Opioid-induced ventilatory impairment

Overview of opioid-induced ventilatory impairment

Opioid-induced ventilatory impairment¹ is one of the most common causes of serious opioid-induced harm and death. Opioid-induced ventilatory impairment is associated with three interlinked mechanisms:

central respiratory depression—depression of respiratory drive leading to reduced respiratory rate or depth of breathing
sedation—depression of consciousness
upper airway obstruction—depression of muscle tone (may manifest as snoring).

All opioids can cause opioid-induced ventilatory impairment, but the relative risk is higher with:

full mu-receptor agonists
opioid doses that exceed the patient’s opioid requirements
frequent administration of opioids
use of opioids for opioid-nonresponsive pain
administration of opioids by multiple routes (except when a patient on long-term opioid therapy requires another route of opioid administration for acute pain management)
continuous infusions of opioid or use of modified-release opioids (including transdermal patches) for acute pain
co-administration of sedatives (eg alcohol, benzodiazepines, cannabis, gabapentinoids, antipsychotics)
comorbidities (eg obesity, sleep-disordered breathing, chronic obstructive pulmonary disease, tonsillar hypertrophy, cardiac disease, kidney disease, neurological disease)
recent airway surgery, tonsillectomy or adenoidectomy (in children)
infants
patients older than 65 years.

Seek specialist advice before prescribing opioids for patients at increased risk of opioid-induced ventilatory impairment. Risk of opioid-induced ventilatory impairment is reduced when there is a primary opioid prescriber.

Pain acts as a physiological antagonist to opioid-induced ventilatory impairment—the risk of opioid-induced ventilatory impairment is reduced if opioids are titrated to the pain. Early detection of opioid-induced ventilatory impairment helps to prevent excessive opioid dosing and serious harm—monitor all patients for indicators of opioid-induced ventilatory impairment following opioid administration.

Note: Early detection of opioid-induced ventilatory impairment helps to prevent excessive opioid dosing and serious harm.

Indicators of opioid-induced ventilatory impairment

Monitoring for indicators of opioid-induced ventilatory impairment allows for prompt intervention before serious harm or death occurs.

Measuring end-tidal or blood partial pressure of carbon dioxide is the most reliable way to detect opioid-induced ventilatory impairment. The ability to do this on a repeated or continuous basis is limited to settings with staffing and resources that allow immediate resuscitation, and a surrogate measure must usually be used (eg sedation score).

Opioid-induced ventilatory impairment is almost invariably accompanied by excessive sedation—regularly monitor for sedation using a sedation score in all patients receiving an opioid. A sedation score of 2 or more is a more reliable clinical indicator of early opioid-induced ventilatory impairment than respiratory rate.

Note: A sedation score of 2 or more is a more reliable clinical indicator of early opioid-induced ventilatory impairment than reduced respiratory rate.

For patients treated in the community, educate the patient and their carer or family about signs of sedation (eg sleepiness, trouble staying awake), and advise them to seek medical attention if sedation occurs. Increased vigilance is required for patients:

at increased risk of opioid-induced ventilatory impairment
who are physically unwell (eg dehydrated, kidney impairment)
who have had an increase in opioid dose.

In some circumstances, ‘take-home naloxone’ may be appropriate.

Table 1. An example of a sedation scoring system
[NB1]
Sedation score	State of consciousness
0	awake and alert
1	easy to rouse and remains awake
2	easy to rouse, but unable to remain awake
3	difficult to rouse
Note: NB1: A sedation score of 2 indicates early opioid-induced ventilatory impairment. The aim is to titrate an opioid to a sedation score of less than 2.

Respiratory rate alone is an unreliable indicator of opioid-induced ventilatory impairment because it may remain within a normal range even in the presence of significant opioid-induced ventilatory impairment. Suspect opioid-induced ventilatory impairment in patients with respiratory rates lower than the limit of the normal range for their age (see Lower limit of normal respiratory rate range by age).

Table 2. Lower limit of normal respiratory rate range by age
[NB1]
Age	Lower limit of normal respiratory rate range
less than 1 year	30 breaths per minute
1 to 12 years	20 breaths per minute
12 to 17 years	15 breaths per minute
older than 17 years	8 breaths per minute
Note: NB1: Suspect opioid-induced ventilatory impairment in patients with respiratory rates below these values. Respiratory rate may remain within the normal range despite significant opioid-induced ventilatory impairment.

Note: Respiratory rate may remain within the normal range despite significant opioid-induced ventilatory impairment.

Hypoxaemia (less than 92% oxygen saturation on pulse oximetry) when a patient is breathing room air may indicate significant opioid-induced ventilatory impairment; however, it cannot reliably predict early opioid-induced ventilatory impairment. The use of supplemental oxygen to prevent hypoxaemia (eg following surgery) makes pulse oximetry unreliable to detect opioid-induced ventilatory impairment.

Note: The use of supplemental oxygen can mask detection of opioid-induced ventilatory impairment by pulse oximetry.

Management for opioid-induced ventilatory impairment

If opioid-induced ventilatory impairment is suspected (see Indicators of opioid-induced ventilatory impairment), management strategies include:

reducing subsequent opioid doses
withholding or stopping the opioid
administering naloxone.

The management strategy depends on the severity of opioid-induced ventilatory impairment and support of airway and breathing. For patients who are slightly sedated, but remain easy to rouse, closely monitor them and reduce subsequent opioid doses. For patients who are difficult to rouse or hypoventilating, stop the opioid and administer naloxone.

If opioid poisoning is suspected, additional management strategies are required; see:

If a patient has ongoing pain following an episode of opioid-induced ventilatory impairment, consider restarting the opioid at 50% of the previous dose once the patient’s sedation score is 0 or 1, and their respiratory rate is within normal limits for their age.