Setting: emergency department (ED)
CC: “I feel confused and my mouth is dry.”
VS: BP: 104/68 mm Hg; P: 112 beats/minute; T: 99.8°F; R: 22 breaths/minute
HPI: A 23-year-old man with a history of depression is brought to the ED because of confusion developing over the past several hours. He has been drinking alcohol and taking a number of unknown substances. He became more disoriented and obtunded just as he passed through the triage process in the ED and went to the bathroom. The staff were concerned that he had taken something in the bathroom.
The ED is the most “time-sensitive” part of the hospital. It is where the computer-based case simulation (CCS) is meant to evaluate your proper understanding of the right order in which to give treatments and do tests. It isnot being “picky” to insist you know the right timing and sequence of patient management.
Which of these is most important to do first?
a. Give naloxone, thiamine, and dextrose.
b. Test acetaminophen and aspirin levels.
c. Do a urine or blood toxicology screen.
d. Order gastric emptying (lavage).
e. Give oxygen.
f. Do an endotracheal intubation.
Answer a. Give naloxone, thiamine, and dextrose.
Prescription opiate overdose is markedly increasing. Patients are far more likely to die of a prescription opiate overdose than an illegal opiate such as heroin. Naloxone works instantly, and if the patient’s altered mental status is from opiates, you will know immediately. Naloxone works before you even leave the patient’s bedside. There is no significant danger from acute opiate withdrawal. Dextrose and thiamine are routinely given to every person with acute mental status changes of unclear etiology.
Diagnostic testing with toxicology screening is important, but not as important as instantly reversing opiate intoxication or hypoglycemia. Oxygen is not important in the absence of hypoxia or respiratory distress.
Do not intubate, when you might be able to just wake the person up with naloxone.
Fast reversal with naloxone is better than lavage.
Get aspirin and acetaminophen levels on every overdose.
PMHX:
Depression
Anxiety
Medications:
Alprazolam
Amitriptyline
PE:
General: lethargic, increasingly sleepy
Neurologic: stuporous; incomplete examination because of inability to follow commands
Head, ears, eyes, nose, throat (HEENT): dilated pupils
Abdomen: decreased bowel sounds
Cardiovascular: tachycardia only
Skin: hot, dry, flushed
Initial Orders:
Naloxone, thiamine, dextrose
Urine toxicology screen
Aspirin and acetaminophen levels
Comprehensive metabolic panel (CHEM-20)
Patients often ingest aspirin or acetaminophen in conjunction with the drug overdose.
Move the clock forward only 5 minutes and do an “Interval History.” If naloxone is going to work, it will take immediate effect.
Interval History: “There is no effect with naloxone, dextrose, or thiamine. The patient remains confused and delirious. The urine toxicology, chemistry, and drug levels have been collected and sent to the laboratory.”
On CCS, medications are considered as administered or given instantly. You must move the clock forward, however, to see the effect.
Why not give flumazenil to patients (such as this one) with altered mental status of unclear etiology?
a. Benzodiazepine overdose is rare.
b. Acute benzodiazepine withdrawal causes seizures.
c. Benzodiazepine overdose is not fatal.
d. Flumazenil is ineffective.
e. You should give it.
Answer b. Acute benzodiazepine withdrawal causes seizures.
Flumazenil is an immediate antagonist of benzodiazepines, which should result in an immediate reversal of benzodiazepine effect. That is why it causes seizures. In this case with potential tricyclic antidepressant (TCA) overdose evident from the first sentence, it is even more likely to cause seizures. TCA overdose produces seizures. Being on benzodiazepines protects against those seizures.
Flumazenil creates benzodiazepine withdrawal.
The case is moved forward and there is no improvement in altered mental status.
PE:
HEENT: dilated pupils
Neurological: lethargic, disoriented
Skin: dry, warm
TCA antihistamine effect creates disorientation and lethargy.
What is the most urgent step?
a. TCA level
b. Electrocardiogram (ECG)
c. Calcium chloride
d. Pyridostigmine
Answer b. Electrocardiogram (ECG)
ECG is the most urgent step because it detects the most common cause of death in TCA overdose, which is cardiac arrhythmia (Figure 11-1). TCA level is important, but not as important as seeing if we have life-threatening TCA toxicity.
Figure 11-1. Electrocardiogram (ECG) with manifestations of cyclic antidepressant toxicity. The right axis deviation of the terminal 40 msec of the QRS complex is because of cyclic antidepressant toxicity. Note the large R wave in lead aVR and S wave in lead I. (Reproduced with permission from Tintinalli JE, et al. Tintinalli’s Emergency Medicine, A Comprehensive Study Guide, 7th ed. New York: McGraw-Hill; 2011.)
Pyridostigmine does increase ACh, but this will have no effect on TCA overdose.
The patient continues to be lethargic.
ECG: wide QRS (>120 msec)
With this additional information, what is the most urgent step?
a. Bicarbonate
b. Atropine
c. Lidocaine
d. Amiodarone
Answer a. Bicarbonate
Bicarbonate administration will protect the heart. This is the fastest way to reverse the effect of TCAs on the heart. Bicarbonate is not given to increase excretion of TCA. There will be no effect on the blood level of TCAs. It is given entirely to reverse the possibility of an imminent arrhythmia.
Lidocaine and amiodarone are used when there actually is an arrhythmia that has developed. We never use these agents prophylactically.
Always test acetaminophen and aspirin levels with drug overdose!
Co-ingestion is common.
The patient is given a stat dose of intravenous (IV) bicarbonate. Move the clock forward. A repeat ECG shows the QRS duration has gone back to 100 msec.
TCAs have a quinidine-like effect on the heart.
TCAs inhibit fast sodium ion (Na+) channels in phase 0.
Transfer the patient to the intensive care unit (ICU).
Orders:
Repeat ECG in 1 hour
Telemetry monitoring
Repeat dose of bicarbonate
What is the mechanism of decreased bowel sounds in this patient?
a. Increased ACh
b. Decreased ACh
c. Decreased norepinephrine
d. Increased serotonin
Answer b. Decreased ACh
TCAs inhibit the effect of ACh throughout the body. The anticholinergic effect of TCAs causes constipation and it also explains the diminished bowel sounds with a TCA overdose.
The anticholinergic effect of TCAs can also cause dilated pupils and dry skin.
Sweat production is stimulated by ACh.
The only effect that ACh has on the sympathetic system is in the production of sweat.
After the administration of bicarbonate and transfer of the patient to the ICU, there is an improvement in the ECG. Over the next few hours, the patient’s mental status starts to improve.
• TCAs cause death by:
Wide QRS and arrhythmia
Seizures
• TCAs cause seizures by:
Increasing central nervous system (CNS) norepinephrine levels
Decreasing the inhibitory effect of gamma-aminobutyric acid (GABA) on neurons
Over the next 12 to 24 hours, the patient starts to wake up.
Reports:
Amitriptyline level elevated
Chemistries normal
Repeat ECG (second hospital day): normal QRS
When the ECG and QRS are normal without the use of bicarbonate, the patient can be safely transferred to regular hospital floor. If there is a question of possible intentional overdose, always get a psychiatric evaluation. For a patient like this with a history or depression and anxiety, psychiatric evaluation is beneficial as well.
Adverse Effects of TCA
• Dry mouth
• Constipation
• Urine retention
• Dry eyes
Adverse Effect Mechanism
• Inhibition of ACh