Opioid-Induced Ventilatory Impairment

Introduction

• Opioids reduce pain by binding to opioid receptors.^1-3
  • Opioid receptors are located throughout the CNS and in other locations, such as the gastrointestinal tract.³
  • Opioids also have secondary side effects such as constipation when effects are exerted on the gastrointestinal system and ventilatory impairment when effects are exerted on the brainstem.^2,3
• OIVI is a phenomenon in which ventilation is usually reduced after opioid administration.^1,2
  • In comparison to opioid-induced respiratory depression (OIRD), OIVI is a more comprehensive term, as respiratory depression is only one of the causes of ventilatory impairment in the setting of opioid use.^1,3,4
  • If untreated, OIVI can cause end-organ damage, cardiac arrest, and death.^1,4
• The incidence of OIVI is very difficult to capture due to the heterogeneity in its assessment and definition.
  • Some reports cite an incidence ranging from 0.15 to 1.1% of all postsurgical patients experience OIVI.⁵
  • 75% of OIVI cases occur within the first 24 hours of surgery.⁵
• Ventilation can be measured using various markers/indicators.^2,3
  • Surrogate indicators:
  • Oxygen saturation (SpO₂)
  • Respiratory rate (RR)
  • Direct indicators:
  • Arterial carbon dioxide concentration (PaCO₂)
  • Minute ventilation (RR x tidal volume)

Causes and Mechanisms of OIVI

• Causes of OIVI can be grouped into three main categories.^1,2,4
  • Respiratory depression
  • Decreased level of consciousness
  • Upper airway obstruction
• Respiratory depression^1,3
  • It is mostly mediated by mu-opioid receptors within the CNS.⁴
  • Activation of mu-opioid receptors at specific sites in the CNS leads to changes in respiratory rhythm and a blunting of the hypercapnic ventilatory response (HCVR).³
  • Respiratory rhythm²
    • Defined by two parameters: RR and tidal volume
    • If depressed, the result will be shallow breathing and possible apnea, leading to hypoventilation.
    • Mediated in the pre-Botzinger complex
  • HCVR²
    • Ventilation is typically controlled by carbon dioxide (CO₂)
    • Hypoventilation causes an increase in CO₂, which is sensed by chemoreceptors (as an increase in CSF acidosis) that then leads to an increase in ventilation
    • Opioids blunt the ventilatory response to hypercarbia, thereby leading to hypercarbia and, ultimately, hypoxia.^1,2,4
    • Areas in the brain that mediate this are chemoreceptors in the parabrachial and Kolliker fuse nuclei.³
• Decreased level of consciousness^1,3
  • Occurs due to direct action within the CNS²
  • Continuum of sedation is highly variable along PaCO₂ ranges from 48-148 mmHg⁴
  • This leads to a decreased response to a stimulus and ability to stay alert.⁴
  • Sedation frequently precedes respiratory depression^2,4
    • A decreased level of consciousness has been found to be a more reliable indicator of OIVI than oxygen saturation or RR.^1,4
• Upper airway obstruction^1,3
  • Occurs due to suppression of supraglottic muscle tone
  • Effects are amplified in patients with existing obstructive sleep apnea.⁴

Risk Factors

• Commonly cited risk factors for OIVI include:^1,3,4
  • Advanced age
  • Obstructive sleep apnea
  • Obesity
  • Concomitant use of other CNS depressants, such as benzodiazepines and alcohol
  • High opioid doses, particularly when initiating therapy or escalating doses

Monitoring for OIVI

• All patients receiving opioids for the management of acute postoperative pain should be monitored for OIVI.^5-7
• Monitoring strategies include:
  • Continuous pulse oximetry
    • Recommended for all patients: The recommendation is for universal monitoring instead of monitoring only high-risk patients.
    • Advantages: easily accessible, inexpensive, and comfortable to wear.⁵
    • Disadvantages: Can provide false reassurance when supplemental oxygen is used.⁸
    • Critical threshold alarms are an issue as too high threshold alarms lead to alarm fatigue, but too low alarms lead to late responses to respiratory depression.
  • Capnography
    • It should be used if supplemental oxygen is required.
    • Capnography is considered qualitative in nonintubated patients, given the inconsistent correlation between PaCO₂ (arterial partial pressure of carbon dioxide) and ETCO₂ (end-tidal carbon dioxide) in non-ventilated patients.^5,8
    • Disadvantages: expense and comfort tolerance⁸
  • Modified Early Warning Score (MEWS)
    • It uses multiple monitors to create an algorithm based on their thresholds.⁵
    • Disadvantages: need for electronic medical records and robust response protocols⁵
  • Bioimpedance models
    • It uses surface electrodes to detect changes in ventilation.⁵
    • Disadvantages: Cost, comfort tolerance, and motion artifacts lead to alarm fatigue⁵
  • Bedside clinical assessments of the level of consciousness/sedation.^6,7
    • Higher sensitivity, sensitivity and reliability was noted when the assessment was completed by a skilled clinician.⁷
• An ideal system would assess changes in ventilation using multiple parameters and be directly coupled to the medication delivery system to stop medication while personnel are alerted immediately.⁵
• It is best to use a central location to monitor all the patient’s ventilation and oxygenation.^6,7

Implications in the Pediatric Population

• Much of literature regarding OIVI is in the adult population, but not all this data can be extrapolated to the pediatric population, given the different disease processes unique to each cohort.⁸
• Pediatric risk factors for OIVI include⁸
  • Premature, age <1 year
  • Developmental delay
  • Neurological or respiratory dysfunction
  • Polypharmacy, supplemental oxygen
  • ENT surgery
• Incidence
  • Like adults, 75% of cases of OIVI occur within the first 24 hours postsurgery.^5,8
• Monitoring recommendations⁸
  • APSF recommends continuous oxygenation and ventilation monitoring when patients are receiving supplemental oxygen while on opioid therapy.
  • The Society for Pediatric Anesthesia recommends extra vigilance for neonates, children with obstructive sleep apnea, neuromuscular disorders, cognitive impairments, and patients starting opioid therapy or escalating opioids in conjunction with CNS depressants.
    • Regular assessments of the level of sedation
    • Admission to a monitored environment when initiating opioids in infants under 3 months of age
    • Continuous monitoring of respiratory rate and electrocardiogram for patients on supplemental oxygen
  • Expert opinion supports continuous respiratory rate and pulse oximetry monitoring for 24 hours for patients receiving initial doses of parenteral opioids or opioid patient-controlled analgesia unless the patient is awake and actively being observed.
• Monitors⁸
  • Besides pulse oximetry and capnography, other available methods include:
    • Transthoracic impedance plethysmography
      • Assesses respiratory rate
      • Disadvantages: motion artifact
    • Transcutaneous CO₂ monitor
      • Measures skin surface partial pressure of CO₂
      • Disadvantages: lack of ability to monitor breath to breath; therefore, delayed identification of acute changes
    • Noninvasive respiratory volume monitor
      • Measures respiratory rate, tidal volume, minute ventilation
      • Disadvantages: limited accuracy in spontaneously ventilating patients and rare availability.