Figure 66.1. Rumack–Matthew nomogram. (Courtesy of Graham Walker, MD.)
Critical management
- Activated charcoal can be given as a gastric decontaminant:
- It is most effective if given in the first hour.
- It can absorb co-ingestants as well.
- It is harmful if aspirated. The patient must be alert and cooperative.
- It is most effective if given in the first hour.
- Gastric lavage is rarely indicated.
- It can be considered in cases of recent highly toxic co-ingestions.
- N-Acetylcysteine (NAC) is life saving if given early enough.
- Draw an acetaminophen level and plot it on the nomogram if the time of ingestion is known.
- Note that the nomogram starts at 4 hours post ingestion. Levels drawn earlier than this will generally not be helpful to guide treatment.
- Begin treatment if the level is above the treatment line on the nomogram.
- Preparing the appropriate NAC infusion should be done after discussion with a pharmacist.
- N-Acetylcysteine has been shown to completely reverse the effect of an acetaminophen overdose if administered within 8 hours after the ingestion. It still offers protective effects up to 24 hours after ingestion although the success rate decreases proportionally to the delay.
- If a patient presents at 8 hours or later after a toxic ingestion, do not delay treatment while waiting for an acetaminophen level.
- NAC can be given orally or intravenously (IV).
- Oral NAC can cause nausea and vomiting, making its administration sometimes difficult.
- IV NAC can rarely cause anaphylactoid reactions.
- The intravenous route has not been shown to be superior to the oral regimen, but intravenous treatment is usually preferred.
- Oral NAC can cause nausea and vomiting, making its administration sometimes difficult.
- Therapy is discontinued once acetaminophen metabolism is complete (level <10 micrograms/mL) and liver injury is resolving (normal or near normal enzymes, absence of encephalopathy or coagulopathy).
- Draw an acetaminophen level and plot it on the nomogram if the time of ingestion is known.
- Some patients with severe overdoses and meeting certain criteria may be candidates for liver transplantation. Various scoring systems exist to help decide which patients should be referred to a liver transplantation center:
- King’s College Criteria (Table 66.1)
- Lactic acidosis >3.5 mg/dL after early fluid resuscitation
- Phosphorus >3.75 mg/dL at 48 hours
- Apache II score >15.
- King’s College Criteria (Table 66.1)
Table 66.1. King’s College Criteria
| pH <7.30 or all three of the following: |
| INR >6.5 (PTT >100 seconds) |
| Creatinine >3.4 mg/dL |
| Grade 3 or 4 hepatic encephalopathy |
Sudden deterioration
- These patients can develop sepsis with multi-organ failure.
- Initiate hemodynamic support with intravenous fluids and vasopressors or inotropes as per the early goal-directed therapy protocol.
- Respiratory support with oxygen, noninvasive ventilation, or intubation may be required.
- Initiate hemodynamic support with intravenous fluids and vasopressors or inotropes as per the early goal-directed therapy protocol.
- ARDS should be managed by endotracheal intubation and ventilator settings in accordance with the ARDSNet guidelines.
- Patients with evidence of renal failure should have their electrolytes checked and corrected. Hemodialysis may have to be initiated after consultation with a nephrologist.
- Cerebral edema and herniation are very difficult to treat successfully. Mannitol, hypertonic saline, or cranial decompression can be attempted in the rapidly decompensating patient.
Aspirin
Overview
- Aspirin (acetylsalicylic acid, ASA) is a weak acid that is widely used and is present in many mixed preparations.
- It is rapidly absorbed in its uncharged, nonionized form, in the acidic environment of the stomach.
- In nontoxic ingestions, the majority of the salicylate is protein-bound and free salicylate is mostly ionized.
- In overdose, albumin becomes saturated and free salicylate concentration increases:
- As acidosis worsens, more salicylate exists in nonionized form.
- This crosses into tissues and exerts toxicity, especially in the central nervous system (CNS).
- As acidosis worsens, more salicylate exists in nonionized form.
- Aspirin is normally metabolized by the liver through conjugation.
- In overdose, enzymes become saturated and renal elimination becomes important.
Presentation
Classic presentation
- May be asymptomatic
- Tinnitus or impaired hearing
- Hyperventilation
- Nausea and vomiting
- Hyperthermia
- Dehydration
- Mixed acid–base disturbance:
- Respiratory alkalosis from direct stimulation of the medulla
- Anion gap metabolic acidosis from uncoupling of oxidative phosphorylation.
- Respiratory alkalosis from direct stimulation of the medulla
Critical presentation
- Cerebral edema resulting in altered mental status, coma, convulsions
- Pulmonary edema
- Coagulopathy
- Acute renal failure
- Gastrointestinal (GI) hemorrhage
- Severe acid–base imbalance.
Diagnosis and evaluation
- A good history is critical, including the amount of drug taken and the time of ingestion.
- Early signs usually include tinnitus, nausea, and vomiting.
- On examination the patient may be hyperthermic, tachycardic, hyperpneic, diaphoretic, and confused.
- A salicylate level should be ordered even though it does not always correlate with toxicity.
- Electrolytes should be checked specifically for renal function and potassium level:
- Renal failure will prevent elimination of salicylates.
- Hypokalemia will hinder urinary alkalinization.
- Renal failure will prevent elimination of salicylates.
- Arterial or venous blood gas to monitor pH.
- Lactic acid concentration.
- Always check an acetaminophen level in any suspected toxic overdose as co-ingestion is common.
Critical management
- Activated charcoal should be given as gastric decontaminant.
- It can absorb co-ingestants as well.
- It is harmful if aspirated. The patient should be alert and cooperative.
- It can absorb co-ingestants as well.
- Gastric emptying with lavage can be considered in early presentations of massive overdoses.
- Aggressive fluid resuscitation is indicated as most patients are hypovolemic due to vomiting, tachypnea, and hyperthermia.
- Airway management:
- Although endotracheal intubation may be necessary for airway protection, attempt to avoid intubation if possible as it is difficult for the ventilator to maintain as high a minute ventilation as a tachypneic person.
- The patient may not tolerate even a brief episode of apnea if severely acidemic.
- Consider awake intubation.
- If awake intubation is not possible, consider a sodium bicarbonate bolus with 100 mEq of sodium bicarbonate prior to the initiation of rapid sequence intubation.
- Although endotracheal intubation may be necessary for airway protection, attempt to avoid intubation if possible as it is difficult for the ventilator to maintain as high a minute ventilation as a tachypneic person.
- Ventilator settings:
- These patients are usually acidemic and will require a high minute ventilation to compensate for the metabolic acidosis.
- An arterial or venous blood gas should be drawn 10–15 minutes after intubation and the tidal volume and respiratory rates should be adjusted to achieve a PaCO2 of 35–40 mmHg.
- These patients are usually acidemic and will require a high minute ventilation to compensate for the metabolic acidosis.
- Urinary alkalinization is the mainstay of therapy.
- It is achieved by administering a sodium bicarbonate bolus followed by a drip:
- Bolus 1–2 mEq/kg IV.
- Prepare a drip by mixing three ampules (50 mEq each) of sodium bicarbonate in 1 liter of D5W. Run at twice the maintenance rate.
- Titrate to a urine pH >7.5.
- Consider adding 40 mEq of potassium chloride to fluids.
- Do not mix the sodium bicarbonate into normal saline or the solution will be hypertonic.
- Bolus 1–2 mEq/kg IV.
- Alkaline urine will trap salicylate ions and allow for excretion.
- Alkalinization of serum relative to CSF will prevent transfer of salicylate into the brain.
- Maintain normal potassium levels by repleting if necessary as hypokalemia will prevent the excretion of acid into the urine.
- It is achieved by administering a sodium bicarbonate bolus followed by a drip:
- Serial salicylate levels should be checked to monitor therapy effects.
- Continue therapy until the levels are at or below 30 mg/dL.
- Concretions of aspirin may exist in the GI tract and cause a delayed peak of salicylate level.
- Continue therapy until the levels are at or below 30 mg/dL.
- Hemodialysis is the definitive treatment:
- Treats acid–base disturbances and removes salicylate from blood.
| • Indications for hemodialysis in aspirin overdose |
| • End-organ damage such as altered mental status, acute lung injury, or coagulopathy |
| • Renal failure resulting in the inability to eliminate the drug |
| • Inability to tolerate the necessary fluid load for alkalinization |
| • Refractory acidemia |
| • Absolute serum concentrations >100 mg/dL in acute ingestions, or 60 mg/dL in chronic ingestions |
| • Clinical deterioration despite alkalinization and other supportive management |
Sudden deterioration
- Decline in mental status, coma, or seizure can be caused by cerebral edema.
- Any alteration in mental status should lead to consideration for hemodialysis.
- Fluid overload can result in pulmonary edema and respiratory failure.
- Dialysis should be initiated in patients that are not able to tolerate the fluid load necessary for urine alkalinization.
- Intubation may be necessary and should be done early before the development of severe acidemia.
- Dialysis should be initiated in patients that are not able to tolerate the fluid load necessary for urine alkalinization.
- Patients with salicylate overdose are also at risk of life-threatening GI bleeding and administration of blood product should be initiated in those patients.
Tricyclic antidepressants
Overview
- Tricyclic antidepressants (TCAs) are mostly used for the treatment of neuropathic and chronic pain.
- TCAs are rapidly absorbed in the GI tract.
- They have multiple physiological effects.
- Sodium channel blockade:
- Type Ia (quinidine-like) dysrhythmic effect: blocks fast inward sodium channels at phase 0 of myocyte depolarization.
- Decreases conduction with QRS prolongation.
- Negative inotropy.
- Type Ia (quinidine-like) dysrhythmic effect: blocks fast inward sodium channels at phase 0 of myocyte depolarization.
- Anticholinergic effect: mental status changes, seizures, coma.
- Alpha-1 adrenergic blockade: vasodilation, hypotension.
- Antihistamine effect: sedation.
- Serotonin, norepinephrine, and dopamine reuptake inhibition:
- Sodium channel blockade:
- Death is most often due to refractory hypotension and cardiovascular collapse.
Presentation
Classic/critical presentation
- Anticholinergic effects initially predominate:
- Sinus tachycardia, hypertension, agitation, pupillary dilation, dry and flushed skin, hyperthermia.
- QRS complex widening on ECG with terminal R wave in lead aVR.
- Rapid deterioration usually occurs within 30–60 minutes of presentation.
- Altered mental status, coma, seizures.
- Ventricular dysrhythmias.
- Hypotension.
Diagnosis and evaluation
- The diagnosis is made based on history, clinical presentation and ECG findings (Figure 66.2).
- A dose of >10 mg/kg of most TCAs is considered life-threatening.
- ECG findings:
- The most common findings are sinus tachycardia and a right axis deviation.
- QRS prolongation (>100 milliseconds):
- <100 milliseconds: no significant toxicity.
- >100 milliseconds: 30% will have seizures.
- >160 milliseconds: 60% will have ventricular dysrhythmias.
- <100 milliseconds: no significant toxicity.
- Rightward deviation of the terminal 40 milliseconds of QRS.
- Lead aVR: large (>3 mm) terminal R wave or R/S ratio >0.7.
- The most common findings are sinus tachycardia and a right axis deviation.
- Quantitative and qualitative tests for TCAs are not helpful in the acute management.
Figure 66.2. Classic ECG changes after TCA overdose: sinus tachycardia, QRS duration >100 milliseconds, right axis deviation, terminal R wave in aVR (or S wave in I or aVL).
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