Case 5 – When Naloxone Doesn’t Help

Case #5: When Naloxone Doesn’t Help
Author: Michael Gottlieb, MD
Peer Reviewer: Michele Zell Kanter, PharmD, DABAT

A 23-year-old male is brought to the ED by paramedics after being found unresponsive on a park bench. Upon presentation, he is lethargic with brief periods of apnea that resolve without treatment. There is no additional history from the paramedics. His fingerstick glucose was normal and he was given 2 rounds of naloxone 2mg IV en route without changes in his respiratory status. On exam, he has no signs of head trauma, his pupils are 3 mm bilaterally and reactive to light, and he is noted to have scattered bullae on his posterior lower legs. The remainder of the exam is non-focal.

Initial VS: Temp: 95.0 HR: 70 BP: 92/60 RR: 6 O2: 94% on RA

His family has been notified and will arrive in 15 minutes.

What is the most likely toxicologic etiology of this patient’s presentation?
Opioids, benzodiazepines (BZDs), and barbiturates should be high in the differential diagnosis of toxic ingestions. However, given the lack of response to naloxone combined with reactive pupils, opioids are less likely the cause for his symptoms. Although both BZDs and barbiturates can present similarly, bullae (although rare) are more classically associated with barbiturates.

The family arrives and states that he takes Fioricet (butalbital, acetaminophen, and caffeine) for migraine headaches and that recently he has been increasing the doses because his headaches were poorly controlled.

What other clinical symptoms might you expect to see with this patient?
General: Hypothermia
CNS: Drowsiness, Disinhibition, Ataxia, Confusion, Coma, Pseudo-‘brain death’*
Cardiovascular: Hypotension
Pulmonary: Respiratory depression
GI: Decreased bowel sounds, Ileus
Skin: Bullae (rare)

*Note: Barbiturates may mimic brain death in high doses, by causing apnea, inhibition of reflexes/brainstem responses, and even blunting of the EEG waveforms.

What are some special treatments you could consider for this patient?
Consider multi-dose activated charcoal (MDAC), alkaline diuresis with sodium bicarbonate (NaHCO3), and/or hemodialysis (in severe cases).

MDAC: Mix 50-100 g in a “slurry” with water and give PO immediately, followed by 12.5-25 g in water given PO every four hours.
NaHCO3: Give 3-4 mEq/kg/hr via IV infusion with goal of serum pH: 7.5 and urine pH: 8.0. Monitor the serum potassium and be aware of the high sodium load in patients with underlying CHF.

Note: Recall the mnemonic for MDAC treatment:

A: Aminophylline (theophylline)
B: Barbiturates
C: Carbamazepine
D: Dapsone
Q: Quinine

What further testing should you order?
Check a barbiturate level, APAP Level, ASA Level, and a blood alcohol level. Consider additional testing based upon the clinical scenario.

Note: Serum barbiturate levels do not correlate strongly with cerebral concentration or clinical symptoms. As a general rule, levels > 10 mg/dL for long-acting barbiturates, > 5 mg/dL for intermediate-acting barbiturates, and > 2 mg/dL for short-acting barbiturates are considered high-risk ingestions.


Chyka PA, Seger D, Krenzelok EP, et al. Position paper: Single-dose activated charcoal. Clin Toxicol (Phila). 2005;43(2):61-87.

Coupey SM. Barbiturates. Pediatr Rev. 1997 Aug;18(8):260-4.

Lindberg MC, Cunningham A, Lindberg NH. Acute phenobarbital intoxication. South Med J. 1992 Aug;85(8):803-7.

McCarron MM, Schulze BW, Walberg CB, et al. Short-acting barbiturate overdosage. Correlation of intoxication score with serum barbiturate concentration. JAMA. 1982 Jul 2;248(1):55-61.

Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol. 1999;37(6):731-51.

Proudfoot AT, Krenzelok EP, Vale JA. Position Paper on urine alkalinization. J Toxicol Clin Toxicol. 2004;42(1):1-26.

Return to Case List