Overdoses


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.

  • 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.

    • 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).

  • 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.


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.

  • 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).

  • 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.

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.

  • 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.

  • 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.

  • 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.

  • 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.

    • 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.

  • 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.

  • 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.

  • 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.

    • Anticholinergic effect: mental status changes, seizures, coma.
    • Alpha-1 adrenergic blockade: vasodilation, hypotension.
    • Antihistamine effect: sedation.
    • Serotonin, norepinephrine, and dopamine reuptake inhibition:

      • Antidepressant effect at therapeutic doses.
      • In overdose, transient hypertension is followed by hypotension and bradycardia as catecholamines are depleted.
      • Also contributes to agitation and seizures.

  • 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.

    • Rightward deviation of the terminal 40 milliseconds of QRS.

      • Lead aVR: large (>3 mm) terminal R wave or R/S ratio >0.7.

  • 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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Feb 17, 2017 | Posted by in CRITICAL CARE | Comments Off on Overdoses

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