What should be done for a patient with opioid overdose who shows no response to the initial dose of naloxone (naloxone hydrochloride) nasal spray after 2-3 minutes?

From the Guidelines

If a patient with opioid overdose shows no response to the initial dose of naloxone nasal spray after 2-3 minutes, the most appropriate action is to administer a second dose of naloxone immediately using a new nasal spray device. This recommendation is based on the understanding that the lack of response to initial naloxone may be due to several factors, including high opioid concentration or the opioid having a stronger binding affinity than naloxone 1.

Key Considerations:

• The patient should be closely monitored for signs of respiratory depression, which may return after the effects of naloxone wear off, given its shorter duration of action compared to many opioids.
• Continue rescue breathing or CPR if the patient is not breathing adequately while waiting for the medication to take effect, as standard BLS and/or ACLS measures should continue if return of spontaneous breathing does not occur 1.
• Additional doses of naloxone may be given every 2-3 minutes using new devices until emergency medical help arrives or the person responds.
• It is crucial not to delay activating emergency response systems while awaiting the patient’s response to naloxone or other interventions, as lay and trained responders should prioritize standard resuscitative measures over naloxone administration in cases of cardiac arrest 1.

Administration and Monitoring:

• Use a new nasal spray device for each administration to ensure the patient receives the full dose of naloxone.
• Administer the second dose in the alternate nostril to maximize absorption.
• After giving the second dose, continue to monitor the patient closely for any signs of improvement or deterioration, and be prepared to administer additional doses as needed until medical help arrives. Given the potential for recurrent CNS and/or respiratory depression after naloxone administration, especially with long-acting or sustained-release opioids, prolonged observation may be necessary 1.

From the FDA Drug Label

If the desired degree of counteraction and improvement in respiratory functions are not obtained, it may be repeated at two to three minute intervals The patient should be given a second dose of naloxone.

• Key consideration: The same device should not be used for a second dose, as the device is designed for a single use.
• Correct action: Give a second dose of nasal spray using a new device. 2

From the Research

Next Steps After Initial Naloxone Administration

If a patient shows no response to the initial dose of naloxone nasal spray after 2-3 minutes, the following steps can be considered:

• Administering a Second Dose: According to 3, laypeople should always have access to at least two dose kits for their interim intervention, implying that a second dose may be necessary if there is no initial response.
• Using a New Device for the Second Dose: The study 3 suggests that having multiple doses available is crucial, but it does not specify whether the same device should be used. However, logically, using a new device for each dose would ensure the correct dosage is administered, as the nasal spray devices are designed for single use.
• Other Considerations: While the provided studies do not directly address the specific actions to take after an initial dose of naloxone nasal spray is ineffective, general first aid principles for unconscious patients, such as ensuring the airway is clear and considering CPR if the patient is not breathing, are relevant. However, the specific next steps in the context of naloxone administration and opioid overdose are best guided by the principle of administering additional naloxone if available and safe to do so.

Relevant Findings

• Naloxone Administration: Studies 4, 5, and 6 highlight the effectiveness of intranasal naloxone in reversing opioid overdoses, with 6 noting successful reversals in 98.8% of cases.
• Timing and Dosage: 3 mentions that the effect of naloxone depends on several factors, including the type of opioid used, and suggests that higher doses may be needed for certain types of overdoses, like those involving fentanyl.
• Community and Layperson Use: The feasibility and success of layperson-administered naloxone are supported by 5 and 7, emphasizing the importance of access to naloxone and proper training for its use.

Decision Making

Given the information and the context of the question:

• The most appropriate action after 2-3 minutes with no response to the initial dose of naloxone nasal spray would be to give a second dose of nasal spray using a new device, as this aligns with the principle of ensuring adequate naloxone dosage for reversal of opioid effects, considering the potential for variable response based on the opioid involved and individual patient factors 3, 6.