volume crystalloid administration could lead to profound metabolic acidosis and electrolyte disturbances.
Alcohol dehydrogenase becomes quickly saturated at even low concentrations of ethanol, therefore elimination follows zero-order kinetics and a constant amount of alcohol is eliminated over time (typically 15- 20 mg/dL per hour). People with alcohol abuse disorders typically metabolize alcohol at a higher rate (approximately 25-35 mg/dL per hour). Although hemodialysis can remove ethanol, it is typically reserved only for extreme cases causing severe hemodynamic instability.
A 23-year-old female is admitted to the ICU after ingesting a bottle of medication in a suicide attempt. In the emergency department, the patient complained of abdominal pain and ringing in her ears, and would tell the physicians only that she bought the bottle of “pain medication” from a neighborhood convenience store earlier in the day. On arrival to the ICU, she is tachypneic and lethargic.
What acid-base disturbance would you expect on blood gas analysis?
The patient likely ingested salicylates, probably from aspirin (acetylsalicylic acid). Of the other common over-the-counter pain relievers, acetaminophen (Tylenol) manifests its toxicity with delayed liver damage. Common nonsteroidal anti-inflammatory medications (NSAIDs) such as ibuprofen (Motrin, Advil) or naproxen (Aleve) are typically well-tolerated, except in very large overdoses (above 100 mg/kg). Opioid pain medications, while not available over-the-counter in the United States, typically present with respiratory suppression.
Salicylate toxicity is most often seen in the context of aspirin overdoses but is also present in other common household products such as PeptoBismol (bismuth subsalicylate), topical salicylate creams (Aspercreme, Bengay), and oil of wintergreen, which can be particularly concentrated.
Initially, salicylates directly stimulate the medullary respiratory center, producing tachypnea and a metabolic alkalosis. As the salicylate is metabolized, it interferes with aerobic metabolism by uncoupling oxidative phosphorylation in the mitochondria, producing a metabolic acidosis.
In addition to the classic metabolic disturbances, salicylates initially provoke gastrointestinal distress with nausea, vomiting, and diarrhea, as well as tachypnea. As the poisoning progresses, tinnitus (ringing in the ears) occurs because of both central and peripheral effects. Late signs of salicylate toxicity include altered mental status, cerebral and pulmonary edema, hyperthermia, seizures, and ultimately death from cardiovascular collapse.
An 18-year-old male is admitted to your ICU after ingesting two “handfuls” of generic pain medications. In the emergency department, acetaminophen was not detected and a salicylate level was 20 mg/dL (therapeutic reference range 10-30 mg/dL). Upon arrival to the ICU, the patient complains of mild nausea and is mildly tachypneic. Lab testing in the ICU is notable for a pH of 7.50 and a repeat salicylate level of 35 mg/dL.
What should be your next step in clinical management?
Correct Answer: B
As evidenced by the rising salicylate level, the patient ingested aspirin (acetylsalicylic acid). Interestingly, aspirin tablets can aggregate in the stomach in overdose, forming a bezoar and delaying absorption. Given the rising salicylate level, empiric treatment for salicylate overdose should be initiated.
The mainstay of treatment for salicylate poisoning is administration of sodium bicarbonate. Because salicylic acid is a weak acid, alkalinization of the urine shifts the form of salicylic acid to the deprotonated form, “trapping” the ion in the urine and increasing excretion. Raising the serum pH limits tissue distribution by the same mechanism, “trapping” the ionic form in the bloodstream and out of sensitive areas such as the central nervous system. Given the rising salicylate level, high index of suspicion, and development of tachypnea, empiric sodium bicarbonate should be administered. Note that an elevated pH should not be seen as a contraindication to initiation of sodium bicarbonate therapy. In severe overdoses, hemodialysis may be indicated.
Although the initial stage of salicylate toxicity manifests as a respiratory alkalosis due to direct stimulation of the respiratory centers of the medulla, a profound metabolic acidosis develops later in the ingestion as a result of decoupling of oxidative phosphorylation. The minute ventilation required for respiratory compensation can be very high; therefore, endotracheal intubation should be reserved only for severe cases and should be performed quickly because of the risk for worsening acidosis from inadequate ventilation and resulting cardiovascular collapse.
Monitoring of the salicylate level can help guide therapy; it should be measured every 2 hours in an acute overdose until it drops below the toxic threshold. As the salicylate level is increasing, discharging the patient is premature.
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