VA ICU Report 1.26.18: Suboxone in the hospitalized patient

Case summary: Thanks to the effervescent Ugo for presenting a fascinating rapid response case from the VA– a 54M with PMH severe kyphosis and opiate addiction on suboxone (buprenorphine/naloxone), who was admitted to Orthopedics for elbow I+D, found to have encephalopathy and acute on chronic respiratory acidosis.

Top pearls:

  1. Buprenorphine is a very high affinity partial agonist at the mu opioid receptor that displaces most opiates AND requires higher, continuous, and more prolonged doses of naloxone to reverse.
  2. Patients on suboxone who have acute pain can receive concurrent opiates but will likely need higher doses and close monitoring for respiratory depression.
  3. When assessing if CO2 narcosis is 2/2 opiates versus an alternative cause, remember to look for pinpoint pupils as a clue to opiate intoxication (NB: pupillary constriction does not habituate/resolve with chronic opioids).
  4. A structured approach to hypercapnea includes extra- (e.g. decreased minute ventilation) and intra-pulmonary (e.g. V/Q mismatch) processes, as well as increased CO2 production.

Buprenorphine/suboxone in the hospitalized patient

  • Reviewing the mechanisms of action of these drugs helps explain some of the intricacies of their inpatient management.
    • Buprenorphine: very high affinity partial agonist at the mu opioid receptor and a weak antagonist at the kappa receptor. It will displace opioid full agonists from the receptor. Partial agonist effects imbue buprenorphine with several clinically desirable pharmacologic properties: lower abuse potential; lower level of physical dependence (less severe withdrawal syndrome); a ceiling effect, with respect to clinical effects, at higher doses; and greater safety in overdose compared with opioid full agonists.
    • Naloxone: has negligible bioavailability via the sublingual or oral routes but was added to buprenorphine in an effort to deter intravenous abuse of suboxone
  • 2 issues that will increasingly come up for hospitalized patients on suboxone:
    • 1) Respiratory depression:
      • Part of suboxone’s appeal is the belief that it causes less significant respiratory depression because its partial agonist properties prevent complete activation of mu-opioid receptors, making it safer in overdose.
      • But suboxone, like all opioids, can cause respiratory depression! There is, however, a purported “ceiling effect,” i.e. it can only cause a certain level of respiratory depression even with increasing doses.
      • Risk factors for respiratory depression to think about and reverse: concurrent sedating meds, high doses, low body weight (i.e. cachexia or pediatric patients), concurrent medical illness (i.e. altered drug metabolism from renal or liver dysfunction)
      • How do we reverse suboxone in this setting: In typical opiate overdose, we might trial a bolus of IV naloxone (e.g. 0.4mg), which has both diagnostic and therapeutic utility. Higher, continuous, and prolonged doses of naloxone are required to displace suboxone’s high-affinity binding to opiate receptors and compete with rebinding during suboxone’s long half-life. In clinical trials, a suggested dose is: naloxone bolus dose of 2–3 mg, followed by a continuous infusion of 4 mg/h (which caused full reversal within 40–60 min. Recall that this will cause acute opiate withdrawal, which you should treat with supportive measures (e.g. clonidine, loperamide, etc.).
    • 2) Pain control:
      • What is the best method of acute pain control for patients on suboxone? Do not stop suboxone! It’s important to trial non-opiate medications if possible (e.g. nerve blocks). However, opiates should be used if indicated, with the understanding that higher doses will be required, and that patients should be monitored closely for respiratory depression.


Anesthesiology 7 2006, Vol.105, 51-57.

Differential diagnosis of respiratory acidosis

  • Decreased minute ventilation (global hypoventilation/extra-pulmonary):
    • Decreased central respiratory drive (e.g. sedatives, central apnea, stroke)
    • Decreased neuromuscular fxn (e.g. ALS, myasthenia gravis, GBS)
    • Decreased thoracic ribcage fxn (e.g. kyphoscoliosis, ankylosing spondylitis)
    • Metabolic disorders (e.g. hypophos, hypothyroidism)
    • Toxins/poisonings/drugs (e.g. tetanus, botulism, neuromuscular blockade)
  • V/Q mismatch (gas exchange problems/intra-pulmonary causes):
    • Anatomic: short, shallow breathing
    • Physiologic: PE, pulmonary vascular disease, dynamic hyperinflation or small airway obstruction (COPD/asthma), ILD
  • Increased CO2 production: hyperpyrexia, thyrotoxicosis, extreme exercise
  • Upper airway disorders: angioedema, laryngeal or tracheal stenosis, vocal cord paralysis, epiglotitis, retropharyngeal abscess, foreign body

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