Part 2 in a Four-part Series
A 57-year-old man presented with acute onset altered mental status. His family said he had been behaving normally. Prior to dinner, however, he became difficult to arouse, and was speaking gibberish. He was somnolent but arousable to physical stimuli on arrival in the ED.
He answered questions inappropriately and would then go back to sleep. His past medical history was consistent with hypertension, hypercholesterolemia, and spinal fusion a month ago. His medications included lisinopril, atorvastatin, and hydrocodone. His vital signs were a blood pressure of 110/65 mm Hg, heart rate of 90 bpm, temperature of 98.5°F, respiratory rate of 6 bpm, and pulse oxygen of 95% on room air. He had no focal neurologic deficits and pupils at 3-2 mm bilaterally.
How Naloxone Works and the Correct Dosage
Naloxone works as a competitive mu opioid-receptor antagonist. The dosage is empirical and depends on the amount of opioid taken, the type of opioid, and how dependent the patient is on opioids.
All three factors should be considered before administering naloxone. The initial dose should be small (0.04 mg), followed by escalating doses (0.5 mg, 1 mg, 2 mg, 4 mg, 10 mg, 15 mg) every two to three minutes until there is a response. (N Engl J Med 2012;367:146.) More potent opioids, such as synthetic fentanyl analogs and buprenorphine, may require higher levels of naloxone. Patients who are opioid-dependent like the patient in this case will have precipitated withdrawal even at levels as low as 0.4 mg. Use of the minimum effective dose followed by quick escalation to achieve reversal is the most prudent treatment strategy. A continuous infusion is indicated for recurrent symptoms.
Selecting Patients for Naloxone
The indication for administering naloxone is the presence of respiratory depression. These patients generally do not have a problem of oxygenation but rather of ventilation; they should not be automatically treated with supplemental oxygen. In fact, supplemental oxygen may be a detriment to these patients because it can cause a falsely elevated oxygen saturation on the pulse oximeter and subsequently a delay in the recognition of hypoventilation.
Optimal monitoring should be done with a continuous end-tidal CO2; otherwise a pulse oximeter that can measure the respiratory rate is useful. If patients develop respiratory depression as measured by their respiratory rate, end-tidal CO2, or CO2 measured on a VBG, they should be administered naloxone and observed.
Disposition of Opioid-Intoxicated Patients after Receiving Naloxone
Disposition depends on the opioid that the patient used. For patients who say they used heroin, a short-acting opiate, a single dose of naloxone should suffice. These patients can be monitored for three to four hours.
The vitals and observations that may predict safe discharge in these patients:
- They can mobilize as usual.
- Oxygen saturation of >92% on room air
- Respiratory rate of >10 bpm and <20 bpm
- Temperature >35°C and <37.5°C
- Heart rate >50 bpm and <100 bpm Glasgow Coma Scale of 15
The patient should meet all of these criteria without verbal or physical stimuli.
Some clinicians recommend a prescription of naloxone for these patients to help in case of future overdoses. Patients taking longer-acting opioids (i.e., oxycodone, hydrocodone, methadone, and buprenorphine) or who require additional administration of naloxone during an observation period should be admitted to the hospital to a monitored bed. Pediatric patients with an accidental ingestion of one of these longer-acting opioids should be admitted for a 24-hour observation. Fentanyl derivatives generally require such large doses of naloxone for reversal that these patients should be admitted directly to an ICU or a step-down unit.
Timing of Naloxone Prescription
Due to the severity of the opioid epidemic, recent legislation has focused on increasing the availability of naloxone not only to emergency responders but also to the public. President Barack Obama signed the Comprehensive Addiction and Recovery Act in 2016 to increase the availability of naloxone to first responders and the public. There are several formulations from which providers can choose to prescribe to patients, but some are cost-prohibitive. The provider should educate the patient and his friends and family members about the use and limitations of naloxone.
Naloxone Product Manufacturer Previous cost Cost (2016)
Injectable or intranasal, Amphastar $20.34 (2009) $39.60
1 mg/mL vial (2 mL)
(mucosal atomizer separate)
0.4 mg/mL vial (10 mL) Hospira $62.29 (2012) $142.49
0.4 mg/mL vial (1 mL) Mylan $23.72 (2014) $23.72
0.4 mg/mL vial (1 mL) West-Ward $20.40 (2015) $20.40
Auto-injector, two-pack Kaleo $690 (2014) $4,500
of single-use prefilled
Nasal spray, two-pack Adapt Pharma $150 (2015) $150
of single-use intranasal
Chart adapted N Engl J Med 2016;375:2213.
Nasal Narcan produced by Adapt Pharma.
The patient was a chronic opiate user, so was administered 0.04 mg IV naloxone. His respirations increased to 12 bpm, and he remained somnolent but was easily arousable to voice. When awake, he was alert and oriented. After one hour, he required another 0.04 mg IV naloxone. The patient was admitted to a step-down unit for observation because he was known to be prescribed oxycodone, and he was placed on a naloxone infusion at two-third of the effective naloxone dose.